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1.
  • Vogel, Jacob W., et al. (författare)
  • Four distinct trajectories of tau deposition identified in Alzheimer’s disease
  • 2021
  • Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:5, s. 871-881
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These ‘subtypes’ were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of ‘typical AD’ and a revisiting of tau pathological staging. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
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2.
  • Ades, M., et al. (författare)
  • Global Climate : in State of the climate in 2019
  • 2020
  • Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 101:8, s. S17-S127
  • Tidskriftsartikel (refereegranskat)
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3.
  • Ades, M., et al. (författare)
  • GLOBAL CLIMATE
  • 2020
  • Ingår i: BULLETIN OF THE AMERICAN METEOROLOGICAL SOCIETY. - 0003-0007 .- 1520-0477. ; 101:8
  • Tidskriftsartikel (refereegranskat)
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4.
  • Agudo, I., et al. (författare)
  • Panning for gold, but finding helium: Discovery of the ultra-stripped supernova SN 2019wxt from gravitational-wave follow-up observations
  • 2023
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 675
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results from multi-wavelength observations of a transient discovered during an intensive follow-up campaign of S191213g, a gravitational wave (GW) event reported by the LIGO-Virgo Collaboration as a possible binary neutron star merger in a low latency search. This search yielded SN 2019wxt, a young transient in a galaxy whose sky position (in the 80% GW contour) and distance (∼150 Mpc) were plausibly compatible with the localisation uncertainty of the GW event. Initially, the transienta's tightly constrained age, its relatively faint peak magnitude (Mi ∼ -16.7 mag), and the r-band decline rate of ∼1 mag per 5 days appeared suggestive of a compact binary merger. However, SN 2019wxt spectroscopically resembled a type Ib supernova, and analysis of the optical-near-infrared evolution rapidly led to the conclusion that while it could not be associated with S191213g, it nevertheless represented an extreme outcome of stellar evolution. By modelling the light curve, we estimated an ejecta mass of only ∼0.1 M·, with 56Ni comprising ∼20% of this. We were broadly able to reproduce its spectral evolution with a composition dominated by helium and oxygen, with trace amounts of calcium. We considered various progenitor channels that could give rise to the observed properties of SN 2019wxt and concluded that an ultra-stripped origin in a binary system is the most likely explanation. Disentangling genuine electromagnetic counterparts to GW events from transients such as SN 2019wxt soon after discovery is challenging: in a bid to characterise this level of contamination, we estimated the rate of events with a volumetric rate density comparable to that of SN 2019wxt and found that around one such event per week can occur within the typical GW localisation area of O4 alerts out to a luminosity distance of 500 Mpc, beyond which it would become fainter than the typical depth of current electromagnetic follow-up campaigns.
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  • Burrascano, S., et al. (författare)
  • Where are we now with European forest multi-taxon biodiversity and where can we head to?
  • 2023
  • Ingår i: Biological Conservation. - 0006-3207. ; 284
  • Tidskriftsartikel (refereegranskat)abstract
    • The European biodiversity and forest strategies rely on forest sustainable management (SFM) to conserve forest biodiversity. However, current sustainability assessments hardly account for direct biodiversity indicators. We focused on forest multi-taxon biodiversity to: i) gather and map the existing information; ii) identify knowledge and research gaps; iii) discuss its research potential. We established a research network to fit data on species, standing trees, lying deadwood and sampling unit description from 34 local datasets across 3591 sampling units. A total of 8724 species were represented, with the share of common and rare species varying across taxonomic classes: some included many species with several rare ones (e.g., Insecta); others (e.g., Bryopsida) were repre-sented by few common species. Tree-related structural attributes were sampled in a subset of sampling units (2889; 2356; 2309 and 1388 respectively for diameter, height, deadwood and microhabitats). Overall, multi-taxon studies are biased towards mature forests and may underrepresent the species related to other develop-mental phases. European forest compositional categories were all represented, but beech forests were over-represented as compared to thermophilous and boreal forests. Most sampling units (94%) were referred to a habitat type of conservation concern. Existing information may support European conservation and SFM stra-tegies in: (i) methodological harmonization and coordinated monitoring; (ii) definition and testing of SFM in-dicators and thresholds; (iii) data-driven assessment of the effects of environmental and management drivers on multi-taxon forest biological and functional diversity, (iv) multi-scale forest monitoring integrating in-situ and remotely sensed information.
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  • Khaleva, E, et al. (författare)
  • Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA)
  • 2023
  • Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 61:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) working group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies.MethodsCOMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult, and paediatric clinicians, pharmaceutical representatives and health regulators from across Europe. Evidence included a systematic review of development, validity, and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients’ and carers’ views about outcome measures. It was discussed using a modified GRADE Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria.ResultsBoth adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire, and Asthma Control Test (ACT) or Childhood-ACT while the adult COM includes the Severe Asthma Questionnaire and the Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately).ConclusionsThis patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.
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  • Khaleva, E, et al. (författare)
  • Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA)
  • 2023
  • Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 61:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) working group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies.MethodsCOMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult, and paediatric clinicians, pharmaceutical representatives and health regulators from across Europe. Evidence included a systematic review of development, validity, and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients’ and carers’ views about outcome measures. It was discussed using a modified GRADE Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria.ResultsBoth adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire, and Asthma Control Test (ACT) or Childhood-ACT while the adult COM includes the Severe Asthma Questionnaire and the Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately).ConclusionsThis patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.
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  • Osborn, H. P., et al. (författare)
  • Two warm Neptunes transiting HIP 9618 revealed by TESS and Cheops
  • 2023
  • Ingår i: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 523:2, s. 3069-3089
  • Tidskriftsartikel (refereegranskat)abstract
    • HIP 9618 (HD 12572, TOI-1471, TIC 306263608) is a bright (G = 9.0 mag) solar analogue. TESS photometry revealed the star to have two candidate planets with radii of 3.9 ± 0.044 R (HIP 9618 b) and 3.343 ± 0.039 R (HIP 9618 c). While the 20.77291 d period of HIP 9618 b was measured unambiguously, HIP 9618 c showed only two transits separated by a 680-d gap in the time series, leaving many possibilities for the period. To solve this issue, CHEOPS performed targeted photometry of period aliases to attempt to recover the true period of planet c, and successfully determined the true period to be 52.56349 d. High-resolution spectroscopy with HARPS-N, SOPHIE, and CAFE revealed a mass of 10.0 ± 3.1M for HIP 9618 b, which, according to our interior structure models, corresponds to a 6.8 ± 1.4 per cent gas fraction. HIP 9618 c appears to have a lower mass than HIP 9618 b, with a 3-sigma upper limit of <18M. Follow-up and archival RV measurements also reveal a clear long-term trend which, when combined with imaging and astrometric information, reveal a low-mass companion (0.08+−000512M☉) orbiting at 26.0+−111900 au. This detection makes HIP 9618 one of only five bright (K < 8 mag) transiting multiplanet systems known to host a planet with P > 50 d, opening the door for the atmospheric characterization of warm (Teq < 750 K) sub-Neptunes.
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  • Shupe, M. D., et al. (författare)
  • Overview of the MOSAiC expedition : Atmosphere
  • 2022
  • Ingår i: Elementa. - : University of California Press. - 2325-1026. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • With the Arctic rapidly changing, the needs to observe, understand, and model the changes are essential. To support these needs, an annual cycle of observations of atmospheric properties, processes, and interactions were made while drifting with the sea ice across the central Arctic during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition from October 2019 to September 2020. An international team designed and implemented the comprehensive program to document and characterize all aspects of the Arctic atmospheric system in unprecedented detail, using a variety of approaches, and across multiple scales. These measurements were coordinated with other observational teams to explore crosscutting and coupled interactions with the Arctic Ocean, sea ice, and ecosystem through a variety of physical and biogeochemical processes. This overview outlines the breadth and complexity of the atmospheric research program, which was organized into 4 subgroups: atmospheric state, clouds and precipitation, gases and aerosols, and energy budgets. Atmospheric variability over the annual cycle revealed important influences from a persistent large-scale winter circulation pattern, leading to some storms with pressure and winds that were outside the interquartile range of past conditions suggested by long-term reanalysis. Similarly, the MOSAiC location was warmer and wetter in summer than the reanalysis climatology, in part due to its close proximity to the sea ice edge. The comprehensiveness of the observational program for characterizing and analyzing atmospheric phenomena is demonstrated via a winter case study examining air mass transitions and a summer case study examining vertical atmospheric evolution. Overall, the MOSAiC atmospheric program successfully met its objectives and was the most comprehensive atmospheric measurement program to date conducted over the Arctic sea ice. The obtained data will support a broad range of coupled-system scientific research and provide an important foundation for advancing multiscale modeling capabilities in the Arctic. 
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  • Tommasini, R., et al. (författare)
  • Accepted Tutorials at The Web Conference 2022
  • 2022
  • Ingår i: WWW 2022 - Companion Proceedings of the Web Conference 2022. - New York, NY, USA : Association for Computing Machinery (ACM). ; , s. 391-399
  • Konferensbidrag (refereegranskat)abstract
    • This paper summarizes the content of the 20 tutorials that have been given at The Web Conference 2022: 85% of these tutorials are lecture style, and 15% of these are hands on. 
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  • Muehlenbein, MP, et al. (författare)
  • Traveller exposures to animals: a GeoSentinel analysis
  • 2020
  • Ingår i: Journal of travel medicine. - : Oxford University Press (OUP). - 1708-8305 .- 1195-1982. ; 27:7
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundHuman coexistence with other animals can result in both intentional and unintentional contact with a variety of mammalian and non-mammalian species. International travellers are at risk for such encounters; travellers risk injury, infection and possibly death from domestic and wild animal bites, scratches, licks and other exposures. The aim of the present analysis was to understand the diversity and distribution of animal-related exposures among international travellers.MethodsData from January 2007 through December 2018 from the GeoSentinel Surveillance Network were reviewed. Records were included if the exposure was non-migration travel with a diagnosis of an animal (dog, cat, monkey, snake or other) bite or other exposure (non-bite); records were excluded if the region of exposure was not ascertainable or if another, unrelated acute diagnosis was reported.ResultsA total of 6470 animal exposures (bite or non-bite) were included. The majority (71%) occurred in Asia. Travellers to 167 countries had at least one report of an animal bite or non-bite exposure. The majority (76%) involved dogs, monkeys and cats, although a wide range of wild and domestic species were involved. Almost two-thirds (62.6%) of 4395 travellers with information available did not report a pretravel consultation with a healthcare provider.ConclusionsMinimizing bites and other animal exposures requires education (particularly during pretravel consultations) and behavioral modification. These should be supplemented by the use of pre-exposure rabies vaccination for travellers to high-risk countries (especially to those with limited access to rabies immunoglobulin), as well as encouragement of timely (in-country) post-exposure prophylaxis for rabies and Macacine alphaherpesvirus 1 (herpesvirus B) when warranted.
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  • Zheng, TH, et al. (författare)
  • Genome-wide analysis of 944 133 individuals provides insights into the etiology of haemorrhoidal disease
  • 2021
  • Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 70:8, s. 1538-1549
  • Tidskriftsartikel (refereegranskat)abstract
    • Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date.DesignWe conducted a GWAS meta-analysis of 218 920 patients with HEM and 725 213 controls of European ancestry. Using GWAS summary statistics, we performed multiple genetic correlation analyses between HEM and other traits as well as calculated HEM polygenic risk scores (PRS) and evaluated their translational potential in independent datasets. Using functional annotation of GWAS results, we identified HEM candidate genes, which differential expression and coexpression in HEM tissues were evaluated employing RNA-seq analyses. The localisation of expressed proteins at selected loci was investigated by immunohistochemistry.ResultsWe demonstrate modest heritability and genetic correlation of HEM with several other diseases from the GI, neuroaffective and cardiovascular domains. HEM PRS validated in 180 435 individuals from independent datasets allowed the identification of those at risk and correlated with younger age of onset and recurrent surgery. We identified 102 independent HEM risk loci harbouring genes whose expression is enriched in blood vessels and GI tissues, and in pathways associated with smooth muscles, epithelial and endothelial development and morphogenesis. Network transcriptomic analyses highlighted HEM gene coexpression modules that are relevant to the development and integrity of the musculoskeletal and epidermal systems, and the organisation of the extracellular matrix.ConclusionHEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction.
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  • Santos-Valente, E, et al. (författare)
  • Biologicals in childhood severe asthma: the European PERMEABLE survey on the status quo
  • 2021
  • Ingår i: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 7:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Severe asthma is a rare disease in children, for which three biologicals, anti-immunoglobulin E, anti-interleukin-5 and anti-IL4RA antibodies, are available in European countries. While global guidelines exist on who should receive biologicals, knowledge is lacking on how those guidelines are implemented in real life and which unmet needs exist in the field. In this survey, we aimed to investigate the status quo and identify open questions in biological therapy of childhood asthma across Europe.MethodsStructured interviews regarding experience with biologicals, regulations on access to the different treatment options, drug selection, therapy success and discontinuation of therapy were performed. Content analysis was used to analyse data.ResultsWe interviewed 37 experts from 25 European countries and Turkey and found a considerable range in the number of children treated with biologicals per centre. All participating countries provide public access to at least one biological. Most countries allow different medical disciplines to prescribe biologicals to children with asthma, and only a few restrict therapy to specialised centres. We observed significant variation in the time point at which treatment success is assessed, in therapy duration and in the success rate of discontinuation. Most participating centres intend to apply a personalised medicine approach in the future to match patients a priori to available biologicals.ConclusionSubstantial differences exist in the management of childhood severe asthma across Europe, and the need for further studies on biomarkers supporting selection of biologicals, on criteria to assess therapy response and on how/when to end therapy in stable patients is evident.
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  • Lennon, J. T., et al. (författare)
  • Priorities, opportunities, and challenges for integrating microorganisms into Earth system models for climate change prediction
  • 2024
  • Ingår i: mBio. - 2161-2129 .- 2150-7511.
  • Tidskriftsartikel (refereegranskat)abstract
    • Climate change jeopardizes human health, global biodiversity, and sustainability of the biosphere. To make reliable predictions about climate change, scientists use Earth system models (ESMs) that integrate physical, chemical, and biological processes occurring on land, the oceans, and the atmosphere. Although critical for catalyzing coupled biogeochemical processes, microorganisms have traditionally been left out of ESMs. Here, we generate a "top 10" list of priorities, opportunities, and challenges for the explicit integration of microorganisms into ESMs. We discuss the need for coarse-graining microbial information into functionally relevant categories, as well as the capacity for microorganisms to rapidly evolve in response to climate-change drivers. Microbiologists are uniquely positioned to collect novel and valuable information necessary for next-generation ESMs, but this requires data harmonization and transdisciplinary collaboration to effectively guide adaptation strategies and mitigation policy.
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  • Studnicka, Michael, et al. (författare)
  • COPD : Should Diagnosis Match Physiology?
  • 2020
  • Ingår i: Chest. - : Elsevier BV. - 0012-3692 .- 1931-3543. ; 157:2, s. 473-475
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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  • van Meel, Evelien R., et al. (författare)
  • Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: a meta-analysis of 150 000 European children
  • 2022
  • Ingår i: European Respiratory Journal. - : EUROPEAN RESPIRATORY SOC JOURNALS LTD. - 0903-1936 .- 1399-3003. ; 60:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age. Methods We used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow at 75% of FVC (FEF75%) and asthma at a median (range) age of 7 (4-15) years. Results Children with early-life lower, not upper, respiratory tract infections had a lower school-age FEV1, FEV1/FVC and FEF75% (z-score range: -0.09 (95% CI -0.14- -0.04) to -0.30 (95% CI -0.36- -0.24)). Children with early-life lower respiratory tract infections had a higher increased risk of school-age asthma than those with upper respiratory tract infections (OR range: 2.10 (95% CI 1.98-2.22) to 6.30 (95% CI 5.64-7.04) and 1.25 (95% CI 1.18-1.32) to 1.55 (95% CI 1.47-1.65), respectively). Adjustment for preceding respiratory tract infections slightly decreased the strength of the effects. Observed associations were similar for those with and without early-life wheezing as a proxy for early-life asthma. Conclusions Our findings suggest that early-life respiratory tract infections affect development of chronic obstructive respiratory diseases in later life, with the strongest effects for lower respiratory tract infections.
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  • Fawole, H. O., et al. (författare)
  • Is the association between physical activity and fatigue mediated by physical function or depressive symptoms in symptomatic knee osteoarthritis? The Multicenter Osteoarthritis Study
  • 2021
  • Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 50:5, s. 372-380
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To examine whether physical activity (PA) was associated with fatigue, and quantify the extent of potential mediation through depressive symptoms or physical function (PF) on the relationship between PA and fatigue in symptomatic knee osteoarthritis (KOA). Method: This longitudinal study used data from the Multicenter Osteoarthritis Study (n = 484), comprising subjects aged ≥ 50 years. Baseline PA was quantified via an ankle-worn accelerometer. The outcome was fatigue, measured using a 0–10 rating scale at 2 year follow-up. Mediators included gait speed as a measure of PF and depressive symptoms at 2 year follow-up. Mediation analysis was carried out after adjustment for baseline confounders. Stratified analysis by baseline fatigue status [no/low (< 4) and high (≥ 4) fatigue] was performed. Results: A significant direct association was found between PA and fatigue at 2 years [unstandardized coefficient (B) = −0.054; 95% confidence interval (CI) −0.107, −0.002, p = 0.041]. The PA–fatigue relationship was not mediated by gait speed (B = −0.006; 95% CI −0.018, 0.001) or depressive symptoms (B = 0.009; 95% CI 0.009, 0.028). In the subgroup with high baseline fatigue, direct associations were found between PA and fatigue (gait speed model:, B = −0.107; 95% CI −0.212, −0.002, p = 0.046; depressive symptoms model: B = −0.110; 95% CI −0.120, −0.020, p = 0.017); but in the no/low baseline fatigue group, no significant association was found between PA and fatigue. Conclusion: In the symptomatic KOA population, higher baseline PA was directly associated with reduced fatigue 2 years later, especially in those with high baseline fatigue. However, this relationship was not mediated by depressive symptoms or PF.
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  • Hevesi, Z, et al. (författare)
  • Preclinical Establishment of a Divalent Vaccine against SARS-CoV-2
  • 2022
  • Ingår i: Vaccines. - : MDPI AG. - 2076-393X. ; 10:4
  • Tidskriftsartikel (refereegranskat)abstract
    • First-generation vaccines against SARS-CoV-2 do not provide adequate immune protection. Therefore, we engineered a divalent gene construct combining the receptor-binding domain (RBD) of the spike protein and the immunodominant region of the viral nucleocapsid. This fusion protein was produced in either E. coli or a recombinant baculovirus system. Subsequently, the fusion protein was mixed with adjuvant and administered to mice in a prime-booster mode. Mice (72%) produced an IgG response against both proteins (titer: 10−4–10−5) 14 days after the first booster injection, which was increased to 100% by a second booster. Comparable IgG responses were detected against the delta, gamma and omicron variants of the RBD region. Durability testing revealed IgGs beyond 90 days. In addition, cytolytic effector cell molecules were increased in lymphocytes isolated from peripheral blood. Ex vivo stimulation of T cells by nucleocapsid and RBD peptides showed antigen-specific upregulation of CD44 among the CD4+ and CD8+ T cells of vaccinated mice. No side effect was documented in the central nervous system. Cumulatively, these data represent a proof-of-principle approach alternative to existing mRNA vaccination strategies.
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  • Hill, S. C., et al. (författare)
  • Magnetospheric Sources of Theta Aurora: A Case Study Comparing Observations With SWMF Global Simulation
  • 2024
  • Ingår i: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 51:10
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the first high resolution global MHD with coupled inner magnetosphere simulation results of an observed theta aurora event. We use the Space Weather Modeling Framework in the Geospace configuration, which produces accurate field aligned current closure in the ionosphere that is integral to theta aurora formation. At the location of the observed theta aurora, the simulation produces a narrow channel of Joule heating along both open and closed field lines, and between a pair of oppositely directed field-aligned current sheets in the ionosphere. We demonstrate that this Joule heating pattern that we identify as theta aurora maps to a reconnection region at the magnetotail flanks as well as in the distant magnetotail. The theta aurora maps to a cross-tail current disruption and field-aligned current source region in a highly twisted magnetotail.
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  • van Dalen, Elvira C., et al. (författare)
  • Coronary artery disease surveillance among childhood, adolescent and young adult cancer survivors : A systematic review and recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group
  • 2021
  • Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 156, s. 127-137
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Coronary artery disease (CAD) is a concerning late outcome for cancer survivors. However, uniform surveillance guidelines are lacking. Aim: To harmonise international recommendations for CAD surveillance for survivors of childhood, adolescent and young adult (CAYA) cancers. Methods: A systematic literature review was performed and evidence graded using the Grading of Recommendations, Assessment, Development and Evaluation criteria. Eligibility included English language studies, a minimum of 20 off-therapy cancer survivors assessed for CAD, and 75% diagnosed prior to age 35 years. All study designs were included, and a multidisciplinary guideline panel formulated and graded recommendations. Results: 32 of 522 identified articles met eligibility criteria. The prevalence of CAD ranged from 0 to 72% and was significantly increased compared to control populations. The risk of CAD was increased among survivors who received radiotherapy exposing the heart, especially at doses >15 Gy (moderate-quality evidence). The guideline panel agreed that healthcare providers and CAYA cancer survivors treated with radiotherapy exposing the heart should be counselled about the increased risk for premature CAD. While the evidence is insufficient to support primary screening, monitoring and early management of modifiable cardiovascular risk factors are recommended. Initiation and frequency of surveillance should be based on the intensity of treatment exposures, family history, and presence of co-morbidities but at least by age 40 years and at a minimum of every 5 years. All were strong recommendations. Conclusion: These systematically assessed and harmonised recommendations for CAD surveillance will inform care and guide research concerning this critical outcome for CAYA cancer survivors.
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  • Werdan, K., et al. (författare)
  • Curriculum Kardiologie 2., aktualisierte Auflage
  • 2020
  • Ingår i: KARDIOLOGE. - : SPRINGER HEIDELBERG. - 1864-9718 .- 1864-9726. ; 14:6, s. 505-536
  • Tidskriftsartikel (refereegranskat)abstract
    • The updated second edition of the "Curriculum cardiology", first edition 2013, aims to show which competences a cardiologist should nowadays master. It is very pleasing that in this second edition representatives of the Young German Cardiac Society (Young DGK) have contributed as authors. The increasing specialization within cardiology should, however, only represent one side of the coin: there must also still be a common foundation of cardiology, embedded in the discipline "internal medicine". This foundation includes the basis of theoretical knowledge, practical skills (competence levels I-III) and an occupational and professional attitude of the (prospective) cardiologist. New additions to the advanced training since the first edition of the curriculum in 2013 are, for example a chapter on digital cardiology, the further training in psychocardiology, which was newly introduced into the model further training regulations and finally also the explicit formulation of shared decision making in the interests of cardiac patients. The curriculum should give the prospective cardiologist the possibility to structure the further training as efficiently as possible and ultimately to retain and expand that which has been learned in the sense of a "professional lifelong" qualification. The curriculum also aims to reach the trainers and the Medical Councils and demonstrate which contents and skills should be mediated in the further training to become a cardiologist from the perspective of the German Cardiac Society (DGK).
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39.
  • An, T., et al. (författare)
  • Evolving parsec-scale radio structure in the most distant blazar known
  • 2020
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Blazars are a sub-class of quasars with Doppler boosted jets oriented close to the line of sight, and thus efficient probes of supermassive black hole growth and their environment, especially at high redshifts. Here we report on Very Long Baseline Interferometry observations of a blazar J0906 + 6930 at z = 5.47, which enabled the detection of polarised emission and measurement of jet proper motion at parsec scales. The observations suggest a less powerful jet compared with the general blazar population, including lower proper motion and bulk Lorentz factor. This coupled with a previously inferred high accretion rate indicate a transition from an accretion radiative power to a jet mechanical power based transfer of energy and momentum to the surrounding gas. While alternative scenarios could not be fully ruled out, our results indicate a possibly nascent jet embedded in and interacting with a dense medium resulting in a jet bending.
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40.
  • Badi, Yusef Eamon, et al. (författare)
  • Mapping atopic dermatitis and anti–IL-22 response signatures to type 2–low severe neutrophilic asthma
  • 2022
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 149:1, s. 89-101
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Transcriptomic changes in patients who respond clinically to biological therapies may identify responses in other tissues or diseases.Objective: We sought to determine whether a disease signature identified in atopic dermatitis (AD) is seen in adults with severe asthma and whether a transcriptomic signature for patients with AD who respond clinically to anti–IL-22 (fezakinumab [FZ]) is enriched in severe asthma.Methods: An AD disease signature was obtained from analysis of differentially expressed genes between AD lesional and nonlesional skin biopsies. Differentially expressed genes from lesional skin from therapeutic superresponders before and after 12 weeks of FZ treatment defined the FZ-response signature. Gene set variation analysis was used to produce enrichment scores of AD and FZ-response signatures in the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes asthma cohort.Results: The AD disease signature (112 upregulated genes) encompassing inflammatory, T-cell, TH2, and TH17/TH22 pathways was enriched in the blood and sputum of patients with asthma with increasing severity. Patients with asthma with sputum neutrophilia and mixed granulocyte phenotypes were the most enriched (P <.05). The FZ-response signature (296 downregulated genes) was enriched in asthmatic blood (P <.05) and particularly in neutrophilic and mixed granulocytic sputum (P <.05). These data were confirmed in sputum of the Airway Disease Endotyping for Personalized Therapeutics cohort. IL-22 mRNA across tissues did not correlate with FZ-response enrichment scores, but this response signature correlated with TH22/IL-22 pathways.Conclusions: The FZ-response signature in AD identifies severe neutrophilic asthmatic patients as potential responders to FZ therapy. This approach will help identify patients for future asthma clinical trials of drugs used successfully in other chronic diseases.
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41.
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42.
  • Cheng, X-P, et al. (författare)
  • Compact Bright Radio-loud AGNs. III. A Large VLBA Survey at 43 GHz
  • 2020
  • Ingår i: Astrophysical Journal, Supplement Series. - : American Astronomical Society. - 1538-4365 .- 0067-0049. ; 247:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results from the 43 GHz Very Long Baseline Array (VLBA) observations of 124 compact radio-loud active galactic nuclei (AGNs) that were conducted between 2014 November and 2016 May. The typical dimensions of the restoring beam in each image are about 0.5 mas x 0.2 mas. The highest resolution of 0.2 mas corresponds to a physical size of 0.02 pc for the lowest redshift source in the sample. The 43 GHz very long baseline interferometry (VLBI) images of 97 AGNs are presented for the first time. We study the source compactness on milliarcsecond and submilliarcsecond scales, and suggest that 95 sources in our sample are suitable for future space VLBI observations. By analyzing our data supplemented with other VLBA AGN surveys from the literature, we find that the core brightness temperature increases with increasing frequency below a break frequency similar to 7 GHz, and decreases between similar to 7 and 240 GHz but increases again above 240 GHz in the rest frame of the sources. This indicates that the synchrotron opacity changes from optically thick to thin. We also find a strong statistical correlation between radio and gamma-ray flux densities. Our correlation is tighter than those in the literature derived from lower-frequency VLBI data, suggesting that the gamma-ray emission is produced more cospatially with the 43 GHz VLBA core emission. This correlation can also be extrapolated to the unbeamed AGN population, implying that a universal gamma-ray production mechanism might be at work for all types of AGNs.
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43.
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44.
  • Gurvits, Leonid I., et al. (författare)
  • THEZA: TeraHertz Exploration and Zooming-in for Astrophysics
  • 2021
  • Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 51:3, s. 559-594
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper presents the ESA Voyage 2050 White Paper for a concept of TeraHertz Exploration and Zooming-in for Astrophysics (THEZA). It addresses the science case and some implementation issues of a space-borne radio interferometric system for ultra-sharp imaging of celestial radio sources at the level of angular resolution down to (sub-) microarcseconds. THEZA focuses at millimetre and sub-millimetre wavelengths (frequencies above similar to 300 GHz), but allows for science operations at longer wavelengths too. The THEZA concept science rationale is focused on the physics of spacetime in the vicinity of supermassive black holes as the leading science driver. The main aim of the concept is to facilitate a major leap by providing researchers with orders of magnitude improvements in the resolution and dynamic range in direct imaging studies of the most exotic objects in the Universe, black holes. The concept will open up a sizeable range of hitherto unreachable parameters of observational astrophysics. It unifies two major lines of development of space-borne radio astronomy of the past decades: Space VLBI (Very Long Base-line Interferometry) and mm- and sub-mm astrophysical studies with "single dish" instruments. It also builds upon the recent success of the Earth-based Event Horizon Telescope (EHT) - the first-ever direct image of a shadow of the super-massive black hole in the centre of the galaxy M87. As an amalgam of these three major areas of modern observational astrophysics, THEZA aims at facilitating a breakthrough in high-resolution high image quality studies in the millimetre and sub-millimetre domain of the electromagnetic spectrum.
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45.
  • Kun, Emma, et al. (författare)
  • Follow-up on the Supermassive Black Hole Binary Candidate J1048+7143: Successful Prediction of the Next Gamma-Ray Flare and Refined Binary Parameters in the Framework of the Jet Precession Model
  • 2024
  • Ingår i: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 963:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Analyzing single-dish and very long baseline interferometry radio, as well as Fermi Large Area Telescope γ-ray observations, we explained the three major flares in the γ-ray light curve of FSRQ J1048+7143 with the spin-orbit precession of the dominant mass black hole in a supermassive black hole binary system. Here, we report on the detection of a fourth γ-ray flare from J1048+7143, appearing in the time interval that was predicted in our previous work. Including this new flare, we constrained the mass ratio into a narrow range of 0.062 < q < 0.088, and consequently we were able to further constrain the parameters of the hypothetical supermassive binary black hole at the heart of J1048+7143. We predict the occurrence of the fifth major γ-ray flare that would appear only if the jet will still lay close to our line of sight. The fourth major γ-ray flare also shows the two-subflare structure, further strengthening our scenario in which the occurrence of the subflares is the signature of the precession of a spine-sheath jet structure that quasiperiodically interacts with a proton target, e.g., clouds in the broad-line region.
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46.
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47.
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48.
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49.
  • Tang, Weiyi, et al. (författare)
  • Database of nitrification and nitrifiers in the global ocean
  • 2023
  • Ingår i: EARTH SYSTEM SCIENCE DATA. - 1866-3508 .- 1866-3516. ; 15:11, s. 5039-5077
  • Tidskriftsartikel (refereegranskat)abstract
    • As a key biogeochemical pathway in the marine nitrogen cycle, nitrification (ammonia oxidation and nitrite oxidation) converts the most reduced form of nitrogen - ammonium-ammonia (NH-NH3) - into the oxidized species nitrite (NO) and nitrate (NO). In the ocean, these processes are mainly performed by ammonia-oxidizing archaea (AOA) and bacteria (AOB) and nitrite-oxidizing bacteria (NOB). By transforming nitrogen speciation and providing substrates for nitrogen removal, nitrification affects microbial community structure; marine productivity (including chemoautotrophic carbon fixation); and the production of a powerful greenhouse gas, nitrous oxide (N2O). Nitrification is hypothesized to be regulated by temperature, oxygen, light, substrate concentration, substrate flux, pH and other environmental factors. Although the number of field observations from various oceanic regions has increased considerably over the last few decades, a global synthesis is lacking, and understanding how environmental factors control nitrification remains elusive. Therefore, we have compiled a database of nitrification rates and nitrifier abundance in the global ocean from published literature and unpublished datasets. This database includes 2393 and 1006 measurements of ammonia oxidation and nitrite oxidation rates and 2242 and 631 quantifications of ammonia oxidizers and nitrite oxidizers, respectively. This community effort confirms and enhances our understanding of the spatial distribution of nitrification and nitrifiers and their corresponding drivers such as the important role of substrate concentration in controlling nitrification rates and nitrifier abundance. Some conundrums are also revealed, including the inconsistent observations of light limitation and high rates of nitrite oxidation reported from anoxic waters. This database can be used to constrain the distribution of marine nitrification, to evaluate and improve biogeochemical models of nitrification, and to quantify the impact of nitrification on ecosystem functions like marine productivity and N2O production. This database additionally sets a baseline for comparison with future observations and guides future exploration (e.g., measurements in the poorly sampled regions such as the Indian Ocean and method comparison and/or standardization). The database is publicly available at the Zenodo repository: https://doi.org/10.5281/zenodo.8355912 (Tang et al., 2023).
  •  
50.
  • Tao, Feng, et al. (författare)
  • Microbial carbon use efficiency promotes global soil carbon storage
  • 2023
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 618:7967, s. 981-985
  • Tidskriftsartikel (refereegranskat)abstract
    • Soils store more carbon than other terrestrial ecosystems. How soil organic carbon (SOC) forms and persists remains uncertain, which makes it challenging to understand how it will respond to climatic change. It has been suggested that soil microorganisms play an important role in SOC formation, preservation and loss. Although microorganisms affect the accumulation and loss of soil organic matter through many pathways, microbial carbon use efficiency (CUE) is an integrative metric that can capture the balance of these processes. Although CUE has the potential to act as a predictor of variation in SOC storage, the role of CUE in SOC persistence remains unresolved. Here we examine the relationship between CUE and the preservation of SOC, and interactions with climate, vegetation and edaphic properties, using a combination of global-scale datasets, a microbial-process explicit model, data assimilation, deep learning and meta-analysis. We find that CUE is at least four times as important as other evaluated factors, such as carbon input, decomposition or vertical transport, in determining SOC storage and its spatial variation across the globe. In addition, CUE shows a positive correlation with SOC content. Our findings point to microbial CUE as a major determinant of global SOC storage. Understanding the microbial processes underlying CUE and their environmental dependence may help the prediction of SOC feedback to a changing climate.
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