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Loss of surface CD19 expression by leukemic cells leads to resistance and relapse to CD19-targeted CAR-T therapies. Here the authors show that loss of SPPL3 in malignant B cells results in hyperglycosylation of CD19.

Introduction: Limited research exists on substance-related acute toxicity deaths (ATDs) in older adults (=60 years) in Canada. This study aims to examine and describe the sociodemographic characteristics, health histories and circumstances of death for accidental ATDs among older adults. Methods: Following a retrospective descriptive analysis of all coroner and medical examiner files on accidental substance-related ATDs in older adults in Canada from 2016 to 2017, proportions and mortality rates for coroner and medical examiner data were compared with general population data on older adults from the 2016 Census. Chisquare tests were conducted for categorical variables where possible. Results: From 2016 to 2017, there were 705 documented accidental ATDs in older adults. Multiple substances contributed to 61% of these deaths. Fentanyl, cocaine and ethanol (alcohol) were the most common substances contributing to death. Heart disease (33%), chronic pain (27%) and depression (26%) were commonly documented. Approximately 84% of older adults had contact with health care services in the year preceding their death. Only 14% were confirmed as having their deaths witnessed. Conclusions: Findings provide insight into the demographic, contextual and medical history factors that may influence substance-related ATDs in older adults and suggest key areas for prevention. [ABSTRACT FROM AUTHOR]

In 2023, a major Hollywood film company celebrated its 100th birthday, and almost no one blinked an eye. That studio was Warner Brothers, which was founded on 4 April 1923 by brothers Harry, Albert, Sam, and Jack Warner. But on 16 October 2023, another major Hollywood film company—the Walt Disney Company, founded on 16 October 1923 by brothers Walt and Roy Disney—celebrated its 100th birthday with much more fanfare. In early 2023, it began a year-long celebration of its centenary. The first thing it did was launch an entire product line—Disney Eras—in which Disney’s history was celebrated, decade by decade, with merchandise that either reproduced or evoked important places, moments, and characters of the studio’s history.

Abstract Breast Cancer is the most common cancer among women globally. Despite significant improvements in overall survival, many tumours are refractory to therapy and so novel approaches are required to improve patient outcomes. We have evaluated patient-derived explants (PDEs) as a novel preclinical platform for breast cancer (BC) and implemented cutting-edge digital pathology and multi-immunofluorescent approaches for investigating biomarker changes in both tumour and stromal areas at endpoint. Short-term culture of intact fragments of BCs as PDEs retained an intact immune microenvironment, and tumour architecture was augmented by the inclusion of autologous serum in the culture media. Cell death/proliferation responses to FET chemotherapy in BC-PDEs correlated significantly with BC patient progression-free survival (p = 0.012 and p = 0.0041, respectively) and cell death responses to the HER2 antibody therapy trastuzumab correlated significantly with HER2 status (p = 0.018). These studies show that the PDE platform combined with digital pathology is a robust preclinical approach for informing clinical responses to chemotherapy and antibody-directed therapies in breast cancer. Furthermore, since BC-PDEs retain an intact tumour architecture over the short-term, they facilitate the preclinical testing of anti-cancer agents targeting the tumour microenvironment.

Abstract Background Cameroon is one of the countries with the highest burden of malaria. Since 2018, there has been an ongoing conflict in the country, which has reduced access to healthcare for populations in affected regions, and little is known about the impact on access to malaria services. The objective of this study was to understand the current situation regarding access to malaria services in Cameroon to inform the design of interventions to remove barriers and encourage the use of available services. Methods A qualitative research study was carried out to understand the barriers preventing communities accessing care, the uptake of community health worker (CHW) services, and to gather perceptions on community engagement approaches, to assess whether these could be an appropriate mechanism to encourage uptake of community health worker (CHW) services. Twenty-nine focus group discussions and 11 in-depth interviews were carried out between May and July 2021 in two regions of Cameroon, Southwest and Littoral. Focus group discussions were held with CHWs and community members and semi-structured, in-depth interviews were conducted with key stakeholders including regional government staff, council staff, community leaders and community-based organisations. The data were analysed thematically; open, descriptive coding was combined with exploration of pre-determined investigative areas. Results The study confirmed that access to healthcare has become increasingly challenging in conflict-affected areas. Although the Ministry of Health are providing CHWs to improve access, several barriers remain that limit uptake of these services including awareness, availability, cost, trust in competency, and supply of testing and treatment. This study found that communities were supportive of community engagement approaches, particularly the community dialogue approach. Conclusion Communities in conflict-affected regions of Cameroon continue to have limited access to healthcare services, in part due to poor use of CHW services provided. Community engagement approaches can be an effective way to improve the awareness and use of CHWs. However, these approaches alone will not be sufficient to resolve all the challenges faced by conflict-affected communities when accessing health and malaria services. Additional interventions are needed to increase the availability of CHWs, improve the supply of diagnostic tests and treatments and to reduce the cost of treatment for all.

Abstract Background Malaria remains a major global health problem often worsened by political instability and armed conflict. The purpose of the study was to explore community knowledge, attitudes and practices on malaria prevention, and to understand the burden of malaria and health-seeking behaviours of caregivers of children under-five in conflict-affected communities of the South West and Littoral Regions of Cameroon. Methods A cross-sectional survey involving internally displaced persons (IDPS), host population, and their children under-five was conducted across 80 communities. The survey was conducted from May to June 2021. Participants were interviewed using a structured questionnaire. Malaria prevalence for children under-five was determined using rapid diagnostic tests (RDT) on blood samples. Association between variables and displacement status was measured using chi square test and multivariate logistic regression model was fitted to identify factors associated with adequate knowledge on malaria prevention. Results A total of 2386 adults participated in the study and 1543 RDTs were conducted for children under-five. Adequate levels of knowledge and attitudes on malaria prevention was recorded among 1258 (52.9%) of the participants, with very strong evidence to suggest the level to be higher among the host (59.5%) compared to the IDPs (49.5%) and returnees (39.7%) (p

Multiple sclerosis (MS) is a chronic neuroinflammatory disease characterized by central nervous system demyelination and axonal degeneration. Fatigue affects a major portion of MS patients, significantly impairing their daily activities and quality of life. Despite its prevalence, the mechanisms underlying fatigue in MS are poorly understood, and measuring fatigue remains a challenging task. This study evaluates the efficacy of automated speech analysis in detecting fatigue in MS patients. MS patients underwent a detailed clinical assessment and performed a comprehensive speech protocol. Using features from three different free speech tasks and a proprietary cognition score, our support vector machine model achieved an AUC on the ROC of 0.74 in detecting fatigue. Using only free speech features evoked from a picture description task we obtained an AUC of 0.68. This indicates that specific free speech patterns can be useful in detecting fatigue. Moreover, cognitive fatigue was significantly associated with lower speech ratio in free speech (ρ = −0.283, p = 0.001), suggesting that it may represent a specific marker of fatigue in MS patients. Together, our results show that automated speech analysis, of a single narrative free speech task, offers an objective, ecologically valid and low-burden method for fatigue assessment. Speech analysis tools offer promising potential applications in clinical practice for improving disease monitoring and management.

Introduction Traditionally, wards in acute care hospitals consist predominately of multioccupancy bays with some single rooms. There is an increasing global trend towards a higher proportion of single rooms in hospitals, with the UK National Health Service (NHS) advocating for single-room provision in all new hospital builds. There is limited evidence on the impact of a ward environment incorporating mostly single and some multioccupancy bays on patient care and organisational outcomes.Methods and analyses This study will assess the impact of a newly designed 28-bedded ward environment, with 20 single rooms and two four-bedded bays, on patient and staff experiences and outcomes in an acute NHS Trust in East England. The study is divided into two work packages (WP)—WP1 is a quantitative data extraction of routinely collected patient and staff data while WP2 is a mixed-methods process evaluation consisting of one-to-one, in-depth, semistructured interviews with staff, qualitative observations of work processes on the ward and a quantitative data evaluation of routinely collected process evaluation data from patients and staff.Ethics and dissemination Ethical approval was obtained from the UK Health Research Authority (IRAS ID: 334395). Study findings will be shared with key stakeholders, published in peer-reviewed high-impact journals and presented at relevant conferences.

Abstract Background Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disease caused by inherited or de novo germline pathogenic variants in TP53. Individuals with LFS have a 70–100% lifetime risk of developing cancer. The current standard of care involves annual surveillance with whole-body and brain MRI (WB-MRI) and clinical review; however, there are no chemoprevention agents licensed for individuals with LFS. Preclinical studies in LFS murine models show that the anti-diabetic drug metformin is chemopreventive and, in a pilot intervention trial, short-term use of metformin was well-tolerated in adults with LFS. However, metformin’s mechanism of anticancer activity in this context is unclear. Methods Metformin in adults with Li-Fraumeni syndrome (MILI) is a Precision-Prevention phase II open-labelled unblinded randomised clinical trial in which 224 adults aged ≥ 16 years with LFS are randomised 1:1 to oral metformin (up to 2 mg daily) plus annual MRI surveillance or annual MRI surveillance alone for up to 5 years. The primary endpoint is to compare cumulative cancer-free survival up to 5 years (60 months) from randomisation between the intervention (metformin) and control (no metformin) arms. Secondary endpoints include a comparison of cumulative tumour-free survival at 5 years, overall survival at 5 years and clinical characteristics of emerging cancers between trial arms. Safety, toxicity and acceptability of metformin; impact of metformin on quality of life; and impact of baseline lifestyle risk factors on cancer incidence will be assessed. Exploratory end-points will evaluate the mechanism of action of metformin as a cancer preventative, identify biomarkers of response or carcinogenesis and assess WB-MRI performance as a diagnostic tool for detecting cancers in participants with LFS by assessing yield and diagnostic accuracy of WB-MRI. Discussion Alongside a parallel MILI study being conducted by collaborators at the National Cancer Institute (NCI), MILI is the first prevention trial to be conducted in this high-risk group. The MILI study provides a unique opportunity to evaluate the efficacy of metformin as a chemopreventive alongside exploring its mechanism of anticancer action and the biological process of mutated P53-driven tumourigenesis. Trial registration ISRCTN16699730. Registered on 28 November 2022. URL: https://www.isrctn.com/ EudraCT/CTIS number 2022-000165-41.

There have been few, if any, open data and information management policies openly published from natural science collections. This paper contextualises the rationale for publishing the Open Information and Exceptions Policy of the Natural History Museum, London and provides the policy itself. The policy outlines how the Natural History Museum puts the principle of 'open by default' into practice; and includes sections on purpose and scope, relationship to relevant legislation (which always takes precedence over the policy), the categories of possible exceptions to open information release, what happens when exceptions are declared, relations to UK government information security classifications and definition of terms.

Many larger museums and archives have begun to implement a centralized approach to digitization of collections by creating Digitization Coordinator positions. This new effort has initiated a singular vision for digitization that incorporates priorities, workflows, and resources to greatly improve the efficiency and throughput of digitization in collections. Smaller institutions are now starting to see the benefit of creating a more structured cross-disciplinary approach to digitization, allowing for better awareness and resourcing of digitization needs.The workshop brought together natural sciences digitization professionals from the USA and EU, highlighting lessons learned and best practices to realize the benefits of a coordinated approach including advocacy for digitization, accelerating digitization efficiency and, ultimately, increasing digital collections access and usability to address societal challenges, such as biodiversity decline. Insights, lessons learned and initial thoughts on best practices are described, and the supporting workshop resources are shared so that others can benefit.

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (

Background Long-term survival after lung transplantation is limited compared with other organ transplants. The main cause is development of progressive immune-mediated damage to the lung allograft. This damage, which can develop via multiple immune pathways, is captured under the umbrella term chronic lung allograft dysfunction (CLAD). Despite the availability of powerful immunosuppressive drugs, there are presently no treatments proven to reverse or reliably halt the loss of lung function caused by CLAD. The aim of the E-CLAD UK trial is to determine whether the addition of immunomodulatory therapy, in the form of extracorporeal photopheresis (ECP), to standard care is more efficacious at stabilising lung function in CLAD compared with standard care alone.Methods and analysis E-CLAD UK is a Phase II clinical trial of an investigational medicinal product (Methoxsalen) delivered to a buffy coat prepared via an enclosed ECP circuit. Target recruitment is 90 bilateral lung transplant patients identified as having CLAD and being treated at one of the five UK adult lung transplant centres. Participants will be randomised 1:1 to intervention plus standard of care, or standard of care alone. Intervention will comprise nine ECP cycles spread over 20 weeks, each course involving two treatments of ECP on consecutive days. All participants will be followed up for a period of 24 weeks.The primary outcome is lung function stabilisation derived from change in forced expiratory volume in one second and forced vital capacity at 12 and 24 weeks compared with baseline at study entry. Other parameters include change in exercise capacity, health-related quality of life and safety. A mechanistic study will seek to identify molecular or cellular markers linked to treatment response and qualitative interviews will explore patient experiences of CLAD and the ECP treatment.A patient and public advisory group is integral to the trial from design to implementation, developing material to support the consent process and interview materials.Ethics and dissemination The East Midlands—Derby Research Ethics Committee has provided ethical approval (REC 22/EM/0218). Dissemination will be via publications, patient-friendly summaries and presentation at scientific meetings.Trial registration number EudraCT number 2022-002659-20; ISRCTN 10615985.

Abstract Strength training recommendations have been embedded within the UK’s Chief Medical Officers’ physical activity guidelines since 2011. There is limited evidence that these recommendations are used by exercise instructors in the community to underpin strength training prescription in the older adult population. This study aimed to explore exercise instructors’ awareness and utilisation of the guidelines when prescribing strength training to older adults. Fifteen exercise instructors working with older adults in the UK participated in one online interview. A general inductive approach was conducted and thematic analysis allowed for major themes to be identified from the raw data. We found that most exercise instructors (n = 9), but not all (n = 6), were aware of the guidelines. Only one instructor (n = 1) had reportedly implemented the guidelines into their practice; other instructors reported that the guidelines were irrelevant. Instead, each of the instructors had their preferred sources of information that they relied on to underpin their exercise prescription, and each had their own interpretation of ‘evidence-based strength training.’ This individualised interpretation resulted in exceptionally varied prescription in the community and does not necessarily align with the progressive, evidence-based prescription known to build muscular strength. We suggest that (i) more detail on how to build muscular strength be embedded within the guidelines, (ii) a handbook on how to implement the guidelines be made available, (iii) theoretical and practical teaching materials and courses be updated, and/or (iv) a re-(education) of exercise instructors already in the field may be necessary to bring about a consistent, evidence-based strength prescription necessary for the best possible health and longevity outcomes for our ageing population.

There are approximately 1.5 billion specimens kept in European Natural History Collections. The mission for the Distributed System of Scientific Collections (DiSSCo) is to unite all these specimens into a one-stop e-science infrastructure of digital specimens. This is a monumental digitisation task and criteria for how to prioritise this effort are, therefore, crucial for the success of the project. In this report, we have reviewed the literature and designed and conducted surveys of the digitisation plans and criteria used by DiSSCo Partners to understand the prioritisation criteria used in the digitisation of natural history collections. As an attempt to provide some guidance for the digitisation of specimens, we suggest that an organisation (e.g. DiSSCo or an individual institution) that is planning to digitise natural history collections considers four categories of prioritisation criteria: Relevance, Data quality, Cost and Feasibility.

Tens of millions of images from biological collections have become available online over the last two decades. In parallel, there has been a dramatic increase in the capabilities of image analysis technologies, especially those involving machine learning and computer vision. While image analysis has become mainstream in consumer applications, it is still used only on an artisanal basis in the biological collections community, largely because the image corpora are dispersed. Yet, there is massive untapped potential for novel applications and research if images of collection objects could be made accessible in a single corpus. In this paper, we make the case for infrastructure that could support image analysis of collection objects. We show that such infrastructure is entirely feasible and well worth investing in.

Abstract Background The Active Connected Engaged [ACE] study is a multi-centre, pragmatic, two-arm, parallel-group randomised controlled trial [RCT] with an internal pilot phase. The ACE study incorporates a multi-level mixed methods process evaluation including a systems mapping approach and an economic evaluation. ACE aims to test the effectiveness and cost-effectiveness of a peer-volunteer led active ageing intervention designed to support older adults at risk of mobility disability to become more physically and socially active within their communities and to reduce or reverse, the progression of functional limitations associated with ageing. Methods/design Community-dwelling, older adults aged 65 years and older (n = 515), at risk of mobility disability due to reduced lower limb physical functioning (Short Physical Performance Battery (SPPB) score of 4–9 inclusive) will be recruited. Participants will be randomised to receive either a minimal control intervention or ACE, a 6-month programme underpinned by behaviour change theory, whereby peer volunteers are paired with participants and offer them individually tailored support to engage them in local physical and social activities to improve lower limb mobility and increase their physical activity. Outcome data will be collected at baseline, 6, 12 and 18 months. The primary outcome analysis (difference in SPPB score at 18 months) will be undertaken blinded to group allocation. Primary comparative analyses will be on an intention-to-treat (ITT) basis with due emphasis placed on confidence intervals. Discussion ACE is the largest, pragmatic, community-based randomised controlled trial in the UK to target this high-risk segment of the older population by mobilising community resources (peer volunteers). A programme that can successfully engage this population in sufficient activity to improve strength, coordination, balance and social connections would have a major impact on sustaining health and independence. ACE is also the first study of its kind to conduct a full economic and comprehensive process evaluation of this type of community-based intervention. If effective and cost-effective, the ACE intervention has strong potential to be implemented widely in the UK and elsewhere. Trial registration ISRCTN, ISRCTN17660493. Registered on 30 September 2021. Trial Sponsor: University of Birmingham, Contact: Dr Birgit Whitman, Head of Research Governance and Integrity; Email: researchgovernance@contacts.bham.ac.uk. Protocol Version 5 22/07/22.

As a highly decentralised research infrastructure, the Distributed System of Scientific Collections (DiSSCo) will need to develop cross-institutional teams, adopting work practices where individual staff are intensively working collectively on common tasks in a distributed environment. These flexible and distributed working practices will be essential to the delivery of the research infrastructure across a wide range of delivery partners and a geographically dispersed set of scarce resources and skills, particularly in more technical roles. Since work to consider secondment and distributed working in DiSSCo was first envisaged, there has been a step change in distributed working owing to the Covid-19 pandemic and lockdowns or other restrictions to where work could take place. This report examines distributed team working practices and how they have changed, through interviews with a range of key roles across DiSSCo Prepare institutions. It briefly examines key project management and technical team delivery techniques. It documents how some of these approaches have been piloted within DiSSCo Prepare for the development, testing and delivery of DiSSCo Policy and Digital Maturity tools. Finally, bringing this together with previous work on secondment policies and practices for DiSSCo, we make recommendations about how secondment and distributed team working can be approached to enhance DiSSCo capabilities and the likelihood of successful implementation of the research infrastructure.

Abstract Antimicrobial resistance (AMR) is a social and biological problem. Although resistance to antimicrobials is a natural phenomenon, many human behaviors are increasing the pressure on microbes to develop resistance which is resulting in many commonly used treatments becoming ineffective. These behaviors include unregulated use of antimicrobial medicines, pesticides and agricultural chemicals, the disposal of heavy metals and other pollutants into the environment, and human-induced climatic change. Addressing AMR thus calls for changes in the behaviors which drive resistance. Community engagement for antimicrobial resistance (CE4AMR) is an international and interdisciplinary network focused on tackling behavioural drivers of AMR at community level. Since 2019 this network has worked within Low-Middle Income Countries (LMICs), predominantly within Southeast Asia, to tackle behavioral drivers of AMR can be mitigated through bottom-up solutions championed by local people. This commentary presents seven Key Concepts identified from across the CE4AMR portfolio as integral to tackling AMR. We suggest it be used to guide future interventions aimed at addressing AMR via social, participatory, and behavior-change approaches.

The Distributed System of Scientific Collections (DiSSCo) is a new world-class Research Infrastructure (RI) for Natural Science Collections. The DiSSCo RI aims to create a new business model for one European collection that digitally unifies all European natural science assets under common access, curation, policies and practices that ensure that all the data is easily Findable, Accessible, Interoperable and Reusable (FAIR principles). DiSSCo represents the largest ever formal agreement between natural history museums, botanic gardens and collection-holding institutions in the world.DiSSCo entered the European Roadmap for Research Infrastructures in 2018 and launched its main preparatory phase project (DiSSCo Prepare) in 2020. DiSSCo Prepare is the primary vehicle through which DiSSCo reaches the overall maturity necessary for its construction and eventual operation. DiSSCo Prepare raises DiSSCo’s implementation readiness level (IRL) across the five dimensions: technical, scientific, data, organisational and financial. Each dimension of implementation readiness is separately addressed by specific Work Packages (WP) with distinct targets, actions and tasks that will deliver DiSSCo’s Construction Masterplan. This comprehensive and integrated Masterplan will be the product of the outputs of all of its content related tasks and will be the project’s final output. It will serve as the blueprint for construction of the DiSSCo RI, including establishing it as a legal entity.DiSSCo Prepare builds on the successful completion of DiSSCo’s design study, ICEDIG and the outcomes of other DiSSCo-linked projects such as SYNTHESYS+ and MOBILISE.This paper is an abridged version of the original DiSSCo Prepare grant proposal. It contains the overarching scientific case for DiSSCo Prepare, alongside a description of our major activities.

Abstract Frailty is a medical condition common in older adults characterised by diminished strength and reduced physiologic function in which individuals are more vulnerable to multiple adverse health outcomes. Pre-frailty is an intermediate stage associated with some minor health outcomes. However, the main risk is progression toward moderate/severe frailty. Evidence shows physical activity interventions to be effective in slowing or modifying the progression of frailty. Researchers at the University of Manchester are developing a behaviour change intervention targeting pre-frail older adults, signposting them to group-based physical activity classes known to be effective for delaying/slowing frailty. This paper reports on the initial intervention development work with key stakeholders exploring the practicality of taking forward this intervention and identifying uncertainties to be explored in the feasibility stage. These included issues around physical activity messaging, the use of the term ‘frail’, identification/recruitment of pre-frail older adults, and the acceptability of behaviour change techniques. There was overwhelming support for a proactive approach to addressing pre-frailty issues. Given that a large proportion of older adults are estimated to be pre-frail, interventions aimed at this group have the potential to support healthy ageing, positively impacting on frailty outcomes and providing wider population health benefits.

UK natural science collections hold over 137 million items, an unrivalled source of data about 4.56 billion years of planetary development and hundreds of years of biological change, including the differences made by humans — but the scientific, commercial, and societal benefits of these collections are constrained by the limits of physical access, and by highly fragmented digitisation efforts with less than 10% digitally available. Following work with Frontier Economics in 2021, which showed potential for £2 billion in benefits to the UK economy from digitising all UK natural science collections, in 2022–23 the Natural History Museum London worked, with analytical support from McKinsey and Company, to understand the impact of what has already been digitised and shared by UK natural science collections — what is the demand for these data, what are they used for, and how does this deliver efficient, effective and impactful research?This study focuses on usage via the Global Biodiversity Information Facility, the largest source of relevant usage data, examining 7.6 million records from twelve UK institutions. While these UK collections data are just 0.3% of total GBIF occurrences, they are cited in 12% of peer reviewed publications citing GBIF data, showing the disproportionate impact of UK collections data and the historical, geographical, and taxonomic richness that they bring. Researchers have already benefited from more than £18 million of efficiency savings from digital UK specimen data. Data from natural science collections held in the UK are uniquely impactful resources, vital to a future in which people and planet thrive, and a step change in the pace of digitisation is needed to unlock their potential for researchers, policymakers, and society.

Background System mapping has mainly been used to develop theories and understanding of complex systems; to hypothesise how an intervention might work in a complex system or to inform intervention development. There are a few examples of the use of system mapping as part of process evaluation. In this paper, we describe an innovative approach to using system mapping as part of the process evaluation of a randomised controlled trial of the Active, Connected, Engaged (ACE) community-based active ageing programme.Method Ten participatory workshops were held across three of the ACE sites (Cardiff, Stoke-on-Trent and Manchester, UK). These involved over 100 participants, volunteers and stakeholders (from National Health Service, statutory and voluntary sectors). Their aim was to gather area-specific information on participants’ barriers and facilitators to physical activity and the needs of peer volunteers and service providers; and create ‘baseline’ system maps before the launch of the programme in the three areas of ACE delivery.Results System maps were produced showing the main outcome (physical activity) and the interactions between the key motivators and barriers described by older people, as well as ideas from stakeholders and volunteers about how these barriers can be addressed. Findings led to refinements to ACE intervention processes and the study’s logic model.Conclusions System mapping helped to refine the ACE processes and fine-tune the logic model. The value of this approach will increase in the next phase when it will be used to explore any changes to the physical activity system including changes to stakeholders’ ways of working and collaborating to tackle barriers to activity following the completion of the ACE trial.Trial registration number ISRCTN17660493.

Abstract Maximal exercise capacity is reduced at altitude or during hypoxia at sea level. It has been suggested that this might reflect increased right ventricular afterload due to hypoxic pulmonary vasoconstriction. We have shown previously that the pulmonary vascular sensitivity to hypoxia is enhanced by sustained isocapnic hypoxia, and inhibited by intravenous iron. In this study, we tested the hypothesis that elevated pulmonary artery pressure contributes to exercise limitation during acute hypoxia. Twelve healthy volunteers performed incremental exercise tests to exhaustion breathing 12% oxygen, before and after sustained (8‐h) isocapnic hypoxia at sea level. Intravenous iron sucrose (n = 6) or saline placebo (n = 6) was administered immediately before the sustained hypoxia. In the placebo group, there was a substantial (12.6 ± 1.5 mmHg) rise in systolic pulmonary artery pressure (SPAP) during sustained hypoxia, but no associated fall in maximal exercise capacity breathing 12% oxygen. In the iron group, the rise in SPAP during sustained hypoxia was markedly reduced (3.4 ± 1.0 mmHg). There was a small rise in maximal exercise capacity following sustained hypoxia within the iron group, but no overall effect of iron, compared with saline. These results do not support the hypothesis that elevated SPAP inhibits maximal exercise capacity during acute hypoxia in healthy volunteers.

Abstract Introduction Patient decision aids (PtDA) complement shared decision‐making with healthcare professionals and improve decision quality. However, PtDA often lack theoretical underpinning. We are codesigning a PtDA to help people with increased genetic cancer risks manage choices. The aim of an innovative workshop described here was to engage with the people who will use the PtDA regarding the theoretical underpinning and logic model outlining our hypothesis of how the PtDA would lead to more informed decision‐making. Methods Short presentations about psychological and behavioural theories by an expert were interspersed with facilitated, small‐group discussions led by patients. Patients were asked what is important to them when they make health decisions, what theoretical constructs are most meaningful and how this should be applied to codesign of a PtDA. An artist created a visual summary. Notes from patient discussions and the artwork were analysed using reflexive thematic analysis. Results The overarching theme was: It's personal. Contextual factors important for decision‐making were varied and changed over time. There was no one ‘best fit’ theory to target support needs in a PtDA, suggesting an inductive, flexible framework approach to programme theory would be most effective. The PtDA logic model was revised based on patient feedback. Conclusion Meaningful codesign of PtDA including discussions about the theoretical mechanisms through which they support decision‐making has the potential to lead to improved patient care through understanding the intricately personal nature of health decisions, and tailoring content and format for holistic care. Patient Contribution Patients with lived experience were involved in codesign and coproduction of this workshop and analysis as partners and coauthors. Patient discussions were the primary data source. Facilitators provided a semi‐structured guide, but they did not influence the patient discussions or provide clinical advice. The premise of this workshop was to prioritise the importance of patient lived experience: to listen, learn, then reflect together to understand and propose ideas to improve patient care through codesign of a PtDA.

Objectives Clinical communication needs of teenagers and young adults with cancer (TYACs) are increasingly recognised to differ significantly from younger children and older adults. We sought to understand who is present with TYACs, TYACs’ experiences of triadic communication and its impact. We generated three research questions to focus this review: (1) Who is present with TYACs in healthcare consultations/communication?, (2) What are TYACs’ experiences of communication with the supporter present? and (3) What is the impact of a TYAC’s supporter being present in the communication?Design Systematic review with narrative synthesis.Data sources The search was conducted across six databases: Medline, CINAHL, Embase, PsycINFO, Web of Science and AMED for all publications up to December 2023.Eligibility criteria for selecting studies Included papers were empirical research published after 2005; participants had malignant disease, diagnosed aged 13–24 years (for over 50% of participants); the research addressed any area of clinical communication.Data extraction and synthesis Three independent reviewers undertook full-text screening. A review-specific data extraction form was used to record participant characteristics and methods from each included paper and results relevant to the three review questions.Results A total of 8480 studies were identified in the search, of which 36 fulfilled the inclusion criteria. We found that mothers were the most common supporter present in clinical communication encounters. TYACs’ experiences of triadic communication are paradoxical in nature—the supporter can help or hinder the involvement of the young person in care-related communication. Overall, young people are not included in clinical communication and decisions at their preferred level.Conclusion Triadic communication in TYACs’ care is common, complex and dynamic. Due to the degree of challenge and nuances raised, healthcare professionals need further training on effective triadic communication.PROSPERO registration number CRD42022374528.

IntroductionReducing waiting times is a major policy objective in publicly-funded healthcare systems. However, reductions in waiting times can produce a demand response, which may offset increases in capacity. Early detection and diagnosis of cancer is a policy focus in many OECD countries, but prolonged waiting periods for specialist confirmation of diagnosis could impede this goal. We examine whether urgent GP referrals for suspected cancer patients are responsive to local hospital waiting times.MethodWe used annual counts of referrals from all 6,667 general practices to all 185 hospital Trusts in England between April 2012 and March 2018. Using a practice-level measure of local hospital waiting times based on breaches of the two-week maximum waiting time target, we examined the relationship between waiting times and urgent GP referrals for suspected cancer. To identify whether the relationship is driven by differences between practices or changes over time, we estimated three regression models: pooled linear regression, a between-practice estimator, and a within-practice estimator.ResultsTen percent higher rates of patients breaching the two-week wait target in local hospitals were associated with higher volumes of referrals in the pooled linear model (4.4%; CI 2.4% to 6.4%) and the between-practice estimator (12.0%; CI 5.5% to 18.5%). The relationship was not statistically significant using the within-practice estimator (1.0%; CI -0.4% to 2.5%).ConclusionThe positive association between local hospital waiting times and GP demand for specialist diagnosis was caused by practices with higher levels of referrals facing longer local waiting times. Temporal changes in waiting times faced by individual practices were not related to changes in their referral volumes. GP referrals for diagnostic cancer services were not found to respond to waiting times in the short-term. In this setting, it may therefore be possible to reduce waiting times by increasing supply without consequently increasing demand.

Abstract Background Menopause can significantly hasten bone loss. Mobile phones provide an efficient way to manage, track and understand menopause using apps. A previous review of menopause apps found numerous apps designed to help women manage menopause. However, it did not use validated measures to assess the quality of the apps and did not focus on content related to osteoporosis. Methods This app review aligns with the updated Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The keywords used to search for the apps were “menopause” and “menopausal”. Apps were included if they were in English, for individuals or groups and had a lifestyle focus. Apps that looked at other aspects of women’s health, required external devices, cost to download, or were symptom-tracking were excluded. The quality and functionality were assessed using the Mobile App Rating Scale and IMS Institute for Healthcare Informatics Functionality score. Data were synthesised descriptively. Results Twenty-eight apps were selected and reviewed from the 236 apps screened from the Apple store and Google play store. Only 57% of the apps reviewed (n = 16) had content on osteoporosis which was educational in purpose. The readability of the apps was complex and best understood by university graduates. The average functionality score of the apps reviewed was 4.57 out of 11 and that of quality is 3.1 out of 5, both of which need improvement. Conclusions Existing menopause apps need more input from experts to improve the quality and functionality, using simple language. More emphasis on specific health problems during menopause, including osteoporosis, is required. Trial registration Not relevant.

Abstract The use of artificial intelligence (AI) has the potential to improve the assessment of lesions suspicious of melanoma, but few clinical studies have been conducted. We validated the accuracy of an open-source, non-commercial AI algorithm for melanoma diagnosis and assessed its potential impact on dermatologist decision-making. We conducted a prospective, observational clinical study to assess the diagnostic accuracy of the AI algorithm (ADAE) in predicting melanoma from dermoscopy skin lesion images. The primary aim was to assess the reliability of ADAE’s sensitivity at a predefined threshold of 95%. Patients who had consented for a skin biopsy to exclude melanoma were eligible. Dermatologists also estimated the probability of melanoma and indicated management choices before and after real-time exposure to ADAE scores. All lesions underwent biopsy. Four hundred thirty-five participants were enrolled and contributed 603 lesions (95 melanomas). Participants had a mean age of 59 years, 54% were female, and 96% were White individuals. At the predetermined 95% sensitivity threshold, ADAE had a sensitivity of 96.8% (95% CI: 91.1–98.9%) and specificity of 37.4% (95% CI: 33.3–41.7%). The dermatologists’ ability to assess melanoma risk significantly improved after ADAE exposure (AUC 0.7798 vs. 0.8161, p = 0.042). Post-ADAE dermatologist decisions also had equivalent or higher net benefit compared to biopsying all lesions. We validated the accuracy of an open-source melanoma AI algorithm and showed its theoretical potential for improving dermatology experts’ ability to evaluate lesions suspicious of melanoma. Larger randomized trials are needed to fully evaluate the potential of adopting this AI algorithm into clinical workflows.

Abstract Background Anemia is estimated to cause 115,000 maternal deaths each year. In Nepal, 46% of pregnant women have anemia. As part of an integrated anemia-prevention strategy, family engagement and counseling of pregnant women can increase compliance to iron folic acid tablets, but marginalized women often have lower access to these interventions. We implemented the VALID (Virtual antenatal intervention for improved diet and iron intake) randomized controlled trial to test a family-focused virtual counseling mHealth intervention designed to inclusively increase iron folic acid compliance in rural Nepal; here we report findings from our process evaluation research. Methods We conducted semi structured interviews with 20 pregnant women who had received the intervention, eight husbands, seven mothers-in-laws and four health workers. We did four focus groups discussions with intervention implementers, 39 observations of counseling, and used routine monitoring data in our evaluation. We used inductive and deductive analysis of qualitative data, and descriptive statistics of monitoring data. Results We were able to implement the intervention largely as planned and all participants liked the dialogical counseling approach and use of story-telling to trigger conversation. However, an unreliable and inaccessible mobile network impeded training families about how to use the mobile device, arrange the counseling time, and conduct the counseling. Women were not equally confident using mobile devices, and the need to frequently visit households to troubleshoot negated the virtual nature of the intervention for some. Women’s lack of agency restricted both their ability to speak freely and their mobility, which meant that some women were unable to move to areas with better mobile reception. It was difficult for some women to schedule the counseling, as there were competing demands on their time. Family members were difficult to engage because they were often working outside the home; the small screen made it difficult to interact, and some women were uncomfortable speaking in front of family members. Conclusions It is important to understand gender norms, mobile access, and mobile literacy before implementing an mHealth intervention. The contextual barriers to implementation meant that we were not able to engage family members as much as we had hoped, and we were not able to minimize in-person contact with families. We recommend a flexible approach to mHealth interventions which can be responsive to local context and the situation of participants. Home visits may be more effective for those women who are most marginalized, lack confidence in using a mobile device, and where internet access is poor.

Abstract Objective: To examine the trajectories of BMI in Indonesian adults from 1993 to 2014, investigating different patterns by sex and birth cohort. Design: Longitudinal study: secondary data analysis of the Indonesian Family Life Survey, a large-scale population-based longitudinal study, had their height and weight measured up to five times throughout the 21-year study period (1993–2014). The change in BMI across time was estimated using group-based trajectory models, then differences by sex and birth cohort were investigated using random effect (mixed) models. Setting: Thirteen out of twenty-seven provinces in Indonesia. Participants: Indonesian adults aged 19 years and older (n 42 537) were included in the analysis. Results: Mean BMI in adults increased between 1993 (21·4 kg/m2) and 2014 (23·5 kg/m2). The group-based trajectory model found three distinct groups with mean BMI increasing more rapidly in the most recent time periods. The first group (56·7 % of participants) had a mean BMI entirely within the normal weight range; the second group (34·7 %) started in the normal weight category and were obese, on average by the end of the study period; and the third group (8·6 %) were always in the obese category, on average. The shape of these three trajectories differed by gender (P < 0·001) and birth cohort (P < 0·001). Conclusions: The mean BMI among Indonesian adults has increased between 1993 and 2014, driven by those in the most recent birth cohorts. Our findings support the urgent need for targeted overweight and obesity prevention and intervention programmes in Indonesia.

We searched for the prevalence of actionable somatic mutations in exon 2 of the KRAS gene in western Mexican patients with CRC. Tumor tissue DNA samples from 150 patients with sporadic CRC recruited at the Civil Hospital of Guadalajara were analyzed. Mutations in exon 2 of the KRAS gene were identified using Sanger sequencing, and the data were analyzed considering clinical–pathological characteristics. Variants in codon 12 (rs121913529 G>A, G>C, and G>T) and codon 13 (rs112445441 G>A) were detected in 26 patients (with a prevalence of 17%). No significant associations were found between these variants and clinical–pathological characteristics (p > 0.05). Furthermore, a comprehensive search was carried out in PubMed/NCBI and Google for the prevalence of KRAS exon 2 mutations in Latin American populations. The 17 studies included 12,604 CRC patients, with an overall prevalence of 30% (95% CI = 0.26–0.35), although the prevalence ranged from 13 to 43% across the different data sources. Determining the variation and frequency of KRAS alleles in CRC patients will enhance their potential to receive targeted treatments and contribute to the understanding of the genomic profile of CRC.

Moebius syndrome is a collection of orofacial anomalies with highly variable features affecting many different systems but characterised by bilateral facial palsy and absent eye abduction. We largely regard Moebius syndrome as a diagnosis of exclusion. Lack of awareness and knowledge means that children often fall between services, leading to treatment delays and difficulty interfacing with social care and schools, with long-term impact on physical health and psychosocial development. We developed a multidisciplinary team comprising core clinicians (lead physician, geneticist, speech and language therapist, psychologist and specialist nurse) and an expanded group to encompass the other affected systems. The interactions between our specialties lead to the development of a treatment protocol, which we present. The protocol harnesses the aspects of care of children with a range of other rare diseases at a specialised paediatric centre and synthesises them into a holistic approach for MBS and related conditions. Management is sequenced on an “ABC-style” basis, with airway, feeding, vision and speech taking priority in the early years. We define management priorities as airway stabilisation with swallow assessment, ocular surface protection and maintenance of nutritional support. Management principles for issues such as speech, reflux, drooling and sleep issues are outlined. In later years, psychological support has a prominent role geared towards monitoring and interventions for low mood, self-esteem and bullying.

Abstract We assessed the PREDICT v 2.2 for prognosis of breast cancer patients with pathogenic germline BRCA1 and BRCA2 variants, using follow-up data from 5453 BRCA1/2 carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC). PREDICT for estrogen receptor (ER)-negative breast cancer had modest discrimination for BRCA1 carrier patients overall (Gönen & Heller unbiased concordance 0.65 in CIMBA, 0.64 in BCAC), but it distinguished clearly the high-mortality group from lower risk categories. In an analysis of low to high risk categories by PREDICT score percentiles, the observed mortality was consistently lower than the expected mortality, but the confidence intervals always included the calibration slope. Altogether, our results encourage the use of the PREDICT ER-negative model in management of breast cancer patients with germline BRCA1 variants. For the PREDICT ER-positive model, the discrimination was slightly lower in BRCA2 variant carriers (concordance 0.60 in CIMBA, 0.65 in BCAC). Especially, inclusion of the tumor grade distorted the prognostic estimates. The breast cancer mortality of BRCA2 carriers was underestimated at the low end of the PREDICT score distribution, whereas at the high end, the mortality was overestimated. These data suggest that BRCA2 status should also be taken into consideration with tumor characteristics, when estimating the prognosis of ER-positive breast cancer patients.

Objectives To engage children who have experienced cancer, childhood cancer survivors, their families and professionals to systematically identify and prioritise research questions about childhood cancer to inform the future research agenda.Design James Lind Alliance Priority Setting Partnership.Setting UK health service and community.Methods A steering group oversaw the initiative. Potential research questions were collected in an online survey, then checked to ensure they were unanswered. Shortlisting via a second online survey identified the highest priority questions. A parallel process with children was undertaken. A final consensus workshop was held to determine the Top 10 priorities.Participants Children and survivors of childhood cancer, diagnosed before age 16, their families, friends and professionals who work with this population.Results Four hundred and eighty-eight people submitted 1299 potential questions. These were refined into 108 unique questions; 4 were already answered and 3 were under active study, therefore, removed. Three hundred and twenty-seven respondents completed the shortlisting survey. Seventy-one children submitted questions in the children’s surveys, eight children attended a workshop to prioritise these questions. The Top 5 questions from children were taken to the final workshop where 23 questions in total were discussed by 25 participants (young adults, carers and professionals). The top priority was ‘can we find effective and kinder (less burdensome, more tolerable, with fewer short and long-term effects) treatments for children with cancer, including relapsed cancer?’Conclusions We have identified research priorities for children’s cancer from the perspectives of children, survivors, their families and the professionals who care for them. Questions reflect the breadth of the cancer experience, including diagnosis, relapse, hospital experience, support during/after treatment and the long-term impact of cancer. These should inform funding of future research as they are the questions that matter most to the people who could benefit from research.

BackgroundThe Maternal Mortality Rate (MMR) in Tanzania is 78 times higher than that of the UK. Obstetric haemorrhage accounts for two-thirds of these deaths in Mbeya, Tanzania. A lack of healthcare providers' (HCPs') competencies has been the key attribute. This study measured the impact on HCP's competencies from a blended training programme on obstetric haemorrhage.MethodsA “before and after” cohort study was undertaken with HCPs in 4 hospitals in the Mbeya region of Tanzania between August 2021 and April 2022. A multidisciplinary cohort of 34 HCPs (doctors, nurses, midwives, anaesthetists and radiologists) were enrolled on a blended face-to-face and virtual training course. The training was delivered by a multidisciplinary team (MDT) from London, UK, assisted by local multidisciplinary trainers from Mbeya, Tanzania and covered anaesthetic, obstetrics, haematology and sonographic use.ResultsThere were 33 HCP in the cohort of trainees where 30/33 (90.9%) of HCPs improved their Anaesthesia skills with a mean score improvement of 26% i.e., 0.26 (−0.009 −0.50), 23 HCPs (69.7%) improved obstetric skills 18% i.e., 0.18 (−0.16 to 0.50), 19 (57.6%), (57.6%) improved competences in Haematology 15%.i.e., 0.15 (−0.33 to 0.87), 20 out of 29 HCPs with ultrasound access (68.8%) improved Sonographic skills 13%.i.e., 0.13 (−0.31 to 0.54). All 33 HCPs (100%) presented a combined change with the mean score improvement of difference of 25% i.e., 0.25 (0.05–0.66). The deaths attributed to obstetric haemorrhage, the mortality rate declined from 76/100,000 to 21/100,000 live births. Actual number of deaths due to obstetric haemorrhage declined from 8 before training to 3 after the completion of the training.ConclusionThis comprehensive blended training on anaesthetic surgical, haematological, and sonographic management of obstetric haemorrhage delivers a significant positive impact on the detection, management and outcomes of obstetric haemorrhage.

AbstractConscientious objection (CO) on the part of healthcare providers is a growing threat to safe abortion access. In South Africa, evidence suggests that this legal clause may be manipulated as a justification for public-sector healthcare providers to exempt themselves from their duties to provide essential reproductive health services as required by national laws and protocols. This qualitative study improves our understanding of the definitions, perspectives, and use of CO among providers, staff, and facility managers in South Africa, and CO’s effect on public-sector abortion availability. Using 18 focus group discussions and 23 in-depth interviews, we examined CO attitudes and behaviours of staff from health facilities that provide abortion care in Gauteng, Limpopo, KwaZulu-Natal, and Eastern Cape Provinces. We find that CO is invoked for a variety of reasons, some unrelated to the legal basis for objection. There have been progressive shifts in attitudes towards abortion over time, but stigma against women and girls who seek abortion remains substantial among staff at facilities providing abortion. Providers who offer abortion services also report high levels of discrimination and isolation from colleagues. Such factors, combined with operational barriers to offering quality abortion care (such as lack of training support or financial incentives) and lack of clarity on CO definitions and procedures, may incentivise some providers to invoke CO inappropriately. Dissemination of national guidelines on CO should be prioritised to reduce ambiguity, and interventions addressing abortion stigma should be considered for all facility staff to safeguard abortion availability in South Africa.

B-acute lymphoblastic leukemia (B-ALL) consists of dozens of subtypes defined by distinct gene expression profiles (GEP) and various genetic lesions. With the application of transcriptome sequencing (RNA sequencing [RNA-seq]), multiple novel subtypes have been identified, which lead to an advanced B-ALL classification and risk-stratification system. However, the complexity of analyzing RNA-seq data for B-ALL classification hinders the implementation of the new B-ALL taxonomy. Here, we introduce Molecular Diagnosis of Acute Lymphoblastic Leukemia (MD-ALL), an integrative platform featuring sensitive and accurate B-ALL classification based on GEP and sentinel genetic alterations from RNA-seq data. In this study, we systematically analyzed 2,955 B-ALL RNA-seq samples and generated a reference dataset representing all the reported B-ALL subtypes. Using multiple machine learning algorithms, we identified the feature genes and then established highly sensitive and accurate models for B-ALL classification using either bulk or single-cell RNA-seq data. Importantly, this platform integrates multiple aspects of key genetic lesions acquired from RNA-seq data, which include sequence mutations, large-scale copy number variations, and gene rearrangements, to perform comprehensive and definitive B-ALL classification. Through validation in a hold-out cohort of 974 samples, our models demonstrated superior performance for B-ALL classification compared with alternative tools. Moreover, to ensure accessibility and user-friendly navigation even for users with limited or no programming background, we developed an interactive graphical user interface for this MD-ALL platform, using the R Shiny package. In summary, MD-ALL is a user-friendly B-ALL classification platform designed to enable integrative, accurate, and comprehensive B-ALL subtype classification. MD-ALL is available from https://github.com/gu-lab20/MD-ALL.

Objectives The objective of this study is to investigate early-to-late postdoctoral clinical academic progression and the experiences of NIHR Clinical Lectureship (CL) fellows, considering enablers and barriers to success, and identifying the factors associated with immediate progression to a clinical academic role following completion of the award.Setting Datasets of CL awardees across the UK.Participants For semistructured interviews, n=40 CL awardees that had finished their award within the previous 5 years. For quantitative analysis, n=1226 completed or currently active CL awardees.Outcome measures The responses from the semistructured interviews to the defined questions on experiences during the award, postaward progression, and enablers and barriers to academic progression. Other primary outcome measures were quantitative data on first destinations postaward, demographic data, and whether an awardee had previously held an NIHR Academic Clinical Fellowship (ACF) or was a recipient of the Academy of Medical Sciences (AMS) Starter Grant.Results CL awardees identified numerous benefits to the award, with the majority achieving their aims. Most awardees progressed to a clinical academic role; however, some returned to a clinical only position, citing concerns around the time pressure associated with balancing clinical and academic responsibilities, and the competition to attain further postdoctoral awards. The region of the award partnership, year of award end and success in applying for an AMS Starter Grant were associated with progression to a clinical academic role. Gender, holding an ACF and having a craft or non-craft specialty had no independent statistical association with clinical academic progression.Conclusions The CL is a valued element of the Integrated Academic Pathway. By addressing issues around later postdoctoral progression opportunities, responding to challenges experienced by CLs, and by understanding the factors identified in this study associated with clinical academic progression, it should be possible to increase the proportion of CLs that become fully independent clinical academic research leaders.Participants 1226 NIHR CLs active or completed on the award between 2006 and 2020.

Background Pulmonary and extrapulmonary incidental findings are frequently identified on CT scans performed for lung cancer screening. Uncertainty regarding their clinical significance and how and when such findings should be reported back to clinicians and participants persists. We examined the prevalence of non-malignant incidental findings within a lung cancer screening cohort and investigated the morbidity and relevant risk factors associated with incidental findings. We quantified the primary and secondary care referrals generated by our protocol.Methods The SUMMIT study (NCT03934866) is a prospective observational cohort study to examine the performance of delivering a low-dose CT (LDCT) screening service to a high-risk population. Spirometry, blood pressure, height/weight and respiratory history were assessed as part of a Lung Health Check. Individuals at high risk of lung cancer were offered an LDCT and returned for two further annual visits. This analysis is a prospective evaluation of the standardised reporting and management protocol for incidental findings developed for the study on the baseline LDCT.Results In 11 115 participants included in this analysis, the most common incidental findings were coronary artery calcification (64.2%) and emphysema (33.4%). From our protocolised management approach, the number of participants requiring review for clinically relevant findings in primary care was 1 in 20, and the number potentially requiring review in secondary care was 1 in 25.Conclusions Incidental findings are common in lung cancer screening and can be associated with reported symptoms and comorbidities. A standardised reporting protocol allows systematic assessment and standardises onward management.

Background: Psychosis is associated with physical health comorbidities. Exercise and a healthy diet can improve cardiometabolic risk and mental wellbeing. This study explores the feasibility, acceptability, and experiences of a physical health group for clients experiencing psychosis. Methods: The group was developed and refined following consultation with service-users and culturally appropriate peer support workers. It included eight weekly sessions. The aims of the group were to provide psychoeducation on healthy living and to build motivation to engage in healthy living. Attendance, completion, and satisfaction were recorded to determine feasibility and acceptability of local service delivery. Clients took part in follow-up qualitative interviews to understand experiences of attending the group. Interviews were analysed using thematic analysis. Results: Twenty-five clients were referred to the group. Overall, 10 clients enrolled in the group. Clients who enrolled in the group attended a median of 4.5 sessions. The mean satisfaction score for all sessions combined was 9.15/10 [SD 1.18]. Seven individual interviews were conducted. Two themes emerged. 1) Positive views towards the group, with clients feeling more aware of the benefits of healthy living, and clients finding the group setting motivating. 2) Considerations when planning healthy living support, which reflected subthemes in difficulties maintaining healthy living and concerns that the group should not be about weight loss. Limitations: Investigations were limited to one mental health provider. Conclusions: It was feasible and acceptable to implement a healthy living group for clients with psychosis in a community mental health team, and this intervention was met with positivity.

Smart speakers and conversational agents have been accepted into our homes for a number of tasks such as playing music, interfacing with the internet of things, and more recently, general chit-chat. However, they have been less readily accepted in our workplaces. This may be due to data privacy and security concerns that exist with commercially available smart speakers. However, one of the reasons for this may be that a smart speaker is simply too abstract and does not portray the social cues associated with a trustworthy work colleague. Here, we present an in-depth mixed method study, in which we investigate this question of embodiment in a serious task-based work scenario of a first responder team. We explore the concepts of trust, engagement, cognitive load, and human performance using a humanoid head style robot, a commercially available smart speaker, and a specially developed dialogue manager. Studying the effect of embodiment on trust, being a highly subjective and multi-faceted phenomena, is clearly challenging, and our results indicate that potentially, the robot, with its anthropomorphic facial features, expressions, and eye gaze, was trusted more than the smart speaker. In addition, we found that embodying a conversational agent helped increase task engagement and performance compared to the smart speaker. This study indicates that embodiment could potentially be useful for transitioning conversational agents into the workplace, and further in situ, “in the wild” experiments with domain workers could be conducted to confirm this.

Abstract Nutrition‐sensitive agriculture (NSA) interventions offer a means to improve the dietary quality of rural, undernourished populations. Their effectiveness could be further increased by understanding how household dynamics enable or inhibit the uptake of NSA behaviours. We used a convergent parallel mixed‐methods design to describe the links between household dynamics—specifically intrahousehold power inequalities and intrahousehold cooperation—and dietary quality and to explore whether household dynamics mediated or modified the effects of NSA interventions tested in a cluster‐randomized trial, Upscaling Participatory Action and Videos for Agriculture and Nutrition (UPAVAN). We use quantitative data from cross‐sectional surveys in 148 village clusters at UPAVAN's baseline and 32 months afterwards (endline), and qualitative data from family case studies and focus group discussions with intervention participants and facilitators. We found that households cooperated to grow and buy nutritious foods, and gendered power inequalities were associated with women's dietary quality, but cooperation and women's use of power was inhibited by several interlinked factors. UPAVAN interventions were more successful in more supportive, cooperative households, and in some cases, the interventions increased women's decision‐making power. However, women's decisions to enter into negotiations with family members depended on whether women deemed the practices promoted by UPAVAN interventions to be feasible, as well as women's confidence and previous cultivation success. We conclude that interventions may be more effective if they can elicit cooperation from the whole household. This will require a move towards more family‐centric intervention models that empower women while involving other family members and accounting for the varied ways that families cooperate and negotiate.