Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42\ub74% vs 44\ub72%; absolute difference \u20131\ub769 [\u20139\ub758 to 6\ub711] p=0\ub767; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5\u20138] vs 6 [5\u20138] cm H2O; p=0\ub70011). ICU mortality was higher in MICs than in HICs (30\ub75% vs 19\ub79%; p=0\ub70004; adjusted effect 16\ub741% [95% CI 9\ub752\u201323\ub752]; p<0\ub70001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0\ub780 [95% CI 0\ub775\u20130\ub786]; p<0\ub70001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. Funding: No funding

Update on the Combined Analysis of Muon Measurements from Nine Air Shower Experiments

Over the last two decades, various experiments have measured muon densities in extensive air showers over several orders of magnitude in primary energy. While some experiments observed differences in the muon densities between simulated and experimentally measured air showers, others reported no discrepancies. We will present an update of the meta-analysis of muon measurements from nine air shower experiments, covering shower energies between a few PeV and tens of EeV and muon threshold energies from a few 100 MeV to about 10GeV. In order to compare measurements from different experiments, their energy scale was cross-calibrated and the experimental data has been compared using a universal reference scale based on air shower simulations. Above 10 PeV, we find a muon excess with respect to simulations for all hadronic interaction models, which is increasing with shower energy. For EPOS-LHC and QGSJet-II.04 the significance of the slope of the increase is analyzed in detail under different assumptions of the individual experimental uncertainties

An indication of anisotropy in arrival directions of utra-high-energy cosmic rays through comparison to the flux pattern of extragalactic gamma-ray sources

CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPERJ - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE RIO DE JANEIROFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOMCTIC - MINISTÉRIO DA CIÊNCIA, TECNOLOGIA, INOVAÇÕES E COMUNICAÇÕESA new analysis of the data set from the Pierre Auger Observatory provides evidence for anisotropy in the arrival directions of ultra-high-energy cosmic rays on an intermediate angular scale, which is indicative of excess arrivals from strong, nearby sources. The data consist of 5514 events above 20 EeV with zenith angles up to 80 degrees. recorded before 2017 April 30. Sky models have been created for two distinct populations of extragalactic gamma-ray emitters: active galactic nuclei from the second catalog of hard Fermi-LAT sources (2FHL) and starburst galaxies from a sample that was examined with Fermi-LAT. Flux-limited samples, which include all types of galaxies from the Swift-BAT and 2MASS surveys, have been investigated for comparison. The sky model of cosmic-ray density constructed using each catalog has two free parameters, the fraction of events correlating with astrophysical objects, and an angular scale characterizing the clustering of cosmic rays around extragalactic sources. A maximum-likelihood ratio test is used to evaluate the best values of these parameters and to quantify the strength of each model by contrast with isotropy. It is found that the starburst model fits the data better than the hypothesis of isotropy with a statistical significance of 4.0 sigma, the highest value of the test statistic being for energies above 39 EeV. The three alternative models are favored against isotropy with 2.7 sigma-3.2 sigma significance. The origin of the indicated deviation from isotropy is examined and prospects for more sensitive future studies are discussed.8532110CNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPERJ - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE RIO DE JANEIROFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOMCTIC - MINISTÉRIO DA CIÊNCIA, TECNOLOGIA, INOVAÇÕES E COMUNICAÇÕESCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFINEP - FINANCIADORA DE ESTUDOS E PROJETOSFAPERJ - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE RIO DE JANEIROFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOMCTIC - MINISTÉRIO DA CIÊNCIA, TECNOLOGIA, INOVAÇÕES E COMUNICAÇÕESSem informaçãoSem informaçãoSem informaçãoSem informaçãoSem informaçãoAgências de fomento estrangeiras apoiaram essa pesquisa, mais informações acesse artig

Inferences on mass composition and tests of hadronic interactions from 0.3 to 100 EeV using the water-Cherenkov detectors of the Pierre Auger Observatory

CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFINANCIADORA DE ESTUDOS E PROJETOS - FINEPFUNDAÇÃO CARLOS CHAGAS FILHO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIRO - FAPERJFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPWe present a new method for probing the hadronic interaction models at ultrahigh energy and extracting details about mass composition. This is done using the time profiles of the signals recorded with the water-Cherenkov detectors of the Pierre Auger Observatory. The profiles arise from a mix of the muon and electromagnetic components of air showers. Using the risetimes of the recorded signals, we define a new parameter, which we use to compare our observations with predictions from simulations. We find, first, inconsistencies between our data and predictions over a greater energy range and with substantially more events than in previous studies. Second, by calibrating the new parameter with fluorescence measurements from observations made at the Auger Observatory, we can infer the depth of shower maximum X-max for a sample of over 81,000 events extending from 0.3 to over 100 EeV. Above 30 EeV, the sample is nearly 14 times larger than what is currently available from fluorescence measurements and extending the covered energy range by half a decade. The energy dependence of < X-max gt; is compared to simulations and interpreted in terms of the mean of the logarithmic mass. We find good agreement with previous work and extend the measurement of the mean depth of shower maximum to greater energies than before, reducing significantly the statistical uncertainty associated with the inferences about mass composition.9612122CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFINANCIADORA DE ESTUDOS E PROJETOS - FINEPFUNDAÇÃO CARLOS CHAGAS FILHO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIRO - FAPERJFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFINANCIADORA DE ESTUDOS E PROJETOS - FINEPFUNDAÇÃO CARLOS CHAGAS FILHO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIRO - FAPERJFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPSem informaçãoSem informaçãoSem informação1999/05404-32010/07359-6The successful installation, commissioning, and operation of the Pierre Auger Observatory would not have been possible without the strong commitment and effort from the technical and administrative staff in Malargue. We are very grateful to the following agencies and organizations for financial support: (Argentina) Comision Nacional de Energia Atomica; Agencia Nacional de Promocion Cientifica y Tecnologica (ANPCyT); Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); Gobierno de la Provincia de Mendoza; Municipalidad de Malargue; and NDM Holdings and Valle Las Lenas in gratitude for their continuing cooperation over land access; (Australia) the Australian Research Council; (Brazil) Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq); Financiadora de Estudos e Projetos (FINEP); Fundacao de Amparo a Pesquisa do Estado de Rio de Janeiro (FAPERJ); Sao Paulo Research Foundation (FAPESP) Grants No. 2010/07359-6 and No. 1999/05404-3; Ministerio de Ciencia e Tecnologia (MCT); (Czech Republic) Grants No. MSMT CR LG15014, LO1305, LM2015038, and CZ.02.1.01/0.0/0.0/16\_013/0001402; (France) Centre de Calcul IN2P3/CNRS; Centre National de la Recherche Scientifique (CNRS); Conseil Regional Ile-de-France; Departement Physique Nucleaire et Corpusculaire (PNC-IN2P3/CNRS); Departement Sciences de l'Univers (SDU-INSU/CNRS); Institut Lagrange de Paris (ILP) Grant No. LABEX ANR-10-LABX-63 within the Investissements d'Avenir Programme Grant No. ANR-11-IDEX-0004-02; (Germany) Bundesministerium fur Bildung und Forschung (BMBF); Deutsche Forschungsgemeinschaft (DFG); Finanzministerium Baden-Wurttemberg; Helmholtz Alliance for Astroparticle Physics (HAP); Helmholtz-Gemeinschaft Deutscher Forschungszentren (HGF); Ministerium fur Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen; Ministerium fur Wissenschaft, Forschung und Kunst des Landes Baden-Wurttemberg; (Italy) Istituto Nazionale di Fisica Nucleare (INFN); Istituto Nazionale di Astrofisica (INAF); Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR); CETEMPS Center of Excellence; Ministero degli Affari Esteri (MAE); (Mexico) Consejo Nacional de Ciencia y Tecnologia (CONACYT) Grant No. 167733; Universidad Nacional Autonoma de Mexico (UNAM); PAPIIT DGAPA-UNAM; (Netherlands) Ministerie van Onderwijs, Cultuur en Wetenschap; Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO); Stichting voor Fundamenteel Onderzoek der Materie (FOM); (Poland) National Centre for Research and Development, Grants No. ERA-NET-ASPERA/01/11 and No. ERA-NET-ASPERA/02/11; National Science Centre, Grants No. 2013/08/M/ST9/00322, No. 2013/08/M/ST9/00728, No. HARMONIA 5-2013/10/M/ST9/00062, and No. UMO-2016/22/M/ST9/00198; (Portugal) Portuguese national funds and FEDER funds within Programa Operacional Factores de Competitividade through Fundacao para a Ciencia e a Tecnologia (COMPETE); (Romania) Romanian Authority for Scientific Research ANCS; CNDI-UEFISCDI partnership projects Grants No. 20/2012, No. 194/2012, and No. PN 16 42 01 02; (Slovenia) Slovenian Research Agency; (Spain) Comunidad de Madrid; Fondo Europeo de Desarrollo Regional (FEDER) funds; Ministerio de Economia y Competitividad; Xunta de Galicia; European Community 7th Framework Program Grant No. FP7-PEOPLE-2012-IEF-328826; (USA) Department of Energy, Contracts No. DE-AC02-07CH11359, No. DE-FR02-04ER41300, No. DE-FG02-99ER41107, and No. DE-SC0011689; National Science Foundation, Grant No. 0450696; The Grainger Foundation; Marie Curie-IRSES/EPLANET (European Union); European Particle Physics Latin American Network; European Union 7th Framework Program, Grant No. PIRSES-2009-GA-246806; European Union's Horizon 2020 Research and Innovation Programme (Grant No. 646623); and UNESCO

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Search for new Higgs bosons via same-sign top quark pair production in association with a jet in proton-proton collisions at √s = 13 TeV

Data availability: Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the CMS policy as stated in “CMS data preservation, re-use and open access policy” available online at: https://cms-docdb.cern.ch/cgi-bin/PublicDocDB/RetrieveFile?docid=6032&filename=CMSDataPolicyV1.2.pdf&version=2 .A preprint of this article is available online at arXiv:2311.03261v2 [hep-ex] https://arxiv.org/abs/2311.03261v2 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/TOP-22-010 (CMS Public Pages)A search is presented for new Higgs bosons in proton-proton (pp) collision events in which a same-sign top quark pair is produced in association with a jet, via the pp → tH/A → tt¯c and pp → tH/A → tt¯u processes. Here, H and A represent the extra scalar and pseudoscalar boson, respectively, of the second Higgs doublet in the generalized two-Higgs-doublet model (g2HDM). The search is based on pp collision data collected at a center-of-mass energy of 13 TeV with the CMS detector at the LHC, corresponding to an integrated luminosity of 138 fb−1. Final states with a same-sign lepton pair in association with jets and missing transverse momentum are considered. New Higgs bosons in the 200-1000 GeV mass range and new Yukawa couplings between 0.1 and 1.0 are targeted in the search, for scenarios in which either H or A appear alone, or in which they coexist and interfere. No significant excess above the standard model prediction is observed. Exclusion limits are derived in the context of the g2HDM.SCOAP3

Search for long-lived heavy neutral leptons with lepton flavour conserving or violating decays to a jet and a charged lepton

A preprint version of the article is available at arXiv:2312.07484v3 [hep-ex], https://arxiv.org/abs/2312.07484 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/EXO-21-013 (CMS Public Pages)A search for long-lived heavy neutral leptons (HNLs) is presented, which considers the hadronic final state and coupling scenarios involving all three lepton generations in the 2-20 GeV HNL mass range for the first time. Events comprising two leptons (electrons or muons) and jets are analyzed in a data sample of proton-proton collisions, recorded with the CMS experiment at the CERN LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 138 fb−1. A novel jet tagger, based on a deep neural network, has been developed to identify jets from an HNL decay using various features of the jet and its constituent particles. The network output can be used as a powerful discriminating tool to probe a broad range of HNL lifetimes and masses. Contributions from background processes are determined from data. No excess of events in data over the expected background is observed. Upper limits on the HNL production cross section are derived as functions of the HNL mass and the three coupling strengths VℓN to each lepton generation ℓ and presented as exclusion limits in the coupling-mass plane, as lower limits on the HNL lifetime, and on the HNL mass. In this search, the most stringent limit on the coupling strength is obtained for pure muon coupling scenarios; values of |VμN|2 > 5 (4) × 10−7 are excluded for Dirac (Majorana) HNLs with a mass of 10 GeV at a confidence level of 95% that correspond to proper decay lengths of 17 (10) mm.SCOAP3

A tumor-targeted trimeric 4-1BB-agonistic antibody induces potent anti-tumor immunity without systemic toxicity

The costimulation of immune cells using first-generation anti-4-1BB monoclonal antibodies (mAbs) has demonstrated anti-tumor activity in human trials. Further clinical development, however, is restricted by significant off-tumor toxicities associated with FcγR interactions. Here, we have designed an Fc-free tumor-targeted 4-1BB-agonistic trimerbody, 1D8N/CEGa1, consisting of three anti-4-1BB single-chain variable fragments and three anti-EGFR single-domain antibodies positioned in an extended hexagonal conformation around the collagen XVIII homotrimerization domain. The1D8N/CEGa1 trimerbody demonstrated high-avidity binding to 4-1BB and EGFR and a potent in vitro costimulatory capacity in the presence of EGFR. The trimerbody rapidly accumulates in EGFR-positive tumors and exhibits anti-tumor activity similar to IgG-based 4-1BB-agonistic mAbs. Importantly, treatment with 1D8N/CEGa1 does not induce systemic inflammatory cytokine production or hepatotoxicity associated with IgG-based 4-1BB agonists. These results implicate FcγR interactions in the 4-1BB-agonist-associated immune abnormalities, and promote the use of the non-canonical antibody presented in this work for safe and effective costimulatory strategies in cancer immunotherapy