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Bluetongue (BT) is a Culicoides midge-borne hemorrhagic disease affecting cervids and ruminant livestock species, resulting in significant economic losses from animal production and trade restrictions. Experimental animal infections using the α/β interferon receptor knockout IFNAR mouse model and susceptible target species are critical for understanding viral pathogenesis, virulence, and evaluating vaccines. However, conducting experimental vector-borne transmission studies with the vector itself are logistically difficult and experimentally problematic. Therefore, experimental infections are induced by hypodermic injection with virus typically derived from baby hamster kidney (BHK) cells. Unfortunately, for many U.S. BTV serotypes, it is difficult to replicate the severity of the disease seen in natural, midge-transmitted infections by injecting BHK-derived virus into target host animals. Using the IFNAR BTV murine model, we compared the virulence of traditional BHK cell-derived BTV-17 with C. sonorensis midge (W8) cell-derived BTV-17 to determine whether using cells of the transmission vector would provide an in vitro virulence aspect of vector-transmitted virus. At both low and high doses, mice inoculated with W8-BTV-17 had an earlier onset of viremia, earlier onset and peak of clinical signs, and significantly higher mortality compared to mice inoculated with BHK-BTV-17. Our results suggest using a Culicoides W8 cell-derived inoculum may provide an in vitro vector-enhanced infection to more closely represent disease levels seen in natural midge-transmitted infections while avoiding the logistical and experimental complexity of working with live midges.

A solar sail propelled small satellite mission concept to intercept and potentially rendezvous with newly discovered transient interstellar objects (ISOs) is described. The mission concept derives from the proposal for a technology demonstration mission for exiting the solar system at high velocity, eventually to reach the focal region of the solar gravitational lens. The ISO mission concept is to fly a solar sail toward a holding orbit around the Sun and when the ISO orbit is confirmed, target the sailcraft to reach an escape velocity of over 6 AU/year. This would permit rapid response to a new ISO discovery and an intercept within 10 AU from the Sun. Two new proven interplanetary technologies are utilized to enable such a mission: i) interplanetary smallsats, such as those demonstrated by the MarCO mission, and ii) solar sails, such as demonstrated by LightSail and IKAROS missions and developed for NEA Scout and Solar Cruiser missions. Current technology work suggests that already within this decade such a mission could fly and reach an ISO moving through the solar system. It might enable the first encounter with an ISO to allow for imaging and spectroscopy, measurements of size and mass, potentially giving a unique information about the object’s origin and composition. A similar approach may be used to allow for a sample return.

Research regarding autistic children's sibling relationship quality is mixed, although some literature suggests poorer quality compared to children with other disabilities or who are neurotypical. Little is known about how the clinical characteristics of autistic children relate to parent perceptions of sibling relationship quality. We drew data from a subsample of 119 children on the autism spectrum, ages 10-11 years, from an ongoing longitudinal study. Hierarchical multiple regressions tested the extent to which children's autism symptoms, behavioral difficulties, and communication abilities related to four domains of parent-rated sibling relationship quality. We also examined communication ability as a moderator of the effect of behavioral difficulties on parent-rated sibling relationship quality. More severe autism symptoms were associated with lower levels of conflict and rivalry, whereas higher communication ability was related to more relative status/power, but also conflict. Communication ability moderated the effect of behavioral difficulties such that behavioral difficulties were more closely associated with less warmth/closeness when children had weaker communication skills; behavioral difficulties were not significantly associated with other domains of sibling relationship quality. Findings underscore the importance of considering clinical characteristics and multiple domains of relationship quality to better understand how parents view the relationships between autistic children and their siblings.

Introduction Between 2009/2010 and 2019/2020, England witnessed an increase in suspected head and neck cancer (sHNC) referrals from 140 to 404 patients per 100 000 population. 1 in 10 patients are not seen within the 2-week target, contributing to patient anxiety. We will develop a pathway for sHNC referrals, based on the Head and Neck Cancer Risk Calculator. The evolution of a patient-reported symptom-based risk stratification system to redesign the sHNC referral pathway (EVEREST-HN) Programme comprises six work packages (WPs). This protocol describes WP1 and WP2. WP1 will obtain an understanding of language to optimise the SYmptom iNput Clinical (SYNC) system patient-reported symptom questionnaire for sHNC referrals and outline requirements for the SYNC system. WP2 will codesign key elements of the SYNC system, including the SYNC Questionnaire, and accompanying behaviour change materials.Methods and analysis WP1 will be conducted at three acute National Health Service (NHS) trusts with variation in service delivery models and ensuring a broad mixture of social, economic and cultural backgrounds of participants. Up to 150 patients with sHNC (n=50 per site) and 15 clinicians (n=5 per site) will be recruited. WP1 will use qualitative methods including interviews, observation and recordings of consultations. Rapid qualitative analysis and inductive thematic analysis will be used to analyse the data. WP2 will recruit lay patient representatives to participate in online focus groups (n=8 per focus group), think-aloud technique and experience-based codesign and will be analysed using qualitative and quantitative approaches.Ethics and dissemination The committee for clinical research at The Royal Marsden, a research ethics committee and the Health Research Authority approved this protocol. All participants will give informed consent. Ethical issues of working with patients on an urgent cancer diagnostic pathway have been considered. Findings will be disseminated via journal publications, conference presentations and public engagement activities.

Background Falls are the most common safety incident reported by acute hospitals. The National Institute of Health and Care Excellence recommends multifactorial falls risk assessment and tailored interventions, but implementation is variable. Aim To determine how and in what contexts multifactorial falls risk assessment and tailored interventions are used in acute National Health Service hospitals in England. Design Realist review and multisite case study. (1) Systematic searches to identify stakeholders’ theories, tested using empirical data from primary studies. Review of falls prevention policies of acute Trusts. (2) Theory testing and refinement through observation, staff interviews (n = 50), patient and carer interviews (n = 31) and record review (n = 60). Setting Three Trusts, one orthopaedic and one older person ward in each. Results Seventy-eight studies were used for theory construction and 50 for theory testing. Four theories were explored. (1) Leadership: wards had falls link practitioners but authority to allocate resources for falls prevention resided with senior nurses. (2) Shared responsibility: a key falls prevention strategy was patient supervision. This fell to nursing staff, constraining the extent to which responsibility for falls prevention could be shared. (3) Facilitation: assessments were consistently documented but workload pressures could reduce this to a tick-box exercise. Assessment items varied. While individual patient risk factors were identified, patients were categorised as high or low risk to determine who should receive supervision. (4) Patient participation: nursing staff lacked time to explain to patients their falls risks or how to prevent themselves from falling, although other staff could do so. Sensitive communication could prevent patients taking actions that increase their risk of falling. Limitations Within the realist review, we completed synthesis for only two theories. We could not access patient records before observations, preventing assessment of whether care plans were enacted. Conclusions (1) Leadership: There should be a clear distinction between senior nurses’ roles and falls link practitioners in relation to falls prevention; (2) shared responsibility: Trusts should consider how processes and systems, including the electronic health record, can be revised to better support a multidisciplinary approach, and alternatives to patient supervision should be considered; (3) facilitation: Trusts should consider how to reduce documentation burden and avoid tick-box responses, and ensure items included in the falls risk assessment tools align with guidance. Falls risk assessment tools and falls care plans should be presented as tools to support practice, rather than something to be audited; (4) patient participation: Trusts should consider how they can ensure patients receive individualised information about risks and preventing falls and provide staff with guidance on brief but sensitive ways to talk with patients to reduce the likelihood of actions that increase their risk of falling. Future work (1) Development and evaluation of interventions to support multidisciplinary teams to undertake, and involve patients in, multifactorial falls risk assessment and selection and delivery of tailored interventions; (2) mixed method and economic evaluations of patient supervision; (3) evaluation of engagement support workers, volunteers and/or carers to support falls prevention. Research should include those with cognitive impairment and patients who do not speak English. Study registration This study is registered as PROSPERO CRD42020184458. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR129488) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 5. See the NIHR Funding and Awards website for further award information. Plain language summary Many accidental falls by older people in hospitals could be avoided. There are guidelines to prevent falls, but some hospitals are better at following them than others. This study aimed to find out why. First, we looked at research and hospitals’ falls policies for ideas about what stops falls. With advice from service users, we tested these ideas in four hospitals in England, watching how falls were prevented on wards for older people and people who need bone care, and talking to 50 staff, 28 patients and 3 carers. We found the following: Falls leadership: wards had staff called falls link practitioners who supported falls prevention, but senior nurses, not link practitioners, made the most important decisions. Sharing responsibility: patients with falls risks were monitored to try to stop falls. Because only nursing teams were always present to monitor patients, they had most responsibility for preventing falls. This limited sharing responsibility with other staff. Computer tools: nurses used computers to record prevention work, but high workloads could make this a ‘tick-box’ exercise. Computer tools reminded them to do this, although tools varied. Patients had individual falls plans, but they were also ranked more generally as high or low risk of falling, with ‘high-risk’ patients being monitored. Patient involvement: nursing staff did not have time to explain to patients how to prevent falls, but other staff could have such conversations. Many patients had problems like dementia and found it difficult to follow safety advice, although some could take steps to keep safe, with sensitive staff support. We need to involve patients, carers and different staff in falls prevention. Hospitals could develop computer systems to support this, think how to involve more ward staff, and provide guidance on helpful ways to talk with patients about falls. Scientific summary Background Inpatient falls are the most common safety incident reported by acute hospitals and can cause both physical and non-physical harm. The National Institute of Health and Care Excellence (NICE) guideline on falls in older people recommends a multifactorial falls risk assessment (MFRA) and interventions tailored to address the patient’s identified risk factors for all inpatients aged 65 years and older, or 50–64 years and judged to be at higher risk of falling due to an underlying condition. This approach is estimated to reduce the incidence of inpatient falls by 25–30%. However, there is substantial unexplained variation between hospitals in adherence to this guideline. Objectives Use secondary data to develop a theory that explains what supports and constrains routine use of MFRA and falls prevention interventions. Refine the theory through mixed method data collection across three acute hospital Trusts. Translate the theory into guidance to support MFRA and prevention and, in turn, adherence to the NICE guideline. Methods Throughout the study, we were supported by DW, the lay member of the project management group, and the Lay Research Group (a group of service users and carers who had either fallen themselves or cared for someone who fell in hospital). We first undertook a realist review. In Phase 1, systematic searches were undertaken for commentary-type articles, studies mentioning theories/conceptual models for falls risk assessment, and systematic reviews. Additionally, a search of professional/trade journals and an advanced Google search were undertaken. Titles, abstracts and full texts were screened for relevance. Data about contexts, mechanisms and outcomes were extracted from included papers, and referenced substantive theories were noted. Data were summarised in matrices, used to construct context mechanism outcome configurations (CMOcs). To determine which CMOcs should be taken forward for testing in Phase 2, the Lay Research Group and Study Steering Committee (SSC) (comprised of clinicians, academics, and a lay member, with expertise including falls prevention, risk assessment, patient safety and implementation science) ranked them, giving top rankings to statements they believed most likely to work in practice. The Lay Research Group was also asked to highly rank statements likely to have greatest impact for patients and carers. In Phase 2 of the realist review, systematic searches for the four concepts ranked highly by both the Lay Research Group and SSC were conducted across a range of databases. Titles, abstracts and full texts were screened for relevance. In Phase 3 of the realist review, data extraction was conducted using NVivo, coding sections of manuscripts to facilitate theory testing. Researchers analysed two CMOcs: one focused on implementation – facilitation – and one focused on falls risk reduction – patient participation. Narrative summaries were written and used to refine the initial CMOcs. Included texts were appraised using the mixed methods appraisal tool (MMAT). To assess strength of the body of evidence for the refined CMOcs, we used Grades of Recommendation, Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual). As an additional source of evidence, we undertook an advanced Google search for the policies of 25 acute Trusts regarding falls risk assessment and prevention. We assessed adherence of these policies to the NICE guideline on falls in older people by checking whether a falls risk prediction tool was recommended; whether the approach recommended involved tailoring interventions to patients’ individual risk factors; and by looking for specific elements of the assessments undertaken (such as whether continence and cognitive impairment are assessed), as specified by NICE and captured in the National Audit of Inpatient Falls (NAIF). We then conducted a multisite case study to further refine the theories across three NHS acute Trusts in England. Trusts were selected to ensure variation in key indicators in the NAIF and in health IT, and to include both teaching and district general hospitals. In each Trust, we collected data in one older person ward and one orthopaedic ward. Data were collected through 251.25 hours of ethnographic observations of falls prevention practices, interviews with staff (n = 50), patients (n = 28) and carers (n = 3), and a review of patient clinical records (n = 60). We also received routinely collected data on the number of falls and falls-related harms. The Lay Research Group contributed to the development of the observation protocol and interview topic guides for patients and carers. Observations took place at different times of day, including night shifts, and different days of the week, including weekends. The record review extracted data on (1) whether a falls risk assessment was completed for the patient on admission and within 6 hours; (2) whether a care plan was documented for the patient and if this was completed on a day or night shift; and (3) whether the care plan was updated and if updates were completed on a day or night shift. Qualitative data analysis followed the steps of framework analysis. The Lay Research Group contributed, providing a patient perspective. Descriptive statistics were produced for the record review data, broken down by ward. Narratives were written and used to refine the CMOcs. Online presentations at each case site acted as a form of respondent validation and an opportunity to gather participants’ perspectives on the implications of the research for practice. Findings In the realist review, 78 studies were used for theory construction and 50 for theory testing. Four theory areas were explored: (1) leadership; (2) shared responsibility; (3) facilitation via MFRA tools and (4) patient participation. The leadership theory developed in the theory construction phase of the realist review suggested that where falls prevention is prioritised by organisations, for example, in organisational policy and provision of resources, falls leaders/champions (staff trained and dedicated to supporting delivery of multifactorial falls prevention strategies on their wards, e.g. by offering training and education to new staff) inspire and support delivery of the strategy in a consistent and co-ordinated way, so all eligible patients receive a MFRA and tailored intervention strategies. This theory was tested through the review of Trust policies and multisite case study. The review of Trust policies found organisational-level policies, in the main, reflect NICE guidance. The role of falls link practitioners was identified in all three sites. Link practitioners were expected to act as role models for falls reduction in their clinical areas, and provide advice and education around assessment, intervention and management of patients who had fallen or were at risk of falling. They were also expected to facilitate regular audits of falls management practice on wards and raise any patient safety concerns. However, pressures of work on wards, aggravated by coronavirus disease 2019, meant it was not always possible to fulfil such duties. Similarly, it could be difficult for them to attend the training they were entitled to. Despite these challenges, documentation of the falls risk assessment and care plan was largely consistent across sites. Ultimate responsibility for falls prevention resided with senior nurses (the ward manager or the nurse-in-charge of the shift), who would monitor, remind and support staff to deliver falls prevention practices while also being sensitive to the pressures staff were under. They had authority to make decisions related to allocation of resources, such as which patients should be moved to cohort bays (bays where patients considered to be at high risk of falling were placed, with a staff member always present), and they would escalate patient safety concerns to hospital managers. Formal training about Trusts’ falls prevention policies was provided by organisational teams for new starters on induction. Messaging was also a key strategy, for example, through visual displays and reminders about expectations and policy on wards. The initial theory of shared responsibility suggested that, where there is a culture of learning from errors, if information about patients’ falls risks is effectively communicated between ward staff (e.g. through posters/safety huddles/handovers), staff will develop a sense of shared responsibility for falls prevention and become more vigilant of patients at risk from falls, supporting implementation of multifactorial strategies to prevent falls. This theory was tested through the case study. Undertaking MFRAs was the responsibility of nurses; this documentation was rarely accessed by other professional groups. Instead, communication between professional groups was primarily verbal, both formal, for example, in multidisciplinary team meetings and safety huddles, and informal. Additionally, visual communication tools were used, such as patient bed boards, on which information about patient transfer and mobilisation needs was recorded. Symbols such as a falling leaf were also displayed to identify patients at risk of falling. However, information on bed boards was often variable or incomplete. A key falls prevention strategy across all wards was patient supervision, for example, provision of one-to-one care and use of cohort bays, responsibility for which fell to nursing staff, constraining the extent to which responsibility for falls prevention could be shared among the multidisciplinary team. The initial facilitation theory concerned MFRA tools (including health IT) that reflect best practice recommendations, are relatively quick and easy to use, and easily integrated into existing workflows. The theory stated that, where staff educated about falls risks and prevention practices had access to such tools, they will complete them with patients because they facilitate implementation of recommended practice, helping to ensure all eligible patients receive a comprehensive MFRA and appropriate interventions. This theory was tested through the realist review and case study. Review findings suggested that, where tools are clearly visible to staff in their work routines, they can prompt documentation of a falls risk assessment. Following an assessment, documentation and delivery of interventions can be constrained by changes in patient condition, movement between wards, intervention availability, and communication between different professional groups. Health IT can facilitate delivery of falls prevention practices by automating processes and reducing work for clinicians but can also introduce additional tasks. There was variation across case sites in the number and type of assessment items included in the falls risk assessment tools within the electronic health record (EHR). Nurses perceived the tools as practice prompts, but competing priorities on nurse time could reduce tool use to a tick-box exercise. While all tools identified individual patient risk factors, stratification of patients as high or low risk was used to determine which patients should receive supervision. The initial patient participation theory suggested that, where patients have capacity to engage in the MFRA process, and a patient-centred approach is taken that involves them and their carers, patients will understand their strategy and have the confidence/reassurance to participate in specific interventions, thereby reducing their risk of falling. This theory was tested through the realist review and multisite case study. Review findings suggested that interventions that encourage cognitively intact patients to participate in falls prevention practices are associated with a reduction in falls. However, patient participation in falls prevention strategies can be constrained by patients not wanting to disturb busy nurses by requesting help, not perceiving or believing they are at risk of falls, and not understanding their falls risks. Patient participation is supported by staff who understand patients’ circumstances through meaningful, directed interactions, enabling staff to personalise falls prevention messages to improve patient knowledge, skills and confidence to participate. There is little research examining patient participation interventions with cognitively impaired patients. In the case study, workload pressures meant nursing staff had little time to explain to patients why they were at risk of falling or what they could do to prevent themselves from falling, although other staff could have such conversations and pass information to nurses. Many patients had cognitive impairments, which constrained the extent to which they could participate in interventions. Wards were often not staffed sufficiently for staff to respond to patient needs, leading to patients mobilising alone, although the quality of the interaction between staff and patients (including some cognitively impaired patients) could reduce the likelihood of patients taking actions that increased their risk of falling. Participants in the case site presentations agreed with the analysis. Key themes regarding implications were (1) the need for the lessons learnt to be disseminated to all professional groups, through leaflets and training materials; and (2) the need for leaflets for patients and carers, individualised to patients, providing them with information about their falls risks and how to prevent falls. Limitations A limitation of the review is that we were only able to complete data synthesis for two CMOcs. Limitations of the case study are that our observations focused on nursing staff, as they were most present on the wards, and we were unable to access patient records prior to observations, preventing assessment of whether care plans were enacted. Additionally, we did not manage to recruit patient participants who did not speak English; while we had information sheets translated into the three most spoken non-English languages across the case sites, all patients we met could speak English. Conclusions Implications for practice (1) Leadership: There should be a clear distinction between senior nurses’ roles and falls link practitioners in relation to fall prevention; (2) shared responsibility: Trusts should consider how processes and systems, including EHRs, can be revised to better support a multidisciplinary approach, and alternatives to patient supervision should be considered; (3) facilitation: Trusts should consider how to reduce documentation burden and avoid tick-box responses and ensure that items included in the falls risk assessment tools align with guidance. Falls risk assessment tools and falls care plans should be presented as tools to support practice, rather than something to be audited; (4) patient participation: Trusts should consider how they can ensure patients receive individualised information about risks and preventing falls and provide staff with guidance on brief but sensitive ways to talk with patients to reduce the likelihood of actions that increase their risk of falling. Recommendations for research Future research on falls risk assessment and prevention should include those with cognitive impairment and patients who do not speak the main language of the country in which the research is taking place: development and mixed method and economic evaluation of interventions to support multidisciplinary teams to undertake, and involve patients in, MFRA and selection and delivery of tailored interventions mixed method and economic evaluations of cohort bays and one-to-one care, comparing this to tailored alternatives mixed method and economic evaluations of engagement support workers, volunteers, and/or carers to support falls prevention. Study registration This study is registered on PROSPERO CRD42020184458. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR129488) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 5. See the NIHR Funding and Awards website for further award information.

Background:. Fracture-related infection is one of the most challenging complications in orthopaedic trauma surgery. However, the effect of infection on functional and pain-related outcomes has not been well established. The aims of this study were to evaluate functional recovery for patients with fracture and a deep surgical site infection compared with patients with fracture without infection and to evaluate whether pain severity, social support, and preinjury mental health have a moderating effect on the magnitude and direction of the relationship between deep surgical site infection and functional recovery. Methods:. This is a secondary retrospective cohort study using prospectively collected data from the VANCO trial (Local Antibiotic Therapy to Reduce Infection After Operative Treatment of Fractures at High Risk of Infection) and the OXYGEN (Supplemental Perioperative Oxygen to Reduce Surgical Site Infection After High Energy Fracture Surgery) trial. In this study, 2,116 patients with tibial plateau, pilon, or calcaneal fractures at high risk for infection were included. Patients were divided into cohorts of patients who experienced a deep surgical site infection and those who did not. The primary outcome measure was the functional outcome using the Veterans RAND 12-Item Health Survey (VR-12). Results:. After controlling for covariates, deep surgical site infection was independently associated with functional outcome, with a 3.3-point reduction in the VR-12 Physical Component Score, and pain severity was independently associated with functional outcome, with a 2.5-point reduction in the VR-12 Physical Component Score. Furthermore, the Brief Pain Inventory pain severity demonstrated an important moderating effect on the relationship between infection and functional outcome. In patients with lower pain scores, infection had a large negative impact on functional outcome, whereas, in patients with higher pain scores, infection had no significant impact on functional outcome. Furthermore, the functional outcome in the entire cohort remains at only 61% of baseline. Conclusions:. This study documents the negative impact of postoperative infection on functional recovery after injury, as well as the novel finding of pain severity as an important moderating factor. This study emphasizes not only the importance of developing effective interventions designed to reduce postoperative infection, but also the role that factors that moderate pain severity plays in limiting recovery of physical function. Level of evidence:. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Large and densely sampled sensor datasets can contain a range of complex stochastic structures that are difficult to accommodate in conventional linear models. This can confound attempts to build a more complete picture of an animal's behavior by aggregating information across multiple asynchronous sensor platforms. The Livestock Informatics Toolkit (LIT) has been developed in R to better facilitate knowledge discovery of complex behavioral patterns across Precision Livestock Farming (PLF) data streams using novel unsupervised machine learning and information theoretic approaches. The utility of this analytical pipeline is demonstrated using data from a 6-month feed trial conducted on a closed herd of 185 mix-parity organic dairy cows. Insights into the tradeoffs between behaviors in time budgets acquired from ear tag accelerometer records were improved by augmenting conventional hierarchical clustering techniques with a novel simulation-based approach designed to mimic the complex error structures of sensor data. These simulations were then repurposed to compress the information in this data stream into robust empirically-determined encodings using a novel pruning algorithm. Nonparametric and semiparametric tests using mutual and pointwise information subsequently revealed complex nonlinear associations between encodings of overall time budgets and the order that cows entered the parlor to be milked.

It is critical that educators have explicit opportunities to understand and apply Catholic Social Teaching in both educating, forming, and evangelizing PK-16 students. To enhance Catholic identity in the school environment, this action research study describes a model developed to assist school leaders and educators in reflecting upon the dimensions and application of Catholic teaching on education. Specifically, the study addresses the question: what opportunities could enhance school leaders' and educators' knowledge related to the pedagogical and professional, relational, formational and evangelistic education (PROFEss) dimensions of learning. Knowledge of these (PROFEss) dimensions afford educators and school leaders the ability to articulate and implement their Catholic identity in myriads of school types, including private, public, virtual, and homeschool environments.

Abstract Background Falls are the most common safety incident reported by acute hospitals. In England national guidance recommends delivery of a multifactorial falls risk assessment (MFRA) and interventions tailored to address individual falls risk factors. However, there is variation in how these practices are implemented. This study aimed to explore the variation by examining what supports or constrains delivery of MFRAs and tailored interventions in acute hospitals. Methods A realist review of literature was conducted with searches completed in three stages: (1) to construct hypotheses in the form of Context, Mechanism, Outcome configurations (CMOc) about how MFRAs and interventions are delivered, (2) to scope the breadth and depth of evidence available in Embase to test the CMOcs, and (3) following prioritisation of CMOcs, to refine search strategies for use in multiple databases. Citations were managed in EndNote; titles, abstracts, and full texts were screened, with 10% independently screened by two reviewers. Results Two CMOcs were prioritised for testing labelled: Facilitation via MFRA tools, and Patient Participation in interventions. Analysis indicated that MFRA tools can prompt action, but the number and type of falls risk factors included in tools differ across organisations leading to variation in practice. Furthermore, the extent to which tools work as prompts is influenced by complex ward conditions such as changes in patient condition, bed swaps, and availability of falls prevention interventions. Patient participation in falls prevention interventions is more likely where patient directed messaging takes individual circumstances into account, e.g., not wanting to disturb nurses by using the call bell. However, interactions that elicit individual circumstances can be resource intensive and patients with cognitive impairment may not be able to participate despite appropriately directed messaging. Conclusions Organisations should consider how tools can be developed in ways that better support consistent and comprehensive identification of patients’ individual falls risk factors and the complex ward conditions that can disrupt how tools work as facilitators. Ward staff should be supported to deliver patient directed messaging that is informed by their individual circumstances to encourage participation in falls prevention interventions, where appropriate. Trial registration PROSPERO: CRD42020184458.

Abstract Radio occultation (RO) by the Earth's atmosphere of the transmitted signals of the Global Navigation Satellite Systems' satellites has improved numerical weather prediction, has benefited atmospheric process studies, and benchmarked climate change by its strong traceability to the international definition of the second. Until now, research with RO has been isolated to the few centers that actually process the data and impracticable elsewhere because of limitations on data formats, organization and volume of the data, download bandwidth, and the lack of a database that can be queried before downloading data. We announce the availability of RO data in the Registry of Open Data of Amazon Web Services (AWS). RO data are freely available for download for the user and free to process and store for the manager of the repository. RO data as processed by the COSMIC Program Office at the University Corporation for Atmospheric Research, by the Radio Occultation Meteorology Satellite Application Facility (ROM SAF), by EUMETSAT, and by the NASA Jet Propulsion Laboratory are available beginning with calibrated (excess) phase, extending to bending angle and refractivity and to retrievals of pressure, temperature and water vapor. The same RO repository also contains a metadata database that permits simple querying, filtering, and download of data using a Python application programming interface provided by this same project. Four tutorial demonstrations are provided as jupyter notebooks to provide representative samples of code to perform common research activities with RO data, including database querying and analysis, inter‐center comparison of RO retrieval performance, and atmospheric process studies.

Backgrounds & Aims: The efficacy of immune checkpoint inhibitor (ICI) therapy for liver cancer remains limited. As the hypoxic liver environment regulates adenosine signaling, we tested the efficacy of adenosine A2a receptor (A2aR) inhibition in combination with ICI treatment in murine models of liver cancer. Methods: RNA expression related to the adenosine pathway was analyzed from public databases. Peripheral blood mononuclear cells of 13 patients with hepatocellular carcinoma (HCC) were examined by flow cytometry. The following murine cell lines were used: SB-1, RIL175, and Hep55.1c (liver cancer), CT26 (colon cancer), and B16–F10 (melanoma). C57BL/6 and BALB/c mice were used for orthotopic tumor models and were treated with SCH58261, an A2aR inhibitor, in combination with anti-PD1 therapy. Results: RNA expression of ADORA2A in tumor tissues derived from patients with HCC was higher than in tissues from other cancer types. A2aR+ T cells in peripheral blood from patients with HCC were highly proliferative after immunotherapy. Likewise, in an orthotopic murine model, A2aR expression on T cells increased following anti-PD1 treatment, and the expression of A2aR on T cells increased more in tumor-bearing mice compared with tumor-free mice. The combination of SCH58261 and anti-PD1 led to activation of T cells and reductions in tumor size in orthotopic liver cancer models. In contrast, SCH58261 monotherapy was ineffective in orthotopic liver cancer models and the combination was ineffective in the subcutaneous tumor models tested. CD4+ T-cell depletion attenuated the efficacy of the combination therapy. Conclusion: A2aR inhibition and anti-PD1 therapy had a synergistic anti-tumor effect in murine liver cancer models. Impact and implications: Adenosine A2a receptor (A2aR)-expressing T cells in the liver increased in tumor-bearing mice and after anti-PD1 treatment. The combination of an A2aR inhibitor and anti-PD1 treatment had potent anti-tumor effects in two murine models of orthotopic liver cancer. Adenosine A2a receptor blockade promotes immunotherapy efficacy in murine models, highlighting putative clinical benefits for advanced stage liver cancer patients.

Emotion dysregulation is common among autistic people, yet few measures have received psychometric evaluation in this population. We examined the factor structure, reliability, and validity of a commonly-used measure of emotion dysregulation, the "Difficulties with Emotion Regulation Scale" ("DERS"), in a sample of 156 autistic adolescents and adults. Data were drawn from the NIH National Database for Autism Research (NDAR) and an author's existing dataset. Results demonstrated that the factor structure generally conformed to the original 6-factor model, with modifications. Reliability analyses revealed good-to-excellent internal consistencies. Validity analyses indicated that the "DERS" was positively associated with measures of anxiety, depression, and alexithymia. Our findings provide preliminary evidence for the utility of the "DERS" in a small autistic sample, with minor modifications.

Background: Over 40 years of research implicates perfectionism in eating disorders in childhood and adolescence. However, the nature of this relationship remains understudied. To address this gap, we performed a systematic review and a meta-analysis to quantify the magnitude of the associations between perfectionism (i.e., unidimensional perfectionism, perfectionistic strivings, and perfectionistic concerns) and eating-related symptoms during childhood and adolescence. Methods: The literature search was conducted using five electronic databases in accordance with PRISMA guidelines: MEDLINE, Embase, CINAHL Complete, APA PsycINFO, and EMB Reviews. A total of 904 studies were identified; a total of 126 were included in the systematic review, and 65 in the meta-analysis (N = 29,268). Sensitivity analyses were also carried out to detect potential differences in age and clinical status. Results: All the associations we investigated were both significant and positive. Small effect sizes were found between eating global scores and unidimensional perfectionism, perfectionistic strivings, and perfectionistic concerns (res = 0.19, res = 0.21, res = 0.12, respectively) and remained significant in each age group in both clinical and community samples. Perfectionistic concerns were moderately associated with all eating measures, especially in community samples and samples with a mean age under 14. Conclusions: Psychological interventions specially designed to target perfectionistic concerns in the early stages of development may help prevent the onset or reduce the intensity of eating-related symptoms during childhood and adolescence.

Youth mental health interventions in the UK increasingly use goal-setting procedures to shape services and measure outcomes in ways that are intended to be meaningful to service users. This research article questions this premise, departing with the ethnographic observation that many young people do not seem to welcome the invitation or requirement to direct their therapeutic aims and set the terms for service evaluation in the form of goals. I will show that goal-setting procedures are examples of a broader field of complex ethico-political dilemmas navigated by mental health service staff. While wanting to enable young people to be healthy agents, staff are simultaneously critically aware of the risk of imposing normative, unrealistic and unfair expectations onto young people. I propose that these staff are engaged in a specific form of ethico-political practice, which I call ‘nested ethics’. I use this term to describe instances where staff ethically evaluate their own conduct in line with the capacity to enable the ethical life of another person (youth, in this case). Viewing goal-setting processes as an example of an uneasy politics of nested ethics enables a new perspective from which to advance debates about the enablement of service user choice within care provisions.

Plain English summary Involving members of the public in all stages of research as equal partners is a powerful way to make research more relevant. This paper shares an example of such involvement, from a study about falls prevention in English hospitals. Developed by a team of lay people and professional researchers, the paper looks at how we worked together, drawing on evaluations we carried out about how the study took patient and public perspectives into account, and on personal reflections we wrote. Public involvement had a positive effect on the project and the individuals involved, but there were also difficulties. Positive impacts included lay people ensuring the study focused on what mattered most to patients and their families and feeling they had done right by their personal experience of the study’s subject. Negative impacts included the potential for people to feel overwhelmed by the changes in organisations or in wider society needed to address the issues being explored by a research study, which could cause them to question why they became involved in the first place. The paper ends with practical recommendations about working together, covering things such as helping lay people with the emotional impact of involvement from the beginning to the end of projects; finding ways to ensure everybody is treated in the same way and solving practical problems; and tips on leading and supporting groups of this kind, especially with personal issues like trusting each other.