| 1. |
- Schael, S, et al.
(författare)
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Precision electroweak measurements on the Z resonance
- 2006
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 2. |
- Munn-Chernoff, M. A., et al.
(författare)
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Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
- 2021
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Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r(g)], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from similar to 2400 to similar to 537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r(g) = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r(g) = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r(g) = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r(gs) = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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| 3. |
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| 4. |
- Watson, H. J., et al.
(författare)
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Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:8
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Tidskriftsartikel (refereegranskat)abstract
- Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness(1), affecting 0.9-4% of women and 0.3% of men(2-4), with twin-based heritability estimates of 50-60%(5). Mortality rates are higher than those in other psychiatric disorders(6), and outcomes are unacceptably poor(7). Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)(8,9) and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
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| 5. |
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| 6. |
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| 7. |
- Bryois, J., et al.
(författare)
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Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
- 2020
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:5, s. 482-493
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 8. |
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| 9. |
- Balabanski, Anna H., et al.
(författare)
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Incidence of stroke in indigenous populations of countries with a very high human development index : a systematic review
- 2024
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Ingår i: Neurology. - : American Academy of Neurology. - 0028-3878 .- 1526-632X. ; 102:5
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Forskningsöversikt (refereegranskat)abstract
- Background and objectives: Cardiovascular disease contributes significantly to disease burden among many Indigenous populations. However, data on stroke incidence in Indigenous populations are sparse. We aimed to investigate what is known of stroke incidence in Indigenous populations of countries with a very high Human Development Index (HDI), locating the research in the broader context of Indigenous health.Methods: We identified population-based stroke incidence studies published between 1990 and 2022 among Indigenous adult populations of developed countries using PubMed, Embase, and Global Health databases, without language restriction. We excluded non-peer-reviewed sources, studies with fewer than 10 Indigenous people, or not covering a 35- to 64-year minimum age range. Two reviewers independently screened titles, abstracts, and full-text articles and extracted data. We assessed quality using "gold standard" criteria for population-based stroke incidence studies, the Newcastle-Ottawa Scale for risk of bias, and CONSIDER criteria for reporting of Indigenous health research. An Indigenous Advisory Board provided oversight for the study.Results: From 13,041 publications screened, 24 studies (19 full-text articles, 5 abstracts) from 7 countries met the inclusion criteria. Age-standardized stroke incidence rate ratios were greater in Aboriginal and Torres Strait Islander Australians (1.7-3.2), American Indians (1.2), Sámi of Sweden/Norway (1.08-2.14), and Singaporean Malay (1.7-1.9), compared with respective non-Indigenous populations. Studies had substantial heterogeneity in design and risk of bias. Attack rates, male-female rate ratios, and time trends are reported where available. Few investigators reported Indigenous stakeholder involvement, with few studies meeting any of the CONSIDER criteria for research among Indigenous populations.Discussion: In countries with a very high HDI, there are notable, albeit varying, disparities in stroke incidence between Indigenous and non-Indigenous populations, although there are gaps in data availability and quality. A greater understanding of stroke incidence is imperative for informing effective societal responses to socioeconomic and health disparities in these populations. Future studies into stroke incidence in Indigenous populations should be designed and conducted with Indigenous oversight and governance to facilitate improved outcomes and capacity building.
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| 10. |
- Balabanski, Anna H., et al.
(författare)
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The Incidence of Stroke in Indigenous Populations of Countries With a Very High Human Development Index : A Systematic Review Protocol
- 2021
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Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 12
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Forskningsöversikt (refereegranskat)abstract
- Background and Aims: Despite known Indigenous health and socioeconomic disadvantage in countries with a Very High Human Development Index, data on the incidence of stroke in these populations are sparse. With oversight from an Indigenous Advisory Board, we will undertake a systematic review of the incidence of stroke in Indigenous populations of developed countries or regions, with comparisons between Indigenous and non-Indigenous populations of the same region, though not between different Indigenous populations.Methods: Using PubMed, OVID-EMBASE, and Global Health databases, we will examine population-based incidence studies of stroke in Indigenous adult populations of developed countries published 1990-current, without language restriction. Non-peer-reviewed sources, studies including <10 Indigenous People, or with insufficient data to determine incidence, will be excluded. Two reviewers will independently validate the search strategies, screen titles and abstracts, and record reasons for rejection. Relevant articles will undergo full-text screening, with standard data extracted for all studies included. Quality assessment will include Sudlow and Warlow's criteria for population-based stroke incidence studies, the Newcastle-Ottawa Scale for risk of bias, and the CONSIDER checklist for Indigenous research.Results: Primary outcomes include crude, age-specific and/or age-standardized incidence of stroke. Secondary outcomes include overall stroke rates, incidence rate ratio and case-fatality. Results will be synthesized in figures and tables, describing data sources, populations, methodology, and findings. Within-population meta-analysis will be performed if, and where, methodologically sound and comparable studies allow this.Conclusion: We will undertake the first systematic review assessing disparities in stroke incidence in Indigenous populations of developed countries. Data outputs will be disseminated to relevant Indigenous stakeholders to inform public health and policy research.
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| 11. |
- Ip, H. F., et al.
(författare)
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Genetic association study of childhood aggression across raters, instruments, and age
- 2021
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association metaanalysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE= 0.0038). We found no genome-wide significant SNPs for AGG(overall). The gene-based analysis returned three significant genes: ST3GAL3 (P= 1.6E-06), PCDH7 (P= 2.0E-06), and IPO13 (P= 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from r(g)= 0.46 between self- and teacher-assessment to r(g)d= 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range r(g): 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r(g)=-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |r(g)| : 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
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| 12. |
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| 13. |
- Maron, David J., et al.
(författare)
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Initial Invasive or Conservative Strategy for Stable Coronary Disease
- 2020
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 382:15, s. 1395-1407
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Tidskriftsartikel (refereegranskat)abstract
- Background: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain.Methods: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction.Results: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32).Conclusions: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, .) Patients with stable coronary disease were randomly assigned to an initial invasive strategy with angiography and revascularization if appropriate or to medical therapy alone. At 3.2 years, there was no significant difference between the groups with respect to the estimated rate of ischemic events. The findings were sensitive to the definition of myocardial infarction.
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| 14. |
- Nguyen, Dan D., et al.
(författare)
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Health Status and Clinical Outcomes in Older Adults With Chronic Coronary Disease
- 2023
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 81:17, s. 1697-1709
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Whether initial invasive management in older vs younger adults with chronic coronary disease and moderate or severe ischemia improves health status or clinical outcomes is unknown. OBJECTIVES The goal of this study was to examine the impact of age on health status and clinical outcomes with invasive vs conservative management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial.METHODS: One-year angina-specific health status was assessed with the 7-item Seattle Angina Questionnaire (SAQ) (score range 0-100; higher scores indicate better health status). Cox proportional hazards models estimated the treatment effect of invasive vs conservative management as a function of age on the composite clinical outcome of cardiovascular death, myocardial infarction, or hospitalization for resuscitated cardiac arrest, unstable angina, or heart failure.RESULTS: Among 4,617 participants, 2,239 (48.5%) were aged <65 years, 1,713 (37.1%) were aged 65 to 74 years, and 665 (14.4%) were aged $75 years. Baseline SAQ summary scores were lower in participants aged <65 years. Fully adjusted differences in 1-year SAQ summary scores (invasive minus conservative) were 4.90 (95% CI: 3.56-6.24) at age 55 years, 3.48 (95% CI: 2.40-4.57) at age 65 years, and 2.13 (95% CI: 0.75-3.51) at age 75 years (Pinteraction = 0.008). Improvement in SAQ Angina Frequency was less dependent on age (Pinteraction = 0.08). There were no age differences between invasive vs conservative management on the composite clinical outcome (Pinteraction = 0.29).CONCLUSIONS: Older patients with chronic coronary disease and moderate or severe ischemia had consistent improvement in angina frequency but less improvement in angina-related health status with invasive management compared with younger patients. Invasive management was not associated with improved clinical outcomes in older or younger patients.
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| 15. |
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| 16. |
- Watson, Hunna J., et al.
(författare)
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Common Genetic Variation and Age of Onset of Anorexia Nervosa
- 2022
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Ingår i: BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE. - : Elsevier BV. - 2667-1743. ; 2:4, s. 368-378
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
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| 17. |
- Allen, R. C., et al.
(författare)
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Energetic ions in the Venusian system : Insights from the first Solar Orbiter flyby
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656
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Tidskriftsartikel (refereegranskat)abstract
- The Solar Orbiter flyby of Venus on 27 December 2020 allowed for an opportunity to measure the suprathermal to energetic ions in the Venusian system over a large range of radial distances to better understand the acceleration processes within the system and provide a characterization of galactic cosmic rays near the planet. Bursty suprathermal ion enhancements (up to similar to 10 keV) were observed as far as similar to 50R(V) downtail. These enhancements are likely related to a combination of acceleration mechanisms in regions of strong turbulence, current sheet crossings, and boundary layer crossings, with a possible instance of ion heating due to ion cyclotron waves within the Venusian tail. Upstream of the planet, suprathermal ions are observed that might be related to pick-up acceleration of photoionized exospheric populations as far as 5R(V) upstream in the solar wind as has been observed before by missions such as Pioneer Venus Orbiter and Venus Express. Near the closest approach of Solar Orbiter, the Galactic cosmic ray (GCR) count rate was observed to decrease by approximately 5 percent, which is consistent with the amount of sky obscured by the planet, suggesting a negligible abundance of GCR albedo particles at over 2 R-V. Along with modulation of the GCR population very close to Venus, the Solar Orbiter observations show that the Venusian system, even far from the planet, can be an effective accelerator of ions up to similar to 30 keV. This paper is part of a series of the first papers from the Solar Orbiter Venus flyby.
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| 18. |
- Aran, A., et al.
(författare)
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Evidence for local particle acceleration in the first recurrent galactic cosmic ray depression observed by Solar Orbiter : The ion event on 19 June 2020
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656
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Tidskriftsartikel (refereegranskat)abstract
- Context. In mid-June 2020, the Solar Orbiter (SolO) mission reached its first perihelion at 0.51 au and started its cruise phase, with most of the in situ instruments operating continuously.Aims. We present the in situ particle measurements of the first proton event observed after the first perihelion obtained by the Energetic Particle Detector (EPD) suite on board SolO. The potential solar and interplanetary (IP) sources of these particles are investigated.Methods. Ion observations from similar to 20 keV to similar to 1 MeV are combined with available solar wind data from the Radio and Plasma Waves (RPW) instrument and magnetic field data from the magnetometer on board SolO to evaluate the energetic particle transport conditions and infer the possible acceleration mechanisms through which particles gain energy. We compare > 17-20 MeV ion count rate measurements for two solar rotations, along with the solar wind plasma data available from the Solar Wind Analyser (SWA) and RPW instruments, in order to infer the origin of the observed galactic cosmic ray (GCR) depressions.Results. The lack of an observed electron event and of velocity dispersion at various low-energy ion channels and the observed IP structure indicate a local IP source for the low-energy particles. From the analysis of the anisotropy of particle intensities, we conclude that the low-energy ions were most likely accelerated via a local second-order Fermi process. The observed GCR decrease on 19 June, together with the 51.8-1034.0 keV nuc(-1) ion enhancement, was due to a solar wind stream interaction region (SIR). The observation of a similar GCR decrease in the next solar rotation favours this interpretation and constitutes the first observation of a recurrent GCR decrease by SolO. The analysis of the recurrence times of this SIR suggests that it is the same SIR responsible for the He-4 events previously measured in April and May. Finally, we point out that an IP structure more complex than a common SIR cannot be discarded, mainly due to the lack of solar wind temperature measurements and the lack of a higher cadence of solar wind velocity observations.
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| 19. |
- Bangalore, Sripal, et al.
(författare)
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Management of Coronary Disease in Patients with Advanced Kidney Disease.
- 2020
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 382:17, s. 1608-1618
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease.METHODS: We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest.RESULTS: At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P = 0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P = 0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P = 0.03).CONCLUSIONS: Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).
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| 20. |
- Cordova, Reynalda, et al.
(författare)
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Consumption of ultra-processed foods associated with weight gain and obesity in adults : A multi-national cohort study
- 2021
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Ingår i: Clinical Nutrition. - : Elsevier. - 0261-5614 .- 1532-1983. ; 40:9, s. 5079-5088
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is a worldwide shift towards increased consumption of ultra-processed foods (UPF) with concurrent rising prevalence of obesity. We examined the relationship between the consumption of UPF and weight gain and risk of obesity.Methods: This prospective cohort included 348 748 men and women aged 25–70 years. Participants were recruited between 1992 and 2000 from 9 European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Two body weight measures were available, at baseline and after a median follow-up time of 5 years. Foods and drinks were assessed at baseline by dietary questionnaires and classified according to their degree of processing using NOVA classification. Multilevel mixed linear regression was used to estimate the association between UPF consumption and body weight change (kg/5 years). To estimate the relative risk of becoming overweight or obese after 5 years we used Poisson regression stratified according to baseline body mass index (BMI).Results: After multivariable adjustment, higher UPF consumption (per 1 SD increment) was positively associated with weight gain (0·12 kg/5 years, 95% CI 0·09 to 0·15). Comparing highest vs. lowest quintile of UPF consumption was associated with a 15% greater risk (95% CI 1·11, 1·19) of becoming overweight or obese in normal weight participants, and with a 16% greater risk (95% CI 1·09, 1·23) of becoming obese in participants who were overweight at baseline.Conclusions: These results are supportive of public health campaigns to substitute UPF for less processed alternatives for obesity prevention and weight management.
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| 21. |
- Fleischhacker, W Wolfgang, et al.
(författare)
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Metabolic risk factors in first-episode schizophrenia : baseline prevalence and course analysed from the European First-Episode Schizophrenia Trial
- 2013
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Ingår i: International Journal of Neuropsychopharmacology. - 1461-1457 .- 1469-5111. ; 16:5, s. 987-995
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Tidskriftsartikel (refereegranskat)abstract
- Available data on antipsychotic-induced metabolic risks are often constrained by potential confounding effects due to prior antipsychotic treatment. In this study, we assessed the baseline prevalence of metabolic abnormalities and changes following treatment with five commonly-used antipsychotic drugs (haloperidol, amisulpride, olanzapine, quetiapine or ziprasidone) in first-episode, partially antipsychotic-naive patients with schizophrenia in the European first-episode schizophrenia trial (EUFEST). Overall baseline prevalence of metabolic syndrome (MetS) was 6.0%, with similar rates observed in the antipsychotic-naive patients (5.7%, 9/157) and in the other patients with only a brief prior exposure to antipsychotics (6.1%, 20/326). These results are consistent with the MetS prevalence rate estimated in a general population of similar age. Examination of individual risk factors showed 58.5% of subjects had one or more elevated metabolic risks at baseline: 28.5% demonstrated suboptimal HDL; 24.2% hypertension; 17.7% hypertriglyceridemia; 8.2% abdominal obesity; 7.3% hyperglycaemia. Increase in body weight (kg/month) occurred in patients treated with haloperidol (0.62 s.e. 0.11), amisulpride (0.76 s.e. 0.08), olanzapine (0.98 s.e. 0.07) and quetiapine (0.58 s.e. 0.09), which was significantly greater than that in the ziprasidone group (0.18 s.e. 0.10). The incidence rate of new diabetes cases over a 52-wk follow-up period was 0.82% (4/488). More patients experienced worsening rather than improvement of hypertriglyceridemia or hyperglycaemia in all treatment groups. Our findings suggest that in first-episode, partially antipsychotic-naive patients, the baseline prevalence rate of MetS appears to be no higher than that in the general population, but serious underlying individual risk factors nevertheless existed.
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| 22. |
- Hagström, Emil, et al.
(författare)
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Association Between Very Low Levels of High-Density Lipoprotein Cholesterol and Long-term Outcomes of Patients With Acute Coronary Syndrome Treated Without Revascularization : Insights From the TRILOGY ACS Trial
- 2016
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Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 39:6, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- Background: Low levels of high-density lipoprotein cholesterol (HDL-C; < 40 mg/dL) are associated with increased risk of cardiovascular events, but it is unclear whether lower thresholds (< 30 mg/dL) are associated with increased hazard.Hypothesis: Very low levels of HDL-C may provide prognostic information in acute coronary syndrome (ACS) patients treated medically without revascularization.Methods: We examined data from 9064/9326 ACS patients enrolled in the TRILOGY ACS trial. Participants were randomized to clopidogrel or prasugrel plus aspirin. Study treatments continued for 6 to 30 months. Relationships between baseline HDL-C and the composite of cardiovascular death, myocardial infarction (MI), or stroke, and individual endpoints of death (cardiovascular and all-cause), MI, and stroke, adjusted for baseline characteristics through 30 months, were analyzed. The HDL-C was evaluated as a dichotomous variable-very low (< 30 mg/dL) vs higher (>= 30 mg/dL)-and continuously.Results: Median baseline HDL-C was 42mg/dL (interquartile range, 34-49mg/dL) with little variation over time. Frequency of the composite endpoint was similar for very low vs higher baseline HDL-C, with no risk difference between groups (hazard ratio [ HR]: 1.13, 95% confidence interval [ CI]: 0.95-1.34). Similar findings were seen for MI and stroke. However, risks for cardiovascular (HR: 1.42, 95% CI: 1.13-1.78) and all-cause death (HR: 1.36, 95% CI: 1.11-1.67) were higher in patients with very low baseline HDL-C.Conclusions: Medically managed ACS patients with very low baseline HDL-C levels have higher risk of long-term cardiovascular and all-cause death but similar risks for nonfatal ischemic outcomes vs patients with higher baseline HDL-C.
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| 23. |
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| 24. |
- Kollhoff, A., et al.
(författare)
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The first widespread solar energetic particle event observed by Solar Orbiter on 2020 November 29
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656
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Tidskriftsartikel (refereegranskat)abstract
- Context. On 2020 November 29, the first widespread solar energetic particle (SEP) event of solar cycle 25 was observed at four widely separated locations in the inner (≲1 AU) heliosphere. Relativistic electrons as well as protons with energies > 50 MeV were observed by Solar Orbiter (SolO), Parker Solar Probe, the Solar Terrestrial Relations Observatory (STEREO)-A and multiple near-Earth spacecraft. The SEP event was associated with an M4.4 class X-ray flare and accompanied by a coronal mass ejection and an extreme ultraviolet (EUV) wave as well as a type II radio burst and multiple type III radio bursts.Aims. We present multi-spacecraft particle observations and place them in context with source observations from remote sensing instruments and discuss how such observations may further our understanding of particle acceleration and transport in this widespread event.Methods. Velocity dispersion analysis (VDA) and time shift analysis (TSA) were used to infer the particle release times at the Sun. Solar wind plasma and magnetic field measurements were examined to identify structures that influence the properties of the energetic particles such as their intensity. Pitch angle distributions and first-order anisotropies were analyzed in order to characterize the particle propagation in the interplanetary medium.Results. We find that during the 2020 November 29 SEP event, particles spread over more than 230° in longitude close to 1 AU. The particle onset delays observed at the different spacecraft are larger as the flare–footpoint angle increases and are consistent with those from previous STEREO observations. Comparing the timing when the EUV wave intersects the estimated magnetic footpoints of each spacecraft with particle release times from TSA and VDA, we conclude that a simple scenario where the particle release is only determined by the EUV wave propagation is unlikely for this event. Observations of anisotropic particle distributions at SolO, Wind, and STEREO-A do not rule out that particles are injected over a wide longitudinal range close to the Sun. However, the low values of the first-order anisotropy observed by near-Earth spacecraft suggest that diffusive propagation processes are likely involved.
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| 25. |
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| 26. |
- Papadimitriou, Nikos, et al.
(författare)
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A Prospective Diet-Wide Association Study for Risk of Colorectal Cancer in EPIC
- 2022
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Ingår i: Clinical Gastroenterology and Hepatology. - : Saunders Elsevier. - 1542-3565 .- 1542-7714. ; 20:4, s. 864-873.e13
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Evidence regarding the association of dietary exposures with colorectal cancer (CRC) risk is not consistent with a few exceptions. Therefore, we conducted a diet-wide association study (DWAS) in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the associations between several dietary exposures with CRC risk.Methods: The association of 92 food and nutrient intakes with CRC risk was assessed in 386,792 participants, 5069 of whom developed incident CRC. Correction for multiple comparisons was performed using the false discovery rate, and emerging associations were examined in the Netherlands Cohort Study (NLCS). Multiplicative gene-nutrient interactions were also tested in EPIC based on known CRC-associated loci.Results: In EPIC, alcohol, liquor/spirits, wine, beer/cider, soft drinks, and pork were positively associated with CRC, whereas milk, cheese, calcium, phosphorus, magnesium, potassium, riboflavin, vitamin B6, beta carotene, fruit, fiber, nonwhite bread, banana, and total protein intakes were inversely associated. Of these 20 associations, 13 were replicated in the NLCS, for which a meta-analysis was performed, namely alcohol (summary hazard ratio [HR] per 1-SD increment in intake: 1.07; 95% confidence interval [CI], 1.04–1.09), liquor/spirits (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02–1.06), wine (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02–1.07), beer/cider (HR per 1-SD increment in intake, 1.06; 95% CI, 1.04–1.08), milk (HR per 1-SD increment in intake, 0.95; 95% CI, 0.93–0.98), cheese (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94–0.99), calcium (HR per 1-SD increment in intake, 0.93; 95% CI, 0.90–0.95), phosphorus (HR per 1-SD increment in intake, 0.92; 95% CI, 0.90–0.95), magnesium (HR per 1-SD increment in intake, 0.95; 95% CI, 0.92–0.98), potassium (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94–0.99), riboflavin (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92–0.97), beta carotene (HR per 1-SD increment in intake, 0.96; 95% CI, 0.93–0.98), and total protein (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92–0.97). None of the gene-nutrient interactions were significant after adjustment for multiple comparisons.Conclusions: Our findings confirm a positive association for alcohol and an inverse association for dairy products and calcium with CRC risk, and also suggest a lower risk at higher dietary intakes of phosphorus, magnesium, potassium, riboflavin, beta carotene, and total protein.
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| 27. |
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| 28. |
- Reynolds, Harmony R., et al.
(författare)
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Sex Differences in Revascularization, Treatment Goals, and Outcomes of Patients With Chronic Coronary Disease : Insights From the ISCHEMIA Trial
- 2024
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Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundWomen with chronic coronary disease are generally older than men and have more comorbidities but less atherosclerosis. We explored sex differences in revascularization, guideline‐directed medical therapy, and outcomes among patients with chronic coronary disease with ischemia on stress testing, with and without invasive management.Methods and ResultsThe ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial randomized patients with moderate or severe ischemia to invasive management with angiography, revascularization, and guideline‐directed medical therapy, or initial conservative management with guideline‐directed medical therapy alone. We evaluated the primary outcome (cardiovascular death, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) and other end points, by sex, in 1168 (22.6%) women and 4011 (77.4%) men. Invasive group catheterization rates were similar, with less revascularization among women (73.4% of invasive‐assigned women revascularized versus 81.2% of invasive‐assigned men; P<0.001). Women had less coronary artery disease: multivessel in 60.0% of invasive‐assigned women and 74.8% of invasive‐assigned men, and no ≥50% stenosis in 12.3% versus 4.5% (P<0.001). In the conservative group, 4‐year catheterization rates were 26.3% of women versus 25.6% of men (P=0.72). Guideline‐directed medical therapy use was lower among women with fewer risk factor goals attained. There were no sex differences in the primary outcome (adjusted hazard ratio [HR] for women versus men, 0.93 [95% CI, 0.77–1.13]; P=0.47) or the major secondary outcome of cardiovascular death/myocardial infarction (adjusted HR, 0.93 [95% CI, 0.76–1.14]; P=0.49), with no significant sex‐by‐treatment‐group interactions.ConclusionsWomen had less extensive coronary artery disease and, therefore, lower revascularization rates in the invasive group. Despite lower risk factor goal attainment, women with chronic coronary disease experienced similar risk‐adjusted outcomes to men in the ISCHEMIA trial.
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| 29. |
- Spertus, John A, et al.
(författare)
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Health-Status Outcomes with Invasive or Conservative Care in Coronary Disease.
- 2020
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 382:15, s. 1408-1419
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients.METHODS: We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency.RESULTS: At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina).CONCLUSIONS: In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).
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| 30. |
- Steinholtz, Linda, et al.
(författare)
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GABAA Receptor Availability in Relation to Cortical Excitability in Depressed and Healthy : A Positron Emission Tomography and Transcranial Magnetic Stimulation Study.
- 2024
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Ingår i: Neuropsychobiology. - : S. Karger. - 0302-282X .- 1423-0224. ; 83:1, s. 17-27
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Gamma-aminobutyric acid (GABA) deficiency is suggested in depressive disorders, along with alterations in cortical excitability. However, whether these excitability changes are related to GABAA receptor availability is largely unknown. Our aim was to assess the correlation between these measures in depressed patients and healthy controls.METHODS: Twenty-eight patients with a major depressive episode, measured before and after participating in a clinical trial with repetitive transcranial magnetic stimulation (TMS), and 15 controls underwent [11C]flumazenil positron emission tomography to assess GABAA receptor availability and paired pulse TMS (ppTMS) to evaluate cortical excitability. Both whole-brain voxel-wise GABAA receptor availability and mean values from left hand motor cortex and left paracentral lobule were correlated to the ppTMS outcomes: short-interval intracortical inhibition reflecting GABAA receptor activity, long-interval intracortical inhibition representing GABAB receptor activity, intracortical facilitation reflecting glutamate N-methyl-D-aspartate-receptor activity, as well as the resting motor threshold (rMT), considered a global measure of corticospinal excitability.RESULTS: No significant differences in baseline GABAA receptor availability or cortical excitability were found between patients and controls. Additionally, no correlations were observed between baseline measurements of GABAA receptor availability and TMS outcomes. Changes in GABAA receptor availability in the hand motor cortex, between pre- and post-assessments, were inversely related to pre-post changes in hand rMT.CONCLUSION: We found that a change in GABAA receptor availability was inversely related to a change in rMT, suggesting a link between GABA deficiency and increased rMT previously observed in depressive episodes. The results highlight the complex mechanisms governing cortical excitability measures and offer new insight into their properties during the depressive state.
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