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Sökning: WFRF:(Topp S)

  • Resultat 1-10 av 29
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  • van Rheenen, W, et al. (författare)
  • Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
  • 2021
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 53:12, s. 1636-
  • Tidskriftsartikel (refereegranskat)abstract
    • Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.
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  • Rees, R. M., et al. (författare)
  • Nitrous oxide emissions from European agriculture - an analysis of variability and drivers of emissions from field experiments
  • 2013
  • Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4170 .- 1726-4189. ; 10:4, s. 2671-2682
  • Tidskriftsartikel (refereegranskat)abstract
    • Nitrous oxide emissions from a network of agricultural experiments in Europe and Zimbabwe were used to explore the relative importance of site and management controls of emissions. At each site, a selection of management interventions were compared within replicated experimental designs in plot based experiments. Arable experiments were conducted at Beano in Italy, El Encin in Spain, Foulum in Denmark, Logården in Sweden, Maulde in Belgium, Paulinenaue in Germany, Harare in Zimbabwe and Tulloch in the UK. Grassland experiments were conducted at Crichton, Nafferton and Peaknaze in the UK, Gödöllö in Hungary, Rzecin in Poland, Zarnekow in Germany and Theix in France. Nitrous oxide emissions were measured at each site over a period of at least two years using static chambers. Emissions varied widely between sites and as a result of manipulation treatments. Average site emissions (throughout the study period) varied between 0.04 and 21.21 kg N2O-N ha−1 yr−1, with the largest fluxes and variability associated with the grassland sites. Total nitrogen addition was found to be the single most important determinant of emissions, accounting for 15% of the variance (using linear regression) in the data from the arable sites (p < 0.0001), and 77% in the grassland sites. The annual emissions from arable sites were significantly greater than those that would be predicted by IPCC default emission factors. Variability in N2O within sites that occurred as a result of manipulation treatments was greater than that resulting from site to site and year to year variation, highlighting the importance of management interventions in contributing to greenhouse gas mitigation.
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  • Boxall, A. B. A., et al. (författare)
  • Pharmaceuticals and Personal Care Products in the Environment: What Are the Big Questions?
  • 2012
  • Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 120:9, s. 1221-1229
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Over the past 10-15 years, a substantial amount of work has been done by the scientific, regulatory, and business communities to elucidate the effects and risks of pharmaceuticals and personal care products (PPCPs) in the environment. OBJECTIVE: This review was undertaken to identify key outstanding issues regarding the effects of PPCPs on human and ecological health in order to ensure that future resources will be focused on the most important areas. DATA SOURCES: To better understand and manage the risks of PPCPs in the environment, we used the "key question" approach to identify the principle issues that need to be addressed. Initially, questions were solicited from academic, government, and business communities around the world. A list of 101 questions was then discussed at an international expert workshop, and a top-20 list was developed. Following the workshop, workshop attendees ranked the 20 questions by importance. DATA SYNTHESIS: The top 20 priority questions fell into seven categories: a) prioritization of substances for assessment, b) pathways of exposure, c) bioavailability and uptake, a effects characterization, e) risk and relative risk, f) antibiotic resistance, and g) risk management. CONCLUSIONS: A large body of information is now available on PPCPs in the environment. This exercise prioritized the most critical questions to aid in development of future research programs on the topic.
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  • Jarvis, S., et al. (författare)
  • Case gender and severity in cerebral palsy varies with intrauterine growth
  • 2005
  • Ingår i: Arch Dis Child. - 1468-2044. ; 90:5, s. 474-9
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: There is an unexplained excess of cerebral palsy among male babies. There is also variation in the proportion of more severe cases by birth weight. It has recently been shown that the rate of cerebral palsy increases as intrauterine size deviates up or down from an optimum about one standard deviation heavier than population mean weight-for-gestation. AIMS: To determine whether the gender ratio or the severity of cases also varies with intrauterine size. METHODS: A total of 3454 cases of cerebral palsy among single births between 1976 and 1990 with sufficient data to assign case severity (based on intellectual impairment and walking ability) and to compare weight-for-gestation at birth to sex specific fetal growth standards, were aggregated from nine separate registers in five European countries. RESULTS: The greater the degree to which growth deviates either up or down from optimal weight-for-gestation at birth, the higher is the rate of cerebral palsy, the larger is the proportion of male cases, and the more severe is the functional disability. Compared to those with optimum growth the risk of more severe cerebral palsy in male babies is 16 times higher for those with a birth weight below the 3rd centile and four times higher when birth weight is above the 97th centile. In contrast, for mild cerebral palsy in female babies the excess risks at these growth extremes are about half these magnitudes. CONCLUSIONS: Among singleton children with cerebral palsy, abnormal intrauterine size, either small or large, is associated with more severe disability and male sex.
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