| 1. |
- Baird, Denis A., et al.
(författare)
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Identification of Novel Loci Associated With Hip Shape : A Meta-Analysis of Genomewide Association Studies.
- 2019
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Ingår i: Journal of Bone and Mineral Research. - : Wiley-Blackwell. - 0884-0431 .- 1523-4681. ; 34:2, s. 241-251
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to report the first genomewide association study (GWAS) meta-analysis of dual-energy X-ray absorptiometry (DXA)-derived hip shape, which is thought to be related to the risk of both hip osteoarthritis and hip fracture. Ten hip shape modes (HSMs) were derived by statistical shape modeling using SHAPE software, from hip DXA scans in the Avon Longitudinal Study of Parents and Children (ALSPAC; adult females), TwinsUK (mixed sex), Framingham Osteoporosis Study (FOS; mixed), Osteoporotic Fractures in Men study (MrOS), and Study of Osteoporotic Fractures (SOF; females) (total N = 15,934). Associations were adjusted for age, sex, and ancestry. Five genomewide significant (p < 5 × 10-9 , adjusted for 10 independent outcomes) single-nucleotide polymorphisms (SNPs) were associated with HSM1, and three SNPs with HSM2. One SNP, in high linkage disequilibrium with rs2158915 associated with HSM1, was associated with HSM5 at genomewide significance. In a look-up of previous GWASs, three of the identified SNPs were associated with hip osteoarthritis, one with hip fracture, and five with height. Seven SNPs were within 200 kb of genes involved in endochondral bone formation, namely SOX9, PTHrP, RUNX1, NKX3-2, FGFR4, DICER1, and HHIP. The SNP adjacent to DICER1 also showed osteoblast cis-regulatory activity of GSC, in which mutations have previously been reported to cause hip dysplasia. For three of the lead SNPs, SNPs in high LD (r2 > 0.5) were identified, which intersected with open chromatin sites as detected by ATAC-seq performed on embryonic mouse proximal femora. In conclusion, we identified eight SNPs independently associated with hip shape, most of which were associated with height and/or mapped close to endochondral bone formation genes, consistent with a contribution of processes involved in limb growth to hip shape and pathological sequelae. These findings raise the possibility that genetic studies of hip shape might help in understanding potential pathways involved in hip osteoarthritis and hip fracture. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
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| 2. |
- Ballegaard, Soren, et al.
(författare)
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In Ischemic Heart Disease, Reduced Sensitivity to Pressure at the Sternum Accompanies Lower Mortality after Five Years: Evidence from a Randomized Controlled Trial
- 2023
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Ingår i: JOURNAL OF CLINICAL MEDICINE. - 2077-0383. ; 12:24
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Tidskriftsartikel (refereegranskat)abstract
- Background: Autonomic nervous system dysfunction (ANSD) is associated with negative prognosis of ischemic heart disease (IHD). Elevated periosteal pressure sensitivity (PPS) at the sternum relates to ANSD and sympathetic hyperactivity. Two previous observational case-control studies of the effect of reduction of PPS suggested lower all-cause mortality from IHD and stroke. We now used a specific daily, adjunct, non-pharmacological program of reduction of elevated PPS to test the hypothetical association between the intervention and reduced all-cause mortality in patients with stable IHD in a randomized controlled trial (RCT). Methods: We completed active (n = 106) and passive interventions (n = 107) and compared the five-year mortalities. We also compared the five-year individual all-cause mortality of each participant to approximately 35.000 members of the general population of Denmark. Pooling the mortality data from the active group of the RCT with the two preliminary studies, we registered the mortality following active intervention of 1.168 person-years, compared to 40 million person-years of the pooled general population. Results: We recorded fewer deaths of the active RCT intervention group than of the corresponding control group from the general population (p = 0.01), as well as of the passive RCT intervention group (p = 0.035). The meta-analysis of the three studies together demonstrated reduced 4.2-year all-cause mortality of 60% (p = 0.007). Conclusions: The test of the hypothetical effect of an intervention aimed at the attenuation of ANSD accompanied by a lowered PPS revealed reduced all-cause mortality in patients with stable IHD.
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| 3. |
- Dörpinghaus, Jens, et al.
(författare)
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A novel link prediction approach on clinical knowledge graphs utilizing graph structures
- 2022
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Ingår i: Proceedings of the of the 17th Conference on ComputerScience and Intelligence Systems. - : Polish information processing society (PTI). - 9788396242396 - 9788396589705 - 9788396589712 ; , s. 43-52
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Konferensbidrag (refereegranskat)abstract
- This paper presents a novel approach towards link prediction in clinical knowledge graphs. They play a central role in linking data from different data sources and are widely used in big data integration, especially for connecting data from different domains. We present a knowledge graph initially built on data from a clinical trial on Spinocerebellar ataxia type 3 (SCA3), which is a rare autosomal dominant inherited disorder. The contributions of this paper are (1) to create a feasible data representation schema capable of handling clinical imaging data in a knowledge graph and to (2) convert the data efficiently into a knowledge graph. Due to the limited amount of patient-nodes usually common methods for link prediction and graph embeddings are problematic and thus we will (3) present a novel approach for link prediction utilising graph structures and Conditional Random Fields. In addition, we present (4) an extensive evaluation underlining the importance of (a) data management and (b) further research on link prediction using graph structures.
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| 4. |
- Jorgensen, Marie B., et al.
(författare)
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Implementation of physical coordination training and cognitive behavioural training interventions at cleaning workplaces - secondary analyses of a randomised controlled trial
- 2012
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Ingår i: Ergonomics. - : Informa UK Limited. - 0014-0139 .- 1366-5847. ; 55:7, s. 762-772
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Tidskriftsartikel (refereegranskat)abstract
- This study evaluates the implementation of physical coordination training (PCT) and cognitive behavioural training (CBTr) interventions in a randomised controlled trial at nine cleaners' workplaces. Female cleaners (n - 294) were randomised into a PCT, a CBTr or a reference (REF) group. Both 12-week interventions were performed in groups guided by an instructor. Records were kept on intervention dose (adherence) unanticipated events at the work place (context) and quality of intervention delivery (fidelity). Participant adherence was 37% in the PCT and 49% in the CBTr interventions. Optimal implementation was reached by only 6% in PCT and 42% in the CBTr. Analysis of the barriers to successful implementation indicated that the intervention process is sensitive to unanticipated events. In order to succeed in improving the health of high-risk populations such as cleaners and to correctly interpret intervention effects, more research on implementation is needed. Trial registration: ISRCTN96241850. Practitioner Summary: Both physical coordination training and cognitive behavioural training are potential effective workplace interventions among low educated job groups with high physical work demands. However, thorough consideration should be given to feasibility in the design of interventions. The optimal intervention should be tailored to closely match the implementation context and be robust and flexible to minimise susceptibility to changes in work organisation.
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| 5. |
- Meitzner, Rico, et al.
(författare)
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Impact of P3HT materials properties and layer architecture on OPV device stability
- 2019
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Ingår i: Solar Energy Materials and Solar Cells. - : Elsevier BV. - 0927-0248. ; 202
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Tidskriftsartikel (refereegranskat)abstract
- We report a cooperative study conducted between different laboratories to investigate organic solar cell degradation with respect to P3HT material properties and different solar cell architectures. Various batches of P3HT were collected from different suppliers reflecting commercial availability as well as properties variability. Among the materials properties explicitly considered were the molar mass, dispersity, regio-regularity, impurities by trace metals and intrinsic doping evaluated from radical concentrations. Each of the participating laboratories contributing test devices applied their own layer stack, i.e. their own device architecture and layout. This variation was appreciated as another parameter for evaluation. Even though a large amount of devices failed due to extrinsic degradation effects, indeed, some materials properties were found to be more important than others for obtaining long lifetimes and high stability of P3HT-based polymer solar cells.
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| 6. |
- Tobias, Jonathan H., et al.
(författare)
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Femoral neck width genetic risk score is a novel independent risk factor for hip fractures
- 2024
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Ingår i: JOURNAL OF BONE AND MINERAL RESEARCH. - 0884-0431 .- 1523-4681. ; 39:3, s. 241-251
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Tidskriftsartikel (refereegranskat)abstract
- Femoral neck width (FNW) derived from DXA scans may provide a useful adjunct to hip fracture prediction. Therefore, we investigated whether FNW is related to hip fracture risk independently of femoral neck bone mineral density (FN-BMD), using a genetic approach. FNW was derived from points automatically placed on the proximal femur using hip DXA scans from 38 150 individuals (mean age 63.8 yr, 48.0% males) in UK Biobank (UKB). Genome-wide association study (GWAS) identified 71 independent genome-wide significant FNW SNPs, comprising genes involved in cartilage differentiation, hedgehog, skeletal development, in contrast to SNPs identified by FN-BMD GWAS which primarily comprised runx1/Wnt signaling genes (MAGMA gene set analyses). FNW and FN-BMD SNPs were used to generate genetic instruments for multivariable Mendelian randomization. Greater genetically determined FNW increased risk of all hip fractures (odds ratio [OR] 1.53; 95% CI, 1.29-1.82 per SD increase) and femoral neck fractures (OR 1.58;1.30-1.92), but not trochanteric or forearm fractures. In contrast, greater genetically determined FN-BMD decreased fracture risk at all 4 sites. FNW and FN-BMD SNPs were also used to generate genetic risk scores (GRSs), which were examined in relation to incident hip fracture in UKB (excluding the FNW GWAS population; n = 338 742, 3222 cases) using a Cox proportional hazards model. FNW GRS was associated with increased risk of all incident hip fractures (HR 1.08;1.05-1.12) and femoral neck fractures (hazard ratio [HR] 1.10;1.06-1.15), but not trochanteric fractures, whereas FN-BMD GRS was associated with reduced risk of all hip fracture types. We conclude that the underlying biology regulating FNW and FN-BMD differs, and that DXA-derived FNW is causally related to hip fractures independently of FN-BMD, adding information beyond FN-BMD for hip fracture prediction. Hence, FNW derived from DXA analyses or a FNW GRS may contribute clinically useful information beyond FN-BMD for hip fracture prediction. Femoral neck width (FNW) derived from DXA scans may provide useful information about hip fracture prediction, over and above that provided by BMD measurements. Therefore, we investigated whether FNW is related to hip fracture risk independently of BMD, using a genetic approach. FNW was derived from points automatically placed on the hip in DXA scans obtained from 38 150 individuals (mean age 63.8 yr, 48.0% males) in UK Biobank. Seventy-one distinct genetic factors were found to be associated with FNW. Individuals who were predicted by their genes to have greater FNW had a higher risk of hip but not forearm fractures. In contrast, those with greater genetically determined BMD of the femoral neck had a lower risk of both hip and forearm fractures. We conclude that the underlying biology regulating FNW and BMD of the femoral neck differs, and that FNW derived from DXA analyses may contribute clinically useful information beyond BMD for hip fracture prediction.
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