Endangered Archaeology in the Middle East and North Africa: Introducing the EAMENA Project

This project uses satellite imagery and historic aerial photographs to discover and interpret archaeological sites. It has created an open access database of archaeological records that provides basic information so that the sites can be better under- stood and preserved in the future. The threats to sites in the Middle East and North Africa are increasing and creating a record of previously unrecorded sites using this methodology may be our the last chance before they are destroyed

Endangered Archaeology in the Middle East and North Africa: Introducing the EAMENA Project

This project uses satellite imagery and historic aerial photographs to discover and interpret archaeological sites. It has created an open access database of archaeological records that provides basic information so that the sites can be better under- stood and preserved in the future. The threats to sites in the Middle East and North Africa are increasing and creating a record of previously unrecorded sites using this methodology may be our the last chance before they are destroyed

A novel theatre-based behaviour change approach for influencing community uptake of schistosomiasis control measures

Background: Appropriate behaviour change with regard to safe water contact practices will facilitate the elimination of schistosomiasis as a public health concern. Various approaches to effecting this change have been trialled in the field but with limited sustainable outcomes. Our case study assessed the effectiveness of a novel theatre-based behaviour change technique (BCT), in combination with cohort awareness raising and capacity training intervention workshops. Methodology: Our study was carried out in Mwanza, Tanzania and Kemise, Ethiopia. We adapted the Risk, Attitude, Norms, Ability, and Self-regulation (RANAS) framework and four phases using a mixed methods approach. Participatory project phase engagement an11 qualitative formative data were used to guide the design of an acceptable, holistic intervention. Initial baseline (BL) data was collected using quantitative questionnaire surveys with 804 participants in Tanzania and 617 in Ethiopia, followed by the theatre-based BCT and capacity training intervention workshops. Post-intervention (PI) survey was carried out after six months, with a participant return rate of 65% in Tanzania and 60% in Ethiopia. Results: The intervention achieved a significant improvement in the knowledge of schistosomiasis transmission being associated with poorly managed sanitation and risky water contact. Participants in Tanzania increased their uptake of preventive chemotherapy (Male: BL:56%; PI:73%, Female: BL:43%; PI:50%). There was a significant increase in the selection of sanitation (Tanzania: BL:13%; PI:21%, Ethiopia: BL:63%; PI:90%), safe water and avoiding/minimising contact with infested waters as prevention methods in Tanzania and Ethiopia. Some of the participants in Tanzania followed on from the study by building their own latrines. Conclusions: This study showed substantial positive behaviour changes in schistosomiasis control can be achieved using theatre-based BCT intervention and disease awareness training. With appropriate sensitisation, education and stakeholder engagement approaches, community members were more open to minimising risk-associated contact with contaminated water sources and were mobilised to implement preventive measures

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Informing Royal Navy People Strategy: Understanding Career Aspirations and Behaviours of Naval Personnel

Following a series of imposed redundancies in the Royal Navy (RN) there was a need to understand the career desires of remaining personnel and how these interact with important organisational behaviours and turnover. Taking a social psychology perspective, this thesis addresses criticisms over the high use of non-working populations in research and provides the first empirical evidence for the utility, applicability and relevance of specific psychological theories to the RN. Chapter 2 explores the relationship between career anchors and psychological contract violation, organisational commitment and turnover. Evidence was found for the applicability and potential generalisability of civilian-based research to the RN. RN career anchor preferences were similar to some non-military organisations, and these preferences differentially influenced the variables explored. Chapter 3 presents an intervention developed to support newly appointed Career Managers to increase awareness of human resource issues, representing the first exploration of induction on later attitudes of ‘experienced newcomers’ in the RN. The induction did not influence attitudes; although time did, indicating the importance of role clarity. Chapter 4 provides a critical literature review of work-family conflict (WFC) and its influence on turnover intentions of military personnel and effects on military spouses. The expected negative relationship between WFC and turnover was found, although not consistently; types of satisfaction mediated this relationship, and WFC was linked to stress. Chapter 5 provides new empirical understanding of the interactions between ethos, organisational identity, and engagement on career motivation, perceived future opportunities and intentions to stay. Differences in these constructs were also explored between discrete RN groupings. The relationship between identity and ethos, and engagement, identity and ethos were explored to advance theoretical understanding of these constructs, finishing with an extension to Chapter 2 through revisiting career anchors. In conclusion, this thesis provides new contextual insights, interactions and relationships for academic knowledge, psychological theory and addresses a practical organisational issue within a highly regarded and inaccessible organisation. The outcomes provide the first empirical evidence of career-related behaviours within the RN, and more generally indicate the applicability of civilian based psychological theories to a military population, in particular, career anchors, ethos and focus on opportunities and their importance for people strategy decisions supporting evidence-based decision making within the workplace

Trajectories of multiple adolescent health risk behaviors in a low-income African American population

This study examined interdependent trajectories of sexual risk, substance use, and conduct problems among 12–18 year-old African American youth who were followed annually as part of the Mobile Youth Study (MYS). We used growth-mixture modeling (GMM) to model the development of these three outcomes in the 1406 participants who met the inclusion criteria. Results indicate that there were four distinct classes: normative low risk (74.3% of sample); increasing high risk takers (11.9%); adolescent-limited conduct problems and drug risk with high risky sex (8.0%); and early experimenters (5.8%) The higher risk classes had higher rates of pregnancy and Sexually Transmitted Infections (STI) diagnoses than the normative sample at each of the ages we examined. Differing somewhat from our hypothesis, all of the non-normative classes exhibited high sexual risk behavior. While prevention efforts should be focused on addressing all three risk behaviors, the high rate of risky sexual behavior in the 25% of the sample that fall into the three non-normative classes, underscores an urgent need for improved sex education, including teen pregnancy and HIV/STI prevention, in this community