81 research outputs found

    A Novel Role for Mc1r in the Parallel Evolution of Depigmentation in Independent Populations of the Cavefish Astyanax mexicanus

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    The evolution of degenerate characteristics remains a poorly understood phenomenon. Only recently has the identification of mutations underlying regressive phenotypes become accessible through the use of genetic analyses. Focusing on the Mexican cave tetra Astyanax mexicanus, we describe, here, an analysis of the brown mutation, which was first described in the literature nearly 40 years ago. This phenotype causes reduced melanin content, decreased melanophore number, and brownish eyes in convergent cave forms of A. mexicanus. Crosses demonstrate non-complementation of the brown phenotype in F2 individuals derived from two independent cave populations: Pachón and the linked Yerbaniz and Japonés caves, indicating the same locus is responsible for reduced pigmentation in these fish. While the brown mutant phenotype arose prior to the fixation of albinism in Pachón cave individuals, it is unclear whether the brown mutation arose before or after the fixation of albinism in the linked Yerbaniz/Japonés caves. Using a QTL approach combined with sequence and functional analyses, we have discovered that two distinct genetic alterations in the coding sequence of the gene Mc1r cause reduced pigmentation associated with the brown mutant phenotype in these caves. Our analysis identifies a novel role for Mc1r in the evolution of degenerative phenotypes in blind Mexican cavefish. Further, the brown phenotype has arisen independently in geographically separate caves, mediated through different mutations of the same gene. This example of parallelism indicates that certain genes are frequent targets of mutation in the repeated evolution of regressive phenotypes in cave-adapted species

    A randomized controlled trial to prevent glycemic relapse in longitudinal diabetes care: Study protocol (NCT00362193)

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    BACKGROUND: Diabetes is a common disease with self-management a key aspect of care. Large prospective trials have shown that maintaining glycated hemoglobin less than 7% greatly reduces complications but translating this level of control into everyday clinical practice can be difficult. Intensive improvement programs are successful in attaining control in patients with type 2 diabetes, however, many patients experience glycemic relapse once returned to routine care. This early relapse is, in part, due to decreased adherence in self-management behaviors. OBJECTIVE: This paper describes the design of the Glycemic Relapse Prevention study. The purpose of this study is to determine the optimal frequency of maintenance intervention needed to prevent glycemic relapse. The primary endpoint is glycemic relapse, which is defined as glycated hemoglobin greater than 8% and an increase of 1% from baseline. METHODS: The intervention consists of telephonic contact by a nurse practitioner with a referral to a dietitian if indicated. This intervention was designed to provide early identification of self-care problems, understanding the rationale behind the self-care lapse and problem solve to find a negotiated solution. A total of 164 patients were randomized to routine care (least intensive), routine care with phone contact every three months (moderate intensity) or routine care with phone contact every month (most intensive). CONCLUSION: The baseline patient characteristics are similar across the treatment arms. Intervention fidelity analysis showed excellent reproducibility. This study will provide insight into the important but poorly understood area of glycemic relapse prevention

    General self-efficacy and the effect of hospital workplace violence on doctors’ stress and job satisfaction in China

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    Objectives: This study aims at exploring associations of general self-efficacy (GSE), workplace violence and doctors' work-related attitudes. Material and Methods: In this study a cross-sectional survey design was applied. Questionnaires were administrated to 758 doctors working in 9 hospitals of Zhengzhou, Henan province, China, between June and October 2010. General information on age, gender, and years of working was collected, and the doctors' experience and witnessing workplace violence, job satisfaction, job initiative, occupational stress as well as GSE were measured. General linear regression analysis was performed in association analyses. Results: Both experiencing and witnessing workplace violence were significantly positively correlated with the level of occupational stress but significantly negatively correlated with job satisfaction, job initiative, and GSE. General self-efficacy significantly modified relationships between both experiencing and witnessing workplace violence with occupational stress (β = 0.49 for experiencing violence; β = 0.43 for witnessing violence; p 0.05). The levels of occupational stress declined significantly with the increase of GSE, while job satisfaction increased significantly along with its increase. The effects of GSE on occupational stress and job satisfaction weakened as the frequency of violence increased. Conclusions: The findings suggest that GSE can modify effects of workplace violence on health care workers' stress and job satisfaction. Enhancing GSE in combination with stress reduction may lead to facilitating health care workers' recovery from workplace violence, and thereby improving their work-related attitudes

    Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England

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    The SARS-CoV-2 lineage B.1.1.7, designated variant of concern (VOC) 202012/01 by Public Health England1, was first identified in the UK in late summer to early autumn 20202. Whole-genome SARS-CoV-2 sequence data collected from community-based diagnostic testing for COVID-19 show an extremely rapid expansion of the B.1.1.7 lineage during autumn 2020, suggesting that it has a selective advantage. Here we show that changes in VOC frequency inferred from genetic data correspond closely to changes inferred by S gene target failures (SGTF) in community-based diagnostic PCR testing. Analysis of trends in SGTF and non-SGTF case numbers in local areas across England shows that B.1.1.7 has higher transmissibility than non-VOC lineages, even if it has a different latent period or generation time. The SGTF data indicate a transient shift in the age composition of reported cases, with cases of B.1.1.7 including a larger share of under 20-year-olds than non-VOC cases. We estimated time-varying reproduction numbers for B.1.1.7 and co-circulating lineages using SGTF and genomic data. The best-supported models did not indicate a substantial difference in VOC transmissibility among different age groups, but all analyses agreed that B.1.1.7 has a substantial transmission advantage over other lineages, with a 50% to 100% higher reproduction number

    Spaces of Abandonment: Genealogies, Lives and Critical Horizons

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    Abandonment has a long presence in Western cultural, philosophical and legal canon, though most contemporary critical debates focus on its sovereign and juridico-political functions. This article considers the concept of abandonment through its more nuanced and multidimensional appearances: at once a political technology and a material economy, a juridical category and a sphere of intimacy. Following the longer conceptual history of abandonment, from its Greco-Roman sources to the present, the article sheds light on abandonment as a systemic political technology, its evolution and significance in different social and political contexts. Drawing on notions of abandonment that remain outside Western intellectual corpus—primarily in early Jewish jurisprudence—this article seeks a more nuanced and expansive understanding of this concept. Closely reading a case documenting the fatal abandonment of one Palestinian man in 2008, the article highlights a myriad of agents, materialities, relations and infrastructures that join in the production and perpetuation of the abandoned present
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