503 research outputs found

    A Closer Look at Self-Esteem, Perceived Social Support, and Coping Strategy: A Prospective Study of Depressive Symptomatology Across the Transition to College

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    The first year of college is a significant life transition, which is often characterized by stress and may contribute to the development or exacerbation of depressive symptoms. Due to the considerable negative outcomes that are associated with depressive symptoms across the lifespan, it is important to understand the mechanisms and pathways through which depressive symptoms arise. This prospective study examines the mediating and moderating roles of perceived social support and disengagement coping on the association between self-esteem and depressive symptomatology in a sample of 1,118 first-year college students. Results of longitudinal cross-lagged path analyses indicate that self-esteem predicts depressive symptomatology via perceived social support and disengagement coping. The association between self-esteem and perceived social support appear to be bidirectional, in that level of self-esteem predicts perceived social support, and vice versa. Furthermore, disengagement coping was found to moderate the effect of self-esteem on depressive symptomatology, in that increased levels of disengagement coping led to greater depressive symptoms within the context of both high and low self-esteem. However, this pattern was not observed at lower levels of disengagement coping, which indicates high levels of disengagement coping as a particular risk factor for depressive symptomatology, diminishing the advantage of high self-esteem

    Partisan Asymmetries in Online Political Activity

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    We examine partisan differences in the behavior, communication patterns and social interactions of more than 18,000 politically-active Twitter users to produce evidence that points to changing levels of partisan engagement with the American online political landscape. Analysis of a network defined by the communication activity of these users in proximity to the 2010 midterm congressional elections reveals a highly segregated, well clustered partisan community structure. Using cluster membership as a high-fidelity (87% accuracy) proxy for political affiliation, we characterize a wide range of differences in the behavior, communication and social connectivity of left- and right-leaning Twitter users. We find that in contrast to the online political dynamics of the 2008 campaign, right-leaning Twitter users exhibit greater levels of political activity, a more tightly interconnected social structure, and a communication network topology that facilitates the rapid and broad dissemination of political information.Comment: 17 pages, 10 figures, 6 table

    Acute gamma-secretase inhibition of nonhuman primate CNS shifts amyloid precursor protein (APP) metabolism from amyloid-beta production to alternative APP fragments without amyloid-beta rebound

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    The accumulation of amyloid beta (Aβ) in Alzheimer’s disease is caused by an imbalance of production and clearance, which leads to increased soluble Aβ species and extracellular plaque formation in the brain. Multiple Aβ-lowering therapies are currently in development: an important goal is to characterize the molecular mechanisms of action and effects on physiological processing of Aβ, as well as other amyloid precursor protein (APP) metabolites, in models which approximate human Aβ physiology. To this end, we report the translation of the human in vivo stable-isotope-labeling kinetics (SILK) method to a rhesus monkey cisterna magna ported (CMP) nonhuman primate model, and use the model to test the mechanisms of action of a γ-secretase inhibitor (GSI). A major concern of inhibiting the enzymes which produce Aβ (β- and γ-secretase) is that precursors of Aβ may accumulate and cause a rapid increase in Aβ production when enzyme inhibition discontinues. In this study, the GSI MK-0752 was administered to conscious CMP rhesus monkeys in conjunction with in vivo stable isotope labeling, and dose-dependently reduced newly generated CNS Aβ. In contrast to systemic Aβ metabolism, CNS Aβ production was not increased after the GSI was cleared. These results indicate that most of the CNS APP was metabolized to products other than Aβ, including C-terminal truncated forms of Aβ: 1–14, 1–15 and 1–16; this demonstrates an alternative degradation pathway for CNS amyloid precursor protein during γ-secretase inhibition

    PET/CT Imaging of Zr-89-N-sucDf-Pembrolizumab in Healthy Cynomolgus Monkeys

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    PURPOSE: Programmed cell death-1 receptor (PD-1) and its ligand (PD-L1) are the targets for immunotherapy in many cancer types. Although PD-1 blockade has therapeutic effects, the efficacy differs between patients. Factors contributing to this variability are PD-L1 expression levels and immune cells present in tumors. However, it is not well understood how PD-1 expression in the tumor microenvironment impacts immunotherapy response. Thus, imaging of PD-1-expressing immune cells is of interest. This study aims to evaluate the biodistribution of Zirconium-89 (89Zr)-labeled pembrolizumab, a humanized IgG4 kappa monoclonal antibody targeting PD-1, in healthy cynomolgus monkeys as a translational model of tracking PD-1-positive immune cells. PROCEDURES: Pembrolizumab was conjugated with the tetrafluorophenol-N-succinyl desferal-Fe(III) ester (TFP-N-sucDf) and subsequently radiolabeled with 89Zr. Four cynomolgus monkeys with no previous exposure to humanized monoclonal antibodies received tracer only or tracer co-injected with pembrolizumab intravenously over 5 min. Thereafter, a static whole-body positron emission tomography (PET) scan was acquired with 10 min per bed position on days 0, 2, 5, and 7. Image-derived standardized uptake values (SUVmean) were quantified by region of interest (ROI) analysis. RESULTS: 89Zr-N-sucDf-pembrolizumab was synthesized with high radiochemical purity (> 99 %) and acceptable molar activity (> 7 MBq/nmol). In animals dosed with tracer only, 89Zr-N-sucDf-pembrolizumab distribution in lymphoid tissues such as mesenteric lymph nodes, spleen, and tonsils increased over time. Except for the liver, low radiotracer distribution was observed in all non-lymphoid tissue including the lung, muscle, brain, heart, and kidney. When a large excess of pembrolizumab was co-administered with a radiotracer, accumulation in the lymph nodes, spleen, and tonsils was reduced, suggestive of target-mediated accumulation. CONCLUSIONS: 89Zr-N-sucDf-pembrolizumab shows preferential uptake in the lymphoid tissues including the lymph nodes, spleen, and tonsils. 89Zr-N-sucDf-pembrolizumab may be useful in tracking the distribution of a subset of immune cells in non-human primates and humans. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02760225

    Innovation and HRM : absences and politics

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    This article analyses the role of HRM practices in the implementation of an innovative cross-functional approach to new product development (concurrent engineering, CE) in Eurotech Industries. Contrary to CE methodology stipulations, and despite supportive conditions, HRM received scant attention in the implementation process. Organizational power and politics were clearly involved in this situation, and this article explores how their play created such HRM &lsquo;absences&rsquo;. The article builds on a four-dimensional view of power in order to provide a deeper understanding of the embedded, interdependent and political nature of HRM practice and innovation.<br /

    Coping with the effects of fear of failure in young elite athletes

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    Coping with stress is an important element in effective functioning at the elite level in sports, and fear of failure (FF) is an example of a stressor that athletes experience. Three issues underpin the present preliminary study. First, the prevalence of problems attributed to FF in achievement settings. Second, sport is a popular and significant achievement domain for children and adolescents. Third, there is a lack of research on FF in sport among this population. Therefore, the objectives of the study were to examine the effects of FF on young athletes and to find out their coping responses to the effects of FF. Interviews were conducted individually with nine young elite ath­letes (5 males, 4 females; ages 14-17 years). It was inferred from the data that FF affected the athletes' well-being, interpersonal behavior, sport performance, and schoolwork. The athletes employed a combination of problem-focused, emotion-fo­cused, and avoidance-focused coping strategies, with avoidance strategies being the most frequently reported

    Association between perceived built environmental attributes and physical activity among adults in South Africa

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    Background: To investigate the association between perceived environmental attributes and leisure-time and transport-related physical activity. Methods: This was a cross-sectional survey involving 671 South Africans aged ?35 years from urban and rural settings. International Physical Activity Questionnaire and Neighbourhood Walkability Scale were used to collect data. Multivariable logistic regressions were used to investigate the associations. Results: Significant urban vs. rural differences were apparent in the distribution of most attributes of neighborhood environment. After adjusting for gender, age, setting and relevant interaction terms, proximity to local stores was significantly associated with leisure-time physical activity (OR: 4.26; 95% CI, 1.00-18.08); while proximity to transit stops (2.44; 1.48-4.02), pleasant scenery (1.93; 1.07-3.46), sidewalks (2.36; 1.25-4.44), shade from trees (2.14; 1.19-3.85), traffic (2.17; 91.21-3.91) and well-lit streets (2.01; 1.04-3.89) were significantly associated with walking for leisure. Four-way intersections (4.54; 1.54-13.43), pleasant scenery (3.84; 1.35-10.99), traffic (0.28; 0.09-0.89), sidewalks (3.75; 1.06-13.27) and crosswalks were associated with transport related physical activity. Proximity to transit stops (2.12; 1.17-3.84) and well maintained sidewalks (2.69; 2.20-10.02) were significantly associated with total physical activity. Significant interactions by setting were apparent in some of the associations. Conclusion: Some, but not all attributes of a neighborhood environment were significantly associated in expected directions with the three physical activity domains in this mixed urban and rural population. This study highlights the need for policy strategies aimed at improving or maintaining these perceived environmental attributes to promote physical activity.IS
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