DEVELOPING A FLEXIBLE THERMAL PROTECTION SYSTEM FOR MARS ENTRY: THERMAL DESIGN AND TESTING

Flexible Thermal Protection Systems (FTPS) are a key technology needed to enable novel inflatable and deployable aerodynamic decelerators. A development campaign is underway to raise the European FTPS technology readiness level from 2 to 3, advancing design and test capability. An FTPS suitable for a reference Mars landing mission is being designed. The FTPS has three functional layers: outer layers of Nextel 440 BF-20 fabric; insulation layers of SIGRATHERM GFA5 graphite felt and Pyrogel XTE aerogel; and a silicone-coated Kevlar fabric gas barrier. The density, specific heat capacity and thermal diffusivity of candidate materials was measured. Results were then used in thermal simulations to define a baseline layup. The layup thermal conductance was assessed in thermocouple-instrumented layup tests. Layups including joints were also tested and found not to have significantly different conductance. Layup test thermal simulations showed good agreement with the experimental data. Future work will include arc-jet tests and thermal model optimisation

DEVELOPING A FLEXIBLE THERMAL PROTECTION SYSTEM FOR MARS ENTRY: SYSTEMS ENGINEERING, MECHANICAL DESIGN AND MANUFACTURING PROCESSES

A flexible thermal protection system (FTPS) is needed to enable the use of deployable and inflatable hypersonic decelerators. These decelerators could increase entry vehicle drag area beyond that of a conventional rigid heatshield, enabling Mars missions with greater landed masses and higher-elevation landing sites than can be currently achieved. An FTPS is essential to protect the hypersonic decelerator and payload from atmospheric entry aerothermal loads; conventional rigid heatshields are constrained by the available space within the launcher fairing. An ESA technology development is ongoing to raise the European FTPS technology readiness level from 2 to 3 and to define an FTPS that may be integrated with a Mars-entry inflatable hypersonic decelerator. This paper presents the FTPS requirements, material selection, mechanical characterisation and manufacturing technique development

A surgical team simulation to improve teamwork and communication across two continents: ViSIOT™ proof-of-concept study

Background: Team communication in operating rooms is problematic worldwide, and can negatively impact patient safety. Although initiatives such as the World Health Organization’s Surgical Safety Checklist have been introduced to improve communication, patient safety continues to be compromised globally, warranting the development of new interventions. Video-based social science methods have contributed to the study of communication in UK ORs through actual observations of surgical teams in practice. Drawing on this, the authors have developed a surgical team simulation-training model (ViSIOT™). A proof-of-concept study was conducted in the UK and USA to assess if the ViSIOT™ simulation-training has applicability and acceptability beyond the UK. Methods: ViSIOT™ training was conducted at two simulation centers in the UK and USA over a 10-month period. All surgical team participants completed a questionnaire (that assessed design, education, satisfaction and self-confidence in relation to the training). Descriptive and inferential statistics were performed for the quantitative data and thematic analysis was conducted for the qualitative data. Results: There was strong agreement from all participants in terms of their perception of the course across all sub-sections measured. Nine themes from the qualitative data were identified. The two countries shared most themes, however, some emerged that were unique to each country. Conclusions: Practical developments in the course design, technology and recruitment were identified. Evidence of the course applicability in the USA provides further affirmation of the universal need for team communication training within ORs. Further studies are required to assess its effectiveness in improving communication in OR practice

Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma.

ADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal cell carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between tumor molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates with clinical response. T cell receptor (TCR) analysis reveals a significantly higher number of expanded TCR clones pre-treatment in responders suggesting pre-existing immunity. Maintenance of highly similar clusters of TCRs post-treatment predict response, suggesting ongoing antigen engagement and survival of families of T cells likely recognizing the same antigens. In responders, nivolumab-bound CD8+ T cells are expanded and express GZMK/B. Our data suggest nivolumab drives both maintenance and replacement of previously expanded T cell clones, but only maintenance correlates with response. We hypothesize that maintenance and boosting of a pre-existing response is a key element of anti-PD-1 mode of action

Functional immune responses against SARS-CoV-2 variants of concern after fourth COVID-19 vaccine dose or infection in patients with blood cancer

Summary Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886) we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralising antibody titres (NAbT) using a live virus microneutralization assay against wild-type (WT), Delta, Omicron BA.1 and BA.2 and T cell responses against WT and Omicron BA.1 using an activation-induced marker (AIM) assay. The proportion of patients with detectable NAb titres and T cell responses after the fourth vaccine dose increases compared to those after the third vaccine dose. Patients who received B cell-depleting therapies within 12 months before vaccination have the greatest risk of not having detectable NAbT. In addition, we report immune responses in 57 patients with breakthrough infections after vaccination

Effectiveness and Cost-effectiveness of Outpatient Physiotherapy After Knee Replacement for Osteoarthritis: Study Protocol for a Randomised Controlled Trial

Background: Primary total knee replacement is a common operation that is performed to provide pain relief and restore functional ability. Inpatient physiotherapy is routinely provided after surgery to enhance recovery prior to hospital discharge. However, international variation exists in the provision of outpatient physiotherapy after hospital discharge. While evidence indicates that outpatient physiotherapy can improve short-term function, the longer term benefits are unknown. The aim of this randomised controlled trial is to evaluate the long-term clinical effectiveness and cost-effectiveness of a 6-week group-based outpatient physiotherapy intervention following knee replacement. Methods/design: Two hundred and fifty-six patients waiting for knee replacement because of osteoarthritis will be recruited from two orthopaedic centres. Participants randomised to the usual-care group (n = 128) will be given a booklet about exercise and referred for physiotherapy if deemed appropriate by the clinical care team. The intervention group (n = 128) will receive the same usual care and additionally be invited to attend a group-based outpatient physiotherapy class starting 6 weeks after surgery. The 1-hour class will be run on a weekly basis over 6 weeks and will involve task-orientated and individualised exercises. The primary outcome will be the Lower Extremity Functional Scale at 12 months post-operative. Secondary outcomes include: quality of life, knee pain and function, depression, anxiety and satisfaction. Data collection will be by questionnaire prior to surgery and 3, 6 and 12 months after surgery and will include a resource-use questionnaire to enable a trial-based economic evaluation. Trial participation and satisfaction with the classes will be evaluated through structured telephone interviews. The primary statistical and economic analyses will be conducted on an intention-to-treat basis with and without imputation of missing data. The primary economic result will estimate the incremental cost per quality-adjusted life year gained from this intervention from a National Health Services (NHS) and personal social services perspective. Discussion: This research aims to benefit patients and the NHS by providing evidence on the long-term effectiveness and cost-effectiveness of outpatient physiotherapy after knee replacement. If the intervention is found to be effective and cost-effective, implementation into clinical practice could lead to improvement in patients’ outcomes and improved health care resource efficiency

Functional antibody and T-cell immunity following SARS-CoV-2 infection, including by variants of concern, in patients with cancer: the CAPTURE study

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study (NCT03226886) integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2-positive, 94 were symptomatic and 2 patients died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies, 82% had neutralizing antibodies against WT, whereas neutralizing antibody titers (NAbT) against the Alpha, Beta, and Delta variants were substantially reduced. Whereas S1-reactive antibody levels decreased in 13% of patients, NAbT remained stable up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment-specific, but presented compensatory cellular responses, further supported by clinical. Overall, these findings advance the understanding of the nature and duration of immune response to SARS-CoV-2 in patients with cancer

The Welfare Implications of Using Exotic Tortoises as Ecological Replacements

<div><h3>Background</h3><p>Ecological replacement involves the introduction of non-native species to habitats beyond their historical range, a factor identified as increasing the risk of failure for translocations. Yet the effectiveness and success of ecological replacement rely in part on the ability of translocatees to adapt, survive and potentially reproduce in a novel environment. We discuss the welfare aspects of translocating captive-reared non-native tortoises, <em>Aldabrachelys gigantea</em> and <em>Astrochelys radiata</em>, to two offshore Mauritian islands, and the costs and success of the projects to date.</p> <h3>Methodology/Principal Findings</h3><p>Because tortoises are long-lived, late-maturing reptiles, we assessed the progress of the translocation by monitoring the survival, health, growth, and breeding by the founders. Between 2000 and 2011, a total of 26 <em>A. gigantea</em> were introduced to Ile aux Aigrettes, and in 2007 twelve sexually immature <em>A. gigantea</em> and twelve male <em>A. radiata</em> were introduced to Round Island, Mauritius. Annual mortality rates were low, with most animals either maintaining or gaining weight. A minimum of 529 hatchlings were produced on Ile aux Aigrettes in 11 years; there was no potential for breeding on Round Island. Project costs were low. We attribute the success of these introductions to the tortoises’ generalist diet, habitat requirements, and innate behaviour.</p> <h3>Conclusions/Significance</h3><p>Feasibility analyses for ecological replacement and assisted colonisation projects should consider the candidate species’ welfare during translocation and in its recipient environment. Our study provides a useful model for how this should be done. In addition to serving as ecological replacements for extinct Mauritian tortoises, we found that releasing small numbers of captive-reared <em>A. gigantea</em> and <em>A. radiata</em> is cost-effective and successful in the short term. The ability to release small numbers of animals is a particularly important attribute for ecological replacement projects since it reduces the potential risk and controversy associated with introducing non-native species.</p> </div