Background Regular physical activity is the prime modality for the prevention of numerous non-communicable diseases and has also been advocated for resilience against COVID-19 and other infectious diseases. However, there is currently no systematic and quantitative evidence synthesis of the association between physical activity and the strength of the immune system. Objective To examine the association between habitual physical activity and (1) the risk of community-acquired infectious disease, (2) laboratory‐assessed immune parameters, and (3) immune response to vaccination. Methods We conducted a systemic review and meta-analysis according to PRISMA guidelines. We searched seven databases (MEDLINE, Embase, Cochrane CENTRAL, Web of Science, CINAHL, PsycINFO, and SportDiscus) up to April 2020 for randomised controlled trials and prospective observational studies were included if they compared groups of adults with different levels of physical activity and reported immune system cell count, the concentration of antibody, risk of clinically diagnosed infections, risk of hospitalisation and mortality due to infectious disease. Studies involving elite athletes were excluded. The quality of the selected studies was critically examined following the Cochrane guidelines using ROB2 and ROBINS_E. Data were pooled using an inverse variance random-effects model. Results Higher level of habitual physical activity is associated with a 31% risk reduction (hazard ratio 0.69, 95% CI 0.61–0.78, 6 studies, N = 557,487 individuals) of community-acquired infectious disease and 37% risk reduction (hazard ratio 0.64, 95% CI 0.59–0.70, 4 studies, N = 422,813 individuals) of infectious disease mortality. Physical activity interventions resulted in increased CD4 cell counts (32 cells/µL, 95% CI 7–56 cells/µL, 24 studies, N = 1112 individuals) and salivary immunoglobulin IgA concentration (standardised mean difference 0.756, 95% CI 0.146–1.365, 7 studies, N = 435 individuals) and decreased neutrophil counts (704 cells/µL, 95% CI 68–1340, 6 studies, N = 704 individuals) compared to controls. Antibody concentration after vaccination is higher with an adjunct physical activity programme (standardised mean difference 0.142, 95% CI 0.021–0.262, 6 studies, N = 497 individuals). Conclusion Regular, moderate to vigorous physical activity is associated with reduced risk of community-acquired infectious diseases and infectious disease mortality, enhances the first line of defence of the immune system, and increases the potency of vaccination. Protocol registration The original protocol was prospectively registered with PROSPERO (CRD42020178825).

The Aurora kinases have been the subject of considerable interest as targets for the development of new anticancer agents. While evidence suggests inhibition of Aurora B kinase gives rise to the more pronounced antiproliferative phenotype, the most clinically advanced agents reported to date typically inhibit both Aurora A and B. We have discovered a series of pyrazoloquinazolines, some of which show greater than 1000-fold selectivity for Aurora B over Aurora A kinase activity, in recombinant enzyme assays. These compounds have been designed for parenteral administration and achieve high levels of solubility by virtue of their ability to be delivered as readily activated phosphate derivatives. The prodrugs are comprehensively converted to the des-phosphate form in vivo, and the active species have advantageous pharmacokinetic properties and safety pharmacology profiles. The compounds display striking in vivo activity, and compound 5 (AZD1152) has been selected for clinical evaluation and is currently in phase 1 clinical trials.

Background The delivery of healthcare during the COVID pandemic has had a significant impact on front line staff. Nurses who work with respiratory patients, have been at the forefront of the pandemic response. Lessons can be learnt from these nurses’ experiences in order to support these nurses during the existing pandemic and retain and mobilise this skilled workforce for future pandemics. Methods This study explores UK nurses’ experiences of working in a respiratory environment during the COVID-19 pandemic. An e-survey was distributed via professional respiratory societies the survey included a resilience scale, the GAD7 (anxiety) and the PHQ9 (depression) tools. Demographic data was collected on age, gender, ethnicity, nursing experience and background, clinical role in the pandemic, and home-life and work balance. Results Two hundred and fifty-five responses were received for the survey, predominately women (89%, 226/255), aged over 35 (79%, 202/255). Nearly 21% (40/191) experiencing moderate to severe or severe symptoms of anxiety. Similar levels are seen for depression (15.7%, 30/191). 18.9% (34/180) had a low or very low resilience score. Regression analysis showed that for both depression and anxiety variables, age and years of qualification provided the best model fit.  Younger nurses with less experience have higher levels of anxiety and depression and had lower resilience. Conclusion This cohort experienced significant levels of anxiety and depression, with moderate to high levels of resilience. Support mechanisms and interventions need to be put in place to support all nurses during pandemic outbreaks, particularly younger or less experienced staff.

Objectives: To determine