505 research outputs found

    Composite Fermion Metals from Dyon Black Holes and S-Duality

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    We propose that string theory in the background of dyon black holes in four-dimensional anti-de Sitter spacetime is holographic dual to conformally invariant composite Dirac fermion metal. By utilizing S-duality map, we show that thermodynamic and transport properties of the black hole match with those of composite fermion metal, exhibiting Fermi liquid-like. Built upon Dirac-Schwinger-Zwanziger quantization condition, we argue that turning on magnetic charges to electric black hole along the orbit of Gamma(2) subgroup of SL(2,Z) is equivalent to attaching even unit of statistical flux quanta to constituent fermions. Being at metallic point, the statistical magnetic flux is interlocked to the background magnetic field. We find supporting evidences for proposed holographic duality from study of internal energy of black hole and probe bulk fermion motion in black hole background. They show good agreement with ground-state energy of composite fermion metal in Thomas-Fermi approximation and cyclotron motion of a constituent or composite fermion excitation near Fermi-point.Comment: 30 pages, v2. 1 figure added, minor typos corrected; v3. revised version to be published in JHE

    Dronedarone in high-risk permanent atrial fibrillation

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    BACKGROUND: Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation. METHODS: We assigned patients who were at least 65 years of age with at least a 6-month history of permanent atrial fibrillation and risk factors for major vascular events to receive dronedarone or placebo. The first coprimary outcome was stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes. The second coprimary outcome was unplanned hospitalization for a cardiovascular cause or death. RESULTS: After the enrollment of 3236 patients, the study was stopped for safety reasons. The first coprimary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29; 95% confidence interval [CI], 1.34 to 3.94; P = 0.002). There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group (hazard ratio, 2.11; 95% CI, 1.00 to 4.49; P = 0.046), including death from arrhythmia in 13 patients and 4 patients, respectively (hazard ratio, 3.26; 95% CI, 1.06 to 10.00; P = 0.03). Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group (hazard ratio, 2.32; 95% CI, 1.11 to 4.88; P = 0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group (hazard ratio, 1.81; 95% CI, 1.10 to 2.99; P = 0.02). CONCLUSIONS: Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients. (Funded by Sanofi-Aventis; PALLAS ClinicalTrials.gov number, NCT01151137.) Copyright © 2011 Massachusetts Medical Society. All rights reserved.published_or_final_versio

    How does it really feel to act together? : Shared emotions and the phenomenology of we-agency

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    Research on the phenomenology of agency for joint action has so far focused on the sense of agency and control in joint action, leaving aside questions on how it feels to act together. This paper tries to fill this gap in a way consistent with the existing theories of joint action and shared emotion. We first reconstruct Pacherie’s (Phenomenology and the Cognitive Sciences, 13, 25–46, 2014) account on the phenomenology of agency for joint action, pointing out its two problems, namely (1) the necessary trade-off between the sense of self- and we-agency; and (2) the lack of affective phenomenology of joint action in general. After elaborating on these criticisms based on our theory of shared emotion, we substantiate the second criticism by discussing different mechanisms of shared affect—feelings and emotions—that are present in typical joint actions. We show that our account improves on Pacherie’s, first by introducing our agentive model of we-agency to overcome her unnecessary dichotomy between a sense of self- and we-agency, and then by suggesting that the mechanisms of shared affect enhance not only the predictability of other agents’ actions as Pacherie highlights, but also an agentive sense of we-agency that emerges from shared emotions experienced in the course and consequence of joint action.Peer reviewe

    The clinical utility of the continuous performance test and objective measures of activity for diagnosing and monitoring ADHD in children: a systematic review

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    Attention deficit hyperactivity disorder (ADHD) is typically diagnosed using clinical observation and subjective informant reports. Once children commence ADHD medication, robust monitoring is required to detect partial or non-responses. The extent to which neuropsychological continuous performance tests (CPTs) and objective measures of activity can clinically aid the assessment and titration process in ADHD is not fully understood. This review describes the current evidence base for the use of CPTs and objectively measured activity to support the diagnostic procedure and medication management for children with ADHD. Four databases (PsycINFO, Medline, Allied and Complementary Medicine (AMED) and PsycARTICLES) were systematically searched to understand the current evidence base for: (1) the use of CPTs to aid clinical assessment of ADHD; (2) the use of CPTs to aid medication management; (3) the clinical utility of objective measures of activity in ADHD. Sixty relevant articles were identified. The search revealed six commercially available CPTs that had been reported on for their clinical use. There were mixed findings with regard to the use of CPTs to assess and manage medication, with contrasting evidence on their ability to support clinical decision making. There was a strong evidence base for the use of objective measures of activity to aid ADHD/non-ADHD group differentiation, which appears sensitive to medication effects and would also benefit from further research on their clinical utility. The findings suggest that combining CPTs and an objective measure of activity may be particularly useful as a clinical tool and worthy of further pursuit

    Scoring docking conformations using predicted protein interfaces

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    BACKGROUND: Since proteins function by interacting with other molecules, analysis of protein-protein interactions is essential for comprehending biological processes. Whereas understanding of atomic interactions within a complex is especially useful for drug design, limitations of experimental techniques have restricted their practical use. Despite progress in docking predictions, there is still room for improvement. In this study, we contribute to this topic by proposing T-PioDock, a framework for detection of a native-like docked complex 3D structure. T-PioDock supports the identification of near-native conformations from 3D models that docking software produced by scoring those models using binding interfaces predicted by the interface predictor, Template based Protein Interface Prediction (T-PIP). RESULTS: First, exhaustive evaluation of interface predictors demonstrates that T-PIP, whose predictions are customised to target complexity, is a state-of-the-art method. Second, comparative study between T-PioDock and other state-of-the-art scoring methods establishes T-PioDock as the best performing approach. Moreover, there is good correlation between T-PioDock performance and quality of docking models, which suggests that progress in docking will lead to even better results at recognising near-native conformations. CONCLUSION: Accurate identification of near-native conformations remains a challenging task. Although availability of 3D complexes will benefit from template-based methods such as T-PioDock, we have identified specific limitations which need to be addressed. First, docking software are still not able to produce native like models for every target. Second, current interface predictors do not explicitly consider pairwise residue interactions between proteins and their interacting partners which leaves ambiguity when assessing quality of complex conformations

    A novel, rapid method to compare the therapeutic windows of oral anticoagulants using the Hill coefficient

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    A central challenge in designing and administering effective anticoagulants is achieving the proper therapeutic window and dosage for each patient. The Hill coefficient, nH, which measures the steepness of a dose-response relationship, may be a useful gauge of this therapeutic window. We sought to measure the Hill coefficient of available anticoagulants to gain insight into their therapeutic windows. We used a simple fluorometric in vitro assay to determine clotting activity in platelet poor plasma after exposure to various concentrations of anticoagulants. The Hill coefficient for argatroban was the lowest, at 1.7±0.2 (95% confidence interval, CI), and the Hill coefficient for fondaparinux was the highest, at 4.5±1.3 (95% CI). Thus, doubling the dose of fondaparinux from its IC50 would decrease coagulation activity by nearly a half, whereas doubling the dose of argatroban from its IC50 would decrease coagulation activity by merely one quarter. These results show a significant variation among the Hill coefficients, suggesting a similar variation in therapeutic windows among anticoagulants in our assay

    Estimating the role of casual contact from the community in transmission of Bordetella pertussis to young infants

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    The proportion of infant pertussis cases due to transmission from casual contact in the community has not been estimated since before the introduction of pertussis vaccines in the 1950s. This study aimed to estimate the proportion of pertussis transmission due to casual contact using demographic and clinical data from a study of 95 infant pertussis cases and their close contacts enrolled at 14 hospitals in France, Germany, Canada, and the U.S. between February 2003 and September 2004. A complete case analysis was conducted as well as multiple imputation (MI) to account for missing data for participants and close contacts who did not participate. By considering all possible close contacts, the MI analysis estimated 66% of source cases were close contacts, implying the minimum attributable proportion of infant cases due to transmission from casual contact with community members was 34% (95% CI = 24%, 44%). Estimates from the complete case analysis were comparable but less precise. Results were sensitive to changes in the operational definition of a source case, which broadened the range of MI point estimates of transmission from casual community contact to 20%–47%. We conclude that casual contact appears to be responsible for a substantial proportion of pertussis transmission to young infants
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