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The dorsal stream vulnerability hypothesis posits that the dorsal stream, responsible for visual motion and visuo-motor processing, may be particularly vulnerable during neurodevelopment. Consistent with this, autism spectrum disorder (ASD) has been associated with deficits in global motion integration, though deficits in ventral stream tasks, such as form identification, have also been reported. In the current study, we examined whether a similar pattern of results is found in a cohort of 381 children born with neurodevelopmental risk factors and exhibiting a wide spectrum of caregiver-reported autistic traits. Methods: We examined the associations between global motion perception, global form perception, fine motor function, visual-motor integration, and autistic traits (autism spectrum quotient, AQ) using linear regression, accounting for possible interactions with sex and other factors relevant to neurodevelopment. Results: All assessments of dorsal stream function were significantly associated with AQ such that worse performance predicted higher AQ scores. We also observed a significant sex interaction, with worse global form perception associated with higher AQ in boys (n = 202) but not girls (n = 179). Conclusion: We found widespread associations between dorsal stream functions and autistic traits. These associations were observed in a large group of children with a range of AQ scores, demonstrating a range of visual function across the full spectrum of autistic traits. In addition, ventral function was associated with AQ in boys but not girls. Sex differences in the associations between visual processing and neurodevelopment should be considered in the designs of future studies.

Nanoparticle-mediated mRNA delivery has emerged as a promising therapeutic modality, but its growth is still limited by the discovery and optimization of effective and well-tolerated delivery strategies. Lipid nanoparticles containing charged or ionizable lipids are an emerging standard for in vivo mRNA delivery, so creating facile, tunable strategies to synthesize these key lipid-like molecules is essential to advance the field. Here, we generate a library of N-substituted glycine oligomers, peptoids, and undertake a multistage down-selection process to identify lead candidate peptoids as the ionizable component in our Nutshell nanoparticle platform. First, we identify a promising peptoid structural motif by clustering a library of >200 molecules based on predicted physical properties and evaluate members of each cluster for reporter gene expression in vivo. Then, the lead peptoid motif is optimized using design of experiments methodology to explore variations on the charged and lipophilic portions of the peptoid, facilitating the discovery of trends between structural elements and nanoparticle properties. We further demonstrate that peptoid-based Nutshells leads to expression of therapeutically relevant levels of an anti-respiratory syncytial virus antibody in mice with minimal tolerability concerns or induced immune responses compared to benchmark ionizable lipid, DLin-MC3-DMA. Through this work, we present peptoid-based nanoparticles as a tunable delivery platform that can be optimized toward a range of therapeutic programs.

Abstract Background Antenatal corticosteroids are recommended for women at risk of preterm birth from 24 to 34 weeks’ gestation as they reduce neonatal morbidity and mortality, but evidence regarding their long-term effects on offspring is limited. This study assessed general health and social outcomes 50 years after antenatal exposure to corticosteroids. Methods We assessed 424 adult offspring of women who participated in the first randomised, double-blind, placebo-controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome. The first 717 mothers received two intramuscular injections of betamethasone (6 mg betamethasone sodium phosphate and 6 mg betamethasone acetate) or placebo given 24 h apart and the subsequent 398 received two injections of double dose betamethasone (12 mg betamethasone sodium phosphate and 12 mg betamethasone acetate) or equivalent volume of placebo. Follow-up included a health questionnaire and consent for access to administrative data sources. Outcome categories included mental health (depression, anxiety, bipolar affective disorder, schizophrenia and treatment or hospital admission for any mental health disorder), general health (chronic kidney disease, cancer diagnosis, bone fracture, oral health, allergies, functional difficulties and physical activity) and social outcomes (educational attainment, employment and criminal convictions). Investigators remained blinded to treatment allocation. Analyses were adjusted for gestational age at entry, sex and clustering. Results We assessed 424 adult offspring (46% of survivors; mean [SD] age 49.3 [1.0] years; 212 [50%] female). There was no difference in mental health, general health and social outcomes between those exposed to betamethasone and those exposed to placebo, with the exception that osteoporotic site fracture in adulthood was more likely to have occurred in the betamethasone group compared with placebo (adjusted relative risk 1.57, 95% CI 1.00, 2.48, p = 0.05). No dose–effect relationship was evident and there was no difference in the proportion with at least one fracture. Follow-up rate and lack of in-person assessments were the main limitations. Conclusions There is no evidence that antenatal corticosteroids have clinically important effects on general health and social outcomes up to 50 years of age.

Abstract Background The path of a complaint and patient satisfaction with complaint resolution is often dependent on the responses of healthcare professionals (HCPs). It is therefore important to understand the influences shaping HCP behaviour. This systematic review aimed to (1) identify the key actors, behaviours and factors influencing HCPs’ responses to complaints, and (2) apply behavioural science frameworks to classify these influences and provide recommendations for more effective complaints handling behaviours. Methods A systematic literature review of UK published and unpublished (so-called grey literature) studies was conducted (PROSPERO registration: CRD42022301980). Five electronic databases [Scopus, MEDLINE/Ovid, Embase, Cumulated Index to Nursing and Allied Health Literature (CINAHL) and Health Management Information Consortium (HMIC)] were searched up to September 2021. Eligibility criteria included studies reporting primary data, conducted in secondary and tertiary care, written in English and published between 2001 and 2021 (studies from primary care, mental health, forensic, paediatric or dental care services were excluded). Extracted data included study characteristics, participant quotations from qualitative studies, results from questionnaire and survey studies, case studies reported in commentaries and descriptions, and summaries of results from reports. Data were synthesized narratively using inductive thematic analysis, followed by deductive mapping to the Theoretical Domains Framework (TDF). Results In all, 22 articles and three reports met the inclusion criteria. A total of 8 actors, 22 behaviours and 24 influences on behaviour were found. Key factors influencing effective handling of complaints included HCPs’ knowledge of procedures, communication skills and training, available time and resources, inherent contradictions within the role, role authority, HCPs’ beliefs about their ability to handle complaints, beliefs about the value of complaints, managerial and peer support and organizational culture and emotions. Themes mapped onto nine TDF domains: knowledge, skills, environmental context and resources, social/professional role and identity, social influences, beliefs about capability, intentions and beliefs about consequences and emotions. Recommendations were generated using the Behaviour Change Wheel approach. Conclusions Through the application of behavioural science, we identified a wide range of individual, social/organizational and environmental influences on complaints handling. Our behavioural analysis informed recommendations for future intervention strategies, with particular emphasis on reframing and building on the positive aspects of complaints as an underutilized source of feedback at an individual and organizational level.

In our first article, we outlined some of the reasons for reading failure at the Early Childhood level and beyond, discussed common challenges students face, and explored essential components for quality reading instruction. We'll revisit the students you met in the first article to provide a window into how the Science of Reading can be incorporated into the Early Childhood classroom. We'll introduce new strategies and materials that integrate best practices through a Montessori lens for all learners. We'll show how these same strategies and materials can become interventions when used with increased intensity, frequency, and differentiation. Core Montessori principles, such as independence, multisensory instruction, and isolation of difficulty, remain central elements of the lesson.

Abstract Background The global discourse on future health care emphasises that learning to collaborate across professions is crucial to assure patient safety and meet the changing demands of health care. The research on interprofessional education (IPE) is diverse but with gaps in curricula design and how IPE is enacted in practice. Purpose and aims This research project will identify. 1) how IPE in clinical placements emerges, evolves, and is enacted by students when embedded in local health care practices, 2) factors critical for the design of IPE for students at clinical placements across the four countries. Methods A study involving four countries (Sweden, Norway, Australia and New Zealand) using the theory of practice architectures will be undertaken between 2023 and 2027. The project is designed as an international, collaborative multiple-case ethnographic study, using the theoretical framework of practice architectures (TPA). It will include four ethnographic case studies of IPE, one in each country. Data will be collected in the following sequence: (1) participant observation of students during interprofessional placements, (2) interviews with students at clinical placement and stakeholders/professionals, (3) Non-clinical documents may be used to support the analysis, and collection of photos may be use as memory aids for documenting context. An analysis of “sayings, doings and relatings” will address features of the cultural- discursive, material-economic, social-political elements making up the three key dimensions of TPA. Each of the four international cases will be analysed separately. A cross case analysis will be undertaken to establish common learning and critical IPE design elements across the four collaborating universities. Discussion The use of TPA framework and methodology in the analysis of data will make it possible to identify comparable dimensions across the four research sites, enabling core questions to be addressed critical for the design of IPE. The ethnographic field studies will generate detailed descriptions that take account of country-specific cultural and practice contexts. The study will also generate new knowledge as to how IPE can be collaboratively researched.

Audrey McKinlay,1,2 Michelle Albicini,2 Phillip S Kavanagh31Department of Psychology, University of Canterbury, Christchurch, New Zealand; 2Department of Psychology and Psychiatry, Monash University Clayton, VIC, Australia; 3School of Psychology, Social Work and Social Policy, University of South Australia, ADL, AustraliaAbstract: It is now well accepted that theory of mind (ToM) functioning is impaired in Parkinson's disease (PD) patients. However, what remain unknown are the functions that underlie this impairment. It has been suggested that cognitive skills may be key in this area of functioning; however, many of the cognitive tests used to assess this have relied on intact visuospatial abilities. This study aimed to examine whether deficits in ToM were generated by cognitive or visuospatial dysfunction and the mediating effect of visuospatial function on ToM performance. Fifty PD patients (31 male, 19 female; mean age = 66.34 years) and 49 healthy controls (16 male, 33 female; mean age = 67.29 years) completed a ToM task (reading the mind in the eyes) and visuospatial task (line orientation). The results revealed that current cognitive status was a significant predictor for performance on the ToM task, and that 54% of the total effect of cognitive status on ToM was mediated by visuospatial abilities. It was concluded that visuospatial functioning plays an important mediating role for the relationship between executive dysfunction and affective ToM deficits in PD patients, and that visuospatial deficits may directly contribute to the presence of affective ToM difficulties seen in individuals with PD.Keywords: Parkinson's disease, theory of mind, visuospatial function, social cognition, executive function

Bacteria sense population density via the cell-cell communication system called quorum sensing (QS). The evolution of QS and its maintenance or loss in mixed bacterial communities is highly relevant to understanding how cell-cell signaling impacts bacterial fitness and competition, particularly under varying environmental conditions such as nutrient availability. We uncovered a phenomenon in which Vibrio cells grown in minimal medium optimize expression of the methionine and tetrahydrofolate (THF) synthesis genes via QS. Strains that are genetically "locked" at high cell density grow slowly in minimal glucose media and suppressor mutants accumulate via inactivating mutations in metF (methylenetetrahydrofolate reductase) and luxR (the master QS transcriptional regulator). In mixed cultures, QS mutant strains initially coexist with wild-type, but as glucose is depleted, wild-type outcompetes the QS mutants. Thus, QS regulation of methionine/THF synthesis is a fitness benefit that links nutrient availability and cell density, preventing accumulation of QS-defective mutants.

Introduction Health interventions that require significant change to individual lifestyles or social norms can pose a challenge for widespread public acceptability and uptake. At the same time, over the last two decades, there has been increasing attention paid to the rise of populist movements globally, defined by ‘the people’ pushing against ‘an elite’ viewed as depriving the people of their sovereignty. To understand potential overlap in these two areas, this study aims to synthesise existing international evidence on linkages between populist attitudes and reduced uptake, acceptability, adherence and/or effectiveness of public health interventions. The goal of this work is to create a conceptual framework that can be used to inform policy strategies aimed at widening the impact of public health interventions.Methods and analysis A systematic review will be performed via searches across databases and websites relevant to public health and social science research, informed by preliminary searches on the topic. There will be no language restrictions, but included studies will be limited to those produced since 2008, the year of the global financial crisis, from which most current literature on populism dates. Risk of bias will be assessed using validated tools according to study design. Due to expected heterogeneity across included studies, this will be a systematic review without meta-analysis. Findings will be synthesised narratively, and the strength of the evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. The review will be reported according to the Systematic Reviews without Meta-Analysis reporting guidelines.Ethics and dissemination Ethical review is not required for this study. Public dissemination will be informed via consultation with our Patient and Public Involvement and Engagement Strategy Group, along with reporting via peer-reviewed publication, relevant international conferences, a policy brief and a workshop with public health and communications experts.PROSPERO registration number CRD42024513124.

Abstract This work presents a study of piezoelectric zinc oxide (ZnO) thin films deposited by a novel post‐reactive sputtering method. The process utilizes a rotating drum with DC magnetron sputtering deposition onto substrates with subsequent DC plasma‐assisted oxidation of the deposited metal to metal oxide. The paper analyzes the influence of plasmaassisted magnetron sputtering (PA‐MS) deposition parameters (O2 plasma source power, O2 flow, and Ar flow) on the morphological, structural, optical, and piezoelectric properties of ZnO thin films. Design of experiments has been utilized to evaluate the role of these parameters on the growth rate (rg) and the properties of resulting films. Results indicate a predominant influence of the plasma power on the rg over other parameters. Among the eight tested samples, three of them show high crystal quality with high intensity (0001) diffraction peak, characteristic of the wurtzite crystalline structure of ZnO, and one of them exhibits piezoelectric coefficient values of ≈11pC N−1. That sample corresponding to a ZnO film deposited at the lowest rg of 0.075 nm s−1, confirmed the key role of the deposition parameters on the piezoelectric response of films, and demonstrated PA‐MS as a promising technique to produce high‐quality piezoelectric thin films.

Motion artifacts can be a significant noise source in biomagnetic measurements when magnetic sensors are not separated from the signal source. In ambient environments, motion artifacts can be up to ten times stronger than the desired signals, varying with environmental conditions. This study evaluates the variability of these artifacts and the effectiveness of a gradiometer in reducing them in such settings. To achieve these objectives, we first measured the single channel output in varying magnetic field conditions to observe the effect of homogeneous and gradient background fields. Our analysis revealed that the variability in motion artifact within an ambient environment is primarily influenced by the gradient magnetic field rather than the homogeneous one. Subsequently, we configured a gradiometer in parallel and vertical alignment with the direction of vibration (X-axis). Our findings indicated that in a gradient background magnetic field ranging from 1 nT/mm to 10 nT/mm, the single-channel sensor output exhibited a change of 164.97 pT per mm unit increase, while the gradiometer output showed a change of only 0.75 pT/mm within the same range. Upon repositioning the gradiometer vertically (Y direction), perpendicular to the direction of vibration, the single-channel output slope increased to 196.85 pT, whereas the gradiometer output only increased by 1.06 pT/mm for the same range. Our findings highlight the influence of ambient environments on motion artifacts and demonstrate the potential of gradiometers to mitigate these effects. In the future, we plan to record biomagnetic signals both inside and outside the shielded room to compare the efficacy of different gradiometer designs under varying environmental conditions.

Abstract Background The sudden introduction of social distancing measures in response to the COVID-19 pandemic resulted in significant lifestyle changes for the UK population. People living with physical disabilities were deemed to be at greater risk of complications following COVID-19 infection and were subjected to stricter social distancing guidelines. But gaps remain in our understanding of how the COVID-19 pandemic and associated restrictions affected the ability to access support, health and wellbeing of people with physical disabilities. Such understanding is vital to ensure equitable future pandemic preparedness for people living with physical disabilities. Methods We conducted qualitative semi-structured interviews with 31 people living in the UK between May 2020 and January 2022. All participants self-identified as having a physical disability that affected their mobility, sight, or hearing. We analysed the data using reflexive thematic analysis. Results Six themes were identified that described the impact of the pandemic on ability to access support, health and wellbeing: (i) adaptations to healthcare provision led to difficulties in managing health and wellbeing; (ii) exacerbations of inequalities in access to public space due to social distancing guidelines; (iii) experiences of hostility from able-bodied people; (iv) loss of social lives and encounters; (v) difficulties maintaining distance from others and subsequent fear of infection and (vi) strategies to support wellbeing and coping when confined to the home. Conclusion The COVID-19 pandemic exacerbated existing health and social inequalities experienced by disabled people. The disproportionate impact of the pandemic on service provision and social connections resulted in challenging circumstances for disabled people who faced unmet medical needs, deteriorating health, and at times, hostile public spaces. Disabled people’s experiences need to be incorporated into future pandemic or health-related emergency planning to ensure equality of access to services and public spaces to ensure their health and wellbeing is supported and maintained.

Abstract In Māori and Pacific adults, the CREBRF rs373863828 minor (A) allele is associated with increased body mass index (BMI) but reduced incidence of type-2 and gestational diabetes mellitus. In this prospective cohort study of Māori and Pacific infants, nested within a nutritional intervention trial for pregnant women with obesity and without pregestational diabetes, we investigated whether the rs373863828 A allele is associated with differences in growth and body composition from birth to 12–18 months’ corrected age. Infants with and without the variant allele were compared using generalised linear models adjusted for potential confounding by gestation length, sex, ethnicity and parity, and in a secondary analysis, additionally adjusted for gestational diabetes. Carriage of the rs373863828 A allele was not associated with altered growth and body composition from birth to 6 months. At 12–18 months, infants with the rs373863828 A allele had lower whole-body fat mass [FM 1.4 (0.7) vs. 1.7 (0.7) kg, aMD −0.4, 95% CI −0.7, 0.0, P = 0.05; FM index 2.2 (1.1) vs. 2.6 (1.0) kg/m2 aMD −0.6, 95% CI −1.2,0.0, P = 0.04]. However, this association was not significant after adjustment for gestational diabetes, suggesting that it may be mediated, at least in part, by the beneficial effect of CREBRF rs373863828 A allele on maternal glycemic status.

Background Calls have been made for paramedics to have some form of care pathway that they could use to safely divert adults with epilepsy away from emergency departments and instigate ambulatory care improvements. Different configurations are possible. To know which to prioritise for implementation/evaluation, there is a need to determine which are acceptable to service users and likely National Health Service-feasible. Objective(s) (1) Identify configurations being considered, (2) understand service users’ views of them and current provision, (3) identify what sort of care service users want and (4) determine which configuration(s) is considered to achieve optimal balance in meeting users’ preference and being National Health Service-feasible. Design Service providers were surveyed to address objective 1. Interviews with service users addressed objective 2. Objective 3 was addressed by completing discrete choice experiments. These determined users’ care preferences for different seizure scenarios. Objective 4 was addressed by completing ‘knowledge exchange’ workshops. At these, stakeholders considered the findings on users’ stated preferences and judged different pathway configurations against Michie’s ‘acceptability, practicability, effectiveness, affordability, side-effects and equity’ feasibility criteria. Setting This project took place in England. The survey recruited representatives from neurology and neuroscience centres and from urgent and emergency care providers. For the interviews, recruitment occurred via third-sector support groups. Recruitment for discrete choice experiments occurred via the North West Ambulance Service NHS Trust and public advert. Workshop participants were recruited from neurology and neuroscience centres, urgent and emergency care providers, support groups and commissioning networks. Participants Seventy-two services completed the survey. Interviews were conducted with 25 adults with epilepsy (and 5 relatives) who had emergency service contact in the prior 12 months. Discrete choice experiments were completed by 427 adults with epilepsy (and 167 relatives) who had ambulance service contact in the prior 12 months. Workshops were completed with 27 stakeholders. Results The survey identified a range of pathway configurations. They differed in where they would take the patient and their potential to instigate ambulatory care improvements. Users had been rarely consulted in designing them. The discrete choice experiments found that users want a configuration of care markedly different to that offered. Across the seizure scenarios, users wanted their paramedic to have access to their medical records; for an epilepsy specialist (e.g. an epilepsy nurse, neurologist) to be available to advise; for their general practitioner to receive a report; for the incident to generate an appointment with an epilepsy specialist; for the care episode to last < 6 hours; and there was a pattern of preference to avoid conveyance to emergency departments and stay where they were. Stakeholders judged this configuration to be National Health Service-feasible within 5–10 years, with some elements being immediately deployable. Limitations The discrete choice experiment sample was broadly representative, but those reporting recent contact with an epilepsy specialist were over-represented. Conclusions Users state they want a configuration of care that is markedly different to current provision. The configuration they prefer was, with support and investment, judged to likely be National Health Service-feasible. The preferred configuration should now be developed and evaluated to determine its actual deliverability and efficacy. Study registration The study is registered as researchregistry4723. 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: 17/05/62) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 24. See the NIHR Funding and Awards website for further award information. Plain language summary Ambulances often attend to people with epilepsy. Most of them are taken to the hospital’s accident and emergency department. This typically has little benefit since most patients are already diagnosed and visit the accident and emergency department with non-emergency states. To change things, National Health Service organisations want an ‘alternative care pathway’ for paramedics to use. It could mean the person is not taken to the accident and emergency department but cared for elsewhere. Our project brought stakeholders together to develop an alternative care pathway that includes things important to patients and carers but is also National Health Service-feasible. Seventy National Health Service organisations first told us via a survey and a workshop which pathways they were considering and which might be feasible. Thirty people with epilepsy and their family members and friends were then interviewed. They explained what is wanted after a seizure and problems with current care. One problem was that going to the accident and emergency department does not lead to them getting a follow-up appointment with an epilepsy specialist to check their treatment is right. Using ‘discrete choice experiments’, around 430 people with epilepsy who recently contacted the ambulance service and 170 of their family and friends were asked to make a choice between alternative packages of care, to say which pathway they would prefer in different seizure situations. The results were clear. People wanted care different from what National Health Service organisations told us was available. The choice experiment showed everyone prefers pathways where paramedics have access to their medical records, an epilepsy specialist is available to advise the paramedic, the general practitioner gets a report and they get an appointment with an epilepsy specialist in the future. Everyone wants to avoid long episodes of care (6 hours) and after a typical seizure people with epilepsy want to stay at home. Three workshops were run with paramedics, epilepsy specialists and managers. They said the alternative care pathway wanted by users could be National Health Service-feasible. There is a need to implement and evaluate it now. Scientific summary Background Emergency department (ED) visits for epilepsy are common, costly, often clinically unnecessary and typically lead to little benefit for epilepsy management. An alternative care pathway (CP), which diverts people with epilepsy (PWE) away from ED when ‘999’ is called and leads to care elsewhere, could potentially generate savings and instigate improvements in the person’s ambulatory care. This project sought to identify the optimal configuration, ensuring the CP is both acceptable to service users and NHS-feasible. A key method used was discrete choice experiments (DCEs). They involved users being presented with hypothetical seizure scenarios and making a number of choices to say which CP configuration, described according to a fixed set of characteristics (attributes), they would prefer. The project’s aims were as follows. Aims and objectives Work Package 1 Systematically identify alternative CPs being considered by NHS services and describe extent to which service users have been involved in their design. Understand decision-making processes of PWE and their significant others (SOs) for seeking ED care and their concerns and expectations regarding alternative CPs. Identify attributes of postseizure care that PWE and their SOs (close family and friends) consider important. Work Package 2 Determine users’ and SOs’ preferences for postseizure care using DCEs and identify subgroup differences. Estimate utility of different CP configurations to service users and subgroup differences. Work Package 3 Hold expert workshops at which stakeholders, informed of the DCE evidence, would identify the optimal alternative CP/s for seizures that could be recommended for implementation and evaluation. Methods Work Package 1 Work Package 1a. Survey of service providers England’s ambulance services, epilepsy services and a random sample of its EDs were surveyed (April–June 2019). They were asked what alternative CPs they were considering and the extent to which they had consulted users. Work Package 1b. Interviews with service users Semistructured interviews were conducted in Southeast England with a purposive sample of PWE (April–September 2019). They also completed a ranking exercise to identify the characteristics (attributes) of postseizure care they considered most important. Participants were recruited from third-sector user groups and via a research newsletter. To be eligible, the person needed to be (1) aged ≥ 18, (2) have been diagnosed with epilepsy for ≥ 1 year, (3) had contacted the emergency services in the previous 12 months and (4) be able to provide informed consent and complete an interview in English. People with epilepsy were invited to be interviewed along with a SO. Work Package 1c. Knowledge exchange event Work Package (WP) 1b and 1c findings were used to select a set of candidate attributes that could be used to describe CPs within the DCE. To ensure attributes were features of alternative CPs and the levels likely NHS-feasible, a 1-day ‘knowledge exchange’ event was run (October 2019). Participants were representatives from ambulance and epilepsy services. They were identified for participation via WP1a. Work Package 2 Work Package 2a. Discrete choice experiment design panel and pilot A DCE design panel used evidence from WPs 1a–c to generate the DCE survey, using a D-efficient experimental design (Ngene 1.2.1, ChoiceMetrics, Sydney, Australia). The survey’s purpose was to obtain data of users’ care preferences for three separate scenarios, namely, a ‘typical seizure at home’, a ‘typical seizure in public’ and an ‘atypical seizure’. It, and vignettes describing the different seizure scenarios, was iteratively refined and finalised based on piloting. Work Package 2b. Formal discrete choice experiment A sample of n = 348 adults with epilepsy (and their SOs) from the target population was sought to complete the DCE. They filled in the DCE via an online platform. Participants were recruited via two routes between July and November 2020: (1) from the Merseyside area via the North West Ambulance Service and (2) nationally via public advert. PWE needed to (1) be aged ≥ 18 years, have a diagnosis of epilepsy, (2) have been seen by the ambulance service in prior 12 months and (3) be able to provide informed consent and independently complete the survey in English. Significant others needed to be aged ≥ 16. Data were analysed using a random-effects logit model. Preference weights were estimated for each attribute. Data from PWE and SOs were analysed separately, thus creating six seizure contexts for which preferences were modelled (three seizure scenarios × two participant types). Work Package 3 To identify which CP configuration(s) represented the optimal balance between user preference and NHS feasibility, three online ‘knowledge exchange’ workshops were run. Attendees were representatives from the ambulance service, from epilepsy services and commissioning. Service user representatives were also present. Commissioning and managerial representation was secured via national professional bodies. The DCE findings from WP2 were disseminated, and attendees were introduced to Michie et al.’s affordability, practicability, effectiveness, acceptability, side-effects and equity (APEASE) feasibility criteria. Nominal group techniques were then utilised, with stakeholders sharing views on the extent to which they considered the attribute levels favoured by users to be NHS-feasible. The groups then specified the levels for each attribute they believed represented the optimal balance. Results Work Package 1 Work Package 1a. Survey of service providers Clinical leads and managers from 72 (82.8%) of the invited services responded. Sixty per cent were considering or using an alternative CP change; only 21.2% had consulted service users on it. A range of CP configurations were reported. Some involved caring for PWE at home, ‘on scene’ or in some instances conveying them to an urgent treatment centre. The potential of configurations to improve ambulatory care varied. Work Package 1b. Semistructured interviews with service users Thirty service users (25 PWE and 5 SOs) were interviewed. The average age of PWE was 37 years; mean years was diagnosed 21. Participants provided insights into the challenges service users experience and disruptions they experience due to inadequate information transfer and co-ordination between ambulatory and urgent and emergency care services. Interviews highlighted some initial concerns users had with some possible CP configurations. The ranking exercise provided an approximation of the factors contributing to the ‘decision calculus’ users use when considering postseizure care options. Six attributes appeared most important: (1) whether the ambulance crew would have access to their medical records or care plan, (2) where the CP would take them, (3) how long it would take for them to be assessed, monitored and treated during the emergency episode, (4) extent to which the emergency care provider could request advice from an epilepsy specialist (e.g. epilepsy nurse, neurologist), (5) whether the CP would mean their usual care provider/s would be informed of the incident and, finally, (6) whether any follow-up from the epilepsy specialist would be instigated. Work Package 1c. Knowledge exchange event Thirteen representatives attended the workshop (n = 6 paramedics, n = 4 neurologists, n = 2 epilepsy nurse specialists and n = 1 user group representative). Participants agreed the six attributes identified by WP1b were all characteristics of an alternative CP, plausible and could be ‘traded’. Much of the event focused on identifying attribute levels that were considered feasible. Work Package 2 Work Package 2a. Discrete choice experiment design panel and pilot The panel decided that the six attributes identified in the formative work should be used to describe the CP options within the DCEs. Accordingly, DCEs for the three seizure scenarios were developed with the intention that participants would be randomised to each complete DCEs for two of three seizure scenarios, achieving a 1 : 1 : 1 allocation ratio. The six attributes and their associated levels (between 2 and 4) had the potential to generate 288 possible CP configurations. Use of an efficient experimental design meant that for each of the seizure scenarios a person would consider 24 CPs that were paired into 12 binary choices. The presentation of the DCE was finalised following pilot interviews. The final labels used for the attributes were as follows: (1) ‘The paramedic has access to medical records or a care plan’; (2) ‘What happens next’; (3) ‘Time’; (4) ‘Epilepsy specialists today’; (5) ‘GP told’; (6) ‘Additional contact with an epilepsy specialist’. Work Package 2b. Formal discrete choice experiment Useable submissions to the DCE survey were secured from n = 594 participants (n = 427 PWE; n = 167 SOs). Most (81.1%) were recruited via the public advertisement route. When participants from the two recruitment routes were merged to form a single sample, it was broadly representative of the target population. Two exceptions were its younger age and higher proportion reporting recent contact with an epilepsy specialist. The main ways that the SO participants knew someone with epilepsy was that they were the patient’s parents. The characteristics of the PWE known by SOs differed from those of the PWE taking part themselves (e.g. more learning disability). Across the three seizure scenarios, both PWE and SOs preferred CP configurations that differed from the way care is currently provided. Using coefficients from the random-effects logit models, the expected utility to service users for all possible CP configurations was calculated for the six seizure contexts. Care pathways were then ranked: rank 1 = most preferred; 288 = least preferred. The highest rank that the CP configuration approximating current care achieved was 220/288. There was similarity across the seizure contexts in terms of which attribute levels featured in the top-ranked configurations. In fact, three of the six contexts shared the same top-ranked configuration. For all six contexts, the highest-ranked CP configurations included (1) the paramedic having access to medical records or a care plan, (2) an epilepsy specialist (e.g. epilepsy nurse, neurologist) being available to advise the attending paramedic, (3) the patient’s GP being notified of the incident and (4) an appointment with an epilepsy specialist within 2–3 weeks being booked for the patient. The only attributes that varied within the top-ranked configurations were ‘What happens next’ and ‘Time’. For five of them, the top configuration involved the patient staying ‘where they were’. For the remaining ones – namely, for an ‘atypical seizure’ when considered by a SO – it involved the patient being conveyed to an urgent treatment centre. Different attributes had different levels of effect on preference. Providing crews with access to the medical records or care plan of the patient being attended to and having a specialist able to advise the paramedics had the strongest and consistent positive effect. Not all intended subgroup analyses could be completed due to insufficient cases. Those which could, showed social deprivation, recruitment route, presence of an intellectual impairment, contact with an epilepsy specialist in the prior 12 months, familiarity with the seizure scenario and whether the person with epilepsy had a care plan were not significantly related to preference. Work Package 3 Twenty-seven stakeholders attended a workshop. They included 10 ambulance clinicians, 8 epilepsy specialists, 5 commissioners and 4 patient and public involvement (PPI) representatives. Stakeholders believed the attribute levels preferred by service users were broadly feasible in the next 5–10 years. They identified those where most investment/work was required for them to be deliverable. Stakeholders were of the view that there was sufficient commonality in users’ preferences across the six seizure contexts for a single CP to be deployed. The groups were of the same position as to which configurations represented the optimum. They comprised of the following: (1) ambulance clinicians having access to medical records, (2) the person typically staying where they were, (3) the time taken being < 6 hours (be it 1, 2 or 3 hours), (4) crews being able to be advised by a specialist (an epilepsy nurse or neurologist) on the day, (5) for the person’s GP to be notified and, finally, for the incident to result in an appointment being made for the patient to have a follow-up appointment with an epilepsy specialist (be it within 1 week or 2–3 weeks). When attribute levels were restricted to these, the number of CP configurations for consideration reduced from 288 to 18. Evidence from WP2b showed these 18 included the configurations most preferred by service users for each scenario. Moreover, the evidence indicated that all 18 would be expected to hold more utility to users than the configuration representing current care. Conclusions By working collaboratively with service users from the target population, clinicians and commissioners, this project has provided clear answers to a pressing service delivery question. It provides evidence indicating that for common seizure scenarios, users appear open to paramedics not conveying them to ED and how poorly current care aligns with their preferences. Our project has also shown what postseizure care service users appear to want and that limited differences exist for different seizure scenarios. This appears to support the deployment of a single CP configuration. The study also provided evidence on the estimated improvement in utility that would result from individual attribute changes. This could be used to prioritise CP changes. Importantly, service providers and commissioners were found to be of the view that the CP configuration favoured by users could be NHS-feasible within 5–10 years, and they identified which attribute levels require the most work. It is important to now take the evidence this project has captured on people’s stated preferences and views and seek to implement one of the possible 18 CP configurations and evaluate it to determine its actual feasibility and efficacy in practice. Implications for NHS service commissioning, policy and practice The project identified a refined set of CP configurations that are considered optimal and the most promising candidates for formal evaluation. Pressures on acute services have intensified since our project was completed. This may incentivise ambulance services to use our findings and implement some form of alternative CP before an evaluation has occurred. Not all ambulance services would have the infrastructure and/or relationships with partner organisations to immediately implement the entire CP configuration considered optimal. Commissioners, policy-makers and service providers could support the development of the systems – such as shared record initiatives – to permit it to be offered. Identifying eligible people for the DCE survey via the NHS ambulance service was time-consuming compared to using public adverts. This could be made for efficient by embedding processes within NHS records systems to temporarily ‘strip’ them, including free-text fields, of confidential data. This would enable trained individuals not involved in a person’s care to screen anonymised records. Recommendations for research Using the attribute levels specified by stakeholders as representing the optimum, one of the possible 18 CP configurations should be evaluated for its efficacy. Any evaluation should consider short- (e.g. rates of recontact, death) and long-term outcomes (e.g. proportion of PWE ‘unknown’ to specialists brought to their attention). A cluster-randomised controlled trial would likely provide the most rigorous evidence. However, an alternative, faster evaluation approach may be needed to ensure evidence is generated in an acceptable time frame. Other ways to reduce unnecessary ED attendance warrant research attention. One is how to address ambulance crews’ requests for support in identifying persons suitable for non-conveyance. Attention is also needed on users’ seizure first aid confidence and knowledge. Study registration This study is registered as researchregistry4723. 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: 17/05/62) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 24. See the NIHR Funding and Awards website for further award information.

Low blood concentrations of glucose (hypoglycaemia) soon after birth are common because of the delayed metabolic transition from maternal to endogenous neonatal sources of glucose. Because glucose is the main energy source for the brain, severe hypoglycaemia can cause neuroglycopenia (inadequate supply of glucose to the brain) and, if severe, permanent brain injury. Routine screening of infants at risk and treatment when hypoglycaemia is detected are therefore widely recommended. Robust evidence to support most aspects of management is lacking, however, including the appropriate threshold for diagnosis and optimal monitoring. Treatment is usually initially more feeding, with buccal dextrose gel, followed by intravenous dextrose. In infants at risk, developmental outcomes after mild hypoglycaemia seem to be worse than in those who do not develop hypoglycaemia, but the reasons for these observations are uncertain. Here, the current understanding of the pathophysiology of neonatal hypoglycaemia and recent evidence regarding its diagnosis, management, and outcomes are reviewed. Recommendations are made for further research priorities.

One of the main priorities of the Integrated Care Systems (ICS) is to expand the number of ‘virtual wards’ and deliver multidisciplinary care for patients closer to home. We present to you the Specialist Neurological Rehabilitation Service (SNRS) which has demonstrated over the last 7 years that intensive neurological rehabilitation can be delivered successfully in the patients’ own homes. A novel commissioning model has been used in partnership with different NHS trusts to provide a unified neurorehabilitation service with both inpatient hospital beds and virtual beds in the patients’ own homes. While patients are on the virtual bed pathway, they remain under the care of the Consultant in Rehabilitation Medicine with support from the Clinical Nurse Specialist and have access to diagnostics/interventions and clinic reviews. The patients get daily intensive MDT therapy input from the skilled community team who provide the same frequency of therapy sessions at home (as they would get in a level 2 inpatient neurorehabilitation unit). This pathway is supporting the earlier discharge of patients from hospital. Additionally, the analysis of data from the virtual bed pathway shows that rehabilitation outcomes in patients’ own homes are similar to those of bedded units for this subset of patients with complex neurological needs. This illustrates that the virtual ward model can be successfully implemented in neurorehabilitation.

Abstract Background There has been little exploration of the effect of fragility fractures on patient perceptions of their age. The common assumption is that fractures “happen to old people”. In individuals with a fragility fracture, our objective was to explore the experience of feeling old after sustaining a fragility fracture. Methods A secondary analysis of data from 145 community-dwelling women and men participating in six qualitative primary studies was conducted relying on a phenomenological approach. Participants were English-speaking, 45 years and older, who had sustained a recent fragility fracture or reported a history of previous fragility fractures. Data for the analysis included direct statements about feeling old as well any discussions relevant to age post-fracture. Results We highlight two interpretations based on how individuals with a history of fragility fracture talked about age: (1) Participants described feeling old post-fracture. Several participants made explicit statements about being “old”. However, the majority of participants discussed experiences post-fracture that implied that they felt old and had resigned themselves to being old. This appeared to entail a shift in thinking and perception of self that was permanent and had become a part of their identity; and (2) Perceptions of increasing age after sustaining a fracture were reinforced by health care providers, family, and friends. Conclusions Our findings challenge the notion that fractures “happen to old people” and suggest that fractures can make people feel old. Careful consideration of how bone health messages are communicated to patients post-fracture by health care providers is warranted. (Word Count: 248)

We describe a rapid prototyping process for silicon nitride photonic integrated circuits operating at wavelengths around 1.3 and 1.5 μm. Moderate confinement silicon nitride waveguides and other essential integrated photonic components, such as fiber-chip couplers, microring resonators, multimode interference-based 3-dB power splitters, and subwavelength grating metamaterial waveguides, were fabricated and characterized and are reported. The prototyping platform features a 400-nm-thick layer of silicon nitride grown via low-pressure chemical vapour deposition onto 4” silicon thermal oxide wafers and uses direct-write electron beam lithography to define single mode waveguide structures that exhibit losses of

Early Childhood Education and Care (ECEC) in Australia is facing a workforce crisis. A knowledge gap around educators studying to pursue a career in ECEC, particularly in long day care (LDC), has prompted research with Australian educators who engage in further education and training while working in LDC services. The paper examines 32 biographical interviews from an Australian Research Council Linkage project Identifying Effective Strategies to Grow and Sustain a Professional Early Years Workforce. Research reported here applies a social constructivist framework to investigate the personal and structural characteristics of educators studying at Certificate III, Diploma, Bachelor and Master levels of Australia's regulated qualifications and training system. An important finding is that the legislative provisions of Australia's National Quality Framework is a key driver for educator engagement in education and training. The paper highlights the importance of clear qualification pathways in raising the professionalism of the ECEC workforce in Australia.

Social researchers have been adapting methods and practices in response to COVID-19. In the wake of these adaptations, but still in the midst of intersecting crises that the pandemic has exacerbated or shifted (e.g. health-social-political-economic), researchers face a future suffused with methodological uncertainties. This paper presents a Collaborative Research Manifesto that responds to this by promoting markers for meaningful collaborations in future research. The manifesto was co-written primarily through a series of workshops and events that were designed to identify challenges within, and potential for, collaborative research. Through this exploratory collaborative qualitative process, we highlight what the future of such research could look like and describe methodological commitments that collaborative researchers should embody. The discussion draws on wider methodological literature to articulate the key role that 'collaborative research' can offer in uncertain times whilst being sensitive of the limitations of our assertive and radical programme.

Reading is one of the most well-studied aspects of human learning. Since the 1950s, with more interest, research tools, and funding available, the body of reading research has exploded: Every year, hundreds of new scientific papers are published. However, there has been a detrimental lag in ensuring this science is understood by the people who need it most: teachers. This gap between research and practice exists for many reasons: Classroom teachers have limited access to the studies (most articles are only accessible to college students and professors); they have limited time to sort through the hundreds of new findings each year; and the "Reading Wars" of the past century stifled professional learning and dialogue (Kilpatrick, 2015). In the first article in a two-part series, the authors who are educators at the Montessori School of Denver, examines their journey into the Science of Reading started with a supportive administration that recognized the need for well-resourced professional development in response to student needs. In their next article, they will cover specific examples and ideas for bringing the Science of Reading into the Early Childhood classroom.

BackgroundAntenatal corticosteroids for women at risk of preterm birth reduce neonatal morbidity and mortality, but there is limited evidence regarding their effects on long-term health. This study assessed cardiovascular outcomes at 50 years after antenatal exposure to corticosteroids.Methods and findingsWe assessed the adult offspring of women who participated in the first randomised, double-blind, placebo-controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome (RDS) (1969 to 1974). The first 717 mothers received 2 intramuscular injections of 12 mg betamethasone or placebo 24 h apart and the subsequent 398 received 2 injections of 24 mg betamethasone or equivalent volume of placebo. Follow-up included a health questionnaire and consent to access administrative data sources. The co-primary outcomes were the prevalence of cardiovascular risk factors (any of hypertension, hyperlipidaemia, diabetes mellitus, gestational diabetes mellitus, or prediabetes) and age at first major adverse cardiovascular event (MACE) (cardiovascular death, myocardial infarction, coronary revascularisation, stroke, admission for peripheral vascular disease, and admission for heart failure). Analyses were adjusted for gestational age at entry, sex, and clustering. Of 1,218 infants born to 1,115 mothers, we followed up 424 (46% of survivors; 212 [50%] female) at mean (standard deviation) age 49.3 (1.0) years. There were no differences between those exposed to betamethasone or placebo for cardiovascular risk factors (159/229 [69.4%] versus 131/195 [67.2%]; adjusted relative risk 1.02, 95% confidence interval [CI] [0.89, 1.18;]; p = 0.735) or age at first MACE (adjusted hazard ratio 0.58, 95% CI [0.23, 1.49]; p = 0.261). There were also no differences in the components of these composite outcomes or in any of the other secondary outcomes. Key limitations were follow-up rate and lack of in-person assessments.ConclusionsThere is no evidence that antenatal corticosteroids increase the prevalence of cardiovascular risk factors or incidence of cardiovascular events up to 50 years of age. Established benefits of antenatal corticosteroids are not outweighed by an increase in adult cardiovascular disease.

Abstract Background Bronchopulmonary dysplasia (BPD), an inflammatory-mediated chronic lung disease, is common in extremely preterm infants born before 28 weeks’ gestation and is associated with an increased risk of adverse neurodevelopmental and respiratory outcomes in childhood. Effective and safe prophylactic therapies for BPD are urgently required. Systemic corticosteroids reduce rates of BPD in the short term but are associated with poorer neurodevelopmental outcomes if given to ventilated infants in the first week after birth. Intratracheal administration of corticosteroid admixed with exogenous surfactant could overcome these concerns by minimizing systemic sequelae. Several small, randomized trials have found intratracheal budesonide in a surfactant vehicle to be a promising therapy to increase survival free of BPD. The primary objective of the PLUSS trial is to determine whether intratracheal budesonide mixed with surfactant increases survival free of bronchopulmonary dysplasia (BPD) at 36 weeks’ postmenstrual age (PMA) in extremely preterm infants born before 28 weeks’ gestation. Methods An international, multicenter, double-blinded, randomized trial of intratracheal budesonide (a corticosteroid) mixed with surfactant for extremely preterm infants to increase survival free of BPD at 36 weeks’ postmenstrual age (PMA; primary outcome). Extremely preterm infants aged

Background Antenatal corticosteroids for women at risk of preterm birth reduce neonatal morbidity and mortality, but there is limited evidence regarding their effects on long-term health. This study assessed cardiovascular outcomes at 50 years after antenatal exposure to corticosteroids. Methods and findings We assessed the adult offspring of women who participated in the first randomised, double-blind, placebo-controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome (RDS) (1969 to 1974). The first 717 mothers received 2 intramuscular injections of 12 mg betamethasone or placebo 24 h apart and the subsequent 398 received 2 injections of 24 mg betamethasone or equivalent volume of placebo. Follow-up included a health questionnaire and consent to access administrative data sources. The co-primary outcomes were the prevalence of cardiovascular risk factors (any of hypertension, hyperlipidaemia, diabetes mellitus, gestational diabetes mellitus, or prediabetes) and age at first major adverse cardiovascular event (MACE) (cardiovascular death, myocardial infarction, coronary revascularisation, stroke, admission for peripheral vascular disease, and admission for heart failure). Analyses were adjusted for gestational age at entry, sex, and clustering. Of 1,218 infants born to 1,115 mothers, we followed up 424 (46% of survivors; 212 [50%] female) at mean (standard deviation) age 49.3 (1.0) years. There were no differences between those exposed to betamethasone or placebo for cardiovascular risk factors (159/229 [69.4%] versus 131/195 [67.2%]; adjusted relative risk 1.02, 95% confidence interval [CI] [0.89, 1.18;]; p = 0.735) or age at first MACE (adjusted hazard ratio 0.58, 95% CI [0.23, 1.49]; p = 0.261). There were also no differences in the components of these composite outcomes or in any of the other secondary outcomes. Key limitations were follow-up rate and lack of in-person assessments. Conclusions There is no evidence that antenatal corticosteroids increase the prevalence of cardiovascular risk factors or incidence of cardiovascular events up to 50 years of age. Established benefits of antenatal corticosteroids are not outweighed by an increase in adult cardiovascular disease., Author(s): Anthony G. B. Walters 1, Greg D. Gamble 1, Caroline A. Crowther 1, Stuart R. Dalziel 2,3, Carl L. Eagleton 1, Christopher J. D. McKinlay 2, Barry J. Milne [...]