2,932 research outputs found

    Relative entropy under mappings by stochastic matrices

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    AbstractThe relative g-entropy of two finite, discrete probability distributions x = (x1,…,xn) and y = (y1,…,yn) is defined as Hg(x,y) = Σkxkg (yk/kk - 1), where g:(-1,∞)→R is convex and g(0) = 0. When g(t) = -log(1 + t), then Hg(x,y) = Σkxklog(xk/yk), the usual relative entropy. Let Pn = {x ∈ Rn : σixi = 1, xi > 0 ∀i}. Our major results is that, for any m × n column-stochastic matrix A, the contraction coefficient defined as ηğ(A) = sup{Hg(Ax,Ay)/Hg(x,y) : x,y ∈ Pn, x ≠ y} satisfies ηg(A) ⩽1 - α(A), where α(A) = minj,kΣi min(aij, aik) is Dobrushin's coefficient of ergodicity. Consequently, ηg(A) < 1 if and only if A is scrambling. Upper and lower bounds on αg(A) are established. Analogous results hold for Markov chains in continuous time

    The Fusion Loops of the Initial Prefusion Conformation of Herpes Simplex Virus 1 Fusion Protein Point Toward the Membrane

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    All enveloped viruses, including herpesviruses, must fuse their envelope with the host membrane to deliver their genomes into target cells, making this essential step subject to interference by antibodies and drugs. Viral fusion is mediated by a viral surface protein that transits from an initial prefusion conformation to a final postfusion conformation. Strikingly, the prefusion conformation of the herpesvirus fusion protein, gB, is poorly understood. Herpes simplex virus (HSV), a model system for herpesviruses, causes diseases ranging from mild skin lesions to serious encephalitis and neonatal infections. Using cryo-electron tomography and subtomogram averaging, we have characterized the structure of the prefusion conformation and fusion intermediates of HSV-1 gB. To this end, we have set up a system that generates microvesicles displaying full-length gB on their envelope. We confirmed proper folding of gB by nondenaturing electrophoresis-Western blotting with a panel of monoclonal antibodies (MAbs) covering all gB domains. To elucidate the arrangement of gB domains, we labeled them by using (i) mutagenesis to insert fluorescent proteins at specific positions, (ii) coexpression of gB with Fabs for a neutralizing MAb with known binding sites, and (iii) incubation of gB with an antibody directed against the fusion loops. Our results show that gB starts in a compact prefusion conformation with the fusion loops pointing toward the viral membrane and suggest, for the first time, a model for gB’s conformational rearrangements during fusion. These experiments further illustrate how neutralizing antibodies can interfere with the essential gB structural transitions that mediate viral entry and therefore infectivity

    A review of fMRI simulation studies

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    Simulation studies that validate statistical techniques for fMRI data are challenging due to the complexity of the data. Therefore, it is not surprising that no common data generating process is available (i.e. several models can be found to model BOLD activation and noise). Based on a literature search, a database of simulation studies was compiled. The information in this database was analysed and critically evaluated focusing on the parameters in the simulation design, the adopted model to generate fMRI data, and on how the simulation studies are reported. Our literature analysis demonstrates that many fMRI simulation studies do not report a thorough experimental design and almost consistently ignore crucial knowledge on how fMRI data are acquired. Advice is provided on how the quality of fMRI simulation studies can be improved

    Estimating the number needed to treat from continuous outcomes in randomised controlled trials: methodological challenges and worked example using data from the UK Back Pain Exercise and Manipulation (BEAM) trial

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    Background Reporting numbers needed to treat (NNT) improves interpretability of trial results. It is unusual that continuous outcomes are converted to numbers of individual responders to treatment (i.e., those who reach a particular threshold of change); and deteriorations prevented are only rarely considered. We consider how numbers needed to treat can be derived from continuous outcomes; illustrated with a worked example showing the methods and challenges. Methods We used data from the UK BEAM trial (n = 1, 334) of physical treatments for back pain; originally reported as showing, at best, small to moderate benefits. Participants were randomised to receive 'best care' in general practice, the comparator treatment, or one of three manual and/or exercise treatments: 'best care' plus manipulation, exercise, or manipulation followed by exercise. We used established consensus thresholds for improvement in Roland-Morris disability questionnaire scores at three and twelve months to derive NNTs for improvements and for benefits (improvements gained+deteriorations prevented). Results At three months, NNT estimates ranged from 5.1 (95% CI 3.4 to 10.7) to 9.0 (5.0 to 45.5) for exercise, 5.0 (3.4 to 9.8) to 5.4 (3.8 to 9.9) for manipulation, and 3.3 (2.5 to 4.9) to 4.8 (3.5 to 7.8) for manipulation followed by exercise. Corresponding between-group mean differences in the Roland-Morris disability questionnaire were 1.6 (0.8 to 2.3), 1.4 (0.6 to 2.1), and 1.9 (1.2 to 2.6) points. Conclusion In contrast to small mean differences originally reported, NNTs were small and could be attractive to clinicians, patients, and purchasers. NNTs can aid the interpretation of results of trials using continuous outcomes. Where possible, these should be reported alongside mean differences. Challenges remain in calculating NNTs for some continuous outcomes

    Behind the confession: Relating false confession, interrogative compliance, personality traits, and psychopathy

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    The present study further supports the established notion that personality traits contribute to the phenomenon of false confessions and compliance in an interrogative setting. Furthermore, the study provides an investigation into the more recent interest in the potential effect of psychopathic traits in this context. A sample of university students (N = 607) completed questionnaires measuring psychopathic traits, interrogative compliance, and the big five personality factors. Of these, only 4.9% (n=30) claimed to have falsely confessed to an academic or criminal offense, with no participant taking the blame for both types of offense. Across measures the big five personality traits were the strongest predictors of compliance. The five personality traits accounted for 17.9 % of the total variance in compliance, with neuroticism being the strongest predictor, followed by openness and agreeableness. Psychopathy accounted for 3.3% of variance, with the lifestyle facet being the only significant predictor. After controlling for the big five personality factors, psychopathy only accounted for a small percentage of interrogative compliance, indicating that interrogators should take into account a person’s personality traits during the interrogation.N/

    The new COSMIN guidelines confront traditional concepts of responsiveness

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    The recently published "COSMIN" guidelines aim to rate properties of outcome instruments and state two issues with regard to responsiveness which is the instrument's ability to detect change over time. These issues are comparison of score changes with change of an external criterion using correlations and the judgement of traditional methods as inappropriate. The latter are the "transition" concept, a global rating of change, and parametric measures of responsiveness, for example, effect sizes. It can be shown that the methodology proposed by the guidelines has important weaknesses and that denunciation of traditional methods is not appropriate. Some claims of the guidelines about responsiveness do not match the demands of clinical reality and confront findings of numerous epidemiological studies

    Narratives of self and identity in women's prisons: stigma and the struggle for self-definition in penal regimes

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    A concern with questions of selfhood and identity has been central to penal practices in women's prisons, and to the sociology of women's imprisonment. Studies of women's prisons have remained preoccupied with women prisoners’ social identities, and their apparent tendency to adapt to imprisonment through relationships. This article explores the narratives of women in two English prisons to demonstrate the importance of the self as a site of meaning for prisoners and the central place of identity in micro-level power negotiations in prisons

    Soybean Flour and Wheat Germ Proportions in Artificial Diet and Their Effect on the Growth Rates of the Tobacco Budworm, Heliothis virescens

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    Soybean flour and wheat germ are the two most important protein components of wheat germ-based insect artificial diets. The effect of modifying the proportion of these two ingredients in a Noctuidae-specific diet was investigated utilizing the tobacco budworm Heliothis virescens (F.) (Lepidoptera: Noctuidae), with the goal of developing a suboptimal diet that, without drastically affecting this insect's growth and reproductive rates, could manifest subtle negative effects in this insect. The original diet formula contained 2.51% protein. When the proportions of soybean flour and wheat germ were changed to 2.15% protein the net reproductive rate of the first generation was significantly lower. In the second generation, the net reproductive rate, development time, percent female survivorship, fertility, intrinsic rate of increase, finite rate of increase and female longevity were significantly lower in both the 2.15% and 2.26% protein diets. The survival rate of immatures to the adult stage was 1% in the 2.05% protein diet in the first generation. Interestingly, females exposed to these suboptimal diets produced a significantly higher number of eggs but the survival of their larvae was significantly reduced. It is evident from these results that modifications to the protein content and the nutrient composition profile of the original wheat germ-based insect artificial formula can be used to produce subtle negative effects on the growth of tobacco budworm
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