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Abstract Long-term datasets provide context and understanding of complex ecological processes, including temporal variations in species diversity and ecosystem dynamics. This dataset is comprised of body length measurements (mm) of more than 380,000 larval or juvenile fish of 30 species from five English river catchments collected almost monthly over two decades. Such information can be used to determine growth rates, future recruitment success, population structure and compliance with monitoring protocols and conservation objectives. The dataset provides a baseline for analysing the impacts of anthropogenic disturbances such as climate change, pollution and habitat degradation, and, given that many fish populations are size structured with a positive relationship between fish body length and various biological attributes such as swimming ability, survival and fecundity, it will be invaluable for investigating natural and human- induced disturbances.

Abstract Social prescribing has become a global phenomenon. A Delphi study was recently conducted with 48 social prescribing experts from 26 countries to establish global agreement on the definition of social prescribing. We reflect on the use and utility of the outputs of this work, and where we go from here.

Abstract Background Digital health interventions have the potential to improve linkage to care after HIV self-testing (HIVST). This study aimed to understand clients’ and providers’ perceptions of benefits, and barriers of a digital health intervention designed to improve linkage to care after HIV self-testing in Tanzania. Methods This exploratory qualitative research study was conducted in Hai and Moshi, districts in Kilimanjaro region, Tanzania. Four health facilities were selected based on their involvement in an HIVST pilot program implemented by Elizabeth Glassier Pediatric AIDS Foundation (EGPAF) Tanzania through the USAID funded program. The study included female index clients and their partners, and healthcare providers at the healthcare facilities. We used a semi-structured interview guide with open-ended questions for data collection. Data collection was conducted from 16th January 2023 to 3rd February 2023. Thematic analysis of the qualitative data was conducted, guided by the Health Belief Model (HBM), and results were developed in collaboration with the community partners. Results A total of 42 participants were included in the study, comprising 9 male clients, 17 female index clients, and 16 health care workers (HCWs) (4 male and 12 female) who were involved in delivering HIVST services. The study’s findings revealed mixed feelings about the use of a digital health intervention. Majority of participants perceived digital health as a valuable intervention for enhancing linkage to care, improved health outcomes, improved communication with healthcare workers, and increased privacy. Therefore, they supported scale-up of a digital health intervention. Participants also expressed that the potential benefits of a digital health intervention include the convenience of accessing healthcare services from the comfort of their homes or any location. However, a few participants expressed concerns about potential risks associated with sending health-related text messages. They feared that recipients might not be in a safe space, leading to stigma and avoidance of engagement. A few female participants expressed concerns about confidentiality breaches, particularly regarding shared phones with family or friends. Fear of being judged or misunderstood by others could deter them from reading or acting upon these messages. Most participants recommended tailored strategies that prioritize confidentiality and trust. Recognizing these psychological aspects is vital for customizing digital health interventions to effectively address participants’ concerns. Conclusions Digital health interventions may improve the linkage of HIV self-testers to care. Recommendations include personalized and culturally relevant communication and technical accessibility to make interventions effective and inclusive. This study provides valuable insights for designing patient-centered interventions for HIV care and treatment.

Abstract Background The global nursing shortages exacerbated by the COVID-19 pandemic necessitated a drastic reorganization in nursing practices. Work routines, the composition of teams and subsequently mundane nursing practices were all altered to sustain the accessibility and quality of care. These dramatic changes demanded a reshaping of the nurses’ work environment. The aim of this study was to explore how nurses reshaped their work environment in the early stages of the COVID-19 pandemic. Methods A descriptive study comprising 26 semi-structured interviews conducted in a large Dutch teaching hospital between June and September 2020. Participants were nurses (including intensive care unit nurses), outpatient clinic assistants, nurse managers, and management (including one member of the Nurse Practice Council). The interviews were analysed with open, axial, and selective coding. Results We identified five themes: 1) the Nursing Staff Deployment Plan created new micro-teams with complementary roles to meet the care needs of COVID-19 infected patients; 2) nurse-led adaptations effectively managed the increased workload, thereby ensuring the quality of care; 3) continuous professional development ensured adequate competence levels for all roles; 4) interprofessional collaboration resulted in experienced solidarity, a positive atmosphere, and increased autonomy for nurses; and, 5) supportive managers reduced nurses’ stress and improved work conditions. Conclusions This study showed that nurses positively reshaped their work environment during the COVID-19 pandemic. They contributed to innovative solutions in an environment of equal interprofessional collaboration, which led to greater respect for their knowledge and competencies, enhanced their autonomy and improved management support.

Abstract Climate change is rapidly transforming the coastal margins of Greenland. At the same time, there is increasing recognition that marine‐terminating glaciers provide unique and critical habitats to ice‐associated top predators. We investigated the connection between a top predator occupying glacial fjord systems in Northwest Greenland and the properties of Atlantic‐origin water and marine‐terminating glaciers through a multiyear interdisciplinary project. Using passive acoustic monitoring, we quantified the summer presence and autumn departure of narwhals (Monodon monoceros) at glacier fronts in Melville Bay and modeled what glacier fjord physical attributes are associated with narwhal occurrence. We found that narwhals are present at glacier fronts after Greenland Ice Sheet peak summer runoff and they remain there during the period when the water column is becoming colder and fresher. Narwhals occupied glacier fronts when ocean temperatures ranged from −0.6 to 0.8°C and salinities between 33.2 and 34.0 psu at around 200 m depth and they departed on their southbound migration between October and November. Narwhals' departure was approximately 4 weeks later in 2019 than in 2018, after an extreme 2019 summer heatwave event that also delayed sea ice formation by 2 months. Our study provides further support for the niche conservative narwhal's preference for cold ocean temperatures. These results may inform projections about how future changes will impact narwhal subpopulations, especially those occupying Greenland glacial fjords.

Abstract Background Social prescribing (SP) is a non-clinical approach, most commonly based in healthcare units, that aims to address non-medical health-related social needs by connecting individuals with community-based services. This qualitative study explores the perception of Portuguese older adults regarding the benefits of SP and their willingness to participate in SP initiatives. Methods Three face-to-face focus group sessions were conducted with 23 participants in different cities in Portugal. Open and semi-open questions were used to guide the discussions and thematic analysis was used to analyze the data. Results The participants recognized the potential benefits of SP for older adults, including diversifying leisure activities, improving mental health, and complementing existing support systems. They highlighted the need for external support, usually in the form of link workers, to facilitate personalized referrals and consider individual characteristics and preferences. While some participants expressed reluctance to engage in SP due to their existing busy schedules and a perceived sense of imposition, others showed openness to having new experiences and recognized the potential value of SP in promoting activity. Barriers to participation, including resistance to change, mobility issues, and family responsibilities, were identified. Conclusions The study emphasizes the importance of a person-centered and co-designed approach to SP, involving older adults in the planning and implementation of interventions. The findings provide valuable insights for the development of SP programs tailored to the unique needs and aspirations of older adults in Portugal, ultimately promoting active and healthy aging. Future research should consider the perspectives of family doctors and include a broader representation of older adults from diverse geographic areas.

Introduction: We sought to describe the range of emergency medicine (EM) resident physicians’ perceptions and experiences of working and training during the initial coronavirus 2019 (COVID-19) pandemic surge at two, large-volume, urban training hospitals in Brooklyn, New York. Methods: A total of 25 EM resident physicians who worked at either of two large emergency departments (ED) from March 15–April 11, 2020 participated in semi-structured interviews conducted in July and August 2020. Interviews were conducted by the authors who were also emergency medicine resident physicians working in the ED during this time. We asked open-ended questions to residents about their experiences and emotions at work and outside of work, including their relationship with co-workers, patients, and their community. The interviews were audio-recorded and transcribed. We then conducted a thematic analysis to identify, classify, and define themes from interview transcripts. Iterative commonalities and differences between interview response themes were grouped to create a broadly applicable narrative of the residents’ perceptions and experiences of working and training during this initial wave of a novel pandemic. Interviewees also responded to a demographics survey. Results: Study participants described four major aspects of their perceptions and experiences of working and training during the stated time, including emotional challenges such as anxiety and feeling underappreciated; protective thoughts, including camaraderie, and sense of duty; workplace challenges such as limited knowledge surrounding COVID-19 and a higher volume of acute patients; and adaptive strategies including increased communication with ED administrators. Conclusion: Emergency medicine residents have a unique perspective and were key frontline hospital responders during a prolonged disaster and mass triage event within a local health system. Considering the chronic case and mortality fluctuations and new variants of COVID-19, as well as the anticipation of future infectious disease pandemics, we believe it is important for key decision-makers in resident education, hospital administration, and all levels of public health management to inform themselves about residents’ emotional and workplace challenges when establishing hospital and residency program disaster protocols.

Background In many countries, infant vaccination with acellular pertussis (aP) vaccines has replaced use of more reactogenic whole-cell pertussis (wP) vaccines. Based on immunological and epidemiological evidence, we hypothesised that substituting the first aP dose in the routine vaccination schedule with wP vaccine might protect against IgE-mediated food allergy. We aimed to compare reactogenicity, immunogenicity, and IgE-mediated responses of a mixed wP/aP primary schedule versus the standard aP-only schedule. Methods and findings OPTIMUM is a Bayesian, 2-stage, double-blind, randomised trial. In stage one, infants were assigned (1:1) to either a first dose of a pentavalent wP combination vaccine (DTwP-Hib-HepB, Pentabio PT Bio Farma, Indonesia) or a hexavalent aP vaccine (DTaP-Hib-HepB-IPV, Infanrix hexa, GlaxoSmithKline, Australia) at approximately 6 weeks old. Subsequently, all infants received the hexavalent aP vaccine at 4 and 6 months old as well as an aP vaccine at 18 months old (DTaP-IPV, Infanrix-IPV, GlaxoSmithKline, Australia). Stage two is ongoing and follows the above randomisation strategy and vaccination schedule. Ahead of ascertainment of the primary clinical outcome of allergist-confirmed IgE-mediated food allergy by 12 months old, here we present the results of secondary immunogenicity, reactogenicity, tetanus toxoid IgE-mediated immune responses, and parental acceptability endpoints. Serum IgG responses to diphtheria, tetanus, and pertussis antigens were measured using a multiplex fluorescent bead-based immunoassay; total and specific IgE were measured in plasma by means of the ImmunoCAP assay (Thermo Fisher Scientific). The immunogenicity of the mixed schedule was defined as being noninferior to that of the aP-only schedule using a noninferiority margin of 2/3 on the ratio of the geometric mean concentrations (GMR) of pertussis toxin (PT)-IgG 1 month after the 6-month aP. Solicited adverse reactions were summarised by study arm and included all children who received the first dose of either wP or aP. Parental acceptance was assessed using a 5-point Likert scale. The primary analyses were based on intention-to-treat (ITT); secondary per-protocol (PP) analyses were also performed. The trial is registered with ANZCTR (ACTRN12617000065392p). Between March 7, 2018 and January 13, 2020, 150 infants were randomised (75 per arm). PT-IgG responses of the mixed schedule were noninferior to the aP-only schedule at approximately 1 month after the 6-month aP dose [GMR = 0·98, 95% credible interval (0·77 to 1·26); probability (GMR > 2/3) > 0·99; ITT analysis]. At 7 months old, the posterior median probability of quantitation for tetanus toxoid IgE was 0·22 (95% credible interval 0·12 to 0·34) in both the mixed schedule group and in the aP-only group. Despite exclusions, the results were consistent in the PP analysis. At 6 weeks old, irritability was the most common systemic solicited reaction reported in wP (65 [88%] of 74) versus aP (59 [82%] of 72) vaccinees. At the same age, severe systemic reactions were reported among 14 (19%) of 74 infants after wP and 8 (11%) of 72 infants after aP. There were 7 SAEs among 5 participants within the first 6 months of follow-up; on blinded assessment, none were deemed to be related to the study vaccines. Parental acceptance of mixed and aP-only schedules was high (71 [97%] of 73 versus 69 [96%] of 72 would agree to have the same schedule again). Conclusions Compared to the aP-only schedule, the mixed schedule evoked noninferior PT-IgG responses, was associated with more severe reactions, but was well accepted by parents. Tetanus toxoid IgE responses did not differ across the study groups. Trial registration Trial registered at the Australian and New Zealand Clinical 207 Trial Registry (ACTRN12617000065392p)., Author(s): Gladymar Pérez Chacón 1,2, Marie J. Estcourt 3, James Totterdell 3, Julie A. Marsh 1, Kirsten P. Perrett 4,5, Dianne E. Campbell 6,7, Nicholas Wood 7,8, Michael Gold 9, [...]

In monotocous mammals, most individuals experience the birth of a younger sibling. This period may induce losses in maternal care and can be physiologically, energetically and emotionally challenging for the older sibling, yet has rarely been studied in wild primates. We used behavioural data collected from a natural population of mandrills to investigate changes in maternal care and mother–juvenile relationship throughout the transition to siblinghood (TTS), by comparing juveniles who recently experienced the birth of a younger sibling, to juveniles who did not. We found that the TTS was associated with an abrupt cessation of the weaning process for the juvenile, and to a decrease in maternal affiliation. Juveniles’ reactions were sex-specific, as males associated less with their mother, while females tended to groom their mother more often after the birth of their sibling. Despite the substantial loss of maternal care, juveniles did not show an increase in conflict or anxiety-related behaviours. This study contributes to explain why short interbirth intervals often pose a risk to juveniles’ survival in monotocous primates. Our results contrast existing studies and further highlight the importance of examining the TTS in species and populations with various life histories and ecologies.

BackgroundIn many countries, infant vaccination with acellular pertussis (aP) vaccines has replaced use of more reactogenic whole-cell pertussis (wP) vaccines. Based on immunological and epidemiological evidence, we hypothesised that substituting the first aP dose in the routine vaccination schedule with wP vaccine might protect against IgE-mediated food allergy. We aimed to compare reactogenicity, immunogenicity, and IgE-mediated responses of a mixed wP/aP primary schedule versus the standard aP-only schedule.Methods and findingsOPTIMUM is a Bayesian, 2-stage, double-blind, randomised trial. In stage one, infants were assigned (1:1) to either a first dose of a pentavalent wP combination vaccine (DTwP-Hib-HepB, Pentabio PT Bio Farma, Indonesia) or a hexavalent aP vaccine (DTaP-Hib-HepB-IPV, Infanrix hexa, GlaxoSmithKline, Australia) at approximately 6 weeks old. Subsequently, all infants received the hexavalent aP vaccine at 4 and 6 months old as well as an aP vaccine at 18 months old (DTaP-IPV, Infanrix-IPV, GlaxoSmithKline, Australia). Stage two is ongoing and follows the above randomisation strategy and vaccination schedule. Ahead of ascertainment of the primary clinical outcome of allergist-confirmed IgE-mediated food allergy by 12 months old, here we present the results of secondary immunogenicity, reactogenicity, tetanus toxoid IgE-mediated immune responses, and parental acceptability endpoints. Serum IgG responses to diphtheria, tetanus, and pertussis antigens were measured using a multiplex fluorescent bead-based immunoassay; total and specific IgE were measured in plasma by means of the ImmunoCAP assay (Thermo Fisher Scientific). The immunogenicity of the mixed schedule was defined as being noninferior to that of the aP-only schedule using a noninferiority margin of 2/3 on the ratio of the geometric mean concentrations (GMR) of pertussis toxin (PT)-IgG 1 month after the 6-month aP. Solicited adverse reactions were summarised by study arm and included all children who received the first dose of either wP or aP. Parental acceptance was assessed using a 5-point Likert scale. The primary analyses were based on intention-to-treat (ITT); secondary per-protocol (PP) analyses were also performed. The trial is registered with ANZCTR (ACTRN12617000065392p). Between March 7, 2018 and January 13, 2020, 150 infants were randomised (75 per arm). PT-IgG responses of the mixed schedule were noninferior to the aP-only schedule at approximately 1 month after the 6-month aP dose [GMR = 0·98, 95% credible interval (0·77 to 1·26); probability (GMR > 2/3) > 0·99; ITT analysis]. At 7 months old, the posterior median probability of quantitation for tetanus toxoid IgE was 0·22 (95% credible interval 0·12 to 0·34) in both the mixed schedule group and in the aP-only group. Despite exclusions, the results were consistent in the PP analysis. At 6 weeks old, irritability was the most common systemic solicited reaction reported in wP (65 [88%] of 74) versus aP (59 [82%] of 72) vaccinees. At the same age, severe systemic reactions were reported among 14 (19%) of 74 infants after wP and 8 (11%) of 72 infants after aP. There were 7 SAEs among 5 participants within the first 6 months of follow-up; on blinded assessment, none were deemed to be related to the study vaccines. Parental acceptance of mixed and aP-only schedules was high (71 [97%] of 73 versus 69 [96%] of 72 would agree to have the same schedule again).ConclusionsCompared to the aP-only schedule, the mixed schedule evoked noninferior PT-IgG responses, was associated with more severe reactions, but was well accepted by parents. Tetanus toxoid IgE responses did not differ across the study groups.Trial registrationTrial registered at the Australian and New Zealand Clinical 207 Trial Registry (ACTRN12617000065392p).

Autoimmune blistering disorders (AIBDs) are a heterogeneous group of approximately a dozen entities comprising pemphigus and pemphigoid disorders and dermatitis herpetiformis. The exact diagnosis of AIBDs is critical for both prognosis and treatment and is based on the clinical appearance combined with the detection of tissue-bound and circulating autoantibodies. While blisters and erosions on the skin and/or inspectable mucosal surfaces are typical, lesions may be highly variable with erythematous, urticarial, prurigo-like, or eczematous manifestations. While direct immunofluorescence microscopy (IFM) of a perilesional biopsy is still the diagnostic gold standard, the molecular identification of the major target antigens opened novel therapeutic avenues. At present, most AIBDs can be diagnosed by the detection of autoantigen-specific serum antibodies by enzyme-linked immunosorbent assay (ELISA) or indirect IFM when the clinical picture is known. This is achieved by easily available and highly specific and sensitive assays employing recombinant immunodominant fragments of the major target antigens, i.e., desmoglein 1 (for pemphigus foliaceus), desmoglein 3 (for pemphigus vulgaris), envoplakin (for paraneoplastic pemphigus), BP180/type XVII collagen (for bullous pemphigoid, pemphigoid gestationis, and mucous membrane pemphigoid), laminin 332 (for mucous membrane pemphigoid), laminin β4 (for anti-p200 pemphigoid), type VII collagen (for epidermolysis bullosa acquisita and mucous membrane pemphigoid), and transglutaminase 3 (for dermatitis herpetiformis). Indirect IFM on tissue substrates and in-house ELISA and immunoblot tests are required to detect autoantibodies in some AIBD patients including those with linear IgA disease. Here, a straightforward modern approach to diagnosing AIBDs is presented including diagnostic criteria according to national and international guidelines supplemented by long-term in-house expertise.

Background: Multiple cardiovascular outcomes trials (CVOTs) have shown the efficacy of GLP-1RAs in reducing major adverse cardiovascular events (MACEs) for high-risk patients. However, some CVOTs failed to demonstrate cardiovascular benefits. Objectives: We analyzed the impact of GLP-1RA on cardiovascular and renal outcomes in patients with or without T2DM, with subgroup analysis based on sex, estimated glomerular filtration rate (eGFR), body mass index (BMI), and history of cardiovascular disease (CVD). Methods: A comprehensive database search for placebo-controlled RCTs on GLP-1RA treatment was conducted until April 2024. Data extraction and quality assessment were carried out, employing a robust statistical analysis using a random effects model to determine outcomes with log odds ratios and 95 % confidence intervals (CIs). Results: A total of 13 CVOTs comprising 83,258 patients were included. GLP-1RAs significantly reduced MACE (OR 0.86, 95 % CI: 0.80 to 0.94, p < 0.01) all-cause mortality OR 0.87, 95 % CI: 0.82 to 0.93, p < 0.001, CV mortality (OR 0.87, 95 % CI: 0.81 to 0.94, p < 0.001), stroke (fatal: OR 0.74, 95 % CI: 0.56 to 0.96, p = 0.03; non-fatal: OR 0.87, 95 % CI: 0.79 to 0.96, p = 0.005), coronary revascularization (OR 0.86, 95 % CI: 0.74 to 0.99, p = 0.023), and composite kidney outcome (OR 0.76, 95 % CI: 0.67 to 0.85, p < 0.001. GLP-1RA significantly reduced MACE in both sexes. Furthermore, GLP-1RA reduced MACE regardless of CVD history, BMI, and eGFR level. Conclusion: Significant reductions in MACE, overall and CV mortality, stroke, coronary revascularization, and composite kidney outcome with GLP-1RA treatment were noted across all subgroups.

Background/Objectives: To date, nearly 300 lentiviral-based gene therapy clinical trials have been conducted, with eight therapies receiving regulatory approval for commercialization. These advances, along with the increased number of advanced-phase clinical trials, have prompted contract development and manufacturing organizations (CDMOs) to develop innovative strategies to address the growing demand for large-scale batches of lentiviral vectors (LVVs). Consequently, manufacturers have focused on optimizing processes under good manufacturing practices (GMPs) to improve cost-efficiency, increase process robustness, and ensure regulatory compliance. Nowadays, the LVV production process mainly relies on the transient transfection of four plasmids encoding for the lentiviral helper genes and the transgene. While this method is efficient at small scales and has also proven to be scalable, the industry is exploring alternative processes due to the high cost of GMP reagents, and the batch-to-batch variability predominantly attributed to the transfection step. Methods: Here, we report the development and implementation of a reliable and clinical-grade envisioned platform based on the generation of stable producer cell lines (SCLs) from an initial well-characterized lentiviral packaging cell line (PCL). Results: This platform enables the production of VSV-G-pseudotyped LVVs through a fully transfection-free manufacturing process. Our data demonstrate that the developed platform will facilitate successful technological transfer to large-scale LVV production for clinical application. Conclusions: With this simple and robust stable cell line generation strategy, we address key concerns associated with the costs and reproducibility of current manufacturing processes.

Objectives Systematically measuring the work environment of healthcare employees is key to continuously improving the quality of care and addressing staff shortages. In this study, we systematically analyse the responses to the one open-ended question posed in the Dutch version of the Culture of Care Barometer (CoCB-NL) to examine (1) if the responses offered new insights into healthcare employees’ perceptions of their work environment and (2) if the original CoCB had any themes missing.Design Retrospective text analysis using Rigorous and Accelerated Data Reduction technique.Setting University hospital in the Netherlands using the CoCB-NL as part of the annual employee survey.Participants All hospital employees were invited to participate in the study (N=14 671). In total, 2287 employees responded to the open-ended question.Results 2287 comments were analysed. Comments that contained more than one topic were split according to topic, adding to the total (n=2915). Of this total, 372 comments were excluded because they lacked content or respondents indicated they had nothing to add. Subsequently, 2543 comments were allocated to 33 themes. Most comments (n=2113) addressed the 24 themes related to the close-ended questions in the CoCB-NL. The themes most commented on concerned questions on ‘organisational support’. The remaining 430 comments covered nine additional themes that addressed concerns about work environment factors (team connectedness, team effectiveness, corporate vision, administrative burden and performance pressure) and themes (diversity and inclusion, legal frameworks and collective bargaining, resilience and work–life balance, and personal matters).Conclusions Analysing responses to the open-ended question in the CoCB-NL led to new insights into relevant elements of the work environment and missing themes in the COCB-NL. Moreover, the analysis revealed important themes that not only require attention from healthcare organisations to ensure adequate improvements in their employees’ work environment but should also be considered to further develop the CoCB-NL.

Introduction Dementia is a complex medical condition that poses significant challenges to healthcare systems and support services. People living with dementia (PLWD) and their carers experience complex needs often exacerbated by social isolation and challenges in accessing support. Social prescribing (SP) seeks to enable PLWD and their carers to access community and voluntary sector resources to support them address such needs. Existing research, however, does not describe what SP interventions are currently in place in dementia care. Little is known about the needs these interventions are designed to address, the reasons that lead PLWD and their carers to participate in them, their effectiveness and the extent to which they could increase positive health outcomes if adopted and how.Methods and analysis A complex intervention systematic review of SP for PLWD and/or their carers will be conducted using an iterative logic model approach. Six electronic (MEDLINE, EMBASE, PsycINFO, CINAHL, Scopus and Cochrane/CENTRAL) and two grey literature databases (EThOS and CORE) were searched for publications between 1 January 2003 and June 2023, supplemented by handsearching of reference lists of included studies. Study selection, data extraction and risk of bias assessment, using Gough’s Weight of Evidence Framework, will be independently performed by two reviewers. A narrative approach will be employed to synthesise and report quantitative and qualitative data. Reporting will be informed by the Preferred Reporting Items for Systematic Review and Meta-Analysis Complex Interventions extension statement and checklist.Ethics and dissemination No ethical approval is required due to this systematic review operating only with secondary sources. Findings will be disseminated through peer-reviewed publications, conference presentations and meetings with key stakeholders including healthcare professionals, patient and carer groups, community organisations (eg, the Social Prescribing Network and the Evidence Collaborative at the National Academy for Social Prescribing), policymakers and funding bodies.PROSPERO registration number CRD42023428625.

Introduction Measure Yourself Concerns and Wellbeing is a validated person-centred outcome measure, piloted as a core monitoring tool to understand what matters to people living with frailty in Gloucestershire. This paper describes the acceptability of MYCaW used in this setting, and the development of a framework for analysing personalised concerns from people living with frailty.Methods MYCaW was implemented in the Complex Care at Home service and South Cotswold Frailty Service from November 2020 onwards. MYCaW was completed at the person’s first meeting with a community matron and then 3 months later. Nineteen staff completed an anonymous survey to provide feedback on the acceptability of the tool. A framework of concerns bespoke to people living with frailty was created via iterative rounds of independent coding of 989 concerns from 526 people. The inter-rater reliability of the framework was determined by using the Cronbach alpha test.Results MYCaW was simple to use and helped health professionals’ discussions to be patient focused. A pictorial scale accompanying the Numerical Rating Scale was developed and tested to help people engage with scoring their concerns and well-being more easily. A framework of concerns from people living with frailty was produced with five main supercategories: Mental and Emotional Concerns; Physical Concerns; Healthcare and Service Provision Concerns, Concerns with General Health and Well-being and Practical Concerns. Inter-rater reliability was kappa=0.905.Conclusions MYCaW was acceptable as a core monitoring tool for people living with frailty and enabled a systematic approach to opening ‘What Matters to Me’ conversations. The personalised data generated valuable insights into how the frailty services positively impacted the outcomes for people living with frailty. The coding framework demonstrated a wide range of concerns—many linked to inequalities and not identified on existing outcome measures recommended for people living with frailty.

Summary: CRISPR-Cas immune systems provide bacteria with adaptive immunity against bacteriophages, but they are often transcriptionally repressed to mitigate auto-immunity. In some cases, CRISPR-Cas expression increases in response to a phage infection, but the mechanisms of induction are largely unknown, and it is unclear whether induction occurs strongly and quickly enough to benefit the bacterial host. In S. pyogenes, Cas9 is both an immune effector and auto-repressor of CRISPR-Cas expression. Here, we show that phage-encoded anti-CRISPR proteins relieve Cas9 auto-repression and trigger a rapid increase in CRISPR-Cas levels during a single phage infective cycle. As a result, fewer cells succumb to lysis, leading to a striking survival benefit after multiple rounds of infection. CRISPR-Cas induction also reduces lysogeny, thereby limiting a route for horizontal gene transfer. Altogether, we show that Cas9 is not only a CRISPR-Cas effector and repressor but also a phage sensor that can mount an anti-anti-CRISPR transcriptional response.