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Abstract Background Individuals with transfusion-dependent β-thalassemia (TDT) experience symptoms and functional impacts that reduce their health-related quality of life. However, EQ-5D-derived health utility index scores in TDT often indicate good HRQoL, suggesting the EQ-5D may not adequately capture the impact of TDT. This study explored the disease and treatment burden of TDT and examined the appropriateness of the EQ-5D-5L descriptive system (DS) in measuring HRQoL in TDT. Methods Adults with TDT in the United Kingdom, United States, and France completed a background questionnaire and EQ-5D-5L DS, followed by 60-minute semi-structured interviews on symptoms and HRQoL impacts of TDT (concept elicitation) and appropriateness of EQ-5D-5L DS (cognitive debrief). Transcribed interviews were analyzed using thematic and content analyses. The relationship between TDT symptoms and impacts were summarized in a conceptual model. EQ-5D-5L DS was mapped to concepts identified in the qualitative data to assess its capture of HRQoL concepts. Participants’ EQ-5D-5L DS scores were compared to their qualitative descriptions for each dimension to assess their concordance. Results Thirty participants in the United States (n = 14 [46.7%]), United Kingdom. (n = 12 [40.0%]), and France (n = 4 [13.3%]) completed the study (73.3% female; mean age = 28.4 years [standard deviation (SD) = 5.1]; mean annual red blood cell transfusion [RBCT] frequency = 18.4 [SD = 7.6]). Participants reported TDT symptoms and impacts on HRQoL, all fluctuating across the RBCT cycle. EQ-5D-5L DS did not fully capture 11 of 16 (68.8%) HRQoL concepts reported. Most participants (n = 20/27 [74.1%]) reported that EQ-5D-5L DS did not capture important aspects of living with TDT, and 42.9% (n = 12/28) reported negative/neutral overall impressions of EQ-5D-5L DS. The highest degree of discordance between participants’ qualitative data and EQ-5D-5L DS dimension scores was observed with mobility (42.3%) and self-care (34.6%), where the qualitative descriptions relating to these dimensions were worse than their quantitative scores. Conclusion Current findings suggest that EQ-5D-5L DS lacks content validity and the derived health utility index score may not fully represent the burden of disease in TDT.

Abstract Background Activated phosphoinositide 3-kinase delta syndrome (APDS) is an ultra-rare primary immunodeficiency, with only 256 cases reported globally. This study aimed to explore the disease burden of APDS from the perspective of individuals with APDS and their caregivers. Methods Qualitative interviews were conducted with healthcare providers (HCPs), individuals with APDS and caregivers, to explore the symptoms and health-related quality of life (HRQoL) impact of APDS. Some individuals and caregivers also completed a narrative account exercise. All interviews were audio recorded and transcribed. Data were analysed using thematic analysis and saturation was recorded. Results Semi-structured qualitative interviews were conducted with healthcare providers (HCPs), individuals with APDS and caregivers. Individuals and caregivers had the option of completing a narrative account exercise. Six HCPs participated in an interview. Seven participants completed the narrative account exercise (N = 5 caregivers and N = 2 individuals with APDS) and 12 took part in an interview (N = 4 caregivers and N = 8 individuals with APDS). Themes identified from HCPs interviews included symptoms, clinical manifestations, HRQoL impacts and treatments/management of APDS. The narrative account exercise identified similar themes, but with the addition to the journey to diagnosis. These themes were explored during the individual/caregiver interviews. Reported clinical manifestations and symptoms of APDS included susceptibility to infections, lymphoproliferation, gastrointestinal (GI) disorders, fatigue, bodily pain, and breathing difficulties. HRQoL impacts of living with APDS included negative impacts to daily activities, including work, education and social and leisure activities, physical functioning, as well as emotional well-being, such as concern for the future, and interpersonal relationships. Impacts to caregiver HRQoL included negative impacts to physical health, work, emotional well-being, interpersonal relationships and family life and holidays. The management of APDS included the use of healthcare services and medications including immunoglobulin replacement therapy (IRT), rapamycin, prophylactic antibiotics, leniolisib, as well as medical procedures due to complications. Conclusions APDS has a high disease burden and there is an unmet need for licensed, more targeted treatments which modify disease progression. This study was the first to describe the day-to-day experience and HRQoL impact of APDS from the perspective of individuals living with the condition, caregivers and treating physicians.

Introduction There is a lack of evidence that the benefits of screening for atrial fibrillation (AF) outweigh the harms. Following the completion of the Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) pilot trial, the aim of the main SAFER trial is to establish whether population screening for AF reduces incidence of stroke risk.Methods and analysis Approximately 82 000 people aged 70 years and over and not on oral anticoagulation are being recruited from general practices in England. Patients on the palliative care register or residents in a nursing home are excluded. Eligible people are identified using electronic patient records from general practices and sent an invitation and consent form to participate by post. Consenting participants are randomised at a ratio of 2:1 (control:intervention) with clustering by household. Those randomised to the intervention arm are sent an information leaflet inviting them to participate in screening, which involves use of a handheld single-lead ECG four times a day for 3 weeks. ECG traces identified by an algorithm as possible AF are reviewed by cardiologists. Participants with AF are seen by a general practitioner for consideration of anticoagulation. The primary outcome is stroke. Major secondary outcomes are: death, major bleeding and cardiovascular events. Follow-up will be via electronic health records for an average of 4 years. The primary analysis will be by intention-to-treat using time-to-event modelling. Results from this trial will be combined with follow-up data from the cluster-randomised pilot trial by fixed-effects meta-analysis.Ethics and dissemination The London—Central National Health Service Research Ethics Committee (19/LO/1597) provided ethical approval. Dissemination will include public-friendly summaries, reports and engagement with the UK National Screening Committee.Trial registration number ISRCTN72104369.

Summary: Facioscapulohumeral dystrophy (FSHD) is linked to contraction of D4Z4 repeats on chromosome 4q with SMCHD1 mutations acting as a disease modifier. D4Z4 heterochromatin disruption and abnormal upregulation of the transcription factor DUX4, encoded in the D4Z4 repeat, are the hallmarks of FSHD. However, defining the precise effect of D4Z4 contraction has been difficult because D4Z4 repeats are primate-specific and DUX4 expression is very rare in highly heterogeneous patient myocytes. We generated isogenic mutant cell lines harboring D4Z4 and/or SMCHD1 mutations in a healthy human skeletal myoblast line. We found that the mutations affect D4Z4 heterochromatin differently, and that SMCHD1 mutation or disruption of DNA methylation stabilizes otherwise variegated DUX4 target activation in D4Z4 contraction mutant cells, demonstrating the critical role of modifiers. Our study revealed amplification of the DUX4 signal through downstream targets, H3.X/Y and LEUTX. Our results provide important insights into how rare DUX4 expression leads to FSHD pathogenesis.

Objective The ‘To Dip or Not to Dip’ (TDONTD) intervention aims to reduce antibiotic prescribing for urinary tract infection (UTI) by reducing low-value dipstick testing. The aims of this study were to use a qualitative approach to (1) evaluate potential influences on the delivery of the TDONTD intervention in Australian residential aged care homes (RACHs) by identifying perceived barriers and enablers to delivery and acceptance; and (2) propose intervention strategies to address barriers and enhance enablers.Design A qualitative before–after process evaluation of a multisite implementation study using interviews with nurse and pharmacist implementers.Setting This study was conducted in 12 Australian RACHs.Participants Participants included 17 on-site nurse champions and 4 pharmacists (existing contracted providers).Intervention Resources from England’s TDONTD intervention were adapted for an Australian context. Key resources delivered were case-based education, staff training video, clinical pathway and an audit tool.Results Key barriers to TDONTD were beliefs about nursing capabilities in diagnosing infection, beliefs about consequences (fear of missing infection) and social influences (pressure from family, doctors and hospitals). Key enablers were perceived increased nurse and carer knowledge (around UTI and asymptomatic bacteriuria), resources from a credible source, empowerment of nurse champions to apply knowledge and skills in delivering operational change initiatives, pharmacist-delivered education and organisational policy or process change. Of TDONTD’s key components, the clinical pathway substituted dipstick testing in diagnosing UTI, delivery of case-based education was enhanced by their attendance and support of the intervention and the antibiotic audit tool generated feedback that champions shared with staff.Conclusions Our study confirms the core components of TDONTD and strategies to enhance delivery and overcome barriers. To further reduce barriers to TDONTD, broader advocacy work is required to raise awareness of dipstick testing as a low-value test in older persons and by linking it to healthcare professionals and consumer education.

Abstract Objectives To assess the relative productivity of primary medical services in England and the impact of the COVID-19 pandemic on productivity levels. Setting Primary medical services for 59 million patients (98% of the population in England), in 101 clinical commissioning groups (CCGs), across two time periods: period 1, pre-pandemic, April to December 2019 and period 2, pandemic, April to December 2020. Methods We use data envelopment analysis (DEA) to assess relative productivity with four input measures (the number of full-time equivalent general practitioners, nurses, other direct patient contact staff and administrators), and five output measures (face-to-face appointments, remote consultations, home visits, referrals to secondary care and prescriptions). Our units of analysis were CCGs. DEA assigns an efficiency score to a CCG, taking a value between 0 and 100%, by benchmarking it against the most productive CCGs. We use Tobit regression to examine the association between productivity and other factors. Results The mean bias-corrected efficiency score of primary medical services in CCGs was 92.9% (interquartile range 92.0% to 95.7%) in period 1, falling to 90.6% (interquartile range 86.8% to 95.2%) in period 2. In period 1, CCGs with a higher proportion of registered patients aged over 65 years, higher levels of deprivation, lower levels of disease prevalence, higher nurse to GP ratios and higher GP to other direct patient contact staff ratios, achieved statistically significantly higher general practice efficiency scores (p 0.05). Conclusions Our analysis indicates only modest geographic variation in productivity of primary medical services when measured at the level of clinical commissioning groups and a small reduction in productivity during the pandemic. Further work to establish relative productivity of individual GP practices is warranted once sufficient data on appointment rates by GP practice is available.

Abstract Background Familial chylomicronemia syndrome (FCS) is a rare, hereditary, metabolic disorder. FCS causes high levels of triglycerides in the blood, which can lead to abdominal pain, xanthomas, and acute pancreatitis (AP). Volanesorsen, along with adherence to a very low-fat diet is used to reduce triglyceride levels in individuals with FCS. We aimed to understand the symptoms of FCS and their impact on health-related quality of life (HRQoL). Methods Interviews were conducted with individuals with genetically confirmed FCS in the UK and Spain, some of whom had been treated with volanesorsen. Interview guides were developed with input from a patient advocacy group to explore the symptoms, impacts and management of FCS. Interviews were conducted by telephone and were recorded and transcribed. Data were analyzed using thematic analysis and saturation was recorded. Results Seventeen interviews were conducted with individuals with FCS (aged 27–68 years), thirteen of whom were currently/previously treated with volanesorsen. Episodes of AP were the most impactful reported symptom, resulting in severe abdominal pain, nausea, vomiting, fever, bloating and appetite loss. Other symptoms and functional issues included abdominal pain, gastrointestinal symptoms, impaired cognitive function and fatigue. These had an impact on work, social activities, relationships and psychological wellbeing. These symptoms and impacts were illustrated in a conceptual model, including management strategies. The challenges of managing a low-fat diet and experience with volanesorsen were discussed. Conclusion Individuals with FCS experience a range of interrelated symptoms and functional limitations which impact their broader HRQoL. Treatments which alleviate symptoms and reduce the incidence of AP episodes have the potential to improve the HRQoL of these individuals.

Abstract Biocompatibility and the ability to mediate the appropriate flux of ions, urea, and uremic toxins between blood and dialysate components are key parameters for membranes used in dialysis. Oxone-mediated TEMPO-oxidized cellulose nanomaterials have been demonstrated to be excellent additives in the production and tunability of ultrafiltration and dialysis membranes. In the present study, nanocellulose ionic liquid membranes (NC-ILMs) were tested in vitro and ex vivo. An increase in flux of up to two orders of magnitude was observed with increased rejection (about 99.6%) of key proteins compared to that of polysulfone (PSf) and other commercial membranes. NC-ILMs have a sharper molecular weight cut-off than other phase inversion polymeric membranes, allowing for high throughput of urea and a uremic toxin surrogate and limited passage of proteins in dialysis applications. Superior anti-fouling properties were also observed for the NC-ILMs, including a > 5-h operation time with no systemic anticoagulation in blood samples. Finally, NC-ILMs were found to be biocompatible in rat ultrafiltration and dialysis experiments, indicating their potential clinical utility in dialysis and other blood filtration applications. These superior properties may allow for a new class of membranes for use in a wide variety of industrial applications, including the treatment of patients suffering from renal disease.

Purpose – This paper aims to understand how a special library helped firefighters in Illinois navigate the digital revolution by evidencing the elements and forms of work that made its innovative services possible. Design/methodology/approach – The authors examine the history of a special library through a community informatics lens, drawing from sociomaterial perspectives to highlight forms of work often invisible in digital innovation. Data was collected through documentary revision, oral histories and semi-structured interviews. Deductive-inductive coding and constant comparative analysis was used in the analysis. Findings – A historical narrative of the library between 1990 and 2021 highlights three sociotechnical innovations that assisted firefighters through the digital revolution: the facilitated collection, the co-created collection and the inside-out library. To develop these innovations the library drew from institutional relations, personal relations, grants, labor, knowledge of firefighters and technology. Various forms of articulation work brought these elements together to create innovative services. Originality/value – The role of special libraries in addressing the digital divide has not been sufficiently detailed so far; this paper is a contribution in that direction. It also has practical value for professionals working in specialized libraries and information centers.

Research in the global field of artificial intelligence is increasingly hybrid in orientation. Researchers are beholden to the requirements of multiple intersecting spheres, such as scholarly, public, and commercial, each with their own language and logic. Relatedly, collaboration across disciplinary, sector and national borders is increasingly expected, or required. Using a dataset of 93,482 artificial intelligence publications, this article operationalises scholarly, public, and commercial spheres through citations, news mentions, and patent mentions, respectively. High performing publications (99th percentile) for each metric were separated into eight categories of influence. These comprised four blended categories of influence (news, patents and citations; news and patents; news and citations; patents and citations) and three single categories of influence (citations; news; patents), in addition to the ‘Other’ category of non-high performing publications. The article develops and applies two components of a new hybridity lens: evaluative hybridity and generative hybridity. Using multinomial logistic regression, selected aspects of knowledge production – research context, focus, artefacts, and collaborative configurations – were examined. The results elucidate key characteristics of knowledge production in the artificial intelligence field and demonstrate the utility of the proposed lens.

Abstract Qualitative research can enhance the design, conduct and interpretation of trials. Despite this, few trials incorporate qualitative methods, and those that do may not realise their full potential. In this commentary, we highlight how qualitative research can contribute to the design, conduct and day-to-day running of a trial, outlining the working arrangements and relationships that facilitate these contributions. In doing so, we draw on (i) existing frameworks on the role of qualitative research alongside trials and (ii) our experience of integrated qualitative research conducted as part of the feasibility study of the SAFER trial (Screening for Atrial Fibrillation with ECG to Reduce stroke), a cluster randomised controlled trial of screening people aged 70 and above for atrial fibrillation in primary care in England. The activities and presence of the qualitative team contributed to important changes in the design, conduct and day-to-day running of the SAFER feasibility study, and the subsequent main trial, informing diverse decisions concerning trial documentation, trial delivery, timing and content of measures and the information given to participating patients and practices. These included asking practices to give screening results to all participants and not just to ‘screen positive’ participants, and greater recognition of the contribution of practice reception staff to trial delivery. These changes were facilitated by a ‘one research team’ approach that underpinned all formal and informal working processes from the outset and maximised the value of both qualitative and trial coordination expertise. The challenging problems facing health services require a combination of research methods and data types. Our experience and the literature show that the benefits of embedding qualitative research in trials are more likely to be realised if attention is given to both structural factors and relationships from the outset. These include sustained and sufficient funding for qualitative research, embedding qualitative research fully within the trial programme, providing shared infrastructure and resources and committing to relationships based on mutual recognition of and respect for the value of different methods and perspectives. We outline key learning for the planning of future trials. Trial registration: Screening for atrial fibrillation with ECG to reduce stroke ISRCTN16939438 (feasibility study); Screening for atrial fibrillation with ECG to reduce stroke – a randomised controlled trial ISRCTN72104369 .

Abstract Background Aromatic l-amino acid decarboxylase (AADC) deficiency is a rare neurological disorder associated with a range of symptoms and functional impairments. The aim of this study was to describe the experience of AADC deficiency across five different motor milestone health states. Methods Qualitative interviews were conducted with caregivers of individuals with AADC deficiency in Italy, Spain, Portugal and the United States. An interview guide was developed with input from clinical experts and caregivers, and explored the symptoms and impacts of AADC deficiency. Interviews were conducted by telephone and were recorded and transcribed. Data were analysed using thematic analysis and the symptoms and impacts were compared across health states. Results Fourteen caregivers took part, who provided care to 13 individuals with AADC deficiency aged 1–15 years. Six individuals were in the ‘no motor function’ health state, one in the ‘sitting unsupported’ health state, one in the ‘standing/stepping when fully supported’ health state and five in the ‘walking with minimal support’ health state. The results highlight a substantial impact of AADC deficiency, even among those who were able to walk with minimal support. Overall, those with better motor function also had better functional hand use, communication skills, ability to eat and perform other activities independently, and interact with their peers. The burden of caring was high across all health states, but caregivers of individuals in the walking health state were better able to participate in social and leisure activities. Conclusion Individuals with higher levels of motor function had less severe symptoms and were better able to perform their daily, leisure and social activities. Treatments which improve motor function have the potential to improve other aspects of the lives of individuals with AADC deficiency and their caregivers.

The objective of this study is to investigate the application of machine learning techniques to the large-scale human expert evaluation of the impact of academic research. Using publicly available impact case study data from the UK's Research Excellence Framework (2014), we trained five machine learning models on a range of qualitative and quantitative features, including institution, discipline, narrative style (explicit and implicit), and bibliometric and policy indicators. Our work makes two key contributions. Based on the accuracy metric in predicting high- and low-scoring impact case studies, it shows that machine learning models are able to process information to make decisions that resemble those of expert evaluators. It also provides insights into the characteristics of impact case studies that would be favoured if a machine learning approach was applied for their automated assessment. The results of the experiments showed strong influence of institutional context, selected metrics of narrative style, as well as the uptake of research by policy and academic audiences. Overall, the study demonstrates promise for a shift from descriptive to predictive analysis, but suggests caution around the use of machine learning for the assessment of impact case studies.

Introduction Atrial fibrillation (AF) is a common arrhythmia associated with 30% of strokes, as well as other cardiovascular disease, dementia and death. AF meets many criteria for screening, but there is limited evidence that AF screening reduces stroke. Consequently, no countries recommend national screening programmes for AF. The Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) trial aims to determine whether screening for AF is effective at reducing risk of stroke. The aim of the pilot study is to assess feasibility of the main trial and inform implementation of screening and trial procedures.Methods and analysis SAFER is planned to be a pragmatic randomised controlled trial (RCT) of over 100 000 participants aged 70 years and over, not on long-term anticoagulation therapy at baseline, with an average follow-up of 5 years. Participants are asked to record four traces every day for 3 weeks on a hand-held single-lead ECG device. Cardiologists remotely confirm episodes of AF identified by the device algorithm, and general practitioners follow-up with anticoagulation as appropriate. The pilot study is a cluster RCT in 36 UK general practices, randomised 2:1 control to intervention, recruiting approximately 12 600 participants. Pilot study outcomes include AF detection rate, anticoagulation uptake and other parameters to incorporate into sample size calculations for the main trial. Questionnaires sent to a sample of participants will assess impact of screening on psychological health. Process evaluation and qualitative studies will underpin implementation of screening during the main trial. An economic evaluation using the pilot data will confirm whether it is plausible that screening might be cost-effective.Ethics and dissemination The London—Central Research Ethics Committee (19/LO/1597) and Confidentiality Advisory Group (19/CAG/0226) provided ethical approval. Dissemination will be via publications, patient-friendly summaries, reports and engagement with the UK National Screening Committee.Trial registration number ISRCTN72104369.

Abstract Background Levels of self-reported health do not always correlate with levels of physical disability in stroke survivors. We aimed to explore what underlies the difference between subjective self-reported health and objectively measured disability among stroke survivors. Methods Face to face semi-structured interviews were conducted with stroke survivors recruited from a stroke clinic or rehabilitation ward in the UK. Fifteen stroke survivors purposively sampled from the clinic who had discordant self-rated health and levels of disability i.e. reported health as ‘excellent’ or ‘good’ despite significant physical disability (eight), or as ‘fair’ or ‘poor’ despite minimal disability (seven) were compared to each other, and to a control group of 13 stroke survivors with concordant self-rated health and disability levels. Interviews were conducted 4 to 6 months after stroke and data analysed using the constant comparative method informed by Albrecht and Devlieger’s concept of ‘disability paradox’. Results Individuals with ‘excellent’ or ‘good’ self-rated health reported a sense of self-reliance and control over their bodies, focussed on their physical rehabilitation and lifestyle changes and reported few bodily and post-stroke symptoms regardless of level of disability. They also frequently described a positive affect and optimism towards recovery. Some, especially those with ‘good’ self-rated health and significant disability also found meaning from their stroke, reporting a spiritual outlook including practicing daily gratitude and acceptance of limitations. Individuals with minimal disability reporting ‘fair’ or ‘poor’ self-rated health on the other hand frequently referred to their post-stroke physical symptoms and comorbidities and indicated anxiety about future recovery. These differences in psychological outlook clustered with differences in perception of relational and social context including support offered by family and healthcare professionals. Conclusions The disability paradox may be illuminated by patterns of individual attributes and relational dynamics observed among stroke survivors. Harnessing these wider understandings can inform new models of post-stroke care for evaluation.

Abstract Background Duchenne muscular dystrophy is a rare genetic neuromuscular disorder, which can result in early death due to disease progression. Ataluren is indicated for the treatment of nonsense mutation Duchenne muscular dystrophy, in ambulatory individuals aged two years and older. This study explored the impact of caring for an ambulatory individual with nonsense mutation Duchenne muscular dystrophy, as well as the impact of treatment with ataluren on the caregiver experience, using retrospective recall. Methods Qualitative interviews were conducted with caregivers in the UK. Interviews were conducted by telephone, were recorded and transcribed. Data were analysed using thematic analysis and saturation was recorded. Results Ten interviews were conducted with parents of individuals aged 4–19 years. Caregivers reported proximal impacts (physical, emotional, time-related), and distal impacts (work, relationships, social life) of caring for their sons. The relationships between these impacts were illustrated in a conceptual model. Changes to the caregiver experience since initiation with their son’s treatment were discussed. Conclusion Caring for an ambulatory individual with nonsense mutation Duchenne muscular dystrophy has a substantial multifaceted impact on caregivers. Treatments which have the potential to improve symptoms or delay progression, may also have a positive impact on the quality of life of caregivers.

Abstract Background Duchenne muscular dystrophy is a rare genetic neuromuscular disorder, which can result in early death due to disease progression. Ataluren is indicated for the treatment of nonsense mutation Duchenne muscular dystrophy, in ambulatory individuals aged two years and older. This study explored the symptoms and impacts of nonsense mutation Duchenne muscular dystrophy and experience with ataluren. Methods Qualitative interviews were conducted with caregivers in the UK. Interviews were conducted by telephone, were recorded and transcribed. Data were analysed using thematic analysis and saturation was recorded. Results Ten interviews were conducted with parents of individuals aged 4–19 years. Key symptoms included muscle weakness and muscle breakdown, which were associated with limitations in physical function and pain. These impacted individuals’ daily activities, social activities and emotional wellbeing. These concepts and relationships were illustrated in a conceptual model, along with positive and negative moderating factors. Experience with ataluren and changes since initiation with treatment were discussed. Conclusion Individuals with nonsense mutation Duchenne muscular dystrophy experience a range of interrelated symptoms and functional issues which impact their broader health-related quality of life. Treatments which address this high unmet need have the potential to improve the health-related quality of life of these individuals.

Objectives There is insufficient evidence to support national screening programmes for atrial fibrillation (AF). Nevertheless, some practitioners, policy-makers and special interest groups have encouraged introduction of opportunistic screening in primary care in order to reduce the incidence of stroke through earlier detection and treatment of AF. The attitudes of the public towards AF screening are unknown. We aimed to explore why AF screening participants took part in the screening.Design Semistructured longitudinal interview study of participant engagement in the SAFER study (Screening for Atrial Fibrillation with ECG to Reduce stroke). We undertook initial interviews face to face, with up to two follow-up telephone interviews during the screening process. We thematically analysed and synthesised these data to understand shared views of screening participation.Setting 5 primary care practices in the East of England, UK.Participants 23 people taking part in the SAFER study first feasibility phase.Results Participants were supportive of screening for AF, explaining their participation in screening as a ‘good thing to do’. Participants suggested screening could facilitate earlier diagnosis, more effective treatment, and a better future outcome, despite most being unfamiliar with AF. Participating in AF screening helped attenuate participants’ concerns about stroke and demonstrated their commitment to self-care and being a ‘good patient’. Participants felt that the screening test was non-invasive, and they were unlikely to have AF; they therefore considered engaging in AF screening was low risk, with few perceived harms.Conclusions Participants assessed the SAFER AF screening programme to be a legitimate, relevant and safe screening opportunity, and complied obediently with what they perceived to be a recommendation to take part. Their unreserved acceptance of screening benefit and lack of awareness of potential harms suggests that uptake would be high but reinforces the importance of ensuring participants receive balanced information about AF screening initiatives.Trial registration number ISRCTN16939438; Pre-results.

Rationale Clinical trials are the gold standard for testing interventions. COVID-19 has further raised their public profile and emphasised the need to deliver better, faster, more efficient trials for patient benefit. Considerable overlap exists between data required for trials and data already collected routinely in electronic healthcare records (EHRs). Opportunities exist to use these in innovative ways to decrease duplication of effort and speed trial recruitment, conduct and follow-up.Approach The National Institute of Health Research (NIHR), Health Data Research UK and Clinical Practice Research Datalink co-organised a national workshop to accelerate the agenda for ‘data-enabled clinical trials’. Showcasing successful examples and imagining future possibilities, the plenary talks, panel discussions, group discussions and case studies covered: design/feasibility; recruitment; conduct/follow-up; collecting benefits/harms; and analysis/interpretation.Reflection Some notable studies have successfully accessed and used EHR to identify potential recruits, support randomised trials, deliver interventions and supplement/replace trial-specific follow-up. Some outcome measures are already reliably collected; others, like safety, need detailed work to meet regulatory reporting requirements. There is a clear need for system interoperability and a ‘route map’ to identify and access the necessary datasets. Researchers running regulatory-facing trials must carefully consider how data quality and integrity would be assessed. An experience-sharing forum could stimulate wider adoption of EHR-based methods in trial design and execution.Discussion EHR offer opportunities to better plan clinical trials, assess patients and capture data more efficiently, reducing research waste and increasing focus on each trial’s specific challenges. The short-term emphasis should be on facilitating patient recruitment and for postmarketing authorisation trials where research-relevant outcome measures are readily collectable. Sharing of case studies is encouraged. The workshop directly informed NIHR’s funding call for ambitious data-enabled trials at scale. There is the opportunity for the UK to build upon existing data science capabilities to identify, recruit and monitor patients in trials at scale.

Objective Internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals have published breast cancer research gaps that are informing research funding priorities in the UK and worldwide. We aimed to determine the breast cancer research priorities of the public to compare with those identified by clinicians and scientists.Design We conducted a qualitative study and thematic analysis using ‘listening events’ where patients with breast cancer and public representatives used a patient’s breast cancer journey to identify research themes.Participants and setting Female participants were recruited from attendees at participating hospitals and support groups in the northwest of England, including patients, their family and friends as well as staff at a local retail centre.Intervention A framework approach was used to analyse transcribed discussions until thematic saturation was reached.Main outcome measures Breast cancer research priorities were identified from participant discussions and compared with the published gaps identified by scientists and healthcare professionals.Results Thematic saturation was reached after 27 female participants participated in listening events. Our participants consistently focused on improved methods of dissemination of information and improving education on the signs and symptoms of breast cancer. This was not highlighted by scientists or healthcare professionals. There was strong emphasis on quality of life-related issues such as side effects of treatment. There was some agreement between the priorities deduced by our study and those of the professionals in the areas of screening, prevention and breast reconstruction.Conclusion Our study identified some research themes that were not identified by scientists and healthcare professionals in two earlier landmark studies. This highlights the importance of including patients and public representatives when setting research priorities. The results should be used to guide investigators when planning future studies and for funding bodies in allocating resources for future projects.

Given the strong link between religiousness and hope, we sought to further understand the relations of these potentially powerful resources for youth living in adversity. Although existing research suggests that religiousness might be associated with adolescent hope via spirituality and social connections, few studies have tested models that integrate both. Thus, as applied psychologists, the aim of this paper was to test a theoretical model in the lives of youth. Drawing on a Relational Developmental Systems metatheory, we sought to further elucidate the relations between religiousness and hope and to explore how involvement in the faith-based youth-development organization, Compassion International (CI), might facilitate character strengths like hope. In order to do so, we tested whether religiousness was directly and indirectly (via spirituality and social connection) related to hopeful future expectations, using a sample of 9−15-year-olds in El Salvador (M = 11.6 years; n = 888), half of whom were involved in CI and the other half of whom were a locally matched counterfactual sample. Structural equation models revealed that higher levels of religiousness were directly and indirectly associated with higher levels of hope in relation to higher levels of spirituality and social connections among these youth. CI-supported youth reported significantly higher levels of religiousness than the counterfactual sample. Findings suggest that the relationship between religiousness and hope is best understood when it incorporates youth’s spirituality and social connections associated with religion.

ABSTRACT: The concept of a ubiquitous city, or uCity, is gaining attention worldwide. In a uCity, anyone is enabled by information and communication technologies (ICT) to do anything, anywhere, at any time. The uCity concept has spread more quickly than its implementation, which relies on a complex set of interrelated technologies, practices, and actors, including but not limited to the provision of ICT infrastructure, the availability and accessibility of information and services, and the adoption of mobile communication devices by a variety of users. To aid in measuring and implementing a uCity, we explore ways to measure the “ubiquity” of a city, with particular attention given to the first “A” above – i.e., “anyone”. Empirical findings from Chicago highlight: 1) ICT access, 2) the connectivity of institutions and individuals, and 3) the ubiquity of virtuality. A socio-technical perspective and social network and social capital theories guide this study. The underlying social and motivational processes are essential to all aspects of becoming a uCity. KEYWORDS: Ubiquitous city, urban planning, community informatics, Chicago

Neurobiological studies of aging are beginning to link functional changes with a loss of experience-dependent plasticity. In the visual system, age-related functional changes include decreases in visual acuity, orientation selectivity, motion perception, and ocular dominance plasticity. A recent paper has shown that Ube3A, an E3 ubiquitin ligase that is absent in Angelman's Syndrome, is required for experience-dependent plasticity during development of the visual cortex. Knocking out Ube3A during development leads to rigidity of ocular dominance plasticity that is strikingly similar to the reduced plasticity seen in older animals. Furthermore, ubiquitin ligases have been linked with age-related neurodegenerative disorders and longevity. Ubiquitin ligases selectively mark proteins for degradation, and a balance between synaptic proteins and their degradation is important for neural transmission and plasticity. This led us to ask whether normal aging is characterized by a loss of Ube3A in the cortex. We used Western blot analysis in order to quantify Ube3A expression across the life span of humans, macaque monkeys, and cats. We found that Ube3A expression declines across the lifespan in human, monkey, and cat cortex. The losses were substantial (50-80%) in all areas studied which includes V1, V3, V4, frontal, and auditory cortex. In addition, when compared with other synaptic proteins there was a selective loss of Ube3A in human cortex. The progressive loss of Ube3A expression during cortical aging is an important new finding. Furthermore, the selective loss of Ube3A in human cortex highlights a specific vulnerability in human brain aging that may signify a dramatic shift in cortical function and plasticity.

This paper is based on the experiences of two criminological researchers and their reflections of undertaking ethnographic study. We first set out and briefly discuss our methodological standpoint. Then, by examining the differences in our backgrounds and biographies, we begin reflecting on how these influences have impacted upon our motivations for studying and our choice of research areas. We then consider how our biographies have also influenced the fieldwork conducted. We argue that by viewing the researcher as a ‘subjective subject’ – and therefore an integral part of the research process (together with drawing upon the analytic realist concept of ‘reflexive accounting’ (Altheide and Johnson, 1994)) – it is possible to create a more accurate representation of ethnographic research findings. Furthermore, we argue that similar reflexivity might be employed by other researchers, as this process may in itself yield a rich source of valid data.

Sing & Grow is an early intervention music therapy project that provides community group music therapy programs to families with young children who encounter risk factors that may impact on parenting and optimal child development. A variety of evaluation tools were devised and used over the first 3 years of the project. Upon the subsequent funding and expansion of the project at the end of this period, it was necessary to find, test and devise more rigorous, valid and reliable measures to withstand the scrutiny of researchers, and to combat the concerns and criticisms associated with the previous methods of data collection. An action inquiry project was therefore undertaken with two groups of project participants to trial the use of the Parenting Stress Index and Depression, Anxiety and Stress Scales, both recommended by leading psychologists. Key findings that will be discussed include the friction between the deficit-focussed nature of many psychometric tools and the strengths-based approach taken in service delivery, the level of difficulty in terms of literacy and comprehension for vulnerable respondents, and the lack of one tool with the ability to comprehensively measure all aspects of a broad scoping program.