697 research outputs found

    Diffractive Phenomena and Shadowing in Deep-Inelastic Scattering

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    Shadowing effects in deep-inelastic lepton-nucleus scattering probe the mass spectrum of diffractive leptoproduction from individual nucleons. We explore this relationship using current experimental information on both processes. In recent data from the NMC and E665 collaboration, taken at small x << 0.1 and Q^2 < 1 GeV^2, shadowing is dominated by the diffractive excitation and coherent interaction of low mass vector mesons. If shadowing is explored at small x > 1 GeV^2 as discussed at HERA, the situation is different. Here dominant contributions come from the coherent interaction of diffractively produced heavy mass states. Furthermore we observe that the energy dependence of shadowing is directly related to the mass dependence of the diffractive production cross section for free nucleon targets.Comment: 12 pages Latex, 8 figure

    Quantitative cross-species extrapolation between humans and fish: The case of the anti-depressant fluoxetine

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    This article has been made available through the Brunel Open Access Publishing Fund.Fish are an important model for the pharmacological and toxicological characterization of human pharmaceuticals in drug discovery, drug safety assessment and environmental toxicology. However, do fish respond to pharmaceuticals as humans do? To address this question, we provide a novel quantitative cross-species extrapolation approach (qCSE) based on the hypothesis that similar plasma concentrations of pharmaceuticals cause comparable target-mediated effects in both humans and fish at similar level of biological organization (Read-Across Hypothesis). To validate this hypothesis, the behavioural effects of the anti-depressant drug fluoxetine on the fish model fathead minnow (Pimephales promelas) were used as test case. Fish were exposed for 28 days to a range of measured water concentrations of fluoxetine (0.1, 1.0, 8.0, 16, 32, 64 ΞΌg/L) to produce plasma concentrations below, equal and above the range of Human Therapeutic Plasma Concentrations (HTPCs). Fluoxetine and its metabolite, norfluoxetine, were quantified in the plasma of individual fish and linked to behavioural anxiety-related endpoints. The minimum drug plasma concentrations that elicited anxiolytic responses in fish were above the upper value of the HTPC range, whereas no effects were observed at plasma concentrations below the HTPCs. In vivo metabolism of fluoxetine in humans and fish was similar, and displayed bi-phasic concentration-dependent kinetics driven by the auto-inhibitory dynamics and saturation of the enzymes that convert fluoxetine into norfluoxetine. The sensitivity of fish to fluoxetine was not so dissimilar from that of patients affected by general anxiety disorders. These results represent the first direct evidence of measured internal dose response effect of a pharmaceutical in fish, hence validating the Read-Across hypothesis applied to fluoxetine. Overall, this study demonstrates that the qCSE approach, anchored to internal drug concentrations, is a powerful tool to guide the assessment of the sensitivity of fish to pharmaceuticals, and strengthens the translational power of the cross-species extrapolation

    New algorithm improves fine structure of the barley consensus SNP map

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    <p>Abstract</p> <p>Background</p> <p>The need to integrate information from multiple linkage maps is a long-standing problem in genetics. One way to visualize the complex ordinal relationships is with a directed graph, where each vertex in the graph is a bin of markers. When there are no ordering conflicts between the linkage maps, the result is a directed acyclic graph, or DAG, which can then be linearized to produce a consensus map.</p> <p>Results</p> <p>New algorithms for the simplification and linearization of consensus graphs have been implemented as a package for the R computing environment called DAGGER. The simplified consensus graphs produced by DAGGER exactly capture the ordinal relationships present in a series of linkage maps. Using either linear or quadratic programming, DAGGER generates a consensus map with minimum error relative to the linkage maps while remaining ordinally consistent with them. Both linearization methods produce consensus maps that are compressed relative to the mean of the linkage maps. After rescaling, however, the consensus maps had higher accuracy (and higher marker density) than the individual linkage maps in genetic simulations. When applied to four barley linkage maps genotyped at nearly 3000 SNP markers, DAGGER produced a consensus map with improved fine structure compared to the existing barley consensus SNP map. The root-mean-squared error between the linkage maps and the DAGGER map was 0.82 cM per marker interval compared to 2.28 cM for the existing consensus map. Examination of the barley hardness locus at the 5HS telomere, for which there is a physical map, confirmed that the DAGGER output was more accurate for fine structure analysis.</p> <p>Conclusions</p> <p>The R package DAGGER is an effective, freely available resource for integrating the information from a set of consistent linkage maps.</p

    Prevalence, types and demographic features of child labour among school children in Nigeria

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    BACKGROUND: To determine the prevalence, types and demographic features of child labour among school children in Nigeria. METHODS: A cross-sectional interview study of 1675 randomly selected public primary and secondary school pupils aged 5 to less than 18 years was conducted in the Sagamu Local Government Area of Ogun State, Nigeria from October 1998 to September 1999. RESULTS: The overall prevalence of child labour was 64.5%: 68.6% among primary and 50.3% among secondary school pupils. Major economic activities included street trading (43.6%), selling in kiosks and shops (25.4%) and farming (23.6%). No child was involved in bonded labour or prostitution. Girls were more often involved in labour activities than boys (66.8% versus 62.1%, p = 0.048): this difference was most obvious with street trading (p = 0.0004). Most of the children (82.2%) involved in labour activities did so on the instruction of one or both parents in order to contribute to family income. Children of parents with low socio-economic status or of poorly educated parents were significantly involved in labour activities (p = 0.01 and p = 0.001 respectively). Child labour was also significantly associated with increasing number of children in the family size (p = 0.002). A higher prevalence rate of child labour was observed among children living with parents and relations than among those living with unrelated guardians. CONCLUSION: It is concluded that smaller family size, parental education and family economic enhancement would reduce the pressure on parents to engage their children in labour activities

    Different Methods for Modelling Severe Hypoglycaemic Events : Implications for Effectiveness and Cost-Effectiveness Analyses

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    ObjectivesPublished clinical trials report severe hypoglycaemic events in different ways. Some report number of patients who suffered at least one event out of total number randomised and others report number of events for a given total exposure. The different data types can be modelled in different ways; therefore, three models have been used in published Bayesian Network Meta Analyses (NMAs) of hypoglycaemic events; models with a binomial likelihood reporting odds ratios (using a logit link) or hazard ratios (using the complementary log log link) and models with a Poisson likelihood reporting hazard ratios. The objective of this paper is to establish the impact of using different models on effectiveness estimates and the outputs from cost-effectiveness models.MethodsWe analysed a dataset used in a recent NMA conducted to inform NICE guideline recommendations regarding insulin choice for patients with type 1 diabetes using the three previously used models, plus a shared parameter model combining different types of data.ResultsThe relative treatment effects are similar regardless of which model or scale is used. Differences were seen when the probability of having an event on the baseline treatment was calculated using the different models with the logit model giving a baseline probability of 0.07, the clog-log 0.17 and the Poisson 0.29. These translate into differences of up to Β£110 in the cost of a hypoglycaemic event and 0.004 in associated disutility when calculating the absolute probabilities of an event to use in an economic model.ConclusionsWhile choice of outcome measure may not have a significant impact on relative effects for this outcome, care should be taken to ensure that the baseline probabilities used in an economic model are realistic and accurate to avoid over or underestimating costs and effects

    Sodium channel Nav1.6 accumulates at the site of infraorbital nerve injury

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    <p>Abstract</p> <p>Background</p> <p>Sodium channel (NaCh) expressions change following nerve and inflammatory lesions and this change may contribute to the activation of pain pathways. In a previous study we found a dramatic increase in the size and density of NaCh accumulations, and a remodeling of NaChs at intact and altered myelinated sites at a location just proximal to a combined partial axotomy and chromic suture lesion of the rat infraorbital nerve (ION) with the use of an antibody that identifies all NaCh isoforms. Here we evaluate the contribution of the major nodal NaCh isoform, Na<sub>v</sub>1.6, to this remodeling of NaChs following the same lesion. Sections of the ION from normal and ION lesioned subjects were double-stained with antibodies against Na<sub>v</sub>1.6 and caspr (contactin-associated protein; a paranodal protein to identify nodes of Ranvier) and then z-series of optically sectioned images were captured with a confocal microscope. ImageJ (NIH) software was used to quantify the average size and density of Na<sub>v</sub>1.6 accumulations, while additional single fiber analyses measured the axial length of the nodal gap, and the immunofluorescence intensity of Na<sub>v</sub>1.6 in nodes and of caspr in the paranodal region.</p> <p>Results</p> <p>The findings showed a significant increase in the average size and density of Na<sub>v</sub>1.6 accumulations in lesioned IONs when compared to normal IONs. The results of the single fiber analyses in caspr-identified typical nodes showed an increased axial length of the nodal gap, an increased immunofluorescence intensity of nodal Na<sub>v</sub>1.6 and a decreased immunofluorescence intensity of paranodal caspr in lesioned IONs when compared to normal IONs. In the lesioned IONs, Na<sub>v</sub>1.6 accumulations were also seen in association with altered caspr-relationships, such as heminodes.</p> <p>Conclusion</p> <p>The results of the present study identify Na<sub>v</sub>1.6 as one isoform involved in the augmentation and remodeling of NaChs at nodal sites following a combined partial axotomy and chromic suture ION lesion. The augmentation of Na<sub>v</sub>1.6 may result from an alteration in axon-Schwann cell signaling mechanisms as suggested by changes in caspr expression. The changes identified in this study suggest that the participation of Na<sub>v</sub>1.6 should be considered when examining changes in the excitability of myelinated axons in neuropathic pain models.</p

    Correlates of unintended pregnancy among currently pregnant married women in Nepal

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    <p>Abstract</p> <p>Background</p> <p>Women living in every country, irrespective of its development status, have been facing the problem of unintended pregnancy. Unintended pregnancy is an important public health issue in both developing and developed countries because of its negative association with the social and health outcomes for both mothers and children. This study aims to determine the prevalence and the factors influencing unintended pregnancy among currently pregnant married women in Nepal.</p> <p>Methods</p> <p>This paper reports on data drawn from Nepal Demographic and Health Survey (NDHS) which is a nationally representative survey. The analysis is restricted to currently pregnant married women at the time of survey. Association between unintended pregnancy and the explanatory variables was assessed in bivariate analysis using Chi-square tests. Logistic regression was used to assess the net effect of several independent variables on unintended pregnancy.</p> <p>Results</p> <p>More than two-fifth of the currently pregnant women (41%) reported that their current pregnancy was unintended. The results indicate that age of women, age at first marriage, ideal number of children, religion, exposure to radio and knowledge of family planning methods were key predictors of unintended pregnancy. Experience of unintended pregnancy augments with women's age (odds ratio, 1.11). Similarly, increase in the women's age at first marriage reduces the likelihood of unintended pregnancy (odds ratio, 0.93). Those who were exposed to the radio were less likely (odds ratio, 0.63) to have unintended pregnancy compared to those who were not. Furthermore, those women who had higher level of knowledge about family planning methods were less likely to experience unintended pregnancy (odds ratio, 0.60) compared to those having lower level of knowledge.</p> <p>Conclusion</p> <p>One of the important factors contributing to high level of maternal and infant mortality is unintended pregnancy. Programs should aim to reduce unintended pregnancy by focusing on all these identified factors so that infant and maternal mortality and morbidity as well as the need for abortion are decreased and the overall well-being of the family is maintained and enhanced.</p

    The Conserved Tarp Actin Binding Domain Is Important for Chlamydial Invasion

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    The translocated actin recruiting phosphoprotein (Tarp) is conserved among all pathogenic chlamydial species. Previous reports identified single C. trachomatis Tarp actin binding and proline rich domains required for Tarp mediated actin nucleation. A peptide antiserum specific for the Tarp actin binding domain was generated and inhibited actin polymerization in vitro and C. trachomatis entry in vivo, indicating an essential role for Tarp in chlamydial pathogenesis. Sequence analysis of Tarp orthologs from additional chlamydial species and C. trachomatis serovars indicated multiple putative actin binding sites. In order to determine whether the identified actin binding domains are functionally conserved, GST-Tarp fusions from multiple chlamydial species were examined for their ability to bind and nucleate actin. Chlamydial Tarps harbored variable numbers of actin binding sites and promoted actin nucleation as determined by in vitro polymerization assays. Our findings indicate that Tarp mediated actin binding and nucleation is a conserved feature among diverse chlamydial species and this function plays a critical role in bacterial invasion of host cells

    Guidelines for reporting embedded recruitment trials

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    Background: Recruitment to clinical trials is difficult with many trials failing to recruit to target and within time. Embedding trials of recruitment interventions within host trials may provide a successful way to improve this. There are no guidelines for reporting such embedded methodology trials. As part of the Medical Research Council funded Systematic Techniques for Assisting Recruitment to Trials (MRC START) programme designed to test interventions to improve recruitment to trials, we developed guidelines for reporting embedded trials. Methods: We followed a three-phase guideline development process: (1) pre-meeting literature review to generate items for the reporting guidelines; (2) face-to-face consensus meetings to draft the reporting guidelines; and (3)post-meeting feedback review, and pilot testing, followed by finalisation of the reporting guidelines. Results: We developed a reporting checklist based on the Consolidated Standards for Reporting Trials (CONSORT) statement 2010. Embedded trials evaluating recruitment interventions should follow the CONSORT statement 2010 and report all items listed as essential. We used a number of examples to illustrate key issues that arise in embedded trials and how best to report them, including (a) how to deal with description of the host trial; (b) the importance of describing items that may differ in the host and embedded trials (such as the setting and the eligible population); and (c) the importance of identifying clearly the point at which the recruitment interventions were embedded in the host trial. Conclusions: Implementation of these guidelines will improve the quality of reports of embedded recruitment trials while advancing the science, design and conduct of embedded trials as a whole
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