| 1. |
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| 2. |
- Bousquet, Jean, et al.
(författare)
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Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology
- 2019
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:3, s. 864-879
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Tidskriftsartikel (refereegranskat)abstract
- Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
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| 3. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Björkman, Anne, 1981, et al.
(författare)
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Tundra Trait Team: A database of plant traits spanning the tundra biome
- 2018
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Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 27:12, s. 1402-1411
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Tidskriftsartikel (refereegranskat)abstract
- © 2018 The Authors Global Ecology and Biogeography Published by John Wiley & Sons Ltd Motivation: The Tundra Trait Team (TTT) database includes field-based measurements of key traits related to plant form and function at multiple sites across the tundra biome. This dataset can be used to address theoretical questions about plant strategy and trade-offs, trait–environment relationships and environmental filtering, and trait variation across spatial scales, to validate satellite data, and to inform Earth system model parameters. Main types of variable contained: The database contains 91,970 measurements of 18 plant traits. The most frequently measured traits (>1,000 observations each) include plant height, leaf area, specific leaf area, leaf fresh and dry mass, leaf dry matter content, leaf nitrogen, carbon and phosphorus content, leaf C:N and N:P, seed mass, and stem specific density. Spatial location and grain: Measurements were collected in tundra habitats in both the Northern and Southern Hemispheres, including Arctic sites in Alaska, Canada, Greenland, Fennoscandia and Siberia, alpine sites in the European Alps, Colorado Rockies, Caucasus, Ural Mountains, Pyrenees, Australian Alps, and Central Otago Mountains (New Zealand), and sub-Antarctic Marion Island. More than 99% of observations are georeferenced. Time period and grain: All data were collected between 1964 and 2018. A small number of sites have repeated trait measurements at two or more time periods. Major taxa and level of measurement: Trait measurements were made on 978 terrestrial vascular plant species growing in tundra habitats. Most observations are on individuals (86%), while the remainder represent plot or site means or maximums per species. Software format: csv file and GitHub repository with data cleaning scripts in R; contribution to TRY plant trait database (www.try-db.org) to be included in the next version release.
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| 5. |
- Block, Keith I., et al.
(författare)
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Designing a broad-spectrum integrative approach for cancer prevention and treatment
- 2015
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Ingår i: Seminars in Cancer Biology. - : Academic Press. - 1044-579X .- 1096-3650. ; 35, s. S276-S304
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Forskningsöversikt (refereegranskat)abstract
- Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.
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| 6. |
- Zheng, Hou-Feng, et al.
(författare)
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Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7571, s. 112-
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Tidskriftsartikel (refereegranskat)abstract
- The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
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| 7. |
- Baud, Maxime O, et al.
(författare)
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European trends in epilepsy surgery.
- 2018
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Ingår i: Neurology. - 1526-632X. ; 91:2
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Tidskriftsartikel (refereegranskat)abstract
- Resective surgery is effective in treating drug-resistant focal epilepsy, but it remains unclear whether improved diagnostics influence postsurgical outcomes. Here, we compared practice and outcomes over 2 periods 15 years apart.Sixteen European centers retrospectively identified 2 cohorts of children and adults who underwent epilepsy surgery in the period of 1997 to 1998 (n = 562) or 2012 to 2013 (n = 736). Data collected included patient (sex, age) and disease (duration, localization and diagnosis) characteristics, type of surgery, histopathology, Engel postsurgical outcome, and complications, as well as imaging and electrophysiologic tests performed for each case. Postsurgical outcome predictors were included in a multivariate logistic regression to assess the strength of date of surgery as an independent predictor.Over time, the number of operated cases per center increased from a median of 31 to 50 per 2-year period (p = 0.02). Mean disease duration at surgery decreased by 5.2 years (p < 0.001). Overall seizure freedom (Engel class 1) increased from 66.7% to 70.9% (adjusted p = 0.04), despite an increase in complex surgeries (extratemporal and/or MRI negative). Surgeries performed during the later period were 1.34 times (adjusted odds ratio; 95% confidence interval 1.02-1.77) more likely to yield a favorable outcome (Engel class I) than earlier surgeries, and improvement was more marked in extratemporal and MRI-negative temporal epilepsy. The rate of persistent neurologic complications remained stable (4.6%-5.3%, p = 0.7).Improvements in European epilepsy surgery over time are modest but significant, including higher surgical volume, shorter disease duration, and improved postsurgical seizure outcomes. Early referral for evaluation is required to continue on this encouraging trend.
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| 8. |
- Danchin, Nicolas, et al.
(författare)
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Use, patient selection and outcomes of P2Y12 receptor inhibitor treatment in patients with STEMI based on contemporary European registries
- 2016
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Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press (OUP). - 2055-6837 .- 2055-6845. ; 2:3, s. 152-167
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Tidskriftsartikel (refereegranskat)abstract
- Aims Among acute coronary syndromes (ACS), ST-segment elevation myocardial infarction (STEMI) has the most severe early clinical course. We aimed to describe the effectiveness and safety of P2Y12 receptor inhibitors in patients with STEMI based on the data from contemporary European ACS registries. Methods and results Twelve registries provided data in a systematic manner on outcomes in STEMI patients overall, and seven of these also provided data for P2Y12 receptor inhibitor-based dual antiplatelet therapy. The registrieswere heterogeneous in terms of site, patient, and treatment selection, as well as in definition of endpoints (e.g. bleeding events). All-cause death rates based on the data from 84 299 patients (9612 patients on prasugrel, 11 492 on ticagrelor, and 27 824 on clopidogrel) ranged between 0.49 and 6.68% in-hospital, between 3.07 and 7.95% at 30 days (reported in 6 registries), between 8.15 and 9.13% at 180 days, and between 2.41 and 9.58% at 1 year (5 registries). Major bleeding rates were 0.09-3.55% inhospital (8 registries), 0.09-1.65% at 30 days, and 1.96% at 1 year (only 1 registry). Fatal/life-Threatening bleeding was rare occurring between 0.08 and 0.13% in-hospital (4 registries) and 1.96% at 1 year (1 registry). Conclusions Real-world evidence from European contemporary registries shows that death, ischaemic events, and bleeding rates are lower than those reported in Phase III studies of P2Y12 inhibitors. Regarding individual P2Y12 inhibitors, patients on prasugrel, and, to a lesser degree, ticagrelor, had fewer ischaemic and bleeding events at all time points than clopidogrel-Treated patients. These findings are partly related to the fact that the newer agents are used in younger and less ill patients.
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| 9. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 10. |
- Lettino, Maddalena, et al.
(författare)
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Diabetic patients with acute coronary syndromes in contemporary European registries : Characteristics and outcomes
- 2017
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Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press (OUP). - 2055-6837 .- 2055-6845. ; 3:4, s. 198-213
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Tidskriftsartikel (refereegranskat)abstract
- Aims Among patients with acute coronary syndromes (ACS), those with diabetes mellitus (DM) are at particularly high risk of recurrent cardiovascular events and premature death. We aimed to provide a descriptive overview of unadjusted analyses of patient characteristics, ACS management, and outcomes up to 1 year after hospital admission for an ACS/index-ACS event, in patients with DM in contemporary registries in Europe. Methods and results A total of 10 registries provided data in a systematic manner on ACS patients with DM (total n =28 899), and without DM (total n= 97 505). In the DM population, the proportion of patients with ST-Segment Elevation Myocardial Infarction (STEMI) ranged from 22.1% to 64.6% (other patients had non-ST-Segment Elevation Myocardial Infarction (NSTEMI-ACS) or unstable angina). All-cause mortality in the registries ranged from 1.4% to 9.4% in-hospital; 2.8% to 7.9% at 30 days post-discharge; 5.1% to 10.7% at 180 days post-discharge; and 3.3% to 10.5% at 1 year post-discharge. Major bleeding events were reported in up to 3.8% of patients while in hospital (8 registries); up to 1.3% at 30 days (data from two registries only), and 2.0% at 1 year (one registry only). Registries differed substantially in terms of study setting, site, patient selection, definition and schedule of endpoints, and use of various P2Y12 inhibitors. In most, but not all, registries, event rates in DM patients were higher than in patients without DM. Pooled risk ratios comparing cohorts with DM vs. no DM were in-hospital significantly higher in DM for all-cause death (1.66; 95% CI 1.42-1.94), for cardiovascular death (2.33; 1.78 - 3.03), and for major bleeding (1.35; 1.21-1.52). Conclusion These registry data from real-life clinical practice confirm a high risk for recurrent events among DM patients with ACS, with great variation across the different registries.
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| 11. |
- McCarthy, Shane, et al.
(författare)
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A reference panel of 64,976 haplotypes for genotype imputation
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:10, s. 1279-1283
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Tidskriftsartikel (refereegranskat)abstract
- We describe a reference panel of 64,976 human haplotypes at 39,235,157 SNPs constructed using whole-genome sequence data from 20 studies of predominantly European ancestry. Using this resource leads to accurate genotype imputation at minor allele frequencies as low as 0.1% and a large increase in the number of SNPs tested in association studies, and it can help to discover and refine causal loci. We describe remote server resources that allow researchers to carry out imputation and phasing consistently and efficiently.
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| 12. |
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| 13. |
- Peiris, Heshan, et al.
(författare)
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A Syntenic Cross Species Aneuploidy Genetic Screen Links RCAN1 Expression to β-Cell Mitochondrial Dysfunction in Type 2 Diabetes
- 2016
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes (T2D) is a complex metabolic disease associated with obesity, insulin resistance and hypoinsulinemia due to pancreatic β-cell dysfunction. Reduced mitochondrial function is thought to be central to β-cell dysfunction. Mitochondrial dysfunction and reduced insulin secretion are also observed in β-cells of humans with the most common human genetic disorder, Down syndrome (DS, Trisomy 21). To identify regions of chromosome 21 that may be associated with perturbed glucose homeostasis we profiled the glycaemic status of different DS mouse models. The Ts65Dn and Dp16 DS mouse lines were hyperglycemic, while Tc1 and Ts1Rhr mice were not, providing us with a region of chromosome 21 containing genes that cause hyperglycemia. We then examined whether any of these genes were upregulated in a set of ~5,000 gene expression changes we had identified in a large gene expression analysis of human T2D β-cells. This approach produced a single gene, RCAN1, as a candidate gene linking hyperglycemia and functional changes in T2D β-cells. Further investigations demonstrated that RCAN1 methylation is reduced in human T2D islets at multiple sites, correlating with increased expression. RCAN1 protein expression was also increased in db/db mouse islets and in human and mouse islets exposed to high glucose. Mice overexpressing RCAN1 had reduced in vivo glucose-stimulated insulin secretion and their β-cells displayed mitochondrial dysfunction including hyperpolarised membrane potential, reduced oxidative phosphorylation and low ATP production. This lack of β-cell ATP had functional consequences by negatively affecting both glucose-stimulated membrane depolarisation and ATP-dependent insulin granule exocytosis. Thus, from amongst the myriad of gene expression changes occurring in T2D β-cells where we had little knowledge of which changes cause β-cell dysfunction, we applied a trisomy 21 screening approach which linked RCAN1 to β-cell mitochondrial dysfunction in T2D.
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| 14. |
- Santruckova, Hana, et al.
(författare)
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Significance of dark CO2 fixation in arctic soils
- 2018
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Ingår i: Soil Biology and Biochemistry. - : Elsevier BV. - 0038-0717 .- 1879-3428. ; 119, s. 11-21
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Tidskriftsartikel (refereegranskat)abstract
- The occurrence of dark fixation of CO2 by heterotrophic microorganisms in soil is generally accepted, but its importance for microbial metabolism and soil organic carbon (C) sequestration is unknown, especially under C limiting conditions. To fill this knowledge gap, we measured dark (CO2)-C-13 incorporation into soil organic matter and conducted a C-13-labelling experiment to follow the C-13 incorporation into phospholipid fatty acids as microbial biomass markers across soil profiles of four tundra ecosystems in the northern circumpolar region, where net primary productivity and thus soil C inputs are low. We further determined the abundance of various carboxylase genes and identified their microbial origin with metagenomics. The microbial capacity for heterotrophic CO2 fixation was determined by measuring the abundance of carboxylase genes and the incorporation of C-13 into soil C following the augmentation of bioavailable C sources. We demonstrate that dark CO2 fixation occurred ubiquitously in arctic tundra soils, with increasing importance in deeper soil horizons, presumably due to increasing C limitation with soil depth. Dark CO2 fixation accounted on average for 0.4, 1.0, 1.1, and 16% of net respiration in the organic, cryoturbated organic, mineral and permafrost horizons, respectively. Genes encoding anaplerotic enzymes of heterotrophic microorganisms comprised the majority of identified carboxylase genes. The genetic potential for dark CO2 fixation was spread over a broad taxonomic range. The results suggest important regulatory function of CO2 fixation in C limited conditions. The measurements were corroborated by modeling the long-term impact of dark CO2 fixation on soil organic matter. Our results suggest that increasing relative CO2 fixation rates in deeper soil horizons play an important role for soil internal C cycling and can, at least in part, explain the isotopic enrichment with soil depth.
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| 15. |
- Young, Peter R., et al.
(författare)
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Solar Ultraviolet Bursts
- 2018
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Ingår i: Space Science Reviews. - : Springer Science and Business Media LLC. - 0038-6308 .- 1572-9672. ; 214:8
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Forskningsöversikt (refereegranskat)abstract
- The term ultraviolet (UV) burst is introduced to describe small, intense, transient brightenings in ultraviolet images of solar active regions. We inventorize their properties and provide a definition based on image sequences in transition-region lines. Coronal signatures are rare, and most bursts are associated with small-scale, canceling opposite-polarity fields in the photosphere that occur in emerging flux regions, moving magnetic features in sunspot moats, and sunspot light bridges. We also compare UV bursts with similar transition-region phenomena found previously in solar ultraviolet spectrometry and with similar phenomena at optical wavelengths, in particular Ellerman bombs. Akin to the latter, UV bursts are probably small-scale magnetic reconnection events occurring in the low atmosphere, at photospheric and/or chromospheric heights. Their intense emission in lines with optically thin formation gives unique diagnostic opportunities for studying the physics of magnetic reconnection in the low solar atmosphere. This paper is a review report from an International Space Science Institute team that met in 2016-2017.
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| 16. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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| 17. |
- Zeymer, Uwe, et al.
(författare)
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P2Y12 receptor inhibitors in patients with non-STelevation acute coronary syndrome in the real world : Use, patient selection, and outcomes from contemporary European registries
- 2016
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Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press (OUP). - 2055-6837 .- 2055-6845. ; 2:4, s. 229-243
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Tidskriftsartikel (refereegranskat)abstract
- Aims Non-ST-elevation acute coronary syndrome (NSTE-ACS) is present in about 60-70% of patients admitted with acute coronary syndromes in clinical practice. This study provides a 'real-life' overview of NSTE-ACS patient characteristics, dual antiplatelet therapy clinical practice, and outcomes at both the time of discharge from hospital and up to 1-year post-discharge. Methods and results A total of 10 registries (documenting 84 054 NSTE-ACS patients) provided data in a systematic manner on patient characteristics and outcomes for NSTE-ACS in general, and 6 of these (with 52 173 NSTE-ACS patients) also provided more specific data according to P2Y12 receptor inhibitor used. Unadjusted analyses were performed at the study level, and no formal meta-Analysis was performed due to large heterogeneity between studies in the settings, patient characteristics, and outcome definitions. All-cause death rates across registries ranged from 0.76 to 4.79% in-hospital, from 1.61 to 6.65% at 30 days, from 3.66 to 7.16% at 180 days, and from 3.14 to 9.73% at 1 year. Major bleeding events were reported in up to 2.77% of patients while in hospital (in seven registries), up to 1.08% at 30 days (data from one registry only), and 2.06% at 1 year (one registry). Conclusions There were substantial differences in the use of and patient selection for clopidogrel, prasugrel, and ticagrelor, which were associated with differences in short-And long-Term ischaemic and bleeding events. In future registries, data collection should be performed in a more standardized way with respect to endpoints, definitions, and time points.
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| 18. |
- Connolly, Stuart J, et al.
(författare)
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Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial.
- 2018
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Ingår i: Lancet (London, England). - 1474-547X. ; 391:10117, s. 205-218
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Tidskriftsartikel (refereegranskat)abstract
- Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease.In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.Between March 12, 2013, and May 10, 2016, 27395 patients were enrolled to the COMPASS trial, of whom 24824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, p<0·0001). By comparison, treatment with rivaroxaban alone did not significantly improve the primary outcome when compared with treatment with aspirin alone (411 [5%] of 8250 vs 460 [6%] of 8261; HR 0·89, 95% CI 0·78-1·02, p=0·094). Combined rivaroxaban plus aspirin treatment resulted in more major bleeds than treatment with aspirin alone (263 [3%] of 8313 vs 158 [2%] of 8261; HR 1·66, 95% CI 1·37-2·03, p<0·0001), and similarly, more bleeds were seen in the rivaroxaban alone group than in the aspirin alone group (236 [3%] of 8250 vs 158 [2%] of 8261; HR 1·51, 95% CI 1·23-1·84, p<0·0001). The most common site of major bleeding was gastrointestinal, occurring in 130 [2%] patients who received combined rivaroxaban plus aspirin, in 84 [1%] patients who received rivaroxaban alone, and in 61 [1%] patients who received aspirin alone. Rivaroxaban plus aspirin reduced mortality when compared with aspirin alone (262 [3%] of 8313 vs 339 [4%] of 8261; HR 0·77, 95% CI 0·65-0·90, p=0·0012).In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide.Bayer AG.
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| 19. |
- Degrendele, C., et al.
(författare)
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Pesticides in the atmosphere : a comparison of gas-particle partitioning and particle size distribution of legacy and current-use pesticides
- 2016
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus Publications. - 1680-7316 .- 1680-7324. ; 16:3, s. 1531-1544
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Tidskriftsartikel (refereegranskat)abstract
- This study presents a comparison of seasonal variation, gas-particle partitioning, and particle-phase size distribution of organochlorine pesticides (OCPs) and current-use pesticides (CUPs) in air. Two years (2012/2013) of weekly air samples were collected at a background site in the Czech Republic using a high-volume air sampler. To study the particle-phase size distribution, air samples were also collected at an urban and rural site in the area of Brno, Czech Republic, using a cascade impactor separating atmospheric particulates according to six size fractions. Major differences were found in the atmospheric distribution of OCPs and CUPs. The atmospheric concentrations of CUPs were driven by agricultural activities while secondary sources such as volatilization from surfaces governed the atmospheric concentrations of OCPs. Moreover, clear differences were observed in gas-particle partitioning; CUP partitioning was influenced by adsorption onto mineral surfaces while OCPs were mainly partitioning to aerosols through absorption. A predictive method for estimating the gas-particle partitioning has been derived and is proposed for polar and non-polar pesticides. Finally, while OCPs and the majority of CUPs were largely found on fine particles, four CUPs (carbendazim, isoproturon, prochloraz, and terbuthylazine) had higher concentrations on coarse particles (> 3.0 mu m), which may be related to the pesticide application technique. This finding is particularly important and should be further investigated given that large particles result in lower risks from inhalation (re-gardless the toxicity of the pesticide) and lower potential for long-range atmospheric transport.
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| 20. |
- Fox, Anthony D., et al.
(författare)
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Recent changes in the abundance of Common Pochard Aythya ferina breeding in Europe
- 2016
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Ingår i: Wildfowl. - 0954-6324. ; 66, s. 22-40
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Forskningsöversikt (refereegranskat)abstract
- National accounts suggest that the Common Pochard Aythya ferina was an uncommon breeding bird throughout western Europe before 1850. Extensions to the breeding range in the late 19th century were potentially aided by the rapid development of managed fish-ponds in eastern Europe, which provided suitable novel habitat at that time. Expansion into western Europe followed in subsequent decades. Wetland and waterbody eutrophication throughout Europe, which likely provided food and cover for the birds, may have accelerated the rapid expansion from the 1950s until the early 1980s. Widespread declines in the last 30 years, especially in eastern Europe, where breeding numbers are highest, are possibly linked to intensification and/or abandonment of freshwater fish farming and changes in water quality. Studies show that Pochard gain fitness benefits from nesting in Black-headed Gull Chroicocephalus ridibundus colonies and hence has been affected by major losses of European gull colonies in the last 30 years. The spread of alien fish species such as the Carp Cyprinus carpio, which compete with Pochard for food resources, is a problem in the Mediterranean region. Changing predation pressures (in some cases linked to invasive alien mammals) are also implicated in some areas. Relatively modest numbers breeding in the UK, France and the Netherlands have remained stable or increased over the same recent span of years, confirming that different factors currently affect Pochard breeding abundance throughout its range. We urgently need better information relating to key factors affecting Pochard breeding success and abundance, which is currently showing an unfavourable conservation status throughout much of Europe.
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| 21. |
- Lonn, Eva, et al.
(författare)
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Novel Approaches in Primary Cardiovascular Disease Prevention : The HOPE-3 Trial Rationale, Design, and Participants' Baseline Characteristics.
- 2016
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Ingår i: Canadian Journal of Cardiology. - : Elsevier BV. - 0828-282X .- 1916-7075. ; 32:3, s. 311-318
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cholesterol and blood pressure (BP) can be effectively and safely lowered with statin drugs and BP-lowering drugs, reducing major cardiovascular (CV) events by 20%-30% within 5 years in high-risk individuals. However, there are limited data in lower-risk populations. The Heart Outcomes Prevention Evaluation-3 (HOPE-3) trial is evaluating whether cholesterol lowering with a statin drug, BP lowering with low doses of 2 antihypertensive agents, and their combination safely reduce major CV events in individuals at intermediate risk who have had no previous vascular events and have average cholesterol and BP levels.METHODS: A total of 12,705 women 65 years or older and men 55 years or older with at least 1 CV risk factor, no known CV disease, and without any clear indication or contraindication to the study drugs were randomized to rosuvastatin 10 mg/d or placebo and to candesartan/hydrochlorothiazide 16/12.5 mg/d or placebo (2 × 2 factorial design) and will be followed for a mean of 5.8 years. The coprimary study outcomes are the composite of CV death, nonfatal myocardial infarction (MI), and nonfatal stroke and the composite of CV death, nonfatal MI, nonfatal stroke, resuscitated cardiac arrest, heart failure, and arterial revascularization.RESULTS: Participants were recruited from 21 countries in North America, South America, Europe, Asia, and Australia. Mean age at randomization was 66 years and 46% were women.CONCLUSIONS: The HOPE-3 trial will provide new information on cholesterol and BP lowering in intermediate-risk populations with average cholesterol and BP levels and is expected to inform approaches to primary prevention worldwide.
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| 22. |
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| 23. |
- Persson, Carina, 1964, et al.
(författare)
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Greening of the brown-dwarf desert EPIC 212036875b: a 51 M-J object in a 5-day orbit around an F7V star
- 2019
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 628
-
Tidskriftsartikel (refereegranskat)abstract
- Context. Although more than 2000 brown dwarfs have been detected to date, mainly from direct imaging, their characterisation is difficult due to their faintness and model-dependent results. In the case of transiting brown dwarfs, however, it is possible to make direct high-precision observations. Aims. Our aim is to investigate the nature and formation of brown dwarfs by adding a new well-characterised object, in terms of its mass, radius and bulk density, to the currently small sample of less than 20 transiting brown dwarfs. Methods. One brown dwarf candidate was found by the KESPRINT consortium when searching for exoplanets in the K2 space mission Campaign 16 field. We combined the K2 photometric data with a series of multicolour photometric observations, imaging, and radial velocity measurements to rule out false positive scenarios and to determine the fundamental properties of the system. Results. We report the discovery and characterisation of a transiting brown dwarf in a 5.17-day eccentric orbit around the slightly evolved F7V star EPIC 212036875. We find a stellar mass of 1.15 +/- 0.08 M-circle dot, a stellar radius of 1.41 +/- 0.05 R-circle dot, and an age of 5.1 +/- 0.9 Gyr. The mass and radius of the companion brown dwarf are 51 +/- 2 M-J and 0.83 +/- 0.03 R-J, respectively, corresponding to a mean density of 108(-13)(+15) g cm(-3). Conclusions. EPIC 212036875 b is a rare object that resides in the brown-dwarf desert. In the mass-density diagram for planets, brown dwarfs, and stars, we find that all giant planets and brown dwarfs follow the same trend from similar to 0.3 M-J to the turn-over to hydrogen burning stars at similar to 73 M-J. EPIC 212036875 b falls close to the theoretical model for mature H/He dominated objects in this diagram as determined by interior structure models. We argue that EPIC 212036875 b formed via gravitational disc instabilities in the outer part of the disc, followed by a quick migration. Orbital tidal circularisation may have started early in its history for a brief period when the brown dwarf's radius was larger. The lack of spin-orbit synchronisation points to a weak stellar dissipation parameter (Q(star)' greater than or similar to 10(8)), which implies a circularisation timescale of greater than or similar to 23 Gyr, or suggests an interaction between the magnetic and tidal forces of the star and the brown dwarf.
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| 24. |
- Shumilova, Oleksandra, et al.
(författare)
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Simulating rewetting events in intermittent rivers and ephemeral streams : A global analysis of leached nutrients and organic matter
- 2019
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Ingår i: Global Change Biology. - : WILEY. - 1354-1013 .- 1365-2486. ; 25:5, s. 1591-1611
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Tidskriftsartikel (refereegranskat)abstract
- Climate change and human pressures are changing the global distribution and the extent of intermittent rivers and ephemeral streams (IRES), which comprise half of the global river network area. IRES are characterized by periods of flow cessation, during which channel substrates accumulate and undergo physico-chemical changes (preconditioning), and periods of flow resumption, when these substrates are rewetted and release pulses of dissolved nutrients and organic matter (OM). However, there are no estimates of the amounts and quality of leached substances, nor is there information on the underlying environmental constraints operating at the global scale. We experimentally simulated, under standard laboratory conditions, rewetting of leaves, riverbed sediments, and epilithic biofilms collected during the dry phase across 205 IRES from five major climate zones. We determined the amounts and qualitative characteristics of the leached nutrients and OM, and estimated their areal fluxes from riverbeds. In addition, we evaluated the variance in leachate characteristics in relation to selected environmental variables and substrate characteristics. We found that sediments, due to their large quantities within riverbeds, contribute most to the overall flux of dissolved substances during rewetting events (56%-98%), and that flux rates distinctly differ among climate zones. Dissolved organic carbon, phenolics, and nitrate contributed most to the areal fluxes. The largest amounts of leached substances were found in the continental climate zone, coinciding with the lowest potential bioavailability of the leached OM. The opposite pattern was found in the arid zone. Environmental variables expected to be modified under climate change (i.e. potential evapotranspiration, aridity, dry period duration, land use) were correlated with the amount of leached substances, with the strongest relationship found for sediments. These results show that the role of IRES should be accounted for in global biogeochemical cycles, especially because prevalence of IRES will increase due to increasing severity of drying events.
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| 25. |
- Trnka, Miroslav, et al.
(författare)
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Priority questions in multidisciplinary drought research
- 2018
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Ingår i: Climate Research (CR). - : Inter-Research Science Center. - 0936-577X .- 1616-1572. ; 75, s. 241-260
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Tidskriftsartikel (refereegranskat)abstract
- Addressing timely and relevant questions across amultitude of spatio-temporal scales,state-of-the-art interdisciplinary drought research will likely increase in importance under projectedclimate change. Given the complexity of the various direct and indirect causes and consequences of adrier world, scientific tasks need to be coordinated efficiently. Drought-related research endeavorsranging from individual projects to global initiatives therefore require prioritization. Here, wepresent 60 priority questions for optimizing future drought research. This topical catalogue reflectsthe experience of 65 scholars from 21 countries and almost 20 fields of research in both naturalsciences and the humanities. The set of drought-related questions primarily covers drought monitoring,impacts, forecasting, climatology, adaptation, as well as planning and policy. The questionshighlight the increasingly important role of remote sensing techniques in drought monitoring, importanceof drought forecasting and understanding the relationships between drought parametersand drought impacts, but also challenges of drought adaptation and preparedness policies.
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| 26. |
- Verheyen, Kris, et al.
(författare)
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201 Combining Biodiversity Resurveys across Regions to Advance Global Change Research
- 2017
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Ingår i: BioScience. - : Oxford University Press (OUP). - 0006-3568 .- 1525-3244. ; 67:1, s. 73-83
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Tidskriftsartikel (refereegranskat)abstract
- More and more ecologists have started to resurvey communities sampled in earlier decades to determine long-term shifts in community composition and infer the likely drivers of the ecological changes observed. However, to assess the relative importance of and interactions among multiple drivers, joint analyses of resurvey data from many regions spanning large environmental gradients are needed. In this article, we illustrate how combining resurvey data from multiple regions can increase the likelihood of driver orthogonality within the design and show that repeatedly surveying across multiple regions provides higher representativeness and comprehensiveness, allowing us to answer more completely a broader range of questions. We provide general guidelines to aid the implementation of multiregion resurvey databases. In so doing, we aim to encourage resurvey database development across other community types and biomes to advance global environmental change research.
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| 27. |
- Vogt, Viola Lara, et al.
(författare)
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Current standards of neuropsychological assessment in epilepsy surgery centers across Europe.
- 2017
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Ingår i: Epilepsia. - : Wiley. - 1528-1167 .- 0013-9580. ; 58:3, s. 343-355
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Tidskriftsartikel (refereegranskat)abstract
- We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty-six epilepsy centers and members of "E-PILEPSY" (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co-normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe.
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| 28. |
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| 29. |
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| 30. |
- Ambarki, Khalid, et al.
(författare)
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Accuracy of Parenchymal Cerebral Blood Flow Measurements Using Pseudocontinuous Arterial Spin-labeling in Healthy Volunteers
- 2015
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Ingår i: American Journal of Neuroradiology. - 0195-6108 .- 1936-959X. ; 36:10, s. 1816-1821
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: The arterial spin-labeling method for CBF assessment is widely available, but its accuracy is not fully established. We investigated the accuracy of a whole-brain arterial spin-labeling technique for assessing the mean parenchymal CBF and the effect of aging in healthy volunteers. Phase-contrast MR imaging was used as the reference method. MATERIALS AND METHODS: Ninety-two healthy volunteers were included: 49 young (age range, 20-30 years) and 43 elderly (age range, 65-80 years). Arterial spin-labeling parenchymal CBF values were averaged over the whole brain to quantify the mean pCBF(ASL) value. Total. CBF was assessed with phase-contrast MR imaging as the sum of flows in the internal carotid and vertebral arteries, and subsequent division by brain volume returned the pCBF(PCMRI) value. Accuracy was considered as good as that of the reference method if the systematic difference was less than 5 mL/min/100 g of brain tissue and if the 95% confidence intervals were equal to or better than +/- 10 mL/min/100 g. RESULTS: pCBF(ASL) correlated to pCBF(PCMRI) (r = 0.73; P < .001). Significant differences were observed between the pCBF(ASL) and pCBF(PCMRI) values in the young (P = .001) and the elderly (P < .001) volunteers. The systematic differences (mean 2 standard deviations) were -4 +/- 14 mL/min/100 g in the young subjects and 6 +/- 12 mL/min/100 g in the elderly subjects. Young subjects showed higher values than the elderly subjects for pCBF(PCMRI) (young, 57 +/- 8 mL/min/100 g; elderly, 54 +/- 7 mL/min/100 g; P = .05) and pCBF(ASL) (young, 61 +/- 10 mL/min/100 g; elderly, 48 +/- 10 mL/min/100 g; P < .001). CONCLUSIONS: The limits of agreement were too wide for the arterial spin-labeling method to be considered satisfactorily accurate, whereas the systematic overestimation in the young subjects and underestimation in the elderly subjects were close to acceptable. The age-related decrease in parenchymal CBF was augmented in arterial spin-labeling compared with phase-contrast MR imaging.
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| 31. |
- Ambarki, Khalid, et al.
(författare)
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Partial Volume Correction of Cerebral Perfusion Estimates Obtained by Arterial Spin Labeling
- 2015
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Ingår i: 16th Nordic-Baltic Conference on Biomedical Engineering. - Cham : Springer International Publishing. - 9783319129662 - 9783319129679 ; , s. 17-19
-
Konferensbidrag (refereegranskat)abstract
- Arterial Spin labeling (ASL) is a fully non-invasive MRI method capable to quantify cerebral perfusion. However, gray (GM) and white matter (WM) ASL perfusions are difficult to assess separately due to limited spatial resolution increasing the partial volume effects (PVE). In the present study, ASL PVE correction was implemented based on a regression algorithm in 22 healthy young men. PVE corrected perfusion of GM and WM were compared to previous studies. PVE-corrected GM perfusion was in agreement with literature values. In general, WM perfusion was higher despite the use of PVE correction.
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| 32. |
- Andrade, Pedro, et al.
(författare)
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Regulatory changes in pterin and carotenoid genes underlie balanced color polymorphisms in the wall lizard
- 2019
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:12, s. 5633-5642
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Tidskriftsartikel (refereegranskat)abstract
- Reptiles use pterin and carotenoid pigments to produce yellow, orange, and red colors. These conspicuous colors serve a diversity of signaling functions, but their molecular basis remains unresolved. Here, we show that the genomes of sympatric color morphs of the European common wall lizard (Podarcis muralis), which differ in orange and yellow pigmentation and in their ecology and behavior, are virtually undifferentiated. Genetic differences are restricted to two small regulatory regions near genes associated with pterin [sepiapterin reductase (SPR)] and carotenoid [beta-carotene oxygenase 2 (BCO2)] metabolism, demonstrating that a core gene in the housekeeping pathway of pterin biosynthesis has been coopted for bright coloration in reptiles and indicating that these loci exert pleiotropic effects on other aspects of physiology. Pigmentation differences are explained by extremely divergent alleles, and haplotype analysis revealed abundant transspecific allele sharing with other lacertids exhibiting color polymorphisms. The evolution of these conspicuous color ornaments is the result of ancient genetic variation and cross-species hybridization.
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| 33. |
- Beniczky, Sándor, et al.
(författare)
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Standardized computer-based organized reporting of EEG : SCORE - Second version
- 2017
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Ingår i: Clinical Neurophysiology. - : Elsevier BV. - 1388-2457. ; 128:11, s. 2334-2346
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Tidskriftsartikel (refereegranskat)abstract
- Standardized terminology for computer-based assessment and reporting of EEG has been previously developed in Europe. The International Federation of Clinical Neurophysiology established a taskforce in 2013 to develop this further, and to reach international consensus. This work resulted in the second, revised version of SCORE (Standardized Computer-based Organized Reporting of EEG), which is presented in this paper. The revised terminology was implemented in a software package (SCORE EEG), which was tested in clinical practice on 12,160 EEG recordings. Standardized terms implemented in SCORE are used to report the features of clinical relevance, extracted while assessing the EEGs. Selection of the terms is context sensitive: initial choices determine the subsequently presented sets of additional choices. This process automatically generates a report and feeds these features into a database. In the end, the diagnostic significance is scored, using a standardized list of terms. SCORE has specific modules for scoring seizures (including seizure semiology and ictal EEG patterns), neonatal recordings (including features specific for this age group), and for Critical Care EEG Terminology. SCORE is a useful clinical tool, with potential impact on clinical care, quality assurance, data-sharing, research and education.
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| 34. |
- Bhatt, Deepak L., et al.
(författare)
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Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study
- 2019
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Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 42:5, s. 498-505
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Tidskriftsartikel (refereegranskat)abstract
- In the setting of prior myocardial infarction, the oral antiplatelet ticagrelor added to aspirin reduced the risk of recurrent ischemic events, especially, in those with diabetes mellitus. Patients with stable coronary disease and diabetes are also at elevated risk and might benefit from dual antiplatelet therapy. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS, NCT01991795) is a Phase 3b randomized, double-blinded, placebo-controlled trial of ticagrelor vs placebo, on top of low dose aspirin. Patients >= 50 years with type 2 diabetes receiving anti-diabetic medications for at least 6 months with stable coronary artery disease as determined by a history of previous percutaneous coronary intervention, bypass grafting, or angiographic stenosis of >= 50% of at least one coronary artery were enrolled. Patients with known prior myocardial infarction (MI) or stroke were excluded. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint is Thrombolysis in Myocardial Infarction major bleeding. A total of 19 220 patients worldwide have been randomized and at least 1385 adjudicated primary efficacy endpoint events are expected to be available for analysis, with an expected average follow-up of 40 months (maximum 58 months). Most of the exposure is on a 60 mg twice daily dose, as the dose was lowered from 90 mg twice daily partway into the study. The results may revise the boundaries of efficacy for dual antiplatelet therapy and whether it has a role outside acute coronary syndromes, prior myocardial infarction, or percutaneous coronary intervention.
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| 35. |
- Brudzinska-Kosior, Anna, et al.
(författare)
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Polybrominated diphenyl ethers (PBDEs) in herbaceous Centaurium erythraea affected by various sources of environmental pollution
- 2015
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Ingår i: Journal of Environmental Science and Health. Part A. - : Taylor & Francis. - 1093-4529 .- 1532-4117. ; 50:13, s. 1369-1375
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Tidskriftsartikel (refereegranskat)abstract
- Polybrominated diphenyl ethers (PBDEs) are persistent xenobiotics with harmful effects on humans and wildlife. Their levels in the environment and accumulation in biota must be carefully controlled especially in species harvested from wild populations and commonly used as medicines. Our objective has been to determine PBDE concentrations (BDEs 28, 47, 66, 85, 99, 100, 153, 154, 183 and 209) in Centaurium erythraea collected at sites with various levels of environmental pollution. PBDE congener profiles in C. erythraea were dominated by BDE209, which accounted for 47-89% of the total PBDE burden in the plants. Principal Component and Classification Analysis, which classifies the concentration of PBDEs in C. erythraea, allowed us to distinguish the pattern of these compounds characteristic for the origin of pollution: BDEs 28, 47, 66, 85, 99, 100 for lignite and general chemical industry and the vicinity of an expressway and BDEs 183 and 209 for a thermal power plant and ferrochrome smelting industry. Careful selection of sites with C. erythraea for medicinal purposes is necessary as this herb can accumulate PBDEs while growing at polluted sites.
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| 36. |
- Büntgen, Ulf, et al.
(författare)
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Tree-Ring Amplification of the Early Nineteenth-Century Summer Cooling in Central Europe
- 2015
-
Ingår i: Journal of Climate. - 0894-8755 .- 1520-0442. ; 28:13, s. 5272-5288
-
Forskningsöversikt (refereegranskat)abstract
- Annually resolved and absolutely dated tree-ring chronologies are the most important proxy archives to reconstruct climate variability over centuries to millennia. However, the suitability of tree-ring chronologies to reflect the “true” spectral properties of past changes in temperature and hydroclimate has recently been debated. At issue is the accurate quantification of temperature differences between early nineteenth-century cooling and recent warming. In this regard, central Europe (CEU) offers the unique opportunity to compare evidence from instrumental measurements, paleomodel simulations, and proxy reconstructions covering both the exceptionally hot summer of 2003 and the year without summer in 1816. This study uses 565 Swiss stone pine (Pinus cembra) ring width samples from high-elevation sites in the Slovakian Tatra Mountains and Austrian Alps to reconstruct CEU summer temperatures over the past three centuries. This new temperature history is compared to different sets of instrumental measurements and state-of-the-art climate model simulations. All records independently reveal the coolest conditions in the 1810s and warmest after 1996, but the ring width–based reconstruction overestimates the intensity and duration of the early nineteenth-century summer cooling by approximately 1.5°C at decadal scales. This proxy-specific deviation is most likely triggered by inflated biological memory in response to reduced warm season temperature, together with changes in radiation and precipitation following the Tambora eruption in April 1815. While suggesting there exists a specific limitation in ring width chronologies to capture abrupt climate perturbations with increased climate system inertia, the results underline the importance of alternative dendrochronological and wood anatomical parameters, including stable isotopes and maximum density, to assess the frequency and severity of climatic extremes.
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| 37. |
- Fronzek, Stefan, et al.
(författare)
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Classifying multi-model wheat yield impact response surfaces showing sensitivity to temperature and precipitation change
- 2018
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Ingår i: Agricultural Systems. - : Elsevier BV. - 0308-521X. ; 159, s. 209-224
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Tidskriftsartikel (refereegranskat)abstract
- Crop growth simulation models can differ greatly in their treatment of key processes and hence in their response to environmental conditions. Here, we used an ensemble of 26 process-based wheat models applied at sites across a European transect to compare their sensitivity to changes in temperature (-2 to +9°C) and precipitation (-50 to +50%). Model results were analysed by plotting them as impact response surfaces (IRSs), classifying the IRS patterns of individual model simulations, describing these classes and analysing factors that may explain the major differences in model responses.The model ensemble was used to simulate yields of winter and spring wheat at four sites in Finland, Germany and Spain. Results were plotted as IRSs that show changes in yields relative to the baseline with respect to temperature and precipitation. IRSs of 30-year means and selected extreme years were classified using two approaches describing their pattern.The expert diagnostic approach (EDA) combines two aspects of IRS patterns: location of the maximum yield (nine classes) and strength of the yield response with respect to climate (four classes), resulting in a total of 36 combined classes defined using criteria pre-specified by experts. The statistical diagnostic approach (SDA) groups IRSs by comparing their pattern and magnitude, without attempting to interpret these features. It applies a hierarchical clustering method, grouping response patterns using a distance metric that combines the spatial correlation and Euclidian distance between IRS pairs. The two approaches were used to investigate whether different patterns of yield response could be related to different properties of the crop models, specifically their genealogy, calibration and process description.Although no single model property across a large model ensemble was found to explain the integrated yield response to temperature and precipitation perturbations, the application of the EDA and SDA approaches revealed their capability to distinguish: (i) stronger yield responses to precipitation for winter wheat than spring wheat; (ii) differing strengths of response to climate changes for years with anomalous weather conditions compared to period-average conditions; (iii) the influence of site conditions on yield patterns; (iv) similarities in IRS patterns among models with related genealogy; (v) similarities in IRS patterns for models with simpler process descriptions of root growth and water uptake compared to those with more complex descriptions; and (vi) a closer correspondence of IRS patterns in models using partitioning schemes to represent yield formation than in those using a harvest index.Such results can inform future crop modelling studies that seek to exploit the diversity of multi-model ensembles, by distinguishing ensemble members that span a wide range of responses as well as those that display implausible behaviour or strong mutual similarities.
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| 38. |
- Gorkhover, Tais, et al.
(författare)
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Femtosecond X-ray Fourier holography imaging of free-flying nanoparticles
- 2018
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Ingår i: Nature Photonics. - : Springer Science and Business Media LLC. - 1749-4885 .- 1749-4893. ; 12:3, s. 150-153
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Tidskriftsartikel (refereegranskat)abstract
- Ultrafast X-ray imaging on individual fragile specimens such as aerosols 1 , metastable particles 2 , superfluid quantum systems 3 and live biospecimens 4 provides high-resolution information that is inaccessible with conventional imaging techniques. Coherent X-ray diffractive imaging, however, suffers from intrinsic loss of phase, and therefore structure recovery is often complicated and not always uniquely defined 4,5 . Here, we introduce the method of in-flight holography, where we use nanoclusters as reference X-ray scatterers to encode relative phase information into diffraction patterns of a virus. The resulting hologram contains an unambiguous three-dimensional map of a virus and two nanoclusters with the highest lateral resolution so far achieved via single shot X-ray holography. Our approach unlocks the benefits of holography for ultrafast X-ray imaging of nanoscale, non-periodic systems and paves the way to direct observation of complex electron dynamics down to the attosecond timescale.
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| 39. |
- Halim, Sharif A., et al.
(författare)
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Frequency, clinical and angiographic characteristics, and outcomes of high-risk non-ST-segment elevation acute coronary syndromes patients with left circumflex culprit lesions
- 2016
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 203, s. 708-713
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Tidskriftsartikel (refereegranskat)abstract
- Background: The relationship between culprit vessel, infarct size, and outcomes in non-ST-segment elevation acute coronary syndromes (NSTE ACS) is unclear. In some reports, the left circumflex artery (LCX) was more often the culprit at angiography than the right coronary artery (RCA) or left anterior descending artery (LAD), and infarcts were larger with LCX culprits. Methods: We determined culprit vessel frequency and initial patency (TIMI flow grade), median fold elevation of peak troponin above the upper limit of normal, and outcomes (30-day death or myocardial infarction [MI] and 1-year mortality) by culprit vessel in high-risk NSTE ACS patients in the EARLY ACS trial. Results: Of 9406 patients, 2066 (22.0%) had angiographic core laboratory data. We evaluated 1774 patients for whom the culprit artery was not the left main, a bypass graft, or branch vessel. The culprit was the LCX in 560 (31.6%), LAD in 653 (36.8%), and RCA in 561 (31.6%) patients. There were fewer women (24.1%) and more prior MI (25.5%) among patients with a culprit LCX compared with those with a culprit LAD or RCA. Patients with LCX (21.2%) and RCA (27.5%) culprits more often had an occluded artery (TIMI 0/1) than did those with LAD (11.3%). Peak troponin elevation was significantly higher for LCX than RCA or LAD culprits. LCX culprit vessels were not associated with worse 30-day or 1-year outcomes in adjusted models. Conclusions: Among patientswith NSTE ACS, the frequencies of LCX, LAD, and RCA culprits were similar. Although LCX lesions were associated with higher peak troponin levels, there was no difference in short-or intermediateterm outcomes by culprit artery.
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| 40. |
- Heldbjerg, Henning, et al.
(författare)
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Contrasting population trends of common starlings (Sturnus vulgaris) across Europe
- 2019
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Ingår i: Ornis Fennica. - 0030-5685. ; 96:4, s. 153-168
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Tidskriftsartikel (refereegranskat)abstract
- The greatest loss of biodiversity in the EU has occurred on agricultural land. The Common Starling (Sturnus vulgaris) is one of the many numerous and widespread European farmland breeding bird species showing major population declines linked to European agricultural intensification. Here we present results based on monitoring data collected since 1975 in 24 countries to examine the influence of changing extent of grassland and cattle abundance (based on results of earlier studies showing the importance of lowland cattle grazed grassland for the species), wintering provenance and temperature on national breeding population trends of Starlings across Europe. Positive Starling population trends in Central-East Europe contrast with negative trends in North and West Europe. Based on this indicative approach, we found some support for the importance of cattle stock and no support for grassland, temperature or wintering provenance to explain Starling population trends in Europe. However, we acknowledge such a European-wide analysis may conceal regional differences in responses and suggest that currently accessible national land use data might be insufficient to describe the detailed current changes in animal husbandry and grassland management that may be responsible for changes in food availability and hence breeding Starling abundance and their differences across Europe. Reviewing results from local studies relating Starling population trends to local agricultural change offer contradictory results, suggesting complex interacting processes at work. We recommend combining national datasets on demography, land-use/agricultural practices and from autecological research to better explain the reasons for contrasting Starling trends across Europe, to enable us to predict how changing agriculture will affect Starlings and potentially suggest mitigation measures to restore local populations where possible.
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| 41. |
- Jacobsen, Carsten Suhr, et al.
(författare)
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Inter-laboratory testing of the effect of DNA blocking reagent G2 on DNA extraction from low-biomass clay samples
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Here we show that a commercial blocking reagent (G2) based on modified eukaryotic DNA significantly improved DNA extraction efficiency. We subjected G2 to an inter-laboratory testing, where DNA was extracted from the same clay subsoil using the same batch of kits. The inter-laboratory extraction campaign revealed large variation among the participating laboratories, but the reagent increased the number of PCR-amplified16S rRNA genes recovered from biomass naturally present in the soils by one log unit. An extensive sequencing approach demonstrated that the blocking reagent was free of contaminating DNA, and may therefore also be used in metagenomics studies that require direct sequencing.
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| 42. |
- Karnkowska, Anna, et al.
(författare)
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The Oxymonad Genome Displays Canonical Eukaryotic Complexity in the Absence of a Mitochondrion
- 2019
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Ingår i: Molecular biology and evolution. - : OXFORD UNIV PRESS. - 0737-4038 .- 1537-1719. ; 36:10, s. 2292-2312
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Tidskriftsartikel (refereegranskat)abstract
- The discovery that the protist Monocercomonoides exilis completely lacks mitochondria demonstrates that these organelles are not absolutely essential to eukaryotic cells. However, the degree to which the metabolism and cellular systems of this organism have adapted to the loss of mitochondria is unknown. Here, we report an extensive analysis of the M. exilis genome to address this question. Unexpectedly, we find that M. exilis genome structure and content is similar in complexity to other eukaryotes and less "reduced" than genomes of some other protists from the Metamonada group to which it belongs. Furthermore, the predicted cytoskeletal systems, the organization of endomembrane systems, and biosynthetic pathways also display canonical eukaryotic complexity. The only apparent preadaptation that permitted the loss of mitochondria was the acquisition of the SUF system for Fe-S cluster assembly and the loss of glycine cleavage system. Changes in other systems, including in amino acid metabolism and oxidative stress response, were coincident with the loss of mitochondria but are likely adaptations to the microaerophilic and endobiotic niche rather than the mitochondrial loss per se. Apart from the lack of mitochondria and peroxisomes, we show that M. exilis is a fully elaborated eukaryotic cell that is a promising model system in which eukaryotic cell biology can be investigated in the absence of mitochondria.
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| 43. |
- Kosior, Grzegorz, et al.
(författare)
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Pleurozium schreberi as an ecological indicator of polybrominated diphenyl ethers (PBDEs) in a heavily industrialized urban area
- 2015
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Ingår i: Ecological Indicators. - : Elsevier. - 1470-160X .- 1872-7034. ; 48, s. 492-497
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Tidskriftsartikel (refereegranskat)abstract
- Polybrominated diphenyl ethers (PBDEs) are toxic contaminants with a persistent character and adverse effects on humans and wildlife. Therefore, the deposition of these chemicals in vegetation must be carefully controlled. Our objective was to determine PBDE concentrations (BDEs 28, 47, 66, 85, 99, 100, 153, 154, 183 and 209) in Pleurozium schreberi collected in a heavily industrialized urban agglomeration. High PBDE concentrations in the moss confirm the presence of active sources of atmospheric pollution in an area tested. The distribution of these xenobiotics was related to the vegetation cover being lower in sites surrounded by forests which indicates that PBDEs may have a tendency to be trapped from the air by tree leaves and needles. Congener profiles in P. schreberi were dominated by BDE 209 which was for 79% (in case of the coke smelter) to 95% (in case of the chemical plant) part of the total PBDE burden in this moss. The principal component and classification analysis classifying the concentration of PBDEs in P. schreberi allowed us to distinguish the pattern of these compounds characteristic for the origin of pollution. P. schreberi may be used as a bioindicator for PBDEs in areas contaminated with these chemicals.
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| 44. |
- Lonn, Eva M., et al.
(författare)
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Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease
- 2016
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 374:21, s. 2009-2020
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Antihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher, but its role in persons at intermediate risk and with lower blood pressure is unclear.METHODS In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; the second coprimary outcome additionally included resuscitated cardiac arrest, heart failure, and revascularization. The median follow-up was 5.6 years.RESULTS The mean blood pressure of the participants at baseline was 138.1/81.9 mm Hg; the decrease in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in the placebo group. The first coprimary outcome occurred in 260 participants (4.1%) in the active-treatment group and in 279 (4.4%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P = 0.40); the second coprimary outcome occurred in 312 participants (4.9%) and 328 participants (5.2%), respectively (hazard ratio, 0.95; 95% CI, 0.81 to 1.11; P = 0.51). In one of the three prespecified hypothesis-based subgroups, participants in the subgroup for the upper third of systolic blood pressure (>143.5 mm Hg) who were in the active-treatment group had significantly lower rates of the first and second coprimary outcomes than those in the placebo group; effects were neutral in the middle and lower thirds (P = 0.02 and P = 0.009, respectively, for trend in the two outcomes).CONCLUSIONS Therapy with candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day was not associated with a lower rate of major cardiovascular events than placebo among persons at intermediate risk who did not have cardiovascular disease. ( ClinicalTrials. gov number, NCT00468923.)
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| 45. |
- Lundholm, Ida V., et al.
(författare)
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Considerations for three-dimensional image reconstruction from experimental data in coherent diffractive imaging
- 2018
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Ingår i: IUCrJ. - : International Union of Crystallography. - 2052-2525. ; 5, s. 531-541
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Tidskriftsartikel (refereegranskat)abstract
- Diffraction before destruction using X-ray free-electron lasers (XFELs) has the potential to determine radiation-damage-free structures without the need for crystallization. This article presents the three-dimensional reconstruction of the Melbournevirus from single-particle X-ray diffraction patterns collected at the LINAC Coherent Light Source (LCLS) as well as reconstructions from simulated data exploring the consequences of different kinds of experimental sources of noise. The reconstruction from experimental data suffers from a strong artifact in the center of the particle. This could be reproduced with simulated data by adding experimental background to the diffraction patterns. In those simulations, the relative density of the artifact increases linearly with background strength. This suggests that the artifact originates from the Fourier transform of the relatively flat background, concentrating all power in a central feature of limited extent. We support these findings by significantly reducing the artifact through background removal before the phase-retrieval step. Large amounts of blurring in the diffraction patterns were also found to introduce diffuse artifacts, which could easily be mistaken as biologically relevant features. Other sources of noise such as sample heterogeneity and variation of pulse energy did not significantly degrade the quality of the reconstructions. Larger data volumes, made possible by the recent inauguration of high repetition-rate XFELs, allow for increased signal-to-background ratio and provide a way to minimize these artifacts. The anticipated development of three-dimensional Fourier-volume-assembly algorithms which are background aware is an alternative and complementary solution, which maximizes the use of data.
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| 46. |
- Pasche, Natacha, et al.
(författare)
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Implications of river intrusion and convective mixing on the spatial and temporal variability of under-ice CO2
- 2019
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Ingår i: Inland Waters. - : Informa UK Limited. - 2044-2041 .- 2044-205X. ; 9:2, s. 162-176
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Tidskriftsartikel (refereegranskat)abstract
- Ice-covered periods might significantly contribute to lake emissions at ice-melt, yet a comprehensive understanding of under-ice carbon dioxide (CO2) dynamics is still lacking. This study investigated the processes driving spatiotemporal patterns of under-ice CO2 in large Lake Onego. In March 2015 and 2016, under-ice CO2, dissolved inorganic carbon (DIC), and dissolved organic carbon (DOC) distributions were measured along a river to an open-lake transect. CO2 decreased from 120/129 μmol L−1 in the river to 51/98 μmol L−1 in the bay, and 34/36 μmol L−1 in the open lake, while DOC decreased from 1.18/1.55 mmol L−1 in the river to 0.67/1.04 mmol L−1 in the bay in 2015 and 2016, respectively. These decreases in concentrations with increasing distance from the river mouth indicate that river discharge modulates spatial patterns of under-ice CO2. The variability between the 2 years was mainly driven by river discharge and ice transparency affecting the extent of under-ice convection. Higher discharge during winter 2016 resulted in higher CO2 concentrations in the bay. By contrast, intensive under-ice convection led to lower, more homogeneously distributed CO2 in 2015. In conclusion, the river-to-bay transition zone is characterized by strong CO2 variability and is therefore an important zone to consider when assessing the CO2 budget of large lakes.
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| 47. |
- Pavón-Jordán, Diego, et al.
(författare)
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Habitat- and species-mediated short- and long-term distributional changes in waterbird abundance linked to variation in European winter weather
- 2019
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Ingår i: Diversity and Distributions. - : Wiley. - 1366-9516. ; 25:2, s. 225-239
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Many species are showing distribution shifts in response to environmental change. We explored (a) the effects of inter-annual variation in winter weather conditions on non-breeding distributional abundance of waterbirds exploiting different habitats (deep-water, shallow water, farmland) and (b) the long-term shift in the population centroid of these species and investigate its link to changes in weather conditions. Location: Europe. Methods: We fitted generalized additive mixed Models to a large-scale, 24-year dataset (1990–2013) describing the winter distributional abundance of 25 waterbird species. We calculated the annual and long-term (3-year periods) population centroid of each species and used the winter North Atlantic Oscillation (NAO) index to explain the inter-annual and long-term shifts in their location. Results: (a) Year-to-year southwestwards shifts in the population centroids of deep- and shallow-water species were linked to negative NAO values. Shallow-water species shifted northeastwards associated with positive NAO values and the distance shifted increased with increasing NAO. Deep-water species shifted northeastwards up to zero NAO indices, but showed no further increase at higher NAO values. (b) Deep-water species showed long-term northeastwards shifts in distributional abundance throughout the 1990s and the 2000s. Shallow-water species, on the other hand, shifted northeastwards during the 1990s and early 2000s, but southwestwards thereafter. There were no significant links between the NAO and year-to-year movements or long-term shifts in farmland species’ population centroid. Main Conclusions: We provide evidence for a link between both year-to-year and long-term changes in waterbird winter distributional abundances at large geographical scales to short- and long-term changes in winter weather conditions. We also show that species using shallow water, deep-water and farmland habitats responded differently, especially at high NAO values. As well as important ecological implications, these findings contribute to the development of future conservation measures for these species under current and future climate change.
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| 48. |
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| 49. |
- Stephens, Philip A., et al.
(författare)
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Consistent response of bird populations to climate change on two continents
- 2016
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 352:6281, s. 84-87
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Tidskriftsartikel (refereegranskat)abstract
- Global climate change is a major threat to biodiversity. Large-scale analyses have generally focused on the impacts of climate change on the geographic ranges of species and on phenology, the timing of ecological phenomena. We used long-term monitoring of the abundance of breeding birds across Europe and the United States to produce, for both regions, composite population indices for two groups of species: those for which climate suitability has been either improving or declining since 1980. The ratio of these composite indices, the climate impact indicator (CII), reflects the divergent fates of species favored or disadvantaged by climate change. The trend in CII is positive and similar in the two regions. On both continents, interspecific and spatial variation in population abundance trends are well predicted by climate suitability trends.
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| 50. |
- Vinereanu, Dragos, et al.
(författare)
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Outcomes in anticoagulated patients with atrial fibrillation and with mitral or aortic valve disease
- 2018
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Ingår i: Heart. - : BMJ PUBLISHING GROUP. - 1355-6037 .- 1468-201X. ; 104:15, s. 1292-1299
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess stroke/systemic embolism, major bleeding and other outcomes, and treatment effect of apixaban versus warfarin, in patients with atrial fibrillation (AF) and different types of valvular heart disease (VHD), using data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial.Methods: There were 14 793 patients with known VHD status, categorised as having moderate or severe mitral regurgitation (MR) (n=3382), aortic regurgitation (AR) (n=842) or aortic stenosis (AS) (n=324); patients with moderate or severe mitral stenosis were excluded from the trial. Baseline characteristics, efficacy and safety outcomes were compared between each type and no significant VHD. Treatment effect was assessed using an adjusted model.Results: Patients with MR or AR had similar rates of stroke/systemic embolism and bleeding compared with patients without MR or AR, respectively. Patients with AS had significantly higher event rates (presented as rate per 100 patient-years of follow-up) of stroke/systemic embolism (3.47 vs 1.36; adjusted HR (adjHR) 2.21, 95% CI 1.35 to 3.63), death (8.30 vs 3.53; adjHR 1.92, 95% CI 1.41 to 2.61), major bleeding (5.31 vs 2.53; adjHR 1.80, 95% CI 1.19 to 2.75) and intracranial bleeding (1.29 vs 0.51; adjHR 2.54, 95% CI 1.08 to 5.96) than patients without AS. The superiority of apixaban over warfarin on stroke/systemic embolism was similar in patients with versus without MR (HR 0.69, 95% CI 0.46 to 1.04 vs HR 0.79, 95% CI 0.63 to 1.00; interaction P value 0.52), with versus without AR (HR 0.57, 95% CI 0.27 to 1.20 vs HR 0.78, 95% CI 0.63 to 0.96; interaction P value 0.52), and with versus without AS (HR 0.44, 95% CI 0.17 to 1.13 vs HR 0.79, 95% CI 0.64 to 0.97; interaction P value 0.19). For each of the primary and secondary efficacy and safety outcomes, there was no evidence of a different effect of apixaban over warfarin in patients with any VHD subcategory.Conclusions; In anticoagulated patients with AF, AS is associated with a higher risk of stroke/systemic embolism, bleeding and death. The efficacy and safety benefits of apixaban compared with warfarin were consistent, regardless of presence of MR, AR or AS.
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