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1.
  • Mahajan, Anubha, et al. (författare)
  • Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
  • 2022
  • Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
  • Tidskriftsartikel (refereegranskat)abstract
    • We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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2.
  • Chown, Ryan, et al. (författare)
  • PDRs4All: IV. An embarrassment of riches: Aromatic infrared bands in the Orion Bar
  • 2024
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 685
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Mid-infrared observations of photodissociation regions (PDRs) are dominated by strong emission features called aromatic infrared bands (AIBs). The most prominent AIBs are found at 3.3, 6.2, 7.7, 8.6, and 11.2 µm. The most sensitive, highest-resolution infrared spectral imaging data ever taken of the prototypical PDR, the Orion Bar, have been captured by JWST. These high-quality data allow for an unprecedentedly detailed view of AIBs. Aims. We provide an inventory of the AIBs found in the Orion Bar, along with mid-IR template spectra from five distinct regions in the Bar: the molecular PDR (i.e. the three H2 dissociation fronts), the atomic PDR, and the H II region. Methods. We used JWST NIRSpec IFU and MIRI MRS observations of the Orion Bar from the JWST Early Release Science Program, PDRs4All (ID: 1288). We extracted five template spectra to represent the morphology and environment of the Orion Bar PDR. We investigated and characterised the AIBs in these template spectra. We describe the variations among them here. Results. The superb sensitivity and the spectral and spatial resolution of these JWST observations reveal many details of the AIB emission and enable an improved characterization of their detailed profile shapes and sub-components. The Orion Bar spectra are dominated by the well-known AIBs at 3.3, 6.2, 7.7, 8.6, 11.2, and 12.7 µm with well-defined profiles. In addition, the spectra display a wealth of weaker features and sub-components. The widths of many AIBs show clear and systematic variations, being narrowest in the atomic PDR template, but showing a clear broadening in the H II region template while the broadest bands are found in the three dissociation front templates. In addition, the relative strengths of AIB (sub-)components vary among the template spectra as well. All AIB profiles are characteristic of class A sources as designated by Peeters (2022, A&A, 390, 1089), except for the 11.2 µm AIB profile deep in the molecular zone, which belongs to class B11.2. Furthermore, the observations show that the sub-components that contribute to the 5.75, 7.7, and 11.2 µm AIBs become much weaker in the PDR surface layers. We attribute this to the presence of small, more labile carriers in the deeper PDR layers that are photolysed away in the harsh radiation field near the surface. The 3.3/11.2 AIB intensity ratio decreases by about 40% between the dissociation fronts and the H II region, indicating a shift in the polycyclic aromatic hydrocarbon (PAH) size distribution to larger PAHs in the PDR surface layers, also likely due to the effects of photochemistry. The observed broadening of the bands in the molecular PDR is consistent with an enhanced importance of smaller PAHs since smaller PAHs attain a higher internal excitation energy at a fixed photon energy. Conclusions. Spectral-imaging observations of the Orion Bar using JWST yield key insights into the photochemical evolution of PAHs, such as the evolution responsible for the shift of 11.2 µm AIB emission from class B11.2 in the molecular PDR to class A11.2 in the PDR surface layers. This photochemical evolution is driven by the increased importance of FUV processing in the PDR surface layers, resulting in a “weeding out” of the weakest links of the PAH family in these layers. For now, these JWST observations are consistent with a model in which the underlying PAH family is composed of a few species: the so-called ‘grandPAHs’.
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3.
  • De Putte, Dries Van, et al. (författare)
  • PDRs4All VIII. Mid-infrared emission line inventory of the Orion Bar
  • 2024
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 687
  • Tidskriftsartikel (refereegranskat)abstract
    • Context . Mid-infrared emission features are important probes of the properties of ionized gas and hot or warm molecular gas, which are difficult to probe at other wavelengths. The Orion Bar photodissociation region (PDR) is a bright, nearby, and frequently studied target containing large amounts of gas under these conditions. Under the “PDRs4All” Early Release Science Program for JWST, a part of the Orion Bar was observed with MIRI integral field unit (IFU) spectroscopy, and these high-sensitivity IR spectroscopic images of very high angular resolution (0.2′′) provide a rich observational inventory of the mid-infrared (MIR) emission lines, while resolving the H II region, the ionization front, and multiple dissociation fronts. Aims . We list, identify, and measure the most prominent gas emission lines in the Orion Bar using the new MIRI IFU data. An initial analysis summarizes the physical conditions of the gas and demonstrates the potential of these new data and future IFU observations with JWST. Methods. The MIRI IFU mosaic spatially resolves the substructure of the PDR, its footprint cutting perpendicularly across the ionization front and three dissociation fronts. We performed an up-to-date data reduction, and extracted five spectra that represent the ionized, atomic, and molecular gas layers. We identified the observed lines through a comparison with theoretical line lists derived from atomic data and simulated PDR models. The identified species and transitions are summarized in the main table of this work, with measurements of the line intensities and central wavelengths. Results . We identified around 100 lines and report an additional 18 lines that remain unidentified. The majority consists of H I recombination lines arising from the ionized gas layer bordering the PDR. The H I line ratios are well matched by emissivity coefficients from H recombination theory, but deviate by up to 10% because of contamination by He I lines. We report the observed emission lines of various ionization stages of Ne, P, S, Cl, Ar, Fe, and Ni. We show how the Ne III/Ne II, S IV/S III, and Ar III/Ar II ratios trace the conditions in the ionized layer bordering the PDR, while Fe III/Fe II and Ni III/Ni II exhibit a different behavior, as there are significant contributions to Fe II and Ni II from the neutral PDR gas. We observe the pure-rotational H2 lines in the vibrational ground state from 0–0 S(1) to 0–0 S(8), and in the first vibrationally excited state from 1–1 S(5) to 1–1 S(9). We derive H2 excitation diagrams, and for the three observed dissociation fronts, the rotational excitation can be approximated with one thermal (∼700 K) component representative of an average gas temperature, and one nonthermal component (∼2700 K) probing the effect of UV pumping. We compare these results to an existing model of the Orion Bar PDR, and find that the predicted excitation matches the data qualitatively, while adjustments to the parameters of the PDR model are required to reproduce the intensity of the 0–0 S(6) to S(8) lines.
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4.
  • Habart, Emilie, et al. (författare)
  • PDRs4All II. JWST’s NIR and MIR imaging view of the Orion Nebula
  • 2024
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 685
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The James Webb Space Telescope (JWST) has captured the most detailed and sharpest infrared (IR) images ever taken of the inner region of the Orion Nebula, the nearest massive star formation region, and a prototypical highly irradiated dense photo-dissociation region (PDR). Aims. We investigate the fundamental interaction of far-ultraviolet (FUV) photons with molecular clouds. The transitions across the ionization front (IF), dissociation front (DF), and the molecular cloud are studied at high-angular resolution. These transitions are relevant to understanding the effects of radiative feedback from massive stars and the dominant physical and chemical processes that lead to the IR emission that JWST will detect in many Galactic and extragalactic environments. Methods. We utilized NIRCam and MIRI to obtain sub-arcsecond images over ∼150′′ and 42′′ in key gas phase lines (e.g., Pa α, Br α, [FeII] 1.64 µm, H2 1–0 S(1) 2.12 µm, 0–0 S(9) 4.69 µm), aromatic and aliphatic infrared bands (aromatic infrared bands at 3.3–3.4 µm, 7.7, and 11.3 µm), dust emission, and scattered light. Their emission are powerful tracers of the IF and DF, FUV radiation field and density distribution. Using NIRSpec observations the fractional contributions of lines, AIBs, and continuum emission to our NIRCam images were estimated. A very good agreement is found for the distribution and intensity of lines and AIBs between the NIRCam and NIRSpec observations. Results. Due to the proximity of the Orion Nebula and the unprecedented angular resolution of JWST, these data reveal that the molecular cloud borders are hyper structured at small angular scales of ∼0.1–1′′ (∼0.0002–0.002 pc or ∼40–400 au at 414 pc). A diverse set of features are observed such as ridges, waves, globules and photoevaporated protoplanetary disks. At the PDR atomic to molecular transition, several bright features are detected that are associated with the highly irradiated surroundings of the dense molecular condensations and embedded young star. Toward the Orion Bar PDR, a highly sculpted interface is detected with sharp edges and density increases near the IF and DF. This was predicted by previous modeling studies, but the fronts were unresolved in most tracers. The spatial distribution of the AIBs reveals that the PDR edge is steep and is followed by an extensive warm atomic layer up to the DF with multiple ridges. A complex, structured, and folded H0/H2 DF surface was traced by the H2 lines. This dataset was used to revisit the commonly adopted 2D PDR structure of the Orion Bar as our observations show that a 3D “terraced” geometry is required to explain the JWST observations. JWST provides us with a complete view of the PDR, all the way from the PDR edge to the substructured dense region, and this allowed us to determine, in detail, where the emission of the atomic and molecular lines, aromatic bands, and dust originate. Conclusions. This study offers an unprecedented dataset to benchmark and transform PDR physico-chemical and dynamical models for the JWST era. A fundamental step forward in our understanding of the interaction of FUV photons with molecular clouds and the role of FUV irradiation along the star formation sequence is provided.
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5.
  • Peeters, Els, et al. (författare)
  • PDRs4All: III. JWST's NIR spectroscopic view of the Orion Bar
  • 2024
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 685
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. JWST has taken the sharpest and most sensitive infrared (IR) spectral imaging observations ever of the Orion Bar photodis-sociation region (PDR), which is part of the nearest massive star-forming region the Orion Nebula, and often considered to be the 'prototypical'strongly illuminated PDR. Aims. We investigate the impact of radiative feedback from massive stars on their natal cloud and focus on the transition from the H II region to the atomic PDR -crossing the ionisation front (IF) -, and the subsequent transition to the molecular PDR -crossing the dissociation front (DF). Given the prevalence of PDRs in the interstellar medium and their dominant contribution to IR radiation, understanding the response of the PDR gas to far-ultraviolet (FUV) photons and the associated physical and chemical processes is fundamental to our understanding of star and planet formation and for the interpretation of any unresolved PDR as seen by JWST. Methods. We used high-resolution near-IR integral field spectroscopic data from NIRSpec on JWST to observe the Orion Bar PDR as part of the PDRs4All JWST Early Release Science programme. We constructed a 3″ × 25″ spatio-spectral mosaic covering 0.97-5.27 μm at a spectral resolution R of ~2700 and an angular resolution of 0.075″-0.173″. To study the properties of key regions captured in this mosaic, we extracted five template spectra in apertures centred on the three H2 dissociation fronts, the atomic PDR, and the H II region. This wealth of detailed spatial-spectral information was analysed in terms of variations in the physical conditions-incident UV field, density, and temperature -of the PDR gas. Results. The NIRSpec data reveal a forest of lines including, but not limited to, He I, H I, and C I recombination lines; ionic lines (e.g. Fe III and Fe II); O I and N I fluorescence lines; aromatic infrared bands (AIBs, including aromatic CH, aliphatic CH, and their CD counterparts); pure rotational and ro-vibrational lines from H2; and ro-vibrational lines from HD, CO, and CH+, with most of them having been detected for the first time towards a PDR. Their spatial distribution resolves the H and He ionisation structure in the Huygens region, gives insight into the geometry of the Bar, and confirms the large-scale stratification of PDRs. In addition, we observed numerous smaller-scale structures whose typical size decreases with distance from θ1 Ori C and IR lines from C I, if solely arising from radiative recombination and cascade, reveal very high gas temperatures (a few 1000 K) consistent with the hot irradiated surface of small-scale dense clumps inside the PDR. The morphology of the Bar, in particular that of the H2 lines, reveals multiple prominent filaments that exhibit different characteristics. This leaves the impression of a 'terraced'transition from the predominantly atomic surface region to the CO-rich molecular zone deeper in. We attribute the different characteristics of the H2 filaments to their varying depth into the PDR and, in some cases, not reaching the C+/C/CO transition. These observations thus reveal what local conditions are required to drive the physical and chemical processes needed to explain the different characteristics of the DFs and the photochemical evolution of the AIB carriers. Conclusions. This study showcases the discovery space created by JWST to further our understanding of the impact radiation from young stars has on their natal molecular cloud and proto-planetary disk, which touches on star and planet formation as well as galaxy evolution.
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6.
  • 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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7.
  • Berné, O., et al. (författare)
  • Formation of the methyl cation by photochemistry in a protoplanetary disk
  • 2023
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 621:7977, s. 56-59
  • Tidskriftsartikel (refereegranskat)abstract
    • Forty years ago, it was proposed that gas-phase organic chemistry in the interstellar medium can be initiated by the methyl cation CH3+ (refs. 1–3), but so far it has not been observed outside the Solar System 4,5. Alternative routes involving processes on grain surfaces have been invoked 6,7. Here we report James Webb Space Telescope observations of CH3+ in a protoplanetary disk in the Orion star-forming region. We find that gas-phase organic chemistry is activated by ultraviolet irradiation.
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8.
  • Berne, Olivier, et al. (författare)
  • PDRs4All : A JWST Early Release Science Program on Radiative Feedback from Massive Stars
  • 2022
  • Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 134:1035
  • Tidskriftsartikel (refereegranskat)abstract
    • Massive stars disrupt their natal molecular cloud material through radiative and mechanical feedback processes. These processes have profound effects on the evolution of interstellar matter in our Galaxy and throughout the universe, from the era of vigorous star formation at redshifts of 1-3 to the present day. The dominant feedback processes can be probed by observations of the Photo-Dissociation Regions (PDRs) where the far-ultraviolet photons of massive stars create warm regions of gas and dust in the neutral atomic and molecular gas. PDR emission provides a unique tool to study in detail the physical and chemical processes that are relevant for most of the mass in inter- and circumstellar media including diffuse clouds, proto-planetary disks, and molecular cloud surfaces, globules, planetary nebulae, and star-forming regions. PDR emission dominates the infrared (IR) spectra of star-forming galaxies. Most of the Galactic and extragalactic observations obtained with the James Webb Space Telescope (JWST) will therefore arise in PDR emission. In this paper we present an Early Release Science program using the MIRI, NIRSpec, and NIRCam instruments dedicated to the observations of an emblematic and nearby PDR: the Orion Bar. These early JWST observations will provide template data sets designed to identify key PDR characteristics in JWST observations. These data will serve to benchmark PDR models and extend them into the JWST era. We also present the Science-Enabling products that we will provide to the community. These template data sets and Science-Enabling products will guide the preparation of future proposals on star-forming regions in our Galaxy and beyond and will facilitate data analysis and interpretation of forthcoming JWST observations.
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9.
  • Grasselli, Giacomo, et al. (författare)
  • ESICM guidelines on acute respiratory distress syndrome : definition, phenotyping and respiratory support strategies
  • 2023
  • Ingår i: Intensive Care Medicine. - : Springer Nature. - 0342-4642 .- 1432-1238. ; 49, s. 727-759
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients' representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.
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10.
  • Bastard, Paul, et al. (författare)
  • Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1.
  • 2021
  • Ingår i: The Journal of experimental medicine. - 1540-9538. ; 218:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti-IFN-β and another anti-IFN-ε, but none had anti-IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.
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11.
  • Gonzalez, Arantxa, et al. (författare)
  • Cardiac remodelling - Part 1: From cells and tissues to circulating biomarkers. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology
  • 2022
  • Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 24:6, s. 927-943
  • Forskningsöversikt (refereegranskat)abstract
    • Cardiac remodelling refers to changes in left ventricular structure and function over time, with a progressive deterioration that may lead to heart failure (HF) development (adverse remodelling) or vice versa a recovery (reverse remodelling) in response to HF treatment. Adverse remodelling predicts a worse outcome, whilst reverse remodelling predicts a better prognosis. The geometry, systolic and diastolic function and electric activity of the left ventricle are affected, as well as the left atrium and on the long term even right heart chambers. At a cellular and molecular level, remodelling involves all components of cardiac tissue: cardiomyocytes, fibroblasts, endothelial cells and leucocytes. The molecular, cellular and histological signatures of remodelling may differ according to the cause and severity of cardiac damage, and clearly to the global trend toward worsening or recovery. These processes cannot be routinely evaluated through endomyocardial biopsies, but may be reflected by circulating levels of several biomarkers. Different classes of biomarkers (e.g. proteins, non-coding RNAs, metabolites and/or epigenetic modifications) and several biomarkers of each class might inform on some aspects on HF development, progression and long-term outcomes, but most have failed to enter clinical practice. This may be due to the biological complexity of remodelling, so that no single biomarker could provide great insight on remodelling when assessed alone. Another possible reason is a still incomplete understanding of the role of biomarkers in the pathophysiology of cardiac remodelling. Such role will be investigated in the first part of this review paper on biomarkers of cardiac remodelling.
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12.
  • 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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13.
  • Aimo, Alberto, et al. (författare)
  • Cardiac remodelling - Part 2: Clinical, imaging and laboratory findings. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology
  • 2022
  • Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 24:6, s. 944-958
  • Forskningsöversikt (refereegranskat)abstract
    • In patients with heart failure, the beneficial effects of drug and device therapies counteract to some extent ongoing cardiac damage. According to the net balance between these two factors, cardiac geometry and function may improve (reverse remodelling, RR) and even completely normalize (remission), or vice versa progressively deteriorate (adverse remodelling, AR). RR or remission predict a better prognosis, while AR has been associated with worsening clinical status and outcomes. The remodelling process ultimately involves all cardiac chambers, but has been traditionally evaluated in terms of left ventricular volumes and ejection fraction. This is the second part of a review paper by the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology dedicated to ventricular remodelling. This document examines the proposed criteria to diagnose RR and AR, their prevalence and prognostic value, and the variables predicting remodelling in patients managed according to current guidelines. Much attention will be devoted to RR in patients with heart failure with reduced ejection fraction because most studies on cardiac remodelling focused on this setting.
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14.
  • Arheimer, Berit, et al. (författare)
  • The IAHS Science for Solutions decade, with Hydrology Engaging Local People IN a Global world (HELPING)
  • 2024
  • Ingår i: Hydrological Sciences Journal. - 0262-6667 .- 2150-3435.
  • Tidskriftsartikel (refereegranskat)abstract
    • The new scientific decade (2023-2032) of the International Association of Hydrological Sciences (IAHS) aims at searching for sustainable solutions to undesired water conditions - may it be too little, too much or too polluted. Many of the current issues originate from global change, while solutions to problems must embrace local understanding and context. The decade will explore the current water crises by searching for actionable knowledge within three themes: global and local interactions, sustainable solutions and innovative cross-cutting methods. We capitalise on previous IAHS Scientific Decades shaping a trilogy; from Hydrological Predictions (PUB) to Change and Interdisciplinarity (Panta Rhei) to Solutions (HELPING). The vision is to solve fundamental water-related environmental and societal problems by engaging with other disciplines and local stakeholders. The decade endorses mutual learning and co-creation to progress towards UN sustainable development goals. Hence, HELPING is a vehicle for putting science in action, driven by scientists working on local hydrology in coordination with local, regional, and global processes.
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15.
  • Berné, O., et al. (författare)
  • A far-ultraviolet-driven photoevaporation flow observed in a protoplanetary disk
  • 2024
  • Ingår i: Science. - 0036-8075 .- 1095-9203. ; 383:6686, s. 988-992
  • Tidskriftsartikel (refereegranskat)abstract
    • Most low-mass stars form in stellar clusters that also contain massive stars, which are sources of far-ultraviolet (FUV) radiation. Theoretical models predict that this FUV radiation produces photodissociation regions (PDRs) on the surfaces of protoplanetary disks around low-mass stars, which affects planet formation within the disks. We report James Webb Space Telescope and Atacama Large Millimeter Array observations of a FUV-irradiated protoplanetary disk in the Orion Nebula. Emission lines are detected from the PDR; modeling their kinematics and excitation allowed us to constrain the physical conditions within the gas. We quantified the mass-loss rate induced by the FUV irradiation and found that it is sufficient to remove gas from the disk in less than a million years. This is rapid enough to affect giant planet formation in the disk.
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16.
  • Caly, H., et al. (författare)
  • Machine learning analysis of pregnancy data enables early identification of a subpopulation of newborns with ASD
  • 2021
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify newborns at risk of developing ASD and to detect ASD biomarkers early after birth, we compared retrospectively ultrasound and biological measurements of babies diagnosed later with ASD or neurotypical (NT) that are collected routinely during pregnancy and birth. We used a supervised machine learning algorithm with a cross-validation technique to classify NT and ASD babies and performed various statistical tests. With a minimization of the false positive rate, 96% of NT and 41% of ASD babies were identified with a positive predictive value of 77%. We identified the following biomarkers related to ASD: sex, maternal familial history of auto-immune diseases, maternal immunization to CMV, IgG CMV level, timing of fetal rotation on head, femur length in the 3rd trimester, white blood cell count in the 3rd trimester, fetal heart rate during labor, newborn feeding and temperature difference between birth and one day after. Furthermore, statistical models revealed that a subpopulation of 38% of babies at risk of ASD had significantly larger fetal head circumference than age-matched NT ones, suggesting an in utero origin of the reported bigger brains of toddlers with ASD. Our results suggest that pregnancy follow-up measurements might provide an early prognosis of ASD enabling pre-symptomatic behavioral interventions to attenuate efficiently ASD developmental sequels.
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17.
  • Celutkiene, Jelena, et al. (författare)
  • Role of cardiovascular imaging in cancer patients receiving cardiotoxic therapies : a position statement on behalf of the Heart Failure Association (HFA), the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the European Society of Cardiology (ESC)
  • 2020
  • Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 22:9, s. 1504-1524
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiovascular (CV) imaging is an important tool in baseline risk assessment and detection of CV disease in oncology patients receiving cardiotoxic cancer therapies. This position statement examines the role of echocardiography, cardiac magnetic resonance, nuclear cardiac imaging and computed tomography in the management of cancer patients. The Imaging and Cardio-Oncology Study Groups of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the European Association of Cardiovascular Imaging (EACVI) and the Cardio-Oncology Council of the ESC have evaluated the current evidence for the value of modern CV imaging in the cardio-oncology field. The most relevant echocardiographic parameters, including global longitudinal strain and three-dimensional ejection fraction, are proposed. The protocol for baseline pre-treatment evaluation and specific surveillance algorithms or pathways for anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor tyrosine kinase inhibitors, BCr-Abl tyrosine kinase inhibitors, proteasome inhibitors and immune checkpoint inhibitors are presented. The indications for CV imaging after completion of oncology treatment are considered. The typical consequences of radiation therapy and the possibility of their identification in the long term are also summarized. Special populations are discussed including female survivors planning pregnancy, patients with carcinoid disease, patients with cardiac tumours and patients with right heart failure. Future directions and ongoing CV imaging research in cardio-oncology are discussed.
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18.
  • Cuni-Sanchez, Aida, et al. (författare)
  • High aboveground carbon stock of African tropical montane forests
  • 2021
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 596:7873, s. 536-542
  • Tidskriftsartikel (refereegranskat)abstract
    • Tropical forests store 40–50per cent of terrestrial vegetation carbon. However, spatial variations in aboveground live tree biomass carbon (AGC) stocks remain poorly understood, in particular in tropical montane forests. Owing to climatic and soil changes with increasing elevation, AGC stocks are lower in tropical montane forests compared with lowland forests. Here we assemble and analyse a dataset of structurally intact old-growth forests (AfriMont) spanning 44 montane sites in 12 African countries. We find that montane sites in the AfriMont plot network have a mean AGC stock of 149.4megagrams of carbon per hectare (95% confidence interval 137.1–164.2), which is comparable to lowland forests in the African Tropical Rainforest Observation Network4 and about 70per cent and 32per cent higher than averages from plot networks in montane and lowland forests in the Neotropics, respectively. Notably, our results are two-thirds higher than the Intergovernmental Panel on Climate Change default values for these forests in Africa8. We find that the low stem density and high abundance of large trees of African lowland forests is mirrored in the montane forests sampled. This carbon store is endangered: we estimate that 0.8 million hectares of old-growth African montane forest have been lost since 2000. We provide country-specific montane forest AGC stock estimates modelled from our plot network to helpto guide forest conservation and reforestation interventions. Our findings highlight the need for conserving these biodiverse and carbon-rich ecosystems.
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19.
  • Delrez, Laetitia, et al. (författare)
  • Transit detection of the long-period volatile-rich super-Earth nu(2) Lupi d with CHEOPS
  • 2021
  • Ingår i: Nature Astronomy. - : Springer Science and Business Media LLC. - 2397-3366. ; :5, s. 775-787
  • Tidskriftsartikel (refereegranskat)abstract
    • Exoplanets transiting bright nearby stars are key objects for advancing our knowledge of planetary formation and evolution. The wealth of photons from the host star gives detailed access to the atmospheric, interior and orbital properties of the planetary companions. nu(2) Lupi (HD 136352) is a naked-eye (V = 5.78) Sun-like star that was discovered to host three low-mass planets with orbital periods of 11.6, 27.6 and 107.6 d via radial-velocity monitoring(1). The two inner planets (b and c) were recently found to transit(2), prompting a photometric follow-up by the brand new Characterising Exoplanets Satellite (CHEOPS). Here, we report that the outer planet d is also transiting, and measure its radius and mass to be 2.56 +/- 0.09 R-circle plus and 8.82 +/- 0.94 M-circle plus, respectively. With its bright Sun-like star, long period and mild irradiation (similar to 5.7 times the irradiation of Earth), nu(2) Lupi d unlocks a completely new region in the parameter space of exoplanets amenable to detailed characterization. We refine the properties of all three planets: planet b probably has a rocky mostly dry composition, while planets c and d seem to have retained small hydrogen-helium envelopes and a possibly large water fraction. This diversity of planetary compositions makes the nu(2) Lupi system an excellent laboratory for testing formation and evolution models of low-mass planets.
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20.
  • Elyajouri, Meriem, et al. (författare)
  • PDRs4All V. Modelling the dust evolution across the illuminated edge of the Orion Bar
  • 2024
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 685
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Interstellar dust particles, in particular carbonaceous nano-grains (like polycyclic aromatic hydrocarbons, fullerenes, and amorphous hydrogenated carbon), are critical players for the composition, energy budget, and dynamics of the interstellar medium (ISM). The dust properties, specifically the composition and size of dust grains are not static; instead, they exhibit considerable evolution triggered by variations in local physical conditions such as the density and gas temperature within the ISM, as is the case in photon-dominated regions (PDRs). The evolution of dust and its impact on the local physical and chemical conditions is thus a key question for understanding the first stages of star formation. Aims. From the extensive spectral and imaging data of the JWST PDRs4All program, we study the emission of dust grains within the Orion Bar – a well-known, highly far-UV (FUV)-irradiated PDR situated at the intersection between cold, dense molecular clouds, and warm ionized regions. The Orion Bar because of its edge-on geometry provides an exceptional benchmark for characterizing dust evolution and the associated driving processes under varying physical conditions. Our goal is to constrain the local properties of dust by comparing its emission to models. Taking advantage of the recent JWST data, in particular the spectroscopy of dust emission, we identify new constraints on dust and further previous works of dust modelling. Methods. To characterize interstellar dust across the Orion Bar, we follow its emission as traced by JWST NIRCam (at 3.35 and 4.8 µm) and MIRI (at 7.7, 11.3, 15.0, and 25.5 µm) broad band images, along with NIRSpec and MRS spectroscopic observations. First, we constrain the minimum size and hydrogen content of carbon nano-grains from a comparison between the observed dust emission spectra and the predictions of the Heterogeneous dust Evolution Model for Interstellar Solids (THEMIS) coupled to the numerical code DustEM. Using this dust model, we then perform 3D radiative transfer simulations of dust emission with the SOC code (Scattering with OpenCL) and compare to data obtained along well chosen profiles across the Orion Bar. Results. The JWST data allows us, for the first time, to spatially resolve the steep variation of dust emission at the illuminated edge of the Orion Bar PDR. By considering a dust model with carbonaceous nano-grains and submicronic coated silicate grains, we derive unprecedented constraints on the properties of across the Orion Bar. To explain the observed emission profiles with our simulations, we find that the nano-grains must be strongly depleted with an abundance (relative to the gas) 15 times less than in the diffuse ISM. The NIRSpec and MRS spectroscopic observations reveal variations in the hydrogenation of the carbon nano-grains. The lowest hydrogenation levels are found in the vicinity of the illuminating stars suggesting photo-processing while more hydrogenated nano-grains are found in the cold and dense molecular region, potentially indicative of larger grains.
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21.
  • Maasri, Alain, et al. (författare)
  • A global agenda for advancing freshwater biodiversity research
  • 2022
  • Ingår i: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 25:2, s. 255-263
  • Tidskriftsartikel (refereegranskat)abstract
    • Global freshwater biodiversity is declining dramatically, and meeting the challenges of this crisis requires bold goals and the mobilisation of substantial resources. While the reasons are varied, investments in both research and conservation of freshwater biodiversity lag far behind those in the terrestrial and marine realms. Inspired by a global consultation, we identify 15 pressing priority needs, grouped into five research areas, in an effort to support informed stewardship of freshwater biodiversity. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated actions towards its sustainable management and conservation. 
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22.
  • Moreau, Thomas, et al. (författare)
  • Benchopt : Reproducible, efficient and collaborative optimization benchmarks
  • 2022
  • Ingår i: Advances in Neural Information Processing Systems 35 - 36th Conference on Neural Information Processing Systems, NeurIPS 2022. - 1049-5258. - 9781713871088 ; 35, s. 25404-25421
  • Konferensbidrag (refereegranskat)abstract
    • Numerical validation is at the core of machine learning research as it allows to assess the actual impact of new methods, and to confirm the agreement between theory and practice. Yet, the rapid development of the field poses several challenges: researchers are confronted with a profusion of methods to compare, limited transparency and consensus on best practices, as well as tedious re-implementation work. As a result, validation is often very partial, which can lead to wrong conclusions that slow down the progress of research. We propose Benchopt, a collaborative framework to automate, reproduce and publish optimization benchmarks in machine learning across programming languages and hardware architectures. Benchopt simplifies benchmarking for the community by providing an off-the-shelf tool for running, sharing and extending experiments. To demonstrate its broad usability, we showcase benchmarks on three standard learning tasks: ℓ2-regularized logistic regression, Lasso, and ResNet18 training for image classification. These benchmarks highlight key practical findings that give a more nuanced view of the state-of-the-art for these problems, showing that for practical evaluation, the devil is in the details. We hope that Benchopt will foster collaborative work in the community hence improving the reproducibility of research findings.
  •  
23.
  • Moreira, Andre L., et al. (författare)
  • A Grading System for Invasive Pulmonary Adenocarcinoma : A Proposal From the International Association for the Study of Lung Cancer Pathology Committee
  • 2020
  • Ingår i: Journal of Thoracic Oncology. - : ELSEVIER SCIENCE INC. - 1556-0864 .- 1556-1380. ; 15:10, s. 1599-1610
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: A grading system for pulmonary adenocarcinoma has not been established. The International Association for the Study of Lung Cancer pathology panel evaluated a set of histologic criteria associated with prognosis aimed at establishing a grading system for invasive pulmonary adenocarcinoma. Methods: A multi-institutional study involving multiple cohorts of invasive pulmonary adenocarcinomas was conducted. A cohort of 284 stage I pulmonary adenocarcinomas was used as a training set to identify histologic features associated with patient outcomes (recurrence-free survival [RFS] and overall survival [OS]). Receiver operating characteristic curve analysis was used to select the best model, which was validated (n = 212) and tested (n = 300, including stage I-III) in independent cohorts. Reproducibility of the model was assessed using kappa statistics. Results: The best model (area under the receiver operating characteristic curve [AUC] = 0.749 for RFS and 0.787 for OS) was composed of a combination of predominant plus high-grade histologic pattern with a cutoff of 20% for the latter. The model consists of the following: grade 1, lepidic predominant tumor; grade 2, acinar or papillary predominant tumor, both with no or less than 20% of high-grade patterns; and grade 3, any tumor with 20% or more of high-grade patterns (solid, micropapillary, or complex gland). Similar results were seen in the validation (AUC = 0.732 for RFS and 0.787 for OS) and test cohorts (AUC = 0.690 for RFS and 0.743 for OS), confirming the predictive value of the model. Interobserver reproducibility revealed good agreement (k = 0.617). Conclusions: A grading system based on the predominant and high-grade patterns is practical and prognostic for invasive pulmonary adenocarcinoma. (C) 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
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24.
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25.
  • Nunez, Julio, et al. (författare)
  • Congestion in heart failure: a circulating biomarker-based perspective. A review from the Biomarkers Working Group of the Heart Failure Association, European Society of Cardiology
  • 2022
  • Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 24:10, s. 1751-1766
  • Forskningsöversikt (refereegranskat)abstract
    • Congestion is a cardinal sign of heart failure (HF). In the past, it was seen as a homogeneous epiphenomenon that identified patients with advanced HF. However, current evidence shows that congestion in HF varies in quantity and distribution. This updated view advocates for a congestive-driven classification of HF according to onset (acute vs. chronic), regional distribution (systemic vs. pulmonary), compartment of distribution (intravascular vs. extravascular), and clinical vs. subclinical. Thus, this review will focus on the utility of circulating biomarkers for assessing and managing the different fluid overload phenotypes. This discussion focused on the clinical utility of the natriuretic peptides, carbohydrate antigen 125 (also called mucin 16), bio-adrenomedullin and mid-regional pro-adrenomedullin, ST2 (also known as interleukin-1 receptor-like 1), cluster of differentiation 146, troponin, C-terminal pro-endothelin-1, and parameters of haemoconcentration. The utility of circulation biomarkers on top of clinical evaluation, haemodynamics, and imaging needs to be better determined by dedicated studies. Some multiparametric frameworks in which these tools contribute to management are proposed.
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26.
  • Reinke, Beth A, et al. (författare)
  • Diverse aging rates in ectothermic tetrapods provide insights for the evolution of aging and longevity
  • 2022
  • Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 376:6600, s. 1459-1466
  • Tidskriftsartikel (refereegranskat)abstract
    • Comparative studies of mortality in the wild are necessary to understand the evolution of aging; yet, ectothermic tetrapods are underrepresented in this comparative landscape, despite their suitability for testing evolutionary hypotheses. We present a study of aging rates and longevity across wild tetrapod ectotherms, using data from 107 populations (77 species) of nonavian reptiles and amphibians. We test hypotheses of how thermoregulatory mode, environmental temperature, protective phenotypes, and pace of life history contribute to demographic aging. Controlling for phylogeny and body size, ectotherms display a higher diversity of aging rates compared with endotherms and include phylogenetically widespread evidence of negligible aging. Protective phenotypes and life-history strategies further explain macroevolutionary patterns of aging. Analyzing ectothermic tetrapods in a comparative context enhances our understanding of the evolution of aging.
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27.
  • Stoop, Thomas F., et al. (författare)
  • Pathological complete response in patients with resected pancreatic adenocarcinoma after preoperative chemotherapy
  • 2024
  • Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 7:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking.Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy.Design, Setting, and Participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months.Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection.Main Outcomes and Measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively.Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89).Conclusions and Relevance: This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.
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28.
  • Wright, Gillian, et al. (författare)
  • The Mid-infrared Instrument for JWST and Its In-flight Performance
  • 2023
  • Ingår i: Publications of the Astronomical Society of the Pacific. - 0004-6280 .- 1538-3873. ; 135:1046
  • Tidskriftsartikel (refereegranskat)abstract
    • The Mid-Infrared Instrument (MIRI) extends the reach of the James Webb Space Telescope (JWST) to 28.5 μm. It provides subarcsecond-resolution imaging, high sensitivity coronagraphy, and spectroscopy at resolutions of λ/Δλ ∼ 100-3500, with the high-resolution mode employing an integral field unit to provide spatial data cubes. The resulting broad suite of capabilities will enable huge advances in studies over this wavelength range. This overview describes the history of acquiring this capability for JWST. It discusses the basic attributes of the instrument optics, the detector arrays, and the cryocooler that keeps everything at approximately 7 K. It gives a short description of the data pipeline and of the instrument performance demonstrated during JWST commissioning. The bottom line is that the telescope and MIRI are both operating to the standards set by pre-launch predictions, and all of the MIRI capabilities are operating at, or even a bit better than, the level that had been expected. The paper is also designed to act as a roadmap to more detailed papers on different aspects of MIRI.
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29.
  • Balci, Deniz, et al. (författare)
  • Revival of associating liver partition and portal vein ligation for staged hepatectomy for perihilar cholangiocarcinoma: An international multicenter study with promising outcomes
  • 2023
  • Ingår i: Surgery. - : MOSBY-ELSEVIER. - 0039-6060 .- 1532-7361. ; 173:6, s. 1398-1404
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Associating liver partition and portal vein ligation for staged hepatectomy for per-ihilar cholangiocarcinoma has been considered to be contraindicated due to the initial poor results. Given the recent reports of improved outcomes, we aimed to collect the recent expe-riences of different centers performing associating liver partition and portal vein ligation for staged hepatectomy for perihilar cholangiocarcinoma to analyze factors related to improved outcomes. Methods: This proof-of-concept study collected contemporary cases of associating liver partition and portal vein ligation for staged hepatectomy for perihilar cholangiocarcinoma and analyzed for morbidity, short and long-term survival, and factors associated with outcomes. Results: In total, 39 patients from 8 centers underwent associating liver partition and portal vein ligation for staged hepatectomy for perihilar cholangiocarcinoma from 2010 to 2020. The median preoperative future liver remnant volume was 323 mL (155-460 mL). The median future liver remnant increase was 58.7% (8.9%-264. 5%) with a median interstage interval of 13 days (6-60 days). Post-stage 1 and post-stage 2 biliary leaks occurred in 2 (7.7%) and 4 (15%) patients. Six patients (23%) after stage 1 and 6 (23%) after stage 2 experienced grade 3 or higher complica-tions. Two patients (7.7%) died within 90 days after stage 2. The 1-, 3-, and 5-year survival was 92%, 69%, and 55%, respectively. A subgroup analysis revealed poor survival for patients under-going additional vascular resection and lymph node positivity. Lymph node-negative patients showed excellent survival demonstrated by 1-, 3-, and 5-year survival of 86%, 86%, and 86%. Conclusion: This study highlights that the critical attitude toward associating liver partition and portal vein ligation for staged hepatectomy for perihilar cholangiocarcinoma needs to be revised. In selected patients with perihilar cholangiocarcinoma, associating liver partition and portal vein ligation for staged hepatectomy can achieve favorable survival that compares to the outcome of established surgical treatment strategies reported in benchmark studies for perihilar cholangiocarcinoma including 1-stage hepatectomy and liver transplantation. (c) 2023 Elsevier Inc. All rights reserved.
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30.
  • Berndt, Sonja, I, et al. (författare)
  • Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
  • 2022
  • Ingår i: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 36:12, s. 2835-2844
  • Tidskriftsartikel (refereegranskat)abstract
    • Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.
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31.
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32.
  • Devos, David, et al. (författare)
  • Trial of Deferiprone in Parkinson’s Disease
  • 2022
  • Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 387:22, s. 2045-2055
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUNDIron content is increased in the substantia nigra of persons with Parkinson's disease and may contribute to the pathophysiology of the disorder. Early research suggests that the iron chelator deferiprone can reduce nigrostriatal iron content in persons with Parkinson's disease, but its effects on disease progression are unclear.METHODSWe conducted a multicenter, phase 2, randomized, double-blind trial involving participants with newly diagnosed Parkinson's disease who had never received levodopa. Participants were assigned (in a 1:1 ratio) to receive oral deferiprone at a dose of 15 mg per kilogram of body weight twice daily or matched placebo for 36 weeks. Dopaminergic therapy was withheld unless deemed necessary for symptom control. The primary outcome was the change in the total score on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS; range, 0 to 260, with higher scores indicating more severe impairment) at 36 weeks. Secondary and exploratory clinical outcomes at up to 40 weeks included measures of motor and nonmotor disability. Brain iron content measured with the use of magnetic resonance imaging was also an exploratory outcome.RESULTSA total of 372 participants were enrolled; 186 were assigned to receive deferiprone and 186 to receive placebo. Progression of symptoms led to the initiation of dopaminergic therapy in 22.0% of the participants in the deferiprone group and 2.7% of those in the placebo group. The mean MDS-UPDRS total score at baseline was 34.3 in the deferiprone group and 33.2 in the placebo group and increased (worsened) by 15.6 points and 6.3 points, respectively (difference, 9.3 points; 95% confidence interval, 6.3 to 12.2; P<0.001). Nigrostriatal iron content decreased more in the deferiprone group than in the placebo group. The main serious adverse events with deferiprone were agranulocytosis in 2 participants and neutropenia in 3 participants.CONCLUSIONSIn participants with early Parkinson's disease who had never received levodopa and in whom treatment with dopaminergic medications was not planned, deferiprone was associated with worse scores in measures of parkinsonism than those with placebo over a period of 36 weeks.
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33.
  • Feng, Shaohong, et al. (författare)
  • Dense sampling of bird diversity increases power of comparative genomics
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7833
  • Tidskriftsartikel (refereegranskat)abstract
    • Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
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34.
  • Fernandez, Gimena, et al. (författare)
  • Ghrelin Action in the PVH of Male Mice : Accessibility, Neuronal Targets, and CRH Neurons Activation
  • 2023
  • Ingår i: Endocrinology. - : Endocrine Society. - 0013-7227 .- 1945-7170. ; 164:11
  • Tidskriftsartikel (refereegranskat)abstract
    • The hormone ghrelin displays several well-characterized functions, including some with pharmaceutical interest. The receptor for ghrelin, the growth hormone secretagogue receptor (GHSR), is expressed in the hypothalamic paraventricular nucleus (PVH), a critical hub for the integration of metabolic, neuroendocrine, autonomic, and behavioral functions. Here, we performed a neuroanatomical and functional characterization of the neuronal types mediating ghrelin actions in the PVH of male mice. We found that fluorescent ghrelin mainly labels PVH neurons immunoreactive for nitric oxide synthase 1 (NOS1), which catalyze the production of nitric oxide [NO]). Centrally injected ghrelin increases c-Fos in NOS1 PVH neurons and NOS1 phosphorylation in the PVH. We also found that a high dose of systemically injected ghrelin increases the ghrelin level in the cerebrospinal fluid and in the periventricular PVH, and induces c-Fos in NOS1 PVH neurons. Such a high dose of systemically injected ghrelin activates a subset of NOS1 PVH neurons, which do not express oxytocin, via an arcuate nucleus-independent mechanism. Finally, we found that pharmacological inhibition of NO production fully abrogates ghrelin-induced increase of calcium concentration in corticotropin-releasing hormone neurons of the PVH whereas it partially impairs ghrelin-induced increase of plasma glucocorticoid levels. Thus, plasma ghrelin can directly target a subset of NO-producing neurons of the PVH that is involved in ghrelin-induced activation of the hypothalamic-pituitary-adrenal neuroendocrine axis.
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35.
  • Fittipaldi, Antonela S., et al. (författare)
  • Ghrelin proteolysis increases in plasma of men, but not women, with obesity
  • 2023
  • Ingår i: Life Sciences. - : Elsevier. - 0024-3205 .- 1879-0631. ; 313
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Since plasma ghrelin can undergo des-acylation and proteolysis, the aim of this study was to investigate the extent to which an enhancement of these reactions is associated to the decrease of ghrelin in plasma after food intake or in individuals with obesity.Main methods: we performed an intervention cross-sectional study, in which levels of ghrelin, desacyl-ghrelin (DAG), glucose, insulin, ghrelin des-acylation and ghrelin proteolysis were assessed in plasma before and after a test meal in 40 people (n = 21 males) with normal weight (NW, n = 20) or overweight/obesity (OW/OB, n = 20).Key findings: Preprandial ghrelin and DAG levels were lower, whereas preprandial ghrelin proteolysis was -4.6-fold higher in plasma of males with OW/OB. In males, ghrelin proteolysis positively correlated with glycemia. Ghrelin and DAG levels were also lower in females with OW/OB, but preprandial ghrelin proteolysis was not different between females with NW or OW/OB. Ghrelin and DAG levels decreased postprandially in males and females, independently of BMI, and ghrelin proteolysis increased postprandially-2 folds only in individuals with NW. Ghrelin des-acylation remained unaffected by BMI or feeding status in both sexes.Significance: Current study shows that ghrelin proteolysis increases in males with obesity as well as after meal in lean individuals. Therefore, ghrelin proteolysis may be an important checkpoint and, consequently, a putative pharmacological target to control circulating ghrelin levels in humans.
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36.
  • Grant, Sierra L., et al. (författare)
  • MINDS. The Detection of 13 CO 2 with JWST-MIRI Indicates Abundant CO 2 in a Protoplanetary Disk
  • 2023
  • Ingår i: Astrophysical Journal Letters. - 2041-8213 .- 2041-8205. ; 947:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present JWST-MIRI Medium Resolution Spectrometer (MRS) spectra of the protoplanetary disk around the low-mass T Tauri star GW Lup from the MIRI mid-INfrared Disk Survey Guaranteed Time Observations program. Emission from 12CO213CO2, H2O, HCN, C2H2, and OH is identified with 13CO2 being detected for the first time in a protoplanetary disk. We characterize the chemical and physical conditions in the inner few astronomical units of the GW Lup disk using these molecules as probes. The spectral resolution of JWST-MIRI MRS paired with high signal-to-noise data is essential to identify these species and determine their column densities and temperatures. The Q branches of these molecules, including those of hot bands, are particularly sensitive to temperature and column density. We find that the 12CO2 emission in the GW Lup disk is coming from optically thick emission at a temperature of ∼400 K. 13CO2 is optically thinner and based on a lower temperature of ∼325 K, and thus may be tracing deeper into the disk and/or a larger emitting radius than 12CO2. The derived N CO 2 / N H 2 O ratio is orders of magnitude higher than previously derived for GW Lup and other targets based on Spitzer-InfraRed-Spectrograph data. This high column density ratio may be due to an inner cavity with a radius in between the H2O and CO2 snowlines and/or an overall lower disk temperature. This paper demonstrates the unique ability of JWST to probe inner disk structures and chemistry through weak, previously unseen molecular features.
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37.
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38.
  • Hwang, Bernice, et al. (författare)
  • The impact of insect herbivory on biogeochemical cycling in broadleaved forests varies with temperature
  • 2024
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Herbivorous insects alter biogeochemical cycling within forests, but the magnitude of these impacts, their global variation, and drivers of this variation remain poorly understood. To address this knowledge gap and help improve biogeochemical models, we established a global network of 74 plots within 40 mature, undisturbed broadleaved forests. We analyzed freshly senesced and green leaves for carbon, nitrogen, phosphorus and silica concentrations, foliar production and herbivory, and stand-level nutrient fluxes. We show more nutrient release by insect herbivores at non-outbreak levels in tropical forests than temperate and boreal forests, that these fluxes increase strongly with mean annual temperature, and that they exceed atmospheric deposition inputs in some localities. Thus, background levels of insect herbivory are sufficiently large to both alter ecosystem element cycling and influence terrestrial carbon cycling. Further, climate can affect interactions between natural populations of plants and herbivores with important consequences for global biogeochemical cycles across broadleaved forests.
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39.
  • Jonason, Peter K., et al. (författare)
  • Country-level correlates of the Dark Triad traits in 49 countries
  • 2020
  • Ingår i: Journal of personality. - : Wiley. - 0022-3506 .- 1467-6494. ; 88:6, s. 1252-1267
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The Dark Triad traits (i.e., narcissism, psychopathy, Machiavellianism) capture individual differences in aversive personality to complement work on other taxonomies, such as the Big Five traits. However, the literature on the Dark Triad traits relies mostly on samples from English-speaking (i.e., Westernized) countries. We broadened the scope of this literature by sampling from a wider array of countries.Method: We drew on data from 49 countries (N = 11,723; 65.8% female;Age(Mean) = 21.53) to examine how an extensive net of country-level variables in economic status (e.g., Human Development Index), social relations (e.g., gender equality), political orientations (e.g., democracy), and cultural values (e.g., embeddedness) relate to country-level rates of the Dark Triad traits, as well as variance in the magnitude of sex differences in them.Results: Narcissism was especially sensitive to country-level variables. Countries with more embedded and hierarchical cultural systems weremorenarcissistic. Also, sex differences in narcissism werelargerinmoredeveloped societies: Women were less likely to be narcissistic in developed (vs. less developed) countries.Conclusions: We discuss the results based on evolutionary and social role models of personality and sex differences. That higher country-level narcissism was more common in less developed countries, whereas sex differences in narcissism were larger in more developed countries, is more consistent with evolutionary than social role models.
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40.
  • Klompstra, Leonie, et al. (författare)
  • Measuring physical activity with activity monitors in patients with heart failure: from literature to practice. A position paper from the Committee on Exercise Physiology and Training of the Heart Failure Association of the European Society of Cardiology
  • 2021
  • Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844.
  • Tidskriftsartikel (refereegranskat)abstract
    • The aims of this paper were to provide an overview of available activity monitors used in research in patients with heart failure and to identify the key criteria in the selection of the most appropriate activity monitor for collecting, reporting, and analysing physical activity in heart failure research. This study was conducted in three parts. First, the literature was systematically reviewed to identify physical activity concepts and activity monitors used in heart failure research. Second, an additional scoping literature search for validation of these activity monitors was conducted. Third, the most appropriate criteria in the selection of activity monitors were identified. Nine activity monitors were evaluated in terms of size, weight, placement, costs, data storage, water resistance, outcomes and validation, and cut-off points for physical activity intensity levels were discussed. The choice of a monitor should depend on the research aims, study population and design regarding physical activity. If the aim is to motivate patients to be active or set goals, a less rigorously tested tool can be considered. On the other hand, if the aim is to measure physical activity and its changes over time or following treatment adjustment, it is important to choose a valid activity monitor with a storage and battery longevity of at least one week. The device should provide raw data and valid cut-off points should be chosen for analysing physical activity intensity levels. Other considerations in choosing an activity monitor should include data storage location and ownership and the upfront costs of the device.
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41.
  • Ledent, Alice, et al. (författare)
  • What do tropical cryptogams reveal? Strong genetic structure in Amazonian bryophytes
  • 2020
  • Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 228:2, s. 640-650
  • Tidskriftsartikel (refereegranskat)abstract
    • Lowland tropical bryophytes have been perceived as excellent dispersers. In such groups, the inverse isolation hypothesis proposes that spatial genetic structure is erased beyond the limits of short-distance dispersal. Here, we determine the influence of environmental variation and geographic barriers on the spatial genetic structure of a widely dispersed and phylogenetically independent sample of Amazonian bryophytes. Single nucleotide polymorphism data were produced from a restriction site-associated DNA sequencing protocol for 10 species and analyzed through F-statistics and Mantel tests. Neither isolation-by-environment nor the impact of geographic barriers were recovered from the analyses. However, significant isolation-by-distance patterns were observed for 8 out of the 10 investigated species beyond the scale of short-distance dispersal (> 1 km), offering evidence contrary to the inverse isolation hypothesis. Despite a cadre of life-history traits and distributional patterns suggesting that tropical bryophytes are highly vagile, our analyses reveal spatial genetic structures comparable to those documented for angiosperms, whose diaspores are orders of magnitude larger. Dispersal limitation for tropical bryophytes flies in the face of traditional assumptions regarding their dispersal potential, and suggests that the plight of this component of cryptic biodiversity is more dire than previously considered in light of accelerated forest fragmentation in the Amazon.
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42.
  • Leibovitzh, Haim, et al. (författare)
  • Immune response and barrier dysfunction-related proteomic signatures in preclinical phase of Crohn's disease highlight earliest events of pathogenesis
  • 2023
  • Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 72:8, s. 1462-1471
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The measure of serum proteome in the preclinical state of Crohn's disease (CD) may provide insight into biological pathways involved in CD pathogenesis. We aimed to assess associations of serum proteins with future CD onset and with other biomarkers predicting CD risk in a healthy at-risk cohort.DESIGN: In a nested case-control study within the Crohn's and Colitis Canada Genetics Environment Microbial Project (CCC-GEM) cohort, which prospectively follows healthy first-degree relatives (FDRs), subjects who developed CD (n=71) were matched with four FDRs remaining healthy (n=284). Using samples at recruitment, serum protein profiles using the Olink Proximity Extension Assay platform was assessed for association with future development of CD and with other baseline biomarkers as follows: serum antimicrobial antibodies (AS: positive antibody sum) (Prometheus); faecal calprotectin (FCP); gut barrier function using the fractional excretion of lactulose-to-mannitol ratio (LMR) assay.RESULTS: We identified 25 of 446 serum proteins significantly associated with future development of CD. C-X-C motif chemokine 9 (CXCL9) had the highest OR with future risk of CD (OR=2.07 per SD, 95% CI 1.58 to 2.73, q=7.9e-5), whereas matrix extracellular phosphoglycoprotein had the lowest OR (OR 0.44, 95% CI 0.29 to 0.66, q=0.02). Notably, CXCL9 was the only analyte significantly associated with all other CD-risk biomarkers with consistent direction of effect (FCP: OR=2.21; LMR: OR=1.67; AS: OR=1.59) (q<0.05 for all).CONCLUSION: We identified serum proteomic signatures associated with future CD development, reflecting potential early biological processes of immune and barrier dysfunction.
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43.
  • Li, Jun, et al. (författare)
  • ALPPS for Locally Advanced Intrahepatic Cholangiocarcinoma: Did Aggressive Surgery Lead to the Oncological Benefit? An International Multi-center Study
  • 2020
  • Ingår i: Annals of Surgical Oncology. - : SPRINGER. - 1068-9265 .- 1534-4681. ; 27, s. 1372-1384
  • Tidskriftsartikel (refereegranskat)abstract
    • Background ALPPS is found to increase the resectability of primary and secondary liver malignancy at the advanced stage. The aim of the study was to verify the surgical and oncological outcome of ALPPS for intrahepatic cholangiocarcinoma (ICC). Methods The study cohort was based on the ALPPS registry with patients from 31 international centers between August 2009 and January 2018. Propensity score matched patients receiving chemotherapy only were selected from the SEER database as controls for the survival analysis. Results One hundred and two patients undergoing ALPPS were recruited, 99 completed the second stage with median inter-stage duration of 11 days. The median kinetic growth rate was 23 ml/day. R0 resection was achieved in 87 (85%). Initially high rates of morbidity and mortality decreased steadily to a 29% severe complication rate and 7% 90-day morbidity in the last 2 years. Post-hepatectomy liver failure remained the main cause of 90-day mortality. Multivariate analysis revealed insufficient future liver remnant at the stage-2 operation (FLR2) to be the only risk factor for severe complications (OR 2.91, p = 0.02). The propensity score matching analysis showed a superior overall survival in the ALPPS group compared to palliative chemotherapy (median overall survival: 26.4 months vs 14 months; 1-, 2-, and 3-year survival rates: 82.4%, 70.5% and 39.6% vs 51.2%, 21.4% and 11.3%, respectively, p amp;lt; 0.01). The survival benefit, however, was not confirmed in the subgroup analysis for patients with insufficient FLR2 or multifocal ICC. Conclusion ALPPS showed high efficacy in achieving R0 resections in locally advanced ICC. To get the most oncological benefit from this aggressive surgery, ALPPS would be restricted to patients with single lesions and sufficient FLR2.
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44.
  • Lindén, Elin, et al. (författare)
  • Circum-Arctic distribution of chemical anti-herbivore compounds suggests biome-wide trade-off in defence strategies in Arctic shrubs
  • 2022
  • Ingår i: Ecography. - : John Wiley & Sons. - 0906-7590 .- 1600-0587. ; :11
  • Tidskriftsartikel (refereegranskat)abstract
    • Spatial variation in plant chemical defence towards herbivores can help us understand variation in herbivore top–down control of shrubs in the Arctic and possibly also shrub responses to global warming. Less defended, non-resinous shrubs could be more influenced by herbivores than more defended, resinous shrubs. However, sparse field measurements limit our current understanding of how much of the circum-Arctic variation in defence compounds is explained by taxa or defence functional groups (resinous/non-resinous). We measured circum-Arctic chemical defence and leaf digestibility in resinous (Betula glandulosa, B. nana ssp. exilis) and non-resinous (B. nana ssp. nana, B. pumila) shrub birches to see how they vary among and within taxa and functional groups. Using liquid chromatography–mass spectrometry (LC–MS) metabolomic analyses and in vitro leaf digestibility via incubation in cattle rumen fluid, we analysed defence composition and leaf digestibility in 128 samples from 44 tundra locations.We found biogeographical patterns in anti-herbivore defence where mean leaf triterpene concentrations and twig resin gland density were greater in resinous taxa and mean concentrations of condensing tannins were greater in non-resinous taxa. This indicates a biome-wide trade-off between triterpene- or tannin-dominated defences. However, we also found variations in chemical defence composition and resin gland density both within and among functional groups (resinous/non-resinous) and taxa, suggesting these categorisations only partly predict chemical herbivore defence. Complex tannins were the only defence compounds negatively related to in vitro digestibility, identifying this previously neglected tannin group as having a potential key role in birch anti-herbivore defence.We conclude that circum-Arctic variation in birch anti-herbivore defence can be partly derived from biogeographical distributions of birch taxa, although our detailed mapping of plant defence provides more information on this variation and can be used for better predictions of herbivore effects on Arctic vegetation.
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45.
  • Manry, Jérémy, et al. (författare)
  • The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.
  • 2022
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:21
  • Tidskriftsartikel (refereegranskat)abstract
    • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
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46.
  • McDevitt, Allan D., et al. (författare)
  • Next-generation phylogeography resolves post-glacial colonization patterns in a widespread carnivore, the red fox (Vulpes vulpes), in Europe
  • 2022
  • Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 31:3, s. 993-1006
  • Tidskriftsartikel (refereegranskat)abstract
    • Carnivores tend to exhibit a lack of (or less pronounced) genetic structure at continental scales in both a geographic and temporal sense and this can confound the identification of post-glacial colonization patterns in this group. In this study we used genome-wide data (using genotyping by sequencing [GBS]) to reconstruct the phylogeographic history of a widespread carnivore, the red fox (Vulpes vulpes), by investigating broad-scale patterns of genomic variation, differentiation and admixture amongst contemporary populations in Europe. Using 15,003 single nucleotide polymorphisms (SNPs) from 524 individuals allowed us to identify the importance of refugial regions for the red fox in terms of endemism (e.g., Iberia). In addition, we tested multiple post-glacial recolonization scenarios of previously glaciated regions during the Last Glacial Maximum using an Approximate Bayesian Computation (ABC) approach that were unresolved from previous studies. This allowed us to identify the role of admixture from multiple source population post-Younger Dryas in the case of Scandinavia and ancient land-bridges in the colonization of the British Isles. A natural colonization of Ireland was deemed more likely than an ancient human-mediated introduction as has previously been proposed and potentially points to a larger mammalian community on the island in the early post-glacial period. Using genome-wide data has allowed us to tease apart broad-scale patterns of structure and diversity in a widespread carnivore in Europe that was not evident from using more limited marker sets and provides a foundation for next-generation phylogeographic studies in other non-model species. 
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47.
  • Metra, Marco, et al. (författare)
  • Pre-discharge and early post-discharge management of patients hospitalized for acute heart failure: A scientific statement by the Heart Failure Association of the ESC
  • 2023
  • Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 25:7, s. 1115-1131
  • Tidskriftsartikel (refereegranskat)abstract
    • Acute heart failure is a major cause of urgent hospitalizations. These are followed by marked increases in death and rehospitalization rates, which then decline exponentially though they remain higher than in patients without a recent hospitalization. Therefore, optimal management of patients with acute heart failure before discharge and in the early post-discharge phase is critical. First, it may prevent rehospitalizations through the early detection and effective treatment of residual or recurrent congestion, the main manifestation of decompensation. Second, initiation at pre-discharge and titration to target doses in the early post-discharge period, of guideline-directed medical therapy may improve both short- and long-term outcomes. Third, in chronic heart failure, medical treatment is often left unchanged, so the acute heart failure hospitalization presents an opportunity for implementation of therapy. The aim of this scientific statement by the Heart Failure Association of the European Society of Cardiology is to summarize recent findings that have implications for clinical management both in the pre-discharge and the early post-discharge phase after a hospitalization for acute heart failure.
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48.
  • Mullens, Wilfried, et al. (författare)
  • Integration of implantable device therapy in patients with heart failure. A clinical consensus statement from the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC)
  • 2024
  • Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844.
  • Tidskriftsartikel (refereegranskat)abstract
    • Implantable devices form an integral part of the management of patients with heart failure (HF) and provide adjunctive therapies in addition to cornerstone drug treatment. Although the number of these devices is growing, only few are supported by robust evidence. Current devices aim to improve haemodynamics, improve reverse remodelling, or provide electrical therapy. A number of these devices have guideline recommendations and some have been shown to improve outcomes such as cardiac resynchronization therapy, implantable cardioverter-defibrillators and long-term mechanical support. For others, more evidence is still needed before large-scale implementation can be strongly advised. Of note, devices and drugs can work synergistically in HF as improved disease control with devices can allow for further optimization of drug therapy. Therefore, some devices might already be considered early in the disease trajectory of HF patients, while others might only be reserved for advanced HF. As such, device therapy should be integrated into HF care programmes. Unfortunately, implementation of devices, including those with the greatest evidence, in clinical care pathways is still suboptimal. This clinical consensus document of the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC) describes the physiological rationale behind device-provided therapy and also device-guided management, offers an overview of current implantable device options recommended by the guidelines and proposes a new integrated model of device therapy as a part of HF care.
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49.
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50.
  • Nolan, Jerry P., et al. (författare)
  • ERC-ESICM guidelines on temperature control after cardiac arrest in adults
  • 2022
  • Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572. ; 172, s. 229-236
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of these guidelines is to provide evidence‑based guidance for temperature control in adults who are comatose after resuscitation from either in-hospital or out-of-hospital cardiac arrest, regardless of the underlying cardiac rhythm. These guidelines replace the recommendations on temperature management after cardiac arrest included in the 2021 post-resuscitation care guidelines co-issued by the European Resuscitation Council (ERC) and the European Society of Intensive Care Medicine (ESICM). The guideline panel included thirteen international clinical experts who authored the 2021 ERC-ESICM guidelines and two methodologists who participated in the evidence review completed on behalf of the International Liaison Committee on Resuscitation (ILCOR) of whom ERC is a member society. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations. The panel provided suggestions on guideline implementation and identified priorities for future research. The certainty of evidence ranged from moderate to low. In patients who remain comatose after cardiac arrest, we recommend continuous monitoring of core temperature and actively preventing fever (defined as a temperature > 37.7 °C) for at least 72 hours. There was insufficient evidence to recommend for or against temperature control at 32–36 °C or early cooling after cardiac arrest. We recommend not actively rewarming comatose patients with mild hypothermia after return of spontaneous circulation (ROSC) to achieve normothermia. We recommend not using prehospital cooling with rapid infusion of large volumes of cold intravenous fluids immediately after ROSC.
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