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1.
  • Anzt, Hartwig, et al. (författare)
  • An environment for sustainable research software in Germany and beyond: current state, open challenges, and call for action
  • 2020
  • Ingår i: F1000 Research. - : F1000 Research Ltd. - 2046-1402. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Research software has become a central asset in academic research. It optimizes existing and enables new research methods, implements and embeds research knowledge, and constitutes an essential research product in itself. Research software must be sustainable in order to understand, replicate, reproduce, and build upon existing research or conduct new research effectively. In other words, software must be available, discoverable, usable, and adaptable to new needs, both now and in the future. Research software therefore requires an environment that supports sustainability. Hence, a change is needed in the way research software development and maintenance are currently motivated, incentivized, funded, structurally and infrastructurally supported, and legally treated. Failing to do so will threaten the quality and validity of research. In this paper, we identify challenges for research software sustainability in Germany and beyond, in terms of motivation, selection, research software engineering personnel, funding, infrastructure, and legal aspects. Besides researchers, we specifically address political and academic decision-makers to increase awareness of the importance and needs of sustainable research software practices. In particular, we recommend strategies and measures to create an environment for sustainable research software, with the ultimate goal to ensure that software-driven research is valid, reproducible and sustainable, and that software is recognized as a first class citizen in research. This paper is the outcome of two workshops run in Germany in 2019, at deRSE19 - the first International Conference of Research Software Engineers in Germany - and a dedicated DFG-supported follow-up workshop in Berlin.
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2.
  • Biurrun, Idoia, et al. (författare)
  • Benchmarking plant diversity of Palaearctic grasslands and other open habitats
  • 2021
  • Ingår i: Journal of Vegetation Science. - Oxford : John Wiley & Sons. - 1100-9233 .- 1654-1103. ; 32:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Journal of Vegetation Science published by John Wiley & Sons Ltd on behalf of International Association for Vegetation Science.Aims: Understanding fine-grain diversity patterns across large spatial extents is fundamental for macroecological research and biodiversity conservation. Using the GrassPlot database, we provide benchmarks of fine-grain richness values of Palaearctic open habitats for vascular plants, bryophytes, lichens and complete vegetation (i.e., the sum of the former three groups). Location: Palaearctic biogeographic realm. Methods: We used 126,524 plots of eight standard grain sizes from the GrassPlot database: 0.0001, 0.001, 0.01, 0.1, 1, 10, 100 and 1,000 m2 and calculated the mean richness and standard deviations, as well as maximum, minimum, median, and first and third quartiles for each combination of grain size, taxonomic group, biome, region, vegetation type and phytosociological class. Results: Patterns of plant diversity in vegetation types and biomes differ across grain sizes and taxonomic groups. Overall, secondary (mostly semi-natural) grasslands and natural grasslands are the richest vegetation type. The open-access file ”GrassPlot Diversity Benchmarks” and the web tool “GrassPlot Diversity Explorer” are now available online (https://edgg.org/databases/GrasslandDiversityExplorer) and provide more insights into species richness patterns in the Palaearctic open habitats. Conclusions: The GrassPlot Diversity Benchmarks provide high-quality data on species richness in open habitat types across the Palaearctic. These benchmark data can be used in vegetation ecology, macroecology, biodiversity conservation and data quality checking. While the amount of data in the underlying GrassPlot database and their spatial coverage are smaller than in other extensive vegetation-plot databases, species recordings in GrassPlot are on average more complete, making it a valuable complementary data source in macroecology. © 2021 The Authors.
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3.
  • Marto, João Pedro, et al. (författare)
  • Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.
  • 2023
  • Ingår i: Neurology. - 1526-632X. ; 100:7
  • Tidskriftsartikel (refereegranskat)abstract
    • COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT).Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60).Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis.The study was registered under ClinicalTrials.gov identifier NCT04895462.
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4.
  • Andersson, Jan, 1965-, et al. (författare)
  • Regeringsuppdrag synfält : utredning om förutsättningar för undantag från de medicinska kraven för individer med synfältsbortfall
  • 2022
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • I regeringsuppdraget (I2021/ 02412) framgår att VTI, i samarbete med Trafikverket och Transportstyrelsen, ska utreda förutsättningarna för undantagshantering från de medicinska föreskrifterna med avseende på synfältsbortfall (B-körkort). Vidare ska tre aspekter beaktas: hur andra länder gör, konsekvenser för den enskilde samt samhällsekonomiska konsekvenser. Slutrapporten påvisar att Sverige med gällande rättsligt ramverk inte kan genomföra de förslag som slutrapporten föreslår. Det innebär att det kommer att krävas juridiska förändringar. Givet att dessa förändringar genomförs och att ett nytt förfaringssätt nyttjas visar slutrapporten på att a) positiva effekter för den enskilde individen uppstår, b) samhällsekonomiska vinster uppstår och c) en rättssäker och rättvis prövning är möjlig. Slutrapporten redovisar dessutom hur ett urval av andra länder har hanterat handläggningen av individer med synfältsbortfall givet samma EU-direktiv som Sverige regleras av. Det framgår också av undersökningen att samtliga länder, som en förutsättning för undantag från de föreskrivna kraven avseende synfält, tillämpar krav eller rekommendationer om att ett praktiskt körprov ska utgöra del i underlaget för bedömning av körförmågan. Kunskapsläget med avseende på körförmågebedömningar för individer med synfältsbortfall redovisas och där framgår med tydlighet att perimetrin som Sverige utnyttjar som underlag för återkallelse av körkort inte kan predicera individers körförmåga. Perimetrin är dock viktig eftersom individer med synfältsbortfall som grupp kan vara olämpliga förare. Slutsatsen som forskningslitteraturen enstämmigt lyfter är att det behövs förarprov (på väg eller i en simulator) för att kunna genomföra en valid bedömning. Slutligen innehåller slutrapporten vilka problem (aktiviteter) som kvarstår för att skapa en lämplig och kvalitetssäkrad process. Dessutom presenteras den kronologiska ordning på aktiviteter som behöver genomföras. Kronologin krävs eftersom resultatet av lämplig metod och aktör påverkar det vidare arbetet med avseende på utformning av körprov och rättsligt ramverk. Slutrapportens slutsats är att Sverige har möjligheten att genomföra en förändring med avsevärda nyttor. Detta eftersom de valda aktörerna och de valda metoderna existerar idag och därför endast behöver utvecklas i viss mån för att säkerställa att individer med synfältsbortfall erbjuds en kvalitetssäkrad, rättssäker och rättvis process som dessutom bedöms vara samhällsekonomiskt lönsam.
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5.
  • Folkersen, Lasse, et al. (författare)
  • Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
  • 2020
  • Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
  • Tidskriftsartikel (refereegranskat)abstract
    • Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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6.
  • Jones, Benedict C, et al. (författare)
  • To which world regions does the valence-dominance model of social perception apply?
  • 2021
  • Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
  • Tidskriftsartikel (refereegranskat)abstract
    • Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
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7.
  • Kanoni, Stavroula, et al. (författare)
  • Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
  • 2022
  • Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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8.
  • Ntalla, Ioanna, et al. (författare)
  • Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
  • 2020
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
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9.
  • Peters, Ruth, et al. (författare)
  • An investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis.
  • 2020
  • Ingår i: Neurology. - 1526-632X. ; 94:3
  • Tidskriftsartikel (refereegranskat)abstract
    • High blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data.To identify suitable studies, MEDLINE, Embase, and PsycINFO and preexisting study consortia were searched from inception to December 2017. Authors of prospective longitudinal human studies or trials of antihypertensives were contacted for data sharing and collaboration. Outcome measures were incident dementia or incident cognitive decline (classified using the reliable change index method). Data were separated into mid and late-life (>65 years) and each antihypertensive class was compared to no treatment and to treatment with other antihypertensives. Meta-analysis was used to synthesize data.Over 50,000 participants from 27 studies were included. Among those aged >65 years, with the exception of diuretics, we found no relationship by class with incident cognitive decline or dementia. Diuretic use was suggestive of benefit in some analyses but results were not consistent across follow-up time, comparator group, and outcome. Limited data precluded meaningful analyses in those ≤65 years of age.Our findings, drawn from the current evidence base, support clinical freedom in the selection of antihypertensive regimens to achieve blood pressure goals.The review was registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42016045454.
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10.
  • Petrescu, Ana Maria Roxana, et al. (författare)
  • The consolidated European synthesis of CO2emissions and removals for the European Union and United Kingdom : 1990-2018
  • 2021
  • Ingår i: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 13:5, s. 2363-2406
  • Forskningsöversikt (refereegranskat)abstract
    • Reliable quantification of the sources and sinks of atmospheric carbon dioxide (CO2), including that of their trends and uncertainties, is essential to monitoring the progress in mitigating anthropogenic emissions under the Kyoto Protocol and the Paris Agreement. This study provides a consolidated synthesis of estimates for all anthropogenic and natural sources and sinks of CO2 for the European Union and UK (EU27 + UK), derived from a combination of state-of-the-art bottom-up (BU) and top-down (TD) data sources and models. Given the wide scope of the work and the variety of datasets involved, this study focuses on identifying essential questions which need to be answered to properly understand the differences between various datasets, in particular with regards to the less-well-characterized fluxes from managed ecosystems. The work integrates recent emission inventory data, process-based ecosystem model results, data-driven sector model results and inverse modeling estimates over the period 1990-2018. BU and TD products are compared with European national greenhouse gas inventories (NGHGIs) reported under the UNFCCC in 2019, aiming to assess and understand the differences between approaches. For the uncertainties in NGHGIs, we used the standard deviation obtained by varying parameters of inventory calculations, reported by the member states following the IPCC Guidelines. Variation in estimates produced with other methods, like atmospheric inversion models (TD) or spatially disaggregated inventory datasets (BU), arises from diverse sources including within-model uncertainty related to parameterization as well as structural differences between models. In comparing NGHGIs with other approaches, a key source of uncertainty is that related to different system boundaries and emission categories (CO2 fossil) and the use of different land use definitions for reporting emissions from land use, land use change and forestry (LULUCF) activities (CO2 land). At the EU27 + UK level, the NGHGI (2019) fossil CO2 emissions (including cement production) account for 2624 Tg CO2 in 2014 while all the other seven bottom-up sources are consistent with the NGHGIs and report a mean of 2588 (± 463 Tg CO2). The inversion reports 2700 Tg CO2 (± 480 Tg CO2), which is well in line with the national inventories. Over 2011-2015, the CO2 land sources and sinks from NGHGI estimates report-90 Tg C yr-1 ± 30 Tg C yr-1 while all other BU approaches report a mean sink of-98 Tg C yr-1 (± 362 Tg of C from dynamic global vegetation models only). For the TD model ensemble results, we observe a much larger spread for regional inversions (i.e., mean of 253 Tg C yr-1 ± 400 Tg C yr-1). This concludes that (a) current independent approaches are consistent with NGHGIs and (b) their uncertainty is too large to allow a verification because of model differences and probably also because of the definition of "CO2 flux"obtained from different approaches. The referenced datasets related to figures are visualized.
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