208 research outputs found
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Polymorphism discovery and association analyses of the interferon genes in type 1 diabetes.
BACKGROUND: The aetiology of the autoimmune disease type 1 diabetes (T1D) involves many genetic and environmental factors. Evidence suggests that innate immune responses, including the action of interferons, may also play a role in the initiation and/or pathogenic process of autoimmunity. In the present report, we have adopted a linkage disequilibrium (LD) mapping approach to test for an association between T1D and three regions encompassing 13 interferon alpha (IFNA) genes, interferon omega-1 (IFNW1), interferon beta-1 (IFNB1), interferon gamma (IFNG) and the interferon consensus-sequence binding protein 1 (ICSBP1). RESULTS: We identified 238 variants, most, single nucleotide polymorphisms (SNPs), by sequencing IFNA, IFNB1, IFNW1 and ICSBP1, 98 of which where novel when compared to dbSNP build 124. We used polymorphisms identified in the SeattleSNP database for INFG. A set of tag SNPs was selected for each of the interferon and interferon-related genes to test for an association between T1D and this complex gene family. A total of 45 tag SNPs were selected and genotyped in a collection of 472 multiplex families. CONCLUSION: We have developed informative sets of SNPs for the interferon and interferon related genes. No statistical evidence of a major association between T1D and any of the interferon and interferon related genes tested was found.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are
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Discovery, linkage disequilibrium and association analyses of polymorphisms of the immune complement inhibitor, decay-accelerating factor gene (DAF/CD55) in type 1 diabetes.
BACKGROUND: Type 1 diabetes (T1D) is a common autoimmune disease resulting from T-cell mediated destruction of pancreatic beta cells. Decay accelerating factor (DAF, CD55), a glycosylphosphatidylinositol-anchored membrane protein, is a candidate for autoimmune disease susceptibility based on its role in restricting complement activation and evidence that DAF expression modulates the phenotype of mice models for autoimmune disease. In this study, we adopt a linkage disequilibrium (LD) mapping approach to test for an association between the DAF gene and T1D. RESULTS: Initially, we used HapMap II genotype data to examine LD across the DAF region. Additional resequencing was required, identifying 16 novel polymorphisms. Combining both datasets, a LD mapping approach was adopted to test for association with T1D. Seven tag SNPs were selected and genotyped in case-control (3,523 cases and 3,817 controls) and family (725 families) collections. CONCLUSION: We obtained no evidence of association between T1D and the DAF region in two independent collections. In addition, we assessed the impact of using only HapMap II genotypes for the selection of tag SNPs and, based on this study, found that HapMap II genotypes may require additional SNP discovery for comprehensive LD mapping of some genes in common disease.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are
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Development of an integrated genome informatics, data management and workflow infrastructure: a toolbox for the study of complex disease genetics.
The genetic dissection of complex disease remains a significant challenge. Sample-tracking and the recording, processing and storage of high-throughput laboratory data with public domain data, require integration of databases, genome informatics and genetic analyses in an easily updated and scaleable format. To find genes involved in multifactorial diseases such as type 1 diabetes (T1D), chromosome regions are defined based on functional candidate gene content, linkage information from humans and animal model mapping information. For each region, genomic information is extracted from Ensembl, converted and loaded into ACeDB for manual gene annotation. Homology information is examined using ACeDB tools and the gene structure verified. Manually curated genes are extracted from ACeDB and read into the feature database, which holds relevant local genomic feature data and an audit trail of laboratory investigations. Public domain information, manually curated genes, polymorphisms, primers, linkage and association analyses, with links to our genotyping database, are shown in Gbrowse. This system scales to include genetic, statistical, quality control (QC) and biological data such as expression analyses of RNA or protein, all linked from a genomics integrative display. Our system is applicable to any genetic study of complex disease, of either large or small scale.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are
T1DBase: integration and presentation of complex data for type 1 diabetes research
T1DBase () [Smink et al. (2005) Nucleic Acids Res., 33, D544–D549; Burren et al. (2004) Hum. Genomics, 1, 98–109] is a public website and database that supports the type 1 diabetes (T1D) research community. T1DBase provides a consolidated T1D-oriented view of the complex data world that now confronts medical researchers and enables scientists to navigate from information they know to information that is new to them. Overview pages for genes and markers summarize information for these elements. The Gene Dossier summarizes information for a list of genes. GBrowse [Stein et al. (2002) Genome Res., 10, 1599–1610] displays genes and other features in their genomic context, and Cytoscape [Shannon et al. (2003) Genome Res., 13, 2498–2504] shows genes in the context of interacting proteins and genes. The Beta Cell Gene Atlas shows gene expression in β cells, islets, and related cell types and lines, and the Tissue Expression Viewer shows expression across other tissues. The Microarray Viewer shows expression from more than 20 array experiments. The Beta Cell Gene Expression Bank contains manually curated gene and pathway annotations for genes expressed in β cells. T1DMart is a query tool for markers and genotypes. PosterPages are ‘home pages’ about specific topics or datasets. The key challenge, now and in the future, is to provide powerful informatics capabilities to T1D scientists in a form they can use to enhance their research
Error-analysis and comparison to analytical models of numerical waveforms produced by the NRAR Collaboration
The Numerical-Relativity-Analytical-Relativity (NRAR) collaboration is a
joint effort between members of the numerical relativity, analytical relativity
and gravitational-wave data analysis communities. The goal of the NRAR
collaboration is to produce numerical-relativity simulations of compact
binaries and use them to develop accurate analytical templates for the
LIGO/Virgo Collaboration to use in detecting gravitational-wave signals and
extracting astrophysical information from them. We describe the results of the
first stage of the NRAR project, which focused on producing an initial set of
numerical waveforms from binary black holes with moderate mass ratios and
spins, as well as one non-spinning binary configuration which has a mass ratio
of 10. All of the numerical waveforms are analysed in a uniform and consistent
manner, with numerical errors evaluated using an analysis code created by
members of the NRAR collaboration. We compare previously-calibrated,
non-precessing analytical waveforms, notably the effective-one-body (EOB) and
phenomenological template families, to the newly-produced numerical waveforms.
We find that when the binary's total mass is ~100-200 solar masses, current EOB
and phenomenological models of spinning, non-precessing binary waveforms have
overlaps above 99% (for advanced LIGO) with all of the non-precessing-binary
numerical waveforms with mass ratios <= 4, when maximizing over binary
parameters. This implies that the loss of event rate due to modelling error is
below 3%. Moreover, the non-spinning EOB waveforms previously calibrated to
five non-spinning waveforms with mass ratio smaller than 6 have overlaps above
99.7% with the numerical waveform with a mass ratio of 10, without even
maximizing on the binary parameters.Comment: 51 pages, 10 figures; published versio
Clinical Equivalence of Generic Clozapine
Objective: To determine if mental health service utilization increases when patients are converted to generic clozapine.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44320/1/10597_2005_Article_5981.pd
A relação entre o nÃvel voluntário de transparência e o custo de capital próprio das empresas brasileiras não-financeiras
O objetivo principal desta pesquisa é verificar empiricamente a existência de relação significativa entre o nÃvel de disclosure voluntário de informações e custo de capital próprio de empresas brasileiras não financeiras. É esperado que um maior nÃvel de disclosure esteja relacionado a um menor custo de capital próprio pela redução do risco percebido pelos investidores. A fim de medir o nÃvel de disclosure voluntário das empresas foi utilizado um questionário desenvolvido para este fim. O custo de capital próprio foi obtido com base em informações publicamente disponÃveis das empresas. Foi encontrada uma relação negativa e significante entre as variáveis de interesse, indicando que as empresas que mais divulgam informações voluntariamente conseguem captar capital próprio a uma taxa mais barata
Outcomes of obstructed abdominal wall hernia: results from the UK national small bowel obstruction audit
Background:
Abdominal wall hernia is a common surgical condition. Patients may present in an emergency with bowel obstruction, incarceration or strangulation. Small bowel obstruction (SBO) is a serious surgical condition associated with significant morbidity. The aim of this study was to describe current management and outcomes of patients with obstructed hernia in the UK as identified in the National Audit of Small Bowel Obstruction (NASBO).
Methods:
NASBO collated data on adults treated for SBO at 131 UK hospitals between January and March 2017. Those with obstruction due to abdominal wall hernia were included in this study. Demographics, co-morbidity, imaging, operative treatment, and in-hospital outcomes were recorded. Modelling for factors associated with mortality and complications was undertaken using Cox proportional hazards and multivariable regression modelling.
Results:
NASBO included 2341 patients, of whom 415 (17·7 per cent) had SBO due to hernia. Surgery was performed in 312 (75·2 per cent) of the 415 patients; small bowel resection was required in 198 (63·5 per cent) of these operations. Non-operative management was reported in 35 (54 per cent) of 65 patients with a parastomal hernia and in 34 (32·1 per cent) of 106 patients with an incisional hernia. The in-hospital mortality rate was 9·4 per cent (39 of 415), and was highest in patients with a groin hernia (11·1 per cent, 17 of 153). Complications were common, including lower respiratory tract infection in 16·3 per cent of patients with a groin hernia. Increased age was associated with an increased risk of death (hazard ratio 1·05, 95 per cent c.i. 1·01 to 1·10; P = 0·009) and complications (odds ratio 1·05, 95 per cent c.i. 1·02 to 1·09; P = 0·001).
Conclusion:
NASBO has highlighted poor outcomes for patients with SBO due to hernia, highlighting the need for quality improvement initiatives in this group
Relative equity market valuation conditions and acquirers’ gains
We examine whether the relative equity market valuation conditions (EMVCs) in the merging firms countries help acquirers’ managers to time the announcements of domestic and foreign target acquisitions. After controlling for several deal- and merging firms-specific features we find that acquisition activity, as well as acquirers gains, are significantly higher during periods of high-EMVCs at home, irrespective of the domicile of the target. We also find that the higher foreign acquirers’ gains that reaped during periods of high-EMVCs at home are realized by deals of targets based in the RoW (=World-G7), rather than G6 (=G7-UK) countries, which is due to the low correlation of EMVCs between the U.K. (home) and the RoW countries. Moreover, acquisition of targets domiciled in the RoW (G6) countries yield higher (lower) gains than domestic targets during periods of high-EMVCs at home. This suggests that the relative EMVCs between the merging firms’ countries allow acquirers’ managers to time the market and acquire targets at a discount, particularly in countries in which acquirers’ stocks are likely to be more overvalued than the targets’ stocks
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