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- Gusev, A, et al.
(författare)
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Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation
- 2016
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 10979-
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Tidskriftsartikel (refereegranskat)abstract
- Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.
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- Fellström, Bengt, 1942-, et al.
(författare)
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Risk factors for reaching renal endpoints in the Assessment of Lescol in Renal Transplantation (ALERT) trial
- 2005
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 79:2, s. 205-212
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Tidskriftsartikel (refereegranskat)abstract
- Background. The aim of the study was to identity risk factors for long-term renal transplant function and development of chronic allograft nephropathy (CAN) in renal transplant recipients included in the Assessment of Lescol in Renal Transplantation (ALERT) trial. Methods. The ALERT trial was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin, 40 and 80 mg/day, in renal transplant recipients who were randomized to receive fluvastatin (Lescol) (n=1,050) or placebo (n=1,052) over 5 to 6 years of follow-up. Renal endpoints including graft loss or doubling of serum creatinine or death were analyzed by univariate and multivariate regression analysis in the placebo group. Results. There were 137 graft losses (13.5%) in the placebo group, mainly caused by CAN (82%). Univariate risk factors for graft loss or doubling of serum creatinine were as follows: serum creatinine, proteinuria, hypertension, pulse pressure, time since transplantation, donor age, human leukocyte antigen-DR mismatches, treatment for rejection, low high-density lipoprotein cholesterol, and smoking. Multivariate analysis revealed independent risk factors for graft loss as follows: serum creatinine (relative risk [RR], 3.12 per 100-µM increase), proteinuria (RR, 1.64 per 1-g/24 hr increase), and pulse pressure (RR, 1.12 per 10 mm Hg), whereas age was a protective factor. With patient death in the composite endpoint, diabetes mellitus, smoking, age, and number of transplantations were also risk factors. Conclusions. Independent risk factors for graft loss or doubling of serum creatinine or patient death are mainly related to renal transplant function, proteinuria, and blood pressure, which emphasizes the importance of renoprotective treatment regimens in this population.
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- Holdaas, H., et al.
(författare)
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Effect of fluvastatin on cardiac outcomes in renal transplant recipients : A multicentre, randomised, placebo-controlled trial
- 2003
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 361:9374, s. 2024-2031
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Tidskriftsartikel (refereegranskat)abstract
- Background: Renal transplant recipients are at increased risk of premature cardiovascular disease. Although statins reduce cardiovascular risk in the general population, their efficacy and safety in renal transplant recipients have not been established. We investigated the effects of fluvastatin on cardiac and renal endpoints in this population. Methods: We did a multicentre, randomised, double-blind, placebo-controlled trial in 2102 renal transplant recipients with total cholesterol 4·0-9·0 mmol/L. We randomly assigned patients fluvastatin (n=1050) or placebo (n=1052) and follow up was for 5-6 years. The primary endpoint was the occurrence of a major adverse cardiac event, defined as cardiac death, non-fatal myocardial infarction (MI), or coronary intervention procedure. Secondary endpoints were individual cardiac events, combined cardiac death or non-fatal MI, cerebrovascular events, non-cardiovascular death, all-cause mortality, and graft loss or doubling of serum creatinine. Analysis was by intention to treat. Findings: After a mean follow-up of 5·1 years, fluvastatin lowered LDL cholesterol concentrations by 32%. Risk reduction with fluvastatin for the primary endpoint (risk ratio 0·83 [95% CI 0·64-1·06], p=0·139) was not significant, although there were fewer cardiac deaths or non-fatal MI (70 vs 104, 0·65 [0·48-0·88] p=0·005) in the fluvastatin group than in the placebo group. Coronary intervention procedures and other secondary endpoints did not differ significantly between groups. Interpretation: Although cardiac deaths and non-fatal MI seemed to be reduced, fluvastatin did not generally reduce rates of coronary intervention procedures or mortality. Overall effects of fluvastatin were similar to those of statins in other populations.
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- Fellström, Bengt, 1947-, et al.
(författare)
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Renal dysfunction as a risk factor for mortality and cardiovascular disease in renal transplantation : experience from the Assessment of Lescol in Renal Transplantation trial
- 2005
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Ingår i: Transplantation. - : Lippincott, Williams and Wilkins. - 0041-1337 .- 1534-6080. ; 79:9, s. 1160-1163
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Renal-transplant recipients have shortened life expectancy primarily because of premature cardiovascular disease. Traditional and nontraditional risk factors for cardiovascular disease are prevalent in renal patients. In renal-transplant recipients, immunosuppressive therapy can be nephrotoxic and aggravate cardiovascular disease risk factors. Renal dysfunction has been established as a risk factor for cardiovascular disease and mortality in different populations. We evaluated the effects of baseline renal-transplant function on mortality and cardiovascular and renal endpoints in 1,052 placebo-treated patients of the Assessment of Lescol in Renal Transplantation trial. METHODS: All renal-transplant recipients were on cyclosporine-based immunosuppressive therapy. Follow-up was 5 to 6 years, and endpoints included cardiac death, noncardiovascular death, all-cause mortality, major adverse cardiac event (MACE), stroke, nonfatal myocardial infarction, and graft loss. RESULTS: Baseline serum creatinine was strongly and independently associated with increased cardiac, noncardiovascular, and all-cause mortality, as well as MACE and graft loss. Serum creatinine was not a risk factor for stroke or nonfatal myocardial infarction. CONCLUSIONS: Elevated baseline serum creatinine in renal-transplant recipients is a strong and independent risk factor for all-cause, noncardiovascular and cardiac mortality, MACE, and graft loss.
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- Riska, Kaj, et al.
(författare)
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Ice performance of the Swedish multi-purpose icebreaker Tor Viking II
- 2002
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Ingår i: 16th international conference on Port and ocean engineering under Arctic conditions; ice engineering applied to offshore regions, Aug. 12-17, 2001, Ottawa, ON, Canada.. - : National Research Council of Canada. ; , s. 849-865
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Konferensbidrag (refereegranskat)
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- Selroos, Olof, et al.
(författare)
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Asthma control and steroid doses 5 years after early or delayed introduction of inhaled corticosteroids in asthma: a real-life study
- 2004
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 98:3, s. 254-262
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated asthma control and medication use 5 years after introduction of an inhaled corticosteroid (budesonide via Turbuhaler(R)) in 462 patients with persistent asthma and symptoms of different duration. An early treatment group with symptoms for <2 years (group A) was compared with a delayed treatment group (group B) (median duration 5 years and 3 months). Most patients received budesonide 400 μg twice daily as initial dose. We report 5-year follow-up data on 404 patients (group A n = 253; group B n = 151) and on a few more patients after treatment for 6 months, 1 year and 3 years. At 5 years the mean maintenance doses of budesonide were 412 μg (A) and 825 μg (B), respectively (P < 0.001). Nevertheless, treatment goals (normal lung function, normal exercise tolerance, minimal use of reliever medication, no asthma exacerbations) were all statistically significantly more frequently achieved in group A. At 5 years group B patients also used significantly more additional asthma medications, e.g. inhaled tong-acting beta(2)-agonists by 64% compared with 6% in group A. In group A 43 patients (117%) had been able to stop budesonide treatment compared to five patients (3%) in group B. A subgroup of group B patients with higher mean baseline FEV1 values than group A showed nevertheless significantly poorer response. No treatment-related serious adverse events were reported. Budesonide was well tolerated in both groups. Conclusion: Duration of asthma symptoms when starting treatment with an inhaled corticosteroid is an important determinant for the response. Early treatment gives significantly better airway function and asthma control than delayed treatment and at tower maintenance doses.
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