Phase 1/2 Study of Agent-797, an Allogeneic Invariant Natural Killer T (Inkt) Cell Therapy, in Subjects with Moderate to Severe Acute Respiratory Distress Syndrome (Ards) Secondary to Sars-Cov-2 (Covid-19)

Background AgenT-797 is a novel allogeneic iNKT cell therapy demonstrating activity in malignances and serious viral infections (i.e., SARS-CoV-2). In response to inflammatory injury, iNKTs home to critical organs, including lungs, dampen proinflammatory cytokines and protect epithelial tissues. INKTs drive response through activation of innate and adaptive immunity, recruitment/trans-activation of NK, B, and T cells, and myeloid cells via contact and soluble mediators. iNKTs represent a novel and attractive potential immunotherapy for viral ARDS. This analysis presents results from an ongoing phase 1/2 study of agenT-797 in mechanically ventilated patients with moderate to severe ARDS secondary to COVID- 19;NCT04582201. Methods As of February 2022, patients on mechanical ventilation with confirmed moderate to severe (Berlin Definition) ARDS, secondary to COVID-19 were treated with a single infusion of agenT-797 at 100, 300, or 1000 x 106 iNKT cells. Primary endpoint was safety and secondarily, time to extubation, prevention of secondary infections, persistence and alloimmunity were evaluated. Clinical benefit was defined as improvement/resolution of viral ARDS evaluated as time to extubation and survival at 30 days post-infusion. Results Twenty evaluable patients were treated with agenT-797 with a median age of 66 years (range 26-77;85% >=65y). Patients enrolled early in pandemic (pre-vaccines) and were heavily pre-treated with remdesivir, steroids and/or tocilizumab. No dose-limiting toxicities were observed. Tolerability was favorable with no cytokine release syndrome (CRS), neurotoxicity, or severe immune-related AEs. One SAE was deemed possibly related to agenT-797 (Dyspnea, Grade 4). The most frequent AEs deemed possibly related was pyrexia (grade 1;n=6). Survival was 70% (14/20) in this predominantly elderly, mechanically ventilated population. Early signals of reduction in ARDS symptoms, rapid extubation, and reduction in secondary infections were observed. AgenT-797 was detected in peripheral blood up to day 6 post-infusion, consistent with a rapid translocation from blood to tissue. Spikes in the blood during D1 and D2 showed a dose-proportional relationship, however, increased dose did not lead to prolonged peripheral persistence. Additional translational and biomarker evaluation is underway. Conclusions In patients with severe viral ARDS secondary to SARS-COV-2, agenT-797 demonstrated encouraging survival and disease mitigating benefit with a favorable tolerability profile. The deep and broad activity observed is likely attributed to iNKT cells' ability to promote viral clearance, home to the lungs, and reduce inflammation. These findings support the potential for a variant-agnostic therapy for patients with viral ARDS, a condition for which there are currently no effective therapies.

Low Testosterone on Hospital Admission with COVID-19 Infection Is Associated with Increased Mortality

Objective: Males, despite equal sex-related susceptibility to COVID-19, appear at a greater risk of poor clinical outcomes and death. This suggests that serum testosterone could be a mediator. The aim of this retrospective study was to evaluate the association between serum total testosterone (TT), other prognostic indicators, and mortality in men with COVID-19. Methods: Of the 110 men consecutively admitted to Walsall Manor Hospital (with COVID-19 related symptoms) tested for SARS-CoV-2, 85 were positive and 27 of these men died. Serum TT was compared (rank-sum test) between men negative and positive for SARS-CoV-2, and this was followed by establishing factors associated with mortality in the latter group (rank-sum, logistic, Cox regression analyses). No patient was on testosterone therapy (TTh). Results: No significant difference (p = 0.12, rank-sum test) in serum TT between men positive [median TT (IQR) = 3.9 (1.9-7.22) nmol/L, 0 days (median) postadmission] and negative [median TT (IQR) = 5.9 (2.69-10.1) nmol/L, 2 days (median) postadmission] for SARS-CoV-2 was observed. Serum TT was lower (p = 0.0011, rank-sum test) in men with COVID-19 who died [median TT (IQR) = 2.0 (1.5-3.6) nmol/L] compared with survivors [median TT (IQR) = 5.0 (2.6-9.4) nmol/L]. Comorbidities obtained via medication history were not associated with mortality. Mortality (logistic regression) was associated with only age and serum TT (odds ratio: 0.77, 95% confidence intervals [CI]: 0.64-0.91). Survival (Cox regression) was inversely associated with serum TT (continuous variable, hazard ratio [HR]: 0.85) (95% CI: 0.74-0.98), stratified by median, TT ≥3.9 nmol/L (reference, TT <3.9 nmol/L), HR: 0.24 (95% CI: 0.089-0.63). Conclusions: Serum TT was inversely associated with mortality in men with COVID-19 and requires measurement at admission and while managing long COVID. Future research should establish whether low serum TT, possibly associated with negative acute phase response, contributes to poorer prognosis and a role for TTh. © Mark Livingston et al., 2022;Published by Mary Ann Liebert, Inc. 2022.

Low Testosterone on Hospital Admission with COVID-19 infection is associated with increased mortality

Objective: Men appear at greater risk of poor clinical outcomes and death from Covid-19. This suggests that serum testosterone could be a mediator. The aim of this retrospective study was to evaluate the association between serum total testosterone (TT), other prognostic indicators, and mortality in men with COVID-19. Methods: 110 men consecutively admitted to a district general hospital (with COVID-19 related symptoms) tested for SARS-CoV-2, 85 were positive and 27 of these men died. Serum TT was compared (rank-sum test) between men negative and positive for SARS-CoV-2. Factors associated with mortality in the latter group were analysed. Results: No significant difference was found (p=0.12, rank-sum test) in serum TT between men positive and negative for SARS-CoV-2. Serum TT was lower (p=0.0011, rank-sum test) in men with COVID-19 who died (median TT 2.0nmol/L) compared with survivors (median TT 5.0nmol/L). Mortality (logistic regression) was associated with age and serum TT (odds ratio: 0.77, 95% confidence intervals (CI): 0.64, 0.91). Survival (Cox regression) was inversely associated with serum TT (continuous variable, hazard ratio (HR): 0.85 (95% CI: 0.74, 0.98), stratified by median, TT ≥ 3.9nmol/L (reference, TT < 3.9nmol/L), HR:0.24, (95% CI: 0.089, 0.63). Conclusions: Serum TT was inversely associated with mortality in men with COVID-19 and requires measurement at admission and whilst managing long COVID. Future research should establish whether low serum TT, possibly associated with negative acute phase response, contributes to a poorer prognosis and a role for testosterone therapy.

A novel eLearning tool for ongoing radiation therapist education on pelvic radiotherapy late effects

Purpose or Objective The late effects (LEs) of pelvic radiotherapy (RT) have a significant detrimental impact on a patient's quality of life;as such, within the UK there is a national drive to improve aftercare, with enhanced provision of patient information through the National Health Service (NHS) and various charities. A requirement to improve Radiation Therapists' knowledge, awareness and confidence surrounding pelvic LEs has been observed, highlighting a demand for further training. Traditional pedagogical methods pose barriers within busy clinical settings, thus eLearning methods may prove more feasible. This study aimed to investigate the effectiveness of a novel, interactive eLearning tool as an innovative pedagogical approach to increase Radiation Therapists' knowledge and confidence on the LEs of pelvic RT, and to improve their perception of their professional responsibilities to provide such patient information. Materials and Methods The study was conducted within a single UK RT institution over a 12-month period with a recruitment of 27 Radiation Therapists. Our novel eLearning tool was designed, implemented and disseminated to participants via the hospital's Blended Learning portal, providing flexible, asynchronous access. Pre- and post-intervention Likert-scale questionnaires and focus groups were utilised to provide baseline assessment and ascertain changes in levels of knowledge, confidence and perceived responsibility surrounding pelvic RT LEs. Statistical analysis using a Wilcoxon signed-rank test was conducted on paired data from pre- and post-intervention questionnaires (n=23) to provide quantitative results, whilst thematic analysis provided qualitative results. Results Whilst this was a mixed-methods study, the quantitative results are presented here. Statistically significant increases in knowledge (p=0.002), confidence (p=0.006) and responsibility (p=0.026) surrounding pelvic RT LEs were reported following the eLearning intervention compared to baseline scores, rejecting the null hypothesis. Examples of the results are shown in figures 1 and 2. $Φg Conclusion We believe this study is the first of its kind, investigating eLearning to improve pelvic RT LE knowledge, confidence and responsibility amongst UK Radiation Therapists. Our novel, robust eLearning tool proved successful in achieving these aims, and the eLearning tool has now been disseminated across all NHS hospitals within the regional ‘Cancer Alliance' and is also being used at a novel pelvic RT LEs clinic. This has led to increased knowledge of pelvic RT LEs across the wider oncology team, including consultants, nurses and other professionals. Project recommendations have led to introduction of a new Masters module on LEs at a UK University, further enhancing the knowledge of the Radiation Therapist workforce. With the severe, ongoing impact of COVID-19 on healthcare departments, such innovative online tools are crucial to ensure staff have remote, asynchronous access to learning content.

SEMPRE Autumn 2020 Conference: The Role of Music Psychology Research in a Complex World

Each year, the Society for Education, Music and Psychology Research (SEMPRE) hosts two conferences, covering a range of themes within music education and psychology research. The Autumn 2020 conference took place on September 9–11. The theme of the conference was ‘The role of music psychology research in a complex world: Implications, applications, and debates’;a particularly appropriate theme given the complex and challenging nature of 2020. Owing to the COVID-19 pandemic, this conference was hosted virtually by the University of Leeds. This report provides an overview of the conference, reflects on its key themes, and discusses the opportunities and challenges of online conferencing. © The Author(s) 2020.

Caremark and ESG, Perfect Together: A Practical Approach to Implementing an Integrated, Efficient, and Effective Caremark and EESG Strategy

With increased calls from investors, legislators, and academics for corporations to consider employee, environmental, social, and governance factors ("EESG") when making decisions, boards and managers are struggling to situate EESG within their existing reporting and organizational structures. Building on an emerging literature connecting EESG with corporate compliance, this Essay argues that EESG is best understood as an extension of the board's duty to implement and monitor a compliance program under Caremark. If a company decides to do more than the legal minimum, it will simultaneously satisfy legitimate demands for strong EESG programs and promote compliance with the law. Building on that insight, we explain how boards can marry existing corporate compliance programs with budding EESG programs. By integrating compliance and EESG, corporations can meet growing societal demands in an effective and efficient manner that capitalizes on existing structures. Lastly, we address how EESG and corporate compliance responsibilities should be allocated at the board and senior management level. Instead of separating compliance and EESG oversight, this Essay suggests that boards embrace a functional approach, delegating similar compliance and EESG oversight to the same committee and managers. By situating EESG within the board's existing fiduciary duties, this Essay provides academics, legislators, investors, and managers with a novel framework to conceptualize EESG while also offering a path forward for boards struggling to place the current EESG movement within their existing corporate structure.

COVID-19, Remote Court Hearings, Automated Decision-making and Access to Justice

Audiovisual links hearings, prompted by COVID-19, are not necessarily a major change from the present way that courts are operating. They may be no more than a supplementary facility that leaves the basic character of the judiciary and court proceedings untouched. As presently organised, the changes that have already been adopted would not have much impact on Professor Susskind's third change concerning "access to justice". Radically redrafting the arrangements for public institutions identified as "courts" afford special difficulties in countries operating under written constitutions. It is not easy to convert such courts into a "helping" agency of the executive government. Constitutionally, courts must be kept separate from the Executive. Law reform also cannot be performed successfully without a deep knowledge of our legal history;an appreciation of its values that go beyond efficiency and cost saving;and an understanding of the role of the courtroom in the whole-of-government institutional tapestry. The constitutional and historic barriers to the introduction of Professor Susskind's ideas for change to improve access to justice suggest that there is a continuing future for Australian Dispute Resolution, particularly mediation and arbitration.