Recipient tissue microenvironment determines developmental path of intestinal innate lymphoid progenitors.

Innate lymphoid cells (ILCs) are critical in maintaining tissue homeostasis, and during infection and inflammation. Here we identify, by using combinatorial reporter mice, a rare ILC progenitor (ILCP) population, resident to the small intestinal lamina propria (siLP) in adult mice. Transfer of siLP-ILCP into recipients generates group 1 ILCs (including ILC1 and NK cells), ILC2s and ILC3s within the intestinal microenvironment, but almost exclusively group 1 ILCs in the liver, lung and spleen. Single cell gene expression analysis and high dimensional spectral cytometry analysis of the siLP-ILCPs and ILC progeny indicate that the phenotype of the group 1 ILC progeny is also influenced by the tissue microenvironment. Thus, a local pool of siLP-ILCP can contribute to pan-ILC generation in the intestinal microenvironment but has more restricted potential in other tissues, with a greater propensity than bone marrow-derived ILCPs to favour ILC1 and ILC3 production. Therefore, ILCP potential is influenced by both tissue of origin and the microenvironment during development. This may provide additional flexibility during the tuning of immune reactions.

ILC2-derived LIF licences progress from tissue to systemic immunity.

Migration and homing of immune cells are critical for immune surveillance. Trafficking is mediated by combinations of adhesion and chemokine receptors that guide immune cells, in response to chemokine signals, to specific locations within tissues and the lymphatic system to support tissue-localized immune reactions and systemic immunity1,2. Here we show that disruption of leukaemia inhibitory factor (LIF) production from group 2 innate lymphoid cells (ILC2s) prevents immune cells leaving the lungs to migrate to the lymph nodes (LNs). In the absence of LIF, viral infection leads to plasmacytoid dendritic cells (pDCs) becoming retained in the lungs where they improve tissue-localized, antiviral immunity, whereas chronic pulmonary allergen challenge leads to marked immune cell accumulation and the formation of tertiary lymphoid structures in the lung. In both cases immune cells fail to migrate to the lymphatics, leading to highly compromised LN reactions. Mechanistically, ILC2-derived LIF induces the production of the chemokine CCL21 from lymphatic endothelial cells lining the pulmonary lymphatic vessels, thus licensing the homing of CCR7+ immune cells (including dendritic cells) to LNs. Consequently, ILC2-derived LIF dictates the egress of immune cells from the lungs to regulate tissue-localized versus systemic immunity and the balance between allergen and viral responsiveness in the lungs.

DIALOR (DIgitAL cOaching for fRailty): protocol for a single-arm mixed-methods feasibility study of a digital health coaching intervention for older people with frailty in primary care.

BACKGROUND: Multidomain interventions in older adults offer the best opportunity to prevent, delay or reverse existing symptoms in the earlier stages of frailty and improve independence but can be costly, and difficult to deliver at scale. However, digital health interventions enable personalised care and empowerment through self-management of long-term conditions, used at any time and when combined with health coaching offer the potential to enhance well-being and facilitate the achievement of health-related goals. We aim to evaluate the feasibility and acceptability of a digital health platform for long-term disease management combined with health coaching for people living with mild-moderate frailty, targeting self-identified goals-activity, nutrition, mood, enhancing social engagement and well-being. METHODS AND ANALYSIS: This is a non-randomised feasibility, single-group, pretest/post-test study, using qualitative and quantitative methods. The digital health coaching intervention (DIALOR-DIgitAL cOaching for fRailty) has been developed for implementation to older adults, aged 65 years or older with mild to moderate frailty and diagnosis of one or more long-term health conditions in the community. Participants will receive 12 weeks of health coaching and have access to a mobile health platform for 6 months. The primary outcome measure is the acceptability and feasibility of DIALOR along with a range of secondary outcome measures (including frailty, functioning measures, quality of life, social engagement, diet quality and self-reported indicators) collected at baseline and at 6 months. The findings will inform whether a wider effectiveness trial is feasible and if so, how it should be designed. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Southeast Scotland Research Ethics Committee 02 (reference: 22/SS/0064). Research findings will be disseminated in a range of different ways to engage different audiences, including publishing in open-access peer-reviewed journals, conference presentations, social media, dissemination workshop with patients, carers, and healthcare professionals and on institution websites.

Diagnostic yield from cardiac gene testing for inherited cardiac conditions and re-evaluation of pre-ACMG variants of uncertain significance.

BACKGROUND: Inherited cardiomyopathies (HCM, DCM, ACM) and cardiac ion channelopathies (long QT/Brugada syndromes, CPVT) are associated with significant morbidity and mortality; however, diagnosis of a familial pathogenic variant in a proband allows for subsequent cascade screening of their at-risk relatives. AIMS: We investigated the diagnostic yield from cardiac gene panel testing and reviewed variants of uncertain significance from patients attending three specialist cardiogenetics services in Ireland in the years 2002 to 2020. RESULTS: Reviewing molecular genetic diagnostic reports of 834 patients from 820 families, the initial diagnostic yield of pathogenic/likely pathogenic variants was 237/834 patients (28.4%), increasing to 276/834 patients (33.1%) following re-evaluation of cases with variant(s) of uncertain significance. Altogether, 42/85 patients with VUS reviewed (49.4%) had a re-classification that could change their clinical management. Females were more likely to carry pathogenic/likely pathogenic variants than males (139/374, 37.2% vs 137/460, 29.8%, respectively, p = 0.03), and the diagnostic yields were highest in the 0 to < 2 years age group (6/12, 50.0%) and amongst those tested for cardiomyopathy gene panels (13/35, 37.1%). Variants in the MYBPC3/MYH7 (87/109, 79.8%) and KCNQ1/KCNH2 (91/100, 91.0%) genes were the predominant genetic causes for hypertrophic cardiomyopathy and long QT syndrome, respectively. CONCLUSION: Our study highlights the importance of collation and review of pre-ACMG genetic variants to increase diagnostic utility of genetic testing for inherited heart disease. Almost half of patients with pre-ACMG VUS reviewed had their variant re-classified to likely pathogenic/likely benign which resulted in a positive clinical impact for patients and their families.

Towards an improved dementia care experience in clinical radiography practice: A state-of-the-art review.

INTRODUCTION: The increasing global incidence rate of dementia and associated co/multimorbidity has consequently led to a rise in the number of people with dementia (PwD) requiring clinical radiography care services. This review aims to explore and integrate findings from diverse settings with a focus on the experiences of PwD and stakeholders, towards the development of a holistic approach for dementia care and management within the context of radiography services. METHOD: An electronic search was performed across the following databases: PUBMED, CINAHL, Medline, SCOPUS, and ScienceDirect for articles published from January 2009 and June 2023. Articles were included if they fulfilled a predefined criteria mainly focused on experiences of PwD and/or other stakeholders when using the radiography services. Data obtained from the included studies were analysed using a result-based convergent synthesis. RESULT: Eleven studies from diverse settings met the inclusion criteria. A mix of both positive and negative experiences of PwD and stakeholders were reported following visits to radiology and radiotherapy departments were highlighted across settings. The findings were themed around the need for: person-centred care, effective communication, attitudinal changes of staff, specialised and improved clinical environment and inclusion of caregivers for the care of PwD. DISCUSSION: This study emphasise the critical importance of adopting holistic approaches to caring for PwD. This involves adopting a person-centred approach, actively involving caregivers, effective communication, and adequate training for radiographers to provide quality services, all in dementia-friendly environments. CONCLUSION: The experiences of various stakeholders highlight the need for a more holistic approach and strategy for the care and management of PwD within the context of the radiography services. This calls for an urgent need for a comprehensive strategy that includes awareness creation of staff to enhance the quality of care and the overall experience for PwD using the radiography services.

Implementation of a geriatric oncology service at the Royal Marsden Hospital.

INTRODUCTION: Despite significant evidence supporting the benefits of comprehensive oncogeriatric assessment in the management of older patients with cancer, the adoption of specialised geriatric oncology programs in the United Kingdom remains limited. Descriptions of clinic structure and models, patient demographics and baseline characteristics, resource utilisation, and predictors of resource utilisation are lacking in this population, which may complicate or impede the planning, resourcing, and development of further services in this subspecialty on a national and regional basis. MATERIALS AND METHODS: Between November 2021 and April 2023, 244 patients commencing systemic anticancer treatment at the Royal Marsden Hospital, London underwent geriatric screening using the Senior Adult Oncology Programme-3 (SAOP3) screening tool. Baseline clinical factors (sex, age, Charlson Comorbidity Index score, Cumulative Illness Rating Scale-Geriatric [CIRS-G] score, Katz Index score, Barthel Index score, treatment intent, and Eastern Cooperative Oncology Group Performance Status [ECOG-PS]) were assessed as predictors of geriatric impairments and need for multidisciplinary referral and intervention using a negative binomial regression analysis. Referral rates to multidisciplinary teams were assessed against ECOG-PS score using point-biserial correlation, as well as against a historical control using descriptive statistics. RESULTS: The median age of participants was 77; 75.8% were female. Breast cancer was the most prevalent diagnosis (61.9%). Most patients (67.6%) were undergoing treatment in the palliative setting. Two hundred eleven (86.5%) patients were identified as having at least one geriatric impairment. Six hundred forty-nine multidisciplinary referrals were made, of which 583 (86.7%) were accepted by the referred patient. Higher ECOG PS was positively associated with geriatric impairments in physiotherapy, occupational therapy, dietetics, pharmacy, and welfare rights domains, as well as with the overall number of geriatric impairments. DISCUSSION: The Royal Marsden Senior Adult Oncology Programme represents the first geriatric oncology service in a tertiary cancer centre in the United Kingdom. Following implementation of SAOP3 screening, we observed a substantial increase in referrals to all multidisciplinary teams, suggestive of previously underrecognized needs among this population. The need for multidisciplinary intervention was strongly correlated with baseline ECOG-PS score, but not with other measured clinical variables, including comorbidity or functional indices.

A Tailored mHealth App for Improving Health and Well-Being Behavioral Transformation in UK Police Workers: Usability Testing via a Mixed Methods Study.

BACKGROUND: When considering the policing environment of 2022, many roles previously in the domain of warranted officers (police officer) are now performed by nonwarranted police staff equivalents. These police staff roles have expanded rapidly into other areas such as investigations, custody, and contact management, which were traditionally seen as police officer functions and put staff under some of the same stresses as police officers. A UK police force requested help in investigating technologies that could be used to improve health and well-being for both officers and staff. OBJECTIVE: The aim of this study was to create a health and well-being app for police officers and staff, which considered the unique requirements of the users throughout the designing, building, prototyping, and testing stages. METHODS: This study involved quantitative approaches (demographic web-based survey questions and the System Usability Scale) and qualitative approaches (open web-based survey questions and semistructured interviews). Unsupervised usability testing of a prototype app was undertaken by members (N=48) of the commissioning client using their smartphones. After completing a preregistration application for screening purposes, participants downloaded a trial version of the app. Then, they completed a web-based questionnaire after testing the app for 10 days. A subsample of participants (9/48, 19%) was interviewed. Deductive thematic analysis was undertaken to identify key themes and subthemes. RESULTS: Data collected during usability testing concerned the 6 domains of the app-food and diet, activity, fluid intake, sleep, good mental health, and financial well-being-and informed the creation of improved design during prototyping. Some usability and design issues and suggestions for improvements were also addressed and implemented-including shift management and catch-up cards-during this cycle of development. CONCLUSIONS: This study highlights the importance of coparticipation with officers and staff across the entire development cycle, to coproduce a human-centered design methodology to enable the development of a considered and user-centered solution. It demonstrates the need for producing a multifunctional tool rather than focusing purely on an individual element for this user group. It also highlights how linking and being able to track optional, personalized elements of health data against one another, cross-referenced to individual shift patterns, might help to inform and provide users with a chance for reflection and therefore influence behavior change.

Effectiveness of digital technologies to engage and support the wellbeing of people with dementia and family carers at home and in care homes: A scoping review.

Use of digital technologies to support meaningful engagement of people with dementia and carers increased during the COVID-19 pandemic. The purpose of this scoping review was to determine the effectiveness of digital technologies in supporting the engagement and wellbeing of people with dementia and family carers at home and in care homes. Studies published in peer reviewed literature were identified across four databases (CINAHL, Medline, PUBMED, PsychINFO). Sixteen studies met the inclusion criteria. Findings indicate that digital technologies can potentially support the wellbeing of people with dementia and family carers, although only a few studies had measured impact on wellbeing, as many were reporting on technology at proof-of-concept stage rather than commercially ready products. Moreover, current studies lacked meaningful involvement of people with dementia, family carers, and care professionals in the design of the technology. Future research should bring together people with dementia, family carers, care professionals and designers to coproduce digital technologies with researchers and evaluate them using robust methodologies. Codesign should start early in the intervention development phase and continue until implementation. There is a need for real world applications that nurture social relationships by focusing on how digital technologies can support more personalised, adaptive forms of care. Developing the evidence base to identify what makes digital technologies effective in supporting the wellbeing of people with dementia is crucial. Future interventions should therefore consider the needs and preferences of people with dementia, their families, and professional carers, as well as the suitability and sensitivity of wellbeing outcome measures.

Developing a consensus to support health and social care professionals and patients manage nutrition in the context of COVID-19 recovery.

BACKGROUND: The long-term effects on people who have had COVID-19 affect nutrition and can be influenced by diet conversely. Specific nutritional guidelines, however, were scarce at the beginning of 2020, and empirical literature was also lacking. Conventional research methodologies needed to be adapted to review the available literature that could be relevant to the United Kingdom and policy documents as well as collect the views of health and care staff. The aim of this paper is to describe the method to develop consensus statements from experts to address the necessary nutritional support and what emerged from this. METHODS: A nominal group technique (NGT) was adapted to the virtual world; we purposefully selected a range of professionals (dietitians, nurses, occupational therapists, etc.) and patients with long-term effects of COVID to present them with the most updated evidence and aim to reach key guidelines to address COVID-19 recovery. RESULTS: We were able to reach consensus statements that were developed and reviewed by relevant healthcare staff at the front line to address the nutritional needs of patients recovering from COVID-19 and those suffering from its long-term effects. This adapted NGT process led us to understand that a virtual repository of concise guidelines and recommendations was needed. This was developed to be freely accessed by both patients recovering from COVID-19 and health professionals who manage them. CONCLUSIONS: We successfully obtained key consensus statements from the adapted NGT, which showed the need for the nutrition and COVID-19 knowledge hub. This hub has been developed, updated, reviewed, endorsed and improved across the subsequent 2 years.

Frail2Fit study protocol: a feasibility and acceptability study of a virtual multimodal intervention delivered by volunteers to improve functional outcomes in older adults with frailty after discharge from hospital.

INTRODUCTION: Physical activity (PA) and replete nutritional status are key to maintaining independence and improving frailty status among frail older adults. In response to the COVID-19 pandemic, healthcare has increasingly turned to virtual modes of delivery and there is interest in the use of trained volunteers to deliver PA and nutrition interventions. We aim to evaluate the feasibility and acceptability of training hospital volunteers to deliver an online intervention, comprising exercise, behaviour change and nutrition support, to older people with frailty after discharge from hospital. METHODS: We will use a quasi-experimental mixed methods approach. Hospital volunteers (n=6) will be trained to deliver an online, 3-month, multimodal intervention to frail (Clinical Frailty Scale ≥5) adults ≥65 years (n=30) after discharge from hospital. Feasibility will be assessed by determining the number of volunteers recruited, trained and retained at the end of the study; the proportion of intervention sessions delivered; participant recruitment, retention and adherence to the intervention. To determine the acceptability of the intervention, interviews will be conducted among a purposive sample of older adults, and volunteers. Secondary outcomes will include physical function, appetite, well-being, quality of life, anxiety and depression, self-efficacy for managing chronic disease and PA. Outcomes will be measured at baseline, 3 months and 6 months. ANALYSIS: Descriptive statistics will be used to describe feasibility and adherence to the intervention. Secondary outcomes at baseline will be compared at 3 and 6 months. Interviews will be transcribed verbatim and analysed using thematic analysis. ETHICS AND DISSEMINATION: Health Research Authority ethical approval was obtained on 30 May 2022 (reference: 22/WA/0155). Results will be disseminated through peer-reviewed journal articles, volunteer organisations, National Health Service communication systems and social media platforms. A toolkit will be developed to facilitate roll out of volunteer training. TRIAL REGISTRATION NUMBER: NCT05384730.

Navigating COVID-19 Educational Challenges: Transitioning an In-Person Mentoring Program to a Virtual Learning Environment.

Nursing professional development practitioners and leadership staff implemented a second Transitional Mentor Education Program. The pilot program was classroom based; however, with pandemic restrictions, a shift to deliver a hybrid mentoring program was needed. Learning needs, clinician well-being, and professional development were addressed. Regardless of the method of educational delivery, the nurses in Phase 2 achieved the same outcomes as the pilot program, including increased clinical confidence, communication, integration of stress reduction strategies, and reflective practice.

Identification of aceNKPs, a committed common progenitor population of the ILC1 and NK cell continuum.

The development of innate lymphoid cell (ILC) transcription factor reporter mice has shown a previously unexpected complexity in ILC hematopoiesis. Using novel polychromic mice to achieve higher phenotypic resolution, we have characterized bone marrow progenitors that are committed to the group 1 ILC lineage. These common ILC1/NK cell progenitors (ILC1/NKP), which we call "aceNKPs", are defined as lineage-Id2+IL-7Rα+CD25-α4ß7-NKG2A/C/E+Bcl11b-. In vitro, aceNKPs differentiate into group 1 ILCs, including NK-like cells that express Eomes without the requirement for IL-15, and produce IFN-γ and perforin upon IL-15 stimulation. Following reconstitution of Rag2-/-Il2rg-/- hosts, aceNKPs give rise to a spectrum of mature ILC1/NK cells (regardless of their tissue location) that cannot be clearly segregated into the traditional ILC1 and NK subsets, suggesting that group 1 ILCs constitute a dynamic continuum of ILCs that can develop from a common progenitor. In addition, aceNKP-derived ILC1/NK cells effectively ameliorate tumor burden in a model of lung metastasis, where they acquired a cytotoxic NK cell phenotype. Our results identify the primary ILC1/NK progenitor that lacks ILC2 or ILC3 potential and is strictly committed to ILC1/NK cell production irrespective of tissue homing.

Re-examining globalization and the history of science: Ottoman and Middle Eastern experiences.

For several decades historians of science have interrogated the relationship between empire and science, largely focusing on European imperial powers. At the same time, scholars have sought alternatives to an early diffusionist model of the spread of modern science, seeking to capture the multi-directional and dialogic development of science and its institutions in most parts of the globe. The papers in this special issue illuminate these questions with added attention to particular claims about the exceptionalism - or not - of Islamic societies' approach to science, modernity and politics. Each contribution centres individuals and groups who engaged with science theoretically or practically, taking seriously their analytical categories and how they understood and grappled with the social, economic and intellectual transformations happening around them. Collectively, these studies make the case for Middle Eastern and Ottoman history as useful sites for furthering our field's understanding of processes of the globalization of science and how authority, politics and science have been and continue to be interconnected.

Systematic realist synthesis of health-related and lifestyle interventions designed to decrease overweight, obesity and unemployment in adults.

BACKGROUND: Obesity and unemployment are complex social and health issues with underlying causes that are interconnected. While a clear link has been established, there is lack of evidence on the underlying causal pathways and how health-related interventions could reduce obesity and unemployment using a holistic approach. OBJECTIVES: The aim of this realist synthesis was to identify the common strategies used by health-related interventions to reduce obesity, overweight and unemployment and to determine for whom and under what circumstances these interventions were successful or unsuccessful and why. METHODS: A realist synthesis approach was used. Systematic literature searches were conducted in Cochrane library, Medline, SocIndex, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and PsychInfo. The evidence from included studies were synthesised into Context-Mechanism-Outcome configurations (CMOcs) to better understand when and how programmes work, for which participants and to refine the final programme theory. RESULTS: A total of 83 articles met the inclusion criteria. 8 CMOcs elucidating the contexts of the health-related interventions, underlying mechanisms and outcomes were identified. Interventions that were tailored to the target population using multiple strategies, addressing different aspects of individual and external environments led to positive outcomes for reemployment and reduction of obesity. CONCLUSION: This realist synthesis presents a broad array of contexts, mechanisms underlying the success of health-related interventions to reduce obesity and unemployment. It provides novel insights and key factors that influence the success of such interventions and highlights a need for participatory and holistic approaches to maximise the effectiveness of programmes designed to reduce obesity and unemployment. TRIAL REGISTRATION: PROSPERO 2020 CRD42020219897 .

Improving nutrition and hydration in older people with dementia in care homes.

Dementia can have significant adverse effects on people's ability to eat and drink sufficiently. People with dementia can experience malnutrition and unintentional weight loss at any stage of the condition, but these occur more often in the middle and late stages. It is important that nurses and care staff working in care homes have the appropriate knowledge and skills to provide optimal nutritional care to residents, thereby improving their health, well-being and quality of life. This article provides an overview of nutrition and hydration issues commonly experienced by people with dementia. It explores common causes of suboptimal nutrition and hydration, outlines tools for nutritional screening and assessment and discusses interventions to improve the nutritional care of care home residents with dementia.

Prevention, identification and management of malnutrition in older people in the community.

Malnutrition, specifically undernutrition, is a significant health concern among older people, yet it is under-detected and under-treated in the community. The causes of malnutrition are complex and multifactorial, and the risk has been exacerbated by the coronavirus disease 2019 (COVID-19) pandemic due to social isolation and loneliness, which can affect older people's appetite and thus reduce their nutritional intake. This article discusses the causes and consequences of malnutrition in older people and describes what is involved in malnutrition screening, person-centred care planning and treatment. The author considers various approaches to overcoming the barriers associated with identifying malnutrition in older people in the community and outlines the role of the nurse in the effective management of malnutrition in this population.

Young adult preferences for digital health interventions to support adherence to inhaled corticosteroids in asthma: a qualitative study.

Objective: Adherence to inhaled corticosteroids (ICS) among young adults living with asthma is low and in need of appropriate intervention. Digital health interventions (DHIs) have demonstrated potential to improve ICS adherence; however, young adult preferences for these DHIs and how their use could support adherence in this population remain understudied. Therefore, this study aimed to explore young adult preferences for ICS adherence supports and potential DHI features to deliver these supports, in order to improve adherence behaviour throughout this critical developmental stage of the lifespan. Methods: Qualitative, semi-structured interviews were conducted with 13 young adults living with asthma. Analysis followed an inductive, reflexive thematic approach. Results: Participant's age ranged from 18 to 30 years (M = 24.7; 8 female). Three themes were developed from the analysis: 'Enabling young adults to find their 'own way of knowing', 'Support for making a habit of adherence', and 'Providing accessible information' which included the sub-themes: 'Education on asthma self-management and medication', 'Self-monitoring information' and 'Personal feedback on outcomes of adherence'. Suggested features to deliver these supports included a medication and prescription refill reminder, adherence charts, symptom and trigger monitoring, rewards for adherence, visual representations of lungs demonstrating the impact of adherence and lung function monitoring. Conclusion: DHIs may offer an appropriate solution to improve suboptimal adherence to ICS in young adults. However, it is crucial that young adult preferences for adherence supports and features are integrated into these interventions in order to optimise engagement and support adherence behaviour in this population.