Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Gaia Data Release 3: Mapping the asymmetric disc of the Milky Way

With the most recent Gaia data release the number of sources with complete 6D phase space information (position and velocity) has increased to well over 33 million stars, while stellar astrophysical parameters are provided for more than 470 million sources, in addition to the identification of over 11 million variable stars. Using the astrophysical parameters and variability classifications provided in Gaia DR3, we select various stellar populations to explore and identify non-axisymmetric features in the disc of the Milky Way in both configuration and velocity space. Using more about 580 thousand sources identified as hot OB stars, together with 988 known open clusters younger than 100 million years, we map the spiral structure associated with star formation 4-5 kpc from the Sun. We select over 2800 Classical Cepheids younger than 200 million years, which show spiral features extending as far as 10 kpc from the Sun in the outer disc. We also identify more than 8.7 million sources on the red giant branch (RGB), of which 5.7 million have line-of-sight velocities, allowing the velocity field of the Milky Way to be mapped as far as 8 kpc from the Sun, including the inner disc. The spiral structure revealed by the young populations is consistent with recent results using Gaia EDR3 astrometry and source lists based on near infrared photometry, showing the Local (Orion) arm to be at least 8 kpc long, and an outer arm consistent with what is seen in HI surveys, which seems to be a continuation of the Perseus arm into the third quadrant. Meanwhile, the subset of RGB stars with velocities clearly reveals the large scale kinematic signature of the bar in the inner disc, as well as evidence of streaming motions in the outer disc that might be associated with spiral arms or bar resonances. (abridged

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure: an analysis of the LUNG SAFE database

Background: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). Methods: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. Results: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. Conclusions: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. Trial registration: NCT02010073. Registered on 12 December 2013

Spontaneous Breathing in Early Acute Respiratory Distress Syndrome: Insights From the Large Observational Study to UNderstand the Global Impact of Severe Acute Respiratory FailurE Study

OBJECTIVES: To describe the characteristics and outcomes of patients with acute respiratory distress syndrome with or without spontaneous breathing and to investigate whether the effects of spontaneous breathing on outcome depend on acute respiratory distress syndrome severity. DESIGN: Planned secondary analysis of a prospective, observational, multicentre cohort study. SETTING: International sample of 459 ICUs from 50 countries. PATIENTS: Patients with acute respiratory distress syndrome and at least 2 days of invasive mechanical ventilation and available data for the mode of mechanical ventilation and respiratory rate for the 2 first days. INTERVENTIONS: Analysis of patients with and without spontaneous breathing, defined by the mode of mechanical ventilation and by actual respiratory rate compared with set respiratory rate during the first 48 hours of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Spontaneous breathing was present in 67% of patients with mild acute respiratory distress syndrome, 58% of patients with moderate acute respiratory distress syndrome, and 46% of patients with severe acute respiratory distress syndrome. Patients with spontaneous breathing were older and had lower acute respiratory distress syndrome severity, Sequential Organ Failure Assessment scores, ICU and hospital mortality, and were less likely to be diagnosed with acute respiratory distress syndrome by clinicians. In adjusted analysis, spontaneous breathing during the first 2 days was not associated with an effect on ICU or hospital mortality (33% vs 37%; odds ratio, 1.18 [0.92-1.51]; p = 0.19 and 37% vs 41%; odds ratio, 1.18 [0.93-1.50]; p = 0.196, respectively ). Spontaneous breathing was associated with increased ventilator-free days (13 [0-22] vs 8 [0-20]; p = 0.014) and shorter duration of ICU stay (11 [6-20] vs 12 [7-22]; p = 0.04). CONCLUSIONS: Spontaneous breathing is common in patients with acute respiratory distress syndrome during the first 48 hours of mechanical ventilation. Spontaneous breathing is not associated with worse outcomes and may hasten liberation from the ventilator and from ICU. Although these results support the use of spontaneous breathing in patients with acute respiratory distress syndrome independent of acute respiratory distress syndrome severity, the use of controlled ventilation indicates a bias toward use in patients with higher disease severity. In addition, because the lack of reliable data on inspiratory effort in our study, prospective studies incorporating the magnitude of inspiratory effort and adjusting for all potential severity confounders are required

Epidemiology and patterns of tracheostomy practice in patients with acute respiratory distress syndrome in ICUs across 50 countries

Background: To better understand the epidemiology and patterns of tracheostomy practice for patients with acute respiratory distress syndrome (ARDS), we investigated the current usage of tracheostomy in patients with ARDS recruited into the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG-SAFE) study. Methods: This is a secondary analysis of LUNG-SAFE, an international, multicenter, prospective cohort study of patients receiving invasive or noninvasive ventilation in 50 countries spanning 5 continents. The study was carried out over 4 weeks consecutively in the winter of 2014, and 459 ICUs participated. We evaluated the clinical characteristics, management and outcomes of patients that received tracheostomy, in the cohort of patients that developed ARDS on day 1-2 of acute hypoxemic respiratory failure, and in a subsequent propensity-matched cohort. Results: Of the 2377 patients with ARDS that fulfilled the inclusion criteria, 309 (13.0%) underwent tracheostomy during their ICU stay. Patients from high-income European countries (n = 198/1263) more frequently underwent tracheostomy compared to patients from non-European high-income countries (n = 63/649) or patients from middle-income countries (n = 48/465). Only 86/309 (27.8%) underwent tracheostomy on or before day 7, while the median timing of tracheostomy was 14 (Q1-Q3, 7-21) days after onset of ARDS. In the subsample matched by propensity score, ICU and hospital stay were longer in patients with tracheostomy. While patients with tracheostomy had the highest survival probability, there was no difference in 60-day or 90-day mortality in either the patient subgroup that survived for at least 5 days in ICU, or in the propensity-matched subsample. Conclusions: Most patients that receive tracheostomy do so after the first week of critical illness. Tracheostomy may prolong patient survival but does not reduce 60-day or 90-day mortality. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013

ANTARES and IceCube Combined Search for Neutrino Point-like and Extended Sources in the Southern Sky

[EN] A search for point-like and extended sources of cosmic neutrinos using data collected by the ANTARES and IceCube neutrino telescopes is presented. The data set consists of all the track-like and shower-like events pointing in the direction of the Southern Sky included in the nine-year ANTARES point-source analysis, combined with the throughgoing track-like events used in the seven-year IceCube point-source search. The advantageous ¿eld of view of ANTARES and the large size of IceCube are exploited to improve the sensitivity in the Southern Sky by a factor of ~2 compared to both individual analyses. In this work, the Southern Sky is scanned for possible excesses of spatial clustering, and the positions of preselected candidate sources are investigated. In addition, special focus is given to the region around the Galactic Center, whereby a dedicated search at the location of SgrA* is performed, and to the location of the supernova remnant RXJ 1713.7-3946. No signi¿cant evidence for cosmic neutrino sources is found, and upper limits on the ¿ux from the various searches are presented.The authors of the IceCube Collaboration acknowledge the support from the following agencies and institutions: USA-U.S. National Science Foundation-Office of Polar Programs, U.S. National Science Foundation-Physics Division, Wisconsin Alumni Research Foundation, Center for High Throughput Computing (CHTC) at the University of Wisconsin-Madison, Open Science Grid (OSG), Extreme Science and Engineering Discovery Environment (XSEDE), U.S. Department of Energy-National Energy Research Scientific Computing Center, Particle astrophysics research computing center at the University of Maryland, Institute for Cyber-Enabled Research at Michigan State University, and Astroparticle physics computational facility at Marquette University; Belgium-Funds for Scientific Research (FRS-FNRS and FWO), FWO Odysseus and Big Science programmes, and Belgian Federal Science Policy Office (Belspo); Germany-Bundesministerium fur Bildung und Forschung (BMBF), Deutsche Forschungsgemeinschaft (DFG), Helmholtz Alliance for Astroparticle Physics (HAP), Initiative and Networking Fund of the Helmholtz Association, Deutsches Elektronen Synchrotron (DESY), and High Performance Computing Cluster of the RWTH Aachen; Sweden-Swedish Research Council, Swedish Polar Research Secretariat, Swedish National Infrastructure for Computing (SNIC), and Knut and Alice Wallenberg Foundation; Australia - Australian Research Council; Canada-Natural Sciences and Engineering Research Council of Canada, Calcul Quebec, Compute Ontario, Canada Foundation for Innovation, WestGrid, and Compute Canada; Denmark-Villum Fonden, Danish National Research Foundation (DNRF), Carlsberg Foundation; New Zealand-Marsden Fund; Japan-Japan Society for Promotion of Science (JSPS) and Institute for Global Prominent Research (IGPR) of Chiba University; Korea-National Research Foundation of Korea (NRF); Switzerland-Swiss National Science Foundation (SNSF); United Kingdom-Department of Physics, University of Oxford.Albert, A.; Andre, M.; Anghinolfi, M.; Anton, G.; Ardid Ramírez, M.; Aubert, J.; Aublin, J.... (2020). ANTARES and IceCube Combined Search for Neutrino Point-like and Extended Sources in the Southern Sky. The Astrophysical Journal. 892(2):1-12. https://doi.org/10.3847/1538-4357/ab7afbS112892

Combined search for neutrinos from dark matter self-annihilation in the Galactic Center with ANTARES and IceCube

[EN] We present the results of the first combined dark matter search targeting the Galactic Center using the ANTARES and IceCube neutrino telescopes. For dark matter particles with masses from 50 to 1000 GeV, the sensitivities on the self-annihilation cross section set by ANTARES and IceCube are comparable, making this mass range particularly interesting for a joint analysis. Dark matter self-annihilation through the ¿+¿¿, ¿+¿¿, b¯b, and W+W¿ channels is considered for both the Navarro-Frenk-White and Burkert halo profiles. In the combination of 2101.6 days of ANTARES data and 1007 days of IceCube data, no excess over the expected background is observed. Limits on the thermally averaged dark matter annihilation cross section h¿A¿i are set. These limits present an improvement of up to a factor of 2 in the studied dark matter mass range with respect to the individual limits published by both collaborations. When considering dark matter particles with a mass of 200 GeV annihilating through the ¿þ¿¿ channel, the value obtained for the limit is 7.44 × 10¿24 cm3 s¿1 for the Navarro-Frenk-White halo profile. For the purpose of this joint analysis, the model parameters and the likelihood are unified, providing a benchmark for forthcoming dark matter searches performed by neutrino telescopes.The authors from the ANTARES Collaboration acknowledge the financial support of the following funding agencies: Centre National de la Recherche Scientifique (CNRS), Commissariat a l'energie atomique et auxenergies alternatives (CEA), Commission Europeenne (FEDER fund and Marie Curie Program), Institut Universitaire de France (IUF), IdEx program and UnivEarthS Labex program at Sorbonne Paris Cite (ANR-10-LABX-0023 and ANR-11IDEX-0005-02), Labex OCEVU (ANR-11-LABX-0060) and the A*MIDEX project (ANR-11-IDEX-0001-02), Region Ile-de-France (DIM-ACAV), Region Alsace (contrat CPER), Region Provence-Alpes-Cote d'Azur, Departement du Var and Ville de La Seyne-sur-Mer, France; Bundesministerium fur Bildung und Forschung (BMBF), Germany; Istituto Nazionale di Fisica Nucleare (INFN), Italy; Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), the Netherlands; Council of the President of the Russian Federation for young scientists and leading scientific schools supporting grants, Russia; Executive Unit for Financing Higher Education, Research, Development and Innovation (UEFISCDI), Romania; Ministerio de Ciencia, Innovacion, Investigacion y Universidades (MCIU): Programa Estatal de Generacion de Conocimiento (refs. PGC2018-096663-B-C41, -A-C42, -B-C43, -B-C44) (MCIU/FEDER), Severo Ochoa Centre of Excellence and MultiDark Consolider (MCIU), Junta de Andalucia (ref. SOMM17/6104/UGR), Generalitat Valenciana: Grisolia (ref. GRISOLIA/2018/119), Spain; Ministry of Higher Education, Scientific Research and Professional Training, Morocco. We also acknowledge the technical support of Ifremer, AIM and Foselev Marine for the sea operation and CC-IN2P3 for the computing facilities. The authors from the IceCube Collaboration gratefully acknowledge the support from the following agencies and institutions: USA-U.S. National Science Foundation-Office of Polar Programs, U.S. National Science Foundation-Physics Division, Wisconsin Alumni Research Foundation, Center for High Throughput Computing (CHTC) at the University of Wisconsin-Madison, Open Science Grid (OSG), Extreme Science and Engineering Discovery Environment (XSEDE), U.S. Department of Energy-National Energy Research Scientific Computing Center, Particle astrophysics research computing center at the University of Maryland, Institute for Cyber-Enabled Research at Michigan State University, and Astroparticle physics computational facility at Marquette University; Belgium-Funds for Scientific Research (FRS-FNRS and FWO), FWO Odysseus and Big Science programmes, and Belgian Federal Science Policy Office (Belspo); Germany-Bundesministerium fur Bildung und Forschung (BMBF), Deutsche Forschungsgemeinschaft (DFG), Helmholtz Alliance for Astroparticle Physics (HAP), Initiative and Networking Fund of the Helmholtz Association, Germany-Deutsches Elektronen Synchrotron (DESY), and High Performance Computing cluster of the RWTH Aachen; Sweden-Swedish Research Council, Swedish Polar Research Secretariat, Swedish National Infrastructure for Computing (SNIC), and Knut and Alice Wallenberg Foundation; Australia-Australian Research Council; Canada-Natural Sciences and Engineering Research Council of Canada, Calcul Quebec, Compute Ontario, Canada Foundation for Innovation, WestGrid, and Compute Canada; Denmark-Villum Fonden, Danish National Research Foundation (DNRF), Carlsberg Foundation; New Zealand-Marsden Fund; Japan-Japan Society for Promotion of Science (JSPS) and Institute for Global Prominent Research (IGPR) of Chiba University; Korea-National Research Foundation of Korea (NRF); Switzerland-Swiss National Science Foundation (SNSF); United Kingdom-Department of Physics, University of Oxford. The IceCube collaboration acknowledges the significant contributions to this manuscript from Sebastian Baur, Nadege Iovine and Sara Rebecca Gozzini.Albert, A.; Andre, M.; Anghinolfi, M.; Ardid Ramírez, M.; Aubert, J.; Aublin, J.; Baret, B.... (2020). Combined search for neutrinos from dark matter self-annihilation in the Galactic Center with ANTARES and IceCube. Physical Review D: covering particles, fields, gravitation, and cosmology. 102(8):1-13. https://doi.org/10.1103/PhysRevD.102.082002S113102