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1.
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2.
  • Eriksson, Hanna, et al. (författare)
  • Later stage at diagnosis and worse survival in cutaneous malignant melanoma among men living alone : a nationwide population-based study from Sweden
  • 2014
  • Ingår i: Journal of Clinical Oncology. - American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 32:13, s. 1356-1364
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>PURPOSE:</p><p>To investigate the association between cohabitation status, clinical stage at diagnosis, and disease-specific survival in cutaneous malignant melanoma (CMM).</p><p>METHODS:</p><p>This nationwide population-based study included 27,235 patients from the Swedish Melanoma Register diagnosed with a primary invasive CMM between 1990 and 2007 and linked data to nationwide, population-based registers followed up through 2012.</p><p>RESULTS:</p><p>After adjustment for age at diagnosis, level of education, living area, period of diagnosis, and tumor site, the odds ratios (ORs) of higher stage at diagnosis were significantly increased among men living alone versus men living with a partner (stage II v stage I: OR, 1.42; 95% CI, 1.29 to 1.57; stage III or IV v stage I: OR, 1.43; 95% CI, 1.14 to 1.79). The OR for stage II versus stage I disease was also increased among women living alone (OR, 1.15; 95% CI, 1.04 to 1.28). After adjustments for the factors listed earlier, the CMM-specific survival was significantly decreased among men living alone (hazard ratio [HR] for death, 1.48; 95% CI, 1.33 to 1.65; P &lt; .001). After additional adjustments for all potential and established prognostic factors, CMM-specific survival among men living alone versus men living with a partner remained significantly decreased (HR, 1.31; 95% CI, 1.18 to 1.46; P &lt; .001), suggesting a residual adverse effect on survival not accounted for by these parameters.</p><p>CONCLUSION:</p><p>In all age groups among men, living alone is significantly associated with reduced CMM-specific survival, partially attributed to a more advanced stage at diagnosis. This emphasizes the need for improved prevention and early detection strategies for this group.</p>
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3.
  • Eriksson, Hanna, et al. (författare)
  • Low level of education is associated with later stage at diagnosis and reduced survival in cutaneous malignant melanoma : A nationwide population-based study in Sweden
  • 2013
  • Ingår i: European Journal of Cancer. - Elsevier. - 0959-8049 .- 1879-0852. ; 49:12, s. 2705-2716
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>BACKGROUND:</p><p>A worse outcome has been reported for cutaneous malignant melanoma (CMM) patients with low socioeconomic status. We have investigated the association between level of education, clinical stage at diagnosis (stage at diagnosis) and CMM-specific survival in Sweden.</p><p>METHODS:</p><p>We identified 27,235 patients from the Swedish Melanoma Register diagnosed with a primary invasive CMM between 1990 and 2007 and linked data to nationwide, population-based, health and census registers with a follow-up to 2010.</p><p>RESULTS:</p><p>The odds ratio (OR) of higher disease stage at diagnosis was significantly increased in lower education groups (OR stage II versus I=1.6; 95% confidence interval (CI)=1.5-1.7. OR stage III-IV versus I=2.3; 95% CI=1.8-2.9). The risk of dying of CMM, was significantly increased in patients with low (hazard ratio (HR) low versus high=2.02; 95% CI=1.80-2.26; p&lt;0.0001) and intermediate (HR intermediate versus high=1.35; 95% CI=1.20-1.51; p&lt;0.0001) level of education. After adjustment for age, gender, stage at diagnosis and other known prognostic factors, the HRs remained significant for low versus high (HR=1.13; 95% CI=1.01-1.27; p=0.04) but not for intermediate versus high (HR=1.11; 95% CI=0.99-1.24; p=0.08) education. The HR associated with low level of education was significantly higher among female patients, patients &lt;55years, patients with truncal tumours and during the first 5years after diagnosis.</p><p>CONCLUSION:</p><p>Lower level of education is associated with reduced CMM-specific survival, which may at least partially be attributed to a more advanced stage at diagnosis. These results emphasise the need for improved early detection strategies.</p>
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4.
  • Gaulton, Kyle J, et al. (författare)
  • Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
  • 2015
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1546-1718. ; 47:12, s. 1415-1415
  • 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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5.
  • Heaf, James, et al. (författare)
  • Why do physicians prescribe dialysis? A prospective questionnaire study
  • 2017
  • Ingår i: PLoS ONE. - Public Library of Science. - 1932-6203. ; 12:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction The incidence of unplanned dialysis initiation (DI) with consequent increased comorbidity, mortality and reduced modality choice remains high, but the optimal timing of dialysis initiation (DI) remains controversial, and there is a lack of studies of specific reasons for DI. We investigated why and when physicians prescribe dialysis and hypothesized that physician motivation for DI is an independent factor which may have clinical consequences. Methods In the Peridialysis study, an ongoing multicenter prospective study assessing the causes and timing of DI and consequences of unplanned dialysis, physicians in 11 hospitals were asked to describe their primary, secondary and further reasons for prescribing DI. The stated reasons for DI were analyzed in relation to clinical and biochemical data at DI, and characteristics of physicians. Results In 446 patients (median age 67 years; 38% females; diabetes 25.6%), DI was prescribed by 84 doctors who stated 23 different primary reasons for DI. The primary indication was clinical in 63% and biochemical in 37%; 23% started for life-threatening conditions. Reduced renal function accounted for only 19% of primary reasons for DI but was a primary or contributing reason in 69%. The eGFR at DI was 7.2 ±3.4 ml/min/1.73 m2, but varied according to comorbidity and cause of DI. Patients with cachexia, anorexia and pulmonary stasis (34% with heart failure) had the highest eGFR (8.2–9.8 ml/min/1.73 m2), and those with edema, “low GFR”, and acidosis, the lowest (4.6–6.1 ml/min/1.73 m2). Patients with multiple comorbidity including diabetes started at a high eGFR (8.7 ml/min/1.73 m2). Physician experience played a role in dialysis prescription. Non-specialists were more likely to prescribe dialysis for life-threatening conditions, while older and more experienced physicians were more likely to start dialysis for clinical reasons, and at a lower eGFR. Female doctors started dialysis at a higher eGFR than males (8.0 vs. 7.1 ml/min/1.73 m2). Conclusions DI was prescribed mainly based on clinical reasons in accordance with current recommendations while low renal function accounted for only 19% of primary reasons for DI. There are considerable differences in physicians´ stated motivations for DI, related to their age, clinical experience and interpretation of biochemical variables. These differences may be an independent factor in the clinical treatment of patients, with consequences for the risk of unplanned DI.
6.
  • Jernberg, Tomas, et al. (författare)
  • Impact of ischaemic heart disease severity and age on risk of cardiovascular outcome in diabetes patients in Sweden : : A nationwide observational study
  • 2019
  • Ingår i: BMJ Open. - British Medical Journal Publishing Group. - 2044-6055. ; 9:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To compare short-term cardiovascular (CV) outcome in type 2 diabetes (T2D) patients without ischaemic heart disease (IHD), with IHD but no prior myocardial infarction (MI), and those with prior MI; and assess the impact on risk of age when initiating first-time glucose-lowering drug (GLD). Design Cohort study linking morbidity, mortality and medication data from Swedish national registries. Participants First-time users of GLD during 2007-2016. Outcomes Predicted cumulative incidence for the CV outcome (MI, stroke and CV mortality) was estimated. A Cox model was developed where age at GLD start and CV risk was modelled. Results 260 070 first-time GLD users were included, 221 226 (85%) had no IHD, 16 294 (6%) had stable IHD-prior MI and 22 550 (9%) had IHD+MI. T2D patients without IHD had a lower risk of CV outcome compared with the IHD populations (±prior MI), (3-year incidence 4.78% vs 5.85% and 8.04%). The difference in CV outcome was primarily driven by a relative greater MI risk among the IHD patients. For T2D patients without IHD, an almost linear association between age at start of GLD and relative risk was observed, whereas in IHD patients, the younger (<60 years) patients had a relative greater risk compared with older patients. Conclusions T2D patients without IHD had a lower risk of the CV outcome compared with the T2D populations with IHD, primarily driven by a greater risk of MI. For T2D patients without IHD, an almost linear association between age at start of GLD and relative risk was observed, whereas in IHD patients, the younger patients had a relative greater risk compared with older patients. Our findings suggest that intense risk prevention should be the key strategy in the management of T2D patients, especially for younger patients.
7.
  • Lindholm, Carl-Johan, et al. (författare)
  • Experimental analysis of stresses in curved sandwich structures
  • 2015
  • Ingår i: 20th International Conference on Composite Materials.
  • Konferensbidrag (övrigt vetenskapligt)abstract
    • Some studies indicate that the cross-section of large wind turbine blades subjected to wind and gravity loads will ovalise due to the Brazier effects [1,2]. This feature could however not be verified by numerical experiments of a FE model of a fictive 61.5 m blade, based on the NREL 5MW reference turbine [3], subjected to simplified load cases. Accurate prediction of failure modes of sandwich structures based on finite element calculations are highly important if accurate predictions of such features in large wind turbine blades are to be investigated.In this study, an experimental setup designed to cause deflection and stress patterns in the core similar to what might be achieved by the Brazier effect in a wind turbine blade subjected to severe wind loads has been carried out. The test set up will highlight stress in the through-thickness direction, causing classical shell theory to be circumspect as a modelling tool. By designing specimens with different foam core material properties, stiffness and strength, different failure modes were observed in the test. Through the use of combinations of solid and shell elements and geometrically nonlinear analyses, the experimental effects were shown to be predictable by an otherwise linear FE model.
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8.
  • Lindholm, Carl-Johan, et al. (författare)
  • Experimental analysis of stresses in sandwich structures due to the brazier effect
  • 2015
  • Ingår i: ICCM International Conferences on Composite Materials. ; 2015-July
  • Konferensbidrag (refereegranskat)abstract
    • © 2015 International Committee on Composite Materials. All rights reserved. Some studies indicate that the cross-section of large wind turbine blades subjected to wind and gravity loads will ovalise due to the Brazier effects [1,2]. This feature could however not be verified by numerical experiments of a FE model of a fictive 61.5 m blade, based on the NREL 5MW reference turbine [3], subjected to simplified load cases. Accurate prediction of failure modes of sandwich structures based on finite element calculations are highly important if accurate predictions of such features in large wind turbine blades are to be investigated. In this study, an experimental setup designed to cause deflection and stress patterns in the core similar to what might be achieved by the Brazier effect in a wind turbine blade subjected to severe wind loads has been carried out. The test set up will highlight stress in the through-thickness direction, causing classical shell theory to be circumspect as a modelling tool. By designing specimens with different foam core material properties, stiffness and strength, different failure modes were observed in the test. Through the use of combinations of solid and shell elements and geometrically nonlinear analyses, the experimental effects were shown to be predictable by an otherwise linear FE model.
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9.
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10.
  • Morris, Andrew P., et al. (författare)
  • Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes
  • 2012
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1546-1718. ; 44:9, s. 981-981
  • Tidskriftsartikel (refereegranskat)abstract
    • To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genomewide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.
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