| 31. |
- Strandberg, Gustav, et al.
(författare)
-
Regional climate model simulations for Europe at 6 and 0.2 k BP : sensitivity to changes in anthropogenic deforestation
- 2014
-
Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 10:2, s. 661-680
-
Tidskriftsartikel (refereegranskat)abstract
- This study aims to evaluate the direct effects of anthropogenic deforestation on simulated climate at two contrasting periods in the Holocene, similar to 6 and similar to 0.2 k BP in Europe. We apply We apply the Rossby Centre regional climate model RCA3, a regional climate model with 50 km spatial resolution, for both time periods, considering three alternative descriptions of the past vegetation: (i) potential natural vegetation (V) simulated by the dynamic vegetation model LPJ-GUESS, (ii) potential vegetation with anthropogenic land use (deforestation) from the HYDE3.1 (History Database of the Global Environment) scenario (V + H3.1), and (iii) potential vegetation with anthropogenic land use from the KK10 scenario (V + KK10). The climate model results show that the simulated effects of deforestation depend on both local/regional climate and vegetation characteristics. At similar to 6 k BP the extent of simulated deforestation in Europe is generally small, but there are areas where deforestation is large enough to produce significant differences in summer temperatures of 0.5-1 degrees C. At similar to 0.2 k BP, extensive deforestation, particularly according to the KK10 model, leads to significant temperature differences in large parts of Europe in both winter and summer. In winter, deforestation leads to lower temperatures because of the differences in albedo between forested and unforested areas, particularly in the snow-covered regions. In summer, deforestation leads to higher temperatures in central and eastern Europe because evapotranspiration from unforested areas is lower than from forests. Summer evaporation is already limited in the southernmost parts of Europe under potential vegetation conditions and, therefore, cannot become much lower. Accordingly, the albedo effect dominates in southern Europe also in summer, which implies that deforestation causes a decrease in temperatures. Differences in summer temperature due to deforestation range from -1 degrees C in south-western Europe to +1 degrees C in eastern Europe. The choice of anthropogenic land-cover scenario has a significant influence on the simulated climate, but uncertainties in palaeoclimate proxy data for the two time periods do not allow for a definitive discrimination among climate model results.
|
|
| 32. |
- Thanassoulis, George, et al.
(författare)
-
Genetic Associations with Valvular Calcification and Aortic Stenosis
- 2013
-
Ingår i: New England Journal of Medicine. - 0028-4793. ; 368:6, s. 503-512
-
Tidskriftsartikel (refereegranskat)abstract
- Background Limited information is available regarding genetic contributions to valvular calcification, which is an important precursor of clinical valve disease. Methods We determined genomewide associations with the presence of aortic-valve calcification (among 6942 participants) and mitral annular calcification (among 3795 participants), as detected by computed tomographic (CT) scanning; the study population for this analysis included persons of white European ancestry from three cohorts participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (discovery population). Findings were replicated in independent cohorts of persons with either CT-detected valvular calcification or clinical aortic stenosis. Results One SNP in the lipoprotein(a) (LPA) locus (rs10455872) reached genomewide significance for the presence of aortic-valve calcification (odds ratio per allele, 2.05; P = 9.0x10(-10)), a finding that was replicated in additional white European, African-American, and Hispanic-American cohorts (P<0.05 for all comparisons). Genetically determined Lp(a) levels, as predicted by LPA genotype, were also associated with aortic-valve calcification, supporting a causal role for Lp(a). In prospective analyses, LPA genotype was associated with incident aortic stenosis (hazard ratio per allele, 1.68; 95% confidence interval [CI], 1.32 to 2.15) and aortic-valve replacement (hazard ratio, 1.54; 95% CI, 1.05 to 2.27) in a large Swedish cohort; the association with incident aortic stenosis was also replicated in an independent Danish cohort. Two SNPs (rs17659543 and rs13415097) near the proinflammatory gene IL1F9 achieved genomewide significance for mitral annular calcification (P = 1.5x10(-8) and P = 1.8x10(-8), respectively), but the findings were not replicated consistently. Conclusions Genetic variation in the LPA locus, mediated by Lp(a) levels, is associated with aortic-valve calcification across multiple ethnic groups and with incident clinical aortic stenosis. (Funded by the National Heart, Lung, and Blood Institute and others.)
|
|
| 33. |
- van der Harst, Pim, et al.
(författare)
-
Seventy-five genetic loci influencing the human red blood cell
- 2012
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
-
Tidskriftsartikel (refereegranskat)abstract
- Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
|
|
| 34. |
- Wells, Quinn S., et al.
(författare)
-
Accelerating Biomarker Discovery Through Electronic Health Records, Automated Biobanking, and Proteomics
- 2019
-
Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 73:17, s. 2195-2205
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Circulating biomarkers can facilitate diagnosis and risk stratification for complex conditions such as heart failure (HF). Newer molecular platforms can accelerate biomarker discovery, but they require significant resources for data and sample acquisition. Objectives: The purpose of this study was to test a pragmatic biomarker discovery strategy integrating automated clinical biobanking with proteomics. Methods: Using the electronic health record, the authors identified patients with and without HF, retrieved their discarded plasma samples, and screened these specimens using a DNA aptamer-based proteomic platform (1,129 proteins). Candidate biomarkers were validated in 3 different prospective cohorts. Results: In an automated manner, plasma samples from 1,315 patients (31% with HF) were collected. Proteomic analysis of a 96-patient subset identified 9 candidate biomarkers (p < 4.42 × 10 −5 ). Two proteins, angiopoietin-2 and thrombospondin-2, were associated with HF in 3 separate validation cohorts. In an emergency department–based registry of 852 dyspneic patients, the 2 biomarkers improved discrimination of acute HF compared with a clinical score (p < 0.0001) or clinical score plus B-type natriuretic peptide (p = 0.02). In a community-based cohort (n = 768), both biomarkers predicted incident HF independent of traditional risk factors and N-terminal pro–B-type natriuretic peptide (hazard ratio per SD increment: 1.35 [95% confidence interval: 1.14 to 1.61; p = 0.0007] for angiopoietin-2, and 1.37 [95% confidence interval: 1.06 to 1.79; p = 0.02] for thrombospondin-2). Among 30 advanced HF patients, concentrations of both biomarkers declined (80% to 84%) following cardiac transplant (p < 0.001 for both). Conclusions: A novel strategy integrating electronic health records, discarded clinical specimens, and proteomics identified 2 biomarkers that robustly predict HF across diverse clinical settings. This approach could accelerate biomarker discovery for many diseases.
|
|
| 35. |
- Acosta, Stefan, et al.
(författare)
-
B-type natriuretic peptide for prediction of incident clinically significant abdominal aortic aneurysm : A population-based prospective study
- 2018
-
Ingår i: Vascular Medicine. - 1477-0377. ; 23:1, s. 46-51
-
Tidskriftsartikel (refereegranskat)abstract
- Pathogenesis of abdominal aortic aneurysm (AAA) is unclear. The aim of this study was to evaluate inflammatory and hemodynamic plasma biomarkers as predictors for AAA in the prospective longitudinal cohort of middle-aged individuals from the cardiovascular cohort of the Malmö Diet and Cancer Study ( n=5551; 1991-94). C-reactive protein, cystatin C, copeptin, N-terminal pro-B-type natriuretic peptide (N-BNP), midregional pro-atrial natriuretic peptide (MR-proANP) and conventional risk factors at baseline were measured in patients with incident AAA during follow-up and compared to individuals without a diagnosis of AAA. Subjects were followed until 31 December 2013. Multivariable analyses were expressed in terms of hazard ratios (HR) per 1 standard deviation increment of each respective log-transformed plasma biomarker in the Cox proportional hazard models. Mean follow-up time was 20.7 years. Cumulative incidence of AAA was 1.5% (men 2.9%, women 0.5%). Mean age of individuals with incident AAA was 59.7 years at study entry and AAA was diagnosed on average 14 years later. Adjusting for age, sex, smoking, body mass index, hypertension and diabetes mellitus, N-BNP (HR 1.29; 95% CI 1.03-1.62), but not MR-proANP (HR 1.20; 95% CI 0.95-1.50), was independently associated with incident AAA. In conclusion, the plasma biomarker N-BNP was associated with future development of AAA, which implies that this marker is a sensitive indicator of early subclinical cardiovascular disease.
|
|
| 36. |
- Acosta, Stefan, et al.
(författare)
-
Circulating Midregional Proadrenomedullin and Risk of Incident Abdominal Aortic Aneurysm : A Prospective Longitudinal Cohort Study
- 2018
-
Ingår i: Angiology. - : SAGE Publications. - 0003-3197 .- 1940-1574. ; 69:4, s. 333-338
-
Tidskriftsartikel (refereegranskat)abstract
- Prospective clinical plasma biomarker studies in abdominal aortic aneurysm (AAA) pathogenesis have been hampered by the need for very large cohorts and long follow-up time. The main aim of the present study was to evaluate the association of adrenomedullin, a cardiovascular (CV) stress marker, and incident AAA risk. Prospective longitudinal cohort of middle-aged individuals from the CV cohort of the Malmö Diet and Cancer Study (n = 5551; 1991-1994) was assessed. Plasma concentrations of midregional proadrenomedullin (MR-proADM), C-reactive protein (CRP), and conventional risk factors were measured at baseline. Incidence of AAA was studied up to December 31, 2013. Cumulative incidence of AAA was 1.5% (men 2.9%, women 0.5%). Mean age of individuals with incident AAA was 59.7 years at study entry, and AAA was diagnosed on average 14 years later. Adjusting for age, gender, smoking, body mass index, hypertension, diabetes mellitus, and CRP, MR-proADM (hazard ratio: 1.28; 95% confidence interval: 1.01-1.62) was independently associated with incident AAA. The plasma biomarker MR-proADM seems to be a marker of AAA risk, implying that AAA development may be driven by long-standing CV stress on the aortic wall.
|
|
| 37. |
- Acosta, Stefan, et al.
(författare)
-
Lp-PLA2 activity and mass for prediction of incident abdominal aortic aneurysms : A prospective longitudinal cohort study
- 2017
-
Ingår i: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 262, s. 14-18
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aims The pathogenesis of abdominal aortic aneurysm (AAA) shares several common pathways with atherosclerosis. Prospective clinical plasma biomarker studies in AAA have been hampered by the need for very large cohorts and long follow-up time. Methods We analyzed a prospective longitudinal cohort of middle-aged individuals from the cardiovascular cohort of the Malmö Diet and Cancer study (n = 5551; 1991-94). The plasma biomarkers lipoprotein-associated phospholipase A2 (Lp-PLA2 activity and mass), proneurotensin and C-reactive protein, and conventional risk factors at baseline were measured in patients with incident AAA during follow-up, and compared to individuals without a diagnosis of AAA. Subjects were followed until December 31st, 2013. Multivariable analyses were expressed in terms of hazard ratios (HR) per 1 standard deviation increment of each respective log-transformed plasma biomarker in the Cox proportional hazard models. Results Cumulative incidence of AAA was 1.5% (men 2.9%, women 0.5%) during a median follow-up period of 20.7 years. Overall, 84 individuals had an incident AAA, of whom 22 (26.2%) were operated on and 16 (19.0%) had ruptured. Mean age of individuals with incident AAA was 59.7 years at study entry and AAA was diagnosed on average 14 years later. When adjusting for age, gender, smoking, body mass index, hypertension, and diabetes mellitus, Lp-PLA2 activity (HR 1.40; 95% CI 1.15–1.72) and Lp-PLA2 mass (HR 1.23; 95% CI 1.00–1.51) were independently associated with incident AAA. Conclusions The plasma biomarkers Lp-PLA2 activity and mass were markers of AAA risk and this implies that AAA is an athero-thrombotic related disease.
|
|
| 38. |
- Adamsson Eryd, Samuel, et al.
(författare)
-
Carotid intima-media thickness is associated with incidence of hospitalized atrial fibrillation.
- 2014
-
Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 233:2, s. 673-678
-
Tidskriftsartikel (refereegranskat)abstract
- Carotid intima-media thickness (IMT) is a measure of arterial thickening and a risk predictor for myocardial infarction and stroke. It is unclear whether IMT also predicts atrial fibrillation (AF). We explored the association between IMT and incidence of first AF hospitalization in a population-based cohort.
|
|
| 39. |
- Adamsson Eryd, Samuel, et al.
(författare)
-
Ceruloplasmin and atrial fibrillation: evidence of causality from a population-based Mendelian randomization study.
- 2014
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 275:2, s. 164-171
-
Tidskriftsartikel (refereegranskat)abstract
- Inflammatory diseases and inflammatory markers secreted by the liver, including C-reactive protein (CRP) and ceruloplasmin, have been associated with incident atrial fibrillation (AF). Genetic studies have not supported a causal relationship between CRP and AF, but the relationship between ceruloplasmin and AF has not been studied. The purpose of this Mendelian randomization study was to explore whether genetic polymorphisms in the gene encoding ceruloplasmin are associated with elevated ceruloplasmin levels, and whether such genetic polymorphisms are also associated with the incidence of AF.
|
|
| 40. |
- Adamsson Eryd, Samuel, et al.
(författare)
-
Incidence of Coronary Events and Case Fatality Rate in Relation to Blood Lymphocyte and Neutrophil Counts.
- 2012
-
Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 32, s. 533-837
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Elevated levels of blood leukocytes have been associated with acute coronary events (CEs), but data on leukocyte subclasses are limited. This study aimed to explore whether blood lymphocyte and neutrophil counts are associated with incidence of CEs and with fatal outcome in subjects who subsequently experienced a first CE. METHODS AND RESULTS: Neutrophil and lymphocyte counts were measured in 27 419 subjects from the general population without a history of CEs, heart failure, or atrial fibrillation. Incidence of CEs was studied in relation to leukocyte counts during a mean follow-up of 13.6 years. Neutrophil but not lymphocyte counts were significantly associated with incidence of CEs. After adjustments for confounding factors, the hazard ratios (95% confidence interval) were 1.00 (reference), 1.07 (0.94-1.23), 1.09 (0.95-1.25), and 1.39 (1.22-1.59) for subjects with neutrophils in the first, second, third, and fourth (highest) sex-specific quartiles, respectively (P for trend <0.001). Of the 1965 subject who had a CE, 471 subjects died on the first day of the CE, in- or outside hospital. The proportions of subjects who died the first day were 19%, 21%, 25%, and 28%, respectively in the first, second, third, and fourth quartiles (P for trend <0.001). CONCLUSIONS: Increased neutrophil counts are associated with incidence of CEs and increased case-fatality rate after a CE.
|
|
