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Abstract Contrary to common chemical intuition, cation-π interactions can persist in polar, aqueous reaction solutions, rather than in dry non-coordinative solvent systems. This account highlights how alkali ion-π interactions impart distinctive structure-influencing supramolecular forces that can be exploited in the preparation of nanoscopic metal-organic capsules. The incorporation of alkali ions from polar solutions into molecular pockets promotes the assembly of otherwise inaccessible capsular entities whose structures are distinctive to those of common polyoxovanadate clusters in which {V=O} moieties usually point radially to the outside, shielding the molecular entities. The applied concept is exemplified by homologous {V20} and {V30} cages, composed of inverted, hemispherical {V5O9} units. The number and geometrical organization of these {V5O9} sub-units in these cages are associated with prevailing cation- $$\pi$$ π interactions and competing steric effects. The stereoisomers of these resulting nano-sized objects are comparable to Alfred Werner-type structural isomers of simple mononuclear complexes in-line with fundamental coordination chemistry principles.

This paper uses insider research within a Cultural Historical Activity Theory (CHAT) framework to examine the lived induction-to-teaching experiences of twelve new academics at a case-study Northern UK university. A CHAT lens foregrounds contradictions as a source for change in the induction-to-teaching process. Data generated through semi-structured interviews with these academics were analysed and, informed by CHAT, allowed us to discern contradictions in sociocultural and structural aspects of the induction activity systems which significantly impact new academics' experiences. Examining these contradictions enabled us to identify interventions for enhancing academic induction policy and practice within the case-study University, but also more widely.

Background: The social, cultural, and ethnic diversity of healthcare workers should match that of the U.S. population to improve health outcomes and decrease health disparities. The population's diversity is increasing, though many health care professions lack diversity in their academic programs. The holistic admissions (HA) process considers an applicant's unique experiences, achievements, and traits in addition to academic metrics when making admission decisions. HA has been shown to be an effective strategy to increase cohort diversity by considering the whole person instead of focusing on academic metrics. Purpose: This study explored the extent to which U.S. Doctor of Physical Therapy (DPT) programs are implementing HA in their admissions process to diversify their admitted cohorts. The study further examined how programs defined "diversity." Methods: Using a cross-sectional, descriptive research design, 272 accredited DPT programs were invited to complete an online survey to collect data on admissions practices. Cross-tabulation was used to analyze coded responses. Inductive thematic analysis was used for open-ended responses. Results: Thirty-five (71.4%) of the 52 respondents reported they were currently or were planning to use HA in their respective DPT program. Most respondents (88.6%) reported a positive experience, including an increase in student cohort diversity without a decrease in graduation rate. Four themes emerged as the definition of "diversity": ethnicity (i.e., under-represented minorities), other demographics, life experiences, and challenges overcome. Conclusion: Although this study represents a sample of DPT programs, the data show most programs using HA and have experienced increased diversity without a risk to academic performance.

Abstract Active gate driving (AGD) is a promising concept for achieving high‐performance power transistor switching. This is particularly crucial for Silicon Carbide (SiC) MOSFETs since their inherently fast switching characteristics give rise to severe overshoots and oscillations which translate into increased levels of electromagnetic interference (EMI) emissions. In this paper, an AGD strategy using a single‐pulse applied during the switching transient is considered for a 1200 V 400 A SiC MOSFET module. The effect of single‐pulse timing, load current, and temperature on the switching performance is analyzed in detail. The radiated EMI reduction benefits are quantified by H‐field and E‐field probes. A conceptual closed‐loop AGD approach is presented and compared to open‐loop operation. For the transistor turn‐off case under full load current of 400 A, experimental results show that it is possible to reduce voltage overshoot by 43.3%, voltage and current oscillations by 69.7% and 52.2% respectively, and EMI by 76.6%, with a trade‐off in the switching energy by a relatively minor increase of 18.2%, compared to the conventional gate driving case. For the turn‐on case, current overshoot was reduced by 32.7%, EMI by 52%, voltage and current oscillations by 54.6% and 52.8%, respectively, with a penalty of 50.9% increase in the switching loss.

Abstract Understanding how influence is seeded and spreads through social networks is an increasingly important study area. While there are many methods to identify seed nodes that are used to initialize a spread of influence, the idea of using methods for selecting driver nodes from the control field in the context of seed selection has not been explored yet. In this work, we present the first study of using control approaches as seed selection methods. We employ a Minimum Dominating Set to develop a candidate set of driver nodes. We propose methods based upon driver nodes (i.e. Driver-Random, Driver-Degree, Driver-Closeness, Driver-Betweenness, Driver-Degree-Closeness-Betweenness, Driver-Kempe, Driver-Ranked) for selecting seeds from this set. These methods make use of centrality measures to rank the driver nodes in terms of their potential as seed nodes. We compare proposed methods to existing approaches using the Linear Threshold model on both real and synthetic networks. Our experiment results show that the proposed methods consistently outperform the benchmarks. We conclude that using driver nodes as seeds in the influence spread results in faster and thus more effective spread than when applying traditional methods.

Summary: Background: Intrapartum-related neonatal encephalopathy (NE) is a leading cause of childhood mortality and morbidity. Continuous electroencephalography (EEG) is gold standard for neonatal brain monitoring; however, low-income country data is lacking. We examined EEG in a Ugandan cohort with NE to describe feasibility, background activity, seizure prevalence and burden, and associations with clinical presentation and outcome. Methods: Neonates with NE were recruited from a single hospital referral centre in Kampala, Uganda (Oct 2019–Oct 2020) and underwent EEG monitoring. Feasibility was assessed as to whether EEG monitoring of diagnostic quality could be achieved from days 1–5. Evolution of clinical presentation was assessed by Sarnat classification and daily Thompson score was performed. EEG background severity was graded at 12, 24, 48 and 72 h after birth, and at time of Thompson score. Seizures were annotated remotely by experts and assessed for frequency, duration, burden, and status epilepticus. Early childhood outcome was assessed at follow up, and adverse outcome defined as death or neurodevelopmental impairment (NDI) at 18–24 months of age. Findings: In this prospective feasibility cohort study, diagnostic quality EEGs were recorded for 50 of 51 recruited neonates (median duration 71.4 h, IQR 52.4–72.2), indicating feasibility. Of 39 participants followed to 18–24 months, 13 died and 7 had NDI. Daily Thompson score and EEG background grade were strongly correlated across all timepoints (days 1–5). Thompson score of ≥7 was most predictive of moderate-severe EEG background abnormality (AUC 0.83). Prognostic accuracy of moderate-severe EEG background grade to predict NDI was high (AUC 0.74). Electrographic seizures were seen in 52% (26); median seizure burden was high at 264 min (IQR 27.8–523.7, range 1.3–1374.1); half (13) had status epilepticus. Interpretation: EEG monitoring was feasible as a research tool in this sub-Saharan Africa setting. EEG background activity correlated strongly with scored neurological assessment and predicted adverse early childhood outcome. Seizure prevalence and burden, including status epilepticus, were high in this uncooled cohort with important potential longer-term implications for survivors. Funding: Bill & Melinda Gates Foundation grant number OPP1210890; Wellcome Trust Innovator award (209325/Z/17/Z).

The successful use of human induced pluripotent stem cells (iPSCs) for research or clinical applications requires the development of robust, efficient, and reproducible cryopreservation protocols. After cryopreservation, the survival rate of iPSCs is suboptimal and cell line-dependent. We assessed the use of ice recrystallization inhibitors (IRIs) for cryopreservation of human iPSCs. A toxicity screening study was performed to assess specific small-molecule carbohydrate-based IRIs and concentrations for further evaluation. Then, a cryopreservation study compared the cryoprotective efficiency of 15 mM IRIs in 5 % or 10 % DMSO-containing solutions and with CryoStor® CS10. Three iPSC lines were cryopreserved as single-cell suspensions in the cryopreservation solutions and post-thaw characteristics, including pluripotency and differential gene expression were assessed. We demonstrate the fitness-for-purpose of 15 mM IRI in 5 % DMSO as an efficient cryoprotective solution for iPSCs in terms of post-thaw recovery, viability, pluripotency, and transcriptomic changes. This mRNA sequencing dataset has the potential to be used for molecular mechanism analysis relating to cryopreservation. Use of IRIs can reduce DMSO concentrations and its associated toxicities, thereby improving the utility, effectiveness, and efficiency of cryopreservation.

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.

Context In the context of iterative feedback loops to support real-time policy decision making, and an emphasis on speeding up adoption of evidence-based interventions, qualitative healthcare researchers are increasingly expected to produce rapid results and products. Traditional qualitative methods have been adapted for this purpose.Objective To develop and apply a rapid analysis framework in a process evaluation for the VICTORION-Spirit study; a ground-breaking hybrid trial examining real-world delivery of inclisiran—a cholesterol-lowering treatment—in primary care.Design We developed a rapid analysis framework, using a summary template, to analyse data from semistructured telephone interviews.Setting Primary care in Greater Manchester, UK.Participants Patients who had received inclisiran as part of the VICTORION-Spirit trial (56), providers delivering inclisiran (28) and representatives from the Academic Health Science Network (8) participated in the original study.Results The rapid analysis framework we developed and applied comprised six steps: (1) creating a summary template based on the five Consolidated Framework for Implementation Research domains; (2) test-driving, refining and finalising the summary template; (3) completing the template soon after each interview using field notes; (4) discussing analysis as a team; (5) transferring summaries to a matrix; and (6) using the summary matrix to inform presentations and interim reports for stakeholders. Our rapid analysis framework saved time and improved efficiency, as we were able to feedback barriers to stakeholders in real time via presentations.Conclusions Rapid analysis in applied healthcare research can produce timely and trustworthy findings. Our rapid analysis framework would be useful within studies where there is a need to feedback to stakeholders and adjust implementation strategies accordingly in real time. Thus, supporting successful implementation efforts and accelerating adoption.Trial registration number NCT04807400, 19/03/2021.

Abstract Optogenetics has transformed studies of neural circuit function, but remains challenging to apply to non-human primates (NHPs). A major challenge is delivering intense, spatiotemporally-precise, patterned photostimulation across large volumes in deep tissue. Such stimulation is critical, for example, to modulate selectively deep-layer corticocortical feedback circuits. To address this need, we have developed the Utah Optrode Array (UOA), a 10×10 glass needle waveguide array fabricated atop a novel opaque optical interposer, and bonded to an electrically addressable µLED array. In vivo experiments with the UOA demonstrated large-scale, spatiotemporally precise, activation of deep circuits in NHP cortex. Specifically, the UOA permitted both focal (confined to single layers/columns), and widespread (multiple layers/columns) optogenetic activation of deep layer neurons, as assessed with multi-channel laminar electrode arrays, simply by varying the number of activated µLEDs and/or the irradiance. Thus, the UOA represents a powerful optoelectronic device for targeted manipulation of deep-layer circuits in NHP models.

Abstract Background Acid Sphingomyelinase Deficiency (ASMD) is an ultra-rare autosomal recessive lysosomal storage disorder characterized by intracellular lipid accumulation resulting from reduced function of acid sphingomyelinase. Olipudase alfa, an enzyme replacement therapy, was recently approved in several countries for the treatment of the non-neurologic manifestations of ASMD. Studies demonstrate improvement in organomegaly, pulmonary function and lipid profiles with olipudase alfa, yet little is known about its impact on quality of life (QoL) for patients and caregivers. The purpose of this study is to better understand the real-life impact of ASMD on patients and caregivers and assess how olipudase alfa impacts QoL for pediatric patients and their caregivers. Methods Caregivers of pediatric patients (≤ 18 years of age) with a confirmed diagnosis of ASMD that received olipudase alfa for at least 12 months were recruited in early 2022 through national patient organizations to participate in a global online questionnaire followed by semi-structured interviews. Ten caregivers of patients with ASMD who utilized olipudase alfa as an experimental therapy for pediatric patients participated in the study. Quantitative analysis of the results was undertaken, and qualitative data was analyzed using an inductive thematic approach. Results Ten eligible participants completed questionnaires, and 8 of the 10 went on to participate in structured interviews. Symptom burden of ASMD and impact on symptomatology and quality of life after olipudase alfa use are reported here. Five themes emerged from analysis: (1) ASMD is a systemic disease with a wide array of manifestations that significantly impact QoL; (2) Olipudase alfa was associated with improvements in all non-neurologic manifestations of ASMD; (3) Participants perceived the risk associated with olipudase alfa to be low and the benefits to greatly outweigh any risk or burden; (4) Participants reported an unmet need to treat the neurologic manifestations of the disease despite the benefits of olipudase alfa in the management of non-neurological symptoms; (5) Participants felt all patients with ASMD need access to olipudase alfa based on the life-changing experience they perceived. Conclusions These findings highlight the sustained positive impact olipudase alfa had in many domains that are deemed important to patients and families living with ASMD and outline the extensive unmet need for patients and families living with ASMD.

Multi-institutional educational partnerships are a promising approach to developing the skilled technical workforce. Inexorably, the ability to maintain such partnership networks that support skilled technical workforce education was disrupted by COVID-19. The purpose of this study is to explore Southwest Virginia's science, technology, engineering, and mathematics (STEM)-focused multi-institutional partnership networks, to inventory the disruptive impacts of COVID-19, and to identify how partnership stakeholders navigated these challenges to prepare students for the skilled technical workforce. This work presents a single-case study design, highlighting the evolving landscape of STEM workforce education partnership networks in Southwest Virginia throughout the pandemic. The team conducted interviews with 19 regional stakeholders focused on the participants' role throughout the pandemic, barriers to STEM workforce education presented by public health and economic factors, and innovative strategies to sustain and expand partnership networks through COVID-19. Two key themes emerged from this study: successful partners maintained network connections through adaptive interactions and actors within the network served as brokers to leverage their connections and expand partnerships in the face of adversity. By taking a contextual view of the role of partnership networks in creating equitable STEM workforce pathways during COVID-19, we develop rich insights into partnership formation, collaboration, resource allocation, and programming amidst challenges to their success.

The use of tailored language, which involves a clinician’s ability to adapt communication styles and employ accessible terms and concepts, has long been touted as key to engaging men with mental health services. Metaphors are one communication device that can provide men with ways through which to meaningfully express themselves and communicate their mental distress experiences. Using qualitative photovoice research, the current study examined how New Zealand-based men ( n = 21) communicatively constructed their meaning of mental distress through metaphors. Analysis of interview data was used to derive three metaphor groupings men consistently drew on to articulate their lived experiences: metaphors of emotions ( darkness and weight ), metaphors of survival ( battle and entity ), and metaphors of disembodiments ( debility and entrapment ). The findings highlight the power of metaphors as a tool for men in communicating their experiences of mental distress and are valuable for health professionals to contemplate across an array of contexts. The implications and importance of a metaphor-enriched perspective for engaging men in professional health care settings and services are discussed.

Background In 2017, the Canadian Partnership Against Cancer, a Canadian federally sponsored organisation, initiated a national multijurisdictional quality improvement (QI) initiative to maximise the use of synoptic data to drive cancer system improvements, known as the Evidence for Surgical Synoptic Quality Improvement Programme. The goal of our study was to evaluate the outcomes, determinants and learning of this nationally led initiative across six jurisdictions in Canada, integrating a mix of cancer surgery disease sites and clinicians.Methods A mixed-methods evaluation (surveys, semistructured interviews and focus groups) of this initiative was focused on the ability of each jurisdiction to use synoptic reporting data to successfully implement and sustain QI projects to beyond the completion of the initiative and the lessons learnt in the process. Resources provided to the jurisdictions included operational funding, training in QI methodology, national forums, expert coaches, and ad hoc monitoring and support. The programme emphasised foundational concepts of the QI process including data literacy, audit and feedback reports, communities of practice (CoP) and positive deviance methodology.Results 101 CoP meetings were held and 337 clinicians received feedback reports. There were 23 projects, and 22 of 23 (95%) showed improvements with 15 of 23 (65%) achieving the proposed targets. Enablers of effective data utilisation/feedback reports for QI included the need for clinicians to trust the data, have comparative data for feedback, and the engagement of both data scientists and clinicians in designing feedback reports. Enablers of sustainability of QI within each jurisdiction included QI training for clinicians, the ability to continue CoP meetings, executive and broad stakeholder engagement, and the ability to use pre-existing organisational infrastructures and processes. Barriers to continue QI work included lack of funding for core team members, lack of automated data collection processes and lack of clinician incentives (financial and other).Conclusion Success and sustainability in data-driven QI in cancer surgery require skills in QI methodology, data literacy and feedback, dedicated supportive personnel and an environment that promotes the process of collective learning and shared accountability. Building these capabilities in jurisdictional teams, tailoring interventions to facility contexts and strong leadership engagement will create the capacity for continued success in QI for cancer surgery.

Variations in local strain, defect densities, and composition of hybrid metal-halide perovskites have been reported to create heterogeneous energy landscapes in thin films, which impact charge-carrier diffusion and recombination dynamics. Here, we employ one- and two-photon transient absorption spectroscopy to selectively probe the dynamics of charge carriers from surface and bulk regions of methylammonium lead bromide thin films. Differences in the transient absorption spectra indicate that an energy gradient of approximately 100 meV is formed between the higher band-gap surface and lower band-gap bulk regions. Thus, during their lifetime, photoexcited carriers move away from the surface to recombine in the bulk, where our experiments detect long-lived charge populations despite the significant band splitting that has conventionally been assumed to inhibit efficient radiative recombination. Supported by first-principles calculations, we demonstrate that bright emission can still arise from the bulk with states that occupy a wide range of momenta in the vicinity of the band extrema, which show strong dipole transitions. Our results report that photoexcitations in the hybrid perovskites avoid defect-rich surface regions, and that particularly strong emission is generated from accumulated excitation populations in the bulk.

BackgroundSeveral scales have been developed in the past two decades to evaluate Niemann-Pick disease Type C (NPC) severity in clinical practice and trials. However, a lack of clarity concerning which scale to use in each setting is preventing the use of standardised assessments across the world, resulting in incomparable data sets and clinical trial outcome measures. This study aimed to establish agreed approaches for the use of NPC severity scales in clinical practice and research.MethodsA Delphi method of consensus development was used, comprising three survey rounds. In Round 1, participants were asked nine multiple-choice and open-ended questions to gather opinions on the six severity scales and domains. In Rounds 2 and 3, questions aimed to gain consensus on the opinions revealed in Round 1 using a typical Likert scale.ResultsNineteen experts, active in NPC paediatric and adult research and treatment, participated in this study. Of these, 16/19 completed Rounds 1 and 2 and 19/19 completed Round 3. Consensus (defined as ≥ 70% agreement or neutrality, given the study aim to identify the severity scales that the clinical community would accept for international consistency) was achieved for 66.7% of the multiple-choice questions in Round 2 and 83% of the multiple-choice questions in Round 3. Consensus was almost reached (68%) on the use of the 5-domain NPCCSS scale as the first choice in clinical practice. Consensus was reached (74%) for the 17-domain NPCCSS scale as the first choice in clinical trial settings, but the domains measured in the 5-domain scale should be prioritised as the primary endpoints. Experts called for educational and training materials on how to apply the NPCCSS (17- and 5-domains) for clinicians working in NPC.ConclusionsIn achieving a consensus on the use of the 17-domain NPCCSS scale as the first choice for assessing clinical severity of NPC in clinical trial settings but prioritising the domains in the 5-domain NPCCSS scale for routine clinical practice, this study can help to inform future discussion around the use of the existing NPC clinical severity scales. For routine clinical practice, the study helps provide clarity on which scale is favoured by a significant proportion of a representative body of experts, in this case, the 5-domain NPCCSS scale.

ObjectiveTo assess the effects of neural mobilisation on nerve function and nerve structure of patients with peripheral neuropathic pain.MethodsA systematic review with meta-analysis was conducted. Medline, Embase, CINAHL, Cochrane Library, and World Health Organization International Clinical Trials Registry Platform were searched without restrictions. Eligibility criteria included controlled trials or quasi-experimental studies comparing neural mobilisation versus sham, active or inactive control in adults with peripheral neuropathic pain. Primary outcomes were the change in peripheral nerve cross-sectional area. Secondary outcomes included nerve echogenicity, nerve excursion and nerve conduction. Random effects meta-analysis was conducted. Risk of bias was assessed with the Cochrane Collaboration tool, and certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation framework.ResultsEleven randomised controlled trials and four quasi-experimental studies (total sample = 722 participants) were included. Thirteen studies included participants with carpal tunnel syndrome. Two studies examined the cross-sectional area, revealing improvements (i.e., a reduction) in the cross-sectional area after the neural mobilisation. Neural mobilisation improved motor [mean difference = 2.95 (95%CI 1.67 to 4.22)] and sensory conduction velocity in short-term [mean difference = 11.74 (95%CI 7.06 to 16.43)], compared to control. Neural mobilisation did not alter distal motor or sensory latency.ConclusionNeural mobilisation seems to improve (i.e., a reduced) the cross-sectional area (very low-quality evidence) and sensory conduction velocity (very low-quality evidence). Neural mobilisation was superior to control in improving motor conduction velocity in patients with peripheral neuropathic pain with moderate quality evidence. Distal motor or sensory latency presented similar results compared to other interventions. Our findings should be interpreted cautiously since most studies included patients with carpal tunnel syndrome.

Transient killer whales have been documented hunting marine mammals across a variety of habitats. However, relatively little has been reported about their predatory behaviours near deep submarine canyons and oceanic environments. We used a long-term database of sightings and encounters with these predators in and around the Monterey Submarine Canyon, California to describe foraging behaviour, diet, seasonal occurrence, and habitat use patterns. Transient killer whales belonging to the outer coast subpopulation were observed within the study area 261 times from 2006-2021. Occurrences, behaviours, and group sizes all varied seasonally, with more encounters occurring in the spring as grey whales migrated northward from their breeding and calving lagoons in Mexico (March-May). Groups of killer whales foraged exclusively in open water, with individuals within the groups following the contours of the submarine canyon as they searched for prey. Focal follows revealed that killer whales spent 51% of their time searching for prey (26% of their time along the shelf-break and upper slope of the canyon, and 25% in open water). The remainder of their time was spent pursuing prey (10%), feeding (23%), travelling (9%), socializing (6%), and resting (1%). Prey species during 87 observed predation events included California sea lions, grey whale calves, northern elephant seals, minke whales, common dolphins, Pacific white-sided dolphins, Dall's porpoise, harbour porpoise, harbour seals, and sea birds. The calculated kill rates (based on 270 hours of observing 50 predation events) were 0.26 California sea lions per killer whale over 24 hours, 0.11 grey whale calves, and 0.15 for all remaining prey species combined. These behavioural observations provide insights into predator-prey interactions among apex predators over submarine canyons and deep pelagic environments.

Nucleases are ubiquitous in the environment, present in biospecimens and widely used in many laboratory processes. However, in the wrong context, as contaminants, they have catastrophic potential because of their ability to rapidly degrade nucleic acids whilst retaining high resilience to inactivation. Although laboratories undertake rigorous precautions to prevent nuclease contamination, such measures are not infallible. In 2015, we devised and integrated a novel routine nuclease testing regimen into our Quality Management System that uses cleavable, fluorescent DNA and RNA substrates to detect, monitor and control for nuclease contamination in our laboratory processes, equipment and consumables. The testing regimen enables us to identify higher-risk activities, design our laboratory workflows such that risk is minimized and help fulfil our obligations in respect of ISO 20387:2018 General Requirements for Biobanking and ISO 17025 Testing and Calibrations Laboratory standards, both of which stipulate that environmental conditions in our laboratory must be monitored with defined quality control criteria. In seventeen rounds of testing (30 Test Items per round), 1.1 % of RNase tests and 0.2 % of DNase tests returned elevated nuclease levels (≥2.90 x 10−9 U RNase or 1.67 x 10−3 U DNase) and we were able to take remedial action. In no instance was an elevated nuclease level consequential in terms of an impact on sample quality. We present our protocols, results and observations.

We report on a set of high-precision measurements of nuclear binding and excitation energies, as well as nuclear spins, magnetic dipole and electric quadrupole moments of neutron-rich silver isotopes, 113−123Ag. The measurements were performed using the JYFLTRAP mass spectrometer and the collinear laser spectroscopy beamline at the Ion Guide Isotope Separator On-Line (IGISOL) facility. For the first time, we can firmly establish the ordering of the long-lived Iπ=1/2−,7/2+ states in these isotopes, and pin down the inversion of these two levels at either A=121(N=74) or A=123(N=76). We compare these findings to calculations performed with density functional theory (DFT), from which we establish the crucial role that the spin-orbit strength and time-odd mean fields play in the simultaneous description of electromagnetic moments and nuclear binding.