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| 52. |
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| 53. |
- Gateva, Vesela, et al.
(författare)
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A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:11, s. 1228-1233
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have recently identified at least 15 susceptibility loci for systemic lupus erythematosus (SLE). To confirm additional risk loci, we selected SNPs from 2,466 regions that showed nominal evidence of association to SLE (P < 0.05) in a genome-wide study and genotyped them in an independent sample of 1,963 cases and 4,329 controls. This replication effort identified five new SLE susceptibility loci (P < 5 x 10(-8)): TNIP1 (odds ratio (OR) = 1.27), PRDM1 (OR = 1.20), JAZF1 (OR = 1.20), UHRF1BP1 (OR = 1.17) and IL10 (OR = 1.19). We identified 21 additional candidate loci with P< or = 1 x 10(-5). A candidate screen of alleles previously associated with other autoimmune diseases suggested five loci (P < 1 x 10(-3)) that may contribute to SLE: IFIH1, CFB, CLEC16A, IL12B and SH2B3. These results expand the number of confirmed and candidate SLE susceptibility loci and implicate several key immunologic pathways in SLE pathogenesis.
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| 54. |
- Gurholt, Tiril P., et al.
(författare)
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Population-based body-brain mapping links brain morphology with anthropometrics and body composition
- 2021
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Understanding complex body-brain processes and the interplay between adipose tissue and brain health is important for understanding comorbidity between psychiatric and cardiometabolic disorders. We investigated associations between brain structure and anthropometric and body composition measures using brain magnetic resonance imaging (MRI; n=24,728) and body MRI (n=4973) of generally healthy participants in the UK Biobank. We derived regional and global measures of brain morphometry using FreeSurfer and tested their association with (i) anthropometric measures, and (ii) adipose and muscle tissue measured from body MRI. We identified several significant associations with small effect sizes. Anthropometric measures showed negative, nonlinear, associations with cerebellar/cortical gray matter, and brain stem structures, and positive associations with ventricular volumes. Subcortical structures exhibited mixed effect directionality, with strongest positive association for accumbens. Adipose tissue measures, including liver fat and muscle fat infiltration, were negatively associated with cortical/cerebellum structures, while total thigh muscle volume was positively associated with brain stem and accumbens. Regional investigations of cortical area, thickness, and volume indicated widespread and largely negative associations with anthropometric and adipose tissue measures, with an opposite pattern for thigh muscle volume. Self-reported diabetes, hypertension, or hypercholesterolemia were associated with brain structure. The findings provide new insight into physiological body-brain associations suggestive of shared mechanisms between cardiometabolic risk factors and brain health. Whereas the causality needs to be determined, the observed patterns of body-brain relationships provide a foundation for understanding the underlying mechanisms linking psychiatric disorders with obesity and cardiovascular disease, with potential for the development of new prevention strategies.
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| 55. |
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| 56. |
- Hom, Geoffrey, et al.
(författare)
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Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX.
- 2008
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 358:9, s. 900-909
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease in which the risk of disease is influenced by complex genetic and environmental contributions. Alleles of HLA-DRB1, IRF5, and STAT4are established susceptibility genes; there is strong evidence for the existence of additional risk loci.METHODS: We genotyped more than 500,000 single-nucleotide polymorphisms (SNPs) in DNA samples from 1311 case subjects with SLE and 1783 control subjects; all subjects were North Americans of European descent. Genotypes from 1557 additional control subjects were obtained from public data repositories. We measured the association between the SNPs and SLE after applying strict quality-control filters to reduce technical artifacts and to correct for the presence of population stratification. Replication of the top loci was performed in 793 case subjects and 857 control subjects from Sweden.RESULTS: Genetic variation in the region upstream from the transcription initiation site of the gene encoding B lymphoid tyrosine kinase (BLK) and C8orf13 (chromosome 8p23.1) was associated with disease risk in both the U.S. and Swedish case–control series (rs13277113; odds ratio, 1.39; P=1×10−10) and also with altered levels of messenger RNA in B-cell lines. In addition, variants on chromosome 16p11.22, near the genes encoding integrin alpha M (ITGAM, or CD11b) and integrin alpha X (ITGAX), were associated with SLE in the combined sample (rs11574637; odds ratio, 1.33; P=3×10−11).
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| 57. |
- Horwood, Joshua T. M., et al.
(författare)
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Flow Instabilities in Gas Turbine Chute Seals
- 2020
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Ingår i: Journal of engineering for gas turbines and power. - : ASME. - 0742-4795 .- 1528-8919. ; 142:2
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Tidskriftsartikel (refereegranskat)abstract
- The ingress of hot annulus gas into stator-rotor cavities is an important topic to engine designers. Rim-seals reduce the pressurized purge required to protect highly stressed components. This paper describes an experimental and computational study of flow through a turbine chute seal. The computations-which include a 360 deg domain-were undertaken using dlr trace's time-marching solver. The experiments used a low Reynolds number turbine rig operating with an engine-representative flow structure. The simulations provide an excellent prediction of cavity pressure and swirl, and good overall agreement of sealing effectiveness when compared to experiment. Computation of flow within the chute seal showed strong shear gradients which influence the pressure distribution and secondary-flow field near the blade leading edge. High levels of shear across the rim-seal promote the formation of large-scale structures at the wheel-space periphery; the number and speed of which were measured experimentally and captured, qualitatively and quantitatively, by computations. A comparison of computational domains ranging from 30 deg to 360 deg indicates that steady features of the flow are largely unaffected by sector size. However, differences in large-scale flow structures were pronounced with a 60 deg sector and suggest that modeling an even number of blades in small sector simulations should be avoided.
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| 58. |
- Horwood, Joshua T. M., et al.
(författare)
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FLOW INSTABILITIES IN GAS TURBINE CHUTE SEALS
- 2019
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Ingår i: PROCEEDINGS OF THE ASME TURBO EXPO. - : ASME Press.
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Konferensbidrag (refereegranskat)abstract
- The ingress of hot annulus gas into stator-rotor cavities is an important topic to engine designers. Rim-seals reduce the pressurised purge required to protect highly-stressed components. This paper describes an experimental and computational study of flow through a turbine chute seal. The computations which include a 360 degrees domain - were undertaken using DLR TRACE's time-marching solver. The experiments used a low Reynolds number turbine rig operating with an engine-representative flow structure. The simulations provide an excellent prediction of cavity pressure and swirl, and good overall agreement of sealing effectiveness when compared to experiment. Computation of flow within the chute seal showed strong shear gradients which influence the pressure distribution and secondary-flow field near the blade leading edge. High levels of shear across the rim-seal promote the formation of large-scale structures at the wheel-space periphery; the number and speed of which were measured experimentally and captured, qualitatively and quantitatively, by computations. A comparison of computational domains ranging from 30 degrees to 360 degrees indicate that steady features of the flow are largely unaffected by sector size. However, differences in large-scale flow structures were pronounced with a 60 degrees sector and suggest that modelling an even number of blades in small sector simulations should be avoided.
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| 59. |
- Iliodromiti, Stamatina, et al.
(författare)
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Liver, visceral and subcutaneous fat in men and women of South Asian and white European descent : a systematic review and meta-analysis of new and published data
- 2023
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 66:1, s. 44-56
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Forskningsöversikt (refereegranskat)abstract
- Aims/hypothesis South Asians have a two- to fivefold higher risk of developing type 2 diabetes than those of white European descent. Greater central adiposity and storage of fat in deeper or ectopic depots are potential contributing mechanisms. We collated existing and new data on the amount of subcutaneous (SAT), visceral (VAT) and liver fat in adults of South Asian and white European descent to provide a robust assessment of potential ethnic differences in these factors. Methods We performed a systematic review of the Embase and PubMed databases from inception to August 2021. Unpublished imaging data were also included. The weighted standardised mean difference (SMD) for each adiposity measure was estimated using random-effects models. The quality of the studies was assessed using the ROBINS-E tool for risk of bias and overall certainty of the evidence was assessed using the GRADE approach. The study was pre-registered with the OSF Registries (https://osf. io/w5bf9). Results We summarised imaging data on SAT, VAT and liver fat from eight published and three previously unpublished datasets, including a total of 1156 South Asian and 2891 white European men, and 697 South Asian and 2271 white European women. Despite South Asian men having a mean BMI approximately 0.5-0.7 kg/m(2) lower than white European men (depending on the comparison), nine studies showed 0.34 SMD (95% CI 0.12, 0.55; I-2 =83%) more SAT and seven studies showed 0.56 SMD (95% CI 0.14, 0.98; I-2 =93%) more liver fat, but nine studies had similar VAT (-0.03 SMD; 95% CI -0.24, 0.19;1 2 =85%) compared with their white European counterparts. South Asian women had an approximately 0.9 kg/m(2) lower BMI but 0.31 SMD (95% CI 0.14, 0.48; I-2=53%) more liver fat than their white European counterparts in five studies. Subcutaneous fat levels (0.03 SMD; 95% CI -0.17, 0.23; I-2 =72%) and VAT levels (0.04 SMD; 95% CI -0.16, 0.24; I-2 =71%) did not differ significantly between ethnic groups in eight studies of women. Conclusions/interpretation South Asian men and women appear to store more ectopic fat in the liver compared with their white European counterparts with similar BMI levels. Given the emerging understanding of the importance of liver fat in diabetes pathogenesis, these findings help explain the greater diabetes risks in South Asians.
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