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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. |
- 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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| 6. |
- Kaucka, M., et al.
(författare)
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Altered developmental programs and oriented cell divisions lead to bulky bones during salamander limb regeneration
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- There are major differences in duration and scale at which limb development and regeneration proceed, raising the question to what extent regeneration is a recapitulation of development. We address this by analyzing skeletal elements using a combination of micro-CT imaging, molecular profiling and clonal cell tracing. We find that, in contrast to development, regenerative skeletal growth is accomplished based entirely on cartilage expansion prior to ossification, not limiting the transversal cartilage expansion and resulting in bulkier skeletal parts. The oriented extension of salamander cartilage and bone appear similar to the development of basicranial synchondroses in mammals, as we found no evidence for cartilage stem cell niches or growth plate-like structures during neither development nor regeneration. Both regenerative and developmental ossification in salamanders start from the cortical bone and proceeds inwards, showing the diversity of schemes for the synchrony of cortical and endochondral ossification among vertebrates. Normal limb development relies on synchronized formation of cartilage and bone. Here, the authors show that in salamander limb regeneration these processes are decoupled: ossification occurs after the final size of regenerating cartilage is reached, allowing fast regeneration and leading to bulky bones.
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| 7. |
- Sperl, L, et al.
(författare)
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EDUCATIONAL NEEDS AMONG HEALTH PROFESSIONALS IN RHEUMATOLOGY: LOW AWARENESS OF EULAR OFFERINGS AND UNFAMILIARITY WITH COURSE CONTENT AS A MAJOR BARRIER - A EULAR FUNDED EUROPEAN SURVEY
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 139-140
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Health professionals in rheumatology (HPRs) should participate in post-graduate or continuous education to update and advance their knowledge and skills. This can improve patient outcomes and increase quality of care.1 EULAR aims to become a leading provider of postgraduate education for HPRs.ObjectivesThe aims of this study were to evaluate the current motivations for participating in postgraduate education of HPRs, identify barriers and facilitators for participation in postgraduate education, and evaluate participation in the current educational offerings of EULAR for HPRs across Europe.MethodsAn online survey was developed and distributed in collaboration with the EULAR Standing Committee of Education and Training (ESCET) and the Paediatric Rheumatology European Society (PReS). The questionnaire was translated by national HPR representatives in 24 languages to cover the 25 national member organisations. Barriers were assessed using 5-point Likert scales, higher scores representing higher barriers. Quantitative data were analysed using descriptive statistics. In addition, we ran the Latent Dirichlet Allocation (LDA) on the answers to the open questions. LDA is an unsupervised probabilistic topic modelling technique that extracts the meanings of a pre-defined number of topics. Design of the survey and reporting of results were done according to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES).ResultsThe online questionnaire was accessed 3,589 times but only 667 complete responses were recorded. HPRs from 34 European countries responded to the survey; 80% of whom were women. The highest-ranked educational need was prevention, including lifestyle interventions and professional development. Although EULAR was well known among HPRs, only 32.1% of HPRs in adult care and 18.6% of HPRs in paediatric care have ever heard of the EULAR School of Rheumatology (Table 1 A).Table 1.A: Feedback on EULAR. Data are presented separately for HPRs in adult and paediatric care; except for the filter questions, no mandatory questions were included in the survey. To clarify the number of responses per question, the number of valid answers for each question was reported.VariablesHPRs in adult careHPRs in paediatric careHave you ever heard of the EULAR School of Rheumatology?61443 I am not sure, n(%)62 (10.1%)7 (16.3%) No, n(%)355 (57.8%)28 (65.1%) Yes, n(%)197 (32.1%)8 (18.6%)Are you aware of courses offered by the EULAR School of Rheumatology? (sub question)1978 I am not sure, n(%)30 (15.2%)2 (25.0%) No, n(%)63 (32.0%)5 (62.5%) Yes, n(%)104 (52.8%)1 (12.5%)Have you ever attended one of the EULAR School of Rheumatology courses? (sub question)1031 I am not sure, n(%)1 (1.0%)0 No, n(%)47 (45.6%)0 Yes, n(%)55 (53.4%)1 (100%)Have you ever participated in a EULAR annual congress meeting?61843 I am not sure, n(%)11 (1.8%)0 No, n(%)457 (73.9%)39 (90.7%) Yes, n(%)150 (24.3%)4 (9.3%)The main barriers to participation in EULAR’s educational offerings were identified by HPRs in adult care and in paediatric care (respectively) as: the unfamiliarity with the course content (3.48 [±1.50]; 3.92 [±1.46]), the associated costs (3.44 [±1.35]; 3.69 [±1.28]) and English language (2.59 [±1.50]; 2.80 [±1.34]).ConclusionEULAR is well-known by HPRs in Europe, however, awareness of educational offerings is low and barriers to participation are numerous. To become the leading provider of postgraduate training by 2023, EULAR could use a “franchise” model that can be tailored to local conditions. This could be achieved by strengthening national organizations by actively involving them in the development of training programs and disseminating these programs and offerings through their networks.References[1]World Health Organization. Health workforce: Education and training: World Health Organization; 2019 [Available from: https://www.who.int/hrh/education/en/ accessed November, 2019 2019.Disclosure of InterestsLisa Sperl: None declared, Tanja Stamm Speakers bureau: AbbVie, Novartis, Roche, Sanofi, and Takeda, Consultant of: AbbVie and Sanofi Genzyme, Grant/research support from: AbbVie and Roche, Margaret Renn Andrews: None declared, Mathilda Bjork: None declared, Carina Boström: None declared, Jeannette Cappon: None declared, Jenny de la Torre-Aboki: None declared, Annette de Thurah: None declared, Andrea Domjan: None declared, Razvan Dragoi Speakers bureau: Received speaker fees last year from: Pfizer, Elly Lilly, Sandoz, Abbvie, Secom, EwoPharma, Fernando Estevez-Lopez: None declared, Ricardo J. O. Ferreira: None declared, George E. Fragoulis: None declared, Jolanta Grygielska: None declared, Katti Korve: None declared, Marja Leena Kukkurainen: None declared, Christel Madelaine-Bonjour: None declared, Andrea Marques: None declared, Jorit Meesters: None declared, Rikke Helene Moe: None declared, Ellen Moholt: None declared, Erika Mosor: None declared, Claudia Naimer-Stach: None declared, Mwidimi Ndosi: None declared, Polina Pchelnikova: None declared, Jette Primdahl: None declared, Polina Putrik: None declared, Anne-Kathrin Rausch Osthoff: None declared, Hana Smucrova: None declared, Sinisa Stefanac: None declared, Marco Testa: None declared, Leti van Bodegom-Vos: None declared, Wilfred Peter: None declared, Heidi A. Zangi: None declared, Olena Zimba: None declared, T.P.M. Vliet Vlieland: None declared, Valentin Ritschl: None declared
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| 8. |
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| 9. |
- Knuuttila, M., et al.
(författare)
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Intratumoral androgen levels are linked to TMPRSS2-ERG fusion in prostate cancer
- 2018
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Ingår i: Endocrine-Related Cancer. - : Bioscientifica. - 1351-0088 .- 1479-6821. ; 25:9, s. 807-819
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Tidskriftsartikel (refereegranskat)abstract
- Intratumoral androgen biosynthesis is one of the mechanisms involved in the progression of prostate cancer, and an important target for novel prostate cancer therapies. Using gas chromatography-tandem mass spectrometry and genome-wide RNA sequencing, we have analyzed androgen concentrations and androgen-regulated gene expression in cancerous and morphologically benign prostate tissue specimens and serum samples obtained from 48 primary prostate cancer patients. Intratumoral dihydrotestosterone (DHT) concentrations were significantly higher in the cancerous tissues compared to benign prostate (P < 0.001). The tissue/serum ratios of androgens were highly variable between the patients, indicating individual patterns of androgen metabolism and/or uptake of androgens within the prostate tissue. An unsupervised hierarchical clustering analysis of intratissue androgen concentrations indicated that transmembrane protease, serine 2/ETS-related gene (TMPRSS2-ERG)-positive patients have different androgen profiles compared to TMPRSS2-ERG- negative patients. TMPRSS2-ERG gene fusion status was also associated with an enhanced androgen-regulated gene expression, along with altered intratumoral androgen metabolism, demonstrated by reduced testosterone concentrations and increased DHT/testosterone ratios in TMPRSS2-ERG-positive tumors. TMPRSS2-ERG-positive and - negative prostate cancer specimens have distinct intratumoral androgen profiles, possibly due to activation of testosterone-independent DHT biosynthesis via the alternative pathway in TMPRSS2-ERG-positive tumors. Thus, patients with TMPRSS2-ERG-positive prostate cancer may benefit from novel inhibitors targeting the alternative DHT biosynthesis.
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| 10. |
- 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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