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Among the rare meteorological phenomena that exist are long-lived spheroidal air plasmas. Of these, lightning balls are best characterized. Closely related are earth-lights, tornadic lights and Unpredictable Flying Objects (UFOs). Early physicists took all such phenomena to be plasmas and would refer to them as electric fire or fireballs. Many physicists today do not accept that these light emitting objects are plasmas because they neglect a variety of influences that result from chemical change. Stability results mainly from entropy production as an ionized, metastable form of nitrous acid, produced at an air plasma surface, refrigerates the surface through its conversion to the stable acid. It is then oxidized to nitric acid in an aerosol form, which restricts the inflow of air to the plasma surface. This can explain the “ surface tension” of lightning balls early, as hypothesized by Stakhanov (1979). Studies of earth-lights (Teodorani, 2004) imply that these are plasma balls held together by the same forces as those providing mechanical stability to lightning balls. Studies of flame balls in space support this view. UFOs and earth-lights are structured similarly but the plasma components of UFOs can be held together by far stronger forces. Potentially, air plasmas have important technological implications since they are all powered by extracting and using chemical energy from the air. Crucially, this energy can only be extracted from air whose temperature is below 150 C. If air plasmas could be prepared artificially, they would prove invaluable in supplying ample carbon-free electrical energy.

Objective To estimate the cost-effectiveness of craniotomy, compared with decompressive craniectomy (DC) in UK patients undergoing evacuation of acute subdural haematoma (ASDH).Design Economic evaluation undertaken using health resource use and outcome data from the 12-month multicentre, pragmatic, parallel-group, randomised, Randomised Evaluation of Surgery with Craniectomy for Patients Undergoing Evacuation-ASDH trial.Setting UK secondary care.Participants 248 UK patients undergoing surgery for traumatic ASDH were randomised to craniotomy (N=126) or DC (N=122).Interventions Surgical evacuation via craniotomy (bone flap replaced) or DC (bone flap left out with a view to replace later: cranioplasty surgery).Main outcome measures In the base-case analysis, costs were estimated from a National Health Service and Personal Social Services perspective. Outcomes were assessed via the quality-adjusted life-years (QALY) derived from the EuroQoL 5-Dimension 5-Level questionnaire (cost-utility analysis) and the Extended Glasgow Outcome Scale (GOSE) (cost-effectiveness analysis). Multiple imputation and regression analyses were conducted to estimate the mean incremental cost and effect of craniotomy compared with DC. The most cost-effective option was selected, irrespective of the level of statistical significance as is argued by economists.Results In the cost-utility analysis, the mean incremental cost of craniotomy compared with DC was estimated to be −£5520 (95% CI −£18 060 to £7020) with a mean QALY gain of 0.093 (95% CI 0.029 to 0.156). In the cost-effectiveness analysis, the mean incremental cost was estimated to be −£4536 (95% CI −£17 374 to £8301) with an OR of 1.682 (95% CI 0.995 to 2.842) for a favourable outcome on the GOSE.Conclusions In a UK population with traumatic ASDH, craniotomy was estimated to be cost-effective compared with DC: craniotomy was estimated to have a lower mean cost, higher mean QALY gain and higher probability of a more favourable outcome on the GOSE (though not all estimated differences between the two approaches were statistically significant).Ethics Ethical approval for the trial was obtained from the North West—Haydock Research Ethics Committee in the UK on 17 July 2014 (14/NW/1076).Trial registration number ISRCTN87370545.

Objectives Mycophenolate mofetil (MMF) and azathioprine (AZA) are immunomodulatory treatments in interstitial lung disease (ILD). This systematic review aimed to evaluate the efficacy of MMF or AZA on pulmonary function in ILD.Design Population included any ILD diagnosis, intervention included MMF or AZA treatment, outcome was delta change from baseline in per cent predicted forced vital capacity (%FVC) and gas transfer (diffusion lung capacity of carbon monoxide, %DLco). The primary endpoint compared outcomes relative to placebo comparator, the secondary endpoint assessed outcomes in treated groups only.Eligibility criteria Randomised controlled trials (RCTs) and prospective observational studies were included. No language restrictions were applied. Retrospective studies and studies with high-dose concomitant steroids were excluded.Data synthesis The systematic search was performed on 9 May. Meta-analyses according to drug and outcome were specified with random effects, I2 evaluated heterogeneity and Grading of Recommendations, Assessment, Development and Evaluation evaluated certainty of evidence. Primary endpoint analysis was restricted to RCT design, secondary endpoint included subgroup analysis according to prospective observational or RCT design.Results A total of 2831 publications were screened, 12 were suitable for quantitative synthesis. Three MMF RCTs were included with no significant effect on the primary endpoints (%FVC 2.94, 95% CI −4.00 to 9.88, I2=79.3%; %DLco −2.03, 95% CI −4.38 to 0.32, I2=0.0%). An overall 2.03% change from baseline in %FVC (95% CI 0.65 to 3.42, I2=0.0%) was observed in MMF, and RCT subgroup summary estimated a 4.42% change from baseline in %DLCO (95% CI 2.05 to 6.79, I2=0.0%). AZA studies were limited. All estimates were considered very low certainty evidence.Conclusions There were limited RCTs of MMF or AZA and their benefit in ILD was of very low certainty. MMF may support preservation of pulmonary function, yet confidence in the effect was weak. To support high certainty evidence, RCTs should be designed to directly assess MMF efficacy in ILD.PROSPERO registration number CRD42023423223.

Background Medicine prescribing, monitoring and administration in care homes can be significantly enhanced. Effective interventions to improve pharmaceutical care and resident outcomes are required. The enablement of pharmacists to prescribe provides an opportunity for pharmacist independent prescribers to assume responsibility for improving pharmaceutical care, medication-related outcomes and resident safety whilst reducing general practitioner workload. Objective(s) To determine the effectiveness and cost-effectiveness of pharmacist independent prescribing in care homes. Design Development work was undertaken through five work packages before the delivery of the definitive trial. Triads of pharmacist independent prescribers, care home and general practice with responsibility over 20 care home residents were recruited and cluster randomised to intervention or usual care for 6 months. Researchers were blinded at recruitment stage only. Recruitment of 880 residents was required to provide 80% statistical power, to show a 21% reduction in falls over 6 months, assuming 20% attrition. Randomisation was undertaken electronically at triad level, stratified by geographical area. Intention-to-treat analysis undertaken using a negative binomial model. Parameters were estimated using a generalised estimating equation approach. Costs were captured from an NHS perspective. Quality of life (EuroQol; five domain; five level) was collected by proxy to enable cost/quality-adjusted life-year estimation. A concurrent process evaluation was performed. Safety was monitored through a review of pharmacist independent prescriber activities, independent concerns reporting and review of adverse events. Participants Forty-nine triads of general practitioners, pharmacist independent prescribers and care homes were recruited with 454 residents allocated to the intervention arm and 428 to the control arm. Intervention Medication review and care planning, medication reconciliation, staff training, support with care home medication-related procedures, deprescribing and authorisation of monthly prescriptions. Main outcome measure Fall rate per person over 6 months. Results Data for 449 intervention and 427 control residents available for final analysis. The 6-month fall rate ratio in favour of intervention was 0.91 (95% confidence interval 0.66 to 1.26; p=0.58). No significant difference in secondary outcomes was identified except Drug Burden Index (rate ratio 0.83, 95% confidence interval 0.75 to 0.92; p

Several aspects of physics have been adversely effected by the fact that vapor phase electrochemistry has proved impossible to quantify. By the end of the 19th century, physicists had encountered several strange observations that appeared to involve chemistry. Eventually, it was realized that, in a moist gas, no rate process involving ions is quantifiable since we possess no valid relationship between the concentrations of electrolytes and their thermodynamic activities. There are both technical and societal reasons for this problem. Until both problems have been addressed, no reliable quantitative conclusions can be drawn for any system where ionic electrostriction in a moist gas is important. The most obvious consequences of the missing science are misconceptions concerning naturally contained air plasmas such as ball lightning, tornadic lights, and unpredictable flying objects (UFOs). None of these phenomena violates any known law of physics, but this only becomes clear once the absence of applicable, strictly valid theories is accepted. Fortunately, partial solutions to the problem exist if use is made of qualitative arguments. Using this approach, it can be seen that all the apparently anomalous characteristics of atmospheric plasmas result from a balance between different physical and chemical driving forces. A better understanding of the chemical consequences of electrostriction should have two long-term benefits. One relates to understanding the corrosive properties of high-pressure steam. The other concerns the specific chemical processes that stabilize air plasmas. If stable air plasmas could be simulated, a plentiful supply of carbon-free energy would become available.

Introduction Many people quit smoking during pregnancy, but postpartum smoking relapse is common. Maintaining smoking abstinence achieved during pregnancy is key to improving maternal and child health. There are no evidence-based interventions for preventing postpartum smoking relapse. This trial aims to determine whether an intervention to prevent postpartum relapse is effective and cost-effective.Methods and analysis A randomised controlled trial of a complex intervention to prevent postpartum smoking relapse (BabyBreathe), with internal pilot, economic and process evaluations. Participants are adults who are pregnant and who report having quit smoking in the 12 months before, or during pregnancy. Participants are eligible if they read and understand English, and provide informed consent. Following consent and biochemical validation of smoking abstinence, participants are randomised to intervention or usual care/control (no specific relapse prevention support). The BabyBreathe intervention consists of manualised advice from a trained member of the health visiting service, health information leaflets for participants and partners, access to the BabyBreathe website and app. At the time of birth, participants are posted the BabyBreathe box and support is provided by text message for up to 12 months postpartum. Target sample size is 880, recruiting across midwifery services at four hubs in England and Scotland and through remote advertising in England, Scotland, Wales and Northern Ireland. Outcomes are collected at 6 and 12 months. The primary outcome is self-reported sustained smoking abstinence at 12 months, carbon monoxide verified. Secondary outcomes include self-reported abstinence, time to relapse, partner smoking status and quality of life.Ethics and dissemination The trial was approved by the North West Preston Research Ethics committee (21/NW/0017). Dissemination will include publication in peer-reviewed journals, presentation at academic and public conferences including patient and public involvement and to policymakers and practitioners.Trial registration number ISRCTN70307341

Introduction Over 50% of older adults are prescribed a medicine where the risk of harm outweighs the chances of benefit. During a hospital admission, older adults and carers expect medicines to be reviewed for appropriateness and any inappropriate medicines proactively deprescribed. While the principle of proactive deprescribing is an expectation of good prescribing practice, it is yet to become routine. The CompreHensive geriAtRician-led MEdication Review (CHARMER) study aims to develop and test a five-component behaviour change intervention to equip geriatricians and pharmacists to proactively deprescribe inappropriate medicines with older adults in hospital. This study aims to test the feasibility and acceptability of study processes and CHARMER implementation.Methods and analysis A two-arm purposive allocation feasibility study is being undertaken at four acute hospitals in England, UK (three intervention and one control). The target sample is 400 patients across all hospitals. Primary outcome measures are: (1) participant recruitment rate and (2) participant attrition rate. Secondary outcome measures are: (1) hospital readmission rate; (2) mortality rate and (3) quality of life. Quantitative data will be checked for completeness and quality, and practitioner and patient demographics descriptively analysed. We will undertake a rapid qualitative analysis on observations, interviews and study meeting minutes data. A subsequent thematic analysis will be undertaken with codes mapped to the Theoretical Domains Framework and Normalisation Process Theory. Triangulation of qualitative and quantitative data will be undertaken.Ethics and dissemination Ethics approval was obtained from Wales Research Ethics Committee 1 (IRAS ID 312494) and study approval from the Health Research Authority (22/WA/0087). Informed consent will be sought from all hospital staff involved in data collection activities and for patients involved in enhanced data collection activities. The findings of this study will be disseminated in peer-reviewed journals and conference presentations.Trial registration ISRCTN11899506.

The Local Volume Complete Cluster Survey is an ongoing program to observe nearly a hundred low-redshift X-ray-luminous galaxy clusters (redshifts 0.03 < z < 0.12 and X-ray luminosities in the 0.1–2.4 keV band L _X500c > 10 ^44 erg s ^−1 ) with the Dark Energy Camera, capturing data in the u , g , r , i , z bands with a 5 σ point source depth of approximately 25th–26th AB magnitudes. Here, we map the aperture masses in 58 galaxy cluster fields using weak gravitational lensing. These clusters span a variety of dynamical states, from nearly relaxed to merging systems, and approximately half of them have not been subject to detailed weak lensing analysis before. In each cluster field, we analyze the alignment between the 2D mass distribution described by the aperture mass map, the 2D red-sequence (RS) galaxy distribution, and the brightest cluster galaxy (BCG). We find that the orientations of the BCG and the RS distribution are strongly aligned throughout the interiors of the clusters: the median misalignment angle is 19° within 2 Mpc. We also observe the alignment between the orientations of the RS distribution and the overall cluster mass distribution (by a median difference of 32° within 1 Mpc), although this is constrained by galaxy shape noise and the limitations of our cluster sample size. These types of alignment suggest long-term dynamical evolution within the clusters over cosmic timescales.

This paper uses a new measure of human capital, which distinguishes both quality and quantity components, to estimate the long-term effect of the COVID-19-related school closures on aggregate productivity through the human capital channel. Productivity losses build up over time and are estimated to range between 0.4% and 2.1% after 45 years, for 12 weeks and 2 years of school closure, respectively. These results appear to be broadly consistent with earlier findings in the literature. Two opposing effects might influence these estimates. Online teaching would lower economic costs while learning losses in tertiary education (not considered here) would inflate them. Policies aimed at improving the quality of education and adult training will be needed to offset or, at least, alleviate the impact of the pandemic on human capital.

In 'A Reflexive Autoethnographic Fragment: Epiphany in a Milk Float', David Turner uses autoethnographic writing to begin to reflexively consider how his life history might have led him to an interest in a particular topic of study that he was about to embark on as part of research on the development of expertise in sports coaching, associated with a Professional Doctorate in Education course.

Background: Borderline personality disorder is a severe mental health condition characterised by a pattern of emotional instability, interpersonal dysfunction, disturbed self-image and impulsive behaviour, including self-harm. Symptoms of borderline personality disorder typically emerge during adolescence. Although there is compelling evidence in support of early intervention for borderline personality disorder, current evidence-based interventions are resource intensive, with the result that few young people access timely treatment. Therefore, there is an urgent need for accessible interventions to facilitate early intervention for adolescents with borderline personality disorder symptoms. Objectives: The first objective was to adapt a brief psychological treatment for adolescent borderline personality disorder that had previously been delivered within secondary mental health services for co-delivery within schools and colleges. The second objective was to assess the feasibility of evaluating the clinical effectiveness and cost-effectiveness of this intervention in a future randomised controlled trial. Design: We first conducted a rapid evidence synthesis of barriers to and facilitators of the implementation of indicated mental health interventions for adolescents within educational settings and piloted the prototype intervention with three schools/colleges. Based on the findings of the evidence synthesis and pilot, we refined the intervention and study procedures in preparation for a feasibility randomised controlled trial. The feasibility randomised controlled trial involved 12 schools and colleges, whose pastoral staff members received training to deliver the intervention alongside a mental health practitioner. Participants were randomised in a 1 : 1 ratio to receive either the BEST (Brief Education Supported Treatment) intervention plus treatment as usual or treatment as usual alone. Participants were assessed pre randomisation (baseline) and at 12 and 24 weeks post randomisation. Mixed-methods process data were collected to understand how the intervention was implemented, to assess acceptability and to monitor contamination of the control arm. Participants: Young people eligible to participate were aged 13–18 years, reported symptoms of borderline personality disorder above an established threshold and had a history of repeated self-harm. Results: The intervention was refined based on findings of the rapid evidence synthesis, which included 50 studies, feedback from staff participants in the pilot and analysis of session recordings. In the feasibility randomised controlled trial, we randomised 32 participants prior to the premature closure of recruitment. The rate of recruitment was slower than anticipated but would probably have narrowly surpassed our progression criterion over the full recruitment window. Participant retention was high (89.5% at 12 weeks and 73.7% at 24 weeks) and the performance of the proposed outcome measures was satisfactory. We did not find any evidence that participants allocated to the treatment-as-usual arm received the BEST intervention or its components. Fidelity of intervention delivery was high (93.5% of recordings rated as adherent) and the intervention was viewed as offering benefits for individual participants, practitioners involved in co-delivery and the wider school/college. Limitations: The feasibility randomised controlled trial was disrupted by the closure of schools and colleges in response to the COVID-19 pandemic. This reduced the window for participant recruitment and limited the data that could be collected. Conclusions: The refined BEST intervention was able to be delivered successfully within schools and colleges and was found to be acceptable to staff and young people. The findings provide support for continuing this programme of research and would inform the design of a future trial. Trial registration: This trial is registered as ISRCTN16862589. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 10, No. 37. See the NIHR Journals Library website for further project information.

Abstract Background A colorectal resection is standard treatment for patients with colorectal cancer (CRC). However, the procedure results in significant post-operative mortality and reduced quality of life. Maximising pre-operative cardiopulmonary fitness could improve post-surgical outcomes. PREPARE-ABC is a multi-centre, three-armed, randomised controlled trial investigating the effects of exercise interventions, with motivational support on short and longer-term recovery outcomes in CRC patients undergoing major lower-gastrointestinal surgery. The trial included an internal pilot phase with parallel process evaluation. The aim of the process evaluation was to optimise intervention implementation for the main trial. Methods Mixed methods process evaluation conducted in 14 UK hospitals between November 2016 and March 2018. Data included a site profile questionnaire and telephone scoping interview with hospital staff, 34 qualitative observations of standard care and 14 observations of intervention delivery, 13 semi-structured interviews with healthcare professionals (HCPs) and 28 semi-structured interviews with patients. Data analysis focused on describing intervention delivery within each arm, assessing fidelity, acceptability and how variation in delivery was linked to contextual characteristics. Results Standard care exercise advice was typically limited to maintaining current activity levels, and with lead-in time to surgery affecting whether any exercise advice was provided. Variation in HCP capacity affected the ability of colorectal units to deploy staff to deliver the intervention. Patients’ exercise history and motivation prior to surgery influenced HCP perceptions and delivery of the motivational components. Observations indicated a high level of fidelity to delivery of the exercise interventions. All but one of the 28 interviewed patients reported increasing exercise levels as a result of receiving the intervention, with most finding them motivational and greatly valuing the enhanced level of social support (versus standard care) provided by staff. Conclusion Hospital-supervised and home-based exercise interventions were highly acceptable for most patients undergoing surgery for CRC. Delivery of pre- and post-operative exercise within the CRC care pathway is feasible but systematic planning of capacity and resources is required to optimise implementation.

Cross-country estimation work consistently finds that coefficients on statutory pension ages are positive and highly statistically significant in explaining labour force participation at older ages. However, the estimated effects are surprisingly modest when translated into the implied effect on the average effective age of retirement, which typically only increases by about 2 months for every year by which the statutory retirement age increases. This paper shows that grouping countries with similar pension systems, allowing for time heterogeneity and introducing other modelling choices, can improve the estimates of the effect of changes to the pension system. In countries in which there are alternative early retirement pathways or voluntary private pension systems, the effect of changes in statutory retirement ages tends to be dampened. However, for other countries, the effect of changes in statutory pension ages can be around two to three times larger than the typical finding from pooled country estimations.Keywords: pension funds, defined contribution system, life-cycle investing

Objectives To assess practice in the care of adults with suspected community-acquired bacterial meningitis in the UK and Ireland.Design Retrospective cohort study.Setting 64 UK and Irish hospitals.Participants 1471 adults with community-acquired meningitis of any aetiology in 2017.Results None of the audit standards, from the 2016 UK Joint Specialists Societies guideline on diagnosis and management of meningitis, were met in all cases. With respect to 20 of 30 assessed standards, clinical management provided for patients was in line with recommendations in less than 50% of cases. 45% of patients had blood cultures taken within an hour of admission, 0.5% had a lumbar puncture within 1 hour, 26% within 8 hours. 28% had bacterial molecular diagnostic tests on cerebrospinal fluid. Median time to first dose of antibiotics was 3.2 hours (IQR 1.3–9.2). 80% received empirical parenteral cephalosporins. 55% ≥60 years and 31% of immunocompromised patients received anti-Listeria antibiotics. 21% received steroids. Of the 1471 patients, 20% had confirmed bacterial meningitis. Among those with bacterial meningitis, pneumococcal aetiology, admission to intensive care and initial Glasgow Coma Scale Score less than 14 were associated with in-hospital mortality (adjusted OR (aOR) 2.08, 95% CI 0.96 to 4.48; aOR 4.28, 95% CI 1.81 to 10.1; aOR 2.90, 95% CI 1.26 to 6.71, respectively). Dexamethasone therapy was weakly associated with a reduction in mortality in both those with proven bacterial meningitis (aOR 0.57, 95% CI 0.28 to 1.17) and with pneumococcal meningitis (aOR 0.47, 95% CI 0.20 to 1.10).Conclusion This study demonstrates that clinical care for patients with meningitis in the UK is not in line with current evidence-based national guidelines. Diagnostics and therapeutics should be targeted for quality improvement strategies. Work should be done to improve the impact of guidelines, understand why they are not followed and, once published, ensure they translate into changed practice.

Background: Despite the importance of reducing treatment burden for people with cystic fibrosis (CF), it has not been fully understood as a concept. This study aims to quantify the treatment burden perceived by CF adults and explore the association between different validated treatment burden measures. Methods: This is a cross-sectional observational study of CF adults attending a single large UK adult center. Participants completed an online survey that contained three different treatment burden scales; CF Questionnaire-Revised (CFQ-R) subscale, CF Quality of Life (CFQoL) subscale, and the generic multimorbidity treatment burden questionnaire (MTBQ). Results: Among 101 participants, the median reported treatment burden by the CFQ-R subscale was 55.5 (IQR 33.3 – 66.6), the CFQoL subscale was 66.6 (IQR 46.6 – 86.6), and the MTBQ reversed global score was 84.6 (IQR 73.1 – 92.3). No correlation was found between respondents’ demographic or clinical variables and treatment burden measured via any of the three measures. All treatment burden measures showed correlations against each other. More treatments were associated with high treatment burden as measured by the CFQ-R, CFQoL subscales, and the MTBQ. However, longer treatment time and more complex treatment plans were correlated with high treatment burden as measured by the CFQ-R and CFQoL subscales, but not with the MTBQ. Conclusions: Treatment burden is a substantial issue in CF. Currently, the only available way to evaluate it is with the CF-specific quality of life measure treatment burden subscales (CFQ-R and CFQoL); both indicated that treatment burden increases with more treatments, longer treatment time, and more complex treatments.

Abstract The COVID-19 pandemic has led to widespread shortages of personal protective equipment (PPE) for healthcare workers, including of N95 masks (filtering facepiece respirators; FFRs). These masks are intended for single use but their sterilization and subsequent reuse has the potential to substantially mitigate shortages. Here we investigate PPE sterilization using ionized hydrogen peroxide (iHP), generated by SteraMist equipment (TOMI; Frederick, MD), in a sealed environment chamber. The efficacy of sterilization by iHP was assessed using bacterial spores in biological indicator assemblies. After one or more iHP treatments, five models of N95 masks from three manufacturers were assessed for retention of function based on their ability to form an airtight seal (measured using a quantitative fit test) and filter aerosolized particles. Filtration testing was performed at a university lab and at a National Institute for Occupational Safety and Health (NIOSH) pre-certification laboratory. The data demonstrate that N95 masks sterilized using SteraMist iHP technology retain filtration efficiency up to ten cycles, the maximum number tested to date. A typical iHP environment chamber with a volume of ~ 80 m3 can treat ~ 7000 masks and other items (e.g. other PPE, iPADs), making this an effective approach for a busy medical center.

Abstract Background Depression is a common health problem during adolescence and is associated with adverse academic, social and health outcomes. To meet the demand for treatment for adolescent depression, there is a need for evidence-based interventions suitable for delivery outside of specialist Child and Adolescent Mental Health Services (CAMHS). Interpersonal Counselling for Adolescents (IPC-A) is a brief manualised intervention for adolescent depression suitable for delivery by staff who are not qualified health professionals following participation in a brief training course. While initial piloting within Local Authority services has generated promising results, the effectiveness and cost-effectiveness of IPC-A has yet to be established. This study aims to assess the feasibility of a randomised controlled trial (RCT), evaluating the effectiveness and cost-effectiveness of IPC-A delivered by staff without core professional training in comparison to current provision. Method Feasibility RCT with process evaluation using ethnographic methodology. Eligible young people (n = 60) will be randomised in a 1:1 ratio to receive either IPC-A or treatment as usual (TAU). Participants will be assessed pre-randomisation (baseline) and followed up at 5, 10 and 23 weeks post-randomisation. A parallel process evaluation will generate understanding of intervention implementation across services and explore the acceptability of the intervention from the perspective of young people and other key stakeholders. Participants Young people aged 12–18 years presenting to non-specialist services with symptoms of depression. Youth workers, young people and stakeholders will participate in the process evaluation. Discussion The need for effective and accessible interventions for young people with mild/sub-threshold depression who, in most cases, do not meet the threshold for mainstream mental health services is long overdue. The primary output of this feasibility trial will be the design of the subsequent full-scale trial. If the results of the current study indicate that this would be feasible, we intend to progress to a multi-site, assessor-blind, superiority RCT of the effectiveness and cost-effectiveness of IPC-A in comparison to TAU for adolescents presenting to non-specialist services with depressive symptoms. If satisfactory solutions to any problems encountered cannot be identified, alternative research designs will be considered. If proven effective, an IPC-A training programme could be implemented. Trial registry ISRCTN registry, ISRCTN82180413 , Registered 31 December 2019.

Abstract Background Cognitive impairment and dementia following cerebrovascular disease are increasingly common in the UK. One potential strategy to prevent post-stroke cognitive decline is multimodal vascular risk factor management. However, its efficacy remains uncertain and its application in vulnerable patients with incident cerebrovascular disease and early cognitive impairment has not been assessed. The primary aim of this study was to assess the feasibility of recruitment and retention of patients with early cognitive impairment post-stroke or transient ischaemic attack (TIA) to a trial of enhanced vascular risk factor management combining primary and secondary care. Methods In this single centre, open label trial adults with a recent stroke or TIA and mild cognitive impairment (MCI) were randomised 1:1 to a three-monthly multimodal vascular risk factor intervention jointly delivered by the trial team and General Practitioner (GP), or control (defined as usual care from the GP). Chosen risk factors were blood pressure (BP), total cholesterol, blood glucose (HbA1C) in those with diabetes, and heart rate and adequacy of anticoagulation in those with atrial fibrillation (AF). Similar patients with normal cognition were enrolled in an embedded observational cohort and also received usual care from the GP. Repeat cognitive screening was undertaken in all participants after 12 months. Results Seventy three participants were recruited to the randomised trial and 94 to the observational cohort (21.8% of those screened). From the randomised trial 35/73 (47.9%) dropped out before final follow-up. In all groups guideline based rates of risk factor control were mostly poor at baseline and did not significantly improve during follow-up. The observational cohort demonstrated greater decline in cognitive test scores at 12 months, with no difference between the randomised groups. Conclusions Recruitment to such a study was feasible, but retention of participants was difficult and generally poor rates of risk factor control suggested insufficient application of the intervention. Consequently, successful scaling up of the trial would require protocol changes with less reliance on primary care services. Any future trial should include participants with normal cognition post-stroke as they may be at greatest risk of cognitive decline. Trial registration ISRCTN, ISRCTN42688361 . Registered 16 April 2015.

Abstract Background Exercise may be a promising target for depression interventions. However, evidence for a beneficial effect of exercise interventions on the prevention of depression differs substantially across different studies. Methods A systematic search was performed up to July 2018 using PubMed, Embase, PsycINFO, and Cochrane. Articles were included if a meta-analysis of randomized controlled trials was performed that examined the effect of exercise interventions on the onset of depression or depressive symptoms in the general population. Meta-analyses focusing on treatment of diagnosed depression were excluded. Two authors independently screened the articles and graded the quality of included meta-analyses using AMSTAR 2. Results Eight meta-analyses were included that showed little overlap in 134 included studies. All meta-analyses reported on depressive symptoms rather than onset of depression. Five of these were rated as moderate quality and three of low quality. Six meta-analyses found significant effects, and two found non-significant effects of exercise interventions in reducing depressive symptoms in children, adolescents, adults and the elderly (effect sizes ranging from − 0.10 to − 0.81). Scarce evidence did not allow to draw conclusions about the role of sex and characteristics of exercise on depression. However, some findings suggest that low intensity exercise was as effective as high intensity exercise. Heterogeneity among primary studies was high, likely caused by differences in study quality and exercise characteristics. Conclusions The evidence from this study suggests that exercise interventions have a beneficial effect on depressive symptoms in the general population across a wide age-range.

The teaching of history is an important way in which the older generation, who control education systems, curricula, content choice and so on, pass on to the younger generation ideas, especially the idea of nationhood, which they hope will form the basis for future national cohesion. The younger generation, however, receive these messages and interpret then through the lens of their own experiences, experiences that they do not share with the older generation. Consequently, the idea of history is re-formed and reformulated by each generation. This paper looks at the role of textbooks, principally history textbooks, in that process. The style of textbooks is to present history as uncontentious, a descriptive account of facts and events. In practice, however, textbooks can only present an arbitrary selection from history, and a crucial decision made by educators is when to start their account – the beginning of history – as this can radically affect the interpretation of events. This facsimile of neutrality stands in sharp contrast to the professional historians’ hope that the teaching of history can develop a critical sense of important and contested events in history. The discussion is illustrated with examples of how history is presented in China and Japan, and how the conflicting accounts serve the interests of the policies adopted by the older generation, but may have unanticipated consequences for the younger generation.

Abstract Background Prescribing, monitoring and administration of medicines in care homes could be improved. Research has identified the need for one person to assume overall responsibility for the management of medicines within each care home. and shown that a pharmacist independent prescriber service is feasible in this context. Aims and objectives To conduct a cluster randomised controlled trial to determine the effectiveness and cost-effectiveness of a pharmacist-independent prescribing service in care homes compared to usual general practitioner (GP)-led care. Objectives To perform a definitive randomised controlled trial (RCT) with an internal pilot to determine the intervention’s effectiveness and cost-effectiveness and enable modelling beyond the end of the trial. Methods This protocol is for a cluster RCT with a 3-month internal pilot to confirm that recruitment is achievable, and there are no safety concerns. The unit of randomisation is a triad comprising a pharmacist-independent prescriber (PIP) based in a GP practice with sufficient registered patients resident in one or more care homes to allow recruitment of an average of 20 participants. In the intervention group, the PIP will, in collaboration with the GP: assume responsibility for prescribing and managing residents’ medicines including medication review and pharmaceutical care planning; support systematic ordering and administration in the care home, GP practice and supplying pharmacy; train care home and GP practice staff; communicate with GP practice, care home, supplying community pharmacy and study team. The intervention will last 6 months. The primary outcome will be resident falls at 6 months. Secondary outcomes include resident health-related quality of life, falls at 3 months, medication burden, medication appropriateness, mortality and hospitalisations. A full health economic analysis will be undertaken. The target sample size is 880 residents (440) in each arm) from 44 triads. This number is sufficient to detect a decrease in fall rate from 1.5 per individual to 1.178 (relative reduction of 21%) with 80% power and an ICC of 0.05 or less. Discussion Recruitment is on-going and the trial should complete in early 2020. The trial results will have implications for the future management of residents in care homes and the ongoing implementation of independent pharmacist prescribing. Trial registration ISRCTN, ID: 17847169. Registered on 15 December 2017.

Backgrounds. Infection and inflammation play an important role in prostate cancer (PCa) etiology and pathogenesis. However, the environmental drivers for PCa are not fully understood. Methods. In a cross-sectional study, we analyzed circulating fungal microbiome in plasma samples from age and race-matched healthy control men (n=34) and preoperative PCa patients (n=31). Results. The fungal community in the plasma exhibited differences between individuals with PCa and healthy controls according to the beta diversity; there was no difference in the alpha diversity. Moreover, the relative abundance of several fungi differed between the two study groups from the class to species levels. The most significant differences were Filobasidiales family, Pyronemataceae family, and Cryptococcus ater species, which were enriched in PCa patients compared to controls. The increased Bipolaris genus was associated with low prostate-specific antigen (PSA) levels, increased Sordariomycetes class was associated with severe pathological stage, and decreased Phoma herbarum species was associated with disease relapse, compared to corresponding controls. Several fungi from class to species levels were increased in the controls compared to patients. Conclusion. This is the first study to show plasma distinct fungal microbiome and its associations with PSA levels, relapse, and pathology stages in PCa patients.

This paper introduces a growth method—suboxide molecular-beam epitaxy (S-MBE)—which enables a drastic enhancement in the growth rates of Ga2O3 and related materials to over 1 μm h−1 in an adsorption-controlled regime, combined with excellent crystallinity. Using a Ga + Ga2O3 mixture with an oxygen mole fraction of x(O) = 0.4 as an MBE source, we overcome kinetic limits that had previously hampered the adsorption-controlled growth of Ga2O3 by MBE. We present growth rates up to 1.6 μm h−1 and 1.5 μm h−1 for Ga2O3/Al2O3 and Ga2O3/Ga2O3 structures, respectively, with very high crystalline quality at unparalleled low growth temperature for this level of perfection. We combine thermodynamic knowledge of how to create molecular beams of targeted suboxides with a kinetic model developed for the S-MBE of III–VI compounds to identify appropriate growth conditions. Using S-MBE, we demonstrate the growth of phase-pure, smooth, and high-purity homoepitaxial Ga2O3 films that are thicker than 4.5 μm. With the high growth rate of S-MBE, we anticipate a significant improvement to vertical Ga2O3-based devices. We describe and demonstrate how this growth method can be applied to a wide range of oxides. With respect to growth rates and crystalline quality, S-MBE rivals leading synthesis methods currently used for the production of Ga2O3-based devices.

The development of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka and colleagues in 2006 has led to a potential new paradigm in cellular therapeutics, including the possibility of producing patient-specific, disease-specific and immune matched allogeneic cell therapies. One can envisage two routes to immunologically compatible iPSC therapies: using genetic modification to generate a ‘universal donor’ with reduced expression of Human Leukocyte Antigens (HLA) and other immunological targets or developing a haplobank containing iPSC lines specifically selected to provide HLA matched products to large portions of the population. HLA matched lines can be stored in a designated physical or virtual global bank termed a ‘haplobank’. The process of ‘iPSC haplobanking’ refers to the banking of iPSC cell lines, selected to be homozygous for different HLA haplotypes, from which therapeutic products can be derived and matched immunologically to patient populations.By matching iPSC and derived products to a patient’s HLA class I and II molecules, one would hope to significantly reduce the risk of immune rejection and the use of immunosuppressive medication. Immunosuppressive drugs are used in several conditions (including autoimmune disease and in transplantation procedures) to reduce rejection of infused cells, or transplanted tissue and organs, due to major and minor histocompatibility differences between donor and recipient. Such regimens can lead to immune compromise and pathological consequences such as opportunistic infections or malignancies due to decreased cancer immune surveillance. In this article, we will discuss what is practically involved if one is developing and executing an iPSC haplobanking strategy.

Introduction Self-management and remaining physically active are first-line recommendations for the care of patients with low back pain (LBP). With a lifetime prevalence of up to 85%, novel approaches to support behavioural self-management are needed. Internet interventions may provide accessible support for self-management of LBP in primary care. The aim of this randomised controlled trial is to determine the clinical and cost-effectiveness of the ‘SupportBack’ internet intervention, with or without physiotherapist telephone support in reducing LBP-related disability in primary care patients.Methods and analysis A three-parallel arm, multicentre randomised controlled trial will compare three arms: (1) usual primary care for LBP; (2) usual primary care for LBP and an internet intervention; (3) usual primary care for LBP and an internet intervention with additional physiotherapist telephone support. Patients with current LBP and no indicators of serious spinal pathology are identified and invited via general practice list searches and mailouts or opportunistic recruitment following LBP consultations. Participants undergo a secondary screen for possible serious spinal pathology and are then asked to complete baseline measures online after which they are randomised to an intervention arm. Follow-ups occur at 6 weeks, 3, 6 and 12 months. The primary outcome is physical function (using the Roland and Morris Disability Questionnaire) over 12 months (repeated measures design). Secondary outcomes include pain intensity, troublesome days in pain over the last month, pain self-efficacy, catastrophising, kinesophobia, health-related quality of life and cost-related measures for a full health economic analysis. A full mixed-methods process evaluation will be conducted.Ethics and dissemination This trial has been approved by a National Health Service Research Ethics Committee (REC Ref: 18/SC/0388). Results will be disseminated through peer-reviewed journals, conferences, communication with practices and patient groups. Patient representatives will support the implementation of our full dissemination strategy.Trial registration number ISRCTN14736486.

Physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) models can serve as a powerful framework for predicting the influence as well as the interaction of formulation, genetic polymorphism and co-medication on the pharmacokinetics and pharmacodynamics of drug substances. In this study, flurbiprofen, a potent non-steroid anti-inflammatory drug, was chosen as a model drug. Flurbiprofen has absolute bioavailability of ~95% and linear pharmacokinetics in the dose range of 50–300 mg. Its absorption is considered variable and complex, often associated with double peak phenomena, and its pharmacokinetics are characterized by high inter-subject variability, mainly due to its metabolism by the polymorphic CYP2C9 (fmCYP2C9 ≥ 0.71). In this study, by leveraging in vitro, in silico and in vivo data, an integrated PBPK/PD model with mechanistic absorption was developed and evaluated against clinical data from PK, PD, drug-drug and gene-drug interaction studies. The PBPK model successfully predicted (within 2-fold) 36 out of 38 observed concentration-time profiles of flurbiprofen as well as the CYP2C9 genetic effects after administration of different intravenous and oral dosage forms over a dose range of 40–300 mg in both Caucasian and Chinese healthy volunteers. All model predictions for Cmax, AUCinf and CL/F were within two-fold of their respective mean or geometric mean values, while 90% of the predictions of Cmax, 81% of the predictions of AUCinf and 74% of the predictions of Cl/F were within 1.25 fold. In addition, the drug-drug and drug-gene interactions were predicted within 1.5-fold of the observed interaction ratios (AUC, Cmax ratios). The validated PBPK model was further expanded by linking it to an inhibitory Emax model describing the analgesic efficacy of flurbiprofen and applying it to explore the effect of formulation and genetic polymorphisms on the onset and duration of pain relief. This comprehensive PBPK/PD analysis, along with a detailed translational biopharmaceutic framework including appropriately designed biorelevant in vitro experiments and in vitro-in vivo extrapolation, provided mechanistic insight on the impact of formulation and genetic variations, two major determinants of the population variability, on the PK/PD of flurbiprofen. Clinically relevant specifications and potential dose adjustments were also proposed. Overall, the present work highlights the value of a translational PBPK/PD approach, tailored to target populations and genotypes, as an approach towards achieving personalized medicine.

Shipping emissions are likely to increase significantly in the coming decades, alongside increasing emphasis on the sustainability and environmental impacts of the maritime transport sector. Exhaust gas cleaning systems (“scrubbers”), using seawater or fresh water as cleaning media for sulfur dioxide, are progressively used by shipping companies to comply with emissions regulations. Little is known about the chemical composition of the scrubber effluent and its ecological consequences for marine life and biogeochemical processes. If scrubbers become a central tool for atmospheric pollution reduction from shipping, modeling, and experimental studies will be necessary to determine the ecological and biogeochemical effects of scrubber wash water discharge on the marine environment. Furthermore, attention must be paid to the regulation and enforcement of environmental protection standards concerning scrubber use. Close collaboration between natural scientists and social scientists is crucial for progress toward sustainable shipping and protection of the marine environment.

In Colchester, Britain's oldest recorded town, during the Roman period there were areas which were clearly used solely as cemeteries. One of the most significant is at Butt Road, which includes a late Roman probable Christian cemetery with an associated building, apparently a church, that overlies and developed from a pagan inhumation cemetery. DNA was extracted from the long bones (femurs) of 29 individuals, mostly from a large complex of burials centered on two timber vaults. These were thought to comprise a number of family groupings, deduced from osteological analysis, stratigraphical and other considerations. The use of a modified version of the silica-based purification method recovered nanogram quantities of DNA/gram of bone. Two-stage amplification, incorporating primer-extension preamplification-polymerase chain reaction, permitted simultaneous amplification of both mitochondrial and nuclear DNA. Sequence-specific oligonucleotide probes yielded human leukocyte antigen (HLA)-DR typing of seven samples, with four revealing the infrequent HLA-DR10 genotype. Examination of the control region of mitochondrial DNA (mtDNA) by direct sequencing revealed polymorphisms yet to be reported in the modern population. HLA-DRB typing and mtDNA analysis affirmatively supported kinship among some, if not all, individuals in the “vault complex” and demonstrate a continental European origin of the individuals investigated.

Community pharmacies are commonly used to screen for patients with diabetes. The aim of this paper is to estimate the cost per test and cost per appropriately referred patient from a pharmacy perspective using a one-year decision tree model. One-way sensitivity analysis was performed to estimate the effect of geographical location and patient self-referral rate. Data was used from 164 patients screened and located in an area with average social deprivation and largely white European inhabitants and 172 patients in an area with higher social deprivation (lower than average ability to access society’s resources) and a mixed ethnicity population in England. The diabetes screening consisted of initial risk assessment via questionnaire followed by HbA1c test for those identified as high risk. The cost per person screened was estimated as £28.65. The cost per appropriately referred patient with type 2 diabetes was estimated to range from £7638 to £11,297 in deprived mixed ethnicity and non-deprived areas respectively. This increased to £12,730 and £18,828, respectively, if only 60% of patients referred chose to inform their general practitioner (GP). The cost per test and identification rates through community pharmacies was similar to that reported through medical practices. Locating services in areas of suspected greater diabetes prevalence and increasing the proportion of patients who follow pharmacist advice to attend their medical practice improves cost-effectiveness.

New energy, transport, computer and telecommunication technologies require an increasing supply of rare earth elements (REEs). As a consequence, adequate and robust detection methods become essential for the exploration and discovery of new deposits, the improved characterization of existing deposits and the future recycling of today’s high-tech products. Within this paper, we investigate the potential of combining passive reflectance (imaging and point sampling) with laser stimulated luminescence (point sampling) spectroscopic measurements across the visible, near and shortwave infrared for REE detection in non-invasive near-field mineral exploration. We analyse natural REE-bearing mineral samples from main REE-deposits around the world and focus on challenges such as the discrimination of overlapping spectroscopic features and the influence of the mineral type on detectability, feature position and mineral matrix luminescence. We demonstrate that the cross-validation of results from both methods increases the robustness and sensitivity, provides the potential for semi-quantification and enables the time- and cost-efficient detection of economically important REE, including Ce, Pr, Nd, Sm, Eu, Dy, Er, Yb and potentially also Ho and Tm.

We elaborate the need for a quality-controlled chemical speciation model for seawater and related natural waters, work which forms the major focus of SCOR Working Group 145. Model development is based on Pitzer equations for the seawater electrolyte and trace components. These equations can be used to calculate activities of dissolved ions and molecules and, in combination with thermodynamic equilibrium constants, chemical speciation. The major tasks to be addressed are ensuring internal consistency of the Pitzer model parameters (expressing the interactions between pairs and triplets of species, which ultimately determines the calculated activities), assessing uncertainties, and identifying important data gaps that should be addressed by new measurements. It is recognised that natural organic matter plays an important role in many aquatic ecosystems, and options for including this material in a Pitzer-based model are discussed. The process of model development begins with the core components which include the seawater electrolyte and the weak acids controlling pH. This core model can then be expanded by incorporating additional chemical components, changing the standard seawater composition and/or broadening the range of temperature and pressure, without compromising its validity. Seven important areas of application are identified: open ocean acidification; micro-nutrient biogeochemistry and geochemical tracers; micro-nutrient behaviour in laboratory studies; water quality in coastal and estuarine waters; cycling of nutrients and trace metals in pore waters; chemical equilibria in hydrothermal systems; brines and salt lakes.

Homelessness among Indigenous peoples is an important issue in Canada and internationally. Research was conducted in seven metropolitan areas in the four western provinces of Canada to explore current services with the aim of developing a best practices framework to end homelessness for Aboriginal peoples. Sequential mixed methods were used. Key results found agreement that Aboriginal peoples were overrepresented among the homeless and policy determined the approach to and comprehensiveness of services provided. Funding, lack of time, and lack of resources were highlighted as issues. Gaps identified included a lack of partnership, cross-cultural collaboration, cultural safety, and evaluation and research in service provision. Best practices included ensuring cultural safety, fostering partnerships among agencies, implementing Aboriginal governance, ensuring adequate and sustainable funding, equitable employment of Aboriginal staff, incorporating cultural reconnection, and undertaking research and evaluation to guide policy and practices related to homelessness among Aboriginal peoples.

Background: By 2011, the Health Technology Assessment (HTA) programme had published the results of over 100 trials with another 220 in progress. The aim of the project was to develop and pilot ‘metadata’ on clinical trials funded by the HTA programme. Objectives: The aim of the project was to develop and pilot questions describing clinical trials funded by the HTA programme in terms of it meeting the needs of the NHS with scientifically robust studies. The objectives were to develop relevant classification systems and definitions for use in answering relevant questions and to assess their utility. Data sources: Published monographs and internal HTA documents. Review methods: A database was developed, ‘populated’ using retrospective data and used to answer questions under six prespecified themes. Questions were screened for feasibility in terms of data availability and/or ease of extraction. Answers were assessed by the authors in terms of completeness, success of the classification system used and resources required. Each question was scored to be retained, amended or dropped. Results: One hundred and twenty-five randomised trials were included in the database from 109 monographs. Neither the International Standard Randomised Controlled Trial Number nor the term ‘randomised trial’ in the title proved a reliable way of identifying randomised trials. Only limited data were available on how the trials aimed to meet the needs of the NHS. Most trials were shown to follow their protocols but updates were often necessary as hardly any trials recruited as planned. Details were often lacking on planned statistical analyses, but we did not have access to the relevant statistical plans. Almost all the trials reported on cost-effectiveness, often in terms of both the primary outcome and quality-adjusted life-years. The cost of trials was shown to depend on the number of centres and the duration of the trial. Of the 78 questions explored, 61 were well answered, 33 fully with 28 requiring amendment were the analysis updated. The other 17 could not be answered with readily available data. Limitations: The study was limited by being confined to 125 randomised trials by one funder. Conclusions: Metadata on randomised controlled trials can be expanded to include aspects of design, performance, results and costs. The HTA programme should continue and extend the work reported here. Funding: The National Institute for Health Research HTA programme.

Background: Antibiotics are still prescribed to most patients attending primary care with acute sore throat, despite evidence that there is modest benefit overall from antibiotics. Targeting antibiotics using either clinical scoring methods or rapid antigen detection tests (RADTs) could help. However, there is debate about which groups of streptococci are important (particularly Lancefield groups C and G), and uncertainty about the variables that most clearly predict the presence of streptococci. Objective: This study aimed to compare clinical scores or RADTs with delayed antibiotic prescribing. Design: The study comprised a RADT in vitro study; two diagnostic cohorts to develop streptococcal scores (score 1; score 2); and, finally, an open pragmatic randomised controlled trial with nested qualitative and cost-effectiveness studies. Setting: The setting was UK primary care general practices. Participants: Participants were patients aged ≥ 3 years with acute sore throat. Interventions: An internet program randomised patients to targeted antibiotic use according to (1) delayed antibiotics (control group), (2) clinical score or (3) RADT used according to clinical score. Main outcome measures: The main outcome measures were self-reported antibiotic use and symptom duration and severity on seven-point Likert scales (primary outcome: mean sore throat/difficulty swallowing score in the first 2–4 days). Results: The IMI TestPack Plus Strep A (Inverness Medical, Bedford, UK) was sensitive, specific and easy to use. Lancefield group A/C/G streptococci were found in 40% of cohort 2 and 34% of cohort 1. A five-point score predicting the presence of A/C/G streptococci [FeverPAIN: Fever; Purulence; Attend rapidly (≤ 3 days); severe Inflammation; and No cough or coryza] had moderate predictive value (bootstrapped estimates of area under receiver operating characteristic curve: 0.73 cohort 1, 0.71 cohort 2) and identified a substantial number of participants at low risk of streptococcal infection. In total, 38% of cohort 1 and 36% of cohort 2 scored ≤ 1 for FeverPAIN, associated with streptococcal percentages of 13% and 18%, respectively. In an adaptive trial design, the preliminary score (score 1; n = 1129) was replaced by FeverPAIN (n = 631). For score 1, there were no significant differences between groups. For FeverPAIN, symptom severity was documented in 80% of patients, and was lower in the clinical score group than in the delayed prescribing group (–0.33; 95% confidence interval –0.64 to –0.02; p = 0.039; equivalent to one in three rating sore throat a slight rather than moderately bad problem), and a similar reduction was observed for the RADT group (–0.30; –0.61 to 0.00; p = 0.053). Moderately bad or worse symptoms resolved significantly faster (30%) in the clinical score group (hazard ratio 1.30; 1.03 to 1.63) but not the RADT group (1.11; 0.88 to 1.40). In the delayed group, 75/164 (46%) used antibiotics, and 29% fewer used antibiotics in the clinical score group (risk ratio 0.71; 0.50 to 0.95; p = 0.018) and 27% fewer in the RADT group (0.73; 0.52 to 0.98; p = 0.033). No significant differences in complications or reconsultations were found. The clinical score group dominated both other groups for both the cost/quality-adjusted life-years and cost/change in symptom severity analyses, being both less costly and more effective, and cost-effectiveness acceptability curves indicated the clinical score to be the most likely to be cost-effective from an NHS perspective. Patients were positive about RADTs. Health professionals’ concerns about test validity, the time the test took and medicalising self-limiting illness lessened after using the tests. For both RADTs and clinical scores, there were tensions with established clinical experience. Conclusions: Targeting antibiotics using a clinical score (FeverPAIN) efficiently improves symptoms and reduces antibiotic use. RADTs used in combination with FeverPAIN provide no clear advantages over FeverPAIN alone, and RADTs are unlikely to be incorporated into practice until health professionals’ concerns are met and they have experience of using them. Clinical scores also face barriers related to clinicians’ perceptions of their utility in the face of experience. This study has demonstrated the limitation of using one data set to develop a clinical score. FeverPAIN, derived from two data sets, appears to be valid and its use improves outcomes, but diagnostic studies to confirm the validity of FeverPAIN in other data sets and settings are needed. Experienced clinicians need to identify barriers to the use of clinical scoring methods. Implementation studies that address perceived barriers in the use of FeverPAIN are needed. Trial registration: Current Controlled Trials ISRCTN32027234. Source of funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 6. See the NIHR Journals Library website for further project information.

The title compound, C9H11NOS, exhibits a unique structural motif, with free rotation of the aliphatic oxathiane ring about the C—C bond connecting this moiety to the aromatic pyridine ring. The structure elucidation was undertaken due to its potential as a bidentate ligand for organometallic complexes. The oxathiane ring adopts the expected chair conformation, with the S atom in proximity to the N atom on the pyridine ring. The corresponding S—C—C—N torsion angle is 69.07 (14)°. In the crystal, molecules aggregate as centrosymmetric pairs connected by pairs of C—H...N hydrogen bonds.

Faculty in the Chemistry and Environmental Science programs at St. Mary's University in San Antonio, Texas, collaborated to develop an undergraduate course in Field-Based Environmental Chemistry. The course was developed and implemented as a 2-semester, 1-semester, and online, synchronous course offered during the 2020/21 COVID-19 pandemic. As part of the course, chemistry and environmental science majors designed and executed a sampling and laboratory analysis plan for monitoring the physical and chemical conditions of soil and/or water in a local, urban setting. As part of a goal to help students develop communication skills, they presented their work to stakeholders from the local community. Through participation in an active learning model, students demonstrated significant gains in the student learning outcomes. Students in the 2-semester sequence showed gains in their understanding of the scientific process, more comfort with the uncertainty and the ambiguity of natural environments, and appreciation fo