8 research outputs found

    Genetics and epidemiology of mutational barcode-defined clonal hematopoiesis

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    Publisher Copyright: © 2023, The Author(s).Clonal hematopoiesis (CH) arises when a substantial proportion of mature blood cells is derived from a single hematopoietic stem cell lineage. Using whole-genome sequencing of 45,510 Icelandic and 130,709 UK Biobank participants combined with a mutational barcode method, we identified 16,306 people with CH. Prevalence approaches 50% in elderly participants. Smoking demonstrates a dosage-dependent impact on risk of CH. CH associates with several smoking-related diseases. Contrary to published claims, we find no evidence that CH is associated with cardiovascular disease. We provide evidence that CH is driven by genes that are commonly mutated in myeloid neoplasia and implicate several new driver genes. The presence and nature of a driver mutation alters the risk profile for hematological disorders. Nevertheless, most CH cases have no known driver mutations. A CH genome-wide association study identified 25 loci, including 19 not implicated previously in CH. Splicing, protein and expression quantitative trait loci were identified for CD164 and TCL1A.Peer reviewe

    The Helicobacter pylori Genome Project : insights into H. pylori population structure from analysis of a worldwide collection of complete genomes

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    Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics

    Climate change and primary industries : Impacts, adaptation and mitigation in the Nordic countries

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    Climate change is expected to have a profound impact on natural resources, and thus on the primary industries (agriculture, forestry and fisheries) in the Nordic countries. Climate change induces risks but also creates possibilities for new production systems on land and in the ocean. Climatic changes also represent great challenges for policy-making and management regimes. The current knowledge base on natural resources in the Nordic region needs to be expanded to fully address the impacts of climate change. In particular it is important to address the need for improved policies and new policy instruments. The research programme Climate Change Impacts, Adaptation and Mitigation in Nordic Primary Industries is a coordinated set of thematic research networks with the objective to create a Nordic knowledge base on climate change interactions with primary industries in the Nordic region

    Occupational issues of adults with ADHD

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    Background: ADHD is a common neurodevelopmental disorder that persists into adulthood. Its symptoms cause impairments in a number of social domains, one of which is employment. We wish to produce a consensus statement on how ADHD affects employment. Methods: This consensus development conference statement was developed as a result of a joint international meeting held in July 2010. The consensus committee was international in scope (United Kingdom, mainland Europe, United Arab Emirates) and consisted of individuals from a broad range of backgrounds (Psychiatry, Occupational Medicine, Health Economists, Disability Advisors). The objectives of the conference were to discuss some of the occupational impairments adults with ADHD may face and how to address these problems from an inclusive perspective. Furthermore the conference looked at influencing policy and decision making at a political level to address impaired occupational functioning in adults with ADHD and fears around employing people with disabilities in general. Results: The consensus was that there were clear weaknesses in the current arrangements in the UK and internationally to address occupational difficulties. More so, Occupational Health was not wholly integrated and used as a means of making positive changes to the workplace, but rather as a superfluous last resort that employers tried to avoid. Furthermore the lack of cross professional collaboration on occupational functioning in adults with ADHD was a significant problem. Conclusions: Future research needs to concentrate on further investigating occupational functioning in adults with ADHD and pilot exploratory initiatives and tools, leading to a better and more informed understanding of possible barriers to employment and potential schemes to put in place to address these problems
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