Healthy publics: Enabling cultures and environments for health

This is the final version of the article. Available from the publisher via the DOI in this recordDespite extraordinary advances in biomedicine and associated gains in human health and well-being, a growing number of health and well-being related challenges have remained or emerged in recent years. These challenges are often ‘more than biomedical’ in complexion, being social, cultural and environmental in terms of their key drivers and determinants, and underline the necessity of a concerted policy focus on generating healthy societies. Despite the apparent agreement on this diagnosis, the means to produce change are seldom clear, even when the turn to health and well-being requires sizable shifts in our understandings of public health and research practices. This paper sets out a platform from which research approaches, methods and translational pathways for enabling health and wellbeing can be built. The term ‘healthy publics’ allows us to shift the focus of public health away from ‘the public’ or individuals as targets for intervention, and away from the view that culture acts as a barrier to efficient biomedical intervention, towards a greater recognition of the public struggles that are involved in raising health issues, questioning what counts as healthy and unhealthy and assembling the evidence and experience to change practices and outcomes. Creating the conditions for health and well-being, we argue, requires an engaged research process in which public experiments in building and repairing social and material relations are staged and sustained even if, and especially when, the fates of those publics remain fragile and buffeted by competing and often more powerful public formations.The authors would like to acknowledge the Wellcome Trust for funding the Centre for Cultures and Environments of Health (grant reference 203109/Z/16/Z). All authors are lead members of the Wellcome Centre for Cultures and Environments of Health at the University of Exeter

Lessons learnt from a discontinued randomised controlled trial:Adalimumab injection compared with placebo for patients receiving physiotherapy treatment for sciatica (Subcutaneous Injection of Adalimumab Trial compared with Control: SCIATiC)

Background Adalimumab, a biological treatment targeting tumour necrosis factor α, might be useful in sciatica. This paper describes the challenges faced when developing a new treatment pathway for a randomised controlled trial of adalimumab for people with sciatica, as well as the reasons why the trial discussed was stopped early. Methods A pragmatic, parallel group, randomised controlled trial with blinded (masked) participants, clinicians, outcome assessment and statistical analysis was conducted in six UK sites. Participants were identified and recruited from general practices, musculoskeletal services and outpatient physiotherapy clinics. They were adults with persistent symptoms of sciatica of 1 to 6 months’ duration with moderate to high level of disability. Eligibility was assessed by research physiotherapists according to clinical criteria, and participants were randomised to receive two doses of adalimumab (80 mg then 40 mg 2 weeks later) or saline placebo subcutaneous injections in the posterior lateral thigh. Both groups were referred for a course of physiotherapy. Outcomes were measured at baseline, 6-week, 6-month and 12-month follow-up. The main outcome measure was disability measured using the Oswestry Disability Index. The planned sample size was 332, with the first 50 in an internal pilot phase. Results The internal pilot phase was discontinued after 10 months from opening owing to low recruitment (two of the six sites active, eight participants recruited). There were several challenges: contractual delays; one site did not complete contract negotiations, and two sites signed contracts shortly before trial closure; site withdrawal owing to patient safety concerns; difficulties obtaining excess treatment costs; and in the two sites that did recruit, recruitment was slower than planned because of operational issues and low uptake by potential participants. Conclusions Improved patient care requires robust clinical research within contexts in which treatments can realistically be provided. Step changes in treatment, such as the introduction of biologic treatments for severe sciatica, raise complex issues that can delay trial initiation and retard recruitment. Additional preparatory work might be required before testing novel treatments. A randomised controlled trial of tumour necrosis factor-α blockade is still needed to determine its cost-effectiveness in severe sciatica

Understanding disadvantaged adolescents’ perception of health literacy through a systematic development of peer vignettes

Background: Adolescence represents a crucial phase of life where health behaviours, attitudes and social determinants can have lasting impacts on health quality across the life course. Unhealthy behaviour in young people is generally more common in low socioeconomic groups. Nevertheless, all adolescents should have a fair opportunity to attain their full health potential. Health literacy is positioned as a potential mediating factor to improve health, but research regarding health literacy in adolescents and socially disadvantaged populations is limited. As part of Phase one of the Ophelia (OPtimising HEalth LIterAcy) framework, The purpose of this study was to explore the perceptions of socially disadvantaged Irish adolescents in relation to health literacy and related behaviours, and utilise this data to develop relevant vignettes. Methods: A convergent mixed method design was used to co-create the vignettes. Questionnaires were completed by 962 adolescents (males n=553, females n=409, Mean age=13.97±0.96years) from five participating disadvantaged schools in Leinster, Ireland. Focus groups were also conducted in each school (n = 31). Results were synthesised using cluster and thematic analysis, to develop nine vignettes that represented typical male and female subgroups across the schools with varying health literacy profiles. These vignettes were then validated through triangular consensus with students, teachers, and researchers. Discussion: The co-creation process was a participatory methodology which promoted the engagement and autonomy of the young people involved in the project. The vignettes themselves provide an authentic and tangible description of the health issues and health literacy profiles of adolescents in this context. Application of these vignettes in workshops involving students and teachers, will enable meaningful engagement in the discussion of health literacy and health-related behaviours in Irish young people, and the potential co-designing of strategies to address health literacy in youth. Conclusion: As guided by the Ophelia framework, the use of authentic, interactive and participatory research methods, such as the co-creation of vignettes, is particularly important in groups that are underserved by traditional research methods. The approach used in this study could be adapted to other contexts to represent and understand stakeholders’ perceptions of health, with a view to explore, and ultimately improve, health literacy

COVID-19 seroprevalence after the first UK wave of the pandemic and its association with the physical and mental wellbeing of secondary care healthcare workers

Objectives To determine the seroprevalence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antibody status amongst healthcare workers (HCWs) working through the first wave of the Coronavirus (COVID-19) pandemic in 2020. To examine the association of seroprevalence and self-reported COVID-19 symptoms with occupation, sex, and ethnicity; and how these factors were associated with physical and mental wellbeing. Design Single-centre cohort study. Setting Large public hospital in the United Kingdom. Intervention All HCWs who had been tested for anti-SARS-CoV-2 immunoglobulin (Ig) G nucleocapsid antibody in summer 2020 were asked to complete an electronic survey focusing on their physical and mental health in Winter 2020–21. This survey was comprised of the Short Form 12v2, Physical Component Summary (PCS), Mental Component Summary (MCS), and Generalised Anxiety Disorder 7-item (GAD-7) questionnaires. Results 7604/9781 (77.7%) HCWs were antibody tested, of which 1082 completed the full survey. Antibody testing was conducted between 17/06/20–30/07/20, during which time our seroprevalence rate was 28% (299/1082). Of those self-reporting COVID-19 symptoms, 51% (201/395) were antibody positive. Antibody-positive participants had lower PCS scores (p = 0.016), indicating poorer physical health. Lower PCS scores were also found in those deemed high risk for COVID-19 by their GP (p = 0.001), and those aged >44 years (p = 0.009). Antibody-negative participants had lower MCS scores (p = 0.044), indicating poorer mental health. Those who self-reported COVID-19 symptoms had lower PCS scores (p

COVID-19 seroprevalence after the first UK wave of the pandemic and its association with the physical and mental wellbeing of secondary care healthcare workers

© 2022 The Authors. Published by Elsevier. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1016/j.bbih.2022.100492Objectives: To determine the seroprevalence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antibody status amongst healthcare workers (HCWs) working through the first wave of the Coronavirus (COVID-19) pandemic in 2020. To examine the association of seroprevalence and self-reported COVID-19 symptoms with occupation, sex, and ethnicity; and how these factors were associated with physical and mental wellbeing. Design: Single-centre cohort study. Setting: Large public hospital in the United Kingdom. Intervention: All HCWs who had been tested for anti-SARS-CoV-2 immunoglobulin (Ig) G nucleocapsid antibody in summer 2020 were asked to complete an electronic survey focusing on their physical and mental health in Winter 2020–21. This survey was comprised of the Short Form 12v2, Physical Component Summary (PCS), Mental Component Summary (MCS), and Generalised Anxiety Disorder 7-item (GAD-7) questionnaires. Results: 7604/9781 (77.7%) HCWs were antibody tested, of which 1082 completed the full survey. Antibody testing was conducted between 17/06/20–30/07/20, during which time our seroprevalence rate was 28% (299/1082). Of those self-reporting COVID-19 symptoms, 51% (201/395) were antibody positive. Antibody-positive participants had lower PCS scores (p = 0.016), indicating poorer physical health. Lower PCS scores were also found in those deemed high risk for COVID-19 by their GP (p = 0.001), and those aged >44 years (p = 0.009). Antibody-negative participants had lower MCS scores (p = 0.044), indicating poorer mental health. Those who self-reported COVID-19 symptoms had lower PCS scores (p=<0.001) than those with no symptoms. Lower MCS scores were found in women (p = 0.001), Caucasians (p = 0.018), non-clinicians (p = 0.001), and those aged <44 years (p = 0.009). Significantly higher GAD-7 anxiety scores were evident in staff aged <44 years (p = 0.023), and those with self-reported COVID symptoms (p = 0.031). Doctors had lower GAD-7 anxiety scores (p = 0.009). Conclusion: Self-reported symptoms did not correlate with seroprevalence; data surrounding this can be useful for future workforce planning. Interventions are needed to reduce the mental and physical burden of the pandemic on HCWs. Further work is needed to identify which particular HCWs may require further support, to ensure well-being and effective patient care. Trial registration: Sponsor Protocol number - 2020COV112, Clinicaltrials.gov number -NCT04527432.This work was supported by National Institute of Health and Care Research (sponsor number 2020COV112). Abbott Laboratories provided the SARS-CoV-2 Immunoglobin (Ig) test kits used in this study.Published versio

DNA Polymerase Epsilon Deficiency Causes IMAGe Syndrome with Variable Immunodeficiency.

During genome replication, polymerase epsilon (Pol ε) acts as the major leading-strand DNA polymerase. Here we report the identification of biallelic mutations in POLE, encoding the Pol ε catalytic subunit POLE1, in 15 individuals from 12 families. Phenotypically, these individuals had clinical features closely resembling IMAGe syndrome (intrauterine growth restriction [IUGR], metaphyseal dysplasia, adrenal hypoplasia congenita, and genitourinary anomalies in males), a disorder previously associated with gain-of-function mutations in CDKN1C. POLE1-deficient individuals also exhibited distinctive facial features and variable immune dysfunction with evidence of lymphocyte deficiency. All subjects shared the same intronic variant (c.1686+32C>G) as part of a common haplotype, in combination with different loss-of-function variants in trans. The intronic variant alters splicing, and together the biallelic mutations lead to cellular deficiency of Pol ε and delayed S-phase progression. In summary, we establish POLE as a second gene in which mutations cause IMAGe syndrome. These findings add to a growing list of disorders due to mutations in DNA replication genes that manifest growth restriction alongside adrenal dysfunction and/or immunodeficiency, consolidating these as replisome phenotypes and highlighting a need for future studies to understand the tissue-specific development roles of the encoded proteins

Innovative methods of community engagement: towards a low carbon climate resilient future

The proceedings of the Innovative Methods of Community Engagement: Toward a Low Carbon, Climate Resilient Future workshop have been developed by the Imagining2050 team in UCC and the Secretariat to the National Dialogue on Climate Action (NDCA). The NDCA also funded the workshop running costs. The proceedings offer a set of recommendations and insights into leveraging different community engagement approaches and methodologies in the area of climate action. They draw from interdisciplinary knowledge and experiences of researchers for identifying, mobilizing and mediating communities. The work presented below derives from a workshop held in the Environmental Research Institute in UCC on the 17th January 2019. These proceedings are complementary to an earlier workshop also funded by the NDCA and run by MaREI in UCC, titled ‘How do we Engage Communities in Climate Action? – Practical Learnings from the Coal Face’. The earlier workshop looked more closely at community development groups and other non-statutory organizations doing work in the area of climate change

Ecological impacts of non-native Pacific oysters (Crassostrea gigas) and management measures for protected areas in Europe

Pacific oysters are now one of the most ‘globalised’ marine invertebrates. They dominate bivalve aquaculture production in many regions and wild populations are increasingly becoming established, with potential to displace native species and modify habitats and ecosystems. While some fishing communities may benefit from wild populations, there is now a tension between the continued production of Pacific oysters and risk to biodiversity, which is of particular concern within protected sites. The issue of the Pacific oyster therefore locates at the intersection between two policy areas: one concerning the conservation of protected habitats, the other relating to livelihoods and the socio-economics of coastal aquaculture and fishing communities. To help provide an informed basis for management decisions, we first summarise evidence for ecological impacts of wild Pacific oysters in representative coastal habitats. At local scales, it is clear that establishment of Pacific oysters can significantly alter diversity, community structure and ecosystem processes, with effects varying among habitats and locations and with the density of oysters. Less evidence is available to evaluate regional-scale impacts. A range of management measures have been applied to mitigate negative impacts of wild Pacific oysters and we develop recommendations which are consistent with the scientific evidence and believe compatible with multiple interests. We conclude that all stakeholders must engage in regional decision making to help minimise negative environmental impacts, and promote sustainable industry development

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome