SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

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

Water levels in continuously monitored wells in the Yucca Mountain Area, Nevada, 1989

Water levels have been monitored hourly in 16 wells representing 24 intervals in the Yucca Mountain area, Nevada. Water levels were monitored using pressure transducers and were recorded by data loggers. The pressure transducers were periodically calibrated by raising and lowering them in the wells. The water levels were normally measured at approximately the same time that the transducers were calibrated. Where the transducer output appeared reasonable, it was converted to water levels using the calibrations and manual water-level measurements. The amount of transducer output that was converted to water levels ranged from zero for one interval to 100 percent for one interval. Fifteen of the wells were completed in Tertiary volcanic rocks and one well was completed in Paleozoic carbonate rocks. Each well monitored from one to four depth intervals. Water-level fluctuation caused by barometric pressure changes and earth tides were observed. Transducer output is presented in graphic form and, where appropriate, water-level altitude is presented in graphical and tabular form

Simulated effects of climate change on the Death Valley regional ground-water flow system, Nevada and California

The US Geological Survey, in cooperation with the US Department of Energy, is evaluating the geologic and hydrologic characteristics of the Death Valley regional flow system as part of the Yucca Mountain Project. As part of the hydrologic investigation, regional, three-dimensional conceptual and numerical ground-water-flow models have been developed to assess the potential effects of past and future climates on the regional flow system. A simulation that is based on climatic conditions 21,000 years ago was evaluated by comparing the simulated results to observation of paleodischarge sites. Following acceptable simulation of a past climate, a possible future ground-water-flow system, with climatic conditions that represent a doubling of atmospheric carbon dioxide, was simulated. The steady-state simulations were based on the present-day, steady-state, regional ground-water-flow model. The finite-difference model consisted of 163 rows, 153 columns, and 3 layers and was simulated using MODFLOWP. Climate changes were implemented in the regional ground-water-flow model by changing the distribution of ground-water recharge. Global-scale, average-annual, simulated precipitation for both past- and future-climate conditions developed elsewhere were resampled to the model-grid resolution. A polynomial function that represents the Maxey-Eakin method for estimating recharge from precipitation was used to develop recharge distributions for simulation

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at (Formula presented.) TeV with ATLAS

Abstract: Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of (Formula presented.) TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9+ 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations.[Figure not available: see fulltext.]

Measurements of fiducial and differential cross sections for Higgs boson production in the diphoton decay channel at S=8 TeV with ATLAS

Abstract: Measurements of fiducial and differential cross sections are presented for Higgs boson production in proton-proton collisions at a centre-of-mass energy of (formula presented) TeV. The analysis is performed in the H → γγ decay channel using 20.3 fb−1 of data recorded by the ATLAS experiment at the CERN Large Hadron Collider. The signal is extracted using a fit to the diphoton invariant mass spectrum assuming that the width of the resonance is much smaller than the experimental resolution. The signal yields are corrected for the effects of detector inefficiency and resolution. The pp → H → γγ fiducial cross section is measured to be 43.2 ±9.4(stat.) − 2.9+ 3.2 (syst.) ±1.2(lumi)fb for a Higgs boson of mass 125.4GeV decaying to two isolated photons that have transverse momentum greater than 35% and 25% of the diphoton invariant mass and each with absolute pseudorapidity less than 2.37. Four additional fiducial cross sections and two cross-section limits are presented in phase space regions that test the theoretical modelling of different Higgs boson production mechanisms, or are sensitive to physics beyond the Standard Model. Differential cross sections are also presented, as a function of variables related to the diphoton kinematics and the jet activity produced in the Higgs boson events. The observed spectra are statistically limited but broadly in line with the theoretical expectations.[Figure not available: see fulltext.

Search for supersymmetry in events with large missing transverse momentum, jets, and at least one tau lepton in 20 fb−1 of (fromula presented) proton-proton collision data with the ATLAS detector

A search for supersymmetry (SUSY) in events with large missing transverse momentum, jets, at least one hadronically decaying tau lepton and zero or one additional light leptons (electron/muon), has been performed using 20.3fb−1 of proton-proton collision data at (formula presented) recorded with the ATLAS detector at the Large Hadron Collider. No excess above the Standard Model background expectation is observed in the various signal regions and 95% confidence level upper limits on the visible cross section for new phenomena are set. The results of the analysis are interpreted in several SUSY scenarios, significantly extending previous limits obtained in the same final states. In the framework of minimal gauge-mediated SUSY breaking models, values of the SUSY breaking scale Λ below 63 TeV are excluded, independently of tan β. Exclusion limits are also derived for an mSUGRA/CMSSM model, in both the R-parity-conserving and R-parity-violating case. A further interpretation is presented in a framework of natural gauge mediation, in which the gluino is assumed to be the only light coloured sparticle and gluino masses below 1090 GeV are excluded

Measurement of flow harmonics with multi-particle cumulants in Pb+Pb collisions at (Formula presented.) TeV with the ATLAS detector

ATLAS measurements of the azimuthal anisotropy in lead–lead collisions at (Formula presented.) TeV are shown using a dataset of approximately 7 (Formula presented.) collected at the LHC in 2010. The measurements are performed for charged particles with transverse momenta (Formula presented.) GeV and in the pseudorapidity range (Formula presented.). The anisotropy is characterized by the Fourier coefficients, (Formula presented.), of the charged-particle azimuthal angle distribution for (Formula presented.)–4. The Fourier coefficients are evaluated using multi-particle cumulants calculated with the generating function method. Results on the transverse momentum, pseudorapidity and centrality dependence of the (Formula presented.), is obtained from the two-, four-, six- and eight-particle cumulants while higher-order coefficients, (Formula presented.) and (Formula presented.), are determined with two- and four-particle cumulants. Flow harmonics (Formula presented.) measured with four-particle cumulants are significantly reduced compared to the measurement involving two-particle cumulants. A comparison to (Formula presented.) measurements obtained using different analysis methods and previously reported by the LHC experiments is also shown. Results of measurements of flow fluctuations evaluated with multi-particle cumulants are shown as a function of transverse momentum and the collision centrality. Models of the initial spatial geometry and its fluctuations fail to describe the flow fluctuations measurements

Measurement of the Z/γ∗ boson transverse momentum distribution in pp collisions at √s = 7 TeV with the ATLAS detector

This paper describes a measurement of the Z/γ* boson transverse momentum spectrum using ATLAS proton-proton collision data at a centre-of-mass energy of √s = TeV at the LHC. The measurement is performed in the Z/γ* → e+e− and Z/γ* → μ+μ− channels, using data corresponding to an integrated luminosity of 4.7 fb−1. Normalized differential cross sections as a function of the Z/γ* boson transverse momentum are measured for transverse momenta up to 800 GeV. The measurement is performed inclusively for Z/γ* rapidities up to 2.4, as well as in three rapidity bins. The channel results are combined, compared to perturbative and resummed QCD calculations and used to constrain the parton shower parameters of Monte Carlo generators

Search for squarks and gluinos with the ATLAS detector in final states with jets and missing transverse momentum using s=8 TeV proton-proton collision data

Abstract: A search for squarks and gluinos in final states containing high-pT jets, missing transverse momentum and no electrons or muons is presented. The data were recorded in 2012 by the ATLAS experiment in (formula presented) TeV proton-proton collisions at the Large Hadron Collider, with a total integrated luminosity of 20.3 fb−1. Results are interpreted in a variety of simplified and specific supersymmetry-breaking models assuming that R-parity is conserved and that the lightest neutralino is the lightest supersymmetric particle. An exclusion limit at the 95% confidence level on the mass of the gluino is set at 1330 GeV for a simplified model incorporating only a gluino and the lightest neutralino. For a simplified model involving the strong production of first- and second-generation squarks, squark masses below 850 GeV (440 GeV) are excluded for a massless lightest neutralino, assuming mass degenerate (single light-flavour) squarks. In mSUGRA/CMSSM models with tan β = 30, A0 = −2m0 and μ > 0, squarks and gluinos of equal mass are excluded for masses below 1700 GeV. Additional limits are set for non-universal Higgs mass models with gaugino mediation and for simplified models involving the pair production of gluinos, each decaying to a top squark and a top quark, with the top squark decaying to a charm quark and a neutralino. These limits extend the region of supersymmetric parameter space excluded by previous searches with the ATLAS detector.[Figure not available: see fulltext.