1,721,230 research outputs found

    Dunn, Graham

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    Crystallographic and biochemical analysis of three distinct hydrolases : Dermatophagoides pteronyssinus 1 (Der p1), momordin and the bacterial carbon-carbon hydrolase, MhpC

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    MhpC is one of six enzymes derived from the mhp operon, which collectively give rise to meta-cleavage pathway for the degradation of 3-(3-hydroxyphenyl)propionic acids (3-HPP) in Escherichia coli. These enzymes work in tandem to convert 3-HPP to metabolites which can then be fed into the Kreb's cycle for energy release. The role of MhpC in this pathway is to convert 2-hydroxy-6-ketonona-2,4-diene-1,9-dioate to 2-hydroxy-penta-2, 4-dienoate and succinate. This reaction involves the breaking of a carbon-carbon bond, which constitutes a rare catalytic event in nature. Elucidating the catalytic mechanism of MhpC will provide invaluable information at the molecular level contributing to the understanding of how biodegradation of environmental pollutants can be achieved.The MhpC structure has been solved using Multiwavelength Anomalous Dispersion (M.A.D.) phasing to obtain the protein phase information from 32 selenomethionine sites in the MhpC asymmetric unit. The enzyme belongs to the α/β hydrolase fold family. Mechanistic studies can now be undertaken involving the analysis of the interactions of various ligands bound in at the active site.Momordin is a ribosome inactivating protein (RIP) from the seeds of the bitter gourd, Momordica charantia. RIPs exist in two main classes. Type II RIPs, such as ricin, possess two subunits, the A- and B-chains. The A-chain is a toxin which targets ribosomes, whilst the B-chain is a lectin responsible for facilitating A-chain entry into cells. Type 1 RIPs, in contrast, are monomeric toxins, which share homology with type II RIP A-chains.</p

    Describing, explaining or predicting mental health care costs: A guide to regression models - Methodological review

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    Background: Analysis of the patterns of variation in health care costs and the determinants of these costs (including treatment differences) is an increasingly important aspect of research into the performance of mental health services. Aims: To encourage both investigators of the variation in health care costs and the consumers of their investigations to think more critically about the precise aims of these investigations and the choice of statistical methods appropriate to achieve them. Method: We briefly describe examples of regression models that might be of use in the prediction of mental health costs and how one might choose which one to use for a particular research project. Conclusions: If the investigators are primarily interested in explanatory mechanisms then they should seriously consider generalised linear models (but with careful attention being paid to the appropriate error distribution). Further insight is likely to be gained through the use of two-part models. For prediction we recommend regression on raw costs using ordinary least-square methods. Whatever method is used, investigators should consider how robust their methods might be to incorrect distributional assumptions (particularly in small samples) and they should not automatically assume that methods such as bootstrapping will allow them to ignore these problems

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    The effects of reducing worry in patients with persecutory delusions: study protocol for a randomized controlled trial

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    BACKGROUND: Our approach to advancing the treatment of psychosis is to focus on key single symptoms and develop interventions that target the mechanisms that maintain them. In our theoretical research we have found worry to be an important factor in the development and maintenance of persecutory delusions. Worry brings implausible ideas to mind, keeps them there, and makes the experience distressing. Therefore the aim of the trial is to test the clinical efficacy of a cognitive-behavioral intervention for worry for patients with persecutory delusions and determine how the worry treatment might reduce delusions.METHODS: An explanatory randomized controlled trial - called the Worry Intervention Trial (WIT) - with 150 patients with persecutory delusions will be carried out. Patients will be randomized to the worry intervention in addition to standard care or to standard care. Randomization will be carried out independently, assessments carried out single-blind, and therapy competence and adherence monitored. The study population will be individuals with persecutory delusions and worry in the context of a schizophrenia spectrum diagnosis. They will not have responded adequately to previous treatment. The intervention is a six-session cognitive-behavioral treatment provided over eight weeks. The control condition will be treatment as usual, which is typically antipsychotic medication and regular appointments. The principal hypotheses are that a worry intervention will reduce levels of worry and that it will also reduce the persecutory delusions. Assessments will be carried out at 0 weeks (baseline), 8 weeks (post treatment) and 24 weeks (follow-up). The statistical analysis strategy will follow the intention-to-treat principle and involve the use of linear mixed models to evaluate and estimate the relevant between- and within-subjects effects (allowing for the possibility of missing data). Both traditional regression and newer instrumental variables analyses will examine mediation. The trial is funded by the UK Medical Research Council (MRC)/NHS National Institute of Health Research (NIHR) Efficacy and Mechanism Evaluation (EME) Programme.DISCUSSION: This will be the first large randomized controlled trial specifically focused upon persecutory delusions. The project will produce a brief, easily administered intervention that can be readily used in mental health services.Trial registration Current Controlled Trials ISRCTN23197625

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    The interaction of affective with psychotic processes: A test of the effects of worrying on working memory, jumping to conclusions, and anomalies of experience in patients with persecutory delusions

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    Worry has traditionally been considered in the study of common emotional disorders such as anxiety and depression, but recent studies indicate that worry may be a causal factor in the occurrence and persistence of persecutory delusions. The effect of worry on processes traditionally associated with psychosis has not been tested. The aim of the study was to examine the short-term effects of a bout of worry on three cognitive processes typically considered markers of psychosis: working memory, jumping to conclusions, and anomalous internal experience. Sixty-seven patients with persecutory delusions in the context of a non-affective psychotic disorder were randomised to a worry induction, a worry reduction, or a neutral control condition. They completed tests of the cognitive processes before and after the randomisation condition. The worry induction procedure led to a significant increase in worry. The induction of worry did not affect working memory or jumping to conclusions, but it did increase a range of mild anomalous experiences including feelings of unreality, perceptual alterations, and temporal disintegration. Worry did not affect the occurrence of hallucinations. The study shows that a period of worry causes a range of subtle odd perceptual disturbances that are known to increase the likelihood of delusions. It demonstrates an interaction between affective and psychotic processes in patients with delusions.<br/
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