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Showing papers by "University of Barcelona published in 2020"


Journal ArticleDOI
TL;DR: In this article, the authors present guidelines for the management of patients with coronary artery disease (CAD), which is a pathological process characterized by atherosclerotic plaque accumulation in the epicardial arteries.
Abstract: Coronary artery disease (CAD) is a pathological process characterized by atherosclerotic plaque accumulation in the epicardial arteries, whether obstructive or non-obstructive. This process can be modified by lifestyle adjustments, pharmacological therapies, and invasive interventions designed to achieve disease stabilization or regression. The disease can have long, stable periods but can also become unstable at any time, typically due to an acute atherothrombotic event caused by plaque rupture or erosion. However, the disease is chronic, most often progressive, and hence serious, even in clinically apparently silent periods. The dynamic nature of the CAD process results in various clinical presentations, which can be conveniently categorized as either acute coronary syndromes (ACS) or chronic coronary syndromes (CCS). The Guidelines presented here refer to the management of patients with CCS. The natural history of CCS is illustrated in Figure 1.

3,448 citations


Journal ArticleDOI
Paul Bastard1, Paul Bastard2, Paul Bastard3, Lindsey B. Rosen4, Qian Zhang1, Eleftherios Michailidis1, Hans-Heinrich Hoffmann1, Yu Zhang4, Karim Dorgham3, Quentin Philippot3, Quentin Philippot2, Jérémie Rosain2, Jérémie Rosain3, Vivien Béziat3, Vivien Béziat2, Vivien Béziat1, Jeremy Manry2, Jeremy Manry3, Elana Shaw4, Liis Haljasmägi5, Pärt Peterson5, Lazaro Lorenzo3, Lazaro Lorenzo2, Lucy Bizien2, Lucy Bizien3, Sophie Trouillet-Assant6, Kerry Dobbs4, Adriana Almeida de Jesus4, Alexandre Belot6, Anne Kallaste7, Emilie Catherinot, Yacine Tandjaoui-Lambiotte2, Jérémie Le Pen1, Gaspard Kerner3, Gaspard Kerner2, Benedetta Bigio1, Yoann Seeleuthner3, Yoann Seeleuthner2, Rui Yang1, Alexandre Bolze, András N Spaan8, András N Spaan1, Ottavia M. Delmonte4, Michael S. Abers4, Alessandro Aiuti9, Giorgio Casari9, Vito Lampasona9, Lorenzo Piemonti9, Fabio Ciceri9, Kaya Bilguvar10, Richard P. Lifton10, Richard P. Lifton1, Marc Vasse, David M. Smadja3, Mélanie Migaud3, Mélanie Migaud2, Jérôme Hadjadj3, Benjamin Terrier3, Darragh Duffy11, Lluis Quintana-Murci12, Lluis Quintana-Murci11, Diederik van de Beek13, Lucie Roussel14, Donald C. Vinh14, Stuart G. Tangye15, Stuart G. Tangye16, Filomeen Haerynck17, David Dalmau18, Javier Martinez-Picado19, Javier Martinez-Picado20, Petter Brodin21, Petter Brodin22, Michel C. Nussenzweig23, Michel C. Nussenzweig1, Stéphanie Boisson-Dupuis3, Stéphanie Boisson-Dupuis2, Stéphanie Boisson-Dupuis1, Carlos Rodríguez-Gallego, Guillaume Vogt3, Trine H. Mogensen24, Trine H. Mogensen25, Andrew J. Oler4, Jingwen Gu4, Peter D. Burbelo4, Jeffrey I. Cohen4, Andrea Biondi26, Laura Rachele Bettini26, Mariella D'Angiò26, Paolo Bonfanti26, Patrick Rossignol27, Julien Mayaux3, Frédéric Rieux-Laucat3, Eystein S. Husebye28, Eystein S. Husebye29, Eystein S. Husebye30, Francesca Fusco, Matilde Valeria Ursini, Luisa Imberti31, Alessandra Sottini31, Simone Paghera31, Eugenia Quiros-Roldan32, Camillo Rossi, Riccardo Castagnoli33, Daniela Montagna33, Amelia Licari33, Gian Luigi Marseglia33, Xavier Duval, Jade Ghosn3, Hgid Lab4, Covid Clinicians5, Covid-Storm Clinicians§4, CoV-Contact Cohort§3, Amsterdam Umc Covid Biobank2, Amsterdam Umc Covid Biobank1, Amsterdam Umc Covid Biobank3, Covid Human Genetic Effort1, John S. Tsang4, Raphaela Goldbach-Mansky4, Kai Kisand5, Michail S. Lionakis4, Anne Puel2, Anne Puel1, Anne Puel3, Shen-Ying Zhang2, Shen-Ying Zhang3, Shen-Ying Zhang1, Steven M. Holland4, Guy Gorochov3, Emmanuelle Jouanguy2, Emmanuelle Jouanguy1, Emmanuelle Jouanguy3, Charles M. Rice1, Aurélie Cobat3, Aurélie Cobat1, Aurélie Cobat2, Luigi D. Notarangelo4, Laurent Abel3, Laurent Abel2, Laurent Abel1, Helen C. Su4, Jean-Laurent Casanova 
23 Oct 2020-Science
TL;DR: A means by which individuals at highest risk of life-threatening COVID-19 can be identified is identified, and the hypothesis that neutralizing auto-Abs against type I IFNs may underlie critical CO VID-19 is tested.
Abstract: Interindividual clinical variability in the course of SARS-CoV-2 infection is immense. We report that at least 101 of 987 patients with life-threatening COVID-19 pneumonia had neutralizing IgG auto-Abs against IFN-ω (13 patients), the 13 types of IFN-α (36), or both (52), at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1,227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 were men. A B cell auto-immune phenocopy of inborn errors of type I IFN immunity underlies life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.

1,913 citations


Journal ArticleDOI
Peter J. Campbell1, Gad Getz2, Jan O. Korbel3, Joshua M. Stuart4  +1329 moreInstitutions (238)
06 Feb 2020-Nature
TL;DR: The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.
Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18.

1,600 citations


Journal ArticleDOI
TL;DR: In previously untreated patients with confirmed AML who were ineligible for intensive chemotherapy, overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received zsitidine alone.
Abstract: Background Older patients with acute myeloid leukemia (AML) have a dismal prognosis, even after treatment with a hypomethylating agent. Azacitidine added to venetoclax had promising effica...

1,097 citations


Journal ArticleDOI
TL;DR: In patients with severe Covid-19 not requiring mechanical ventilation, a randomized, open-label, phase 3 trial involving hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation of 94% or less while they were breathing ambient air, and radiologic evidence of pneumonia, the magnitude of benefit cannot be determined.
Abstract: Background Remdesivir is an RNA polymerase inhibitor with potent antiviral activity in vitro and efficacy in animal models of coronavirus disease 2019 (Covid-19). Methods We conducted a ra...

1,086 citations


Journal ArticleDOI
TL;DR: The interconnectedness of the world made society vulnerable to this infection, but it also provides the infrastructure to address previous system failings by disseminating good practices that can result in sustained, efficient, and equitable delivery of mental health-care delivery.

958 citations


Journal ArticleDOI
TL;DR: This expert Consensus Statement, endorsed by the ENS-CCA, summarizes the latest advances in CCA, including classification, genetics and treatment, and provides recommendations for CCA management and priorities across basic, translational and clinical research.
Abstract: Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that can arise at any point of the biliary tree Their incidence is increasing globally, currently accounting for ~15% of all primary liver cancers and ~3% of gastrointestinal malignancies The silent presentation of these tumours combined with their highly aggressive nature and refractoriness to chemotherapy contribute to their alarming mortality, representing ~2% of all cancer-related deaths worldwide yearly The current diagnosis of CCA by non-invasive approaches is not accurate enough, and histological confirmation is necessary Furthermore, the high heterogeneity of CCAs at the genomic, epigenetic and molecular levels severely compromises the efficacy of the available therapies In the past decade, increasing efforts have been made to understand the complexity of these tumours and to develop new diagnostic tools and therapies that might help to improve patient outcomes In this expert Consensus Statement, which is endorsed by the European Network for the Study of Cholangiocarcinoma, we aim to summarize and critically discuss the latest advances in CCA, mostly focusing on classification, cells of origin, genetic and epigenetic abnormalities, molecular alterations, biomarker discovery and treatments Furthermore, the horizon of CCA for the next decade from 2020 onwards is highlighted

926 citations


Journal ArticleDOI
Richard J. Abbott1, T. D. Abbott2, Sheelu Abraham3, Fausto Acernese4  +1334 moreInstitutions (150)
TL;DR: In this paper, the authors reported the observation of a compact binary coalescence involving a 222 −243 M ⊙ black hole and a compact object with a mass of 250 −267 M ⋆ (all measurements quoted at the 90% credible level) The gravitational-wave signal, GW190814, was observed during LIGO's and Virgo's third observing run on 2019 August 14 at 21:10:39 UTC and has a signal-to-noise ratio of 25 in the three-detector network.
Abstract: We report the observation of a compact binary coalescence involving a 222–243 M ⊙ black hole and a compact object with a mass of 250–267 M ⊙ (all measurements quoted at the 90% credible level) The gravitational-wave signal, GW190814, was observed during LIGO's and Virgo's third observing run on 2019 August 14 at 21:10:39 UTC and has a signal-to-noise ratio of 25 in the three-detector network The source was localized to 185 deg2 at a distance of ${241}_{-45}^{+41}$ Mpc; no electromagnetic counterpart has been confirmed to date The source has the most unequal mass ratio yet measured with gravitational waves, ${0112}_{-0009}^{+0008}$, and its secondary component is either the lightest black hole or the heaviest neutron star ever discovered in a double compact-object system The dimensionless spin of the primary black hole is tightly constrained to ≤007 Tests of general relativity reveal no measurable deviations from the theory, and its prediction of higher-multipole emission is confirmed at high confidence We estimate a merger rate density of 1–23 Gpc−3 yr−1 for the new class of binary coalescence sources that GW190814 represents Astrophysical models predict that binaries with mass ratios similar to this event can form through several channels, but are unlikely to have formed in globular clusters However, the combination of mass ratio, component masses, and the inferred merger rate for this event challenges all current models of the formation and mass distribution of compact-object binaries

913 citations


Journal ArticleDOI
Jens Kattge1, Gerhard Bönisch2, Sandra Díaz3, Sandra Lavorel  +751 moreInstitutions (314)
TL;DR: The extent of the trait data compiled in TRY is evaluated and emerging patterns of data coverage and representativeness are analyzed to 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.
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.

882 citations


Journal ArticleDOI
R. Abbott1, T. D. Abbott2, Sheelu Abraham3, Fausto Acernese4  +1332 moreInstitutions (150)
TL;DR: It is inferred that the primary black hole mass lies within the gap produced by (pulsational) pair-instability supernova processes, with only a 0.32% probability of being below 65 M⊙, which can be considered an intermediate mass black hole (IMBH).
Abstract: On May 21, 2019 at 03:02:29 UTC Advanced LIGO and Advanced Virgo observed a short duration gravitational-wave signal, GW190521, with a three-detector network signal-to-noise ratio of 14.7, and an estimated false-alarm rate of 1 in 4900 yr using a search sensitive to generic transients. If GW190521 is from a quasicircular binary inspiral, then the detected signal is consistent with the merger of two black holes with masses of 85_{-14}^{+21} M_{⊙} and 66_{-18}^{+17} M_{⊙} (90% credible intervals). We infer that the primary black hole mass lies within the gap produced by (pulsational) pair-instability supernova processes, with only a 0.32% probability of being below 65 M_{⊙}. We calculate the mass of the remnant to be 142_{-16}^{+28} M_{⊙}, which can be considered an intermediate mass black hole (IMBH). The luminosity distance of the source is 5.3_{-2.6}^{+2.4} Gpc, corresponding to a redshift of 0.82_{-0.34}^{+0.28}. The inferred rate of mergers similar to GW190521 is 0.13_{-0.11}^{+0.30} Gpc^{-3} yr^{-1}.

876 citations


Journal ArticleDOI
TL;DR: The most recent data release from the Sloan Digital Sky Surveys (SDSS-IV) is DR16 as mentioned in this paper, which is the fourth and penultimate from the fourth phase of the survey.
Abstract: This paper documents the sixteenth data release (DR16) from the Sloan Digital Sky Surveys; the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the southern hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey (TDSS) and new data from the SPectroscopic IDentification of ERosita Survey (SPIDERS) programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library "MaStar"). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17).

Journal ArticleDOI
TL;DR: Social disconnectedness predicted higher subsequent perceived isolation, which in turn predicted higher depression symptoms and anxiety symptoms, and the reverse pathways were statistically supported as well, suggesting bi-directional influences.
Abstract: Summary Background Research indicates that social isolation and loneliness increase the risk of mental disorders, but less is known about the distinct contributions of different aspects of isolation. We aimed to distinguish the pathways through which social disconnectedness (eg, small social network, infrequent social interaction) and perceptions of social isolation (eg, loneliness, perceived lack of support) contribute to anxiety and depression symptom severity in community-residing older adults aged 57–85 years at baseline. Methods We did a longitudinal mediation analysis with data from the National Social Life, Health, and Aging Project (NSHAP). The study included individuals from the USA born between 1920 and 1947. Validated measures on social disconnectedness, perceived isolation, and depression and anxiety symptoms were used. Structural equation modelling was used to construct complete longitudinal path models. Findings Using data from 3005 adults aged 57–85 years, we identified two significant longitudinal mediation patterns with symptoms of depression, and two with anxiety symptoms. Overall, social disconnectedness predicted higher subsequent perceived isolation (β=0·09; p Interpretation Social network structure and function are strongly intertwined with anxiety and depression symptoms in the general population of older adults. Public health initiatives could reduce perceived isolation by facilitating social network integration and participation in community activities, thereby protecting against the development of affective disorders. Funding Nordea-fonden.

Journal ArticleDOI
TL;DR: The reserve, resilience, and protective factors professional interest area established a whitepaper workgroup to develop consensus definitions for cognitive reserve, brain reserve, and brain maintenance and evaluated measures that have been used to implement these concepts in research settings and developed guidelines for research that explores or utilizes these concepts.
Abstract: Several concepts, which in the aggregate get might be used to account for "resilience" against age- and disease-related changes, have been the subject of much research. These include brain reserve, cognitive reserve, and brain maintenance. However, different investigators have use these terms in different ways, and there has never been an attempt to arrive at consensus on the definition of these concepts. Furthermore, there has been confusion regarding the measurement of these constructs and the appropriate ways to apply them to research. Therefore the reserve, resilience, and protective factors professional interest area, established under the auspices of the Alzheimer's Association, established a whitepaper workgroup to develop consensus definitions for cognitive reserve, brain reserve, and brain maintenance. The workgroup also evaluated measures that have been used to implement these concepts in research settings and developed guidelines for research that explores or utilizes these concepts. The workgroup hopes that this whitepaper will form a reference point for researchers in this area and facilitate research by supplying a common language.

Journal ArticleDOI
Sadaf G. Sepanlou1, Saeid Safiri2, Catherine Bisignano3, Kevin S Ikuta4  +198 moreInstitutions (106)
TL;DR: Mortality, prevalence, and DALY estimates are compared with those expected according to the Socio-demographic Index (SDI) as a proxy for the development status of regions and countries, and a significant increase in age-standardised prevalence rate of decompensated cirrhosis between 1990 and 2017.

Journal ArticleDOI
TL;DR: In this paper, a combined analysis of the latest neutrino oscillation data presented at the Neutrino2020 conference shows that previous hints for the neutrinos mass ordering have significantly decreased, and normal ordering (NO) is favored only at the 1.6σ level.
Abstract: Our herein described combined analysis of the latest neutrino oscillation data presented at the Neutrino2020 conference shows that previous hints for the neutrino mass ordering have significantly decreased, and normal ordering (NO) is favored only at the 1.6σ level. Combined with the χ2 map provided by Super-Kamiokande for their atmospheric neutrino data analysis the hint for NO is at 2.7σ. The CP conserving value δCP = 180° is within 0.6σ of the global best fit point. Only if we restrict to inverted mass ordering, CP violation is favored at the ∼ 3σ level. We discuss the origin of these results — which are driven by the new data from the T2K and NOvA long-baseline experiments —, and the relevance of the LBL-reactor oscillation frequency complementarity. The previous 2.2σ tension in ∆m221 preferred by KamLAND and solar experiments is also reduced to the 1.1σ level after the inclusion of the latest Super-Kamiokande solar neutrino results. Finally we present updated allowed ranges for the oscillation parameters and for the leptonic Jarlskog determinant from the global analysis.

Journal ArticleDOI
TL;DR: Their added-value in the development of alternative, more effective antibiotics against multi-resistant Gram-negative bacteria has been highlighted and their production methods, physicochemical characterization, and pharmacokinetics are reviewed.
Abstract: Metal-based nanoparticles have been extensively investigated for a set of biomedical applications. According to the World Health Organization, in addition to their reduced size and selectivity for bacteria, metal-based nanoparticles have also proved to be effective against pathogens listed as a priority. Metal-based nanoparticles are known to have non-specific bacterial toxicity mechanisms (they do not bind to a specific receptor in the bacterial cell) which not only makes the development of resistance by bacteria difficult, but also broadens the spectrum of antibacterial activity. As a result, a large majority of metal-based nanoparticles efficacy studies performed so far have shown promising results in both Gram-positive and Gram-negative bacteria. The aim of this review has been a comprehensive discussion of the state of the art on the use of the most relevant types of metal nanoparticles employed as antimicrobial agents. A special emphasis to silver nanoparticles is given, while others (e.g., gold, zinc oxide, copper, and copper oxide nanoparticles) commonly used in antibiotherapy are also reviewed. The novelty of this review relies on the comparative discussion of the different types of metal nanoparticles, their production methods, physicochemical characterization, and pharmacokinetics together with the toxicological risk encountered with the use of different types of nanoparticles as antimicrobial agents. Their added-value in the development of alternative, more effective antibiotics against multi-resistant Gram-negative bacteria has been highlighted.

Journal ArticleDOI
TL;DR: Gaia Early Data Release 3 contains astrometry and photometry results for about 1.8 billion sources based on observations collected by the ESA Gaia satellite during the first 34 months of operations as discussed by the authors.
Abstract: Gaia Early Data Release 3 contains astrometry and photometry results for about 1.8 billion sources based on observations collected by the ESA Gaia satellite during the first 34 months of operations. This paper focuses on the photometric content, describing the input data, the algorithms, the processing, and the validation of the results. Particular attention is given to the quality of the data and to a number of features that users may need to take into account to make the best use of the EDR3 catalogue. The treatment of the BP and RP background has been updated to include a better estimation of the local background, and the detection of crowding effects has been used to exclude affected data from the calibrations. The photometric calibration models have also been updated to account for flux loss over the whole magnitude range. Significant improvements in the modelling and calibration of the point and line spread functions have also helped to reduce a number of instrumental effects that were still present in DR2. EDR3 contains 1.806 billion sources with G-band photometry and 1.540 billion sources with BP and RP photometry. The median uncertainty in the G-band photometry, as measured from the standard deviation of the internally calibrated mean photometry for a given source, is 0.2 mmag at magnitude G=10 to 14, 0.8 mmag at G=17, and 2.6 mmag at G=19. The significant magnitude term found in the Gaia DR2 photometry is no longer visible, and overall there are no trends larger than 1 mmag/mag. Using one passband over the whole colour and magnitude range leaves no systematics above the 1% level in magnitude in any of the bands, and a larger systematic is present for a very small sample of bright and blue sources. A detailed description of the residual systematic effects is provided. Overall the quality of the calibrated mean photometry in EDR3 is superior with respect to DR2 for all bands.

Journal ArticleDOI
TL;DR: Lenvatinib plus pembrolizumab has promising antitumor activity in uHCC, and toxicities were manageable, with no unexpected safety signals.
Abstract: PURPOSE The immunomodulatory effect of lenvatinib (a multikinase inhibitor) on tumor microenvironments may contribute to antitumor activity when combined with programmed death receptor-1 (PD-1) sig...

Journal ArticleDOI
TL;DR: The recommendations for the management of LVV have been updated to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice.
Abstract: BACKGROUND Since the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations. METHODS Using EULAR standardised operating procedures for EULAR-endorsed recommendations, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 13 countries. We modified existing recommendations and created new recommendations. RESULTS Three overarching principles and 10 recommendations were formulated. We recommend that a suspected diagnosis of LVV should be confirmed by imaging or histology. High dose glucocorticoid therapy (40-60 mg/day prednisone-equivalent) should be initiated immediately for induction of remission in active giant cell arteritis (GCA) or Takayasu arteritis (TAK). We recommend adjunctive therapy in selected patients with GCA (refractory or relapsing disease, presence of an increased risk for glucocorticoid-related adverse events or complications) using tocilizumab. Methotrexate may be used as an alternative. Non-biological glucocorticoid-sparing agents should be given in combination with glucocorticoids in all patients with TAK and biological agents may be used in refractory or relapsing patients. We no longer recommend the routine use of antiplatelet or anticoagulant therapy for treatment of LVV unless it is indicated for other reasons. CONCLUSIONS We have updated the recommendations for the management of LVV to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice.

Journal ArticleDOI
TL;DR: This Health Policy paper uses an adapted framework to examine the approaches taken by nine high-income countries and regions that have started to ease COVID-19 restrictions: five in the Asia Pacific region (ie, Hong Kong [Special Administrative Region], Japan, New Zealand, Singapore, and South Korea) and four in Europe (IE, Germany, Norway, Spain, and the UK).

Journal ArticleDOI
07 May 2020
TL;DR: This Primer by Ramos-Casals and colleagues summarizes the epidemiology, mechanisms, diagnosis and treatment of immune-related adverse events and should be prescribed carefully to reduce the potential of short-term and long-term complications.
Abstract: Cancer immunotherapies have changed the landscape of cancer treatment during the past few decades. Among them, immune checkpoint inhibitors, which target PD-1, PD-L1 and CTLA-4, are increasingly used for certain cancers; however, this increased use has resulted in increased reports of immune-related adverse events (irAEs). These irAEs are unique and are different to those of traditional cancer therapies, and typically have a delayed onset and prolonged duration. IrAEs can involve any organ or system. These effects are frequently low grade and are treatable and reversible; however, some adverse effects can be severe and lead to permanent disorders. Management is primarily based on corticosteroids and other immunomodulatory agents, which should be prescribed carefully to reduce the potential of short-term and long-term complications. Thoughtful management of irAEs is important in optimizing quality of life and long-term outcomes.

Journal ArticleDOI
TL;DR: The majority of individuals with SCD will not show progressive cognitive decline, and an individually tailored diagnostic process might be reasonable to identify or exclude underlying medical conditions in an individual withSCD who actively seeks medical help.
Abstract: A growing awareness about brain health and Alzheimer's disease in the general population is leading to an increasing number of cognitively unimpaired individuals, who are concerned that they have reduced cognitive function, to approach the medical system for help. The term subjective cognitive decline (SCD) was conceived in 2014 to describe this condition. Epidemiological data provide evidence that the risk for mild cognitive impairment and dementia is increased in individuals with SCD. However, the majority of individuals with SCD will not show progressive cognitive decline. An individually tailored diagnostic process might be reasonable to identify or exclude underlying medical conditions in an individual with SCD who actively seeks medical help. An increasing number of studies are investigating the link between SCD and the very early stages of Alzheimer's disease and other neurodegenerative diseases.

Journal ArticleDOI
Richard J. Abbott1, T. D. Abbott2, Sheelu Abraham3, Fausto Acernese4  +1330 moreInstitutions (149)
TL;DR: In this article, the authors reported the observation of gravitational waves from a binary-black-hole coalescence during the first two weeks of LIGO and Virgo's third observing run.
Abstract: We report the observation of gravitational waves from a binary-black-hole coalescence during the first two weeks of LIGO’s and Virgo’s third observing run. The signal was recorded on April 12, 2019 at 05∶30∶44 UTC with a network signal-to-noise ratio of 19. The binary is different from observations during the first two observing runs most notably due to its asymmetric masses: a ∼30 M⊙ black hole merged with a ∼8 M⊙ black hole companion. The more massive black hole rotated with a dimensionless spin magnitude between 0.22 and 0.60 (90% probability). Asymmetric systems are predicted to emit gravitational waves with stronger contributions from higher multipoles, and indeed we find strong evidence for gravitational radiation beyond the leading quadrupolar order in the observed signal. A suite of tests performed on GW190412 indicates consistency with Einstein’s general theory of relativity. While the mass ratio of this system differs from all previous detections, we show that it is consistent with the population model of stellar binary black holes inferred from the first two observing runs.

Journal ArticleDOI
TL;DR: The ESC Guidelines for the management of patients with supraventricular tachycardia as discussed by the authors were developed in collaboration with the Association for European Paediatric and Congenital Cardiology (AEPC).
Abstract: 2019 ESC Guidelines for the management of patients with supraventricular tachycardia : The Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC): Developed in collaboration with the Association for European Paediatric and Congenital Cardiology (AEPC)

Journal ArticleDOI
TL;DR: A global survey covering 196 dry inland waters shows that their CO2 emissions share fundamental drivers and constitute a substantial fraction of the carbon cycled by inland waters, increasing current inland water carbon flux estimates by 6%.
Abstract: Many inland waters exhibit complete or partial desiccation, or have vanished due to global change, exposing sediments to the atmosphere. Yet, data on carbon dioxide (CO2) emissions from these sedim ...


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Lennart Lindegren1, Sergei A. Klioner2, Jose M Hernandez3, Alex Bombrun3, M. Ramos-Lerate3, H. Steidelmüller2, Ulrich Bastian4, M. Biermann4, A. de Torres3, E. Gerlach2, R. Geyer2, Thomas Hilger2, David Hobbs1, U. Lammers3, Paul J. McMillan1, C.A. Stephenson3, J. Castañeda5, Michael Davidson6, C. Fabricius5, G. Gracia-Abril4, Jordi Portell5, Nicholas Rowell6, David Teyssier3, F. Torra5, S. Bartolomé5, M. Clotet5, N. Garralda5, J.J. González-Vidal5, J. Torra5, U. Abbas7, Martin Altmann8, Martin Altmann4, E. Anglada Varela3, L. Balaguer-Núñez5, Zoltan Balog4, Zoltan Balog9, C. Barache8, Ugo Becciani7, M. Bernet5, Stefano Bertone10, Stefano Bertone11, Stefano Bertone7, Luciana Bianchi, S. Bouquillon8, Anthony G. A. Brown12, Beatrice Bucciarelli7, D. Busonero7, A. G. Butkevich7, R. Buzzi7, Rossella Cancelliere13, T. Carlucci8, Patrick Charlot14, Maria-Rosa L. Cioni15, Mariateresa Crosta7, C. Crowley3, E. F. del Peloso4, E. del Pozo3, Ronald Drimmel7, P. Esquej3, Agnes Fienga8, Agnes Fienga14, E. Fraile3, Mario Gai7, M. Garcia-Reinaldos3, Raphael Guerra3, Nigel Hambly6, M. Hauser9, K. Janßen15, Stefan Jordan4, Z. Kostrzewa-Rutkowska12, Z. Kostrzewa-Rutkowska16, Massimiliano Lattanzi7, Massimiliano Lattanzi13, S. Liao7, E. Licata7, Tim Lister17, W. Löffler4, Jon Marchant18, A. Masip5, Francois Mignard14, Alexey Mints15, D. Molina5, Alcione Mora3, Roberto Morbidelli7, C. P. Murphy3, C. Pagani19, Pasquale Panuzzo8, X. Peñalosa Esteller5, E. Poggio7, P. Re Fiorentin7, Alberto Riva7, A. Sagristà Sellés4, V. Sanchez Gimenez5, M. Sarasso7, Eva Sciacca7, H. I. Siddiqui20, Richard L. Smart7, D. Souami8, D. Souami21, Alessandro Spagna7, Iain A. Steele18, F. Taris8, E. Utrilla3, W. van Reeven3, Alberto Vecchiato7 
TL;DR: Gaia Early Data Release 3 (Gaia EDR3) as discussed by the authors contains results for 1.812 billion sources in the magnitude range G = 3 to 21 based on observations collected by the European Space Agency Gaia satellite during the first 34 months of its operational phase.
Abstract: Gaia Early Data Release 3 (Gaia EDR3) contains results for 1.812 billion sources in the magnitude range G = 3 to 21 based on observations collected by the European Space Agency Gaia satellite during the first 34 months of its operational phase. We describe the input data, the models, and the processing used for the astrometric content of Gaia EDR3, as well as the validation of these results performed within the astrometry task. The processing broadly followed the same procedures as for Gaia DR2, but with significant improvements to the modelling of observations. For the first time in the Gaia data processing, colour-dependent calibrations of the line- and point-spread functions have been used for sources with well-determined colours from DR2. In the astrometric processing these sources obtained five-parameter solutions, whereas other sources were processed using a special calibration that allowed a pseudocolour to be estimated as the sixth astrometric parameter. Compared with DR2, the astrometric calibration models have been extended, and the spin-related distortion model includes a self-consistent determination of basic-angle variations, improving the global parallax zero point. Gaia EDR3 gives full astrometric data (positions at epoch J2016.0, parallaxes, and proper motions) for 1.468 billion sources (585 million with five-parameter solutions, 882 million with six parameters), and mean positions at J2016.0 for an additional 344 million. Solutions with five parameters are generally more accurate than six-parameter solutions, and are available for 93% of the sources brighter than G = 17 mag. The median uncertainty in parallax and annual proper motion is 0.02-0.03 mas at magnitude G = 9 to 14, and around 0.5 mas at G = 20. Extensive characterisation of the statistical properties of the solutions is provided, including the estimated angular power spectrum of parallax bias from the quasars.

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TL;DR: In this paper, a consensus is emerging that the underlying causes and future dynamics of so-called Arctic greening and browning trends are more complex, variable and inherently scale-dependent than previously thought.
Abstract: As the Arctic warms, vegetation is responding, and satellite measures indicate widespread greening at high latitudes. This ‘greening of the Arctic’ is among the world’s most important large-scale ecological responses to global climate change. However, a consensus is emerging that the underlying causes and future dynamics of so-called Arctic greening and browning trends are more complex, variable and inherently scale-dependent than previously thought. Here we summarize the complexities of observing and interpreting high-latitude greening to identify priorities for future research. Incorporating satellite and proximal remote sensing with in-situ data, while accounting for uncertainties and scale issues, will advance the study of past, present and future Arctic vegetation change.

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TL;DR: The results support the addition of neoadjuvant nivolumab to platinum-based chemotherapy in patients with resectable stage IIIA NSCLC and could change the perception of locally advanced lung cancer as a potentially lethal disease to one that is curable.
Abstract: Summary Background Non-small-cell lung cancer (NSCLC) is terminal in most patients with locally advanced stage disease. We aimed to assess the antitumour activity and safety of neoadjuvant chemoimmunotherapy for resectable stage IIIA NSCLC. Methods This was an open-label, multicentre, single-arm phase 2 trial done at 18 hospitals in Spain. Eligible patients were aged 18 years or older with histologically or cytologically documented treatment-naive American Joint Committee on Cancer-defined stage IIIA NSCLC that was deemed locally to be surgically resectable by a multidisciplinary clinical team, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received neoadjuvant treatment with intravenous paclitaxel (200 mg/m2) and carboplatin (area under curve 6; 6 mg/mL per min) plus nivolumab (360 mg) on day 1 of each 21-day cycle, for three cycles before surgical resection, followed by adjuvant intravenous nivolumab monotherapy for 1 year (240 mg every 2 weeks for 4 months, followed by 480 mg every 4 weeks for 8 months). The primary endpoint was progression-free survival at 24 months, assessed in the modified intention-to-treat population, which included all patients who received neoadjuvant treatment, and in the per-protocol population, which included all patients who had tumour resection and received at least one cycle of adjuvant treatment. Safety was assessed in the modified intention-to-treat population. This study is registered with ClinicalTrials.gov , NCT03081689 , and is ongoing but no longer recruiting patients. Findings Between April 26, 2017, and Aug 25, 2018, we screened 51 patients for eligibility, of whom 46 patients were enrolled and received neoadjuvant treatment. At the time of data cutoff (Jan 31, 2020), the median duration of follow-up was 24·0 months (IQR 21·4–28·1) and 35 of 41 patients who had tumour resection were progression free. At 24 months, progression-free survival was 77·1% (95% CI 59·9–87·7). 43 (93%) of 46 patients had treatment-related adverse events during neoadjuvant treatment, and 14 (30%) had treatment-related adverse events of grade 3 or worse; however, none of the adverse events were associated with surgery delays or deaths. The most common grade 3 or worse treatment-related adverse events were increased lipase (three [7%]) and febrile neutropenia (three [7%]). Interpretation Our results support the addition of neoadjuvant nivolumab to platinum-based chemotherapy in patients with resectable stage IIIA NSCLC. Neoadjuvant chemoimmunotherapy could change the perception of locally advanced lung cancer as a potentially lethal disease to one that is curable. Funding Bristol-Myers Squibb, Instituto de Salud Carlos III, European Union's Horizon 2020 research and innovation programme.

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TL;DR: The first single-centre experience of COVID-19 in patients infected with HIV-1 is described, to the authors' knowledge, including clinical characteristics, antiviral and antiretroviral treatment, and outcomes.