, a runner who demonstrates considerably less than 45?of knee flexion may

, a runner who demonstrates considerably less than 45?of knee flexion may suggest Aprotinin web reduced shock absorption, and (R)-K-13675 dose intervention may be warranted. Some data exist suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj., a runner who demonstrates considerably less than 45?of knee flexion may suggest reduced shock absorption, and intervention may be warranted. Some data exist suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj.

Ampal CA1 subfield in individuals with MCI compared to NCI (Fig.

Ampal CA1 subfield in individuals with MCI compared to NCI (Fig. 4), which correlated with the subject’s Mini-Mental State Exam score (MMSE), but not with NFT Braak stage or apolipoprotein E (ApoE) status, a genetic risk factor for AD (Scheff et al., 2006). Unlike the outer molecular layer, CA1 receives input from the Schaffer collaterals arising from CA3 and not from the glutamatergic purchase BMS-214662 neurons of the entorhinal cortex, suggesting differential responses to synapse loss within the hippocampus based upon afferent innervation or chemical phenotype, some of which precipitate synaptic reorganization. A recent report characterized changes in the dendritic branching of the basilar tree of hippocampal CA1 pyramidal neurons. In this study, formalin-fixed tissue autopsy obtained from University of Kentucky Alzheimer’s Disease Center who died with a clinical diagnosis of NCI, MCI or AD was prepared for Golgi impregnation (Fig. 5). Camera lucida drawings of the basilar tree of randomly selected CA1 neurons were analyzed for alterations in dendritic arbor Pyrvinium pamoate supplier amount, distribution and complexity (Mervis et al., 2013). Quantitation showed a significant increase in dendritic length (18 ) and complexity (23 ) in CA1 neurons in MCI compared to NCI. Conversely, there was a significant reduction in branch length (-39 ) and arbor complexity (-25 ) during the progression from MCI to AD (Fig. 5). These findings suggest that the observed increase in CA1 dendritic parameters from NCI to MCI may be another example of a neuroplastic compensatory response to a loss of afferent input early in the course of the disease, which is not maintained as the disease progresses. The role that the reported reduction in total synapse number plays in CA1 neuroplasticity remains unknown. However, these examples of early CA1 neural reorganization may represent a viable window for potential therapeutic strategies aimed at restoring or maintaining hippocampal function during the transition from MCI to AD. Future studies should determine whether alterations in specific synapse subtypes (i.e., perforated vs. non-perforated) are differentially affected and their relation to cognitive decline and brain pathology during the onset of AD. Interestingly, the size of the synaptic contacts was found to be substantially larger in AD cortex compared to non-demented aged controls (Scheff et al., 1990), which was suggested to be part of a compensatory mechanism found in regions of the neocortex and hippocampus (see review Scheff and Price, 2006). These investigators found that as the number of synapses declined in a given region, the size of the residualAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagesynapses increased. This synaptic compensatory response was also observed early in the course of the AD (DeKosky and Scheff, 1990). Neuronal structural alterations may not be the only factor(s) contributing to cognitive decline and hippocampal plasticity in MCI. For example, studies have reported significant reductions in synaptic vesicle trafficking-related genes in the AD brain, which interrupt the efficacy of normal synaptic transmission (Yao et al., 2003; Murphy et al., 2003; Kennedy et al., 2005). Counts et al. (2014) examined progressive changes in the expression classes of synaptic gene within single CA1 neurons in subjects who died with a clinical diagnosis of NCI, MCI or moderate AD obtain.Ampal CA1 subfield in individuals with MCI compared to NCI (Fig. 4), which correlated with the subject’s Mini-Mental State Exam score (MMSE), but not with NFT Braak stage or apolipoprotein E (ApoE) status, a genetic risk factor for AD (Scheff et al., 2006). Unlike the outer molecular layer, CA1 receives input from the Schaffer collaterals arising from CA3 and not from the glutamatergic neurons of the entorhinal cortex, suggesting differential responses to synapse loss within the hippocampus based upon afferent innervation or chemical phenotype, some of which precipitate synaptic reorganization. A recent report characterized changes in the dendritic branching of the basilar tree of hippocampal CA1 pyramidal neurons. In this study, formalin-fixed tissue autopsy obtained from University of Kentucky Alzheimer’s Disease Center who died with a clinical diagnosis of NCI, MCI or AD was prepared for Golgi impregnation (Fig. 5). Camera lucida drawings of the basilar tree of randomly selected CA1 neurons were analyzed for alterations in dendritic arbor amount, distribution and complexity (Mervis et al., 2013). Quantitation showed a significant increase in dendritic length (18 ) and complexity (23 ) in CA1 neurons in MCI compared to NCI. Conversely, there was a significant reduction in branch length (-39 ) and arbor complexity (-25 ) during the progression from MCI to AD (Fig. 5). These findings suggest that the observed increase in CA1 dendritic parameters from NCI to MCI may be another example of a neuroplastic compensatory response to a loss of afferent input early in the course of the disease, which is not maintained as the disease progresses. The role that the reported reduction in total synapse number plays in CA1 neuroplasticity remains unknown. However, these examples of early CA1 neural reorganization may represent a viable window for potential therapeutic strategies aimed at restoring or maintaining hippocampal function during the transition from MCI to AD. Future studies should determine whether alterations in specific synapse subtypes (i.e., perforated vs. non-perforated) are differentially affected and their relation to cognitive decline and brain pathology during the onset of AD. Interestingly, the size of the synaptic contacts was found to be substantially larger in AD cortex compared to non-demented aged controls (Scheff et al., 1990), which was suggested to be part of a compensatory mechanism found in regions of the neocortex and hippocampus (see review Scheff and Price, 2006). These investigators found that as the number of synapses declined in a given region, the size of the residualAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagesynapses increased. This synaptic compensatory response was also observed early in the course of the AD (DeKosky and Scheff, 1990). Neuronal structural alterations may not be the only factor(s) contributing to cognitive decline and hippocampal plasticity in MCI. For example, studies have reported significant reductions in synaptic vesicle trafficking-related genes in the AD brain, which interrupt the efficacy of normal synaptic transmission (Yao et al., 2003; Murphy et al., 2003; Kennedy et al., 2005). Counts et al. (2014) examined progressive changes in the expression classes of synaptic gene within single CA1 neurons in subjects who died with a clinical diagnosis of NCI, MCI or moderate AD obtain.

Monly used and widely available OTC medications and nutritional supplements were

Monly used and widely available OTC medications and nutritional supplements were safe and posed no short- or long-term threat to their health. Many used such products to improve their running performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be SKF-96365 (hydrochloride)MedChemExpress SKF-96365 (hydrochloride) dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product recommended as an effective and legal substance by another runner or by a retail sales clerk may contain substances that are either banned by agencies such as WADA and/or may pose a serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.NIH-PA Author BIM-22493 biological activity Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.Monly used and widely available OTC medications and nutritional supplements were safe and posed no short- or long-term threat to their health. Many used such products to improve their running performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product recommended as an effective and legal substance by another runner or by a retail sales clerk may contain substances that are either banned by agencies such as WADA and/or may pose a serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.

Ions in Barrett’s Esophagus [113,114] and ulcerative colitis [115], among a variety

Ions in Barrett’s Esophagus [113,114] and ulcerative colitis [115], among a variety of other cancer-predisposing diseases. Navin et al recently used the profile of CGH-identified copy number changes to study the clonal architecture of different regions of advanced breast cancers through phylogenetic inference [116]. Direct genomic sequencing provides the most detailed means possible of identifying clonal mutant markers. In contrast to conventional capillary-based techniques where individual PCR products or bacterial clones must be sequenced individually, a powerful new class of “Next Generation” sequencing technologies allows for simultaneous genotyping of tens of billions of base pairs [117]. The rapidly decreasing costs associated with these platforms have recently made it feasible to sequence the entire aggregate genome of a tissue sample without any regional targeting. From a clone detection perspective this means that multiple types of mutations of all functional varieties (both likely passengers and suspected drivers) can be simultaneously assessed. While it only takes a single clonal mutation to identify an expanded population, the redundancy conferred by screening the entire genome provides a huge amount of additional lineage data with the potential to be used for subanalyses such as approximation of a clone’s mitotic age or the phylogenetic relationship between different clones. The digital manner in which these novel sequencing technologies operate lend them a much greater dynamic range of sensitivity than conventional techniques, making it possible to resolve populations that are subclonal relative to a collected sample. Such an ability means that in situations where spatial coherence of an expanding clone is not maintained, for example in myelodysplasia preceding blood cancers, detection at an early stage can still be accomplished [118]. Similarly, a tolerance for clone mixing should allow for convenient, minimally invasive sampling techniques that disrupt cohesive growth patterns in epithelial tissues such as cell isolation from lavage, scrapings or body fluids rather than biopsy. The relatively high error rate of individual sequencing reads currently limits the average depth to which rare subclonal mutations can be accurately detected to about 2 orders of magnitude below pure clonality [26]. A variety of improvements at the level of chemistry, hardware and analysis are continuing to enhance this resolution for all current platforms [118,119]. An even newer generation of exotic “Fourth Generation” sequencing technologies on the horizon promises ultra-long read lengths with the ability to continuously re-sequence theNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPagesame molecule for extremely accurate detection of rare molecular populations [120?22]. The pace of innovation in this area is staggering. Perhaps the only thing that can be stated with certainty about the technologies that will be available five years in the I-CBP112 web future is that they will look nothing like those from five years in the past.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript9. The complex interpretation of clonality: false negatives, positives and Cibinetide web assumptionsThe reasoning associated with clonality determination is complex and many potential confounders exist. In this section we highlight seven important ideas for consi.Ions in Barrett’s Esophagus [113,114] and ulcerative colitis [115], among a variety of other cancer-predisposing diseases. Navin et al recently used the profile of CGH-identified copy number changes to study the clonal architecture of different regions of advanced breast cancers through phylogenetic inference [116]. Direct genomic sequencing provides the most detailed means possible of identifying clonal mutant markers. In contrast to conventional capillary-based techniques where individual PCR products or bacterial clones must be sequenced individually, a powerful new class of “Next Generation” sequencing technologies allows for simultaneous genotyping of tens of billions of base pairs [117]. The rapidly decreasing costs associated with these platforms have recently made it feasible to sequence the entire aggregate genome of a tissue sample without any regional targeting. From a clone detection perspective this means that multiple types of mutations of all functional varieties (both likely passengers and suspected drivers) can be simultaneously assessed. While it only takes a single clonal mutation to identify an expanded population, the redundancy conferred by screening the entire genome provides a huge amount of additional lineage data with the potential to be used for subanalyses such as approximation of a clone’s mitotic age or the phylogenetic relationship between different clones. The digital manner in which these novel sequencing technologies operate lend them a much greater dynamic range of sensitivity than conventional techniques, making it possible to resolve populations that are subclonal relative to a collected sample. Such an ability means that in situations where spatial coherence of an expanding clone is not maintained, for example in myelodysplasia preceding blood cancers, detection at an early stage can still be accomplished [118]. Similarly, a tolerance for clone mixing should allow for convenient, minimally invasive sampling techniques that disrupt cohesive growth patterns in epithelial tissues such as cell isolation from lavage, scrapings or body fluids rather than biopsy. The relatively high error rate of individual sequencing reads currently limits the average depth to which rare subclonal mutations can be accurately detected to about 2 orders of magnitude below pure clonality [26]. A variety of improvements at the level of chemistry, hardware and analysis are continuing to enhance this resolution for all current platforms [118,119]. An even newer generation of exotic “Fourth Generation” sequencing technologies on the horizon promises ultra-long read lengths with the ability to continuously re-sequence theNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPagesame molecule for extremely accurate detection of rare molecular populations [120?22]. The pace of innovation in this area is staggering. Perhaps the only thing that can be stated with certainty about the technologies that will be available five years in the future is that they will look nothing like those from five years in the past.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript9. The complex interpretation of clonality: false negatives, positives and assumptionsThe reasoning associated with clonality determination is complex and many potential confounders exist. In this section we highlight seven important ideas for consi.

. This exploratory analysis can provide further information on functional similarities between

. This exploratory analysis can provide further information on functional similarities between regions, and, more specifically, on the extent to which activation profiles of category-selective regions are inherited from EVC. As for the replicability of within-category ranking (Fig. 5), we combined data across subjects either by concatenating or averaging the activation profiles across subjects. The concatenation MLN1117 web approach is sensitive to inter-region correlations of activation profiles even if the particular activation profiles differ across subjects. The averaging approach is sensitive to inter-region correlations of activation profiles that are consistent across subjects. We investigated the inter-region correlations for (1) the full activation profile, (2) the within-face activation profile, and (3) the withinplace activation profile. Statistical inference was performed by a standard one-sided test on Spearman’s r. p CBR-5884 biological activity values were corrected8658 ?J. Neurosci., June 20, 2012 ?32(25):8649 ?Mur et al. ?Single-Image Activation of Category Regionsfor multiple testing using Bonferroni correction based on the total number of tests performed. Figure 7 shows the inter-region correlation results. The main pattern that emerges is that activation profiles are correlated between hemispheres for corresponding regions, and between hIT and EVC (red blocks on diagonals). We subsequently inspected the within-face correlation between FFA and EVC, and the within-place correlation between PPA and EVC. The within-face activation profile was correlated between left but not right FFA and EVC, and the within-place activation profile was not significantly correlated between PPA and EVC. Results were similar across ROI sizes. These results suggest that EVC is not a major contributor to the within-category activation profiles of PPA and right FFA. We then inspected the correlation between category-selective regions (FFA/PPA) and EVC for the full activation profile (top row). The full activation profile was correlated between EVC and both categoryselective regions, especially PPA. One interpretation of this finding would be that some degree of category selectivity is already present at the level of EVC, implying that low-level feature differences contribute to some extent to categoryselective responses. For places, this seems a plausible interpretation, consistent with our finding that single-image activation of EVC can discriminate places from nonplaces at an above-chance level (Fig. 2). For faces, this interpretation seems less likely: the correlation between EVC and FFA is not significant for the subjectaverage activation profile, suggesting that the correlation is driven by subjectspecific effects (e.g., idiosyncratic arousal effects) and not by face-selectivity of responses (shared across subjects in FFA). Categorical, yet graded Figure 8 summarizes our results. Singleimage activation profiles of categoryselective regions (1) show near-perfect discrimination of preferred from nonpreferred images and no preference inversions for particular object images, (2) show a step-like drop-off at the category boundary, and (3) are graded within and outside the preferred category. It can further be noted that single-image category selectivity is stronger in right than left FFA. In addition, gradedness seems to be more pronounced in FFA; the category step seems to be more pronounced in PPA. In sum, our findings indicate that the activation profiles of category-selec-Figure.. This exploratory analysis can provide further information on functional similarities between regions, and, more specifically, on the extent to which activation profiles of category-selective regions are inherited from EVC. As for the replicability of within-category ranking (Fig. 5), we combined data across subjects either by concatenating or averaging the activation profiles across subjects. The concatenation approach is sensitive to inter-region correlations of activation profiles even if the particular activation profiles differ across subjects. The averaging approach is sensitive to inter-region correlations of activation profiles that are consistent across subjects. We investigated the inter-region correlations for (1) the full activation profile, (2) the within-face activation profile, and (3) the withinplace activation profile. Statistical inference was performed by a standard one-sided test on Spearman’s r. p values were corrected8658 ?J. Neurosci., June 20, 2012 ?32(25):8649 ?Mur et al. ?Single-Image Activation of Category Regionsfor multiple testing using Bonferroni correction based on the total number of tests performed. Figure 7 shows the inter-region correlation results. The main pattern that emerges is that activation profiles are correlated between hemispheres for corresponding regions, and between hIT and EVC (red blocks on diagonals). We subsequently inspected the within-face correlation between FFA and EVC, and the within-place correlation between PPA and EVC. The within-face activation profile was correlated between left but not right FFA and EVC, and the within-place activation profile was not significantly correlated between PPA and EVC. Results were similar across ROI sizes. These results suggest that EVC is not a major contributor to the within-category activation profiles of PPA and right FFA. We then inspected the correlation between category-selective regions (FFA/PPA) and EVC for the full activation profile (top row). The full activation profile was correlated between EVC and both categoryselective regions, especially PPA. One interpretation of this finding would be that some degree of category selectivity is already present at the level of EVC, implying that low-level feature differences contribute to some extent to categoryselective responses. For places, this seems a plausible interpretation, consistent with our finding that single-image activation of EVC can discriminate places from nonplaces at an above-chance level (Fig. 2). For faces, this interpretation seems less likely: the correlation between EVC and FFA is not significant for the subjectaverage activation profile, suggesting that the correlation is driven by subjectspecific effects (e.g., idiosyncratic arousal effects) and not by face-selectivity of responses (shared across subjects in FFA). Categorical, yet graded Figure 8 summarizes our results. Singleimage activation profiles of categoryselective regions (1) show near-perfect discrimination of preferred from nonpreferred images and no preference inversions for particular object images, (2) show a step-like drop-off at the category boundary, and (3) are graded within and outside the preferred category. It can further be noted that single-image category selectivity is stronger in right than left FFA. In addition, gradedness seems to be more pronounced in FFA; the category step seems to be more pronounced in PPA. In sum, our findings indicate that the activation profiles of category-selec-Figure.

In living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic

In living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic Ca-phosphate in pelagic sediments has long been studied by a number of investigators17,18,21?4,40?2. Some have suggested that biogenic Ca-phosphate incorporates REY via pore water in the sediment column23,40. Others have argued that Ca-phosphate takes up REY from a variety of carrier phases (e.g. Fe n-oxyhydroxides, pellets, and organic debris) that absorb REY from seawater and are readily decomposed at the sediment ater interface17,22,41,42. Although the StatticMedChemExpress Stattic complete process remains an open question, the characteristic REY patterns indicate that seawater is the ultimate source of the REY presently captured in biogenic Ca-phosphate22,25,41 (Fig. 4m). Simple quantitative estimation in this study suggested the possibility that seawater can contain the flux of REY precipitation required to explain the observed very high REY concentrations ( REY + Ce > 1,000 ppm) in bulk REY-rich mud with a sedimentation rate less than 0.5 m/Myr (Supplementary Fig. S19). Such circumstances may Necrosulfonamide price facilitate the concentration of REY in biogenic Ca-phosphate via diffusion of REY from seawater or the transfer of REY from original carriers to Ca-phosphate during the early diagenetic processes because of the prolonged exposure to seawater at the sediment surface and in the bioturbated and well-ventilated uppermost sediment layer17,18,22,41. In addition, biogenic Ca-phosphate enriched in REY might be stabilised through recrystallisation as insoluble apatite17. Moreover, the amount of Ca-phosphate in a unit volume of sediment also increases with a depression of the sedimentation rate17,18. Hence, the low sedimentation rate is considered to be crucial for the formation of REY-rich mud. Actually, the spatiotemporal distribution of high-IC1, -IC4, and -IC7 muds overlapped with the oligotrophic North Pacific and South Pacific gyres and with water depths greater than the CCD, both of which prevented the fast accumulation of dilutive components with low REY content such as biogenic carbonate and silica. If we assume that deep-sea sediments can continuously acquire REY from the overlying deep-sea water prior to burial, the REY-enrichment in sediments can occur in a time scale of 105 years considering the sedimentation rate of <0.5 m/Myr with a typical thickness of 0.1 m for the well-ventilated uppermost sediment layer43. This timescale of REY enrichment is significantly longer than that of global ocean circulation, which is 103 years44. Both IC1 and IC4 indicated statistical independent geochemical features of pelagic red clay mainly composed of detrital aluminosilicates involving abundant Si, Al, Fe, Mg, and K without significant contributions of biogenic carbonate and silica. Fe and Mn of hydrothermal or hydrogenous origins could have also been incorporated without dilution in high-IC1 and high-IC4 sediments, resulting in an increase in the contents of these elements. In addition, in deposition slow enough to allow biogenic Ca-phosphate grains to concentrate REY and to accumulate significantly in the sediment, the P and REY contents of these sediments also increase concurrently. Although sediments enriched in biogenic Ca-phosphate contain several percent of Ca, the significant dilution effect of biogenic carbonate, which contains several tens of percent of Ca, generally creates negative trends in these ICs as a whole in the spaces of Ca and other elements, including REY. The differenc.In living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic Ca-phosphate in pelagic sediments has long been studied by a number of investigators17,18,21?4,40?2. Some have suggested that biogenic Ca-phosphate incorporates REY via pore water in the sediment column23,40. Others have argued that Ca-phosphate takes up REY from a variety of carrier phases (e.g. Fe n-oxyhydroxides, pellets, and organic debris) that absorb REY from seawater and are readily decomposed at the sediment ater interface17,22,41,42. Although the complete process remains an open question, the characteristic REY patterns indicate that seawater is the ultimate source of the REY presently captured in biogenic Ca-phosphate22,25,41 (Fig. 4m). Simple quantitative estimation in this study suggested the possibility that seawater can contain the flux of REY precipitation required to explain the observed very high REY concentrations ( REY + Ce > 1,000 ppm) in bulk REY-rich mud with a sedimentation rate less than 0.5 m/Myr (Supplementary Fig. S19). Such circumstances may facilitate the concentration of REY in biogenic Ca-phosphate via diffusion of REY from seawater or the transfer of REY from original carriers to Ca-phosphate during the early diagenetic processes because of the prolonged exposure to seawater at the sediment surface and in the bioturbated and well-ventilated uppermost sediment layer17,18,22,41. In addition, biogenic Ca-phosphate enriched in REY might be stabilised through recrystallisation as insoluble apatite17. Moreover, the amount of Ca-phosphate in a unit volume of sediment also increases with a depression of the sedimentation rate17,18. Hence, the low sedimentation rate is considered to be crucial for the formation of REY-rich mud. Actually, the spatiotemporal distribution of high-IC1, -IC4, and -IC7 muds overlapped with the oligotrophic North Pacific and South Pacific gyres and with water depths greater than the CCD, both of which prevented the fast accumulation of dilutive components with low REY content such as biogenic carbonate and silica. If we assume that deep-sea sediments can continuously acquire REY from the overlying deep-sea water prior to burial, the REY-enrichment in sediments can occur in a time scale of 105 years considering the sedimentation rate of <0.5 m/Myr with a typical thickness of 0.1 m for the well-ventilated uppermost sediment layer43. This timescale of REY enrichment is significantly longer than that of global ocean circulation, which is 103 years44. Both IC1 and IC4 indicated statistical independent geochemical features of pelagic red clay mainly composed of detrital aluminosilicates involving abundant Si, Al, Fe, Mg, and K without significant contributions of biogenic carbonate and silica. Fe and Mn of hydrothermal or hydrogenous origins could have also been incorporated without dilution in high-IC1 and high-IC4 sediments, resulting in an increase in the contents of these elements. In addition, in deposition slow enough to allow biogenic Ca-phosphate grains to concentrate REY and to accumulate significantly in the sediment, the P and REY contents of these sediments also increase concurrently. Although sediments enriched in biogenic Ca-phosphate contain several percent of Ca, the significant dilution effect of biogenic carbonate, which contains several tens of percent of Ca, generally creates negative trends in these ICs as a whole in the spaces of Ca and other elements, including REY. The differenc.

, a runner who demonstrates considerably less than 45?of knee flexion may

, a runner who demonstrates considerably less than 45?of knee 3-MA price flexion may suggest reduced shock absorption, and intervention may be warranted. Some data exist order Oxaliplatin suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj., a runner who demonstrates considerably less than 45?of knee flexion may suggest reduced shock absorption, and intervention may be warranted. Some data exist suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj.

Ampal CA1 subfield in individuals with MCI compared to NCI (Fig.

Ampal CA1 subfield in individuals with MCI compared to NCI (Fig. 4), which correlated with the subject’s Mini-Mental State Exam score (MMSE), but not with NFT Braak stage or apolipoprotein E (ApoE) status, a genetic risk factor for AD (Scheff et al., 2006). Unlike the outer molecular layer, CA1 receives input from the Schaffer collaterals arising from CA3 and not from the glutamatergic neurons of the entorhinal cortex, suggesting differential responses to synapse loss within the Litronesib price hippocampus based upon afferent innervation or chemical phenotype, some of which precipitate synaptic reorganization. A recent report characterized changes in the dendritic branching of the basilar tree of hippocampal CA1 pyramidal neurons. In this study, formalin-fixed tissue autopsy obtained from University of Kentucky Alzheimer’s Disease Center who died with a clinical diagnosis of NCI, MCI or AD was prepared for Golgi impregnation (Fig. 5). Camera lucida drawings of the basilar tree of randomly selected CA1 neurons were analyzed for alterations in dendritic arbor amount, distribution and complexity (Mervis et al., 2013). Quantitation showed a significant increase in dendritic length (18 ) and complexity (23 ) in CA1 neurons in MCI compared to NCI. Conversely, there was a significant reduction in branch length (-39 ) and arbor complexity (-25 ) during the progression from MCI to AD (Fig. 5). These findings suggest that the observed increase in CA1 dendritic parameters from NCI to MCI may be another example of a neuroplastic compensatory response to a loss of afferent input early in the course of the disease, which is not maintained as the disease progresses. The role that the reported reduction in total synapse number plays in CA1 neuroplasticity remains unknown. However, these examples of early CA1 neural reorganization may represent a viable window for potential therapeutic strategies aimed at restoring or maintaining hippocampal function during the transition from MCI to AD. Future ML240MedChemExpress ML240 studies should determine whether alterations in specific synapse subtypes (i.e., perforated vs. non-perforated) are differentially affected and their relation to cognitive decline and brain pathology during the onset of AD. Interestingly, the size of the synaptic contacts was found to be substantially larger in AD cortex compared to non-demented aged controls (Scheff et al., 1990), which was suggested to be part of a compensatory mechanism found in regions of the neocortex and hippocampus (see review Scheff and Price, 2006). These investigators found that as the number of synapses declined in a given region, the size of the residualAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagesynapses increased. This synaptic compensatory response was also observed early in the course of the AD (DeKosky and Scheff, 1990). Neuronal structural alterations may not be the only factor(s) contributing to cognitive decline and hippocampal plasticity in MCI. For example, studies have reported significant reductions in synaptic vesicle trafficking-related genes in the AD brain, which interrupt the efficacy of normal synaptic transmission (Yao et al., 2003; Murphy et al., 2003; Kennedy et al., 2005). Counts et al. (2014) examined progressive changes in the expression classes of synaptic gene within single CA1 neurons in subjects who died with a clinical diagnosis of NCI, MCI or moderate AD obtain.Ampal CA1 subfield in individuals with MCI compared to NCI (Fig. 4), which correlated with the subject’s Mini-Mental State Exam score (MMSE), but not with NFT Braak stage or apolipoprotein E (ApoE) status, a genetic risk factor for AD (Scheff et al., 2006). Unlike the outer molecular layer, CA1 receives input from the Schaffer collaterals arising from CA3 and not from the glutamatergic neurons of the entorhinal cortex, suggesting differential responses to synapse loss within the hippocampus based upon afferent innervation or chemical phenotype, some of which precipitate synaptic reorganization. A recent report characterized changes in the dendritic branching of the basilar tree of hippocampal CA1 pyramidal neurons. In this study, formalin-fixed tissue autopsy obtained from University of Kentucky Alzheimer’s Disease Center who died with a clinical diagnosis of NCI, MCI or AD was prepared for Golgi impregnation (Fig. 5). Camera lucida drawings of the basilar tree of randomly selected CA1 neurons were analyzed for alterations in dendritic arbor amount, distribution and complexity (Mervis et al., 2013). Quantitation showed a significant increase in dendritic length (18 ) and complexity (23 ) in CA1 neurons in MCI compared to NCI. Conversely, there was a significant reduction in branch length (-39 ) and arbor complexity (-25 ) during the progression from MCI to AD (Fig. 5). These findings suggest that the observed increase in CA1 dendritic parameters from NCI to MCI may be another example of a neuroplastic compensatory response to a loss of afferent input early in the course of the disease, which is not maintained as the disease progresses. The role that the reported reduction in total synapse number plays in CA1 neuroplasticity remains unknown. However, these examples of early CA1 neural reorganization may represent a viable window for potential therapeutic strategies aimed at restoring or maintaining hippocampal function during the transition from MCI to AD. Future studies should determine whether alterations in specific synapse subtypes (i.e., perforated vs. non-perforated) are differentially affected and their relation to cognitive decline and brain pathology during the onset of AD. Interestingly, the size of the synaptic contacts was found to be substantially larger in AD cortex compared to non-demented aged controls (Scheff et al., 1990), which was suggested to be part of a compensatory mechanism found in regions of the neocortex and hippocampus (see review Scheff and Price, 2006). These investigators found that as the number of synapses declined in a given region, the size of the residualAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagesynapses increased. This synaptic compensatory response was also observed early in the course of the AD (DeKosky and Scheff, 1990). Neuronal structural alterations may not be the only factor(s) contributing to cognitive decline and hippocampal plasticity in MCI. For example, studies have reported significant reductions in synaptic vesicle trafficking-related genes in the AD brain, which interrupt the efficacy of normal synaptic transmission (Yao et al., 2003; Murphy et al., 2003; Kennedy et al., 2005). Counts et al. (2014) examined progressive changes in the expression classes of synaptic gene within single CA1 neurons in subjects who died with a clinical diagnosis of NCI, MCI or moderate AD obtain.

Monly used and widely available OTC medications and nutritional supplements were

Monly used and widely available OTC medications and nutritional supplements were safe and posed no short- or long-term threat to their health. Many used such products to improve their running performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product recommended as an effective and legal substance by another runner or by a retail sales clerk may contain substances that are either banned by agencies such as WADA and/or may pose a serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping Pamapimod web regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding Resiquimod mechanism of action harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.Monly used and widely available OTC medications and nutritional supplements were safe and posed no short- or long-term threat to their health. Many used such products to improve their running performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product recommended as an effective and legal substance by another runner or by a retail sales clerk may contain substances that are either banned by agencies such as WADA and/or may pose a serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.

Deration when interpreting experimental findings. (i) Identification of a mutation in

Deration when interpreting experimental findings. (i) Identification of a AZD-8835 chemical information mutation in a clonal population does not indicate causality Any mutation in a cell that undergoes clonal expansion will be passed onto progeny, irrespective of functional status (Fig. 3A,B). Given the size of the genome, more mutations carried by a neoplastic clone will be passengers than drivers [27, 29, 30]. To demonstrate driver status, supporting functional studies and/or repeated observations of a mutated loci in neoplastic clones from independent individuals are needed. (ii) Mutational marking of a clone is stochastic and not guaranteed A clone may exist and not be detected if none of the genomic sites being screened carry a unique mutation permitting it to be distinguished from the germline (Fig. 3C). The more sites examined, the higher the probability of Cycloheximide manufacturer Detection becomes. Restricting a marker panel to suspected driver sites precludes detection of pathological clones driven by unknown factors. (iii) Elevated mutation rates facilitate clone detection but are not an absolute requirement Screening of mutational hotspots makes it practical with conventional technologies to have a reasonable probability of detecting a clone by random passenger mutations. Clones derived from a mutator lineage or cells residing in a highly mutagenic environment should be more densely marked with identifiable passengers (Fig. 3D), potentially reducing the number of markers needing to be interrogated to identify them. Emerging high-throughput sequencing technologies will eventually obviate the need to restrict screening to a fraction of the genome. (iv) Identification of one or more clonal mutations is not proof of genetic instability in the absence of collateral information Detection of a mutation requires clonal expansion with most traditional methods of aggregate DNA analysis. The probability of identifying clonal mutations in an expanded population is a function of the number of sites screened, the mutability of these sites and the number of cell divisions having occurred in the lineage leading up to the final expansion. Particularly when considering hotspots, mutations will be occasionally detectable in any clonally-derived population at a statistically definable frequency. Because mutations are not routinely encountered in normal tissues, it is tempting to explain their presence in preneoplastic populations as the result of “genetic instability” (an elevated mutation rate). However, the phenomenon is more precisely explained by the fact that expansion does not routinely occur in most normal tissues. An elevated mutation rate itself will have no observable effect on clonal mutation frequency in the absence of expansion (Fig. 3E). To determine mutation rate from a clonal mutation frequency it is necessary to (A) know that the population being assessed is clonal and (B) have some metric of the number of cell divisions that occurred in the period between the zygote and the founding of the final clonalSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPageoutgrowth. To infer that a rate is elevated, it is also necessary to know the normal in vivo mutation rate, which is, in turn, impossible to measure by this approach given that large clonal expansions do not routinely occur in normal adult tissue. Considering these complexities, the lack of resolution as to whether mutation rates are elevated in cancer is not surprising [1,8?1]. (v) Detectabili.Deration when interpreting experimental findings. (i) Identification of a mutation in a clonal population does not indicate causality Any mutation in a cell that undergoes clonal expansion will be passed onto progeny, irrespective of functional status (Fig. 3A,B). Given the size of the genome, more mutations carried by a neoplastic clone will be passengers than drivers [27, 29, 30]. To demonstrate driver status, supporting functional studies and/or repeated observations of a mutated loci in neoplastic clones from independent individuals are needed. (ii) Mutational marking of a clone is stochastic and not guaranteed A clone may exist and not be detected if none of the genomic sites being screened carry a unique mutation permitting it to be distinguished from the germline (Fig. 3C). The more sites examined, the higher the probability of detection becomes. Restricting a marker panel to suspected driver sites precludes detection of pathological clones driven by unknown factors. (iii) Elevated mutation rates facilitate clone detection but are not an absolute requirement Screening of mutational hotspots makes it practical with conventional technologies to have a reasonable probability of detecting a clone by random passenger mutations. Clones derived from a mutator lineage or cells residing in a highly mutagenic environment should be more densely marked with identifiable passengers (Fig. 3D), potentially reducing the number of markers needing to be interrogated to identify them. Emerging high-throughput sequencing technologies will eventually obviate the need to restrict screening to a fraction of the genome. (iv) Identification of one or more clonal mutations is not proof of genetic instability in the absence of collateral information Detection of a mutation requires clonal expansion with most traditional methods of aggregate DNA analysis. The probability of identifying clonal mutations in an expanded population is a function of the number of sites screened, the mutability of these sites and the number of cell divisions having occurred in the lineage leading up to the final expansion. Particularly when considering hotspots, mutations will be occasionally detectable in any clonally-derived population at a statistically definable frequency. Because mutations are not routinely encountered in normal tissues, it is tempting to explain their presence in preneoplastic populations as the result of “genetic instability” (an elevated mutation rate). However, the phenomenon is more precisely explained by the fact that expansion does not routinely occur in most normal tissues. An elevated mutation rate itself will have no observable effect on clonal mutation frequency in the absence of expansion (Fig. 3E). To determine mutation rate from a clonal mutation frequency it is necessary to (A) know that the population being assessed is clonal and (B) have some metric of the number of cell divisions that occurred in the period between the zygote and the founding of the final clonalSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPageoutgrowth. To infer that a rate is elevated, it is also necessary to know the normal in vivo mutation rate, which is, in turn, impossible to measure by this approach given that large clonal expansions do not routinely occur in normal adult tissue. Considering these complexities, the lack of resolution as to whether mutation rates are elevated in cancer is not surprising [1,8?1]. (v) Detectabili.

Rhetorical functions of language, typography and editorial voice as well as

PD168393 solubility rhetorical functions of language, typography and editorial voice as well as the use of such radical literary tactics as exposure, ridicule and critique. This article does not merely aim to point up the similarities between The Lancet and its political contemporaries; it intends to show how such stylistic devices were marshalled in the pursuit of a specific political agenda. Of course splenetic prose was not the sole preserve of the radical `left’ and RRx-001 chemical information neither was it particularly novel. Similar tactics had been in use since the later 1700s by `King and Country’ Tories, a position from which Wakley’s mentor and collaborator, William Cobbett, had only moved in 1806.14 However, during the early decades of the nineteenth century it was the radical and revolutionary press which made this style their own, and it was these conventions that Wakley sought to emulate. This was particularly true of his predilection for insult and defamation, and the main body of this article comprises a detailed analysis of a trial for libel in 1828 between Wakely and the Guy’s Hospital surgeon, Bransby Cooper. Through a close analysis of Wakley’s rhetorical, legal and performative strategies, as well as a critical reading of a number of contemporary satirical prints, it demonstrates how this trial functioned as the platform for a much broader critique of the established medical `system’ and provided a powerful means for Wakley to align himself with the cultures of popular radicalism. However, whatever parallels and connections Wakley sought to draw between the medical and the political, the reality was rather more complex. In the final section,567. Smith, The Politics of Language, 1791 ?819 (Oxford, 1984); I. McCalman, Radical Underworld: Prophets, Revolutionaries and Pornographers, 1795?1840 (Cambridge, 1988); J. A. Epstein, Radical Expression: Political Language, Ritual and Symbol in England, 1790 ?1850 (Oxford, 1994); E. Hadley, Melodramatic Tactics: Theatricalised Dissent in the English13O. 12ibid.,Marketplace, 1800 ?1885 (Stanford, 1995); L. Nattrass, William Cobbett: The Politics of Style (Cambridge, 1995); K. Gilmartin, Print Politics: The Press and Radical Opposition in Early Nineteenth-Century England (Cambridge, 1996). 14For example, see J. J. Sack, From Jacobite to Conservative: Reaction and Orthodoxy in Britain, c.1760 ?832 (Cambridge, 1993).Social HistoryVOL.39 :NO.therefore, this article examines the tensions and ambiguities within Wakley’s political persona by reading them against the altered circumstances of the 1820s, particularly the rise of a more philosophic reformism. In so doing, it seeks not merely to place political radicalism at the heart of contemporary medical culture but, more ambitiously perhaps, to establish a more prominent place for medicine in accounts of the history of early nineteenth-century reform, as a potential bridge between the popular radicalism of the immediate post-war years and the reformist utilitarianism of the 1830s.WAKLEY, COBBETT AND RADICAL STYLEThere was little in Thomas Wakley’s early upbringing to suggest a natural inclination towards political radicalism, for he was born in 1795 into that bulwark of pre-modern political order, the prosperous farming family.15 One of eleven children and the youngest of eight sons, he attended boarding school in Somerset, followed by a series of apprenticeships with local apothecaries and surgeons, enrolling as a student at the United Hospitals Medical School of Guy’s and St Tho.Rhetorical functions of language, typography and editorial voice as well as the use of such radical literary tactics as exposure, ridicule and critique. This article does not merely aim to point up the similarities between The Lancet and its political contemporaries; it intends to show how such stylistic devices were marshalled in the pursuit of a specific political agenda. Of course splenetic prose was not the sole preserve of the radical `left’ and neither was it particularly novel. Similar tactics had been in use since the later 1700s by `King and Country’ Tories, a position from which Wakley’s mentor and collaborator, William Cobbett, had only moved in 1806.14 However, during the early decades of the nineteenth century it was the radical and revolutionary press which made this style their own, and it was these conventions that Wakley sought to emulate. This was particularly true of his predilection for insult and defamation, and the main body of this article comprises a detailed analysis of a trial for libel in 1828 between Wakely and the Guy’s Hospital surgeon, Bransby Cooper. Through a close analysis of Wakley’s rhetorical, legal and performative strategies, as well as a critical reading of a number of contemporary satirical prints, it demonstrates how this trial functioned as the platform for a much broader critique of the established medical `system’ and provided a powerful means for Wakley to align himself with the cultures of popular radicalism. However, whatever parallels and connections Wakley sought to draw between the medical and the political, the reality was rather more complex. In the final section,567. Smith, The Politics of Language, 1791 ?819 (Oxford, 1984); I. McCalman, Radical Underworld: Prophets, Revolutionaries and Pornographers, 1795?1840 (Cambridge, 1988); J. A. Epstein, Radical Expression: Political Language, Ritual and Symbol in England, 1790 ?1850 (Oxford, 1994); E. Hadley, Melodramatic Tactics: Theatricalised Dissent in the English13O. 12ibid.,Marketplace, 1800 ?1885 (Stanford, 1995); L. Nattrass, William Cobbett: The Politics of Style (Cambridge, 1995); K. Gilmartin, Print Politics: The Press and Radical Opposition in Early Nineteenth-Century England (Cambridge, 1996). 14For example, see J. J. Sack, From Jacobite to Conservative: Reaction and Orthodoxy in Britain, c.1760 ?832 (Cambridge, 1993).Social HistoryVOL.39 :NO.therefore, this article examines the tensions and ambiguities within Wakley’s political persona by reading them against the altered circumstances of the 1820s, particularly the rise of a more philosophic reformism. In so doing, it seeks not merely to place political radicalism at the heart of contemporary medical culture but, more ambitiously perhaps, to establish a more prominent place for medicine in accounts of the history of early nineteenth-century reform, as a potential bridge between the popular radicalism of the immediate post-war years and the reformist utilitarianism of the 1830s.WAKLEY, COBBETT AND RADICAL STYLEThere was little in Thomas Wakley’s early upbringing to suggest a natural inclination towards political radicalism, for he was born in 1795 into that bulwark of pre-modern political order, the prosperous farming family.15 One of eleven children and the youngest of eight sons, he attended boarding school in Somerset, followed by a series of apprenticeships with local apothecaries and surgeons, enrolling as a student at the United Hospitals Medical School of Guy’s and St Tho.

Ez-Triana, sp. n. http://zoobank.org/84DCE9B2-79E9-

Ez-Triana, sp. n. http://zoobank.org/84DCE9B2-79E9-47CF-8CC2-8DA9F53F3AD1 http://species-id.net/wiki/Apanteles_franciscopizarroi Figs. 74 Type locality. COSTA RICA, Guanacaste, ACG, Sector Santa Rosa, Bosque Humedo, 290m, 10.85145, -85.60801. Holotype. in CNC. Specimen labels: 1. DHJPAR0013119. 2. 17 Jan. 2000, Bosque Humedo Trap. Description. Mequitazine side effects Female. Body color: body mostly dark except for some sternites which may be pale. Antenna color: scape, pedicel, and flagellum dark. Coxae color (pro-, meso-, metacoxa): pale, pale, dark. Femora color (pro-, meso-, metafemur): pale, pale, mostly pale but posterior 0.2 or less dark. Tibiae color (pro-, meso-, metatibia): pale, pale, anteriorly pale/posteriorly dark. Tegula and humeral complex color: both pale. Pterostigma color: dark. Fore wing veins color: partially pigmented (a few veins may be dark but most are pale). Antenna length/body length: antenna about as long as body (head to apex of metasoma); if slightly shorter, at least extending beyond anterior 0.7 metasoma length. Body in lateral view: not distinctly flattened dorso entrally. Body Linaprazan site length (head to apex of metasoma): 2.1?.2 mm. Fore wing length: 2.3?.4 mm. Ocular cellar line/posterior ocellus diameter: 2.0?.2. In-Jose L. Fernandez-Triana et al. / ZooKeys 383: 1?65 (2014)terocellar distance/posterior ocellus diameter: 1.7?.9. Antennal flagellomerus 2 length/width: 2.6?.8. Antennal flagellomerus 14 length/width: 1.4?.6. Length of flagellomerus 2/length of flagellomerus 14: 1.7?.9. Tarsal claws: with single basal spine ike seta. Metafemur length/width: 3.4?.5. Metatibia inner spur length/ metabasitarsus length: 0.4?.5. Anteromesoscutum: mostly with deep, dense punctures (separated by less than 2.0 ?its maximum diameter). Mesoscutellar disc: with a few sparse punctures. Number of pits in scutoscutellar sulcus: 11 or 12. Maximum height of mesoscutellum lunules/maximum height of lateral face of mesoscutellum: 0.2?.3. Propodeum areola: completely defined by carinae, including transverse carina extending to spiracle. Propodeum background sculpture: partly sculptured, especially on anterior 0.5. Mediotergite 1 length/width at posterior margin: 2.0?.2. Mediotergite 1 shape: mostly parallel ided for 0.5?.7 of its length, then narrowing posteriorly so mediotergite anterior width >1.1 ?posterior width. Mediotergite 1 sculpture: mostly sculptured, excavated area centrally with transverse striation inside and/or a polished knob centrally on posterior margin of mediotergite. Mediotergite 2 width at posterior margin/length: 3.6?.9. Mediotergite 2 sculpture: with some sculpture, mostly near posterior margin. Outer margin of hypopygium: with a wide, medially folded, transparent, semi esclerotized area; usually with 4 or more pleats. Ovipositor thickness: about same width throughout its length. Ovipositor sheaths length/metatibial length: 1.0?.1. Length of fore wing veins r/2RS: 1.1?.3. Length of fore wing veins 2RS/2M: 1.4?.6. Length of fore wing veins 2M/(RS+M)b: 1.1?1.3. Pterostigma length/width: 3.1?.5. Point of insertion of vein r in pterostigma: about half way point length of pterostigma. Angle of vein r with fore wing anterior margin: more or less perpendicular to fore wing margin. Shape of junction of veins r and 2RS in fore wing: distinctly but not strongly angled. Male. Unknown. Molecular data. Sequences in BOLD: 2, barcode compliant sequences: 2. Biology/ecology. Malaise-trapped. Distribution. Costa Rica, ACG. Etymology. We dedicate this spe.Ez-Triana, sp. n. http://zoobank.org/84DCE9B2-79E9-47CF-8CC2-8DA9F53F3AD1 http://species-id.net/wiki/Apanteles_franciscopizarroi Figs. 74 Type locality. COSTA RICA, Guanacaste, ACG, Sector Santa Rosa, Bosque Humedo, 290m, 10.85145, -85.60801. Holotype. in CNC. Specimen labels: 1. DHJPAR0013119. 2. 17 Jan. 2000, Bosque Humedo Trap. Description. Female. Body color: body mostly dark except for some sternites which may be pale. Antenna color: scape, pedicel, and flagellum dark. Coxae color (pro-, meso-, metacoxa): pale, pale, dark. Femora color (pro-, meso-, metafemur): pale, pale, mostly pale but posterior 0.2 or less dark. Tibiae color (pro-, meso-, metatibia): pale, pale, anteriorly pale/posteriorly dark. Tegula and humeral complex color: both pale. Pterostigma color: dark. Fore wing veins color: partially pigmented (a few veins may be dark but most are pale). Antenna length/body length: antenna about as long as body (head to apex of metasoma); if slightly shorter, at least extending beyond anterior 0.7 metasoma length. Body in lateral view: not distinctly flattened dorso entrally. Body length (head to apex of metasoma): 2.1?.2 mm. Fore wing length: 2.3?.4 mm. Ocular cellar line/posterior ocellus diameter: 2.0?.2. In-Jose L. Fernandez-Triana et al. / ZooKeys 383: 1?65 (2014)terocellar distance/posterior ocellus diameter: 1.7?.9. Antennal flagellomerus 2 length/width: 2.6?.8. Antennal flagellomerus 14 length/width: 1.4?.6. Length of flagellomerus 2/length of flagellomerus 14: 1.7?.9. Tarsal claws: with single basal spine ike seta. Metafemur length/width: 3.4?.5. Metatibia inner spur length/ metabasitarsus length: 0.4?.5. Anteromesoscutum: mostly with deep, dense punctures (separated by less than 2.0 ?its maximum diameter). Mesoscutellar disc: with a few sparse punctures. Number of pits in scutoscutellar sulcus: 11 or 12. Maximum height of mesoscutellum lunules/maximum height of lateral face of mesoscutellum: 0.2?.3. Propodeum areola: completely defined by carinae, including transverse carina extending to spiracle. Propodeum background sculpture: partly sculptured, especially on anterior 0.5. Mediotergite 1 length/width at posterior margin: 2.0?.2. Mediotergite 1 shape: mostly parallel ided for 0.5?.7 of its length, then narrowing posteriorly so mediotergite anterior width >1.1 ?posterior width. Mediotergite 1 sculpture: mostly sculptured, excavated area centrally with transverse striation inside and/or a polished knob centrally on posterior margin of mediotergite. Mediotergite 2 width at posterior margin/length: 3.6?.9. Mediotergite 2 sculpture: with some sculpture, mostly near posterior margin. Outer margin of hypopygium: with a wide, medially folded, transparent, semi esclerotized area; usually with 4 or more pleats. Ovipositor thickness: about same width throughout its length. Ovipositor sheaths length/metatibial length: 1.0?.1. Length of fore wing veins r/2RS: 1.1?.3. Length of fore wing veins 2RS/2M: 1.4?.6. Length of fore wing veins 2M/(RS+M)b: 1.1?1.3. Pterostigma length/width: 3.1?.5. Point of insertion of vein r in pterostigma: about half way point length of pterostigma. Angle of vein r with fore wing anterior margin: more or less perpendicular to fore wing margin. Shape of junction of veins r and 2RS in fore wing: distinctly but not strongly angled. Male. Unknown. Molecular data. Sequences in BOLD: 2, barcode compliant sequences: 2. Biology/ecology. Malaise-trapped. Distribution. Costa Rica, ACG. Etymology. We dedicate this spe.

Provides valuable benchmarks for science communication on the platforms within the

Provides valuable benchmarks for science communication on the platforms within the study as well as for future platforms. Also, the items do not represent a randomly distributed, year-round sample. “Throwback RG7666MedChemExpress RG7666 Thursday” items, for example, were posted only on Thursdays, “Guess What It Is” items were posted only on Mondays, and “Wow” items were posted only on Tuesdays. The 8 weeks included in the sample were not randomly distributed but represent only the end of thePLOS ONE | DOI:10.1371/journal.pone.0156409 May 27,14 /Engagement with Particle Physics on CERN’s Vesatolimod site Social Media Platformscalendar year. These temporal characteristics of the sample add further possible confounding factors to the study. Next, while the number of users for some platforms was high, two platforms had relatively few followers during the time of the study: Twitter French and Instagram. Hence, when outliers appeared on these platforms, it could be a result of chance. Additionally, when focusing on visit duration and retention rate, often the numbers that clicked-through in the first place were so small as to be only the hardened fans determined to spend time to find out more. Future work could include setting thresholds for inclusion in datasets, or devising measures that integrate numbers of users who clicked through and the time they spent on site. Finally, another limitation stems from the reliance on datasets provided by for-profit corporations such as Engagor. Engagor does not divulge the algorithms used to generate the data. Future work could focus on developing open, free tools for generating social media analytics for research purposes.Evidence-Based Insights for PracticeHow does our research inform practice? Specifically the practice of using social media for science communication. Here, we provide some evidence-based insights with examples (Table 9).NewsWith the increased prevalence of social media, news stories from an organisation are no longer confined to traditional media. Many people, especially younger generations, get their news directly from social media [48], either receiving it directly from the organisation or via a share from their social network. With such a wealth of news on social media, audiences react by liking, commenting, sharing and clicking-through, but stay very little time on the webpage, quickly consuming the content and moving on. This type of post is therefore more focused on marketing and engagement and less on education in terms of the social media strategy.Images and AnimationUsers respond more readily to images than text on social media [49,50]. In order to control for this variable, all posts in the study contained an image. Furthermore, Facebook algorithms are configured to promote image-based posts to a wider audience. In this study, animations were also used on Twitter and Google+, receiving a relatively strong reaction in terms of likes and shares [51,52]. Of the 35 high engagement items, more than half were not news related but involved beautiful images (e.g. [53]) or surprising images (e.g. [54]). Meaning that an organisation can use imagery on social media for all three strategic themes: marketing, engagement andTable 9. Content characteristics and related user behaviour on social media. Likes News Image Animation Video/Virtual tour on webpage Discussion Clickbait Tailored content Human story doi:10.1371/journal.pone.0156409.t009 Comments Shares Click-throughs Visit duration Retention ratePLOS ONE | DOI.Provides valuable benchmarks for science communication on the platforms within the study as well as for future platforms. Also, the items do not represent a randomly distributed, year-round sample. “Throwback Thursday” items, for example, were posted only on Thursdays, “Guess What It Is” items were posted only on Mondays, and “Wow” items were posted only on Tuesdays. The 8 weeks included in the sample were not randomly distributed but represent only the end of thePLOS ONE | DOI:10.1371/journal.pone.0156409 May 27,14 /Engagement with Particle Physics on CERN’s Social Media Platformscalendar year. These temporal characteristics of the sample add further possible confounding factors to the study. Next, while the number of users for some platforms was high, two platforms had relatively few followers during the time of the study: Twitter French and Instagram. Hence, when outliers appeared on these platforms, it could be a result of chance. Additionally, when focusing on visit duration and retention rate, often the numbers that clicked-through in the first place were so small as to be only the hardened fans determined to spend time to find out more. Future work could include setting thresholds for inclusion in datasets, or devising measures that integrate numbers of users who clicked through and the time they spent on site. Finally, another limitation stems from the reliance on datasets provided by for-profit corporations such as Engagor. Engagor does not divulge the algorithms used to generate the data. Future work could focus on developing open, free tools for generating social media analytics for research purposes.Evidence-Based Insights for PracticeHow does our research inform practice? Specifically the practice of using social media for science communication. Here, we provide some evidence-based insights with examples (Table 9).NewsWith the increased prevalence of social media, news stories from an organisation are no longer confined to traditional media. Many people, especially younger generations, get their news directly from social media [48], either receiving it directly from the organisation or via a share from their social network. With such a wealth of news on social media, audiences react by liking, commenting, sharing and clicking-through, but stay very little time on the webpage, quickly consuming the content and moving on. This type of post is therefore more focused on marketing and engagement and less on education in terms of the social media strategy.Images and AnimationUsers respond more readily to images than text on social media [49,50]. In order to control for this variable, all posts in the study contained an image. Furthermore, Facebook algorithms are configured to promote image-based posts to a wider audience. In this study, animations were also used on Twitter and Google+, receiving a relatively strong reaction in terms of likes and shares [51,52]. Of the 35 high engagement items, more than half were not news related but involved beautiful images (e.g. [53]) or surprising images (e.g. [54]). Meaning that an organisation can use imagery on social media for all three strategic themes: marketing, engagement andTable 9. Content characteristics and related user behaviour on social media. Likes News Image Animation Video/Virtual tour on webpage Discussion Clickbait Tailored content Human story doi:10.1371/journal.pone.0156409.t009 Comments Shares Click-throughs Visit duration Retention ratePLOS ONE | DOI.

Categories. They rather correspond to properties of the fluxes in each

Categories. They rather correspond to properties of the (-)-Blebbistatin side effects fluxes in each category.PLOS ONE | DOI:10.1371/journal.pone.0120882 March 31,11 /A Generic Model of Dyadic Social RelationshipsTable 5. Detection of categories of action fluxes in data sets of dyadic interactions. Category 1 2 3 4 5 6 Pattern of observed fluxesX Alternated fluxes A! B and A XRepresentative relationship B A!B X A !B ;Y Y B, and separately, alternated fluxes A! B and A X ; XRMT EM NullNo fluxes between A and BX Alternated fluxes A! B and A X Alternated fluxes A! B and A X Fluxes A! B and A XB[A ! B and A ! B] Y X A!B YX [A! B and A X XXYMP ARYBB, not systematically alternatedB]CS AsocialFluxes A! BXA! BXPatterns of action fluxes expected to be observed in each category. X and Y are social actions belonging to a set S of size N. A and B are agents. doi:10.1371/journal.pone.0120882.t?Linked to the previous point, we stress that the patterns given in that table are not mutually disjoint. They should thus be tested in a certain order. MP should be tested before AR and CS, and category 6 (asocial) should be tested after all other categories. Let us illustrate that point with an example: if A and B are in an MP relationship, one observes alternated fluxes X X Y A ! B and A Y B, as well as alternated fluxes A ! B and A X B, re-written as [A ! B andY Y A ! B]. Yet, A and B’s relationship will also respond positive to a CS test, because non-alterX X nated fluxes A ! B and A X B are present overall in the relationship (indicative of CS for X), Y as well as non-alternated fluxes A ! B and A Y B (CS for Y). In that case, the alternation that marks an MP relationship should prevail in the observer’s interpretation because it is very unlikely to happen by chance alone.?A tolerance level should be defined for the alternation of fluxes (in EM, MP and AR). For instance, the alternation of fluxes in an EM relationship does not need to be strict. In real conditions, people can be flexible and take several turns in a row before the other party reciprocates. Occasional cheating or inexact record keeping can also occur within an otherwise stable relationship. Hence, a low tolerance could lead to false negatives, whereby the observer would miss situations of EM, MP and AR. On the other hand, high tolerance levels might lead to wrong interpretations: fluxes could be falsely interpreted as manifestations of EM, MP or AR. The adequate tolerance level may vary per data set or relationship and may be checked against the individuals’ communications, if available. ?Relationships may change over time. Individuals may initiate a certain relationship that transforms over time into another, linked to increased trust (or mistrust), availability of resources in the environment, and so on. To detect such changes, analyses can be carried out over different time windows. ?In any real data set, individuals may belong to larger social units that interact with each other. If blindly applied to all pairs of individuals, our model may miss these high-level effects. For instance, say that agent A from group G1 attacked B from group G2. Agent C from G2, feeling very close to B (perhaps in a CS way), decides to punish A and attacks her in an eye-for-an-eye, tooth-for-a-tooth fashion (EM). If one knows nothing of the groups exisX tence, one analyzes separately the pairs (A, B) and (A, C). From the EPZ-5676 site observations A ! B and A X C, one concludes to the presence of an asocial interaction (category 6) between A and B,PLO.Categories. They rather correspond to properties of the fluxes in each category.PLOS ONE | DOI:10.1371/journal.pone.0120882 March 31,11 /A Generic Model of Dyadic Social RelationshipsTable 5. Detection of categories of action fluxes in data sets of dyadic interactions. Category 1 2 3 4 5 6 Pattern of observed fluxesX Alternated fluxes A! B and A XRepresentative relationship B A!B X A !B ;Y Y B, and separately, alternated fluxes A! B and A X ; XRMT EM NullNo fluxes between A and BX Alternated fluxes A! B and A X Alternated fluxes A! B and A X Fluxes A! B and A XB[A ! B and A ! B] Y X A!B YX [A! B and A X XXYMP ARYBB, not systematically alternatedB]CS AsocialFluxes A! BXA! BXPatterns of action fluxes expected to be observed in each category. X and Y are social actions belonging to a set S of size N. A and B are agents. doi:10.1371/journal.pone.0120882.t?Linked to the previous point, we stress that the patterns given in that table are not mutually disjoint. They should thus be tested in a certain order. MP should be tested before AR and CS, and category 6 (asocial) should be tested after all other categories. Let us illustrate that point with an example: if A and B are in an MP relationship, one observes alternated fluxes X X Y A ! B and A Y B, as well as alternated fluxes A ! B and A X B, re-written as [A ! B andY Y A ! B]. Yet, A and B’s relationship will also respond positive to a CS test, because non-alterX X nated fluxes A ! B and A X B are present overall in the relationship (indicative of CS for X), Y as well as non-alternated fluxes A ! B and A Y B (CS for Y). In that case, the alternation that marks an MP relationship should prevail in the observer’s interpretation because it is very unlikely to happen by chance alone.?A tolerance level should be defined for the alternation of fluxes (in EM, MP and AR). For instance, the alternation of fluxes in an EM relationship does not need to be strict. In real conditions, people can be flexible and take several turns in a row before the other party reciprocates. Occasional cheating or inexact record keeping can also occur within an otherwise stable relationship. Hence, a low tolerance could lead to false negatives, whereby the observer would miss situations of EM, MP and AR. On the other hand, high tolerance levels might lead to wrong interpretations: fluxes could be falsely interpreted as manifestations of EM, MP or AR. The adequate tolerance level may vary per data set or relationship and may be checked against the individuals’ communications, if available. ?Relationships may change over time. Individuals may initiate a certain relationship that transforms over time into another, linked to increased trust (or mistrust), availability of resources in the environment, and so on. To detect such changes, analyses can be carried out over different time windows. ?In any real data set, individuals may belong to larger social units that interact with each other. If blindly applied to all pairs of individuals, our model may miss these high-level effects. For instance, say that agent A from group G1 attacked B from group G2. Agent C from G2, feeling very close to B (perhaps in a CS way), decides to punish A and attacks her in an eye-for-an-eye, tooth-for-a-tooth fashion (EM). If one knows nothing of the groups exisX tence, one analyzes separately the pairs (A, B) and (A, C). From the observations A ! B and A X C, one concludes to the presence of an asocial interaction (category 6) between A and B,PLO.

(10). These impacts pose significant challenges to the continued provisioning of ecosystem

(10). These impacts pose significant challenges to the continued provisioning of ecosystem services from the ocean: challenges that may seem overwhelming now, but even more so in light of the difficulties in addressing the complex drivers and reversing trends. In short, threats to ocean life and the provision of vital ecosystem services are unquestionably serious and pressures on ocean TirabrutinibMedChemExpress ONO-4059 resources are escalating. Glimmers of Hope for Sustainable Use of the Ocean Despite these daunting challenges, there is reason for cautious hope. Around the globe, many positive changes are underway: awareness, attitudes, and social norms are changing; economic incentives are shifting; efforts to educate consumers are increasing; new policies are leading to stronger mandates and more effective governance, compliance, and enforcement; and practices are changing with the development of better AZD3759 biological activity technologies, new products, and business strategies that reflect the circular economy (11), greater engagement of scientists, and improved understanding of trade-offs. As a result, effective models for change based in naturalThe grand challenge for humanity is to meet the basic needs of people in an equitable manner today while simultaneously restoring and maintaining ecosystem functioning for future generations. We must do so in the face of growing numbers of people and the concomitant need for resources, and with environmental changes, such as climate change, already underway. The ocean is integral to this global mission. Ocean and coastal ecosystems provide a range of critical ecosystem services that people depend upon, such as food, oxygen, climate regulation, control of pests, protection from storm surges, recreational opportunities, and cultural value (1, 2). The ocean is home to rich biodiversity and plays key roles in many global processes, from primary production to nutrient cycling to climate and weather (3). Ocean-based activities and livelihoods are both enabled by and affect complex interactions among ecological, social, and economic systems. The global market value of marine and coastal resources and industries is estimated at 3 trillion per year (4). Over 3 billion people depend upon the oceans to provide their primary source of protein, and marine fisheries directly or indirectly employ over 200 million people (4). Other benefits, such as cultural or inspirational values, are harder towww.pnas.org/cgi/doi/10.1073/pnas.This article arises from the 2016 Annual Sackler Lecture, “Enough with the doom and gloom! Holistic approaches bring hope for people and the ocean,” presented by Jane Lubchenco on March 14, at the National Academy of Sciences in Washington, DC. The lecture was part of the Arthur M. Sackler Colloquium of the National Academy of Sciences, “Coupled Human and Environmental Systems,” held March 14?5. The complete program and video recordings of most presentations are available on the NAS website at www.nasonline.org/Coupled_Human_and_Environmental_Systems. Author contributions: J.L. and S.A.L. designed research; J.L., E.B.C.-C., J.N.R., and S.A.L. performed research; and J.L., E.B.C.-C., J.N.R., and S.A.L. wrote the paper. The authors declare no conflict of interest. This article is a PNAS Direct Submission. A.P.G. is a Guest Editor invited by the Editorial Board.To whom correspondence should be addressed. Email: [email protected] | December 20, 2016 | vol. 113 | no. 51 | 14507?ENVIRONMENTAL SCIENCESSUSTAINABILITY SCIENCEquantify.(10). These impacts pose significant challenges to the continued provisioning of ecosystem services from the ocean: challenges that may seem overwhelming now, but even more so in light of the difficulties in addressing the complex drivers and reversing trends. In short, threats to ocean life and the provision of vital ecosystem services are unquestionably serious and pressures on ocean resources are escalating. Glimmers of Hope for Sustainable Use of the Ocean Despite these daunting challenges, there is reason for cautious hope. Around the globe, many positive changes are underway: awareness, attitudes, and social norms are changing; economic incentives are shifting; efforts to educate consumers are increasing; new policies are leading to stronger mandates and more effective governance, compliance, and enforcement; and practices are changing with the development of better technologies, new products, and business strategies that reflect the circular economy (11), greater engagement of scientists, and improved understanding of trade-offs. As a result, effective models for change based in naturalThe grand challenge for humanity is to meet the basic needs of people in an equitable manner today while simultaneously restoring and maintaining ecosystem functioning for future generations. We must do so in the face of growing numbers of people and the concomitant need for resources, and with environmental changes, such as climate change, already underway. The ocean is integral to this global mission. Ocean and coastal ecosystems provide a range of critical ecosystem services that people depend upon, such as food, oxygen, climate regulation, control of pests, protection from storm surges, recreational opportunities, and cultural value (1, 2). The ocean is home to rich biodiversity and plays key roles in many global processes, from primary production to nutrient cycling to climate and weather (3). Ocean-based activities and livelihoods are both enabled by and affect complex interactions among ecological, social, and economic systems. The global market value of marine and coastal resources and industries is estimated at 3 trillion per year (4). Over 3 billion people depend upon the oceans to provide their primary source of protein, and marine fisheries directly or indirectly employ over 200 million people (4). Other benefits, such as cultural or inspirational values, are harder towww.pnas.org/cgi/doi/10.1073/pnas.This article arises from the 2016 Annual Sackler Lecture, “Enough with the doom and gloom! Holistic approaches bring hope for people and the ocean,” presented by Jane Lubchenco on March 14, at the National Academy of Sciences in Washington, DC. The lecture was part of the Arthur M. Sackler Colloquium of the National Academy of Sciences, “Coupled Human and Environmental Systems,” held March 14?5. The complete program and video recordings of most presentations are available on the NAS website at www.nasonline.org/Coupled_Human_and_Environmental_Systems. Author contributions: J.L. and S.A.L. designed research; J.L., E.B.C.-C., J.N.R., and S.A.L. performed research; and J.L., E.B.C.-C., J.N.R., and S.A.L. wrote the paper. The authors declare no conflict of interest. This article is a PNAS Direct Submission. A.P.G. is a Guest Editor invited by the Editorial Board.To whom correspondence should be addressed. Email: [email protected] | December 20, 2016 | vol. 113 | no. 51 | 14507?ENVIRONMENTAL SCIENCESSUSTAINABILITY SCIENCEquantify.

Are a useful method for gaining insight into phenomena where little

Are a useful method for gaining insight into phenomena where little is known [44]. When focus group data has been collected from multiple groups and multiple sites, researchers can have increased confidence in the reliability and validity of the findings [45]. The focus groups were guided by following questions. (1) Perceptions of Professional Socialization. (a) What comes to mind when you hear the phrase “professional socialization”? (b) Share memories of your experiences becoming socialized into the role of Licensed Practical Nurse and developing your identity in this role. (c) How is the experience of developing your new role and identity as a Registered Nurse the same? How is it different? (2) Formal Academic Experiences: Online Classes and Clinical Practicums. (a) Talk about experiences you have had so far in your online university classes where you “felt like” a Registered Nurse and not a Licensed Practical Nurse? Have there been times in your online4 [54] (page 85) maintained by both moderators during and immediately following the sessions further increased the dependability of our findings. Practical issues such as organizing groups at a time and place to minimize disruption and avoiding power differential dynamics [55] were addressed. The groups were held when participants, who were normally separated by distance, were together in the same city for a required practicum experience. They were held at change of shift in lieu of a post conference. Knowing the power differential between students and teachers, moderators who did not have teaching responsibilities in the Post LPN to BN program were chosen to facilitate the focus groups. Instructors were not present during any of the discussions and had no involvement with the transcript data. Participants were recruited through a Letter of Invitation sent via email by a Research Assistant who was also not involved with the program. Four focus groups were held with 5 to 9 participants each. All the students who were invited chose to participate. We reasoned that this may have been because they were all from out of town and appreciated an opportunity to interact and share their views. Pseudonyms ensured participant confidentiality. Full ethical approval was granted by the university. The following two overarching themes emerged from analyzing the data. First, Post LPN to BN students need little, if any, further legitimation to affirm their identities as “nurse.” Second, practicum interactions with instructors and new clinical experiences are key socializing agents.Nursing Research and Practice They talked about opportunities where demonstrating professional authority in their workplace further established their identity as “nurse”: “Working your first night shift . . . in your new role. The culture of night shift–it’s different.” “The first time I cared for a palliative purchase 6-Methoxybaicalein patient and was there when they passed. Talking with the Pleconaril chemical information family. My first job that I had as an LPN, I was alone on the floor as the only official nurse for more than half of my shift. I had the full responsibility of all 60 residents in my care . . . that all happened as an LPN.” From the Post LPN to BN students’ perspective, the notion that socialization into the role of “nurse” would occur for them at this point in their career was insulting: “I almost feel a little bit insulted to think that I would feel any less professional as an LPN than I do as an RN. I feel equally professional in both roles.” “My buddy nurse ac.Are a useful method for gaining insight into phenomena where little is known [44]. When focus group data has been collected from multiple groups and multiple sites, researchers can have increased confidence in the reliability and validity of the findings [45]. The focus groups were guided by following questions. (1) Perceptions of Professional Socialization. (a) What comes to mind when you hear the phrase “professional socialization”? (b) Share memories of your experiences becoming socialized into the role of Licensed Practical Nurse and developing your identity in this role. (c) How is the experience of developing your new role and identity as a Registered Nurse the same? How is it different? (2) Formal Academic Experiences: Online Classes and Clinical Practicums. (a) Talk about experiences you have had so far in your online university classes where you “felt like” a Registered Nurse and not a Licensed Practical Nurse? Have there been times in your online4 [54] (page 85) maintained by both moderators during and immediately following the sessions further increased the dependability of our findings. Practical issues such as organizing groups at a time and place to minimize disruption and avoiding power differential dynamics [55] were addressed. The groups were held when participants, who were normally separated by distance, were together in the same city for a required practicum experience. They were held at change of shift in lieu of a post conference. Knowing the power differential between students and teachers, moderators who did not have teaching responsibilities in the Post LPN to BN program were chosen to facilitate the focus groups. Instructors were not present during any of the discussions and had no involvement with the transcript data. Participants were recruited through a Letter of Invitation sent via email by a Research Assistant who was also not involved with the program. Four focus groups were held with 5 to 9 participants each. All the students who were invited chose to participate. We reasoned that this may have been because they were all from out of town and appreciated an opportunity to interact and share their views. Pseudonyms ensured participant confidentiality. Full ethical approval was granted by the university. The following two overarching themes emerged from analyzing the data. First, Post LPN to BN students need little, if any, further legitimation to affirm their identities as “nurse.” Second, practicum interactions with instructors and new clinical experiences are key socializing agents.Nursing Research and Practice They talked about opportunities where demonstrating professional authority in their workplace further established their identity as “nurse”: “Working your first night shift . . . in your new role. The culture of night shift–it’s different.” “The first time I cared for a palliative patient and was there when they passed. Talking with the family. My first job that I had as an LPN, I was alone on the floor as the only official nurse for more than half of my shift. I had the full responsibility of all 60 residents in my care . . . that all happened as an LPN.” From the Post LPN to BN students’ perspective, the notion that socialization into the role of “nurse” would occur for them at this point in their career was insulting: “I almost feel a little bit insulted to think that I would feel any less professional as an LPN than I do as an RN. I feel equally professional in both roles.” “My buddy nurse ac.

, a runner who demonstrates considerably less than 45?of knee flexion may

, a runner who demonstrates considerably less than 45?of knee flexion may suggest PD0325901 custom synthesis reduced shock absorption, and PM01183 supplier intervention may be warranted. Some data exist suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj., a runner who demonstrates considerably less than 45?of knee flexion may suggest reduced shock absorption, and intervention may be warranted. Some data exist suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj.

Ampal CA1 subfield in individuals with MCI compared to NCI (Fig.

Ampal CA1 subfield in individuals with MCI compared to NCI (Fig. 4), which correlated with the subject’s Mini-Mental State Exam score (MMSE), but not with NFT Braak stage or apolipoprotein E (ApoE) status, a genetic risk factor for AD (Scheff et al., 2006). Unlike the outer molecular layer, CA1 receives input from the Schaffer collaterals arising from CA3 and not from the glutamatergic neurons of the entorhinal cortex, suggesting differential responses to synapse loss within the hippocampus based upon afferent innervation or chemical phenotype, some of which precipitate synaptic reorganization. A recent report characterized changes in the dendritic branching of the basilar tree of hippocampal CA1 pyramidal neurons. In this study, formalin-fixed tissue autopsy obtained from University of Kentucky Alzheimer’s Disease Center who died with a Shikonin web clinical diagnosis of NCI, MCI or AD was prepared for Golgi impregnation (Fig. 5). Camera lucida drawings of the basilar tree of randomly selected CA1 neurons were analyzed for alterations in dendritic arbor amount, distribution and complexity (Mervis et al., 2013). Quantitation showed a significant increase in dendritic length (18 ) and complexity (23 ) in CA1 neurons in MCI compared to NCI. Conversely, there was a significant reduction in branch length (-39 ) and arbor complexity (-25 ) during the progression from MCI to AD (Fig. 5). These findings suggest that the observed increase in CA1 dendritic parameters from NCI to MCI may be another example of a neuroplastic compensatory response to a loss of afferent input early in the course of the disease, which is not maintained as the disease progresses. The role that the reported reduction in total synapse number plays in CA1 neuroplasticity remains unknown. However, these examples of early CA1 neural reorganization may represent a viable window for potential therapeutic strategies aimed at restoring or maintaining hippocampal function during the transition from MCI to AD. Future studies should determine whether alterations in specific synapse subtypes (i.e., perforated vs. non-perforated) are differentially affected and their relation to cognitive decline and brain pathology during the onset of AD. Interestingly, the size of the synaptic contacts was found to be substantially larger in AD cortex compared to non-demented aged controls (Scheff et al., 1990), which was suggested to be part of a compensatory mechanism found in regions of the neocortex and hippocampus (see review Scheff and Price, 2006). These investigators found that as the number of synapses declined in a given region, the size of the residualAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagesynapses increased. This synaptic compensatory response was also observed early in the course of the AD (DeKosky and Scheff, 1990). Neuronal structural alterations may not be the only factor(s) contributing to cognitive decline and hippocampal plasticity in MCI. For example, studies have reported significant reductions in synaptic vesicle trafficking-related genes in the AD brain, which interrupt the efficacy of normal synaptic transmission (Yao et al., 2003; Murphy et al., 2003; Kennedy et al., 2005). Counts et al. (2014) GW9662 biological activity examined progressive changes in the expression classes of synaptic gene within single CA1 neurons in subjects who died with a clinical diagnosis of NCI, MCI or moderate AD obtain.Ampal CA1 subfield in individuals with MCI compared to NCI (Fig. 4), which correlated with the subject’s Mini-Mental State Exam score (MMSE), but not with NFT Braak stage or apolipoprotein E (ApoE) status, a genetic risk factor for AD (Scheff et al., 2006). Unlike the outer molecular layer, CA1 receives input from the Schaffer collaterals arising from CA3 and not from the glutamatergic neurons of the entorhinal cortex, suggesting differential responses to synapse loss within the hippocampus based upon afferent innervation or chemical phenotype, some of which precipitate synaptic reorganization. A recent report characterized changes in the dendritic branching of the basilar tree of hippocampal CA1 pyramidal neurons. In this study, formalin-fixed tissue autopsy obtained from University of Kentucky Alzheimer’s Disease Center who died with a clinical diagnosis of NCI, MCI or AD was prepared for Golgi impregnation (Fig. 5). Camera lucida drawings of the basilar tree of randomly selected CA1 neurons were analyzed for alterations in dendritic arbor amount, distribution and complexity (Mervis et al., 2013). Quantitation showed a significant increase in dendritic length (18 ) and complexity (23 ) in CA1 neurons in MCI compared to NCI. Conversely, there was a significant reduction in branch length (-39 ) and arbor complexity (-25 ) during the progression from MCI to AD (Fig. 5). These findings suggest that the observed increase in CA1 dendritic parameters from NCI to MCI may be another example of a neuroplastic compensatory response to a loss of afferent input early in the course of the disease, which is not maintained as the disease progresses. The role that the reported reduction in total synapse number plays in CA1 neuroplasticity remains unknown. However, these examples of early CA1 neural reorganization may represent a viable window for potential therapeutic strategies aimed at restoring or maintaining hippocampal function during the transition from MCI to AD. Future studies should determine whether alterations in specific synapse subtypes (i.e., perforated vs. non-perforated) are differentially affected and their relation to cognitive decline and brain pathology during the onset of AD. Interestingly, the size of the synaptic contacts was found to be substantially larger in AD cortex compared to non-demented aged controls (Scheff et al., 1990), which was suggested to be part of a compensatory mechanism found in regions of the neocortex and hippocampus (see review Scheff and Price, 2006). These investigators found that as the number of synapses declined in a given region, the size of the residualAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagesynapses increased. This synaptic compensatory response was also observed early in the course of the AD (DeKosky and Scheff, 1990). Neuronal structural alterations may not be the only factor(s) contributing to cognitive decline and hippocampal plasticity in MCI. For example, studies have reported significant reductions in synaptic vesicle trafficking-related genes in the AD brain, which interrupt the efficacy of normal synaptic transmission (Yao et al., 2003; Murphy et al., 2003; Kennedy et al., 2005). Counts et al. (2014) examined progressive changes in the expression classes of synaptic gene within single CA1 neurons in subjects who died with a clinical diagnosis of NCI, MCI or moderate AD obtain.

Monly used and widely available OTC medications and nutritional supplements were

Monly used and widely available OTC medications and nutritional supplements were safe and posed no short- or long-term threat to their health. Many used such products to improve their running performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product recommended as an effective and legal substance by another runner or by a retail sales clerk may contain substances that are either banned by agencies such as WADA and/or may pose a purchase GS-5816 serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.Monocrotaline solubility Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.Monly used and widely available OTC medications and nutritional supplements were safe and posed no short- or long-term threat to their health. Many used such products to improve their running performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product recommended as an effective and legal substance by another runner or by a retail sales clerk may contain substances that are either banned by agencies such as WADA and/or may pose a serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.

Deration when interpreting experimental findings. (i) Identification of a mutation in

Deration when interpreting experimental findings. (i) Identification of a mutation in a clonal population does not indicate causality Any mutation in a cell that undergoes clonal expansion will be passed onto progeny, irrespective of functional status (Fig. 3A,B). Given the size of the genome, more mutations carried by a neoplastic clone will be passengers than drivers [27, 29, 30]. To demonstrate driver status, supporting functional studies and/or repeated observations of a mutated loci in neoplastic clones from independent individuals are needed. (ii) Mutational marking of a clone is stochastic and not guaranteed A clone may exist and not be detected if none of the genomic sites being screened carry a unique mutation permitting it to be distinguished from the germline (Fig. 3C). The more sites examined, the higher the probability of detection becomes. Restricting a marker panel to suspected driver sites precludes detection of pathological clones driven by unknown factors. (iii) Elevated mutation rates facilitate clone detection but are not an absolute requirement Screening of mutational hotspots makes it practical with conventional technologies to have a reasonable probability of detecting a clone by random passenger mutations. Clones derived from a mutator lineage or cells residing in a highly mutagenic environment should be more densely marked with identifiable passengers (Fig. 3D), potentially reducing the number of markers needing to be interrogated to identify them. Emerging high-throughput sequencing technologies will eventually Luteolin 7-O-��-D-glucosideMedChemExpress Cynaroside obviate the need to restrict screening to a fraction of the genome. (iv) Identification of one or more clonal mutations is not proof of genetic instability in the absence of collateral information Detection of a mutation requires clonal expansion with most traditional methods of aggregate DNA analysis. The probability of identifying clonal mutations in an expanded population is a function of the number of sites screened, the mutability of these sites and the number of cell divisions having occurred in the lineage leading up to the final expansion. Particularly when considering hotspots, mutations will be occasionally detectable in any clonally-derived population at a statistically definable frequency. Because mutations are not routinely encountered in normal tissues, it is tempting to explain their presence in preneoplastic populations as the result of “genetic instability” (an elevated mutation rate). However, the phenomenon is more precisely explained by the fact that expansion does not routinely occur in most normal tissues. An elevated mutation rate itself will have no observable effect on clonal mutation frequency in the absence of expansion (Fig. 3E). To determine mutation rate from a clonal mutation frequency it is necessary to (A) know that the population being assessed is clonal and (B) have some metric of the number of cell divisions that occurred in the period between the zygote and the founding of the final clonalSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPageoutgrowth. To infer that a rate is elevated, it is also necessary to know the normal in vivo mutation rate, which is, in turn, impossible to measure by this approach given that large clonal expansions do not routinely occur in normal adult tissue. Considering these complexities, the lack of resolution as to whether mutation rates are elevated in cancer is not DS5565 chemical information surprising [1,8?1]. (v) Detectabili.Deration when interpreting experimental findings. (i) Identification of a mutation in a clonal population does not indicate causality Any mutation in a cell that undergoes clonal expansion will be passed onto progeny, irrespective of functional status (Fig. 3A,B). Given the size of the genome, more mutations carried by a neoplastic clone will be passengers than drivers [27, 29, 30]. To demonstrate driver status, supporting functional studies and/or repeated observations of a mutated loci in neoplastic clones from independent individuals are needed. (ii) Mutational marking of a clone is stochastic and not guaranteed A clone may exist and not be detected if none of the genomic sites being screened carry a unique mutation permitting it to be distinguished from the germline (Fig. 3C). The more sites examined, the higher the probability of detection becomes. Restricting a marker panel to suspected driver sites precludes detection of pathological clones driven by unknown factors. (iii) Elevated mutation rates facilitate clone detection but are not an absolute requirement Screening of mutational hotspots makes it practical with conventional technologies to have a reasonable probability of detecting a clone by random passenger mutations. Clones derived from a mutator lineage or cells residing in a highly mutagenic environment should be more densely marked with identifiable passengers (Fig. 3D), potentially reducing the number of markers needing to be interrogated to identify them. Emerging high-throughput sequencing technologies will eventually obviate the need to restrict screening to a fraction of the genome. (iv) Identification of one or more clonal mutations is not proof of genetic instability in the absence of collateral information Detection of a mutation requires clonal expansion with most traditional methods of aggregate DNA analysis. The probability of identifying clonal mutations in an expanded population is a function of the number of sites screened, the mutability of these sites and the number of cell divisions having occurred in the lineage leading up to the final expansion. Particularly when considering hotspots, mutations will be occasionally detectable in any clonally-derived population at a statistically definable frequency. Because mutations are not routinely encountered in normal tissues, it is tempting to explain their presence in preneoplastic populations as the result of “genetic instability” (an elevated mutation rate). However, the phenomenon is more precisely explained by the fact that expansion does not routinely occur in most normal tissues. An elevated mutation rate itself will have no observable effect on clonal mutation frequency in the absence of expansion (Fig. 3E). To determine mutation rate from a clonal mutation frequency it is necessary to (A) know that the population being assessed is clonal and (B) have some metric of the number of cell divisions that occurred in the period between the zygote and the founding of the final clonalSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPageoutgrowth. To infer that a rate is elevated, it is also necessary to know the normal in vivo mutation rate, which is, in turn, impossible to measure by this approach given that large clonal expansions do not routinely occur in normal adult tissue. Considering these complexities, the lack of resolution as to whether mutation rates are elevated in cancer is not surprising [1,8?1]. (v) Detectabili.

. This exploratory analysis can provide further information on functional similarities between

. This exploratory analysis can SCR7 clinical trials provide further information on functional similarities between regions, and, more specifically, on the extent to which activation profiles of category-selective AMG9810 site regions are inherited from EVC. As for the replicability of within-category ranking (Fig. 5), we combined data across subjects either by concatenating or averaging the activation profiles across subjects. The concatenation approach is sensitive to inter-region correlations of activation profiles even if the particular activation profiles differ across subjects. The averaging approach is sensitive to inter-region correlations of activation profiles that are consistent across subjects. We investigated the inter-region correlations for (1) the full activation profile, (2) the within-face activation profile, and (3) the withinplace activation profile. Statistical inference was performed by a standard one-sided test on Spearman’s r. p values were corrected8658 ?J. Neurosci., June 20, 2012 ?32(25):8649 ?Mur et al. ?Single-Image Activation of Category Regionsfor multiple testing using Bonferroni correction based on the total number of tests performed. Figure 7 shows the inter-region correlation results. The main pattern that emerges is that activation profiles are correlated between hemispheres for corresponding regions, and between hIT and EVC (red blocks on diagonals). We subsequently inspected the within-face correlation between FFA and EVC, and the within-place correlation between PPA and EVC. The within-face activation profile was correlated between left but not right FFA and EVC, and the within-place activation profile was not significantly correlated between PPA and EVC. Results were similar across ROI sizes. These results suggest that EVC is not a major contributor to the within-category activation profiles of PPA and right FFA. We then inspected the correlation between category-selective regions (FFA/PPA) and EVC for the full activation profile (top row). The full activation profile was correlated between EVC and both categoryselective regions, especially PPA. One interpretation of this finding would be that some degree of category selectivity is already present at the level of EVC, implying that low-level feature differences contribute to some extent to categoryselective responses. For places, this seems a plausible interpretation, consistent with our finding that single-image activation of EVC can discriminate places from nonplaces at an above-chance level (Fig. 2). For faces, this interpretation seems less likely: the correlation between EVC and FFA is not significant for the subjectaverage activation profile, suggesting that the correlation is driven by subjectspecific effects (e.g., idiosyncratic arousal effects) and not by face-selectivity of responses (shared across subjects in FFA). Categorical, yet graded Figure 8 summarizes our results. Singleimage activation profiles of categoryselective regions (1) show near-perfect discrimination of preferred from nonpreferred images and no preference inversions for particular object images, (2) show a step-like drop-off at the category boundary, and (3) are graded within and outside the preferred category. It can further be noted that single-image category selectivity is stronger in right than left FFA. In addition, gradedness seems to be more pronounced in FFA; the category step seems to be more pronounced in PPA. In sum, our findings indicate that the activation profiles of category-selec-Figure.. This exploratory analysis can provide further information on functional similarities between regions, and, more specifically, on the extent to which activation profiles of category-selective regions are inherited from EVC. As for the replicability of within-category ranking (Fig. 5), we combined data across subjects either by concatenating or averaging the activation profiles across subjects. The concatenation approach is sensitive to inter-region correlations of activation profiles even if the particular activation profiles differ across subjects. The averaging approach is sensitive to inter-region correlations of activation profiles that are consistent across subjects. We investigated the inter-region correlations for (1) the full activation profile, (2) the within-face activation profile, and (3) the withinplace activation profile. Statistical inference was performed by a standard one-sided test on Spearman’s r. p values were corrected8658 ?J. Neurosci., June 20, 2012 ?32(25):8649 ?Mur et al. ?Single-Image Activation of Category Regionsfor multiple testing using Bonferroni correction based on the total number of tests performed. Figure 7 shows the inter-region correlation results. The main pattern that emerges is that activation profiles are correlated between hemispheres for corresponding regions, and between hIT and EVC (red blocks on diagonals). We subsequently inspected the within-face correlation between FFA and EVC, and the within-place correlation between PPA and EVC. The within-face activation profile was correlated between left but not right FFA and EVC, and the within-place activation profile was not significantly correlated between PPA and EVC. Results were similar across ROI sizes. These results suggest that EVC is not a major contributor to the within-category activation profiles of PPA and right FFA. We then inspected the correlation between category-selective regions (FFA/PPA) and EVC for the full activation profile (top row). The full activation profile was correlated between EVC and both categoryselective regions, especially PPA. One interpretation of this finding would be that some degree of category selectivity is already present at the level of EVC, implying that low-level feature differences contribute to some extent to categoryselective responses. For places, this seems a plausible interpretation, consistent with our finding that single-image activation of EVC can discriminate places from nonplaces at an above-chance level (Fig. 2). For faces, this interpretation seems less likely: the correlation between EVC and FFA is not significant for the subjectaverage activation profile, suggesting that the correlation is driven by subjectspecific effects (e.g., idiosyncratic arousal effects) and not by face-selectivity of responses (shared across subjects in FFA). Categorical, yet graded Figure 8 summarizes our results. Singleimage activation profiles of categoryselective regions (1) show near-perfect discrimination of preferred from nonpreferred images and no preference inversions for particular object images, (2) show a step-like drop-off at the category boundary, and (3) are graded within and outside the preferred category. It can further be noted that single-image category selectivity is stronger in right than left FFA. In addition, gradedness seems to be more pronounced in FFA; the category step seems to be more pronounced in PPA. In sum, our findings indicate that the activation profiles of category-selec-Figure.

In living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic

In living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic Stattic site Ca-phosphate in pelagic sediments has long been studied by a number of investigators17,18,21?4,40?2. Some have suggested that biogenic Ca-phosphate incorporates REY via pore water in the sediment column23,40. Others have argued that Ca-phosphate takes up REY from a variety of carrier phases (e.g. Fe n-oxyhydroxides, pellets, and organic debris) that absorb REY from seawater and are readily decomposed at the sediment ater interface17,22,41,42. Although the complete process remains an open question, the characteristic REY patterns indicate that seawater is the ultimate source of the REY presently captured in biogenic Ca-phosphate22,25,41 (Fig. 4m). Simple quantitative estimation in this study suggested the possibility that seawater can contain the flux of REY precipitation required to explain the observed very high REY concentrations ( REY + Ce > 1,000 ppm) in bulk REY-rich mud with a sedimentation rate less than 0.5 m/Myr (Supplementary Fig. S19). Such circumstances may facilitate the concentration of REY in biogenic Ca-phosphate via diffusion of REY from seawater or the transfer of REY from original carriers to Ca-phosphate SIS3 custom synthesis during the early diagenetic processes because of the prolonged exposure to seawater at the sediment surface and in the bioturbated and well-ventilated uppermost sediment layer17,18,22,41. In addition, biogenic Ca-phosphate enriched in REY might be stabilised through recrystallisation as insoluble apatite17. Moreover, the amount of Ca-phosphate in a unit volume of sediment also increases with a depression of the sedimentation rate17,18. Hence, the low sedimentation rate is considered to be crucial for the formation of REY-rich mud. Actually, the spatiotemporal distribution of high-IC1, -IC4, and -IC7 muds overlapped with the oligotrophic North Pacific and South Pacific gyres and with water depths greater than the CCD, both of which prevented the fast accumulation of dilutive components with low REY content such as biogenic carbonate and silica. If we assume that deep-sea sediments can continuously acquire REY from the overlying deep-sea water prior to burial, the REY-enrichment in sediments can occur in a time scale of 105 years considering the sedimentation rate of <0.5 m/Myr with a typical thickness of 0.1 m for the well-ventilated uppermost sediment layer43. This timescale of REY enrichment is significantly longer than that of global ocean circulation, which is 103 years44. Both IC1 and IC4 indicated statistical independent geochemical features of pelagic red clay mainly composed of detrital aluminosilicates involving abundant Si, Al, Fe, Mg, and K without significant contributions of biogenic carbonate and silica. Fe and Mn of hydrothermal or hydrogenous origins could have also been incorporated without dilution in high-IC1 and high-IC4 sediments, resulting in an increase in the contents of these elements. In addition, in deposition slow enough to allow biogenic Ca-phosphate grains to concentrate REY and to accumulate significantly in the sediment, the P and REY contents of these sediments also increase concurrently. Although sediments enriched in biogenic Ca-phosphate contain several percent of Ca, the significant dilution effect of biogenic carbonate, which contains several tens of percent of Ca, generally creates negative trends in these ICs as a whole in the spaces of Ca and other elements, including REY. The differenc.In living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic Ca-phosphate in pelagic sediments has long been studied by a number of investigators17,18,21?4,40?2. Some have suggested that biogenic Ca-phosphate incorporates REY via pore water in the sediment column23,40. Others have argued that Ca-phosphate takes up REY from a variety of carrier phases (e.g. Fe n-oxyhydroxides, pellets, and organic debris) that absorb REY from seawater and are readily decomposed at the sediment ater interface17,22,41,42. Although the complete process remains an open question, the characteristic REY patterns indicate that seawater is the ultimate source of the REY presently captured in biogenic Ca-phosphate22,25,41 (Fig. 4m). Simple quantitative estimation in this study suggested the possibility that seawater can contain the flux of REY precipitation required to explain the observed very high REY concentrations ( REY + Ce > 1,000 ppm) in bulk REY-rich mud with a sedimentation rate less than 0.5 m/Myr (Supplementary Fig. S19). Such circumstances may facilitate the concentration of REY in biogenic Ca-phosphate via diffusion of REY from seawater or the transfer of REY from original carriers to Ca-phosphate during the early diagenetic processes because of the prolonged exposure to seawater at the sediment surface and in the bioturbated and well-ventilated uppermost sediment layer17,18,22,41. In addition, biogenic Ca-phosphate enriched in REY might be stabilised through recrystallisation as insoluble apatite17. Moreover, the amount of Ca-phosphate in a unit volume of sediment also increases with a depression of the sedimentation rate17,18. Hence, the low sedimentation rate is considered to be crucial for the formation of REY-rich mud. Actually, the spatiotemporal distribution of high-IC1, -IC4, and -IC7 muds overlapped with the oligotrophic North Pacific and South Pacific gyres and with water depths greater than the CCD, both of which prevented the fast accumulation of dilutive components with low REY content such as biogenic carbonate and silica. If we assume that deep-sea sediments can continuously acquire REY from the overlying deep-sea water prior to burial, the REY-enrichment in sediments can occur in a time scale of 105 years considering the sedimentation rate of <0.5 m/Myr with a typical thickness of 0.1 m for the well-ventilated uppermost sediment layer43. This timescale of REY enrichment is significantly longer than that of global ocean circulation, which is 103 years44. Both IC1 and IC4 indicated statistical independent geochemical features of pelagic red clay mainly composed of detrital aluminosilicates involving abundant Si, Al, Fe, Mg, and K without significant contributions of biogenic carbonate and silica. Fe and Mn of hydrothermal or hydrogenous origins could have also been incorporated without dilution in high-IC1 and high-IC4 sediments, resulting in an increase in the contents of these elements. In addition, in deposition slow enough to allow biogenic Ca-phosphate grains to concentrate REY and to accumulate significantly in the sediment, the P and REY contents of these sediments also increase concurrently. Although sediments enriched in biogenic Ca-phosphate contain several percent of Ca, the significant dilution effect of biogenic carbonate, which contains several tens of percent of Ca, generally creates negative trends in these ICs as a whole in the spaces of Ca and other elements, including REY. The differenc.

, a runner who demonstrates considerably less than 45?of knee flexion may

, a runner who demonstrates considerably less than 45?of knee SF 1101 chemical information flexion may Pan-RAS-IN-1 price suggest reduced shock absorption, and intervention may be warranted. Some data exist suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj., a runner who demonstrates considerably less than 45?of knee flexion may suggest reduced shock absorption, and intervention may be warranted. Some data exist suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj.

Ampal CA1 subfield in individuals with MCI compared to NCI (Fig.

Ampal CA1 subfield in individuals with MCI compared to NCI (Fig. 4), which correlated with the subject’s Mini-Mental State Exam score (MMSE), but not with NFT Braak stage or apolipoprotein E (ApoE) status, a genetic risk factor for AD (Scheff et al., 2006). Unlike the outer molecular layer, CA1 receives input from the Schaffer collaterals arising from CA3 and not from the glutamatergic neurons of the entorhinal cortex, suggesting differential responses to synapse loss within the hippocampus based upon afferent innervation or chemical phenotype, some of which precipitate synaptic reorganization. A recent report characterized changes in the dendritic branching of the basilar tree of hippocampal CA1 pyramidal neurons. In this study, formalin-fixed tissue autopsy obtained from University of Kentucky Alzheimer’s Disease Center who died with a clinical diagnosis of NCI, MCI or AD was prepared for Golgi impregnation (Fig. 5). Camera lucida drawings of the basilar tree of randomly selected CA1 neurons were analyzed for alterations in dendritic arbor amount, distribution and LY317615 custom synthesis complexity (Mervis et al., 2013). Quantitation showed a significant increase in dendritic length (18 ) and complexity (23 ) in CA1 neurons in MCI compared to NCI. Conversely, there was a significant reduction in branch length (-39 ) and arbor complexity (-25 ) during the progression from MCI to AD (Fig. 5). These findings suggest that the observed increase in CA1 dendritic parameters from NCI to MCI may be another example of a neuroplastic compensatory response to a loss of afferent input early in the EnzastaurinMedChemExpress LY317615 course of the disease, which is not maintained as the disease progresses. The role that the reported reduction in total synapse number plays in CA1 neuroplasticity remains unknown. However, these examples of early CA1 neural reorganization may represent a viable window for potential therapeutic strategies aimed at restoring or maintaining hippocampal function during the transition from MCI to AD. Future studies should determine whether alterations in specific synapse subtypes (i.e., perforated vs. non-perforated) are differentially affected and their relation to cognitive decline and brain pathology during the onset of AD. Interestingly, the size of the synaptic contacts was found to be substantially larger in AD cortex compared to non-demented aged controls (Scheff et al., 1990), which was suggested to be part of a compensatory mechanism found in regions of the neocortex and hippocampus (see review Scheff and Price, 2006). These investigators found that as the number of synapses declined in a given region, the size of the residualAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagesynapses increased. This synaptic compensatory response was also observed early in the course of the AD (DeKosky and Scheff, 1990). Neuronal structural alterations may not be the only factor(s) contributing to cognitive decline and hippocampal plasticity in MCI. For example, studies have reported significant reductions in synaptic vesicle trafficking-related genes in the AD brain, which interrupt the efficacy of normal synaptic transmission (Yao et al., 2003; Murphy et al., 2003; Kennedy et al., 2005). Counts et al. (2014) examined progressive changes in the expression classes of synaptic gene within single CA1 neurons in subjects who died with a clinical diagnosis of NCI, MCI or moderate AD obtain.Ampal CA1 subfield in individuals with MCI compared to NCI (Fig. 4), which correlated with the subject’s Mini-Mental State Exam score (MMSE), but not with NFT Braak stage or apolipoprotein E (ApoE) status, a genetic risk factor for AD (Scheff et al., 2006). Unlike the outer molecular layer, CA1 receives input from the Schaffer collaterals arising from CA3 and not from the glutamatergic neurons of the entorhinal cortex, suggesting differential responses to synapse loss within the hippocampus based upon afferent innervation or chemical phenotype, some of which precipitate synaptic reorganization. A recent report characterized changes in the dendritic branching of the basilar tree of hippocampal CA1 pyramidal neurons. In this study, formalin-fixed tissue autopsy obtained from University of Kentucky Alzheimer’s Disease Center who died with a clinical diagnosis of NCI, MCI or AD was prepared for Golgi impregnation (Fig. 5). Camera lucida drawings of the basilar tree of randomly selected CA1 neurons were analyzed for alterations in dendritic arbor amount, distribution and complexity (Mervis et al., 2013). Quantitation showed a significant increase in dendritic length (18 ) and complexity (23 ) in CA1 neurons in MCI compared to NCI. Conversely, there was a significant reduction in branch length (-39 ) and arbor complexity (-25 ) during the progression from MCI to AD (Fig. 5). These findings suggest that the observed increase in CA1 dendritic parameters from NCI to MCI may be another example of a neuroplastic compensatory response to a loss of afferent input early in the course of the disease, which is not maintained as the disease progresses. The role that the reported reduction in total synapse number plays in CA1 neuroplasticity remains unknown. However, these examples of early CA1 neural reorganization may represent a viable window for potential therapeutic strategies aimed at restoring or maintaining hippocampal function during the transition from MCI to AD. Future studies should determine whether alterations in specific synapse subtypes (i.e., perforated vs. non-perforated) are differentially affected and their relation to cognitive decline and brain pathology during the onset of AD. Interestingly, the size of the synaptic contacts was found to be substantially larger in AD cortex compared to non-demented aged controls (Scheff et al., 1990), which was suggested to be part of a compensatory mechanism found in regions of the neocortex and hippocampus (see review Scheff and Price, 2006). These investigators found that as the number of synapses declined in a given region, the size of the residualAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagesynapses increased. This synaptic compensatory response was also observed early in the course of the AD (DeKosky and Scheff, 1990). Neuronal structural alterations may not be the only factor(s) contributing to cognitive decline and hippocampal plasticity in MCI. For example, studies have reported significant reductions in synaptic vesicle trafficking-related genes in the AD brain, which interrupt the efficacy of normal synaptic transmission (Yao et al., 2003; Murphy et al., 2003; Kennedy et al., 2005). Counts et al. (2014) examined progressive changes in the expression classes of synaptic gene within single CA1 neurons in subjects who died with a clinical diagnosis of NCI, MCI or moderate AD obtain.

Monly used and widely available OTC medications and nutritional supplements were

Monly used and widely available OTC medications and nutritional supplements were safe and posed no short- or long-term threat to their health. Many used such products to improve their running performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product recommended as an effective and legal substance by another runner or by a retail sales clerk may contain substances that are either banned by agencies such as WADA and/or may pose a serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.BAY1217389 custom synthesis NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public purchase GS-5816 AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.Monly used and widely available OTC medications and nutritional supplements were safe and posed no short- or long-term threat to their health. Many used such products to improve their running performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product recommended as an effective and legal substance by another runner or by a retail sales clerk may contain substances that are either banned by agencies such as WADA and/or may pose a serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.

Deration when interpreting experimental findings. (i) Identification of a mutation in

Deration when interpreting experimental findings. (i) Identification of a mutation in a clonal population does not indicate causality Any mutation in a cell that undergoes clonal expansion will be passed onto progeny, irrespective of functional status (Fig. 3A,B). Given the size of the genome, more mutations carried by a neoplastic clone will be passengers than drivers [27, 29, 30]. To demonstrate driver status, supporting functional studies and/or repeated observations of a mutated loci in neoplastic clones from independent individuals are needed. (ii) Mutational marking of a clone is stochastic and not guaranteed A clone may exist and not be detected if none of the genomic sites being screened carry a unique mutation permitting it to be distinguished from the germline (Fig. 3C). The more sites examined, the higher the probability of detection becomes. Restricting a marker panel to suspected driver sites precludes detection of pathological clones driven by unknown factors. (iii) Elevated mutation rates facilitate clone detection but are not an absolute requirement Screening of mutational hotspots makes it practical with conventional technologies to have a reasonable probability of detecting a clone by random passenger mutations. Clones derived from a mutator lineage or cells residing in a highly mutagenic environment should be more densely marked with CynarosideMedChemExpress Luteolin 7-glucoside identifiable passengers (Fig. 3D), potentially reducing the number of markers needing to be interrogated to identify them. Emerging high-throughput sequencing technologies will eventually obviate the need to restrict screening to a fraction of the genome. (iv) Identification of one or more clonal mutations is not proof of genetic instability in the absence of collateral information Detection of a mutation requires clonal expansion with most traditional methods of aggregate DNA analysis. The probability of identifying clonal mutations in an expanded population is a function of the number of sites screened, the mutability of these sites and the number of cell divisions having occurred in the lineage leading up to the final expansion. Particularly when considering hotspots, mutations will be occasionally detectable in any clonally-derived population at a statistically definable frequency. Because mutations are not routinely encountered in XR9576 web normal tissues, it is tempting to explain their presence in preneoplastic populations as the result of “genetic instability” (an elevated mutation rate). However, the phenomenon is more precisely explained by the fact that expansion does not routinely occur in most normal tissues. An elevated mutation rate itself will have no observable effect on clonal mutation frequency in the absence of expansion (Fig. 3E). To determine mutation rate from a clonal mutation frequency it is necessary to (A) know that the population being assessed is clonal and (B) have some metric of the number of cell divisions that occurred in the period between the zygote and the founding of the final clonalSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPageoutgrowth. To infer that a rate is elevated, it is also necessary to know the normal in vivo mutation rate, which is, in turn, impossible to measure by this approach given that large clonal expansions do not routinely occur in normal adult tissue. Considering these complexities, the lack of resolution as to whether mutation rates are elevated in cancer is not surprising [1,8?1]. (v) Detectabili.Deration when interpreting experimental findings. (i) Identification of a mutation in a clonal population does not indicate causality Any mutation in a cell that undergoes clonal expansion will be passed onto progeny, irrespective of functional status (Fig. 3A,B). Given the size of the genome, more mutations carried by a neoplastic clone will be passengers than drivers [27, 29, 30]. To demonstrate driver status, supporting functional studies and/or repeated observations of a mutated loci in neoplastic clones from independent individuals are needed. (ii) Mutational marking of a clone is stochastic and not guaranteed A clone may exist and not be detected if none of the genomic sites being screened carry a unique mutation permitting it to be distinguished from the germline (Fig. 3C). The more sites examined, the higher the probability of detection becomes. Restricting a marker panel to suspected driver sites precludes detection of pathological clones driven by unknown factors. (iii) Elevated mutation rates facilitate clone detection but are not an absolute requirement Screening of mutational hotspots makes it practical with conventional technologies to have a reasonable probability of detecting a clone by random passenger mutations. Clones derived from a mutator lineage or cells residing in a highly mutagenic environment should be more densely marked with identifiable passengers (Fig. 3D), potentially reducing the number of markers needing to be interrogated to identify them. Emerging high-throughput sequencing technologies will eventually obviate the need to restrict screening to a fraction of the genome. (iv) Identification of one or more clonal mutations is not proof of genetic instability in the absence of collateral information Detection of a mutation requires clonal expansion with most traditional methods of aggregate DNA analysis. The probability of identifying clonal mutations in an expanded population is a function of the number of sites screened, the mutability of these sites and the number of cell divisions having occurred in the lineage leading up to the final expansion. Particularly when considering hotspots, mutations will be occasionally detectable in any clonally-derived population at a statistically definable frequency. Because mutations are not routinely encountered in normal tissues, it is tempting to explain their presence in preneoplastic populations as the result of “genetic instability” (an elevated mutation rate). However, the phenomenon is more precisely explained by the fact that expansion does not routinely occur in most normal tissues. An elevated mutation rate itself will have no observable effect on clonal mutation frequency in the absence of expansion (Fig. 3E). To determine mutation rate from a clonal mutation frequency it is necessary to (A) know that the population being assessed is clonal and (B) have some metric of the number of cell divisions that occurred in the period between the zygote and the founding of the final clonalSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPageoutgrowth. To infer that a rate is elevated, it is also necessary to know the normal in vivo mutation rate, which is, in turn, impossible to measure by this approach given that large clonal expansions do not routinely occur in normal adult tissue. Considering these complexities, the lack of resolution as to whether mutation rates are elevated in cancer is not surprising [1,8?1]. (v) Detectabili.

Faces or places at any ROI size. We additionally performed a

Faces or places at any ROI size. We additionally performed a modified version of our analysis, which is sensitive to subject-unique activation profiles. This analysis again showed a significant category step for right FFA and right and left PPA at all ROI sizes. Left FFA now showed a significant category step at three of five ROI sizes ( p 0.05, with p 0.0025 for 55 voxels). There was no evidence for a category step in hIT and EVC. Results for gradedness within the preferred category (Fig. 6 B) were consistent with the results on the replicability of withincategory ranking reported in the previous section (Fig. 5B). Bothleft and right FFA showed graded within-face activation profiles. Left FFA showed gradedness at the smallest two ROI sizes ( p 0.0025) and right FFA at all ROI sizes ( p 0.0025) except the largest one. Right but not left PPA showed a graded within-place activation profile at three of five ROI sizes ( p 0.0025 for 23 voxels, p 0.05 for 55 and 128 voxels). hIT and EVC showed graded within-place but not within-face activation Linaprazan manufacturer profiles at most or all ROI sizes ( p 0.05, with p 0.0025 in several cases). The subject-unique analysis showed similar results for FFA and PPA. For hIT and EVC, gradedness within places disappeared, while gradedness within faces remained absent. The lack of within-place and within-face gradedness in hIT for the subject-unique analysis forms the only inconsistency with the replicability-of-withincategory-ranking results (Fig. 5B, left column), and suggests that the subject-unique activation profiles for faces and places in hIT do not fall off linearly. (The category-step-and-gradedness analysis modeled the falloff of activation as linear within preferred and within nonpreferred categories, whereas the replicability-ofwithin-category-ranking analysis is sensitive to nonlinear graded activation profiles.) Category-selective regions FFA and PPA also showed graded activation profiles for nonpreferred images at most ROI sizes (Fig. 6 B). This effect likely reflects both between- and withincategory activation differences among the nonpreferred images. In any case, this finding indicates that the activation profile of category-selective regions is graded for images outside the preferred category. hIT and EVC did not show graded activation profiles for nonplaces or nonfaces (except for nonfaces in EVC at the smallest ROI size, p 0.05, data not shown). The subjectunique group analysis showed similar results for FFA. For PPA, gradedness within nonplaces disappeared at most ROI sizes. Results for hIT did not change, while EVC now exhibited gradedness within nonfaces and nonplaces at a small number of ROI sizes ( p 0.05). In sum, our findings indicate that the category boundary has a special status in category-selective regions, especially in right FFA and right and left PPA. The presence of a drop-off of activation at the category boundary in the absence of gradedness would suggest a binary response profile. purchase GLPG0187 However, category-selective regions showed gradedness of activation within (except left PPA) and outside the preferred category in addition to the category step at the boundary. This suggests that a binary response function is not sufficient to explain the activation profiles of categoryselective regions. Correlation of activation profiles across regions Our results suggest functional similarities between certain regions, which we explored further by rank-correlating activation profiles between ROIs (Fig. 7).Faces or places at any ROI size. We additionally performed a modified version of our analysis, which is sensitive to subject-unique activation profiles. This analysis again showed a significant category step for right FFA and right and left PPA at all ROI sizes. Left FFA now showed a significant category step at three of five ROI sizes ( p 0.05, with p 0.0025 for 55 voxels). There was no evidence for a category step in hIT and EVC. Results for gradedness within the preferred category (Fig. 6 B) were consistent with the results on the replicability of withincategory ranking reported in the previous section (Fig. 5B). Bothleft and right FFA showed graded within-face activation profiles. Left FFA showed gradedness at the smallest two ROI sizes ( p 0.0025) and right FFA at all ROI sizes ( p 0.0025) except the largest one. Right but not left PPA showed a graded within-place activation profile at three of five ROI sizes ( p 0.0025 for 23 voxels, p 0.05 for 55 and 128 voxels). hIT and EVC showed graded within-place but not within-face activation profiles at most or all ROI sizes ( p 0.05, with p 0.0025 in several cases). The subject-unique analysis showed similar results for FFA and PPA. For hIT and EVC, gradedness within places disappeared, while gradedness within faces remained absent. The lack of within-place and within-face gradedness in hIT for the subject-unique analysis forms the only inconsistency with the replicability-of-withincategory-ranking results (Fig. 5B, left column), and suggests that the subject-unique activation profiles for faces and places in hIT do not fall off linearly. (The category-step-and-gradedness analysis modeled the falloff of activation as linear within preferred and within nonpreferred categories, whereas the replicability-ofwithin-category-ranking analysis is sensitive to nonlinear graded activation profiles.) Category-selective regions FFA and PPA also showed graded activation profiles for nonpreferred images at most ROI sizes (Fig. 6 B). This effect likely reflects both between- and withincategory activation differences among the nonpreferred images. In any case, this finding indicates that the activation profile of category-selective regions is graded for images outside the preferred category. hIT and EVC did not show graded activation profiles for nonplaces or nonfaces (except for nonfaces in EVC at the smallest ROI size, p 0.05, data not shown). The subjectunique group analysis showed similar results for FFA. For PPA, gradedness within nonplaces disappeared at most ROI sizes. Results for hIT did not change, while EVC now exhibited gradedness within nonfaces and nonplaces at a small number of ROI sizes ( p 0.05). In sum, our findings indicate that the category boundary has a special status in category-selective regions, especially in right FFA and right and left PPA. The presence of a drop-off of activation at the category boundary in the absence of gradedness would suggest a binary response profile. However, category-selective regions showed gradedness of activation within (except left PPA) and outside the preferred category in addition to the category step at the boundary. This suggests that a binary response function is not sufficient to explain the activation profiles of categoryselective regions. Correlation of activation profiles across regions Our results suggest functional similarities between certain regions, which we explored further by rank-correlating activation profiles between ROIs (Fig. 7).

Items each represented 16 different topics that received high engagement in just

Items each represented 16 different RP54476 chemical information topics that received high engagement in just one platform (hereafter: “unique” Nutlin (3a) biological activity high-engagement items). These data indicate an association between high engagement and item topic (2(47) = 80.054, n = 214, p < 0.01, Cramer’s V = 0.612).PLOS ONE | DOI:10.1371/journal.pone.0156409 May 27,13 /Engagement with Particle Physics on CERN’s Social Media PlatformsTable 8. Recurring high engagement topics. Recurring High Engagement Topic Code 1. 2. 3. 4. 5. 6. Fabiola Open Data Pipes 1st Computer CMS Dishwasher Type News News Guess What It Is Throwback Thursday Wow Wow Image Caption “CERN Council selects Italian physicist, Dr Fabiola Gianotti, as CERN’s next Director-General” “CERN launches Open Data Portal to make public the data of LHC experiments” “CERN’s cooling ventilation systems get refreshed” “The Ferranti Mercury, CERN’s 1st ‘central’ computer” “The LHC’s Compact Muon Solenoid (CMS) detector” “That’s right, a CERN dishwasher for circuit boards” Recurred as High Engagement Item on. . . Facebook, Twitter English, Twitter French Facebook, Google+, Twitter English, Twitter French Google+, Twitter French Facebook, Twitter English Instagram, Twitter English, Twitter French Facebook, Google+, Instagram, Twitter English, Twitter Frenchdoi:10.1371/journal.pone.0156409.tSome characteristics of the high-engagement topics are that they may have referred to (1) news items receiving attention from traditional media (e.g. the “Fabiola” topic), or (2) a surprising or awe-inspiring image (e.g. “CMS”, “Dishwasher” and “Pipes”) (Table 8).Research LimitationsThe main methodological limitation in this study stems from the architecture of the platforms. The items posted were not necessarily seen by all CERN’s subscribers. The “organic reach” is determined by the technical settings of the platforms, and may be affected by many different variables. For example, one study found that organic reach increases on a given Facebook item if another item was posted on the platform the day before [30]. The results are based on data collected from October to December 2014, however changes may have occurred since then at multiple levels: from the CERN social media strategy and behaviour, to the architecture of the platforms, as well as the audiences, their preferences and the general online communication landscape. Concerning CERN’s strategy and posting behaviour, this has remained consistent with the data-taking period. However, platform architectures are regularly changed and updated. Since our findings indicate that the platform itself influences user behaviour, it follows that changes in the platform may have an effect. For example, Twitter has implemented a new feed algorithm [43]. Google+ has been fully redesigned [44]. Facebook have not only changed the way that content from pages are delivered to the audience [45], they are also placing more and more emphasis on video content, particularly live or immersive videos, over other types of content [46]. One recent Facebook update now allows people to express their feelings as “reactions” to the information published [47]. These changes call for more elaborate future research in this topic, with fine-tuned analysis that looks at both the comments and the reaction icons. The online communication landscape in general has become more mobile, with some audiences shifting to other social media platforms such as Snapchat. Notwithstanding the dynamics of this field, our systematic study still.Items each represented 16 different topics that received high engagement in just one platform (hereafter: “unique” high-engagement items). These data indicate an association between high engagement and item topic (2(47) = 80.054, n = 214, p < 0.01, Cramer’s V = 0.612).PLOS ONE | DOI:10.1371/journal.pone.0156409 May 27,13 /Engagement with Particle Physics on CERN’s Social Media PlatformsTable 8. Recurring high engagement topics. Recurring High Engagement Topic Code 1. 2. 3. 4. 5. 6. Fabiola Open Data Pipes 1st Computer CMS Dishwasher Type News News Guess What It Is Throwback Thursday Wow Wow Image Caption “CERN Council selects Italian physicist, Dr Fabiola Gianotti, as CERN’s next Director-General” “CERN launches Open Data Portal to make public the data of LHC experiments” “CERN’s cooling ventilation systems get refreshed” “The Ferranti Mercury, CERN’s 1st ‘central’ computer” “The LHC’s Compact Muon Solenoid (CMS) detector” “That’s right, a CERN dishwasher for circuit boards” Recurred as High Engagement Item on. . . Facebook, Twitter English, Twitter French Facebook, Google+, Twitter English, Twitter French Google+, Twitter French Facebook, Twitter English Instagram, Twitter English, Twitter French Facebook, Google+, Instagram, Twitter English, Twitter Frenchdoi:10.1371/journal.pone.0156409.tSome characteristics of the high-engagement topics are that they may have referred to (1) news items receiving attention from traditional media (e.g. the “Fabiola” topic), or (2) a surprising or awe-inspiring image (e.g. “CMS”, “Dishwasher” and “Pipes”) (Table 8).Research LimitationsThe main methodological limitation in this study stems from the architecture of the platforms. The items posted were not necessarily seen by all CERN’s subscribers. The “organic reach” is determined by the technical settings of the platforms, and may be affected by many different variables. For example, one study found that organic reach increases on a given Facebook item if another item was posted on the platform the day before [30]. The results are based on data collected from October to December 2014, however changes may have occurred since then at multiple levels: from the CERN social media strategy and behaviour, to the architecture of the platforms, as well as the audiences, their preferences and the general online communication landscape. Concerning CERN’s strategy and posting behaviour, this has remained consistent with the data-taking period. However, platform architectures are regularly changed and updated. Since our findings indicate that the platform itself influences user behaviour, it follows that changes in the platform may have an effect. For example, Twitter has implemented a new feed algorithm [43]. Google+ has been fully redesigned [44]. Facebook have not only changed the way that content from pages are delivered to the audience [45], they are also placing more and more emphasis on video content, particularly live or immersive videos, over other types of content [46]. One recent Facebook update now allows people to express their feelings as “reactions” to the information published [47]. These changes call for more elaborate future research in this topic, with fine-tuned analysis that looks at both the comments and the reaction icons. The online communication landscape in general has become more mobile, with some audiences shifting to other social media platforms such as Snapchat. Notwithstanding the dynamics of this field, our systematic study still.

E, and thalamus. In addition, in HC, correlation with the PE

E, and thalamus. In addition, in HC, correlation with the PE signal was also observed in dorsal anterior cingulate cortex and posterior parietal cortex, implying that executive processes were engaged. Interestingly, those regions were not differentially associated with the PE signal in patients, suggesting that abnormalities in PE in patients originate from bottom-up rather than top-down processing. Like others, we observed abnormal PE signals in patients who were medicated (mainly second-generation antipsychotics), indicating that dopamine D2 blockade does not normalize PE abnormalities. Interestingly, a study in first-episode patients found normalization of a reward anticipation-related ventral striatum hypofunction after treatment.33 It remains to be determined whether treatment does in fact reduce, but obviously not normalize, PE abnormalities, and whether treatment has a differential effect on PE dysfunction in first episode compared with chronic patients with schizophrenia. Our finding of L-660711 sodium saltMedChemExpress MK-571 (sodium salt) elevated SN Glx in SZ is consistent with previous finding of elevated Glx measured in the striatum,15 putatively suggesting excessive glutamate release from cortical glutamatergic projections to basal ganglia. However, although elevated striatum Glx was observed in unmedicated patients, our observations derive from medicated patients. The participants enrolled in this study overlap with those included in a prior report where,npj Schizophrenia (2015)SN glutamate and prediction error in schizophrenia DM White et al6 although no differences in Glx were observed, the Glx/N-acetylaspartate ratio was significantly elevated in patients, possibly indexing a glutamatergic dysfunction.16 Our findings are also consistent with the identification of abnormal expression of Nmethyl-D-aspartate receptor-associated LY2510924 chemical information intracellular proteins in the SN in schizophrenia.34 In addition to cortical projections, glutamatergic projections to the ventral tegmental area originate from subcortical structures, including the subthalamic nucleus and the pedunculopontine tegmentum.35 Increased SN Glx might also reflect a local, rather than a projected disturbance. Recent optogenetic studies in rodents have demonstrated that mesolimbic dopaminergic neurons release glutamate in the nucleus accumbens, suggesting colocalization of glutamate and dopamine receptors in some midbrain neurons.36,37 Glutamatergic abnormalities have now been identified in schizophrenia in the basal ganglia, hippocampus, and medial prefrontal cortex.15,38?0 It remains to be determined whether these abnormalities originate from a similar local dysfunction, such as -aminobutyric acid interneuron abnormalities, or whether they are connected, one impacting the others, and the extent to which they are affected by treatment. In HC, we observed a correlation between the PE signal and SN Glx in the SN. Given that the burst firing of dopamine neurons recorded during PE signals can be driven by application of glutamate to dopamine neurons or by stimulation of glutamatergic afferents,41 it is tempting to speculate that this correlation reflects the drive of glutamatergic projections to dopamine neurons in the SN. In the context of elevated SN Glx, the correlation between PE signal and Glx was not present in patients, suggesting that glutamatergic dysfunction could contribute to aberrant PE signaling. Consistent with our findings, low-dose administration of the N-methyl-D-aspartate antagonist ketamine disrupts error-dep.E, and thalamus. In addition, in HC, correlation with the PE signal was also observed in dorsal anterior cingulate cortex and posterior parietal cortex, implying that executive processes were engaged. Interestingly, those regions were not differentially associated with the PE signal in patients, suggesting that abnormalities in PE in patients originate from bottom-up rather than top-down processing. Like others, we observed abnormal PE signals in patients who were medicated (mainly second-generation antipsychotics), indicating that dopamine D2 blockade does not normalize PE abnormalities. Interestingly, a study in first-episode patients found normalization of a reward anticipation-related ventral striatum hypofunction after treatment.33 It remains to be determined whether treatment does in fact reduce, but obviously not normalize, PE abnormalities, and whether treatment has a differential effect on PE dysfunction in first episode compared with chronic patients with schizophrenia. Our finding of elevated SN Glx in SZ is consistent with previous finding of elevated Glx measured in the striatum,15 putatively suggesting excessive glutamate release from cortical glutamatergic projections to basal ganglia. However, although elevated striatum Glx was observed in unmedicated patients, our observations derive from medicated patients. The participants enrolled in this study overlap with those included in a prior report where,npj Schizophrenia (2015)SN glutamate and prediction error in schizophrenia DM White et al6 although no differences in Glx were observed, the Glx/N-acetylaspartate ratio was significantly elevated in patients, possibly indexing a glutamatergic dysfunction.16 Our findings are also consistent with the identification of abnormal expression of Nmethyl-D-aspartate receptor-associated intracellular proteins in the SN in schizophrenia.34 In addition to cortical projections, glutamatergic projections to the ventral tegmental area originate from subcortical structures, including the subthalamic nucleus and the pedunculopontine tegmentum.35 Increased SN Glx might also reflect a local, rather than a projected disturbance. Recent optogenetic studies in rodents have demonstrated that mesolimbic dopaminergic neurons release glutamate in the nucleus accumbens, suggesting colocalization of glutamate and dopamine receptors in some midbrain neurons.36,37 Glutamatergic abnormalities have now been identified in schizophrenia in the basal ganglia, hippocampus, and medial prefrontal cortex.15,38?0 It remains to be determined whether these abnormalities originate from a similar local dysfunction, such as -aminobutyric acid interneuron abnormalities, or whether they are connected, one impacting the others, and the extent to which they are affected by treatment. In HC, we observed a correlation between the PE signal and SN Glx in the SN. Given that the burst firing of dopamine neurons recorded during PE signals can be driven by application of glutamate to dopamine neurons or by stimulation of glutamatergic afferents,41 it is tempting to speculate that this correlation reflects the drive of glutamatergic projections to dopamine neurons in the SN. In the context of elevated SN Glx, the correlation between PE signal and Glx was not present in patients, suggesting that glutamatergic dysfunction could contribute to aberrant PE signaling. Consistent with our findings, low-dose administration of the N-methyl-D-aspartate antagonist ketamine disrupts error-dep.

No mothers had been taught STS (RRAny [STS care]: 1.28; 95 CI: 0.92?.79; RR

No mothers had been taught STS (RRAny [STS care]: 1.28; 95 CI: 0.92?.79; RR> 2 h [STS care]: 1.64; 95 CI: 0.80?.39), thereby suggesting that mothers discussed their STS practice with each other [37]. Qualitative findings also indicate that KMC mothers support other mothers starting the practice on the ward. In South Africa, for example, KMC mothers supported each other on the ward in various ways: “they reminded each other about the importance of KMC for their babies; discussed how to comfort their babies, and how to kangaroo the infants properly, as demonstrated; and exchanged ideas on how to minimise discomfort” [22]. Similar experiences were found in Mozambique [59] and Mexico, Indonesia, and Ethiopia. Interestingly, “Support from staff or community health workers” was the fourth-highestranked enabler for practice across publications but fell to seventh when looking only at publications from LMIC. Although further research is needed, this finding, combined with the finding that support from family, friends, and other mothers is a top enabler to practice, indicates that the community may play a critical role in promoting KMC practice in low-resource settings. Going forward, it will be important for researchers and implementers to understand how the community can complement a facility-based approach to scale-up with community engagement activities, drive demand for the practice, and ensure infants receive quality KMC care.Physical environment and resourcing factors can be barriers to practice, but these are under-studied in the community setting”Issues with facility environment / resources” emerged as the top barrier to practice for mothers, and this factor includes an array of different issues. These issues included crowdedness and noisiness [22,50,60], lack of privacy [61,62], lack of food and supplies [40,54], and uncomfortable beds [13,22]. It is important to remember that, due to the nature of KMC guidelines, facility-related issues may be over-represented in these findings. Data regarding nurses’ barriers to adoption also suggests that resource-related factors, such as workload, play an important role in the implementation of KMC. It is also important to note that there is a paucity of information available on physical and resourcing barriers to practice for mothers practicing KMC in the community. Of the 103 articles included in this review, only 16 focused on community-initiated KMC or had a substantial focus on community-based practice and perspectives. Thus, although a lack of resources in thePLOS ONE | DOI:10.1371/journal.pone.0125643 May 20,14 /Barriers and Enablers of KMCcommunity, such as comfortable beds and readily available food, may be an equally common barrier, the data on this topic is currently limited by the focus of existing literature. Of course, SP600125 mechanism of action institution-initiated KMC is more commonly accepted as an evidence-based practice [3], which may account for some of the lack of research on practice Quinoline-Val-Asp-Difluorophenoxymethylketone web outside the facility. However, because facility and community practice of KMC actually represent a continuum, with infants moving back and forth between the two, there is still opportunity to study community barriers to practice, even within a facility-initiated KMC program [24].Directions for Future Research and PracticeThis systematic review prioritizes the main factors that influence KMC practice, and, in doing so, highlights some key areas that implementers and implementation researchers may need to focus on when pr.No mothers had been taught STS (RRAny [STS care]: 1.28; 95 CI: 0.92?.79; RR> 2 h [STS care]: 1.64; 95 CI: 0.80?.39), thereby suggesting that mothers discussed their STS practice with each other [37]. Qualitative findings also indicate that KMC mothers support other mothers starting the practice on the ward. In South Africa, for example, KMC mothers supported each other on the ward in various ways: “they reminded each other about the importance of KMC for their babies; discussed how to comfort their babies, and how to kangaroo the infants properly, as demonstrated; and exchanged ideas on how to minimise discomfort” [22]. Similar experiences were found in Mozambique [59] and Mexico, Indonesia, and Ethiopia. Interestingly, “Support from staff or community health workers” was the fourth-highestranked enabler for practice across publications but fell to seventh when looking only at publications from LMIC. Although further research is needed, this finding, combined with the finding that support from family, friends, and other mothers is a top enabler to practice, indicates that the community may play a critical role in promoting KMC practice in low-resource settings. Going forward, it will be important for researchers and implementers to understand how the community can complement a facility-based approach to scale-up with community engagement activities, drive demand for the practice, and ensure infants receive quality KMC care.Physical environment and resourcing factors can be barriers to practice, but these are under-studied in the community setting”Issues with facility environment / resources” emerged as the top barrier to practice for mothers, and this factor includes an array of different issues. These issues included crowdedness and noisiness [22,50,60], lack of privacy [61,62], lack of food and supplies [40,54], and uncomfortable beds [13,22]. It is important to remember that, due to the nature of KMC guidelines, facility-related issues may be over-represented in these findings. Data regarding nurses’ barriers to adoption also suggests that resource-related factors, such as workload, play an important role in the implementation of KMC. It is also important to note that there is a paucity of information available on physical and resourcing barriers to practice for mothers practicing KMC in the community. Of the 103 articles included in this review, only 16 focused on community-initiated KMC or had a substantial focus on community-based practice and perspectives. Thus, although a lack of resources in thePLOS ONE | DOI:10.1371/journal.pone.0125643 May 20,14 /Barriers and Enablers of KMCcommunity, such as comfortable beds and readily available food, may be an equally common barrier, the data on this topic is currently limited by the focus of existing literature. Of course, institution-initiated KMC is more commonly accepted as an evidence-based practice [3], which may account for some of the lack of research on practice outside the facility. However, because facility and community practice of KMC actually represent a continuum, with infants moving back and forth between the two, there is still opportunity to study community barriers to practice, even within a facility-initiated KMC program [24].Directions for Future Research and PracticeThis systematic review prioritizes the main factors that influence KMC practice, and, in doing so, highlights some key areas that implementers and implementation researchers may need to focus on when pr.

Rties of the whole distribution and thus fail to identify informative

Rties of the whole distribution and thus fail to identify informative trends in the response distribution. The straightforward assumptions of a linear GSK-1605786 web relationship between IVs and DV, and that the linear relationship increases smoothly across the range of the IVs, were tested by dividing each IV into quartiles [84]. Gender, disability status and household-SES levels were taken as fixed Trichostatin A msds factors and each IV was regressed to the school belongingness score, using General Linear Model Analysis of Variance (ANOVA). In instances where the school belongingness score appeared to vary in a linear fashion across the three or four quartile categories of the IV; the IV was reverted to its original continuous scale. The final presentation of IVs thus varied as a function of whether their marginal mean estimates supported a consistent linear trend across the school belongingness score. Dummy variables were created to represent categorical IVs (personal, family and school contextual factors) incorporated into the regression models. The assumptions of linear regression were tested by undertaking preliminary screening of the data through examination of residuals; examination of the scatterplot of residuals against predicted values; and testing for multivariate outliers [80]. No obvious pattern to the errors was detected through examination of the residual scatterplots. No multivariate outliers were found in any of the steps [80].Development of the model of student belongingness in primary schoolA three-step process was followed to develop the model of primary school belongingness. Step 1: Covariates. Linear regression models with interaction terms were fitted to test the influence of gender, disability, and household-SES on students’ school belonging scores. Interaction terms were dropped from the model if they were found not to be significant. Step 2: Covariates + Identification of student personal factors and contextual factors added in each block. The covariates were added in Step 1 and stepwise backwards elimination was undertaken to identify the significant factors (p < .05) within student personal, family, and school contexts that were associated with belongingness in primary school. Step 3: Rating the explanatory power of independent variables. The explanatory power of factors in blocks was assessed on the basis of how much each factor block added to the prediction of school belongingness, over and above that accounted for by the preceding block [85].PLOS ONE | DOI:10.1371/journal.pone.0123353 April 15,7 /School Belongingness among Primary School StudentsThe order of entry of blocks into the analysis was: Block 1: Covariates (gender, disability, and SES); Block 2: Student personal factors; Block 3: Family factors; and Block 4: School and classroom factors. Output checks from Standard Multiple regression in SPSS that houses the Tolerance, Variance Inflation Factor (VIF) and the Collinearity Diagnostics output suggested multi-collinearity was not a problem [79]. Following convention, a p-value < .05 was taken to indicate a statistically significant association in all tests.Results Characteristic of the study’s sampleCross-sectional data from 395 students, their parents and primary-school class teachers from 75 different primary schools distributed across metropolitan Perth and other major urban centres of Western Australia were used. Students were on average 11.89 years (SD = 0.45 years, median = 12 years). Boys constituted 47.3 (n = 187) of the sa.Rties of the whole distribution and thus fail to identify informative trends in the response distribution. The straightforward assumptions of a linear relationship between IVs and DV, and that the linear relationship increases smoothly across the range of the IVs, were tested by dividing each IV into quartiles [84]. Gender, disability status and household-SES levels were taken as fixed factors and each IV was regressed to the school belongingness score, using General Linear Model Analysis of Variance (ANOVA). In instances where the school belongingness score appeared to vary in a linear fashion across the three or four quartile categories of the IV; the IV was reverted to its original continuous scale. The final presentation of IVs thus varied as a function of whether their marginal mean estimates supported a consistent linear trend across the school belongingness score. Dummy variables were created to represent categorical IVs (personal, family and school contextual factors) incorporated into the regression models. The assumptions of linear regression were tested by undertaking preliminary screening of the data through examination of residuals; examination of the scatterplot of residuals against predicted values; and testing for multivariate outliers [80]. No obvious pattern to the errors was detected through examination of the residual scatterplots. No multivariate outliers were found in any of the steps [80].Development of the model of student belongingness in primary schoolA three-step process was followed to develop the model of primary school belongingness. Step 1: Covariates. Linear regression models with interaction terms were fitted to test the influence of gender, disability, and household-SES on students’ school belonging scores. Interaction terms were dropped from the model if they were found not to be significant. Step 2: Covariates + Identification of student personal factors and contextual factors added in each block. The covariates were added in Step 1 and stepwise backwards elimination was undertaken to identify the significant factors (p < .05) within student personal, family, and school contexts that were associated with belongingness in primary school. Step 3: Rating the explanatory power of independent variables. The explanatory power of factors in blocks was assessed on the basis of how much each factor block added to the prediction of school belongingness, over and above that accounted for by the preceding block [85].PLOS ONE | DOI:10.1371/journal.pone.0123353 April 15,7 /School Belongingness among Primary School StudentsThe order of entry of blocks into the analysis was: Block 1: Covariates (gender, disability, and SES); Block 2: Student personal factors; Block 3: Family factors; and Block 4: School and classroom factors. Output checks from Standard Multiple regression in SPSS that houses the Tolerance, Variance Inflation Factor (VIF) and the Collinearity Diagnostics output suggested multi-collinearity was not a problem [79]. Following convention, a p-value < .05 was taken to indicate a statistically significant association in all tests.Results Characteristic of the study’s sampleCross-sectional data from 395 students, their parents and primary-school class teachers from 75 different primary schools distributed across metropolitan Perth and other major urban centres of Western Australia were used. Students were on average 11.89 years (SD = 0.45 years, median = 12 years). Boys constituted 47.3 (n = 187) of the sa.

Are a useful method for gaining insight into phenomena where little

Are a useful method for gaining insight into phenomena where little is known [44]. When focus group data has been collected from multiple ��-AmatoxinMedChemExpress ��-Amanitin groups and multiple sites, researchers can have increased confidence in the reliability and validity of the findings [45]. The focus groups were guided by Necrostatin-1 manufacturer following questions. (1) Perceptions of Professional Socialization. (a) What comes to mind when you hear the phrase “professional socialization”? (b) Share memories of your experiences becoming socialized into the role of Licensed Practical Nurse and developing your identity in this role. (c) How is the experience of developing your new role and identity as a Registered Nurse the same? How is it different? (2) Formal Academic Experiences: Online Classes and Clinical Practicums. (a) Talk about experiences you have had so far in your online university classes where you “felt like” a Registered Nurse and not a Licensed Practical Nurse? Have there been times in your online4 [54] (page 85) maintained by both moderators during and immediately following the sessions further increased the dependability of our findings. Practical issues such as organizing groups at a time and place to minimize disruption and avoiding power differential dynamics [55] were addressed. The groups were held when participants, who were normally separated by distance, were together in the same city for a required practicum experience. They were held at change of shift in lieu of a post conference. Knowing the power differential between students and teachers, moderators who did not have teaching responsibilities in the Post LPN to BN program were chosen to facilitate the focus groups. Instructors were not present during any of the discussions and had no involvement with the transcript data. Participants were recruited through a Letter of Invitation sent via email by a Research Assistant who was also not involved with the program. Four focus groups were held with 5 to 9 participants each. All the students who were invited chose to participate. We reasoned that this may have been because they were all from out of town and appreciated an opportunity to interact and share their views. Pseudonyms ensured participant confidentiality. Full ethical approval was granted by the university. The following two overarching themes emerged from analyzing the data. First, Post LPN to BN students need little, if any, further legitimation to affirm their identities as “nurse.” Second, practicum interactions with instructors and new clinical experiences are key socializing agents.Nursing Research and Practice They talked about opportunities where demonstrating professional authority in their workplace further established their identity as “nurse”: “Working your first night shift . . . in your new role. The culture of night shift–it’s different.” “The first time I cared for a palliative patient and was there when they passed. Talking with the family. My first job that I had as an LPN, I was alone on the floor as the only official nurse for more than half of my shift. I had the full responsibility of all 60 residents in my care . . . that all happened as an LPN.” From the Post LPN to BN students’ perspective, the notion that socialization into the role of “nurse” would occur for them at this point in their career was insulting: “I almost feel a little bit insulted to think that I would feel any less professional as an LPN than I do as an RN. I feel equally professional in both roles.” “My buddy nurse ac.Are a useful method for gaining insight into phenomena where little is known [44]. When focus group data has been collected from multiple groups and multiple sites, researchers can have increased confidence in the reliability and validity of the findings [45]. The focus groups were guided by following questions. (1) Perceptions of Professional Socialization. (a) What comes to mind when you hear the phrase “professional socialization”? (b) Share memories of your experiences becoming socialized into the role of Licensed Practical Nurse and developing your identity in this role. (c) How is the experience of developing your new role and identity as a Registered Nurse the same? How is it different? (2) Formal Academic Experiences: Online Classes and Clinical Practicums. (a) Talk about experiences you have had so far in your online university classes where you “felt like” a Registered Nurse and not a Licensed Practical Nurse? Have there been times in your online4 [54] (page 85) maintained by both moderators during and immediately following the sessions further increased the dependability of our findings. Practical issues such as organizing groups at a time and place to minimize disruption and avoiding power differential dynamics [55] were addressed. The groups were held when participants, who were normally separated by distance, were together in the same city for a required practicum experience. They were held at change of shift in lieu of a post conference. Knowing the power differential between students and teachers, moderators who did not have teaching responsibilities in the Post LPN to BN program were chosen to facilitate the focus groups. Instructors were not present during any of the discussions and had no involvement with the transcript data. Participants were recruited through a Letter of Invitation sent via email by a Research Assistant who was also not involved with the program. Four focus groups were held with 5 to 9 participants each. All the students who were invited chose to participate. We reasoned that this may have been because they were all from out of town and appreciated an opportunity to interact and share their views. Pseudonyms ensured participant confidentiality. Full ethical approval was granted by the university. The following two overarching themes emerged from analyzing the data. First, Post LPN to BN students need little, if any, further legitimation to affirm their identities as “nurse.” Second, practicum interactions with instructors and new clinical experiences are key socializing agents.Nursing Research and Practice They talked about opportunities where demonstrating professional authority in their workplace further established their identity as “nurse”: “Working your first night shift . . . in your new role. The culture of night shift–it’s different.” “The first time I cared for a palliative patient and was there when they passed. Talking with the family. My first job that I had as an LPN, I was alone on the floor as the only official nurse for more than half of my shift. I had the full responsibility of all 60 residents in my care . . . that all happened as an LPN.” From the Post LPN to BN students’ perspective, the notion that socialization into the role of “nurse” would occur for them at this point in their career was insulting: “I almost feel a little bit insulted to think that I would feel any less professional as an LPN than I do as an RN. I feel equally professional in both roles.” “My buddy nurse ac.

Items each represented 16 different topics that received high engagement in just

Items each Mitochondrial AZD-8055 web division inhibitor 1 supplier represented 16 different topics that received high engagement in just one platform (hereafter: “unique” high-engagement items). These data indicate an association between high engagement and item topic (2(47) = 80.054, n = 214, p < 0.01, Cramer’s V = 0.612).PLOS ONE | DOI:10.1371/journal.pone.0156409 May 27,13 /Engagement with Particle Physics on CERN’s Social Media PlatformsTable 8. Recurring high engagement topics. Recurring High Engagement Topic Code 1. 2. 3. 4. 5. 6. Fabiola Open Data Pipes 1st Computer CMS Dishwasher Type News News Guess What It Is Throwback Thursday Wow Wow Image Caption “CERN Council selects Italian physicist, Dr Fabiola Gianotti, as CERN’s next Director-General” “CERN launches Open Data Portal to make public the data of LHC experiments” “CERN’s cooling ventilation systems get refreshed” “The Ferranti Mercury, CERN’s 1st ‘central’ computer” “The LHC’s Compact Muon Solenoid (CMS) detector” “That’s right, a CERN dishwasher for circuit boards” Recurred as High Engagement Item on. . . Facebook, Twitter English, Twitter French Facebook, Google+, Twitter English, Twitter French Google+, Twitter French Facebook, Twitter English Instagram, Twitter English, Twitter French Facebook, Google+, Instagram, Twitter English, Twitter Frenchdoi:10.1371/journal.pone.0156409.tSome characteristics of the high-engagement topics are that they may have referred to (1) news items receiving attention from traditional media (e.g. the “Fabiola” topic), or (2) a surprising or awe-inspiring image (e.g. “CMS”, “Dishwasher” and “Pipes”) (Table 8).Research LimitationsThe main methodological limitation in this study stems from the architecture of the platforms. The items posted were not necessarily seen by all CERN’s subscribers. The “organic reach” is determined by the technical settings of the platforms, and may be affected by many different variables. For example, one study found that organic reach increases on a given Facebook item if another item was posted on the platform the day before [30]. The results are based on data collected from October to December 2014, however changes may have occurred since then at multiple levels: from the CERN social media strategy and behaviour, to the architecture of the platforms, as well as the audiences, their preferences and the general online communication landscape. Concerning CERN’s strategy and posting behaviour, this has remained consistent with the data-taking period. However, platform architectures are regularly changed and updated. Since our findings indicate that the platform itself influences user behaviour, it follows that changes in the platform may have an effect. For example, Twitter has implemented a new feed algorithm [43]. Google+ has been fully redesigned [44]. Facebook have not only changed the way that content from pages are delivered to the audience [45], they are also placing more and more emphasis on video content, particularly live or immersive videos, over other types of content [46]. One recent Facebook update now allows people to express their feelings as “reactions” to the information published [47]. These changes call for more elaborate future research in this topic, with fine-tuned analysis that looks at both the comments and the reaction icons. The online communication landscape in general has become more mobile, with some audiences shifting to other social media platforms such as Snapchat. Notwithstanding the dynamics of this field, our systematic study still.Items each represented 16 different topics that received high engagement in just one platform (hereafter: “unique” high-engagement items). These data indicate an association between high engagement and item topic (2(47) = 80.054, n = 214, p < 0.01, Cramer’s V = 0.612).PLOS ONE | DOI:10.1371/journal.pone.0156409 May 27,13 /Engagement with Particle Physics on CERN’s Social Media PlatformsTable 8. Recurring high engagement topics. Recurring High Engagement Topic Code 1. 2. 3. 4. 5. 6. Fabiola Open Data Pipes 1st Computer CMS Dishwasher Type News News Guess What It Is Throwback Thursday Wow Wow Image Caption “CERN Council selects Italian physicist, Dr Fabiola Gianotti, as CERN’s next Director-General” “CERN launches Open Data Portal to make public the data of LHC experiments” “CERN’s cooling ventilation systems get refreshed” “The Ferranti Mercury, CERN’s 1st ‘central’ computer” “The LHC’s Compact Muon Solenoid (CMS) detector” “That’s right, a CERN dishwasher for circuit boards” Recurred as High Engagement Item on. . . Facebook, Twitter English, Twitter French Facebook, Google+, Twitter English, Twitter French Google+, Twitter French Facebook, Twitter English Instagram, Twitter English, Twitter French Facebook, Google+, Instagram, Twitter English, Twitter Frenchdoi:10.1371/journal.pone.0156409.tSome characteristics of the high-engagement topics are that they may have referred to (1) news items receiving attention from traditional media (e.g. the “Fabiola” topic), or (2) a surprising or awe-inspiring image (e.g. “CMS”, “Dishwasher” and “Pipes”) (Table 8).Research LimitationsThe main methodological limitation in this study stems from the architecture of the platforms. The items posted were not necessarily seen by all CERN’s subscribers. The “organic reach” is determined by the technical settings of the platforms, and may be affected by many different variables. For example, one study found that organic reach increases on a given Facebook item if another item was posted on the platform the day before [30]. The results are based on data collected from October to December 2014, however changes may have occurred since then at multiple levels: from the CERN social media strategy and behaviour, to the architecture of the platforms, as well as the audiences, their preferences and the general online communication landscape. Concerning CERN’s strategy and posting behaviour, this has remained consistent with the data-taking period. However, platform architectures are regularly changed and updated. Since our findings indicate that the platform itself influences user behaviour, it follows that changes in the platform may have an effect. For example, Twitter has implemented a new feed algorithm [43]. Google+ has been fully redesigned [44]. Facebook have not only changed the way that content from pages are delivered to the audience [45], they are also placing more and more emphasis on video content, particularly live or immersive videos, over other types of content [46]. One recent Facebook update now allows people to express their feelings as “reactions” to the information published [47]. These changes call for more elaborate future research in this topic, with fine-tuned analysis that looks at both the comments and the reaction icons. The online communication landscape in general has become more mobile, with some audiences shifting to other social media platforms such as Snapchat. Notwithstanding the dynamics of this field, our systematic study still.

Our more alternative notations: A ! B, A ! B, Z Y Z

Our more alternative notations: A ! B, A ! B, Z Y Z XY Z X Z Z A ! B, and A ! B. Category 5 (CS) gets one more alternative notation, [A !B and A Z Y Y Z Z Z ZB].Finally, category 6 (asocial) gets two more alternative notations, A !B and A B. For any N ! 2, all of the 2N+1 elementary interactions are included in the representative relationships of the six categories and their alternative notations. This results from the building process of the six categories, with the differentiations covering all possible cases. In the example of N = 3, the above statement is illustrated by the comparison of the sixteen elementary interactions of Table 4 with the six categories and their alternative notations for N = 2 (Table 3), completed by the alternative notations for N = 3 listed above. This concludes the proof of exhaustiveness of the six categories of Table 3 for any number N ! 2 of non-null social actions. With N social actions at hand, richer composite relationships can be represented. Let us translate into our action fluxes representation an example of composite relationship given by Goldman [25] (pp. 344-345). Namely, “two friends may share tapes and records DactinomycinMedChemExpress Actinomycin IV freely with each other (CS), work on a task at which one is an expert and imperiously directs the other (AR), divide equally the cost of gas on a trip (EM), and transfer a bicycle from one to the other S2 S4 S5 S6 S1 S for a market-value price (MP).” This gives [A ! B, A 1 B, A ! B, A ! B, A ! B, A ! B].S2 S4 S6 SHere the relationship was known and we wrote it in terms of action fluxes. The next step is to find out how to identify a relationship when the action fluxes are given. We touch on how to achieve this in the discussion.Discussion Analyzing data setsOur representation in action fluxes provides a tool to identify types of dyadic relationships occurring within potentially large data sets of social interactions. Both collective and dyadic interactions may occur in real social contexts, but our approach applies specifically to the latter. Large data sets can result from any type of online social network or massively multiplayer online role-playing games (MMORPG), for instance. MMORPGs bring hundreds of thousands of players together to cooperate and compete by forming alliances, Vercirnon site trading, fighting, and so on, all the while recording every single action and communication of the players. They are used in quantitative social science, for example by Thurner in the context of the game Pardus [26?8]. Ethnological and anthropological studies can provide rich reports of social interactions occurring in non-artificial settings that could be coded and interpreted with the aid of our categorization. Data sets of dyadic interactions can also be generated by computer simulations such as agent-based models (ABMs) to test specific questions. We offer the sketch of a method to analyze a potentially large data set of dyadic social interactions expressed as action fluxes (“A does X to B”, etc.). Given a data set involving a number of individuals, one needs to consider separately each pair of individuals. For each pair, one shall examine each social action and test into which category of action fluxes it falls, possibly jointly with another social action (in the case of MP and AR). In its second column, Table 5 specifies the patterns of fluxes expected to be observed in each category. Let us stress the following points: ?The patterns of observed fluxes given in Table 5 are not meant as definitions of the.Our more alternative notations: A ! B, A ! B, Z Y Z XY Z X Z Z A ! B, and A ! B. Category 5 (CS) gets one more alternative notation, [A !B and A Z Y Y Z Z Z ZB].Finally, category 6 (asocial) gets two more alternative notations, A !B and A B. For any N ! 2, all of the 2N+1 elementary interactions are included in the representative relationships of the six categories and their alternative notations. This results from the building process of the six categories, with the differentiations covering all possible cases. In the example of N = 3, the above statement is illustrated by the comparison of the sixteen elementary interactions of Table 4 with the six categories and their alternative notations for N = 2 (Table 3), completed by the alternative notations for N = 3 listed above. This concludes the proof of exhaustiveness of the six categories of Table 3 for any number N ! 2 of non-null social actions. With N social actions at hand, richer composite relationships can be represented. Let us translate into our action fluxes representation an example of composite relationship given by Goldman [25] (pp. 344-345). Namely, “two friends may share tapes and records freely with each other (CS), work on a task at which one is an expert and imperiously directs the other (AR), divide equally the cost of gas on a trip (EM), and transfer a bicycle from one to the other S2 S4 S5 S6 S1 S for a market-value price (MP).” This gives [A ! B, A 1 B, A ! B, A ! B, A ! B, A ! B].S2 S4 S6 SHere the relationship was known and we wrote it in terms of action fluxes. The next step is to find out how to identify a relationship when the action fluxes are given. We touch on how to achieve this in the discussion.Discussion Analyzing data setsOur representation in action fluxes provides a tool to identify types of dyadic relationships occurring within potentially large data sets of social interactions. Both collective and dyadic interactions may occur in real social contexts, but our approach applies specifically to the latter. Large data sets can result from any type of online social network or massively multiplayer online role-playing games (MMORPG), for instance. MMORPGs bring hundreds of thousands of players together to cooperate and compete by forming alliances, trading, fighting, and so on, all the while recording every single action and communication of the players. They are used in quantitative social science, for example by Thurner in the context of the game Pardus [26?8]. Ethnological and anthropological studies can provide rich reports of social interactions occurring in non-artificial settings that could be coded and interpreted with the aid of our categorization. Data sets of dyadic interactions can also be generated by computer simulations such as agent-based models (ABMs) to test specific questions. We offer the sketch of a method to analyze a potentially large data set of dyadic social interactions expressed as action fluxes (“A does X to B”, etc.). Given a data set involving a number of individuals, one needs to consider separately each pair of individuals. For each pair, one shall examine each social action and test into which category of action fluxes it falls, possibly jointly with another social action (in the case of MP and AR). In its second column, Table 5 specifies the patterns of fluxes expected to be observed in each category. Let us stress the following points: ?The patterns of observed fluxes given in Table 5 are not meant as definitions of the.

, a runner who demonstrates considerably less than 45?of knee flexion may

, a runner who demonstrates considerably less than 45?of knee TF14016MedChemExpress BKT140 flexion may suggest reduced shock absorption, and intervention may be MG-132MedChemExpress MG-132 warranted. Some data exist suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj., a runner who demonstrates considerably less than 45?of knee flexion may suggest reduced shock absorption, and intervention may be warranted. Some data exist suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj.

Ampal CA1 subfield in individuals with MCI compared to NCI (Fig.

Ampal CA1 subfield in individuals with MCI compared to NCI (Fig. 4), which correlated with the subject’s Mini-Mental State Exam score (MMSE), but not with NFT Braak stage or apolipoprotein E (ApoE) status, a genetic risk factor for AD (Scheff et al., 2006). Unlike the outer molecular layer, CA1 receives input from the Schaffer collaterals arising from CA3 and not from the glutamatergic neurons of the entorhinal cortex, suggesting differential responses to synapse loss within the hippocampus based upon afferent innervation or chemical phenotype, some of which precipitate synaptic reorganization. A recent report characterized changes in the dendritic branching of the basilar tree of hippocampal CA1 pyramidal neurons. In this study, formalin-fixed tissue autopsy obtained from University of Kentucky Alzheimer’s Disease Center who died with a clinical diagnosis of NCI, MCI or AD was prepared for Golgi impregnation (Fig. 5). Camera lucida drawings of the basilar tree of randomly selected CA1 neurons were analyzed for alterations in dendritic arbor amount, distribution and complexity (Mervis et al., 2013). Quantitation showed a Lixisenatide price significant increase in dendritic length (18 ) and complexity (23 ) in CA1 neurons in MCI compared to NCI. Conversely, there was a significant reduction in branch length (-39 ) and arbor complexity (-25 ) during the progression from MCI to AD (Fig. 5). These findings suggest that the observed increase in CA1 dendritic parameters from NCI to MCI may be another example of a neuroplastic compensatory response to a loss of afferent input early in the course of the disease, which is not maintained as the disease progresses. The role that the reported reduction in total synapse number plays in CA1 neuroplasticity remains unknown. However, these examples of early CA1 neural reorganization may represent a viable window for potential therapeutic strategies aimed at restoring or maintaining hippocampal function during the transition from MCI to AD. Future studies should determine whether alterations in specific synapse subtypes (i.e., perforated vs. Fruquintinib custom synthesis non-perforated) are differentially affected and their relation to cognitive decline and brain pathology during the onset of AD. Interestingly, the size of the synaptic contacts was found to be substantially larger in AD cortex compared to non-demented aged controls (Scheff et al., 1990), which was suggested to be part of a compensatory mechanism found in regions of the neocortex and hippocampus (see review Scheff and Price, 2006). These investigators found that as the number of synapses declined in a given region, the size of the residualAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagesynapses increased. This synaptic compensatory response was also observed early in the course of the AD (DeKosky and Scheff, 1990). Neuronal structural alterations may not be the only factor(s) contributing to cognitive decline and hippocampal plasticity in MCI. For example, studies have reported significant reductions in synaptic vesicle trafficking-related genes in the AD brain, which interrupt the efficacy of normal synaptic transmission (Yao et al., 2003; Murphy et al., 2003; Kennedy et al., 2005). Counts et al. (2014) examined progressive changes in the expression classes of synaptic gene within single CA1 neurons in subjects who died with a clinical diagnosis of NCI, MCI or moderate AD obtain.Ampal CA1 subfield in individuals with MCI compared to NCI (Fig. 4), which correlated with the subject’s Mini-Mental State Exam score (MMSE), but not with NFT Braak stage or apolipoprotein E (ApoE) status, a genetic risk factor for AD (Scheff et al., 2006). Unlike the outer molecular layer, CA1 receives input from the Schaffer collaterals arising from CA3 and not from the glutamatergic neurons of the entorhinal cortex, suggesting differential responses to synapse loss within the hippocampus based upon afferent innervation or chemical phenotype, some of which precipitate synaptic reorganization. A recent report characterized changes in the dendritic branching of the basilar tree of hippocampal CA1 pyramidal neurons. In this study, formalin-fixed tissue autopsy obtained from University of Kentucky Alzheimer’s Disease Center who died with a clinical diagnosis of NCI, MCI or AD was prepared for Golgi impregnation (Fig. 5). Camera lucida drawings of the basilar tree of randomly selected CA1 neurons were analyzed for alterations in dendritic arbor amount, distribution and complexity (Mervis et al., 2013). Quantitation showed a significant increase in dendritic length (18 ) and complexity (23 ) in CA1 neurons in MCI compared to NCI. Conversely, there was a significant reduction in branch length (-39 ) and arbor complexity (-25 ) during the progression from MCI to AD (Fig. 5). These findings suggest that the observed increase in CA1 dendritic parameters from NCI to MCI may be another example of a neuroplastic compensatory response to a loss of afferent input early in the course of the disease, which is not maintained as the disease progresses. The role that the reported reduction in total synapse number plays in CA1 neuroplasticity remains unknown. However, these examples of early CA1 neural reorganization may represent a viable window for potential therapeutic strategies aimed at restoring or maintaining hippocampal function during the transition from MCI to AD. Future studies should determine whether alterations in specific synapse subtypes (i.e., perforated vs. non-perforated) are differentially affected and their relation to cognitive decline and brain pathology during the onset of AD. Interestingly, the size of the synaptic contacts was found to be substantially larger in AD cortex compared to non-demented aged controls (Scheff et al., 1990), which was suggested to be part of a compensatory mechanism found in regions of the neocortex and hippocampus (see review Scheff and Price, 2006). These investigators found that as the number of synapses declined in a given region, the size of the residualAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagesynapses increased. This synaptic compensatory response was also observed early in the course of the AD (DeKosky and Scheff, 1990). Neuronal structural alterations may not be the only factor(s) contributing to cognitive decline and hippocampal plasticity in MCI. For example, studies have reported significant reductions in synaptic vesicle trafficking-related genes in the AD brain, which interrupt the efficacy of normal synaptic transmission (Yao et al., 2003; Murphy et al., 2003; Kennedy et al., 2005). Counts et al. (2014) examined progressive changes in the expression classes of synaptic gene within single CA1 neurons in subjects who died with a clinical diagnosis of NCI, MCI or moderate AD obtain.

Monly used and widely available OTC medications and nutritional supplements were

Monly used and widely available OTC medications and nutritional BAY1217389 web supplements were safe and posed no short- or long-term threat to their health. Many used such products to improve their running performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product recommended as an effective and legal substance by another runner or by a retail sales clerk may contain substances that are either banned by agencies such as WADA and/or may pose a serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.NIH-PA purchase Acadesine Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.Monly used and widely available OTC medications and nutritional supplements were safe and posed no short- or long-term threat to their health. Many used such products to improve their running performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product recommended as an effective and legal substance by another runner or by a retail sales clerk may contain substances that are either banned by agencies such as WADA and/or may pose a serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.

Deration when interpreting experimental findings. (i) Identification of a mutation in

Deration when interpreting experimental findings. (i) Identification of a mutation in a clonal population does not indicate causality Any mutation in a cell that undergoes clonal expansion will be passed onto progeny, irrespective of functional status (Fig. 3A,B). Given the size of the genome, more CPI-455MedChemExpress CPI-455 mutations carried by a neoplastic clone will be passengers than drivers [27, 29, 30]. To demonstrate driver status, supporting functional studies and/or repeated observations of a mutated loci in neoplastic clones from independent individuals are needed. (ii) Mutational marking of a clone is stochastic and not guaranteed A clone may exist and not be RR6 web detected if none of the genomic sites being screened carry a unique mutation permitting it to be distinguished from the germline (Fig. 3C). The more sites examined, the higher the probability of detection becomes. Restricting a marker panel to suspected driver sites precludes detection of pathological clones driven by unknown factors. (iii) Elevated mutation rates facilitate clone detection but are not an absolute requirement Screening of mutational hotspots makes it practical with conventional technologies to have a reasonable probability of detecting a clone by random passenger mutations. Clones derived from a mutator lineage or cells residing in a highly mutagenic environment should be more densely marked with identifiable passengers (Fig. 3D), potentially reducing the number of markers needing to be interrogated to identify them. Emerging high-throughput sequencing technologies will eventually obviate the need to restrict screening to a fraction of the genome. (iv) Identification of one or more clonal mutations is not proof of genetic instability in the absence of collateral information Detection of a mutation requires clonal expansion with most traditional methods of aggregate DNA analysis. The probability of identifying clonal mutations in an expanded population is a function of the number of sites screened, the mutability of these sites and the number of cell divisions having occurred in the lineage leading up to the final expansion. Particularly when considering hotspots, mutations will be occasionally detectable in any clonally-derived population at a statistically definable frequency. Because mutations are not routinely encountered in normal tissues, it is tempting to explain their presence in preneoplastic populations as the result of “genetic instability” (an elevated mutation rate). However, the phenomenon is more precisely explained by the fact that expansion does not routinely occur in most normal tissues. An elevated mutation rate itself will have no observable effect on clonal mutation frequency in the absence of expansion (Fig. 3E). To determine mutation rate from a clonal mutation frequency it is necessary to (A) know that the population being assessed is clonal and (B) have some metric of the number of cell divisions that occurred in the period between the zygote and the founding of the final clonalSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPageoutgrowth. To infer that a rate is elevated, it is also necessary to know the normal in vivo mutation rate, which is, in turn, impossible to measure by this approach given that large clonal expansions do not routinely occur in normal adult tissue. Considering these complexities, the lack of resolution as to whether mutation rates are elevated in cancer is not surprising [1,8?1]. (v) Detectabili.Deration when interpreting experimental findings. (i) Identification of a mutation in a clonal population does not indicate causality Any mutation in a cell that undergoes clonal expansion will be passed onto progeny, irrespective of functional status (Fig. 3A,B). Given the size of the genome, more mutations carried by a neoplastic clone will be passengers than drivers [27, 29, 30]. To demonstrate driver status, supporting functional studies and/or repeated observations of a mutated loci in neoplastic clones from independent individuals are needed. (ii) Mutational marking of a clone is stochastic and not guaranteed A clone may exist and not be detected if none of the genomic sites being screened carry a unique mutation permitting it to be distinguished from the germline (Fig. 3C). The more sites examined, the higher the probability of detection becomes. Restricting a marker panel to suspected driver sites precludes detection of pathological clones driven by unknown factors. (iii) Elevated mutation rates facilitate clone detection but are not an absolute requirement Screening of mutational hotspots makes it practical with conventional technologies to have a reasonable probability of detecting a clone by random passenger mutations. Clones derived from a mutator lineage or cells residing in a highly mutagenic environment should be more densely marked with identifiable passengers (Fig. 3D), potentially reducing the number of markers needing to be interrogated to identify them. Emerging high-throughput sequencing technologies will eventually obviate the need to restrict screening to a fraction of the genome. (iv) Identification of one or more clonal mutations is not proof of genetic instability in the absence of collateral information Detection of a mutation requires clonal expansion with most traditional methods of aggregate DNA analysis. The probability of identifying clonal mutations in an expanded population is a function of the number of sites screened, the mutability of these sites and the number of cell divisions having occurred in the lineage leading up to the final expansion. Particularly when considering hotspots, mutations will be occasionally detectable in any clonally-derived population at a statistically definable frequency. Because mutations are not routinely encountered in normal tissues, it is tempting to explain their presence in preneoplastic populations as the result of “genetic instability” (an elevated mutation rate). However, the phenomenon is more precisely explained by the fact that expansion does not routinely occur in most normal tissues. An elevated mutation rate itself will have no observable effect on clonal mutation frequency in the absence of expansion (Fig. 3E). To determine mutation rate from a clonal mutation frequency it is necessary to (A) know that the population being assessed is clonal and (B) have some metric of the number of cell divisions that occurred in the period between the zygote and the founding of the final clonalSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPageoutgrowth. To infer that a rate is elevated, it is also necessary to know the normal in vivo mutation rate, which is, in turn, impossible to measure by this approach given that large clonal expansions do not routinely occur in normal adult tissue. Considering these complexities, the lack of resolution as to whether mutation rates are elevated in cancer is not surprising [1,8?1]. (v) Detectabili.

. This exploratory analysis can provide further information on functional similarities between

. This exploratory analysis can provide further information on functional similarities between regions, and, more specifically, on the extent to which activation profiles of category-selective Biotin-VAD-FMK price regions are inherited from EVC. As for the replicability of within-category ranking (Fig. 5), we combined data PP58 msds across subjects either by concatenating or averaging the activation profiles across subjects. The concatenation approach is sensitive to inter-region correlations of activation profiles even if the particular activation profiles differ across subjects. The averaging approach is sensitive to inter-region correlations of activation profiles that are consistent across subjects. We investigated the inter-region correlations for (1) the full activation profile, (2) the within-face activation profile, and (3) the withinplace activation profile. Statistical inference was performed by a standard one-sided test on Spearman’s r. p values were corrected8658 ?J. Neurosci., June 20, 2012 ?32(25):8649 ?Mur et al. ?Single-Image Activation of Category Regionsfor multiple testing using Bonferroni correction based on the total number of tests performed. Figure 7 shows the inter-region correlation results. The main pattern that emerges is that activation profiles are correlated between hemispheres for corresponding regions, and between hIT and EVC (red blocks on diagonals). We subsequently inspected the within-face correlation between FFA and EVC, and the within-place correlation between PPA and EVC. The within-face activation profile was correlated between left but not right FFA and EVC, and the within-place activation profile was not significantly correlated between PPA and EVC. Results were similar across ROI sizes. These results suggest that EVC is not a major contributor to the within-category activation profiles of PPA and right FFA. We then inspected the correlation between category-selective regions (FFA/PPA) and EVC for the full activation profile (top row). The full activation profile was correlated between EVC and both categoryselective regions, especially PPA. One interpretation of this finding would be that some degree of category selectivity is already present at the level of EVC, implying that low-level feature differences contribute to some extent to categoryselective responses. For places, this seems a plausible interpretation, consistent with our finding that single-image activation of EVC can discriminate places from nonplaces at an above-chance level (Fig. 2). For faces, this interpretation seems less likely: the correlation between EVC and FFA is not significant for the subjectaverage activation profile, suggesting that the correlation is driven by subjectspecific effects (e.g., idiosyncratic arousal effects) and not by face-selectivity of responses (shared across subjects in FFA). Categorical, yet graded Figure 8 summarizes our results. Singleimage activation profiles of categoryselective regions (1) show near-perfect discrimination of preferred from nonpreferred images and no preference inversions for particular object images, (2) show a step-like drop-off at the category boundary, and (3) are graded within and outside the preferred category. It can further be noted that single-image category selectivity is stronger in right than left FFA. In addition, gradedness seems to be more pronounced in FFA; the category step seems to be more pronounced in PPA. In sum, our findings indicate that the activation profiles of category-selec-Figure.. This exploratory analysis can provide further information on functional similarities between regions, and, more specifically, on the extent to which activation profiles of category-selective regions are inherited from EVC. As for the replicability of within-category ranking (Fig. 5), we combined data across subjects either by concatenating or averaging the activation profiles across subjects. The concatenation approach is sensitive to inter-region correlations of activation profiles even if the particular activation profiles differ across subjects. The averaging approach is sensitive to inter-region correlations of activation profiles that are consistent across subjects. We investigated the inter-region correlations for (1) the full activation profile, (2) the within-face activation profile, and (3) the withinplace activation profile. Statistical inference was performed by a standard one-sided test on Spearman’s r. p values were corrected8658 ?J. Neurosci., June 20, 2012 ?32(25):8649 ?Mur et al. ?Single-Image Activation of Category Regionsfor multiple testing using Bonferroni correction based on the total number of tests performed. Figure 7 shows the inter-region correlation results. The main pattern that emerges is that activation profiles are correlated between hemispheres for corresponding regions, and between hIT and EVC (red blocks on diagonals). We subsequently inspected the within-face correlation between FFA and EVC, and the within-place correlation between PPA and EVC. The within-face activation profile was correlated between left but not right FFA and EVC, and the within-place activation profile was not significantly correlated between PPA and EVC. Results were similar across ROI sizes. These results suggest that EVC is not a major contributor to the within-category activation profiles of PPA and right FFA. We then inspected the correlation between category-selective regions (FFA/PPA) and EVC for the full activation profile (top row). The full activation profile was correlated between EVC and both categoryselective regions, especially PPA. One interpretation of this finding would be that some degree of category selectivity is already present at the level of EVC, implying that low-level feature differences contribute to some extent to categoryselective responses. For places, this seems a plausible interpretation, consistent with our finding that single-image activation of EVC can discriminate places from nonplaces at an above-chance level (Fig. 2). For faces, this interpretation seems less likely: the correlation between EVC and FFA is not significant for the subjectaverage activation profile, suggesting that the correlation is driven by subjectspecific effects (e.g., idiosyncratic arousal effects) and not by face-selectivity of responses (shared across subjects in FFA). Categorical, yet graded Figure 8 summarizes our results. Singleimage activation profiles of categoryselective regions (1) show near-perfect discrimination of preferred from nonpreferred images and no preference inversions for particular object images, (2) show a step-like drop-off at the category boundary, and (3) are graded within and outside the preferred category. It can further be noted that single-image category selectivity is stronger in right than left FFA. In addition, gradedness seems to be more pronounced in FFA; the category step seems to be more pronounced in PPA. In sum, our findings indicate that the activation profiles of category-selec-Figure.

In living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic

In living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic Ca-phosphate in pelagic sediments has long been studied by a number of investigators17,18,21?4,40?2. Some have suggested that biogenic Ca-phosphate incorporates REY via pore water in the sediment column23,40. Others have argued that Ca-phosphate takes up REY from a variety of carrier phases (e.g. Fe n-oxyhydroxides, pellets, and organic debris) that absorb REY from seawater and are readily decomposed at the sediment ater interface17,22,41,42. Although the complete process remains an open question, the characteristic REY MK-1439 custom synthesis patterns Stattic site indicate that seawater is the ultimate source of the REY presently captured in biogenic Ca-phosphate22,25,41 (Fig. 4m). Simple quantitative estimation in this study suggested the possibility that seawater can contain the flux of REY precipitation required to explain the observed very high REY concentrations ( REY + Ce > 1,000 ppm) in bulk REY-rich mud with a sedimentation rate less than 0.5 m/Myr (Supplementary Fig. S19). Such circumstances may facilitate the concentration of REY in biogenic Ca-phosphate via diffusion of REY from seawater or the transfer of REY from original carriers to Ca-phosphate during the early diagenetic processes because of the prolonged exposure to seawater at the sediment surface and in the bioturbated and well-ventilated uppermost sediment layer17,18,22,41. In addition, biogenic Ca-phosphate enriched in REY might be stabilised through recrystallisation as insoluble apatite17. Moreover, the amount of Ca-phosphate in a unit volume of sediment also increases with a depression of the sedimentation rate17,18. Hence, the low sedimentation rate is considered to be crucial for the formation of REY-rich mud. Actually, the spatiotemporal distribution of high-IC1, -IC4, and -IC7 muds overlapped with the oligotrophic North Pacific and South Pacific gyres and with water depths greater than the CCD, both of which prevented the fast accumulation of dilutive components with low REY content such as biogenic carbonate and silica. If we assume that deep-sea sediments can continuously acquire REY from the overlying deep-sea water prior to burial, the REY-enrichment in sediments can occur in a time scale of 105 years considering the sedimentation rate of <0.5 m/Myr with a typical thickness of 0.1 m for the well-ventilated uppermost sediment layer43. This timescale of REY enrichment is significantly longer than that of global ocean circulation, which is 103 years44. Both IC1 and IC4 indicated statistical independent geochemical features of pelagic red clay mainly composed of detrital aluminosilicates involving abundant Si, Al, Fe, Mg, and K without significant contributions of biogenic carbonate and silica. Fe and Mn of hydrothermal or hydrogenous origins could have also been incorporated without dilution in high-IC1 and high-IC4 sediments, resulting in an increase in the contents of these elements. In addition, in deposition slow enough to allow biogenic Ca-phosphate grains to concentrate REY and to accumulate significantly in the sediment, the P and REY contents of these sediments also increase concurrently. Although sediments enriched in biogenic Ca-phosphate contain several percent of Ca, the significant dilution effect of biogenic carbonate, which contains several tens of percent of Ca, generally creates negative trends in these ICs as a whole in the spaces of Ca and other elements, including REY. The differenc.In living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic Ca-phosphate in pelagic sediments has long been studied by a number of investigators17,18,21?4,40?2. Some have suggested that biogenic Ca-phosphate incorporates REY via pore water in the sediment column23,40. Others have argued that Ca-phosphate takes up REY from a variety of carrier phases (e.g. Fe n-oxyhydroxides, pellets, and organic debris) that absorb REY from seawater and are readily decomposed at the sediment ater interface17,22,41,42. Although the complete process remains an open question, the characteristic REY patterns indicate that seawater is the ultimate source of the REY presently captured in biogenic Ca-phosphate22,25,41 (Fig. 4m). Simple quantitative estimation in this study suggested the possibility that seawater can contain the flux of REY precipitation required to explain the observed very high REY concentrations ( REY + Ce > 1,000 ppm) in bulk REY-rich mud with a sedimentation rate less than 0.5 m/Myr (Supplementary Fig. S19). Such circumstances may facilitate the concentration of REY in biogenic Ca-phosphate via diffusion of REY from seawater or the transfer of REY from original carriers to Ca-phosphate during the early diagenetic processes because of the prolonged exposure to seawater at the sediment surface and in the bioturbated and well-ventilated uppermost sediment layer17,18,22,41. In addition, biogenic Ca-phosphate enriched in REY might be stabilised through recrystallisation as insoluble apatite17. Moreover, the amount of Ca-phosphate in a unit volume of sediment also increases with a depression of the sedimentation rate17,18. Hence, the low sedimentation rate is considered to be crucial for the formation of REY-rich mud. Actually, the spatiotemporal distribution of high-IC1, -IC4, and -IC7 muds overlapped with the oligotrophic North Pacific and South Pacific gyres and with water depths greater than the CCD, both of which prevented the fast accumulation of dilutive components with low REY content such as biogenic carbonate and silica. If we assume that deep-sea sediments can continuously acquire REY from the overlying deep-sea water prior to burial, the REY-enrichment in sediments can occur in a time scale of 105 years considering the sedimentation rate of <0.5 m/Myr with a typical thickness of 0.1 m for the well-ventilated uppermost sediment layer43. This timescale of REY enrichment is significantly longer than that of global ocean circulation, which is 103 years44. Both IC1 and IC4 indicated statistical independent geochemical features of pelagic red clay mainly composed of detrital aluminosilicates involving abundant Si, Al, Fe, Mg, and K without significant contributions of biogenic carbonate and silica. Fe and Mn of hydrothermal or hydrogenous origins could have also been incorporated without dilution in high-IC1 and high-IC4 sediments, resulting in an increase in the contents of these elements. In addition, in deposition slow enough to allow biogenic Ca-phosphate grains to concentrate REY and to accumulate significantly in the sediment, the P and REY contents of these sediments also increase concurrently. Although sediments enriched in biogenic Ca-phosphate contain several percent of Ca, the significant dilution effect of biogenic carbonate, which contains several tens of percent of Ca, generally creates negative trends in these ICs as a whole in the spaces of Ca and other elements, including REY. The differenc.

(10). These impacts pose significant challenges to the continued provisioning of ecosystem

(10). These impacts pose significant challenges to the continued provisioning of ecosystem services from the ocean: challenges that may seem overwhelming now, but even more so in light of the difficulties in addressing the complex drivers and reversing trends. In short, threats to ocean life and the provision of vital ecosystem services are unquestionably serious and pressures on ocean resources are escalating. Glimmers of Hope for Sustainable Use of the Ocean Despite these daunting challenges, there is reason for cautious hope. Around the globe, many positive changes are underway: awareness, attitudes, and social norms are changing; economic ONO-4059 structure incentives are shifting; efforts to educate consumers are increasing; new policies are leading to stronger mandates and more effective governance, compliance, and enforcement; and practices are changing with the development of better technologies, new products, and business strategies that reflect the circular economy (11), greater engagement of scientists, and improved understanding of trade-offs. As a result, effective models for change based in naturalThe grand challenge for humanity is to meet the basic needs of people in an equitable manner today while simultaneously restoring and maintaining ecosystem functioning for future generations. We must do so in the face of growing numbers of people and the concomitant need for resources, and with environmental changes, such as climate change, already underway. The ocean is integral to this global mission. Ocean and coastal ecosystems provide a range of critical ecosystem services that people depend upon, such as food, oxygen, climate regulation, control of pests, protection from storm surges, recreational opportunities, and cultural value (1, 2). The ocean is home to rich biodiversity and plays key roles in many global processes, from primary production to nutrient cycling to climate and weather (3). Ocean-based activities and livelihoods are both enabled by and affect complex interactions among ecological, social, and economic systems. The global market value of marine and coastal resources and industries is estimated at 3 trillion per year (4). Over 3 billion people depend upon the oceans to provide their primary source of protein, and marine fisheries directly or indirectly employ over 200 million people (4). Other benefits, such as cultural or inspirational values, are harder towww.pnas.org/cgi/doi/10.1073/pnas.This article arises from the 2016 Annual Sackler Lecture, “Enough with the doom and gloom! Holistic approaches bring hope for people and the ocean,” presented by Jane Lubchenco on March 14, at the National Academy of Sciences in GW 4064 chemical information Washington, DC. The lecture was part of the Arthur M. Sackler Colloquium of the National Academy of Sciences, “Coupled Human and Environmental Systems,” held March 14?5. The complete program and video recordings of most presentations are available on the NAS website at www.nasonline.org/Coupled_Human_and_Environmental_Systems. Author contributions: J.L. and S.A.L. designed research; J.L., E.B.C.-C., J.N.R., and S.A.L. performed research; and J.L., E.B.C.-C., J.N.R., and S.A.L. wrote the paper. The authors declare no conflict of interest. This article is a PNAS Direct Submission. A.P.G. is a Guest Editor invited by the Editorial Board.To whom correspondence should be addressed. Email: [email protected] | December 20, 2016 | vol. 113 | no. 51 | 14507?ENVIRONMENTAL SCIENCESSUSTAINABILITY SCIENCEquantify.(10). These impacts pose significant challenges to the continued provisioning of ecosystem services from the ocean: challenges that may seem overwhelming now, but even more so in light of the difficulties in addressing the complex drivers and reversing trends. In short, threats to ocean life and the provision of vital ecosystem services are unquestionably serious and pressures on ocean resources are escalating. Glimmers of Hope for Sustainable Use of the Ocean Despite these daunting challenges, there is reason for cautious hope. Around the globe, many positive changes are underway: awareness, attitudes, and social norms are changing; economic incentives are shifting; efforts to educate consumers are increasing; new policies are leading to stronger mandates and more effective governance, compliance, and enforcement; and practices are changing with the development of better technologies, new products, and business strategies that reflect the circular economy (11), greater engagement of scientists, and improved understanding of trade-offs. As a result, effective models for change based in naturalThe grand challenge for humanity is to meet the basic needs of people in an equitable manner today while simultaneously restoring and maintaining ecosystem functioning for future generations. We must do so in the face of growing numbers of people and the concomitant need for resources, and with environmental changes, such as climate change, already underway. The ocean is integral to this global mission. Ocean and coastal ecosystems provide a range of critical ecosystem services that people depend upon, such as food, oxygen, climate regulation, control of pests, protection from storm surges, recreational opportunities, and cultural value (1, 2). The ocean is home to rich biodiversity and plays key roles in many global processes, from primary production to nutrient cycling to climate and weather (3). Ocean-based activities and livelihoods are both enabled by and affect complex interactions among ecological, social, and economic systems. The global market value of marine and coastal resources and industries is estimated at 3 trillion per year (4). Over 3 billion people depend upon the oceans to provide their primary source of protein, and marine fisheries directly or indirectly employ over 200 million people (4). Other benefits, such as cultural or inspirational values, are harder towww.pnas.org/cgi/doi/10.1073/pnas.This article arises from the 2016 Annual Sackler Lecture, “Enough with the doom and gloom! Holistic approaches bring hope for people and the ocean,” presented by Jane Lubchenco on March 14, at the National Academy of Sciences in Washington, DC. The lecture was part of the Arthur M. Sackler Colloquium of the National Academy of Sciences, “Coupled Human and Environmental Systems,” held March 14?5. The complete program and video recordings of most presentations are available on the NAS website at www.nasonline.org/Coupled_Human_and_Environmental_Systems. Author contributions: J.L. and S.A.L. designed research; J.L., E.B.C.-C., J.N.R., and S.A.L. performed research; and J.L., E.B.C.-C., J.N.R., and S.A.L. wrote the paper. The authors declare no conflict of interest. This article is a PNAS Direct Submission. A.P.G. is a Guest Editor invited by the Editorial Board.To whom correspondence should be addressed. Email: [email protected] | December 20, 2016 | vol. 113 | no. 51 | 14507?ENVIRONMENTAL SCIENCESSUSTAINABILITY SCIENCEquantify.

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ……………………………………………… ….. ………….. 9 FI S Euthynuus affinis Fi red f. 3.20 Y 25 30 skinned single f.

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ……………………………………………… ….. ………….. 9 FI S Euthynuus affinis Fi red f. 3.20 Y 25 30 skinned single f. SB 203580MedChemExpress RWJ 64809 Johnston Brill [83] (kawakawa, Pacific ocean) ………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………….. 10 FI S Euthynuus affinis Fi white f. 3.20 Y 188 30 skinned single f. Johnston Brill [83] (kawakawa, Pacific ocean) ………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………….. 11 FI S Gadus morhua (North Sea Fi myotomal m. fast f., 2?2?84 Y 187 8 skinned single f. Johnston Altringham [84] cod,. temperate). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ………………………………………………. ……………… 12 FI S Gadus morhua (cod) Fi myotomal m. white f. (fast) 84 N 83 8 skinned single f. Altringham Johnston [85] ………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………….. 13. . . . . . . . . . . . . FI. . . . . . . . . . . .S. . . . . . . . . . .Gadus. morhua. .(cod). . . . . . . . . . . . . . . . . . . . . . .Fi. . . . . . . . . . . . . . . . . .myotomal. .m.. .red. .f.. .(slow). . . . . . . . . . . . . . . . . . . . . . . . . . .84. . . . . . . . . . . . . . . . . . . . . . . . . .N. . . . . . . . . . . 186. . . . . . . . . . . . . . . . . . . . .8. . . . . . . . . . . . . .skinned. . 2?. .f.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Altringham. . . . Johnston. .[85]. . . ….. .. . ……… ………… ……. .. …………… … …. . ……… .. . ….. . ……….. …… . …………….. . ………….. ….. (Continued.)rsos.RP5264 web royalsocietypublishing.org R. Soc. open sci. 3:…………………………………………Table 4. (Continued.) motor M (kg) I f (kPa) T ( ) comment referenceno.TyCspeciesgroup…………………… . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ……………………………………………… ….. ………….. 9 FI S Euthynuus affinis Fi red f. 3.20 Y 25 30 skinned single f. Johnston Brill [83] (kawakawa, Pacific ocean) ………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………….. 10 FI S Euthynuus affinis Fi white f. 3.20 Y 188 30 skinned single f. Johnston Brill [83] (kawakawa, Pacific ocean) ………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………….. 11 FI S Gadus morhua (North Sea Fi myotomal m. fast f., 2?2?84 Y 187 8 skinned single f. Johnston Altringham [84] cod,. temperate). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ………………………………………………. ……………… 12 FI S Gadus morhua (cod) Fi myotomal m. white f. (fast) 84 N 83 8 skinned single f. Altringham Johnston [85] ………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………….. 13. . . . . . . . . . . . . FI. . . . . . . . . . . .S. . . . . . . . . . .Gadus. morhua. .(cod). . . . . . . . . . . . . . . . . . . . . . .Fi. . . . . . . . . . . . . . . . . .myotomal. .m.. .red. .f.. .(slow). . . . . . . . . . . . . . . . . . . . . . . . . . .84. . . . . . . . . . . . . . . . . . . . . . . . . .N. . . . . . . . . . . 186. . . . . . . . . . . . . . . . . . . . .8. . . . . . . . . . . . . .skinned. . 2?. .f.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Altringham. . . . Johnston. .[85]. . . ….. .. . ……… ………… ……. .. …………… … …. . ……… .. . ….. . ……….. …… . …………….. . ………….. ….. (Continued.)rsos.royalsocietypublishing.org R. Soc. open sci. 3:…………………………………………Table 4. (Continued.) motor M (kg) I f (kPa) T ( ) comment referenceno.TyCspeciesgroup…………………..

Ating with a significantly increased intake in the evening and/or

Ating with a significantly increased intake in the evening and/or night time, as manifested by one or both of the following: at least 25 of food intake is consumed after the evening meal or at least two episodes of nocturnal eating per week. An important recent addition to core criteria includes the presence of significant distress and/or impairment in functioning. CV205-502 hydrochloride supplement Stunkard’s team recommend further investigation on the pathogenesis of NES, in particular its relationship with traumatic life events, psychiatric comorbidity, the age of onset of NES and course of NES over time. The relationship Tyrphostin AG 490 custom synthesis between NES and other ED also requires further clarification as night-eaters exhibit some features of other ED; previous guidance to separate NES from other ED may have hindered earlier characterisation of NES. Evidence from European and American studies suggests NES features strongly in populations with severe obesity. The complex interplay between depression, impaired sleep and obesity-related comorbidity in severely obese individuals makes understanding NES in this context even more difficult. This review examines evidence to date on the characterisation of NES and concludes by examining the applicability of current NES criteria to individuals with severe obesity. Nutrition and Diabetes (2012) 2, e44; doi:10.1038/nutd.2012.16; published online 10 September 2012 Keywords: obesity; night eating; sleep; circadian rhythmINTRODUCTION The obesity epidemic continues to impact heavily on the health economy, and the need for successful and enduring obesity treatments is essential. Recent years have seen sustained attempts to understand the contribution of disordered eating patterns to the development of obesity. Considerable progress has been made in understanding night eating syndrome (NES), a cluster of behaviours first identified in 1955 by Stunkard,1 a psychiatrist specialising in eating disorders (ED). This narrative review describes the evolution of NES from initial identification to current conceptualisation. Methods of identification, prevalence in varying populations, behavioural and clinical characteristics, and treatment options are discussed. Evolving evidence of the relationship between NES and other ED, sleep-related ED, sleep, depression and anxiety is also considered. The paper concludes by examining the relationship of NES with obesity and the applicability of current NES criteria to a severely obese population.grounds of sample size as even single case reports may be important indicators of future understanding of NES. Reviews, commentaries, reports from professional and non peer-reviewed publications and case reports of other syndromes where discussion of NE was incidental were excluded, yielding 84 studies for potential inclusion, of which 73 have been included in this review.METHODS The Medline, Scopus, PsychInfo and CINAHL databases were searched for all studies published between 1955 and January 2012. One-hundred and ninty-one papers were found using the search terms of NES, night-eating (NE), late night eating, NE behaviour and nocturnal eating. Results were filtered to return studies of human subjects published in English. Only original research was considered for inclusion. The conceptualisation of NES is still evolving, thus papers were not excluded on theEVOLUTION OF DIAGNOSTIC CRITERIA NES is now considered a dysfunction of circadian rhythm with a disassociation between eating and sleeping, characterised by a phase onset delay.Ating with a significantly increased intake in the evening and/or night time, as manifested by one or both of the following: at least 25 of food intake is consumed after the evening meal or at least two episodes of nocturnal eating per week. An important recent addition to core criteria includes the presence of significant distress and/or impairment in functioning. Stunkard’s team recommend further investigation on the pathogenesis of NES, in particular its relationship with traumatic life events, psychiatric comorbidity, the age of onset of NES and course of NES over time. The relationship between NES and other ED also requires further clarification as night-eaters exhibit some features of other ED; previous guidance to separate NES from other ED may have hindered earlier characterisation of NES. Evidence from European and American studies suggests NES features strongly in populations with severe obesity. The complex interplay between depression, impaired sleep and obesity-related comorbidity in severely obese individuals makes understanding NES in this context even more difficult. This review examines evidence to date on the characterisation of NES and concludes by examining the applicability of current NES criteria to individuals with severe obesity. Nutrition and Diabetes (2012) 2, e44; doi:10.1038/nutd.2012.16; published online 10 September 2012 Keywords: obesity; night eating; sleep; circadian rhythmINTRODUCTION The obesity epidemic continues to impact heavily on the health economy, and the need for successful and enduring obesity treatments is essential. Recent years have seen sustained attempts to understand the contribution of disordered eating patterns to the development of obesity. Considerable progress has been made in understanding night eating syndrome (NES), a cluster of behaviours first identified in 1955 by Stunkard,1 a psychiatrist specialising in eating disorders (ED). This narrative review describes the evolution of NES from initial identification to current conceptualisation. Methods of identification, prevalence in varying populations, behavioural and clinical characteristics, and treatment options are discussed. Evolving evidence of the relationship between NES and other ED, sleep-related ED, sleep, depression and anxiety is also considered. The paper concludes by examining the relationship of NES with obesity and the applicability of current NES criteria to a severely obese population.grounds of sample size as even single case reports may be important indicators of future understanding of NES. Reviews, commentaries, reports from professional and non peer-reviewed publications and case reports of other syndromes where discussion of NE was incidental were excluded, yielding 84 studies for potential inclusion, of which 73 have been included in this review.METHODS The Medline, Scopus, PsychInfo and CINAHL databases were searched for all studies published between 1955 and January 2012. One-hundred and ninty-one papers were found using the search terms of NES, night-eating (NE), late night eating, NE behaviour and nocturnal eating. Results were filtered to return studies of human subjects published in English. Only original research was considered for inclusion. The conceptualisation of NES is still evolving, thus papers were not excluded on theEVOLUTION OF DIAGNOSTIC CRITERIA NES is now considered a dysfunction of circadian rhythm with a disassociation between eating and sleeping, characterised by a phase onset delay.

, a runner who demonstrates considerably less than 45?of knee flexion may

, a LurbinectedinMedChemExpress PM01183 runner who demonstrates considerably less than 45?of knee purchase PF-04418948 flexion may suggest reduced shock absorption, and intervention may be warranted. Some data exist suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj., a runner who demonstrates considerably less than 45?of knee flexion may suggest reduced shock absorption, and intervention may be warranted. Some data exist suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj.

Ampal CA1 subfield in individuals with MCI compared to NCI (Fig.

Ampal CA1 subfield in individuals with MCI order Shikonin compared to NCI (Fig. 4), which correlated with the subject’s Mini-Mental State Exam score (MMSE), but not with NFT Braak stage or apolipoprotein E (ApoE) status, a genetic risk factor for AD (Scheff et al., 2006). Unlike the outer molecular layer, CA1 receives input from the Schaffer collaterals arising from CA3 and not from the glutamatergic neurons of the entorhinal cortex, suggesting differential responses to synapse loss within the hippocampus based upon afferent innervation or chemical phenotype, some of which precipitate synaptic reorganization. A recent report characterized changes in the dendritic branching of the basilar tree of hippocampal CA1 pyramidal neurons. In this study, formalin-fixed tissue CBIC2 price autopsy obtained from University of Kentucky Alzheimer’s Disease Center who died with a clinical diagnosis of NCI, MCI or AD was prepared for Golgi impregnation (Fig. 5). Camera lucida drawings of the basilar tree of randomly selected CA1 neurons were analyzed for alterations in dendritic arbor amount, distribution and complexity (Mervis et al., 2013). Quantitation showed a significant increase in dendritic length (18 ) and complexity (23 ) in CA1 neurons in MCI compared to NCI. Conversely, there was a significant reduction in branch length (-39 ) and arbor complexity (-25 ) during the progression from MCI to AD (Fig. 5). These findings suggest that the observed increase in CA1 dendritic parameters from NCI to MCI may be another example of a neuroplastic compensatory response to a loss of afferent input early in the course of the disease, which is not maintained as the disease progresses. The role that the reported reduction in total synapse number plays in CA1 neuroplasticity remains unknown. However, these examples of early CA1 neural reorganization may represent a viable window for potential therapeutic strategies aimed at restoring or maintaining hippocampal function during the transition from MCI to AD. Future studies should determine whether alterations in specific synapse subtypes (i.e., perforated vs. non-perforated) are differentially affected and their relation to cognitive decline and brain pathology during the onset of AD. Interestingly, the size of the synaptic contacts was found to be substantially larger in AD cortex compared to non-demented aged controls (Scheff et al., 1990), which was suggested to be part of a compensatory mechanism found in regions of the neocortex and hippocampus (see review Scheff and Price, 2006). These investigators found that as the number of synapses declined in a given region, the size of the residualAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagesynapses increased. This synaptic compensatory response was also observed early in the course of the AD (DeKosky and Scheff, 1990). Neuronal structural alterations may not be the only factor(s) contributing to cognitive decline and hippocampal plasticity in MCI. For example, studies have reported significant reductions in synaptic vesicle trafficking-related genes in the AD brain, which interrupt the efficacy of normal synaptic transmission (Yao et al., 2003; Murphy et al., 2003; Kennedy et al., 2005). Counts et al. (2014) examined progressive changes in the expression classes of synaptic gene within single CA1 neurons in subjects who died with a clinical diagnosis of NCI, MCI or moderate AD obtain.Ampal CA1 subfield in individuals with MCI compared to NCI (Fig. 4), which correlated with the subject’s Mini-Mental State Exam score (MMSE), but not with NFT Braak stage or apolipoprotein E (ApoE) status, a genetic risk factor for AD (Scheff et al., 2006). Unlike the outer molecular layer, CA1 receives input from the Schaffer collaterals arising from CA3 and not from the glutamatergic neurons of the entorhinal cortex, suggesting differential responses to synapse loss within the hippocampus based upon afferent innervation or chemical phenotype, some of which precipitate synaptic reorganization. A recent report characterized changes in the dendritic branching of the basilar tree of hippocampal CA1 pyramidal neurons. In this study, formalin-fixed tissue autopsy obtained from University of Kentucky Alzheimer’s Disease Center who died with a clinical diagnosis of NCI, MCI or AD was prepared for Golgi impregnation (Fig. 5). Camera lucida drawings of the basilar tree of randomly selected CA1 neurons were analyzed for alterations in dendritic arbor amount, distribution and complexity (Mervis et al., 2013). Quantitation showed a significant increase in dendritic length (18 ) and complexity (23 ) in CA1 neurons in MCI compared to NCI. Conversely, there was a significant reduction in branch length (-39 ) and arbor complexity (-25 ) during the progression from MCI to AD (Fig. 5). These findings suggest that the observed increase in CA1 dendritic parameters from NCI to MCI may be another example of a neuroplastic compensatory response to a loss of afferent input early in the course of the disease, which is not maintained as the disease progresses. The role that the reported reduction in total synapse number plays in CA1 neuroplasticity remains unknown. However, these examples of early CA1 neural reorganization may represent a viable window for potential therapeutic strategies aimed at restoring or maintaining hippocampal function during the transition from MCI to AD. Future studies should determine whether alterations in specific synapse subtypes (i.e., perforated vs. non-perforated) are differentially affected and their relation to cognitive decline and brain pathology during the onset of AD. Interestingly, the size of the synaptic contacts was found to be substantially larger in AD cortex compared to non-demented aged controls (Scheff et al., 1990), which was suggested to be part of a compensatory mechanism found in regions of the neocortex and hippocampus (see review Scheff and Price, 2006). These investigators found that as the number of synapses declined in a given region, the size of the residualAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagesynapses increased. This synaptic compensatory response was also observed early in the course of the AD (DeKosky and Scheff, 1990). Neuronal structural alterations may not be the only factor(s) contributing to cognitive decline and hippocampal plasticity in MCI. For example, studies have reported significant reductions in synaptic vesicle trafficking-related genes in the AD brain, which interrupt the efficacy of normal synaptic transmission (Yao et al., 2003; Murphy et al., 2003; Kennedy et al., 2005). Counts et al. (2014) examined progressive changes in the expression classes of synaptic gene within single CA1 neurons in subjects who died with a clinical diagnosis of NCI, MCI or moderate AD obtain.

Monly used and widely available OTC medications and nutritional supplements were

Monly used and widely available OTC medications and Pepstatin A structure nutritional supplements were safe and posed no short- or long-term threat to their health. Many used such products to improve their running performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product recommended as an effective and legal substance by another runner or by a retail sales clerk may contain substances that are either banned by agencies such as WADA and/or may pose a serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. Velpatasvir biological activity However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.Monly used and widely available OTC medications and nutritional supplements were safe and posed no short- or long-term threat to their health. Many used such products to improve their running performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product recommended as an effective and legal substance by another runner or by a retail sales clerk may contain substances that are either banned by agencies such as WADA and/or may pose a serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.

Deration when interpreting experimental findings. (i) Identification of a mutation in

Deration when interpreting experimental findings. (i) Identification of a mutation in a NSC309132MedChemExpress Zebularine clonal population does not indicate causality Any mutation in a cell that undergoes clonal expansion will be passed onto progeny, irrespective of functional status (Fig. 3A,B). Given the size of the genome, more mutations carried by a neoplastic clone will be passengers than drivers [27, 29, 30]. To demonstrate driver status, supporting functional studies and/or repeated observations of a mutated loci in neoplastic clones from independent individuals are needed. (ii) Mutational marking of a clone is stochastic and not guaranteed A clone may exist and not be detected if none of the genomic sites being screened carry a unique mutation permitting it to be distinguished from the germline (Fig. 3C). The more sites examined, the higher the probability of detection becomes. Restricting a marker panel to suspected driver sites precludes detection of pathological clones driven by unknown factors. (iii) Elevated mutation rates facilitate clone detection but are not an absolute requirement Screening of mutational order Flavopiridol hotspots makes it practical with conventional technologies to have a reasonable probability of detecting a clone by random passenger mutations. Clones derived from a mutator lineage or cells residing in a highly mutagenic environment should be more densely marked with identifiable passengers (Fig. 3D), potentially reducing the number of markers needing to be interrogated to identify them. Emerging high-throughput sequencing technologies will eventually obviate the need to restrict screening to a fraction of the genome. (iv) Identification of one or more clonal mutations is not proof of genetic instability in the absence of collateral information Detection of a mutation requires clonal expansion with most traditional methods of aggregate DNA analysis. The probability of identifying clonal mutations in an expanded population is a function of the number of sites screened, the mutability of these sites and the number of cell divisions having occurred in the lineage leading up to the final expansion. Particularly when considering hotspots, mutations will be occasionally detectable in any clonally-derived population at a statistically definable frequency. Because mutations are not routinely encountered in normal tissues, it is tempting to explain their presence in preneoplastic populations as the result of “genetic instability” (an elevated mutation rate). However, the phenomenon is more precisely explained by the fact that expansion does not routinely occur in most normal tissues. An elevated mutation rate itself will have no observable effect on clonal mutation frequency in the absence of expansion (Fig. 3E). To determine mutation rate from a clonal mutation frequency it is necessary to (A) know that the population being assessed is clonal and (B) have some metric of the number of cell divisions that occurred in the period between the zygote and the founding of the final clonalSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPageoutgrowth. To infer that a rate is elevated, it is also necessary to know the normal in vivo mutation rate, which is, in turn, impossible to measure by this approach given that large clonal expansions do not routinely occur in normal adult tissue. Considering these complexities, the lack of resolution as to whether mutation rates are elevated in cancer is not surprising [1,8?1]. (v) Detectabili.Deration when interpreting experimental findings. (i) Identification of a mutation in a clonal population does not indicate causality Any mutation in a cell that undergoes clonal expansion will be passed onto progeny, irrespective of functional status (Fig. 3A,B). Given the size of the genome, more mutations carried by a neoplastic clone will be passengers than drivers [27, 29, 30]. To demonstrate driver status, supporting functional studies and/or repeated observations of a mutated loci in neoplastic clones from independent individuals are needed. (ii) Mutational marking of a clone is stochastic and not guaranteed A clone may exist and not be detected if none of the genomic sites being screened carry a unique mutation permitting it to be distinguished from the germline (Fig. 3C). The more sites examined, the higher the probability of detection becomes. Restricting a marker panel to suspected driver sites precludes detection of pathological clones driven by unknown factors. (iii) Elevated mutation rates facilitate clone detection but are not an absolute requirement Screening of mutational hotspots makes it practical with conventional technologies to have a reasonable probability of detecting a clone by random passenger mutations. Clones derived from a mutator lineage or cells residing in a highly mutagenic environment should be more densely marked with identifiable passengers (Fig. 3D), potentially reducing the number of markers needing to be interrogated to identify them. Emerging high-throughput sequencing technologies will eventually obviate the need to restrict screening to a fraction of the genome. (iv) Identification of one or more clonal mutations is not proof of genetic instability in the absence of collateral information Detection of a mutation requires clonal expansion with most traditional methods of aggregate DNA analysis. The probability of identifying clonal mutations in an expanded population is a function of the number of sites screened, the mutability of these sites and the number of cell divisions having occurred in the lineage leading up to the final expansion. Particularly when considering hotspots, mutations will be occasionally detectable in any clonally-derived population at a statistically definable frequency. Because mutations are not routinely encountered in normal tissues, it is tempting to explain their presence in preneoplastic populations as the result of “genetic instability” (an elevated mutation rate). However, the phenomenon is more precisely explained by the fact that expansion does not routinely occur in most normal tissues. An elevated mutation rate itself will have no observable effect on clonal mutation frequency in the absence of expansion (Fig. 3E). To determine mutation rate from a clonal mutation frequency it is necessary to (A) know that the population being assessed is clonal and (B) have some metric of the number of cell divisions that occurred in the period between the zygote and the founding of the final clonalSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPageoutgrowth. To infer that a rate is elevated, it is also necessary to know the normal in vivo mutation rate, which is, in turn, impossible to measure by this approach given that large clonal expansions do not routinely occur in normal adult tissue. Considering these complexities, the lack of resolution as to whether mutation rates are elevated in cancer is not surprising [1,8?1]. (v) Detectabili.

Items each represented 16 different topics that received high engagement in just

Items each represented 16 P144 Peptide biological activity different topics that received high engagement in just one platform (hereafter: “unique” U0126-EtOH cancer high-engagement items). These data indicate an association between high engagement and item topic (2(47) = 80.054, n = 214, p < 0.01, Cramer’s V = 0.612).PLOS ONE | DOI:10.1371/journal.pone.0156409 May 27,13 /Engagement with Particle Physics on CERN’s Social Media PlatformsTable 8. Recurring high engagement topics. Recurring High Engagement Topic Code 1. 2. 3. 4. 5. 6. Fabiola Open Data Pipes 1st Computer CMS Dishwasher Type News News Guess What It Is Throwback Thursday Wow Wow Image Caption “CERN Council selects Italian physicist, Dr Fabiola Gianotti, as CERN’s next Director-General” “CERN launches Open Data Portal to make public the data of LHC experiments” “CERN’s cooling ventilation systems get refreshed” “The Ferranti Mercury, CERN’s 1st ‘central’ computer” “The LHC’s Compact Muon Solenoid (CMS) detector” “That’s right, a CERN dishwasher for circuit boards” Recurred as High Engagement Item on. . . Facebook, Twitter English, Twitter French Facebook, Google+, Twitter English, Twitter French Google+, Twitter French Facebook, Twitter English Instagram, Twitter English, Twitter French Facebook, Google+, Instagram, Twitter English, Twitter Frenchdoi:10.1371/journal.pone.0156409.tSome characteristics of the high-engagement topics are that they may have referred to (1) news items receiving attention from traditional media (e.g. the “Fabiola” topic), or (2) a surprising or awe-inspiring image (e.g. “CMS”, “Dishwasher” and “Pipes”) (Table 8).Research LimitationsThe main methodological limitation in this study stems from the architecture of the platforms. The items posted were not necessarily seen by all CERN’s subscribers. The “organic reach” is determined by the technical settings of the platforms, and may be affected by many different variables. For example, one study found that organic reach increases on a given Facebook item if another item was posted on the platform the day before [30]. The results are based on data collected from October to December 2014, however changes may have occurred since then at multiple levels: from the CERN social media strategy and behaviour, to the architecture of the platforms, as well as the audiences, their preferences and the general online communication landscape. Concerning CERN’s strategy and posting behaviour, this has remained consistent with the data-taking period. However, platform architectures are regularly changed and updated. Since our findings indicate that the platform itself influences user behaviour, it follows that changes in the platform may have an effect. For example, Twitter has implemented a new feed algorithm [43]. Google+ has been fully redesigned [44]. Facebook have not only changed the way that content from pages are delivered to the audience [45], they are also placing more and more emphasis on video content, particularly live or immersive videos, over other types of content [46]. One recent Facebook update now allows people to express their feelings as “reactions” to the information published [47]. These changes call for more elaborate future research in this topic, with fine-tuned analysis that looks at both the comments and the reaction icons. The online communication landscape in general has become more mobile, with some audiences shifting to other social media platforms such as Snapchat. Notwithstanding the dynamics of this field, our systematic study still.Items each represented 16 different topics that received high engagement in just one platform (hereafter: “unique” high-engagement items). These data indicate an association between high engagement and item topic (2(47) = 80.054, n = 214, p < 0.01, Cramer’s V = 0.612).PLOS ONE | DOI:10.1371/journal.pone.0156409 May 27,13 /Engagement with Particle Physics on CERN’s Social Media PlatformsTable 8. Recurring high engagement topics. Recurring High Engagement Topic Code 1. 2. 3. 4. 5. 6. Fabiola Open Data Pipes 1st Computer CMS Dishwasher Type News News Guess What It Is Throwback Thursday Wow Wow Image Caption “CERN Council selects Italian physicist, Dr Fabiola Gianotti, as CERN’s next Director-General” “CERN launches Open Data Portal to make public the data of LHC experiments” “CERN’s cooling ventilation systems get refreshed” “The Ferranti Mercury, CERN’s 1st ‘central’ computer” “The LHC’s Compact Muon Solenoid (CMS) detector” “That’s right, a CERN dishwasher for circuit boards” Recurred as High Engagement Item on. . . Facebook, Twitter English, Twitter French Facebook, Google+, Twitter English, Twitter French Google+, Twitter French Facebook, Twitter English Instagram, Twitter English, Twitter French Facebook, Google+, Instagram, Twitter English, Twitter Frenchdoi:10.1371/journal.pone.0156409.tSome characteristics of the high-engagement topics are that they may have referred to (1) news items receiving attention from traditional media (e.g. the “Fabiola” topic), or (2) a surprising or awe-inspiring image (e.g. “CMS”, “Dishwasher” and “Pipes”) (Table 8).Research LimitationsThe main methodological limitation in this study stems from the architecture of the platforms. The items posted were not necessarily seen by all CERN’s subscribers. The “organic reach” is determined by the technical settings of the platforms, and may be affected by many different variables. For example, one study found that organic reach increases on a given Facebook item if another item was posted on the platform the day before [30]. The results are based on data collected from October to December 2014, however changes may have occurred since then at multiple levels: from the CERN social media strategy and behaviour, to the architecture of the platforms, as well as the audiences, their preferences and the general online communication landscape. Concerning CERN’s strategy and posting behaviour, this has remained consistent with the data-taking period. However, platform architectures are regularly changed and updated. Since our findings indicate that the platform itself influences user behaviour, it follows that changes in the platform may have an effect. For example, Twitter has implemented a new feed algorithm [43]. Google+ has been fully redesigned [44]. Facebook have not only changed the way that content from pages are delivered to the audience [45], they are also placing more and more emphasis on video content, particularly live or immersive videos, over other types of content [46]. One recent Facebook update now allows people to express their feelings as “reactions” to the information published [47]. These changes call for more elaborate future research in this topic, with fine-tuned analysis that looks at both the comments and the reaction icons. The online communication landscape in general has become more mobile, with some audiences shifting to other social media platforms such as Snapchat. Notwithstanding the dynamics of this field, our systematic study still.

Our more alternative notations: A ! B, A ! B, Z Y Z

Our more alternative notations: A ! B, A ! B, Z Y Z XY Z X Z Z A ! B, and A ! B. Category 5 (CS) gets one more alternative notation, [A !B and A Z Y Y Z Z Z ZB].Finally, category 6 (asocial) gets two more alternative notations, A !B and A B. For any N ! 2, all of the 2N+1 elementary interactions are included in the representative relationships of the six categories and their alternative notations. This results from the building process of the six categories, with the differentiations covering all possible cases. In the example of N = 3, the above statement is illustrated by the comparison of the sixteen elementary interactions of Table 4 with the six categories and their alternative notations for N = 2 (Table 3), completed by the alternative notations for N = 3 listed above. This concludes the proof of exhaustiveness of the six categories of Table 3 for any number N ! 2 of non-null social actions. With N social actions at hand, richer composite relationships can be represented. Let us translate into our action fluxes representation an example of composite relationship given by Goldman [25] (pp. 344-345). Namely, “two friends may share tapes and records freely with each other (CS), work on a task at which one is an expert and imperiously directs the other (AR), divide equally the cost of gas on a trip (EM), and transfer a bicycle from one to the other S2 S4 S5 S6 S1 S for a market-value price (MP).” This gives [A ! B, A 1 B, A ! B, A ! B, A ! B, A ! B].S2 S4 S6 SHere the relationship was known and we wrote it in terms of action fluxes. The next step is to find out how to identify a relationship when the action fluxes are given. We touch on how to achieve this in the discussion.Discussion Analyzing data setsOur representation in action fluxes provides a tool to identify types of dyadic relationships occurring within potentially large data sets of social interactions. Both collective and dyadic interactions may occur in real social contexts, but our approach applies GSK-1605786 biological activity specifically to the latter. Large data sets can result from any type of online social network or massively multiplayer online role-playing games (MMORPG), for instance. MMORPGs bring hundreds of get PX-478 thousands of players together to cooperate and compete by forming alliances, trading, fighting, and so on, all the while recording every single action and communication of the players. They are used in quantitative social science, for example by Thurner in the context of the game Pardus [26?8]. Ethnological and anthropological studies can provide rich reports of social interactions occurring in non-artificial settings that could be coded and interpreted with the aid of our categorization. Data sets of dyadic interactions can also be generated by computer simulations such as agent-based models (ABMs) to test specific questions. We offer the sketch of a method to analyze a potentially large data set of dyadic social interactions expressed as action fluxes (“A does X to B”, etc.). Given a data set involving a number of individuals, one needs to consider separately each pair of individuals. For each pair, one shall examine each social action and test into which category of action fluxes it falls, possibly jointly with another social action (in the case of MP and AR). In its second column, Table 5 specifies the patterns of fluxes expected to be observed in each category. Let us stress the following points: ?The patterns of observed fluxes given in Table 5 are not meant as definitions of the.Our more alternative notations: A ! B, A ! B, Z Y Z XY Z X Z Z A ! B, and A ! B. Category 5 (CS) gets one more alternative notation, [A !B and A Z Y Y Z Z Z ZB].Finally, category 6 (asocial) gets two more alternative notations, A !B and A B. For any N ! 2, all of the 2N+1 elementary interactions are included in the representative relationships of the six categories and their alternative notations. This results from the building process of the six categories, with the differentiations covering all possible cases. In the example of N = 3, the above statement is illustrated by the comparison of the sixteen elementary interactions of Table 4 with the six categories and their alternative notations for N = 2 (Table 3), completed by the alternative notations for N = 3 listed above. This concludes the proof of exhaustiveness of the six categories of Table 3 for any number N ! 2 of non-null social actions. With N social actions at hand, richer composite relationships can be represented. Let us translate into our action fluxes representation an example of composite relationship given by Goldman [25] (pp. 344-345). Namely, “two friends may share tapes and records freely with each other (CS), work on a task at which one is an expert and imperiously directs the other (AR), divide equally the cost of gas on a trip (EM), and transfer a bicycle from one to the other S2 S4 S5 S6 S1 S for a market-value price (MP).” This gives [A ! B, A 1 B, A ! B, A ! B, A ! B, A ! B].S2 S4 S6 SHere the relationship was known and we wrote it in terms of action fluxes. The next step is to find out how to identify a relationship when the action fluxes are given. We touch on how to achieve this in the discussion.Discussion Analyzing data setsOur representation in action fluxes provides a tool to identify types of dyadic relationships occurring within potentially large data sets of social interactions. Both collective and dyadic interactions may occur in real social contexts, but our approach applies specifically to the latter. Large data sets can result from any type of online social network or massively multiplayer online role-playing games (MMORPG), for instance. MMORPGs bring hundreds of thousands of players together to cooperate and compete by forming alliances, trading, fighting, and so on, all the while recording every single action and communication of the players. They are used in quantitative social science, for example by Thurner in the context of the game Pardus [26?8]. Ethnological and anthropological studies can provide rich reports of social interactions occurring in non-artificial settings that could be coded and interpreted with the aid of our categorization. Data sets of dyadic interactions can also be generated by computer simulations such as agent-based models (ABMs) to test specific questions. We offer the sketch of a method to analyze a potentially large data set of dyadic social interactions expressed as action fluxes (“A does X to B”, etc.). Given a data set involving a number of individuals, one needs to consider separately each pair of individuals. For each pair, one shall examine each social action and test into which category of action fluxes it falls, possibly jointly with another social action (in the case of MP and AR). In its second column, Table 5 specifies the patterns of fluxes expected to be observed in each category. Let us stress the following points: ?The patterns of observed fluxes given in Table 5 are not meant as definitions of the.

. This exploratory analysis can provide further information on functional similarities between

. This exploratory analysis can provide further information on functional similarities between regions, and, more specifically, on the extent to which activation profiles of category-selective regions are inherited from EVC. As for the replicability of within-category ranking (Fig. 5), we combined data across subjects either by concatenating or averaging the activation profiles across subjects. The concatenation approach is sensitive to inter-region correlations of activation profiles even if the particular activation profiles differ across subjects. The averaging approach is sensitive to inter-region correlations of activation profiles that are consistent across subjects. We investigated the inter-region correlations for (1) the full activation profile, (2) the within-face activation profile, and (3) the withinplace activation profile. Statistical inference was performed by a standard one-sided test on Spearman’s r. p values were corrected8658 ?J. Neurosci., June 20, 2012 ?32(25):8649 ?Mur et al. ?Single-Image Activation of Category Regionsfor multiple testing using Bonferroni correction based on the total number of tests performed. Figure 7 shows the inter-region correlation results. The main pattern that emerges is that activation profiles are Pedalitin permethyl ether cost correlated between hemispheres for corresponding regions, and between hIT and EVC (red blocks on diagonals). We subsequently get PP58 inspected the within-face correlation between FFA and EVC, and the within-place correlation between PPA and EVC. The within-face activation profile was correlated between left but not right FFA and EVC, and the within-place activation profile was not significantly correlated between PPA and EVC. Results were similar across ROI sizes. These results suggest that EVC is not a major contributor to the within-category activation profiles of PPA and right FFA. We then inspected the correlation between category-selective regions (FFA/PPA) and EVC for the full activation profile (top row). The full activation profile was correlated between EVC and both categoryselective regions, especially PPA. One interpretation of this finding would be that some degree of category selectivity is already present at the level of EVC, implying that low-level feature differences contribute to some extent to categoryselective responses. For places, this seems a plausible interpretation, consistent with our finding that single-image activation of EVC can discriminate places from nonplaces at an above-chance level (Fig. 2). For faces, this interpretation seems less likely: the correlation between EVC and FFA is not significant for the subjectaverage activation profile, suggesting that the correlation is driven by subjectspecific effects (e.g., idiosyncratic arousal effects) and not by face-selectivity of responses (shared across subjects in FFA). Categorical, yet graded Figure 8 summarizes our results. Singleimage activation profiles of categoryselective regions (1) show near-perfect discrimination of preferred from nonpreferred images and no preference inversions for particular object images, (2) show a step-like drop-off at the category boundary, and (3) are graded within and outside the preferred category. It can further be noted that single-image category selectivity is stronger in right than left FFA. In addition, gradedness seems to be more pronounced in FFA; the category step seems to be more pronounced in PPA. In sum, our findings indicate that the activation profiles of category-selec-Figure.. This exploratory analysis can provide further information on functional similarities between regions, and, more specifically, on the extent to which activation profiles of category-selective regions are inherited from EVC. As for the replicability of within-category ranking (Fig. 5), we combined data across subjects either by concatenating or averaging the activation profiles across subjects. The concatenation approach is sensitive to inter-region correlations of activation profiles even if the particular activation profiles differ across subjects. The averaging approach is sensitive to inter-region correlations of activation profiles that are consistent across subjects. We investigated the inter-region correlations for (1) the full activation profile, (2) the within-face activation profile, and (3) the withinplace activation profile. Statistical inference was performed by a standard one-sided test on Spearman’s r. p values were corrected8658 ?J. Neurosci., June 20, 2012 ?32(25):8649 ?Mur et al. ?Single-Image Activation of Category Regionsfor multiple testing using Bonferroni correction based on the total number of tests performed. Figure 7 shows the inter-region correlation results. The main pattern that emerges is that activation profiles are correlated between hemispheres for corresponding regions, and between hIT and EVC (red blocks on diagonals). We subsequently inspected the within-face correlation between FFA and EVC, and the within-place correlation between PPA and EVC. The within-face activation profile was correlated between left but not right FFA and EVC, and the within-place activation profile was not significantly correlated between PPA and EVC. Results were similar across ROI sizes. These results suggest that EVC is not a major contributor to the within-category activation profiles of PPA and right FFA. We then inspected the correlation between category-selective regions (FFA/PPA) and EVC for the full activation profile (top row). The full activation profile was correlated between EVC and both categoryselective regions, especially PPA. One interpretation of this finding would be that some degree of category selectivity is already present at the level of EVC, implying that low-level feature differences contribute to some extent to categoryselective responses. For places, this seems a plausible interpretation, consistent with our finding that single-image activation of EVC can discriminate places from nonplaces at an above-chance level (Fig. 2). For faces, this interpretation seems less likely: the correlation between EVC and FFA is not significant for the subjectaverage activation profile, suggesting that the correlation is driven by subjectspecific effects (e.g., idiosyncratic arousal effects) and not by face-selectivity of responses (shared across subjects in FFA). Categorical, yet graded Figure 8 summarizes our results. Singleimage activation profiles of categoryselective regions (1) show near-perfect discrimination of preferred from nonpreferred images and no preference inversions for particular object images, (2) show a step-like drop-off at the category boundary, and (3) are graded within and outside the preferred category. It can further be noted that single-image category selectivity is stronger in right than left FFA. In addition, gradedness seems to be more pronounced in FFA; the category step seems to be more pronounced in PPA. In sum, our findings indicate that the activation profiles of category-selec-Figure.

Focus group discussions were analysed for themes [46?8]. Our research team thoroughly

Focus group discussions were analysed for themes [46?8]. Our research team thoroughly read and reread the Pleconaril price transcripts and met regularly to develop a systematic process of thematic analysis. We used investigator triangulation [49, 50] to create and agree upon the categorizations and coding schemes that led to our themes. Our themes appeared consistently in each of the four focus groups. Trustworthiness was established by member checking with participants to ensure authenticity. Several strategies were utilized to increase rigor [45, 51]. Stability was enhanced through the use of multiple focus groups in geographically different areas. Equivalence was achieved through the use of two experienced moderators with complementary styles to achieve “flow, texture and context” and to promote construct validity [51] (page 302). Credibility was strengthened through sustained engagement and observation over the course of four focus groups, researcher triangulation, debriefing as a research team, and member checking. Reflexivity, where researchers strive to understand their own experiences as well as the research question, in order to remain objective, neutral, and nonbiased, was supported through regular face-to-face and teleconference meetings. Transferability was enriched through dense sample description and rich description of the data. Confirmability was PG-1016548 chemical information heightened through peer debriefing and maintaining our audit trail. Dependability was attained by recording a log of our plans, meetings, and ongoing interpretations. Using annotation and memo functions, NVIVO 9 [52] maintained a permanent record of our work. Tracking individual responses in addition to the group account [53] assisted us in avoiding the risk of analyzing data from only vocally dominant members of the groups. Field notes or “descriptions of participants, impressions related to the discussion (and) observations related to group dynamics”3. Research ApproachThis qualitative descriptive project was framed from a constructivist worldview [32?4] and Haas and Shaffir’s [4] sociological theory of professionalization. Haas and Shaffir theorized that legitimation is a central concept in healthcare professionals’ process of socialization. Participants were 27 Post LPN to BN students from a Canadian university who attended a practicum on an acute hospital unit. The main purpose of the research was to describe Post LPN to BN student nurses’ experiences with professional socialization as they transitioned into a more complex nursing role. A secondary purpose of the research was to begin to understand how university faculty can best support and facilitate these students’ professional socialization as they learn to become Registered Nurses (RNs). Data sources included four face-to-face digitally recorded, transcribed focus group discussions which were analyzed for themes. Our rational for collecting and analyzing focus group data centered on our intention to invite our participants to converse and interact in ways that stimulated new insights. Focus group methodology, with its emphasis on group interaction [35?9] and goal of collaborative discussion [40, 41], allowed us to draw out participants’ views and to explore their ideas and conversational exchanges with one another in depth. Focus groups are a rich source of information [42] and a valid method of generating data within a constructionist epistemology where “knowledge is created in situated, [collective] encounters” [43] (page 496). They.Focus group discussions were analysed for themes [46?8]. Our research team thoroughly read and reread the transcripts and met regularly to develop a systematic process of thematic analysis. We used investigator triangulation [49, 50] to create and agree upon the categorizations and coding schemes that led to our themes. Our themes appeared consistently in each of the four focus groups. Trustworthiness was established by member checking with participants to ensure authenticity. Several strategies were utilized to increase rigor [45, 51]. Stability was enhanced through the use of multiple focus groups in geographically different areas. Equivalence was achieved through the use of two experienced moderators with complementary styles to achieve “flow, texture and context” and to promote construct validity [51] (page 302). Credibility was strengthened through sustained engagement and observation over the course of four focus groups, researcher triangulation, debriefing as a research team, and member checking. Reflexivity, where researchers strive to understand their own experiences as well as the research question, in order to remain objective, neutral, and nonbiased, was supported through regular face-to-face and teleconference meetings. Transferability was enriched through dense sample description and rich description of the data. Confirmability was heightened through peer debriefing and maintaining our audit trail. Dependability was attained by recording a log of our plans, meetings, and ongoing interpretations. Using annotation and memo functions, NVIVO 9 [52] maintained a permanent record of our work. Tracking individual responses in addition to the group account [53] assisted us in avoiding the risk of analyzing data from only vocally dominant members of the groups. Field notes or “descriptions of participants, impressions related to the discussion (and) observations related to group dynamics”3. Research ApproachThis qualitative descriptive project was framed from a constructivist worldview [32?4] and Haas and Shaffir’s [4] sociological theory of professionalization. Haas and Shaffir theorized that legitimation is a central concept in healthcare professionals’ process of socialization. Participants were 27 Post LPN to BN students from a Canadian university who attended a practicum on an acute hospital unit. The main purpose of the research was to describe Post LPN to BN student nurses’ experiences with professional socialization as they transitioned into a more complex nursing role. A secondary purpose of the research was to begin to understand how university faculty can best support and facilitate these students’ professional socialization as they learn to become Registered Nurses (RNs). Data sources included four face-to-face digitally recorded, transcribed focus group discussions which were analyzed for themes. Our rational for collecting and analyzing focus group data centered on our intention to invite our participants to converse and interact in ways that stimulated new insights. Focus group methodology, with its emphasis on group interaction [35?9] and goal of collaborative discussion [40, 41], allowed us to draw out participants’ views and to explore their ideas and conversational exchanges with one another in depth. Focus groups are a rich source of information [42] and a valid method of generating data within a constructionist epistemology where “knowledge is created in situated, [collective] encounters” [43] (page 496). They.

Rhetorical functions of language, typography and editorial voice as well as

Rhetorical functions of language, typography and editorial voice as well as the use of such radical literary tactics as exposure, ridicule and critique. This article does not merely aim to point up the similarities between The Lancet and its political contemporaries; it intends to show how such stylistic devices were marshalled in the pursuit of a specific political agenda. Of course splenetic prose was not the sole preserve of the radical `left’ and neither was it particularly novel. Similar tactics had been in use since the later 1700s by `King and Country’ Tories, a position from which Wakley’s mentor and collaborator, William Cobbett, had only moved in 1806.14 However, during the early decades of the nineteenth century it was the radical and revolutionary press which made this style their own, and it was these conventions that Wakley sought to emulate. This was particularly true of his RRx-001 chemical information predilection for insult and defamation, and the main body of this article comprises a detailed analysis of a trial for libel in 1828 between Wakely and the Guy’s Hospital surgeon, Bransby Cooper. Through a close analysis of Wakley’s rhetorical, legal and performative strategies, as well as a critical reading of a number of contemporary satirical prints, it demonstrates how this trial functioned as the platform for a much broader critique of the established medical `system’ and provided a powerful means for Wakley to align himself with the cultures of popular radicalism. However, whatever parallels and connections Wakley sought to draw between the medical and the political, the reality was rather more complex. In the final section,567. Smith, The Politics of Language, 1791 ?819 (Oxford, 1984); I. McCalman, Radical Underworld: Prophets, Revolutionaries and Pornographers, 1795?1840 (Cambridge, 1988); J. A. Epstein, Radical Expression: Political Language, Ritual and Symbol in England, 1790 ?1850 (Oxford, 1994); E. Hadley, Melodramatic Tactics: Theatricalised Dissent in the English13O. 12ibid.,Marketplace, 1800 ?1885 (Stanford, 1995); L. Nattrass, William Cobbett: The Politics of Style (Cambridge, 1995); K. Gilmartin, Print Politics: The Press and Radical Opposition in Early Nineteenth-Century England (Cambridge, 1996). 14For example, see J. J. Sack, From Jacobite to Conservative: Reaction and Orthodoxy in Britain, c.1760 ?832 (Cambridge, 1993).Social HistoryVOL.39 :NO.therefore, this article examines the tensions and ambiguities within Wakley’s political (��)-Zanubrutinib web persona by reading them against the altered circumstances of the 1820s, particularly the rise of a more philosophic reformism. In so doing, it seeks not merely to place political radicalism at the heart of contemporary medical culture but, more ambitiously perhaps, to establish a more prominent place for medicine in accounts of the history of early nineteenth-century reform, as a potential bridge between the popular radicalism of the immediate post-war years and the reformist utilitarianism of the 1830s.WAKLEY, COBBETT AND RADICAL STYLEThere was little in Thomas Wakley’s early upbringing to suggest a natural inclination towards political radicalism, for he was born in 1795 into that bulwark of pre-modern political order, the prosperous farming family.15 One of eleven children and the youngest of eight sons, he attended boarding school in Somerset, followed by a series of apprenticeships with local apothecaries and surgeons, enrolling as a student at the United Hospitals Medical School of Guy’s and St Tho.Rhetorical functions of language, typography and editorial voice as well as the use of such radical literary tactics as exposure, ridicule and critique. This article does not merely aim to point up the similarities between The Lancet and its political contemporaries; it intends to show how such stylistic devices were marshalled in the pursuit of a specific political agenda. Of course splenetic prose was not the sole preserve of the radical `left’ and neither was it particularly novel. Similar tactics had been in use since the later 1700s by `King and Country’ Tories, a position from which Wakley’s mentor and collaborator, William Cobbett, had only moved in 1806.14 However, during the early decades of the nineteenth century it was the radical and revolutionary press which made this style their own, and it was these conventions that Wakley sought to emulate. This was particularly true of his predilection for insult and defamation, and the main body of this article comprises a detailed analysis of a trial for libel in 1828 between Wakely and the Guy’s Hospital surgeon, Bransby Cooper. Through a close analysis of Wakley’s rhetorical, legal and performative strategies, as well as a critical reading of a number of contemporary satirical prints, it demonstrates how this trial functioned as the platform for a much broader critique of the established medical `system’ and provided a powerful means for Wakley to align himself with the cultures of popular radicalism. However, whatever parallels and connections Wakley sought to draw between the medical and the political, the reality was rather more complex. In the final section,567. Smith, The Politics of Language, 1791 ?819 (Oxford, 1984); I. McCalman, Radical Underworld: Prophets, Revolutionaries and Pornographers, 1795?1840 (Cambridge, 1988); J. A. Epstein, Radical Expression: Political Language, Ritual and Symbol in England, 1790 ?1850 (Oxford, 1994); E. Hadley, Melodramatic Tactics: Theatricalised Dissent in the English13O. 12ibid.,Marketplace, 1800 ?1885 (Stanford, 1995); L. Nattrass, William Cobbett: The Politics of Style (Cambridge, 1995); K. Gilmartin, Print Politics: The Press and Radical Opposition in Early Nineteenth-Century England (Cambridge, 1996). 14For example, see J. J. Sack, From Jacobite to Conservative: Reaction and Orthodoxy in Britain, c.1760 ?832 (Cambridge, 1993).Social HistoryVOL.39 :NO.therefore, this article examines the tensions and ambiguities within Wakley’s political persona by reading them against the altered circumstances of the 1820s, particularly the rise of a more philosophic reformism. In so doing, it seeks not merely to place political radicalism at the heart of contemporary medical culture but, more ambitiously perhaps, to establish a more prominent place for medicine in accounts of the history of early nineteenth-century reform, as a potential bridge between the popular radicalism of the immediate post-war years and the reformist utilitarianism of the 1830s.WAKLEY, COBBETT AND RADICAL STYLEThere was little in Thomas Wakley’s early upbringing to suggest a natural inclination towards political radicalism, for he was born in 1795 into that bulwark of pre-modern political order, the prosperous farming family.15 One of eleven children and the youngest of eight sons, he attended boarding school in Somerset, followed by a series of apprenticeships with local apothecaries and surgeons, enrolling as a student at the United Hospitals Medical School of Guy’s and St Tho.

In living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic

In Avasimibe side effects living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic Ca-phosphate in pelagic EPZ004777 site sediments has long been studied by a number of investigators17,18,21?4,40?2. Some have suggested that biogenic Ca-phosphate incorporates REY via pore water in the sediment column23,40. Others have argued that Ca-phosphate takes up REY from a variety of carrier phases (e.g. Fe n-oxyhydroxides, pellets, and organic debris) that absorb REY from seawater and are readily decomposed at the sediment ater interface17,22,41,42. Although the complete process remains an open question, the characteristic REY patterns indicate that seawater is the ultimate source of the REY presently captured in biogenic Ca-phosphate22,25,41 (Fig. 4m). Simple quantitative estimation in this study suggested the possibility that seawater can contain the flux of REY precipitation required to explain the observed very high REY concentrations ( REY + Ce > 1,000 ppm) in bulk REY-rich mud with a sedimentation rate less than 0.5 m/Myr (Supplementary Fig. S19). Such circumstances may facilitate the concentration of REY in biogenic Ca-phosphate via diffusion of REY from seawater or the transfer of REY from original carriers to Ca-phosphate during the early diagenetic processes because of the prolonged exposure to seawater at the sediment surface and in the bioturbated and well-ventilated uppermost sediment layer17,18,22,41. In addition, biogenic Ca-phosphate enriched in REY might be stabilised through recrystallisation as insoluble apatite17. Moreover, the amount of Ca-phosphate in a unit volume of sediment also increases with a depression of the sedimentation rate17,18. Hence, the low sedimentation rate is considered to be crucial for the formation of REY-rich mud. Actually, the spatiotemporal distribution of high-IC1, -IC4, and -IC7 muds overlapped with the oligotrophic North Pacific and South Pacific gyres and with water depths greater than the CCD, both of which prevented the fast accumulation of dilutive components with low REY content such as biogenic carbonate and silica. If we assume that deep-sea sediments can continuously acquire REY from the overlying deep-sea water prior to burial, the REY-enrichment in sediments can occur in a time scale of 105 years considering the sedimentation rate of <0.5 m/Myr with a typical thickness of 0.1 m for the well-ventilated uppermost sediment layer43. This timescale of REY enrichment is significantly longer than that of global ocean circulation, which is 103 years44. Both IC1 and IC4 indicated statistical independent geochemical features of pelagic red clay mainly composed of detrital aluminosilicates involving abundant Si, Al, Fe, Mg, and K without significant contributions of biogenic carbonate and silica. Fe and Mn of hydrothermal or hydrogenous origins could have also been incorporated without dilution in high-IC1 and high-IC4 sediments, resulting in an increase in the contents of these elements. In addition, in deposition slow enough to allow biogenic Ca-phosphate grains to concentrate REY and to accumulate significantly in the sediment, the P and REY contents of these sediments also increase concurrently. Although sediments enriched in biogenic Ca-phosphate contain several percent of Ca, the significant dilution effect of biogenic carbonate, which contains several tens of percent of Ca, generally creates negative trends in these ICs as a whole in the spaces of Ca and other elements, including REY. The differenc.In living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic Ca-phosphate in pelagic sediments has long been studied by a number of investigators17,18,21?4,40?2. Some have suggested that biogenic Ca-phosphate incorporates REY via pore water in the sediment column23,40. Others have argued that Ca-phosphate takes up REY from a variety of carrier phases (e.g. Fe n-oxyhydroxides, pellets, and organic debris) that absorb REY from seawater and are readily decomposed at the sediment ater interface17,22,41,42. Although the complete process remains an open question, the characteristic REY patterns indicate that seawater is the ultimate source of the REY presently captured in biogenic Ca-phosphate22,25,41 (Fig. 4m). Simple quantitative estimation in this study suggested the possibility that seawater can contain the flux of REY precipitation required to explain the observed very high REY concentrations ( REY + Ce > 1,000 ppm) in bulk REY-rich mud with a sedimentation rate less than 0.5 m/Myr (Supplementary Fig. S19). Such circumstances may facilitate the concentration of REY in biogenic Ca-phosphate via diffusion of REY from seawater or the transfer of REY from original carriers to Ca-phosphate during the early diagenetic processes because of the prolonged exposure to seawater at the sediment surface and in the bioturbated and well-ventilated uppermost sediment layer17,18,22,41. In addition, biogenic Ca-phosphate enriched in REY might be stabilised through recrystallisation as insoluble apatite17. Moreover, the amount of Ca-phosphate in a unit volume of sediment also increases with a depression of the sedimentation rate17,18. Hence, the low sedimentation rate is considered to be crucial for the formation of REY-rich mud. Actually, the spatiotemporal distribution of high-IC1, -IC4, and -IC7 muds overlapped with the oligotrophic North Pacific and South Pacific gyres and with water depths greater than the CCD, both of which prevented the fast accumulation of dilutive components with low REY content such as biogenic carbonate and silica. If we assume that deep-sea sediments can continuously acquire REY from the overlying deep-sea water prior to burial, the REY-enrichment in sediments can occur in a time scale of 105 years considering the sedimentation rate of <0.5 m/Myr with a typical thickness of 0.1 m for the well-ventilated uppermost sediment layer43. This timescale of REY enrichment is significantly longer than that of global ocean circulation, which is 103 years44. Both IC1 and IC4 indicated statistical independent geochemical features of pelagic red clay mainly composed of detrital aluminosilicates involving abundant Si, Al, Fe, Mg, and K without significant contributions of biogenic carbonate and silica. Fe and Mn of hydrothermal or hydrogenous origins could have also been incorporated without dilution in high-IC1 and high-IC4 sediments, resulting in an increase in the contents of these elements. In addition, in deposition slow enough to allow biogenic Ca-phosphate grains to concentrate REY and to accumulate significantly in the sediment, the P and REY contents of these sediments also increase concurrently. Although sediments enriched in biogenic Ca-phosphate contain several percent of Ca, the significant dilution effect of biogenic carbonate, which contains several tens of percent of Ca, generally creates negative trends in these ICs as a whole in the spaces of Ca and other elements, including REY. The differenc.

, a runner who demonstrates considerably less than 45?of knee flexion may

, a Pan-RAS-IN-1 chemical information runner who demonstrates MG-132MedChemExpress MG-132 considerably less than 45?of knee flexion may suggest reduced shock absorption, and intervention may be warranted. Some data exist suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj., a runner who demonstrates considerably less than 45?of knee flexion may suggest reduced shock absorption, and intervention may be warranted. Some data exist suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj.

Ampal CA1 subfield in individuals with MCI compared to NCI (Fig.

Ampal CA1 subfield in individuals with MCI compared to NCI (Fig. 4), which correlated with the subject’s Mini-Mental State Exam score (MMSE), but not with NFT Braak stage or apolipoprotein E (ApoE) status, a genetic risk factor for AD (Scheff et al., 2006). Unlike the outer molecular layer, CA1 receives input from the Schaffer collaterals arising from CA3 and not from the glutamatergic neurons of the Procyanidin B1MedChemExpress Procyanidin B1 entorhinal cortex, suggesting differential responses to synapse loss within the hippocampus based upon afferent innervation or chemical phenotype, some of which precipitate synaptic reorganization. A recent report characterized changes in the dendritic branching of the basilar tree of hippocampal CA1 pyramidal neurons. In this study, formalin-fixed tissue autopsy obtained from University of Kentucky Alzheimer’s Disease Center who died with a clinical diagnosis of NCI, MCI or AD was prepared for Golgi impregnation (Fig. 5). Camera lucida drawings of the basilar tree of randomly selected CA1 neurons were analyzed for alterations in dendritic arbor amount, distribution and complexity (Mervis et al., 2013). Quantitation showed a significant increase in dendritic length (18 ) and complexity (23 ) in CA1 neurons in MCI compared to NCI. Conversely, there was a significant reduction in branch length (-39 ) and arbor complexity (-25 ) during the progression from MCI to AD (Fig. 5). These findings suggest that the observed increase in CA1 dendritic parameters from NCI to MCI may be another example of a Enzastaurin web neuroplastic compensatory response to a loss of afferent input early in the course of the disease, which is not maintained as the disease progresses. The role that the reported reduction in total synapse number plays in CA1 neuroplasticity remains unknown. However, these examples of early CA1 neural reorganization may represent a viable window for potential therapeutic strategies aimed at restoring or maintaining hippocampal function during the transition from MCI to AD. Future studies should determine whether alterations in specific synapse subtypes (i.e., perforated vs. non-perforated) are differentially affected and their relation to cognitive decline and brain pathology during the onset of AD. Interestingly, the size of the synaptic contacts was found to be substantially larger in AD cortex compared to non-demented aged controls (Scheff et al., 1990), which was suggested to be part of a compensatory mechanism found in regions of the neocortex and hippocampus (see review Scheff and Price, 2006). These investigators found that as the number of synapses declined in a given region, the size of the residualAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagesynapses increased. This synaptic compensatory response was also observed early in the course of the AD (DeKosky and Scheff, 1990). Neuronal structural alterations may not be the only factor(s) contributing to cognitive decline and hippocampal plasticity in MCI. For example, studies have reported significant reductions in synaptic vesicle trafficking-related genes in the AD brain, which interrupt the efficacy of normal synaptic transmission (Yao et al., 2003; Murphy et al., 2003; Kennedy et al., 2005). Counts et al. (2014) examined progressive changes in the expression classes of synaptic gene within single CA1 neurons in subjects who died with a clinical diagnosis of NCI, MCI or moderate AD obtain.Ampal CA1 subfield in individuals with MCI compared to NCI (Fig. 4), which correlated with the subject’s Mini-Mental State Exam score (MMSE), but not with NFT Braak stage or apolipoprotein E (ApoE) status, a genetic risk factor for AD (Scheff et al., 2006). Unlike the outer molecular layer, CA1 receives input from the Schaffer collaterals arising from CA3 and not from the glutamatergic neurons of the entorhinal cortex, suggesting differential responses to synapse loss within the hippocampus based upon afferent innervation or chemical phenotype, some of which precipitate synaptic reorganization. A recent report characterized changes in the dendritic branching of the basilar tree of hippocampal CA1 pyramidal neurons. In this study, formalin-fixed tissue autopsy obtained from University of Kentucky Alzheimer’s Disease Center who died with a clinical diagnosis of NCI, MCI or AD was prepared for Golgi impregnation (Fig. 5). Camera lucida drawings of the basilar tree of randomly selected CA1 neurons were analyzed for alterations in dendritic arbor amount, distribution and complexity (Mervis et al., 2013). Quantitation showed a significant increase in dendritic length (18 ) and complexity (23 ) in CA1 neurons in MCI compared to NCI. Conversely, there was a significant reduction in branch length (-39 ) and arbor complexity (-25 ) during the progression from MCI to AD (Fig. 5). These findings suggest that the observed increase in CA1 dendritic parameters from NCI to MCI may be another example of a neuroplastic compensatory response to a loss of afferent input early in the course of the disease, which is not maintained as the disease progresses. The role that the reported reduction in total synapse number plays in CA1 neuroplasticity remains unknown. However, these examples of early CA1 neural reorganization may represent a viable window for potential therapeutic strategies aimed at restoring or maintaining hippocampal function during the transition from MCI to AD. Future studies should determine whether alterations in specific synapse subtypes (i.e., perforated vs. non-perforated) are differentially affected and their relation to cognitive decline and brain pathology during the onset of AD. Interestingly, the size of the synaptic contacts was found to be substantially larger in AD cortex compared to non-demented aged controls (Scheff et al., 1990), which was suggested to be part of a compensatory mechanism found in regions of the neocortex and hippocampus (see review Scheff and Price, 2006). These investigators found that as the number of synapses declined in a given region, the size of the residualAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagesynapses increased. This synaptic compensatory response was also observed early in the course of the AD (DeKosky and Scheff, 1990). Neuronal structural alterations may not be the only factor(s) contributing to cognitive decline and hippocampal plasticity in MCI. For example, studies have reported significant reductions in synaptic vesicle trafficking-related genes in the AD brain, which interrupt the efficacy of normal synaptic transmission (Yao et al., 2003; Murphy et al., 2003; Kennedy et al., 2005). Counts et al. (2014) examined progressive changes in the expression classes of synaptic gene within single CA1 neurons in subjects who died with a clinical diagnosis of NCI, MCI or moderate AD obtain.

Monly used and widely available OTC medications and nutritional supplements were

Monly used and widely available OTC medications and nutritional supplements were safe and posed no short- or long-term threat to their health. Many used such products to improve their running performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make Dihexa cost correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product recommended as an effective and legal substance by another runner or by a retail sales clerk may contain substances that are either banned by agencies such as WADA and/or may pose a serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.BAY1217389 web NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.Monly used and widely available OTC medications and nutritional supplements were safe and posed no short- or long-term threat to their health. Many used such products to improve their running performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product recommended as an effective and legal substance by another runner or by a retail sales clerk may contain substances that are either banned by agencies such as WADA and/or may pose a serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.

Deration when interpreting experimental findings. (i) Identification of a mutation in

Deration when interpreting experimental findings. (i) Identification of a mutation in a clonal population does not indicate causality Any mutation in a cell that undergoes clonal expansion will be passed onto progeny, irrespective of functional status (Fig. 3A,B). Given the size of the genome, more mutations carried by a neoplastic clone will be Zebularine chemical information passengers than drivers [27, 29, 30]. To demonstrate driver status, supporting functional studies and/or repeated observations of a mutated loci in neoplastic clones from independent individuals are needed. (ii) Mutational marking of a clone is stochastic and not guaranteed A clone may exist and not be detected if none of the genomic sites being screened carry a unique mutation permitting it to be distinguished from the germline (Fig. 3C). The more sites examined, the higher the probability of detection becomes. Restricting a marker panel to suspected driver sites precludes detection of pathological clones driven by unknown factors. (iii) Elevated mutation rates facilitate clone detection but are not an absolute requirement Screening of mutational hotspots makes it practical with conventional technologies to have a reasonable probability of detecting a clone by random passenger mutations. Clones derived from a mutator lineage or cells residing in a highly mutagenic environment should be more densely marked with identifiable passengers (Fig. 3D), potentially reducing the number of markers needing to be interrogated to identify them. Emerging high-throughput sequencing technologies will eventually obviate the need to restrict screening to a fraction of the genome. (iv) Identification of one or more clonal mutations is not proof of genetic instability in the absence of collateral information Detection of a mutation requires clonal expansion with most traditional methods of aggregate DNA analysis. The probability of identifying clonal mutations in an expanded population is a function of the number of sites screened, the mutability of these sites and the number of cell divisions having purchase 4-Deoxyuridine occurred in the lineage leading up to the final expansion. Particularly when considering hotspots, mutations will be occasionally detectable in any clonally-derived population at a statistically definable frequency. Because mutations are not routinely encountered in normal tissues, it is tempting to explain their presence in preneoplastic populations as the result of “genetic instability” (an elevated mutation rate). However, the phenomenon is more precisely explained by the fact that expansion does not routinely occur in most normal tissues. An elevated mutation rate itself will have no observable effect on clonal mutation frequency in the absence of expansion (Fig. 3E). To determine mutation rate from a clonal mutation frequency it is necessary to (A) know that the population being assessed is clonal and (B) have some metric of the number of cell divisions that occurred in the period between the zygote and the founding of the final clonalSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPageoutgrowth. To infer that a rate is elevated, it is also necessary to know the normal in vivo mutation rate, which is, in turn, impossible to measure by this approach given that large clonal expansions do not routinely occur in normal adult tissue. Considering these complexities, the lack of resolution as to whether mutation rates are elevated in cancer is not surprising [1,8?1]. (v) Detectabili.Deration when interpreting experimental findings. (i) Identification of a mutation in a clonal population does not indicate causality Any mutation in a cell that undergoes clonal expansion will be passed onto progeny, irrespective of functional status (Fig. 3A,B). Given the size of the genome, more mutations carried by a neoplastic clone will be passengers than drivers [27, 29, 30]. To demonstrate driver status, supporting functional studies and/or repeated observations of a mutated loci in neoplastic clones from independent individuals are needed. (ii) Mutational marking of a clone is stochastic and not guaranteed A clone may exist and not be detected if none of the genomic sites being screened carry a unique mutation permitting it to be distinguished from the germline (Fig. 3C). The more sites examined, the higher the probability of detection becomes. Restricting a marker panel to suspected driver sites precludes detection of pathological clones driven by unknown factors. (iii) Elevated mutation rates facilitate clone detection but are not an absolute requirement Screening of mutational hotspots makes it practical with conventional technologies to have a reasonable probability of detecting a clone by random passenger mutations. Clones derived from a mutator lineage or cells residing in a highly mutagenic environment should be more densely marked with identifiable passengers (Fig. 3D), potentially reducing the number of markers needing to be interrogated to identify them. Emerging high-throughput sequencing technologies will eventually obviate the need to restrict screening to a fraction of the genome. (iv) Identification of one or more clonal mutations is not proof of genetic instability in the absence of collateral information Detection of a mutation requires clonal expansion with most traditional methods of aggregate DNA analysis. The probability of identifying clonal mutations in an expanded population is a function of the number of sites screened, the mutability of these sites and the number of cell divisions having occurred in the lineage leading up to the final expansion. Particularly when considering hotspots, mutations will be occasionally detectable in any clonally-derived population at a statistically definable frequency. Because mutations are not routinely encountered in normal tissues, it is tempting to explain their presence in preneoplastic populations as the result of “genetic instability” (an elevated mutation rate). However, the phenomenon is more precisely explained by the fact that expansion does not routinely occur in most normal tissues. An elevated mutation rate itself will have no observable effect on clonal mutation frequency in the absence of expansion (Fig. 3E). To determine mutation rate from a clonal mutation frequency it is necessary to (A) know that the population being assessed is clonal and (B) have some metric of the number of cell divisions that occurred in the period between the zygote and the founding of the final clonalSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPageoutgrowth. To infer that a rate is elevated, it is also necessary to know the normal in vivo mutation rate, which is, in turn, impossible to measure by this approach given that large clonal expansions do not routinely occur in normal adult tissue. Considering these complexities, the lack of resolution as to whether mutation rates are elevated in cancer is not surprising [1,8?1]. (v) Detectabili.

. This exploratory analysis can provide further information on functional similarities between

. This exploratory analysis can provide further information on functional similarities BEZ235 chemical information between regions, and, more specifically, on the extent to which activation profiles of category-selective regions are inherited from EVC. As for the replicability of within-category ranking (Fig. 5), we combined data across subjects either by JWH-133 web concatenating or averaging the activation profiles across subjects. The concatenation approach is sensitive to inter-region correlations of activation profiles even if the particular activation profiles differ across subjects. The averaging approach is sensitive to inter-region correlations of activation profiles that are consistent across subjects. We investigated the inter-region correlations for (1) the full activation profile, (2) the within-face activation profile, and (3) the withinplace activation profile. Statistical inference was performed by a standard one-sided test on Spearman’s r. p values were corrected8658 ?J. Neurosci., June 20, 2012 ?32(25):8649 ?Mur et al. ?Single-Image Activation of Category Regionsfor multiple testing using Bonferroni correction based on the total number of tests performed. Figure 7 shows the inter-region correlation results. The main pattern that emerges is that activation profiles are correlated between hemispheres for corresponding regions, and between hIT and EVC (red blocks on diagonals). We subsequently inspected the within-face correlation between FFA and EVC, and the within-place correlation between PPA and EVC. The within-face activation profile was correlated between left but not right FFA and EVC, and the within-place activation profile was not significantly correlated between PPA and EVC. Results were similar across ROI sizes. These results suggest that EVC is not a major contributor to the within-category activation profiles of PPA and right FFA. We then inspected the correlation between category-selective regions (FFA/PPA) and EVC for the full activation profile (top row). The full activation profile was correlated between EVC and both categoryselective regions, especially PPA. One interpretation of this finding would be that some degree of category selectivity is already present at the level of EVC, implying that low-level feature differences contribute to some extent to categoryselective responses. For places, this seems a plausible interpretation, consistent with our finding that single-image activation of EVC can discriminate places from nonplaces at an above-chance level (Fig. 2). For faces, this interpretation seems less likely: the correlation between EVC and FFA is not significant for the subjectaverage activation profile, suggesting that the correlation is driven by subjectspecific effects (e.g., idiosyncratic arousal effects) and not by face-selectivity of responses (shared across subjects in FFA). Categorical, yet graded Figure 8 summarizes our results. Singleimage activation profiles of categoryselective regions (1) show near-perfect discrimination of preferred from nonpreferred images and no preference inversions for particular object images, (2) show a step-like drop-off at the category boundary, and (3) are graded within and outside the preferred category. It can further be noted that single-image category selectivity is stronger in right than left FFA. In addition, gradedness seems to be more pronounced in FFA; the category step seems to be more pronounced in PPA. In sum, our findings indicate that the activation profiles of category-selec-Figure.. This exploratory analysis can provide further information on functional similarities between regions, and, more specifically, on the extent to which activation profiles of category-selective regions are inherited from EVC. As for the replicability of within-category ranking (Fig. 5), we combined data across subjects either by concatenating or averaging the activation profiles across subjects. The concatenation approach is sensitive to inter-region correlations of activation profiles even if the particular activation profiles differ across subjects. The averaging approach is sensitive to inter-region correlations of activation profiles that are consistent across subjects. We investigated the inter-region correlations for (1) the full activation profile, (2) the within-face activation profile, and (3) the withinplace activation profile. Statistical inference was performed by a standard one-sided test on Spearman’s r. p values were corrected8658 ?J. Neurosci., June 20, 2012 ?32(25):8649 ?Mur et al. ?Single-Image Activation of Category Regionsfor multiple testing using Bonferroni correction based on the total number of tests performed. Figure 7 shows the inter-region correlation results. The main pattern that emerges is that activation profiles are correlated between hemispheres for corresponding regions, and between hIT and EVC (red blocks on diagonals). We subsequently inspected the within-face correlation between FFA and EVC, and the within-place correlation between PPA and EVC. The within-face activation profile was correlated between left but not right FFA and EVC, and the within-place activation profile was not significantly correlated between PPA and EVC. Results were similar across ROI sizes. These results suggest that EVC is not a major contributor to the within-category activation profiles of PPA and right FFA. We then inspected the correlation between category-selective regions (FFA/PPA) and EVC for the full activation profile (top row). The full activation profile was correlated between EVC and both categoryselective regions, especially PPA. One interpretation of this finding would be that some degree of category selectivity is already present at the level of EVC, implying that low-level feature differences contribute to some extent to categoryselective responses. For places, this seems a plausible interpretation, consistent with our finding that single-image activation of EVC can discriminate places from nonplaces at an above-chance level (Fig. 2). For faces, this interpretation seems less likely: the correlation between EVC and FFA is not significant for the subjectaverage activation profile, suggesting that the correlation is driven by subjectspecific effects (e.g., idiosyncratic arousal effects) and not by face-selectivity of responses (shared across subjects in FFA). Categorical, yet graded Figure 8 summarizes our results. Singleimage activation profiles of categoryselective regions (1) show near-perfect discrimination of preferred from nonpreferred images and no preference inversions for particular object images, (2) show a step-like drop-off at the category boundary, and (3) are graded within and outside the preferred category. It can further be noted that single-image category selectivity is stronger in right than left FFA. In addition, gradedness seems to be more pronounced in FFA; the category step seems to be more pronounced in PPA. In sum, our findings indicate that the activation profiles of category-selec-Figure.

Items each represented 16 different topics that received high engagement in just

Items each Nutlin (3a) biological activity represented 16 different topics that received high engagement in just one platform (hereafter: “unique” high-engagement items). These data RG7666 web indicate an association between high engagement and item topic (2(47) = 80.054, n = 214, p < 0.01, Cramer’s V = 0.612).PLOS ONE | DOI:10.1371/journal.pone.0156409 May 27,13 /Engagement with Particle Physics on CERN’s Social Media PlatformsTable 8. Recurring high engagement topics. Recurring High Engagement Topic Code 1. 2. 3. 4. 5. 6. Fabiola Open Data Pipes 1st Computer CMS Dishwasher Type News News Guess What It Is Throwback Thursday Wow Wow Image Caption “CERN Council selects Italian physicist, Dr Fabiola Gianotti, as CERN’s next Director-General” “CERN launches Open Data Portal to make public the data of LHC experiments” “CERN’s cooling ventilation systems get refreshed” “The Ferranti Mercury, CERN’s 1st ‘central’ computer” “The LHC’s Compact Muon Solenoid (CMS) detector” “That’s right, a CERN dishwasher for circuit boards” Recurred as High Engagement Item on. . . Facebook, Twitter English, Twitter French Facebook, Google+, Twitter English, Twitter French Google+, Twitter French Facebook, Twitter English Instagram, Twitter English, Twitter French Facebook, Google+, Instagram, Twitter English, Twitter Frenchdoi:10.1371/journal.pone.0156409.tSome characteristics of the high-engagement topics are that they may have referred to (1) news items receiving attention from traditional media (e.g. the “Fabiola” topic), or (2) a surprising or awe-inspiring image (e.g. “CMS”, “Dishwasher” and “Pipes”) (Table 8).Research LimitationsThe main methodological limitation in this study stems from the architecture of the platforms. The items posted were not necessarily seen by all CERN’s subscribers. The “organic reach” is determined by the technical settings of the platforms, and may be affected by many different variables. For example, one study found that organic reach increases on a given Facebook item if another item was posted on the platform the day before [30]. The results are based on data collected from October to December 2014, however changes may have occurred since then at multiple levels: from the CERN social media strategy and behaviour, to the architecture of the platforms, as well as the audiences, their preferences and the general online communication landscape. Concerning CERN’s strategy and posting behaviour, this has remained consistent with the data-taking period. However, platform architectures are regularly changed and updated. Since our findings indicate that the platform itself influences user behaviour, it follows that changes in the platform may have an effect. For example, Twitter has implemented a new feed algorithm [43]. Google+ has been fully redesigned [44]. Facebook have not only changed the way that content from pages are delivered to the audience [45], they are also placing more and more emphasis on video content, particularly live or immersive videos, over other types of content [46]. One recent Facebook update now allows people to express their feelings as “reactions” to the information published [47]. These changes call for more elaborate future research in this topic, with fine-tuned analysis that looks at both the comments and the reaction icons. The online communication landscape in general has become more mobile, with some audiences shifting to other social media platforms such as Snapchat. Notwithstanding the dynamics of this field, our systematic study still.Items each represented 16 different topics that received high engagement in just one platform (hereafter: “unique” high-engagement items). These data indicate an association between high engagement and item topic (2(47) = 80.054, n = 214, p < 0.01, Cramer’s V = 0.612).PLOS ONE | DOI:10.1371/journal.pone.0156409 May 27,13 /Engagement with Particle Physics on CERN’s Social Media PlatformsTable 8. Recurring high engagement topics. Recurring High Engagement Topic Code 1. 2. 3. 4. 5. 6. Fabiola Open Data Pipes 1st Computer CMS Dishwasher Type News News Guess What It Is Throwback Thursday Wow Wow Image Caption “CERN Council selects Italian physicist, Dr Fabiola Gianotti, as CERN’s next Director-General” “CERN launches Open Data Portal to make public the data of LHC experiments” “CERN’s cooling ventilation systems get refreshed” “The Ferranti Mercury, CERN’s 1st ‘central’ computer” “The LHC’s Compact Muon Solenoid (CMS) detector” “That’s right, a CERN dishwasher for circuit boards” Recurred as High Engagement Item on. . . Facebook, Twitter English, Twitter French Facebook, Google+, Twitter English, Twitter French Google+, Twitter French Facebook, Twitter English Instagram, Twitter English, Twitter French Facebook, Google+, Instagram, Twitter English, Twitter Frenchdoi:10.1371/journal.pone.0156409.tSome characteristics of the high-engagement topics are that they may have referred to (1) news items receiving attention from traditional media (e.g. the “Fabiola” topic), or (2) a surprising or awe-inspiring image (e.g. “CMS”, “Dishwasher” and “Pipes”) (Table 8).Research LimitationsThe main methodological limitation in this study stems from the architecture of the platforms. The items posted were not necessarily seen by all CERN’s subscribers. The “organic reach” is determined by the technical settings of the platforms, and may be affected by many different variables. For example, one study found that organic reach increases on a given Facebook item if another item was posted on the platform the day before [30]. The results are based on data collected from October to December 2014, however changes may have occurred since then at multiple levels: from the CERN social media strategy and behaviour, to the architecture of the platforms, as well as the audiences, their preferences and the general online communication landscape. Concerning CERN’s strategy and posting behaviour, this has remained consistent with the data-taking period. However, platform architectures are regularly changed and updated. Since our findings indicate that the platform itself influences user behaviour, it follows that changes in the platform may have an effect. For example, Twitter has implemented a new feed algorithm [43]. Google+ has been fully redesigned [44]. Facebook have not only changed the way that content from pages are delivered to the audience [45], they are also placing more and more emphasis on video content, particularly live or immersive videos, over other types of content [46]. One recent Facebook update now allows people to express their feelings as “reactions” to the information published [47]. These changes call for more elaborate future research in this topic, with fine-tuned analysis that looks at both the comments and the reaction icons. The online communication landscape in general has become more mobile, with some audiences shifting to other social media platforms such as Snapchat. Notwithstanding the dynamics of this field, our systematic study still.

Taking turns at doing X and in parallel trading X for

Taking turns at doing X and in parallel trading X for Y. This may correspond to a relationship evolving with time from one RM to the other. The generalization of our model to N SP600125 cost PX-478 msds social actions, presented in the next section, helps represent any familiar composite relationship.PLOS ONE | DOI:10.1371/journal.pone.0120882 March 31,9 /A Generic Model of Dyadic Social RelationshipsGeneralization to N social actionsIn real social relationships, the number of occurring social actions is expected to be larger than two, which motivates the generalization of our results to any number N of social actions. This is our third result. For the generalization that follows, we let X and Y be elements of a larger set S of N social actions Si: S = Siji = 1,. . .,N, such that X,Y 2 S, for instance S1 X and S2 Y. Proposition 2: In the general case of N non-null social actions (S1,S2, . . . ,SN 2 S, N ! 2), one still needs exactly the six categories of Table 3 to describe all possible relationships arising ! from the setting A B. S =S =:::=S =;1 2 NS1 =S2 =:::=SN =;Idea of the proof: We show that the proof of exhaustiveness of the six categories of Table 3 carried out for N = 2 holds for any N ! 2. Namely, the same process allows to build the same six mutually disjoint categories of action fluxes, and these categories span the relationship space for any N ! 2. Proof: In the general case of N ! 2 non-null social actions, there are 2N+1 elementary inter2 actions and 2(N+1) -1 relationships. S1 �S2 ! Cases such as A B (where A performs several actions simultaneously) can be writtenSA ! B (where S4 is a bundle of actions). More generally, any number of actions can be bundled SSas in that example. Starting from a set of N social actions, the set S can include all subsets of that set. (The cardinality of S is then 2N.) Hence, any union of two or more subsets (such as S1 and S2 to give S4) gives another subset that is an element of S. Then, because there are still two agents and thus at most two different social actions per elementary interaction, the elementary interactions have the same forms as for N = 2, with additional notations for the social actions. As an illustration, Table 4 shows the sixteen elementary interactions that result from the ! case N = 3, i.e. the model A B. X=Y=Z=; For any N ! 2, looking at an elementary interaction between two individuals, one can still only differentiate between (i) identical or different actions, (ii) interchangeable or non-interchangeable roles, (iii) null or non-null actions. Hence, with more than two actions, this differentiation process leads to the same six disjoint categories, except with more alternative notations than in Table 3. For example, for N = 3, category 1 (EM) gets one more alternative notation than for N = 2, Z Z Z namely A ! B. Category 3 (MP) gets two alternative notations: [A ! B and A ! B], andZ X X X=Y=Z=;Table 4. Sixteen elementary interactions for N = 3 social actions. A!B X A!B X A!B X AX Z Y XA!B Y A!B Y A!B Y AY Z YXA!B Z A!B Z A!B Z AZ Z YXX A! B Y A! B Z A! BBBBA !B ;;This table shows the sixteen elementary interactions arising from our model with N = 3 non-null social ! actions X,Y,Z between two agents A and B, that is, A B. We use simplified notations for theX=Y=Z=; X=Y=Z=;interactions involving one empty flux. doi:10.1371/journal.pone.0120882.tPLOS ONE | DOI:10.1371/journal.pone.0120882 March 31,10 /A Generic Model of Dyadic Social Relationships[A ! B and A ! B]. Category 4 (AR) gets f.Taking turns at doing X and in parallel trading X for Y. This may correspond to a relationship evolving with time from one RM to the other. The generalization of our model to N social actions, presented in the next section, helps represent any familiar composite relationship.PLOS ONE | DOI:10.1371/journal.pone.0120882 March 31,9 /A Generic Model of Dyadic Social RelationshipsGeneralization to N social actionsIn real social relationships, the number of occurring social actions is expected to be larger than two, which motivates the generalization of our results to any number N of social actions. This is our third result. For the generalization that follows, we let X and Y be elements of a larger set S of N social actions Si: S = Siji = 1,. . .,N, such that X,Y 2 S, for instance S1 X and S2 Y. Proposition 2: In the general case of N non-null social actions (S1,S2, . . . ,SN 2 S, N ! 2), one still needs exactly the six categories of Table 3 to describe all possible relationships arising ! from the setting A B. S =S =:::=S =;1 2 NS1 =S2 =:::=SN =;Idea of the proof: We show that the proof of exhaustiveness of the six categories of Table 3 carried out for N = 2 holds for any N ! 2. Namely, the same process allows to build the same six mutually disjoint categories of action fluxes, and these categories span the relationship space for any N ! 2. Proof: In the general case of N ! 2 non-null social actions, there are 2N+1 elementary inter2 actions and 2(N+1) -1 relationships. S1 �S2 ! Cases such as A B (where A performs several actions simultaneously) can be writtenSA ! B (where S4 is a bundle of actions). More generally, any number of actions can be bundled SSas in that example. Starting from a set of N social actions, the set S can include all subsets of that set. (The cardinality of S is then 2N.) Hence, any union of two or more subsets (such as S1 and S2 to give S4) gives another subset that is an element of S. Then, because there are still two agents and thus at most two different social actions per elementary interaction, the elementary interactions have the same forms as for N = 2, with additional notations for the social actions. As an illustration, Table 4 shows the sixteen elementary interactions that result from the ! case N = 3, i.e. the model A B. X=Y=Z=; For any N ! 2, looking at an elementary interaction between two individuals, one can still only differentiate between (i) identical or different actions, (ii) interchangeable or non-interchangeable roles, (iii) null or non-null actions. Hence, with more than two actions, this differentiation process leads to the same six disjoint categories, except with more alternative notations than in Table 3. For example, for N = 3, category 1 (EM) gets one more alternative notation than for N = 2, Z Z Z namely A ! B. Category 3 (MP) gets two alternative notations: [A ! B and A ! B], andZ X X X=Y=Z=;Table 4. Sixteen elementary interactions for N = 3 social actions. A!B X A!B X A!B X AX Z Y XA!B Y A!B Y A!B Y AY Z YXA!B Z A!B Z A!B Z AZ Z YXX A! B Y A! B Z A! BBBBA !B ;;This table shows the sixteen elementary interactions arising from our model with N = 3 non-null social ! actions X,Y,Z between two agents A and B, that is, A B. We use simplified notations for theX=Y=Z=; X=Y=Z=;interactions involving one empty flux. doi:10.1371/journal.pone.0120882.tPLOS ONE | DOI:10.1371/journal.pone.0120882 March 31,10 /A Generic Model of Dyadic Social Relationships[A ! B and A ! B]. Category 4 (AR) gets f.

Are a useful method for gaining insight into phenomena where little

Are a useful method for gaining insight into phenomena where little is known [44]. When focus group data has been collected from multiple groups and multiple sites, researchers can have increased confidence in the reliability and validity of the findings [45]. The focus groups were guided by following questions. (1) Perceptions of Professional Socialization. (a) What comes to mind when you hear the phrase “professional socialization”? (b) Share memories of your experiences becoming socialized into the role of Licensed Practical Nurse and developing your identity in this role. (c) How is the experience of developing your new role and identity as a Registered Nurse the same? How is it different? (2) Formal Academic Experiences: Online Classes and Clinical Practicums. (a) Talk about experiences you have had so far in your online university classes where you “felt like” a Registered Nurse and not a Licensed Practical Nurse? Have there been times in your online4 [54] (page 85) maintained by both moderators during and immediately following the sessions buy L-660711 sodium salt further increased the dependability of our findings. Practical issues such as organizing groups at a time and place to minimize disruption and avoiding power differential dynamics [55] were addressed. The groups were held when participants, who were normally separated by distance, were together in the same city for a required practicum experience. They were held at change of shift in lieu of a post conference. Knowing the power differential between students and teachers, moderators who did not have teaching responsibilities in the Post LPN to BN program were chosen to facilitate the focus groups. Instructors were not present during any of the discussions and had no involvement with the transcript data. Participants were recruited through a Letter of Invitation sent via email by a Research Assistant who was also not involved with the program. Four focus groups were held with 5 to 9 participants each. All the students who were invited chose to participate. We reasoned that this may have been because they were all from out of town and appreciated an opportunity to interact and share their views. Pseudonyms ensured participant confidentiality. Full ethical approval was granted by the university. The following two overarching themes emerged from analyzing the data. First, Post LPN to BN students need little, if any, further legitimation to affirm their identities as “nurse.” Second, practicum interactions with instructors and new clinical experiences are key socializing agents.Nursing Research and Practice They talked about opportunities where demonstrating professional authority in their workplace further established their identity as “nurse”: “Working your first night shift . . . in your new role. The culture of night shift–it’s different.” “The first time I cared for a palliative patient and was there when they passed. Talking with the family. My first job that I had as an LPN, I was alone on the floor as the only official nurse for more than half of my shift. I had the full responsibility of all 60 residents in my care . . . that all happened as an LPN.” From the Post LPN to BN students’ AC220 supplement perspective, the notion that socialization into the role of “nurse” would occur for them at this point in their career was insulting: “I almost feel a little bit insulted to think that I would feel any less professional as an LPN than I do as an RN. I feel equally professional in both roles.” “My buddy nurse ac.Are a useful method for gaining insight into phenomena where little is known [44]. When focus group data has been collected from multiple groups and multiple sites, researchers can have increased confidence in the reliability and validity of the findings [45]. The focus groups were guided by following questions. (1) Perceptions of Professional Socialization. (a) What comes to mind when you hear the phrase “professional socialization”? (b) Share memories of your experiences becoming socialized into the role of Licensed Practical Nurse and developing your identity in this role. (c) How is the experience of developing your new role and identity as a Registered Nurse the same? How is it different? (2) Formal Academic Experiences: Online Classes and Clinical Practicums. (a) Talk about experiences you have had so far in your online university classes where you “felt like” a Registered Nurse and not a Licensed Practical Nurse? Have there been times in your online4 [54] (page 85) maintained by both moderators during and immediately following the sessions further increased the dependability of our findings. Practical issues such as organizing groups at a time and place to minimize disruption and avoiding power differential dynamics [55] were addressed. The groups were held when participants, who were normally separated by distance, were together in the same city for a required practicum experience. They were held at change of shift in lieu of a post conference. Knowing the power differential between students and teachers, moderators who did not have teaching responsibilities in the Post LPN to BN program were chosen to facilitate the focus groups. Instructors were not present during any of the discussions and had no involvement with the transcript data. Participants were recruited through a Letter of Invitation sent via email by a Research Assistant who was also not involved with the program. Four focus groups were held with 5 to 9 participants each. All the students who were invited chose to participate. We reasoned that this may have been because they were all from out of town and appreciated an opportunity to interact and share their views. Pseudonyms ensured participant confidentiality. Full ethical approval was granted by the university. The following two overarching themes emerged from analyzing the data. First, Post LPN to BN students need little, if any, further legitimation to affirm their identities as “nurse.” Second, practicum interactions with instructors and new clinical experiences are key socializing agents.Nursing Research and Practice They talked about opportunities where demonstrating professional authority in their workplace further established their identity as “nurse”: “Working your first night shift . . . in your new role. The culture of night shift–it’s different.” “The first time I cared for a palliative patient and was there when they passed. Talking with the family. My first job that I had as an LPN, I was alone on the floor as the only official nurse for more than half of my shift. I had the full responsibility of all 60 residents in my care . . . that all happened as an LPN.” From the Post LPN to BN students’ perspective, the notion that socialization into the role of “nurse” would occur for them at this point in their career was insulting: “I almost feel a little bit insulted to think that I would feel any less professional as an LPN than I do as an RN. I feel equally professional in both roles.” “My buddy nurse ac.

In living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic

In living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic Necrosulfonamide web Ca-phosphate in pelagic sediments has long been studied by a number of investigators17,18,21?4,40?2. Some have suggested that biogenic Ca-phosphate incorporates REY via pore water in the sediment column23,40. Others have argued that Ca-phosphate takes up REY from a variety of carrier phases (e.g. Fe n-oxyhydroxides, pellets, and organic debris) that absorb REY from seawater and are readily decomposed at the sediment ater interface17,22,41,42. Although the complete process remains an open GW0742 web question, the characteristic REY patterns indicate that seawater is the ultimate source of the REY presently captured in biogenic Ca-phosphate22,25,41 (Fig. 4m). Simple quantitative estimation in this study suggested the possibility that seawater can contain the flux of REY precipitation required to explain the observed very high REY concentrations ( REY + Ce > 1,000 ppm) in bulk REY-rich mud with a sedimentation rate less than 0.5 m/Myr (Supplementary Fig. S19). Such circumstances may facilitate the concentration of REY in biogenic Ca-phosphate via diffusion of REY from seawater or the transfer of REY from original carriers to Ca-phosphate during the early diagenetic processes because of the prolonged exposure to seawater at the sediment surface and in the bioturbated and well-ventilated uppermost sediment layer17,18,22,41. In addition, biogenic Ca-phosphate enriched in REY might be stabilised through recrystallisation as insoluble apatite17. Moreover, the amount of Ca-phosphate in a unit volume of sediment also increases with a depression of the sedimentation rate17,18. Hence, the low sedimentation rate is considered to be crucial for the formation of REY-rich mud. Actually, the spatiotemporal distribution of high-IC1, -IC4, and -IC7 muds overlapped with the oligotrophic North Pacific and South Pacific gyres and with water depths greater than the CCD, both of which prevented the fast accumulation of dilutive components with low REY content such as biogenic carbonate and silica. If we assume that deep-sea sediments can continuously acquire REY from the overlying deep-sea water prior to burial, the REY-enrichment in sediments can occur in a time scale of 105 years considering the sedimentation rate of <0.5 m/Myr with a typical thickness of 0.1 m for the well-ventilated uppermost sediment layer43. This timescale of REY enrichment is significantly longer than that of global ocean circulation, which is 103 years44. Both IC1 and IC4 indicated statistical independent geochemical features of pelagic red clay mainly composed of detrital aluminosilicates involving abundant Si, Al, Fe, Mg, and K without significant contributions of biogenic carbonate and silica. Fe and Mn of hydrothermal or hydrogenous origins could have also been incorporated without dilution in high-IC1 and high-IC4 sediments, resulting in an increase in the contents of these elements. In addition, in deposition slow enough to allow biogenic Ca-phosphate grains to concentrate REY and to accumulate significantly in the sediment, the P and REY contents of these sediments also increase concurrently. Although sediments enriched in biogenic Ca-phosphate contain several percent of Ca, the significant dilution effect of biogenic carbonate, which contains several tens of percent of Ca, generally creates negative trends in these ICs as a whole in the spaces of Ca and other elements, including REY. The differenc.In living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic Ca-phosphate in pelagic sediments has long been studied by a number of investigators17,18,21?4,40?2. Some have suggested that biogenic Ca-phosphate incorporates REY via pore water in the sediment column23,40. Others have argued that Ca-phosphate takes up REY from a variety of carrier phases (e.g. Fe n-oxyhydroxides, pellets, and organic debris) that absorb REY from seawater and are readily decomposed at the sediment ater interface17,22,41,42. Although the complete process remains an open question, the characteristic REY patterns indicate that seawater is the ultimate source of the REY presently captured in biogenic Ca-phosphate22,25,41 (Fig. 4m). Simple quantitative estimation in this study suggested the possibility that seawater can contain the flux of REY precipitation required to explain the observed very high REY concentrations ( REY + Ce > 1,000 ppm) in bulk REY-rich mud with a sedimentation rate less than 0.5 m/Myr (Supplementary Fig. S19). Such circumstances may facilitate the concentration of REY in biogenic Ca-phosphate via diffusion of REY from seawater or the transfer of REY from original carriers to Ca-phosphate during the early diagenetic processes because of the prolonged exposure to seawater at the sediment surface and in the bioturbated and well-ventilated uppermost sediment layer17,18,22,41. In addition, biogenic Ca-phosphate enriched in REY might be stabilised through recrystallisation as insoluble apatite17. Moreover, the amount of Ca-phosphate in a unit volume of sediment also increases with a depression of the sedimentation rate17,18. Hence, the low sedimentation rate is considered to be crucial for the formation of REY-rich mud. Actually, the spatiotemporal distribution of high-IC1, -IC4, and -IC7 muds overlapped with the oligotrophic North Pacific and South Pacific gyres and with water depths greater than the CCD, both of which prevented the fast accumulation of dilutive components with low REY content such as biogenic carbonate and silica. If we assume that deep-sea sediments can continuously acquire REY from the overlying deep-sea water prior to burial, the REY-enrichment in sediments can occur in a time scale of 105 years considering the sedimentation rate of <0.5 m/Myr with a typical thickness of 0.1 m for the well-ventilated uppermost sediment layer43. This timescale of REY enrichment is significantly longer than that of global ocean circulation, which is 103 years44. Both IC1 and IC4 indicated statistical independent geochemical features of pelagic red clay mainly composed of detrital aluminosilicates involving abundant Si, Al, Fe, Mg, and K without significant contributions of biogenic carbonate and silica. Fe and Mn of hydrothermal or hydrogenous origins could have also been incorporated without dilution in high-IC1 and high-IC4 sediments, resulting in an increase in the contents of these elements. In addition, in deposition slow enough to allow biogenic Ca-phosphate grains to concentrate REY and to accumulate significantly in the sediment, the P and REY contents of these sediments also increase concurrently. Although sediments enriched in biogenic Ca-phosphate contain several percent of Ca, the significant dilution effect of biogenic carbonate, which contains several tens of percent of Ca, generally creates negative trends in these ICs as a whole in the spaces of Ca and other elements, including REY. The differenc.

T’s early journalistic style in terms of the conventions of

T’s early journalistic style in terms of the conventions of non-medical publishing.10 In particular, she is concerned to demonstrate how the relative success of the journal can be ascribed to Y-27632 chemical information Wakley’s importation of `entertaining formal components from lay periodicals’, most notably sections on society gossip, theatre reviews and chess puzzles, a contrivance which allowed The Lancet to `navigat[e] the space between general and specialist readers’.11 Though notable for its emphasis on style, Pladek’s account is not wholly satisfying; it is unspecific5 M. Bostetter, `The journalism of Thomas Wakley’ in J. H. Wiener (ed.), Innovators and Preachers: The Role of the Editor in Victorian England (London, 1985), 282. 6J. Loudon and I. Loudon, `Medicine, politics and the medical periodical, 1800 ?0′ in W. F. Bynum, S. Lock and R. Porter (eds), Medical Journals and Medical Knowledge: Historical Essays (London, 1992), 62. 7W. F. Bynum and J. C. Wilson, `Periodical knowledge: medical journals and their editors in nineteenth-century Britain’ in Bynum et al., Medical Journals, op. cit., 38. 8For example, see J. Bulcher, `The Cato Street Conspiracy’, The Lancet, 370: Supplement 1 (1 December 2007), 9 ?4; R. Jones, `Thomas Wakley, plagiarism, libel, and the founding ofThe Lancet’, The Lancet, 371:9622 (26 April 2008), 1410?11. In 1996 The Lancet even established an essay prize in Wakley’s name ?see The Lancet, 348:9022 (27 July 1996), 212. 9Loudon and Loudon, `Medicine, politics’, op. cit., 61; D. Harrison, `All The Lancet’s men: reactionary gentleman physicians vs. radical general practitioners in The Lancet, 1823 ?1832′, Nineteenth-Century Gender Studies, V , 2 (Summer 2009), available online at: http://ncgs journal.com/issue52/harrison.htm 10 B. Pladek, `”A variety of tastes”: The Lancet in the early nineteenth-century periodical press’, Bulletin of the History of Medicine, LXXXV , 4 (2011), 560?6. 11ibid., 560, 572.MayThe Lancet, libel and English medicineabout exactly what kinds of cultural work these literary devices were intended to perform and does not adequately explain why The Lancet’s circulation continued to rise even when they were discontinued after only two years. Moreover, while she alludes to the subject, she explicitly declines to focus on `the journal’s engagement with medical politics’ or its resonances with the broader conventions of radical journalism.12 As this article will demonstrate, however, the significance of The Lancet’s stylistic radicalism can only be fully comprehended by situating it within its immediate political context. Rather than viewing it as the template for modern medical journalism, or as PD168393 msds anticipating later styles of political and social commentary, it understands The Lancet as the product of an early nineteenth-century radical political heritage, as the Political Register or Black Dwarf of medicine. It seeks to extend and deepen the analytical project initiated by Desmond, Warner and Burney whereby the discourses of medical reform are considered in relation to those which sustained the cause of radical political sovereignty. Drawing upon the work of James Epstein, Kevin Gilmartin and others, it views The Lancet in terms of radical stylistics, demonstrating the extent to which it was framed by the literary conventions of the underground political press.13 It opens with a brief account of Wakley’s initiation into radical circles before considering the early editions of The Lancet, with a particular focus on the.T’s early journalistic style in terms of the conventions of non-medical publishing.10 In particular, she is concerned to demonstrate how the relative success of the journal can be ascribed to Wakley’s importation of `entertaining formal components from lay periodicals’, most notably sections on society gossip, theatre reviews and chess puzzles, a contrivance which allowed The Lancet to `navigat[e] the space between general and specialist readers’.11 Though notable for its emphasis on style, Pladek’s account is not wholly satisfying; it is unspecific5 M. Bostetter, `The journalism of Thomas Wakley’ in J. H. Wiener (ed.), Innovators and Preachers: The Role of the Editor in Victorian England (London, 1985), 282. 6J. Loudon and I. Loudon, `Medicine, politics and the medical periodical, 1800 ?0′ in W. F. Bynum, S. Lock and R. Porter (eds), Medical Journals and Medical Knowledge: Historical Essays (London, 1992), 62. 7W. F. Bynum and J. C. Wilson, `Periodical knowledge: medical journals and their editors in nineteenth-century Britain’ in Bynum et al., Medical Journals, op. cit., 38. 8For example, see J. Bulcher, `The Cato Street Conspiracy’, The Lancet, 370: Supplement 1 (1 December 2007), 9 ?4; R. Jones, `Thomas Wakley, plagiarism, libel, and the founding ofThe Lancet’, The Lancet, 371:9622 (26 April 2008), 1410?11. In 1996 The Lancet even established an essay prize in Wakley’s name ?see The Lancet, 348:9022 (27 July 1996), 212. 9Loudon and Loudon, `Medicine, politics’, op. cit., 61; D. Harrison, `All The Lancet’s men: reactionary gentleman physicians vs. radical general practitioners in The Lancet, 1823 ?1832′, Nineteenth-Century Gender Studies, V , 2 (Summer 2009), available online at: http://ncgs journal.com/issue52/harrison.htm 10 B. Pladek, `”A variety of tastes”: The Lancet in the early nineteenth-century periodical press’, Bulletin of the History of Medicine, LXXXV , 4 (2011), 560?6. 11ibid., 560, 572.MayThe Lancet, libel and English medicineabout exactly what kinds of cultural work these literary devices were intended to perform and does not adequately explain why The Lancet’s circulation continued to rise even when they were discontinued after only two years. Moreover, while she alludes to the subject, she explicitly declines to focus on `the journal’s engagement with medical politics’ or its resonances with the broader conventions of radical journalism.12 As this article will demonstrate, however, the significance of The Lancet’s stylistic radicalism can only be fully comprehended by situating it within its immediate political context. Rather than viewing it as the template for modern medical journalism, or as anticipating later styles of political and social commentary, it understands The Lancet as the product of an early nineteenth-century radical political heritage, as the Political Register or Black Dwarf of medicine. It seeks to extend and deepen the analytical project initiated by Desmond, Warner and Burney whereby the discourses of medical reform are considered in relation to those which sustained the cause of radical political sovereignty. Drawing upon the work of James Epstein, Kevin Gilmartin and others, it views The Lancet in terms of radical stylistics, demonstrating the extent to which it was framed by the literary conventions of the underground political press.13 It opens with a brief account of Wakley’s initiation into radical circles before considering the early editions of The Lancet, with a particular focus on the.

Ferent authors or the same authors in different conditions, are counted

Ferent authors or the same authors in different conditions, are counted only once, the number of different motors is approximately 265 (the uncertainty SB 203580 site arises from a few measurements in table 4 which were made on a mixture of distinct fibres or several muscles together).rsos.royalsocietypublishing.org R. Soc. open sci. 3:…………………………………………2.4. Other motor classificationsThe data were also analysed with respect to the structure of motors, their function and the taxonomic position of the organisms. For comparing structures, the original 13 types, from molecules to muscles, were aggregated in five Talmapimod site classes (M1, M2, FI, MU, MV) or two classes (molecular M1 + M2 and non-molecular) as defined above. In some figures and table 5, MF, for which the cross-section was indicated in the articles cited, was shown separately from the other M2 motors. The functional groups were defined by the contribution of the motor to the overall movement of their parent organism, the four basic categories being swimming (Swim), flying (Fly), moving with respect to a solid surface (terrestrial Terr) and no direct contribution to locomotion (non-loc). Examples of non-loc motors are RNA polymerase, cytoplasmic dynein, kinesin, F0 /F1 -ATPase and various muscular motors (heart, diaphragm, wing closer, gill pump, claw closer, larynx, eye). For taxonomic comparisons, groups 5 with number of f values less than 5 (protozoa, algae, fungi, echinoderms, arachnids) were excluded.2.5. Body massFinally, the tensions were analysed with respect to the mass M of the `body’ that the motor contributes to move. For molecular motors this is the mass of the cell from which the motor was extracted. When not reported, cell masses were estimated from other sources or calculated from the cell size. In nonmolecular motors, tensions were analysed with respect to the mass M of the corresponding animal. When not reported, body masses were also estimated from other sources. Note that as a consequence of these choices a different mass was used for a myosin molecule (molecular motor) and a muscle fibre (non-molecular motor) from the same organism. The organisms considered range in mass from the bacterium Escherichia coli (1.3 ?10-15 kg) to the muscular fibre (5 ?10-8 kg) for the cells, and from the mite Archegozetes longisetosus (10-7 kg) to the elephant (2500 kg) for the multicellular organisms. For both f and M, means of a series of equivalent measurements by the same author(s) were preferred when available. When only minimum and maximum values were given, we took their mean.2.6. StatisticsStatistical distributions were compared with the Kolmogorov mirnov test [194]. Multiple distributions were compared with the one-way analysis of variance (ANOVA) and corresponding multiple comparison of means using Tukey ramer adjustment. Slopes of least-square regressions of log10 (f ) versus log10 (M) were compared with 0 using the F test. Details of statistical analyses are given as the electronic supplementary material, tables S1 6 for ANOVA and multiple comparison of means and tables S7 12 for regressions. All tests were performed with the MATLAB STATISTICAL TOOLBOX (The Mathworks, Natick, USA).3. ResultsThe data have been analysed in terms of the maximum force per cross-sectional area f. We consider separately motors made of single molecules (denoted M1) and molecular assemblies (M2, MF) that we collectively call `molecular motors’, whereas the other motors, muscle fibres (FI.Ferent authors or the same authors in different conditions, are counted only once, the number of different motors is approximately 265 (the uncertainty arises from a few measurements in table 4 which were made on a mixture of distinct fibres or several muscles together).rsos.royalsocietypublishing.org R. Soc. open sci. 3:…………………………………………2.4. Other motor classificationsThe data were also analysed with respect to the structure of motors, their function and the taxonomic position of the organisms. For comparing structures, the original 13 types, from molecules to muscles, were aggregated in five classes (M1, M2, FI, MU, MV) or two classes (molecular M1 + M2 and non-molecular) as defined above. In some figures and table 5, MF, for which the cross-section was indicated in the articles cited, was shown separately from the other M2 motors. The functional groups were defined by the contribution of the motor to the overall movement of their parent organism, the four basic categories being swimming (Swim), flying (Fly), moving with respect to a solid surface (terrestrial Terr) and no direct contribution to locomotion (non-loc). Examples of non-loc motors are RNA polymerase, cytoplasmic dynein, kinesin, F0 /F1 -ATPase and various muscular motors (heart, diaphragm, wing closer, gill pump, claw closer, larynx, eye). For taxonomic comparisons, groups 5 with number of f values less than 5 (protozoa, algae, fungi, echinoderms, arachnids) were excluded.2.5. Body massFinally, the tensions were analysed with respect to the mass M of the `body’ that the motor contributes to move. For molecular motors this is the mass of the cell from which the motor was extracted. When not reported, cell masses were estimated from other sources or calculated from the cell size. In nonmolecular motors, tensions were analysed with respect to the mass M of the corresponding animal. When not reported, body masses were also estimated from other sources. Note that as a consequence of these choices a different mass was used for a myosin molecule (molecular motor) and a muscle fibre (non-molecular motor) from the same organism. The organisms considered range in mass from the bacterium Escherichia coli (1.3 ?10-15 kg) to the muscular fibre (5 ?10-8 kg) for the cells, and from the mite Archegozetes longisetosus (10-7 kg) to the elephant (2500 kg) for the multicellular organisms. For both f and M, means of a series of equivalent measurements by the same author(s) were preferred when available. When only minimum and maximum values were given, we took their mean.2.6. StatisticsStatistical distributions were compared with the Kolmogorov mirnov test [194]. Multiple distributions were compared with the one-way analysis of variance (ANOVA) and corresponding multiple comparison of means using Tukey ramer adjustment. Slopes of least-square regressions of log10 (f ) versus log10 (M) were compared with 0 using the F test. Details of statistical analyses are given as the electronic supplementary material, tables S1 6 for ANOVA and multiple comparison of means and tables S7 12 for regressions. All tests were performed with the MATLAB STATISTICAL TOOLBOX (The Mathworks, Natick, USA).3. ResultsThe data have been analysed in terms of the maximum force per cross-sectional area f. We consider separately motors made of single molecules (denoted M1) and molecular assemblies (M2, MF) that we collectively call `molecular motors’, whereas the other motors, muscle fibres (FI.

Ighlight the need to standardize protocols for the extraction and structural

Ighlight the need to standardize protocols for the extraction and structural identification of polar lipids molecular species. The same is valid for the deposit vouchers of buy LDN193189 screened taxa, in order to allow a reliable replication of results, as well as intraand interspecific comparisons.Acknowledgments: Thanks are due for the financial support to CESAM (UID/AMB/50017/2013) and QOPNA (UID/QUI/00062/2013) to FCT/MEC through national funds, and the co-funding by the FEDER, within the PT2020 Partnership Agreement and Compete 2020. E. Maciel benefits from a post-doc grant (SFRH/BPD/104165/2014) financed by FCT. We also acknowledge three anonymous reviewers for their insightful comments on a previous version of this work. Conflicts of Interest: The authors declare no conflict of interest.
Review ArticleThe Interstitial Cystitis Association of America: lessons learned over the past 30 yearsVicki RatnerFounder and President Emeritus, Interstitial Cystitis Association of America, USA Correspondence to: Vicki Ratner, MD. Founder and President Emeritus, Interstitial Cystitis Association of America, 1760 Old Meadow Road, suite 500, McLean, VA 22102, USA. Email: [email protected]: In 1984, interstitial cystitis (IC) was considered a rare psychosomatic disorder in post-menopausal women. In 2014, the Interstitial Cystitis Association of America (ICA) celebrated its 30th anniversary. We’ve come a long way since 1984 and great progress has been made. IC is now recognized as a condition that afflicts both men and women of all ages, including children and teenagers. It is not a psychiatric disorder. Though it was once thought to be an orphan disease (defined as affecting less than 200,000 people), we now know that there are millions of women and men who suffer from IC/BPS (bladder pain syndrome). In looking back over this period, there were seven key reasons why the ICA became so successful: an MS023 site extremely dedicated ICA staff, Board of Directors and volunteers; a very strong Medical Advisory Board and participation of many other urologists from across the country and around the world; cooperation of the media; epidemiological studies; the ICA’s Pilot Research Program; our representation in Congress; and a strong working partnership with the National Institutes of Health (NIH). Our history may prove useful to other advocacy groups.Keywords: Interstitial cystitis/bladder pain syndrome (IC/BPS); bladder pain syndrome; Interstitial Cystitis Association of America (ICA); Interstitial Cystitis Association of America Advocacy Group; Interstitial Cystitis Association of America (ICA)-reasons for success Submitted Aug 01, 2015. Accepted for publication Aug 03, 2015. doi: 10.3978/j.issn.2223-4683.2015.09.02 View this article at: http://dx.doi.org/10.3978/j.issn.2223-4683.2015.09.The beginning In 1983, as a third year medical student, I came down with severe suprapubic pressure, urinary urgency, frequency and burning pain in my bladder. The pain felt like a lit match in my urethra. I was barely able to function, and found it almost impossible to concentrate. I assumed I had a UTI, but a complete work-up was negative and antibiotics failed to reduce the symptoms. In search of a diagnosis and relief from the severity of the symptoms, I sought help from one urologist after another. Many told me that the tests were negative, and that there was nothing they could do for me. Others suggested that I was not cut out to be a doctor and that I should drop out of medical sc.Ighlight the need to standardize protocols for the extraction and structural identification of polar lipids molecular species. The same is valid for the deposit vouchers of screened taxa, in order to allow a reliable replication of results, as well as intraand interspecific comparisons.Acknowledgments: Thanks are due for the financial support to CESAM (UID/AMB/50017/2013) and QOPNA (UID/QUI/00062/2013) to FCT/MEC through national funds, and the co-funding by the FEDER, within the PT2020 Partnership Agreement and Compete 2020. E. Maciel benefits from a post-doc grant (SFRH/BPD/104165/2014) financed by FCT. We also acknowledge three anonymous reviewers for their insightful comments on a previous version of this work. Conflicts of Interest: The authors declare no conflict of interest.
Review ArticleThe Interstitial Cystitis Association of America: lessons learned over the past 30 yearsVicki RatnerFounder and President Emeritus, Interstitial Cystitis Association of America, USA Correspondence to: Vicki Ratner, MD. Founder and President Emeritus, Interstitial Cystitis Association of America, 1760 Old Meadow Road, suite 500, McLean, VA 22102, USA. Email: [email protected]: In 1984, interstitial cystitis (IC) was considered a rare psychosomatic disorder in post-menopausal women. In 2014, the Interstitial Cystitis Association of America (ICA) celebrated its 30th anniversary. We’ve come a long way since 1984 and great progress has been made. IC is now recognized as a condition that afflicts both men and women of all ages, including children and teenagers. It is not a psychiatric disorder. Though it was once thought to be an orphan disease (defined as affecting less than 200,000 people), we now know that there are millions of women and men who suffer from IC/BPS (bladder pain syndrome). In looking back over this period, there were seven key reasons why the ICA became so successful: an extremely dedicated ICA staff, Board of Directors and volunteers; a very strong Medical Advisory Board and participation of many other urologists from across the country and around the world; cooperation of the media; epidemiological studies; the ICA’s Pilot Research Program; our representation in Congress; and a strong working partnership with the National Institutes of Health (NIH). Our history may prove useful to other advocacy groups.Keywords: Interstitial cystitis/bladder pain syndrome (IC/BPS); bladder pain syndrome; Interstitial Cystitis Association of America (ICA); Interstitial Cystitis Association of America Advocacy Group; Interstitial Cystitis Association of America (ICA)-reasons for success Submitted Aug 01, 2015. Accepted for publication Aug 03, 2015. doi: 10.3978/j.issn.2223-4683.2015.09.02 View this article at: http://dx.doi.org/10.3978/j.issn.2223-4683.2015.09.The beginning In 1983, as a third year medical student, I came down with severe suprapubic pressure, urinary urgency, frequency and burning pain in my bladder. The pain felt like a lit match in my urethra. I was barely able to function, and found it almost impossible to concentrate. I assumed I had a UTI, but a complete work-up was negative and antibiotics failed to reduce the symptoms. In search of a diagnosis and relief from the severity of the symptoms, I sought help from one urologist after another. Many told me that the tests were negative, and that there was nothing they could do for me. Others suggested that I was not cut out to be a doctor and that I should drop out of medical sc.

M comments (4.62 IPI/kU, SD 5.41), Google+ “+1″s (4.02 IPI/kU, SD 5.54) and

M comments (4.62 IPI/kU, SD 5.41), Google+ “+1″s (4.02 IPI/kU, SD 5.54) and Google+ clickthroughs (1.47 IPI/kU, SD 2.98) (Fig 2B). Visit durations and MLN9708 biological activity retention rates were highest for Twitter French, with users spending 34.63 seconds on average (SD 46.42), and 10.92 (SD 12.97 ) clicking on on-site links, respectively. Audience size AZD-8055 structure correlated significantly and moderately positively with total shares and clickthroughs, and weakly negatively for visit duration (r = -0.146, p < 0.01) and retention rate (r = -0.175, p < 0.01). No significant correlation was found between audience size and total likes or comments. However, when controlling for audience size, likes, comments, shares and clickthroughs occurred less often as audience sizes grew. Correlations were moderately negative except for the correlation between audience size and likes, which was strongly negative (Fig 2C). In summary, larger audiences correlated with higher engagement rates in total; However, per-user, engagement declined with audience size. Having said that, audience size is not everything. The educational goals of visit durations and retention rates (Table 1, row 1) were similarly attained among Twitter English, Facebook and Google+ although they have very different audience sizes, while users arriving to the URLs through Twitter French stay on the page for a much longer time, by a factor of 2 to 3 (Fig 2D and 2E). This may be a result of the language itself: to convey the same information takes, in general, more words in French than in English [42]. In English, 140 characters can be enough to convey a message. In French, this is not always the case, resulting in enigmatic text that encourages the reader to click through to find out more. Once on the webpage, more French text is used to convey the message than the equivalent English so naturally the time spent on the page increases. If the web page content is tailored to the audience e.g. a full publication in French, the audience is more likely to click further to read additional content.PLOS ONE | DOI:10.1371/journal.pone.0156409 May 27,9 /Engagement with Particle Physics on CERN’s Social Media PlatformsFig 2. Average rates of user interactions with items posted on CERN’s social media platforms. (A) User interaction rates without control for audience size. (B) User interaction rates with control for audience size. (C) Pearson correlations between audience size and user interactions relating to behaviours on the social media platform. (D) Visit durations of visitors arriving by links posted on different platforms, by audience sizes of the platforms. (E) Average retention rates of visitors arriving by links posted on different platforms, by audience sizes of the platforms. (F) Pearson correlations between audience size and user interactions relating to on-site behaviour. *. Correlation is significant at the 0.05 level (2-tailed). **. Correlation is significant at the 0.01 level (2-tailed). Error bars denote the standard error of the mean. doi:10.1371/journal.pone.0156409.gPLOS ONE | DOI:10.1371/journal.pone.0156409 May 27,10 /Engagement with Particle Physics on CERN’s Social Media PlatformsTable 7. User interactions per item with CERN items on different social media platforms, by item type. Item Type GWII Mean N SD News Mean N SD TBT Mean N SD Wow Mean N SD Total Mean N SD 161.68 214 358.81 9.50 214 31.93 64.37 182 143.79 93.08 225 166.11 16.27 225 34.67 5.45 225 8.20 285.93 40 703.74 17.20 40 63.27 115.88 32 244.12 14.M comments (4.62 IPI/kU, SD 5.41), Google+ “+1″s (4.02 IPI/kU, SD 5.54) and Google+ clickthroughs (1.47 IPI/kU, SD 2.98) (Fig 2B). Visit durations and retention rates were highest for Twitter French, with users spending 34.63 seconds on average (SD 46.42), and 10.92 (SD 12.97 ) clicking on on-site links, respectively. Audience size correlated significantly and moderately positively with total shares and clickthroughs, and weakly negatively for visit duration (r = -0.146, p < 0.01) and retention rate (r = -0.175, p < 0.01). No significant correlation was found between audience size and total likes or comments. However, when controlling for audience size, likes, comments, shares and clickthroughs occurred less often as audience sizes grew. Correlations were moderately negative except for the correlation between audience size and likes, which was strongly negative (Fig 2C). In summary, larger audiences correlated with higher engagement rates in total; However, per-user, engagement declined with audience size. Having said that, audience size is not everything. The educational goals of visit durations and retention rates (Table 1, row 1) were similarly attained among Twitter English, Facebook and Google+ although they have very different audience sizes, while users arriving to the URLs through Twitter French stay on the page for a much longer time, by a factor of 2 to 3 (Fig 2D and 2E). This may be a result of the language itself: to convey the same information takes, in general, more words in French than in English [42]. In English, 140 characters can be enough to convey a message. In French, this is not always the case, resulting in enigmatic text that encourages the reader to click through to find out more. Once on the webpage, more French text is used to convey the message than the equivalent English so naturally the time spent on the page increases. If the web page content is tailored to the audience e.g. a full publication in French, the audience is more likely to click further to read additional content.PLOS ONE | DOI:10.1371/journal.pone.0156409 May 27,9 /Engagement with Particle Physics on CERN’s Social Media PlatformsFig 2. Average rates of user interactions with items posted on CERN’s social media platforms. (A) User interaction rates without control for audience size. (B) User interaction rates with control for audience size. (C) Pearson correlations between audience size and user interactions relating to behaviours on the social media platform. (D) Visit durations of visitors arriving by links posted on different platforms, by audience sizes of the platforms. (E) Average retention rates of visitors arriving by links posted on different platforms, by audience sizes of the platforms. (F) Pearson correlations between audience size and user interactions relating to on-site behaviour. *. Correlation is significant at the 0.05 level (2-tailed). **. Correlation is significant at the 0.01 level (2-tailed). Error bars denote the standard error of the mean. doi:10.1371/journal.pone.0156409.gPLOS ONE | DOI:10.1371/journal.pone.0156409 May 27,10 /Engagement with Particle Physics on CERN’s Social Media PlatformsTable 7. User interactions per item with CERN items on different social media platforms, by item type. Item Type GWII Mean N SD News Mean N SD TBT Mean N SD Wow Mean N SD Total Mean N SD 161.68 214 358.81 9.50 214 31.93 64.37 182 143.79 93.08 225 166.11 16.27 225 34.67 5.45 225 8.20 285.93 40 703.74 17.20 40 63.27 115.88 32 244.12 14.

Our more alternative notations: A ! B, A ! B, Z Y Z

Our more purchase GSK-1605786 alternative notations: A ! B, A ! B, Z Y Z XY Z X Z Z A ! B, and A ! B. Category 5 (CS) gets one more alternative notation, [A !B and A Z Y Y Z Z Z ZB].Finally, category 6 (asocial) gets two more alternative notations, A !B and A B. For any N ! 2, all of the 2N+1 elementary interactions are included in the representative relationships of the six categories and their alternative notations. This results from the building process of the six categories, with the differentiations covering all possible cases. In the example of N = 3, the above statement is illustrated by the comparison of the sixteen elementary interactions of Table 4 with the six categories and their alternative notations for N = 2 (Table 3), completed by the alternative notations for N = 3 listed above. This concludes the proof of exhaustiveness of the six categories of Table 3 for any number N ! 2 of non-null social actions. With N social actions at hand, richer composite relationships can be represented. Let us translate into our action fluxes representation an example of composite relationship given by Goldman [25] (pp. 344-345). Namely, “two friends may share tapes and records freely with each other (CS), work on a task at which one is an expert and imperiously directs the other (AR), divide equally the cost of gas on a trip (EM), and transfer a bicycle from one to the other S2 S4 S5 S6 S1 S for a market-value price (MP).” This gives [A ! B, A 1 B, A ! B, A ! B, A ! B, A ! B].S2 S4 S6 SHere the relationship was known and we wrote it in terms of action fluxes. The next step is to find out how to identify a relationship when the action fluxes are given. We touch on how to achieve this in the discussion.Discussion Analyzing data setsOur representation in action fluxes provides a tool to identify types of dyadic relationships occurring within potentially large data sets of social interactions. Both collective and dyadic interactions may occur in real social contexts, but our approach applies specifically to the latter. Large data sets can result from any type of online social network or massively multiplayer online role-playing games (MMORPG), for instance. MMORPGs bring hundreds of thousands of players together to cooperate and compete by forming alliances, trading, fighting, and so on, all the while recording every single action and communication of the players. They are used in quantitative social science, for example by Thurner in the context of the game Pardus [26?8]. Ethnological and anthropological studies can provide rich MK-5172 msds reports of social interactions occurring in non-artificial settings that could be coded and interpreted with the aid of our categorization. Data sets of dyadic interactions can also be generated by computer simulations such as agent-based models (ABMs) to test specific questions. We offer the sketch of a method to analyze a potentially large data set of dyadic social interactions expressed as action fluxes (“A does X to B”, etc.). Given a data set involving a number of individuals, one needs to consider separately each pair of individuals. For each pair, one shall examine each social action and test into which category of action fluxes it falls, possibly jointly with another social action (in the case of MP and AR). In its second column, Table 5 specifies the patterns of fluxes expected to be observed in each category. Let us stress the following points: ?The patterns of observed fluxes given in Table 5 are not meant as definitions of the.Our more alternative notations: A ! B, A ! B, Z Y Z XY Z X Z Z A ! B, and A ! B. Category 5 (CS) gets one more alternative notation, [A !B and A Z Y Y Z Z Z ZB].Finally, category 6 (asocial) gets two more alternative notations, A !B and A B. For any N ! 2, all of the 2N+1 elementary interactions are included in the representative relationships of the six categories and their alternative notations. This results from the building process of the six categories, with the differentiations covering all possible cases. In the example of N = 3, the above statement is illustrated by the comparison of the sixteen elementary interactions of Table 4 with the six categories and their alternative notations for N = 2 (Table 3), completed by the alternative notations for N = 3 listed above. This concludes the proof of exhaustiveness of the six categories of Table 3 for any number N ! 2 of non-null social actions. With N social actions at hand, richer composite relationships can be represented. Let us translate into our action fluxes representation an example of composite relationship given by Goldman [25] (pp. 344-345). Namely, “two friends may share tapes and records freely with each other (CS), work on a task at which one is an expert and imperiously directs the other (AR), divide equally the cost of gas on a trip (EM), and transfer a bicycle from one to the other S2 S4 S5 S6 S1 S for a market-value price (MP).” This gives [A ! B, A 1 B, A ! B, A ! B, A ! B, A ! B].S2 S4 S6 SHere the relationship was known and we wrote it in terms of action fluxes. The next step is to find out how to identify a relationship when the action fluxes are given. We touch on how to achieve this in the discussion.Discussion Analyzing data setsOur representation in action fluxes provides a tool to identify types of dyadic relationships occurring within potentially large data sets of social interactions. Both collective and dyadic interactions may occur in real social contexts, but our approach applies specifically to the latter. Large data sets can result from any type of online social network or massively multiplayer online role-playing games (MMORPG), for instance. MMORPGs bring hundreds of thousands of players together to cooperate and compete by forming alliances, trading, fighting, and so on, all the while recording every single action and communication of the players. They are used in quantitative social science, for example by Thurner in the context of the game Pardus [26?8]. Ethnological and anthropological studies can provide rich reports of social interactions occurring in non-artificial settings that could be coded and interpreted with the aid of our categorization. Data sets of dyadic interactions can also be generated by computer simulations such as agent-based models (ABMs) to test specific questions. We offer the sketch of a method to analyze a potentially large data set of dyadic social interactions expressed as action fluxes (“A does X to B”, etc.). Given a data set involving a number of individuals, one needs to consider separately each pair of individuals. For each pair, one shall examine each social action and test into which category of action fluxes it falls, possibly jointly with another social action (in the case of MP and AR). In its second column, Table 5 specifies the patterns of fluxes expected to be observed in each category. Let us stress the following points: ?The patterns of observed fluxes given in Table 5 are not meant as definitions of the.

Are a useful method for gaining insight into phenomena where little

Are a useful method for Luminespib price gaining insight into phenomena where little is known [44]. When focus group data has been collected from multiple groups and multiple sites, researchers can have Elbasvir site increased confidence in the reliability and validity of the findings [45]. The focus groups were guided by following questions. (1) Perceptions of Professional Socialization. (a) What comes to mind when you hear the phrase “professional socialization”? (b) Share memories of your experiences becoming socialized into the role of Licensed Practical Nurse and developing your identity in this role. (c) How is the experience of developing your new role and identity as a Registered Nurse the same? How is it different? (2) Formal Academic Experiences: Online Classes and Clinical Practicums. (a) Talk about experiences you have had so far in your online university classes where you “felt like” a Registered Nurse and not a Licensed Practical Nurse? Have there been times in your online4 [54] (page 85) maintained by both moderators during and immediately following the sessions further increased the dependability of our findings. Practical issues such as organizing groups at a time and place to minimize disruption and avoiding power differential dynamics [55] were addressed. The groups were held when participants, who were normally separated by distance, were together in the same city for a required practicum experience. They were held at change of shift in lieu of a post conference. Knowing the power differential between students and teachers, moderators who did not have teaching responsibilities in the Post LPN to BN program were chosen to facilitate the focus groups. Instructors were not present during any of the discussions and had no involvement with the transcript data. Participants were recruited through a Letter of Invitation sent via email by a Research Assistant who was also not involved with the program. Four focus groups were held with 5 to 9 participants each. All the students who were invited chose to participate. We reasoned that this may have been because they were all from out of town and appreciated an opportunity to interact and share their views. Pseudonyms ensured participant confidentiality. Full ethical approval was granted by the university. The following two overarching themes emerged from analyzing the data. First, Post LPN to BN students need little, if any, further legitimation to affirm their identities as “nurse.” Second, practicum interactions with instructors and new clinical experiences are key socializing agents.Nursing Research and Practice They talked about opportunities where demonstrating professional authority in their workplace further established their identity as “nurse”: “Working your first night shift . . . in your new role. The culture of night shift–it’s different.” “The first time I cared for a palliative patient and was there when they passed. Talking with the family. My first job that I had as an LPN, I was alone on the floor as the only official nurse for more than half of my shift. I had the full responsibility of all 60 residents in my care . . . that all happened as an LPN.” From the Post LPN to BN students’ perspective, the notion that socialization into the role of “nurse” would occur for them at this point in their career was insulting: “I almost feel a little bit insulted to think that I would feel any less professional as an LPN than I do as an RN. I feel equally professional in both roles.” “My buddy nurse ac.Are a useful method for gaining insight into phenomena where little is known [44]. When focus group data has been collected from multiple groups and multiple sites, researchers can have increased confidence in the reliability and validity of the findings [45]. The focus groups were guided by following questions. (1) Perceptions of Professional Socialization. (a) What comes to mind when you hear the phrase “professional socialization”? (b) Share memories of your experiences becoming socialized into the role of Licensed Practical Nurse and developing your identity in this role. (c) How is the experience of developing your new role and identity as a Registered Nurse the same? How is it different? (2) Formal Academic Experiences: Online Classes and Clinical Practicums. (a) Talk about experiences you have had so far in your online university classes where you “felt like” a Registered Nurse and not a Licensed Practical Nurse? Have there been times in your online4 [54] (page 85) maintained by both moderators during and immediately following the sessions further increased the dependability of our findings. Practical issues such as organizing groups at a time and place to minimize disruption and avoiding power differential dynamics [55] were addressed. The groups were held when participants, who were normally separated by distance, were together in the same city for a required practicum experience. They were held at change of shift in lieu of a post conference. Knowing the power differential between students and teachers, moderators who did not have teaching responsibilities in the Post LPN to BN program were chosen to facilitate the focus groups. Instructors were not present during any of the discussions and had no involvement with the transcript data. Participants were recruited through a Letter of Invitation sent via email by a Research Assistant who was also not involved with the program. Four focus groups were held with 5 to 9 participants each. All the students who were invited chose to participate. We reasoned that this may have been because they were all from out of town and appreciated an opportunity to interact and share their views. Pseudonyms ensured participant confidentiality. Full ethical approval was granted by the university. The following two overarching themes emerged from analyzing the data. First, Post LPN to BN students need little, if any, further legitimation to affirm their identities as “nurse.” Second, practicum interactions with instructors and new clinical experiences are key socializing agents.Nursing Research and Practice They talked about opportunities where demonstrating professional authority in their workplace further established their identity as “nurse”: “Working your first night shift . . . in your new role. The culture of night shift–it’s different.” “The first time I cared for a palliative patient and was there when they passed. Talking with the family. My first job that I had as an LPN, I was alone on the floor as the only official nurse for more than half of my shift. I had the full responsibility of all 60 residents in my care . . . that all happened as an LPN.” From the Post LPN to BN students’ perspective, the notion that socialization into the role of “nurse” would occur for them at this point in their career was insulting: “I almost feel a little bit insulted to think that I would feel any less professional as an LPN than I do as an RN. I feel equally professional in both roles.” “My buddy nurse ac.

Rhetorical functions of language, typography and editorial voice as well as

Rhetorical functions of language, typography and editorial voice as well as the use of such radical literary tactics as exposure, ridicule and critique. This article does not merely aim to point up the similarities between The Lancet and its political contemporaries; it intends to show how such stylistic devices were marshalled in the pursuit of a specific political agenda. Of course splenetic prose was not the sole preserve of the radical `left’ and neither was it particularly novel. Similar tactics had been in use since the later 1700s by `King and Country’ Tories, a position from which Wakley’s mentor and collaborator, William Cobbett, had only moved in 1806.14 However, during the early decades of the nineteenth century it was the radical and revolutionary press which made this style their own, and it was these conventions that Wakley sought to emulate. This was particularly true of his predilection for insult and defamation, and the main body of this article comprises a detailed analysis of a trial for libel in 1828 between Wakely and the Guy’s Hospital surgeon, Bransby Cooper. Through a close analysis of Wakley’s rhetorical, legal and performative strategies, as well as a critical reading of a number of contemporary satirical prints, it demonstrates how this trial functioned as the platform for a much broader critique of the established medical `system’ and provided a powerful means for Wakley to align himself with the cultures of popular radicalism. However, whatever parallels and connections Wakley sought to draw between the medical and the political, the reality was rather more complex. In the final section,567. Smith, The Politics of Language, 1791 ?819 (Oxford, 1984); I. McCalman, Radical Underworld: Prophets, Revolutionaries and Pornographers, 1795?1840 (get RRx-001 Cambridge, 1988); J. A. Epstein, Radical Expression: Political Language, Ritual and Symbol in England, 1790 ?1850 (Oxford, 1994); E. Hadley, Melodramatic Tactics: Theatricalised Dissent in the English13O. 12ibid.,Marketplace, 1800 ?1885 (Stanford, 1995); L. Nattrass, William Cobbett: The Politics of Style (Cambridge, 1995); K. Gilmartin, Print Politics: The Press and Radical Opposition in Early Nineteenth-Century England (Cambridge, 1996). 14For example, see J. J. Sack, From Jacobite to Conservative: Reaction and Orthodoxy in Britain, c.1760 ?832 (Cambridge, 1993).Social HistoryVOL.39 :NO.therefore, this article examines the tensions and ambiguities within Wakley’s political persona by reading them against the altered circumstances of the 1820s, particularly the rise of a more philosophic reformism. In so doing, it seeks not merely to place political radicalism at the heart of contemporary medical culture but, more ambitiously perhaps, to establish a more prominent place for medicine in accounts of the history of early nineteenth-century reform, as a potential bridge between the popular radicalism of the immediate post-war years and the reformist utilitarianism of the 1830s.WAKLEY, COBBETT AND RADICAL STYLEThere was little in Thomas Wakley’s early upbringing to suggest a natural inclination towards political radicalism, for he was born in 1795 into that bulwark of pre-modern political order, the prosperous farming family.15 One of eleven children and the youngest of eight sons, he attended PD168393 web boarding school in Somerset, followed by a series of apprenticeships with local apothecaries and surgeons, enrolling as a student at the United Hospitals Medical School of Guy’s and St Tho.Rhetorical functions of language, typography and editorial voice as well as the use of such radical literary tactics as exposure, ridicule and critique. This article does not merely aim to point up the similarities between The Lancet and its political contemporaries; it intends to show how such stylistic devices were marshalled in the pursuit of a specific political agenda. Of course splenetic prose was not the sole preserve of the radical `left’ and neither was it particularly novel. Similar tactics had been in use since the later 1700s by `King and Country’ Tories, a position from which Wakley’s mentor and collaborator, William Cobbett, had only moved in 1806.14 However, during the early decades of the nineteenth century it was the radical and revolutionary press which made this style their own, and it was these conventions that Wakley sought to emulate. This was particularly true of his predilection for insult and defamation, and the main body of this article comprises a detailed analysis of a trial for libel in 1828 between Wakely and the Guy’s Hospital surgeon, Bransby Cooper. Through a close analysis of Wakley’s rhetorical, legal and performative strategies, as well as a critical reading of a number of contemporary satirical prints, it demonstrates how this trial functioned as the platform for a much broader critique of the established medical `system’ and provided a powerful means for Wakley to align himself with the cultures of popular radicalism. However, whatever parallels and connections Wakley sought to draw between the medical and the political, the reality was rather more complex. In the final section,567. Smith, The Politics of Language, 1791 ?819 (Oxford, 1984); I. McCalman, Radical Underworld: Prophets, Revolutionaries and Pornographers, 1795?1840 (Cambridge, 1988); J. A. Epstein, Radical Expression: Political Language, Ritual and Symbol in England, 1790 ?1850 (Oxford, 1994); E. Hadley, Melodramatic Tactics: Theatricalised Dissent in the English13O. 12ibid.,Marketplace, 1800 ?1885 (Stanford, 1995); L. Nattrass, William Cobbett: The Politics of Style (Cambridge, 1995); K. Gilmartin, Print Politics: The Press and Radical Opposition in Early Nineteenth-Century England (Cambridge, 1996). 14For example, see J. J. Sack, From Jacobite to Conservative: Reaction and Orthodoxy in Britain, c.1760 ?832 (Cambridge, 1993).Social HistoryVOL.39 :NO.therefore, this article examines the tensions and ambiguities within Wakley’s political persona by reading them against the altered circumstances of the 1820s, particularly the rise of a more philosophic reformism. In so doing, it seeks not merely to place political radicalism at the heart of contemporary medical culture but, more ambitiously perhaps, to establish a more prominent place for medicine in accounts of the history of early nineteenth-century reform, as a potential bridge between the popular radicalism of the immediate post-war years and the reformist utilitarianism of the 1830s.WAKLEY, COBBETT AND RADICAL STYLEThere was little in Thomas Wakley’s early upbringing to suggest a natural inclination towards political radicalism, for he was born in 1795 into that bulwark of pre-modern political order, the prosperous farming family.15 One of eleven children and the youngest of eight sons, he attended boarding school in Somerset, followed by a series of apprenticeships with local apothecaries and surgeons, enrolling as a student at the United Hospitals Medical School of Guy’s and St Tho.

, a runner who demonstrates considerably less than 45?of knee flexion may

, a TF14016 site runner who demonstrates considerably less than 45?of knee order OPC-8212 flexion may suggest reduced shock absorption, and intervention may be warranted. Some data exist suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj., a runner who demonstrates considerably less than 45?of knee flexion may suggest reduced shock absorption, and intervention may be warranted. Some data exist suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj.

Ired for creating high affinity complexes between Bet and A3 (Lukic

Ired for creating high affinity complexes between Bet and A3 (Lukic et al., 2013). Interestingly, Bet is expressed at high levels in infected cells, both in culture and in animals, consistent with inactivation of A3 by Bet binding or sequestration (Alke et al., 2001; Lukic et al., 2013). In addition, A3s may be able to inhibit FV replication in both producer as well as target cells (Lochelt et al., 2005), which may be linked to the fact that spumaviruses can initiate reverse transcription in producer cells (Moebes et al., 1997). Therefore, FVs antagonize A3-induced hypermutation using a mechanism distinct from those described above. Interestingly, the betaretroviruses lack a common mechanism to avoid APOBEC-mediated restriction. For example, the Mason-Pfizer monkey virus (MPMV) has been reported to be resistant to expression rhesus monkey A3G by excluding this enzyme from virions (Doehle et al., 2006). The mechanism for A3G exclusion is unclear. Nevertheless, mouse A3, but not rhesus A3G, is bound by MPMV Gag and packaged into viral particles where it inhibits viral infectivity (Doehle et al., 2006). In contrast, the betaretrovirus MMTV packages A3, which then blocks order Aviptadil subsequent reverse transcription (MacMillan et al., 2013). Like many MuLVs, the packaged A3 caused only low-level hypermutation of the proviruses that escaped A3 inhibition (MacMillan et al., 2013). Effects of A3 on MMTV replication were most apparent in mouse strains that express high levels of this deaminase (Okeoma et al., 2009b), whereas the related TBLV, which has an altered LTR and induces T-cell lymphomas, replicates well in mouse strains that express either high or low levels of A3 (Bhadra et al., 2009; Meyers et al., 1989; Mustafa et al., 2003). Furthermore, unlike MPMV, MMTV, and TBLV, complex retroviruses express a doubly spliced mRNA and the Rem precursor protein (Indik et al., 2005; Mertz et al., 2005). The Rem precursor is cleaved intoAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptVirology. Author manuscript; available in PMC 2016 May 01.Harris and DudleyPagean N-terminal signal peptide (Rem-SP) that serves a Rev-like function, whereas the function of the C-terminal 203 amino acid protein has not been determined (Byun et al., 2012; Byun et al., 2010). One possibility is that the activity of the Rem precursor or the C-terminus provides the role of the glycosylated Gag protein of MuLVs.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptAPOBEC3 involvement in endogenous virus and transposon restrictionAlthough the role of APOBECs as anti-viral factors was initially shown with exogenous retroviruses, including HIV-1, subsequent studies demonstrated fundamental roles for these enzymes in suppressing the mobilization of endogenous retroviruses and retrotransposons. These parasitic elements occupy a large fraction of the human genome and, although mostly defective, the remaining functional elements must be exquisitely controlled to prevent excessive genome damage and potential genetic catastrophe. One major family of endogenous parasites that is controlled by APOBEC proteins is comprised of autonomous LINE-1 (L1) transposons and related Pyrvinium embonateMedChemExpress Pyrvinium pamoate non-autonomous Alu transposons, which require L1 gene products for transposition. These elements rely on integration-primed reverse transcription for copying from one location of the genome and inserting in another (i.e., copy and paste mechanism). Initial studies demonstrated L1 restriction.Ired for creating high affinity complexes between Bet and A3 (Lukic et al., 2013). Interestingly, Bet is expressed at high levels in infected cells, both in culture and in animals, consistent with inactivation of A3 by Bet binding or sequestration (Alke et al., 2001; Lukic et al., 2013). In addition, A3s may be able to inhibit FV replication in both producer as well as target cells (Lochelt et al., 2005), which may be linked to the fact that spumaviruses can initiate reverse transcription in producer cells (Moebes et al., 1997). Therefore, FVs antagonize A3-induced hypermutation using a mechanism distinct from those described above. Interestingly, the betaretroviruses lack a common mechanism to avoid APOBEC-mediated restriction. For example, the Mason-Pfizer monkey virus (MPMV) has been reported to be resistant to expression rhesus monkey A3G by excluding this enzyme from virions (Doehle et al., 2006). The mechanism for A3G exclusion is unclear. Nevertheless, mouse A3, but not rhesus A3G, is bound by MPMV Gag and packaged into viral particles where it inhibits viral infectivity (Doehle et al., 2006). In contrast, the betaretrovirus MMTV packages A3, which then blocks subsequent reverse transcription (MacMillan et al., 2013). Like many MuLVs, the packaged A3 caused only low-level hypermutation of the proviruses that escaped A3 inhibition (MacMillan et al., 2013). Effects of A3 on MMTV replication were most apparent in mouse strains that express high levels of this deaminase (Okeoma et al., 2009b), whereas the related TBLV, which has an altered LTR and induces T-cell lymphomas, replicates well in mouse strains that express either high or low levels of A3 (Bhadra et al., 2009; Meyers et al., 1989; Mustafa et al., 2003). Furthermore, unlike MPMV, MMTV, and TBLV, complex retroviruses express a doubly spliced mRNA and the Rem precursor protein (Indik et al., 2005; Mertz et al., 2005). The Rem precursor is cleaved intoAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptVirology. Author manuscript; available in PMC 2016 May 01.Harris and DudleyPagean N-terminal signal peptide (Rem-SP) that serves a Rev-like function, whereas the function of the C-terminal 203 amino acid protein has not been determined (Byun et al., 2012; Byun et al., 2010). One possibility is that the activity of the Rem precursor or the C-terminus provides the role of the glycosylated Gag protein of MuLVs.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptAPOBEC3 involvement in endogenous virus and transposon restrictionAlthough the role of APOBECs as anti-viral factors was initially shown with exogenous retroviruses, including HIV-1, subsequent studies demonstrated fundamental roles for these enzymes in suppressing the mobilization of endogenous retroviruses and retrotransposons. These parasitic elements occupy a large fraction of the human genome and, although mostly defective, the remaining functional elements must be exquisitely controlled to prevent excessive genome damage and potential genetic catastrophe. One major family of endogenous parasites that is controlled by APOBEC proteins is comprised of autonomous LINE-1 (L1) transposons and related non-autonomous Alu transposons, which require L1 gene products for transposition. These elements rely on integration-primed reverse transcription for copying from one location of the genome and inserting in another (i.e., copy and paste mechanism). Initial studies demonstrated L1 restriction.

Monly used and widely available OTC medications and nutritional supplements were

Monly used and widely available OTC medications and nutritional supplements were safe and posed no short- or long-term threat to their health. Many used such products to improve their running performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product recommended as an effective and legal substance by another runner or by a retail sales clerk may contain substances that are either banned by agencies such as WADA and/or may pose a serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.NIH-PA PNPP web Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and SKF-96365 (hydrochloride) web knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.Monly used and widely available OTC medications and nutritional supplements were safe and posed no short- or long-term threat to their health. Many used such products to improve their running performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product recommended as an effective and legal substance by another runner or by a retail sales clerk may contain substances that are either banned by agencies such as WADA and/or may pose a serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.

Deration when interpreting experimental findings. (i) Identification of a mutation in

Deration when interpreting experimental findings. (i) Identification of a AZD-8835 cost mutation in a clonal population does not indicate causality Any mutation in a cell that undergoes clonal expansion will be passed onto progeny, irrespective of functional status (Fig. 3A,B). Given the size of the genome, more mutations carried by a neoplastic clone will be passengers than drivers [27, 29, 30]. To demonstrate driver status, supporting functional studies and/or repeated observations of a mutated loci in neoplastic clones from independent individuals are needed. (ii) Mutational marking of a clone is stochastic and not guaranteed A clone may exist and not be detected if none of the genomic sites being screened carry a unique mutation AZD-8835 site permitting it to be distinguished from the germline (Fig. 3C). The more sites examined, the higher the probability of detection becomes. Restricting a marker panel to suspected driver sites precludes detection of pathological clones driven by unknown factors. (iii) Elevated mutation rates facilitate clone detection but are not an absolute requirement Screening of mutational hotspots makes it practical with conventional technologies to have a reasonable probability of detecting a clone by random passenger mutations. Clones derived from a mutator lineage or cells residing in a highly mutagenic environment should be more densely marked with identifiable passengers (Fig. 3D), potentially reducing the number of markers needing to be interrogated to identify them. Emerging high-throughput sequencing technologies will eventually obviate the need to restrict screening to a fraction of the genome. (iv) Identification of one or more clonal mutations is not proof of genetic instability in the absence of collateral information Detection of a mutation requires clonal expansion with most traditional methods of aggregate DNA analysis. The probability of identifying clonal mutations in an expanded population is a function of the number of sites screened, the mutability of these sites and the number of cell divisions having occurred in the lineage leading up to the final expansion. Particularly when considering hotspots, mutations will be occasionally detectable in any clonally-derived population at a statistically definable frequency. Because mutations are not routinely encountered in normal tissues, it is tempting to explain their presence in preneoplastic populations as the result of “genetic instability” (an elevated mutation rate). However, the phenomenon is more precisely explained by the fact that expansion does not routinely occur in most normal tissues. An elevated mutation rate itself will have no observable effect on clonal mutation frequency in the absence of expansion (Fig. 3E). To determine mutation rate from a clonal mutation frequency it is necessary to (A) know that the population being assessed is clonal and (B) have some metric of the number of cell divisions that occurred in the period between the zygote and the founding of the final clonalSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPageoutgrowth. To infer that a rate is elevated, it is also necessary to know the normal in vivo mutation rate, which is, in turn, impossible to measure by this approach given that large clonal expansions do not routinely occur in normal adult tissue. Considering these complexities, the lack of resolution as to whether mutation rates are elevated in cancer is not surprising [1,8?1]. (v) Detectabili.Deration when interpreting experimental findings. (i) Identification of a mutation in a clonal population does not indicate causality Any mutation in a cell that undergoes clonal expansion will be passed onto progeny, irrespective of functional status (Fig. 3A,B). Given the size of the genome, more mutations carried by a neoplastic clone will be passengers than drivers [27, 29, 30]. To demonstrate driver status, supporting functional studies and/or repeated observations of a mutated loci in neoplastic clones from independent individuals are needed. (ii) Mutational marking of a clone is stochastic and not guaranteed A clone may exist and not be detected if none of the genomic sites being screened carry a unique mutation permitting it to be distinguished from the germline (Fig. 3C). The more sites examined, the higher the probability of detection becomes. Restricting a marker panel to suspected driver sites precludes detection of pathological clones driven by unknown factors. (iii) Elevated mutation rates facilitate clone detection but are not an absolute requirement Screening of mutational hotspots makes it practical with conventional technologies to have a reasonable probability of detecting a clone by random passenger mutations. Clones derived from a mutator lineage or cells residing in a highly mutagenic environment should be more densely marked with identifiable passengers (Fig. 3D), potentially reducing the number of markers needing to be interrogated to identify them. Emerging high-throughput sequencing technologies will eventually obviate the need to restrict screening to a fraction of the genome. (iv) Identification of one or more clonal mutations is not proof of genetic instability in the absence of collateral information Detection of a mutation requires clonal expansion with most traditional methods of aggregate DNA analysis. The probability of identifying clonal mutations in an expanded population is a function of the number of sites screened, the mutability of these sites and the number of cell divisions having occurred in the lineage leading up to the final expansion. Particularly when considering hotspots, mutations will be occasionally detectable in any clonally-derived population at a statistically definable frequency. Because mutations are not routinely encountered in normal tissues, it is tempting to explain their presence in preneoplastic populations as the result of “genetic instability” (an elevated mutation rate). However, the phenomenon is more precisely explained by the fact that expansion does not routinely occur in most normal tissues. An elevated mutation rate itself will have no observable effect on clonal mutation frequency in the absence of expansion (Fig. 3E). To determine mutation rate from a clonal mutation frequency it is necessary to (A) know that the population being assessed is clonal and (B) have some metric of the number of cell divisions that occurred in the period between the zygote and the founding of the final clonalSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPageoutgrowth. To infer that a rate is elevated, it is also necessary to know the normal in vivo mutation rate, which is, in turn, impossible to measure by this approach given that large clonal expansions do not routinely occur in normal adult tissue. Considering these complexities, the lack of resolution as to whether mutation rates are elevated in cancer is not surprising [1,8?1]. (v) Detectabili.

5. Category-selective regions show graded activation profiles for images of their preferred

5. Category-selective regions show graded activation profiles for images of their preferred category. A, If some images consistently activated a region more strongly than other images of the same category (i.e., graded within-category activation profile), the within-category ranking order should replicate across sessions. We computed the replicability of within-category ranking by selecting the samecategorysubsetofimagesinbothsessionsandcorrelatingtheiractivationestimatesusingSpearman’sr.Thisprocedureisillustrated forthewithin-faceactivationprofileinrightFFAdefinedat128voxelsinonespecificsubject.ColorcodingisthesameasinFigure1.B,Group analysisofreplicabilityofwithin-categoryactivationprofilesforcategory-selectiveregionsFFAandPPAandforcontrolregionshITandEVC. Analysis was performed for the image subsets of faces (top) and places (bottom), either using the concatenation approach (left) or the averaging approach (right) for combining single-subject data. Analysis of concatenated single-subject activation profiles is sensitive to replicablerankingregardlessofdifferencesinparticularrankingorderamongsubjects,whileanalysisofsubject-averageactivationprofiles is sensitive to replicable ranking that is consistent among subjects. We performed a standard one-sided test on Spearman’s r to determine whether replicability of within-category activation profiles was significantly higher than expected by chance (H0: r 0). p values were corrected for multiple comparisons as described in buy BMS-5 Figure 1. Black boxes highlight the ROI sizes that results were displayed at in Figures 1 (FFA and PPA) and 2 (hIT and EVC).Mur et al. ?Single-Image Activation of Category RegionsJ. Neurosci., June 20, 2012 ?32(25):8649 ?8662 ?tive regions in IT cortex are categorical, yet graded.DiscussionFFA and PPA might respond more strongly to every single member of their preferred category than to any nonmember We measured single-image activation of human category-selective regions to 96 object images from a wide range of categories, and investigated whether category selectivity holds in general or is INK1117 supplier violated by particular single images. We found good discrimination of preferred from nonpreferred stimuli based on single-image activation of category-selective regions FFA and PPA across a wide range of ROI sizes. Furthermore, we did not find evidence for violations of category-consistent ranking by particular single images, except in left FFA. Together, these findings suggest the possibility that right FFA and left and right PPA respond more strongly to every single member of their preferred category than to any nonmember. This conclusion is consistent with several single-image studies in monkeys that showed strong face-selectivity in the macaque middle and anterior superior temporal sulcus (STS) (Foldiak et al., 2004; ??Tsao et al., 2006). These studies reported cells that responded almost exclusively to faces. It should be noted that many of the recorded cells in the middle macaque face patch, a suggested homolog of FFA located in the STS (Tsao et al., 2003, 2006), also responded significantly to several nonface images (Tsao et al., 2006). These nonface images shared lower-level visual properties with face images (e.g., round shape). However, at the population level (i.e., when responses were averaged across the population of visually responsive cells in the middle face patch), the responses elicited by these nonface images were4 Figure 6. Category steps and graded activation profil.5. Category-selective regions show graded activation profiles for images of their preferred category. A, If some images consistently activated a region more strongly than other images of the same category (i.e., graded within-category activation profile), the within-category ranking order should replicate across sessions. We computed the replicability of within-category ranking by selecting the samecategorysubsetofimagesinbothsessionsandcorrelatingtheiractivationestimatesusingSpearman’sr.Thisprocedureisillustrated forthewithin-faceactivationprofileinrightFFAdefinedat128voxelsinonespecificsubject.ColorcodingisthesameasinFigure1.B,Group analysisofreplicabilityofwithin-categoryactivationprofilesforcategory-selectiveregionsFFAandPPAandforcontrolregionshITandEVC. Analysis was performed for the image subsets of faces (top) and places (bottom), either using the concatenation approach (left) or the averaging approach (right) for combining single-subject data. Analysis of concatenated single-subject activation profiles is sensitive to replicablerankingregardlessofdifferencesinparticularrankingorderamongsubjects,whileanalysisofsubject-averageactivationprofiles is sensitive to replicable ranking that is consistent among subjects. We performed a standard one-sided test on Spearman’s r to determine whether replicability of within-category activation profiles was significantly higher than expected by chance (H0: r 0). p values were corrected for multiple comparisons as described in Figure 1. Black boxes highlight the ROI sizes that results were displayed at in Figures 1 (FFA and PPA) and 2 (hIT and EVC).Mur et al. ?Single-Image Activation of Category RegionsJ. Neurosci., June 20, 2012 ?32(25):8649 ?8662 ?tive regions in IT cortex are categorical, yet graded.DiscussionFFA and PPA might respond more strongly to every single member of their preferred category than to any nonmember We measured single-image activation of human category-selective regions to 96 object images from a wide range of categories, and investigated whether category selectivity holds in general or is violated by particular single images. We found good discrimination of preferred from nonpreferred stimuli based on single-image activation of category-selective regions FFA and PPA across a wide range of ROI sizes. Furthermore, we did not find evidence for violations of category-consistent ranking by particular single images, except in left FFA. Together, these findings suggest the possibility that right FFA and left and right PPA respond more strongly to every single member of their preferred category than to any nonmember. This conclusion is consistent with several single-image studies in monkeys that showed strong face-selectivity in the macaque middle and anterior superior temporal sulcus (STS) (Foldiak et al., 2004; ??Tsao et al., 2006). These studies reported cells that responded almost exclusively to faces. It should be noted that many of the recorded cells in the middle macaque face patch, a suggested homolog of FFA located in the STS (Tsao et al., 2003, 2006), also responded significantly to several nonface images (Tsao et al., 2006). These nonface images shared lower-level visual properties with face images (e.g., round shape). However, at the population level (i.e., when responses were averaged across the population of visually responsive cells in the middle face patch), the responses elicited by these nonface images were4 Figure 6. Category steps and graded activation profil.

In living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic

In living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic Ca-phosphate in pelagic sediments has long been studied by a number of investigators17,18,21?4,40?2. Some have suggested that biogenic Ca-phosphate incorporates REY via pore water in the sediment column23,40. Others have argued that Ca-phosphate takes up REY from a variety of carrier 4-Hydroxytamoxifen web phases (e.g. Fe n-oxyhydroxides, pellets, and organic debris) that absorb REY from seawater and are readily decomposed at the sediment ater interface17,22,41,42. Although the complete process remains an open question, the characteristic REY patterns indicate that seawater is the ultimate source of the REY presently captured in biogenic Ca-phosphate22,25,41 (Fig. 4m). Simple quantitative estimation in this study suggested the possibility that seawater can contain the flux of REY precipitation required to explain the observed very high REY concentrations ( REY + Ce > 1,000 ppm) in bulk REY-rich mud with a sedimentation rate less than 0.5 m/Myr (Supplementary Fig. S19). Such circumstances may facilitate the concentration of REY in biogenic Ca-phosphate via diffusion of REY from seawater or the transfer of REY from original carriers to Ca-phosphate during the early diagenetic processes because of the prolonged exposure to seawater at the sediment surface and in the bioturbated and well-ventilated uppermost sediment layer17,18,22,41. In addition, biogenic Ca-phosphate enriched in REY might be stabilised through recrystallisation as insoluble apatite17. Moreover, the amount of Ca-phosphate in a unit volume of sediment also increases with a depression of the sedimentation rate17,18. Hence, the low sedimentation rate is considered to be crucial for the formation of REY-rich mud. Actually, the GW 4064 cost spatiotemporal distribution of high-IC1, -IC4, and -IC7 muds overlapped with the oligotrophic North Pacific and South Pacific gyres and with water depths greater than the CCD, both of which prevented the fast accumulation of dilutive components with low REY content such as biogenic carbonate and silica. If we assume that deep-sea sediments can continuously acquire REY from the overlying deep-sea water prior to burial, the REY-enrichment in sediments can occur in a time scale of 105 years considering the sedimentation rate of <0.5 m/Myr with a typical thickness of 0.1 m for the well-ventilated uppermost sediment layer43. This timescale of REY enrichment is significantly longer than that of global ocean circulation, which is 103 years44. Both IC1 and IC4 indicated statistical independent geochemical features of pelagic red clay mainly composed of detrital aluminosilicates involving abundant Si, Al, Fe, Mg, and K without significant contributions of biogenic carbonate and silica. Fe and Mn of hydrothermal or hydrogenous origins could have also been incorporated without dilution in high-IC1 and high-IC4 sediments, resulting in an increase in the contents of these elements. In addition, in deposition slow enough to allow biogenic Ca-phosphate grains to concentrate REY and to accumulate significantly in the sediment, the P and REY contents of these sediments also increase concurrently. Although sediments enriched in biogenic Ca-phosphate contain several percent of Ca, the significant dilution effect of biogenic carbonate, which contains several tens of percent of Ca, generally creates negative trends in these ICs as a whole in the spaces of Ca and other elements, including REY. The differenc.In living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic Ca-phosphate in pelagic sediments has long been studied by a number of investigators17,18,21?4,40?2. Some have suggested that biogenic Ca-phosphate incorporates REY via pore water in the sediment column23,40. Others have argued that Ca-phosphate takes up REY from a variety of carrier phases (e.g. Fe n-oxyhydroxides, pellets, and organic debris) that absorb REY from seawater and are readily decomposed at the sediment ater interface17,22,41,42. Although the complete process remains an open question, the characteristic REY patterns indicate that seawater is the ultimate source of the REY presently captured in biogenic Ca-phosphate22,25,41 (Fig. 4m). Simple quantitative estimation in this study suggested the possibility that seawater can contain the flux of REY precipitation required to explain the observed very high REY concentrations ( REY + Ce > 1,000 ppm) in bulk REY-rich mud with a sedimentation rate less than 0.5 m/Myr (Supplementary Fig. S19). Such circumstances may facilitate the concentration of REY in biogenic Ca-phosphate via diffusion of REY from seawater or the transfer of REY from original carriers to Ca-phosphate during the early diagenetic processes because of the prolonged exposure to seawater at the sediment surface and in the bioturbated and well-ventilated uppermost sediment layer17,18,22,41. In addition, biogenic Ca-phosphate enriched in REY might be stabilised through recrystallisation as insoluble apatite17. Moreover, the amount of Ca-phosphate in a unit volume of sediment also increases with a depression of the sedimentation rate17,18. Hence, the low sedimentation rate is considered to be crucial for the formation of REY-rich mud. Actually, the spatiotemporal distribution of high-IC1, -IC4, and -IC7 muds overlapped with the oligotrophic North Pacific and South Pacific gyres and with water depths greater than the CCD, both of which prevented the fast accumulation of dilutive components with low REY content such as biogenic carbonate and silica. If we assume that deep-sea sediments can continuously acquire REY from the overlying deep-sea water prior to burial, the REY-enrichment in sediments can occur in a time scale of 105 years considering the sedimentation rate of <0.5 m/Myr with a typical thickness of 0.1 m for the well-ventilated uppermost sediment layer43. This timescale of REY enrichment is significantly longer than that of global ocean circulation, which is 103 years44. Both IC1 and IC4 indicated statistical independent geochemical features of pelagic red clay mainly composed of detrital aluminosilicates involving abundant Si, Al, Fe, Mg, and K without significant contributions of biogenic carbonate and silica. Fe and Mn of hydrothermal or hydrogenous origins could have also been incorporated without dilution in high-IC1 and high-IC4 sediments, resulting in an increase in the contents of these elements. In addition, in deposition slow enough to allow biogenic Ca-phosphate grains to concentrate REY and to accumulate significantly in the sediment, the P and REY contents of these sediments also increase concurrently. Although sediments enriched in biogenic Ca-phosphate contain several percent of Ca, the significant dilution effect of biogenic carbonate, which contains several tens of percent of Ca, generally creates negative trends in these ICs as a whole in the spaces of Ca and other elements, including REY. The differenc.

, a runner who demonstrates considerably less than 45?of knee flexion may

, a runner who demonstrates considerably less than 45?of knee PD325901MedChemExpress PD325901 flexion may suggest reduced shock absorption, and intervention may be warranted. Some data exist PD0325901 msds suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj., a runner who demonstrates considerably less than 45?of knee flexion may suggest reduced shock absorption, and intervention may be warranted. Some data exist suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj.

Ampal CA1 subfield in individuals with MCI compared to NCI (Fig.

Ampal CA1 subfield in individuals with MCI GW9662 chemical information compared to NCI (Fig. 4), which correlated with the subject’s Mini-Mental State Exam score (MMSE), but not with NFT Braak stage or apolipoprotein E (ApoE) status, a genetic risk factor for AD (Scheff et al., 2006). Unlike the outer molecular layer, CA1 receives input from the Schaffer collaterals arising from CA3 and not from the glutamatergic neurons of the entorhinal cortex, suggesting differential responses to synapse loss within the hippocampus based upon afferent innervation or chemical phenotype, some of which precipitate synaptic reorganization. A recent report characterized changes in the dendritic branching of the basilar tree of hippocampal CA1 pyramidal neurons. In this study, formalin-fixed tissue autopsy obtained from University of Kentucky Alzheimer’s Disease Center who died with a clinical diagnosis of NCI, MCI or AD was prepared for Golgi impregnation (Fig. 5). Camera lucida drawings of the basilar tree of randomly selected CA1 neurons were analyzed for alterations in dendritic arbor amount, distribution and complexity (Mervis et al., 2013). Quantitation Mangafodipir (trisodium)MedChemExpress Mangafodipir (trisodium) showed a significant increase in dendritic length (18 ) and complexity (23 ) in CA1 neurons in MCI compared to NCI. Conversely, there was a significant reduction in branch length (-39 ) and arbor complexity (-25 ) during the progression from MCI to AD (Fig. 5). These findings suggest that the observed increase in CA1 dendritic parameters from NCI to MCI may be another example of a neuroplastic compensatory response to a loss of afferent input early in the course of the disease, which is not maintained as the disease progresses. The role that the reported reduction in total synapse number plays in CA1 neuroplasticity remains unknown. However, these examples of early CA1 neural reorganization may represent a viable window for potential therapeutic strategies aimed at restoring or maintaining hippocampal function during the transition from MCI to AD. Future studies should determine whether alterations in specific synapse subtypes (i.e., perforated vs. non-perforated) are differentially affected and their relation to cognitive decline and brain pathology during the onset of AD. Interestingly, the size of the synaptic contacts was found to be substantially larger in AD cortex compared to non-demented aged controls (Scheff et al., 1990), which was suggested to be part of a compensatory mechanism found in regions of the neocortex and hippocampus (see review Scheff and Price, 2006). These investigators found that as the number of synapses declined in a given region, the size of the residualAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagesynapses increased. This synaptic compensatory response was also observed early in the course of the AD (DeKosky and Scheff, 1990). Neuronal structural alterations may not be the only factor(s) contributing to cognitive decline and hippocampal plasticity in MCI. For example, studies have reported significant reductions in synaptic vesicle trafficking-related genes in the AD brain, which interrupt the efficacy of normal synaptic transmission (Yao et al., 2003; Murphy et al., 2003; Kennedy et al., 2005). Counts et al. (2014) examined progressive changes in the expression classes of synaptic gene within single CA1 neurons in subjects who died with a clinical diagnosis of NCI, MCI or moderate AD obtain.Ampal CA1 subfield in individuals with MCI compared to NCI (Fig. 4), which correlated with the subject’s Mini-Mental State Exam score (MMSE), but not with NFT Braak stage or apolipoprotein E (ApoE) status, a genetic risk factor for AD (Scheff et al., 2006). Unlike the outer molecular layer, CA1 receives input from the Schaffer collaterals arising from CA3 and not from the glutamatergic neurons of the entorhinal cortex, suggesting differential responses to synapse loss within the hippocampus based upon afferent innervation or chemical phenotype, some of which precipitate synaptic reorganization. A recent report characterized changes in the dendritic branching of the basilar tree of hippocampal CA1 pyramidal neurons. In this study, formalin-fixed tissue autopsy obtained from University of Kentucky Alzheimer’s Disease Center who died with a clinical diagnosis of NCI, MCI or AD was prepared for Golgi impregnation (Fig. 5). Camera lucida drawings of the basilar tree of randomly selected CA1 neurons were analyzed for alterations in dendritic arbor amount, distribution and complexity (Mervis et al., 2013). Quantitation showed a significant increase in dendritic length (18 ) and complexity (23 ) in CA1 neurons in MCI compared to NCI. Conversely, there was a significant reduction in branch length (-39 ) and arbor complexity (-25 ) during the progression from MCI to AD (Fig. 5). These findings suggest that the observed increase in CA1 dendritic parameters from NCI to MCI may be another example of a neuroplastic compensatory response to a loss of afferent input early in the course of the disease, which is not maintained as the disease progresses. The role that the reported reduction in total synapse number plays in CA1 neuroplasticity remains unknown. However, these examples of early CA1 neural reorganization may represent a viable window for potential therapeutic strategies aimed at restoring or maintaining hippocampal function during the transition from MCI to AD. Future studies should determine whether alterations in specific synapse subtypes (i.e., perforated vs. non-perforated) are differentially affected and their relation to cognitive decline and brain pathology during the onset of AD. Interestingly, the size of the synaptic contacts was found to be substantially larger in AD cortex compared to non-demented aged controls (Scheff et al., 1990), which was suggested to be part of a compensatory mechanism found in regions of the neocortex and hippocampus (see review Scheff and Price, 2006). These investigators found that as the number of synapses declined in a given region, the size of the residualAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagesynapses increased. This synaptic compensatory response was also observed early in the course of the AD (DeKosky and Scheff, 1990). Neuronal structural alterations may not be the only factor(s) contributing to cognitive decline and hippocampal plasticity in MCI. For example, studies have reported significant reductions in synaptic vesicle trafficking-related genes in the AD brain, which interrupt the efficacy of normal synaptic transmission (Yao et al., 2003; Murphy et al., 2003; Kennedy et al., 2005). Counts et al. (2014) examined progressive changes in the expression classes of synaptic gene within single CA1 neurons in subjects who died with a clinical diagnosis of NCI, MCI or moderate AD obtain.

Depletion prior to collagen immunization results in reduced disease, as pathogenic

Depletion prior to collagen immunization results in reduced disease, as pathogenic autoantibodies can no longer drive autoimmune inflammation (52). Despite evidence that B cells are inflammatory mediators of autoimmunity during CIA, some B cells subsets have also been shown to negatively regulate antigen-specific immune responses during arthritic disease. Mauri et al. (53) have described that in vitro activation of B cells with agonistic CD40 mAb induces production of IL-10 and to a much lesser extent, IFN-. Transfer of these in vitro-activated B cells into collagen-immunized DBA/1 with transgenic T-cell receptors specific for collagen significantly delayed Cyclopamine manufacturer disease onset and ameliorated established disease. The observed effects were attributed to the ability of the transferred B cells to produce IL-10, as B cells derived from IL-10-/- mice were without effect. An immunosuppressive role for B cells during CIA was further described in studies where the CD21hi CD23+ IgM+ transitional 2 marginal zone precursor (T2-MZP) cell population was isolated and transferred to collagen-immunized DBA/1 mice (54). TZ-MZP cell adoptive transfers delayed disease onset and treated established disease via inhibition of Th1-type immune responses in an IL-10-dependent manner. Moreover, adoptive transfer of total splenic B cells from apoptotic cell-treated mice also suppressed autoimmune pathogenesis in an IL-10-dependent manner that encouraged CD4+ T cell IL-10 production, thus verifying the ability of particular B-cell subsets to instigate tolerance and inhibit arthritic inflammation in CIA (22). A role for B10 cells specifically during CIA was investigated by Yang et al. using B cells cultured in vitro with BAFF for 72 h, which is reported to induce IL-10 production in approximately 32 of CD1dhi CD5+ B cells (55). The B10 cell-enriched B cells were then transferred to collagen-immunized DBA/1 mice where they delayed the onset of arthritis and specifically downregulated Th17 responses. Taken together, these studies confirmed the role of B cells during CIA and documented that while some pathogenic B-cell populations certainly contribute to the progression of disease, regulatory B-cell subsets, especially B10 cells, are capable of inhibiting effector T-cell responses during the course of CIA.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptImmunol Rev. Author manuscript; available in PMC 2015 May 01.Candando et al.PageB10 cell regulation of Crotaline biological activity pathogen clearance Unlike autoimmune models in which B10 cells ameliorate disease and improve symptoms, the presence of B10 cells during infection prevents efficient pathogen clearance. During Listeria monocytogenes infection, antibody-mediated B10 cell depletion resulted in reduced bacterial load and enhanced macrophage activity (29). Although B10 cells inhibited innate cells in this model, their regulatory effects were nonetheless dependent upon cognate interactions with T cells, as B10 cells deficient in MHC-II or IL-21R did not affect Listeria responses. These findings clearly document a role for B10 cells in regulating immune system homeostasis, whereby the presence of B10 cells establishes the normal course of pathogen clearance. Remarkably, the depletion of B10 cells thereby enhances immunity and accelerates pathogen clearance. Regulatory B cells have also been implicated in suppression of immune responses during Salmonella typhimurium infection. In this study, B-cell-deficient mice reconsti.Depletion prior to collagen immunization results in reduced disease, as pathogenic autoantibodies can no longer drive autoimmune inflammation (52). Despite evidence that B cells are inflammatory mediators of autoimmunity during CIA, some B cells subsets have also been shown to negatively regulate antigen-specific immune responses during arthritic disease. Mauri et al. (53) have described that in vitro activation of B cells with agonistic CD40 mAb induces production of IL-10 and to a much lesser extent, IFN-. Transfer of these in vitro-activated B cells into collagen-immunized DBA/1 with transgenic T-cell receptors specific for collagen significantly delayed disease onset and ameliorated established disease. The observed effects were attributed to the ability of the transferred B cells to produce IL-10, as B cells derived from IL-10-/- mice were without effect. An immunosuppressive role for B cells during CIA was further described in studies where the CD21hi CD23+ IgM+ transitional 2 marginal zone precursor (T2-MZP) cell population was isolated and transferred to collagen-immunized DBA/1 mice (54). TZ-MZP cell adoptive transfers delayed disease onset and treated established disease via inhibition of Th1-type immune responses in an IL-10-dependent manner. Moreover, adoptive transfer of total splenic B cells from apoptotic cell-treated mice also suppressed autoimmune pathogenesis in an IL-10-dependent manner that encouraged CD4+ T cell IL-10 production, thus verifying the ability of particular B-cell subsets to instigate tolerance and inhibit arthritic inflammation in CIA (22). A role for B10 cells specifically during CIA was investigated by Yang et al. using B cells cultured in vitro with BAFF for 72 h, which is reported to induce IL-10 production in approximately 32 of CD1dhi CD5+ B cells (55). The B10 cell-enriched B cells were then transferred to collagen-immunized DBA/1 mice where they delayed the onset of arthritis and specifically downregulated Th17 responses. Taken together, these studies confirmed the role of B cells during CIA and documented that while some pathogenic B-cell populations certainly contribute to the progression of disease, regulatory B-cell subsets, especially B10 cells, are capable of inhibiting effector T-cell responses during the course of CIA.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptImmunol Rev. Author manuscript; available in PMC 2015 May 01.Candando et al.PageB10 cell regulation of pathogen clearance Unlike autoimmune models in which B10 cells ameliorate disease and improve symptoms, the presence of B10 cells during infection prevents efficient pathogen clearance. During Listeria monocytogenes infection, antibody-mediated B10 cell depletion resulted in reduced bacterial load and enhanced macrophage activity (29). Although B10 cells inhibited innate cells in this model, their regulatory effects were nonetheless dependent upon cognate interactions with T cells, as B10 cells deficient in MHC-II or IL-21R did not affect Listeria responses. These findings clearly document a role for B10 cells in regulating immune system homeostasis, whereby the presence of B10 cells establishes the normal course of pathogen clearance. Remarkably, the depletion of B10 cells thereby enhances immunity and accelerates pathogen clearance. Regulatory B cells have also been implicated in suppression of immune responses during Salmonella typhimurium infection. In this study, B-cell-deficient mice reconsti.

Deration when interpreting experimental findings. (i) Identification of a mutation in

Deration when interpreting experimental findings. (i) Identification of a mutation in a clonal population does not indicate causality Any mutation in a cell that undergoes clonal expansion will be passed onto progeny, irrespective of functional status (Fig. 3A,B). Given the size of the genome, more mutations carried by a neoplastic clone will be passengers than drivers [27, 29, 30]. To demonstrate driver status, supporting functional studies and/or repeated observations of a mutated loci in neoplastic clones from independent individuals are needed. (ii) Mutational marking of a clone is stochastic and not guaranteed A clone may exist and not be detected if none of the genomic sites being screened carry a unique mutation permitting it to be distinguished from the germline (Fig. 3C). The more sites examined, the higher the probability of detection becomes. Restricting a marker panel to suspected driver sites precludes detection of Cynaroside site pathological clones driven by unknown factors. (iii) Elevated mutation rates facilitate clone detection but are not an absolute requirement Screening of mutational hotspots makes it practical with conventional technologies to have a reasonable probability of detecting a clone by random passenger mutations. Clones derived from a mutator lineage or cells residing in a highly mutagenic environment should be more densely marked with identifiable passengers (Fig. 3D), potentially reducing the Z-DEVD-FMK site number of markers needing to be interrogated to identify them. Emerging high-throughput sequencing technologies will eventually obviate the need to restrict screening to a fraction of the genome. (iv) Identification of one or more clonal mutations is not proof of genetic instability in the absence of collateral information Detection of a mutation requires clonal expansion with most traditional methods of aggregate DNA analysis. The probability of identifying clonal mutations in an expanded population is a function of the number of sites screened, the mutability of these sites and the number of cell divisions having occurred in the lineage leading up to the final expansion. Particularly when considering hotspots, mutations will be occasionally detectable in any clonally-derived population at a statistically definable frequency. Because mutations are not routinely encountered in normal tissues, it is tempting to explain their presence in preneoplastic populations as the result of “genetic instability” (an elevated mutation rate). However, the phenomenon is more precisely explained by the fact that expansion does not routinely occur in most normal tissues. An elevated mutation rate itself will have no observable effect on clonal mutation frequency in the absence of expansion (Fig. 3E). To determine mutation rate from a clonal mutation frequency it is necessary to (A) know that the population being assessed is clonal and (B) have some metric of the number of cell divisions that occurred in the period between the zygote and the founding of the final clonalSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPageoutgrowth. To infer that a rate is elevated, it is also necessary to know the normal in vivo mutation rate, which is, in turn, impossible to measure by this approach given that large clonal expansions do not routinely occur in normal adult tissue. Considering these complexities, the lack of resolution as to whether mutation rates are elevated in cancer is not surprising [1,8?1]. (v) Detectabili.Deration when interpreting experimental findings. (i) Identification of a mutation in a clonal population does not indicate causality Any mutation in a cell that undergoes clonal expansion will be passed onto progeny, irrespective of functional status (Fig. 3A,B). Given the size of the genome, more mutations carried by a neoplastic clone will be passengers than drivers [27, 29, 30]. To demonstrate driver status, supporting functional studies and/or repeated observations of a mutated loci in neoplastic clones from independent individuals are needed. (ii) Mutational marking of a clone is stochastic and not guaranteed A clone may exist and not be detected if none of the genomic sites being screened carry a unique mutation permitting it to be distinguished from the germline (Fig. 3C). The more sites examined, the higher the probability of detection becomes. Restricting a marker panel to suspected driver sites precludes detection of pathological clones driven by unknown factors. (iii) Elevated mutation rates facilitate clone detection but are not an absolute requirement Screening of mutational hotspots makes it practical with conventional technologies to have a reasonable probability of detecting a clone by random passenger mutations. Clones derived from a mutator lineage or cells residing in a highly mutagenic environment should be more densely marked with identifiable passengers (Fig. 3D), potentially reducing the number of markers needing to be interrogated to identify them. Emerging high-throughput sequencing technologies will eventually obviate the need to restrict screening to a fraction of the genome. (iv) Identification of one or more clonal mutations is not proof of genetic instability in the absence of collateral information Detection of a mutation requires clonal expansion with most traditional methods of aggregate DNA analysis. The probability of identifying clonal mutations in an expanded population is a function of the number of sites screened, the mutability of these sites and the number of cell divisions having occurred in the lineage leading up to the final expansion. Particularly when considering hotspots, mutations will be occasionally detectable in any clonally-derived population at a statistically definable frequency. Because mutations are not routinely encountered in normal tissues, it is tempting to explain their presence in preneoplastic populations as the result of “genetic instability” (an elevated mutation rate). However, the phenomenon is more precisely explained by the fact that expansion does not routinely occur in most normal tissues. An elevated mutation rate itself will have no observable effect on clonal mutation frequency in the absence of expansion (Fig. 3E). To determine mutation rate from a clonal mutation frequency it is necessary to (A) know that the population being assessed is clonal and (B) have some metric of the number of cell divisions that occurred in the period between the zygote and the founding of the final clonalSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPageoutgrowth. To infer that a rate is elevated, it is also necessary to know the normal in vivo mutation rate, which is, in turn, impossible to measure by this approach given that large clonal expansions do not routinely occur in normal adult tissue. Considering these complexities, the lack of resolution as to whether mutation rates are elevated in cancer is not surprising [1,8?1]. (v) Detectabili.

Faces or places at any ROI size. We additionally performed a

Faces or places at any ROI size. We additionally performed a modified version of our analysis, which is sensitive to subject-unique activation profiles. This analysis again showed a significant category step for right FFA and right and left PPA at all ROI sizes. Left FFA now showed a significant category step at three of five ROI sizes ( p 0.05, with p 0.0025 for 55 voxels). There was no evidence for a category step in hIT and EVC. Results for gradedness AMG9810 site within the preferred category (Fig. 6 B) were consistent with the results on the replicability of withincategory ranking reported in the previous section (Fig. 5B). Bothleft and right FFA showed graded within-face activation profiles. Left FFA showed gradedness at the smallest two ROI sizes ( p 0.0025) and right FFA at all ROI sizes ( p 0.0025) except the largest one. Right but not left PPA showed a graded within-place activation profile at three of five ROI sizes ( p 0.0025 for 23 voxels, p 0.05 for 55 and 128 voxels). hIT and EVC showed graded within-place but not within-face activation profiles at most or all ROI sizes ( p 0.05, with p 0.0025 in several cases). The subject-unique analysis showed similar results for FFA and PPA. For hIT and EVC, gradedness within places disappeared, while gradedness within faces remained absent. The lack of within-place and within-face gradedness in hIT for the subject-unique analysis forms the only inconsistency with the replicability-of-withincategory-ranking results (Fig. 5B, left column), and suggests that the subject-unique activation profiles for faces and places in hIT do not fall off linearly. (The category-step-and-gradedness analysis modeled the falloff of activation as linear within preferred and within nonpreferred categories, whereas the replicability-ofwithin-category-ranking analysis is sensitive to nonlinear graded activation profiles.) Category-selective regions FFA and PPA also showed graded activation profiles for nonpreferred images at most ROI sizes (Fig. 6 B). This effect likely reflects both between- and withincategory activation differences among the nonpreferred images. In any case, this finding indicates that the activation profile of category-selective regions is graded for images outside the preferred category. hIT and EVC did not show graded activation profiles for nonplaces or Mequitazine site nonfaces (except for nonfaces in EVC at the smallest ROI size, p 0.05, data not shown). The subjectunique group analysis showed similar results for FFA. For PPA, gradedness within nonplaces disappeared at most ROI sizes. Results for hIT did not change, while EVC now exhibited gradedness within nonfaces and nonplaces at a small number of ROI sizes ( p 0.05). In sum, our findings indicate that the category boundary has a special status in category-selective regions, especially in right FFA and right and left PPA. The presence of a drop-off of activation at the category boundary in the absence of gradedness would suggest a binary response profile. However, category-selective regions showed gradedness of activation within (except left PPA) and outside the preferred category in addition to the category step at the boundary. This suggests that a binary response function is not sufficient to explain the activation profiles of categoryselective regions. Correlation of activation profiles across regions Our results suggest functional similarities between certain regions, which we explored further by rank-correlating activation profiles between ROIs (Fig. 7).Faces or places at any ROI size. We additionally performed a modified version of our analysis, which is sensitive to subject-unique activation profiles. This analysis again showed a significant category step for right FFA and right and left PPA at all ROI sizes. Left FFA now showed a significant category step at three of five ROI sizes ( p 0.05, with p 0.0025 for 55 voxels). There was no evidence for a category step in hIT and EVC. Results for gradedness within the preferred category (Fig. 6 B) were consistent with the results on the replicability of withincategory ranking reported in the previous section (Fig. 5B). Bothleft and right FFA showed graded within-face activation profiles. Left FFA showed gradedness at the smallest two ROI sizes ( p 0.0025) and right FFA at all ROI sizes ( p 0.0025) except the largest one. Right but not left PPA showed a graded within-place activation profile at three of five ROI sizes ( p 0.0025 for 23 voxels, p 0.05 for 55 and 128 voxels). hIT and EVC showed graded within-place but not within-face activation profiles at most or all ROI sizes ( p 0.05, with p 0.0025 in several cases). The subject-unique analysis showed similar results for FFA and PPA. For hIT and EVC, gradedness within places disappeared, while gradedness within faces remained absent. The lack of within-place and within-face gradedness in hIT for the subject-unique analysis forms the only inconsistency with the replicability-of-withincategory-ranking results (Fig. 5B, left column), and suggests that the subject-unique activation profiles for faces and places in hIT do not fall off linearly. (The category-step-and-gradedness analysis modeled the falloff of activation as linear within preferred and within nonpreferred categories, whereas the replicability-ofwithin-category-ranking analysis is sensitive to nonlinear graded activation profiles.) Category-selective regions FFA and PPA also showed graded activation profiles for nonpreferred images at most ROI sizes (Fig. 6 B). This effect likely reflects both between- and withincategory activation differences among the nonpreferred images. In any case, this finding indicates that the activation profile of category-selective regions is graded for images outside the preferred category. hIT and EVC did not show graded activation profiles for nonplaces or nonfaces (except for nonfaces in EVC at the smallest ROI size, p 0.05, data not shown). The subjectunique group analysis showed similar results for FFA. For PPA, gradedness within nonplaces disappeared at most ROI sizes. Results for hIT did not change, while EVC now exhibited gradedness within nonfaces and nonplaces at a small number of ROI sizes ( p 0.05). In sum, our findings indicate that the category boundary has a special status in category-selective regions, especially in right FFA and right and left PPA. The presence of a drop-off of activation at the category boundary in the absence of gradedness would suggest a binary response profile. However, category-selective regions showed gradedness of activation within (except left PPA) and outside the preferred category in addition to the category step at the boundary. This suggests that a binary response function is not sufficient to explain the activation profiles of categoryselective regions. Correlation of activation profiles across regions Our results suggest functional similarities between certain regions, which we explored further by rank-correlating activation profiles between ROIs (Fig. 7).

Our more alternative notations: A ! B, A ! B, Z Y Z

Our more alternative notations: A ! B, A ! B, Z Y Z XY Z X Z Z A ! B, and A ! B. Category 5 (CS) gets one more alternative notation, [A !B and A Z Y Y Z Z Z ZB].Finally, category 6 (asocial) gets two more alternative notations, A !B and A B. For any N ! 2, all of the 2N+1 elementary interactions are included in the representative relationships of the six categories and their alternative notations. This results from the building process of the six categories, with the differentiations covering all possible cases. In the example of N = 3, the above statement is illustrated by the comparison of the sixteen elementary interactions of Table 4 with the six categories and their alternative GSK-1605786 cost notations for N = 2 (Table 3), completed by the alternative notations for N = 3 listed above. This concludes the proof of exhaustiveness of the six categories of Table 3 for any number N ! 2 of non-null EPZ-5676 chemical information social actions. With N social actions at hand, richer composite relationships can be represented. Let us translate into our action fluxes representation an example of composite relationship given by Goldman [25] (pp. 344-345). Namely, “two friends may share tapes and records freely with each other (CS), work on a task at which one is an expert and imperiously directs the other (AR), divide equally the cost of gas on a trip (EM), and transfer a bicycle from one to the other S2 S4 S5 S6 S1 S for a market-value price (MP).” This gives [A ! B, A 1 B, A ! B, A ! B, A ! B, A ! B].S2 S4 S6 SHere the relationship was known and we wrote it in terms of action fluxes. The next step is to find out how to identify a relationship when the action fluxes are given. We touch on how to achieve this in the discussion.Discussion Analyzing data setsOur representation in action fluxes provides a tool to identify types of dyadic relationships occurring within potentially large data sets of social interactions. Both collective and dyadic interactions may occur in real social contexts, but our approach applies specifically to the latter. Large data sets can result from any type of online social network or massively multiplayer online role-playing games (MMORPG), for instance. MMORPGs bring hundreds of thousands of players together to cooperate and compete by forming alliances, trading, fighting, and so on, all the while recording every single action and communication of the players. They are used in quantitative social science, for example by Thurner in the context of the game Pardus [26?8]. Ethnological and anthropological studies can provide rich reports of social interactions occurring in non-artificial settings that could be coded and interpreted with the aid of our categorization. Data sets of dyadic interactions can also be generated by computer simulations such as agent-based models (ABMs) to test specific questions. We offer the sketch of a method to analyze a potentially large data set of dyadic social interactions expressed as action fluxes (“A does X to B”, etc.). Given a data set involving a number of individuals, one needs to consider separately each pair of individuals. For each pair, one shall examine each social action and test into which category of action fluxes it falls, possibly jointly with another social action (in the case of MP and AR). In its second column, Table 5 specifies the patterns of fluxes expected to be observed in each category. Let us stress the following points: ?The patterns of observed fluxes given in Table 5 are not meant as definitions of the.Our more alternative notations: A ! B, A ! B, Z Y Z XY Z X Z Z A ! B, and A ! B. Category 5 (CS) gets one more alternative notation, [A !B and A Z Y Y Z Z Z ZB].Finally, category 6 (asocial) gets two more alternative notations, A !B and A B. For any N ! 2, all of the 2N+1 elementary interactions are included in the representative relationships of the six categories and their alternative notations. This results from the building process of the six categories, with the differentiations covering all possible cases. In the example of N = 3, the above statement is illustrated by the comparison of the sixteen elementary interactions of Table 4 with the six categories and their alternative notations for N = 2 (Table 3), completed by the alternative notations for N = 3 listed above. This concludes the proof of exhaustiveness of the six categories of Table 3 for any number N ! 2 of non-null social actions. With N social actions at hand, richer composite relationships can be represented. Let us translate into our action fluxes representation an example of composite relationship given by Goldman [25] (pp. 344-345). Namely, “two friends may share tapes and records freely with each other (CS), work on a task at which one is an expert and imperiously directs the other (AR), divide equally the cost of gas on a trip (EM), and transfer a bicycle from one to the other S2 S4 S5 S6 S1 S for a market-value price (MP).” This gives [A ! B, A 1 B, A ! B, A ! B, A ! B, A ! B].S2 S4 S6 SHere the relationship was known and we wrote it in terms of action fluxes. The next step is to find out how to identify a relationship when the action fluxes are given. We touch on how to achieve this in the discussion.Discussion Analyzing data setsOur representation in action fluxes provides a tool to identify types of dyadic relationships occurring within potentially large data sets of social interactions. Both collective and dyadic interactions may occur in real social contexts, but our approach applies specifically to the latter. Large data sets can result from any type of online social network or massively multiplayer online role-playing games (MMORPG), for instance. MMORPGs bring hundreds of thousands of players together to cooperate and compete by forming alliances, trading, fighting, and so on, all the while recording every single action and communication of the players. They are used in quantitative social science, for example by Thurner in the context of the game Pardus [26?8]. Ethnological and anthropological studies can provide rich reports of social interactions occurring in non-artificial settings that could be coded and interpreted with the aid of our categorization. Data sets of dyadic interactions can also be generated by computer simulations such as agent-based models (ABMs) to test specific questions. We offer the sketch of a method to analyze a potentially large data set of dyadic social interactions expressed as action fluxes (“A does X to B”, etc.). Given a data set involving a number of individuals, one needs to consider separately each pair of individuals. For each pair, one shall examine each social action and test into which category of action fluxes it falls, possibly jointly with another social action (in the case of MP and AR). In its second column, Table 5 specifies the patterns of fluxes expected to be observed in each category. Let us stress the following points: ?The patterns of observed fluxes given in Table 5 are not meant as definitions of the.

2.56 36 249.65 12.03 36 21.47 4.14 36 4.31 90.1 40 90.90 3.5 40 4.63 23.19 32 26.70 55.72 36 107.98 18.03 36 60.23 3.61 36 5.47 163.57 94 264.41 10.48 94 24.11 71.04 86 138.18 98.36 107 166.58 13.80 107 19.28 5.84 107 7.88 104.55 40 92.01 5.53 40 6.39 36.13 32 51.27 71.35 46 103.99 23.94 46 42.86 7.00 46 11.98 Likes Comments Shares Click-Throughs Avg. Visit Duration (s) Retention Rate ( )doi

2.56 36 249.65 12.03 36 21.47 4.14 36 4.31 90.1 40 90.90 3.5 40 4.63 23.19 32 26.70 55.72 36 107.98 18.03 36 60.23 3.61 36 5.47 163.57 94 264.41 10.48 94 24.11 71.04 86 138.18 98.36 107 166.58 13.80 107 19.28 5.84 107 7.88 104.55 40 92.01 5.53 40 6.39 36.13 32 51.27 71.35 46 103.99 23.94 46 42.86 7.00 46 11.98 Likes Comments Shares Click-Throughs Avg. Visit Duration (s) Retention Rate ( )doi:10.1371/journal.pone.0156409.tPlatforms, Item Types, and the Interactions Anlotinib web Between ThemOverall, the most popular behaviour on different item types was likes on “Wow” items (285.93 IPI, SD 703.74). “Wow” items also received relatively many click-throughs (142.56 IPI, SD 249.65) and shares (115.88 IPI, SD 244.12). Other notable behaviours include likes on “News” items (163.57 IPI, SD 264.41), click-throughs on “News” items” (98.36 IPI, SD 166.58), and likes on GWII items (104.55 IPI, SD 92.01) (Table 7). A series of ANOVA tests revealed different combined effects of social media purchase FPS-ZM1 platforms and item types on different user behaviours. Likes. There was a significant interaction between platform and item type on the number of likes per user (F (12,194) = 3.46, p < 0.001). Especially, it seems that the combined effect of Wow images and the Instagram platform yields many more likes than any other combination of platform and item type (Fig 3A). Visit duration and retention rate. There was a significant interaction between platform and item type on the average visit duration (per user) (F (9, 209) = 2.629, p < 0.01) and on retention rate (F(9, 209) = 2.075, p < 0.05). Among users who clicked on links, Twitter French users uniquely tended to spend much more time on pages that Guess What It Is links led to than any other user on any other platform or item type (Fig 3B). This interaction is also reflected in retention rate data (Fig 3C). Comments. In the case of comments, platform has a significant effect on user behaviour, but item type does not. For example, platform was found to have a significant effect on the number of comments (per user) (F (4,12) = 31.684, p < 0.001). Post-hoc tests revealed that Instagram had significantly more comments (per user) than any other platform (p < 0.001). However, no significant effect of item type on comments (per user) was found, nor was a significant interaction of platform and item type found.PLOS ONE | DOI:10.1371/journal.pone.0156409 May 27,11 /Engagement with Particle Physics on CERN’s Social Media PlatformsFig 3. Interactions between likes, visit durations and retention rates, by platform and item type. (A) Likes per item per 1,000 followers, by platform and item type. (B) Visit durations (C) Retention rates, by platform and item type. Y-axes show estimated marginal means, which reflect main effects, while controlling for other effects. GWII: Guess What It Is. TBT: Throwback Thursday. doi:10.1371/journal.pone.0156409.gClick-throughs. Similar to commenting, platform was found to have a significant effect on clicking on links (F (3, 209) = 6.956, p < 0.001). Post-hoc tests revealed that on average, links on Google+ received more click-throughs (per user) than links on Facebook or Twitter (p < 0.05). However, no significant effect of item type on click-throughs (per user) was found, nor of the interaction between platform and item type. Sharing. Last but not least, sharing was found to be a unique behaviour in this study, in that no significant effects of item type or platform on shares (per user) were found.Characterizin.2.56 36 249.65 12.03 36 21.47 4.14 36 4.31 90.1 40 90.90 3.5 40 4.63 23.19 32 26.70 55.72 36 107.98 18.03 36 60.23 3.61 36 5.47 163.57 94 264.41 10.48 94 24.11 71.04 86 138.18 98.36 107 166.58 13.80 107 19.28 5.84 107 7.88 104.55 40 92.01 5.53 40 6.39 36.13 32 51.27 71.35 46 103.99 23.94 46 42.86 7.00 46 11.98 Likes Comments Shares Click-Throughs Avg. Visit Duration (s) Retention Rate ( )doi:10.1371/journal.pone.0156409.tPlatforms, Item Types, and the Interactions Between ThemOverall, the most popular behaviour on different item types was likes on “Wow” items (285.93 IPI, SD 703.74). “Wow” items also received relatively many click-throughs (142.56 IPI, SD 249.65) and shares (115.88 IPI, SD 244.12). Other notable behaviours include likes on “News” items (163.57 IPI, SD 264.41), click-throughs on “News” items” (98.36 IPI, SD 166.58), and likes on GWII items (104.55 IPI, SD 92.01) (Table 7). A series of ANOVA tests revealed different combined effects of social media platforms and item types on different user behaviours. Likes. There was a significant interaction between platform and item type on the number of likes per user (F (12,194) = 3.46, p < 0.001). Especially, it seems that the combined effect of Wow images and the Instagram platform yields many more likes than any other combination of platform and item type (Fig 3A). Visit duration and retention rate. There was a significant interaction between platform and item type on the average visit duration (per user) (F (9, 209) = 2.629, p < 0.01) and on retention rate (F(9, 209) = 2.075, p < 0.05). Among users who clicked on links, Twitter French users uniquely tended to spend much more time on pages that Guess What It Is links led to than any other user on any other platform or item type (Fig 3B). This interaction is also reflected in retention rate data (Fig 3C). Comments. In the case of comments, platform has a significant effect on user behaviour, but item type does not. For example, platform was found to have a significant effect on the number of comments (per user) (F (4,12) = 31.684, p < 0.001). Post-hoc tests revealed that Instagram had significantly more comments (per user) than any other platform (p < 0.001). However, no significant effect of item type on comments (per user) was found, nor was a significant interaction of platform and item type found.PLOS ONE | DOI:10.1371/journal.pone.0156409 May 27,11 /Engagement with Particle Physics on CERN’s Social Media PlatformsFig 3. Interactions between likes, visit durations and retention rates, by platform and item type. (A) Likes per item per 1,000 followers, by platform and item type. (B) Visit durations (C) Retention rates, by platform and item type. Y-axes show estimated marginal means, which reflect main effects, while controlling for other effects. GWII: Guess What It Is. TBT: Throwback Thursday. doi:10.1371/journal.pone.0156409.gClick-throughs. Similar to commenting, platform was found to have a significant effect on clicking on links (F (3, 209) = 6.956, p < 0.001). Post-hoc tests revealed that on average, links on Google+ received more click-throughs (per user) than links on Facebook or Twitter (p < 0.05). However, no significant effect of item type on click-throughs (per user) was found, nor of the interaction between platform and item type. Sharing. Last but not least, sharing was found to be a unique behaviour in this study, in that no significant effects of item type or platform on shares (per user) were found.Characterizin.

Are a useful method for gaining insight into phenomena where little

Are a useful method for gaining insight into Necrostatin-1 biological activity phenomena where little is known [44]. When focus group data has been collected from multiple groups and multiple sites, researchers can have increased confidence in the reliability and validity of the findings [45]. The focus groups were guided by following questions. (1) Perceptions of Professional Socialization. (a) What comes to mind when you hear the phrase “professional socialization”? (b) Share memories of your experiences becoming socialized into the role of Licensed Practical Nurse and developing your identity in this role. (c) How is the experience of developing your new role and identity as a Registered Nurse the same? How is it different? (2) Formal Academic Experiences: Online Classes and Clinical Practicums. (a) Talk about experiences you have had so far in your online university classes where you “felt like” a Registered Nurse and not a Licensed Practical Nurse? Have there been times in your online4 [54] (page 85) maintained by both moderators during and immediately following the sessions further increased the dependability of our findings. Practical issues such as organizing groups at a time and place to minimize Necrostatin-1 side effects disruption and avoiding power differential dynamics [55] were addressed. The groups were held when participants, who were normally separated by distance, were together in the same city for a required practicum experience. They were held at change of shift in lieu of a post conference. Knowing the power differential between students and teachers, moderators who did not have teaching responsibilities in the Post LPN to BN program were chosen to facilitate the focus groups. Instructors were not present during any of the discussions and had no involvement with the transcript data. Participants were recruited through a Letter of Invitation sent via email by a Research Assistant who was also not involved with the program. Four focus groups were held with 5 to 9 participants each. All the students who were invited chose to participate. We reasoned that this may have been because they were all from out of town and appreciated an opportunity to interact and share their views. Pseudonyms ensured participant confidentiality. Full ethical approval was granted by the university. The following two overarching themes emerged from analyzing the data. First, Post LPN to BN students need little, if any, further legitimation to affirm their identities as “nurse.” Second, practicum interactions with instructors and new clinical experiences are key socializing agents.Nursing Research and Practice They talked about opportunities where demonstrating professional authority in their workplace further established their identity as “nurse”: “Working your first night shift . . . in your new role. The culture of night shift–it’s different.” “The first time I cared for a palliative patient and was there when they passed. Talking with the family. My first job that I had as an LPN, I was alone on the floor as the only official nurse for more than half of my shift. I had the full responsibility of all 60 residents in my care . . . that all happened as an LPN.” From the Post LPN to BN students’ perspective, the notion that socialization into the role of “nurse” would occur for them at this point in their career was insulting: “I almost feel a little bit insulted to think that I would feel any less professional as an LPN than I do as an RN. I feel equally professional in both roles.” “My buddy nurse ac.Are a useful method for gaining insight into phenomena where little is known [44]. When focus group data has been collected from multiple groups and multiple sites, researchers can have increased confidence in the reliability and validity of the findings [45]. The focus groups were guided by following questions. (1) Perceptions of Professional Socialization. (a) What comes to mind when you hear the phrase “professional socialization”? (b) Share memories of your experiences becoming socialized into the role of Licensed Practical Nurse and developing your identity in this role. (c) How is the experience of developing your new role and identity as a Registered Nurse the same? How is it different? (2) Formal Academic Experiences: Online Classes and Clinical Practicums. (a) Talk about experiences you have had so far in your online university classes where you “felt like” a Registered Nurse and not a Licensed Practical Nurse? Have there been times in your online4 [54] (page 85) maintained by both moderators during and immediately following the sessions further increased the dependability of our findings. Practical issues such as organizing groups at a time and place to minimize disruption and avoiding power differential dynamics [55] were addressed. The groups were held when participants, who were normally separated by distance, were together in the same city for a required practicum experience. They were held at change of shift in lieu of a post conference. Knowing the power differential between students and teachers, moderators who did not have teaching responsibilities in the Post LPN to BN program were chosen to facilitate the focus groups. Instructors were not present during any of the discussions and had no involvement with the transcript data. Participants were recruited through a Letter of Invitation sent via email by a Research Assistant who was also not involved with the program. Four focus groups were held with 5 to 9 participants each. All the students who were invited chose to participate. We reasoned that this may have been because they were all from out of town and appreciated an opportunity to interact and share their views. Pseudonyms ensured participant confidentiality. Full ethical approval was granted by the university. The following two overarching themes emerged from analyzing the data. First, Post LPN to BN students need little, if any, further legitimation to affirm their identities as “nurse.” Second, practicum interactions with instructors and new clinical experiences are key socializing agents.Nursing Research and Practice They talked about opportunities where demonstrating professional authority in their workplace further established their identity as “nurse”: “Working your first night shift . . . in your new role. The culture of night shift–it’s different.” “The first time I cared for a palliative patient and was there when they passed. Talking with the family. My first job that I had as an LPN, I was alone on the floor as the only official nurse for more than half of my shift. I had the full responsibility of all 60 residents in my care . . . that all happened as an LPN.” From the Post LPN to BN students’ perspective, the notion that socialization into the role of “nurse” would occur for them at this point in their career was insulting: “I almost feel a little bit insulted to think that I would feel any less professional as an LPN than I do as an RN. I feel equally professional in both roles.” “My buddy nurse ac.

(10). These impacts pose significant challenges to the continued provisioning of ecosystem

(10). These impacts pose significant challenges to the continued provisioning of ecosystem services from the ocean: challenges that may seem overwhelming now, but even more so in light of the difficulties in addressing the complex drivers and reversing trends. In short, threats to ocean life and the provision of vital ecosystem services are unquestionably serious and pressures on ocean resources are escalating. Glimmers of Hope for Sustainable Use of the Ocean Despite these daunting challenges, there is reason for cautious hope. Around the globe, many positive changes are underway: awareness, attitudes, and social norms are changing; economic incentives are shifting; efforts to buy GW 4064 educate consumers are increasing; new policies are leading to stronger mandates and more effective governance, compliance, and enforcement; and practices are changing with the development of better technologies, new products, and business strategies that reflect the circular economy (11), greater engagement of scientists, and improved understanding of trade-offs. As a result, effective models for change based in naturalThe grand challenge for humanity is to meet the basic needs of PD173074 site people in an equitable manner today while simultaneously restoring and maintaining ecosystem functioning for future generations. We must do so in the face of growing numbers of people and the concomitant need for resources, and with environmental changes, such as climate change, already underway. The ocean is integral to this global mission. Ocean and coastal ecosystems provide a range of critical ecosystem services that people depend upon, such as food, oxygen, climate regulation, control of pests, protection from storm surges, recreational opportunities, and cultural value (1, 2). The ocean is home to rich biodiversity and plays key roles in many global processes, from primary production to nutrient cycling to climate and weather (3). Ocean-based activities and livelihoods are both enabled by and affect complex interactions among ecological, social, and economic systems. The global market value of marine and coastal resources and industries is estimated at 3 trillion per year (4). Over 3 billion people depend upon the oceans to provide their primary source of protein, and marine fisheries directly or indirectly employ over 200 million people (4). Other benefits, such as cultural or inspirational values, are harder towww.pnas.org/cgi/doi/10.1073/pnas.This article arises from the 2016 Annual Sackler Lecture, “Enough with the doom and gloom! Holistic approaches bring hope for people and the ocean,” presented by Jane Lubchenco on March 14, at the National Academy of Sciences in Washington, DC. The lecture was part of the Arthur M. Sackler Colloquium of the National Academy of Sciences, “Coupled Human and Environmental Systems,” held March 14?5. The complete program and video recordings of most presentations are available on the NAS website at www.nasonline.org/Coupled_Human_and_Environmental_Systems. Author contributions: J.L. and S.A.L. designed research; J.L., E.B.C.-C., J.N.R., and S.A.L. performed research; and J.L., E.B.C.-C., J.N.R., and S.A.L. wrote the paper. The authors declare no conflict of interest. This article is a PNAS Direct Submission. A.P.G. is a Guest Editor invited by the Editorial Board.To whom correspondence should be addressed. Email: [email protected] | December 20, 2016 | vol. 113 | no. 51 | 14507?ENVIRONMENTAL SCIENCESSUSTAINABILITY SCIENCEquantify.(10). These impacts pose significant challenges to the continued provisioning of ecosystem services from the ocean: challenges that may seem overwhelming now, but even more so in light of the difficulties in addressing the complex drivers and reversing trends. In short, threats to ocean life and the provision of vital ecosystem services are unquestionably serious and pressures on ocean resources are escalating. Glimmers of Hope for Sustainable Use of the Ocean Despite these daunting challenges, there is reason for cautious hope. Around the globe, many positive changes are underway: awareness, attitudes, and social norms are changing; economic incentives are shifting; efforts to educate consumers are increasing; new policies are leading to stronger mandates and more effective governance, compliance, and enforcement; and practices are changing with the development of better technologies, new products, and business strategies that reflect the circular economy (11), greater engagement of scientists, and improved understanding of trade-offs. As a result, effective models for change based in naturalThe grand challenge for humanity is to meet the basic needs of people in an equitable manner today while simultaneously restoring and maintaining ecosystem functioning for future generations. We must do so in the face of growing numbers of people and the concomitant need for resources, and with environmental changes, such as climate change, already underway. The ocean is integral to this global mission. Ocean and coastal ecosystems provide a range of critical ecosystem services that people depend upon, such as food, oxygen, climate regulation, control of pests, protection from storm surges, recreational opportunities, and cultural value (1, 2). The ocean is home to rich biodiversity and plays key roles in many global processes, from primary production to nutrient cycling to climate and weather (3). Ocean-based activities and livelihoods are both enabled by and affect complex interactions among ecological, social, and economic systems. The global market value of marine and coastal resources and industries is estimated at 3 trillion per year (4). Over 3 billion people depend upon the oceans to provide their primary source of protein, and marine fisheries directly or indirectly employ over 200 million people (4). Other benefits, such as cultural or inspirational values, are harder towww.pnas.org/cgi/doi/10.1073/pnas.This article arises from the 2016 Annual Sackler Lecture, “Enough with the doom and gloom! Holistic approaches bring hope for people and the ocean,” presented by Jane Lubchenco on March 14, at the National Academy of Sciences in Washington, DC. The lecture was part of the Arthur M. Sackler Colloquium of the National Academy of Sciences, “Coupled Human and Environmental Systems,” held March 14?5. The complete program and video recordings of most presentations are available on the NAS website at www.nasonline.org/Coupled_Human_and_Environmental_Systems. Author contributions: J.L. and S.A.L. designed research; J.L., E.B.C.-C., J.N.R., and S.A.L. performed research; and J.L., E.B.C.-C., J.N.R., and S.A.L. wrote the paper. The authors declare no conflict of interest. This article is a PNAS Direct Submission. A.P.G. is a Guest Editor invited by the Editorial Board.To whom correspondence should be addressed. Email: [email protected] | December 20, 2016 | vol. 113 | no. 51 | 14507?ENVIRONMENTAL SCIENCESSUSTAINABILITY SCIENCEquantify.

In living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic

In living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic Ca-phosphate in pelagic sediments has long been studied by a number of investigators17,18,21?4,40?2. Some have suggested that biogenic Ca-phosphate incorporates REY via pore water in the sediment column23,40. Others have argued that Ca-phosphate takes up REY from a variety of carrier phases (e.g. Fe n-oxyhydroxides, pellets, and organic debris) that absorb REY from seawater and are readily decomposed at the sediment ater interface17,22,41,42. Although the complete process remains an open question, the characteristic REY patterns indicate that seawater is the ultimate source of the REY presently captured in biogenic Ca-phosphate22,25,41 (Fig. 4m). Simple quantitative estimation in this study suggested the possibility that seawater can contain the flux of REY precipitation required to explain the observed very high REY concentrations ( REY + Ce > 1,000 ppm) in bulk REY-rich mud with a sedimentation rate less than 0.5 m/Myr (Supplementary Fig. S19). Such circumstances may facilitate the concentration of REY in biogenic Ca-phosphate via diffusion of REY from seawater or the transfer of REY from original carriers to Ca-phosphate during the early diagenetic processes because of the prolonged XAV-939 supplement exposure to seawater at the sediment surface and in the bioturbated and well-ventilated uppermost sediment layer17,18,22,41. In addition, biogenic Ca-phosphate enriched in REY might be stabilised through recrystallisation as insoluble apatite17. Moreover, the amount of Ca-phosphate in a unit volume of sediment also increases with a depression of the sedimentation rate17,18. Hence, the low sedimentation rate is considered to be crucial for the formation of REY-rich mud. Actually, the spatiotemporal distribution of high-IC1, -IC4, and -IC7 muds overlapped with the oligotrophic North Pacific and South Pacific gyres and with water depths greater than the CCD, both of which prevented the fast accumulation of dilutive components with low REY content such as biogenic carbonate and silica. If we assume that deep-sea sediments can BFA mechanism of action continuously acquire REY from the overlying deep-sea water prior to burial, the REY-enrichment in sediments can occur in a time scale of 105 years considering the sedimentation rate of <0.5 m/Myr with a typical thickness of 0.1 m for the well-ventilated uppermost sediment layer43. This timescale of REY enrichment is significantly longer than that of global ocean circulation, which is 103 years44. Both IC1 and IC4 indicated statistical independent geochemical features of pelagic red clay mainly composed of detrital aluminosilicates involving abundant Si, Al, Fe, Mg, and K without significant contributions of biogenic carbonate and silica. Fe and Mn of hydrothermal or hydrogenous origins could have also been incorporated without dilution in high-IC1 and high-IC4 sediments, resulting in an increase in the contents of these elements. In addition, in deposition slow enough to allow biogenic Ca-phosphate grains to concentrate REY and to accumulate significantly in the sediment, the P and REY contents of these sediments also increase concurrently. Although sediments enriched in biogenic Ca-phosphate contain several percent of Ca, the significant dilution effect of biogenic carbonate, which contains several tens of percent of Ca, generally creates negative trends in these ICs as a whole in the spaces of Ca and other elements, including REY. The differenc.In living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic Ca-phosphate in pelagic sediments has long been studied by a number of investigators17,18,21?4,40?2. Some have suggested that biogenic Ca-phosphate incorporates REY via pore water in the sediment column23,40. Others have argued that Ca-phosphate takes up REY from a variety of carrier phases (e.g. Fe n-oxyhydroxides, pellets, and organic debris) that absorb REY from seawater and are readily decomposed at the sediment ater interface17,22,41,42. Although the complete process remains an open question, the characteristic REY patterns indicate that seawater is the ultimate source of the REY presently captured in biogenic Ca-phosphate22,25,41 (Fig. 4m). Simple quantitative estimation in this study suggested the possibility that seawater can contain the flux of REY precipitation required to explain the observed very high REY concentrations ( REY + Ce > 1,000 ppm) in bulk REY-rich mud with a sedimentation rate less than 0.5 m/Myr (Supplementary Fig. S19). Such circumstances may facilitate the concentration of REY in biogenic Ca-phosphate via diffusion of REY from seawater or the transfer of REY from original carriers to Ca-phosphate during the early diagenetic processes because of the prolonged exposure to seawater at the sediment surface and in the bioturbated and well-ventilated uppermost sediment layer17,18,22,41. In addition, biogenic Ca-phosphate enriched in REY might be stabilised through recrystallisation as insoluble apatite17. Moreover, the amount of Ca-phosphate in a unit volume of sediment also increases with a depression of the sedimentation rate17,18. Hence, the low sedimentation rate is considered to be crucial for the formation of REY-rich mud. Actually, the spatiotemporal distribution of high-IC1, -IC4, and -IC7 muds overlapped with the oligotrophic North Pacific and South Pacific gyres and with water depths greater than the CCD, both of which prevented the fast accumulation of dilutive components with low REY content such as biogenic carbonate and silica. If we assume that deep-sea sediments can continuously acquire REY from the overlying deep-sea water prior to burial, the REY-enrichment in sediments can occur in a time scale of 105 years considering the sedimentation rate of <0.5 m/Myr with a typical thickness of 0.1 m for the well-ventilated uppermost sediment layer43. This timescale of REY enrichment is significantly longer than that of global ocean circulation, which is 103 years44. Both IC1 and IC4 indicated statistical independent geochemical features of pelagic red clay mainly composed of detrital aluminosilicates involving abundant Si, Al, Fe, Mg, and K without significant contributions of biogenic carbonate and silica. Fe and Mn of hydrothermal or hydrogenous origins could have also been incorporated without dilution in high-IC1 and high-IC4 sediments, resulting in an increase in the contents of these elements. In addition, in deposition slow enough to allow biogenic Ca-phosphate grains to concentrate REY and to accumulate significantly in the sediment, the P and REY contents of these sediments also increase concurrently. Although sediments enriched in biogenic Ca-phosphate contain several percent of Ca, the significant dilution effect of biogenic carbonate, which contains several tens of percent of Ca, generally creates negative trends in these ICs as a whole in the spaces of Ca and other elements, including REY. The differenc.

Rhetorical functions of language, typography and editorial voice as well as

Rhetorical functions of language, typography and editorial voice as well as the use of such radical literary tactics as exposure, ridicule and critique. This article does not merely aim to point up the similarities between The Lancet and its political contemporaries; it intends to show how such stylistic devices were marshalled in the pursuit of a specific political agenda. Of course splenetic prose was not the sole preserve of the radical `left’ and neither was it particularly novel. Similar tactics had been in use since the later 1700s by `King and Country’ Tories, a position from which Wakley’s mentor and collaborator, William Cobbett, had only moved in 1806.14 However, during the early decades of the nineteenth century it was the radical and revolutionary press which made this style their own, and it was these conventions that Wakley sought to emulate. This was particularly true of his predilection for insult and defamation, and the main body of this article comprises a detailed analysis of a trial for libel in 1828 between Wakely and the Guy’s Hospital surgeon, Bransby Cooper. Through a close analysis of Wakley’s rhetorical, legal and performative strategies, as well as a critical reading of a number of contemporary satirical prints, it demonstrates how this trial functioned as the platform for a much broader critique of the established medical `system’ and provided a powerful means for Wakley to align himself with the cultures of popular radicalism. However, whatever parallels and connections Wakley sought to draw between the medical and the political, the reality was rather more complex. In the final section,567. Smith, The Politics of Language, 1791 ?819 (CP 472295MedChemExpress Tulathromycin A Oxford, 1984); I. McCalman, Radical Underworld: Prophets, Revolutionaries and Pornographers, 1795?1840 (Cambridge, 1988); J. A. Epstein, Radical Expression: Political Language, Ritual and Symbol in England, 1790 ?1850 (Oxford, 1994); E. Hadley, Melodramatic Tactics: Theatricalised Dissent in the English13O. 12ibid.,Marketplace, 1800 ?1885 (Stanford, 1995); L. Nattrass, William Cobbett: The Politics of Style (Cambridge, 1995); K. Gilmartin, Print Politics: The Press and Radical Opposition in Early Nineteenth-Century England (Cambridge, 1996). 14For example, see J. J. Sack, From Jacobite to Conservative: Reaction and TGR-1202 chemical information Orthodoxy in Britain, c.1760 ?832 (Cambridge, 1993).Social HistoryVOL.39 :NO.therefore, this article examines the tensions and ambiguities within Wakley’s political persona by reading them against the altered circumstances of the 1820s, particularly the rise of a more philosophic reformism. In so doing, it seeks not merely to place political radicalism at the heart of contemporary medical culture but, more ambitiously perhaps, to establish a more prominent place for medicine in accounts of the history of early nineteenth-century reform, as a potential bridge between the popular radicalism of the immediate post-war years and the reformist utilitarianism of the 1830s.WAKLEY, COBBETT AND RADICAL STYLEThere was little in Thomas Wakley’s early upbringing to suggest a natural inclination towards political radicalism, for he was born in 1795 into that bulwark of pre-modern political order, the prosperous farming family.15 One of eleven children and the youngest of eight sons, he attended boarding school in Somerset, followed by a series of apprenticeships with local apothecaries and surgeons, enrolling as a student at the United Hospitals Medical School of Guy’s and St Tho.Rhetorical functions of language, typography and editorial voice as well as the use of such radical literary tactics as exposure, ridicule and critique. This article does not merely aim to point up the similarities between The Lancet and its political contemporaries; it intends to show how such stylistic devices were marshalled in the pursuit of a specific political agenda. Of course splenetic prose was not the sole preserve of the radical `left’ and neither was it particularly novel. Similar tactics had been in use since the later 1700s by `King and Country’ Tories, a position from which Wakley’s mentor and collaborator, William Cobbett, had only moved in 1806.14 However, during the early decades of the nineteenth century it was the radical and revolutionary press which made this style their own, and it was these conventions that Wakley sought to emulate. This was particularly true of his predilection for insult and defamation, and the main body of this article comprises a detailed analysis of a trial for libel in 1828 between Wakely and the Guy’s Hospital surgeon, Bransby Cooper. Through a close analysis of Wakley’s rhetorical, legal and performative strategies, as well as a critical reading of a number of contemporary satirical prints, it demonstrates how this trial functioned as the platform for a much broader critique of the established medical `system’ and provided a powerful means for Wakley to align himself with the cultures of popular radicalism. However, whatever parallels and connections Wakley sought to draw between the medical and the political, the reality was rather more complex. In the final section,567. Smith, The Politics of Language, 1791 ?819 (Oxford, 1984); I. McCalman, Radical Underworld: Prophets, Revolutionaries and Pornographers, 1795?1840 (Cambridge, 1988); J. A. Epstein, Radical Expression: Political Language, Ritual and Symbol in England, 1790 ?1850 (Oxford, 1994); E. Hadley, Melodramatic Tactics: Theatricalised Dissent in the English13O. 12ibid.,Marketplace, 1800 ?1885 (Stanford, 1995); L. Nattrass, William Cobbett: The Politics of Style (Cambridge, 1995); K. Gilmartin, Print Politics: The Press and Radical Opposition in Early Nineteenth-Century England (Cambridge, 1996). 14For example, see J. J. Sack, From Jacobite to Conservative: Reaction and Orthodoxy in Britain, c.1760 ?832 (Cambridge, 1993).Social HistoryVOL.39 :NO.therefore, this article examines the tensions and ambiguities within Wakley’s political persona by reading them against the altered circumstances of the 1820s, particularly the rise of a more philosophic reformism. In so doing, it seeks not merely to place political radicalism at the heart of contemporary medical culture but, more ambitiously perhaps, to establish a more prominent place for medicine in accounts of the history of early nineteenth-century reform, as a potential bridge between the popular radicalism of the immediate post-war years and the reformist utilitarianism of the 1830s.WAKLEY, COBBETT AND RADICAL STYLEThere was little in Thomas Wakley’s early upbringing to suggest a natural inclination towards political radicalism, for he was born in 1795 into that bulwark of pre-modern political order, the prosperous farming family.15 One of eleven children and the youngest of eight sons, he attended boarding school in Somerset, followed by a series of apprenticeships with local apothecaries and surgeons, enrolling as a student at the United Hospitals Medical School of Guy’s and St Tho.

, a runner who demonstrates considerably less than 45?of knee flexion may

, a runner who order Oxaliplatin demonstrates considerably less than 45?of knee GW856553X msds flexion may suggest reduced shock absorption, and intervention may be warranted. Some data exist suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj., a runner who demonstrates considerably less than 45?of knee flexion may suggest reduced shock absorption, and intervention may be warranted. Some data exist suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj.

Ampal CA1 subfield in individuals with MCI compared to NCI (Fig.

Ampal CA1 subfield in individuals with MCI compared to NCI (Fig. 4), which correlated with the subject’s Mini-Mental State Exam score (MMSE), but not with NFT Braak stage or apolipoprotein E (ApoE) status, a get GW9662 genetic risk factor for AD (Scheff et al., 2006). Unlike the outer molecular layer, CA1 receives input from the Schaffer collaterals arising from CA3 and not from the glutamatergic neurons of the entorhinal cortex, suggesting differential responses to synapse loss within the hippocampus based upon afferent innervation or chemical phenotype, some of which precipitate synaptic reorganization. A recent report characterized changes in the dendritic branching of the basilar tree of hippocampal CA1 pyramidal neurons. In this study, formalin-fixed tissue autopsy obtained from University of Kentucky Alzheimer’s Disease Center who died with a clinical diagnosis of NCI, MCI or AD was prepared for Golgi impregnation (Fig. 5). Camera lucida drawings of the basilar tree of randomly selected CA1 neurons were analyzed for alterations in dendritic arbor amount, distribution and complexity (Mervis et al., 2013). Quantitation showed a significant increase in dendritic length (18 ) and complexity (23 ) in CA1 neurons in MCI compared to NCI. Conversely, there was a significant reduction in branch length (-39 ) and arbor complexity (-25 ) during the progression from MCI to AD (Fig. 5). These findings suggest that the observed increase in CA1 dendritic parameters from NCI to MCI may be another example of a neuroplastic purchase BMS-214662 compensatory response to a loss of afferent input early in the course of the disease, which is not maintained as the disease progresses. The role that the reported reduction in total synapse number plays in CA1 neuroplasticity remains unknown. However, these examples of early CA1 neural reorganization may represent a viable window for potential therapeutic strategies aimed at restoring or maintaining hippocampal function during the transition from MCI to AD. Future studies should determine whether alterations in specific synapse subtypes (i.e., perforated vs. non-perforated) are differentially affected and their relation to cognitive decline and brain pathology during the onset of AD. Interestingly, the size of the synaptic contacts was found to be substantially larger in AD cortex compared to non-demented aged controls (Scheff et al., 1990), which was suggested to be part of a compensatory mechanism found in regions of the neocortex and hippocampus (see review Scheff and Price, 2006). These investigators found that as the number of synapses declined in a given region, the size of the residualAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagesynapses increased. This synaptic compensatory response was also observed early in the course of the AD (DeKosky and Scheff, 1990). Neuronal structural alterations may not be the only factor(s) contributing to cognitive decline and hippocampal plasticity in MCI. For example, studies have reported significant reductions in synaptic vesicle trafficking-related genes in the AD brain, which interrupt the efficacy of normal synaptic transmission (Yao et al., 2003; Murphy et al., 2003; Kennedy et al., 2005). Counts et al. (2014) examined progressive changes in the expression classes of synaptic gene within single CA1 neurons in subjects who died with a clinical diagnosis of NCI, MCI or moderate AD obtain.Ampal CA1 subfield in individuals with MCI compared to NCI (Fig. 4), which correlated with the subject’s Mini-Mental State Exam score (MMSE), but not with NFT Braak stage or apolipoprotein E (ApoE) status, a genetic risk factor for AD (Scheff et al., 2006). Unlike the outer molecular layer, CA1 receives input from the Schaffer collaterals arising from CA3 and not from the glutamatergic neurons of the entorhinal cortex, suggesting differential responses to synapse loss within the hippocampus based upon afferent innervation or chemical phenotype, some of which precipitate synaptic reorganization. A recent report characterized changes in the dendritic branching of the basilar tree of hippocampal CA1 pyramidal neurons. In this study, formalin-fixed tissue autopsy obtained from University of Kentucky Alzheimer’s Disease Center who died with a clinical diagnosis of NCI, MCI or AD was prepared for Golgi impregnation (Fig. 5). Camera lucida drawings of the basilar tree of randomly selected CA1 neurons were analyzed for alterations in dendritic arbor amount, distribution and complexity (Mervis et al., 2013). Quantitation showed a significant increase in dendritic length (18 ) and complexity (23 ) in CA1 neurons in MCI compared to NCI. Conversely, there was a significant reduction in branch length (-39 ) and arbor complexity (-25 ) during the progression from MCI to AD (Fig. 5). These findings suggest that the observed increase in CA1 dendritic parameters from NCI to MCI may be another example of a neuroplastic compensatory response to a loss of afferent input early in the course of the disease, which is not maintained as the disease progresses. The role that the reported reduction in total synapse number plays in CA1 neuroplasticity remains unknown. However, these examples of early CA1 neural reorganization may represent a viable window for potential therapeutic strategies aimed at restoring or maintaining hippocampal function during the transition from MCI to AD. Future studies should determine whether alterations in specific synapse subtypes (i.e., perforated vs. non-perforated) are differentially affected and their relation to cognitive decline and brain pathology during the onset of AD. Interestingly, the size of the synaptic contacts was found to be substantially larger in AD cortex compared to non-demented aged controls (Scheff et al., 1990), which was suggested to be part of a compensatory mechanism found in regions of the neocortex and hippocampus (see review Scheff and Price, 2006). These investigators found that as the number of synapses declined in a given region, the size of the residualAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagesynapses increased. This synaptic compensatory response was also observed early in the course of the AD (DeKosky and Scheff, 1990). Neuronal structural alterations may not be the only factor(s) contributing to cognitive decline and hippocampal plasticity in MCI. For example, studies have reported significant reductions in synaptic vesicle trafficking-related genes in the AD brain, which interrupt the efficacy of normal synaptic transmission (Yao et al., 2003; Murphy et al., 2003; Kennedy et al., 2005). Counts et al. (2014) examined progressive changes in the expression classes of synaptic gene within single CA1 neurons in subjects who died with a clinical diagnosis of NCI, MCI or moderate AD obtain.

Monly used and widely available OTC medications and nutritional supplements were

Monly used and widely available OTC medications and nutritional supplements were safe and posed no short- or long-term threat to their health. Many used such products to improve their running BAY1217389 chemical information performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product Monocrotaline biological activity recommended as an effective and legal substance by another runner or by a retail sales clerk may contain substances that are either banned by agencies such as WADA and/or may pose a serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.Monly used and widely available OTC medications and nutritional supplements were safe and posed no short- or long-term threat to their health. Many used such products to improve their running performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product recommended as an effective and legal substance by another runner or by a retail sales clerk may contain substances that are either banned by agencies such as WADA and/or may pose a serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.

Ez-Triana, sp. n. http://zoobank.org/84DCE9B2-79E9-

Ez-Triana, sp. n. http://zoobank.org/84DCE9B2-79E9-47CF-8CC2-8DA9F53F3AD1 http://species-id.net/wiki/Apanteles_franciscopizarroi Figs. 74 Type locality. COSTA RICA, Guanacaste, ACG, Sector Santa Rosa, Bosque Humedo, 290m, 10.85145, -85.60801. Holotype. in CNC. Specimen labels: 1. DHJPAR0013119. 2. 17 Jan. 2000, Bosque Humedo Trap. Description. Female. Body color: body mostly dark except for some sternites which may be pale. Antenna color: scape, pedicel, and flagellum dark. Coxae color (pro-, meso-, metacoxa): pale, pale, dark. Femora color (pro-, meso-, metafemur): pale, pale, mostly pale but posterior 0.2 or less dark. Tibiae color (pro-, meso-, metatibia): pale, pale, anteriorly pale/posteriorly dark. Tegula and humeral complex color: both pale. Pterostigma color: dark. Fore wing veins color: partially pigmented (a few veins may be dark but most are pale). Antenna length/body length: antenna about as long as body (head to apex of metasoma); if slightly shorter, at least extending beyond anterior 0.7 metasoma length. Body in lateral view: not distinctly flattened dorso entrally. Body length (head to apex of metasoma): 2.1?.2 mm. Fore wing length: 2.3?.4 mm. Ocular cellar line/posterior ocellus diameter: 2.0?.2. In-Jose L. Fernandez-Triana et al. / ZooKeys 383: 1?65 (2014)terocellar distance/posterior ocellus diameter: 1.7?.9. Antennal flagellomerus 2 length/width: 2.6?.8. Antennal flagellomerus 14 length/width: 1.4?.6. Length of flagellomerus 2/length of flagellomerus 14: 1.7?.9. Tarsal claws: with single basal spine ike seta. Metafemur length/width: 3.4?.5. Pedalitin permethyl ether site Metatibia inner spur length/ metabasitarsus length: 0.4?.5. Anteromesoscutum: mostly with deep, dense punctures (separated by less than 2.0 ?its maximum diameter). Mesoscutellar disc: with a few sparse punctures. Number of pits in scutoscutellar sulcus: 11 or 12. Maximum height of mesoscutellum lunules/maximum height of lateral face of mesoscutellum: 0.2?.3. Propodeum areola: completely defined by carinae, including transverse carina extending to spiracle. Propodeum background sculpture: partly sculptured, especially on anterior 0.5. Mediotergite 1 length/width at posterior margin: 2.0?.2. Mediotergite 1 shape: mostly parallel ided for 0.5?.7 of its length, then JWH-133 custom synthesis narrowing posteriorly so mediotergite anterior width >1.1 ?posterior width. Mediotergite 1 sculpture: mostly sculptured, excavated area centrally with transverse striation inside and/or a polished knob centrally on posterior margin of mediotergite. Mediotergite 2 width at posterior margin/length: 3.6?.9. Mediotergite 2 sculpture: with some sculpture, mostly near posterior margin. Outer margin of hypopygium: with a wide, medially folded, transparent, semi esclerotized area; usually with 4 or more pleats. Ovipositor thickness: about same width throughout its length. Ovipositor sheaths length/metatibial length: 1.0?.1. Length of fore wing veins r/2RS: 1.1?.3. Length of fore wing veins 2RS/2M: 1.4?.6. Length of fore wing veins 2M/(RS+M)b: 1.1?1.3. Pterostigma length/width: 3.1?.5. Point of insertion of vein r in pterostigma: about half way point length of pterostigma. Angle of vein r with fore wing anterior margin: more or less perpendicular to fore wing margin. Shape of junction of veins r and 2RS in fore wing: distinctly but not strongly angled. Male. Unknown. Molecular data. Sequences in BOLD: 2, barcode compliant sequences: 2. Biology/ecology. Malaise-trapped. Distribution. Costa Rica, ACG. Etymology. We dedicate this spe.Ez-Triana, sp. n. http://zoobank.org/84DCE9B2-79E9-47CF-8CC2-8DA9F53F3AD1 http://species-id.net/wiki/Apanteles_franciscopizarroi Figs. 74 Type locality. COSTA RICA, Guanacaste, ACG, Sector Santa Rosa, Bosque Humedo, 290m, 10.85145, -85.60801. Holotype. in CNC. Specimen labels: 1. DHJPAR0013119. 2. 17 Jan. 2000, Bosque Humedo Trap. Description. Female. Body color: body mostly dark except for some sternites which may be pale. Antenna color: scape, pedicel, and flagellum dark. Coxae color (pro-, meso-, metacoxa): pale, pale, dark. Femora color (pro-, meso-, metafemur): pale, pale, mostly pale but posterior 0.2 or less dark. Tibiae color (pro-, meso-, metatibia): pale, pale, anteriorly pale/posteriorly dark. Tegula and humeral complex color: both pale. Pterostigma color: dark. Fore wing veins color: partially pigmented (a few veins may be dark but most are pale). Antenna length/body length: antenna about as long as body (head to apex of metasoma); if slightly shorter, at least extending beyond anterior 0.7 metasoma length. Body in lateral view: not distinctly flattened dorso entrally. Body length (head to apex of metasoma): 2.1?.2 mm. Fore wing length: 2.3?.4 mm. Ocular cellar line/posterior ocellus diameter: 2.0?.2. In-Jose L. Fernandez-Triana et al. / ZooKeys 383: 1?65 (2014)terocellar distance/posterior ocellus diameter: 1.7?.9. Antennal flagellomerus 2 length/width: 2.6?.8. Antennal flagellomerus 14 length/width: 1.4?.6. Length of flagellomerus 2/length of flagellomerus 14: 1.7?.9. Tarsal claws: with single basal spine ike seta. Metafemur length/width: 3.4?.5. Metatibia inner spur length/ metabasitarsus length: 0.4?.5. Anteromesoscutum: mostly with deep, dense punctures (separated by less than 2.0 ?its maximum diameter). Mesoscutellar disc: with a few sparse punctures. Number of pits in scutoscutellar sulcus: 11 or 12. Maximum height of mesoscutellum lunules/maximum height of lateral face of mesoscutellum: 0.2?.3. Propodeum areola: completely defined by carinae, including transverse carina extending to spiracle. Propodeum background sculpture: partly sculptured, especially on anterior 0.5. Mediotergite 1 length/width at posterior margin: 2.0?.2. Mediotergite 1 shape: mostly parallel ided for 0.5?.7 of its length, then narrowing posteriorly so mediotergite anterior width >1.1 ?posterior width. Mediotergite 1 sculpture: mostly sculptured, excavated area centrally with transverse striation inside and/or a polished knob centrally on posterior margin of mediotergite. Mediotergite 2 width at posterior margin/length: 3.6?.9. Mediotergite 2 sculpture: with some sculpture, mostly near posterior margin. Outer margin of hypopygium: with a wide, medially folded, transparent, semi esclerotized area; usually with 4 or more pleats. Ovipositor thickness: about same width throughout its length. Ovipositor sheaths length/metatibial length: 1.0?.1. Length of fore wing veins r/2RS: 1.1?.3. Length of fore wing veins 2RS/2M: 1.4?.6. Length of fore wing veins 2M/(RS+M)b: 1.1?1.3. Pterostigma length/width: 3.1?.5. Point of insertion of vein r in pterostigma: about half way point length of pterostigma. Angle of vein r with fore wing anterior margin: more or less perpendicular to fore wing margin. Shape of junction of veins r and 2RS in fore wing: distinctly but not strongly angled. Male. Unknown. Molecular data. Sequences in BOLD: 2, barcode compliant sequences: 2. Biology/ecology. Malaise-trapped. Distribution. Costa Rica, ACG. Etymology. We dedicate this spe.

Diagnosis and the quality of the received treatment14. Hence the dearth

Diagnosis and the quality of the received treatment14. Hence the dearth of information regarding the determinants of mortality among PLWHA in China called for a detailed retrospective national level investigation to assess the impact of HIV on adult mortality and to identify correlates of total and AIDS-related mortality among adult PLWHA in this country. Our study aimed to evaluate the mortality rate among PLWHA since they were identified/reported and to evaluate the potential correlates of AIDS related and unrelated deaths in this population in China, by analyzing the data from a concurrent cohort study (The National HIV Epidemiology Cohort) which was monitoring mortality among PLWHA in China.MethodThe data used in this current article were obtained from the HIV/AIDS case reporting system (CRS) under the National Center for AIDS/STD Control and Prevention of the Chinese Center for Disease Control and Prevention (China CDC) between 1989 and 2013. The methods were carried out in accordance with the approved guidelines.Recruitment.Detailed information regarding the relevant databases is described elsewhere15. In brief, this retrospective cohort study was based on Chinese HIV/AIDS case report system and SIS3 biological activity treatment database. Any information collected from these two platforms was included in the current study base, while the two systems were linked by a unique personal ID. No additional identification information was collected from the participants. All newly identified HIV cases were reported to the web-based systems either by local hospitals or clinics. Information on demographic characteristics [age, gender, occupation, ethnicity, address, registered place of residency (Hukou) etc.], HIV related risk-behaviors, treatment history, routes of transmission (heterosexual/homosexual/IDU/transfusion of blood or other blood cells) and disease status (HIV/AIDS based on WHO criteria) at the time of diagnosis were also collected from all the registered PLWHA. PLWHA were considered eligible to be recruited for this concurrent cohort study if they were aged 18 years or older and had at least one follow up record since their initial reporting to the national database between January 1, 1989 and June 30, 2012. Frequency of CD4 testing for each participant was also calculated in every six months, and frequency of CD4 testing was defined as the cumulative number of CD4 testing at each year divided by two (every six months).After identification and reporting, all HIV cases were followed up by the local CDCs. The intervals of two follow up varied between three or six months, buy Tirabrutinib depending on the disease status. If already been progressed to AIDS, the patients were followed in every three months, otherwise, they were followed six monthly. Accordingly, during the follow up period, blood samples for CD4 count and viral load testing were collected in every 3 or 6 months from each patient. The patients were appropriately treated as per the criteria. Treatment was indicated for confirmed sero-positive WHO Stage III or IV clinical HIV cases and those who had any of the following: symptomatic disease, extra-pulmonary tuberculosis (TB), laboratory criteria of CD4 count below 350 cells/l or in the absence of CD4 count results: total lymphocyte count below 1200 cells/l)16. The treatment criteria did change over time. Before 2007, only those PLWHA who had progressed to AIDS and had CD4 count <200 cells/l were considered eligible for treatment. This cut-off for CD4 count c.Diagnosis and the quality of the received treatment14. Hence the dearth of information regarding the determinants of mortality among PLWHA in China called for a detailed retrospective national level investigation to assess the impact of HIV on adult mortality and to identify correlates of total and AIDS-related mortality among adult PLWHA in this country. Our study aimed to evaluate the mortality rate among PLWHA since they were identified/reported and to evaluate the potential correlates of AIDS related and unrelated deaths in this population in China, by analyzing the data from a concurrent cohort study (The National HIV Epidemiology Cohort) which was monitoring mortality among PLWHA in China.MethodThe data used in this current article were obtained from the HIV/AIDS case reporting system (CRS) under the National Center for AIDS/STD Control and Prevention of the Chinese Center for Disease Control and Prevention (China CDC) between 1989 and 2013. The methods were carried out in accordance with the approved guidelines.Recruitment.Detailed information regarding the relevant databases is described elsewhere15. In brief, this retrospective cohort study was based on Chinese HIV/AIDS case report system and treatment database. Any information collected from these two platforms was included in the current study base, while the two systems were linked by a unique personal ID. No additional identification information was collected from the participants. All newly identified HIV cases were reported to the web-based systems either by local hospitals or clinics. Information on demographic characteristics [age, gender, occupation, ethnicity, address, registered place of residency (Hukou) etc.], HIV related risk-behaviors, treatment history, routes of transmission (heterosexual/homosexual/IDU/transfusion of blood or other blood cells) and disease status (HIV/AIDS based on WHO criteria) at the time of diagnosis were also collected from all the registered PLWHA. PLWHA were considered eligible to be recruited for this concurrent cohort study if they were aged 18 years or older and had at least one follow up record since their initial reporting to the national database between January 1, 1989 and June 30, 2012. Frequency of CD4 testing for each participant was also calculated in every six months, and frequency of CD4 testing was defined as the cumulative number of CD4 testing at each year divided by two (every six months).After identification and reporting, all HIV cases were followed up by the local CDCs. The intervals of two follow up varied between three or six months, depending on the disease status. If already been progressed to AIDS, the patients were followed in every three months, otherwise, they were followed six monthly. Accordingly, during the follow up period, blood samples for CD4 count and viral load testing were collected in every 3 or 6 months from each patient. The patients were appropriately treated as per the criteria. Treatment was indicated for confirmed sero-positive WHO Stage III or IV clinical HIV cases and those who had any of the following: symptomatic disease, extra-pulmonary tuberculosis (TB), laboratory criteria of CD4 count below 350 cells/l or in the absence of CD4 count results: total lymphocyte count below 1200 cells/l)16. The treatment criteria did change over time. Before 2007, only those PLWHA who had progressed to AIDS and had CD4 count <200 cells/l were considered eligible for treatment. This cut-off for CD4 count c.

-(acyl)PI has its putative active site on the lumenal

-(acyl)PI has its putative active site on the lumenal side of the ER [22]. This would imply that Arv1 acts after the GPI substrate (PI-GlcN) has already been flipped and suggests that the generation of GlcN-(acyl)PI requires a still unknown flippase other than Arv1, as well as the flipping of acyl-CoA. As flc mutants show a severe cell wall phenotype, characteristic also for mutants with compromised GPI protein biosynthesis, we desired to test whether flc mutants have any difficulty in making GlcN-(acyl)PI. We tried to test this by using a microsomal in vitro assay of GPI biosynthesis with UDP-[3H]-GlcNAc added as the substrate [42]. As shown in Fig 8, microsomes incubated with UDP-[3H]-GlcNAc make GlcN-(acyl)PI when they are allowed to make acylCoA in presence of added ATP and CoA. Similar results were obtained with permeabilized cells. In all cases Doxy treated 123ty cells made significantly more GlcN-(acyl)PI than WT, suggesting that the complete depletion of Flc function induces enzymes for GPI biosynthesis. This finding is reminiscent of the increased GPAT and AGPAT Dactinomycin chemical information activities in these cells (Figs 5 and 6C and 6D). Once more, results are ambiguous and suggest that the flipping of GlcN-PIPLOS Genetics | DOI:10.1371/journal.pgen.July 27,12 /Yeast E-MAP for Identification of Membrane Transporters Operating Lipid Flip FlopFig 8. Microsomal GlcN-(acyl)PI synthesis activity in flc mutants is increased. Microsomes were produced from WT or 123ty cells grown for 12 h in the presence of Doxy and sorbitol, and were labeled using 80 nM UDP-[3H]-GlcNAc (4 Ci), 1 mM ATP and 1 mM CoA. In the last lane, to produce GPI (S)-(-)-Blebbistatin cost intermediates without the acyl chain bound to the inositol moiety, CoA and ATP were omitted and 1 mM G3P was added in order to deplete microsomes of preexisting acyl-CoA. Lipids were extracted and separated by TLC. doi:10.1371/journal.pgen.1006160.gand acyl-CoA are normal, but they can’t exclude the possibility that an abnormal permeability or orientation of the ER derived microsomes obviates the need for the corresponding PI-GlcN and acyl-CoA flippases.Cst26 introduces C26 fatty acids into lyso-PIUnrelated to the search of lipid flippases, our attention was caught by the very strong negative interactions of cst26 with elo2 and elo3 deletions in MSP- and MSP/C-E-MAPs (S scores between?9.5 and -11.0). CST26/PSI1 encodes an acyltransferase that transfers stearic acid (C18:0) from C18:0-CoA onto the sn-1 position of lyso-PI [43]. Apart from a further very strong negative interaction with the chitin synthase CHS1, cst26 interacts only with elo2 and elo3, but not elo1 (see below). ELO1 allows elongating FAs up to C18:0. ELO2 and ELO3 are partially redundant, cannot be deleted simultaneously and are required to further elongate FAs up to C26:0. Each of them is required to make C26:0 in sufficient quantity for the ceramide synthases Lag1 and Lac1, for which C26:0-CoA is the preferred substrate [44]. Elo2 and elo3 therefore make markedly reduced amounts of ceramide and mature sphingolipids. However, they grow normally whereas cst26 elo3 cells grow less rapidly (S6 Fig (Comparison of growth rates of elo3, cst26 and elo3 cst26 cells)). While sphingolipids are essential, their presence is dispensable if, due to a gain of function suppressor mutation in SLC1, cells can make PI carrying a very long chain FA in the sn-2 position of the glycerol moiety, even if this form of PI accounts for only a tiny fraction of membrane lipids [45?8]. Moreover, i.-(acyl)PI has its putative active site on the lumenal side of the ER [22]. This would imply that Arv1 acts after the GPI substrate (PI-GlcN) has already been flipped and suggests that the generation of GlcN-(acyl)PI requires a still unknown flippase other than Arv1, as well as the flipping of acyl-CoA. As flc mutants show a severe cell wall phenotype, characteristic also for mutants with compromised GPI protein biosynthesis, we desired to test whether flc mutants have any difficulty in making GlcN-(acyl)PI. We tried to test this by using a microsomal in vitro assay of GPI biosynthesis with UDP-[3H]-GlcNAc added as the substrate [42]. As shown in Fig 8, microsomes incubated with UDP-[3H]-GlcNAc make GlcN-(acyl)PI when they are allowed to make acylCoA in presence of added ATP and CoA. Similar results were obtained with permeabilized cells. In all cases Doxy treated 123ty cells made significantly more GlcN-(acyl)PI than WT, suggesting that the complete depletion of Flc function induces enzymes for GPI biosynthesis. This finding is reminiscent of the increased GPAT and AGPAT activities in these cells (Figs 5 and 6C and 6D). Once more, results are ambiguous and suggest that the flipping of GlcN-PIPLOS Genetics | DOI:10.1371/journal.pgen.July 27,12 /Yeast E-MAP for Identification of Membrane Transporters Operating Lipid Flip FlopFig 8. Microsomal GlcN-(acyl)PI synthesis activity in flc mutants is increased. Microsomes were produced from WT or 123ty cells grown for 12 h in the presence of Doxy and sorbitol, and were labeled using 80 nM UDP-[3H]-GlcNAc (4 Ci), 1 mM ATP and 1 mM CoA. In the last lane, to produce GPI intermediates without the acyl chain bound to the inositol moiety, CoA and ATP were omitted and 1 mM G3P was added in order to deplete microsomes of preexisting acyl-CoA. Lipids were extracted and separated by TLC. doi:10.1371/journal.pgen.1006160.gand acyl-CoA are normal, but they can’t exclude the possibility that an abnormal permeability or orientation of the ER derived microsomes obviates the need for the corresponding PI-GlcN and acyl-CoA flippases.Cst26 introduces C26 fatty acids into lyso-PIUnrelated to the search of lipid flippases, our attention was caught by the very strong negative interactions of cst26 with elo2 and elo3 deletions in MSP- and MSP/C-E-MAPs (S scores between?9.5 and -11.0). CST26/PSI1 encodes an acyltransferase that transfers stearic acid (C18:0) from C18:0-CoA onto the sn-1 position of lyso-PI [43]. Apart from a further very strong negative interaction with the chitin synthase CHS1, cst26 interacts only with elo2 and elo3, but not elo1 (see below). ELO1 allows elongating FAs up to C18:0. ELO2 and ELO3 are partially redundant, cannot be deleted simultaneously and are required to further elongate FAs up to C26:0. Each of them is required to make C26:0 in sufficient quantity for the ceramide synthases Lag1 and Lac1, for which C26:0-CoA is the preferred substrate [44]. Elo2 and elo3 therefore make markedly reduced amounts of ceramide and mature sphingolipids. However, they grow normally whereas cst26 elo3 cells grow less rapidly (S6 Fig (Comparison of growth rates of elo3, cst26 and elo3 cst26 cells)). While sphingolipids are essential, their presence is dispensable if, due to a gain of function suppressor mutation in SLC1, cells can make PI carrying a very long chain FA in the sn-2 position of the glycerol moiety, even if this form of PI accounts for only a tiny fraction of membrane lipids [45?8]. Moreover, i.

US-306389). ca. 3 mi NW of Cananea, road to microwave station N

US-306389). ca. 3 mi NW of Cananea, road to microwave station N of Mexico Highway 2, ca. 7000ft [2135 m], 31.036 , 110.375 , 19 Mar 1982, R.J.Soreng 1780 R.W.Spellenberg (NMC, US, population sample: 5, 2n = 28; Soreng 1990, cpDNA voucher). Santa Cruz, Parry s.n., [Mexican Boundary Survey ] (GH, very sparse pubescent, pubescent to sparse pubescent, intermediates; another label on same GH sheet says Munro 165, G.Thurber Herb.). Sierra del Pinito, [30.5 , 109.5 ], 2500 m, 9 Apr 1977, J.L.Fernandez 3 (ARIZ). Sierra Guacomea, Pozo del Santo Nino, Rancho La Alameda, 31?3’22″N, 110?8’06″W, 1472 m, 5 Apr 2005, A.L.Reina-G. 2005-562, T.R.VanDevender J.FPS-ZM1MedChemExpress FPS-ZM1 Ruiz-C. (ARIZ, US); ditto, Rancho La Arboleda, Arroyo El Volteadero, 31?3’10″N, 110?7’04″W, 1385 m, 2 Apr 2005, T.R.VanDevender 2005-493, A.L.Reina-G. J.Ruiz-C. (ARIZ, US). Discussion. This subspecies has glabrous lemmas and short ligules, and is the most common subspecies of P. fendleriana in Mexico. It is often sexually reproducing with dioecious populations and staminate plants are common, but sometimes apomictic individuals with pistillate spikelets are found. Intermediates have sparsely pubescent lemmas and are almost always pistillate. Distribution maps of the subspecies, distribution of staminate and pistillate plants, and a discussion of the breeding system and fossil record is given in Soreng and Van Devender (1989). Hitchcock (1913) suggestedRobert J. Soreng Paul M. Peterson / PhytoKeys 15: 1?04 (2012)this taxon (P. albescens) is allied to Poa chilensis Trin. (= P. holciformis J. Presl) from Argentina and Chile, a member of P. sect. Dioicopoa E. Desv., but DNA data have shown that is not the case (Gillespie et al. 2009).8b. Poa fendleriana subsp. fendleriana http://species-id.net/wiki/Poa_fendleriana_fendleriana Fig. 8 C Description. Leaf collars often scabrous or hispidulous near the throat; ligules of middle cauline leaves 0.2?.2(?.5) mm long, not decurrent abaxially scabrous, upper margin usually scabrous or ciliolate, apices truncate to rounded; sterile shoot blades usually scabrous or softly puberulent adaxially. Spikelet rachilla usually smooth and glabrous; lemmas long villous on keels and marginal veins, between veins glabrous or infrequently softly puberulent; palea keels and between keels infrequently puberulent. 2n = 56. Distribution. The subspecies is found throughout the range of the species, but is rare to MS-275 price absent from much of the westernmost part of the USA range. In Mexico the subspecies is found in Baja California, Chihuahua, Coahuila, and Sonora. Ecology. Where the ranges of the subspecies overlap this subspecies often occurs in slightly drier and more open habitats than P. subsp. albescens, and more mesic and cooler habitats than P. subsp. longiligula. In Mexico this subspecies can tolerate some disturbance as most of the plants are apomictic, except in Coahuila. The subspecies is found in canyons and rocky slopes, from upper arid grasslands (margins) and chaparral of with scrubby species of Quercus, Arbutus, Juniperus, Vaqualina, and Cercocarpus to Hudsonian coniferous forests. Like P. fendleriana subsp. albescens, this subspecies is primarily restricted to regions with summer monsoons and some winter snows, and ranges from 1900?200 m. Flowering in spring. Specimens examined. Mexico. Baja California: 4.5 mi S of summit of Cerro 1905, Portezuelo de Jamau, 31?4’N, 115?6’W, 1900 m, 20 Apr 1974, R.Moran 21232 (TAES, WYAC intermediate between P. fendleriana subsp.US-306389). ca. 3 mi NW of Cananea, road to microwave station N of Mexico Highway 2, ca. 7000ft [2135 m], 31.036 , 110.375 , 19 Mar 1982, R.J.Soreng 1780 R.W.Spellenberg (NMC, US, population sample: 5, 2n = 28; Soreng 1990, cpDNA voucher). Santa Cruz, Parry s.n., [Mexican Boundary Survey ] (GH, very sparse pubescent, pubescent to sparse pubescent, intermediates; another label on same GH sheet says Munro 165, G.Thurber Herb.). Sierra del Pinito, [30.5 , 109.5 ], 2500 m, 9 Apr 1977, J.L.Fernandez 3 (ARIZ). Sierra Guacomea, Pozo del Santo Nino, Rancho La Alameda, 31?3’22″N, 110?8’06″W, 1472 m, 5 Apr 2005, A.L.Reina-G. 2005-562, T.R.VanDevender J.Ruiz-C. (ARIZ, US); ditto, Rancho La Arboleda, Arroyo El Volteadero, 31?3’10″N, 110?7’04″W, 1385 m, 2 Apr 2005, T.R.VanDevender 2005-493, A.L.Reina-G. J.Ruiz-C. (ARIZ, US). Discussion. This subspecies has glabrous lemmas and short ligules, and is the most common subspecies of P. fendleriana in Mexico. It is often sexually reproducing with dioecious populations and staminate plants are common, but sometimes apomictic individuals with pistillate spikelets are found. Intermediates have sparsely pubescent lemmas and are almost always pistillate. Distribution maps of the subspecies, distribution of staminate and pistillate plants, and a discussion of the breeding system and fossil record is given in Soreng and Van Devender (1989). Hitchcock (1913) suggestedRobert J. Soreng Paul M. Peterson / PhytoKeys 15: 1?04 (2012)this taxon (P. albescens) is allied to Poa chilensis Trin. (= P. holciformis J. Presl) from Argentina and Chile, a member of P. sect. Dioicopoa E. Desv., but DNA data have shown that is not the case (Gillespie et al. 2009).8b. Poa fendleriana subsp. fendleriana http://species-id.net/wiki/Poa_fendleriana_fendleriana Fig. 8 C Description. Leaf collars often scabrous or hispidulous near the throat; ligules of middle cauline leaves 0.2?.2(?.5) mm long, not decurrent abaxially scabrous, upper margin usually scabrous or ciliolate, apices truncate to rounded; sterile shoot blades usually scabrous or softly puberulent adaxially. Spikelet rachilla usually smooth and glabrous; lemmas long villous on keels and marginal veins, between veins glabrous or infrequently softly puberulent; palea keels and between keels infrequently puberulent. 2n = 56. Distribution. The subspecies is found throughout the range of the species, but is rare to absent from much of the westernmost part of the USA range. In Mexico the subspecies is found in Baja California, Chihuahua, Coahuila, and Sonora. Ecology. Where the ranges of the subspecies overlap this subspecies often occurs in slightly drier and more open habitats than P. subsp. albescens, and more mesic and cooler habitats than P. subsp. longiligula. In Mexico this subspecies can tolerate some disturbance as most of the plants are apomictic, except in Coahuila. The subspecies is found in canyons and rocky slopes, from upper arid grasslands (margins) and chaparral of with scrubby species of Quercus, Arbutus, Juniperus, Vaqualina, and Cercocarpus to Hudsonian coniferous forests. Like P. fendleriana subsp. albescens, this subspecies is primarily restricted to regions with summer monsoons and some winter snows, and ranges from 1900?200 m. Flowering in spring. Specimens examined. Mexico. Baja California: 4.5 mi S of summit of Cerro 1905, Portezuelo de Jamau, 31?4’N, 115?6’W, 1900 m, 20 Apr 1974, R.Moran 21232 (TAES, WYAC intermediate between P. fendleriana subsp.

, a runner who demonstrates considerably less than 45?of knee flexion may

, a (R)-K-13675 manufacturer runner who demonstrates considerably less than 45?of knee flexion may suggest reduced shock absorption, and PF-04418948MedChemExpress PF-04418948 intervention may be warranted. Some data exist suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj., a runner who demonstrates considerably less than 45?of knee flexion may suggest reduced shock absorption, and intervention may be warranted. Some data exist suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj.

Ampal CA1 subfield in individuals with MCI compared to NCI (Fig.

Ampal CA1 subfield in individuals with MCI LY317615 site compared to NCI (Fig. 4), which correlated with the subject’s Mini-Mental State Exam score (MMSE), but not with NFT Braak stage or apolipoprotein E (ApoE) status, a genetic risk factor for AD (Scheff et al., 2006). Unlike the outer molecular layer, CA1 receives input from the Schaffer collaterals arising from CA3 and not from the glutamatergic neurons of the entorhinal cortex, suggesting differential responses to synapse loss within the hippocampus based upon afferent innervation or chemical phenotype, some of which precipitate synaptic reorganization. A recent report characterized changes in the dendritic branching of the basilar tree of hippocampal CA1 pyramidal neurons. In this study, formalin-fixed tissue autopsy obtained from University of Kentucky Alzheimer’s Disease Center who died with a clinical diagnosis of NCI, MCI or AD was prepared for Golgi impregnation (Fig. 5). Camera lucida drawings of the basilar tree of randomly selected CA1 neurons were analyzed for alterations in dendritic arbor amount, distribution and complexity (Mervis et al., 2013). Quantitation showed a Lasalocid (sodium) web significant increase in dendritic length (18 ) and complexity (23 ) in CA1 neurons in MCI compared to NCI. Conversely, there was a significant reduction in branch length (-39 ) and arbor complexity (-25 ) during the progression from MCI to AD (Fig. 5). These findings suggest that the observed increase in CA1 dendritic parameters from NCI to MCI may be another example of a neuroplastic compensatory response to a loss of afferent input early in the course of the disease, which is not maintained as the disease progresses. The role that the reported reduction in total synapse number plays in CA1 neuroplasticity remains unknown. However, these examples of early CA1 neural reorganization may represent a viable window for potential therapeutic strategies aimed at restoring or maintaining hippocampal function during the transition from MCI to AD. Future studies should determine whether alterations in specific synapse subtypes (i.e., perforated vs. non-perforated) are differentially affected and their relation to cognitive decline and brain pathology during the onset of AD. Interestingly, the size of the synaptic contacts was found to be substantially larger in AD cortex compared to non-demented aged controls (Scheff et al., 1990), which was suggested to be part of a compensatory mechanism found in regions of the neocortex and hippocampus (see review Scheff and Price, 2006). These investigators found that as the number of synapses declined in a given region, the size of the residualAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagesynapses increased. This synaptic compensatory response was also observed early in the course of the AD (DeKosky and Scheff, 1990). Neuronal structural alterations may not be the only factor(s) contributing to cognitive decline and hippocampal plasticity in MCI. For example, studies have reported significant reductions in synaptic vesicle trafficking-related genes in the AD brain, which interrupt the efficacy of normal synaptic transmission (Yao et al., 2003; Murphy et al., 2003; Kennedy et al., 2005). Counts et al. (2014) examined progressive changes in the expression classes of synaptic gene within single CA1 neurons in subjects who died with a clinical diagnosis of NCI, MCI or moderate AD obtain.Ampal CA1 subfield in individuals with MCI compared to NCI (Fig. 4), which correlated with the subject’s Mini-Mental State Exam score (MMSE), but not with NFT Braak stage or apolipoprotein E (ApoE) status, a genetic risk factor for AD (Scheff et al., 2006). Unlike the outer molecular layer, CA1 receives input from the Schaffer collaterals arising from CA3 and not from the glutamatergic neurons of the entorhinal cortex, suggesting differential responses to synapse loss within the hippocampus based upon afferent innervation or chemical phenotype, some of which precipitate synaptic reorganization. A recent report characterized changes in the dendritic branching of the basilar tree of hippocampal CA1 pyramidal neurons. In this study, formalin-fixed tissue autopsy obtained from University of Kentucky Alzheimer’s Disease Center who died with a clinical diagnosis of NCI, MCI or AD was prepared for Golgi impregnation (Fig. 5). Camera lucida drawings of the basilar tree of randomly selected CA1 neurons were analyzed for alterations in dendritic arbor amount, distribution and complexity (Mervis et al., 2013). Quantitation showed a significant increase in dendritic length (18 ) and complexity (23 ) in CA1 neurons in MCI compared to NCI. Conversely, there was a significant reduction in branch length (-39 ) and arbor complexity (-25 ) during the progression from MCI to AD (Fig. 5). These findings suggest that the observed increase in CA1 dendritic parameters from NCI to MCI may be another example of a neuroplastic compensatory response to a loss of afferent input early in the course of the disease, which is not maintained as the disease progresses. The role that the reported reduction in total synapse number plays in CA1 neuroplasticity remains unknown. However, these examples of early CA1 neural reorganization may represent a viable window for potential therapeutic strategies aimed at restoring or maintaining hippocampal function during the transition from MCI to AD. Future studies should determine whether alterations in specific synapse subtypes (i.e., perforated vs. non-perforated) are differentially affected and their relation to cognitive decline and brain pathology during the onset of AD. Interestingly, the size of the synaptic contacts was found to be substantially larger in AD cortex compared to non-demented aged controls (Scheff et al., 1990), which was suggested to be part of a compensatory mechanism found in regions of the neocortex and hippocampus (see review Scheff and Price, 2006). These investigators found that as the number of synapses declined in a given region, the size of the residualAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagesynapses increased. This synaptic compensatory response was also observed early in the course of the AD (DeKosky and Scheff, 1990). Neuronal structural alterations may not be the only factor(s) contributing to cognitive decline and hippocampal plasticity in MCI. For example, studies have reported significant reductions in synaptic vesicle trafficking-related genes in the AD brain, which interrupt the efficacy of normal synaptic transmission (Yao et al., 2003; Murphy et al., 2003; Kennedy et al., 2005). Counts et al. (2014) examined progressive changes in the expression classes of synaptic gene within single CA1 neurons in subjects who died with a clinical diagnosis of NCI, MCI or moderate AD obtain.

Monly used and widely available OTC medications and nutritional supplements were

Monly used and widely available OTC medications and nutritional supplements were safe and posed no short- or long-term BIM-22493 solubility threat to their health. Many used such products to improve their running performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product recommended as an effective and legal substance by another runner or by a retail sales clerk may contain substances that are either banned by agencies such as WADA and/or may pose a serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.NIH-PA buy Monocrotaline Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.Monly used and widely available OTC medications and nutritional supplements were safe and posed no short- or long-term threat to their health. Many used such products to improve their running performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product recommended as an effective and legal substance by another runner or by a retail sales clerk may contain substances that are either banned by agencies such as WADA and/or may pose a serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.

Deration when interpreting experimental findings. (i) Identification of a mutation in

Deration when interpreting experimental findings. (i) Identification of a mutation in a clonal population does not indicate causality Any mutation in a cell that undergoes clonal expansion will be passed onto progeny, irrespective of functional status (Fig. 3A,B). Given the size of the genome, more mutations carried by a neoplastic clone will be passengers than drivers [27, 29, 30]. To demonstrate driver status, XR9576 custom synthesis supporting functional studies and/or repeated observations of a mutated loci in neoplastic clones from independent individuals are needed. (ii) Mutational marking of a clone is stochastic and not guaranteed A clone may exist and not be detected if none of the genomic sites being screened carry a unique mutation permitting it to be distinguished from the germline (Fig. 3C). The more sites examined, the higher the probability of detection becomes. I-CBP112 site Restricting a marker panel to suspected driver sites precludes detection of pathological clones driven by unknown factors. (iii) Elevated mutation rates facilitate clone detection but are not an absolute requirement Screening of mutational hotspots makes it practical with conventional technologies to have a reasonable probability of detecting a clone by random passenger mutations. Clones derived from a mutator lineage or cells residing in a highly mutagenic environment should be more densely marked with identifiable passengers (Fig. 3D), potentially reducing the number of markers needing to be interrogated to identify them. Emerging high-throughput sequencing technologies will eventually obviate the need to restrict screening to a fraction of the genome. (iv) Identification of one or more clonal mutations is not proof of genetic instability in the absence of collateral information Detection of a mutation requires clonal expansion with most traditional methods of aggregate DNA analysis. The probability of identifying clonal mutations in an expanded population is a function of the number of sites screened, the mutability of these sites and the number of cell divisions having occurred in the lineage leading up to the final expansion. Particularly when considering hotspots, mutations will be occasionally detectable in any clonally-derived population at a statistically definable frequency. Because mutations are not routinely encountered in normal tissues, it is tempting to explain their presence in preneoplastic populations as the result of “genetic instability” (an elevated mutation rate). However, the phenomenon is more precisely explained by the fact that expansion does not routinely occur in most normal tissues. An elevated mutation rate itself will have no observable effect on clonal mutation frequency in the absence of expansion (Fig. 3E). To determine mutation rate from a clonal mutation frequency it is necessary to (A) know that the population being assessed is clonal and (B) have some metric of the number of cell divisions that occurred in the period between the zygote and the founding of the final clonalSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPageoutgrowth. To infer that a rate is elevated, it is also necessary to know the normal in vivo mutation rate, which is, in turn, impossible to measure by this approach given that large clonal expansions do not routinely occur in normal adult tissue. Considering these complexities, the lack of resolution as to whether mutation rates are elevated in cancer is not surprising [1,8?1]. (v) Detectabili.Deration when interpreting experimental findings. (i) Identification of a mutation in a clonal population does not indicate causality Any mutation in a cell that undergoes clonal expansion will be passed onto progeny, irrespective of functional status (Fig. 3A,B). Given the size of the genome, more mutations carried by a neoplastic clone will be passengers than drivers [27, 29, 30]. To demonstrate driver status, supporting functional studies and/or repeated observations of a mutated loci in neoplastic clones from independent individuals are needed. (ii) Mutational marking of a clone is stochastic and not guaranteed A clone may exist and not be detected if none of the genomic sites being screened carry a unique mutation permitting it to be distinguished from the germline (Fig. 3C). The more sites examined, the higher the probability of detection becomes. Restricting a marker panel to suspected driver sites precludes detection of pathological clones driven by unknown factors. (iii) Elevated mutation rates facilitate clone detection but are not an absolute requirement Screening of mutational hotspots makes it practical with conventional technologies to have a reasonable probability of detecting a clone by random passenger mutations. Clones derived from a mutator lineage or cells residing in a highly mutagenic environment should be more densely marked with identifiable passengers (Fig. 3D), potentially reducing the number of markers needing to be interrogated to identify them. Emerging high-throughput sequencing technologies will eventually obviate the need to restrict screening to a fraction of the genome. (iv) Identification of one or more clonal mutations is not proof of genetic instability in the absence of collateral information Detection of a mutation requires clonal expansion with most traditional methods of aggregate DNA analysis. The probability of identifying clonal mutations in an expanded population is a function of the number of sites screened, the mutability of these sites and the number of cell divisions having occurred in the lineage leading up to the final expansion. Particularly when considering hotspots, mutations will be occasionally detectable in any clonally-derived population at a statistically definable frequency. Because mutations are not routinely encountered in normal tissues, it is tempting to explain their presence in preneoplastic populations as the result of “genetic instability” (an elevated mutation rate). However, the phenomenon is more precisely explained by the fact that expansion does not routinely occur in most normal tissues. An elevated mutation rate itself will have no observable effect on clonal mutation frequency in the absence of expansion (Fig. 3E). To determine mutation rate from a clonal mutation frequency it is necessary to (A) know that the population being assessed is clonal and (B) have some metric of the number of cell divisions that occurred in the period between the zygote and the founding of the final clonalSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPageoutgrowth. To infer that a rate is elevated, it is also necessary to know the normal in vivo mutation rate, which is, in turn, impossible to measure by this approach given that large clonal expansions do not routinely occur in normal adult tissue. Considering these complexities, the lack of resolution as to whether mutation rates are elevated in cancer is not surprising [1,8?1]. (v) Detectabili.

. This exploratory analysis can provide further information on functional similarities between

. This exploratory analysis can provide further information on functional similarities between regions, and, more specifically, on the extent to which activation profiles of category-selective regions are inherited from EVC. As for the replicability of within-category ranking (Fig. 5), we combined data across subjects either by concatenating or averaging the activation profiles across subjects. The concatenation approach is sensitive to inter-region correlations of activation profiles even if the particular activation profiles differ across subjects. The averaging approach is sensitive to inter-region correlations of activation profiles that are consistent across subjects. We investigated the inter-region correlations for (1) the full activation profile, (2) the within-face activation profile, and (3) the withinplace activation profile. Statistical inference was performed by a standard one-sided test on Spearman’s r. p values were corrected8658 ?J. Neurosci., June 20, 2012 ?32(25):8649 ?Mur et al. ?Single-Image Activation of Category Regionsfor multiple testing using Bonferroni correction based on the total number of tests performed. Figure 7 shows the inter-region JWH-133MedChemExpress JWH-133 correlation results. The main pattern that emerges is that activation profiles are correlated between hemispheres for corresponding regions, and between hIT and EVC (red blocks on diagonals). We subsequently inspected the within-face correlation between FFA and EVC, and the within-place correlation between PPA and EVC. The within-face activation profile was correlated between left but not right FFA and EVC, and the within-place activation profile was not significantly correlated between PPA and EVC. Results were similar across ROI sizes. These results suggest that EVC is not a major contributor to the within-category activation profiles of PPA and right FFA. We then inspected the correlation between category-selective regions (FFA/PPA) and EVC for the full activation profile (top row). The full activation profile was correlated between EVC and both categoryselective regions, especially PPA. One interpretation of this Pedalitin permethyl ether cost finding would be that some degree of category selectivity is already present at the level of EVC, implying that low-level feature differences contribute to some extent to categoryselective responses. For places, this seems a plausible interpretation, consistent with our finding that single-image activation of EVC can discriminate places from nonplaces at an above-chance level (Fig. 2). For faces, this interpretation seems less likely: the correlation between EVC and FFA is not significant for the subjectaverage activation profile, suggesting that the correlation is driven by subjectspecific effects (e.g., idiosyncratic arousal effects) and not by face-selectivity of responses (shared across subjects in FFA). Categorical, yet graded Figure 8 summarizes our results. Singleimage activation profiles of categoryselective regions (1) show near-perfect discrimination of preferred from nonpreferred images and no preference inversions for particular object images, (2) show a step-like drop-off at the category boundary, and (3) are graded within and outside the preferred category. It can further be noted that single-image category selectivity is stronger in right than left FFA. In addition, gradedness seems to be more pronounced in FFA; the category step seems to be more pronounced in PPA. In sum, our findings indicate that the activation profiles of category-selec-Figure.. This exploratory analysis can provide further information on functional similarities between regions, and, more specifically, on the extent to which activation profiles of category-selective regions are inherited from EVC. As for the replicability of within-category ranking (Fig. 5), we combined data across subjects either by concatenating or averaging the activation profiles across subjects. The concatenation approach is sensitive to inter-region correlations of activation profiles even if the particular activation profiles differ across subjects. The averaging approach is sensitive to inter-region correlations of activation profiles that are consistent across subjects. We investigated the inter-region correlations for (1) the full activation profile, (2) the within-face activation profile, and (3) the withinplace activation profile. Statistical inference was performed by a standard one-sided test on Spearman’s r. p values were corrected8658 ?J. Neurosci., June 20, 2012 ?32(25):8649 ?Mur et al. ?Single-Image Activation of Category Regionsfor multiple testing using Bonferroni correction based on the total number of tests performed. Figure 7 shows the inter-region correlation results. The main pattern that emerges is that activation profiles are correlated between hemispheres for corresponding regions, and between hIT and EVC (red blocks on diagonals). We subsequently inspected the within-face correlation between FFA and EVC, and the within-place correlation between PPA and EVC. The within-face activation profile was correlated between left but not right FFA and EVC, and the within-place activation profile was not significantly correlated between PPA and EVC. Results were similar across ROI sizes. These results suggest that EVC is not a major contributor to the within-category activation profiles of PPA and right FFA. We then inspected the correlation between category-selective regions (FFA/PPA) and EVC for the full activation profile (top row). The full activation profile was correlated between EVC and both categoryselective regions, especially PPA. One interpretation of this finding would be that some degree of category selectivity is already present at the level of EVC, implying that low-level feature differences contribute to some extent to categoryselective responses. For places, this seems a plausible interpretation, consistent with our finding that single-image activation of EVC can discriminate places from nonplaces at an above-chance level (Fig. 2). For faces, this interpretation seems less likely: the correlation between EVC and FFA is not significant for the subjectaverage activation profile, suggesting that the correlation is driven by subjectspecific effects (e.g., idiosyncratic arousal effects) and not by face-selectivity of responses (shared across subjects in FFA). Categorical, yet graded Figure 8 summarizes our results. Singleimage activation profiles of categoryselective regions (1) show near-perfect discrimination of preferred from nonpreferred images and no preference inversions for particular object images, (2) show a step-like drop-off at the category boundary, and (3) are graded within and outside the preferred category. It can further be noted that single-image category selectivity is stronger in right than left FFA. In addition, gradedness seems to be more pronounced in FFA; the category step seems to be more pronounced in PPA. In sum, our findings indicate that the activation profiles of category-selec-Figure.

In living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic

In living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic Ca-phosphate in pelagic sediments has long been studied by a number of investigators17,18,21?4,40?2. Some have suggested that biogenic Ca-phosphate incorporates REY via pore water in the sediment column23,40. Others have argued that Ca-phosphate takes up REY from a variety of carrier phases (e.g. Fe n-oxyhydroxides, pellets, and organic debris) that absorb REY from Stattic web seawater and are readily decomposed at the sediment ater interface17,22,41,42. Although the complete process remains an open question, the characteristic REY GS-4059MedChemExpress GS-4059 patterns indicate that seawater is the ultimate source of the REY presently captured in biogenic Ca-phosphate22,25,41 (Fig. 4m). Simple quantitative estimation in this study suggested the possibility that seawater can contain the flux of REY precipitation required to explain the observed very high REY concentrations ( REY + Ce > 1,000 ppm) in bulk REY-rich mud with a sedimentation rate less than 0.5 m/Myr (Supplementary Fig. S19). Such circumstances may facilitate the concentration of REY in biogenic Ca-phosphate via diffusion of REY from seawater or the transfer of REY from original carriers to Ca-phosphate during the early diagenetic processes because of the prolonged exposure to seawater at the sediment surface and in the bioturbated and well-ventilated uppermost sediment layer17,18,22,41. In addition, biogenic Ca-phosphate enriched in REY might be stabilised through recrystallisation as insoluble apatite17. Moreover, the amount of Ca-phosphate in a unit volume of sediment also increases with a depression of the sedimentation rate17,18. Hence, the low sedimentation rate is considered to be crucial for the formation of REY-rich mud. Actually, the spatiotemporal distribution of high-IC1, -IC4, and -IC7 muds overlapped with the oligotrophic North Pacific and South Pacific gyres and with water depths greater than the CCD, both of which prevented the fast accumulation of dilutive components with low REY content such as biogenic carbonate and silica. If we assume that deep-sea sediments can continuously acquire REY from the overlying deep-sea water prior to burial, the REY-enrichment in sediments can occur in a time scale of 105 years considering the sedimentation rate of <0.5 m/Myr with a typical thickness of 0.1 m for the well-ventilated uppermost sediment layer43. This timescale of REY enrichment is significantly longer than that of global ocean circulation, which is 103 years44. Both IC1 and IC4 indicated statistical independent geochemical features of pelagic red clay mainly composed of detrital aluminosilicates involving abundant Si, Al, Fe, Mg, and K without significant contributions of biogenic carbonate and silica. Fe and Mn of hydrothermal or hydrogenous origins could have also been incorporated without dilution in high-IC1 and high-IC4 sediments, resulting in an increase in the contents of these elements. In addition, in deposition slow enough to allow biogenic Ca-phosphate grains to concentrate REY and to accumulate significantly in the sediment, the P and REY contents of these sediments also increase concurrently. Although sediments enriched in biogenic Ca-phosphate contain several percent of Ca, the significant dilution effect of biogenic carbonate, which contains several tens of percent of Ca, generally creates negative trends in these ICs as a whole in the spaces of Ca and other elements, including REY. The differenc.In living organisms21,23,39 (Fig. 4m). Therefore, the REY-enrichment process by biogenic Ca-phosphate in pelagic sediments has long been studied by a number of investigators17,18,21?4,40?2. Some have suggested that biogenic Ca-phosphate incorporates REY via pore water in the sediment column23,40. Others have argued that Ca-phosphate takes up REY from a variety of carrier phases (e.g. Fe n-oxyhydroxides, pellets, and organic debris) that absorb REY from seawater and are readily decomposed at the sediment ater interface17,22,41,42. Although the complete process remains an open question, the characteristic REY patterns indicate that seawater is the ultimate source of the REY presently captured in biogenic Ca-phosphate22,25,41 (Fig. 4m). Simple quantitative estimation in this study suggested the possibility that seawater can contain the flux of REY precipitation required to explain the observed very high REY concentrations ( REY + Ce > 1,000 ppm) in bulk REY-rich mud with a sedimentation rate less than 0.5 m/Myr (Supplementary Fig. S19). Such circumstances may facilitate the concentration of REY in biogenic Ca-phosphate via diffusion of REY from seawater or the transfer of REY from original carriers to Ca-phosphate during the early diagenetic processes because of the prolonged exposure to seawater at the sediment surface and in the bioturbated and well-ventilated uppermost sediment layer17,18,22,41. In addition, biogenic Ca-phosphate enriched in REY might be stabilised through recrystallisation as insoluble apatite17. Moreover, the amount of Ca-phosphate in a unit volume of sediment also increases with a depression of the sedimentation rate17,18. Hence, the low sedimentation rate is considered to be crucial for the formation of REY-rich mud. Actually, the spatiotemporal distribution of high-IC1, -IC4, and -IC7 muds overlapped with the oligotrophic North Pacific and South Pacific gyres and with water depths greater than the CCD, both of which prevented the fast accumulation of dilutive components with low REY content such as biogenic carbonate and silica. If we assume that deep-sea sediments can continuously acquire REY from the overlying deep-sea water prior to burial, the REY-enrichment in sediments can occur in a time scale of 105 years considering the sedimentation rate of <0.5 m/Myr with a typical thickness of 0.1 m for the well-ventilated uppermost sediment layer43. This timescale of REY enrichment is significantly longer than that of global ocean circulation, which is 103 years44. Both IC1 and IC4 indicated statistical independent geochemical features of pelagic red clay mainly composed of detrital aluminosilicates involving abundant Si, Al, Fe, Mg, and K without significant contributions of biogenic carbonate and silica. Fe and Mn of hydrothermal or hydrogenous origins could have also been incorporated without dilution in high-IC1 and high-IC4 sediments, resulting in an increase in the contents of these elements. In addition, in deposition slow enough to allow biogenic Ca-phosphate grains to concentrate REY and to accumulate significantly in the sediment, the P and REY contents of these sediments also increase concurrently. Although sediments enriched in biogenic Ca-phosphate contain several percent of Ca, the significant dilution effect of biogenic carbonate, which contains several tens of percent of Ca, generally creates negative trends in these ICs as a whole in the spaces of Ca and other elements, including REY. The differenc.

Exacerbated inflammation, but does not alter atherosclerosis.Author ContributionsConceived and designed

Exacerbated inflammation, but does not alter atherosclerosis.Author ContributionsConceived and designed the experiments: SNV KEB. Performed the experiments: SNV FK SB. Analyzed the data: SNV JEK KEB. Contributed reagents/materials/analysis tools: RMB KIA. Wrote the paper: SNV JEK KEB.
For more than a decade after the fall of the Soviet Union, many Eastern European countries struggled with social and political instability. Consider Bulgaria, a country that changed its entire political system in 1989. The term AM152 chemical information Anomie was used to describe the state of BMS-986020 molecular weight society in Bulgaria that emerged after the economy had collapsed and the political system struggled to respond [1, 2]. Anomie has also been used to describe the state of society in countries undergoing massive structural change (e.g., Iran, see [3, 4]), countries that face major social or economic crises [5], countries with a long history of war (e.g., Yugoslavia, Iraq, Afghanistan, see [6, 7]), or societies that face civil unrest (e.g., South Africa, [8]). Anomie has even been used to describe social contexts with relative prosperity, but where income inequality has eroded social capital and trust (e.g., the U.S., [9, 10, 11]), or where rapid economic growth has created instability and unrest (e.g., China, [12]). Despite the fact that anomie is a common experience that many people and societies in the world today share, to date there is no uniform conceptualization and operationalization of this construct. In this paper, we first review the previous conceptualizations and operationalizations of anomie and highlight their shortcomings. Starting from an operationalization of anomie as a perception of the state of society, we develop a scale that disentangles anomie as a state of society from its outcomes at the individual level. In this way, we equip the field with a tool that can be used to develop better insights into the nature of anomie and the experience of those who live in a state of anomie.Anomie: The Concept and its MeasurementEven though anomie has been conceptualized in different ways, perhaps the most well-known approach is to define anomie as a state of society [9?1, 13]. Durkheim [13] proposed that anomie involves the breakdown of social regulation and the rise of moral disruption. Merton [9, 10] extended this thinking and proposed that anomie emerges from the discrepancy between the cultural aspirations of people within a society and the legitimate means available to those people to achieve them. Still focusing on the state of society, Messner and Rosenfeld [11] took a slightly different approach to Merton and focused instead on anomie as a cultural obsession with economic success, manifesting itself as a set of cultural values associated with individualism, achievement orientation, and fetishism of money. Departing somewhat from this well-known work, some have defined anomie as a state of mind. Scholars in this tradition have focused on anomie as an individual’s sense of self-toother alienation or distance [14], or as a set of beliefs, feelings and attitudes in the individual’s mind [15, 16]. In general, these approaches to anomie revolve around a psychological state that can be characterized as a tendency to be self-interested [17], to reject social norms [18, 19], or to feel estranged or isolated from society [14, 20, 21]. In this conceptualization, anomie may also include a sense that life is meaningless [21, 22], where feelings of purposelessness or powerlessness dominate (f.Exacerbated inflammation, but does not alter atherosclerosis.Author ContributionsConceived and designed the experiments: SNV KEB. Performed the experiments: SNV FK SB. Analyzed the data: SNV JEK KEB. Contributed reagents/materials/analysis tools: RMB KIA. Wrote the paper: SNV JEK KEB.
For more than a decade after the fall of the Soviet Union, many Eastern European countries struggled with social and political instability. Consider Bulgaria, a country that changed its entire political system in 1989. The term anomie was used to describe the state of society in Bulgaria that emerged after the economy had collapsed and the political system struggled to respond [1, 2]. Anomie has also been used to describe the state of society in countries undergoing massive structural change (e.g., Iran, see [3, 4]), countries that face major social or economic crises [5], countries with a long history of war (e.g., Yugoslavia, Iraq, Afghanistan, see [6, 7]), or societies that face civil unrest (e.g., South Africa, [8]). Anomie has even been used to describe social contexts with relative prosperity, but where income inequality has eroded social capital and trust (e.g., the U.S., [9, 10, 11]), or where rapid economic growth has created instability and unrest (e.g., China, [12]). Despite the fact that anomie is a common experience that many people and societies in the world today share, to date there is no uniform conceptualization and operationalization of this construct. In this paper, we first review the previous conceptualizations and operationalizations of anomie and highlight their shortcomings. Starting from an operationalization of anomie as a perception of the state of society, we develop a scale that disentangles anomie as a state of society from its outcomes at the individual level. In this way, we equip the field with a tool that can be used to develop better insights into the nature of anomie and the experience of those who live in a state of anomie.Anomie: The Concept and its MeasurementEven though anomie has been conceptualized in different ways, perhaps the most well-known approach is to define anomie as a state of society [9?1, 13]. Durkheim [13] proposed that anomie involves the breakdown of social regulation and the rise of moral disruption. Merton [9, 10] extended this thinking and proposed that anomie emerges from the discrepancy between the cultural aspirations of people within a society and the legitimate means available to those people to achieve them. Still focusing on the state of society, Messner and Rosenfeld [11] took a slightly different approach to Merton and focused instead on anomie as a cultural obsession with economic success, manifesting itself as a set of cultural values associated with individualism, achievement orientation, and fetishism of money. Departing somewhat from this well-known work, some have defined anomie as a state of mind. Scholars in this tradition have focused on anomie as an individual’s sense of self-toother alienation or distance [14], or as a set of beliefs, feelings and attitudes in the individual’s mind [15, 16]. In general, these approaches to anomie revolve around a psychological state that can be characterized as a tendency to be self-interested [17], to reject social norms [18, 19], or to feel estranged or isolated from society [14, 20, 21]. In this conceptualization, anomie may also include a sense that life is meaningless [21, 22], where feelings of purposelessness or powerlessness dominate (f.

We note that the more common complex structure is due to

We note that the more common complex structure is due to a graphically generated initial plus the rest of the text followed by a flourish. This is closely similar to signatures with simple structures, highlighting that Western signatures usually avoid excessive complexity.PLOS ONE | DOI:10.1371/journal.pone.0123254 April 10,16 /Modeling the Lexical WP1066 biological activity morphology of Western Handwritten SignaturesFig 15. Probability of the different text-flourish structures. The colors represent the order in which the signature was written. From initial to final signature, the color order is defined as follows: red, cyan, blue, green and magenta. doi:10.1371/journal.pone.0123254.gThe probability density functions previously represented for each selected feature can be analyzed. We have obtained parameters from each CGP-57148B cancer generalized extreme value approximation. Apart from the generalized extreme values, Table 3 shows the mean and variance of each function, the maximum probable value of the functions, the skewness and kurtorsis, which mainly interprets the function shape, the minimum and maximum values of the GEV and, finally, the mean square error estimator which measures the average of the squares of the errors between real values presented as a histogram and the measured function. These statistical parameters may be useful in further studies on the lexical morphology of signatures. We have studied lexical morphological variability through this paper: i.e. the differences between the parameters which define the particular lexical morphology of a Western signature. Moreover, these signatures have been collected following specific protocols in different laboratories. Therefore, the signatures have similar lexical morphological variability. As a future line of research, it might be desirable to study signatures captured in real scenarios like a bank or a supermarket. It is possible that in such environments we could find greater variability, for example, changes in the number of flourishes or flourish corners, changes in the number of letters and so on.DiscussionAny study of the lexical morphology of handwritten signatures embraces a number of disciplines because of the many factors that influence human signature design and appearance. Therefore, this study of lexical morphology modeling may be applied in several different areas. In the biometric community, a relatively recent development is the synthesis of written signatures, on the basis of modeling the cognitive and neuromotor processes. Some such techniques are focused on the duplication of existing identities [54?0]. Other strategies call for the generation of completely new identities [35?7]. This latter approach requires: signature design, cognitive map modeling, neuromuscular motor simulation and, for off-line signaturePLOS ONE | DOI:10.1371/journal.pone.0123254 April 10,17 /Modeling the Lexical Morphology of Western Handwritten Signaturesgeneration, an ink deposition model for generating realistic signature images. Lexical morphology modeling is required for the signature design stage. Thus text line morphology is one of the features which produces the text distribution. It is often found that important historical documents are not complete or are damaged. This means that researchers have to cope with interpreting missing or degraded material [61?3]. Sometimes, incomplete handwriting signatures can be discovered in these documents. The counted signature parameters described in this paper could be considere.We note that the more common complex structure is due to a graphically generated initial plus the rest of the text followed by a flourish. This is closely similar to signatures with simple structures, highlighting that Western signatures usually avoid excessive complexity.PLOS ONE | DOI:10.1371/journal.pone.0123254 April 10,16 /Modeling the Lexical Morphology of Western Handwritten SignaturesFig 15. Probability of the different text-flourish structures. The colors represent the order in which the signature was written. From initial to final signature, the color order is defined as follows: red, cyan, blue, green and magenta. doi:10.1371/journal.pone.0123254.gThe probability density functions previously represented for each selected feature can be analyzed. We have obtained parameters from each generalized extreme value approximation. Apart from the generalized extreme values, Table 3 shows the mean and variance of each function, the maximum probable value of the functions, the skewness and kurtorsis, which mainly interprets the function shape, the minimum and maximum values of the GEV and, finally, the mean square error estimator which measures the average of the squares of the errors between real values presented as a histogram and the measured function. These statistical parameters may be useful in further studies on the lexical morphology of signatures. We have studied lexical morphological variability through this paper: i.e. the differences between the parameters which define the particular lexical morphology of a Western signature. Moreover, these signatures have been collected following specific protocols in different laboratories. Therefore, the signatures have similar lexical morphological variability. As a future line of research, it might be desirable to study signatures captured in real scenarios like a bank or a supermarket. It is possible that in such environments we could find greater variability, for example, changes in the number of flourishes or flourish corners, changes in the number of letters and so on.DiscussionAny study of the lexical morphology of handwritten signatures embraces a number of disciplines because of the many factors that influence human signature design and appearance. Therefore, this study of lexical morphology modeling may be applied in several different areas. In the biometric community, a relatively recent development is the synthesis of written signatures, on the basis of modeling the cognitive and neuromotor processes. Some such techniques are focused on the duplication of existing identities [54?0]. Other strategies call for the generation of completely new identities [35?7]. This latter approach requires: signature design, cognitive map modeling, neuromuscular motor simulation and, for off-line signaturePLOS ONE | DOI:10.1371/journal.pone.0123254 April 10,17 /Modeling the Lexical Morphology of Western Handwritten Signaturesgeneration, an ink deposition model for generating realistic signature images. Lexical morphology modeling is required for the signature design stage. Thus text line morphology is one of the features which produces the text distribution. It is often found that important historical documents are not complete or are damaged. This means that researchers have to cope with interpreting missing or degraded material [61?3]. Sometimes, incomplete handwriting signatures can be discovered in these documents. The counted signature parameters described in this paper could be considere.

Olism (P = 0.86), but prevalence of low HDL was significantly higher in

Olism (P = 0.86), but prevalence of low HDL was Chaetocin biological activity significantly higher in Necrostatin-1 dose females than in males (65.4 vs. 35.8 ; P < 0.001). In addition, MeS was not significantly associated with age and duration of HD and was not significantly associated with BUN, Cr, Ca, P, immunoreactive parathyroid hormone (iPTH), Alb, Hb, iron, total iron binding capacity (TIBC), ferritin, C-reactive protein (CRP), and Kt/V.Metabolic Syndrome P ValueYes (n = 151) 70 (46.4) 117 (77.5) 81 (53.6)< 0.0001 < 0.0001 0.88 c 0.007 0.43 c 0.18 cAge, yDiabetes mellitus Hypertension Low HDLC65 [20-90] 130 [80-200] 80 [50-100]65 [36-84] 130 [90-200] 80 [50-110] 106 (70.2) 102 (67.5) 25.2 ?4.2 85 (56.3) 116 (76.8) 135 (89.4)Metabolic features Systolic BP, mm HgDiastolic BP, mm HgAbnormal glucose metabolism Elevated triglycerides Abdominal obesity FBS, mmol/L Body mass index, kg/m2 Cholesterol, mmol/L HDLC, mmol/L Creatinine, mol/L Sodium, mmol/L iPTH, ng/L WBC PLT Calcium, mmol/L Hemoglobin, g/L Fe, mol/L CRP TIBC, mol/L AST, kat/L KT/V ALT, kat/L< 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 0.46 c 0.08 0.245 0.68 0.01 0.82 0.12 0.22 0.17 0.39 cSerum laboratory features4.88 [3.33-24.98] 23.56 [6.78-92.46] 777.92 ?238.68 2.56 ?.42 2.28 ?0.18 139.1 ?3.6 5.3 ?0.8 1.45 [0.43-7.55] 3.82 ?0.86 1.26 ?0.22.9 ?3.6.83 [3.05-21.15] 21.74 [6.07-89.96] 751.40 ?203.32 1.58 ?0.36 2.23 ?0.18 138.5 ?3.4 5.13 ?0.6 1.23 [0.59-5.76] 1.06 ?0.26 4.35 ?1.Triglyceride, mmol/L Potassium, mmol/LBlood urea nitrogen, mmol/LPhosphorus, mmol/L1766 ?109/L (806 ?109/L-6236 ?109/L) 1208.44 [26.90-5605] 0.30 [0.07-1.60] 0.28 [0.12-2.29] 421.75 ?93.39 48 [12-192] 26 (17.4) 14 (31.8) 5 (11.4) 44 21 (14.1) 1.18 ?0.25 41 ?6 20 [0-120] 13.60 [3.40-37.95] 52.57 ?9.108 ?2 6 ?109/L (2.76 ?109/L-12.26 ?109/L)254 [11-2000]107 ?17 6.66 ?109/L (2.56 ?109/L-15.76 ?109/L) 1806 ?109/L (676 ?109/L-5016 ?109/L) 890.07 [29.15-4232.90] 0.28 [0.08-2.29] 410.45 ?83.28 1.24 ?0.24 36 [12-144] 46 (30.5) 10 (17.9) 14 (25) 56 42 (27.8) 39 ?5 0.30 [0.08-3.52] 0 [0-120] 13.96 [4.48-39.56] 49.49 ?11.225.5 [8-1516]0.002 c 0.602 0.056 c 0.075 c 0.738 0.06 0.28 0.47 0.Ferritin, mmol/L Albumin, g/LUric acid, mol/L Duration of treatment with hemodialysis, mo History of MI Death MI History of Stroke Stroke0.412 c 0.004 0.008 0.Nephro Urol Mon. 2015;7(1):e32 (57.1) a Data are presented as mean ?SD or No. ( ) or median [range]. b Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BP, blood pressure; CRP, C-reactive protein; FBG, fasting blood sugar; Fe, iron; GIB, gastrointestinal bleeding; HDLC, high-density lipoprotein cholesterol; iPTH, immunoreactive parathyroid hormone; MI, myocardial infarction; PLT, platelet count; TIBC, total iron binding capacity; WBC, white blood cell. c Mann Whitney U test.Others (Sepsis, Cancer, Cirrhosis, Pneumonia, GIB, unknown)25 (56.8)During the study, the CHD occurred more frequently in patients with MeS (42 patients (27.8 )) than in those without MeS (21 patients (14.1 )) (P = 0.004). The rate of death due to CHD was 28.6 (12 patients) in those with MeS and 23.8 (5 patients) in those without MeS, showing no significant differences (Table 2). In addition,Variables Age, yJalalzadeh M et al.Table 3. Metabolic and Laboratory factors of Hemodialysis Patients by Gender a,bMetabolic syndrome Diabetes mellitus Hypertension Low HDLC Female (n = 127) 62.4 ?13.5 105 (82.7) 83 (65.4) 56 (44.1) 78 (61.4) 65 (51.2) 81 (63.8)stroke happened more frequently in the MeS group.Olism (P = 0.86), but prevalence of low HDL was significantly higher in females than in males (65.4 vs. 35.8 ; P < 0.001). In addition, MeS was not significantly associated with age and duration of HD and was not significantly associated with BUN, Cr, Ca, P, immunoreactive parathyroid hormone (iPTH), Alb, Hb, iron, total iron binding capacity (TIBC), ferritin, C-reactive protein (CRP), and Kt/V.Metabolic Syndrome P ValueYes (n = 151) 70 (46.4) 117 (77.5) 81 (53.6)< 0.0001 < 0.0001 0.88 c 0.007 0.43 c 0.18 cAge, yDiabetes mellitus Hypertension Low HDLC65 [20-90] 130 [80-200] 80 [50-100]65 [36-84] 130 [90-200] 80 [50-110] 106 (70.2) 102 (67.5) 25.2 ?4.2 85 (56.3) 116 (76.8) 135 (89.4)Metabolic features Systolic BP, mm HgDiastolic BP, mm HgAbnormal glucose metabolism Elevated triglycerides Abdominal obesity FBS, mmol/L Body mass index, kg/m2 Cholesterol, mmol/L HDLC, mmol/L Creatinine, mol/L Sodium, mmol/L iPTH, ng/L WBC PLT Calcium, mmol/L Hemoglobin, g/L Fe, mol/L CRP TIBC, mol/L AST, kat/L KT/V ALT, kat/L< 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 < 0.0001 0.46 c 0.08 0.245 0.68 0.01 0.82 0.12 0.22 0.17 0.39 cSerum laboratory features4.88 [3.33-24.98] 23.56 [6.78-92.46] 777.92 ?238.68 2.56 ?.42 2.28 ?0.18 139.1 ?3.6 5.3 ?0.8 1.45 [0.43-7.55] 3.82 ?0.86 1.26 ?0.22.9 ?3.6.83 [3.05-21.15] 21.74 [6.07-89.96] 751.40 ?203.32 1.58 ?0.36 2.23 ?0.18 138.5 ?3.4 5.13 ?0.6 1.23 [0.59-5.76] 1.06 ?0.26 4.35 ?1.Triglyceride, mmol/L Potassium, mmol/LBlood urea nitrogen, mmol/LPhosphorus, mmol/L1766 ?109/L (806 ?109/L-6236 ?109/L) 1208.44 [26.90-5605] 0.30 [0.07-1.60] 0.28 [0.12-2.29] 421.75 ?93.39 48 [12-192] 26 (17.4) 14 (31.8) 5 (11.4) 44 21 (14.1) 1.18 ?0.25 41 ?6 20 [0-120] 13.60 [3.40-37.95] 52.57 ?9.108 ?2 6 ?109/L (2.76 ?109/L-12.26 ?109/L)254 [11-2000]107 ?17 6.66 ?109/L (2.56 ?109/L-15.76 ?109/L) 1806 ?109/L (676 ?109/L-5016 ?109/L) 890.07 [29.15-4232.90] 0.28 [0.08-2.29] 410.45 ?83.28 1.24 ?0.24 36 [12-144] 46 (30.5) 10 (17.9) 14 (25) 56 42 (27.8) 39 ?5 0.30 [0.08-3.52] 0 [0-120] 13.96 [4.48-39.56] 49.49 ?11.225.5 [8-1516]0.002 c 0.602 0.056 c 0.075 c 0.738 0.06 0.28 0.47 0.Ferritin, mmol/L Albumin, g/LUric acid, mol/L Duration of treatment with hemodialysis, mo History of MI Death MI History of Stroke Stroke0.412 c 0.004 0.008 0.Nephro Urol Mon. 2015;7(1):e32 (57.1) a Data are presented as mean ?SD or No. ( ) or median [range]. b Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; BP, blood pressure; CRP, C-reactive protein; FBG, fasting blood sugar; Fe, iron; GIB, gastrointestinal bleeding; HDLC, high-density lipoprotein cholesterol; iPTH, immunoreactive parathyroid hormone; MI, myocardial infarction; PLT, platelet count; TIBC, total iron binding capacity; WBC, white blood cell. c Mann Whitney U test.Others (Sepsis, Cancer, Cirrhosis, Pneumonia, GIB, unknown)25 (56.8)During the study, the CHD occurred more frequently in patients with MeS (42 patients (27.8 )) than in those without MeS (21 patients (14.1 )) (P = 0.004). The rate of death due to CHD was 28.6 (12 patients) in those with MeS and 23.8 (5 patients) in those without MeS, showing no significant differences (Table 2). In addition,Variables Age, yJalalzadeh M et al.Table 3. Metabolic and Laboratory factors of Hemodialysis Patients by Gender a,bMetabolic syndrome Diabetes mellitus Hypertension Low HDLC Female (n = 127) 62.4 ?13.5 105 (82.7) 83 (65.4) 56 (44.1) 78 (61.4) 65 (51.2) 81 (63.8)stroke happened more frequently in the MeS group.

, a runner who demonstrates considerably less than 45?of knee flexion may

, a runner who demonstrates considerably less than 45?of knee flexion may MG-132 dose suggest reduced shock absorption, and BKT140 site intervention may be warranted. Some data exist suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj., a runner who demonstrates considerably less than 45?of knee flexion may suggest reduced shock absorption, and intervention may be warranted. Some data exist suggesting that lower knee flexion (<40? may be associated with certain subgroups of patients with patellofemoral pain.22 Knee stiffness, a variable that includes both reduced knee flexion and/or increased knee flexion moment during stance phase, may be associated with tibial stress fractures.23 Hip Extension During Late Stance Reduced hip extension during late stance is a common observation in the recreational runner (Fig. 6). It is traditionally believed that lack of hip extension may be associated with reduced flexibility of the iliopsoas muscle. However, the optimal amount of hip extension during running remains elusive. It is possible that the required amount of hip extension is not the same for each runner, but related to other characteristics of their running form. For example, a fairly slow runner may have a very compact stride, demonstrate approximately 10?of peakAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagehip extension and not require any intervention. However, a different runner, with a long stride and perhaps a faster pace, may also have approximately 10?of hip extension, but also concurrently demonstrate a significant overstride pattern (landing with the foot out in front of the center of mass) with higher impact loading and braking forces. The latter runner may require stride modification or improved hip extension during running to modify these forces that could contribute to injury. Commonly observed compensations for persons with reduced hip extension include (1) increased lumbar spine extension, (2) bounding, a strategy to increase float time to increase overall stride length in the absence of adequate hip extension, (3) increased overstriding, including excessive reaching during initial contact as a strategy to increase stride length, and (4) increased cadence to increase running speed in the presence of a limited hip extension. Trunk LeanAuthor Manuscript Author Manuscript Author ManuscriptOverstridingTrunk lean is a variable that has received little attention in the scientific literature. However, this is not the case in the popular running non eer-reviewed literature. Many running styles, including ChiRunning, pose running, and even barefoot running have included cues for novice runners to increase trunk lean. A focus on leaning “from the ankles,” rather than increasing hip flexion to achieve the trunk lean, seems to be a priority for some styles. Many running experts suggest that trunk lean is a key component to correct running posture. However, very little has been done on the research side of this issue. A recent article by Teng and Powers24 demonstrated that a small increase in trunk lean ( 7? resulted in a significant lowering of the stress across the patellofemoral joint without a significant increase in ankle demand, suggesting that this strategy may be important for runners with patellofemoral pain. The overall findings were that reduced trunk flexion (more upright posture) was associated with greater knee loads. In contrast, increased trunk flexion shifted demand away from the knee joint, and to the hip and ankle (although the latter was not statistically higher).25 However, the authors warn that this study was performed in healthy subj.

Ampal CA1 subfield in individuals with MCI compared to NCI (Fig.

Ampal CA1 subfield in individuals with MCI compared to NCI (Fig. 4), which correlated with the subject’s Mini-Mental State Exam score (MMSE), but not with NFT Braak stage or apolipoprotein E (ApoE) status, a genetic risk factor for AD (Scheff et al., 2006). Unlike the outer molecular layer, CA1 receives input from the Schaffer collaterals arising from CA3 and not from the glutamatergic neurons of the entorhinal cortex, suggesting differential responses to synapse loss within the hippocampus based upon afferent innervation or chemical phenotype, some of which precipitate synaptic reorganization. A recent report characterized changes in the dendritic branching of the basilar tree of hippocampal CA1 pyramidal neurons. In this study, formalin-fixed tissue autopsy obtained from JC-1MedChemExpress CBIC2 University of Kentucky Alzheimer’s Disease Center who died with a clinical diagnosis of NCI, MCI or AD was prepared for Golgi impregnation (Fig. 5). Camera lucida drawings of the basilar tree of randomly selected CA1 neurons were analyzed for alterations in dendritic arbor amount, distribution and complexity (Mervis et al., 2013). Quantitation showed a significant increase in dendritic length (18 ) and complexity (23 ) in CA1 neurons in MCI compared to NCI. Conversely, there was a significant reduction in branch length (-39 ) and arbor complexity (-25 ) during the progression from MCI to AD (Fig. 5). These findings suggest that the observed increase in CA1 dendritic parameters from NCI to MCI may be another example of a neuroplastic compensatory response to a loss of afferent input early in the course of the disease, which is not maintained as the disease progresses. The role that the reported reduction in total synapse number plays in CA1 neuroplasticity remains unknown. However, these examples of early CA1 neural reorganization may represent a viable window for potential therapeutic strategies aimed at Procyanidin B1 biological activity restoring or maintaining hippocampal function during the transition from MCI to AD. Future studies should determine whether alterations in specific synapse subtypes (i.e., perforated vs. non-perforated) are differentially affected and their relation to cognitive decline and brain pathology during the onset of AD. Interestingly, the size of the synaptic contacts was found to be substantially larger in AD cortex compared to non-demented aged controls (Scheff et al., 1990), which was suggested to be part of a compensatory mechanism found in regions of the neocortex and hippocampus (see review Scheff and Price, 2006). These investigators found that as the number of synapses declined in a given region, the size of the residualAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagesynapses increased. This synaptic compensatory response was also observed early in the course of the AD (DeKosky and Scheff, 1990). Neuronal structural alterations may not be the only factor(s) contributing to cognitive decline and hippocampal plasticity in MCI. For example, studies have reported significant reductions in synaptic vesicle trafficking-related genes in the AD brain, which interrupt the efficacy of normal synaptic transmission (Yao et al., 2003; Murphy et al., 2003; Kennedy et al., 2005). Counts et al. (2014) examined progressive changes in the expression classes of synaptic gene within single CA1 neurons in subjects who died with a clinical diagnosis of NCI, MCI or moderate AD obtain.Ampal CA1 subfield in individuals with MCI compared to NCI (Fig. 4), which correlated with the subject’s Mini-Mental State Exam score (MMSE), but not with NFT Braak stage or apolipoprotein E (ApoE) status, a genetic risk factor for AD (Scheff et al., 2006). Unlike the outer molecular layer, CA1 receives input from the Schaffer collaterals arising from CA3 and not from the glutamatergic neurons of the entorhinal cortex, suggesting differential responses to synapse loss within the hippocampus based upon afferent innervation or chemical phenotype, some of which precipitate synaptic reorganization. A recent report characterized changes in the dendritic branching of the basilar tree of hippocampal CA1 pyramidal neurons. In this study, formalin-fixed tissue autopsy obtained from University of Kentucky Alzheimer’s Disease Center who died with a clinical diagnosis of NCI, MCI or AD was prepared for Golgi impregnation (Fig. 5). Camera lucida drawings of the basilar tree of randomly selected CA1 neurons were analyzed for alterations in dendritic arbor amount, distribution and complexity (Mervis et al., 2013). Quantitation showed a significant increase in dendritic length (18 ) and complexity (23 ) in CA1 neurons in MCI compared to NCI. Conversely, there was a significant reduction in branch length (-39 ) and arbor complexity (-25 ) during the progression from MCI to AD (Fig. 5). These findings suggest that the observed increase in CA1 dendritic parameters from NCI to MCI may be another example of a neuroplastic compensatory response to a loss of afferent input early in the course of the disease, which is not maintained as the disease progresses. The role that the reported reduction in total synapse number plays in CA1 neuroplasticity remains unknown. However, these examples of early CA1 neural reorganization may represent a viable window for potential therapeutic strategies aimed at restoring or maintaining hippocampal function during the transition from MCI to AD. Future studies should determine whether alterations in specific synapse subtypes (i.e., perforated vs. non-perforated) are differentially affected and their relation to cognitive decline and brain pathology during the onset of AD. Interestingly, the size of the synaptic contacts was found to be substantially larger in AD cortex compared to non-demented aged controls (Scheff et al., 1990), which was suggested to be part of a compensatory mechanism found in regions of the neocortex and hippocampus (see review Scheff and Price, 2006). These investigators found that as the number of synapses declined in a given region, the size of the residualAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagesynapses increased. This synaptic compensatory response was also observed early in the course of the AD (DeKosky and Scheff, 1990). Neuronal structural alterations may not be the only factor(s) contributing to cognitive decline and hippocampal plasticity in MCI. For example, studies have reported significant reductions in synaptic vesicle trafficking-related genes in the AD brain, which interrupt the efficacy of normal synaptic transmission (Yao et al., 2003; Murphy et al., 2003; Kennedy et al., 2005). Counts et al. (2014) examined progressive changes in the expression classes of synaptic gene within single CA1 neurons in subjects who died with a clinical diagnosis of NCI, MCI or moderate AD obtain.

Monly used and widely available OTC medications and nutritional supplements were

Monly used and widely available OTC medications and nutritional supplements were safe and posed no short- or long-term threat to their health. Many used such products to improve their running performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is purchase Velpatasvir something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product recommended as an effective and legal substance by another runner or by a retail sales clerk may contain H 4065 site substances that are either banned by agencies such as WADA and/or may pose a serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.Monly used and widely available OTC medications and nutritional supplements were safe and posed no short- or long-term threat to their health. Many used such products to improve their running performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product recommended as an effective and legal substance by another runner or by a retail sales clerk may contain substances that are either banned by agencies such as WADA and/or may pose a serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.

Deration when interpreting experimental findings. (i) Identification of a mutation in

Deration when interpreting experimental findings. (i) Identification of a XR9576 web mutation in a clonal population does not indicate causality Any mutation in a cell that undergoes clonal Thonzonium (bromide) web expansion will be passed onto progeny, irrespective of functional status (Fig. 3A,B). Given the size of the genome, more mutations carried by a neoplastic clone will be passengers than drivers [27, 29, 30]. To demonstrate driver status, supporting functional studies and/or repeated observations of a mutated loci in neoplastic clones from independent individuals are needed. (ii) Mutational marking of a clone is stochastic and not guaranteed A clone may exist and not be detected if none of the genomic sites being screened carry a unique mutation permitting it to be distinguished from the germline (Fig. 3C). The more sites examined, the higher the probability of detection becomes. Restricting a marker panel to suspected driver sites precludes detection of pathological clones driven by unknown factors. (iii) Elevated mutation rates facilitate clone detection but are not an absolute requirement Screening of mutational hotspots makes it practical with conventional technologies to have a reasonable probability of detecting a clone by random passenger mutations. Clones derived from a mutator lineage or cells residing in a highly mutagenic environment should be more densely marked with identifiable passengers (Fig. 3D), potentially reducing the number of markers needing to be interrogated to identify them. Emerging high-throughput sequencing technologies will eventually obviate the need to restrict screening to a fraction of the genome. (iv) Identification of one or more clonal mutations is not proof of genetic instability in the absence of collateral information Detection of a mutation requires clonal expansion with most traditional methods of aggregate DNA analysis. The probability of identifying clonal mutations in an expanded population is a function of the number of sites screened, the mutability of these sites and the number of cell divisions having occurred in the lineage leading up to the final expansion. Particularly when considering hotspots, mutations will be occasionally detectable in any clonally-derived population at a statistically definable frequency. Because mutations are not routinely encountered in normal tissues, it is tempting to explain their presence in preneoplastic populations as the result of “genetic instability” (an elevated mutation rate). However, the phenomenon is more precisely explained by the fact that expansion does not routinely occur in most normal tissues. An elevated mutation rate itself will have no observable effect on clonal mutation frequency in the absence of expansion (Fig. 3E). To determine mutation rate from a clonal mutation frequency it is necessary to (A) know that the population being assessed is clonal and (B) have some metric of the number of cell divisions that occurred in the period between the zygote and the founding of the final clonalSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPageoutgrowth. To infer that a rate is elevated, it is also necessary to know the normal in vivo mutation rate, which is, in turn, impossible to measure by this approach given that large clonal expansions do not routinely occur in normal adult tissue. Considering these complexities, the lack of resolution as to whether mutation rates are elevated in cancer is not surprising [1,8?1]. (v) Detectabili.Deration when interpreting experimental findings. (i) Identification of a mutation in a clonal population does not indicate causality Any mutation in a cell that undergoes clonal expansion will be passed onto progeny, irrespective of functional status (Fig. 3A,B). Given the size of the genome, more mutations carried by a neoplastic clone will be passengers than drivers [27, 29, 30]. To demonstrate driver status, supporting functional studies and/or repeated observations of a mutated loci in neoplastic clones from independent individuals are needed. (ii) Mutational marking of a clone is stochastic and not guaranteed A clone may exist and not be detected if none of the genomic sites being screened carry a unique mutation permitting it to be distinguished from the germline (Fig. 3C). The more sites examined, the higher the probability of detection becomes. Restricting a marker panel to suspected driver sites precludes detection of pathological clones driven by unknown factors. (iii) Elevated mutation rates facilitate clone detection but are not an absolute requirement Screening of mutational hotspots makes it practical with conventional technologies to have a reasonable probability of detecting a clone by random passenger mutations. Clones derived from a mutator lineage or cells residing in a highly mutagenic environment should be more densely marked with identifiable passengers (Fig. 3D), potentially reducing the number of markers needing to be interrogated to identify them. Emerging high-throughput sequencing technologies will eventually obviate the need to restrict screening to a fraction of the genome. (iv) Identification of one or more clonal mutations is not proof of genetic instability in the absence of collateral information Detection of a mutation requires clonal expansion with most traditional methods of aggregate DNA analysis. The probability of identifying clonal mutations in an expanded population is a function of the number of sites screened, the mutability of these sites and the number of cell divisions having occurred in the lineage leading up to the final expansion. Particularly when considering hotspots, mutations will be occasionally detectable in any clonally-derived population at a statistically definable frequency. Because mutations are not routinely encountered in normal tissues, it is tempting to explain their presence in preneoplastic populations as the result of “genetic instability” (an elevated mutation rate). However, the phenomenon is more precisely explained by the fact that expansion does not routinely occur in most normal tissues. An elevated mutation rate itself will have no observable effect on clonal mutation frequency in the absence of expansion (Fig. 3E). To determine mutation rate from a clonal mutation frequency it is necessary to (A) know that the population being assessed is clonal and (B) have some metric of the number of cell divisions that occurred in the period between the zygote and the founding of the final clonalSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPageoutgrowth. To infer that a rate is elevated, it is also necessary to know the normal in vivo mutation rate, which is, in turn, impossible to measure by this approach given that large clonal expansions do not routinely occur in normal adult tissue. Considering these complexities, the lack of resolution as to whether mutation rates are elevated in cancer is not surprising [1,8?1]. (v) Detectabili.

Stently activated FFA more strongly than others. The were corrected for

Stently activated FFA more strongly than others. The were corrected for multiple [five] comparisons using PP58MedChemExpress PP58 Bonferroni significant results for group-average activation profiles further correction). Right FFA showed a similar tendency, but results did suggest that within-face activation profiles were similar across the not reach significance. Other regions did not show differential four subjects. This conclusion was supported by visual inspection activation to human versus animal faces. For places, an intuitive of single-subject within-face activation profiles and by intersubsubdivision would be natural versus man-made places. A twoject correlation analyses. Effects were somewhat stronger in left sided t test investigating this distinction did not yield significant than right FFA. Control regions hIT and EVC showed replicable results in any of our ROIs. Consistent with this, a recent patternwithin-face ranking as well, but only for concatenated single-subject information study reported that the natural/manmade distincactivation profiles. This suggests that activation profiles were not8656 ?J. Neurosci., June 20, 2012 ?32(25):8649 ?Mur et al. ?Single-Image Activation of Category RegionsFigure 4. No evidence for any inversions of category preference for particular image pairs in PPA or FFA. Figure 3 showed that most inverted pairs do not replicate. This leaves open the possibility that some inverted pairs do replicate. Here we test the apparently inverted pairs with the largest activation difference (which are least likely to be inverted by noise), using independent data. A, Computation of the average replicated gap. We first find all inverted pairs using session 1 data (step 1). We then sort these pairs according to the size of the activation gap, from the inverted pairs with the largest gaps to the inverted pairs with the smallest gaps (step 2). We estimate the activation gaps for all session 1 inverted pairs using the independent data from session 2 (step 3). Note that these gap estimates are negative for session 1 inverted pairs that do not replicate. For each number k 1…n of session-1 largest-gap inverted pairs, we average the session 2 gap estimates. We then plot these session 2 average replicated gaps versus k (step 4). We also perform this analysis with sessions 1 and 2 in reverse order and average results from the two directions (without assuming independence of the directions in statistical inference). If there are very few true inverted pairs, the leftmost part of the average replicated gap function has the greatest power to reveal these. If there are more true inverted pairs, averaging replicated gaps for more pairs has greater power for revealing the presence of true inverted pairs. B, The average replicated gap (black solid lines) is plotted as a function of the number of largest-gap inverted pairs for FFA, PPA, and EVC. The dark gray error regions indicate / 1 SE of the estimate. If the average replicated gap function does not emerge into the positive range (above the dashed black line), then even the most promising inverted pairs tend to revert to category-preferential order. If the average replicated gap exceeds the pink or red lines, then there is evidence for truly inverted pairs at p 0.05 (pink line) or p 0.01 (red line) and the peak is marked by a circle whose color indicates the level of significance in the same way. The significance thresholds for the peak were computed by Monte Carlo PP58 manufacturer simulation, accounting for multi.Stently activated FFA more strongly than others. The were corrected for multiple [five] comparisons using Bonferroni significant results for group-average activation profiles further correction). Right FFA showed a similar tendency, but results did suggest that within-face activation profiles were similar across the not reach significance. Other regions did not show differential four subjects. This conclusion was supported by visual inspection activation to human versus animal faces. For places, an intuitive of single-subject within-face activation profiles and by intersubsubdivision would be natural versus man-made places. A twoject correlation analyses. Effects were somewhat stronger in left sided t test investigating this distinction did not yield significant than right FFA. Control regions hIT and EVC showed replicable results in any of our ROIs. Consistent with this, a recent patternwithin-face ranking as well, but only for concatenated single-subject information study reported that the natural/manmade distincactivation profiles. This suggests that activation profiles were not8656 ?J. Neurosci., June 20, 2012 ?32(25):8649 ?Mur et al. ?Single-Image Activation of Category RegionsFigure 4. No evidence for any inversions of category preference for particular image pairs in PPA or FFA. Figure 3 showed that most inverted pairs do not replicate. This leaves open the possibility that some inverted pairs do replicate. Here we test the apparently inverted pairs with the largest activation difference (which are least likely to be inverted by noise), using independent data. A, Computation of the average replicated gap. We first find all inverted pairs using session 1 data (step 1). We then sort these pairs according to the size of the activation gap, from the inverted pairs with the largest gaps to the inverted pairs with the smallest gaps (step 2). We estimate the activation gaps for all session 1 inverted pairs using the independent data from session 2 (step 3). Note that these gap estimates are negative for session 1 inverted pairs that do not replicate. For each number k 1…n of session-1 largest-gap inverted pairs, we average the session 2 gap estimates. We then plot these session 2 average replicated gaps versus k (step 4). We also perform this analysis with sessions 1 and 2 in reverse order and average results from the two directions (without assuming independence of the directions in statistical inference). If there are very few true inverted pairs, the leftmost part of the average replicated gap function has the greatest power to reveal these. If there are more true inverted pairs, averaging replicated gaps for more pairs has greater power for revealing the presence of true inverted pairs. B, The average replicated gap (black solid lines) is plotted as a function of the number of largest-gap inverted pairs for FFA, PPA, and EVC. The dark gray error regions indicate / 1 SE of the estimate. If the average replicated gap function does not emerge into the positive range (above the dashed black line), then even the most promising inverted pairs tend to revert to category-preferential order. If the average replicated gap exceeds the pink or red lines, then there is evidence for truly inverted pairs at p 0.05 (pink line) or p 0.01 (red line) and the peak is marked by a circle whose color indicates the level of significance in the same way. The significance thresholds for the peak were computed by Monte Carlo simulation, accounting for multi.

Develop a construct model after the related factors to the quality

Develop a construct model after the related factors to the quality of life of homebound VER-52296 site seniors participating in meal delivery programs are examined and identified.Materials and MethodsSubjects Seniors receiving assistance from meal delivery service in Seoul participated, and a researcher who was knowledgeable about the seniors and the food service program, individuallyThis Research was supported by the Sookmyung Women’s University Research Grants 2012. ?Corresponding Author: Nami Joo, Tel. 82-2-710-9467, Fax. 82-2-710-9469, Email. [email protected] Received: April 2, 2012, Revised: July 18, 2012, Accepted: July 18, 2012 2012 The Korean Nutrition Society and the Korean Society of Community Nutrition This is an Open Access article distributed under the terms of the MK-571 (sodium salt) chemical information Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Seniors’ life quality in meal delivery programsasked them if it was permissible to collect data. The data were collected from 162 senior citizens, from October to November 2010, and approximately 30 to 40 minutes was taken per person. Questionnaire The questionnaire was developed based on the previous studies [7,12-16], adapted and completed through professional advice. The questionnaire items consisted of demographic characteristics of the elderly registered for in the meal delivery service, daily activities, emotional security linked to food, food enjoyment, foodservice satisfaction, and quality of life. The 5-point Likert scale was utilized to evaluate the items; selecting 1 point indicates `strongly disagree’ while checking 5 points denotes `strongly agree.’ Research hypotheses Independent variables were daily activities, emotional security connected to food, food enjoyment, and foodservice satisfaction was introduced as a parameter; the dependent variable was the quality of life. The following hypotheses were set up based on the assumption that the variables of this model were closely related. Hypothesis 1: The daily activities of the elderly who receive the foodservice will significantly affect the foodservice satisfaction. Hypothesis 2: The sense of the emotional security connected to food, of the elderly who take advantage of the foodservice, will significantly affect the foodservice satisfaction. Hypothesis 3: The food enjoyment of the elderly who get the foodservice will significantly affect the foodservice satisfaction. Hypothesis 4: The daily activities of the elderly who get the foodservice will significantly affect the quality of life. Hypothesis 5: The sense of the emotional security linked to food, of the elderly who get the foodservice, will significantly the affect quality of life. Hypothesis 6: The food enjoyment of the elderly who get the foodservice will significantly affect the quality of life. Hypothesis 7: The foodservice satisfaction of the elderly who get the foodservice will significantly affect the quality of life. Variables Daily activities Daily activities denote homebound seniors’ self-caring activities, shopping, and housework, such as food preparation. As they do these activities more, it indicates that their physical conditions are better. This variable was chosen based on previous research [13,16]. Food emotional security Feelings of food insecurity denote a deficiency of a basic human desire. The quest.Develop a construct model after the related factors to the quality of life of homebound seniors participating in meal delivery programs are examined and identified.Materials and MethodsSubjects Seniors receiving assistance from meal delivery service in Seoul participated, and a researcher who was knowledgeable about the seniors and the food service program, individuallyThis Research was supported by the Sookmyung Women’s University Research Grants 2012. ?Corresponding Author: Nami Joo, Tel. 82-2-710-9467, Fax. 82-2-710-9469, Email. [email protected] Received: April 2, 2012, Revised: July 18, 2012, Accepted: July 18, 2012 2012 The Korean Nutrition Society and the Korean Society of Community Nutrition This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Seniors’ life quality in meal delivery programsasked them if it was permissible to collect data. The data were collected from 162 senior citizens, from October to November 2010, and approximately 30 to 40 minutes was taken per person. Questionnaire The questionnaire was developed based on the previous studies [7,12-16], adapted and completed through professional advice. The questionnaire items consisted of demographic characteristics of the elderly registered for in the meal delivery service, daily activities, emotional security linked to food, food enjoyment, foodservice satisfaction, and quality of life. The 5-point Likert scale was utilized to evaluate the items; selecting 1 point indicates `strongly disagree’ while checking 5 points denotes `strongly agree.’ Research hypotheses Independent variables were daily activities, emotional security connected to food, food enjoyment, and foodservice satisfaction was introduced as a parameter; the dependent variable was the quality of life. The following hypotheses were set up based on the assumption that the variables of this model were closely related. Hypothesis 1: The daily activities of the elderly who receive the foodservice will significantly affect the foodservice satisfaction. Hypothesis 2: The sense of the emotional security connected to food, of the elderly who take advantage of the foodservice, will significantly affect the foodservice satisfaction. Hypothesis 3: The food enjoyment of the elderly who get the foodservice will significantly affect the foodservice satisfaction. Hypothesis 4: The daily activities of the elderly who get the foodservice will significantly affect the quality of life. Hypothesis 5: The sense of the emotional security linked to food, of the elderly who get the foodservice, will significantly the affect quality of life. Hypothesis 6: The food enjoyment of the elderly who get the foodservice will significantly affect the quality of life. Hypothesis 7: The foodservice satisfaction of the elderly who get the foodservice will significantly affect the quality of life. Variables Daily activities Daily activities denote homebound seniors’ self-caring activities, shopping, and housework, such as food preparation. As they do these activities more, it indicates that their physical conditions are better. This variable was chosen based on previous research [13,16]. Food emotional security Feelings of food insecurity denote a deficiency of a basic human desire. The quest.

Ding on type of dialysis start. 168 patients were considered as early

Ding on type of dialysis start. 168 GDC-0084 web patients were considered as early referred and with a planned dialysis start, 113 patients were considered as early referred but with a non-planned dialysis start, 63 patients were considered late referred but with planned dialysis start and 203 patients were late referred and had non-planned dialysis start. Planned dialysis patients were 231 of the total population and non-planned dialysis start were 316. doi:10.1371/journal.pone.0155987.gPLOS ONE | DOI:10.1371/journal.pone.buy Nutlin (3a) 0155987 May 26,4 /Referral, Modality and Dialysis Start in an International SettingTable 1. Clinical characteristics according to planning of dialysis start. Population n Males, n ( ) Age, years Weight at dialysis start, Kg Cause of ESRD ( ) Diabetes mellitus, n ( ) Glomerular, n ( ) Inherited, n ( ) Unknown, n ( ) Others, n ( ) Tubulo-interstitial, n ( ) Vascular, n ( ) Biochemistry at dialysis start Serum Creatinine (mg/dl) CCr 24h (ml/min) EPO prescribed, n ( ) Haemoglobin (g/dl) Serum Calcium (mg/dl) Serum Phosphorus (mg/dl) S. Albumin (g/dl) RRT at 1st dialysis session HD, n ( ) PD, n ( ) 1st chronic RRT HD, n ( ) PD, n ( ) 488 (89.2) 59 (10.7) 191 (82.6) 40 (17.3) 297 (94) 19 (6) <0.001 502 (91.7) 45 (8.2) 191 (82.6) 40 (17.3) 311 (98.4) 5 (1.5) <0.001 6.1 (3.3?1.4) 9 (5?6) 209 (38) 10 (7?2) 8.4 (7.3?.9) 4.8 (3.4?.6) 3.6 (2.8?.2) 5.2 (3.3?.2) 9 (5?5) 115 (50) 10 (8?1) 8.8 (7.4?.9) 4.6 (3.4?.4) 3.8 (3.2?.3) 6.8 (3.9?2.5) 8 (4?6) 94 (30) 9 (7?1) 8.3 (7.3?.4) 5.2 (3.6?.7) 3.4 (2.7?.0) <0.001 NS <0.001 <0.001 <0.001 <0.001 <0.001 162 (30) 64 (12) 26 (4.7) 52 (9.5) 56 (10) 62 (11) 125 (23) 74 (32) 27 (12) 18 (8) 11 (5) 15 (6) 19 (8) 67 (29) 88 (28) 37 (12) 8 (2.5) 41 (13) 41 (13) 43 (14) 58 (18) <0.001 Total 547 332 (61) 64 (42?1) 77 (56?00) P dialysis start 231 144 (62) 63 (40?0) 80 (58?7) NP dialysis start 316 188 (59) 64 (43?0) 73 (55?01) NS NS <0.01 P-valueValues are median (10th to 90th percentile), or percentage. Abbreviations: P, planned dialysis start; NP, non-planned dialysis start; ESRD, end stage renal disease; RRT, renal replacement therapy; HD, hemodialysis; PD, peritoneal dialysis; EPO, erythropoietin. doi:10.1371/journal.pone.0155987.tthe patients were referred late to ICS [in Romania (57 ), Poland (50 ) and Hungary (35 )]. Predialysis (GFR <30ml/min) care was provided in ICS more frequently by general nephrologists (68 ) rather than by specialized predialysis staff (29 ). Most patients 479/547 (87 ) received some renal education prior to dialysis start. RRT modality information was provided to 436/547 (80 ) of patients. Of the modality informed patients, final RRT was exclusively based upon patient choice in 57 of cases. The median time from information to dialysis start was 2 months. Patients (246/436; 57 ) signed informed consents at the time of modality provision and at the time of dialysis start (421/547; 77 ). More patients received modality information in the PD group (92 ) compared with 78 in the HD (p = 0.02). Optimal care was observed in 123/547 (23 ) of the patients.Planned versus non-planned startReasons for becoming NP and needing urgent dialysis are presented in Table 2. 316/547 (58 ) started dialysis as NP and 113/316 (36 ) of the NP patients were previously followed up, for at least 3 months, by nephrologists (54 of patients at an ICS clinic vs. 46 byPLOS ONE | DOI:10.1371/journal.pone.0155987 May 26,5 /Referral, Modality and Dialysis Start in an International SettingTable 2. Reasons for non-pl.Ding on type of dialysis start. 168 patients were considered as early referred and with a planned dialysis start, 113 patients were considered as early referred but with a non-planned dialysis start, 63 patients were considered late referred but with planned dialysis start and 203 patients were late referred and had non-planned dialysis start. Planned dialysis patients were 231 of the total population and non-planned dialysis start were 316. doi:10.1371/journal.pone.0155987.gPLOS ONE | DOI:10.1371/journal.pone.0155987 May 26,4 /Referral, Modality and Dialysis Start in an International SettingTable 1. Clinical characteristics according to planning of dialysis start. Population n Males, n ( ) Age, years Weight at dialysis start, Kg Cause of ESRD ( ) Diabetes mellitus, n ( ) Glomerular, n ( ) Inherited, n ( ) Unknown, n ( ) Others, n ( ) Tubulo-interstitial, n ( ) Vascular, n ( ) Biochemistry at dialysis start Serum Creatinine (mg/dl) CCr 24h (ml/min) EPO prescribed, n ( ) Haemoglobin (g/dl) Serum Calcium (mg/dl) Serum Phosphorus (mg/dl) S. Albumin (g/dl) RRT at 1st dialysis session HD, n ( ) PD, n ( ) 1st chronic RRT HD, n ( ) PD, n ( ) 488 (89.2) 59 (10.7) 191 (82.6) 40 (17.3) 297 (94) 19 (6) <0.001 502 (91.7) 45 (8.2) 191 (82.6) 40 (17.3) 311 (98.4) 5 (1.5) <0.001 6.1 (3.3?1.4) 9 (5?6) 209 (38) 10 (7?2) 8.4 (7.3?.9) 4.8 (3.4?.6) 3.6 (2.8?.2) 5.2 (3.3?.2) 9 (5?5) 115 (50) 10 (8?1) 8.8 (7.4?.9) 4.6 (3.4?.4) 3.8 (3.2?.3) 6.8 (3.9?2.5) 8 (4?6) 94 (30) 9 (7?1) 8.3 (7.3?.4) 5.2 (3.6?.7) 3.4 (2.7?.0) <0.001 NS <0.001 <0.001 <0.001 <0.001 <0.001 162 (30) 64 (12) 26 (4.7) 52 (9.5) 56 (10) 62 (11) 125 (23) 74 (32) 27 (12) 18 (8) 11 (5) 15 (6) 19 (8) 67 (29) 88 (28) 37 (12) 8 (2.5) 41 (13) 41 (13) 43 (14) 58 (18) <0.001 Total 547 332 (61) 64 (42?1) 77 (56?00) P dialysis start 231 144 (62) 63 (40?0) 80 (58?7) NP dialysis start 316 188 (59) 64 (43?0) 73 (55?01) NS NS <0.01 P-valueValues are median (10th to 90th percentile), or percentage. Abbreviations: P, planned dialysis start; NP, non-planned dialysis start; ESRD, end stage renal disease; RRT, renal replacement therapy; HD, hemodialysis; PD, peritoneal dialysis; EPO, erythropoietin. doi:10.1371/journal.pone.0155987.tthe patients were referred late to ICS [in Romania (57 ), Poland (50 ) and Hungary (35 )]. Predialysis (GFR <30ml/min) care was provided in ICS more frequently by general nephrologists (68 ) rather than by specialized predialysis staff (29 ). Most patients 479/547 (87 ) received some renal education prior to dialysis start. RRT modality information was provided to 436/547 (80 ) of patients. Of the modality informed patients, final RRT was exclusively based upon patient choice in 57 of cases. The median time from information to dialysis start was 2 months. Patients (246/436; 57 ) signed informed consents at the time of modality provision and at the time of dialysis start (421/547; 77 ). More patients received modality information in the PD group (92 ) compared with 78 in the HD (p = 0.02). Optimal care was observed in 123/547 (23 ) of the patients.Planned versus non-planned startReasons for becoming NP and needing urgent dialysis are presented in Table 2. 316/547 (58 ) started dialysis as NP and 113/316 (36 ) of the NP patients were previously followed up, for at least 3 months, by nephrologists (54 of patients at an ICS clinic vs. 46 byPLOS ONE | DOI:10.1371/journal.pone.0155987 May 26,5 /Referral, Modality and Dialysis Start in an International SettingTable 2. Reasons for non-pl.

Gnificant compression-induced radial expansion of 4.7 ?4.1 after 20 minutes [92]. Madden et al. (2013) showed

Gnificant compression-induced radial expansion of 4.7 ?4.1 after 20 minutes [92]. Madden et al. (2013) showed in vivo that 10?20 compressive strain of buy Grazoprevir cartilage led to about 5?3 cell width strain, depending on the area the cells were located [12]. Similarly, it has recently been calculated that the Green-Lagrange strain for cell width increased by 0.17 ?0.02 when bovine cartilage tissue was compressed with a 15 nominal tissue strain [91]. Extreme tissue strains of 80 cartilage compression increased the cell strain only by an additional 2? [95,96]. This suggests that chondrocytes in vivo are not subjected to more than 15 cell elongation. However, one has to consider that chondrocytes come from different layers within articular cartilage. Within these layers cells experience different physical forces and may therefore respond differently to the same strain magnitudes. Nonetheless, as showed in two of the reviewed papers, chondrocytes might also tolerate higher strains (20 ; 24 ) without inducing catabolic actions, although these strains might rather be un-physiologic [14,52]. There is a fine balance between anabolic and catabolic actions in chondrocytes in response to CTS. We suggest that in a non-inflammatory environment loading protocols below 3 strain, 0.17 Hz and 2 h result in weak or no biological responses. Loading protocols between 3?0 strain, 0.17 Hz–0.5 Hz and 2?2 h tend to induce anabolic responses, whereas above 10 strain, 0.5 Hz and 12 h, catabolic events occur. However, this review not only shows that each of the three loading parameters (magnitude, frequency, duration) but also that the environment of the cell contributes to the shift towards either anabolic or catabolic actions. To provide better comparability of studies and better transition to three-dimensional conditions, we suggest considering the following hints in the future: Loading purchase FT011 conditions should be as physiological as possible and should include pauses. Therefore, we advise to apply loading frequencies between 0.5 and 2.5 Hz, loading magnitudes between 0.5 and 15 , and loading durations shorter than 12 h. Further, culture plates should be uncoated or coated with the cartilagespecific collagen II. Data should be collected not only immediately after the last loading cycle but also after a recovery time. All parameters that could affect the cellular outcome should be explained in details.PLOS ONE | DOI:10.1371/journal.pone.0119816 March 30,20 /Cyclic Tensile Strain and Chondrocyte MetabolismConclusionResults from in vitro experiments with CTS disclose further information about the effect of mechanical signals on the biological response of chondrocytes. Many factors are involved in the synthesis and remodeling of the ECM in response to loading. It is important to look not only at single isolated parameters and to combine information from different studies. A better understanding of the relationship between specific loading parameters and chondrocyte response will be useful for the development of tissue engineered cartilage. Furthermore, the simulation of an inflammatory environment allows new insights into the anabolic capabilities of specific loading protocols in rehabilitation and therapy of degenerative joint disease like osteoarthritis.Supporting InformationS1 Checklist. PRISMA checklist. (PDF)Author ContributionsConceived and designed the experiments: JB FZ GB AN. Analyzed the data: JB FZ GB AN. Wrote the paper: JB FZ GB AN. Literature search: JB AN.Gnificant compression-induced radial expansion of 4.7 ?4.1 after 20 minutes [92]. Madden et al. (2013) showed in vivo that 10?20 compressive strain of cartilage led to about 5?3 cell width strain, depending on the area the cells were located [12]. Similarly, it has recently been calculated that the Green-Lagrange strain for cell width increased by 0.17 ?0.02 when bovine cartilage tissue was compressed with a 15 nominal tissue strain [91]. Extreme tissue strains of 80 cartilage compression increased the cell strain only by an additional 2? [95,96]. This suggests that chondrocytes in vivo are not subjected to more than 15 cell elongation. However, one has to consider that chondrocytes come from different layers within articular cartilage. Within these layers cells experience different physical forces and may therefore respond differently to the same strain magnitudes. Nonetheless, as showed in two of the reviewed papers, chondrocytes might also tolerate higher strains (20 ; 24 ) without inducing catabolic actions, although these strains might rather be un-physiologic [14,52]. There is a fine balance between anabolic and catabolic actions in chondrocytes in response to CTS. We suggest that in a non-inflammatory environment loading protocols below 3 strain, 0.17 Hz and 2 h result in weak or no biological responses. Loading protocols between 3?0 strain, 0.17 Hz–0.5 Hz and 2?2 h tend to induce anabolic responses, whereas above 10 strain, 0.5 Hz and 12 h, catabolic events occur. However, this review not only shows that each of the three loading parameters (magnitude, frequency, duration) but also that the environment of the cell contributes to the shift towards either anabolic or catabolic actions. To provide better comparability of studies and better transition to three-dimensional conditions, we suggest considering the following hints in the future: Loading conditions should be as physiological as possible and should include pauses. Therefore, we advise to apply loading frequencies between 0.5 and 2.5 Hz, loading magnitudes between 0.5 and 15 , and loading durations shorter than 12 h. Further, culture plates should be uncoated or coated with the cartilagespecific collagen II. Data should be collected not only immediately after the last loading cycle but also after a recovery time. All parameters that could affect the cellular outcome should be explained in details.PLOS ONE | DOI:10.1371/journal.pone.0119816 March 30,20 /Cyclic Tensile Strain and Chondrocyte MetabolismConclusionResults from in vitro experiments with CTS disclose further information about the effect of mechanical signals on the biological response of chondrocytes. Many factors are involved in the synthesis and remodeling of the ECM in response to loading. It is important to look not only at single isolated parameters and to combine information from different studies. A better understanding of the relationship between specific loading parameters and chondrocyte response will be useful for the development of tissue engineered cartilage. Furthermore, the simulation of an inflammatory environment allows new insights into the anabolic capabilities of specific loading protocols in rehabilitation and therapy of degenerative joint disease like osteoarthritis.Supporting InformationS1 Checklist. PRISMA checklist. (PDF)Author ContributionsConceived and designed the experiments: JB FZ GB AN. Analyzed the data: JB FZ GB AN. Wrote the paper: JB FZ GB AN. Literature search: JB AN.

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ……………………………………………… ….. ………….. 9 FI S Euthynuus affinis Fi red f. 3.20 Y 25 30 skinned single f.

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ……………………………………………… ….. ………….. 9 FI S Euthynuus affinis Fi red f. 3.20 Y 25 30 skinned single f. Johnston Brill [83] (kawakawa, TGR-1202 biological activity Pacific ocean) ………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………….. 10 FI S Euthynuus affinis Fi white f. 3.20 Y 188 30 skinned single f. Johnston Brill [83] (kawakawa, Pacific ocean) ………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………….. 11 FI S Gadus morhua (North Sea Fi myotomal m. fast f., 2?2?84 Y 187 8 skinned single f. Johnston Altringham [84] cod,. Olmutinib price temperate). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ………………………………………………. ……………… 12 FI S Gadus morhua (cod) Fi myotomal m. white f. (fast) 84 N 83 8 skinned single f. Altringham Johnston [85] ………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………….. 13. . . . . . . . . . . . . FI. . . . . . . . . . . .S. . . . . . . . . . .Gadus. morhua. .(cod). . . . . . . . . . . . . . . . . . . . . . .Fi. . . . . . . . . . . . . . . . . .myotomal. .m.. .red. .f.. .(slow). . . . . . . . . . . . . . . . . . . . . . . . . . .84. . . . . . . . . . . . . . . . . . . . . . . . . .N. . . . . . . . . . . 186. . . . . . . . . . . . . . . . . . . . .8. . . . . . . . . . . . . .skinned. . 2?. .f.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Altringham. . . . Johnston. .[85]. . . ….. .. . ……… ………… ……. .. …………… … …. . ……… .. . ….. . ……….. …… . …………….. . ………….. ….. (Continued.)rsos.royalsocietypublishing.org R. Soc. open sci. 3:…………………………………………Table 4. (Continued.) motor M (kg) I f (kPa) T ( ) comment referenceno.TyCspeciesgroup…………………… . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ……………………………………………… ….. ………….. 9 FI S Euthynuus affinis Fi red f. 3.20 Y 25 30 skinned single f. Johnston Brill [83] (kawakawa, Pacific ocean) ………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………….. 10 FI S Euthynuus affinis Fi white f. 3.20 Y 188 30 skinned single f. Johnston Brill [83] (kawakawa, Pacific ocean) ………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………….. 11 FI S Gadus morhua (North Sea Fi myotomal m. fast f., 2?2?84 Y 187 8 skinned single f. Johnston Altringham [84] cod,. temperate). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ………………………………………………. ……………… 12 FI S Gadus morhua (cod) Fi myotomal m. white f. (fast) 84 N 83 8 skinned single f. Altringham Johnston [85] ………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………….. 13. . . . . . . . . . . . . FI. . . . . . . . . . . .S. . . . . . . . . . .Gadus. morhua. .(cod). . . . . . . . . . . . . . . . . . . . . . .Fi. . . . . . . . . . . . . . . . . .myotomal. .m.. .red. .f.. .(slow). . . . . . . . . . . . . . . . . . . . . . . . . . .84. . . . . . . . . . . . . . . . . . . . . . . . . .N. . . . . . . . . . . 186. . . . . . . . . . . . . . . . . . . . .8. . . . . . . . . . . . . .skinned. . 2?. .f.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Altringham. . . . Johnston. .[85]. . . ….. .. . ……… ………… ……. .. …………… … …. . ……… .. . ….. . ……….. …… . …………….. . ………….. ….. (Continued.)rsos.royalsocietypublishing.org R. Soc. open sci. 3:…………………………………………Table 4. (Continued.) motor M (kg) I f (kPa) T ( ) comment referenceno.TyCspeciesgroup…………………..

G High EngagementFluctuation over time. User engagement with items on CERN

G High EngagementFluctuation over time. User engagement with items on CERN’s social media platforms fluctuated strongly over time. Fig 4 represents the pattern of user interactions with items posted on CERN’s XL880 site Facebook page over the time period studied, normalized by daily audience size. In total, the audience typically engaged with items at a constant rate of interactions throughout the study, as illustrated by the cluster of observations near the x axis. In addition, several outliers were found, some with z-scores as high as 5 or more, meaning that for certain items, user behaviours occurred as often as 5 standard deviations more than the means for those behaviours on the respective platforms. A similar pattern of user behaviour was found in most platforms studied. High-engagement items. Thirty-five (35) high-engagement items were found in the study, comprising more than 16 of the 214 items included in the sample. These were defined as items with at least one user behaviour statistic scoring z 1.96. As an example, the six highengagement items for CERN’s Facebook page are labelled in Fig 4A. The point labelled “Open Data” in Fig 4A, for instance, refers to click-throughs on a link in the Facebook announcement that CERN had launched an Open Data Portal to make the data of LHC experiments publicly available. This item received high standard scores on Facebook in terms of click-throughs per thousand users (z = 5.05) and shares per thousand users (z = 2.47). Hence, it was considered a high engagement item posted on the Facebook platform. (Since the distribution was strongly right-skewed, no low-engagement items were identified in the study.) The lifetime total reach of these Facebook posts, a measure indicating the number of users who JNJ-54781532 price potentially could interact with the post, was similar at 11,490 users (SD 13,900). Most of the posts reached around 10,000 users (Mean 10,300, SD 7,565) except for one outlier, “Dishwasher,” which concerned a dishwasher for circuit boards, and reached over 121,000 users (Fig 4B). This indicates that in not all cases was user engagement necessarily driven by increased reach. Associations between high engagement items and topics. High engagement across platforms is significantly associated with item topic. Six (6) topics were repeatedly popular acrossPLOS ONE | DOI:10.1371/journal.pone.0156409 May 27,12 /Engagement with Particle Physics on CERN’s Social Media PlatformsFig 4. User engagement with scientific content and reach on CERN’s Facebook page over time, October ecember 2014. (A) User engagement with scientific items over time. Zero represents the mean rate for each user behaviour on Facebook per item per 1,000 Facebook followers on the day of sampling: Likes 1.21 IPI/kU (SD 1.86); Comments 0.0779 IPI/kU (SD 0.17), Shares 0.187 IPI/kU (SD 0.32); Click-throughs 0.256 IPI/kU (SD 0.52). pkU: Per Thousand Users. Z: Z-score. The size of CERN’s Facebook audience size grew from 343,000 to 367,000 over the course of the study. (B) Reach of scientific items over time. Reach is the total number of Facebook users the item was served to. doi:10.1371/journal.pone.0156409.gmultiple platforms (hereafter “recurring” high-engagement topics), representing 19 items of the 35 “high engagement” items. For example, the “Open Data” topic received high engagement scores not only on Facebook but also on Google+, Twitter English and Twitter French, making it a recurring high-engagement topic. By contrast, another 16 high-engagement.G High EngagementFluctuation over time. User engagement with items on CERN’s social media platforms fluctuated strongly over time. Fig 4 represents the pattern of user interactions with items posted on CERN’s Facebook page over the time period studied, normalized by daily audience size. In total, the audience typically engaged with items at a constant rate of interactions throughout the study, as illustrated by the cluster of observations near the x axis. In addition, several outliers were found, some with z-scores as high as 5 or more, meaning that for certain items, user behaviours occurred as often as 5 standard deviations more than the means for those behaviours on the respective platforms. A similar pattern of user behaviour was found in most platforms studied. High-engagement items. Thirty-five (35) high-engagement items were found in the study, comprising more than 16 of the 214 items included in the sample. These were defined as items with at least one user behaviour statistic scoring z 1.96. As an example, the six highengagement items for CERN’s Facebook page are labelled in Fig 4A. The point labelled “Open Data” in Fig 4A, for instance, refers to click-throughs on a link in the Facebook announcement that CERN had launched an Open Data Portal to make the data of LHC experiments publicly available. This item received high standard scores on Facebook in terms of click-throughs per thousand users (z = 5.05) and shares per thousand users (z = 2.47). Hence, it was considered a high engagement item posted on the Facebook platform. (Since the distribution was strongly right-skewed, no low-engagement items were identified in the study.) The lifetime total reach of these Facebook posts, a measure indicating the number of users who potentially could interact with the post, was similar at 11,490 users (SD 13,900). Most of the posts reached around 10,000 users (Mean 10,300, SD 7,565) except for one outlier, “Dishwasher,” which concerned a dishwasher for circuit boards, and reached over 121,000 users (Fig 4B). This indicates that in not all cases was user engagement necessarily driven by increased reach. Associations between high engagement items and topics. High engagement across platforms is significantly associated with item topic. Six (6) topics were repeatedly popular acrossPLOS ONE | DOI:10.1371/journal.pone.0156409 May 27,12 /Engagement with Particle Physics on CERN’s Social Media PlatformsFig 4. User engagement with scientific content and reach on CERN’s Facebook page over time, October ecember 2014. (A) User engagement with scientific items over time. Zero represents the mean rate for each user behaviour on Facebook per item per 1,000 Facebook followers on the day of sampling: Likes 1.21 IPI/kU (SD 1.86); Comments 0.0779 IPI/kU (SD 0.17), Shares 0.187 IPI/kU (SD 0.32); Click-throughs 0.256 IPI/kU (SD 0.52). pkU: Per Thousand Users. Z: Z-score. The size of CERN’s Facebook audience size grew from 343,000 to 367,000 over the course of the study. (B) Reach of scientific items over time. Reach is the total number of Facebook users the item was served to. doi:10.1371/journal.pone.0156409.gmultiple platforms (hereafter “recurring” high-engagement topics), representing 19 items of the 35 “high engagement” items. For example, the “Open Data” topic received high engagement scores not only on Facebook but also on Google+, Twitter English and Twitter French, making it a recurring high-engagement topic. By contrast, another 16 high-engagement.

Taking turns at doing X and in parallel trading X for

Taking turns at doing X and in parallel trading X for Y. This may correspond to a relationship evolving with time from one RM to the other. The generalization of our model to N social actions, presented in the next section, helps represent any familiar composite relationship.PLOS ONE | DOI:10.1371/journal.pone.0120882 March 31,9 /A Generic Model of Dyadic Social RelationshipsGeneralization to N social actionsIn real social relationships, the number of occurring social actions is expected to be larger than two, which motivates the generalization of our results to any number N of social actions. This is our third result. For the generalization that follows, we let X and Y be elements of a larger set S of N social actions Si: S = Siji = 1,. . .,N, such that X,Y 2 S, for instance S1 X and S2 Y. Proposition 2: In the general case of N non-null social actions (S1,S2, . . . ,SN 2 S, N ! 2), one still needs exactly the six categories of Table 3 to describe all possible relationships arising ! from the setting A B. S =S =:::=S =;1 2 NS1 =S2 =:::=SN =;Idea of the proof: We show that the proof of exhaustiveness of the six categories of Table 3 carried out for N = 2 holds for any N ! 2. Namely, the same process allows to build the same six mutually disjoint categories of action fluxes, and these categories span the relationship space for any N ! 2. Proof: In the general case of N ! 2 non-null social actions, there are 2N+1 elementary inter2 actions and 2(N+1) -1 relationships. S1 �S2 ! Cases such as A B (where A performs several actions simultaneously) can be writtenSA ! B (where S4 is a bundle of actions). More generally, any number of actions can be bundled SSas in that example. Starting from a set of N social actions, the set S can include all subsets of that set. (The cardinality of S is then 2N.) Hence, any union of two or more subsets (such as S1 and S2 to give S4) gives another subset that is an element of S. Then, because there are still two agents and thus at most two different social actions per elementary interaction, the elementary interactions have the same forms as for N = 2, with additional notations for the social actions. As an illustration, Table 4 shows the sixteen elementary interactions that CCX282-B web result from the ! case N = 3, i.e. the model A B. X=Y=Z=; For any N ! 2, looking at an elementary interaction between two individuals, one can still only differentiate between (i) identical or different actions, (ii) interchangeable or non-interchangeable roles, (iii) null or non-null actions. Hence, with more than two actions, this differentiation process leads to the same six disjoint categories, except with more PXD101 site alternative notations than in Table 3. For example, for N = 3, category 1 (EM) gets one more alternative notation than for N = 2, Z Z Z namely A ! B. Category 3 (MP) gets two alternative notations: [A ! B and A ! B], andZ X X X=Y=Z=;Table 4. Sixteen elementary interactions for N = 3 social actions. A!B X A!B X A!B X AX Z Y XA!B Y A!B Y A!B Y AY Z YXA!B Z A!B Z A!B Z AZ Z YXX A! B Y A! B Z A! BBBBA !B ;;This table shows the sixteen elementary interactions arising from our model with N = 3 non-null social ! actions X,Y,Z between two agents A and B, that is, A B. We use simplified notations for theX=Y=Z=; X=Y=Z=;interactions involving one empty flux. doi:10.1371/journal.pone.0120882.tPLOS ONE | DOI:10.1371/journal.pone.0120882 March 31,10 /A Generic Model of Dyadic Social Relationships[A ! B and A ! B]. Category 4 (AR) gets f.Taking turns at doing X and in parallel trading X for Y. This may correspond to a relationship evolving with time from one RM to the other. The generalization of our model to N social actions, presented in the next section, helps represent any familiar composite relationship.PLOS ONE | DOI:10.1371/journal.pone.0120882 March 31,9 /A Generic Model of Dyadic Social RelationshipsGeneralization to N social actionsIn real social relationships, the number of occurring social actions is expected to be larger than two, which motivates the generalization of our results to any number N of social actions. This is our third result. For the generalization that follows, we let X and Y be elements of a larger set S of N social actions Si: S = Siji = 1,. . .,N, such that X,Y 2 S, for instance S1 X and S2 Y. Proposition 2: In the general case of N non-null social actions (S1,S2, . . . ,SN 2 S, N ! 2), one still needs exactly the six categories of Table 3 to describe all possible relationships arising ! from the setting A B. S =S =:::=S =;1 2 NS1 =S2 =:::=SN =;Idea of the proof: We show that the proof of exhaustiveness of the six categories of Table 3 carried out for N = 2 holds for any N ! 2. Namely, the same process allows to build the same six mutually disjoint categories of action fluxes, and these categories span the relationship space for any N ! 2. Proof: In the general case of N ! 2 non-null social actions, there are 2N+1 elementary inter2 actions and 2(N+1) -1 relationships. S1 �S2 ! Cases such as A B (where A performs several actions simultaneously) can be writtenSA ! B (where S4 is a bundle of actions). More generally, any number of actions can be bundled SSas in that example. Starting from a set of N social actions, the set S can include all subsets of that set. (The cardinality of S is then 2N.) Hence, any union of two or more subsets (such as S1 and S2 to give S4) gives another subset that is an element of S. Then, because there are still two agents and thus at most two different social actions per elementary interaction, the elementary interactions have the same forms as for N = 2, with additional notations for the social actions. As an illustration, Table 4 shows the sixteen elementary interactions that result from the ! case N = 3, i.e. the model A B. X=Y=Z=; For any N ! 2, looking at an elementary interaction between two individuals, one can still only differentiate between (i) identical or different actions, (ii) interchangeable or non-interchangeable roles, (iii) null or non-null actions. Hence, with more than two actions, this differentiation process leads to the same six disjoint categories, except with more alternative notations than in Table 3. For example, for N = 3, category 1 (EM) gets one more alternative notation than for N = 2, Z Z Z namely A ! B. Category 3 (MP) gets two alternative notations: [A ! B and A ! B], andZ X X X=Y=Z=;Table 4. Sixteen elementary interactions for N = 3 social actions. A!B X A!B X A!B X AX Z Y XA!B Y A!B Y A!B Y AY Z YXA!B Z A!B Z A!B Z AZ Z YXX A! B Y A! B Z A! BBBBA !B ;;This table shows the sixteen elementary interactions arising from our model with N = 3 non-null social ! actions X,Y,Z between two agents A and B, that is, A B. We use simplified notations for theX=Y=Z=; X=Y=Z=;interactions involving one empty flux. doi:10.1371/journal.pone.0120882.tPLOS ONE | DOI:10.1371/journal.pone.0120882 March 31,10 /A Generic Model of Dyadic Social Relationships[A ! B and A ! B]. Category 4 (AR) gets f.

Focus group discussions were analysed for themes [46?8]. Our research team thoroughly

Focus group discussions were analysed for themes [46?8]. Our research team Necrostatin-1 dose thoroughly read and reread the transcripts and met regularly to develop a systematic process of thematic analysis. We used investigator triangulation [49, 50] to create and agree upon the categorizations and coding schemes that led to our themes. Our themes appeared consistently in each of the four focus groups. Trustworthiness was established by member checking with participants to ensure authenticity. Several strategies were utilized to increase rigor [45, 51]. Stability was enhanced through the use of multiple focus groups in geographically different areas. Equivalence was achieved through the use of two experienced moderators with complementary styles to achieve “flow, texture and context” and to promote construct validity [51] (page 302). Credibility was strengthened through sustained engagement and observation over the course of four focus groups, researcher triangulation, debriefing as a research team, and member checking. Reflexivity, where researchers strive to understand their own experiences as well as the research question, in order to remain objective, neutral, and nonbiased, was supported through regular face-to-face and teleconference meetings. Transferability was enriched through dense sample description and rich description of the data. Confirmability was heightened through peer debriefing and maintaining our audit trail. Dependability was attained by recording a log of our plans, meetings, and ongoing interpretations. Using annotation and memo functions, NVIVO 9 [52] maintained a permanent record of our work. Tracking individual responses in addition to the group account [53] assisted us in avoiding the risk of analyzing data from only vocally dominant RG7800MedChemExpress RG7800 members of the groups. Field notes or “descriptions of participants, impressions related to the discussion (and) observations related to group dynamics”3. Research ApproachThis qualitative descriptive project was framed from a constructivist worldview [32?4] and Haas and Shaffir’s [4] sociological theory of professionalization. Haas and Shaffir theorized that legitimation is a central concept in healthcare professionals’ process of socialization. Participants were 27 Post LPN to BN students from a Canadian university who attended a practicum on an acute hospital unit. The main purpose of the research was to describe Post LPN to BN student nurses’ experiences with professional socialization as they transitioned into a more complex nursing role. A secondary purpose of the research was to begin to understand how university faculty can best support and facilitate these students’ professional socialization as they learn to become Registered Nurses (RNs). Data sources included four face-to-face digitally recorded, transcribed focus group discussions which were analyzed for themes. Our rational for collecting and analyzing focus group data centered on our intention to invite our participants to converse and interact in ways that stimulated new insights. Focus group methodology, with its emphasis on group interaction [35?9] and goal of collaborative discussion [40, 41], allowed us to draw out participants’ views and to explore their ideas and conversational exchanges with one another in depth. Focus groups are a rich source of information [42] and a valid method of generating data within a constructionist epistemology where “knowledge is created in situated, [collective] encounters” [43] (page 496). They.Focus group discussions were analysed for themes [46?8]. Our research team thoroughly read and reread the transcripts and met regularly to develop a systematic process of thematic analysis. We used investigator triangulation [49, 50] to create and agree upon the categorizations and coding schemes that led to our themes. Our themes appeared consistently in each of the four focus groups. Trustworthiness was established by member checking with participants to ensure authenticity. Several strategies were utilized to increase rigor [45, 51]. Stability was enhanced through the use of multiple focus groups in geographically different areas. Equivalence was achieved through the use of two experienced moderators with complementary styles to achieve “flow, texture and context” and to promote construct validity [51] (page 302). Credibility was strengthened through sustained engagement and observation over the course of four focus groups, researcher triangulation, debriefing as a research team, and member checking. Reflexivity, where researchers strive to understand their own experiences as well as the research question, in order to remain objective, neutral, and nonbiased, was supported through regular face-to-face and teleconference meetings. Transferability was enriched through dense sample description and rich description of the data. Confirmability was heightened through peer debriefing and maintaining our audit trail. Dependability was attained by recording a log of our plans, meetings, and ongoing interpretations. Using annotation and memo functions, NVIVO 9 [52] maintained a permanent record of our work. Tracking individual responses in addition to the group account [53] assisted us in avoiding the risk of analyzing data from only vocally dominant members of the groups. Field notes or “descriptions of participants, impressions related to the discussion (and) observations related to group dynamics”3. Research ApproachThis qualitative descriptive project was framed from a constructivist worldview [32?4] and Haas and Shaffir’s [4] sociological theory of professionalization. Haas and Shaffir theorized that legitimation is a central concept in healthcare professionals’ process of socialization. Participants were 27 Post LPN to BN students from a Canadian university who attended a practicum on an acute hospital unit. The main purpose of the research was to describe Post LPN to BN student nurses’ experiences with professional socialization as they transitioned into a more complex nursing role. A secondary purpose of the research was to begin to understand how university faculty can best support and facilitate these students’ professional socialization as they learn to become Registered Nurses (RNs). Data sources included four face-to-face digitally recorded, transcribed focus group discussions which were analyzed for themes. Our rational for collecting and analyzing focus group data centered on our intention to invite our participants to converse and interact in ways that stimulated new insights. Focus group methodology, with its emphasis on group interaction [35?9] and goal of collaborative discussion [40, 41], allowed us to draw out participants’ views and to explore their ideas and conversational exchanges with one another in depth. Focus groups are a rich source of information [42] and a valid method of generating data within a constructionist epistemology where “knowledge is created in situated, [collective] encounters” [43] (page 496). They.

S of any type, it is critical to execute the analysis

S of any type, it is critical to execute the analysis Vesnarinone web systematically. We present a distal-to-proximal analysis plan. The order of the evaluation is not critical. However, it is extremely important to perform the entire evaluation, including all segments, joints, and whole body variables consistently, to avoid missing subtle yet potentially important kinematic abnormalities. Although numerous freeware options exist with extremely helpful tools for measuring biomechanical variables on running video (angles, distances, etc), it is generally not necessary. Most of the metrics in this article can be easily identified visually on slow motion video, or evaluation when progressing through the video frame by frame. To date, cutoffs for kinematics to be identified as abnormal, or predictive of injury, do not exist. As such, the analyses included here does not provide the reader with specific angles or measures that are “abnormal.” Each metric is described, and indicators of normal kinematics are provided. It is the responsibility of the evaluator toAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagedetermine what threshold for normal and abnormal should be applied to an individual runner and associated with the biomechanical contributor to injury. Phases It is important to 3-Methyladenine side effects identify specific moments within the running cycle that can be used for evaluation. Many of the phases of the running cycle are clear. However, particularly for evaluating stride mechanics, it is important to differentiate between video frames of rapidly evolving events. Take, for example, the images provided in Fig. 1. Fig. 1A is the final frame of the swing phase, Fig. 1B displays initial contact, and Fig. 1C displays loading response (which is identified by the presence of shoe deformation in the image). Different kinematic variables are evaluated on images from different phases of running. It is important for the evaluator to become familiar with identifying each of these phases (and others as described elsewhere in this article). Inconsistent identification of phases of running in evaluating biomechanics of running gait will make performing a reliable analysis impossible.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptSIDE VIEWFoot Strike Pattern Identification of foot strike pattern can be easily performed on slow motion video or by evaluating video in a frame-by-frame manner (Fig. 2). It is recommended to always confirm foot strike pattern in this fashion, because even after considerable practice, it is not uncommon to misidentify a foot strike type when observing running at full speed. Foot strike types can be categorized as forefoot strike (FFS), midfoot strike, and rear foot strike. Recent literature suggests that video-based identification of foot strike patterns by a single rater are highly reliable, although interrater measures was found to be less reliable.17 At this time, there is limited evidence that any 1 foot strike pattern is more or less likely to cause a runner to sustain an injury. However, this is an area of active research and data on this issue are emerging.18,19 One study on competitive collegiate runners suggested that runners with a rear foot strike pattern developed more repetitive overuse injuries when compared with runners with an FFS pattern.20 And although these finding suggest possible association between foot st.S of any type, it is critical to execute the analysis systematically. We present a distal-to-proximal analysis plan. The order of the evaluation is not critical. However, it is extremely important to perform the entire evaluation, including all segments, joints, and whole body variables consistently, to avoid missing subtle yet potentially important kinematic abnormalities. Although numerous freeware options exist with extremely helpful tools for measuring biomechanical variables on running video (angles, distances, etc), it is generally not necessary. Most of the metrics in this article can be easily identified visually on slow motion video, or evaluation when progressing through the video frame by frame. To date, cutoffs for kinematics to be identified as abnormal, or predictive of injury, do not exist. As such, the analyses included here does not provide the reader with specific angles or measures that are “abnormal.” Each metric is described, and indicators of normal kinematics are provided. It is the responsibility of the evaluator toAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptPhys Med Rehabil Clin N Am. Author manuscript; available in PMC 2016 February 01.SouzaPagedetermine what threshold for normal and abnormal should be applied to an individual runner and associated with the biomechanical contributor to injury. Phases It is important to identify specific moments within the running cycle that can be used for evaluation. Many of the phases of the running cycle are clear. However, particularly for evaluating stride mechanics, it is important to differentiate between video frames of rapidly evolving events. Take, for example, the images provided in Fig. 1. Fig. 1A is the final frame of the swing phase, Fig. 1B displays initial contact, and Fig. 1C displays loading response (which is identified by the presence of shoe deformation in the image). Different kinematic variables are evaluated on images from different phases of running. It is important for the evaluator to become familiar with identifying each of these phases (and others as described elsewhere in this article). Inconsistent identification of phases of running in evaluating biomechanics of running gait will make performing a reliable analysis impossible.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptSIDE VIEWFoot Strike Pattern Identification of foot strike pattern can be easily performed on slow motion video or by evaluating video in a frame-by-frame manner (Fig. 2). It is recommended to always confirm foot strike pattern in this fashion, because even after considerable practice, it is not uncommon to misidentify a foot strike type when observing running at full speed. Foot strike types can be categorized as forefoot strike (FFS), midfoot strike, and rear foot strike. Recent literature suggests that video-based identification of foot strike patterns by a single rater are highly reliable, although interrater measures was found to be less reliable.17 At this time, there is limited evidence that any 1 foot strike pattern is more or less likely to cause a runner to sustain an injury. However, this is an area of active research and data on this issue are emerging.18,19 One study on competitive collegiate runners suggested that runners with a rear foot strike pattern developed more repetitive overuse injuries when compared with runners with an FFS pattern.20 And although these finding suggest possible association between foot st.

The simple assumption that amyloid is the driving factor underlying the

The simple assumption that amyloid is the driving factor underlying the clinical symptoms of dementia and the formation (s) of NFTs in AD (Hardy and Allsop, 1991) which has since been modified. Interestingly, Dr. Alzheimer wrote “…the plaques are not the cause of senile dementia, but only an accompanying feature of senile involution of the central nervous system” (Alzheimer, 1911). More recently, Mesulam (1999) stated, “It seems as if the A plaques appear at the wrong time and in the wrong places with respect to the clinical dementia and there is little evidence that they cause the NFT”. In light of the continued lack of efficacy of human anti amyloid strategies in AD, these comments may prove to be prescient. By contrast, NFT pathology displays a highly significant correlation with cognitive impairment in AD (Giannakopoulos et. al., 2003) and occurs within the hippocampus very early in the disease processes (Braak and Braak, 1991). However, clinical pathologic data indicate that the hippocampus remains highly malleable despite the abundance of NFT pathology during the onset of AD (Gary et al., 2014).Hippocampal Aviptadil msds structural plasticity in MCI and ADIn AD, ultrastructural Procyanidin B1 site counts of synapse numbers indicate a reduction in the inner and outer layers of the dentate gyrus (Scheff et al., 1996, 1998), which receives extensive input from the entorhinal cortex (Simonian et al., 1994). Another investigation found a reduction in synapses within the supragranular band below the inner molecular layer in AD (BertoniFredarri et al., 1990). Although decreases in synaptic density are more highly correlated with the degree of cognitive impairment than classic pathological changes related to AD (Terry et al., 1991; Scheff et al., 2006; DeKosky and Scheff, 1990; Scheff and Price, 2003; Sze et al., 1997), very few studies have investigated synaptic contact integrity or evidence for a neuroplastic response in the hippocampus in individuals with MCI or early AD. A series of studies, which combined unbiased stereology with electron microscopy, failed to demonstrate a significant difference in the total number of synapses within the outerNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagemolecular layer of the hippocampus between individuals with aMCI compared to NCI, but there was a significant decrease between early AD and MCI as well as NCI (Scheff et al., 2006). The reduction in synapses in early AD compared to both NCI and MCI did not appear to be associated with a loss of granule cells (West et al., 2004) but likely reflected a loss of afferent innervation from the ipsilateral entorhinal cortex (Hyman et al., 1987; Gomez-Izla et al., 1996; Yasuda et al., 1995; Scharfman and Chao, 2013). Notably, this loss of entorhinal input to the hippocampus has been shown to initiate an extensive sprouting of cholinergic innervation into the molecular layer of the hippocampus (Geddes et al., 1985), where neuritic plaques preferably accumulate, thus leading to a hypothesis that reactive cholinergic sprouting contributes to the pathogenesis of A plaque formation (Geddes et al., 1986). This compensatory structural remodeling within the hippocampus illustrates the neuroplastic capacity of this region to counteract (or contributes to) mounting pathology. By contrast, a subsequent study using the same cohort of cases (Scheff et al., 2006) reported a significant reduction in total synapse number in the striatum radiatum region of the hippoc.The simple assumption that amyloid is the driving factor underlying the clinical symptoms of dementia and the formation (s) of NFTs in AD (Hardy and Allsop, 1991) which has since been modified. Interestingly, Dr. Alzheimer wrote “…the plaques are not the cause of senile dementia, but only an accompanying feature of senile involution of the central nervous system” (Alzheimer, 1911). More recently, Mesulam (1999) stated, “It seems as if the A plaques appear at the wrong time and in the wrong places with respect to the clinical dementia and there is little evidence that they cause the NFT”. In light of the continued lack of efficacy of human anti amyloid strategies in AD, these comments may prove to be prescient. By contrast, NFT pathology displays a highly significant correlation with cognitive impairment in AD (Giannakopoulos et. al., 2003) and occurs within the hippocampus very early in the disease processes (Braak and Braak, 1991). However, clinical pathologic data indicate that the hippocampus remains highly malleable despite the abundance of NFT pathology during the onset of AD (Gary et al., 2014).Hippocampal structural plasticity in MCI and ADIn AD, ultrastructural counts of synapse numbers indicate a reduction in the inner and outer layers of the dentate gyrus (Scheff et al., 1996, 1998), which receives extensive input from the entorhinal cortex (Simonian et al., 1994). Another investigation found a reduction in synapses within the supragranular band below the inner molecular layer in AD (BertoniFredarri et al., 1990). Although decreases in synaptic density are more highly correlated with the degree of cognitive impairment than classic pathological changes related to AD (Terry et al., 1991; Scheff et al., 2006; DeKosky and Scheff, 1990; Scheff and Price, 2003; Sze et al., 1997), very few studies have investigated synaptic contact integrity or evidence for a neuroplastic response in the hippocampus in individuals with MCI or early AD. A series of studies, which combined unbiased stereology with electron microscopy, failed to demonstrate a significant difference in the total number of synapses within the outerNeuroscience. Author manuscript; available in PMC 2016 September 12.Mufson et al.Pagemolecular layer of the hippocampus between individuals with aMCI compared to NCI, but there was a significant decrease between early AD and MCI as well as NCI (Scheff et al., 2006). The reduction in synapses in early AD compared to both NCI and MCI did not appear to be associated with a loss of granule cells (West et al., 2004) but likely reflected a loss of afferent innervation from the ipsilateral entorhinal cortex (Hyman et al., 1987; Gomez-Izla et al., 1996; Yasuda et al., 1995; Scharfman and Chao, 2013). Notably, this loss of entorhinal input to the hippocampus has been shown to initiate an extensive sprouting of cholinergic innervation into the molecular layer of the hippocampus (Geddes et al., 1985), where neuritic plaques preferably accumulate, thus leading to a hypothesis that reactive cholinergic sprouting contributes to the pathogenesis of A plaque formation (Geddes et al., 1986). This compensatory structural remodeling within the hippocampus illustrates the neuroplastic capacity of this region to counteract (or contributes to) mounting pathology. By contrast, a subsequent study using the same cohort of cases (Scheff et al., 2006) reported a significant reduction in total synapse number in the striatum radiatum region of the hippoc.

T’s early journalistic style in terms of the conventions of

T’s early journalistic style in terms of the conventions of non-medical publishing.10 In particular, she is concerned to demonstrate how the relative success of the journal can be ascribed to Wakley’s importation of `entertaining formal components from lay periodicals’, most notably sections on society gossip, theatre reviews and chess puzzles, a contrivance which allowed The Lancet to `navigat[e] the space between general and specialist readers’.11 Though notable for its emphasis on style, Pladek’s account is not wholly satisfying; it is unspecific5 M. Bostetter, `The journalism of Thomas Wakley’ in J. H. Wiener (ed.), Innovators and Preachers: The Role of the Editor in Victorian IsorhamnetinMedChemExpress Isorhamnetin England (London, 1985), 282. 6J. Loudon and I. Loudon, `Medicine, politics and the medical periodical, 1800 ?0′ in W. F. Bynum, S. Lock and R. Porter (eds), Medical Journals and Medical Knowledge: Historical Essays (London, 1992), 62. 7W. F. Bynum and J. C. Wilson, `Periodical knowledge: medical journals and their editors in nineteenth-century Britain’ in Bynum et al., Medical Journals, op. cit., 38. 8For example, see J. Bulcher, `The Cato Street Conspiracy’, The Lancet, 370: Supplement 1 (1 December 2007), 9 ?4; R. Jones, `Thomas Wakley, plagiarism, libel, and the founding ofThe Lancet’, The Lancet, 371:9622 (26 April 2008), 1410?11. In 1996 The Lancet even established an essay prize in Wakley’s name ?see The Lancet, 348:9022 (27 July 1996), 212. 9Loudon and Loudon, `Medicine, politics’, op. cit., 61; D. Harrison, `All The Lancet’s men: reactionary gentleman physicians vs. radical general practitioners in The Lancet, 1823 ?1832′, Nineteenth-Century Gender Studies, V , 2 (Summer 2009), available online at: http://ncgs journal.com/issue52/harrison.htm 10 B. Pladek, `”A variety of tastes”: The Lancet in the early nineteenth-century periodical press’, Bulletin of the History of Medicine, LXXXV , 4 (2011), 560?6. 11ibid., 560, 572.MayThe Lancet, libel and English medicineabout exactly what kinds of cultural work these literary devices were intended to perform and does not adequately explain why The Lancet’s circulation continued to rise even when they were ARQ-092 solubility discontinued after only two years. Moreover, while she alludes to the subject, she explicitly declines to focus on `the journal’s engagement with medical politics’ or its resonances with the broader conventions of radical journalism.12 As this article will demonstrate, however, the significance of The Lancet’s stylistic radicalism can only be fully comprehended by situating it within its immediate political context. Rather than viewing it as the template for modern medical journalism, or as anticipating later styles of political and social commentary, it understands The Lancet as the product of an early nineteenth-century radical political heritage, as the Political Register or Black Dwarf of medicine. It seeks to extend and deepen the analytical project initiated by Desmond, Warner and Burney whereby the discourses of medical reform are considered in relation to those which sustained the cause of radical political sovereignty. Drawing upon the work of James Epstein, Kevin Gilmartin and others, it views The Lancet in terms of radical stylistics, demonstrating the extent to which it was framed by the literary conventions of the underground political press.13 It opens with a brief account of Wakley’s initiation into radical circles before considering the early editions of The Lancet, with a particular focus on the.T’s early journalistic style in terms of the conventions of non-medical publishing.10 In particular, she is concerned to demonstrate how the relative success of the journal can be ascribed to Wakley’s importation of `entertaining formal components from lay periodicals’, most notably sections on society gossip, theatre reviews and chess puzzles, a contrivance which allowed The Lancet to `navigat[e] the space between general and specialist readers’.11 Though notable for its emphasis on style, Pladek’s account is not wholly satisfying; it is unspecific5 M. Bostetter, `The journalism of Thomas Wakley’ in J. H. Wiener (ed.), Innovators and Preachers: The Role of the Editor in Victorian England (London, 1985), 282. 6J. Loudon and I. Loudon, `Medicine, politics and the medical periodical, 1800 ?0′ in W. F. Bynum, S. Lock and R. Porter (eds), Medical Journals and Medical Knowledge: Historical Essays (London, 1992), 62. 7W. F. Bynum and J. C. Wilson, `Periodical knowledge: medical journals and their editors in nineteenth-century Britain’ in Bynum et al., Medical Journals, op. cit., 38. 8For example, see J. Bulcher, `The Cato Street Conspiracy’, The Lancet, 370: Supplement 1 (1 December 2007), 9 ?4; R. Jones, `Thomas Wakley, plagiarism, libel, and the founding ofThe Lancet’, The Lancet, 371:9622 (26 April 2008), 1410?11. In 1996 The Lancet even established an essay prize in Wakley’s name ?see The Lancet, 348:9022 (27 July 1996), 212. 9Loudon and Loudon, `Medicine, politics’, op. cit., 61; D. Harrison, `All The Lancet’s men: reactionary gentleman physicians vs. radical general practitioners in The Lancet, 1823 ?1832′, Nineteenth-Century Gender Studies, V , 2 (Summer 2009), available online at: http://ncgs journal.com/issue52/harrison.htm 10 B. Pladek, `”A variety of tastes”: The Lancet in the early nineteenth-century periodical press’, Bulletin of the History of Medicine, LXXXV , 4 (2011), 560?6. 11ibid., 560, 572.MayThe Lancet, libel and English medicineabout exactly what kinds of cultural work these literary devices were intended to perform and does not adequately explain why The Lancet’s circulation continued to rise even when they were discontinued after only two years. Moreover, while she alludes to the subject, she explicitly declines to focus on `the journal’s engagement with medical politics’ or its resonances with the broader conventions of radical journalism.12 As this article will demonstrate, however, the significance of The Lancet’s stylistic radicalism can only be fully comprehended by situating it within its immediate political context. Rather than viewing it as the template for modern medical journalism, or as anticipating later styles of political and social commentary, it understands The Lancet as the product of an early nineteenth-century radical political heritage, as the Political Register or Black Dwarf of medicine. It seeks to extend and deepen the analytical project initiated by Desmond, Warner and Burney whereby the discourses of medical reform are considered in relation to those which sustained the cause of radical political sovereignty. Drawing upon the work of James Epstein, Kevin Gilmartin and others, it views The Lancet in terms of radical stylistics, demonstrating the extent to which it was framed by the literary conventions of the underground political press.13 It opens with a brief account of Wakley’s initiation into radical circles before considering the early editions of The Lancet, with a particular focus on the.

Monly used and widely available OTC medications and nutritional supplements were

Monly used and widely available OTC medications and nutritional supplements were safe and posed no short- or long-term threat to their health. Many used such products to improve their running performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product recommended as an effective and legal substance by another runner or by a retail sales clerk may BAY1217389 manufacturer contain substances that are either banned by agencies such as WADA and/or may pose a serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.PNPP custom synthesis Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.Monly used and widely available OTC medications and nutritional supplements were safe and posed no short- or long-term threat to their health. Many used such products to improve their running performance, yet their risk normalized or neutralized by their presence at running expos, in running publications and at vitamin retail stores. Well aware that some substances–EPO, anabolic steroids, HGH–are banned and may be dangerous to health, these runners took for granted the surveillance and safety of products they could procure legally, under the belief that is something was not banned it would be safe. This belief makes runners vulnerable to tainted or dangerous products that are freely available and not considered harmful, even though non-elite athletes routinely feel they make correct decisions and engaging in adequate self-surveillance that is required in contemporary neoliberal citizenship (Rose 1999). As such, a product recommended as an effective and legal substance by another runner or by a retail sales clerk may contain substances that are either banned by agencies such as WADA and/or may pose a serious health risk. The recent controversy over the supplement ingredient DMAA illustrates availability cannot be substituted for safety.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSurveill Soc. Author manuscript; available in PMC 2014 November 04.HenningPageTogether, these perceptions and knowledge gaps result in a blind spot in the internalized anti-doping gaze. Runners do the work of self-surveillance believing they are acting as good citizens by conforming to anti-doping regulations and following expert advice on how to be healthy, as far as they understand these rules and recommendations. With regard to nutritional supplements, this self-surveillance blind spot can have major negative health repercussions. WADA and its affiliates claim athlete health is a top priority, yet its policies and methods confuse non-elite runners and lull them into a false sense of security. The nonelites in this research engaged in self-surveillance and did seek to conform to the clean ideal by avoiding what they understood to be prohibited or dangerous substances. However, their knowledge of anti-doping regulations was inadequate for avoiding all but the most commonly discussed prohibited enhancement products. Relying on their incomplete and often incorrect understandings of which substances are potentially harmful, these runners may wrongly presume they are avoiding harmful PEDs by focusing their attention on supplements that are commonly found in drug stores and nutritional supplement shops. This finding demonstrates how the quest to eradicate doping in sports using the surveillancebased system of regulations and banned substances seem to work against the underlying goals of anti-doping agencies in non-elite sports populations.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptAcknowledgmentsThe author was supported by NIDA grant (T32 DA007233); points of view are the author’s alone.
NIH Public AccessAuthor ManuscriptJ Res Adolesc. Author manuscript; available in PMC 2015 June 01.Published in final edited form as: J Res Adolesc. 2014 June 1; 24(2): 235?51. doi:10.1111/jora.12124.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptSerious Delinquency and Gang Participation: Combining and Specializing in Drug Selling, Theft and ViolenceRachel A. Gordon, University of Illinois at Chi.

Deration when interpreting experimental findings. (i) Identification of a mutation in

Deration when interpreting experimental findings. (i) Identification of a mutation in a clonal population does not indicate causality Any mutation in a cell that undergoes clonal expansion will be passed onto progeny, irrespective of functional status (Fig. 3A,B). Given the size of the genome, more mutations carried by a neoplastic clone will be passengers than drivers [27, 29, 30]. To CPI-455 web demonstrate driver status, supporting functional studies and/or repeated observations of a mutated loci in neoplastic clones from independent individuals are needed. (ii) Mutational marking of a clone is stochastic and not guaranteed A clone may exist and not be detected if none of the genomic sites being screened carry a unique mutation permitting it to be distinguished from the germline (Fig. 3C). The more sites examined, the higher the probability of detection becomes. Restricting a marker panel to suspected driver sites precludes detection of pathological clones driven by unknown factors. (iii) Thonzonium (bromide) biological activity elevated mutation rates facilitate clone detection but are not an absolute requirement Screening of mutational hotspots makes it practical with conventional technologies to have a reasonable probability of detecting a clone by random passenger mutations. Clones derived from a mutator lineage or cells residing in a highly mutagenic environment should be more densely marked with identifiable passengers (Fig. 3D), potentially reducing the number of markers needing to be interrogated to identify them. Emerging high-throughput sequencing technologies will eventually obviate the need to restrict screening to a fraction of the genome. (iv) Identification of one or more clonal mutations is not proof of genetic instability in the absence of collateral information Detection of a mutation requires clonal expansion with most traditional methods of aggregate DNA analysis. The probability of identifying clonal mutations in an expanded population is a function of the number of sites screened, the mutability of these sites and the number of cell divisions having occurred in the lineage leading up to the final expansion. Particularly when considering hotspots, mutations will be occasionally detectable in any clonally-derived population at a statistically definable frequency. Because mutations are not routinely encountered in normal tissues, it is tempting to explain their presence in preneoplastic populations as the result of “genetic instability” (an elevated mutation rate). However, the phenomenon is more precisely explained by the fact that expansion does not routinely occur in most normal tissues. An elevated mutation rate itself will have no observable effect on clonal mutation frequency in the absence of expansion (Fig. 3E). To determine mutation rate from a clonal mutation frequency it is necessary to (A) know that the population being assessed is clonal and (B) have some metric of the number of cell divisions that occurred in the period between the zygote and the founding of the final clonalSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPageoutgrowth. To infer that a rate is elevated, it is also necessary to know the normal in vivo mutation rate, which is, in turn, impossible to measure by this approach given that large clonal expansions do not routinely occur in normal adult tissue. Considering these complexities, the lack of resolution as to whether mutation rates are elevated in cancer is not surprising [1,8?1]. (v) Detectabili.Deration when interpreting experimental findings. (i) Identification of a mutation in a clonal population does not indicate causality Any mutation in a cell that undergoes clonal expansion will be passed onto progeny, irrespective of functional status (Fig. 3A,B). Given the size of the genome, more mutations carried by a neoplastic clone will be passengers than drivers [27, 29, 30]. To demonstrate driver status, supporting functional studies and/or repeated observations of a mutated loci in neoplastic clones from independent individuals are needed. (ii) Mutational marking of a clone is stochastic and not guaranteed A clone may exist and not be detected if none of the genomic sites being screened carry a unique mutation permitting it to be distinguished from the germline (Fig. 3C). The more sites examined, the higher the probability of detection becomes. Restricting a marker panel to suspected driver sites precludes detection of pathological clones driven by unknown factors. (iii) Elevated mutation rates facilitate clone detection but are not an absolute requirement Screening of mutational hotspots makes it practical with conventional technologies to have a reasonable probability of detecting a clone by random passenger mutations. Clones derived from a mutator lineage or cells residing in a highly mutagenic environment should be more densely marked with identifiable passengers (Fig. 3D), potentially reducing the number of markers needing to be interrogated to identify them. Emerging high-throughput sequencing technologies will eventually obviate the need to restrict screening to a fraction of the genome. (iv) Identification of one or more clonal mutations is not proof of genetic instability in the absence of collateral information Detection of a mutation requires clonal expansion with most traditional methods of aggregate DNA analysis. The probability of identifying clonal mutations in an expanded population is a function of the number of sites screened, the mutability of these sites and the number of cell divisions having occurred in the lineage leading up to the final expansion. Particularly when considering hotspots, mutations will be occasionally detectable in any clonally-derived population at a statistically definable frequency. Because mutations are not routinely encountered in normal tissues, it is tempting to explain their presence in preneoplastic populations as the result of “genetic instability” (an elevated mutation rate). However, the phenomenon is more precisely explained by the fact that expansion does not routinely occur in most normal tissues. An elevated mutation rate itself will have no observable effect on clonal mutation frequency in the absence of expansion (Fig. 3E). To determine mutation rate from a clonal mutation frequency it is necessary to (A) know that the population being assessed is clonal and (B) have some metric of the number of cell divisions that occurred in the period between the zygote and the founding of the final clonalSemin Cancer Biol. Author manuscript; available in PMC 2011 October 15.Salk and HorwitzPageoutgrowth. To infer that a rate is elevated, it is also necessary to know the normal in vivo mutation rate, which is, in turn, impossible to measure by this approach given that large clonal expansions do not routinely occur in normal adult tissue. Considering these complexities, the lack of resolution as to whether mutation rates are elevated in cancer is not surprising [1,8?1]. (v) Detectabili.

. This exploratory analysis can provide further information on functional similarities between

. This exploratory analysis can provide further information on functional similarities between regions, and, more specifically, on the extent to which activation profiles of category-selective LIMKI 3 site regions are inherited from EVC. As for the replicability of within-category ranking (Fig. 5), we combined data across subjects either by concatenating or averaging the activation profiles across subjects. The concatenation approach is sensitive to inter-region correlations of activation profiles even if the particular activation profiles differ across subjects. The averaging approach is sensitive to inter-region correlations of activation profiles that are consistent across subjects. We investigated the inter-region correlations for (1) the full activation profile, (2) the within-face activation profile, and (3) the withinplace activation profile. Statistical inference was performed by a standard one-sided test on Spearman’s r. p values were corrected8658 ?J. buy PP58 Neurosci., June 20, 2012 ?32(25):8649 ?Mur et al. ?Single-Image Activation of Category Regionsfor multiple testing using Bonferroni correction based on the total number of tests performed. Figure 7 shows the inter-region correlation results. The main pattern that emerges is that activation profiles are correlated between hemispheres for corresponding regions, and between hIT and EVC (red blocks on diagonals). We subsequently inspected the within-face correlation between FFA and EVC, and the within-place correlation between PPA and EVC. The within-face activation profile was correlated between left but not right FFA and EVC, and the within-place activation profile was not significantly correlated between PPA and EVC. Results were similar across ROI sizes. These results suggest that EVC is not a major contributor to the within-category activation profiles of PPA and right FFA. We then inspected the correlation between category-selective regions (FFA/PPA) and EVC for the full activation profile (top row). The full activation profile was correlated between EVC and both categoryselective regions, especially PPA. One interpretation of this finding would be that some degree of category selectivity is already present at the level of EVC, implying that low-level feature differences contribute to some extent to categoryselective responses. For places, this seems a plausible interpretation, consistent with our finding that single-image activation of EVC can discriminate places from nonplaces at an above-chance level (Fig. 2). For faces, this interpretation seems less likely: the correlation between EVC and FFA is not significant for the subjectaverage activation profile, suggesting that the correlation is driven by subjectspecific effects (e.g., idiosyncratic arousal effects) and not by face-selectivity of responses (shared across subjects in FFA). Categorical, yet graded Figure 8 summarizes our results. Singleimage activation profiles of categoryselective regions (1) show near-perfect discrimination of preferred from nonpreferred images and no preference inversions for particular object images, (2) show a step-like drop-off at the category boundary, and (3) are graded within and outside the preferred category. It can further be noted that single-image category selectivity is stronger in right than left FFA. In addition, gradedness seems to be more pronounced in FFA; the category step seems to be more pronounced in PPA. In sum, our findings indicate that the activation profiles of category-selec-Figure.. This exploratory analysis can provide further information on functional similarities between regions, and, more specifically, on the extent to which activation profiles of category-selective regions are inherited from EVC. As for the replicability of within-category ranking (Fig. 5), we combined data across subjects either by concatenating or averaging the activation profiles across subjects. The concatenation approach is sensitive to inter-region correlations of activation profiles even if the particular activation profiles differ across subjects. The averaging approach is sensitive to inter-region correlations of activation profiles that are consistent across subjects. We investigated the inter-region correlations for (1) the full activation profile, (2) the within-face activation profile, and (3) the withinplace activation profile. Statistical inference was performed by a standard one-sided test on Spearman’s r. p values were corrected8658 ?J. Neurosci., June 20, 2012 ?32(25):8649 ?Mur et al. ?Single-Image Activation of Category Regionsfor multiple testing using Bonferroni correction based on the total number of tests performed. Figure 7 shows the inter-region correlation results. The main pattern that emerges is that activation profiles are correlated between hemispheres for corresponding regions, and between hIT and EVC (red blocks on diagonals). We subsequently inspected the within-face correlation between FFA and EVC, and the within-place correlation between PPA and EVC. The within-face activation profile was correlated between left but not right FFA and EVC, and the within-place activation profile was not significantly correlated between PPA and EVC. Results were similar across ROI sizes. These results suggest that EVC is not a major contributor to the within-category activation profiles of PPA and right FFA. We then inspected the correlation between category-selective regions (FFA/PPA) and EVC for the full activation profile (top row). The full activation profile was correlated between EVC and both categoryselective regions, especially PPA. One interpretation of this finding would be that some degree of category selectivity is already present at the level of EVC, implying that low-level feature differences contribute to some extent to categoryselective responses. For places, this seems a plausible interpretation, consistent with our finding that single-image activation of EVC can discriminate places from nonplaces at an above-chance level (Fig. 2). For faces, this interpretation seems less likely: the correlation between EVC and FFA is not significant for the subjectaverage activation profile, suggesting that the correlation is driven by subjectspecific effects (e.g., idiosyncratic arousal effects) and not by face-selectivity of responses (shared across subjects in FFA). Categorical, yet graded Figure 8 summarizes our results. Singleimage activation profiles of categoryselective regions (1) show near-perfect discrimination of preferred from nonpreferred images and no preference inversions for particular object images, (2) show a step-like drop-off at the category boundary, and (3) are graded within and outside the preferred category. It can further be noted that single-image category selectivity is stronger in right than left FFA. In addition, gradedness seems to be more pronounced in FFA; the category step seems to be more pronounced in PPA. In sum, our findings indicate that the activation profiles of category-selec-Figure.

PR sites, the water depths at these sites have been deeper

PR sites, the water depths at these sites have been deeper than the CCD since the Eocene; thus, dilution of the hydrothermal component by biogenic carbonate has not occurred since that time (Fig. 3b; Supplementary Fig. S18). However, the IC7 signal that was maintained at a higher level than that in other areas, together with the Fe n concentrations, showed a stepwise decrease to negative values during the Miocene (Fig. 3f; Supplementary Fig. S18). If plate migration and change in distance from the mid-ocean ridges caused this reduction, the hydrothermal deposition should have gradually and consistently decreased upward from the core bottom. GW0742 supplier Therefore, we consider the possibility that relatively rapid reduction can be attributed to the disappearance of the hydrothermal source owing to subduction of the ridge during the EPZ004777 web mid-Miocene37 (Supplementary Fig. S18). However, other regional factors such as changes in ocean currents resulting in migration of hydrothermal plumes could also affect the IC7 signal intensity.Rare-earth element geochemistry. To further clarify the geochemical interpretations of IC1 and IC4, REY-rich mud samples strongly influenced by either IC1 or IC4 were selected, and their REY-patterns normalised to the post-Archean average Australian shale38 were compared (Fig. 4). Because the variables analysed by ICA do not contain explicit information of each lanthanoid element and Y content, this approach can provide an additional geochemical constraint. The bulk REY-patterns of representative high-IC4 sediments obtained from the eastern South Pacific and central North Pacific are characterised by distinct negative Ce anomalies, positive Y anomalies, and relative enrichment in heavy rare-earth to light rare-earth elements (Fig. 4g ). These features are almost the same as those of biogenic Ca-phosphate22?5 (Fig. 4m), suggesting that the bulk-sediment REY compositions of high-IC4 sediments were predominantly controlled by highly REY-enriched biogenic Ca-phosphate. The representative high-IC1 sediments are distributed in the central South Pacific, central North Pacific, and eastern Indian oceans. The Indian Ocean’s REY-rich mud contains no age-diagnostic fossils3 and is thus not shown in Fig. 3. In contrast to the case of high-IC4 sediments, the bulk REY patterns of high-IC1 sediments were characterised commonly by smaller negative Ce anomalies, almost no Y anomaly, and relatively flat REY patterns (Fig. 4a ). These features can be reasonably explained4 by superimposing the REY pattern of slowly precipitating hydrogenous Fe n oxide ( nO2) showing pronounced positive Ce and negative Y anomaliesScientific RepoRts | 6:29603 | DOI: 10.1038/srepwww.nature.com/scientificreports/(Fig. 4m) on that of biogenic Ca-phosphate in pelagic clay inheriting distinct negative Ce and positive Y anomalies from the seawater22?5 (Fig. 4m). It is noteworthy that the bulk REY abundance in IC1-type REY-rich mud also appeared to be largely attributed to biogenic Ca-phosphate, considering its very high REY concentration (REY + Ce > 20,000 ppm)25 and negative Ce anomalies in the bulk REY compositions. Therefore, the characteristic data distribution in the IC space was confirmed by a different geochemical index using elements not explicitly included in the ICA calculation. Despite the very high concentration of REY in biogenic Ca-phosphate, these elements are not incorporated into Ca-phosphate in significant amounts during the primary skeleton-forming process.PR sites, the water depths at these sites have been deeper than the CCD since the Eocene; thus, dilution of the hydrothermal component by biogenic carbonate has not occurred since that time (Fig. 3b; Supplementary Fig. S18). However, the IC7 signal that was maintained at a higher level than that in other areas, together with the Fe n concentrations, showed a stepwise decrease to negative values during the Miocene (Fig. 3f; Supplementary Fig. S18). If plate migration and change in distance from the mid-ocean ridges caused this reduction, the hydrothermal deposition should have gradually and consistently decreased upward from the core bottom. Therefore, we consider the possibility that relatively rapid reduction can be attributed to the disappearance of the hydrothermal source owing to subduction of the ridge during the mid-Miocene37 (Supplementary Fig. S18). However, other regional factors such as changes in ocean currents resulting in migration of hydrothermal plumes could also affect the IC7 signal intensity.Rare-earth element geochemistry. To further clarify the geochemical interpretations of IC1 and IC4, REY-rich mud samples strongly influenced by either IC1 or IC4 were selected, and their REY-patterns normalised to the post-Archean average Australian shale38 were compared (Fig. 4). Because the variables analysed by ICA do not contain explicit information of each lanthanoid element and Y content, this approach can provide an additional geochemical constraint. The bulk REY-patterns of representative high-IC4 sediments obtained from the eastern South Pacific and central North Pacific are characterised by distinct negative Ce anomalies, positive Y anomalies, and relative enrichment in heavy rare-earth to light rare-earth elements (Fig. 4g ). These features are almost the same as those of biogenic Ca-phosphate22?5 (Fig. 4m), suggesting that the bulk-sediment REY compositions of high-IC4 sediments were predominantly controlled by highly REY-enriched biogenic Ca-phosphate. The representative high-IC1 sediments are distributed in the central South Pacific, central North Pacific, and eastern Indian oceans. The Indian Ocean’s REY-rich mud contains no age-diagnostic fossils3 and is thus not shown in Fig. 3. In contrast to the case of high-IC4 sediments, the bulk REY patterns of high-IC1 sediments were characterised commonly by smaller negative Ce anomalies, almost no Y anomaly, and relatively flat REY patterns (Fig. 4a ). These features can be reasonably explained4 by superimposing the REY pattern of slowly precipitating hydrogenous Fe n oxide ( nO2) showing pronounced positive Ce and negative Y anomaliesScientific RepoRts | 6:29603 | DOI: 10.1038/srepwww.nature.com/scientificreports/(Fig. 4m) on that of biogenic Ca-phosphate in pelagic clay inheriting distinct negative Ce and positive Y anomalies from the seawater22?5 (Fig. 4m). It is noteworthy that the bulk REY abundance in IC1-type REY-rich mud also appeared to be largely attributed to biogenic Ca-phosphate, considering its very high REY concentration (REY + Ce > 20,000 ppm)25 and negative Ce anomalies in the bulk REY compositions. Therefore, the characteristic data distribution in the IC space was confirmed by a different geochemical index using elements not explicitly included in the ICA calculation. Despite the very high concentration of REY in biogenic Ca-phosphate, these elements are not incorporated into Ca-phosphate in significant amounts during the primary skeleton-forming process.

Y number of the Medico-Chirurgical Review) and its extensive circulation (far

Y number of the Medico-Chirurgical Review) and its extensive circulation (far higher than any of its rivals).4 However, perhaps the most frequently noted Y-27632MedChemExpress Y-27632 characteristic is its style. With The Lancet, Wakley broke the mould of medical journalism, employing an acerbic and combative editorial voice which has earned him both the admiration and admonishment of posterity. Mary Bostetter, forA. Desmond, The Politics of Evolution: Morphology, Medicine and Reform in Radical London (Chicago, 1989). 3J. H. Warner, `The idea of science in English medicine: the “decline” of science and the rhetoric of reform, 1815?5′ in R. French and A. Wear (eds), British Medicine in an Age of Reform (London, 1991);