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COVID-19 vaccines are playing a vital role in controlling the COVID-19 pandemic. As SARS-CoV-2 variants encoding mutations in the surface glycoprotein, Spike, continue to emerge, there is increased need to identify immunogens and vaccination regimens that provide the broadest and most durable immune responses. We compared the magnitude and breadth of the neutralizing antibody response, as well as levels of Spike-reactive memory B cells, in individuals receiving a second dose of BNT126b2 at a short (3–4 week) or extended interval (8–12 weeks) and following a third vaccination approximately 6–8 months later. We show that whilst an extended interval between the first two vaccinations can greatly increase the breadth of the immune response and generate a higher proportion of Spike reactive memory B cells, a third vaccination leads to similar levels between the two groups. Furthermore, we show that the third vaccine dose enhances neutralization activity against omicron lineage members BA.1, BA.2 and BA.4/BA.5 and this is further increased following breakthrough infection during the UK omicron wave. These findings are relevant for vaccination strategies in populations where COVID-19 vaccine coverage remains low. Author summary: COVID-19 vaccines have been vital in controlling the current pandemic. With the emergence of SARS-CoV-2 viral variants, it is important to understand factors that influence the neutralization breadth of vaccine responses. Here we study the impact of the interval between the 1st and 2nd BNT162b2 vaccine dose on neutralization breadth and how this is further affected by vaccine boosters and breakthrough infections. [ABSTRACT FROM AUTHOR]

This paper focuses on modelling, control, realisation and performance analysis of a full-scale demonstrator for a novel railway track switch. For over a century, railway track switches (or points) have been allowing trains to safely change between routes. As they are safety-critical elements of the rail network, when they fail, the signalling system will prevent trains from using that route. This means poor reliability (or lack of availability) leads to significant delays and costs; hence there is huge interest from researchers and engineers in improving the overall reliability of track switches. This paper presents new results, which represent a meaningful first step toward a revolution in the way track switches are actuated. A "REPOINT-Light" railway track switch demonstrator is introduced which uses a new concept of locking to allow redundant actuation with three actuator bearers operating under closed-loop feedback control. The new concept, its control system and its mechanical viability are tested in experiments at the Great Central Railway in the UK. To support the design of the actuators and the control system, a dynamic simulation model is developed by co-simulation involving Simulink and Simpack. The experimental results presented are used to validate the models and the paper discusses how the models themselves are used as the vehicle for the design of feedback controllers. Virtual testing of the controllers in simulation is a vital step prior to the implementation and deployment of the controllers in the demonstrator switch. The major contribution of this work is demonstrating, for the first time at full scale on a real-world track switch, that it is possible to use one-out-of-three actuator redundancy to provide fault-tolerant operation of railway track switch. [ABSTRACT FROM AUTHOR]

Objective: The success of pharmacological randomised controlled trials (RCTs) depends on the recruitment of the required number of participants. Recruitment to RCTs for patients with cirrhosis and small oesophageal varices raises specific additional challenges. The objectives of the study were 1) to explore patient perspectives on factors that influence RCT recruitment, 2) to understand factors that influence the success of recruitment from a staff perspective, and 3) to identify opportunities for tailored interventions to improve trial recruitment in this context., Methods: The qualitative study was embedded in a multi-centre blinded RCT (BOPPP trial) and was conducted alongside site opening. Semi-structured interviews were conducted with patients who enrolled to participate in the trial (n = 13), patients who declined to take part (n = 5), and staff who were responsible for recruiting participants to the trial (n = 18). An open approach to data collection and analysis was adopted and the Theoretical Domains Framework (TDF) was used to provide a theoretical lens through which to view influences on behaviour. Data was analysed using thematic analysis., Results: The findings consist of 5 overarching themes that outline trial recruitment influences at the patient, staff, team, organisational and trial levels: i) patient risks and benefits ii) staff attitudes, knowledge and capacity, iii) team-based approach, iv) organisational context and v) Trial collective. Patient-generated themes map onto thirteen of the fourteen TDF domains and staff-generated themes map onto all TDF domains. The overarching themes are not mutually exclusive; with evidence of direct interactions between patient and staff-level themes that influence recruitment behaviours., Conclusions: This study uses a theory-informed approach to gain new insights into improving clinical trial recruitment for patients with cirrhosis and small oesophageal varices. Although people with cirrhosis often display decreased healthcare-seeking behaviours, we found that patients used research to empower themselves to improve their health. Pragmatic trials involving unpredictable populations require staff expertise in building trust, and a deep knowledge of the patient group and their vulnerabilities. RCT recruitment is also more successful when research visits align with what staff identified as the natural rhythm of care., Trial Registration: ISRCTN10324656; https://clinicaltrials.gov/., Competing Interests: The authors have declared that no competing interests exist.