Hadronic processes within collective stellar winds

Recently, we have proposed that the interaction between relativistic protons resulting from Fermi first order acceleration in the superbubble of a stellar OB association or in other nearby accelerator and ions residing in single stellar winds of massive stars could lead to TeV sources without strong counterparts at lower energies. Here we refine this analysis in several directions. We study collective wind configurations produced by a number of massive stars, and obtain densities and expansion velocities of the stellar wind gas that is to be target of hadronic interactions. We study the expected $\gamma$-ray emission from these regions, considering in an approximate way the effect of cosmic ray modulation. We compute secondary particle production (electrons from knock-on interactions and electrons and positrons from charged pion decay), and solve the loss equation with ionization, synchrotron, bremsstrahlung, inverse Compton, and expansion losses. We provide examples where configurations can produce sources for GLAST satellite, and the MAGIC/HESS/VERITAS telescopes in non-uniform ways, i.e., with or without the corresponding counterparts. We show that in all cases we studied no EGRET source is expected. Finally, we comment on HESS J1303-631 and on Cygnus OB 2 and Westerlund 1 as two associations where this scenario could be tested.Comment: Accepted for publication in A&

High energy gamma-ray emission from the starburst nucleus of NGC 253

The high density medium that characterizes the central regions of starburst galaxies and its power to accelerate particles up to relativistic energies make these objects good candidates as $\gamma$-rays sources. In this paper, a self-consistent model of the multifrequency emission of the starburst galaxy NGC 253, from radio to gamma-rays, is presented. The model is in agreement with all current measurements and provides predictions for the high energy behavior of the NGC 253 central region. Prospects for observations with the HESS array and GLAST satellite are especially discussed.Comment: 17 pages, 13 figures. To appear in A&A. Modelling parameters and results are unchanged from the previous version but we enhance here the detail with which they are described. 3 new figures and 1 new section have been added, including a figure showing the consistency of the model with the recently reported HESS observations (astro-ph/0507370) of NGC 25

High-energy gamma-rays from stellar associations

It is proposed that TeV gamma-rays and neutrinos can be produced by cosmic rays (CRs) through hadronic interactions in the innermost parts of the winds of massive O and B stars. Convection prevents low-energy particles from penetrating into the wind, leading to an absence of MeV-GeV counterparts. It is argued that groups of stars located close to the CR acceleration sites in OB stellar associations may be detectable by ground-based Cherenkov telescopes.Comment: 10 pages, 1 figure. Accepted for publication in Astrophysical Journal Letter

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Evolution over Time of Ventilatory Management and Outcome of Patients with Neurologic Disease∗

OBJECTIVES: To describe the changes in ventilator management over time in patients with neurologic disease at ICU admission and to estimate factors associated with 28-day hospital mortality. DESIGN: Secondary analysis of three prospective, observational, multicenter studies. SETTING: Cohort studies conducted in 2004, 2010, and 2016. PATIENTS: Adult patients who received mechanical ventilation for more than 12 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the 20,929 patients enrolled, we included 4,152 (20%) mechanically ventilated patients due to different neurologic diseases. Hemorrhagic stroke and brain trauma were the most common pathologies associated with the need for mechanical ventilation. Although volume-cycled ventilation remained the preferred ventilation mode, there was a significant (p < 0.001) increment in the use of pressure support ventilation. The proportion of patients receiving a protective lung ventilation strategy was increased over time: 47% in 2004, 63% in 2010, and 65% in 2016 (p < 0.001), as well as the duration of protective ventilation strategies: 406 days per 1,000 mechanical ventilation days in 2004, 523 days per 1,000 mechanical ventilation days in 2010, and 585 days per 1,000 mechanical ventilation days in 2016 (p < 0.001). There were no differences in the length of stay in the ICU, mortality in the ICU, and mortality in hospital from 2004 to 2016. Independent risk factors for 28-day mortality were age greater than 75 years, Simplified Acute Physiology Score II greater than 50, the occurrence of organ dysfunction within first 48 hours after brain injury, and specific neurologic diseases such as hemorrhagic stroke, ischemic stroke, and brain trauma. CONCLUSIONS: More lung-protective ventilatory strategies have been implemented over years in neurologic patients with no effect on pulmonary complications or on survival. We found several prognostic factors on mortality such as advanced age, the severity of the disease, organ dysfunctions, and the etiology of neurologic disease