Diagnostic stewardship aiming at expectorated or induced sputum promotes microbial diagnosis in community-acquired pneumonia

Purpose: Studies on aetiology of community-acquired pneumonia (CAP) vary in terms of microbial sampling methods, anatomical locations, and laboratory analyses, since no gold standard exists. In this large, multicentre, retrospective, regional study from Norway, our primary objective was to report the results of a strategic diagnostic stewardship intervention, targeting diagnostic yield from lower respiratory tract sampling. The secondary objective was to report hospitalized CAP aetiology and the diagnostic yield of various anatomical sampling locations. Methods: Medical records from cases diagnosed with hospitalized CAP were collected retrospectively from March throughout May for three consecutive years at six hospitals. Between year one and two, we launched a diagnostic stewardship intervention at the emergency room level for the university teaching hospital only. The intervention was multifaceted aiming at upscaling specimen collection and enhancing collection techniques. Year one at the interventional hospital and every year at the five other emergency hospitals were used for comparison. Results: Of the 1280 included cases of hospitalized CAP, a microbiological diagnosis was established for 29.1% among 1128 blood cultures and 1444 respiratory tract specimens. Blood cultures were positive for a pathogenic respiratory tract microbe in 4.9% of samples, whereas upper and lower respiratory tract samples overall provided a probable microbiological diagnosis in 21.3% and 47.5%, respectively. Expectorated or induced sputum overall provided aetiology in 51.7% of the samples. At the interventional hospital, the number of expectorated or induced sputum samples were significantly increased, and diagnostic yield from expectorated or induced sputum was significantly enhanced from 41.2 to 62.0% after the intervention (p = 0.049). There was an over-representation of samples from the interventional hospital during the study period. Non-typeable Haemophilus influenza and Streptococcus pneumoniae accounted for 25.3% and 24.7% of microbiologically confirmed cases, respectively. Conclusion Expectorated or induced sputum outperformed other sampling methods in providing a reliable microbiological diagnosis for hospitalized CAP. A diagnostic stewardship intervention significantly improved diagnostic yield of lower respiratory tract sampling.publishedVersio

Radiation hard 3D silicon pixel sensors for use in the ATLAS detector at the HL-LHC

The High Luminosity LHC (HL-LHC) upgrade requires the planned Inner Tracker (ITk) of the ATLAS detector to tolerate extremely high radiation doses. Specifically, the innermost parts of the pixel system will have to withstand radiation fluences above 1 × 1016 neqcm-2. Novel 3D silicon pixel sensors offer a superior radiation tolerance compared to conventional planar pixel sensors, and are thus excellent candidates for the innermost parts of the ITk. This paper presents studies of 3D pixel sensors with pixel size 50 × 50 μm2 mounted on the RD53A prototype readout chip. Following a description of the design and fabrication steps, Test Beam results are presented for unirradiated as well as heavily irradiated sensors. For particles passing at perpendicular incidence, it is shown that average efficiencies above 96% are reached for sensors exposed to fluences of 1 × 1016 neqcm-2 when biased to 80 V.publishedVersio

Circulating markers of extracellular matrix remodelling in severe COVID-19 patients

Background Abnormal remodelling of the extracellular matrix (ECM) has generally been linked to pulmonary inflammation and fibrosis and may also play a role in the pathogenesis of severe COVID-19. To further elucidate the role of ECM remodelling and excessive fibrogenesis in severe COVID-19, we examined circulating levels of mediators involved in various aspects of these processes in COVID-19 patients. Methods Serial blood samples were obtained from two cohorts of hospitalised COVID-19 patients (n = 414). Circulating levels of ECM remodelling mediators were quantified by enzyme immunoassays in samples collected during hospitalisation and at 3-month follow-up. Samples were related to disease severity (respiratory failure and/or treatment at the intensive care unit), 60-day total mortality and pulmonary pathology after 3-months. We also evaluated the direct effect of inactivated SARS-CoV-2 on the release of the different ECM mediators in relevant cell lines. Results Several of the measured markers were associated with adverse outcomes, notably osteopontin (OPN), S100 calcium-binding protein A12 and YKL-40 were associated with disease severity and mortality. High levels of ECM mediators during hospitalisation were associated with computed tomography thorax pathology after 3-months. Some markers (i.e. growth differential factor 15, galectin 3 and matrix metalloproteinase 9) were released from various relevant cell lines (i.e. macrophages and lung cell lines) in vitro after exposure to inactivated SARS-CoV-2 suggesting a direct link between these mediators and the causal agent of COVID-19. Conclusion Our findings highlight changes to ECM remodelling and particularly a possible role of OPN, S100A12 and YKL-40 in the pathogenesis of severe COVID-19

Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients

The new SARS-CoV-2 pandemic leads to COVID-19 with respiratory failure, substantial morbidity, and significant mortality. Overactivation of the innate immune response is postulated to trigger this detrimental process. The complement system is a key player in innate immunity. Despite a few reports of local complement activation, there is a lack of evidence that the degree of systemic complement activation occurs early in COVID-19 patients, and whether this is associated with respiratory failure. This study shows that a number of complement activation products are systemically, consistently, and long-lastingly increased from admission and during the hospital stay. Notably, the terminal sC5b-9 complement complex was associated with respiratory failure. Thus, complement inhibition is an attractive therapeutic approach for treatment of COVD-19

Novel 3D Pixel Sensors for the Upgrade of the ATLAS Inner Tracker

The ATLAS experiment will undergo a full replacement of its inner detector to face the challenges posed by the High Luminosity upgrade of the Large Hadron Collider (HL-LHC). The new Inner Tracker (ITk) will have to deal with extreme particle fluences. Due to its superior radiation hardness the 3D silicon sensor technology has been chosen to instrument the innermost pixel layer of ITk, which is the most exposed to radiation damage. Three foundries (CNM, FBK, and SINTEF), have developed and fabricated novel 3D pixel sensors to meet the specifications of the new ITk pixel detector. These are produced in a single-side technology on either Silicon On Insulator (SOI) or Silicon on Silicon (Si-on-Si) bonded wafers by etching both n- and p-type columns from the same side. With respect to previous generations of 3D sensors they feature thinner active substrates and smaller pixel cells of 50 × 50 and 25 × 100 µm2. This paper reviews the main design and technological issues of these novel 3D sensors, and presents their characterization before and after exposure to large radiation doses close to the one expected for the innermost layer of ITk. The performance of pixel modules, where the sensors are interconnected to the recently developed RD53A chip prototype for HL-LHC, has been investigated in the laboratory and at beam tests. The results of these measurements demonstrate the excellent radiation hardness of this new generation of 3D pixel sensors that enabled the project to proceed with the pre-production for the ITk tracker.publishedVersio

Search for resonances decaying into photon pairs in 139 fb−1 of pp collisions at √s = 13 TeV with the ATLAS detector

Searches for new resonances in the diphoton final state, with spin 0 as predicted by theories with an extended Higgs sector and with spin 2 using a warped extra-dimension benchmark model, are presented using 139 fb−1 of √ s =13 TeV pp collision data collected by the ATLAS experiment at the LHC. No significant deviation from the Standard Model is observed and upper limits are placed on the production cross-section times branching ratio to two photons as a function of the resonance mass.publishedVersio

Measurement of the tt¯ tt¯ production cross section in pp collisions at √s = 13 TeV with the ATLAS detector

A measurement of four-top-quark production using proton-proton collision data at a centre-of-mass energy of 13 TeV collected by the ATLAS detector at the Large Hadron Collider corresponding to an integrated luminosity of 139 fb−1 is presented. Events are selected if they contain a single lepton (electron or muon) or an opposite-sign lepton pair, in association with multiple jets. The events are categorised according to the number of jets and how likely these are to contain b-hadrons. A multivariate technique is then used to discriminate between signal and background events. The measured four-top-quark production cross section is found to be 26+17−15 fb, with a corresponding observed (expected) significance of 1.9 (1.0) standard deviations over the background-only hypothesis. The result is combined with the previous measurement performed by the ATLAS Collaboration in the multilepton final state. The combined four-top-quark production cross section is measured to be 24+7−6 fb, with a corresponding observed (expected) signal significance of 4.7 (2.6) standard deviations over the background-only predictions. It is consistent within 2.0 standard deviations with the Standard Model expectation of 12.0 ± 2.4 fb.publishedVersio

Search for R-parity-violating supersymmetry in a final state containing leptons and many jets with the ATLAS experiment using √s = 13 TeV proton–proton collision data

A search for R-parity-violating supersymmetry in final states characterized by high jet multiplicity, at least one isolated light lepton and either zero or at least three b-tagged jets is presented. The search uses 139fb−1 of s√=13 TeV proton–proton collision data collected by the ATLAS experiment during Run 2 of the Large Hadron Collider. The results are interpreted in the context of R-parity-violating supersymmetry models that feature gluino production, top-squark production, or electroweakino production. The dominant sources of background are estimated using a data-driven model, based on observables at medium jet multiplicity, to predict the b-tagged jet multiplicity distribution at the higher jet multiplicities used in the search. Machine-learning techniques are used to reach sensitivity to electroweakino production, extending the data-driven background estimation to the shape of the machine-learning discriminant. No significant excess over the Standard Model expectation is observed and exclusion limits at the 95% confidence level are extracted, reaching as high as 2.4 TeV in gluino mass, 1.35 TeV in top-squark mass, and 320 (365) GeV in higgsino (wino) mass.publishedVersio

Search for new phenomena with top quark pairs in final states with one lepton, jets, and missing transverse momentum in pp collisions at √s = 13 TeV with the ATLAS detector

A search for new phenomena with top quark pairs in final states with one isolated electron or muon, multiple jets, and large missing transverse momentum is performed. Signal regions are designed to search for two-, three-, and four-body decays of the directly pair-produced supersymmetric partner of the top quark (stop). Additional signal regions are designed specifically to search for spin-0 mediators that are produced in association with a pair of top quarks and decay into a pair of dark-matter particles. The search is performed using the Large Hadron Collider proton-proton collision dataset at a centre-of-mass energy of √s = 13 TeV recorded by the ATLAS detector from 2015 to 2018, corresponding to an integrated luminosity of 139 fb−1. No significant excess above the Standard Model background is observed, and limits at 95% confidence level are set in the stop-neutralino mass plane and as a function of the mediator mass or the dark-matter particle mass. Stops are excluded up to 1200 GeV (710 GeV) in the two-body (three-body) decay scenario. In the four-body scenario stops up to 640 GeV are excluded for a stop-neutralino mass difference of 60 GeV. Scalar and pseudoscalar dark-matter mediators are excluded up to 200 GeV when the coupling strengths of the mediator to Standard Model and dark-matter particles are both equal to one and when the mass of the dark-matter particle is 1 GeV.publishedVersio