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Abstract Science is integral to society because it can inform individual, government, corporate, and civil society decision-making on issues such as public health, new technologies or climate change. Yet, public distrust and populist sentiment challenge the relationship between science and society. To help researchers analyse the science-society nexus across different geographical and cultural contexts, we undertook a cross-sectional population survey resulting in a dataset of 71,922 participants in 68 countries. The data were collected between November 2022 and August 2023 as part of the global Many Labs study “Trust in Science and Science-Related Populism” (TISP). The questionnaire contained comprehensive measures for individuals’ trust in scientists, science-related populist attitudes, perceptions of the role of science in society, science media use and communication behaviour, attitudes to climate change and support for environmental policies, personality traits, political and religious views and demographic characteristics. Here, we describe the dataset, survey materials and psychometric properties of key variables. We encourage researchers to use this unique dataset for global comparative analyses on public perceptions of science and its role in society and policy-making.

Abstract Purpose Informal caregivers of people with high grade glioma (HGG) often have high levels of unmet support needs. Routine screening for unmet needs can facilitate appropriate and timely access to supportive care. We aimed to develop a brief screening tool for HGG caregiver unmet needs, based on the Supportive Care Needs Survey—Partners & Caregivers (SCNS-P&C). Methods Secondary analysis was performed on responses to the SCNS-P&C from 188 HGG caregivers, who participated in the Care-IS trial. SCNS-P&C items were assessed against four criteria: factor loadings; prevalence; variation in domain score; diagnostic accuracy. Supplementary analysis was conducted at two timepoints (T1 & T2) on the final selected items to identify caregivers indicating no needs on the screening items but reported a need on the original SCNS-P&C, suggesting they would be “missed” by the screening items. Results Six items performed best against psychometric criteria, capturing two domains: Cancer impact needs and Information and communication needs. Supplementary analysis showed screening items failed to identify only 7.4% (14/188) of caregivers with other unmet needs at T1 and 11.4% (18/158) at T2. Of those missed at T1, only four were missed again at T2. Conclusions We identified six-items for inclusion in a brief screening tool, the SCNS-P&C-6, demonstrating good sensitivity in detecting unmet needs of caregivers of people with HGG. Use of this tool in clinical practice has the potential to improve access to care and the cancer experience for both the caregiver and person with brain tumor.

Abstract We report the development and performance of a novel genomics platform, TempO-LINC, for conducting high-throughput transcriptomic analysis on single cells and nuclei. TempO-LINC works by adding cell-identifying molecular barcodes onto highly selective and high-sensitivity gene expression probes within fixed cells, without having to first generate cDNA. Using an instrument-free combinatorial indexing approach, all probes within the same fixed cell receive an identical barcode, enabling the reconstruction of single-cell gene expression profiles across as few as several hundred cells and up to 100,000 + cells per sample. The TempO-LINC approach is easily scalable based on the number of barcodes and rounds of barcoding performed; however, for the experiments reported in this study, the assay utilized over 5.3 million unique barcodes. TempO-LINC offers a robust protocol for fixing and banking cells and displays high-sensitivity gene detection from multiple diverse sample types. We show that TempO-LINC has a multiplet rate of less than 1.1% and a cell capture rate of ~ 50%. Although the assay can accurately profile the whole transcriptome (19,683 human, 21,400 mouse and 21,119 rat genes), it can be targeted to measure only actionable/informative genes and molecular pathways of interest – thereby reducing sequencing requirements. In this study, we applied TempO-LINC to profile the transcriptomes of more than 90,000 cells across multiple species and sample types, including nuclei from mouse lung, kidney and brain tissues. The data demonstrated the ability to identify and annotate more than 50 unique cell populations and positively correlate expression of cell type-specific molecular markers within them. TempO-LINC is a robust new single-cell technology that is ideal for large-scale applications/studies with high data quality.

Abstract Mixed lineage kinase domain-like (MLKL) is a pseudokinase, best known for its role as the terminal effector of the necroptotic cell death pathway. MLKL-mediated necroptosis has long been linked to various age-related pathologies including neurodegeneration, atherosclerosis and male reproductive decline, however many of these attributions remain controversial. Here, we investigated the role of MLKL and necroptosis in the adult mouse testis: an organ divided into sperm-producing seminiferous tubules and the surrounding testosterone-producing interstitium. We find that sperm-producing cells within seminiferous tubules lack expression of key necroptotic mediators and thus are resistant to a pro-necroptotic challenge. By comparison, coordinated expression of the necroptotic pathway occurs in the testicular interstitium, rendering cells within this compartment, especially the lysozyme-positive macrophages, vulnerable to necroptotic cell death. We also uncover a non-necroptotic role for MLKL in regulating testosterone levels. Thus, MLKL serves two roles in the mouse testes – one involving the canonical response of macrophages to necroptotic insult, and the other a non-canonical function in male reproductive hormone control.

Abstract The role of rare non-coding variation in complex human phenotypes is still largely unknown. To elucidate the impact of rare variants in regulatory elements, we performed a whole-genome sequencing association analysis for height using 333,100 individuals from three datasets: UK Biobank (N = 200,003), TOPMed (N = 87,652) and All of Us (N = 45,445). We performed rare (

Abstract Objective To compare specific perinatal outcomes in nulliparas with a singleton infant in cephalic presentation at term, with and without exposure to the COVID-19 pandemic during pregnancy. We hypothesised that the pandemic conditions in Melbourne may have been an independent contributor to trends in maternal Body Mass Index ≥ 25 kg/m2, macrosomia and caesarean section. Design Multi-centre retrospective cohort study and interrupted time-series analysis. Setting Metropolitan Melbourne, Victoria. Population Singleton infants ≥ 20 weeks gestational age born between 1 January 2019 and 31 March 2022. Main outcome measures Rates of maternal Body Mass Index ≥ 25 kg/m2, macrosomia (birthweight ≥ 4000 g) and caesarean section. Results 25 897 individuals gave birth for the first time to a singleton infant in cephalic presentation at term in the pre-pandemic cohort, and 25 298 in the pandemic-exposed cohort. Interrupted time-series analysis demonstrated no significant additional effect of the pandemic on pre-existing upward trends in maternal Body Mass Index ≥ 25 kg/m2, caesarean section or macrosomia. The rate of maternal Body Mass Index ≥ 25 kg/m2 was higher in the pandemic-exposed cohort compared with the pre-pandemic cohort, (45.82% vs. 44.58% respectively, p = 0.041) as was the overall rate of caesarean section (33.09% vs. 30.80%, p

Abstract Estuaries are a globally important source of methane, but little is known about Australia’s contributions to global estuarine methane emissions. Here we present a first-order Australia-wide assessment of estuarine methane emissions, using methane concentrations from 47 estuaries scaled to 971 Australian estuaries based on geomorphic estuary types and disturbance classes. We estimate total mean (±standard error) estuary annual methane emissions for Australia of 30.56 ± 12.43 Gg CH4 yr−1. Estuarine geomorphology and disturbance interacted to control annual methane emissions through differences in water–air methane flux rates and surface area. Most of Australia’s estuarine surface area (89.8%) has water–air methane fluxes lower than global means, contributing 80.3% of Australia’s total mean annual estuarine methane emissions. Australia is a good analogue for the ~34% of global coastal regions classified as less than moderately disturbed (>40% intact), suggesting that these regions may also have lower methane fluxes. On this basis, recent global estuarine methane emission estimates that do not consider disturbance in their upscaling, probably overestimate global estuarine methane emissions.

Abstract The maternal pregnancy microbiome (including genitourinary and gut) has been linked to important pregnancy/birth and later childhood health outcomes. However, such sampling as part of large population cohort studies is logistically and financially challenging. Many countries routinely collect vaginal or vaginal-rectal swabs in late pregnancy for Group B Streptococcus (GBS) screening, but their utility for population-based research is still unclear. As part of planning for the Generation Victoria population-based cohort study beginning in pregnancy, we assessed the utility and reliability of residual clinical GBS vaginal/vaginal-rectal swabs for generating late pregnancy microbiome data. We carried out a two-phased pilot study. Phase one assessed the level of microbial diversity apparent in ‘residual’ clinical vaginal/vaginal-rectal swabs post clinical testing and storage for 7–10 days at 4 °C (routine clinical practice). Phase two directly assessed the impact of storage time and temperature on the microbial composition of vaginal/vaginal-rectal swabs collected specifically for research purposes. The microbiota composition in the ‘residual’ clinical swabs aligned with published studies. The ‘research’ swabs, stored at 4 °C for up to ten days, showed minimal changes in microbiota profile, compared to swabs examined on the day of collection. In contrast, significant variation in diversity was seen in swabs stored at room temperature for up to 48 h. Residual clinical material from swabs collected primarily for GBS screening in late pregnancy represent a reliable and abundant source of material for assessing the late pregnancy maternal microbiome for research purposes. This represents a low-burden opportunity for population-representative pregnancy studies to assess the potential of late pregnancy microbiome for prediction and understanding maternal and child health outcomes.

A glycoprotein-G-deleted live-attenuated vaccine strain of the infectious laryngotracheitis virus (ILTV), ΔgG-ILTV, is safe and efficacious against ILTV challenge. In the current study, the transcriptome of peripheral blood mononuclear cells (PBMCs) of the ΔgG-ILTV-vaccinated group of specific-pathogen-free chickens were compared to those of the nonvaccinated group at 7 days post-vaccination. Tracheal transcriptomes after challenge with virulent ILTV were compared between groups of the non-vaccinated-challenged and the vaccinated-challenged as well as the non-vaccinated-challenged and the uninfected chickens at 4 to 5 days post-challenge. The clinical outcomes after challenge between these groups were also evaluated. Significant differences were observed in the tracheal transcriptome of the non-vaccinated-challenged birds compared to the other two groups. Enriched gene ontologies and pathways that indicated heightened immune responses and impairments to ciliary and neuronal functions, cell junction components, and potential damages to cartilaginous and extracellular components in the trachea of the non-vaccinated-challenged birds were consistent with their severe tracheal pathology compared to the other two groups. On the contrary, the absence of any difference in the tracheal transcriptome between the vaccinated-challenged and the uninfected birds were reflected by the preservation of tracheal mucosal integrity in both groups and mild infiltration of leukocytes in the vaccinated-challenged birds. The results from this study demonstrated that vaccination with ΔgG-ILTV prevented the changes in tracheal transcriptome induced during ILTV challenge, resulting in clinical protection. Additionally, these results also provide insights into the molecular mechanisms underlying the tracheal pathology induced by ILTV infection.

Aims: This study aimed to (1) evaluate associations between Early and Term structural MRI (sMRI) brain abnormality scores and adverse motor outcomes at 6-years corrected age (CA), (2) determine their diagnostic accuracy in predicting adverse motor outcomes and cerebral palsy (CP) at 6-years CA. Methods: Infants born

Introduction Incontinence is commonly experienced by adults who receive care support in a residential facility or in their own home. These individuals are at risk of developing incontinence‐associated dermatitis (IAD), which is caused by prolonged and repeated exposure of the skin to urine or faeces. An IAD manual was developed providing an evidence-based clinical algorithm and an e-learning training programme for the prevention and treatment of IAD. The aim of the study is to establish the feasibility of conducting a definitive trial to examine the clinical and cost-effectiveness of the IAD manual. The objectives are to assess recruitment and attrition rates, acceptability of the IAD manual and intervention fidelity.Methods and analysis A feasibility cluster randomised controlled trial will be conducted in residential nursing homes and in the homes of people receiving formal care support in London and Hampshire, England. A total of six clusters including n=248 participants who are incontinent of urine, or faeces will be included. At each intervention site, care staff will be trained to implement the IAD manual over a 6-month period. Quantitative outcomes include IAD incidence and severity, IAD-related pain, satisfaction with care and mental health. A qualitative evaluation of care staff and care receivers’ experiences of participation will be conducted. Rates and proportions of each feasibility outcome will be described informing the sample size estimation for a definitive cluster randomised controlled trial. A thematic analysis of the qualitative data will be guided by a logic model detailing potential factors impacting on both the study methodology and adoption of the IAD manual into routine care.Ethics and dissemination The study received the approval of the Queens Square Ethics Committee Health Research Authority 23/LO/036, (Project ID 296167). Results will be disseminated through peer-reviewed open-access journals and international conferencesTrial registration number ISRCTN70866724.

OBJECTIVES:. Patients who survive critical illness navigate arduous and disparate recovery pathways that include referrals and participation in community-based rehabilitation services. Examining rehabilitation pathways during recovery is crucial to understanding the relationship on patient-centered outcomes. Furthermore, an understanding of social determinants of health (SDOH) in relation to outcomes and rehabilitation use will help ensure equitable access for future care. Therefore, there is a need to define and understand patient care pathways, specifically rehabilitation after discharge, through a SDOH lens after surviving a critical illness to improve long-term outcomes. DATA SOURCES:. MEDLINE, PubMed, Web of Science Core Collection (Clarivate), the CINAHL, and the Physiotherapy Evidence Database. STUDY SELECTION AND DATA EXTRACTION:. A systematic review of the literature was completed examining literature from inception to March 2024. Articles were included if post-hospital rehabilitation utilization was reported in adult patients who survived critical illness. Discharge disposition was examined as a proxy for rehabilitation pathways. Patients were grouped by patient diagnosis for grouped analysis and reporting of data. Two independent researchers reviewed manuscripts for inclusion and data were extracted by one reviewer using Covidence. Both reviewers used the Newcastle-Ottawa Scale to assess risk of bias. DATA SYNTHESIS:. Of 72 articles included, only four articles reported detailed rehabilitation utilization. The majority of the studies included were cohort studies (91.7%) with most articles using a retrospective design (56.9%). The most common patient population was acute respiratory diagnoses (51.4%). Most patients were discharged directly home from the hospital (75.4%). Race/ethnicity was the most frequently reported SDOH (43.1%) followed by insurance status (13.9%) and education (13.9%). CONCLUSIONS:. The small number of articles describing rehabilitative utilization allows for limited understanding of rehabilitation pathways following critical illness. The reporting of detailed rehabilitation utilization and SDOH are limited in the literature but may play a vital role in the recovery and outcomes of survivors of critical illness.

Abstract BackgroundSmartphone apps can be used to monitor chronic conditions and offer opportunities for self-assessment conveniently at home. However, few digital studies include older adults. ObjectiveWe aim to describe a new electronic cohort of older adults embedded in the Framingham Heart Study including baseline smartphone survey return rates and survey completion rates by smartphone type (iPhone [Apple Inc] and Android [Google LLC] users). We also aim to report survey results for selected baseline surveys and participant experience with this study’s app. MethodsFramingham Heart Study Offspring and Omni (multiethnic cohort) participants who owned a smartphone were invited to download this study’s app that contained a range of survey types to report on different aspects of health including self-reported measures from the Patient-Reported Outcomes Measurement Information System (PROMIS). iPhone users also completed 4 tasks including 2 cognitive and 2 physical function testing tasks. Baseline survey return and completion rates were calculated for 12 surveys and compared between iPhone and Android users. We calculated standardized scores for the PROMIS surveys. The Mobile App Rating Scale (MARS) was deployed 30 days after enrollment to obtain participant feedback on app functionality and aesthetics. ResultsWe enrolled 611 smartphone users (average age 73.6, SD 6.3 y; n=346, 56.6% women; n=88, 14.4% Omni participants; 478, 78.2% iPhone users) and 596 (97.5%) returned at least 1 baseline survey. iPhone users had higher app survey return rates than Android users for each survey (range 85.5% to 98.3% vs 73.8% to 95.2%, respectively), but survey completion rates did not differ in the 2 smartphone groups. The return rate for the 4 iPhone tasks ranged from 80.9% (380/470) for the gait task to 88.9% (418/470) for the Trail Making Test task. The Electronic Framingham Heart Study participants had better standardized tt ConclusionsWe effectively engaged community-dwelling older adults to use a smartphone app designed to collect health information relevant to older adults. High app survey return rates and very high app survey completion rates were observed along with high participant rating of this study’s app.

Entrustable Professional Activities (EPAs) are an important tool to support individualisation of medical training in a competency-based setting and are increasingly implemented in the clinical speciality training for endocrinologist. This study aims to assess interrater agreement and factors that potentially impact EPA scores. Five known factors that affect entrustment decisions in health profesions training (capability, integrity, reliability, humility, agency) were used in this study. A case-vignette study using standardised written cases. Case vignettes (n = 6) on the topics thyroid disease, pituitary disease, adrenal disease, calcium and bone disorders, diabetes mellitus, and gonadal disorders were written by two endocrinologists and a medical education expert and assessed by endocrinologists experienced in the supervision of residents in training. Primary outcome is the inter-rater agreement of entrustment decisions for endocrine EPAs among raters. Secondary outcomes included the dichotomous interrater agreement (entrusted vs. non-entrusted), and an exploration of factors that impact decision-making. The study protocol was registered and approved by the Ethical Review Board of the Netherlands Association for Medical Education (NVMO-ERB # 2020.2.5). Nine endocrinologists from six different academic regions participated. Overall, the Fleiss Kappa measure of agreement for the EPA level was 0.11 (95% CI: 0.03–0.22) and for the entrustment decision 0.24 (95% CI 0.11–0.37). Of the five features that impacted the entrustment decision, capability was ranked as the most important by a majority of raters (56%–67%) in every case. There is a considerable discrepancy between the EPA levels assigned by different raters. These findings emphasise the need to base entrustment decisions on multiple observations, made by a team of supervisors and enriched with factors other than direct medical competence.

IntroductionWomen are underrepresented in volunteer non-player roles in community sporting clubs, particularly in traditionally male sports such as football (soccer), where participation rates for men and boys remain higher than women and girls. Experiences of women volunteering in community sporting clubs are not well-represented in research literature. By exploring women's experiences volunteering in community Australian Football clubs, the present research aimed to understand the barriers and facilitators of women's participation in volunteer non-player community sport club roles. Our intention is that our findings will provide empirical basis for the design of efficacious evidence-based interventions and initiatives to help close the gender gap of volunteerism rates and experiences, thus facilitating equal opportunities for women to access associated individual social, physical, and mental health benefits of sports volunteering.MethodWe conducted individual semi-structured interviews with six women from four Australian Football clubs, to determine barriers and facilitators to volunteering.ResultsReflexive thematic analysis of barriers generated six themes: high expectations of self, intersectionality (of gender with motherhood or race), constrained resources, interpersonal disconnection, lack of organisational support and structure, and gender role assumptions and stereotypes. Analysis of facilitators produced six themes: having or building confidence, positive reinforcement, social connection, deliberate efforts to engage women, role autonomy and shaping, and supportive culture within a club or governing body.DiscussionFindings revealed that impacts on women's development in non-player roles exist at the individual level, including the interaction of gender, race, and parental status, but also extend beyond this to personal, interpersonal, organisational, and sociocultural factors. Given our research findings we make seven recommendations for governing bodies and community football clubs to enhance volunteering gender equity: 1. Establish support for women by dividing work evenly among volunteers; 2. Provide clear descriptions of non-player roles; 3. Match the skill sets of new women volunteers to suitable roles; 4. Implement mentorship programs to aid collaboration among women who volunteer; 5. Educate communities about gender biases and assumptions; 6. Monitor and seek feedback on gendered task allocation to ensure women's unpaid labour is not disproportionate to men's; and 7. Promote and publicise women in non-player roles to enhance women's visibility and acceptance in community football clubs

Objective: To examine the current literature surrounding the administration of antenatal corticosteroids in pregnancies complicated by diabetes and summarize the reported neonatal and maternal outcomes in exposed and unexposed groups. Data sources: A systematic search was performed in November 2023 using Ovid Medline and Embase databases to identify relevant studies. Study Eligibility Criteria: Articles that reported on the maternal or neonatal outcomes in pregnancies complicated by pre-gestational or gestational diabetes after exposure to antenatal corticosteroids were included in this review. Articles were excluded if they did not separately report on the outcomes experienced by women with diabetes. Methods: Maternal and neonatal outcomes of interest included neonatal respiratory distress syndrome, neonatal hypoglycemia, and maternal hyperglycemia. Key words in this search included combinations of the terms related to pre-gestational and gestational diabetes, antenatal corticosteroids, respiratory distress syndrome, hypoglycemia, and hyperglycemia. Title and abstract screening was conducted in duplicate. Results: There were 19 studies that met the inclusion criteria. There were 13 studies that presented results pertaining to neonatal respiratory distress syndrome, 14 studies discussed neonatal hypoglycemia and 5 studies discussed maternal hyperglycemia. Only 2 included studies were randomized controlled trials with the remaining 17 studies being observational. There was heterogeneity in clinical settings, study populations, type of corticosteroid administered and timing of administration across the included studies. This review found that there is no clear evidence of beneficial effect of corticosteroid administration on neonatal respiratory outcomes in pregnancies complicated by diabetes. Additionally, there was discrepancy between studies reporting on neonatal hypoglycemia with 6 studies reporting an increased incidence in this outcome after antenatal corticosteroid exposure whilst 4 studies found no difference between exposed and unexposed groups. This review identified a specific gap in the reporting of maternal hyperglycemia following antenatal corticosteroids. The limited number of studies that did report this outcome unanimously reported an increased incidence of maternal hyperglycemia after corticosteroid exposure. The majority of studies had small sample sizes of pregnancies both complicated by diabetes and exposed to corticosteroids and therefore lacked sufficient power to make robust conclusions about the influence of antenatal corticosteroids in this group. Conclusion: This review concludes that there are insufficient data regarding the risks and benefits of antenatal corticosteroid administration in pregnancies complicated by diabetes.

Background Sex differences in obesity and fat distribution may in part explain differences in cardiovascular risk in men versus women. We sought to examine sex differences in the associations of obesity and adiposity measures with cardiovascular disease–related protein biomarkers. Methods and Results In a cross‐sectional observational cohort study, we examined whether the association of obesity (body mass index [BMI] and waist circumference) and adiposity measures (visceral adipose tissue) with biomarkers demonstrates effect modification by sex using multiplicative interaction terms in multivariable linear regression models. Among 3143 participants (mean age, 50 years; 49% women), sex modified the association of BMI, waist circumference, and visceral adipose tissue with cardiovascular disease–related protein biomarkers (7 for BMI, 3 for waist circumference, and 23 for visceral adipose tissue, false discovery rate [FDR]‐qint

With the emergence of high-precision radiotherapy technologies such as stereotactic ablative radiotherapy (SABR), MR guided brachytherapy, image guided intensity modulated photon and proton radiotherapy and most recently daily adaptive radiotherapy, reirradiation is increasingly recognized as a viable treatment option for many patients. This includes those with recurrent, metastatic or new malignancies post initial radiotherapy. The primary challenge in reirradiation lies in balancing tumor control against the risk of severe toxicity from cumulative radiation doses to previously irradiated normal tissue.Although technology for precise delivery has advanced at a fast pace, clinical practice of reirradiation still mostly relies on individual expertise, as prospective evidence is scarce, the level of reporting in clinical studies is not standardized and of low quality − especially with respect to cumulative doses received by organs at risk.A recent ESTRO/EORTC initiative proposed a standardized definition of reirradiation and formulated general requirements for minimal reporting in clinical studies [1].As a consequence we found it timely to convene for an international and interdisciplinary meeting with experts in the field to summarize the current evidence, identify knowledge gaps and explore which best practices can be derived for safe reirradiation. The meeting was held on 15.06.2023 in Zurich and was endorsed by the scientific societies SASRO, DEGRO and ESTRO. Here, we report on available evidence and research priorities in the field of reirradiation, as discussed during the meeting.

Background Older people living in care homes are at high risk of poor health outcomes and mortality if they contract coronavirus disease 2019. Protective measures include social distancing and isolation, although implementation is challenging. Objectives To explore the real-life experiences of social distancing and isolation in care homes for older people, and to develop a toolkit of guidance and resources. Design A mixed-methods, phased design. Setting Six care homes in England caring for older adults. Participants Care home staff (n = 31), residents (n = 17), family members (n = 17), senior health and care leaders (n = 13). Methods A rapid review to assess the social distancing and isolation measures used by care homes to control the transmission of coronavirus disease 2019 and other infectious diseases (phase 1), in-depth case studies of six care homes, involving remote individual interviews with staff, residents and families, collection of policies, protocols and routinely collected care home data, remote focus groups with senior health and care leaders (phase 2) and stakeholder workshops to co-design the toolkit (phase 3). Interview and focus group data and care home documents were analysed using thematic analysis and care home data using descriptive statistics. Results The rapid review of 103 records demonstrated limited empirical evidence and the limited nature of policy documentation around social distancing and isolation measures in care homes. The case studies found that social distancing and isolation measures presented moral dilemmas for staff and often were difficult, and sometimes impossible to implement. Social distancing and isolation measures made care homes feel like an institution and denied residents, staff and families of physical touch and other forms of non-verbal communication. This was particularly important for residents with cognitive impairment. Care homes developed new visiting modalities to work around social distancing measures. Residents and families valued the work of care homes to keep residents safe and support remote communication. Social distancing, isolation and related restrictions negatively impacted on residents’ physical, psychological, social and cognitive well-being. There were feelings of powerlessness for families whose loved ones had moved into the care home during the pandemic. It was challenging for care homes to capture frequent updates in policy and guidance. Senior health and care leaders shared that the care home sector felt isolated from the National Health Service, communication from government was described as chaotic, and trauma was inflicted on care home staff, residents, families and friends. These multiple data sources have informed the co-design of a toolkit to care for residents, families, friends and care home staff. Limitations The review included papers published in English language only. The six care homes had a Care Quality Commission rating of either ‘good’ or ‘outstanding’. There was a lack of ethnic diversity in resident and family participants. Conclusions Care homes implemented innovative approaches to social distancing and isolation with varying degrees of success. A legacy of learning can help rebuild trust at multiple levels and address trauma-informed care for residents, families, friends and staff. Future work can include evaluation of the toolkit, research to develop a trauma-informed approach to caring for the care home sector and co-designing and evaluating an intervention to enable residents with different needs to transition to living well in a care home. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR132541) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 45. See the NIHR Funding and Awards website for further award information. Plain language summary Older people living in care homes are at risk of poor health and death if they get coronavirus disease 2019 (COVID-19). To protect older people from COVID-19, care homes use different measures, including social distancing and isolation. These measures can be challenging. Our research aimed to explore the challenges and solutions to using social distancing and isolation in care homes. We reviewed existing evidence to examine how care homes have used social distancing and isolation measures to control the spread of COVID-19 and other contagious diseases. We investigated how social distancing and isolation measures have been used in six care homes in England. We spoke with residents, families and staff. We collected care home documents and other data. We held group discussions with senior health and care leaders. The review showed limited research and the limited nature of policy documentation on social distancing and isolation measures. Interviews revealed that social distancing and isolation measures were difficult, and sometimes impossible, for staff to implement. These measures made care homes feel less homely and inhibited touch, for example hugs. Residents and families valued the work of care homes to keep residents safe and the use of technology for keeping connected. Social distancing, isolation and related restrictions negatively affected residents’ physical, psychological, social and cognitive well-being. There were feelings of powerlessness for families whose loved ones had moved into the care home during the pandemic. It was challenging for care homes to capture frequent updates in policy and guidance. Senior health and care leaders shared that the care home sector felt isolated from the National Health Service, communication from government to the care home sector was described as chaotic and trauma was inflicted on care home staff, residents, families and friends. These findings have been used to design guidance to help care homes implement social distancing and isolation measures both now and for any future outbreaks. Scientific summary Background Older people living in care homes (CHs) (i.e. homes that provide residential and/or nursing care) often have complex health and care needs and are at high risk of poor health outcomes and mortality, especially if they contract coronavirus disease 2019 (COVID-19). To protect older people from COVID-19, CHs use interventions such as social distancing and isolation, but these measures have been reported as challenging. Research is needed to explore and understand the challenges experienced by CHs endeavouring to implement these interventions while mitigating any negative consequences. Objectives The overall aim of the study was to explore and understand the real-life experiences of social distancing and isolation measures for older people living in CHs in England from the perspective of multiple stakeholders, and to develop a toolkit of evidence-informed guidance and resources for CHs now and for future outbreaks. The study objectives were as follows: (1) to investigate the mechanisms and measures used by CHs currently and previously to socially distance and isolate older people to prevent and control the spread of COVID-19 and other infectious and contagious diseases (2) to examine the experiences of residents and families/friends of social distancing and isolation measures during the COVID-19 pandemic, including how these measures impacted upon their well-being and how they adapted to change (3) to explore how registered nurses and care staff adapted to and managed the delivery of personal, social and psychological care for residents with different needs while maintaining social distancing and isolation measures (4) to identify how CH managers, owners and external stakeholders developed, managed and adapted policies, procedures and protocols to implement social distancing and isolation measures including workforce organisation, training and support, use of communal spaces, visiting, and working with external health and social care professionals (5) to use the findings to develop a toolkit of evidence-informed guidance and resources, including a mosaic film, detailing which interventions and strategies for social distancing and isolation work well and which do not work in specific situations and contexts to support decision-making about health and care delivery in CHs and to facilitate resilience-building for future planning. Methods A mixed-methods, phased design was undertaken to identify the challenges, consequences and solutions to implementing social distancing and isolation measures in CHs for older adults to prevent and control the spread of COVID-19. The study was conducted in three phases: (1) a rapid evidence review of measures used to prevent or control the transmission of COVID-19 and other infectious diseases in CHs for older people, following the guidance for conducting rapid reviews1 (2) in-depth case studies of six purposively sampled CHs in England involving individual interviews with care staff, managers, residents and family/friends, the collection of social distancing and isolation policies/protocols and routinely collected CH data, and focus groups with purposively sampled CH owners and external stakeholders. Reporting guidance for qualitative research was used2 (3) development of a toolkit of evidence-informed guidance and resources, and a mosaic film for CHs. The findings from earlier phases were used in two co-design workshops with external stakeholders to develop the toolkit. Findings from the 103 papers included in the rapid review were synthesised using tables and a narrative summary organised around the review questions. Interview audio-recordings were transcribed verbatim and data analysed using thematic analysis. Descriptive summary statistics described the quantitative data collected. For the CH documents, information was collated around the key themes of social distancing, isolation, cohorting, zoning and other restrictions. Concurrent data collection and analysis informed decision-making about the need for further data and from which source. Patient and public involvement (PPI) was an integral part of this study, informing its design, method, analysis and dissemination. PPI group members also participated in online workshops to contribute to the co-design of the toolkit. Results The rapid review highlighted the following: There is a lack of empirical evidence around how measures to prevent or control COVID-19 and other infectious diseases are implemented in CHs. Most papers were grey literature or policy documents, which were mainly descriptive, or opinion based. Furthermore, these interventions were generally mentioned as part of a wider discussion of COVID-19 strategies and were not the primary focus of the papers. Key interventions for preventing and controlling the transmission of COVID-19 and other infectious diseases in CHs for older people include social distancing; isolation of residents and staff; restrictions for residents, family members and staff; zoning and cohorting; and surveillance. Evaluative research on the use of these interventions in CHs is needed urgently. The six case study sites were geographically spread and all had a Care Quality Commission rating of good (n = 4) or outstanding (n = 2). All were part of organisations (ranging in size from 7 to 114 CHs per organisation, and between 767 and 5875 beds per organisation). Four of the CHs were part of privately run organisations, and two were part of voluntary/not-for-profit organisations. One CH had a ‘dual’ registration, three had a ‘nursing’ registration and two were registered as ‘without nursing’. Most provided some specialist care such as for dementia, learning disabilities, physical and mental health problems. The number of beds offered ranged between 37 and 73. One CH comprised a household of 12 residents within a village complex. Care homes varied on the number of positive COVID-19 cases, for example one reported only one case between March 2020 and February 2021, while another reported 27 cases within the month November 2020 alone – this home had opened a specially allocated ‘COVID-ward’. In one CH no residents had died within 28 days of a positive COVID-19 test, while 10 residents had died from another home. Policies and protocols about social distancing and isolation measures were collected from each CH and compared. Key findings were as follows: There was significant variation between CHs in the content, length and level of detail presented in policy and guidance documents. Capturing the frequent updates in guidance was challenging with documents sometimes being repetitive and unclear. Many documents had further, embedded documents or links to government guidance that provided a great deal of information, which might be unrealistic for CH staff to read. Shorter documents were less comprehensive and may not provide the necessary detail to guide CH staff. None of the documents included guidance on staff training and development. Research at the case study sites included individual interviews with 31 CH staff. Key findings were as follows: The impact that the COVID-19 pandemic had upon CH staff must not be underestimated. Staff reported trauma and emotional distress. For many staff, the difficulties experienced during the pandemic were compounded by the government’s response to CHs. Some staff felt they had been abandoned by the government, while others criticised the ‘blanket approach’ to government guidance and the rapidly changing rules for CHs. Care home managers valued the support of their senior leadership to help them interpret and implement government guidance. Staff talked of the difficulties of ‘policing’ social distancing measures while simultaneously trying to maintain a sense of ‘normality’ for their residents. Although staff and residents were supposed to maintain a social distance from each other, this was often impossible to uphold when providing personal care. Care homes were perceived as a resident’s home rather than an institution, which made some staff question whether social distancing was appropriate. Many staff felt that social distancing measures denied residents (and themselves) of the important need for touch, as hugs were felt to have a vital role in CH life. Understanding fully the impact on residents living with dementia was recognised as a challenge and not always possible to achieve. The design and layout of CHs meant that there was not always the physical space for social distancing to be implemented. Staff felt that new admissions to CHs had the most difficult experience with isolation regulations. For some managers, isolation measures went against the ethos of the CH environment and ruined the family feel of the CH. The requirement for residents to isolate when returning from hospital could lead to a reluctance in residents to attend hospital appointments and a disinclination of staff to refer residents for hospital care. Several different resident restrictions were implemented in CHs, but restrictions around residents leaving the home, changes to food preparation/delivery and visitor restrictions were perceived to have the greatest negative impact. On occasions, staff became a target of anger and frustration from residents and their families, who could not comprehend that they were being prevented from seeing each other. Good support from CH management was considered by staff to make the process of implementing these measures easier. Individual interviews were conducted with 17 residents and 17 family members. Key findings were as follows: The experiences of residents and families were varied, and their impact was influenced by the existing pattern of relationships residents and families maintained within and beyond the CH. Residents and families valued the work of the CHs in keeping residents safe. They accepted the need for restrictions. Residents and families appreciated the support they received in communicating with one another virtually and the importance of this communication for residents’ health and well-being. Measures relating to isolation were particularly difficult for residents, particularly for those unable to communicate with the outside world through technology. Measures to make isolation less difficult for residents included ensuring that they were entertained purposefully with regular socially distanced visits from staff and various resources to occupy their time. Creative approaches to activities for residents not isolating were also evidenced, for example indoor gardening, yoga and quizzes. Social distancing made aspects of CH life and social visiting difficult and sometimes unsatisfactory; residents and families missed physical touch and other non-verbal forms of communication. This was particularly important for residents with cognitive impairment. Residents and families were involved with staff in complex judgements of risk, choice and control, which were complicated by two factors. First, families (and some residents) were aware that those in CHs were in the twilight of their lives and that time was ebbing away. Second, many families and residents were also learning how to manage their relationships in the new living context of a CH. Two focus groups were conducted with a purposive sample of 13 external senior health and care leaders. Key findings were as follows: Isolation of the sector: the sector felt cut off from the National Health Service (NHS) and pre-pandemic sources of service and support. Government guidance for CHs and communication processes: ‘chaos’ described the approach to cascading information to CHs, especially in the first wave of the pandemic. Visiting: regulations evolved throughout the different waves of the pandemic and led to variations in interpreting and implementing visiting guidance. Trauma: as the pandemic wore on and the different waves and variants emerged, there was a need to take account of the broader health and well-being of residents, families, visitors and the workforce. Trauma impacted at several different levels – for staff, residents and family members. Implications for practice and policy For practice Implications of the study findings for practice are captured in our toolkit for supporting CHs with social distancing and isolation measures. These are framed around six areas: caring for residents when they are social distancing; caring for residents when they are isolating; supporting residents, families and friends to communicate when visiting is not permitted; supporting visits from families and friends when visiting is allowed but with restrictions; caring for care staff; and caring for managers. For policy The study findings can inform discussions involving CH providers, managers and external stakeholders to enhance understanding of social distancing and isolation measures for residents – consequences, challenges, solutions and learning. Our findings also have implications about how guidelines are developed and disseminated. They reinforce the need for CHs and social care to be considered as an integral part of integrated care systems, to ensure that actions taken during national emergencies fully account for the impact on all parts of health and social care. Our findings can inform discussions about developing digital technologies to help residents with different needs stay connected with families and friends, and for CHs to communicate effectively with residents’ families and friends. Our findings can contribute to the content of the digital hub for the social care workforce. Recommendations for further research This study has identified that research is needed in several areas including the following: Evaluations of the toolkit. Evaluation of social distancing and isolation measures used in CHs to prepare for future pandemics. Research to develop and evaluate remote social interaction for residents living with dementia and their families. Research to understand what a trauma-informed approach looks like for the CH sector – to care for residents, families, friends and staff in CHs caring for older people. Research to co-design and evaluate an intervention to enable residents with different needs to transition to living well in a CH. The study of an intervention that cares for families and friends. Conclusions The CH sector was ill-prepared and under-resourced for the COVID-19 pandemic. During the pandemic and for any further surges, it is paramount that CH services are safe, effective, caring, responsive to individual needs and well-led. The loss of older people living in CHs due to COVID-19 has been substantial; it is essential to learn from this devastation, to understand the consequences, challenges, solutions and to evaluate these solutions. Evidence to support learning and recovery of the CH sector from the pandemic and to inform policy-making is paramount. Care homes need evidence-informed guidance that sets out what and how social distancing and isolation measures should be operationalised, while meeting residents’ individual needs. Our toolkit is designed to capture such innovative approaches. Our study makes an important contribution to this learning and recovery, as one of the first to study the challenges and solutions to implementing social distancing and isolation measures for older people living in CHs in England. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR132541) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 45. See the NIHR Funding and Awards website for further award information.

Purpose This study evaluated the underlying subdomain structure of the Self-Directed Learning Readiness Scale (SDLRS) for medical students and refined the instrument to measure the subdomains to provide evidence for construct validity. Developing self-directed learners is a well-recognized goal amongst medical educators. The SDLRS has been frequently used, however, lack of construct validity makes it difficult to interpret results. Methods To identify the valid subdomains of the SDLRS, items were calibrated with the graded response model (GRM) and results were used to construct a 30-item short form. Short-form validity was evaluated by examining the correspondence between the total scores from the short form and the original instrument for individual students. Results A five-subdomain model explained the SDLRS item response data reasonably well. These included: (1) initiative and independence in learning, (2) self-concept as an effective learner, (3) openness to learning opportunity, (4) love of learning, and (5) acceptance for one’s own learning. The unidimensional GRM for each subdomain fits the data better than multi-dimensional models. The total scores from the refined short form and the original form were correlated at 0.98 and the mean difference was 1.33, providing evidence for validation. Nearly 91% of 179 respondents were accurately classified within the low, average, and high readiness groups. Conclusion Sufficient evidence was obtained for the validity and reliability of the refined 30-item short-form targeting five subdomains to measure medical students’ readiness to engage in self-directed learning.

Abstract Acellular multivalent vaccines for pertussis (DTaP and Tdap) prevent symptomatic disease and infant mortality, but immunity to Bordetella pertussis infection wanes significantly over time resulting in cyclic epidemics of pertussis. The messenger RNA (mRNA) vaccine platform provides an opportunity to address complex bacterial infections with an adaptable approach providing Th1-biased responses. In this study, immunogenicity and challenge models were used to evaluate the mRNA platform with multivalent vaccine formulations targeting both B. pertussis antigens and diphtheria and tetanus toxoids. Immunization with mRNA formulations were immunogenetic, induced antigen specific antibodies, as well as Th1 T cell responses. Upon challenge with either historical or contemporary B. pertussis strains, 6 and 10 valent mRNA DTP vaccine provided protection equal to that of 1/20th human doses of either DTaP or whole cell pertussis vaccines. mRNA DTP immunized mice were also protected from pertussis toxin challenge as measured by prevention of lymphocytosis and leukocytosis. Collectively these pre-clinical mouse studies illustrate the potential of the mRNA platform for multivalent bacterial pathogen vaccines.

Abstract Background Global life expectancy is rising, with the 60 + age group projected to hit 2 billion by 2050. Aging impacts the immune system. A notable marker of immune system aging is the presence of Aging-Related Immune Cell Phenotypes (ARIPs). Despite their importance, links between immune cell phenotypes including ARIPs and mortality are underexplored. We prospectively investigated 16 different immune cell phenotypes using flow cytometry and IL-6 in relation to survival outcome among dementia-free Framingham Heart Study (FHS) offspring cohort participants who attended the seventh exam (1998–2001). Results Among 996 participants (mean age 62 years, range 40 to 88 years, 52% female), the 19-year survival rate was 65%. Adjusting for age, sex, and cytomegalovirus (CMV) serostatus, higher CD4/CD8 and Tc17/CD8 + Treg ratios were significantly associated with lower all-cause mortality (HR: 0.86 [0.76–0.96], 0.84 [0.74–0.94], respectively), while higher CD8 regulatory cell levels (CD8 + CD25 + FoxP3 +) were associated with increased all-cause mortality risk (HR = 1.17, [1.03–1.32]). Elevated IL-6 levels correlated with higher all-cause, cardiovascular, and non-cardiovascular mortality (HR = 1.43 [1.26–1.62], 1.70 [1.31–2.21], and 1.36 [1.18–1.57], respectively). However, after adjusting for cardiovascular risk factors and prevalent cancer alongside age, sex, and CMV, immune cell phenotypes were no longer associated with mortality in our cohort. Nonetheless, IL-6 remained significantly associated with all-cause and cardiovascular mortality (HRs: 1.3 [1.13–1.49], 1.5 [1.12–1.99], respectively). Conclusions In 19-year follow-up, higher Tc17/CD8 + Treg and CD4/CD8 ratios were associated with lower all-cause mortality, while the CD8 + CD25 + FoxP3 + (CD8 + Treg) phenotype showed increased risk. Elevated IL-6 levels consistently correlated with amplified mortality risks. These findings highlight the links between immune phenotypes and mortality, suggesting implications for future research and clinical considerations.

Abstract Estuaries play an important role in connecting the global carbon cycle across the land-to-ocean continuum, but little is known about Australia’s contribution to global CO2 emissions. Here we present an Australia-wide assessment, based on CO2 concentrations for 47 estuaries upscaled to 971 assessed Australian estuaries. We estimate total mean (±SE) estuary CO2 emissions of 8.67 ± 0.54 Tg CO2-C yr−1, with tidal systems, lagoons, and small deltas contributing 94.4%, 3.1%, and 2.5%, respectively. Although higher disturbance increased water-air CO2 fluxes, its effect on total Australian estuarine CO2 emissions was small due to the large surface areas of low and moderately disturbed tidal systems. Mean water-air CO2 fluxes from Australian small deltas and tidal systems were higher than from global estuaries because of the dominance of macrotidal subtropical and tropical systems in Australia, which have higher emissions due to lateral inputs. We suggest that global estuarine CO2 emissions should be upscaled based on geomorphology, but should also consider land-use disturbance, and climate.

Abstract Background Plastic pollution is a severe threat to marine ecosystems. While some microbial enzymes can degrade certain plastics, the ability of the global ocean microbiome to break down diverse environmental plastics remains limited. We employed metatranscriptomic data from an international ocean survey to explore global and regional patterns in microbial plastic degradation potential. Results On a global oceanic scale, we found no significant correlation between levels of plastic pollution and the expression of genes encoding enzymes putatively identified as capable of plastic degradation. Even when looking at different regional scales, ocean depth layers, or plastic types, we found no strong or even moderate correlation between plastic pollution and relative abundances of transcripts for enzymes with presumed plastic biodegradation potential. Our data, however, indicate that microorganisms in the Southern Ocean show a higher potential for plastic degradation, making them more appealing candidates for bioprospecting novel plastic-degrading enzymes. Conclusion Our research contributes to understanding the complex global relationship between plastic pollution and microbial plastic degradation potential. We reveal that the transcription of putative plastic-degrading genes in the global ocean microbiome does not correlate to marine plastic pollution, highlighting the ongoing danger that plastic poses to marine environments threatened by plastic pollution.

Abstract Necroptosis is a lytic form of regulated cell death reported to contribute to inflammatory diseases of the gut, skin and lung, as well as ischemic-reperfusion injuries of the kidney, heart and brain. However, precise identification of the cells and tissues that undergo necroptotic cell death in vivo has proven challenging in the absence of robust protocols for immunohistochemical detection. Here, we provide automated immunohistochemistry protocols to detect core necroptosis regulators – Caspase-8, RIPK1, RIPK3 and MLKL – in formalin-fixed mouse and human tissues. We observed surprising heterogeneity in protein expression within tissues, whereby short-lived immune barrier cells were replete with necroptotic effectors, whereas long-lived cells lacked RIPK3 or MLKL expression. Local changes in the expression of necroptotic effectors occurred in response to insults such as inflammation, dysbiosis or immune challenge, consistent with necroptosis being dysregulated in disease contexts. These methods will facilitate the precise localisation and evaluation of necroptotic signaling in vivo.

ABSTRACT Coinfections are known to play an important role in disease progression and severity. Coinfections are common in cats, but no coinfection studies have investigated the in vitro dynamics between feline viral and bacterial pathogens. In this study, we performed co-culture and invasion assays to investigate the ability of common feline bacterial respiratory pathogens, Chlamydia felis and Mycoplasma felis, to replicate in and invade into Crandell–Rees feline kidney cells. We subsequently investigated how coinfection of these feline cells with each bacterium (C. felis or M. felis) and the common feline viral pathogen, felid alphaherpesvirus 1 (FHV-1), affects replication of each agent in this cell culture system. We also investigated the metabolic impact of each co-pathogen using metabolomic analysis of infected and coinfected cells. C. felis was able to invade and replicate in CRFKs, while M. felis had little capacity to invade. During coinfection, FHV-1 replication was minimally affected by the presence of either bacterial pathogen, but bacterial replication kinetics were more affected, particularly in M. felis. Both C. felis and M. felis replicated to higher levels in the presence of a secondary pathogen. Coinfections resulted in reprogramming of the glycolysis pathway, the pentose phosphate pathway, and the tricarboxylic acid cycle. The distinct metabolic profiles of coinfected cells compared to those of cells infected with just one of these three pathogens, as well as the impact of coinfections on viral or bacterial load, suggest strong interactions between these three pathogens and possible synergistic mechanisms enhancing virulence that need further investigation.IMPORTANCEIn the natural world, respiratory pathogens coexist within their hosts, but their dynamics and interactions remain largely unexplored. Herpesviruses, mycoplasmas, and chlamydias are common and significant causes of acute and chronic respiratory and system disease in animals and people, and these diseases are increasingly found to be polymicrobial. This study investigates how coinfection of feline cells between three respiratory pathogens of cats impact each other as well as the host innate metabolic response to infection. Each of these pathogens have been implicated in the induction of feline upper respiratory tract disease in cats, which is the leading cause of euthanasia in shelters. Understanding how coinfection impacts co-pathogenesis and host responses is critical for improving disease management.

Introduction The growing population of older drivers presents challenges for road safety attributed to age-related declines and increased crash fatality rates. However, enabling older people to maintain their health and independence through continued safe driving is important. This study focuses on the urgent need for cost-effective interventions that reduce crash risk while supporting older drivers to remain driving safely for longer. Our study aims to evaluate the effectiveness of three behavioural interventions for older driver safety. These include an online road-rules refresher workshop, tailored feedback on driving performance and two tailored driving lessons.Methods and analysis A single-blind three-parallel group superiority randomised controlled trial will be conducted with 198 urban licensed drivers aged 65 years and older, allowing for 4% attrition. This sample size provides 80% power to detect a difference with an alpha of 0.05. Participants will be selected based on a standardised on-road test that identifies them as moderately unsafe drivers. Interventions, spanning a 3-month period, aim to improve driving safety. Their effectiveness will be assessed through a standardised on-road assessment of driving safety at 3 months (T1) and 12 months postintervention (T2). Additionally, monthly self-reported driving diaries will provide data on crashes and incidents.This trial has the potential to identify cost-effective approaches for improving safety for older drivers and contribute to evidence-based health policy, clinical practice and guidelines.Ethics and dissemination Ethical approval was obtained by the University of New South Wales Human Research Ethics Committee (HC190439, 22 August 2019). The results of the study will be disseminated in peer-reviewed journals and research conferences.Trial registration number ACTRN12622001515785.

Abstract Background To determine the prevalence, risk factors; and impact on patient health and economic outcomes across the laterality spectrum of multiple sensory impairment (MSI) in a multi-ethnic older Asian population. Methods In this population-based study of Singaporeans aged ≥ 60 years, MSI was defined as concomitant vision (visual acuity > 0.3 logMAR), hearing (pure-tone air conduction average > 25 dB), and olfactory (score

Infection of ruminants such as cattle with Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne’s disease, a disease characterized by chronic inflammation of the small intestine and diarrhoea. Infection with MAP is acquired via the faecal-to-oral route and the pathogen initially invades the epithelial lining of the small intestine. In this study we used an in vitro 3D mouse enteroid model to determine the influence of M cells in infection of the gut epithelia by MAP, in comparison with another bacterial intestinal pathogen of veterinary importance, Salmonella enterica serovar Typhimurium. The differentiation of M cells in the enteroid cultures was induced by stimulation with the cytokine receptor activator of nuclear factor-κB ligand (RANKL), and the effects on MAP and Salmonella uptake and intracellular survival were determined. The presence of M cells in the cultures correlated with increased uptake and intracellular survival of Salmonella, but had no effect on MAP. Interestingly neither pathogen was observed to preferentially accumulate within GP2-positive M cells.

Background: Hepatitis B infection has been associated with the development of gestational diabetes but the underlying mechanism is not known. Objective: To examine associations between viral activity, gestational diabetes mellitus (GDM), and insulin resistance in pregnant people with chronic hepatitis B infection (HBV). Design: Prospective cohort study across three tertiary maternity centres in Melbourne, Australia, between May 2021 and April 2023. Methods: Participants were followed prospectively through pregnancy to evaluate subsequent GDM diagnosis. Demographics, pregnancy outcomes, and markers of viral activity were compared between those with GDM versus those without. Logistic regression analysis was performed pre- and post-adjustment for known confounders. Sub-group analysis of participants from South East Asia (SEA) was performed. Outcome measures included GDM diagnosis, insulin resistance (Homeostatic Model Assessment Insulin Resistance score (HOMA-IR) score), HBV activity as measured by liver function tests, HBV viral load, hepatitis B e antigen, and quantitative hepatitis B surface antigen (quantHBsAg). Results: A total of 113 women were recruited. One third (38/112, 33.9%) developed GDM, mostly diagnosed on isolated postprandial hyperglycaemia (25/38, 65.8%). Over half were born in SEA (66/113, 58.4%). Mean quantHBsAg was significantly lower in those with GDM ( p = 0.044). No other associations were identified between GDM or HOMA-IR and markers of hepatic activity on multivariate logistic regression analysis and on sub-group analysis of those born in SEA. Conclusions: QuantHBsAg was significantly lower in those with GDM; otherwise, no association between GDM and measures of HBV viral activity was found. QuantHBsAg may be useful as an early pregnancy marker for GDM risk and warrants further research.

Background Life's Essential 8 (LE8) is an enhanced metric for cardiovascular health. The interrelations among LE8, biomarkers of aging, and disease risks are unclear. Methods and Results LE8 score was calculated for 5682 Framingham Heart Study participants. We implemented 4 DNA methylation‐based epigenetic age biomarkers, with older epigenetic age hypothesized to represent faster biological aging, and examined whether these biomarkers mediated the associations between the LE8 score and cardiovascular disease (CVD), CVD‐specific mortality, and all‐cause mortality. We found that a 1 SD increase in the LE8 score was associated with a 35% (95% CI, 27–41; P=1.8E‐15) lower risk of incident CVD, a 36% (95% CI, 24–47; P=7E‐7) lower risk of CVD‐specific mortality, and a 29% (95% CI, 22–35; P=7E‐15) lower risk of all‐cause mortality. These associations were partly mediated by epigenetic age biomarkers, particularly the GrimAge and the DunedinPACE scores. The potential mediation effects by epigenetic age biomarkers tended to be more profound in participants with higher genetic risk for older epigenetic age, compared with those with lower genetic risk. For example, in participants with higher GrimAge polygenic scores (greater than median), the mean proportion of mediation was 39%, 39%, and 78% for the association of the LE8 score with incident CVD, CVD‐specific mortality, and all‐cause mortality, respectively. No significant mediation was observed in participants with lower GrimAge polygenic score. Conclusions DNA methylation‐based epigenetic age scores mediate the associations between the LE8 score and incident CVD, CVD‐specific mortality, and all‐cause mortality, particularly in individuals with higher genetic predisposition for older epigenetic age.

BackgroundResting heart rate (HR) and routine physical activity are associated with cardiorespiratory fitness levels. Commercial smartwatches permit remote HR monitoring and step count recording in real-world settings over long periods of time, but the relationship between smartwatch-measured HR and daily steps to cardiorespiratory fitness remains incompletely characterized in the community. ObjectiveThis study aimed to examine the association of nonactive HR and daily steps measured by a smartwatch with a multidimensional fitness assessment via cardiopulmonary exercise testing (CPET) among participants in the electronic Framingham Heart Study. MethodsElectronic Framingham Heart Study participants were enrolled in a research examination (2016-2019) and provided with a study smartwatch that collected longitudinal HR and physical activity data for up to 3 years. At the same examination, the participants underwent CPET on a cycle ergometer. Multivariable linear models were used to test the association of CPET indices with nonactive HR and daily steps from the smartwatch. ResultsWe included 662 participants (mean age 53, SD 9 years; n=391, 59% women, n=599, 91% White; mean nonactive HR 73, SD 6 beats per minute) with a median of 1836 (IQR 889-3559) HR records and a median of 128 (IQR 65-227) watch-wearing days for each individual. In multivariable-adjusted models, lower nonactive HR and higher daily steps were associated with higher peak oxygen uptake (VO2), % predicted peak VO2, and VO2 at the ventilatory anaerobic threshold, with false discovery rate (FDR)–adjusted P values

IntroductionEvolution of a patient-reported symptom-based risk stratification system to redesign the suspected head and neck cancer (HNC) referral pathway (EVEREST-HN) will use a broad and open approach to the nomenclature and symptomatology. It aims to capture and utilise the patient reported symptoms in a modern way to identify patients’ clinical problems more effectively and risk stratify the patient.MethodThe review followed the PRISMA checklist for scoping reviews. A search strategy was carried out using Medline, Embase and Web of Science between January 1st 2012 and October 31st 2023. All titles, abstracts and full paper were screened for eligibility, papers were assessed for inclusion using predetermined criteria. Data was extracted pertaining to the aims, type of study, cancer type, numbers of patients included and symptoms, presenting complaints or signs and symptoms.ResultsThere were 9,331 publications identified in the searches, following title screening 350 abstracts were reviewed for inclusion and 120 were considered for eligibility for the review. 48 publications met the eligibility criteria and were included in the final review. Data from almost 11,000 HNC patients was included. Twenty-one of the publications were from the UK, most were retrospective examination of patient records. Data was extracted and charted according to the anatomical area of the head and neck where the symptoms are subjectively and objectively found, and presented according to lay terms for symptoms, clinical terms for symptoms and the language of objective clinical findings.DiscussionSymptoms of HNC are common presenting complaints, interpreting these along with clinical history, examination and risk factors will inform a clinician’s decision to refer as suspected cancer. UK Head and Neck specialists believe a different way of triaging the referrals is needed to assess the clinical risk of an undiagnosed HNC. EVEREST-HN aims to achieve this using the patient history of their symptoms. This review has highlighted issues in terms of what is considered a symptom, a presenting complaint and a clinical finding or sign.

In this study we develop a robust, structured dynamic model of ABE and hydrogen production using Clostridium BOH3 strain. The model represents simultaneous fermentation of glucose and xylose, and concurrent saccharification and fermentation when grown on a variety of complex feedstocks, using only a single adjustable parameter. The model simulations were developed and validated with experimental data of BOH3 fermentations from the literature. Sugar consumption and ABE production dynamics are successfully predicted at different glucose to xylose ratios, and from hydrolyzed lignocellulose, representative of horticultural waste. Butanol and hydrogen production are in close agreement with the experimental data in simulations with rice starch and food waste as substrates. The sensitivity analysis highlights the important roles of xylose transport and xylose kinase on the xylose consumption and butanol formation, in accordance with experimental findings on how these enzymes enable the efficient xylose utilization by BOH3.

Weeds interfere with lima bean production by reducing crop yield, hindering harvest, and contributing contaminants to harvested beans, yet there are very few trials documenting the impact of weeds on lima bean. This research was designed to evaluate weeds on lima bean yield, quality, as well as Rhizoctonia solani and pod-feeding insects in order to assist in implementing a more integrated approach to pest management. Field studies at four sites evaluated the impact of common cocklebur (Xanthium strumarium L.), jimsonweed (Datura stramonium L.), and ivyleaf morningglory [Ipomoea hederacea (L.) Jacq.] at densities of 0, 7, 10, or 20 plants 10 m-1 row in the presence and absence of Rhizoctonia solani on lima bean (Phaseolus lunatus L.). The planting dates of late June to mid-July represented a typical planting period for the mid-Atlantic region of USA, while one site represented an early planting date in this region (28 May). Differences in response to weed competition for total lima bean yield, marketable yield, yield components, and R. solani discoloration on lima bean occurred at one or more sites. Weed competition from 7 plants 10 m-1 of row or higher, reduced number lima bean pods by as much as 40%. However, weed density had little impact on percentage of flat, plump, or dry pods. Marketable yield was reduced at two sites in response to 7 plants 10-1 row (19% yield loss) and higher weed densities resulted in 29 to 33% yield loss. The presence of lima bean resulted in 40 to 60% reduction of common cocklebur and jimsonweed biomass and burs or seeds compared to weeds grown without crop competition. Weed competition in lima bean was influenced by many factors including weed species and planting date. Weed management is important to not only preserve yield but limit weed seed return to the soil seedbank and maintain harvest efficiency.

BackgroundStudies evaluating the usability of mobile-phone assessments in older adults are limited. ObjectiveThis study aims to identify design-based barriers and facilitators to mobile app survey completion among 2 samples of older adults; those in the Framingham Heart Study and a more diverse sample from a hospital-based setting. MethodsWe used mixed methods to identify challenging and beneficial features of the mobile app in participants from the electronic Framingham Heart Study (n=15; mean age of 72 years; 6/15, 40% women; 15/15, 100% non-Hispanic and White) and among participants recruited from a hospital-based setting (n=15; mean age of 71 years; 7/15, 47% women; 3/15, 20% Hispanic; and 8/15, 53% non-White). A variety of app-based measures with different response formats were tested, including self-reported surveys, pictorial assessments (to indicate body pain sites), and cognitive testing tasks (eg, Trail Making Test and Stroop). Participants completed each measure using a think-aloud protocol, while being audio- and video-recorded with a qualitative interview conducted at the end of the session. Recordings were coded for participant usability errors by 2 pairs of coders. Participants completed the Mobile App Rating Scale to assess the app (response range 1=inadequate to 5=excellent). ResultsIn electronic Framingham Heart Study participants, the average total Mobile App Rating Scale score was 7.6 (SD 1.1), with no significant differences in the hospital-based sample. In general, participants were pleased with the app and found it easy to use. A large minority had at least 1 navigational issue, most committed only once. Most older adults did not have difficulty completing the self-reported multiple-choice measures unless it included lengthy instructions but participants had usability issues with the Stroop and Trail Making Test. ConclusionsOur methods and results help guide app development and app-based survey construction for older adults, while also giving consideration to sociodemographic differences.

Abstract Koala populations across the east coast of Australia are under threat of extinction with little known about the presence or distribution of a potential pathogen, phascolartid gammaherpesvirus 1 (PhaHV-1) across these threatened populations. Co-infections with PhaHV-1 and Chlamydia pecorum may be common and there is currently a limited understanding of the impact of these co-infections on koala health. To address these knowledge gaps, archived clinical and field-collected koala samples were examined by quantitative polymerase chain reaction to determine the distribution of PhaHV-1 in previously untested populations across New South Wales and Queensland. We detected PhaHV-1 in all regions surveyed with differences in detection rate between clinical samples from rescued koalas (26%) and field-collected samples from free-living koalas (8%). This may reflect increased viral shedding in koalas that have been admitted into care. We have corroborated previous work indicating greater detection of PhaHV-1 with increasing age in koalas and an association between PhaHV-1 and C. pecorum detection. Our work highlights the need for continued surveillance of PhaHV-1 in koala populations to inform management interventions, and targeted research to understand the pathogenesis of PhaHV-1 and determine the impact of infection and co-infection with C. pecorum.

Abstract Background Melbourne, Australia, recorded one of the longest and most stringent pandemic lockdowns in 2020, which was associated with an increase in preterm stillbirths among singleton pregnancies. Twin pregnancies may be particularly susceptible to the impacts of pandemic disruptions to maternity care due to their higher background risk of adverse perinatal outcomes. Methods Multicenter retrospective cohort study of all twin pregnancies birthing in public maternity hospitals in Melbourne. Multivariable log-binomial regression models were used to compare perinatal outcomes between a pre-pandemic group to women in whom weeks 20+0 to 40+0 of gestation occurred entirely during one of two lockdown-exposure periods: exposure 1 from 22 March 2020 to 21 March 2021 and exposure 2 from 22 March 2021 to 27 March 2022. Results Total preterm births

Abstract The necroptosis pathway is a lytic, pro-inflammatory mode of cell death that is widely implicated in human disease, including renal, pulmonary, gut and skin inflammatory pathologies. The precise mechanism of the terminal steps in the pathway, where the RIPK3 kinase phosphorylates and triggers a conformation change and oligomerization of the terminal pathway effector, MLKL, are only emerging. Here, we structurally identify RIPK3-mediated phosphorylation of the human MLKL activation loop as a cue for MLKL pseudokinase domain dimerization. MLKL pseudokinase domain dimerization subsequently drives formation of elongated homotetramers. Negative stain electron microscopy and modelling support nucleation of the MLKL tetramer assembly by a central coiled coil formed by the extended, ~80 Å brace helix that connects the pseudokinase and executioner four-helix bundle domains. Mutational data assert MLKL tetramerization as an essential prerequisite step to enable the release and reorganization of four-helix bundle domains for membrane permeabilization and cell death.

Abstract Mitochondria carry their own circular genome and disruption of the mitochondrial genome is associated with various aging-related diseases. Unlike the nuclear genome, mitochondrial DNA (mtDNA) can be present at 1000 s to 10,000 s copies in somatic cells and variants may exist in a state of heteroplasmy, where only a fraction of the DNA molecules harbors a particular variant. We quantify mtDNA heteroplasmy in 194,871 participants in the UK Biobank and find that heteroplasmy is associated with a 1.5-fold increased risk of all-cause mortality. Additionally, we functionally characterize mtDNA single nucleotide variants (SNVs) using a constraint-based score, mitochondrial local constraint score sum (MSS) and find it associated with all-cause mortality, and with the prevalence and incidence of cancer and cancer-related mortality, particularly leukemia. These results indicate that mitochondria may have a functional role in certain cancers, and mitochondrial heteroplasmic SNVs may serve as a prognostic marker for cancer, especially for leukemia.

Abstract Across the globe, 2-3% of humans carry the p.Ser132Pro single nucleotide polymorphism in MLKL, the terminal effector protein of the inflammatory form of programmed cell death, necroptosis. Here we show that this substitution confers a gain in necroptotic function in human cells, with more rapid accumulation of activated MLKLS132P in biological membranes and MLKLS132P overriding pharmacological and endogenous inhibition of MLKL. In mouse cells, the equivalent Mlkl S131P mutation confers a gene dosage dependent reduction in sensitivity to TNF-induced necroptosis in both hematopoietic and non-hematopoietic cells, but enhanced sensitivity to IFN-β induced death in non-hematopoietic cells. In vivo, Mlkl S131P homozygosity reduces the capacity to clear Salmonella from major organs and retards recovery of hematopoietic stem cells. Thus, by dysregulating necroptosis, the S131P substitution impairs the return to homeostasis after systemic challenge. Present day carriers of the MLKL S132P polymorphism may be the key to understanding how MLKL and necroptosis modulate the progression of complex polygenic human disease.

Abstract The current cohort of undergraduate students is often said to value technology and is assumed to prefer immersive, interactive, and personalized learning experiences. In contrast, many educators recognise the value of face-to-face classes and believe that attending class positively impacts student performance. A novel teaching strategy, including traditional lectures and interactive workshops using an educational technology platform were implemented in an undergraduate neurobiology course. Attendance in class and use of lecture capture recording were associated with improved student performance. Further, student attitudes toward the teaching strategy were evaluated via a survey. The survey respondents included those that regularly attended class and those that did not. Overall, irrespective of attendance, students thought that face-to-face classes were beneficial to their learning and the use of active learning activities helped them to understand the course content. The most common reasons for non-attendance in class were attributed to factors such as the class schedule, work and family commitments and were not related to the availability of class recordings and other online resources. In contrast, the most common reasons for attendance in class included the perceived benefit, the standard of teaching and the level of interest in the course. The novel teaching strategy had a positive impact on student learning, and can be used for in-person, online and asynchronous learning, providing a mechanism for educators to cater for students who wish to attend in-person classes as well as providing options for flexible delivery. Graphical Abstract

BackgroundShort-term blood pressure variability (BPV) is associated with arterial stiffness in patients with hypertension. Few studies have examined associations between arterial stiffness and digital home BPV over a mid- to long-term time span, irrespective of underlying hypertension. ObjectiveThis study aims to investigate if arterial stiffness traits were associated with subsequent mid- to long-term home BPV in the electronic Framingham Heart Study (eFHS). We hypothesized that higher arterial stiffness was associated with higher home BPV over up to 1-year follow-up. MethodsAt a Framingham Heart Study research examination (2016-2019), participants underwent arterial tonometry to acquire measures of arterial stiffness (carotid-femoral pulse wave velocity [CFPWV]; forward pressure wave amplitude [FWA]) and wave reflection (reflection coefficient [RC]). Participants who agreed to enroll in eFHS were provided with a digital blood pressure (BP) cuff to measure home BP weekly over up to 1-year follow-up. Participants with less than 3 weeks of BP readings were excluded. Linear regression models were used to examine associations of arterial measures with average real variability (ARV) of week-to-week home systolic (SBP) and diastolic (DBP) BP adjusting for important covariates. We obtained ARV as an average of the absolute differences of consecutive home BP measurements. ARV considers not only the dispersion of the BP readings around the mean but also the order of BP readings. In addition, ARV is more sensitive to measurement-to-measurement BPV compared with traditional BPV measures. ResultsAmong 857 eFHS participants (mean age 54, SD 9 years; 508/857, 59% women; mean SBP/DBP 119/76 mm Hg; 405/857, 47% hypertension), 1 SD increment in FWA was associated with 0.16 (95% CI 0.09-0.23) SD increments in ARV of home SBP and 0.08 (95% CI 0.01-0.15) SD increments in ARV of home DBP; 1 SD increment in RC was associated with 0.14 (95% CI 0.07-0.22) SD increments in ARV of home SBP and 0.11 (95% CI 0.04-0.19) SD increments in ARV of home DBP. After adjusting for important covariates, there was no significant association between CFPWV and ARV of home SBP, and similarly, no significant association existed between CFPWV and ARV of home DBP (P>.05). ConclusionsIn eFHS, higher FWA and RC were associated with higher mid- to long-term ARV of week-to-week home SBP and DBP over 1-year follow-up in individuals across the BP spectrum. Our findings suggest that higher aortic stiffness and wave reflection are associated with higher week-to-week variation of BP in a home-based setting over a mid- to long-term time span.

Across disciplines, qualitative researchers have documented epistemological and practical tensions in the ethical review of community-based and participatory research, with many arguing that ethics committees’ decisions perpetuate the exclusion of marginalised communities from research engagement. In the existing literature, the research team and the ethics committee are often characterised as staunch opponents. Conversely, in our recent qualitative research addressing communication about sexuality with young people with cerebral palsy who use communication methods other than speech (augmentative and alternative communication), we found that constructive collaboration between researchers and committee members yielded novel insights. Co-authored by a multi-disciplinary research team and the former chair of a Human Research Ethics Committee, this reflexive case study identified three key tensions which arose in the ethical review of research involving this purportedly marginalised population, which reflected the wider importance of trust. We propose a series of practical recommendations to support productive collaboration in the pursuit of safe, inclusive and community-driven research.

Abstract Background Little research exists to support the administration of corticosteroids to pregnant women with diabetes. Pregnant women are often excluded from clinical trials due to concerns of harm to the foetus. Aim This study aimed to understand the experiences of women and clinicians of participating in the Prevention of neonatal Respiratory distress with antenatal corticosteroids before Elective Caesarean section in women with Diabetes pilot randomised controlled trial to determine the acceptability of the study protocol. Methods Women and clinicians participating in the pilot trial were invited to complete a telephone interview regarding their experiences of participating. Qualitative data were collected and subsequently analysed using thematic analysis. Results A total of 13 women and nine clinicians were recruited between June 2020 and May 2022 for a telephone interview. Participating in the study was deemed acceptable by women and clinicians. Women chose to participate in the study due to the perceived low risk of harm associated with the intervention and for altruistic reasons. The high level of clinical support and information provided for the duration of the pilot trial was valued by women and clinicians. All clinicians highlighted the importance of conducting the trial to inform evidence‐based practice. Conclusions Pregnant women are more likely to participate in clinical trials when perceived risks are low and they are well‐informed during decision‐making. Clinicians will support clinical trials when they perceive a benefit to practice and feel assured that women receive extensive monitoring and support. Incorporating these factors into study protocols is more likely to be successful in recruiting pregnant women and maintaining the engagement of clinical staff for the duration of clinical trials. Patient or Public Contributions Patients were invited to be participants in this study. A consumer has been included in the planning and oversite of the large multicentre trial.

Abstract Cytotoxicity (i.e. cell death) is the core mechanism by which chemotherapy induces its anti-cancer effects. Unfortunately, this same mechanism underpins the collateral damage it causes to healthy tissues. The gastrointestinal tract is highly susceptible to chemotherapy’s cytotoxicity, resulting in ulcerative lesions (termed gastrointestinal mucositis, GI-M) that impair the functional capacity of the gut leading to diarrhea, anorexia, malnutrition and weight loss, which negatively impact physical/psychological wellbeing and treatment adherence. Preventing these side effects has proven challenging given the overlapping mechanisms that dictate chemotherapy efficacy and toxicity. Here, we report on a novel dietary intervention that, due to its localized gastrointestinal effects, is able to protect the intestinal mucosal from unwanted toxicity without impairing the anti-tumor effects of chemotherapy. The test diet (containing extensively hydrolyzed whey protein and medium chain triglycerides (MCTs)), was investigated in both tumor-naïve and tumor-bearing models to evaluate its effect on GI-M and chemo-efficacy, respectively. In both models, methotrexate was used as the representative chemotherapeutic agent and the diet was provided ad libitum for 14 days prior to treatment. GI-M was measured using the validated biomarker plasma citrulline, and chemo-efficacy defined by tumor burden (cm3/g body weight). The test diet significantly attenuated GI-M (P = 0.03), with associated reductions in diarrhea (P

Macropods are often implicated as the main native Australian reservoir hosts of Coxiella burnetii (Q fever); however, the maintenance and transmission capacity of these species are poorly understood. The objective of this cross-sectional study was to describe the epidemiology of C. burnetii in a high-density population of eastern grey kangaroos (Macropus giganteus) in a peri-urban coastal nature reserve in New South Wales, Australia. Blood, faeces and swabs were collected from forty kangaroos as part of a population health assessment. Frozen and formalin-fixed tissues were also collected from 12 kangaroos euthanised on welfare grounds. Specimens were tested for C. burnetii using PCR, serology, histopathology and immunohistochemistry. A total of 33/40 kangaroos were seropositive by immunofluorescence assay (estimated true seroprevalence 84%, 95% confidence interval [CI] 69% to 93%), with evidence of rising titres in two animals that had been tested four years earlier. The PCR prevalence was 65% (95% CI 48% to 79%), with positive detection in most sample types. There was no evidence of pathology consistent with C. burnetii, and immunohistochemistry of PCR-positive tissues was negative. These findings indicate that kangaroos are competent maintenance hosts of C. burnetii, likely forming a significant part of its animal reservoir at the study site.

Here, we describe GS-9, a novel water-soluble fatty acid-based formulation comprising L-lysine and arachidonic acid, that we have shown to induce ferroptosis. GS-9 forms vesicle-like structures in solution and mediates lipid peroxidation, as evidenced by increased C11-BODIPY fluorescence and an accumulation of toxic malondialdehyde, a downstream product of lipid peroxidation. Ferroptosis inhibitors counteracted GS-9-induced cell death, whereas caspase 3 and 7 or MLKL knock-out cell lines are resistant to GS-9-induced cell death, eliminating other cell death processes such as apoptosis and necroptosis as the mechanism of action of GS-9. We also demonstrate that through their role of sequestering fatty acids, lipid droplets play a protective role against GS-9-induced ferroptosis, as inhibition of lipid droplet biogenesis enhanced GS-9 cytotoxicity. In addition, Fatty Acid Transport Protein 2 was implicated in GS-9 uptake. Overall, this study identifies and characterises the mechanism of GS-9 as a ferroptosis inducer. This formulation of arachidonic acid offers a novel tool for investigating and manipulating ferroptosis in various cellular and anti-cancer contexts.

BackgroundDuring the COVID-19 pandemic, care homes for older adults in England implemented isolation, social distancing and other restriction measures to help protect residents from contracting the virus. Little was known about the physical and psychological impacts that these measures would have upon residents and their relatives.AimTo explore the experiences of residents and their relatives of living restricted lives during the pandemic.MethodsThis qualitative study was conducted as part of a 12-month, mixed-methods, phased design. From six purposively sampled care homes in England, 17 purposively sampled residents (all older adults) and 17 purposively sampled relatives participated in an individual, on-line interview, where they discussed their experiences of the restrictive measures implemented within their care home. Interviews were audio- and video-recorded with participants' permission and analysed using an inductive orientation to thematic analysis, with coding and theme development driven by the data content.ResultsParticipants' experiences of care home restrictions varied; their impact was influenced by the existing pattern of relationships that residents and their relatives maintained within and beyond the care home. It was further influenced by the fact that many residents and relatives were still learning how to manage their relationships in the new context of living in a care home. Social distancing measures made care homes feel less homely and denied residents, staff and relatives physical touch and other forms of non-verbal communication. Many residents expressed a broad sense of gratitude that was associated with safety and well-being beyond the pandemic. As older adults, they put the pandemic, and its associated restrictions, within the larger context of their lives.ConclusionsLearning from the COVID-19 pandemic is paramount for governments, societies, policy makers, care home providers, care homes and their staff, residents and their families and friends, and researchers. Our study makes an important contribution as one of the first to study the impact of implementing isolation, social distancing and other restrictive measures for care home residents and their relatives in England.

Drawing upon data from a study examining experiences of accessing support for pets from the UK animal welfare charity Blue Cross, this paper illuminates reasons why people might not seek support when they need it. This applies to those who are struggling financially and are eligible for, but do not take, free/reduced cost veterinary care, or are having other problems (e.g. the animal’s disruptive behaviour or ill health, struggling to care for the pet due to changing circumstances or health problems, or coping with pet loss). Twenty Blue Cross service users (15 female, five male, age 29–67) took part in individual online interviews using a semi-guided narrative approach, where they were encouraged to share their experiences of reaching out. They were also asked to reflect upon why others may not do the same, and if they had any recommendations for organisations to help them reach these people. Findings echo other studies that highlight a fear of being judged, disclosure and stigma. Guilt, shame, lack of awareness, financial concerns, and wanting to manage independently, all play important roles. These factors have implications for the way support services are advertised and delivered to ensure animals receive the care needed. We describe these reflections and recommendations and identify three broader ideological narratives underpinning participants’ stories: ‘giving back’; ‘equity’, and ‘sacrifice’. These reveal how wider societal attitudes and values shape identities and behaviours. It is vital that support on offer is reframed to explicitly counteract these influences to ensure optimal animal and human welfare.