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- Saevarsdottir, S., et al.
(författare)
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Multiomics analysis of rheumatoid arthritis yields sequence variants that have large effects on risk of the seropositive subset
- 2022
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 81:8
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To find causal genes for rheumatoid arthritis (RA) and its seropositive (RF and/or ACPA positive) and seronegative subsets. Methods We performed a genome-wide association study (GWAS) of 31 313 RA cases (68% seropositive) and similar to 1 million controls from Northwestern Europe. We searched for causal genes outside the HLA-locus through effect on coding, mRNA expression in several tissues and/or levels of plasma proteins (SomaScan) and did network analysis (Qiagen). Results We found 25 sequence variants for RA overall, 33 for seropositive and 2 for seronegative RA, altogether 37 sequence variants at 34 non-HLA loci, of which 15 are novel. Genomic, transcriptomic and proteomic analysis of these yielded 25 causal genes in seropositive RA and additional two overall. Most encode proteins in the network of interferon-alpha/beta and IL-12/23 that signal through the JAK/STAT-pathway. Highlighting those with largest effect on seropositive RA, a rare missense variant in STAT4 (rs140675301-A) that is independent of reported non-coding STAT4-variants, increases the risk of seropositive RA 2.27-fold (p=2.1x10(-9)), more than the rs2476601-A missense variant in PTPN22 (OR=1.59, p=1.3x10(-160)). STAT4 rs140675301-A replaces hydrophilic glutamic acid with hydrophobic valine (Glu128Val) in a conserved, surface-exposed loop. A stop-mutation (rs76428106-C) in FLT3 increases seropositive RA risk (OR=1.35, p=6.6x10(-11)). Independent missense variants in TYK2 (rs34536443-C, rs12720356-C, rs35018800-A, latter two novel) associate with decreased risk of seropositive RA (ORs=0.63-0.87, p=10(-9)-10(-27)) and decreased plasma levels of interferon-alpha/beta receptor 1 that signals through TYK2/JAK1/STAT4. Conclusion Sequence variants pointing to causal genes in the JAK/STAT pathway have largest effect on seropositive RA, while associations with seronegative RA remain scarce.
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- Castro-Tirado, A. J., et al.
(författare)
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GRB 030227 : The first multiwavelength afterglow of an INTEGRAL GRB
- 2003
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 411:1, s. 315-319
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Tidskriftsartikel (refereegranskat)abstract
- We present multiwavelength observations of a gamma-ray burst detected byINTEGRAL (GRB 030227) between 5.3 hours and ~ 1.7days after the event. Here we report the discovery of a dim opticalafterglow (OA) that would not have been detected by many previoussearches due to its faintess (R ~ 23). This OA was seen to declinefollowing a power law decay with index alpha R = -0.95 +/-0.16. The spectral index beta_ opt/NIR yielded -1.25 +/- 0.14. Thesevalues may be explained by a relativistic expansion of a fireball (withp = 2.0) in the cooling regime. We also find evidence for inverseCompton scattering in X-rays.Based on observations with INTEGRAL, an ESA project with instruments andscience data centre funded by ESA member states (especially the PIcountries: Denmark, France, Germany, Italy, Switzerland, Spain), CzechRepublic and Poland, and with the participation of Russia and the USA.Also partially based on observations collected by the Gamma-Ray BurstCollaboration at ESO (GRACE) at the European Southern Observatory, Chile(ESO Large Programme 165.H-0464).
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- Chernet, Selam, 1984, et al.
(författare)
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Online variation of wind turbine controller parameter for mitigation of SSR in DFIG based wind farms
- 2017
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Ingår i: ECCE 2016 - IEEE Energy Conversion Congress and Exposition, Proceedings. - 2329-3721. - 9781509007370 ; , s. Article no 7855310-
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Konferensbidrag (refereegranskat)abstract
- The aim of this paper is to investigate the risk for Subsynchronous Resonance (SSR) conditions in Doubly Fed Induction Generator (DFIG) based wind farms connected to series-compensated transmission lines. The well-known IEEE First Benchmark Model for SSR studies is adopted and the impact of the turbine controller parameters on the risk for unstable conditions is analyzed. In particular, it is shown through frequency domain studies that a reduction of the closed-loop bandwidth of the current controller that regulates the rotor current effectively reduces the risk for SSR. Simulation results are presented to validate the theoretical findings.
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- Gallo, Valentina, et al.
(författare)
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Smoking and risk for amyotrophic lateral sclerosis : analysis of the EPIC cohort
- 2009
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Ingår i: Annals of Neurology. - New York : J. Wiley & Sons. - 0364-5134 .- 1531-8249. ; 65:4, s. 378-385
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Cigarette smoking has been reported as "probable" risk factor for Amyotrophic Lateral Sclerosis (ALS), a poorly understood disease in terms of aetiology. The extensive longitudinal data of the European Prospective Investigation into Cancer and Nutrition (EPIC) were used to evaluate age-specific mortality rates from ALS and the role of cigarette smoking on the risk of dying from ALS. Methods: A total of 517,890 healthy subjects were included, resulting in 4,591,325 person-years. ALS cases were ascertained through death certificates. Cox hazard models were built to investigate the role of smoking on the risk of ALS, using packs/years and smoking duration to study dose-response. Results: A total of 118 subjects died from ALS, resulting in a crude mortality rate of 2.69 per 100,000/year. Current smokers at recruitment had an almost two-fold increased risk of dying from ALS compared to never smokers (HR = 1.89, 95% C.I. 1.14-3.14), while former smokers at the time of enrollment had a 50% increased risk (HR = 1.48, 95% C.I. 0.94-2.32). The number of years spent smoking increased the risk of ALS (p for trend = 0.002). Those who smoked more than 33 years had more than a two-fold increased risk of ALS compared with never smokers (HR = 2.16, 95% C.I. 1.33-3.53). Conversely, the number of years since quitting smoking was associated with a decreased risk of ALS compared with continuing smoking. Interpretation: These results strongly support the hypothesis of a role of cigarette smoking in aetiology of ALS. We hypothesize that this could occur through lipid peroxidation via formaldehyde exposure.
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- Lund Andersen, Jane, 1986-, et al.
(författare)
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A topographic hinge-zone divides coastal and inland ice dynamic regimes in East Antarctica
- 2023
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Ingår i: Communications Earth & Environment. - : Springer Science and Business Media LLC. - 2662-4435. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- The impact of late Cenozoic climate on the East Antarctic Ice Sheet is uncertain. Poorly constrained patterns of relative ice thinning and thickening impair the reconstruction of past ice-sheet dynamics and global sea-level budgets. Here we quantify long-term ice cover of mountains protruding the ice-sheet surface in western Dronning Maud Land, using cosmogenic Chlorine-36, Aluminium-26, Beryllium-10, and Neon-21 from bedrock in an inverse modeling approach. We find that near-coastal sites experienced ice burial up to 75–97% of time since 1 Ma, while interior sites only experienced brief periods of ice burial, generally <20% of time since 1 Ma. Based on these results, we suggest that the escarpment in Dronning Maud Land acts as a hinge-zone, where ice-dynamic changes driven by grounding-line migration are attenuated inland from the coastal portions of the East Antarctic Ice Sheet, and where precipitation-controlled ice-thickness variations on the polar plateau taper off towards the coast.
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- Magnusson, Bertil, et al.
(författare)
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Uncertainty from sampling - a nordtest handbook for sampling planners on sampling quality assurance and uncertainty estimation
- 2008
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Rapport (refereegranskat)abstract
- The handbook provides practical guidance on sampling uncertainty estimation in the Nordtest TR handbook format. The handbook is an extract of and based upon the principles, methods and text of the international Eurachem Guide Estimation of measurement uncertainty arising from sampling. The Eurachem guide is more extensive and provides details on theory and additional examples. The basic reference for the text in this handbook is the above-mentioned Eurachem guide. The overall purpose of this handbook has been to provide those working with investigations, monitoring and control that require sampling with a set of tools for calculation and control of the sampling uncertainty of their sampling procedure. Four examples illustrate the application of different methods and tools, while allowing you to follow all steps of the calculations. Although the examples are given for specific matrices (groundwater, iron ore, baby food and wastewater) the approaches are widely applicable. It is the intention of the project group to make these tools and the understanding of their use available outside the world of analytical chemistry, although the basic principles applied originate from analytical chemistry.
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- Mortensen, J., et al.
(författare)
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Informal caregiving as a risk factor for type 2 diabetes in individuals with favourable and unfavourable psychosocial work environments : A longitudinal multi-cohort study
- 2018
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Ingår i: Diabetes & Metabolism. - : Elsevier BV. - 1262-3636 .- 1878-1780. ; 44:1, s. 38-44
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To examine whether informal caregiving is associated with increased risk of type 2 diabetes (T2D), and whether job strain and social support at work modify the association.METHODS: Individual participant's data were pooled from three cohort studies-the French GAZEL study, the Swedish Longitudinal Occupational Survey of Health (SLOSH) and the British Whitehall II study-a total of 21,243 study subjects. Informal caregiving was defined as unpaid care for a closely related person. Job strain was assessed using the demand-control model, and questions on co-worker and supervisor support were combined in a measure of social support at work. Incident T2D was ascertained using registry-based, clinically assessed and self-reported data.RESULTS: A total of 1058 participants developed T2D during the up to 10 years of follow-up. Neither informal caregiving (OR: 1.09, 95% CI: 0.92-1.30) nor high job strain (OR: 1.04, 95% CI: 0.86-1.26) were associated with T2D risk, whereas low social support at work was a risk factor for T2D (OR: 1.18, 95% CI: 1.02-1.37). Also, informal caregivers who were also exposed to low social support at work were at higher risk of T2D (OR: 1.40, 95% CI: 1.08-1.82) compared with those who were not informal caregivers and had high social support at work (multiplicative test for interaction, P=0.04; additive test for interaction, synergy index=10).CONCLUSION: Informal caregiving was not independently associated with T2D risk. However, low social support at work was a risk factor, and informal caregivers with low social support at work had even higher risks of T2D.
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- Suganuma, Yusuke, et al.
(författare)
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Regional sea-level highstand triggered Holocene ice sheet thinning across coastal Dronning Maud Land, East Antarctica
- 2022
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Ingår i: Communications Earth & Environment. - : Springer Science and Business Media LLC. - 2662-4435. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- The East Antarctic Ice Sheet stores a vast amount of freshwater, which makes it the single largest potential contributor to future sea-level rise. However, the lack of well-constrained geological records of past ice sheet changes impedes model validation, hampers mass balance estimates, and inhibits examination of ice loss mechanisms. Here we identify rapid ice-sheet thinning in coastal Dronning Maud Land from Early to Middle Holocene (9000–5000 years ago) using a deglacial chronology based on in situ cosmogenic nuclide surface exposure dates from central Dronning Maud Land, in concert with numerical simulations of regional and continental ice-sheet evolution. Regional sea-level changes reproduced from our refined ice-load history show a highstand at 9000–8000 years ago. We propose that sea-level rise and a concomitant influx of warmer Circumpolar Deep Water triggered ice shelf breakup via the marine ice sheet instability mechanism, which led to rapid thinning of upstream coastal ice sheet sectors.
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