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1.
  • Kattge, Jens, et al. (författare)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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2.
  • Dima, Danai, et al. (författare)
  • Subcortical volumes across the lifespan : Data from 18,605 healthy individuals aged 3-90 years.
  • 2022
  • Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 452-469
  • Tidskriftsartikel (refereegranskat)abstract
    • Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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3.
  • Fortelius, Mikael, et al. (författare)
  • The Origin and Early History of NOW as It Happened
  • 2023
  • Ingår i: Evolution of Cenozoic Land Mammal Faunas and Ecosystems: 25 years of the NOW database of fossil mammals.. - : Springer. ; , s. 7-32
  • Bokkapitel (refereegranskat)abstract
    • The NOW database of fossil mammals came to be through a confluence of several initiatives spanning multiple decades. The first public version of NOW database was released in 1996 and the first Advisory Board was established the year after. Originally, NOW stood for Neogene of the Old World but with the gradual expansion of the database the acronym was eventually reassigned to stand for New and Old Worlds. The structure of what would become NOW was originally cloned from the ETE database of the Smithsonian Institution and the first NOW version accessible over the internet was a node of the ETE database. The first standalone, online version of NOW was launched in 2005 and the first formal steering group was established in 2009. During its existence, NOW has been funded, directly or indirectly, by several organizations but fundamentally it has always been an unfunded community effort, dependent on voluntary work by the participants.
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4.
  • Frangou, Sophia, et al. (författare)
  • Cortical thickness across the lifespan : Data from 17,075 healthy individuals aged 3-90 years
  • 2022
  • Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 431-451
  • Tidskriftsartikel (refereegranskat)abstract
    • Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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5.
  • Månsdotter, Anna, et al. (författare)
  • Towards capability-adjusted life years in public health and social welfare : results from a Swedish survey on ranking capabilities
  • 2020
  • Ingår i: PLOS ONE. - San Francisco : Public Library of Science. - 1932-6203. ; 15:12
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: The aim of this study was to rank capabilities and suggest a relevant set of capabilities for the Swedish context to inform the development of capability-adjusted life years (CALYs). CALYs is a quality of life measure for policy making based on the capability approach by Amartya Sen.MATERIALS AND METHODS: A Swedish governmental review proposed the following 10 relevant capabilities: time, financial situation, mental/physical health, political resources, knowledge, living environment, occupation, social relations, security, and housing. Researchers in health-related disciplines from 5 universities ranked these capabilities from 1 to 10 (most to least important) in a web-based cross-sectional survey; 115 of 171 responses were eligible.RESULTS: Health, social relations, and financial situation were deemed most important. Stratification by gender, research field, and age group revealed few differences. We found that it was possible to rank capabilities and that health, social relations, and financial situation were ranked highest by a non-representative sample of researchers and doctoral students from health-related disciplines at five Swedish universities.CONCLUSIONS: The revealed ranking is dependent on the metric and must be further explored. The findings support continued development of CALYs for monitoring and evaluating outcomes in public health and social-welfare interventions.
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6.
  • Surendran, Praveen, et al. (författare)
  • Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
  • 2020
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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7.
  • Watson, Hunna J., et al. (författare)
  • Common Genetic Variation and Age of Onset of Anorexia Nervosa
  • 2022
  • Ingår i: BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE. - : Elsevier BV. - 2667-1743. ; 2:4, s. 368-378
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
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8.
  • Wierenga, Lara M., et al. (författare)
  • Greater male than female variability in regional brain structure across the lifespan
  • 2022
  • Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 470-499
  • Tidskriftsartikel (refereegranskat)abstract
    • For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
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9.
  • Abbafati, Cristiana, et al. (författare)
  • 2020
  • Tidskriftsartikel (refereegranskat)
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10.
  • Abé, Christoph, et al. (författare)
  • Longitudinal Structural Brain Changes in Bipolar Disorder: A Multicenter Neuroimaging Study of 1232 Individuals by the ENIGMA Bipolar Disorder Working Group.
  • 2022
  • Ingår i: Biological psychiatry. - : Elsevier BV. - 1873-2402 .- 0006-3223. ; 91:6, s. 582-592
  • Tidskriftsartikel (refereegranskat)abstract
    • Bipolar disorder (BD) is associated with cortical and subcortical structural brain abnormalities. It is unclear whether such alterations progressively change over time, and how this is related to the number of mood episodes. To address this question, we analyzed a large and diverse international sample with longitudinal magnetic resonance imaging (MRI) and clinical data to examine structural brain changes over time in BD.Longitudinal structural MRI and clinical data from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) BD Working Group, including 307 patients with BD and 925 healthy control subjects, were collected from 14 sites worldwide. Male and female participants, aged 40 ± 17 years, underwent MRI at 2 time points. Cortical thickness, surface area, and subcortical volumes were estimated using FreeSurfer. Annualized change rates for each imaging phenotype were compared between patients with BD and healthy control subjects. Within patients, we related brain change rates to the number of mood episodes between time points and tested for effects of demographic and clinical variables.Compared with healthy control subjects, patients with BD showed faster enlargement of ventricular volumes and slower thinning of the fusiform and parahippocampal cortex (0.18
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11.
  • Berbrick, Walter, et al. (författare)
  • Conflict Prevention and Security Cooperation in the Arctic Region : Frameworks of the Future
  • 2020
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • This report, Conflict Prevention and Security Cooperation in the Arctic Region: Frameworks for the Future, captures consensus of the Newport Arctic Scholars Initiative 2020 scholars. Building upon the 2018-2019 NASI work on the limitations of the current cooperative security fora in the Arctic region, this cohort explored existing international frameworks and assessed their abilities to ensure freedom and security in the Arctic through political-military means. NASI 2020 also examined existing frameworks to determine whether they enabled increased dialogue and maritime security cooperation in the region. The frameworks were further evaluated for their abilities to prevent and manage conflict and enhance cooperation on areas of common security and defense interests in the region. Scholars were tasked to identify new frameworks that could be useful in establishing – and maintaining – open channels of communication, preventing conflict, and enhancing cooperation on areas of common security and defense interests among nations and navies in the Arctic region. Finally, the group sought to identify practical arrangements for a future meeting or summit that could bring together states to enhance dialogue on security and cooperation in the Arctic region.
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12.
  • Bonfiglio, Ferdinando, et al. (författare)
  • GWAS of stool frequency provides insights into gastrointestinal motility and irritable bowel syndrome
  • 2021
  • Ingår i: Cell Genomics. - Cambridge, MA, United States : Elsevier. - 2666-979X. ; 1:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Gut dysmotility is associated with constipation, diarrhea, and functional gastrointestinal disorders like irritable bowel syndrome (IBS), although its molecular underpinnings are poorly characterized. We studied stool frequency (defined by the number of bowel movements per day, based on questionnaire data) as a proxy for gut motility in a GWAS meta-analysis including 167,875 individuals from UK Biobank and four smaller population-based cohorts. We identify 14 loci associated with stool frequency (p ≤ 5.0 × 10-8). Gene set and pathway analyses detected enrichment for genes involved in neurotransmitter/neuropeptide signaling and preferentially expressed in enteric motor neurons controlling peristalsis. PheWAS identified pleiotropic associations with dysmotility syndromes and the response to their pharmacological treatment. The genetic architecture of stool frequency correlates with that of IBS, and UK Biobank participants from the top 1% of stool frequency polygenic score distribution were associated with 5× higher risk of IBS with diarrhea. These findings pave the way for the identification of actionable pathological mechanisms in IBS and the dysmotility syndromes.
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13.
  • Bousquet, Jean, et al. (författare)
  • ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice
  • 2021
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
  • Forskningsöversikt (refereegranskat)abstract
    • Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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14.
  • Calnan, Sonya, et al. (författare)
  • Development of Various Photovoltaic‐Driven Water Electrolysis Technologies for Green Solar Hydrogen Generation
  • 2021
  • Ingår i: Solar RRL. - : John Wiley & Sons. - 2367-198X. ; 6:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Direct solar hydrogen generation via a combination of photovoltaics (PV) and water electrolysis can potentially ensure a sustainable energy supply while minimizing greenhouse emissions. The PECSYS project aims at demonstrating asolar-driven electrochemical hydrogen generation system with an area >10 m2 with high efficiency and at reasonable cost. Thermally integrated PV electrolyzers(ECs) using thin-film silicon, undoped, and silver-doped Cu(In,Ga)Se2 and silicon heterojunction PV combined with alkaline electrolysis to form one unit are developed on a prototype level with solar collection areas in the range from 64 to2600 cm2 with the solar-to-hydrogen (StH) efficiency ranging from 4 to 13%. Electrical direct coupling of PV modules to a proton exchange membrane EC test the effects of bifacially (730 cm2 solar collection area) and to study the long-term operation under outdoor conditions (10 m2 collection area) is also investigated. In both cases, StH efficiencies exceeding 10% can be maintained over the test periods used. All the StH efficiencies reported are based on measured gas outflow using mass flow meters.
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15.
  • Dahal, Prabin, et al. (författare)
  • Temporal distribution of Plasmodium falciparum recrudescence following artemisinin-based combination therapy : an individual participant data meta-analysis
  • 2022
  • Ingår i: Malaria Journal. - : Springer Nature. - 1475-2875. ; 21
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The duration of trial follow-up affects the ability to detect recrudescent infections following anti-malarial treatment. The aim of this study was to explore the proportions of recrudescent parasitaemia as ascribed by genotyping captured at various follow-up time-points in treatment efficacy trials for uncomplicated Plasmodium falciparum malaria.Methods: Individual patient data from 83 anti-malarial efficacy studies collated in the WorldWide Antimalarial Resistance Network (WWARN) repository with at least 28 days follow-up were available. The temporal and cumulative distributions of recrudescence were characterized using a Cox regression model with shared frailty on study-sites. Fractional polynomials were used to capture non-linear instantaneous hazard. The area under the density curve (AUC) of the constructed distribution was used to estimate the optimal follow-up period for capturing a P. falciparum malaria recrudescence. Simulation studies were conducted based on the constructed distributions to quantify the absolute overestimation in efficacy due to sub-optimal follow-up.Results: Overall, 3703 recurrent infections were detected in 60 studies conducted in Africa (15,512 children aged < 5 years) and 23 studies conducted in Asia and South America (5272 patients of all ages). Using molecular genotyping, 519 (14.0%) recurrences were ascribed as recrudescent infections. A 28 day artemether-lumefantrine (AL) efficacy trial would not have detected 58% [95% confidence interval (CI) 47-74%] of recrudescences in African children and 32% [95% CI 15-45%] in patients of all ages in Asia/South America. The corresponding estimate following a 42 day dihydroartemisinin-piperaquine (DP) efficacy trial in Africa was 47% [95% CI 19-90%] in children under 5 years old treated with > 48 mg/kg total piperaquine (PIP) dose and 9% [95% CI 0-22%] in those treated with <= 48 mg/kg PIP dose. In absolute terms, the simulation study found that trials limited to 28 days follow-up following AL underestimated the risk of recrudescence by a median of 2.8 percentage points compared to day 63 estimates and those limited to 42 days following DP underestimated the risk of recrudescence by a median of 2.0 percentage points compared to day 42 estimates. The analysis was limited by few clinical trials following patients for longer than 42 days (9 out of 83 trials) and the imprecision of PCR genotyping which overcalls recrudescence in areas of higher transmission biasing the later distribution.Conclusions: Restricting follow-up of clinical efficacy trials to day 28 for AL and day 42 for DP will miss a proportion of late recrudescent treatment failures but will have a modest impact in derived efficacy. The results highlight that as genotyping methods improve consideration should be given for trials with longer duration of follow-up to detect early indications of emerging drug resistance.
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16.
  • Docherty, Anna R, et al. (författare)
  • GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
  • 2023
  • Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
  • Tidskriftsartikel (refereegranskat)abstract
    • Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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17.
  • Eger, Katrien, et al. (författare)
  • The effect of the COVID-19 pandemic on severe asthma care in Europe : will care change for good?
  • 2022
  • Ingår i: ERJ Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 8:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The coronavirus disease 2019 (COVID-19) pandemic has put pressure on healthcare services, forcing the reorganisation of traditional care pathways. We investigated how physicians taking care of severe asthma patients in Europe reorganised care, and how these changes affected patient satisfaction, asthma control and future care. Methods In this European-wide cross-sectional study, patient surveys were sent to patients with a physician-diagnosis of severe asthma, and physician surveys to severe asthma specialists between November 2020 and May 2021. Results 1101 patients and 268 physicians from 16 European countries contributed to the study. Common physician-reported changes in severe asthma care included use of video/phone consultations (46%), reduced availability of physicians (43%) and change to home-administered biologics (38%). Change to phone/video consultations was reported in 45% of patients, of whom 79% were satisfied or very satisfied with this change. Of 709 patients on biologics, 24% experienced changes in biologic care, of whom 92% were changed to home-administered biologics and of these 62% were satisfied or very satisfied with this change. Only 2% reported worsening asthma symptoms associated with changes in biologic care. Many physicians expect continued implementation of video/phone consultations (41%) and home administration of biologics (52%). Conclusions Change to video/phone consultations and home administration of biologics was common in severe asthma care during the COVID-19 pandemic and was associated with high satisfaction levels in most but not all cases. Many physicians expect these changes to continue in future severe asthma care, though satisfaction levels may change after the pandemic.
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18.
  • Etzold, Sophia, et al. (författare)
  • Nitrogen deposition is the most important environmental driver of growth of pure, even-aged and managed European forests
  • 2020
  • Ingår i: Forest Ecology and Management. - : Elsevier BV. - 0378-1127 .- 1872-7042. ; 458
  • Tidskriftsartikel (refereegranskat)abstract
    • Changing environmental conditions may substantially interact with site quality and forest stand characteristics, and impact forest growth and carbon sequestration. Understanding the impact of the various drivers of forest growth is therefore critical to predict how forest ecosystems can respond to climate change. We conducted a continental-scale analysis of recent (1995–2010) forest volume increment data (ΔVol, m3 ha−1 yr−1), obtained from ca. 100,000 coniferous and broadleaved trees in 442 even-aged, single-species stands across 23 European countries. We used multivariate statistical approaches, such as mixed effects models and structural equation modelling to investigate how European forest growth respond to changes in 11 predictors, including stand characteristics, climate conditions, air and site quality, as well as their interactions. We found that, despite the large environmental gradients encompassed by the forests examined, stand density and age were key drivers of forest growth. We further detected a positive, in some cases non-linear effect of N deposition, most pronounced for beech forests, with a tipping point at ca. 30 kg N ha−1 yr−1. With the exception of a consistent temperature signal on Norway spruce, climate-related predictors and ground-level ozone showed much less generalized relationships with ΔVol. Our results show that, together with the driving forces exerted by stand density and age, N deposition is at least as important as climate to modulate forest growth at continental scale in Europe, with a potential negative effect at sites with high N deposition.
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19.
  • Fehlmann, Tobias, et al. (författare)
  • Common diseases alter the physiological age-related blood microRNA profile
  • 2020
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Aging is a key risk factor for chronic diseases of the elderly. MicroRNAs regulate post-transcriptional gene silencing through base-pair binding on their target mRNAs. We identified nonlinear changes in age-related microRNAs by analyzing whole blood from 1334 healthy individuals. We observed a larger influence of the age as compared to the sex and provide evidence for a shift to the 5’ mature form of miRNAs in healthy aging. The addition of 3059 diseased patients uncovered pan-disease and disease-specific alterations in aging profiles. Disease biomarker sets for all diseases were different between young and old patients. Computational deconvolution of whole-blood miRNAs into blood cell types suggests that cell intrinsic gene expression changes may impart greater significance than cell abundance changes to the whole blood miRNA profile. Altogether, these data provide a foundation for understanding the relationship between healthy aging and disease, and for the development of age-specific disease biomarkers.
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20.
  • Gasparovic, Hrvoje, et al. (författare)
  • Impact of progressive aortic regurgitation on outcomes after left ventricular assist device implantation
  • 2022
  • Ingår i: Heart and Vessels. - : Springer Science and Business Media LLC. - 0910-8327 .- 1615-2573. ; 37:12, s. 1985-1994
  • Tidskriftsartikel (refereegranskat)abstract
    • Aortic regurgitation (AR) following continuous flow left ventricular assist device implantation (cf-LVAD) may adversely impact outcomes. We aimed to assess the incidence and impact of progressive AR after cf-LVAD on prognosis, biomarkers, functional capacity and echocardiographic findings. In an analysis of the PCHF-VAD database encompassing 12 European heart failure centers, patients were dichotomized according to the progression of AR following LVAD implantation. Patients with de-novo AR or AR progression (AR_1) were compared to patients without worsening AR (AR_0). Among 396 patients (mean age 53 ± 12 years, 82% male), 153 (39%) experienced progression of AR over a median of 1.4 years on LVAD support. Before LVAD implantation, AR_1 patients were less frequently diabetic, had lower body mass indices and higher baseline NT-proBNP values. Progressive AR did not adversely impact mortality (26% in both groups, HR 0.91 [95% CI 0.61–1.36]; P = 0.65). No intergroup variability was observed in NT-proBNP values and 6-minute walk test results at index hospitalization discharge and at 6-month follow-up. However, AR_1 patients were more likely to remain in NYHA class III and had worse right ventricular function at 6-month follow-up. Lack of aortic valve opening was related to de-novo or worsening AR (P < 0.001), irrespective of systolic blood pressure (P = 0.67). Patients commonly experience de-novo or worsening AR when exposed to continuous flow of contemporary LVADs. While reducing effective forward flow, worsening AR did not influence survival. However, less complete functional recovery and worse RV performance among AR_1 patients were observed. Lack of aortic valve opening was associated with progressive AR.
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21.
  • Gloy, Viktoria, et al. (författare)
  • The evidence base of US Food and Drug Administration approvals of novel cancer therapies from 2000 to 2020
  • 2023
  • Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 152:12, s. 2474-2484
  • Tidskriftsartikel (refereegranskat)abstract
    • Concerns have been raised that regulatory programs to accelerate approval of cancer drugs in cancer may increase uncertainty about benefits and harms for survival and quality of life (QoL). We analyzed all pivotal clinical trials and all non-pivotal randomized controlled trials (RCTs) for all cancer drugs approved for the first time by the FDA between 2000 and 2020. We report regulatory and trial characteristics. Effects on overall survival (OS), progression-free survival and tumor response were summarized in meta-analyses. Effects on QoL were qualitatively summarized. Between 2000 and 2020, the FDA approved 145 novel cancer drugs for 156 indications based on 190 clinical trials. Half of indications (49%) were approved without RCT evidence; 82% had a single clinical trial only. OS was primary endpoint in 14% of trials and QoL data were available from 25%. The median OS benefit was 2.55 months (IQR, 1.33-4.28) with a mean hazard ratio for OS of 0.75 (95%CI, 0.72-0.79, I-2 = 42). Improvement for QoL was reported for 7 (4%) of 156 indications. Over time, priority review was used increasingly and the mean number of trials per indication decreased from 1.45 to 1.12. More trials reported results on QoL (19% in 2000-2005; 41% in 2016-2020). For 21 years, novel cancer drugs have typically been approved based on one single, often uncontrolled, clinical trial, measuring surrogate endpoints. This leaves cancer patients without solid evidence that novel drugs improve their survival or QoL and there is no indication towards improvement.
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22.
  • Govsyeyev, Nicholas, et al. (författare)
  • Rivaroxaban in Patients with Symptomatic Peripheral Artery Disease after Lower Extremity Bypass Surgery with Venous and Prosthetic Conduits
  • 2023
  • Ingår i: Journal of Vascular Surgery. - : Elsevier. - 0741-5214 .- 1097-6809. ; 77:4, s. 1107-1118.e2
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Patients with peripheral artery disease (PAD) requiring lower extremity revascularization (LER) are at high risk of adverse limb and cardiovascular events. VOYAGER PAD demonstrated that rivaroxaban significantly reduced this risk with an overall favorable net benefit in patients undergoing surgical revascularization; however, the efficacy and safety in those treated by surgical bypass including stratified by bypass conduit (venous or prosthetic) has not been described.METHODS: In the VOYAGER PAD trial, patients with PAD after surgical and endovascular infrainguinal LER were randomized to rivaroxaban 2.5 mg twice daily or placebo and followed for a median of 28 months. The primary endpoint was a composite of acute limb ischemia (ALI), major amputation of vascular etiology, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was Thrombolysis in Myocardial Infarction (TIMI) major bleeding. Index procedure details including conduit type (venous or prosthetic) were collected at baseline.RESULTS: Among 6564 randomized, 2185 (33%) underwent surgical LER. Of these, surgical bypass was performed in 1448 (66%), using prosthetic conduit in 773 (53%) and venous in 646 (45%). Adjusting for baseline differences and anatomic factors, the risk for unplanned limb revascularization in the placebo arm was 2.5-fold higher for those receiving prosthetic versus venous conduits (adjHR 2.53, 95% CI 1.65-3.90; p<0.001) while the risk for ALI was 3 times greater (adjHR 3.07, 95% CI 1.84-5.11; p<0.001). Rivaroxaban reduced the primary outcome in patients treated with bypass surgery (HR 0.78, 95% CI 0.62-0.98) with consistent benefits in those receiving venous (HR 0.66, 95% CI 0.49-0.96) and prosthetic (HR 0.87, 95% CI 0.66-1.15) conduits (pinteraction 0.254). In the overall trial, TIMI major bleeding was increased with rivaroxaban; however, numbers in those treated with bypass surgery were low (5 with rivaroxaban, 9 with placebo, HR 0.55, 95% CI 0.18-1.65) and not powered to show statistical significance.CONCLUSIONS: Surgical bypass with prosthetic conduit is associated with significantly higher rates of major adverse limb events relative to venous conduits even after adjusting for patient and anatomic characteristics. Adding rivaroxaban 2.5 mg twice daily to aspirin or dual antiplatelet therapy significantly reduces this risk, increases bleeding, but has a favorable benefit risk in patients treated with bypass surgery and regardless of conduit type. Rivaroxaban should be considered after lower extremity bypass for symptomatic PAD to reduce ischemic complications of the heart, limb, and brain.
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23.
  • Jakus, Nina, et al. (författare)
  • Improved survival of left ventricular assist device carriers in Europe according to implantation eras : results from the PCHF-VAD registry
  • 2022
  • Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 24:7, s. 1305-1315
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Temporal changes in patient selection and major technological developments have occurred in the field of left ventricular assist devices (LVADs), yet analyses depicting this trend are lacking for Europe. We describe the advances of European LVAD programmes from the PCHF-VAD registry across device implantation eras. Methods and results: Of 583 patients from 13 European centres in the registry, 556 patients (mean age 53 ± 12 years, 82% male) were eligible for this analysis. Patients were divided into eras (E) by date of LVAD implantation: E1 from December 2006 to December 2012 (6 years), E2 from January 2013 to January 2020 (7 years). Patients implanted more recently were older with more comorbidities, but less acutely ill. Receiving an LVAD in E2 was associated with improved 1-year survival in adjusted analysis (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.35–0.98; p = 0.043). LVAD implantation in E2 was associated with a significantly lower chance of heart transplantation (adjusted HR 0.40, 95% CI 0.23–0.67; p = 0.001), and lower risk of LVAD-related infections (adjusted HR 0.64, 95% CI 0.43–0.95; p = 0.027), both in unadjusted and adjusted analyses. The adjusted risk of haemocompatibility-related events decreased (HR 0.60, 95% CI 0.39–0.91; p = 0.016), while heart failure-related events increased in E2 (HR 1.67, 95% CI 1.02–2.75; p = 0.043). Conclusion: In an analysis depicting the evolving landscape of continuous-flow LVAD carriers in Europe over 13 years, a trend towards better survival was seen in recent years, despite older recipients with more comorbidities, potentially attributable to increasing expertise of LVAD centres, improved patient selection and pump technology. However, a smaller chance of undergoing heart transplantation was noted in the second era, underscoring the relevance of improved outcomes on LVAD support.
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24.
  • Jones, Michael P., et al. (författare)
  • Clusters of community-dwelling individuals empirically derived from stool diaries correspond with clinically meaningful outcomes
  • 2021
  • Ingår i: European Journal of Gastroenterology and Hepathology. - : Lippincott Williams & Wilkins. - 0954-691X .- 1473-5687. ; 33:1S, s. e740-e745
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Functional gastrointestinal disorders (FGIDs) are diagnosed according to expert consensus criteria based on recall of symptoms over periods of 3 months or longer. Whether the expert opinion concords with underlying disease process and whether individual recall is accurate are both in doubt. This study aimed to identify naturally occurring clusters of individuals with respect to symptom pattern, evaluate their significance, compare cluster profiles with expert opinion and evaluate their temporal stability.Methods  As part of a random population study of FGID-related symptoms, we first explored the use of prospective stool and symptom diaries combined with empirical grouping of individuals into clusters using nonhierarchical cluster analysis.Results The analysis identified two clusters of individuals, one of which was characterized by elevated scores on all domains of symptoms (26% of the sample) and one that was low to average on all domains (74% of the sample). Cluster membership was found to be stable over a long interval. Clusters were found to differ on most domains of quality-of-life (d = 0.46–0.74), self-rated health (d = −0.42) and depression (d = −0.42) but not anxiety. Prevalence of clinically diagnosed irritable bowel syndrome (IBS) was higher in the more impacted cluster (33%) compared with the healthy cluster (13%; P < 0.0001).Conclusion A naturalistic classification of individuals challenges consensus criteria in showing that some IBS individuals have a symptom experience not unlike health. The proposed approach has demonstrated temporal stability over time, unlike consensus criteria. A naturalistic disease classification system may have practical advantages over consensus criteria when supported by a decision-analytic system.
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25.
  • Karlsson, Tomas, 1964-, et al. (författare)
  • The MEFISTO and WPT Electric Field Sensors of the Plasma Wave Investigation on the BepiColombo Mio Spacecraft Measurements of Low and High Frequency Electric Fields at Mercury
  • 2020
  • Ingår i: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 216:8
  • Forskningsöversikt (refereegranskat)abstract
    • This paper describes the design of MEFISTO (Mercury Electric Field In-Situ Tool) and WPT (Wire Probe Antenna) electric field sensors for Plasma Wave Investigation (PWI) on the BepiColombo Mio spacecraft (Mercury Magnetospheric Orbiter, MMO). The two sensors will enable the first observations of electric fields, plasma waves and radio waves in and around the Hermean magnetosphere and exosphere. MEFISTO and WPT are dipole antennas with 31.6 m tip-to-tip length. Each antenna element has a spherical probe at each end of the wire (15 m length). They are extended orthogonally in the spin plane of the spacecraft and enable measurements of the electric field in the frequency range of DC to 10 MHz by the connection to two sets of receivers, EWO for a lower frequency range and SORBET for higher frequencies. In the initial operations after the launch (20 Oct. 2018), we succeeded to confirm the health of both antennas and to release the launch lock of the WPT. After Mercury orbit insertion planned at the end of 2025, both sensors will be fully deployed and activate full operations of the PWI electric field measurements.
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26.
  • Kurilshikov, Alexander, et al. (författare)
  • Large-scale association analyses identify host factors influencing human gut microbiome composition
  • 2021
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 53:2, s. 156-165
  • Tidskriftsartikel (refereegranskat)abstract
    • To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 x 10(-8)) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 x 10(-20)), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 x 10(-10) < P < 5 x 10(-8)) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis.
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27.
  • Lantz, Adam, et al. (författare)
  • Measuring the migration of surgical specialists
  • 2020
  • Ingår i: Surgery (United States). - : Elsevier BV. - 0039-6060 .- 1532-7361. ; 168:3, s. 550-557
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The lack of access to essential surgical care in low-income countries is aggravated by emigration of locally-trained surgical specialists to more affluent regions. Yet, the global diaspora of surgeons, obstetricians, and anesthesiologists from low-income and middle-income countries has never been fully described and compared with those who have remained in their country of origin. It is also unclear whether the surgical workforce is more affected by international migration than other medical specialists. In this study, we aimed to quantify the proportion of surgical specialists originating from low-income and middle-income countries that currently work in high-income countries. Methods: We retrieved surgical workforce data from 48 high-income countries and 102 low-income and middle-income countries using the database of the World Health Organization Global Surgical Workforce. We then compared this domestic workforce with more granular data on the country of initial medical qualification of all surgeons, anesthesiologists, and obstetricians made available for 14 selected high-income countries to calculate the proportion of surgical specialists working abroad. Results: We identified 1,118,804 specialist surgeons, anesthesiologists, or obstetricians from 102 low-income and middle-income countries, of whom 33,021 (3.0%) worked in the 14 included high-income countries. The proportion of surgical specialists abroad was greatest for the African and South East Asian regions (12.8% and 12.1%). The proportion of specialists abroad was not greater for surgeons, anesthesiologists, or obstetricians than for physicians and other medical specialists (P = .465). Overall, the countries with the lowest remaining density of surgical specialists were also the countries from which the largest proportion of graduates were now working in high-income countries (P = .011). Conclusion: A substantial proportion of all surgeons, anesthesiologists, and obstetricians from low-income and middle-income countries currently work in high-income countries. In addition to decreasing migration from areas of surgical need, innovative strategies to retain and strengthen the surgical workforce could involve engaging this large international pool of surgical specialists and instructors.
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28.
  • Lok, Veeleah, et al. (författare)
  • Changes in anxiety and depression during the COVID-19 pandemic in the European population : A meta-analysis of changes and associations with restriction policies
  • 2023
  • Ingår i: European psychiatry. - 0924-9338 .- 1778-3585. ; 66:1
  • Forskningsöversikt (refereegranskat)abstract
    • Background. Early studies of common mental disorders (CMDs) during the COVID-19 pandemic mainly report increases; however, more recent findings have been mixed. Also, studies assessing the effects of restriction measures on CMDs show varied results. The aim of this meta-analysis was to assess changes in levels of CMDs from pre-/early to during the pandemic and the effects of restriction policies in the European population.Methods. We searched for studies assessing both pre-pandemic and peri-pandemic self-reported emotional distress and symptoms of depression or anxiety among nationally/regionally representative samples in Europe and collected microdata from those studies. Estimates of corona containment index were related to changes in CMDs using random-effects meta-regression.Results. Our search strategy resulted in findings from 15 datasets drawn from 8 European countries being included in the meta-analysis. There was no evidence of change in the prevalence of emotional distress, anxiety, or depression from before to during the pandemic; but from early pandemic periods to later periods, there were significant decreases in emotional distress and anxiety. Increased school restrictions and social distancing were associated with small increases in self-reported emotional distress.Conclusions. Despite initial concerns of increased emotional distress and mental illness due to the COVID-19 pandemic, the results from this meta-analysis indicate that there was a decrease in emotional distress and no change in anxiety or depression in the general population in Europe. Overall, our findings support the importance of strong governance when implementing periodic and robust restriction measures to combat the spread of COVID-19.
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29.
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30.
  • Maksimovic, M., et al. (författare)
  • First observations and performance of the RPW instrument on board the Solar Orbiter mission
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 656
  • Tidskriftsartikel (refereegranskat)abstract
    • The Radio and Plasma Waves (RPW) instrument on the ESA Solar Orbiter mission is designed to measure in situ magnetic and electric fields and waves from the continuum up to several hundred kHz. The RPW also observes solar and heliospheric radio emissions up to 16 MHz. It was switched on and its antennae were successfully deployed two days after the launch of Solar Orbiter on February 10, 2020. Since then, the instrument has acquired enough data to make it possible to assess its performance and the electromagnetic disturbances it experiences. In this article, we assess its scientific performance and present the first RPW observations. In particular, we focus on a statistical analysis of the first observations of interplanetary dust by the instrument's Thermal Noise Receiver. We also review the electro-magnetic disturbances that RPW suffers, especially those which potential users of the instrument data should be aware of before starting their research work.
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31.
  • Maksimovic, M., et al. (författare)
  • The Solar Orbiter Radio and Plasma Waves (RPW) instrument
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 642
  • Tidskriftsartikel (refereegranskat)abstract
    • The Radio and Plasma Waves (RPW) instrument on the ESA Solar Orbiter mission is described in this paper. This instrument is designed to measure in-situ magnetic and electric fields and waves from the continuous to a few hundreds of kHz. RPW will also observe solar radio emissions up to 16 MHz. The RPW instrument is of primary importance to the Solar Orbiter mission and science requirements since it is essential to answer three of the four mission overarching science objectives. In addition RPW will exchange on-board data with the other in-situ instruments in order to process algorithms for interplanetary shocks and type III langmuir waves detections.
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32.
  • Mansoor, Rashid, et al. (författare)
  • Haematological consequences of acute uncomplicated falciparum malaria : a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data
  • 2022
  • Ingår i: BMC Medicine. - : Springer Nature. - 1741-7015. ; 20:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundPlasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia.MethodsIndividual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall >= 25% at day 3 and day 7.ResultsA total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to >= 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39-3.05], p < 0.001).ConclusionsIn patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery.
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33.
  • Meili, Kaspar Walter, et al. (författare)
  • An initiative to develop capability-adjusted life years in Sweden (CALY-SWE) : Selecting capabilities with a Delphi panel and developing the questionnaire
  • 2022
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Capability-adjusted life years Sweden (CALY-SWE) are a new Swedish questionnaire-based measure for quality of life based on the capability approach. CALY-SWE are targeted towards use in cost-effectiveness evaluations of social welfare consequences. Here, we first motivate the measure both from a theoretical and from a Swedish policy-making perspective. Then, we outline the core principles of the measure, namely the relation to the capability approach, embedded equity considerations inspired by the fair-innings approach, and the bases for which capabilities should be considered. The aims were to 1) the most vital capabilities for individuals in Sweden, 2) to define a sufficient level of each identified capability to lead a flourishing life, and to 3) develop a complete questionnaire for the measurement of the identified capabilities.Material and methods: For the selection of capabilities, we used a Delphi process with Swedish civil society representants. To inform the questionnaire development, we conducted a web survey in three versions, with each Swedish 500 participants, to assess the distribution of capabilities that resulted from the Delphi process in the Swedish population. Each version was formulated with different strictness so that less strict wordings of a capability level would apply to a larger share of participants. All versions also included questions on inequality aversion regarding financial, educational, and health capabilities.Results: The Delphi process resulted in the following six capabilities: Financial situation & housing, health, social relations, occupations, security, and political & civil rights. We formulated the final phrasing for the questionnaire based on normative reasons and the distribution of capabilities in the population while taking into account inequality aversion.Conclusion: We developed a capability-based model for cost effectiveness economic evaluations of broader social consequences, specific to the Swedish context.
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34.
  • Meili, Kaspar Walter, 1989- (författare)
  • Capability for broader cost-effectiveness in public health and social welfare : developing, valuing, and applyingcapability-adjusted life years Sweden (CALY-SWE)
  • 2024
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Spending in social welfare areas such as healthcare, wider public health, education, and social care consumes a major part of the public budget. Cost-effective resource allocation is a moral obligation towards both taxpayers and beneficiaries: tax money should be used efficiently, and it should be transparently accounted for. After all, economical management of resources is important for sustaining future prosperity and for addressing fundamental challenges such as climate change and demographic shift. In healthcare, cost‐effectiveness using quality-adjusted life years (QALYs) is a well-established tool to inform policymakers. Using cost per QALY implies that health-related quality of life (QoL), and not money, is an end on its own. Moreover, cost per QALY allows one to compare unrelated interventions by measuring the effects on the common QALY scale. However, for actors concerned with broader social welfare, such as the Swedish municipalities, QALYs may be less useful because their measurement focus is largely limited to health. Comparable outcome measures for broader social welfare are still sparsely available and employed, and a context-specific measure for Sweden is lacking. The aim of this thesis was to develop, value, and apply capability-adjusted life years Sweden (CALY‐SWE), a QoL outcome measure conceptually based on the capability approach, for broader social welfare and specific for Sweden.Within study 1, we organized a Delphi panel to select relevant capability attributes and then developed the phrasing for the questionnaire. The resulting questionnaire contains six attributes –health, social relations, financial situation & housing, security, occupation, and political & civil rights – each with three answer levels. The phrasing integrates an implicit threshold so that the sensitivity is focused on the lower range of the scale, thus incorporating equity considerations that relate to sufficientarianism and prioritarianism. In study 2, we developed a value set consisting of all quality weights for the 729 possible CALY-SWE states. We relied on health economic outcome methodology, namely hybrid modelling of discrete choice and time trade-off data that we collected in a cross-sectional web survey with representative sampling. This value set allows to aggregate the CALY-SWE answers into a single quality weight that can be used in cost‐effectiveness analysis to calculate CALYs. In study 3, we applied the CALY-SWE questionnaire and value set to describe the capability distribution in a cross-sectional representative sample of the Swedish population. In a framework of group comparisons, we estimated capability inequalities and shortfalls for different population groups. The results showed that there are capability inequalities for *disadvantage groups* as well as for groups with discriminative inequalities – *plurality groups*, for example between lower and higher education. For study 4, we applied CALY‐SWE in a cost‐effectiveness application to model the effects of a payroll tax reduction in Sweden from 2007 to 2016 (during the financial crisis) on young people not in employment, education, or training (NEET). The intervention was likely cost-effective from a societal perspective, but only with limited probability from a fiscal perspective, although definite statements regarding cost-effectiveness are challenging because a threshold value for a CALY is still lacking. The final chapter discusses the measure’s development, including normative choices, in relation to the Swedish social welfare and policy context, the capability framework as suggested by Amartya Sen, distributive justice, and other outcome measures in cost‐effectiveness evaluations. Important work remains – for example, assessing psychometric properties, developing the conceptualization of the 0 to 1 anchor scale for capability weights, and assessing a threshold value for a CALY. In conclusion, with the questionnaire development, value set elicitation, and demonstration of applications, important steps for CALY‐SWE were accomplished. Cost‐effectiveness evaluations in wider social welfare and public health using CALY-SWE are now possible. 
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35.
  • Meili, Kaspar Walter, 1989-, et al. (författare)
  • Capability inequality: Does disadvantage or plurality matter more for policy? : A Swedish cross-sectional study on the population distribution and group differences of capability using CALY-SWE
  • 2024
  • Ingår i: Social Sciences & Humanities Open. - : Elsevier. - 2590-2911. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • A better understanding of population distributions of capability and inequalities is relevant for public health and social welfare. We surveyed 3639 representatively sampled individuals on background characteristics and on self-reported capability using the capability-adjusted life years Sweden (CALY-SWE) questionnaire, which enables aggregating attribute-level answers into a quality weight score.We analysed the resulting capability distribution by comparing subgroups. Subgroups were formed along axes of inequality that we selected based on theoretical reasoning and relevance. We stratified into groupings of plurality and disadvantage, based on the human dignity principle and the needs and solidarity principle featured in the Swedish platform for healthcare priority-setting. While disadvantage factors come with inherent need-related disadvantages that explain inequality, such as unemployment, no such normatively acceptable reason exist for plurality factors, such as gender.The results averaged per individual showed marked inequalities for the disadvantage groups of individuals with poor self-rated health, long-term sick leave unemployment, and payment difficulties. For plurality groups, the largest inequalities occurred in groups with lower education and groups residing in urban areas, but generally inequalities were lower than disadvantage groups.On the population level, the largest aggregated disability inequalities occurred for self-reported ever NEET (persons who were ever involuntarily not in employment, education or training from age 16 to 29) and payment difficulties groups. Additionally, we assessed the contribution of covariates to these inequalities by counterfactually altering one covariate at a time in a multinomial logistic model of the CALY-SWE attribute-level answers. The most relevant covariates were employment situation, financial difficulties, income, and age group.For policy-making, this indicates the importance of both plurality and disadvantage inequality axes. Prioritization should adopt nuanced contextualizations of inequality when broadening the perspective beyond healthcare to wider public health and social welfare, for example, elderly care and education.
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36.
  • Meili, Kaspar Walter, et al. (författare)
  • Eliciting a value set for the Swedish capability-adjusted life years instrument (CALY-SWE)
  • 2024
  • Ingår i: Quality of Life Research. - : Springer Nature. - 0962-9343 .- 1573-2649. ; 33:1, s. 59-72
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Our aim was to elicit a value set for Capability-Adjusted Life Years Sweden (CALY-SWE); a capability-grounded quality of life instrument intended for use in economic evaluations of social interventions with broad consequences beyond health.Methods: Building on methods commonly used in the quality-adjusted life years EQ-5D context, we collected time-trade off (TTO) and discrete choice experiment (DCE) data through an online survey from a general population sample of 1697 Swedish participants. We assessed data quality using a score based on the severity of inconsistencies. For generating the value set, we compared different model features, including hybrid modeling of DCE and TTO versus TTO data only, censoring of TTO answers, varying intercept, and accommodating for heteroskedasticity. We also assessed the models’ DCE logit fidelity to measure agreement with potentially less-biased DCE data. To anchor the best capability state to 1 on the 0 to 1 scale, we included a multiplicative scaling factor.Results: We excluded 20% of the TTO answers of participants with the largest inconsistencies to improve data quality. A hybrid model with an anchor scale and censoring was chosen to generate the value set; models with heteroskedasticity considerations or individually varying intercepts did not offer substantial improvement. The lowest capability weight was 0.114. Health, social relations, and finance and housing attributes contributed the largest capability gains, followed by occupation, security, and political and civil rights.Conclusion: We elicited a value set for CALY-SWE for use in economic evaluations of interventions with broad social consequences.
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37.
  • Meili, Kaspar Walter, et al. (författare)
  • Perceived changes in capability during the COVID-19 pandemic : A Swedish cross-sectional study from June 2020
  • 2022
  • Ingår i: Scandinavian Journal of Public Health. - : Sage Publications. - 1403-4948 .- 1651-1905. ; 50:1, s. 102-110
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Measures against COVID-19 potentially impact quality of life in different ways. The capability approach by Amartya Sen with a broad and consistent framework for measuring quality of life is suited to capture the various consequences. We aimed to examine (a) whether individuals experienced change in 10 capability dimensions during the first half of 2020, (b) which dimensions were affected most, and (c) whether changes were unequally distributed in terms of gender, education, income, geography, housing, living situation and place of birth.Methods: We assessed self-reported capability change in Sweden in 10 capability dimensions in a cross-sectional online survey among 500 participants on a five-item Likert scale. We analysed the distribution of answers by comparing the balance of positive and negative perceived changes and used mixed effects logistic regression to examine associations with background characteristics of the participants.Results: Reported perceived negative changes outweighed positive changes, and a higher proportion stated negative perceived changes if they also stated having low capability in the same dimension. In the capabilities of financial situation, political resources and health, the proportions of perceived negative change were highest. Odds for perceived negative change compared to no or positive change were higher for higher incomes, living in medium-sized municipalities, being born outside Europe, living in the south of Sweden, and renting instead of owning housing.Conclusions: Self-reported negative capability change, and associated inequalities related to socioeconomic position, place of birth and regional residence should be of concern for policymakers.
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38.
  • Mullins, Niamh, et al. (författare)
  • Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
  • 2022
  • Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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39.
  • Nykänen, Anton, et al. (författare)
  • Toward Accurate Post-Born-Oppenheimer Molecular Simulations on Quantum Computers: An Adaptive Variational Eigensolver with Nuclear-Electronic Frozen Natural Orbitals
  • 2023
  • Ingår i: Journal of Chemical Theory and Computation. - 1549-9626 .- 1549-9618. ; 19:24, s. 9269-9277
  • Tidskriftsartikel (refereegranskat)abstract
    • Nuclear quantum effects such as zero-point energy and hydrogen tunneling play a central role in many biological and chemical processes. The nuclear-electronic orbital (NEO) approach captures these effects by treating selected nuclei quantum mechanically on the same footing as electrons. On classical computers, the resources required for an exact solution of NEO-based models grow exponentially with system size. By contrast, quantum computers offer a means of solving this problem with polynomial scaling. However, due to the limitations of current quantum devices, NEO simulations are confined to the smallest systems described by minimal basis sets, whereas realistic simulations beyond the Born-Oppenheimer approximation require more sophisticated basis sets. For this purpose, we herein extend a hardware-efficient ADAPT-VQE method to the NEO framework in the frozen natural orbital (FNO) basis. We demonstrate on H2 and D2 molecules that the NEO-FNO-ADAPT-VQE method reduces the CNOT count by several orders of magnitude relative to the NEO unitary coupled cluster method with singles and doubles while maintaining the desired accuracy. This extreme reduction in the CNOT gate count is sufficient to permit practical computations employing the NEO method─an important step toward accurate simulations involving nonclassical nuclei and non-Born-Oppenheimer effects on near-term quantum devices. We further show that the method can capture isotope effects, and we demonstrate that inclusion of correlation energy systematically improves the prediction of difference in the zero-point energy (ΔZPE) between isotopes.
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40.
  • Pereira, Joao, et al. (författare)
  • Electrooptic control of the modal distribution in a silicate fiber
  • 2022
  • Ingår i: Optics Express. - : Optica Publishing Group (formerly OSA). - 1094-4087. ; 30:8, s. 12474-12483
  • Tidskriftsartikel (refereegranskat)abstract
    • We demonstrate the use of the electrooptic effect to control the propagation constant of the guided modes in silicate few mode fibers with internal electrodes. The electrooptic effect induces a perturbation of the fiber's refractive index profile that controls intermodal interference. To increase the electrooptic effect the silicate fibers are poled. The response time is in the nanosecond range. 
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41.
  • Petch, Jeremy, et al. (författare)
  • Optimizing warfarin dosing for patients with atrial fibrillation using machine learning
  • 2024
  • Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • While novel oral anticoagulants are increasingly used to reduce risk of stroke in patients with atrial fibrillation, vitamin K antagonists such as warfarin continue to be used extensively for stroke prevention across the world. While effective in reducing the risk of strokes, the complex pharmacodynamics of warfarin make it difficult to use clinically, with many patients experiencing under- and/or over- anticoagulation. In this study we employed a novel implementation of deep reinforcement learning to provide clinical decision support to optimize time in therapeutic International Normalized Ratio (INR) range. We used a novel semi-Markov decision process formulation of the Batch-Constrained deep Q-learning algorithm to develop a reinforcement learning model to dynamically recommend optimal warfarin dosing to achieve INR of 2.0-3.0 for patients with atrial fibrillation. The model was developed using data from 22,502 patients in the warfarin treated groups of the pivotal randomized clinical trials of edoxaban (ENGAGE AF-TIMI 48), apixaban (ARISTOTLE) and rivaroxaban (ROCKET AF). The model was externally validated on data from 5730 warfarin-treated patients in a fourth trial of dabigatran (RE-LY) using multilevel regression models to estimate the relationship between center-level algorithm consistent dosing, time in therapeutic INR range (TTR), and a composite clinical outcome of stroke, systemic embolism or major hemorrhage. External validation showed a positive association between center-level algorithm-consistent dosing and TTR (R-2 = 0.56). Each 10% increase in algorithm-consistent dosing at the center level independently predicted a 6.78% improvement in TTR (95% CI 6.29, 7.28; p < 0.001) and a 11% decrease in the composite clinical outcome (HR 0.89; 95% CI 0.81, 1.00; p = 0.015). These results were comparable to those of a rules-based clinical algorithm used for benchmarking, for which each 10% increase in algorithm-consistent dosing independently predicted a 6.10% increase in TTR (95% CI 5.67, 6.54, p < 0.001) and a 10% decrease in the composite outcome (HR 0.90; 95% CI 0.83, 0.98, p = 0.018). Our findings suggest that a deep reinforcement learning algorithm can optimize time in therapeutic range for patients taking warfarin. A digital clinical decision support system to promote algorithm-consistent warfarin dosing could optimize time in therapeutic range and improve clinical outcomes in atrial fibrillation globally.
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42.
  • Radhoe, Sumant P., et al. (författare)
  • How does age affect outcomes after left ventricular assist device implantation : results from the PCHF-VAD registry
  • 2023
  • Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 10:2, s. 884-894
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Use of left ventricular assist devices (LVADs) in older patients has increased, and assessing outcomes in older LVAD recipients is important. Therefore, this study aimed to investigate associations between age and outcomes after continuous-flow LVAD (cf-LVAD) implantation. Methods and results: Cf-LVAD patients from the multicentre European PCHF-VAD registry were included and categorized into those <50, 50–64, and ≥65 years old. The primary endpoint was all-cause mortality. Among secondary outcomes were heart failure (HF) hospitalizations, right ventricular (RV) failure, haemocompatibility score, bleeding events, non-fatal thromboembolic events, and device-related infections. Of 562 patients, 184 (32.7%) were <50, 305 (54.3%) were aged 50–64, whereas 73 (13.0%) were ≥65 years old. Median follow-up was 1.1 years. Patients in the oldest age group were significantly more often designated as destination therapy (DT) candidates (61%). A 10 year increase in age was associated with a significantly higher risk of mortality (hazard ratio [HR] 1.34, 95% confidence interval [CI] [1.15–1.57]), intracranial bleeding (HR 1.49, 95% CI [1.10–2.02]), and non-intracranial bleeding (HR 1.30, 95% CI [1.09–1.56]), which was confirmed by a higher mean haemocompatibility score (1.37 vs. 0.77, oldest vs. youngest groups, respectively, P = 0.033). Older patients suffered from less device-related infections requiring systemic antibiotics. No age-related differences were observed in HF-related hospitalizations, ventricular arrhythmias, pump thrombosis, non-fatal thromboembolic events, or RV failure. Conclusions: In the PCHF-VAD registry, higher age was associated with increased risk of mortality, and especially with increased risk of major bleeding, which is particularly relevant for the DT population. The risks of HF hospitalizations, pump thrombosis, ventricular arrhythmia, or RV failure were comparable. Strikingly, older patients had less device-related infections.
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43.
  • Radhoe, Sumant P., et al. (författare)
  • Sex-related differences in left ventricular assist device utilization and outcomes : results from the PCHF-VAD registry
  • 2023
  • Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 10:2, s. 1054-1065
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Data on sex and left ventricular assist device (LVAD) utilization and outcomes have been conflicting and mostly confined to US studies incorporating older devices. This study aimed to investigate sex-related differences in LVAD utilization and outcomes in a contemporary European LVAD cohort. Methods and results: This analysis is part of the multicentre PCHF-VAD registry studying continuous-flow LVAD patients. The primary outcome was all-cause mortality. Secondary outcomes included ventricular arrhythmias, right ventricular failure, bleeding, thromboembolism, and the haemocompatibility score. Multivariable Cox regression models were used to assess associations between sex and outcomes. Overall, 457 men (81%) and 105 women (19%) were analysed. At LVAD implant, women were more often in Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 or 2 (55% vs. 41%, P = 0.009) and more often required temporary mechanical circulatory support (39% vs. 23%, P = 0.001). Mean age was comparable (52.1 vs. 53.4 years, P = 0.33), and median follow-up duration was 344 [range 147–823] days for women and 435 [range 190–816] days for men (P = 0.40). No significant sex-related differences were found in all-cause mortality (hazard ratio [HR] 0.79 for female vs. male sex, 95% confidence interval [CI] [0.50–1.27]). Female LVAD patients had a lower risk of ventricular arrhythmias (HR 0.56, 95% CI [0.33–0.95]) but more often experienced right ventricular failure. No significant sex-related differences were found in other outcomes. Conclusions: In this contemporary European cohort of LVAD patients, far fewer women than men underwent LVAD implantation despite similar clinical outcomes. This is important as the proportion of female LVAD patients (19%) was lower than the proportion of females with advanced HF as reported in previous studies, suggesting underutilization. Also, female patients were remarkably more often in INTERMACS profile 1 or 2, suggesting later referral for LVAD therapy. Additional research in female patients is warranted.
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44.
  • Rudolfson, Niclas, et al. (författare)
  • South Africa and the Surgical Diaspora-A Hub for Surgical Migration and Training
  • 2023
  • Ingår i: World Journal of Surgery. - 1432-2323. ; 47:7, s. 1684-1691
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The shortage of trained surgeons, anesthesiologists, and obstetricians is a major contributor to the unmet need for surgical care in low- and middle-income countries, and the shortage is aggravated by migration to higher-income countries.METHODS: We performed a cross-sectional observational study, combining individual-level data of 43,621 physicians from the Health Professions Council of South Africa with data from the registers of 14 high-income countries, and international statistics on surgical workforce, in order to quantify migration to and from South Africa in both absolute and relative terms.RESULTS: Of 6670 surgeons, anesthesiologists, and obstetricians in South Africa, a total of 713 (11%) were foreign medical graduates, and 396 (6%) were from a low- or middle-income country. South Africa was an important destination primarily for physicians originating from low-income countries; 2% of all surgeons, anesthesiologists, and obstetricians from low- and middle-income countries were registered in South Africa, and 6% in the other 14 recipient countries. A total of 1295 (16%) South African surgeons, anesthesiologists, and obstetricians worked in any of the 14 studied high-income countries.CONCLUSION: South Africa is an important regional hub for surgical migration and training. A notable proportion of surgical specialists in South Africa were medical graduates from other low- or middle-income countries, whereas migration out of South Africa to high-income countries was even larger.
  •  
45.
  • Schunk, Stefan J., et al. (författare)
  • Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality
  • 2021
  • Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:18, s. 1742-1756
  • Tidskriftsartikel (refereegranskat)abstract
    • AimsInflammation plays an important role in cardiovascular disease (CVD) development. The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models. Components of the NLRP3 inflammasome pathway such as interleukin-1β can therapeutically be targeted. Associations of genetically determined inflammasome-mediated systemic inflammation with CVD and mortality in humans are unknown.Methods and resultsWe explored the association of genetic NLRP3 variants with prevalent CVD and cardiovascular mortality in 538 167 subjects on the individual participant level in an explorative gene-centric approach without performing multiple testing. Functional relevance of single-nucleotide polymorphisms on NLRP3 inflammasome activation has been evaluated in monocyte-enriched peripheral blood mononuclear cells (PBMCs). Genetic analyses identified the highly prevalent (minor allele frequency 39.9%) intronic NLRP3 variant rs10754555 to affect NLRP3 gene expression. rs10754555 carriers showed significantly higher C-reactive protein and serum amyloid A plasma levels. Carriers of the G allele showed higher NLRP3 inflammasome activation in isolated human PBMCs. In carriers of the rs10754555 variant, the prevalence of coronary artery disease was significantly higher as compared to non-carriers with a significant interaction between rs10754555 and age. Importantly, rs10754555 carriers had significantly higher risk for cardiovascular mortality during follow-up. Inflammasome inducers (e.g. urate, triglycerides, apolipoprotein C3) modulated the association between rs10754555 and mortality.ConclusionThe NLRP3 intronic variant rs10754555 is associated with increased systemic inflammation, inflammasome activation, prevalent coronary artery disease, and mortality. This study provides evidence for a substantial role of genetically driven systemic inflammation in CVD and highlights the NLRP3 inflammasome as a therapeutic target.
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46.
  •  
47.
  • Tahmasian, Masoud, et al. (författare)
  • ENIGMA-Sleep : Challenges, opportunities, and the road map
  • 2021
  • Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 30:6
  • Forskningsöversikt (refereegranskat)abstract
    • Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, individual studies usually have limitations to identifying consistent and reproducible effects, including modest sample sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large-scale multi-centre effort in sleep research, in order to increase the number of samples, and harmonize the methods of data collection, preprocessing and analysis using pre-registered well-established protocols. The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium provides a powerful collaborative framework for combining datasets across individual sites. Recently, we have launched the ENIGMA-Sleep working group with the collaboration of several institutes from 15 countries to perform large-scale worldwide neuroimaging and genetics studies for better understanding the neurobiology of impaired sleep quality in population-based healthy individuals, the neural consequences of sleep deprivation, pathophysiology of sleep disorders, as well as neural correlates of sleep disturbances across various neuropsychiatric disorders. In this introductory review, we describe the details of our currently available datasets and our ongoing projects in the ENIGMA-Sleep group, and discuss both the potential challenges and opportunities of a collaborative initiative in sleep medicine.
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48.
  • Timmins, Iain R., et al. (författare)
  • International pooled analysis of leisure-time physical activity and premenopausal breast cancer in women from 19 cohorts
  • 2024
  • Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 42:8, s. 927-939
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: There is strong evidence that leisure-time physical activity is protective against postmenopausal breast cancer risk but the association with premenopausal breast cancer is less clear. The purpose of this study was to examine the association of physical activity with the risk of developing premenopausal breast cancer.METHODS: We pooled individual-level data on self-reported leisure-time physical activity across 19 cohort studies comprising 547,601 premenopausal women, with 10,231 incident cases of breast cancer. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for associations of leisure-time physical activity with breast cancer incidence. HRs for high versus low levels of activity were based on a comparison of risk at the 90th versus 10th percentiles of activity. We assessed the linearity of the relationship and examined subtype-specific associations and effect modification across strata of breast cancer risk factors, including adiposity.RESULTS: Over a median 11.5 years of follow-up (IQR, 8.0-16.1 years), high versus low levels of leisure-time physical activity were associated with a 6% (HR, 0.94 [95% CI, 0.89 to 0.99]) and a 10% (HR, 0.90 [95% CI, 0.85 to 0.95]) reduction in breast cancer risk, before and after adjustment for BMI, respectively. Tests of nonlinearity suggested an approximately linear relationship (Pnonlinearity = .94). The inverse association was particularly strong for human epidermal growth factor receptor 2-enriched breast cancer (HR, 0.57 [95% CI, 0.39 to 0.84]; Phet = .07). Associations did not vary significantly across strata of breast cancer risk factors, including subgroups of adiposity.CONCLUSION: This large, pooled analysis of cohort studies adds to evidence that engagement in higher levels of leisure-time physical activity may lead to reduced premenopausal breast cancer risk.
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49.
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50.
  • Vallo Hult, Helena, 1976-, et al. (författare)
  • Turning Fear Into Trust : Experiences From Digitalization Of Work In Industry And Healthcare
  • 2022
  • Ingår i: Proceedings of the 16th International Technology, Education and Development Conference (INTED2022) Online Conference. 7-8 March, 2022.. - : IATED. - 9788409377589
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Since the beginning of time, humans have been fascinated and intrigued by new technology, but also frightened of its implications. In the 1980s, Chao and Kozlowski [1] studied the introduction of fully automated lines in mass-production industry, and identified different fear factors influencing the workers willingness to change their work process. This study is more than 30 years old, however their insights are still relevant and tends to become even more important with the introduction of complex technology like ubiquitous and embedded systems, AI, big-data, and collaborative technology [2]. This rapid and ongoing digital transformation will have fundamental implications for the way we organize work and for how we design work processes and production system, not only in the manufacturing industry but in all parts of the working life, including the healthcare sector, schools, service, logistics and society ingeneral. It is also likely to influence and challenge roles and relationships and require new constellations of expertise and professional domains [3, 4]. In this paper, we compare experiences from practice in the manufacturing industry and health  care domains and try to identify how fear of technology-induced change can be turned into trust, through knowledge exchange, competence development, and inclusive project management. In line with [1] we have identified four main fear factors related to digital transformation, in both the industrial context and the healthcare organization:Fear of losing one's jobFear of new, unfamiliar tasks and expectationsFear of change in general but in group relations and roles in specificFear of the actual technologyThe number of manual jobs is decreasing; contrasting feelings of responsibility and loss of control are common when adapting to new conditions in a new work environment; new workplace technology maychange traditional practice and there by lower the autonomy and power of the professions; and new machines could cause physical injury or, with a digital system, lead to security threats, loss of data, orthe sense of intrusiveness [2, 3]. Our studies found, some what contra intuitive, that workers with no or limited knowledge about the technology in use experience less fear. While workers with experience of the technology they interact with, tend to have more fear, and require a larger sense of control to be able to trust the system. We suggest that each of these fears can be addressed and linked to work integrated learning strategies to turn the fear of technology into digital trust by giving the worker tools for better control. Through collaborative competence development and inclusive workplace learning, different solutions can be explored to create conditions for trust. REFERENCES[1] G. T. Chao, and S. W. Kozlowski, “Employee perceptions on the implementation of roboticmanufacturing technology,” Journal of Applied Psychology, vol. 71, no. 1, pp. 70, 1986.[2] S. Zuboff, The age of surveillance capitalism : the fight for the future at the new frontier of power,London: Profile Books, 2019.[3] R. E. Susskind, and D. Susskind, The future of the professions : how technology will transform thework of human experts, USA.: Oxford University Press, 2015.[4] H. Vallo Hult, Digital Work : Coping with Contradictions in Changing Healthcare, Trollhättan:University West, 2021.
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