Engaging rural Australian communities in National Science Week helps increase visibility for women researchers

During a week-long celebration of science, run under the federally-supported National Science Week umbrella, the Catch a Rising Star: women in Queensland research (CaRS) program flew scientists who identify as women to regional and remote communities in the Australian State of Queensland. The aim of the project was twofold: first, to bring science to remote and regional communities in a large, economically diverse state; and second, to determine whether media and public engagement provide career advancement opportunities for women scientists. This paper focuses on the latter goal. The data show: 1) a substantial majority (> 80%) of researchers thought the training and experience provided by the program would help develop her career as a research scientist in the future; 2) the majority (65%) thought the program would help relate her research to end users, industry partners, or stakeholders in the future; and, 3) analytics can help create a compelling narrative around engagement metrics and help to quantify influence. During the weeklong project, scientists reached 600,000 impressions on one social media platform (Twitter) using a program hashtag. The breadth and depth of the project outcomes indicate funding bodies and employers could use similar data as an informative source of metrics to support hiring and promotion decisions. Although this project focused on researchers who identify as women, the lessons learned are applicable to researchers representing a diverse range of backgrounds. Future surveys will help determine whether the CaRS program provided long-term career advantages to participating scientists and communities

Patients' perceived needs of osteoarthritis health information: A systematic scoping review

Background: Optimal management of osteoarthritis requires active patient participation. Understanding patients’ perceived health information needs is important in order to optimize health service delivery and health outcomes in osteoarthritis. We aimed to review the existing literature regarding patients’ perceived health information needs for OA. Methods: A systematic scoping review was performed of publications in MEDLINE, EMBASE, CINAHL and PsycINFO (1990–2016). Descriptive data regarding study design and methodology were extracted and risk of bias assessed. Aggregates of patients’ perceived needs of osteoarthritis health information were categorized. Results: 30 studies from 2876 were included: 16 qualitative, 11 quantitative and 3 mixed-methods studies. Three areas of perceived need emerged: (1) Need for clear communication: terms used were misunderstood or had unintended connotations. Patients wanted clear explanations. (2) Need for information from various sources: patients wanted accessible health professionals with specialist knowledge of arthritis. The Internet, whilst a source of information, was acknowledged to have dubious reliability. Print media, television, support groups, family and friends were utilised to fulfil diverse information needs. (3) Needs of information content: patients desired more information about diagnosis, prognosis, management and prevention. Conclusions: Patients desire more information regarding the diagnosis of osteoarthritis, its impact on daily life and its long-term prognosis. They want more information not only about pharmacological management options, but also non-pharmacological options to help them manage their symptoms. Also, patients wanted this information to be delivered in a clear manner from multiple sources of health information. To address these gaps, more effective communication strategies are required. The use of a variety of sources and modes of delivery may enable the provision of complementary material to provide information more successfully, resulting in better patient adherence to guidelines and improved health outcomes

Expanding ART for Treatment and Prevention of HIV in South Africa: Estimated Cost and Cost-Effectiveness 2011-2050

Background: Antiretroviral Treatment (ART) significantly reduces HIV transmission. We conducted a cost-effectiveness analysis of the impact of expanded ART in South Africa. Methods: We model a best case scenario of 90% annual HIV testing coverage in adults 15-49 years old and four ART eligibility scenarios: CD4 count <200 cells/mm3(current practice), CD4 count <350, CD4 count <500, all CD4 levels. 2011-2050 outcomes include deaths, disability adjusted life years (DALYs), HIV infections, cost, and cost per DALY averted. Service and ART costs reflect South African data and international generic prices. ART reduces transmission by 92%. We conducted sensitivity analyses. Results: Expanding ART to CD4 count <350 cells/mm3prevents an estimated 265,000 (17%) and 1.3 million (15%) new HIV infections over 5 and 40 years, respectively. Cumulative deaths decline 15%, from 12.5 to 10.6 million; DALYs by 14% from 109 to 93 million over 40 years. Costs drop $504 million over 5 years and$3.9 billion over 40 years with breakeven by 2013. Compared with the current scenario, expanding to <500 prevents an additional 585,000 and 3 million new HIV infections over 5 and 40 years, respectively. Expanding to all CD4 levels decreases HIV infections by 3.3 million (45%) and costs by $10 billion over 40 years, with breakeven by 2023. By 2050, using higher ART and monitoring costs, all CD4 levels saves$0.6 billion versus current; other ART scenarios cost $9-194 per DALY averted. If ART reduces transmission by 99$17.5 billion. Sensitivity analyses suggest that poor retention and predominant acute phase transmission reduce DALYs averted by 26% and savings by 7%. Conclusion: Increasing the provision of ART to <350 cells/mm3 may significantly reduce costs while reducing the HIV burden. Feasibility including HIV testing and ART uptake, retention, and adherence should be evaluated

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Learning and Educational Programs for Entrepreneurs

This chapter summarizes the latest studies in entrepreneurial learning in order to highlight their implications for the design of educational programs (Pittaway & Thorpe, 2012). It examines in detail the latest thinking on the subject, summarizes the key concepts and empirical contributions with a particular focus on expanding understanding of ‘situated’, social and contextual learning (Lave & Wenger, 1991). The chapter stems from Pittaway and Thorpe’s (2012: 850) summary of Cope’s framework. Here it highlights critical concepts, such as dynamic temporal phases, forms and characteristics of learning (Cope, 2010) and lays out the underlying principles of each concept. Following this initial framework recent contributions to the subject of entrepreneurial learning, both conceptual and empirical, are presented to provide an up-to-date picture of thinking in the field. The latter part of the chapter highlights implications of current thinking on the design of development programs for entrepreneurs. It focuses on how concepts in this field can be used to enhance efforts to consider, design and deliver educational programs for entrepreneurs. A number of forms of educational practice are recommended based on this analysis. The chapter closes by considering future developments and lines of inquiry in entrepreneurial learnin

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

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

Development of a revised Jalowiec Coping Scale for use by emergency clinicians: a cross-sectional scale development study

Objectives The aim of this study was to develop and validate a scale to measure the coping strategies used by emergency staff in response to workplace stress. To achieve this aim, we developed a refined Jalowiec Coping Scale (JCS), termed the Jalowiec Coping Scale-Emergency Department (JCS-ED) and validated this scale on a sample of emergency clinicians. Design A cross-sectional survey incorporating the JCS, the working environment scale-10 and a measure of workplace stressors was administered between July 2016 and June 2017. The JCS-ED was developed in three stages: 1) item reduction through content matter experts, 2) exploratory factor analysis for further item reduction and to identify the factor structure of the revised scale and 3) confirmatory factor analyses to confirm the factors identified within the exploratory factor analysis. Setting Six Emergency Departments (EDs) in Australia and four in Sweden. There were three tertiary hospitals, five large urban hospitals and two small urban hospitals. Participants Participants were eligible for inclusion if they worked full-time or part-time as medical or nursing staff in the study EDs. The median age of participants was 35 years (IQR: 28-45 years) and they had been working in the ED for a median of 5 years (IQR: 2-10 years). 79% were females and 76% were nurses. Results A total of 875 ED staff completed the survey (response rate 51%). The content matter experts reduced the 60-item scale to 32 items. Exploratory factor analyses then further reduced the scale to 18 items assessing three categories of coping: problem-focussed coping, positive emotion-focussed coping and negative emotion-focussed coping. Confirmatory factor analysis supported this three-factor structure. Negative coping strategies were associated with poor perceptions of the work environment and higher ratings of stress. Conclusions The JCS-ED assesses maladaptive coping strategies along with problem-focussed and emotion-focussed coping styles. It is a short instrument that is likely to be useful in measuring the types of coping strategies employed by staff.Funding Agencies|Emergency Medicine Foundation [EMSS-410R22-2014]</p