408 research outputs found

    Protocol for the Smoking, Nicotine and Pregnancy (SNAP) trial: double-blind, placebo-randomised, controlled trial of nicotine replacement therapy in pregnancy

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    Background: Smoking in pregnancy remains a public health challenge. Nicotine replacement therapy (NRT) is effective for smoking cessation in non-pregnant people, but because women metabolise nicotine and cotinine much faster in pregnancy, it is unclear whether this will be effective for smoking cessation in pregnancy. The NHS Health Technology Assessment Programme (HTA)-funded smoking, nicotine and pregnancy ( SNAP) trial will investigate whether or not nicotine replacement therapy ( NRT) is effective, cost-effective and safe when used for smoking cessation by pregnant women. Methods/Design: Over two years, in 5 trial centres, 1050 pregnant women who are between 12 and 24 weeks pregnant will be randomised as they attend hospital for ante-natal ultrasound scans. Women will receive either nicotine or placebo transdermal patches with behavioural support. The primary outcome measure is biochemically-validated, self-reported, prolonged and total abstinence from smoking between a quit date ( defined before randomisation and set within two weeks of this) and delivery. At six months after childbirth self-reported maternal smoking status will be ascertained and two years after childbirth, self-reported maternal smoking status and the behaviour, cognitive development and respiratory symptoms of children born in the trial will be compared in both groups. Discussion: This trial is designed to ascertain whether or not standard doses of NRT ( as transdermal patches) are effective and safe when used for smoking cessation during pregnancy

    Prevalence of maternal smoking and environmental tobacco smoke exposure during pregnancy and impact on birth weight: retrospective study using Millennium Cohort

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    <p>Abstract</p> <p>Background</p> <p>Meta-analyses of studies investigating the impact of maternal environmental tobacco smoke (ETS) on birth weight have not produced robust findings. Although, ante natal ETS exposure probably reduces infant's birth weights, the scale of this exposure remains unknown. We conducted a large, cohort study to assess the impact of ETS exposure on birth weight whilst adjusting for the many factors known to influence this.</p> <p>Method</p> <p>Retrospective study using interview data from parents of 18,297 children born in 2000/2001 and living in the UK 9 months afterwards (the Millennium Cohort Survey). Comparison of birth weight, sex and gestational age specific (SGA) z score, birth before 37 weeks and birth weight < 2.5 Kg (LBW) in infants born to women exposed to: i) no tobacco smoke, ii) ETS only and iii) maternal smoking whilst pregnant.</p> <p>Results</p> <p>13% of UK infants were exposed to ETS and 36% to maternal smoking ante natally. Compared to no ante natal tobacco smoke exposure, domestic ETS lowered infants' adjusted mean birth weights by 36 g (95% CI, 5 g to 67 g) and this effect showed a dose-response relationship. ETS exposure also caused non-significant increases in the adjusted risks of Low Birth Weight (<2.5 Kg) [OR 1.23 (95% CI, 0.96 to 1.58) and premature birth [OR 1.21 (95% CI, 0.96 to 1.51)], whilst the impacts of maternal smoking were greater and statistically significant.</p> <p>Conclusion</p> <p>UK prevalences of domestic ETS exposure and maternal smoking in pregnancy remain high and ETS exposure lowers infants' birth weights.</p

    Monoamine Oxidase A (MAOA) Gene and Personality Traits from Late Adolescence through Early Adulthood: A Latent Variable Investigation.

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    Very few molecular genetic studies of personality traits have used longitudinal phenotypic data, therefore molecular basis for developmental change and stability of personality remains to be explored. We examined the role of the monoamine oxidase A gene (MAOA) on extraversion and neuroticism from adolescence to adulthood, using modern latent variable methods. A sample of 1,160 male and 1,180 female participants with complete genotyping data was drawn from a British national birth cohort, the MRC National Survey of Health and Development (NSHD). The predictor variable was based on a latent variable representing genetic variations of the MAOA gene measured by three SNPs (rs3788862, rs5906957, and rs979606). Latent phenotype variables were constructed using psychometric methods to represent cross-sectional and longitudinal phenotypes of extraversion and neuroticism measured at ages 16 and 26. In males, the MAOA genetic latent variable (AAG) was associated with lower extraversion score at age 16 (β = -0.167; CI: -0.289, -0.045; p = 0.007, FDRp = 0.042), as well as greater increase in extraversion score from 16 to 26 years (β = 0.197; CI: 0.067, 0.328; p = 0.003, FDRp = 0.036). No genetic association was found for neuroticism after adjustment for multiple testing. Although, we did not find statistically significant associations after multiple testing correction in females, this result needs to be interpreted with caution due to issues related to x-inactivation in females. The latent variable method is an effective way of modeling phenotype- and genetic-based variances and may therefore improve the methodology of molecular genetic studies of complex psychological traits

    GOSim – an R-package for computation of information theoretic GO similarities between terms and gene products

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    <p>Abstract</p> <p>Background</p> <p>With the increased availability of high throughput data, such as DNA microarray data, researchers are capable of producing large amounts of biological data. During the analysis of such data often there is the need to further explore the similarity of genes not only with respect to their expression, but also with respect to their functional annotation which can be obtained from Gene Ontology (GO).</p> <p>Results</p> <p>We present the freely available software package <it>GOSim</it>, which allows to calculate the functional similarity of genes based on various information theoretic similarity concepts for GO terms. <it>GOSim </it>extends existing tools by providing additional lately developed functional similarity measures for genes. These can e.g. be used to cluster genes according to their biological function. Vice versa, they can also be used to evaluate the homogeneity of a given grouping of genes with respect to their GO annotation. <it>GOSim </it>hence provides the researcher with a flexible and powerful tool to combine knowledge stored in GO with experimental data. It can be seen as complementary to other tools that, for instance, search for significantly overrepresented GO terms within a given group of genes.</p> <p>Conclusion</p> <p><it>GOSim </it>is implemented as a package for the statistical computing environment <it>R </it>and is distributed under GPL within the CRAN project.</p

    Simplified Models for LHC New Physics Searches

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    This document proposes a collection of simplified models relevant to the design of new-physics searches at the LHC and the characterization of their results. Both ATLAS and CMS have already presented some results in terms of simplified models, and we encourage them to continue and expand this effort, which supplements both signature-based results and benchmark model interpretations. A simplified model is defined by an effective Lagrangian describing the interactions of a small number of new particles. Simplified models can equally well be described by a small number of masses and cross-sections. These parameters are directly related to collider physics observables, making simplified models a particularly effective framework for evaluating searches and a useful starting point for characterizing positive signals of new physics. This document serves as an official summary of the results from the "Topologies for Early LHC Searches" workshop, held at SLAC in September of 2010, the purpose of which was to develop a set of representative models that can be used to cover all relevant phase space in experimental searches. Particular emphasis is placed on searches relevant for the first ~50-500 pb-1 of data and those motivated by supersymmetric models. This note largely summarizes material posted at http://lhcnewphysics.org/, which includes simplified model definitions, Monte Carlo material, and supporting contacts within the theory community. We also comment on future developments that may be useful as more data is gathered and analyzed by the experiments.Comment: 40 pages, 2 figures. This document is the official summary of results from "Topologies for Early LHC Searches" workshop (SLAC, September 2010). Supplementary material can be found at http://lhcnewphysics.or

    People of the British Isles: preliminary analysis of genotypes and surnames in a UK control population

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    There is a great deal of interest in fine scale population structure in the UK, both as a signature of historical immigration events and because of the effect population structure may have on disease association studies. Although population structure appears to have a minor impact on the current generation of genome-wide association studies, it is likely to play a significant part in the next generation of studies designed to search for rare variants. A powerful way of detecting such structure is to control and document carefully the provenance of the samples involved. Here we describe the collection of a cohort of rural UK samples (The People of the British Isles), aimed at providing a well-characterised UK control population that can be used as a resource by the research community as well as providing fine scale genetic information on the British population. So far, some 4,000 samples have been collected, the majority of which fit the criteria of coming from a rural area and having all four grandparents from approximately the same area. Analysis of the first 3,865 samples that have been geocoded indicates that 75% have a mean distance between grandparental places of birth of 37.3km, and that about 70% of grandparental places of birth can be classed as rural. Preliminary genotyping of 1,057 samples demonstrates the value of these samples for investigating fine scale population structure within the UK, and shows how this can be enhanced by the use of surnames

    Simulating a base population in honey bee for molecular genetic studies

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    <p>Abstract</p> <p>Background</p> <p>Over the past years, reports have indicated that honey bee populations are declining and that infestation by an ecto-parasitic mite (<it>Varroa destructor</it>) is one of the main causes. Selective breeding of resistant bees can help to prevent losses due to the parasite, but it requires that a robust breeding program and genetic evaluation are implemented. Genomic selection has emerged as an important tool in animal breeding programs and simulation studies have shown that it yields more accurate breeding value estimates, higher genetic gain and low rates of inbreeding. Since genomic selection relies on marker data, simulations conducted on a genomic dataset are a pre-requisite before selection can be implemented. Although genomic datasets have been simulated in other species undergoing genetic evaluation, simulation of a genomic dataset specific to the honey bee is required since this species has a distinct genetic and reproductive biology. Our software program was aimed at constructing a base population by simulating a random mating honey bee population. A forward-time population simulation approach was applied since it allows modeling of genetic characteristics and reproductive behavior specific to the honey bee.</p> <p>Results</p> <p>Our software program yielded a genomic dataset for a base population in linkage disequilibrium. In addition, information was obtained on (1) the position of markers on each chromosome, (2) allele frequency, (3) χ<sup>2</sup> statistics for Hardy-Weinberg equilibrium, (4) a sorted list of markers with a minor allele frequency less than or equal to the input value, (5) average r<sup>2</sup> values of linkage disequilibrium between all simulated marker loci pair for all generations and (6) average r<sup>2</sup> value of linkage disequilibrium in the last generation for selected markers with the highest minor allele frequency.</p> <p>Conclusion</p> <p>We developed a software program that takes into account the genetic and reproductive biology specific to the honey bee and that can be used to constitute a genomic dataset compatible with the simulation studies necessary to optimize breeding programs. The source code together with an instruction file is freely accessible at <url>http://msproteomics.org/Research/Misc/honeybeepopulationsimulator.html</url></p

    Time-Space Clustering of Human Brucellosis, California, 1973–1992 1

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    Infection with Brucella spp. continues to pose a human health risk in California despite great strides in eradicating the disease from domestic animals. Clustering of human cases in time and space has important public health implications for understanding risk factors and sources of infection. Temporal-spatial clustering of human brucellosis in California for the 20-year period 1973–1992 was evaluated by the Ederer-Myers-Mantel, Moran’s I, and population-adjusted Moran’s I procedures. Cases were clustered in concentrated agricultural regions in the first 5-year interval (1973–1977). Time-space clustering of human brucellosis cases in California late in the 20-year study period may reflect the distribution of Hispanic populations. Public health programs in California should focus on educating Hispanic populations about the risk of consuming dairy products, such as soft cheeses, made from unpasteurized milk
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