| 1. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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| 2. |
- Dennermalm, Nicklas, et al.
(författare)
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Sex, drugs and techno - a qualitative study on finding the balance between risk, safety and pleasure among men who have sex with men engaging in recreational and sexualised drug use
- 2021
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recreational and sexual drug use among men who have sex with men may result in increased risk of poor health. The aim of this study was to better understand drug use and harm reduction techniques among Swedish men who have sex with men traveling to Berlin in order to improve the health of this population and inform public health strategies.Methods: A qualitative study based on semi-structured interviews with 15 Swedish men aged 23-44 with experience of drug use were recruited through network sampling. Interviews were conducted in Stockholm and Berlin and analysed using content analysis. The interview guide included questions on drug use, context, health and safety.Results: The participants engaged in drug use in both settings and in various contexts. Participants saw themselves as capable of finding a balance between pleasure, safety and risk with the aim to maximize positive effects while minimizing negative ones. The different risks of drug use were known, and participants relied on knowledge, harm reduction strategies and self-defined rules of intake to stay safe and healthy in a broad sense, both short term (i.e. during each session) and long term. Choice of drug and, frequency of intake, multi-use, risk of overdose, risk of HIV, purpose and context of use, how often, etc. were all part of the overall strategy. Knowledge of these methods was spread within the community and on-line rather than from counsellors or other health care providers. However, it did not always translate perfectly into practice and some had experienced overdoses and problematic use.Conclusions: The findings of this study point to the need for increased adoption of harm reduction techniques in this population focusing on mitigating harm and prevention of risk of problematic use or starting injection drugs. Existing traditional services require adaptations to become more accessible and acceptable to sub-groups of drug users, including low-threshold services providing non-judgemental, evidence-based information. This will require funding of alternative providers such as STI/HIV clinics, among others, and health care providers to increase adoption of prevention strategies, specifically pre-exposure prophylaxis for HIV.
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| 3. |
- Gaulton, Kyle J, et al.
(författare)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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| 4. |
- Hudson, Thomas J., et al.
(författare)
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International network of cancer genome projects
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
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Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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| 5. |
- Jackson, Victoria E, et al.
(författare)
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Meta-analysis of exome array data identifies six novel genetic loci for lung function.
- 2018
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Ingår i: Wellcome open research. - : F1000 Research Ltd. - 2398-502X. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV 1), forced vital capacity (FVC) and the ratio of FEV 1 to FVC (FEV 1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10 -7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs ( SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.
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| 6. |
- Målqvist, Mats, 1971-, et al.
(författare)
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Causes and determinants of inequity in maternal and child health in Vietnam
- 2012
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Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 12, s. 641-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Inequities in health are a major challenge for health care planners and policymakers globally. In Vietnam, rapid societal development presents a considerable risk for disadvantaged populations to be left behind. The aim of this review is to map the known causes and determinants of inequity in maternal and child health in Vietnam in order to promote policy action.METHODS:A review was performed through systematic searches of Pubmed and Proquest and manual searches of "grey literature." A thematic content analysis guided by the conceptual framework suggested by the Commission on Social Determinants of Health was performed.RESULTS:More than thirty different causes and determinants of inequity in maternal and child health were identified. Some determinants worth highlighting were the influence of informal fees and the many testimonies of discrimination and negative attitudes from health staff towards women in general and ethnic minorities in particular. Research gaps were identified, such as a lack of studies investigating the influence of education on health care utilization, informal costs of care, and how psychosocial factors mediate inequity.CONCLUSIONS:The evidence of corruption and discrimination as mediators of health inequity in Vietnam calls for attention and indicates a need for more structural interventions such as better governance and anti-discriminatory laws. More research is needed in order to fully understand the pathways of inequities in health in Vietnam and suggest areas for intervention for policy action to reach disadvantaged populations.
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| 7. |
- Målqvist, Mats, 1971-, et al.
(författare)
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Ethnic minority health in Vietnam : a review exposing horizontal inequity
- 2013
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Ingår i: Global Health Action. - : Informa UK Limited. - 1654-9716 .- 1654-9880. ; 6, s. 1-19
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Forskningsöversikt (refereegranskat)abstract
- Background:Equity in health is a pressing concern and reaching disadvantaged populations is necessary to close the inequity gap. To date, the discourse has predominately focussed on reaching the poor. At the same time and in addition to wealth, other structural determinants that influence health outcomes exist, one of which is ethnicity. Inequities based on group belongings are recognised as 'horizontal', as opposed to the more commonly used notion of 'vertical' inequity based on individual characteristics.Objective:The aim of the present review is to highlight ethnicity as a source of horizontal inequity in health and to expose mechanisms that cause and maintain this inequity in Vietnam.Design:Through a systematic search of available academic and grey literature, 49 publications were selected for review. Information was extracted on: a) quantitative measures of health inequities based on ethnicity and b) qualitative descriptions explaining potential reasons for ethnicity-based health inequities.Results:Five main areas were identified: health-care-seeking and utilization, maternal and child health, nutrition, infectious diseases, and oral health and hygiene. Evidence suggests the presence of severe health inequity in health along ethnic lines in all these areas. Research evidence also offers explanations derived from both external and internal group dynamics to this inequity. It is reported that government policies and programs appear to be lacking in culturally adaptation and sensitivity, and examples of bad attitudes and discrimination from health staff toward minority persons were identified. In addition, traditions and patriarchal structures within ethnic minority groups were seen to contribute to the maintenance of harmful health behaviors within these groups.Conclusion:Better understandings of the scope and pathways of horizontal inequities are required to address ethnic inequities in health. Awareness of ethnicity as a determinant of health, not only as a covariate of poverty or living area, needs to be improved, and research needs to be designed with this in mind.
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| 8. |
- Målqvist, Mats, 1971-, et al.
(författare)
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Targeted Interventions for Improved Equity in Maternal and Child Health in Low- and Middle-Income Settings : A Systematic Review and Meta-Analysis
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:6, s. e66453-
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Forskningsöversikt (refereegranskat)abstract
- Background: Targeted interventions to improve maternal and child health is suggested as a feasible and sometimes even necessary strategy to reduce inequity. The objective of this systematic review was to gather the evidence of the effectiveness of targeted interventions to improve equity in MDG 4 and 5 outcomes. Methods and Findings: We identified primary studies in all languages by searching nine health and social databases, including grey literature and dissertations. Studies evaluating the effect of an intervention tailored to address a structural determinant of inequity in maternal and child health were included. Thus general interventions targeting disadvantaged populations were excluded. Outcome measures were limited to indicators proposed for Millennium Development Goals 4 and 5. We identified 18 articles, whereof 15 evaluated various incentive programs, two evaluated a targeted policy intervention, and only one study evaluated an intervention addressing a cultural custom. Meta-analyses of the effectiveness of incentives programs showed a pooled effect size of RR 1.66 (95% CI 1.43-1.93) for antenatal care attendance (four studies with 2,476 participants) and RR 2.37 (95% CI 1.38-4.07) for health facility delivery (five studies with 25,625 participants). Meta-analyses were not performed for any of the other outcomes due to scarcity of studies. Conclusions: The targeted interventions aiming to improve maternal and child health are mainly limited to addressing economic disparities through various incentive schemes like conditional cash transfers and voucher schemes. This is a feasible strategy to reduce inequity based on income. More innovative action-oriented research is needed to speed up progress in maternal and child survival among the most disadvantaged populations through interventions targeting the underlying structural determinants of inequity.
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| 9. |
- Thomsen, Jonas Bjerg, et al.
(författare)
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On Mooring Solutions for Large Wave Energy Converters
- 2017
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Ingår i: Proceedings of the 12th European Wave and Tidal Energy Conference 27th Aug -1st Sept 2017, Cork, Ireland. - 2309-1983.
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Konferensbidrag (refereegranskat)abstract
- The present paper describes the work carriedout in the project ’Mooring Solutions for Large Wave Energy Converters’, which is a Danish research project carried out in aperiod of three years from September 2014, with the aim of reducing cost of the moorings for four wave energy converters and improving the applied design procedure.The paper presents the initial layouts and costs and illustrates which solutions could potentially reduce cost. Different methods foranalysis of the systems were applied, ranging from simplequasi - static analysis to full dynamic analysis and experimental work. The numerical methods were compared to the experimental data, and results showed significant underestimation of tensions inthequasi - static model while reasonable overestimation was found in the dynamic analysis even without major tuning of the model. The dynamic analysis has then been implemented in a meta - model based optimization process with the aim of optimizing the mooring layout for each WEC according to cost of the systems.
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| 10. |
- Thomsen, Sarah, et al.
(författare)
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Feelings of professional fulfilment and exhaustion in mental health personnel: The importance of organisational and individual factors
- 1999
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Ingår i: Psychotherapy and Psychosomatics. - : S. Karger AG. - 0033-3190 .- 1423-0348. ; 68:3, s. 157-164
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mental health personnel are at high risk for mental illness, burnout and suicide. Previous studies of this group of professionals have indicated the importance of organisational factors in explaining burnout, or exhaustion, and work satisfaction. This study looks more systematically at the contribution of organisational and individual factors to work-related exhaustion and to professional fulfillment, an expanded version of job satisfaction. METHODS: A cross-sectional study of 1, 051 psychiatrists and mental health nurses in the city of Stockholm was carried out by postal questionnaire with a previously validated instrument. Multiple and logistic regressions were used to identify predictors of exhaustion and professional fulfillment. RESULTS: Organisational characteristics were found to be more important than individual characteristics in predicting exhaustion and professional fulfillment in mental health professionals. CONCLUSIONS: The results indicate that the psychosocial work environment and well-being of mental health professionals can be improved by concentrating on organisational factors such as efficiency, personal development and goal quality.
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