| 1. |
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| 2. |
- Engström, Gunnar, et al.
(author)
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Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications
- 2024
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In: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49
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Journal article (peer-reviewed)abstract
- Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
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| 3. |
- Folkersen, Lasse, et al.
(author)
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Unraveling Divergent Gene Expression Profiles in Bicuspid and Tricuspid Aortic Valve Patients with Thoracic Aortic Dilatation: The ASAP Study
- 2011
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In: Molecular Medicine. - : Feinstein Institute for Medical Research. - 1076-1551 .- 1528-3658. ; 17:11-12, s. 1365-1373
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Journal article (peer-reviewed)abstract
- Thoracic aortic aneurysm (TAA) is a common complication in patients with a bicuspid aortic valve (BAV), the most frequent congenital heart disorder. For unknown reasons TAA occurs at a younger age, with a higher frequency in BAV patients than in patients with a tricuspid aortic valve (TAV), resulting in an increased risk for aortic dissection and rupture. To investigate the increased TAA incidence in BAV patients, we obtained tissue biopsy samples from nondilated and dilated aortas of 131 BAV and TAV patients. Global gene expression profiles were analyzed from controls and from aortic intima-media and adventitia of patients (in total 345 samples). Of the genes found to be differentially expressed with dilation, only a few (less than4%) were differentially expressed in both BAV and TAV patients. With the use of gene set enrichment analysis, the cell adhesion and extracellular region gene ontology sets were identified as common features of TAA in both BAV and TAV patients. Immune response genes were observed to be particularly overexpressed in the aortic media of dilated TAV samples. The divergent gene expression profiles indicate that there are fundamental differences in TAA etiology in BAV and TAV patients. Immune response activation solely in the aortic media of TAV patients suggests that inflammation is involved in TAA formation in TAV but not in BAV patients. Conversely, genes were identified that were only differentially expressed with dilation in BAV patients. The result has bearing on future clinical studies in which separate analysis of BAV and TAV patients is recommended.
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| 4. |
- Peden, John F., et al.
(author)
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A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease
- 2011
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:4, s. 339-344
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Journal article (peer-reviewed)abstract
- Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD)(1-7), a modest number considering the apparent heritability of CAD(8). All of these variants have been discovered in European populations. We report a meta-analysis of four large genome-wide association studies of CAD, with similar to 575,000 genotyped SNPs in a discovery dataset comprising 15,420 individuals with CAD (cases) (8,424 Europeans and 6,996 South Asians) and 15,062 controls. There was little evidence for ancestry-specific associations, supporting the use of combined analyses. Replication in an independent sample of 21,408 cases and 19,185 controls identified five loci newly associated with CAD (P < 5 x 10(-8) in the combined discovery and replication analysis): LIPA on 10q23, PDGFD on 11q22, ADAMTS7-MORF4L1 on 15q25, a gene rich locus on 7q22 and KIAA1462 on 10p11. The CAD-associated SNP in the PDGFD locus showed tissue-specific cis expression quantitative trait locus effects. These findings implicate new pathways for CAD susceptibility.
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| 5. |
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| 6. |
- Aad, G, et al.
(author)
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Observation and measurements of the production of prompt and non-prompt [Formula: see text] mesons in association with a [Formula: see text] boson in [Formula: see text] collisions at [Formula: see text] with the ATLAS detector.
- 2015
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In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:5
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Journal article (peer-reviewed)abstract
- The production of a [Formula: see text] boson in association with a [Formula: see text] meson in proton-proton collisions probes the production mechanisms of quarkonium and heavy flavour in association with vector bosons, and allows studies of multiple parton scattering. Using [Formula: see text] of data collected with the ATLAS experiment at the LHC in [Formula: see text] collisions at [Formula: see text], the first measurement of associated [Formula: see text] production is presented for both prompt and non-prompt [Formula: see text] production, with both signatures having a significance in excess of [Formula: see text]. The inclusive production cross-sections for [Formula: see text] boson production (analysed in [Formula: see text] or [Formula: see text] decay modes) in association with prompt and non-prompt [Formula: see text] are measured relative to the inclusive production rate of [Formula: see text] bosons in the same fiducial volume to be [Formula: see text] and [Formula: see text] respectively. Normalised differential production cross-section ratios are also determined as a function of the [Formula: see text] transverse momentum. The fraction of signal events arising from single and double parton scattering is estimated, and a lower limit of [Formula: see text] at [Formula: see text] confidence level is placed on the effective cross-section regulating double parton interactions.
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| 7. |
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| 8. |
- Aad, G, et al.
(author)
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Search for direct pair production of a chargino and a neutralino decaying to the 125 GeV Higgs boson in [Formula: see text] TeV [Formula: see text] collisions with the ATLAS detector.
- 2015
-
In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:5
-
Journal article (peer-reviewed)abstract
- A search is presented for the direct pair production of a chargino and a neutralino [Formula: see text], where the chargino decays to the lightest neutralino and the [Formula: see text] boson, [Formula: see text], while the neutralino decays to the lightest neutralino and the 125 GeV Higgs boson, [Formula: see text]. The final states considered for the search have large missing transverse momentum, an isolated electron or muon, and one of the following: either two jets identified as originating from bottom quarks, or two photons, or a second electron or muon with the same electric charge. The analysis is based on 20.3 [Formula: see text] of [Formula: see text] proton-proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with the Standard Model expectations, and limits are set in the context of a simplified supersymmetric model.
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| 9. |
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| 10. |
- Aad, G, et al.
(author)
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Search for Higgs Boson Pair Production in the γγbb[over ¯] Final State Using pp Collision Data at sqrt[s]=8 TeV from the ATLAS Detector.
- 2015
-
In: Physical Review Letters. - 1079-7114. ; 114:8
-
Journal article (peer-reviewed)abstract
- Searches are performed for resonant and nonresonant Higgs boson pair production in the γγbb[over ¯] final state using 20 fb^{-1} of proton-proton collisions at a center-of-mass energy of 8 TeV recorded with the ATLAS detector at the CERN Large Hadron Collider. A 95% confidence level upper limit on the cross section times branching ratio of nonresonant production is set at 2.2 pb, while the expected limit is 1.0 pb. The difference derives from a modest excess of events, corresponding to 2.4 standard deviations from the background-only hypothesis. The limit observed in the search for a narrow X→hh resonance ranges between 0.7 and 3.5 pb as a function of the resonance mass.
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| 11. |
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| 12. |
- Aad, G, et al.
(author)
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Search for production of [Formula: see text] resonances decaying to a lepton, neutrino and jets in [Formula: see text] collisions at [Formula: see text] TeV with the ATLAS detector.
- 2015
-
In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 75:5
-
Journal article (peer-reviewed)abstract
- A search is presented for narrow diboson resonances decaying to [Formula: see text] or [Formula: see text] in the final state where one [Formula: see text] boson decays leptonically (to an electron or a muon plus a neutrino) and the other [Formula: see text] boson decays hadronically. The analysis is performed using an integrated luminosity of 20.3 fb[Formula: see text] of [Formula: see text] collisions at [Formula: see text] TeV collected by the ATLAS detector at the large hadron collider. No evidence for resonant diboson production is observed, and resonance masses below 700 and 1490 GeV are excluded at 95 % confidence level for the spin-2 Randall-Sundrum bulk graviton [Formula: see text] with coupling constant of 1.0 and the extended gauge model [Formula: see text] boson respectively.
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| 13. |
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| 14. |
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| 15. |
- Basu, Samar, et al.
(author)
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Effects of melagatran, a novel direct thrombin inhibitor, during experimental septic shock
- 2000
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In: Expert Opinion on Investigational Drugs. - : Informa Healthcare. - 1354-3784 .- 1744-7658. ; 9:5, s. 1129-1137
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Journal article (peer-reviewed)abstract
- Sepsis and endotoxaemia initiate the generation of thrombin, which is responsible for the conversion of fibrinogen to fibrin, platelet aggregation and acts as an inflammatory mediator affecting numerous types of cells, including myocardial, smooth muscle and endothelial cells. Human Gram-negative septic shock, frequently seen in intensive care units, is a condition with high mortality. This condition can be replicated in the endotoxaemic pig. As many of the toxic effects of sepsis are due to thrombin generation, it was of interest to study, using this porcine experimental septic shock model, whether inhibition of thrombin could alleviate the effects of endotoxaemia. For this purpose melagatran, a direct synthetic thrombin inhibitor with a molecular weight of 429 Da, was employed. Melagatran does not significantly interact with any other enzymes in the coagulation cascade or fibrinolytic enzymes aside from thrombin. Furthermore, melagatran does not require endogenous co-factors such as antithrombin or heparin co-Factor II for its antithrombin effect, which is important, as these inhibitors are often consumed in septic patients. We have shown that melagatran exerts a beneficial effect on renal function, as evaluated by plasma creatinine and urinary output, during experimental septic shock. These effects were most pronounced during the later phase of the experimental period, after the infusion of melagatran had been discontinued. Prevention of intrarenal coagulation may be attributable to this finding. In addition, melagatran had beneficial effects on systemic haemodynamics (left ventricular stroke work index, pulmonary capillary wedge pressure and systemic vascular resistance index) in endotoxaemic pigs. This result may be explained by the ability of melagatran to inhibit thrombin, thereby counteracting thrombin's cellular effects. Thus, it can be seen, using this experimental model of septic shock, that melagatran may help to alleviate some of the damaging effects of endotoxaemia, although more research is required to test this further.
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| 16. |
- Bergström, Göran, 1964, et al.
(author)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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In: Circulation. - Philadelphia : American Heart Association. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
-
Journal article (peer-reviewed)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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| 17. |
- Bergström, Göran, et al.
(author)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
-
In: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
-
Journal article (peer-reviewed)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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| 18. |
- Blomberg, Anders, et al.
(author)
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Chronic Airflow Limitation, Emphysema and Impaired Diffusing Capacity in Relation to Smoking Habits in a Swedish Middle-Aged Population.
- 2024
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In: Annals of the American Thoracic Society. - 2329-6933 .- 2325-6621.
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Journal article (peer-reviewed)abstract
- RATIONALE: Chronic obstructive pulmonary disease (COPD) includes respiratory symptoms and chronic airflow limitation (CAL). In some cases, emphysema and impaired diffusing capacity for carbon monoxide (DLCO) are present, but characteristics and symptoms vary with smoking exposure.OBJECTIVES: To study the prevalence of CAL, emphysema and impaired DLCO in relation to smoking and respiratory symptoms in a middle-aged population.METHODS: We investigated 28,746 randomly invited individuals (52% women) aged 50-64 years across six Swedish sites. We performed spirometry, DLCO, high-resolution computed tomography (HRCT) and asked for smoking habits and respiratory symptoms. CAL was defined as post-bronchodilator forced expiratory volume in 1 second divided by forced expiratory volume (FEV1/FVC)<0.7.RESULTS: The overall prevalence was for CAL 8.8%, for impaired DLCO (DLCOCONCLUSIONS: In this large population-based study of middle-aged people, CAL and impaired DLCO were associated with common respiratory symptoms. Self-reported asthma was not associated with CAL in never-smokers. Our findings suggest that CAL in never-smokers signifies a separate clinical phenotype that may be monitored and, possibly, treated differently from smoking-related COPD. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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| 19. |
- Chernogubova, Ekaterina, et al.
(author)
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Common and Low-Frequency Genetic Variants in the PCSK9 Locus Influence Circulating PCSK9 Levels
- 2012
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In: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 32:6, s. 1526-1534
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Journal article (peer-reviewed)abstract
- Objective- Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that influences plasma low-density lipoprotein concentration and susceptibility to coronary heart disease. Circulating PCSK9 levels show considerable interindividual differences, but the factors responsible for this variation are largely unknown. Methods and Results- We analyzed circulating PCSK9 levels in 4 cohorts of healthy, middle-aged Swedes (n=5722) and found that PCSK9 levels varied over approximate to 50-fold range, showed a positive relationship with plasma low-density lipoprotein-cholesterol concentration, and were associated with plasma triglyceride, fibrinogen, insulin, and glucose concentrations. A genome-wide association study conducted in 2 cohorts (n=1215) failed to uncover common genetic variants robustly associated with variation in circulating PCSK9 level. As expected, the minor allele of the PCSK9 R46L variant was in all cohorts associated with reduced PCSK9 levels and decreased plasma low-density lipoprotein-cholesterol concentrations, but no relationship was observed with the plasma triglyceride concentration. Further mapping of the PCSK9 locus revealed a common polymorphism (rs2479415, minor allele frequency 43.9%), located approximate to 6 kb upstream from PCSK9, which is independently associated with increased circulating PCSK9 levels. Conclusion- Common and low-frequency genetic variants in the PCSK9 locus influence the pronounced interindividual variation in circulating PCSK9 levels in healthy, middle-aged white (predominantly Swedish) subjects.
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| 20. |
- Engström, Gunnar, et al.
(author)
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The Swedish CArdioPulmonary BioImage Study : objectives and design
- 2015
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
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Journal article (peer-reviewed)abstract
- Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
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| 21. |
- Eriksson, Anders D, et al.
(author)
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Alginate impressions for fixed prosthodontics : A 20 year follow up study
- 2004
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In: Swedish Dental Journal. - 0347-9994. ; 28:2, s. 53-59
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Journal article (peer-reviewed)abstract
- The aim of this study was to estimate whether the survival ratios after 20 years of fixed prosthodontics made of alginate impressions was higher, equivalent or lower, compared to the survival ratios, shown in studies, where different impression materia Is were used. 151 females and 104 males were screened regarding the condition and age of the restorations at the an nu a I check-up in one of the authors surgeries. Average ages were 55 and 54 years respectively, when the fixed prosthodontics were seated. A total of 1.271 units were produced during the twenty years, 911 abutment teeth and 360 pontics. The type of prosthetic work was divided into three groups: 1) larger fixed prosthodontics 6-14 units (469), 2) smaller fixed prosthodontics 2-5 units (541) and 3) single crowns (261). The results show that alginate impressions can produce fixed prosthodontics with survival ratios similar to those presented in other studies, after 5 years (99%) 10 years (93-96%) and 15 years (74-96%). After 20 years the survival ratio was 61-63%. In conclusion, fixed prosthodontics made according to the syringe-tray alginate impression method may have the same success rates after 20 years compared to that of fixed prosthodontics presented in previous longitudinal clinical studies where other impression materials had been used. In this study, caries and root fractures were the main reasons for removing abutment teeth and pontics.
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| 22. |
- Eriksson, Anders, et al.
(author)
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Enthymemes in Pauline Argumentation
- 2002
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In: Rhetorical Argumentation in Biblical Texts: Essays from the Lund 2000 Conference. - 1563383551 ; , s. 243-259
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Book chapter (peer-reviewed)
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| 23. |
- Eriksson, Anders, et al.
(author)
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The Old is Better
- 2005
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In: Rhetoric, Ethic and Moral Persuasion in Biblical Discourse: Essays from the 2002 Heidelberg Conference. - 0567028119 ; , s. 52-72
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Book chapter (peer-reviewed)
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| 24. |
- Eriksson, Olof, et al.
(author)
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Quantitative Imaging of Serotonergic Biosynthesis and Degradation in the Endocrine Pancreas
- 2014
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In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 55:3, s. 460-465
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Journal article (peer-reviewed)abstract
- Serotonergic biosynthesis in the endocrine pancreas, of which the islets of Langerhans is the major constituent, has been implicated in insulin release and β cell proliferation. In this study, we investigated the feasibility of quantitative noninvasive imaging of the serotonergic metabolism in the pancreas using the PET tracer (11)C-5-hydroxy-l-tryptophan ((11)C-5-HTP).METHODS: Uptake of (11)C-5-HTP, and its specificity for key enzymes in the serotonergic metabolic pathway, was assessed in vitro (INS-1 and PANC1 cells and human islet and exocrine preparations) and in vivo (nonhuman primates and healthy and diabetic rats).RESULTS: In vitro tracer uptake in endocrine cells (INS-1 and human islets), but not PANC1 and exocrine cells, was mediated specifically by intracellular conversion into serotonin. Pancreatic uptake of (11)C-5-HTP in nonhuman primates was markedly decreased by inhibition of the enzyme dopa decarboxylase, which converts (11)C-5-HTP to (11)C-serotonin and increased after inhibition of monoamine oxidase-A, the main enzyme responsible for serotonin degradation. Uptake in the rat pancreas was similarly modulated by inhibition of monoamine oxidase-A and was reduced in animals with induced diabetes.CONCLUSION: The PET tracer (11)C-5-HTP can be used for quantitative imaging of the serotonergic system in the endocrine pancreas.
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| 25. |
- Eriksson, Olof, et al.
(author)
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The Positron Emission Tomography ligand [11C]5-Hydroxy-Tryptophan can be used as a surrogate marker for the human endocrine pancreas
- 2014
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 63:10, s. 3428-3437
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Journal article (peer-reviewed)abstract
- In humans a well-developed serotonin system is localized to the pancreatic islets while being absent in exocrine pancreas. Assessment of pancreatic serotonin biosynthesis could therefore be used to estimate the human endocrine pancreas. Proof of concept was tested in a prospective clinical trial by comparisons of type 1 diabetic (T1D) patients, with extensive reduction of beta cells, with healthy volunteers (HV).C-peptide negative (i.e. insulin-deficient) T1D subjects (n=10) and HV (n=9) underwent dynamic Positron Emission Tomography with the radiolabeled serotonin precursor [(11)C]5-Hydroxy-Tryptophan ([(11)C]5-HTP).A significant accumulation of [(11)C]5-HTP was obtained in the pancreas of the HV, with large inter-individual variation. A substantial and highly significant reduction (66%) in the pancreatic uptake of [(11)C]5-HTP in T1D subjects was observed, and this was most evident in the corpus and caudal regions of the pancreas where beta-cells normally are the major constituent of the islets.[(11)C]5-HTP retention in the pancreas was reduced in T1D compared to non-diabetic subjects. Accumulation of [(11)C]5-HTP in the pancreas of both HV and subjects with T1D were in agreement with previously reported morphological observations on the beta cell volume implying that [(11)C]5-HTP retention is a useful non-invasive surrogate marker for the human endocrine pancreas.
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| 26. |
- Folkersen, Lasse, et al.
(author)
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Association of genetic risk variants with expression of proximal genes identifies novel susceptibility genes for cardiovascular disease
- 2010
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In: Circulation. - 1942-325X .- 1942-3268. ; 3:4, s. 365-373
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Journal article (peer-reviewed)abstract
- BACKGROUND: Population-based genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with cardiovascular disease or its risk factors. Genes in close proximity to these risk-SNPs are often thought to be pathogenetically important based on their location alone. However, the actual connections between SNPs and disease mechanisms remain largely unknown. METHODS AND RESULTS: To identify novel susceptibility genes, we investigated how 166 SNPs previously found to be associated with increased cardiovascular risk and/or predisposing metabolic traits relate to the expression of nearby genes. Gene expression in 577 samples of aorta, liver, mammary artery, and carotid atherosclerotic plaque was measured using expression arrays. For 47 SNPs, the expression levels of proximal genes (located within 200 kb) were affected (P<0.005). More than 20 of these genes had not previously been identified as candidate genes for cardiovascular or related metabolic traits. SNP-associated gene effects were tissue-specific and the tissue specificity was phenotype-dependent. CONCLUSIONS: This study demonstrates several instances of association between risk-SNPs and genes immediately adjacent to them. It also demonstrates instances in which the associated gene is not the immediately proximal and obvious candidate gene for disease. This shows the necessity of careful studies of genetic marker data as a first step toward application of genome-wide association studies findings in a clinical setting.
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| 27. |
- Folkersen, Lasse, et al.
(author)
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Mapping of 79 loci for 83 plasma protein biomarkers in cardiovascular disease
- 2017
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In: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 13:4
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Journal article (peer-reviewed)abstract
- Recent advances in highly multiplexed immunoassays have allowed systematic large-scale measurement of hundreds of plasma proteins in large cohort studies. In combination with genotyping, such studies offer the prospect to 1) identify mechanisms involved with regulation of protein expression in plasma, and 2) determine whether the plasma proteins are likely to be causally implicated in disease. We report here the results of genome-wide association (GWA) studies of 83 proteins considered relevant to cardiovascular disease (CVD), measured in 3,394 individuals with multiple CVD risk factors. We identified 79 genome-wide significant (p<5e-8) association signals, 55 of which replicated at P<0.0007 in separate validation studies (n = 2,639 individuals). Using automated text mining, manual curation, and network-based methods incorporating information on expression quantitative trait loci (eQTL), we propose plausible causal mechanisms for 25 trans-acting loci, including a potential post-translational regulation of stem cell factor by matrix metalloproteinase 9 and receptor-ligand pairs such as RANK-RANK ligand. Using public GWA study data, we further evaluate all 79 loci for their causal effect on coronary artery disease, and highlight several potentially causal associations. Overall, a majority of the plasma proteins studied showed evidence of regulation at the genetic level. Our results enable future studies of the causal architecture of human disease, which in turn should aid discovery of new drug targets.
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| 28. |
- Gertow, Karl, et al.
(author)
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Identification of the BCAR1-CFDP1-TMEM170A Locus as a Determinant of Carotid Intima-Media Thickness and Coronary Artery Disease Risk
- 2012
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In: Circulation: Cardiovascular Genetics. - 1942-325X .- 1942-3268. ; 5:6, s. 656-665
-
Journal article (peer-reviewed)abstract
- Background-Carotid intima-media thickness (cIMT) is a widely accepted marker of subclinical atherosclerosis. To date, large-scale investigations of genetic determinants of cIMT are sparse. Methods and Results-To identify cIMT-associated genes and genetic variants, a discovery analysis using the Illumina 200K CardioMetabochip was conducted in 3430 subjects with detailed ultrasonographic determinations of cIMT from the IMPROVE (Carotid Intima Media Thickness [IMT] and IMT-Progression as Predictors of Vascular Events in a High Risk European Population) study. Segment-specific IMT measurements of common carotid, bifurcation, and internal carotid arteries, and composite IMT variables considering the whole carotid tree (IMTmean, IMTmax, and IMTmean-max), were analyzed. A replication stage investigating 42 single-nucleotide polymorphisms for association with common carotid IMT was undertaken in 5 independent European cohorts (total n=11 590). A locus on chromosome 16 (lead single-nucleotide polymorphism rs4888378, intronic in CFDP1) was associated with cIMT at significance levels passing multiple testing correction at both stages (array-wide significant discovery P=6.75x10(-7) for IMTmax; replication P=7.24x10(-6) for common cIMT; adjustments for sex, age, and population substructure where applicable; minor allele frequency 0.43 and 0.41, respectively). The protective minor allele was associated with lower carotid plaque score in a replication cohort (P=0.04, n=2120) and lower coronary artery disease risk in 2 case-control studies of subjects with European ancestry (odds ratio [95% confidence interval] 0.83 [0.77-0.90], P=6.53x10(-6), n=13 591; and 0.95 [0.92-0.98], P=1.83x10(-4), n= 82 297, respectively). Queries of human biobank data sets revealed associations of rs4888378 with nearby gene expression in vascular tissues (n=126-138). Conclusions-This study identified rs4888378 in the BCAR1-CFDP1-TMEM170A locus as a novel genetic determinant of cIMT and coronary artery disease risk in individuals of European descent. (Circ Cardiovasc Genet. 2012;5:656-665.)
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| 29. |
- Gustafsson, Torfinn, et al.
(author)
-
Authors' response
- 2023
-
In: Journal of Forensic Sciences. - : John Wiley & Sons. - 0022-1198 .- 1556-4029. ; 68:3, s. 1086-1088
-
Journal article (peer-reviewed)
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| 30. |
- Gustafsson, Torfinn, et al.
(author)
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The utility of histology in assessing the cause of death in medico-legal autopsies in selected trauma deaths : suspension-, immersion-, fire-, and traffic-related
- 2023
-
In: Journal of Forensic Sciences. - : John Wiley & Sons. - 0022-1198 .- 1556-4029. ; 68:2, s. 509-517
-
Journal article (peer-reviewed)abstract
- The goal of a medico-legal autopsy is primarily to determine the cause and manner of death. To this end, the pathologist often uses auxiliary analyses, including histology. However, the utility of routine histology in all medico-legal autopsies is unknown. Earlier studies on the utility of routine histology have shown inconsistent effects, with some studies recommending it and others rejecting it. To study the degree to which histology informs on the underlying cause of death, we sent autopsy reports from suspension-, immersion-, fire-, and traffic-related deaths to senior board-certified forensic pathologists and had them assess the cause of death, first without knowledge of the histological findings and then with knowledge thereof. Fifty cases were identified in each of four subgroups: fire-, immersion-, suspension-, and traffic-related deaths. The autopsy reports were anonymized, and the histological findings and conclusions were removed. Two board-certified forensic pathologists independently reviewed the reports in each subgroup and assessed the manner and underlying cause of death (including their certainty of this assessment on a five-level scale) with and without access to histological findings. The probability of changing the underlying cause of death posthistology was low in all study groups. There was a slight increase in the degree of certainty posthistology in cases where the underlying cause of death was not changed, but only when the antehistology certainty was low. Our results suggest that histology does not meaningfully inform on the underlying cause of death in suspension-, immersion-, fire-, and traffic-related deaths except when antehistology certainty is low.
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| 31. |
- Holmes, Michael V., et al.
(author)
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Secretory Phospholipase A(2)-IIA and Cardiovascular Disease
- 2013
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In: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 62:21, s. 1966-1976
-
Journal article (peer-reviewed)abstract
- Objectives This study sought to investigate the role of secretory phospholipase A(2) (sPLA(2))-IIA in cardiovascular disease. less thanbrgreater than less thanbrgreater thanBackground Higher circulating levels of sPLA(2)-IIA mass or sPLA(2) enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA(2) inhibitor (varespladib) was stopped prematurely for lack of efficacy. less thanbrgreater than less thanbrgreater thanMethods We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA(2)-IIA isoenzyme, as an instrumental variable. less thanbrgreater than less thanbrgreater thanResults PLA2G2A rs11573156 C allele associated with lower circulating sPLA(2)-IIA mass (38% to 44%) and sPLA(2) enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA(2)-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE. less thanbrgreater than less thanbrgreater thanConclusions Reducing sPLA(2)-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events.
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| 32. |
- Ingason, Haukur, et al.
(author)
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The Metro Project : Final report
- 2012
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Reports (other academic/artistic)abstract
- This report compiles the results from the METRO project. The different parts of theproject – design fires, evacuation, integrated fire control, smoke control, extraordinarystrain onconstructions and fire- and rescue operations – are presented separately.The most complicated and expensive part of the project was the performance of thelarge scale fire and explosion tests in the Brunsberg tunnel, where the maximum heatrelease rates measured from the metro wagon was 77 MW.The main results from the project are new recommendations regarding design firesin mass transport systems, identification of key factors for fire and smoke spread in tunnelsand at stations as well as regarding the difficulties for disabled persons to evacuatefrom trains in tunnels, new recommended types of way guiding systems, safer design incase of explosions in trains and evaluation of the fire and rescue services’ possibilitiesand limitations in underground mass transport systems.
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| 33. |
- Joffrin, E., et al.
(author)
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Overview of the JET preparation for deuterium-tritium operation with the ITER like-wall
- 2019
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In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
-
Research review (peer-reviewed)abstract
- For the past several years, the JET scientific programme (Pamela et al 2007 Fusion Eng. Des. 82 590) has been engaged in a multi-campaign effort, including experiments in D, H and T, leading up to 2020 and the first experiments with 50%/50% D-T mixtures since 1997 and the first ever D-T plasmas with the ITER mix of plasma-facing component materials. For this purpose, a concerted physics and technology programme was launched with a view to prepare the D-T campaign (DTE2). This paper addresses the key elements developed by the JET programme directly contributing to the D-T preparation. This intense preparation includes the review of the physics basis for the D-T operational scenarios, including the fusion power predictions through first principle and integrated modelling, and the impact of isotopes in the operation and physics of D-T plasmas (thermal and particle transport, high confinement mode (H-mode) access, Be and W erosion, fuel recovery, etc). This effort also requires improving several aspects of plasma operation for DTE2, such as real time control schemes, heat load control, disruption avoidance and a mitigation system (including the installation of a new shattered pellet injector), novel ion cyclotron resonance heating schemes (such as the three-ions scheme), new diagnostics (neutron camera and spectrometer, active Alfven eigenmode antennas, neutral gauges, radiation hard imaging systems...) and the calibration of the JET neutron diagnostics at 14 MeV for accurate fusion power measurement. The active preparation of JET for the 2020 D-T campaign provides an incomparable source of information and a basis for the future D-T operation of ITER, and it is also foreseen that a large number of key physics issues will be addressed in support of burning plasmas.
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| 34. |
- Lagedal, Rickard, et al.
(author)
-
Impaired Antibody Response Is Associated with Histone-Release, Organ Dysfunction and Mortality in Critically Ill COVID-19 Patients
- 2022
-
In: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 11:12
-
Journal article (peer-reviewed)abstract
- Purpose: the pathophysiologic mechanisms explaining differences in clinical outcomes following COVID-19 are not completely described. This study aims to investigate antibody responses in critically ill patients with COVID-19 in relation to inflammation, organ failure and 30-day survival. Methods: All patients with PCR-verified COVID-19 and gave consent, and who were admitted to a tertiary Intensive care unit (ICU) in Sweden during March-September 2020 were included. Demography, repeated blood samples and measures of organ function were collected. Analyses of anti-SARS-CoV-2 antibodies (IgM, IgA and IgG) in plasma were performed and correlated to patient outcome and biomarkers of inflammation and organ failure. Results: A total of 115 patients (median age 62 years, 77% male) were included prospectively. All patients developed severe respiratory dysfunction, and 59% were treated with invasive ventilation. Thirty-day mortality was 22.6% for all included patients. Patients negative for any anti-SARS-CoV-2 antibody in plasma during ICU admission had higher 30-day mortality compared to patients positive for antibodies. Patients positive for IgM had more ICU-, ventilator-, renal replacement therapy- and vasoactive medication-free days. IgA antibody concentrations correlated negatively with both SAPS3 and maximal SOFA-score and IgM-levels correlated negatively with SAPS3. Patients with antibody levels below the detection limit had higher plasma levels of extracellular histones on day 1 and elevated levels of kidney and cardiac biomarkers, but showed no signs of increased inflammation, complement activation or cytokine release. After adjusting for age, positive IgM and IgG antibodies were still associated with increased 30-day survival, with odds ratio (OR) 7.1 (1.5-34.4) and 4.2 (1.1-15.7), respectively. Conclusion: In patients with severe COVID-19 requiring intensive care, a poor antibody response is associated with organ failure, systemic histone release and increased 30-day mortality.
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| 35. |
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| 36. |
- Lind, Lars, et al.
(author)
-
Obesity is associated with coronary artery stenosis independently of metabolic risk factors : the population-based SCAPIS study
- 2022
-
In: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 362, s. 1-10
-
Journal article (peer-reviewed)abstract
- Background and aims: Previous studies reported divergent results on whether metabolically healthy obesity is associated with increased coronary artery calcium and carotid plaques. We investigated this in a cross-sectional fashion in a large, well-defined, middle-aged population using coronary CT angiography (CCTA) and carotid ultrasound. Methods: In the SCAPIS study (50–65 years, 51% female), CCTA and carotid artery ultrasound were performed in 23,674 individuals without clinical atherosclerotic disease. These subjects were divided into six groups according to BMI (normal weight, overweight, obese) and the presence of metabolic syndrome (MetS) according to the NCEP consensus criteria. Results: The severity of coronary artery stenosis was increased in individuals with obesity without MetS compared to normal-weight individuals without MetS (OR 1.47, 95%CI 1.34–1.62; p < 0.0001), even after adjusting for non-HDL-cholesterol and several lifestyle factors. Such difference was not observed for the presence of carotid artery plaques (OR 0.94, 95%CI 0.87–1.02; p = 0.11). Obese or overweight individuals without any MetS criteria (except the waist criterion) showed significantly more pronounced stenosis in the coronary arteries as compared to the normal-weight individuals, while one criterion was needed to show increased plaque prevalence in the carotid arteries. High blood pressure was the most important single criterion for increased atherosclerosis in this respect. Conclusions: Individuals with obesity without MetS showed increased severity of coronary artery stenosis, but no increased occurrence of carotid artery plaques compared to normal-weight individuals without MetS, further emphasizing that obesity is not a benign condition even in the absence of MetS.
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| 37. |
- Locke, Adam E, et al.
(author)
-
Genetic studies of body mass index yield new insights for obesity biology.
- 2015
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
-
Journal article (peer-reviewed)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 38. |
- Malinovschi, Andrei, 1978-, et al.
(author)
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Consequences of Using Post- or Prebronchodilator Reference Values in Interpreting Spirometry
- 2023
-
In: American Journal of Respiratory and Critical Care Medicine. - : American Thoracic Society. - 1073-449X .- 1535-4970. ; 208:4, s. 461-471
-
Journal article (peer-reviewed)abstract
- RATIONALE: Post-bronchodilator (BD) spirometry is used for diagnosis of chronic obstructive pulmonary disease (COPD). However, pre-BD reference values are used for spirometry interpretation.OBJECTIVES: To compare the resulting prevalence rates of abnormal spirometry and study the consequences of using pre- or post-BD reference values generated within the Swedish CArdioPulmonary bioImage Study (SCAPIS) when interpreting post-BD spirometry in a general population.METHODS: SCAPIS reference values for post-BD and pre-BD spirometry were based on 10,156 and 1,498 never-smoking, healthy participants, respectively. We studied the associations of abnormal spirometry, defined by using pre- or post-BD reference values, with respiratory burden in the SCAPIS general population (28,851 individuals).MEASUREMENTS AND MAIN RESULTS: Bronchodilation resulted in higher predicted median and lower limit of normal (LLN) for FEV1/FVC ratio. The prevalence of post-BD FEV1/FVC < pre-bronchodilator LLN was 4.8% and that of post-BD FEV1/FVC < post-bronchodilator LLN was 9.9% for the general population. An additional 5.1% was identified as having an abnormal post-BD FEV1/FVC ratio and this group had more respiratory symptoms, emphysema (13.5% vs. 4.1%, p<0.001) and self-reported physician-diagnosed COPD (2.8% vs. 0.5%, p<0.001) than subjects with post-BD FEV1/FVC ratio > LLN for both pre- and post-bronchodilation).CONCLUSIONS: Pre- and post-bronchodilator spirometry reference values differ with regard to FEV1/FVC ratio. Use of post-bronchodilator reference values doubled the population prevalence of airflow obstruction; this was related to a higher respiratory burden. Using post-bronchodilator reference values when interpreting post-bronchodilator spirometry might enable identification of individuals with mild disease and be clinically relevant.
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| 39. |
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| 40. |
- Paloschi, Valentina, et al.
(author)
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Impaired Splicing of Fibronectin Is Associated With Thoracic Aortic Aneurysm Formation in Patients With Bicuspid Aortic Valve
- 2011
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In: Arteriosclerosis, Thrombosis and Vascular Biology. - : American Heart Association. - 1079-5642 .- 1524-4636. ; 31:3, s. 691-697
-
Journal article (peer-reviewed)abstract
- OBJECTIVE:Thoracic aortic aneurysm is a common complication in patients with bicuspid aortic valve (BAV). Alternatively spliced extra domain A (EDA) of fibronectin (FN) has an essential role in tissue repair. Here we analyze the expression of FN spliceforms in dilated and nondilated ascending aorta of tricuspid aortic valve (TAV) and BAV patients.METHODS AND RESULTS:The mRNA expression was analyzed in the ascending aorta by Affymetrix Exon arrays in patients with TAV (n=40) and BAV (n=69). EDA and extra domain B (EDB) expression was increased in dilated aorta from TAV patients compared with nondilated aorta (P<0.001 and P<0.05, respectively). In contrast, EDA expression was not increased in dilated aorta from BAV patients (P=0.25), whereas EDB expression was upregulated (P<0.01). The expression of EDA correlated with maximum aortic diameter in TAV (ρ=0.58) but not in BAV (ρ=0.15) patients. Protein analyses of EDA-FN showed concordant results. Transforming growth factor-β treatment influenced the splicing of FN and enhanced the formation of EDA-containing FN in cultured medial cells from TAV patients but not in cells derived from BAV patients. Gene set enrichment analysis together with multivariate and univariate data analyses of mRNA expression suggested that differences in the transforming growth factor-β signaling pathway may explain the impaired EDA inclusion in BAV patients.CONCLUSIONS:Decreased EDA expression may contribute to increased aneurysm susceptibility of BAV patients.
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| 41. |
- Raghavan, Maanasa, et al.
(author)
-
Genomic evidence for the Pleistocene and recent population history of Native Americans
- 2015
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 349:6250
-
Journal article (peer-reviewed)abstract
- Howand when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we found that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (ka) and after no more than an 8000-year isolation period in Beringia. After their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 ka, one that is now dispersed across North and South America and the other restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians (including Siberians) and, more distantly, Australo-Melanesians. Putative "Paleoamerican" relict populations, including the historical Mexican Pericues and South American Fuego-Patagonians, are not directly related to modern Australo-Melanesians as suggested by the Paleoamerican Model.
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| 42. |
- Sandling, Johanna K., et al.
(author)
-
A candidate gene study of the type I interferon pathway implicates IKBKE and IL8 as risk loci for SLE
- 2011
-
In: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 19:4, s. 479-484
-
Journal article (peer-reviewed)abstract
- Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease in which the type I interferon pathway has a crucial role. We have previously shown that three genes in this pathway, IRF5, TYK2 and STAT4, are strongly associated with risk for SLE. Here, we investigated 78 genes involved in the type I interferon pathway to identify additional SLE susceptibility loci. First, we genotyped 896 single-nucleotide polymorphisms in these 78 genes and 14 other candidate genes in 482 Swedish SLE patients and 536 controls. Genes with P<0.01 in the initial screen were then followed up in 344 additional Swedish patients and 1299 controls. SNPs in the IKBKE, TANK, STAT1, IL8 and TRAF6 genes gave nominal signals of association with SLE in this extended Swedish cohort. To replicate these findings we extracted data from a genomewide association study on SLE performed in a US cohort. Combined analysis of the Swedish and US data, comprising a total of 2136 cases and 9694 controls, implicates IKBKE and IL8 as SLE susceptibility loci (P(meta)=0.00010 and P(meta)=0.00040, respectively). STAT1 was also associated with SLE in this cohort (P(meta)=3.3 × 10(-5)), but this association signal appears to be dependent of that previously reported for the neighbouring STAT4 gene. Our study suggests additional genes from the type I interferon system in SLE, and highlights genes in this pathway for further functional analysis.
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| 43. |
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| 44. |
- Shungin, Dmitry, et al.
(author)
-
New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
-
Journal article (peer-reviewed)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 45. |
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| 46. |
- Simonsson, Bengt, et al.
(author)
-
Combination of pegylated IFN-alpha 2b with imatinib increases molecular response rates in patients with low- or intermediate-risk chronic myeloid leukemia
- 2011
-
In: Blood. - Washington D.C. : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 118:12, s. 3228-3235
-
Journal article (peer-reviewed)abstract
- Biologic and clinical observations suggest that combining imatinib with IFN-alpha may improve treatment outcome in chronic myeloid leukemia (CML). We randomized newly diagnosed chronic-phase CML patients with a low or intermediate Sokal risk score and in imatinib-induced complete hematologic remission either to receive a combination of pegylated IFN-alpha 2b (Peg-IFN-alpha 2b) 50 mu g weekly and imatinib 400 mg daily (n = 56) or to receive imatinib 400 mg daily monotherapy (n = 56). The primary endpoint was the major molecular response (MMR) rate at 12 months after randomization. In both arms, 4 patients (7%) discontinued imatinib treatment (1 because of blastic transformation in imatinib arm). In addition, in the combination arm, 34 patients (61%) discontinued Peg-IFN-alpha 2b, most because of toxicity. The MMR rate at 12 months was significantly higher in the imatinib plus Peg-IFN-alpha 2b arm (82%) compared with the imatinib monotherapy arm (54%; intention-to-treat, P = .002). The MMR rate increased with the duration of Peg-IFN-alpha 2b treatment (andlt; 12-week MMR rate 67%, andgt; 12-week MMR rate 91%). Thus, the addition of even relatively short periods of Peg-IFN-alpha 2b to imatinib markedly increased the MMR rate at 12 months of therapy. Lower doses of Peg-IFN-alpha 2b may enhance tolerability while retaining efficacy and could be considered in future protocols with curative intent.
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| 47. |
- Sundström, Johan, Professor, 1971-, et al.
(author)
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Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults
- 2019
-
In: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.
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| 48. |
- Torén, Kjell, 1952, et al.
(author)
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The ratio FEV1/FVC and its association to respiratory symptoms-A Swedish general population study
- 2021
-
In: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 41:2, s. 181-191
-
Journal article (peer-reviewed)abstract
- Chronic airflow limitation (CAL) can be defined as fixed ratio of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) any respiratory symptom. In a cross-sectional general population study, 15,128 adults (50-64 years of age), 7,120 never-smokers and 8,008 ever-smokers completed a respiratory questionnaire and performed FEV1 and FVC after bronchodilation. We calculated different ratios of FEV1/FVC from 0.40 to 1.0 using 0.70 as reference category. We analysed odds ratios (OR) between different ratios and any respiratory symptom using adjusted multivariable logistic regression. Among all subjects, regardless of smoking habits, the lowest odds for any respiratory symptom was at FEV1/FVC = 0.82, OR 0.48 (95% CI 0.41-0.56). Among never-smokers, the lowest odds for any respiratory symptom was at FEV1/FVC = 0.81, OR 0.53 (95% CI 0.41-0.70). Among ever-smokers, the odds for any respiratory symptom was lowest at FEV1/FVC = 0.81, OR 0.43 (95% CI 0.16-1.19), although the rate of inclining in odds was small in the upper part, that is FEV1/FVC = 0.85 showed similar odds, OR 0.45 (95% CI 0.38-0.55). We concluded that the odds for any respiratory symptoms continuously decreased with higher FEV1/FVC ratios and reached a minimum around 0.80-0.85, with similar results among never-smokers. These results indicate that the optimal threshold associated with respiratory symptoms may be higher than 0.70 and this should be further investigated in prospective longitudinal studies.
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| 49. |
- Östgren, Carl Johan, et al.
(author)
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Prevalence of atherosclerosis in individuals with prediabetes and diabetes compared to normoglycaemic individuals-a Swedish population-based study.
- 2023
-
In: Cardiovascular diabetology. - : BioMed Central (BMC). - 1475-2840. ; 22:1
-
Journal article (peer-reviewed)abstract
- Patients with type 2 diabetes have an increased risk of death and cardiovascular events and people with diabetes or prediabetes have been found to have increased atherosclerotic burden in the coronary and carotid arteries. This study will estimate the cross-sectional prevalence of atherosclerosis in the coronary and carotid arteries in individuals with prediabetes and diabetes, compared with normoglycaemic individuals in a large population-based cohort.The 30,154 study participants, 50-64years, were categorized according to their fasting glycaemic status or self-reported data as normoglycaemic, prediabetes, and previously undetected or known diabetes. Prevalence of affected coronary artery segments, severity of stenosis and coronary artery calcium score (CACS) were determined by coronary computed tomography angiography. Total atherosclerotic burden was assessed in the 11 clinically most relevant segments using the Segment Involvement Score and as the presence of any coronary atherosclerosis. The presence of atherosclerotic plaque in the carotid arteries was determined by ultrasound examination.Study participants with prediabetes (n=4804, 16.0%) or diabetes (n=2282, 7.6%) had greater coronary artery plaque burden, more coronary stenosis and higher CACS than normoglycaemic participants (all, p<0.01). Among male participants with diabetes 35.3% had CACS≥100 compared to 16.1% among normoglycaemic participants. For women, the corresponding figures were 8.9% vs 6.1%. The prevalence of atherosclerosis in the coronary arteries was higher in participants with previously undetected diabetes than prediabetes, but lower than in patients with known diabetes. The prevalence of any plaque in the carotid arteries was higher in participants with prediabetes or diabetes than in normoglycaemic participants.In this large population-based cohort of currently asymptomatic people, the atherosclerotic burden in the coronary and carotid arteries increased with increasing degree of dysglycaemia. The finding that the atherosclerotic burden in the coronary arteries in the undetected diabetes category was midway between the prediabetes category and patients with known diabetes may have implications for screening strategies and tailored prevention interventions for people with dysglycaemia in the future.
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| 50. |
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