| 1. |
- Debette, Stéphanie, et al.
(författare)
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Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 47, s. 78-83
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Tidskriftsartikel (refereegranskat)abstract
- Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year)1. Minor cervical traumas, infection, migraine and hypertension are putative risk factors1–3, and inverse associations with obesity and hypercholesterolemia are described3,4. No confirmed genetic susceptibility factors have been identified using candidate gene approaches5. We performed genome-wide association studies (GWAS) in 1 1,393 CeAD cases and 1 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69–0.82; P = 4.46 × 1 10−10), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 1 × 1 10−3; combined P = 1 1.00 × 1 10−1111). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction6–9. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.
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| 2. |
- Polach, Oldrich, et al.
(författare)
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Validation of simulation models in the context of railway vehicle acceptance
- 2015
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Ingår i: Proceedings of the Institution of mechanical engineers. Part F, journal of rail and rapid transit. - : SAGE Publications. - 0954-4097 .- 2041-3017. ; 229:6, s. 729-754
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Tidskriftsartikel (refereegranskat)abstract
- The evaluation of a reliable validation method, criteria and limit values suitable for model validation in the context of vehicle acceptance was one of the objectives of the DynoTRAIN project. The presented investigations represent a unique amount of testing, simulations, comparisons with measurements, and validation evaluations. The on-track measurements performed in four European countries included several different vehicles on a test train equipped to simultaneously record track irregularities and rail profiles. The simulations were performed using vehicle models built with the use of different simulation tools by different partners. The comparisons between simulation and measurement results were conducted for over 1000 simulations using a set of the same test sections for all vehicle models. The results were assessed by three different validation approaches: comparing values according to EN 14363; by subjective engineering judgement by project partners; and using so-called validation metrics, i.e. computable measures developed with the aim of increasing objectivity while still maintaining the level of agreement with engineering judgement. The proposed validation method uses the values computed by analogy with EN 14363 and provides validation limits that can be applied to a set of deviations between simulation and measurement values.
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| 3. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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