Comparative Assessment of the Binding and Neutralisation Activity of Bispecific Antibodies Against SARS-CoV-2 Variants.

Neutralising antibodies against SARS-CoV-2 are a vital component in the fight against COVID-19 pandemic, having the potential of both therapeutic and prophylactic applications. Bispecific antibodies (BsAbs) against SARS-CoV-2 are particularly promising, given their ability to bind simultaneously to two distinct sites of the receptor-binding domain (RBD) of the viral spike protein. Such antibodies are complex molecules associated with multi-faceted mechanisms of action that require appropriate bioassays to ensure product quality and manufacturing consistency. We developed procedures for biolayer interferometry (BLI) and a cell-based virus neutralisation assay, the focus reduction neutralisation test (FRNT). Using both assays, we tested a panel of five BsAbs against different spike variants (Ancestral, Delta and Omicron) to evaluate the use of these analytical methods in assessing binding and neutralisation activities of anti-SARS-CoV-2 therapeutics. We found comparable trends between BLI-derived binding affinity and FRNT-based virus neutralisation activity. Antibodies that displayed high binding affinity against a variant were often followed by potent neutralisation at lower concentrations, whereas those with low binding affinity also demonstrated reduced neutralisation activity. The results support the utility of BLI and FRNT assays in measuring variant-specific binding and virus neutralisation activity of anti-SARS-CoV-2 antibodies

A Core Outcome Set for Pediatric Critical Care

Objectives: More children are surviving critical illness but are at risk of residual or new health conditions. An evidence-informed and stakeholder-recommended core outcome set is lacking for pediatric critical care outcomes. Our objective was to create a multinational, multistakeholder-recommended pediatric critical care core outcome set for inclusion in clinical and research programs.Design: A two-round modified Delphi electronic survey was conducted with 333 invited research, clinical, and family/advocate stakeholders. Stakeholders completing the first round were invited to participate in the second. Outcomes scoring greater than 69% “critical” and less than 15% “not important” advanced to round 2 with write-in outcomes considered. The Steering Committee held a virtual consensus conference to determine the final components.Setting: Multinational survey.Patients: Stakeholder participants from six continents representing clinicians, researchers, and family/advocates.Measurements and Main Results: Overall response rates were 75% and 82% for each round. Participants voted on seven Global Domains and 45 Specific Outcomes in round 1, and six Global Domains and 30 Specific Outcomes in round 2. Using overall (three stakeholder groups combined) results, consensus was defined as outcomes scoring greater than 90% “critical” and less than 15% “not important” and were included in the final PICU core outcome set: four Global Domains (Cognitive, Emotional, Physical, and Overall Health) and four Specific Outcomes (Child Health-Related Quality of Life, Pain, Survival, and Communication). Families (n = 21) suggested additional critically important outcomes that did not meet consensus, which were included in the PICU core outcome set—extended.Conclusions: The PICU core outcome set and PICU core outcome set—extended are multistakeholder-recommended resources for clinical and research programs that seek to improve outcomes for children with critical illness and their families

Differentiation of Colletotrichum gloeosporioides isolates by using total proteins and esterase electrophoretic patterns and extracellular enzymes production Diferenciação de isolados de Colletotrichum gloeosporioides por meio de padrões eletroforéticos de proteínas totais e isoesterase, e produção de enzimas extracelulares

Isolates of Colletotrichum gloeosporioides (ISO-1, ISO-2, ISO-3, ISO-4, ISO-5 and ISO-6), the causal agent of anthracnose disease on mango fruits, were characterized by electrophoretic patterns of total proteins and esterase in polyacrylamida gel, and also, by production of extracellular enzymes on specific solid substrate. The electrophoretic analysis showed variation in number, intensity of coloration and position of the bands in the gel at each studied system tested. In contrast to the monomorphic behavior to total proteins, high esterase polymorfism was observed indicating difference among isolates. All isolates showed the activity of extracellular enzymes such as amylase, lipase, and protease with some variation among them. The proteolitic activity seemed to be more accentuated than the two other enzymes studied.<br>Isolados de Colletotrichum gloeosporioides (ISO-1, ISO-2, ISO-3, ISO-4, ISO-5 e ISO-6), agente causal da antracnose em frutos de mangueira, foram caracterizados por meio de padrões eletroforéticos de proteínas totais e esterase, em gel de poliacrilamida e produção de enzimas extracelulares, em substratos sólidos específicos. A análise eletroforética mostrou variação no número, intensidade de coloração e posição das bandas no gel, dentro dos dois sistemas estudados. Verificou-se polimorfismo em relação a esterase, mostrando maior diferença entre os isolados, enquanto que nas proteínas totais, observou-se comportamento aparentemente uniforme. Quanto à produção de enzimas extracelulares: amilase, lípase e protease, todos os isolados, embora variando em comportamento, apresentaram atividade para essas enzimas, sendo aparentemente mais acentuada à atividade proteolítica

Scientific Computing Plan for the ECCE Detector at the Electron Ion Collider

The Electron Ion Collider (EIC) is the next generation of precision QCD facility to be built at Brookhaven National Laboratory in conjunction with Thomas Jefferson National Laboratory. There are a significant number of software and computing challenges that need to be overcome at the EIC. During the EIC detector proposal development period, the ECCE consortium began identifying and addressing these challenges in the process of producing a complete detector proposal based upon detailed detector and physics simulations. In this document, the software and computing efforts to produce this proposal are discussed; furthermore, the computing and software model and resources required for the future of ECCE are described

Open Heavy Flavor Studies for the ECCE Detector at the Electron Ion Collider

International audienceThe ECCE detector has been recommended as the selected reference detector for the future Electron-Ion Collider (EIC). A series of simulation studies have been carried out to validate the physics feasibility of the ECCE detector. In this paper, detailed studies of heavy flavor hadron and jet reconstruction and physics projections with the ECCE detector performance and different magnet options will be presented. The ECCE detector has enabled precise EIC heavy flavor hadron and jet measurements with a broad kinematic coverage. These proposed heavy flavor measurements will help systematically study the hadronization process in vacuum and nuclear medium especially in the underexplored kinematic region

Design of the ECCE Detector for the Electron Ion Collider

International audienceThe EIC Comprehensive Chromodynamics Experiment (ECCE) detector has been designed to address the full scope of the proposed Electron Ion Collider (EIC) physics program as presented by the National Academy of Science and provide a deeper understanding of the quark-gluon structure of matter. To accomplish this, the ECCE detector offers nearly acceptance and energy coverage along with excellent tracking and particle identification. The ECCE detector was designed to be built within the budget envelope set out by the EIC project while simultaneously managing cost and schedule risks. This detector concept has been selected to be the basis for the EIC project detector

Scientific Computing Plan for the ECCE Detector at the Electron Ion Collider

The Electron Ion Collider (EIC) is the next generation of precision QCD facility to be built at Brookhaven National Laboratory in conjunction with Thomas Jefferson National Laboratory. There are a significant number of software and computing challenges that need to be overcome at the EIC. During the EIC detector proposal development period, the ECCE consortium began identifying and addressing these challenges in the process of producing a complete detector proposal based upon detailed detector and physics simulations. In this document, the software and computing efforts to produce this proposal are discussed; furthermore, the computing and software model and resources required for the future of ECCE are described

Design and Simulated Performance of Calorimetry Systems for the ECCE Detector at the Electron Ion Collider

We describe the design and performance the calorimeter systems used in the ECCE detector design to achieve the overall performance specifications cost-effectively with careful consideration of appropriate technical and schedule risks. The calorimeter systems consist of three electromagnetic calorimeters, covering the combined pseudorapdity range from -3.7 to 3.8 and two hadronic calorimeters. Key calorimeter performances which include energy and position resolutions, reconstruction efficiency, and particle identification will be presented

Evaluation of longitudinal double-spin asymmetry measurements in semi-inclusive deep-inelastic scattering from the proton for the ECCE detector design

The evaluation of the measurement of double-spin asymmetries for charge-separated pions and kaons produced in deep-inelastic scattering from the proton using the ECCE detector design concept is presented, for the combinations of lepton and hadron beam energies of 5 × 41 GeV2 and 18 × 275 GeV2. The study uses unpolarised simulated data that are processed through a full GEANT simulation of the detector. These data are then reweighted at the parton level with DSSV helicity distributions and DSS fragmentation functions, in order to generate the relevant asymmetries, and subsequently analysed. The performed analysis shows that the ECCE detector concept provides the resolution and acceptance, with a broad coverage in kinematic phase space, needed for a robust extraction of asymmetries. This, in turn, allows for a precise extraction of sea-quark helicity distributions