3,108 research outputs found

    High Heritability Is Compatible with the Broad Distribution of Set Point Viral Load in HIV Carriers.

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    Set point viral load in HIV patients ranges over several orders of magnitude and is a key determinant of disease progression in HIV. A number of recent studies have reported high heritability of set point viral load implying that viral genetic factors contribute substantially to the overall variation in viral load. The high heritability is surprising given the diversity of host factors associated with controlling viral infection. Here we develop an analytical model that describes the temporal changes of the distribution of set point viral load as a function of heritability. This model shows that high heritability is the most parsimonious explanation for the observed variance of set point viral load. Our results thus not only reinforce the credibility of previous estimates of heritability but also shed new light onto mechanisms of viral pathogenesis

    General Evidentiary Objections Still Valid in Maryland

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    Characterization of Cytokeratin 8 in Cancer

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    A Cytokeratin 8 (K8)/Green Fluorescent Protein (GFP) fusion construct was created to better understand the behavior of K8 within cancer cells. This intermediate filament (IF) protein is a member of the cytoskeletal gene family, along with actin and tubulin. IFs are normally expressed in a tissue-specific and differentiation-dependent manner, in which their role is more supportive than essential to the cell. Such roles include rigidity of cellular shape, protein trafficking, cellular locomotion, and cell-signaling platforms. K8 mutation, over-expression, and aberrant post translational modifications have been observed in various carcinoma cell lines to be the cause of several phenotypes, including apoptosis inhibition, drug resistance, transformation, Mallory-Denk body formation, localization at the plasma membrane, and secretion of the protein. To study these abnormal phenotypes, the K8 gene was isolated and inserted into the GFP over expression vector. Transfecting this vector into HeLa cells allowed for the study of K8 within a well-defined cervical cancer cell line. This study was intended to provide answers to K8\u27s localization at the plasma membrane in carcinoma cell models while avoiding criticisms to previous immunohistochemical localization studies. A cellular model of K8 processing that exhibits established phenotypes found in the literature was thus created and has the potential to address several paramount questions related to K8\u27s role in supporting the development and progression of cancer. It could also be utilized as an assay for the discovery of K8 filament formation inhibitors, which may prove useful in combination with current chemotherapeutics. The model could also be used to provide weight to diagnostics, such as the CAncer REcognition test, which utilizes antibodies against K8 as biomarkers for malignancy via an Enzyme-Link ImmunoSorbent Assay

    Building Psychosocial Assets And Wellbeing Among Adolescent Girls: A Randomized Controlled Trial

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    We conducted a randomized controlled trial of a 5-month resilience-based program (Girls First Resilience Curriculum or RC) among 2308 rural adolescent girls at 57 government schools in Bihar, India. Local women with at least a 10th grade education served as group facilitators. Girls receiving RC improved more (vs. controls) on emotional resilience, self-efficacy, social-emotional assets, psychological wellbeing, and social wellbeing. Effects were not detected on depression. There was a small, statistically significant negative effect on anxiety (though not likely clinically significant). Results suggest psychosocial assets and wellbeing can be improved for girls in high-poverty, rural schools through a brief school-day program. To our knowledge, this is one of the largest developing country trials of a resilience-based school-day curriculum for adolescents. (C) 2015 The Authors. Published by Elsevier Ltd on behalf of The Foundation for Professionals in Services for Adolescents. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

    Fostering Emotional, Social, Physical And Educational Wellbeing In Rural India: The Methods Of A Multi-Arm Randomized Controlled Trial Of Girls First

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    Background: There are 600 million girls in low and middle income countries (LMICs), many of whom are at great risk for poor health and education. There is thus great need for programs that can effectively improve wellbeing for these girls. Although many interventions have been developed to address these issues, most focus on health and education without integrating attention to social and emotional factors. This omission is unfortunate, as nascent evidence indicates that these factors are closely related to health and education. This paper describes the methods of a 4-arm randomized controlled trial among 3,560 adolescent girls in rural Bihar, India that tested whether adding an intervention targeting social-emotional issues (based on a “resilience framework”) to an adolescent health intervention would improve emotional, social, physical, and educational wellbeing to a greater extent than its components and a control group. Study arms were: (1) Girls First, a combination of the Girls First Resilience Curriculum (RC) and the Girls First Health Curriculum (HC); (2) Girls First Resilience Curriculum (RC) alone; (3) Girls First Health Curriculum (HC) alone; and (4) a school-as-usual control group (SC). Methods: Seventy-six schools were randomized (19 per condition) and 74 local women with a tenth grade education were trained and monitored to facilitate the program. Quantitative data were collected from 3,560 girls over 4 assessment points with very low rates of participant attrition. Qualitative assessments were conducted with a subset of 99 girls and 27 facilitators. Results and conclusions: In this article, we discuss guiding principles that facilitated trial implementation, including integrating diverse local and non-local sources of knowledge, focusing on flexibility of planning and implementation, prioritizing systematic measurement selection, and striking a balance between scientific rigor and real-world feasibility

    Inequality and Procedural Justice in Social Dilemmas

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    This study investigates the influence of resource inequality and the fairness of the allocation procedure of unequal resources on cooperative behavior in social dilemmas. We propose a simple formal behavioral model that incorporates conflicting selfish and social motivations. This model allows us to predict how inequality influences cooperative behavior. Allocation of resources is manipulated by three treatments that vary in terms of procedural justice: allocating resources randomly, based on merit, and based on ascription. As predicted, procedural justice influences cooperation significantly. Moreover, gender is found to be an important factor interacting with the association between procedural justice and cooperative behavior.

    Training school teachers to promote mental and social well-being in low and middle income countries : lessons to facilitate scale-up from a participatory action research trial of youth first in India

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    Mental and social wellbeing (MSWB) promotion programs could improve mental health and other outcomes for youth in Low and Middle Income Countries (LMICs). Unfortunately, few such programs have progressed to scale-up and few studies have detailed processes and considerations that could facilitate doing so. This study begins to fill these gaps, describing key findings from training and supporting government middle school teachers to deliver the Youth First Resilience Curriculum, a MSWB promotion program, in Bihar, India. We conducted a Participatory Action Research trial of the resilience curriculum among 792 middle school youth and 55 teachers at 15 government schools. Participant-observations, exit interviews, and group discussions were conducted and analyzed via multiple rounds of coding to generate thematic findings. A number of schools showed relatively high levels of interest, session reliability and fidelity, student interaction and teacher facilitative abilities, but there was great variation within the sample. Three leverage points emerged to facilitate future scale-up: factors for successful site assessment and program initiation, supporting teacher success via interest and motivation, and responding to varied teacher skill levels. These points represent critical focus areas for practitioners and policy-makers as more MSWB promotion programs begin to scale in LMICs.peer-reviewe

    GRIS observations of the galactic center and the gamma ray galactic diffuse continuum

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    On two flights in 1988, the Gamma-Ray Imaging Spectrometer (GRIS) discovered the galactic center in a high state (greater than 1 x 10(exp -3) ph/(sq cm sec)) of positron annihilation line emission (511 keV) after nearly a decade of failed attempts to confirm the exciting early results of balloon and satellite instruments. These two flights represented the first flights of a new generation of high resolution germanium spectrometers designed to achieve significantly greater sensitivity for astrophysical observations. During the fall flight, an observation of the galactic plane at 335 degrees longitude was also performed. This observation showed a very low level of 511 keV emission (2 +/- 1 x 10(exp -4) ph/(sq cm sec)), confirming the galactic center origin of the line, and a high level of hard x-ray and gamma-ray continuum emission (1 x 10(exp -4) ph/(sq cm sec keV) at 100 keV), which we attribute to galactic diffuse emission. Improved fits to the spectrum of the galactic center are presented with the proposed diffuse component subtracted. We conclude that our galactic center continuum spectrum is consistent with the sum of the 1E1740.7-2942 spectrum observed by SIGMA/GRANAT and our 1 = 335 degree galactic plane spectrum. The predicted diffuse flux should be easily measurable by the Oriented Scintillation Spectrometer Experiment (OSSE) experiment on the Gamma Ray Observatory (GRO)
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