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| 2. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 3. |
- Voight, Benjamin F., et al.
(författare)
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Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:7, s. 579-589
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Tidskriftsartikel (refereegranskat)abstract
- By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 x 10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.
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| 4. |
- Rosengren, Annika, 1951, et al.
(författare)
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Socioeconomic status and risk of cardiovascular disease in 20 low-income, middle-income, and high-income countries: the Prospective Urban Rural Epidemiologic (PURE) study
- 2019
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Ingår i: Lancet Global Health. - : Elsevier BV. - 2214-109X. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- Background Socioeconomic status is associated with differences in risk factors for cardiovascular disease incidence and outcomes, including mortality However, it is unclear whether the associations between cardiovascular disease and common measures of socioeconomic status-wealth and education-differ among high-income, middle-income, and low-income countries, and, if so, why these differences exist. We explored the association between education and household wealth and cardiovascular disease and mortality to assess which marker is the stronger predictor of outcomes, and examined whether any differences in cardiovascular disease by socioeconomic status parallel differences in risk factor levels or differences in management. Methods In this large-scale prospective cohort study, we recruited adults aged between 35 years and 70 years from 367 urban and 302 rural communities in 20 countries. We collected data on families and households in two questionnaires, and data on cardiovascular risk factors in a third questionnaire, which was supplemented with physical examination. We assessed socioeconomic status using education and a household wealth index. Education was categorised as no or primary school education only, secondary school education, or higher education, defined as completion of trade school, college, or university. Household wealth, calculated at the household level and with household data, was defined by an index on the basis of ownership of assets and housing characteristics. Primary outcomes were major cardiovascular disease (a composite of cardiovascular deaths, strokes, myocardial infarction, and heart failure), cardiovascular mortality, and all-cause mortality. Information on specific events was obtained from participants or their family. Findings Recruitment to the study began on Jan 12, 2001, with most participants enrolled between Jan 6, 2005, and Dec 4, 2014. 160 299 (87.9%) of 182 375 participants with baseline data had available follow-up event data and were eligible for inclusion. After exclusion of 6130 (3.8%) participants without complete baseline or follow-up data, 154 169 individuals remained for analysis, from five low-income, 11 middle-income, and four high-income countries. Participants were followed-up for a mean of 7.5 years. Major cardiovascular events were more common among those with low levels of education in all types of country studied, but much more so in low-income countries. After adjustment for wealth and other factors, the HR (low level of education vs high level of education) was 1.23 (95% CI 0.96-1.58) for high-income countries, 1.59 (1.42-1.78) in middle-income countries, and 2.23 (1.79-2.77) in low-income countries (p(interaction)<0 .0001). We observed similar results for all-cause mortality, with HRs of 1.50 (1.14-1.98) for high-income countries, 1.80 (1.58-2.06) in middle-income countries, and 2.76 (2.29-3.31) in low-income countries (p(interaction)<0. 0001). By contrast, we found no or weak associations between wealth and these two outcomes. Differences in outcomes between educational groups were not explained by differences in risk factors, which decreased as the level of education increased in high-income countries, but increased as the level of education increased in low-income countries (p(interaction)<0.0001). Medical care (eg, management of hypertension, diabetes, and secondary prevention) seemed to play an important part in adverse cardiovascular disease outcomes because such care is likely to be poorer in people with the lowest levels of education compared to those with higher levels of education in low-income countries; however, we observed less marked differences in care based on level of education in middle-income countries and no or minor differences in high-income countries. Interpretation Although people with a lower level of education in low-income and middle-income countries have higher incidence of and mortality from cardiovascular disease, they have better overall risk factor profiles. However, these individuals have markedly poorer health care. Policies to reduce health inequities globally must include strategies to overcome barriers to care, especially for those with lower levels of education. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.
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| 5. |
- Blenckner, Thorsten, et al.
(författare)
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The Baltic Health Index (BHI): Assessing the social-ecological status of the Baltic Sea
- 2021
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Ingår i: People and Nature. - : Wiley. - 2575-8314. ; 3:2, s. 359-375
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Tidskriftsartikel (refereegranskat)abstract
- Improving the health of coastal and open sea marine ecosystems represents a substantial challenge for sustainable marine resource management, since it requires balancing human benefits and impacts on the ocean. This challenge is often exacerbated by incomplete knowledge and lack of tools that measure ocean and coastal ecosystem health in a way that allows consistent monitoring of progress towards predefined management targets. The lack of such tools often limits capabilities to enact and enforce effective governance. We introduce the Baltic Health Index (BHI) as a transparent, collaborative and repeatable assessment tool. The Index complements existing, more ecological-oriented, approaches by including a human dimension on the status of the Baltic Sea, an ecosystem impacted by multiple anthropogenic pressures and governed by a multitude of comprehensive national and international policies. Using a large amount of social-ecological data available, we assessed the health of the Baltic Sea for nine goals that represent the status towards set targets, for example, clean waters, biodiversity, food provision, natural products extraction and tourism. Our results indicate that the overall health of the Baltic Sea is suboptimal (a score of 76 out of 100), and a substantial effort is required to reach the management objectives and associated targets. Subregionally, the lowest BHI scores were measured for carbon storage, contaminants and lasting special places (i.e. marine protected areas), albeit with large spatial variation. Overall, the likely future status of all goals in the BHI averaged for the entire Baltic Sea is better than the present status, indicating a positive trend towards a healthier Baltic Sea. However, in some Baltic Sea basins, the trend for specific goals was decreasing, highlighting locations and issues that should be the focus of management priorities. The BHI outcomes can be used to identify both pan-Baltic and subregional scale management priorities and to illustrate the interconnectedness between goals linked by cumulative pressures. Hence, the information provided by the BHI tool and its further development will contribute towards the fulfilment of the UN Agenda 2030 and its Sustainability Development Goals. A free Plain Language Summary can be found within the Supporting Information of this article. A free Plain Language Summary can be found within the Supporting Information of this article.
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| 6. |
- Duffy, J. E., et al.
(författare)
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Biodiversity mediates top-down control in eelgrass ecosystems: a global comparative-experimental approach
- 2015
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Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 18:7, s. 696-705
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Tidskriftsartikel (refereegranskat)abstract
- Nutrient pollution and reduced grazing each can stimulate algal blooms as shown by numerous experiments. But because experiments rarely incorporate natural variation in environmental factors and biodiversity, conditions determining the relative strength of bottom-up and top-down forcing remain unresolved. We factorially added nutrients and reduced grazing at 15 sites across the range of the marine foundation species eelgrass (Zostera marina) to quantify how top-down and bottom-up control interact with natural gradients in biodiversity and environmental forcing. Experiments confirmed modest top-down control of algae, whereas fertilisation had no general effect. Unexpectedly, grazer and algal biomass were better predicted by cross-site variation in grazer and eelgrass diversity than by global environmental gradients. Moreover, these large-scale patterns corresponded strikingly with prior small-scale experiments. Our results link global and local evidence that biodiversity and top-down control strongly influence functioning of threatened seagrass ecosystems, and suggest that biodiversity is comparably important to global change stressors.
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| 7. |
- Temmink, R. J. M., et al.
(författare)
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Mimicry of emergent traits amplifies coastal restoration success
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Restoration is becoming a vital tool to counteract coastal ecosystem degradation. Modifying transplant designs of habitat-forming organisms from dispersed to clumped can amplify coastal restoration yields as it generates self-facilitation from emergent traits, i.e. traits not expressed by individuals or small clones, but that emerge in clumped individuals or large clones. Here, we advance restoration science by mimicking key emergent traits that locally suppress physical stress using biodegradable establishment structures. Experiments across (sub)tropical and temperate seagrass and salt marsh systems demonstrate greatly enhanced yields when individuals are transplanted within structures mimicking emergent traits that suppress waves or sediment mobility. Specifically, belowground mimics of dense root mats most facilitate seagrasses via sediment stabilization, while mimics of aboveground plant structures most facilitate marsh grasses by reducing stem movement. Mimicking key emergent traits may allow upscaling of restoration in many ecosystems that depend on self-facilitation for persistence, by constraining biological material requirements and implementation costs.
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| 8. |
- Bostrom, P, et al.
(författare)
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Is irisin a human exercise gene? Reply
- 2012
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Ingår i: NATURE. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 488:7413, s. E10-E11
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 9. |
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| 10. |
- Kjellberg, A, et al.
(författare)
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Hyperbaric oxygen for treatment of long COVID-19 syndrome (HOT-LoCO): protocol for a randomised, placebo-controlled, double-blind, phase II clinical trial
- 2022
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 12:11, s. e061870-
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Tidskriftsartikel (refereegranskat)abstract
- Long COVID-19, where symptoms persist 12 weeks after the initial SARS-CoV-2-infection, is a substantial problem for individuals and society in the surge of the pandemic. Common symptoms are fatigue, postexertional malaise and cognitive dysfunction. There is currently no effective treatment and the underlying mechanisms are unknown, although several hypotheses exist, with chronic inflammation as a common denominator. In prospective studies, hyperbaric oxygen therapy (HBOT) has been suggested to be effective for the treatment of similar syndromes such as chronic fatigue syndrome and fibromyalgia. A case series has suggested positive effects of HBOT in long COVID-19. This randomised, placebo-controlled clinical trial will explore HBOT as a potential treatment for long COVID-19. The primary objective is to evaluate if HBOT improves health-related quality of life (HRQoL) for patients with long COVID-19 compared with placebo/sham. The main secondary objective is to evaluate whether HBOT improves endothelial function, objective physical performance and short-term HRQoL.Methods and analysisA randomised, placebo-controlled, double-blind, phase II clinical trial in 80 previously healthy subjects debilitated due to long COVID-19, with low HRQoL. Clinical data, HRQoL questionnaires, blood samples, objective tests and activity metre data will be collected at baseline. Subjects will be randomised to a maximum of 10 treatments with hyperbaric oxygen or sham treatment over 6 weeks. Assessments for safety and efficacy will be performed at 6, 13, 26 and 52 weeks, with the primary endpoint (physical domains in RAND 36-Item Health Survey) and main secondary endpoints defined at 13 weeks after baseline. Data will be reviewed by an independent data safety monitoring board.Ethics and disseminationThe trial is approved by the Swedish National Institutional Review Board (2021–02634) and the Swedish Medical Products Agency (5.1-2020-36673). Positive, negative and inconclusive results will be published in peer-reviewed scientific journals with open access.Trial registration numberNCT04842448.
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