Structural Studies on Alkylisocyanate Polymers by Thermal Degradation Tandem Mass Spectrometry

AbstractHomopolymers and copolymers of alkylisocyanates having n-hexyl, 2,6-dimethylheptyl, 3,7-dimethyloctyl, and (2,2-dimethyl-1,3-dioxolan-4-yl)methyl substituents underwent thermal degradation in the course of desorption electron ionization to yield trimers and monomers that were characterized in situ by tandem mass spectrometry. The trimers were trisubstituted cyanuric acids, the protonated molecules displaying a characteristic series of alkene eliminations on collision-induced dissociation to yield protonated cyanuric acid, m/z 130. Confirmation of the identity of the pyrolysates was obtained by using two types of MS3 experiments: the reaction intermediate scan and the two-dimensional familial scan. The ion chemistry of the trimers and of the protonated monomer, the alkylisocyanate, was elucidated. Among the many interesting fragmentation processes undergone by the ionized trimers were α and β CC bond cleavages and charge-remote fragmentations, which provided information on branching in the alkyl substituent. The dioxolane-containing substituent showed unique ion chemistry. The monomer distribution in the copolymers was deduced from the abundances of the various protonated trimers. The distribution was found to be random in all copolymers except that containing the dioxolane substituent

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

ILC Reference Design Report Volume 1 - Executive Summary

The International Linear Collider (ILC) is a 200-500 GeV center-of-mass high-luminosity linear electron-positron collider, based on 1.3 GHz superconducting radio-frequency (SCRF) accelerating cavities. The ILC has a total footprint of about 31 km and is designed for a peak luminosity of 2x10^34 cm^-2s^-1. This report is the Executive Summary (Volume I) of the four volume Reference Design Report. It gives an overview of the physics at the ILC, the accelerator design and value estimate, the detector concepts, and the next steps towards project realization.The International Linear Collider (ILC) is a 200-500 GeV center-of-mass high-luminosity linear electron-positron collider, based on 1.3 GHz superconducting radio-frequency (SCRF) accelerating cavities. The ILC has a total footprint of about 31 km and is designed for a peak luminosity of 2x10^34 cm^-2s^-1. This report is the Executive Summary (Volume I) of the four volume Reference Design Report. It gives an overview of the physics at the ILC, the accelerator design and value estimate, the detector concepts, and the next steps towards project realization

ILC Reference Design Report Volume 4 - Detectors

This report, Volume IV of the International Linear Collider Reference Design Report, describes the detectors which will record and measure the charged and neutral particles produced in the ILC's high energy e+e- collisions. The physics of the ILC, and the environment of the machine-detector interface, pose new challenges for detector design. Several conceptual designs for the detector promise the needed performance, and ongoing detector R&D is addressing the outstanding technological issues. Two such detectors, operating in push-pull mode, perfectly instrument the ILC interaction region, and access the full potential of ILC physics.This report, Volume IV of the International Linear Collider Reference Design Report, describes the detectors which will record and measure the charged and neutral particles produced in the ILC's high energy e+e- collisions. The physics of the ILC, and the environment of the machine-detector interface, pose new challenges for detector design. Several conceptual designs for the detector promise the needed performance, and ongoing detector R&D is addressing the outstanding technological issues. Two such detectors, operating in push-pull mode, perfectly instrument the ILC interaction region, and access the full potential of ILC physics

ILC Reference Design Report Volume 3 - Accelerator

The International Linear Collider (ILC) is a 200-500 GeV center-of-mass high-luminosity linear electron-positron collider, based on 1.3 GHz superconducting radio-frequency (SCRF) accelerating cavities. The ILC has a total footprint of about 31 km and is designed for a peak luminosity of 2x10^34 cm^-2 s^-1. The complex includes a polarized electron source, an undulator-based positron source, two 6.7 km circumference damping rings, two-stage bunch compressors, two 11 km long main linacs and a 4.5 km long beam delivery system. This report is Volume III (Accelerator) of the four volume Reference Design Report, which describes the design and cost of the ILC.The International Linear Collider (ILC) is a 200-500 GeV center-of-mass high-luminosity linear electron-positron collider, based on 1.3 GHz superconducting radio-frequency (SCRF) accelerating cavities. The ILC has a total footprint of about 31 km and is designed for a peak luminosity of 2x10^34 cm^-2 s^-1. The complex includes a polarized electron source, an undulator-based positron source, two 6.7 km circumference damping rings, two-stage bunch compressors, two 11 km long main linacs and a 4.5 km long beam delivery system. This report is Volume III (Accelerator) of the four volume Reference Design Report, which describes the design and cost of the ILC

International Linear Collider Reference Design Report Volume 2: PHYSICS AT THE ILC

This article reviews the physics case for the ILC. Baseline running at 500 GeV as well as possible upgrades and options are discussed. The opportunities on Standard Model physics, Higgs physics, Supersymmetry and alternative theories beyond the Standard Model are described.This article reviews the physics case for the ILC. Baseline running at 500 GeV as well as possible upgrades and options are discussed. The opportunities on Standard Model physics, Higgs physics, Supersymmetry and alternative theories beyond the Standard Model are described