| 1. |
- 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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| 2. |
- Styrkarsdottir, Unnur, et al.
(författare)
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Whole-genome sequencing identifies rare genotypes in COMP and CHADL associated with high risk of hip osteoarthritis
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:5, s. 801-805
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Tidskriftsartikel (refereegranskat)abstract
- We performed a genome-wide association study of total hip replacements, based on variants identified through whole-genome sequencing, which included 4,657 Icelandic patients and 207,514 population controls. We discovered two rare signals that strongly associate with osteoarthritis total hip replacement: a missense variant, c.1141G>C (p.Asp369His), in the COMP gene (allelic frequency = 0.026%, P = 4.0 × 10-12, odds ratio (OR) = 16.7) and a frameshift mutation, rs532464664 (p.Val330Glyfs∗106), in the CHADL gene that associates through a recessive mode of inheritance (homozygote frequency = 0.15%, P = 4.5 × 10-18, OR = 7.71). On average, c.1141G>C heterozygotes and individuals homozygous for rs532464664 had their hip replacement operation 13.5 years and 4.9 years earlier than others (P = 0.0020 and P = 0.0026), respectively. We show that the full-length CHADL transcript is expressed in cartilage. Furthermore, the premature stop codon introduced by the CHADL frameshift mutation results in nonsense-mediated decay of the mutant transcripts.
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| 3. |
- Abdoullaye, Doukary, et al.
(författare)
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Permanent genetic resources added to molecular ecology resources database 1 August 2009 - 30 September 2009
- 2010
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:1, s. 232-236
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Tidskriftsartikel (refereegranskat)abstract
- This article documents the addition of 238 microsatellite marker loci and 72 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Adelges tsugae, Artemisia tridentata, Astroides calycularis, Azorella selago, Botryllus schlosseri, Botrylloides violaceus, Cardiocrinum cordatum var. glehnii, Campylopterus curvipennis, Colocasia esculenta, Cynomys ludovicianus, Cynomys leucurus, Cynomys gunnisoni, Epinephelus coioides, Eunicella singularis, Gammarus pulex, Homoeosoma nebulella, Hyla squirella, Lateolabrax japonicus, Mastomys erythroleucus, Pararge aegeria, Pardosa sierra, Phoenicopterus ruber ruber and Silene latifolia. These loci were cross-tested on the following species: Adelges abietis, Adelges cooleyi, Adelges piceae, Pineus pini, Pineus strobi, Tubastrea micrantha, three other Tubastrea species, Botrylloides fuscus, Botrylloides simodensis, Campylopterus hemileucurus, Campylopterus rufus, Campylopterus largipennis, Campylopterus villaviscensio, Phaethornis longuemareus, Florisuga mellivora, Lampornis amethystinus, Amazilia cyanocephala, Archilochus colubris, Epinephelus lanceolatus, Epinephelus fuscoguttatus, Symbiodinium temperate-A clade, Gammarus fossarum, Gammarus roeselii, Dikerogammarus villosus and Limnomysis benedeni. This article also documents the addition of 72 sequencing primer pairs and 52 allele specific primers for Neophocaena phocaenoides.
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| 4. |
- 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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| 5. |
- Kerkhof, H. J. M., et al.
(författare)
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Recommendations for standardization and phenotype definitions in genetic studies of osteoarthritis: the TREAT-OA consortium
- 2011
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 19:3, s. 254-264
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To address the need for standardization of osteoarthritis (OA) phenotypes by examining the effect of heterogeneity among symptomatic (SOA) and radiographic osteoarthritis (ROA) phenotypes. Methods: Descriptions of OA phenotypes of the 28 studies involved in the TREAT-OA consortium were collected. We investigated whether different OA definitions result in different association results by creating various hip OA definitions in one large population based cohort (the Rotterdam Study I (RSI)) and testing those for association with gender, age and body mass index using one-way ANOVA. For ROA, we standardized the hip-, knee- and hand ROA definitions and calculated prevalence's of ROA before and after standardization in nine cohort studies. This procedure could only be performed in cohort studies and standardization of SOA definitions was not feasible at this moment. Results: In this consortium, all studies with SOA phenotypes (knee, hip and hand) used a different definition and/or assessment of OA status. For knee-, hip- and hand ROA five, four and seven different definitions were used, respectively. Different hip ROA definitions do lead to different association results. For example, we showed in the RSI that hip OA defined as "at least definite joint space narrowing (JSN) and one definite osteophyte" was not associated with gender (P=0.22), but defined as "at least one definite osteophyte" was significantly associated with gender (P=3 x 10(-9)). Therefore, a standardization process was undertaken for ROA definitions. Before standardization a wide range of ROA prevalence's was observed in the nine cohorts studied. After standardization the range in prevalence of knee- and hip ROA was small. Conclusion: Phenotype definitions influence the prevalence of OA and association with clinical variables. ROA phenotypes within the TREAT-OA consortium were standardized to reduce heterogeneity and improve power in future genetics studies. (C) 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 6. |
- Styrkarsdottir, Unnur, et al.
(författare)
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GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Bone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (N = 13,608 – 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area (P = 2.3 × 10 −42 , β = −0.090) and confers risk of hip fracture (P = 1.0 × 10 −8 , OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density.
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| 7. |
- Hasson, H., et al.
(författare)
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To do or not to do - Balancing governance and professional autonomy to abandon low-value practices : A study protocol
- 2019
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Ingår i: Implementation Science. - : BioMed Central Ltd.. - 1748-5908. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many interventions used in health care lack evidence of effectiveness and may be unnecessary or even cause harm, and should therefore be de-implemented. Lists of such ineffective, low-value practices are common, but these lists have little chance of leading to improvements without sufficient knowledge regarding how de-implementation can be governed and carried out. However, decisions regarding de-implementation are not only a matter of scientific evidence; the puzzle is far more complex with political, economic, and relational interests play a role. This project aims at exploring the governance of de-implementation of low-value practices from the perspectives of national and regional governments and senior management at provider organizations. Methods: Theories of complexity science and organizational alignment are used, and interviews are conducted with stakeholders involved in the governance of low-value practice de-implementation, including national and regional governments (focusing on two contrasting regions in Sweden) and senior management at provider organizations. In addition, an ongoing process for governing de-implementation in accordance with current recommendations is followed over an 18-month period to explore how governance is conducted in practice. A framework for the governance of de-implementation and policy suggestions will be developed to guide de-implementation governance. Discussion: This study contributes to knowledge about the governance of de-implementation of low-value care practices. The study provides rich empirical data from multiple system levels regarding how de-implementation of low-value practices is currently governed. The study also makes a theoretical contribution by applying the theories of complexity and organizational alignment, which may provide generalizable knowledge about the interplay between stakeholders across system levels and how and why certain factors influence the governance of de-implementation. The project employs a solution-oriented perspective by developing a framework for de-implementation of low-value practices and suggesting practical strategies to improve the governance of de-implementation. The framework and strategies can thereafter be evaluated for validity and impact in future studies.
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| 8. |
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| 9. |
- 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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| 10. |
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| 11. |
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| 12. |
- Pfeffer, M. A., et al.
(författare)
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Ground-Based measurements of the 2014-2015 holuhraun volcanic cloud (Iceland)
- 2018
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Ingår i: Geosciences (Switzerland). - : MDPI AG. - 2076-3263. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- The 2014-2015 Bárðarbunga fissure eruption at Holuhraun in central Iceland was distinguished by the high emission of gases, in total 9.6 Mt SO 2 , with almost no tephra. This work collates all ground-based measurements of this extraordinary eruption cloud made under particularly challenging conditions: remote location, optically dense cloud with high SO 2 column amounts, low UV intensity, frequent clouds and precipitation, an extensive and hot lava field, developing ramparts, and high-latitude winter conditions. Semi-continuous measurements of SO 2 flux with three scanning DOAS instruments were augmented by car traverses along the ring-road and along the lava. The ratios of other gases/SO 2 were measured by OP-FTIR, MultiGAS, and filter packs. Ratios of SO 2 /HCl = 30-110 and SO 2 /HF = 30-130 show a halogen-poor eruption cloud. Scientists on-site reported extremely minor tephra production during the eruption. OPC and filter packs showed low particle concentrations similar to non-eruption cloud conditions. Three weather radars detected a droplet-rich eruption cloud. Top of eruption cloud heights of 0.3-5.5 km agl were measured with ground-and aircraft-based visual observations, web camera and NicAIR II infrared images, triangulation of scanning DOAS instruments, and the location of SO 2 peaks measured by DOAS traverses. Cloud height and emission rate measurements were critical for initializing gas dispersal simulations for hazard forecasting.
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| 13. |
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| 14. |
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| 15. |
- Brady, K., et al.
(författare)
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CD40 employs p38 MAP kinase in IgE isotype switching
- 2001
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 289:1, s. 276-281
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Tidskriftsartikel (refereegranskat)abstract
- IgE switching requires the prior induction of CE germline transcripts which is mediated by the concerted binding of STAT-6 and NF kappaB to the CE promoter. These transcription factors are regulated by IL-4 and CD40, respectively. However the latter can effect other signaling pathways and the present study explores the role of p38 MAPK in induction of CE germline transcripts. CD40 and IL-4, both alone and in synergy, were initially shown to activate the CE promoter in a B cell lymphoma cell line. Under the same conditions CD40 caused activation of p38 MAPK, whereas IL-4 was ineffective. The p38 MAPK inhibitor, SB203580, and a dominant negative form of p38 MAPK decreased the CD40 activation of the CE promoter by reducing the ability of CD40 to increase the transactivation potential of NF kappaB. This study suggests that p38 MAPK is crucially important in mediating CD40 activation of NFKB which acts to induce CE germline transcripts, ultimately facilitating IgE switching. (C) 2001 Academic Press.
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| 16. |
- De La Torre, Amanda, 1976-, et al.
(författare)
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Genetic architecture and genomic patterns of gene flow between hybridizing species of Picea
- 2015
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Ingår i: Heredity. - : Nature Publishing Group. - 0018-067X .- 1365-2540. ; 115:2, s. 153-164
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Tidskriftsartikel (refereegranskat)abstract
- Hybrid zones provide an opportunity to study the effects of selection and gene flow in natural settings. We employed nuclear microsatellites (single sequence repeat (SSR)) and candidate gene single-nucleotide polymorphism markers (SNPs) to characterize the genetic architecture and patterns of interspecific gene flow in the Picea glauca x P. engelmannii hybrid zone across a broad latitudinal (40-60 degrees) and elevational (350-3500 m) range in western North America. Our results revealed a wide and complex hybrid zone with broad ancestry levels and low interspecific heterozygosity, shaped by asymmetric advanced-generation introgression, and low reproductive barriers between parental species. The clinal variation based on geographic variables, lack of concordance in clines among loci and the width of the hybrid zone points towards the maintenance of species integrity through environmental selection. Congruency between geographic and genomic clines suggests that loci with narrow clines are under strong selection, favoring either one parental species (directional selection) or their hybrids (overdominance) as a result of strong associations with climatic variables such as precipitation as snow and mean annual temperature. Cline movement due to past demographic events (evidenced by allelic richness and heterozygosity shifts from the average cline center) may explain the asymmetry in introgression and predominance of P. engelmannii found in this study. These results provide insights into the genetic architecture and fine-scale patterns of admixture, and identify loci that may be involved in reproductive barriers between the species.
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| 17. |
- Evangelou, Evangelos, et al.
(författare)
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A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip
- 2014
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 73:12, s. 2130-2136
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. Methods We performed a two-stage meta-analysis on more than 78 000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used. Results We accumulated 11 277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the NCOA3 (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9x10(-9) and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p= 5.6x10(-8)) and follow-up studies (p=7.3x10(-4)). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9x10(-7), OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2x10(-6), OR=1.27 in male specific analysis). Conclusions Novel genetic loci for hip OA were found in this meta-analysis of GWAS.
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| 18. |
- Farina, D., et al.
(författare)
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Toward higher-performance bionic limbs for wider clinical use
- 2021
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Ingår i: Nature Biomedical Engineering. - : Springer Science and Business Media LLC. - 2157-846X. ; 7:4, s. 473-85
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Tidskriftsartikel (refereegranskat)abstract
- Most prosthetic limbs can autonomously move with dexterity, yet they are not perceived by the user as belonging to their own body. Robotic limbs can convey information about the environment with higher precision than biological limbs, but their actual performance is substantially limited by current technologies for the interfacing of the robotic devices with the body and for transferring motor and sensory information bidirectionally between the prosthesis and the user. In this Perspective, we argue that direct skeletal attachment of bionic devices via osseointegration, the amplification of neural signals by targeted muscle innervation, improved prosthesis control via implanted muscle sensors and advanced algorithms, and the provision of sensory feedback by means of electrodes implanted in peripheral nerves, should all be leveraged towards the creation of a new generation of high-performance bionic limbs. These technologies have been clinically tested in humans, and alongside mechanical redesigns and adequate rehabilitation training should facilitate the wider clinical use of bionic limbs. This Perspective argues that technologies for the neural interfacing of robotic devices with the body that have been clinically tested in humans should be leveraged toward the creation of a new generation of high-performance bionic limbs.
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| 19. |
- Granath, J., et al.
(författare)
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Stress management : A randomized study of cognitive behavioural therapy and yoga
- 2006
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Ingår i: Cognitive Behaviour Therapy. - : Informa UK Limited. - 1650-6073 .- 1651-2316. ; 35:1, s. 3-10
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Tidskriftsartikel (refereegranskat)abstract
- In this study, a stress management program based on cognitive behavioural therapy principles was compared with a Kundaliniyoga program. A study sample of 26 women and 7 men from a large Swedish company were divided randomly into 2 groups for each of the different forms of intervention; a total of 4 groups. The groups were instructed by trained group leaders and 10 sessions were held with each of groups, over a period of 4 months. Psychological (self-rated stress and stress behaviour, anger, exhaustion, quality of life) and physiological (blood pressure, heart rate, urinary catecholamines, salivary cortisol) measurements obtained before and after treatment showed significant improvements on most of the variables in both groups as well as medium-to-high effect sizes. However, no significant difference was found between the 2 programs. The results indicate that both cognitive behaviour therapy and yoga are promising stress management techniques.
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| 20. |
- Hajihoseini, H., et al.
(författare)
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Effect of substrate bias on properties of HiPIMS deposited vanadium nitride films
- 2018
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Ingår i: Thin Solid Films. - : Elsevier B.V.. - 0040-6090 .- 1879-2731. ; 663, s. 126-130
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Tidskriftsartikel (refereegranskat)abstract
- We report on the effect of varying the substrate bias on the morphology, composition, structural, and electrical properties of vanadium nitride films deposited by high power impulse magnetron sputtering (HiPIMS). The optimum substrate bias is found to be −50 V, which gives the highest film density, the lowest electrical resistivity, and the lowest surface roughness at the highest deposition rate. We demonstrate how increasing the substrate bias voltage leads to a highly textured film. The preferred orientation of the film changes from (111) to (200) as the substrate bias voltage is increased. An X-ray pole scan shows that the (111) plane grows parallel to the SiO2 substrate when the substrate is grounded while it is gradually replaced by the (200) plane as the substrate bias voltage is increased up to −200 V. The lowest electrical resistivity is measured as 48.4 μΩ cm for the VN film deposited under substrate bias of −50 V. This is among the lowest room temperature values that have been reported for a VN film. We found that the nitrogen concentration presents a decline by 6.5 percentage points as the substrate bias is changed from ground to −200 V.
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| 21. |
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| 22. |
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| 23. |
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| 24. |
- Ingvarsson, S., et al.
(författare)
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Why do they do it? : A grounded theory study of the use of low-value care among primary health care physicians
- 2020
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Ingår i: Implementation Science. - : BioMed Central Ltd. - 1748-5908. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of low-value care (LVC) is widespread and has an impact on both the use of resources and the quality of care. However, few studies have thus far studied the factors influencing the use of LVC from the perspective of the practitioners themselves. The aim of this study is to understand why physicians within primary care use LVC. Methods: Six primary health care centers in the Stockholm Region were purposively selected. Focus group discussions were conducted with physicians (n = 31) working in the centers. The discussions were coded inductively using a grounded theory approach. Results: Three main reasons for performing LVC were identified. Uncertainty and disagreement about what not to do was related to being unaware of the LVC status of a practice, guidelines perceived as conflicting, guidelines perceived to be irrelevant for the target patient population, or a lack of trust in the guidelines. Perceived pressure from others concerned patient pressure, pressure from other physicians, or pressure from the health care system. A desire to do something for the patients was associated with the fact that the visit in itself prompts action, symptoms to relieve, or that patients' emotions need to be reassured. The three reasons are interdependent. Uncertainty and disagreement about what not to do have made it more difficult to handle the pressure from others and to refrain from doing something for the patients. The pressure from others and the desire to do something for the patients enhanced the uncertainty and disagreement about what not to do. Furthermore, the pressure from others influenced the desire to do something for the patients. Conclusions: Three reasons work together to explain primary care physicians’ use of LVC: uncertainty and disagreement about what not to do, perceived pressure from others, and the desire to do something for the patients. The reasons may, in turn, be influenced by the health care system, but the decision nevertheless seemed to be up to the individual physician. The findings suggest that the de-implementation of LVC needs to address the three reasons from a systems perspective.
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| 25. |
- Ingvarsson-Sundström, Anne, 1964-, et al.
(författare)
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Stable Isotope Analysis of the Middle Helladic Population from two cemeteries at Asine : Barbouna and the East Cemetery
- 2009
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Ingår i: Mediterranean Archaeology and Archaeometry. - Rhodes : The University of the Aegean. - 1108-9628. ; 9:2, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we report the results of the stable carbon and nitrogen isotope analyses of humans from two Middle Bronze Age cemeteries at Asine, Greece: Barbouna (n=6) and the East Cemetery (n=13). In general, the dietary pattern of adults and juveniles shows a heavy reliance on mainly terrestrial foods; C3 plants and a varying amount of animal protein (meat, milk or dairy products). The high nitrogen values of some individuals from the East cemetery indicate a substantial consumption of animal protein, although the carbon values show that no detectable amounts of marine foods, or C4 plants such as millet had been consumed. High nitrogen values as well as the high slaughter age of domestic animals, as found in previous studies point towards a significant utilization of milk and dairy products at Asine. A low increase of nitrogen values in subadults younger than one years of age from Barbouna compared to females at the East cemetery indicates that these children may have been fed breast milk as well as supplementary foods. Therefore, despite the poor preservation and uneven sample size, the Asine isotopic data give us information on diet during the MH period, as well as variation between the members of the community.
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| 26. |
- Ingvarsson, T, et al.
(författare)
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Assessment of primary hip osteoarthritis: comparison of radiographic methods using colon radiographs : comparison of radiographic methods using colon radiographs
- 2000
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 59:8, s. 650-653
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To compare the reliability of quantitative measurement of minimum hip joint space with a qualitative global assessment of radiological features for estimating the prevalence of primary osteoarthritis (OA) of the hip in colon radiographs.METHODS: All colon radiographs from patients aged 35 or older, taken at three different radiographic departments in Iceland during the years 1990-96, were examined. A total of 3002 hips in 638 men and 863 women were analysed. Intraobserver and interobserver reliability was assessed by measuring 147 randomly selected radiographs (294 hips) twice by the same observer, and 87 and 98 randomly selected radiographs (174 and 196 hips) by two additional independent observers. Minimum hip joint space was measured with a millimetre ruler, and global assessment of radiological features by a published atlas.RESULTS: With a minimum joint space of 2.5 mm or less as definition for OA, 212 hips were defined as having OA. When the global Kellgren and Lawrence assessment with grade 2 (definite narrowing in the presence of definite osteophytes) or higher as definition for OA was used, 202 hips showed OA. However, only 166 hips were diagnosed as OA with both systems. With 2.0 or 3.0 mm minimum joint space as cut off point, the difference between the two methods increased. Both intrarater and interrater reliability was significantly higher with joint space measurement than with global assessment.CONCLUSIONS: Overall prevalence of radiological OA was similar with the two methods. However, the quantitative measurement of minimum hip joint space had a better within-observer and between-observer reliability than qualitative global assessment of radiographic features of hip OA. It is thus suggested that minimum joint space measurement is a preferable method in epidemiological studies of radiological hip OA.
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| 27. |
- Keller, Stephen R, et al.
(författare)
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Local selection across a latitudinal gradient shapes nucleotide diversity in balsam poplar, Populus balsamifera L
- 2011
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Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 188:4, s. 941-952
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Tidskriftsartikel (refereegranskat)abstract
- Molecular studies of adaptive evolution often focus on detecting selective sweeps driven by positive selection on a species-wide scale; however, much adaptation is local, particularly of ecologically important traits. Here, we look for evidence of range-wide and local adaptation at candidate genes for adaptive phenology in balsam poplar, Populus balsamifera, a widespread forest tree whose range extends across environmental gradients of photoperiod and growing season length. We examined nucleotide diversity of 27 poplar homologs of the flowering-time network-a group of genes that control plant developmental phenology through interactions with environmental cues such as photoperiod and temperature. Only one gene, ZTL2, showed evidence of reduced diversity and an excess of fixed replacement sites, consistent with a species-wide selective sweep. Two other genes, LFY and FRI, harbored high levels of nucleotide diversity and exhibited elevated differentiation between northern and southern accessions, suggesting local adaptation along a latitudinal gradient. Interestingly, FRI has also been identified as a target of local selection between northern and southern accessions of Arabidopsis thaliana, indicating that this gene may be commonly involved in ecological adaptation in distantly related species. Our findings suggest an important role for local selection shaping molecular diversity and reveal limitations of inferring molecular adaptation from analyses designed only to detect species-wide selective sweeps.
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| 28. |
- Nilsen, P., et al.
(författare)
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Theories, models and frameworks for de-implementation of low-value care : A scoping review of the literature
- 2020
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Ingår i: Implementation Research and Practice. - 2633-4895.
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Tidskriftsartikel (refereegranskat)abstract
- Achieving an evidence-based practice not only depends on implementation of evidence-based interventions (programs, methods, etc.) but also requires de-implementing interventions that are not evidence-based, that is, low-value care (LVC). Thus, de-implementation is the other side of the coin of an evidence-based practice. However, this is quite a new topic and knowledge is lacking concerning how de-implementation and implementation processes and determinants might differ. It is almost mandatory for implementation researchers to use theories, models, and frameworks (i.e., “theoretical approaches”) to describe, guide, or explain implementation processes and determinants. To what extent are such approaches also used with regard to de-implementation of LVC? And what are the characteristics of such approaches when analyzing de-implementation processes? We reviewed the literature to explore issues such as these. We identified only 10 studies describing theoretical approaches that have been used concerning de-implementation of LVC. Five studies presented approaches developed specifically for de-implementation of LVC and five studies applied an already-existing approach usually applied to analyze implementation processes. Most of the theoretical approaches we found suggest a multi-level understanding of de-implementation of LVC, that is, successfully de-implementing LVC may require strategies that target teams, departments, and organizations and merely focus on individual health care practitioners. The findings point to the need for more research to identify the most important processes and determinants for successful de-implementation of LVC, and to explore differences between de-implementation and implementation. In terms of practice and policy implications, the study underscores the relevance of addressing multiple levels when attempting to de-implement LVC.
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| 29. |
- Nilsen, P, et al.
(författare)
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Theories, models, and frameworks for de-implementation of low-value care: A scoping review of the literature
- 2020
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Ingår i: Implementation research and practice. - : SAGE Publications. - 2633-4895. ; 1, s. 2633489520953762-
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this scoping review was to identify theories, models, and frameworks for understanding the processes and determinants of de-implementing low-value care (LVC). We investigated theories, models, and frameworks developed specifically for de-implementation of LVC (conceptual studies) and those that were originally developed for implementation of evidence-based practices but were applied in studies to analyze de-implementation of LVC (empirical studies). Methods: We performed a scoping review to identify theories, models, and frameworks used to describe, guide, or explain de-implementation of LVC, encompassing four stages following the identification of the research question: (1) identifying relevant studies; (2) study selection; (3) charting the data; and (4) collating, summarizing, and reporting the results. The database searches yielded 9,642 citations. After removing duplicates, 6,653 remained for the abstract screening process. After screening the abstracts, 76 citations remained. Of these, 10 studies were included in the review. Results: We identified 10 studies describing theories, models, and frameworks that have been used to understand de-implementation of LVC. Five studies presented theories, models, or frameworks developed specifically for de-implementation of LVC (i.e., conceptual studies) and five studies applied an existing theory, model, or framework concerning implementation of evidence-based practices (i.e., empirical studies). Conclusion: Most of the theories, models, and frameworks that are used to analyze LVC suggest a multi-level understanding of de-implementation of LVC. The role of the patient is inconsistent in these theories, models, and frameworks; patients are accounted for in some but not in others. The findings point to the need for more research to identify the most important processes and determinants for successful de-implementation of LVC and to explore differences between de-implementation and implementation. Plain language abstract Achieving an evidence-based practice not only depends on implementation of evidence-based interventions (programs, methods, etc.) but also requires de-implementing interventions that are not evidence-based, that is, low-value care (LVC). Thus, de-implementation is the other side of the coin of an evidence-based practice. However, this is quite a new topic and knowledge is lacking concerning how de-implementation and implementation processes and determinants might differ. It is almost mandatory for implementation researchers to use theories, models, and frameworks (i.e., “theoretical approaches”) to describe, guide, or explain implementation processes and determinants. To what extent are such approaches also used with regard to de-implementation of LVC? And what are the characteristics of such approaches when analyzing de-implementation processes? We reviewed the literature to explore issues such as these. We identified only 10 studies describing theoretical approaches that have been used concerning de-implementation of LVC. Five studies presented approaches developed specifically for de-implementation of LVC and five studies applied an already-existing approach usually applied to analyze implementation processes. Most of the theoretical approaches we found suggest a multi-level understanding of de-implementation of LVC, that is, successfully de-implementing LVC may require strategies that target teams, departments, and organizations and merely focus on individual health care practitioners. The findings point to the need for more research to identify the most important processes and determinants for successful de-implementation of LVC, and to explore differences between de-implementation and implementation. In terms of practice and policy implications, the study underscores the relevance of addressing multiple levels when attempting to de-implement LVC.
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| 30. |
- Panahabadi, Rahele, et al.
(författare)
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Genome-Wide Association Mapping of Mixed Linkage (1,3;1,4)-beta-Glucan and Starch Contents in Rice Whole Grain
- 2021
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Ingår i: Frontiers in Plant Science. - : Frontiers Media SA. - 1664-462X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The glucan content of rice is a key factor defining its nutritional and economic value. Starch and its derivatives have many industrial applications such as in fuel and material production. Non-starch glucans such as (1,3;1,4)-beta-D-glucan (mixed-linkage beta-glucan, MLG) have many benefits in human health, including lowering cholesterol, boosting the immune system, and modulating the gut microbiome. In this study, the genetic variability of MLG and starch contents were analyzed in rice (Oryza sativa L.) whole grain, by performing a new quantitative analysis of the polysaccharide content of rice grains. The 197 rice accessions investigated had an average MLG content of 252 mu g/mg, which was negatively correlated with the grain starch content. A new genome-wide association study revealed seven significant quantitative trait loci (QTLs) associated with the MLG content and two QTLs associated with the starch content in rice whole grain. Novel genes associated with the MLG content were a hexose transporter and anthocyanidin 5,3-O-glucosyltransferase. Also, the novel gene associated with the starch content was a nodulin-like domain. The data pave the way for a better understanding of the genes involved in determining both MLG and starch contents in rice grains and should facilitate future plant breeding programs.
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| 31. |
- Panahabadi, Rahele, et al.
(författare)
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Genome-wide association study for lignocellulosic compounds and fermentable sugar in rice straw
- 2022
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Ingår i: The Physical Educator. - : Wiley. - 0031-8981 .- 1940-3372. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Cellulose and lignin are the two main components of secondary plant cell walls with substantial impact on stalk in the field and on straw during industrial processing. The amount of fermentable sugar that can be accessed is another important parameter affecting various industrial applications. In the present study, genetic variability of rice (Oryza sativa L.) genotypes for cellulose, lignin, and fermentable sugars contents was analyzed in rice straw. A genome-wide association study of 33,484 single nucleotide polymorphisms (SNPs) with a minor allele frequency (MAF) >0.05 was performed. The genome-wide association study identified seven, three, and three genomic regions to be significantly associated with cellulose, lignin, and fermentable sugar contents, respectively. Candidate genes in the associated genomic regions were enzymes mainly involved in cell wall metabolism. Novel SNP markers associated with cellulose were tagged to GH16, peroxidase, GT6, GT8, and CSLD2. For lignin content, Villin protein, OsWAK1/50/52/53, and GH16 were identified. For fermentable sugar content, UTP-glucose-1-phosphate uridylyltransferase, BRASSINOSTEROID INSENSITIVE 1, and receptor-like protein kinase 5 were found. The results of this study should improve our understanding of the genetic basis of the factors that might be involved in biosynthesis, turnover, and modification of major cell wall components and saccharides in rice straw.
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| 32. |
- Rendón-Anaya, Martha, et al.
(författare)
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Adaptive Introgression Facilitates Adaptation to High Latitudes in European Aspen (Populus tremula L.)
- 2021
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Ingår i: Molecular biology and evolution. - : Oxford University Press. - 0737-4038 .- 1537-1719. ; 38:11, s. 5034-5050
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Tidskriftsartikel (refereegranskat)abstract
- Understanding local adaptation has become a key research area given the ongoing climate challenge and the concomitant requirement to conserve genetic resources. Perennial plants, such as forest trees, are good models to study local adaptation given their wide geographic distribution, largely outcrossing mating systems, and demographic histories. We evaluated signatures of local adaptation in European aspen (Populus tremula) across Europe by means of whole-genome resequencing of a collection of 411 individual trees. We dissected admixture patterns between aspen lineages and observed a strong genomic mosaicism in Scandinavian trees, evidencing different colonization trajectories into the peninsula from Russia, Central and Western Europe. As a consequence of the secondary contacts between populations after the last glacial maximum, we detected an adaptive introgression event in a genome region of ∼500 kb in chromosome 10, harboring a large-effect locus that has previously been shown to contribute to adaptation to the short growing seasons characteristic of Northern Scandinavia. Demographic simulations and ancestry inference suggest an Eastern origin—probably Russian—of the adaptive Nordic allele which nowadays is present in a homozygous state at the north of Scandinavia. The strength of introgression and positive selection signatures in this region is a unique feature in the genome. Furthermore, we detected signals of balancing selection, shared across regional populations, that highlight the importance of standing variation as a primary source of alleles that facilitate local adaptation. Our results, therefore, emphasize the importance of migration–selection balance underlying the genetic architecture of key adaptive quantitative traits.
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| 33. |
- Styrkarsdottir, Unnur, et al.
(författare)
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Severe osteoarthritis of the hand associates with common variants within the ALDH1A2 gene and with rare variants at 1p31.
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 46:5, s. 498-502
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Tidskriftsartikel (refereegranskat)abstract
- Osteoarthritis is the most common form of arthritis and is a major cause of pain and disability in the elderly. To search for sequence variants that confer risk of osteoarthritis of the hand, we carried out a genome-wide association study (GWAS) in subjects with severe hand osteoarthritis, using variants identified through the whole-genome sequencing of 2,230 Icelanders. We found two significantly associated loci in the Icelandic discovery set: at 15q22 (frequency of 50.7%, odds ratio (OR) = 1.51, P = 3.99 × 10(-10)) in the ALDH1A2 gene and at 1p31 (frequency of 0.02%, OR = 50.6, P = 9.8 × 10(-10)). Among the carriers of the variant at 1p31 is a family with several members in whom the risk allele segregates with osteoarthritis. The variants within the ALDH1A2 gene were confirmed in replication sets from The Netherlands and the UK, yielding an overall association of OR = 1.46 and P = 1.1 × 10(-11) (rs3204689).
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| 34. |
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| 35. |
- Sultan, M. T., et al.
(författare)
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Photoluminescence study of Si1-xGex nanoparticles in various oxide matrices
- 2021
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Ingår i: 2021 International Semiconductor Conference (Cas). - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 21-24
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Konferensbidrag (refereegranskat)abstract
- We investigate the photoluminescence properties of structures comprising of Si1-xGex nanoparticles (NPs) within SiO2, GeO2, TiO2 and Ta2O5 oxide matrices. Of the investigated structures, it was observed that the structures with GeO2 and TiO2 matrices provide increased spectral response (at similar to 907 and 844 nm respectively) and increased PL intensity. The improved PL characteristic have been attributed to increased diffusion barrier against oxygen which otherwise would result in formation of unwanted oxide at the film-oxide interface, thereby deteriorating the optical properties.
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| 36. |
- Tirkkonen, M, et al.
(författare)
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Distinct somatic genetic changes associated with tumor progression in carriers of BRCA1 and BRCA2 germ-line mutations
- 1997
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Ingår i: Cancer Research. - 0008-5472. ; 57:7, s. 7-1222
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Tidskriftsartikel (refereegranskat)abstract
- BRCA1 and BRCA2 mutations confer increased risk for development of breast cancer, but a number of additional, currently largely unknown, somatic genetic defects must also accumulate in the breast epithelial cells before malignancy develops. To evaluate the nature of these additional somatic genetic defects, we performed a genome-wide survey by comparative genomic hybridization on breast cancers from 21 BRCA1 mutation carriers, 15 BRCA2 mutation carriers, and 55 unselected controls. The total number of genetic changes was almost two times higher in tumors from both BRCA1 and BRCA2 mutation carriers than in the control group. In BRCA1 tumors, losses of 5q (86%), 4q (81%), 4p (64%), 2q (40%), and 12q (40%) were significantly more common than in the control group (7-13%). BRCA2 tumors were characterized by a higher frequency of 13q (73%) and 6q (60%) losses and gains of 17q22-q24 (87%) and 20q13 (60%) as compared to the prevalence of these changes in the control group (12-18%). In conclusion, accumulation of somatic genetic changes during tumor progression may follow a unique pathway in individuals genetically predisposed to cancer, especially by the BRCA1 gene. Activation or loss of genes in the affected chromosomal regions may be selected for during tumor progression in cells lacking functional BRCA1 or BRCA2. Identification of such genes could provide targets for therapeutic intervention and early diagnosis.
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