114 research outputs found

    [Review of] Robert J. Norrell. Reaping the Whirlwind: The Civil Rights Movement in Tuskegee

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    Reaping the Whirlwind is a case study of the black American struggle for civil rights and racial democracy in a unique community of the Black Belt South. It is a story of Tuskegee\u27s white political hegemony and the black elite\u27s early cooperation with and later mild challenge to that dominance. In 1880, as a result of collaboration between white politicians and Tuskegee\u27s black leadership, the Democrats secured political control of the Alabama state legislature. The following year, as pay-off for the deal, Tuskegee Institute was established with Booker T. Washington at the helm, and the goal became one of making Tuskegee a model community for safeguarding racial cooperation through black political subordination. Tuskegee\u27s white merchants, former slaveowners, and educators alike encouraged black educational opportunities ( separate and unequal )

    HPTN 071 (PopART): A Cluster-Randomized Trial of the Population Impact of an HIV Combination Prevention Intervention Including Universal Testing and Treatment: Mathematical Model

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    BACKGROUND: The HPTN 052 trial confirmed that antiretroviral therapy (ART) can nearly eliminate HIV transmission from successfully treated HIV-infected individuals within couples. Here, we present the mathematical modeling used to inform the design and monitoring of a new trial aiming to test whether widespread provision of ART is feasible and can substantially reduce population-level HIV incidence. METHODS AND FINDINGS: The HPTN 071 (PopART) trial is a three-arm cluster-randomized trial of 21 large population clusters in Zambia and South Africa, starting in 2013. A combination prevention package including home-based voluntary testing and counseling, and ART for HIV positive individuals, will be delivered in arms A and B, with ART offered universally in arm A and according to national guidelines in arm B. Arm C will be the control arm. The primary endpoint is the cumulative three-year HIV incidence. We developed a mathematical model of heterosexual HIV transmission, informed by recent data on HIV-1 natural history. We focused on realistically modeling the intervention package. Parameters were calibrated to data previously collected in these communities and national surveillance data. We predict that, if targets are reached, HIV incidence over three years will drop by >60% in arm A and >25% in arm B, relative to arm C. The considerable uncertainty in the predicted reduction in incidence justifies the need for a trial. The main drivers of this uncertainty are possible community-level behavioral changes associated with the intervention, uptake of testing and treatment, as well as ART retention and adherence. CONCLUSIONS: The HPTN 071 (PopART) trial intervention could reduce HIV population-level incidence by >60% over three years. This intervention could serve as a paradigm for national or supra-national implementation. Our analysis highlights the role mathematical modeling can play in trial development and monitoring, and more widely in evaluating the impact of treatment as prevention

    Preliminary psychometric properties of the Acceptance and Action Questionnaire – II: A revised measure of psychological flexibility and acceptance.

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    The present research describes the development and psychometric evaluation of a second version of the Acceptance and Action Questionnaire (AAQ-II), which assesses the construct referred to as, variously, acceptance, experiential avoidance and psychological inflexibility. Results from 2,816 participants across six samples indicate the satisfactory structure, reliability, and validity of this measure. For example, the mean alpha coefficient is .84 (.78 - .88), and the 3- and 12-month test-retest reliability is .81 and .79, respectively. Results indicate that AAQ-II scores concurrently, longitudinally, and incrementally predict a range of outcomes, from mental health to work absence rates,that are consistent with its underlying theory. The AAQ-II also demonstrates appropriate discriminant validity. The AAQ-II appears to measure the same concept as the AAQ-I (r = .97), but with better psychometric consistency

    Quantifying the role of woody debris in providing bioenergetically favorable habitat for juvenile salmon

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    The habitat complexity of a riverine ecosystem influences the bioenergetics of drift feeding fish. We coupled hydrodynamic and bioenergetic models to assess the influence of habitat complexity generated by large woody debris (LWD) on the growth potential of juvenile Chinook salmon (Oncorhynchus tshawytscha) in a river that lacked large wood. Simulations indicated how LWD diversified the flow field, creating pronounced velocity gradients, which enhanced fish feeding and resting activities at the sub-meter scale. Fluid drag created by individual wood structures increased under higher wood loading amounts, leading to a 5-19% reduction in the reach-averaged velocity. The reach-scale growth potential was asymptotically related to wood loading, suggesting that the river became saturated with LWD and additional loading would produce minimal benefit for the configurations we simulated. In the scenario we analyzed for illustration, LWD additions could quadruple the potential growth area available before that limit was reached for the configurations selected for demonstration. Wood depletion in the world's rivers has been documented extensively, leading to widespread attempts by river managers to reverse this trend by adding wood to simplified aquatic habitats. However, systematic prediction of the effects of wood on fish growth has not been previously accomplished. We offer a quantitative approach for assessing the influence of wood on habitat potential for fish growth at the microhabitat and reach-scales. © 2014 Elsevier B.V

    The development and initial validation of The Cognitive Fusion Questionnaire

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    Acceptance and Commitment Therapy (ACT) emphasizes the relationship a person has with their thoughts and beliefs as potentially more relevant than belief content in predicting the emotional and behavioral consequences of cognition. In ACT, ‘defusion’ interventions aim to ‘unhook’ thoughts from actions and to create psychological distance between a person and their thoughts, beliefs, memories and self-stories. A number of similar concepts have been described in the psychology literature (e.g. decentering, metacognition, mentalization and mindfulness) suggesting converging evidence that how we relate to mental events may be of critical importance. Whilst there are some good measures of these related processes, none of them provides an adequate operationalization of cognitive fusion. Despite the centrality of cognitive fusion in the ACT model, there is as yet no agreed measure of cognitive fusion. This paper presents the construction and development of a brief, self-report measure of cognitive fusion: The Cognitive Fusion Questionnaire (CFQ). The results of a series of studies involving over 1800 people across diverse samples show good preliminary evidence of the CFQ’s factor structure, reliability, temporal stability, validity, discriminant validity, and sensitivity to treatment effects. The potential uses of the CFQ in research and clinical practice are outlined

    Projected outcomes of universal testing and treatment in a generalised HIV epidemic in Zambia and South Africa (the HPTN 071 [PopART] trial): a modelling study

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    Background The long-term impact of universal home-based testing and treatment as part of universal testing and treatment (UTT) on HIV incidence is unknown. We made projections using a detailed individual-based model of the effect of the intervention delivered in the HPTN 071 (PopART) cluster-randomised trial. Methods In this modelling study, we fitted an individual-based model to the HIV epidemic and HIV care cascade in 21 high prevalence communities in Zambia and South Africa that were part of the PopART cluster-randomised trial (intervention period Nov 1, 2013, to Dec 31, 2017). The model represents coverage of home-based testing and counselling by age and sex, delivered as part of the trial, antiretroviral therapy (ART) uptake, and any changes in national guidelines on ART eligibility. In PopART, communities were randomly assigned to one of three arms: arm A received the full PopART intervention for all individuals who tested positive for HIV, arm B received the intervention with ART provided in accordance with national guidelines, and arm C received standard of care. We fitted the model to trial data twice using Approximate Bayesian Computation, once before data unblinding and then again after data unblinding. We compared projections of intervention impact with observed effects, and for four different scenarios of UTT up to Jan 1, 2030 in the study communities. Findings Compared with standard of care, a 51% (95% credible interval 40–60) reduction in HIV incidence is projected if the trial intervention (arms A and B combined) is continued from 2020 to 2030, over and above a declining trend in HIV incidence under standard of care. Interpretation A widespread and continued commitment to UTT via home-based testing and counselling can have a substantial effect on HIV incidence in high prevalence communities. Funding National Institute of Allergy and Infectious Diseases, US President's Emergency Plan for AIDS Relief, International Initiative for Impact Evaluation, Bill & Melinda Gates Foundation, National Institute on Drug Abuse, and National Institute of Mental Health

    Genetic drivers of heterogeneity in type 2 diabetes pathophysiology.

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    Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

    Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

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    Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care
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