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Sökning: WFRF:(Alfonso F)

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41.
  • Axfors, Cathrine, et al. (författare)
  • Association between convalescent plasma treatment and mortality in COVID-19 : a collaborative systematic review and meta-analysis of randomized clinical trials
  • 2021
  • Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, ). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I-2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care.
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42.
  • Bousquet, J. Jean, et al. (författare)
  • Next-generation ARIA care pathways for rhinitis and asthma : a model for multimorbid chronic diseases
  • 2019
  • Ingår i: Clinical and Translational Allergy. - : BMC. - 2045-7022. ; 9
  • Forskningsöversikt (refereegranskat)abstract
    • Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.Main body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Sante as a Good Practice in the field of digitally-enabled, integrated, person-centred care.Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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43.
  • Davies, Stuart J., et al. (författare)
  • ForestGEO: Understanding forest diversity and dynamics through a global observatory network
  • 2021
  • Ingår i: Biological Conservation. - : Elsevier BV. - 0006-3207. ; 253
  • Tidskriftsartikel (refereegranskat)abstract
    • ForestGEO is a network of scientists and long-term forest dynamics plots (FDPs) spanning the Earth's major forest types. ForestGEO's mission is to advance understanding of the diversity and dynamics of forests and to strengthen global capacity for forest science research. ForestGEO is unique among forest plot networks in its large-scale plot dimensions, censusing of all stems ≥1 cm in diameter, inclusion of tropical, temperate and boreal forests, and investigation of additional biotic (e.g., arthropods) and abiotic (e.g., soils) drivers, which together provide a holistic view of forest functioning. The 71 FDPs in 27 countries include approximately 7.33 million living trees and about 12,000 species, representing 20% of the world's known tree diversity. With >1300 published papers, ForestGEO researchers have made significant contributions in two fundamental areas: species coexistence and diversity, and ecosystem functioning. Specifically, defining the major biotic and abiotic controls on the distribution and coexistence of species and functional types and on variation in species' demography has led to improved understanding of how the multiple dimensions of forest diversity are structured across space and time and how this diversity relates to the processes controlling the role of forests in the Earth system. Nevertheless, knowledge gaps remain that impede our ability to predict how forest diversity and function will respond to climate change and other stressors. Meeting these global research challenges requires major advances in standardizing taxonomy of tropical species, resolving the main drivers of forest dynamics, and integrating plot-based ground and remote sensing observations to scale up estimates of forest diversity and function, coupled with improved predictive models. However, they cannot be met without greater financial commitment to sustain the long-term research of ForestGEO and other forest plot networks, greatly expanded scientific capacity across the world's forested nations, and increased collaboration and integration among research networks and disciplines addressing forest science.
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44.
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45.
  • Falstad, Niklas, 1987, et al. (författare)
  • Hidden or missing outflows in highly obscured galaxy nuclei?
  • 2019
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 623
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding the nuclear growth and feedback processes in galaxies requires investigating their often obscured central regions. One way to do this is to use (sub)millimeter line emission from vibrationally excited HCN (HCN-vib), which is thought to trace warm and highly enshrouded galaxy nuclei. It has been suggested that the most intense HCN-vib emission from a galaxy is connected to a phase of nuclear growth that occurs before the nuclear feedback processes have been fully developed. Aims. We aim to investigate if there is a connection between the presence of strong HCN-vib emission and the development of feedback in (ultra)luminous infrared galaxies ((U)LIRGs). Methods. We collected literature and archival data to compare the luminosities of rotational lines of HCN-vib, normalized to the total infrared luminosity, to the median velocities of 119 μm OH absorption lines, potentially indicating outflows, in a total of 17 (U)LIRGs. Results. The most HCN-vib luminous systems all lack signatures of significant molecular outflows in the far-infrared OH absorption lines. However, at least some of the systems with bright HCN-vib emission have fast and collimated outflows that can be seen in spectral lines at longer wavelengths, including in millimeter emission lines of CO and HCN (in its vibrational ground state) and in radio absorption lines of OH. Conclusions. We conclude that the galaxy nuclei with the highest L HCN-vib /L IR do not drive wide-angle outflows that are detectable using the median velocities of far-infrared OH absorption lines. This is possibly because of an orientation effect in which sources oriented in such a way that their outflows are not along our line of sight also radiate a smaller proportion of their infrared luminosity in our direction. It could also be that massive wide-angle outflows destroy the deeply embedded regions responsible for bright HCN-vib emission, so that the two phenomena cannot coexist. This would strengthen the idea that vibrationally excited HCN traces a heavily obscured stage of evolution before nuclear feedback mechanisms are fully developed.
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46.
  • Gorski, Mark, 1989, et al. (författare)
  • A spectacular galactic scale magnetohydrodynamic powered wind in ESO 320-G030
  • 2024
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 684
  • Tidskriftsartikel (refereegranskat)abstract
    • How galaxies regulate nuclear growth through gas accretion by supermassive black holes (SMBHs) is one of the most fundamental questions in galaxy evolution. One potential way to regulate nuclear growth is through a galactic wind that removes gas from the nucleus. It is unclear whether galactic winds are powered by jets, mechanical winds, radiation, or via magnetohydrodynamic (MHD) processes. Compact obscured nuclei represent a significant phase of galactic nuclear growth. These galaxies hide growing SMBHs or unusual starbursts in their very opaque, extremely compact (r < 100 pc) centres. They are found in approximately 30% of the luminous and ultra-luminous infrared galaxy population. Here, we present high-resolution ALMA observations (∼30 mas, ∼5 pc) of ground-state and vibrationally excited HCN towards ESO 320-G030 (IRAS 11506-3851). ESO 320-G030 is an isolated luminous infrared galaxy known to host a compact obscured nucleus and a kiloparsec-scale molecular wind. Our analysis of these high-resolution observations excludes the possibility of a starburst-driven wind, a mechanically or energy driven active galactic nucleus wind, and exposes a molecular MDH wind. These results imply that the nuclear evolution of galaxies and the growth of SMBHs are similar to the growth of hot cores or protostars where gravitational collapse of the nuclear torus drives a MHD wind. These results mean galaxies are capable, in part, of regulating the evolution of their nuclei without feedback.
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47.
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48.
  • Kroes, JA, et al. (författare)
  • Evaluation of real-world mepolizumab use in severe asthma across Europe: the SHARP experience with privacy-preserving federated analysis
  • 2023
  • Ingår i: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 9:2
  • Tidskriftsartikel (refereegranskat)abstract
    • An objective of the Severe Heterogeneous Asthma Registry, Patient-centered (SHARP) is to produce real-world evidence on a pan-European scale by linking non-standardized, patient-level registry-data. Mepolizumab has shown clinical efficacy in RCTs and prospective real-world studies and could therefore serve as a proof of principle for this novel approach.AimTo harmonize data from 10 national severe asthma registries and characterize patients receiving mepolizumab, assess its effectiveness on annual exacerbations and maintenance oral glucocorticoid (OCS) use, and evaluate treatment patterns.MethodsIn this observational cohort study, registry data (5871 patients) were extracted for harmonization. Where harmonization was possible, patients who initiated mepolizumab between 1-1-2016 and 31-12-2021 were examined. Changes of a 12 (range 11–18) months period in frequent (≥2) exacerbations, maintenance OCS use and dose were analyzed in a privacy-preserving manner using meta-analysis of generalized estimating equation parameters. Periods before and during the COVID-19 pandemic were analyzed separately.ResultsIn 912 patients who fulfilled selection criteria mepolizumab significantly reduced frequent exacerbations (OR;95%CI: 0.18;0.13–0.25), maintenance OCS use (OR;95%CI: 0.75;0.61–0.92) and dose (mean; 95%CI: −3.93 mg·day−1; −5.24–2.62) in the Pre-Pandemic group, with similar trends in the Pandemic group. Marked heterogeneity was observed between registries in patient characteristics and mepolizumab treatment patterns.ConclusionsBy harmonizing patient-level registry data and applying federated analysis, SHARP demonstrated the real-wold effectiveness of mepolizumab on asthma exacerbations and maintenance OCS use in severe asthma patients across Europe, consistent with previous evidence. This paves the way for future pan-European real-world severe asthma studies using patient-level data in a privacy-proof manner.
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50.
  • Liu, Xueping, et al. (författare)
  • Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration.
  • 2019
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P=3.96×10-14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.
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