| 1. |
- Estrada, Karol, et al.
(författare)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 2. |
- Averfalk, Helge, 1988-, et al.
(författare)
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Large heat pumps in Swedish district heating systems
- 2017
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Ingår i: Renewable & sustainable energy reviews. - Kidlington : Pergamon Press. - 1364-0321 .- 1879-0690. ; 79, s. 1275-1284
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Tidskriftsartikel (refereegranskat)abstract
- Power-to-heat solutions like heat pumps and electric boilers are foreseen to be possible future tools to stabilise international power markets with high proportions of variable power supply. Temporary low cost electricity can be used for heat generation at times with high availability of wind and solar power through substitution of ordinary heat supply, hence contributing to increased energy system sustainability. Power-to-heat installations in district heating systems are competitive due to low specific investment and installation costs for large electric boilers, heat pumps, and heat storages. Several large-scale heat pumps were installed in Swedish district heating systems during the 1980s, since a national electricity surplus from new nuclear power existed for some years. The aim of this paper is to summarise the accumulated operation experiences from these large Swedish heat pumps to support and facilitate planning of future power-to-heat solutions with heat pumps in district heating systems. Gained experiences consider; installed capacities, capacity utilisation, heat sources used, refrigerant replacements, refrigerant leakages, and wear of mechanical components. The major conclusion is that many of the large thirty-year-old heat pumps are still in operation, but with reduced capacity utilisation due to internal competition from waste and biomass cogeneration plants in the district heating systems.
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| 3. |
- Averfalk, Helge, 1988-, et al.
(författare)
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On the use of surplus electricity in district heating systems
- 2014
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Ingår i: Proceedings from the 14th International Symposium on District Heating and Cooling. - Stockholm : Swedish District Heating Association. - 9789185775248 ; , s. 469-474
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Konferensbidrag (refereegranskat)abstract
- Maintained balance between supply and demand is a fundamental prerequisite for proper operation of electric power grids. For this end, power systems rely on accessibility to various balancing technologies and solutions by which fluctuations in supply and demand can be promptly met. In this paper, balancing approaches in the case of surplus electricity supply, due to long-term, seasonal, or short-term causes, are discussed on the basis mainly of compiled experiences from the Swedish national power grid. In Sweden, a structural long-term electricity surplus was created in the 1980s when several new nuclear plants were commissioned and built. One of four explicit domestic power-to-heat solutions initiated to maximize the utilization of this surplus electricity, as export capacities were limited, was the introduction of large scale electric boilers and compressor heat pumps in district heating systems. In retrospective, this solution not only satisfied the primary objective by providing additional electricity demand to balance the power grid, but represents today – from an energy systems perspective – a contemporary example of increased system flexibility by the attainment of higher integration levels between power and heat sectors. As European power supply will be reshaped to include higher proportions of fluctuating supply technologies (e.g. wind and solar), causing occasional but recurring short-term electricity surpluses, the unique Swedish experiences may provide valuable input in the development of rational responses to future balancing challenges. The main conclusions from this study are that district heating systems can add additional balancing capabilities to power systems, if equipped with electrical heat supply technologies, hereby contributing to higher energy system flexibility. Consequently, district heating systems also have a discrete but key role in the continued integration of renewable intermittent power supply technologies in the future European energy system.
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| 4. |
- Dieppe, Paul, et al.
(författare)
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Variations in the pre-operative status of patients coming to primary hip replacement for osteoarthritis in European orthopaedic centres
- 2009
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Total hip joint replacement (THR) is a high volume, effective intervention for hip osteoarthritis (OA). However, indications and determinants of outcome remain unclear. The 'EUROHIP consortium' has undertaken a cohort study to investigate these questions. This paper describes the variations in disease severity in this cohort and the relationships between clinical and radiographic severity, and explores some of the determinants of variation. Methods: A minimum of 50 consecutive, consenting patients coming to primary THR for primary hip OA in each of the 20 participating orthopaedic centres entered the study. Pre-operative data included demographics, employment and educational attainment, drug utilisation, and involvement of other joints. Each subject completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC - Likert version 3.1). Other data collected at the time of surgery included the prosthesis used and American Society of Anaesthesiologists (ASA) status. Preoperative radiographs were read by the same three readers for Kellgren and Lawrence (K&L) grading and Osteoarthritis Research Society International (OARSI) atlas features. Regression analyses were carried out. Results: Data from 1327 subjects has been analysed. The mean age of the group was 65.7 years, and there were more women (53.4%) than men. Most (79%) were ASA status 1 or 2. Reported disease duration was 5 years or less in 69.2%. Disease in other joint sites was common. Radiographs were available in 1051 subjects and the K&L grade was 3 or 4 in 95.8%. There was much more variation in clinical severity (WOMAC score); the mean total WOMAC score was 59.2 (SD 16.1). The radiographic severity showed no correlation with WOMAC scores. Significantly higher WOMAC scores (worse disease) were seen in older people, women, those with obesity, those with worse general health, and those with lower educational attainment. Conclusion: 1. Clinical disease severity varies widely at the time of THR for OA. 2. In advanced hip OA clinical severity shows no correlation with radiographic severity. 3. Simple scores of pain and disability do not reflect the complexity of decision-making about who should have a THR.
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| 6. |
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| 7. |
- Oei, Ling, et al.
(författare)
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A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus
- 2014
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Ingår i: Journal of Medical Genetics. - : BMJ Publishing Group. - 0022-2593 .- 1468-6244. ; 51:2, s. 122-131
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk.AIM: To identify CNVs associated with osteoporotic bone fracture risk.METHOD: We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies.RESULTS: A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p=8.69×10(-5)). We performed an in silico meta-analysis in four studies with CNV microarray data and the association with fracture risk was replicated (OR 3.11, 95% CI 1.01 to 8.22; p=0.02). The prevalence of this deletion showed geographic diversity, being absent in additional samples from Australia, Canada, Poland, Iceland, Denmark, and Sweden, but present in the Netherlands (0.34%), Spain (0.33%), USA (0.23%), England (0.15%), Scotland (0.10%), and Ireland (0.06%), with insufficient evidence for association with fracture risk.CONCLUSIONS: These results suggest that deletions in the 6p25.1 locus may predispose to higher risk of fracture in a subset of populations of European origin; larger and geographically restricted studies will be needed to confirm this regional association. This is a first step towards the evaluation of the role of rare CNVs in osteoporosis.
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| 8. |
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| 9. |
- Willems, S. M., et al.
(författare)
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Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 × 10-8) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality. © The Author(s) 2017.
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