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| 10. |
- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 11. |
- Kaptoge, S., et al.
(författare)
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World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions
- 2019
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Ingår i: Lancet Global Health. - : Elsevier BV. - 2214-109X. ; 7:10
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Tidskriftsartikel (refereegranskat)abstract
- Background To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. Methods In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. Findings Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0.685 (95% CI 0 . 629-0 741) to 0.833 (0 . 783-0- 882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt. Interpretation We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.
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| 12. |
- Patrignani, C., et al.
(författare)
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REVIEW OF PARTICLE PHYSICS : Particle Data Group
- 2016
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Ingår i: Chinese Physics C. - : IOP Publishing. - 1674-1137 .- 2058-6132. ; 40:10
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Tidskriftsartikel (refereegranskat)abstract
- The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,062 new measurements from 721 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as supersymmetric particles, heavy bosons, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as Higgs Boson Physics, Supersymmetry, Grand Unified Theories, Neutrino Mixing, Dark Energy, Dark Matter, Cosmology, Particle Detectors, Colliders, Probability and Statistics. Among the 117 reviews are many that are new or heavily revised, including new reviews on Pentaquarks and Inflation. The complete Review is published online in a journal and on the website of the Particle Data Group (http://pdg.lbl.gov). The printed PDG Book contains the Summary Tables and all review articles but no longer includes the detailed tables from the Particle Listings. A Booklet with the Summary Tables and abbreviated versions of some of the review articles is also available.
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| 13. |
- Zhou, XP, et al.
(författare)
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Non-coding variability at the APOE locus contributes to the Alzheimer's risk
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3310-
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression of APOE and its nearby genes in the human brain and blood. High-throughput genome-wide chromosome conformation capture analysis further supports the roles of these risk haplotypes in modulating chromatin states and gene expression in the brain. Our findings provide compelling evidence for additional risk factors in the APOE locus that contribute to AD pathogenesis.
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| 14. |
- Fitzmaurice, C., et al.
(författare)
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Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-years for 32 Cancer Groups, 1990 to 2015. A Systematic Analysis for the Global Burden of Disease Study
- 2017
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Ingår i: Jama Oncology. - : American Medical Association (AMA). - 2374-2445 .- 2374-2437. ; 3:4, s. 524-548
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Cancer is the second leading cause of death worldwide. Current estimates on the burden of cancer are needed for cancer control planning. OBJECTIVE To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 32 cancers in 195 countries and territories from 1990 to 2015. EVIDENCE REVIEW Cancer mortality was estimated using vital registration system data, cancer registry incidence data (transformed to mortality estimates using separately estimated mortality to incidence [MI] ratios), and verbal autopsy data. Cancer incidence was calculated by dividing mortality estimates through the modeled MI ratios. To calculate cancer prevalence, MI ratios were used to model survival. To calculate YLDs, prevalence estimates were multiplied by disability weights. The YLLs were estimated by multiplying age-specific cancer deaths by the reference life expectancy. DALYs were estimated as the sum of YLDs and YLLs. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility. Countries were categorized by SDI quintiles to summarize results. FINDINGS In 2015, there were 17.5 million cancer cases worldwide and 8.7 million deaths. Between 2005 and 2015, cancer cases increased by 33%, with population aging contributing 16%, population growth 13%, and changes in age-specific rates contributing 4%. For men, the most common cancer globallywas prostate cancer (1.6 million cases). Tracheal, bronchus, and lung cancerwas the leading cause of cancer deaths and DALYs in men (1.2 million deaths and 25.9 million DALYs). For women, the most common cancerwas breast cancer (2.4 million cases). Breast cancerwas also the leading cause of cancer deaths and DALYs forwomen (523000 deaths and 15.1 million DALYs). Overall, cancer caused 208.3 million DALYs worldwide in 2015 for both sexes combined. Between 2005 and 2015, age-standardized incidence rates for all cancers combined increased in 174 of 195 countries or territories. Age-standardized death rates (ASDRs) for all cancers combined decreased within that timeframe in 140 of 195 countries or territories. Countries with an increase in the ASDR due to all cancers were largely located on the African continent. Of all cancers, deaths between 2005 and 2015 decreased significantly for Hodgkin lymphoma (-6.1%[95% uncertainty interval (UI), -10.6% to -1.3%]). The number of deaths also decreased for esophageal cancer, stomach cancer, and chronic myeloid leukemia, although these results were not statistically significant. CONCLUSION AND RELEVANCE As part of the epidemiological transition, cancer incidence is expected to increase in the future, further straining limited health care resources. Appropriate allocation of resources for cancer prevention, early diagnosis, and curative and palliative care requires detailed knowledge of the local burden of cancer. The GBD 2015 study results demonstrate that progress is possible in the war against cancer. However, the major findings also highlight an unmet need for cancer prevention efforts, including tobacco control, vaccination, and the promotion of physical activity and a healthy diet.
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| 15. |
- Romagnoni, A, et al.
(författare)
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Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10351-
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Tidskriftsartikel (refereegranskat)abstract
- Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.
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| 16. |
- Liu, C, et al.
(författare)
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A DNA methylation biomarker of alcohol consumption.
- 2018
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23, s. 422-433
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Tidskriftsartikel (refereegranskat)abstract
- The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90-0.99) for current heavy alcohol intake (⩾42 g per day in men and ⩾28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P<1 × 10(-7). Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P<1 × 10(-7). In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.
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| 17. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 18. |
- Ergun, R. E., et al.
(författare)
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Drift waves, intense parallel electric fields, and turbulence associated with asymmetric magnetic reconnection at the magnetopause
- 2017
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Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 44:7, s. 2978-2986
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Tidskriftsartikel (refereegranskat)abstract
- Observations of magnetic reconnection at Earth's magnetopause often display asymmetric structures that are accompanied by strong magnetic field (B) fluctuations and large-amplitude parallel electric fields (E-||). The B turbulence is most intense at frequencies above the ion cyclotron frequency and below the lower hybrid frequency. The B fluctuations are consistent with a thin, oscillating current sheet that is corrugated along the electron flow direction (along the X line), which is a type of electromagnetic drift wave. Near the X line, electron flow is primarily due to a Hall electric field, which diverts ion flow in asymmetric reconnection and accompanies the instability. Importantly, the drift waves appear to drive strong parallel currents which, in turn, generate large-amplitude (similar to 100mV/m) E-|| in the form of nonlinear waves and structures. These observations suggest that turbulence may be common in asymmetric reconnection, penetrate into the electron diffusion region, and possibly influence the magnetic reconnection process.
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| 19. |
- Ergun, R. E., et al.
(författare)
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Magnetospheric Multiscale observations of large-amplitude, parallel, electrostatic waves associated with magnetic reconnection at the magnetopause
- 2016
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Ingår i: Geophysical Research Letters. - : Blackwell Publishing. - 0094-8276 .- 1944-8007. ; 43:11, s. 5626-5634
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Tidskriftsartikel (refereegranskat)abstract
- We report observations from the Magnetospheric Multiscale satellites of large-amplitude, parallel, electrostatic waves associated with magnetic reconnection at the Earth's magnetopause. The observed waves have parallel electric fields (E-||) with amplitudes on the order of 100mV/m and display nonlinear characteristics that suggest a possible net E-||. These waves are observed within the ion diffusion region and adjacent to (within several electron skin depths) the electron diffusion region. They are in or near the magnetosphere side current layer. Simulation results support that the strong electrostatic linear and nonlinear wave activities appear to be driven by a two stream instability, which is a consequence of mixing cold (<10eV) plasma in the magnetosphere with warm (similar to 100eV) plasma from the magnetosheath on a freshly reconnected magnetic field line. The frequent observation of these waves suggests that cold plasma is often present near the magnetopause.
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| 20. |
- Lavraud, B., et al.
(författare)
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Currents and associated electron scattering and bouncing near the diffusion region at Earth's magnetopause
- 2016
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 43:7, s. 3042-3050
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Tidskriftsartikel (refereegranskat)abstract
- Based on high-resolution measurements from NASA's Magnetospheric Multiscale mission, we present the dynamics of electrons associated with current systems observed near the diffusion region of magnetic reconnection at Earth's magnetopause. Using pitch angle distributions (PAD) and magnetic curvature analysis, we demonstrate the occurrence of electron scattering in the curved magnetic field of the diffusion region down to energies of 20 eV. We show that scattering occurs closer to the current sheet as the electron energy decreases. The scattering of inflowing electrons, associated with field-aligned electrostatic potentials and Hall currents, produces a new population of scattered electrons with broader PAD which bounce back and forth in the exhaust. Except at the center of the diffusion region the two populations are collocated and appear to behave adiabatically: the inflowing electron PAD focuses inward (toward lower magnetic field), while the bouncing population PAD gradually peaks at 90 degrees away from the center (where it mirrors owing to higher magnetic field and probable field-aligned potentials).
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| 21. |
- Ergun, R. E., et al.
(författare)
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Magnetospheric Multiscale Satellites Observations of Parallel Electric Fields Associated with Magnetic Reconnection
- 2016
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 116:23
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Tidskriftsartikel (refereegranskat)abstract
- We report observations from the Magnetospheric Multiscale satellites of parallel electric fields (E-vertical bar vertical bar) associated with magnetic reconnection in the subsolar region of the Earth's magnetopause. E-vertical bar vertical bar events near the electron diffusion region have amplitudes on the order of 100 mV/m, which are significantly larger than those predicted for an antiparallel reconnection electric field. This Letter addresses specific types of E-vertical bar vertical bar events, which appear as large-amplitude, near unipolar spikes that are associated with tangled, reconnected magnetic fields. These E-vertical bar vertical bar events are primarily in or near a current layer near the separatrix and are interpreted to be double layers that may be responsible for secondary reconnection in tangled magnetic fields or flux ropes. These results are telling of the three-dimensional nature of magnetopause reconnection and indicate that magnetopause reconnection may be often patchy and/or drive turbulence along the separatrix that results in flux ropes and/or tangled magnetic fields.
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| 22. |
- Ergun, R. E., et al.
(författare)
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Magnetic Reconnection, Turbulence, and Particle Acceleration : Observations in the Earth's Magnetotail
- 2018
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Ingår i: Geophysical Research Letters. - : Blackwell Publishing Ltd. - 0094-8276 .- 1944-8007. ; 45:8, s. 3338-3347
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Tidskriftsartikel (refereegranskat)abstract
- We report observations of turbulent dissipation and particle acceleration from large-amplitude electric fields (E) associated with strong magnetic field (B) fluctuations in the Earth's plasma sheet. The turbulence occurs in a region of depleted density with anti-earthward flows followed by earthward flows suggesting ongoing magnetic reconnection. In the turbulent region, ions and electrons have a significant increase in energy, occasionally >100 keV, and strong variation. There are numerous occurrences of |E| >100 mV/m including occurrences of large potentials (>1 kV) parallel to B and occurrences with extraordinarily large J · E (J is current density). In this event, we find that the perpendicular contribution of J · E with frequencies near or below the ion cyclotron frequency (fci) provide the majority net positive J · E. Large-amplitude parallel E events with frequencies above fci to several times the lower hybrid frequency provide significant dissipation and can result in energetic electron acceleration.
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| 23. |
- Eriksson, S., et al.
(författare)
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Magnetospheric Multiscale Observations of the Electron Diffusion Region of Large Guide Field Magnetic Reconnection
- 2016
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 117:1
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Tidskriftsartikel (refereegranskat)abstract
- We report observations from the Magnetospheric Multiscale (MMS) satellites of a large guide field magnetic reconnection event. The observations suggest that two of the four MMS spacecraft sampled the electron diffusion region, whereas the other two spacecraft detected the exhaust jet from the event. The guide magnetic field amplitude is approximately 4 times that of the reconnecting field. The event is accompanied by a significant parallel electric field (E-parallel to)that is larger than predicted by simulations. The high-speed (similar to 300 km/s) crossing of the electron diffusion region limited the data set to one complete electron distribution inside of the electron diffusion region, which shows significant parallel heating. The data suggest that E-parallel to is balanced by a combination of electron inertia and a parallel gradient of the gyrotropic electron pressure.
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| 24. |
- Haycock, Philip C., et al.
(författare)
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Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
- 2017
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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| 25. |
- Machiela, Mitchell J., et al.
(författare)
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Characterization of Large Structural Genetic Mosaicism in Human Autosomes
- 2015
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 96:3, s. 487-497
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Tidskriftsartikel (refereegranskat)abstract
- Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 3 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
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| 26. |
- Wilder, F. D., et al.
(författare)
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Observations of large-amplitude, parallel, electrostatic waves associated with the Kelvin-Helmholtz instability by the magnetospheric multiscale mission
- 2016
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Ingår i: Geophysical Research Letters. - : Blackwell Publishing. - 0094-8276 .- 1944-8007. ; 43:17, s. 8859-8866
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Tidskriftsartikel (refereegranskat)abstract
- On 8 September 2015, the four Magnetospheric Multiscale spacecraft encountered a Kelvin-Helmholtz unstable magnetopause near the dusk flank. The spacecraft observed periodic compressed current sheets, between which the plasma was turbulent. We present observations of large-amplitude (up to 100 mV/m) oscillations in the electric field. Because these oscillations are purely parallel to the background magnetic field, electrostatic, and below the ion plasma frequency, they are likely to be ion acoustic-like waves. These waves are observed in a turbulent plasma where multiple particle populations are intermittently mixed, including cold electrons with energies less than 10 eV. Stability analysis suggests a cold electron component is necessary for wave growth.
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| 27. |
- Meyer, Peter A., et al.
(författare)
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Data publication with the structural biology data grid supports live analysis
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Access to experimental X-ray diffraction image data is fundamental for validation and reproduction of macromolecular models and indispensable for development of structural biology processing methods. Here, we established a diffraction data publication and dissemination system, Structural Biology Data Grid (SBDG; data. sbgrid. org), to preserve primary experimental data sets that support scientific publications. Data sets are accessible to researchers through a community driven data grid, which facilitates global data access. Our analysis of a pilot collection of crystallographic data sets demonstrates that the information archived by SBDG is sufficient to reprocess data to statistics that meet or exceed the quality of the original published structures. SBDG has extended its services to the entire community and is used to develop support for other types of biomedical data sets. It is anticipated that access to the experimental data sets will enhance the paradigm shift in the community towards a much more dynamic body of continuously improving data analysis.
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| 28. |
- Müller, T D, et al.
(författare)
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Ghrelin.
- 2015
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Ingår i: Molecular metabolism. - : Elsevier BV. - 2212-8778. ; 4:6, s. 437-60
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Tidskriftsartikel (refereegranskat)abstract
- The gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor. Increasing evidence supports more complicated and nuanced roles for the hormone, which go beyond the regulation of systemic energy metabolism.
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| 29. |
- Sakornsakolpat, Phuwanat, et al.
(författare)
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Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 494-505
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Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 x 10-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.
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| 30. |
- Stawarz, J. E., et al.
(författare)
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Observations of turbulence in a Kelvin-Helmholtz event on 8 September 2015 by the Magnetospheric Multiscale mission
- 2016
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Ingår i: Journal of Geophysical Research - Space Physics. - : Blackwell Publishing. - 2169-9380 .- 2169-9402. ; 121:11, s. 11021-11034
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Tidskriftsartikel (refereegranskat)abstract
- Spatial and high-time-resolution properties of the velocities, magnetic field, and 3-D electric field within plasma turbulence are examined observationally using data from the Magnetospheric Multiscale mission. Observations from a Kelvin-Helmholtz instability (KHI) on the Earth's magnetopause are examined, which both provides a series of repeatable intervals to analyze, giving better statistics, and provides a first look at the properties of turbulence in the KHI. For the first time direct observations of both the high-frequency ion and electron velocity spectra are examined, showing differing ion and electron behavior at kinetic scales. Temporal spectra exhibit power law behavior with changes in slope near the ion gyrofrequency and lower hybrid frequency. The work provides the first observational evidence for turbulent intermittency and anisotropy consistent with quasi two-dimensional turbulence in association with the KHI. The behavior of kinetic-scale intermittency is found to have differences from previous studies of solar wind turbulence, leading to novel insights on the turbulent dynamics in the KHI.
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| 31. |
- Eriksson, S., et al.
(författare)
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Magnetospheric Multiscale observations of magnetic reconnection associated with Kelvin-Helmholtz waves
- 2016
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Ingår i: Geophysical Research Letters. - : Blackwell Publishing. - 0094-8276 .- 1944-8007. ; 43:11, s. 5606-5615
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Tidskriftsartikel (refereegranskat)abstract
- The four Magnetospheric Multiscale (MMS) spacecraft recorded the first direct evidence of reconnection exhausts associated with Kelvin-Helmholtz (KH) waves at the duskside magnetopause on 8 September 2015 which allows for local mass and energy transport across the flank magnetopause. Pressure anisotropy-weighted Walen analyses confirmed in-plane exhausts across 22 of 42 KH-related trailing magnetopause current sheets (CSs). Twenty-one jets were observed by all spacecraft, with small variations in ion velocity, along the same sunward or antisunward direction with nearly equal probability. One exhaust was only observed by the MMS-1,2 pair, while MMS-3,4 traversed a narrow CS (1.5 ion inertial length) in the vicinity of an electron diffusion region. The exhausts were locally 2-D planar in nature as MMS-1,2 observed almost identical signatures separated along the guide-field. Asymmetric magnetic and electric Hall fields are reported in agreement with a strong guide-field and a weak plasma density asymmetry across the magnetopause CS.
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| 32. |
- Wilder, F. D., et al.
(författare)
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Observations of whistler mode waves with nonlinear parallel electric fields near the dayside magnetic reconnection separatrix by the Magnetospheric Multiscale mission
- 2016
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Ingår i: Geophysical Research Letters. - : Blackwell Publishing. - 0094-8276 .- 1944-8007. ; 43:12, s. 5909-5917
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Tidskriftsartikel (refereegranskat)abstract
- We show observations from the Magnetospheric Multiscale (MMS) mission of whistler mode waves in the Earth's low-latitude boundary layer (LLBL) during a magnetic reconnection event. The waves propagated obliquely to the magnetic field toward the X line and were confined to the edge of a southward jet in the LLBL. Bipolar parallel electric fields interpreted as electrostatic solitary waves (ESW) are observed intermittently and appear to be in phase with the parallel component of the whistler oscillations. The polarity of the ESWs suggests that if they propagate with the waves, they are electron enhancements as opposed to electron holes. The reduced electron distribution shows a shoulder in the distribution for parallel velocities between 17,000 and 22,000 km/s, which persisted during the interval when ESWs were observed, and is near the phase velocity of the whistlers. This shoulder can drive Langmuir waves, which were observed in the high-frequency parallel electric field data.
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| 33. |
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| 34. |
- Eastwood, J. P., et al.
(författare)
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Guide Field Reconnection : Exhaust Structure and Heating
- 2018
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Ingår i: Geophysical Research Letters. - : AMER GEOPHYSICAL UNION. - 0094-8276 .- 1944-8007. ; 45:10, s. 4569-4577
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Tidskriftsartikel (refereegranskat)abstract
- Magnetospheric Multiscale observations are used to probe the structure and temperature profile of a guide field reconnection exhaust similar to 100 ion inertial lengths downstream from the X-line in the Earth's magnetosheath. Asymmetric Hall electric and magnetic field signatures were detected, together with a density cavity confined near 1 edge of the exhaust and containing electron flow toward the X-line. Electron holes were also detected both on the cavity edge and at the Hall magnetic field reversal. Predominantly parallel ion and electron heating was observed in the main exhaust, but within the cavity, electron cooling and enhanced parallel ion heating were found. This is explained in terms of the parallel electric field, which inhibits electron mixing within the cavity on newly reconnected field lines but accelerates ions. Consequently, guide field reconnection causes inhomogeneous changes in ion and electron temperature across the exhaust.
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| 35. |
- Machiela, Mitchell J, et al.
(författare)
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Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
- 2016
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.
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| 36. |
- Wilder, F. D., et al.
(författare)
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The nonlinear behavior of whistler waves at the reconnecting dayside magnetopause as observed by the Magnetospheric Multiscale mission : A case study
- 2017
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Ingår i: Journal of Geophysical Research - Space Physics. - : Blackwell Publishing Ltd. - 2169-9380 .- 2169-9402. ; 122:5, s. 5487-5501
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Tidskriftsartikel (refereegranskat)abstract
- We show observations of whistler mode waves in both the low-latitude boundary layer (LLBL) and on closed magnetospheric field lines during a crossing of the dayside reconnecting magnetopause by the Magnetospheric Multiscale (MMS) mission on 11 October 2015. The whistlers in the LLBL were on the electron edge of the magnetospheric separatrix and exhibited high propagation angles with respect to the background field, approaching 40°, with bursty and nonlinear parallel electric field signatures. The whistlers in the closed magnetosphere had Poynting flux that was more field aligned. Comparing the reduced electron distributions for each event, the magnetospheric whistlers appear to be consistent with anisotropy-driven waves, while the distribution in the LLBL case includes anisotropic backward resonant electrons and a forward resonant beam at near half the electron-Alfvén speed. Results are compared with the previously published observations by MMS on 19 September 2015 of LLBL whistler waves. The observations suggest that whistlers in the LLBL can be both beam and anisotropy driven, and the relative contribution of each might depend on the distance from the X line.
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| 37. |
- Burisch, J, et al.
(författare)
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Natural disease course of Crohn's disease during the first 5 years after diagnosis in a European population-based inception cohort: an Epi-IBD study
- 2019
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 68:3, s. 423-433
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Tidskriftsartikel (refereegranskat)abstract
- The Epi-IBD cohort is a prospective population-based inception cohort of unselected patients with inflammatory bowel disease from 29 European centres covering a background population of almost 10 million people. The aim of this study was to assess the 5-year outcome and disease course of patients with Crohn’s disease (CD).DesignPatients were followed up prospectively from the time of diagnosis, including collection of their clinical data, demographics, disease activity, medical therapy, surgery, cancers and deaths. Associations between outcomes and multiple covariates were analysed by Cox regression analysis.ResultsIn total, 488 patients were included in the study. During follow-up, 107 (22%) patients received surgery, while 176 (36%) patients were hospitalised because of CD. A total of 49 (14%) patients diagnosed with non-stricturing, non-penetrating disease progressed to either stricturing and/or penetrating disease. These rates did not differ between patients from Western and Eastern Europe. However, significant geographic differences were noted regarding treatment: more patients in Western Europe received biological therapy (33%) and immunomodulators (66%) than did those in Eastern Europe (14% and 54%, respectively, P<0.01), while more Eastern European patients received 5-aminosalicylates (90% vs 56%, P<0.05). Treatment with immunomodulators reduced the risk of surgery (HR: 0.4, 95% CI 0.2 to 0.6) and hospitalisation (HR: 0.3, 95% CI 0.2 to 0.5).ConclusionDespite patients being treated early and frequently with immunomodulators and biological therapy in Western Europe, 5-year outcomes including surgery and phenotype progression in this cohort were comparable across Western and Eastern Europe. Differences in treatment strategies between Western and Eastern European centres did not affect the disease course. Treatment with immunomodulators reduced the risk of surgery and hospitalisation.
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| 38. |
- Ergun, R. E., et al.
(författare)
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Magnetic Reconnection in Three Dimensions : Observations of Electromagnetic Drift Waves in the Adjacent Current Sheet
- 2019
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Ingår i: Journal of Geophysical Research - Space Physics. - : AMER GEOPHYSICAL UNION. - 2169-9380 .- 2169-9402. ; 124:12, s. 10104-10118
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Tidskriftsartikel (refereegranskat)abstract
- Magnetic reconnection at the subsolar magnetopause is persistently accompanied by strong fluctuations of the magnetic field (B), plasma density (n), and all components of the electric field (E) and current (J). The strongest fluctuations are at frequencies below the lower hybrid frequency and observed in a thin, intense current sheet adjacent to the electron diffusion region. In this current sheet, the background magnitudes of B and n are changing considerably, creating an inhomogeneous plasma environment. We show that the fluctuations in B and n are consistent with an oscillatory displacement of the current sheet in the surface normal direction. The displacement is propagating parallel to the magnetic reconnection X line. Wavelengths are on the order of or longer than the thickness of the current sheet to which they are confined, so we label these waves electromagnetic drift waves. E and J fluctuations are more complex than a simple displacement. They have significant variations in the component along B, which suggest that the drift waves also may be confined along B. The current sheet is supported by an electron drift driven by normal electric field, which, in turn, is balanced by an ion pressure gradient. We suggest that wave growth comes from an instability related to the drift between the electrons and ions. We discuss the possibility that drift waves can displace or penetrate into the electron diffusion region giving magnetic reconnection three-dimensional structure. Drift waves may corrugate the X line, possibly breaking the X line and generating turbulence.
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| 39. |
- Gingell, I, et al.
(författare)
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Observations of Magnetic Reconnection in the Transition Region of Quasi-Parallel Shocks
- 2019
-
Ingår i: Geophysical Research Letters. - : AMER GEOPHYSICAL UNION. - 0094-8276 .- 1944-8007. ; 46:3, s. 1177-1184
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Tidskriftsartikel (refereegranskat)abstract
- Using observations of Earth's bow shock by the Magnetospheric Multiscale mission, we show for the first time that active magnetic reconnection is occurring at current sheets embedded within the quasi-parallel shock's transition layer. We observe an electron jet and heating but no ion response, suggesting we have observed an electron-only mode. The lack of ion response is consistent with simulations showing reconnection onset on sub-ion time scales. We also discuss the impact of electron heating in shocks via reconnection.
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| 40. |
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| 41. |
- Ergun, R. E., et al.
(författare)
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Magnetic Reconnection in Three Dimensions : Modeling and Analysis of Electromagnetic Drift Waves in the Adjacent Current Sheet
- 2019
-
Ingår i: Journal of Geophysical Research - Space Physics. - : AMER GEOPHYSICAL UNION. - 2169-9380 .- 2169-9402. ; 124:12, s. 10085-10103
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Tidskriftsartikel (refereegranskat)abstract
- We present a model of electromagnetic drift waves in the current sheet adjacent to magnetic reconnection at the subsolar magnetopause. These drift waves are potentially important in governing 3-D structure of subsolar magnetic reconnection and in generating turbulence. The drift waves propagate nearly parallel to the X line and are confined to a thin current sheet. The scale size normal to the current sheet is significantly less than the ion gyroradius and can be less than or on the order of the wavelength. The waves also have a limited extent along the magnetic field (B), making them a three-dimensional eigenmode structure. In the current sheet, the background magnitudes of B and plasma density change significantly, calling for a treatment that incorporates an inhomogeneous plasma environment. Using detailed examination of Magnetospheric Multiscale observations, we find that the waves are best represented by series of electron vortices, superimposed on a primary electron drift, that propagate along the current sheet (parallel to the X line). The waves displace or corrugate the current sheet, which also potentially displaces the electron diffusion region. The model is based on fluid behavior of electrons, but ion motion must be treated kinetically. The strong electron drift along the X line is likely responsible for wave growth, similar to a lower hybrid drift instability. Contrary to a classical lower hybrid drift instability, however, the strong changes in the background B and n(o), the normal confinement to the current sheet, and the confinement along B are critical to the wave description.
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| 42. |
- Feigin, VL, et al.
(författare)
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Update on the Global Burden of Ischemic and Hemorrhagic Stroke in 1990-2013: The GBD 2013 Study
- 2015
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Ingår i: Neuroepidemiology. - : S. Karger AG. - 1423-0208 .- 0251-5350. ; 45:3, s. 161-176
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Global stroke epidemiology is changing rapidly. Although age-standardized rates of stroke mortality have decreased worldwide in the past 2 decades, the absolute numbers of people who have a stroke every year, and live with the consequences of stroke or die from their stroke, are increasing. Regular updates on the current level of stroke burden are important for advancing our knowledge on stroke epidemiology and facilitate organization and planning of evidence-based stroke care. <b><i>Objectives:</i></b> This study aims to estimate incidence, prevalence, mortality, disability-adjusted life years (DALYs) and years lived with disability (YLDs) and their trends for ischemic stroke (IS) and hemorrhagic stroke (HS) for 188 countries from 1990 to 2013. <b><i>Methodology:</i></b> Stroke incidence, prevalence, mortality, DALYs and YLDs were estimated using all available data on mortality and stroke incidence, prevalence and excess mortality. Statistical models and country-level covariate data were employed, and all rates were age-standardized to a global population. All estimates were produced with 95% uncertainty intervals (UIs). <b><i>Results:</i></b> In 2013, there were globally almost 25.7 million stroke survivors (71% with IS), 6.5 million deaths from stroke (51% died from IS), 113 million DALYs due to stroke (58% due to IS) and 10.3 million new strokes (67% IS). Over the 1990-2013 period, there was a significant increase in the absolute number of DALYs due to IS, and of deaths from IS and HS, survivors and incident events for both IS and HS. The preponderance of the burden of stroke continued to reside in developing countries, comprising 75.2% of deaths from stroke and 81.0% of stroke-related DALYs. Globally, the proportional contribution of stroke-related DALYs and deaths due to stroke compared to all diseases increased from 1990 (3.54% (95% UI 3.11-4.00) and 9.66% (95% UI 8.47-10.70), respectively) to 2013 (4.62% (95% UI 4.01-5.30) and 11.75% (95% UI 10.45-13.31), respectively), but there was a diverging trend in developed and developing countries with a significant increase in DALYs and deaths in developing countries, and no measurable change in the proportional contribution of DALYs and deaths from stroke in developed countries. <b><i>Conclusion:</i></b> Global stroke burden continues to increase globally. More efficient stroke prevention and management strategies are urgently needed to halt and eventually reverse the stroke pandemic, while universal access to organized stroke services should be a priority.
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| 43. |
- Johlander, Andreas, et al.
(författare)
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Rippled Quasiperpendicular Shock Observed by the Magnetospheric Multiscale Spacecraft
- 2016
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 117:16
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Tidskriftsartikel (refereegranskat)abstract
- Collisionless shock nonstationarity arising from microscale physics influences shock structure and particle acceleration mechanisms. Nonstationarity has been difficult to quantify due to the small spatial and temporal scales. We use the closely spaced (subgyroscale), high-time-resolution measurements from one rapid crossing of Earth's quasiperpendicular bow shock by the Magnetospheric Multiscale (MMS) spacecraft to compare competing nonstationarity processes. Using MMS's high-cadence kinetic plasma measurements, we show that the shock exhibits nonstationarity in the form of ripples.
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| 44. |
- Vicedo-Cabrera, A. M., et al.
(författare)
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Temperature-related mortality impacts under and beyond Paris Agreement climate change scenarios
- 2018
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Ingår i: Climatic Change. - : Springer. - 0165-0009 .- 1573-1480. ; 150:3-4, s. 391-402
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Tidskriftsartikel (refereegranskat)abstract
- The Paris Agreement binds all nations to undertake ambitious efforts to combat climate change, with the commitment to “hold warming well below 2 °C in global mean temperature (GMT), relative to pre-industrial levels, and to pursue efforts to limit warming to 1.5 °C”. The 1.5 °C limit constitutes an ambitious goal for which greater evidence on its benefits for health would help guide policy and potentially increase the motivation for action. Here we contribute to this gap with an assessment on the potential health benefits, in terms of reductions in temperature-related mortality, derived from the compliance to the agreed temperature targets, compared to more extreme warming scenarios. We performed a multi-region analysis in 451 locations in 23 countries with different climate zones, and evaluated changes in heat and cold-related mortality under scenarios consistent with the Paris Agreement targets (1.5 and 2 °C) and more extreme GMT increases (3 and 4 °C), and under the assumption of no changes in demographic distribution and vulnerability. Our results suggest that limiting warming below 2 °C could prevent large increases in temperature-related mortality in most regions worldwide. The comparison between 1.5 and 2 °C is more complex and characterized by higher uncertainty, with geographical differences that indicate potential benefits limited to areas located in warmer climates, where direct climate change impacts will be more discernible.
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| 45. |
- Chen, L. -J, et al.
(författare)
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Electron Bulk Acceleration and Thermalization at Earth's Quasiperpendicular Bow Shock
- 2018
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 120:22
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Tidskriftsartikel (refereegranskat)abstract
- Electron heating at Earth's quasiperpendicular bow shock has been surmised to be due to the combined effects of a quasistatic electric potential and scattering through wave-particle interaction. Here we report the observation of electron distribution functions indicating a new electron heating process occurring at the leading edge of the shock front. Incident solar wind electrons are accelerated parallel to the magnetic field toward downstream, reaching an electron-ion relative drift speed exceeding the electron thermal speed. The bulk acceleration is associated with an electric field pulse embedded in a whistler-mode wave. The high electron-ion relative drift is relaxed primarily through a nonlinear current-driven instability. The relaxed distributions contain a beam traveling toward the shock as a remnant of the accelerated electrons. Similar distribution functions prevail throughout the shock transition layer, suggesting that the observed acceleration and thermalization is essential to the cross-shock electron heating.
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| 46. |
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| 47. |
- Goodrich, K. A., et al.
(författare)
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Impulsively Reflected Ions : A Plausible Mechanism for Ion Acoustic Wave Growth in Collisionless Shocks
- 2019
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Ingår i: Journal of Geophysical Research - Space Physics. - : American Geophysical Union (AGU). - 2169-9380 .- 2169-9402. ; 124:3, s. 1855-1865
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Tidskriftsartikel (refereegranskat)abstract
- We present recent high time resolution observations from an oblique (43 degrees) shock crossing from the Magnetospheric Multiscale mission. Short-duration bursts between 10 and 100 ms of ion acoustic waves are observed in this event alongside a persistent reflected ion population. High time resolution (150 ms) particle measurements show strongly varying ion distributions between successive measurements, implying that they are bursty and impulsive by nature. Such signatures are consistent with ion bursts that are impulsively reflected at various points within the shock. We find that, after instability analysis using a Fried-Conte dispersion solver, the insertion of dispersive ion bursts into an already stable ion distribution can lead to wave growth in the ion acoustic mode for short durations of time. We find that impulsively reflected ions are a plausible mechanism for ion acoustic wave growth in the terrestrial bow shock and, furthermore, suggest that wave growth can lead to a small but measurable momentum exchange between the solar wind ions and the reflected population.
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| 48. |
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| 49. |
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| 50. |
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