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To report our experience using version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). Two reviewers independently applied RoB 2 to results of interest in a large systematic review of complex interventions and reached consensus. We recorded the time taken, and noted and discussed our difficulties using the tool, and the resolutions we adopted. We explored the time taken with regression analysis and summarized our experience of implementing the tool. We assessed risk of bias in 860 results of interest in 113 studies. Staff resource averaged 358 minutes per study (SD 183). Number of results (β = 22) and reports (β = 14) per study and experience of the team (β = −6) significantly affected assessment time. To implement the tool consistently, we developed cut points for missingness and considerations of balance regarding missingness, assumed some concerns with intervention deviations unless otherwise prevented or investigated, some concerns with measurements from unblinded self-reporting participants, and judged low risk of selection for certain dichotomous outcomes despite the absence of an analysis plan. The RoB 2 tool and guidance are useful but resource-intensive and challenging to implement. Critical appraisal tools and reporting guidelines should detail risk of bias implementation. Improved guidance focusing on implementation could assist reviewers.

Stroke is a leading cause of serious, long-term disability, the effects of which may be prolonged with physical, emotional, social, and financial consequences not only for those affected but also for their family and friends. Evidence for the effectiveness of stroke unit care and the benefits of thrombolysis have transformed treatment for people after stroke. Previously viewed nihilistically, stroke is now seen as a medical emergency with clear evidence-based care pathways from hospital admission to discharge. However, stroke remains a complex clinical condition that requires health professionals to work together to bring to bear their collective knowledge and specialist skills for the benefit of stroke survivors. Multidisciplinary team working is regarded as fundamental to delivering effective care across the stroke pathway. This paper discusses the contribution of team working in improving recovery at key points in the post-stroke pathway.

Self-management is a promising approach to improve quality of life after stroke. However, evidence for the appropriateness and effectiveness of self-management for stroke survivors with aphasia is limited. This article reports on the process used to develop a supported self-management intervention for stroke survivors with aphasia (SSWA) using co-production and behaviour change theory. Preparatory research included systematic reviews, and qualitative interviews and focus groups with SSWA, family members and speech and language therapists (SLTs). We conducted six, 2 hour long intervention development workshops with key stakeholders. The workshops were informed by principles of co-production and the intervention development process outlined by the Behaviour Change Wheel (BCW). We also incorporated the findings of our preparatory research within workshops. Each workshop included an introduction, 1-2 co-production tasks and time for feedback at the end of the session. Data were analysed on an ongoing basis so that findings could be used to feed in to subsequent workshops and intervention development. Workshop participants (n = 12) included; SSWA (n = 5), family members (n = 3) and SLTs (n = 4). Together, participants engaged with accessible and participatory co-production tasks which aligned with the BCW framework. Participants engaged in discussion to define self-management in behavioural terms (behavioural diagnosis) and to identify what needed to change to support self-management. Participant's co-produced solutions for supporting self-management and discussed options to implement these in practice. Prototype materials were generated by the research team and evaluated by participants. Intervention functions and behaviour change techniques (BCTs) were mapped to the solutions generated by participants by the research team, after the final workshop. A supported self-management intervention for SSWA was developed which will be delivered by SLTs through community stroke services. This paper reports the process we used to integrate co-production work with behaviour change theory to develop a complex self-management intervention. This is of relevance for researchers looking to harness the strengths of co-production methods and theory in intervention design. Future research will feasibility test the supported self-management intervention developed. This paper provides transparency to our intervention development process which will help others to better interpret the findings of our feasibility work.

WebStructural details of how oncogenic human papilloma viruses induce cancer by targeting the tumour suppressor p53 for ubiquitin-mediated degradation. Viral hijack of p53 tumour suppressor Oncogenic human papillomaviruses induce cancer by targeting the tumour suppressor p53 for ubiquitin-mediated degradation. Katia Zanier and colleagues now reveal structural details of how this viral hijacking occurs. They solve the structure of a ternary complex revealing the interaction between the HPV16 oncoprotein E6, the LxxLL motif of the cellular ubiquitin ligase E6AP, and the core domain of p53. The p53 pro-apoptotic tumour suppressor is mutated or functionally altered in most cancers. In epithelial tumours induced by ‘high-risk’ mucosal human papilloma viruses, including human cervical carcinoma and a growing number of head-and-neck cancers 1 , p53 is degraded by the viral oncoprotein E6 (ref. 2 ). In this process, E6 binds to a short leucine (L)-rich LxxLL consensus sequence within the cellular ubiquitin ligase E6AP 3 . Subsequently, the E6/E6AP heterodimer recruits and degrades p53 (ref. 4 ). Neither E6 nor E6AP are separately able to recruit p53 (refs 3 , 5 ), and the precise mode of assembly of E6, E6AP and p53 is unknown. Here we solve the crystal structure of a ternary complex comprising full-length human papilloma virus type 16 (HPV-16) E6, the LxxLL motif of E6AP and the core domain of p53. The LxxLL motif of E6AP renders the conformation of E6 competent for interaction with p53 by structuring a p53-binding cleft on E6. Mutagenesis of critical positions at the E6–p53 interface disrupts p53 degradation. The E6-binding site of p53 is distal from previously described DNA- and protein-binding surfaces of the core domain. This suggests that, in principle, E6 may avoid competition with cellular factors by targeting both free and bound p53 molecules. The E6/E6AP/p53 complex represents a prototype of viral hijacking of both the ubiquitin-mediated protein degradation pathway and the p53 tumour suppressor pathway. The present structure provides a framework for the design of inhibitory therapeutic strategies against oncogenesis mediated by human papilloma virus.

Background Research protocols regarding the use of ActiGraph wGT3X+ accelerometers in care home residents are yet to be established. The purpose of this study was to identify the minimal wear time criteria required to achieve reliable estimates of physical activity (PA) and sedentary behaviour (SB) in older care home residents. Methods Ninety-four older adults from 14 care homes wore an ActiGraph wGT3X+ accelerometer on the right hip for 7 consecutive days. A pragmatic, staged approach was adopted in order to explore the effect of: monitoring day; minimum daily wear time and number of wear days on estimates of four outcomes derived from the accelerometer data: counts . day − 1 , counts . minute − 1 , PA time and SB time. Results Data from 91 participants (mean age: 84 ± 9 years, 34% male) was included in the analysis. No effect of monitoring day was observed. Lowering the daily wear time to ≥ 8 h (compared to ≥10 h) had no effect on the outcomes of interest. Four days of monitoring was sufficient to provide reliable estimates of all four outcomes. Conclusion In this study, a minimum wear time criterion of ≥ 8 h on any 4 days was required to derive reliable estimates of PA and SB from ActiGraph wGT3X+ accelerometer data in older care home residents.

(1) Background: This study presents an adaptive, contactless, and privacy-preserving respiratory-rate monitoring system based on thermal imaging, designed for real-time operation on embedded edge hardware. The system continuously processes temperature data from a compact thermal camera without external computation, enabling practical deployment for home or clinical vital-sign monitoring. (2) Methods: Thermal frames are captured using a 256×192 TOPDON TC001 camera and processed entirely on an NVIDIA Jetson Orin Nano. A YOLO-based detector localizes the nostril region in every even frame (stride = 2) to reduce the computation load, while a Kalman filter predicts the ROI position on skipped frames to maintain spatial continuity and suppress motion jitter. From the stabilized ROI, a temperature-based breathing signal is extracted and analyzed through an adaptive median–MAD hysteresis algorithm that dynamically adjusts to signal amplitude and noise variations for breathing phase detection. Respiratory rate (RR) is computed from inter-breath intervals (IBI) validated within physiological constraints. (3) Results: Ten healthy subjects participated in six experimental conditions including resting, paced breathing, speech, off-axis yaw, posture (supine), and distance variations up to 2.0 m. Across these conditions, the system attained a MAE of 0.57±0.36 BPM and an RMSE of 0.64±0.42 BPM, demonstrating stable accuracy under motion and thermal drift. Compared with peak-based and FFT spectral baselines, the proposed method reduced errors by a large margin across all conditions. (4) Conclusions: The findings confirm that accurate and robust respiratory-rate estimation can be achieved using a low-resolution thermal sensor running entirely on an embedded edge device. The combination of YOLO-based nostril detector, Kalman ROI prediction, and adaptive MAD–hysteresis phase that self-adjusts to signal variability provides a compact, efficient, and privacy-preserving solution for non-invasive vital-sign monitoring in real-world environments.

(1) Background: Detecting long-lie incidents—where individuals remain immobile after a fall—is essential for timely intervention and preventing severe health consequences. However, most existing systems focus only on fall detection, neglect post-fall monitoring, and raise privacy concerns, especially in real-time, non-invasive applications; (2) Methods: This study proposes a lightweight, privacy-preserving, long-lie detection system utilizing thermal imaging and a soft-voting ensemble classifier. A low-resolution thermal camera captured simulated falls and activities of daily living (ADL) performed by ten healthy participants. Human pose keypoints were extracted using MediaPipe, followed by the computation of five handcrafted postural features. The top three classifiers—automatically selected based on cross-validation performance—formed the soft-voting ensemble. Long-lie conditions were identified through post-fall immobility monitoring over a defined period, using rule-based logic on posture stability and duration; (3) Results: The ensemble model achieved high classification performance with accuracy, precision, recall, and an F1 score of 0.98. Real-time deployment on a Raspberry Pi 5 demonstrated the system is capable of accurately detecting long-lie incidents based on continuous monitoring over 15 min, with minimal posture variation; (4) Conclusion: The proposed system introduces a novel approach to long-lie detection by integrating privacy-aware sensing, interpretable posture-based features, and efficient edge computing. It demonstrates strong potential for deployment in homecare settings. Future work includes validation with older adults and integration of vital sign monitoring for comprehensive assessment.

Background Older adults are the most sedentary and fastest-growing demographic, yet adults aged ≥ 75 years are underrepresented in sedentary behaviour research. This study qualitatively explored how this age group perceives sedentary behaviour, the activities they perform in sitting and standing, and the barriers and facilitators to reducing their sedentary behaviour. Methods Four focus groups were conducted with a consistent group of 6 community-dwelling older adults aged ≥ 75 years from West Yorkshire were held between October-December 2022. Audio recordings and focus group notes were transcribed verbatim and an inductive and deductive thematic analysis was conducted. The activities performed in sitting and standing were charted to the ecological model of sedentary behaviour, and barriers and facilitators to reducing sedentary time were charted to the Capability Opportunity Motivation-Behaviour (COM-B) framework. Results Participants were largely unaware of their sedentary behaviour or the associated health risks. Sitting activities were predominantly leisurely in nature, and occurred in older adults’ homes. Barriers and facilitators to reducing sedentary behaviour were mapped to the COM-B model. Key influences included physical and mental health, environmental constraints, social support, ingrained routines, and limited awareness of the health impacts of prolonged sitting. Analytical themes included the perceived progression of sedentary behaviour throughout older adulthood; the impact of prolonged sitting on sleep; and the role of social connectedness in reducing sedentary time. Conclusions This study provided insights into older adults’ reports of sedentary behaviour progressing throughout older adulthood. When compared to the wider literature, sedentary behaviour in adults aged ≥ 75 years present similarly to a younger subset of older adults with regards to the activities performed in sitting, and the barriers and facilitators to reducing their sedentary time. However, the activities performed in sitting may be performed for longer, and the barriers to reducing sedentary behaviour may present more frequently. Social support appears valuable when attempting to reduce sedentary time, however, further research is necessary to explore the views of older adults who are socially isolated.

Background Older adults are the fastest-growing and most sedentary group in society. As sedentary behaviour is associated with deleterious health outcomes, reducing sedentary time may improve overall well-being. This mixed-methods systematic review aimed to systematically review quantitative and qualitative studies examining interventions to reduce sedentary behaviour in community-dwelling older adults (aged ≥ 65 years). Methods Medline, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Cinahl, SportDiscus, and PEDRO were searched from inception to July 2025. We included quantitative studies (randomised-controlled trials (RCTs) and cluster RCTs), qualitative studies (semi-structured interviews or focus groups), and mixed-method studies exploring interventions to reduce sedentary behaviour in community-dwelling older adults. Studies were appraised using the Mixed Method Appraisal Tool. Quantitative evidence was meta-analysed; qualitative evidence was thematically synthesised, with both combined in a mixed-method synthesis. The Behaviour Change Techniques employed were charted and analysed. Results Fifty-six studies (16 RCTs, 30 qualitative, and 10 mixed-method studies) were included. When pooled, interventions reduced sedentary behaviour by 27.53 min/day (95% CI: − 57.43 to 2.37), with greater reductions observed via self-report (–83.65 min/day) than device measures (–11.61 min/day). Using ≥ 11 BCTs (-24.01 min/day) was more effective than using 1–10 ( 9.24 min/day). Analytical themes included what sitting means to older adults, expectations of ageing, and social influence in older adults. The mixed-method synthesis identified that existing interventions are limited by recruited samples that are not representative of the wider population of older adults, and intervention design and outcome measurement selection that is not consistent with older adults’ priorities. Conclusions Interventions to reduce sedentary behaviour in community-dwelling older adults are somewhat effective at reducing sedentary time. Future research should focus on inclusive recruitment strategies to recruit underrepresented populations, incorporate outcome measures valued by older adults, and align intervention content with their preferences. PROSPERO registration number CRD42021264954.

Understanding recovery is important for patients with stroke and their families, including how much recovery is expected and how long it might take. These conversations can however be uncomfortable for stroke unit staff, particularly when they involve breaking bad news. This study aimed to begin development of a novel complex intervention to improve conversations about recovery on stroke units. Informed by previously collected qualitative data, we used the Behaviour Change Wheel (BCW) approach to identify possible 1. barriers to communication about recovery on stroke units; 2. Intervention Functions; 3. Behaviour Change Techniques (BCTs) to incorporate in an intervention. We subsequently sought stroke professionals' perspectives through an online survey. Respondents rated the importance of barriers for intervention inclusion and evaluated the usefulness and feasibility of the suggested BCTs. Our behavioural diagnosis identified a target behaviour of provision of information about recovery by stroke unit professionals to patients and carers. Twelve possible barriers to this behaviour were identified, with six potential Intervention Functions to address them, and 29 BCTs. Forty-eight multidisciplinary professionals responded to the survey. The six barriers rated as most important to address were: lack of confidence; perceptions of insufficient communication skills; lack of knowledge of the benefits; difficulties in deciding when and in what format to provide information; absence of private spaces for discussions; and lack of generic written information to support conversations. The developed intervention strategy comprised twelve clinically feasible and useful BCTs, encompassing the Intervention Functions of Training, Enablement, Persuasion, and Environmental restructuring. The BCW approach was successfully used to begin development of an intervention to improve conversations about recovery on the stroke unit; our survey enabled incorporation of stakeholder perspectives. Further development work is required to design intervention materials and test whether the strategies are effective in improving staff and patient outcomes.