| 1. |
- Hollestelle, Antoinette, et al.
(författare)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Tidskriftsartikel (refereegranskat)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 2. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 3. |
- Couch, Fergus J., et al.
(författare)
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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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| 4. |
- Zeng, Chenjie, et al.
(författare)
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Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus
- 2016
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. Method: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. Results: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 x 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 x 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 x 10(-4)) identified in the general populations, and rs113824616 (P = 7 x 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. Conclusion: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.
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| 5. |
- Aboagye, Emmanuel, et al.
(författare)
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Individual preferences for physical exercise as secondary prevention for non-specific low back pain : a discrete choice experiment
- 2017
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Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Exercise is effective in improving non-specific low back pain (LBP). Certain components of physical exercise, such as the type, intensity and frequency of exercise, are likely to influence participation among working adults with non-specific LBP, but the value and relative importance of these components remain unknown. The study's aim was to examine such specific components and their influence on individual preferences for exercise for secondary prevention of non-specific LBP among working adults. Methods: In a discrete choice experiment, working individuals with non-specific LBP answered a webbased questionnaire. Each respondent was given ten pairs of hypothetical exercise programs and asked to choose one option from each pair. The choices comprised six attributes of exercise (i.e., type of training, design, intensity, frequency, proximity and incentives), each with either three or four levels. A conditional logit regression that reflected the random utility model was used to analyze the responses. Results: The final study population consisted of 112 participants. The participants' preferred exercise option was aerobic (i.e., cardiovascular) rather than strength training, group exercise with trainer supervision, rather than individual or unsupervised exercise. They also preferred high intensity exercise performed at least once or twice per week. The most popular types of incentive were exercise during working hours and a wellness allowance rather than coupons for sports goods. The results show that the relative value of some attribute levels differed between young adults (age <= 44 years) and older adults (age <= 45 years) in terms of the level of trainer supervision required, exercise intensity, travel time to exercise location and financial incentives. For active study participants, exercise frequency (i.e., twice per week, 1.15; CI: 0.25; 2.06) influenced choice of exercise. For individuals with more than one child, travel time (i.e., 20 minutes, - 0.55; CI: 0.65; 3.26) was also an influential attribute for choice of exercise, showing that people with children at home preferred to exercise close to home. Conclusions: This study adds to our knowledge about what types of exercise working adults with back pain are most likely to participate in. The exercise should be a cardiovascular type of training carried out in a group with trainer supervision. It should also be of high intensity and preferably performed twice per week during working hours. Coupons for sports goods do not appear to motivate physical activity among workers with LBP. The findings of the study could have a substantial impact on the planning and development of exercise provision and promotion strategies to improve non-specific LBP. Providers and employers may be able to improve participation in exercise programs for adults with non-specific LBP by focusing on the exercise components which are the most attractive. This in turn would improve satisfaction and adherence to exercise interventions aimed at preventing recurrent non-specific LBP.
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| 6. |
- Arapovic-Johansson, Bozana, et al.
(författare)
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Participatory work place intervention for stress prevention in primary health care. A randomized controlled trial
- 2018
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Ingår i: European Journal of Work and Organizational Psychology. - : Routledge. - 1359-432X .- 1464-0643. ; 27:2, s. 219-234
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study is to explore whether a participatory, organizational intervention can reduce work-related risk factors, and thereby prevent stress-related ill health. We build on the job demand-control and effort-reward imbalance models of stress. It is a two-armed randomized trial, with one primary health care unit receiving the intervention and a two-unit control group. Validated questionnaires for the assessment of psychosocial work environment and health were administered, at the baseline and at 6 and 12-month follow up. The primary outcome was job strain. Secondary outcomes were effort-reward imbalance, exhaustion, sleep, and recovery. Group-level objective data on workload and data about relevant processes during the study were continuously collected. The changes in the intervention group with regard to job strain, effort-reward imbalance, exhaustion, sleep and recovery were not statistically different from changes in the control group. For the non-exhausted employees though, reward was significantly higher at follow up compared to baseline, but only in the intervention group. An important piece of information is that the objective workload was statistically significantly higher in the intervention group throughout the study. Not all the components of the intervention were implemented as intended. Context and process information, such as objective data and implementation fidelity are necessary for a valid interpretation of the results.
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| 7. |
- Björklund, Christina, et al.
(författare)
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Workplace Bullying as Experienced by Managers and How They Cope : A Qualitative Study of Swedish Managers
- 2019
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 16:23
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of the study was to describe factors that contribute to the occurrence of workplace bullying, that enable it to continue and the coping strategies managers use when they are bullied. Methods: A qualitative study design was applied. Twenty-two managers from the private and public sectors were interviewed. Data were analyzed by means of content analysis. Results: Several factors could be linked to the bullying: being new in the managerial position; lack of clarity about roles and expectations; taking over a work group with ongoing conflicts; reorganizations. The bullying usually lasted for quite some time. Factors that allowed the bullying to continue were passive bystanders and the bullies receiving support from higher management. The managers in this study adopted a variety of problem-focused and emotion-focused coping strategies. However, in the end most chose to leave the organization. Only four remained in their managerial position at the time of the interview. Conclusions: The study concludes that bullying can occur in all types of organization. To prevent it we need to look primarily at organizational factors. Social support is also crucial for managers' ability to cope successfully with bullying.
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| 8. |
- Blanton, Michael R., et al.
(författare)
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Sloan Digital Sky Survey IV : Mapping the Milky Way, Nearby Galaxies, and the Distant Universe
- 2017
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Ingår i: Astronomical Journal. - : IOP Publishing Ltd. - 0004-6256 .- 1538-3881. ; 154:1
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Tidskriftsartikel (refereegranskat)abstract
- We describe the Sloan Digital Sky Survey IV (SDSS-IV), a project encompassing three major spectroscopic programs. The Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2) is observing hundreds of thousands of Milky Way stars at high resolution and. high signal-to-noise ratios in the near-infrared. The Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey is obtaining spatially resolved spectroscopy for thousands of nearby galaxies (median z similar to 0.03). The extended Baryon Oscillation Spectroscopic Survey (eBOSS) is mapping the galaxy, quasar, and neutral gas distributions between z similar to 0.6 and 3.5 to constrain cosmology using baryon acoustic oscillations, redshift space distortions, and the shape of the power spectrum. Within eBOSS, we are conducting two major subprograms: the SPectroscopic IDentification of eROSITA Sources (SPIDERS), investigating X-ray AGNs. and galaxies in X-ray clusters, and the Time Domain Spectroscopic Survey (TDSS), obtaining spectra of variable sources. All programs use the 2.5 m Sloan Foundation Telescope at the. Apache Point Observatory; observations there began in Summer 2014. APOGEE-2 also operates a second near-infrared spectrograph at the 2.5 m du Pont Telescope at Las Campanas Observatory, with observations beginning in early 2017. Observations at both facilities are scheduled to continue through 2020. In keeping with previous SDSS policy, SDSS-IV provides regularly scheduled public data releases; the first one, Data Release 13, was made available in 2016 July.
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| 9. |
- Bramberg, Elisabeth Bjork, et al.
(författare)
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Development of evidence-based practice in occupational health services in Sweden : a 3-year follow-up of attitudes, barriers and facilitators
- 2017
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer. - 0340-0131 .- 1432-1246. ; 90:4, s. 335-348
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Tidskriftsartikel (refereegranskat)abstract
- The Swedish government initiated an investigation of how to secure and develop the competence of the occupational health services. The primary aim of the present study was to investigate whether the development of evidence-based practice (EBP) in the Swedish occupational health services in relation to attitudes, knowledge and use improved during the first 3 years of the government's initiative. The study has a mixed methods design combining questionnaires and interviews with data collection at baseline and at 3-year follow-up. The response rate was 66% at baseline and 63% at follow-up. The results show that practitioners' knowledge of EBP was moderate at baseline and improved at follow-up (p = 0.002; 95% CI 0.01; 0.21). Practitioners experienced lower levels of organizational and managerial support for EBP at follow-up (p < 0.001; 95% CI 0.18; 0.38). The results revealed that managers viewed responsibility for implementing EBP as a matter for individual practitioners rather than as an organizational issue. Occupational health service managers and practitioners are generally positive to EBP. However, the findings emphasize the need to educate managers in how to support EBP at the organizational level by creating an infrastructure for EBP in the OHS.
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| 10. |
- Busch, Hillevi, et al.
(författare)
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The effects of multimodal rehabilitation on pain-related sickness absence : an observational study
- 2018
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Ingår i: Disability and Rehabilitation. - : Taylor & Francis. - 0963-8288 .- 1464-5165. ; 40:14, s. 1646-1653
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The aim of the current study was to examine the effects on sickness absence of multimodal rehabilitation delivered within the framework of a national implementation of evidence based rehabilitation, the rehabilitation guarantee for nonspecific musculoskeletal pain.Method: This was an observational matched controlled study of all persons receiving multimodal rehabilitation from the last quarter of 2009 until the end of 2010. The matching was based on age, sex, sickness absence the quarter before intervention start and pain-related diagnosis. The participants were followed by register data for 6 or 12 months. The matched controls received rehabilitation in accordance with treatment-as-usual.Results: Of the participants, 54% (N = 3636) were on registered sickness absence at baseline and the quarter before rehabilitation. The average difference in number of days of sickness absence between the participants who received multimodal rehabilitation and the matched controls was to the advantage of the matched controls, 14.7 days (CI 11.7; 17.7, p ≤ 0.001) at 6-month follow-up and 9.5 days (CI 6.7; 12.3, p ≤ 0.001) at 12-month follow-up. A significant difference in newly granted disability pensions was found in favor of the intervention.Conclusions: When implemented nationwide, multimodal rehabilitation appears not to reduce sickness absence compared to treatment-as-usual.Implications for RehabilitationA nationwide implementation of multimodal rehabilitation was not effective in reducing sickness absence compared to treatment-as-usual for persons with nonspecific musculoskeletal pain.Multimodal rehabilitation was effective in reducing the risk of future disability pension for persons with nonspecific musculoskeletal pain compared to treatment-as-usual.To be effective in reducing sick leave multimodal rehabilitation must be started within 60 days of sick leave.The evidence for positive effect of multimodal rehabilitation is mainly for sick listed patients. Prevention of sick leave for persons not being on sick leave should not be extrapolated from evidence for multimodal rehabilitation.
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