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Background General practice is facing an unprecedented challenge in managing the consequences of the pandemic. In the midst of a policy drive to balance remote and in-person service provision, substantial workload pressures remain, together with increasing prevalence of long-term conditions, and declining staff numbers and morale. To address these challenges, some practices in the UK have been delivering video and hybrid group consultations (VHGCs) providing clinical care to multiple patients at the same time. Despite positive initial findings and enthusiasm, there are still gaps in our understanding of the influence VHGCs have on patient experience, healthcare utilisation, quality, safety, equity and affordability. Objectives To generate an in-depth understanding of VHGCs for chronic conditions in general practice, surface assumptions and sociotechnical dynamics, inform practice and extend theorisation. Methods Mixed-methods, multi-site research study using co-design and participatory methods, from qualitative, quantitative and cost-related perspectives. WP1 includes a national, cross-sectional survey on VHGC provision across the UK. In WP2 we will engage patients and general practice staff in co-design workshops to develop VHGC models with emphasis on digital inclusion and equity. In WP3 we will carry out a mixed-methods process evaluation in up to 10 GP practices across England (5 sites already running VHGCs and 5 comparison sites). Qualitative methods will include interviews, focus groups and ethnographic observation to examine the experiences of patients, carers, clinical and non-clinical NHS staff, commissioners and policy-makers. Quantitative methods will examine the impact of VHGCs on healthcare utilisation in primary and secondary care, patient satisfaction, engagement and activation. We will also assess value for money of group and individual care models from a health economics perspective. Conclusions We aim to develop transferable learning on sociotechnical change in healthcare delivery, using VHGCs as an exemplar of technology-supported innovation. Findings will also inform the design of a future study.

BackgroundOnline appointment booking is a commonly used tool in several industries. There is limited evidence about the benefits and challenges of using online appointment booking in health care settings. Potential benefits include convenience and the ability to track appointments, although some groups of patients may find it harder to engage with online appointment booking. We sought to understand how patients in England used and experienced online appointment booking. ObjectiveThis study aims to describe and compare the characteristics of patients in relation to their use of online appointment booking in general practice and investigate patients’ views regarding online appointment booking arrangements. MethodsThis was a mixed methods study set in English general practice comprising a retrospective analysis of the General Practice Patient Survey (GPPS) and semistructured interviews with patients. Data used in the retrospective analysis comprised responses to the 2018 and 2019 GPPS analyzed using mixed-effects logistic regression. Semistructured interviews with purposively sampled patients from 11 general practices in England explored experiences of and views on online appointment booking. Framework analysis was used to allow for comparison with the findings of the retrospective analysis. ResultsThe retrospective analysis included 1,327,693 GPPS responders (2018-2019 combined). We conducted 43 interviews with patients with a variety of experiences and awareness of online appointment booking; of these 43 patients, 6 (14%) were from ethnic minority groups. In the retrospective analysis, more patients were aware that online appointment booking was available (581,224/1,288,341, 45.11%) than had experience using it (203,184/1,301,694, 15.61%). There were deprivation gradients for awareness and use and a substantial decline in both awareness and use in patients aged >75 years. For interview participants, age and life stage were factors influencing experiences and perceptions, working patients valued convenience, and older patients preferred to use the telephone. Patients with long-term conditions were more aware of (odds ratio [OR] 1.43, 95% CI 1.41-1.44) and more likely to use (OR 1.65, 95% CI 1.63-1.67) online appointment booking. Interview participants with long-term conditions described online appointment booking as useful for routine nonurgent appointments. Patients in deprived areas were clustered in practices with low awareness and use of online appointment booking among GPPS respondents (OR for use 0.65, 95% CI 0.64-0.67). Other key findings included the influence of the availability of appointments online and differences in the registration process for accessing online booking. ConclusionsWhether and how patients engage with online appointment booking is influenced by the practice with which they are registered, whether they live with long-term conditions, and their deprivation status. These factors should be considered in designing and implementing online appointment booking and have implications for patient engagement with the wider range of online services offered in general practice.

Objective The increase in reliance on online services for general practice has the potential to increase inequalities within some populations. Patients with a mental health condition are one such group. Digital facilitation is defined as a range of processes, procedures, and people, which seek to support NHS patients in using online services. This study aimed to examine the views and experiences of digital facilitation in primary care amongst patients living with a mental health condition. Methods Semi-structured interviews were conducted with patients living with a mental health condition, recruited from general practices across England participating in the Di-Facto study. Thematic analysis was conducted on interview transcripts. Results Interviews were conducted with ten participants with a mental health condition, recruited from five general practices. Three themes were identified: (1) familiarity with online services; (2) experiences of those using online services; (3) the need for digital facilitation. The need for digital facilitation was identified in the registration for online services, and in trusting online services. Conclusions Online services offer convenience for patients, but registration for the use of such services remains a potential area of difficulty. Participants had difficulties with registering for online services and had concerns about trust in using them. Support offered by general practices in using online services needs to be varied and adaptable to meet the needs of individual patients.

Summary: Background: Bacille Calmette-Guérin (BCG) vaccination has off-target (non-specific) effects that are associated with protection against unrelated infections and decreased all-cause mortality in infants. We aimed to determine whether BCG vaccination prevents febrile and respiratory infections in adults. Methods: This randomised controlled phase 3 trial was done in 36 healthcare centres in Australia, Brazil, the Netherlands, Spain, and the United Kingdom. Healthcare workers were randomised to receive BCG-Denmark (single 0.1 ml intradermal injection) or no BCG in a 1:1 ratio using a web-based procedure, stratified by stage, site, age, and presence of co-morbidity. The difference in occurrence of febrile or respiratory illness were measured over 12 months (prespecified secondary outcome) using the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020, and April 1, 2021, 6828 healthcare workers were randomised to BCG-Denmark (n = 3417) or control (n = 3411; no intervention or placebo) groups. The 12-month adjusted estimated risk of ≥1 episode of febrile or respiratory illness was 66.8% in the BCG group (95% CI 65.3%–68.2%), compared with 63.4% in the control group (95% CI 61.8%–65.0%), a difference of +3.4 percentage points (95% CI +1.3% to +5.5%; p 0.002). The adjusted estimated risk of a severe episode (defined as being incapacitated for ≥3 consecutive days or hospitalised) was 19.4% in the BCG group (95% CI 18.0%–20.7%), compared with 18.8% in the control group (95% CI 17.4%–20.2%) a difference of +0.6 percentage points (95% CI −1.3% to +2.5%; p 0.6). Both groups had a similar number of episodes of illness, pneumonia, and hospitalisation. There were three deaths, all in the control group. There were no safety concerns following BCG vaccination. Interpretation: In contrast to the beneficial off-target effects reported following neonatal BCG in infants, a small increased risk of symptomatic febrile or respiratory illness was observed in the 12 months following BCG vaccination in adults. There was no evidence of a difference in the risk of severe disease. Funding: Bill & Melinda Gates Foundation, Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, the National Health and Medical Research Council, the Swiss National Science Foundation and individual donors.

Abstract Background The National Health Service (NHS) and general practice are increasingly adopting digital services. These services can impact both positively and negatively upon patient experiences, and access to digital services is not equal amongst all groups. Within a wider project examining digital facilitation (the Di-Facto study) our team conducted a patient survey amongst English primary care practices aiming to investigate patient views of what supports uptake and use of web-based services. This paper reports on the analysis of the free-text responses from the patient survey. Methods The Di-Facto patient survey was distributed to practices in eight clinical commissioning groups (CCGs) in England between 2021–2022. We examined free-text responses to two questions relating to access to primary care web-based and support for web-based services. We used qualitative reflexive thematic analysis based on a six-stage process to analyse responses. Results Of the 3051 patients who responded to the Di-Facto survey, 2246 provided a free-text response. We present our findings in two major themes: systems and structures and their impact on use of web-based services, and ‘what works for me’, a description of how respondents described what worked, or did not work in terms of their interactions with web-based services. Respondents described how the technology, such as poor practice website design, confusion over multiple digital apps, data security and concerns about eConsultation offerings impacted on use of web-based services. Respondents described practice level barriers, such as a lack of or inconsistent provision, which prevented optimal use of web-based services. Respondents described personal and technical barriers that impacted on their use of digital services, and described which web-based services worked well for them. Respondents felt that web-based services were not a replacement for face-to-face interactions with a doctor. Conclusions This analysis of free-text responses from a large patient survey highlights the system, practice, and person level barriers and facilitators to use of digital services in primary care. With an increasing push towards digital solutions in NHS primary care, practices should consider the design, rollout and communication of their web-based services to support patient access.

Disease prevention is a cornerstone of herd management for minimizing preweaning calf mortality. However, scientific evidence about the usefulness of practices in herds is scarce. The first objective was for a group of veterinarians to determine which practices are most useful considering their effectiveness, ease of implementation, and economic feasibility. A second objective was for them to define which practices should be included in a tool to facilitate discussions between producers and veterinarians. Expert opinions and consensus were determined using a modified Delphi approach. During two questionnaire rounds, participants scored the effectiveness, ease of implementation, and economic feasibility of each practice. Overall scores for each practice were calculated, and feedback reports were sent to participants between rounds showing the groups’ median responses. Consensus on which practices should be included in the tool was targeted during the workshops. Twelve veterinary experts participated. Administering clostridial vaccines and providing calves with colostrum in case they had not nursed were considered practices that were ‘always useful for all herds’. However, most practices had intermediate levels of usefulness, and among these, antibiotics were considered the least useful. Nevertheless, all practices discussed during the workshops attained a consensus about being included in the future tool to facilitate on-farm discussions.

Summary: Background: The COVID-19 pandemic led to the rapid development and deployment of several highly effective vaccines against SARS-CoV-2. Recent studies suggest that these vaccines may also have off-target effects on the immune system. We sought to determine and compare the off-target effects of the adenovirus vector ChAdOx1-S (Oxford-AstraZeneca) and modified mRNA BNT162b2 (Pfizer-BioNTech) vaccines on immune responses to unrelated pathogens. Methods: Prospective sub-study within the BRACE trial. Blood samples were collected from 284 healthcare workers before and 28 days after ChAdOx1-S or BNT162b2 vaccination. SARS-CoV-2-specific antibodies were measured using ELISA, and whole blood cytokine responses to specific (SARS-CoV-2) and unrelated pathogen stimulation were measured by multiplex bead array. Findings: Both vaccines induced robust SARS-CoV-2 specific antibody and cytokine responses. ChAdOx1-S vaccination increased cytokine responses to heat-killed (HK) Candida albicans and HK Staphylococcus aureus and decreased cytokine responses to HK Escherichia coli and BCG. BNT162b2 vaccination decreased cytokine response to HK E. coli and had variable effects on cytokine responses to BCG and resiquimod (R848). After the second vaccine dose, BNT162b2 recipients had greater specific and off-target cytokine responses than ChAdOx1-S recipients. Interpretation: ChAdOx1-S and BNT162b2 vaccines alter cytokine responses to unrelated pathogens, indicative of potential off-target effects. The specific and off-target effects of these vaccines differ in their magnitude and breadth. The clinical relevance of these findings is uncertain and needs further study. Funding: Bill & Melinda Gates Foundation, National Health and Medical Research Council, Swiss National Science Foundation and the Melbourne Children’s. BRACE trial funding is detailed in acknowledgements.

Background: Recent policy initiatives seeking to address the workforce crisis in general practice have promoted greater multidisciplinarity. Evidence is lacking on how changes in staffing and the relational climate in practice teams affect the experiences of staff and patients. Aim: To synthesise evidence on how the composition of the practice workforce and team climate affect staff job satisfaction and burnout, and the processes and quality of care for patients. Design & setting: A systematic literature review of international evidence. Method: Four different searches were carried out using MEDLINE, Embase, Cochrane Library, CINAHL, PsycINFO, and Web of Science. Evidence from English language articles from 2012–2022 was identified, with no restriction on study design. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed and data were synthesised thematically. Results: In total, 11 studies in primary healthcare settings were included, 10 from US integrated healthcare systems, one from Canada. Findings indicated that when teams are understaffed and work environments are stressful, patient care and staff wellbeing suffer. However, a good relational climate can buffer against burnout and protect patient care quality in situations of high workload. Good team dynamics and stable team membership are important for patient care coordination and job satisfaction. Female physicians are at greater risk of burnout. Conclusion: Evidence regarding team composition and team climate in relation to staff and patient outcomes in general practice remains limited. Challenges exist when drawing conclusions across different team compositions and definitions of team climate. Further research is needed to explore the conditions that generate a ‘good’ climate.

Cow-calf surveillance data provide critical information about changing herd demographics, productivity, health, and management as well as the opportunity to investigate the impact of differing management practices. A national cow-calf network was established to collect baseline information on herd health, production performance measures, and management. Questionnaires were used to collect information on herd attributes as well as data for the calving season, breeding, pregnancy testing, and weaning for herds from across Canada. From 2018 to 2022, a total of 565 calving record questionnaires, representing 110,658 calving female records from 171 herds were returned, along with 543 herd breeding to weaning questionnaires. Suggested benchmark values based on the 25th percentiles from Western and Eastern Canada were determined to be

Abstract Background Anabolic–androgenic steroids (AAS) mimic the effects of testosterone and may include testosterone itself; they are used for body enhancement within the general population. AAS use has been linked with increased mortality, cardiovascular disease, mental health disorders, and infertility. AAS-induced hypogonadism can persist for an uncertain time period despite cessation, during which men may report physical and neuropsychiatric symptoms. In an attempt to mitigate these symptoms and expedite testicular recovery, many men self-administer post-cycle-therapy (PCT), typically involving human chorionic gonadotrophin (hCG) and selective oestrogen receptor modulators (SERMs), which are known to potently stimulate testicular function. However, this practice has no objective evidence of effectiveness to lessen the severity or duration of hypogonadal symptoms. Methods An anonymous survey of four-hundred-and-seventy men using AAS explored the symptoms they experienced when ceasing AAS use; the effect of PCT on relieving their symptoms, and their perceived role for health service support. Results The majority of respondents were white, aged 18–30 years old, and working in skilled manual work. 51.7% (n = 243) reported no issues with AAS use, but 35.3% reported increased aggression. 65.1% (n = 306) of respondents had attempted AAS cessation and 95.1% of these experienced at least one symptom upon AAS cessation. Low mood, tiredness and reduced libido were reported in 72.9%, 58.5% and 57.0% of men stopping AAS use, respectively, with only 4.9% reporting no symptoms. PCT had been used by 56.5% of respondents with AAS cessation and mitigated cravings to restart AAS use, withdrawal symptoms and suicidal thoughts by 60%, 60% and 50%, respectively. The effect of stopping AAS on body composition and recovery of testosterone or fertility was a concern in 60.5% and 52.4%, respectively. Most respondents felt PCT should be prescribed under medical supervision in the community. Conclusions Our survey suggests that the majority of men stopping AAS use are using some form of PCT. Some self-reported symptoms of AAS-induced hypogonadism such as cravings to restart AAS use reduce by 60% and suicidal thoughts reduce by 50%. These individuals are concerned about the negative effect of AAS use and cessation. This study provides crucial information for planning future research to evaluate the effects of PCT on symptoms when men stop AAS use.

Abstract Measurements of W-boson production at the LHC have reached percent-level precision and impose challenging demands on theoretical predictions. Such predictions directly limit the precision of measurements of fundamental quantities such as the W-boson mass and the weak mixing angle. A dominant source of uncertainty in predictions is from higher-order QCD effects. We present a calculation of W-boson production at the level of α s 3 $$ {\alpha}_s^3 $$ at fixed order and including transverse-momentum resummation. We further show predictions for a direct comparison with low-pileup ATLAS transverse-momentum and fiducial cross-section measurements at s $$ \sqrt{s} $$ = 5.02 TeV. We discuss in detail the impact of modern PDFs. Our calculation including the matching to W+jet production at NNLO will be publicly available the upcoming CuTe-MCFM release and allows for theory-data comparison at the state-of-the-art level.

Abstract Background The NHS Talking Therapies for Anxiety and Depression programme (‘TTad’; formerly Improving Access to Psychological Therapies ‘IAPT’) delivers high-intensity cognitive behavioural therapy (CBT) to over 200,000 individuals each year for common mental health problems like depression and anxiety. More than half of these individuals experience comorbid personality difficulties, who show poorer treatment outcomes. TTad therapists report feeling unskilled to work with clients with personality difficulties, and enhancing the training of TTad therapists may lead to improved treatment outcomes for individuals presenting with secondary personality difficulties alongside depression and anxiety. Methods This is a pre-post non-randomised mixed-method feasibility study, exploring the feasibility and acceptability of a 1-day training workshop for high-intensity (HI) CBT therapists. The workshop is focused on understanding and assessing personality difficulties and adapting HICBT treatments for anxiety and depression to accommodate client needs. The feasibility and acceptability of the workshop and the evaluation procedures will be investigated. It will be examined to what extent the workshop provision leads to improvements in therapist skills and confidence and explored to what extent the training has the potential to enhance clinical outcomes for this client group. Discussion This feasibility study will provide data on the acceptability and feasibility of delivering brief therapist training to adapt usual HICBT to optimise care for individuals with secondary personality difficulties seeking treatment in TTad services for a primary problem of depression and/or anxiety. The study will also evaluate proof of concept that such an approach has the potential to improve clinical outcomes for those with secondary personality difficulties and report any possible harms identified. The study will inform the design of a future randomised controlled trial designed to test the effectiveness and cost-effectiveness of the training. Trial registration ISRCTN81104604 . Submitted on 6th June 2022. Registration date: 3rd January 2023.

ObjectivesThe objectives of this study were to (i) evaluate the prevalence of pre-iridal monocellular and fibrovascular membranes in canine globes affected with congenital glaucoma associated with anterior segment dysgenesis (ASD), primary glaucoma associated with goniodysgenesis (GD), and secondary glaucoma, and (ii) examine the associations between monocellular and fibrovascular membranes by breed, gender, age and histopathologic ocular changes on light microscopic examination.MethodsRecords of dogs who had eyes enucleated due to blindness and uncontrolled glaucoma were reviewed. Glaucoma was categorized clinically and histologically into three groups: congenital/ASD, primary/GD, and secondary glaucoma. The presence or absence and type of pre-iridal membrane (monocellular or fibrovascular) and other intraocular histologic findings were reviewed and compared statistically for each group.ResultsIn total, 108 canine globes (101 dogs) were included. Pre-iridal monocellular membranes were identified with light microscopy in 10 out of 19 congenital/ASD, 29 out of 40 primary, and 23 out of 49 secondary glaucoma globes. Fibrovascular membranes were observed in 3 out of 19 congenital/ASD, 9 out of 40 in primary, and 24 out of 49 secondary glaucoma globes. There were no associations between the type of membrane and breed, gender, or age. Peripheral anterior synechiae were more common in globes with fibrovascular membranes, and uveal atrophy was more common in globes with monocellular membranes.ConclusionPre-iridal monocellular membranes are common in all types of canine glaucoma. They are identified with light microscopy most easily in cases of primary glaucoma, and they are masked by pre-iridal fibrovascular membranes in other forms of glaucoma.

Acute esophageal necrosis (AEN) or black esophagus is a rare cause of mortality in patients with gastrointestinal bleeding. We present a case of a 54-year-old female who presented with diabetic ketoacidosis (DKA) and developed melena eventually attributed to AEN. The esophagogastroduodenoscopy (EGD) identified severe inflammation with black discoloration consistent with acute esophageal necrosis in the middle and lower esophagus. The patient was managed with intravenous pantoprazole and total parenteral nutrition (TPN) until she was able to tolerate an adequate diet. Black esophagus should be added to the differential diagnosis of patients with DKA who develop gastrointestinal bleeding. This need is stressed by the fact that early treatment is essential to reducing complications and mortality associated with the condition.

Summary: Background: Recurrences of herpes simplex virus (HSV) in the orofacial region (herpes labialis or cold sores) impact quality-of-life. We aimed to study whether the bacille Calmette-Guérin (BCG) vaccine can attenuate cold sore recurrences through off-target immunomodulatory effects. Methods: In this nested randomised controlled trial within the multicentre, phase 3 BRACE trial, 6828 healthcare workers were randomised in 36 sites in Australia, the Netherlands, Spain, the United Kingdom and Brazil, to receive BCG-Denmark or no BCG (1:1 ratio using a web-based procedure) and followed for 12 months with 3-monthly questionnaires. Exclusion criteria included contraindication to BCG vaccine or previous vaccination with BCG within the past year, any other live-attenuated vaccine within the last month, or any COVID-specific vaccine. The intervention group received one intradermal dose of 0.1 mL of BCG-Denmark corresponding to 2−8 x 105 colony forming units of Mycobacterium bovis, Danish strain 1331. The primary outcome was the difference in restricted mean survival time (i.e., time to first cold-sore recurrence), in participants with frequent recurrent herpes labialis (≥4 recurrences/year), analysed by intention-to-treat. Secondary outcomes addressed additional questions, including analyses in other sub-populations. Adverse events were monitored closely during the first 3 months and were reported in all participants who received one dose of study drug according to intervention received. The BRACE trial is registered with ClinicalTrials.gov, NCT04327206. Findings: Between March 30, 2020 and February 18, 2021, 84 individuals with frequent recurrent cold sores were randomly assigned to BCG (n = 38) or control (n = 46). The average time to first cold-sore recurrence was 1.55 months longer in the BCG group (95% CI 0.27–2.82, p = 0.02) than the control group (hazard ratio 0.54, 95% CI 0.32–0.91; intention-to-treat). The beneficial effect of BCG was greater in the as-treated population (difference 1.91 months, 95% CI 0.69–3.12, p = 0.003; hazard ratio 0.45, 95% CI 0.26–0.76). In prespecified subgroup analyses, only sex modified the treatment effect (interaction p = 0.007), with benefit restricted to males. Over 12 months, a greater proportion of participants in the BCG group compared with the control group reported a decrease in duration (61% vs 21%), severity (74% vs 21%), frequency (55% vs 21%), and impact on quality of life (42% vs 15%) of cold sore recurrences. In participants who had ever had a cold sore, there was also a decrease in self-reported burden of recurrences in the BCG group. In participants who had never had a cold sore, there was an increased risk of a first episode in the BCG group (risk difference 1.4%; 95% CI 0.3–2.6%, p = 0.02). There were no safety concerns. Interpretation: BCG-Denmark vaccination had a beneficial effect on herpes labialis, particularly in males with frequent recurrences, but may increase the risk of a first cold sore. Funding: Bill & Melinda Gates Foundation, the Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, and individual donors.

Background: A large number of epidemiologic studies across the world indicate a growing link between obesity and diabetes. The metropolitan city of Chennai in South India is experiencing an alarming increase in diabetes and obesity. Aim: The aim of this study was to determine the prevalence of and risk factors for diabetes and obesity together termed as “diabesity” among adults in urban Chennai. Materials and Methods: This was a community-based cross-sectional door-to-door study done as part of a large National Institute of Health and Care Research (NIHR)––a funded project aimed to understand patterns and determinants of health in South Asia. Of the 200 wards in Chennai, 34 wards were surveyed in the main project and two wards were selected randomly for this substudy. Five community enumeration blocks were selected using a systematic sampling technique. Participants aged ≥18 years were selected using a consecutive sampling method. Results: Of the 1138 participants studied, the prevalence of diabesity was found to be 34.3%(n = 390). Of the study participants, 74.8% had obesity (61.9%––generalized obesity; 68.5%––abdominal obesity) and 43.0% had diabetes. As age increased, the diabesity risk also increased gradually from 30 to 39 years (odds ratio [OR]: 3.6[95%, confidence interval [CI]: 1.4–8.9]) to 50–59 years (OR: 5.4[95%, CI: 2.2–13.2]), whereas there was a slight decrease in risk after 60 years (OR: 5.1[95%, CI: 2.1–12.3]). Females had nearly twice the risk of diabesity compared to men (OR: 1.8, P < 0.001), and physically inactive individuals had 1.7 times increased risk (P < 0.001). Conclusion: We report in this study that the prevalence of the dual metabolic defect (diabesity) is alarmingly high in urban Chennai. This study was an attempt to understand the epidemiology of diabesity.

Abstract Purpose Endoscopic transsphenoidal surgery (ETSS) is an increasingly utilized approach for resection of pituitary tumors. Prior studies have evaluated preoperative tumor size, location, and extent as prognostic factors for surgical resection. There is little data on the relationship between preoperative pituitary tumor radiographic morphology and surgical outcomes. Study Design Retrospective longitudinal study. Setting Single tertiary care institution. Subjects and Methods Preoperative magnetic resonance imaging and computed tomography scans from patients undergoing ETSS for pituitary tumor resections from 2007 to 2017 were retrospectively evaluated. A neuroradiologist classified these pituitary tumors into six morphologic groups, each defined by volume, dimensions, extension, and shape. Surgical difficulty, rates of incomplete resection, and postoperative complications were then stratified in relation to the morphologic groups. Results Pituitary tumors from 131 patients were classified from preoperative imaging into six characteristic morphologies: (1) microtumor, (2) round, (3) transverse oblong, (4) superior‐inferior oblong, (5) bilobed, and (6) large lobulated. Tumors that were characterized with the large lobulated, bilobed, and transverse oblong morphologies correlated with higher rates of postoperative evidence of residual tumor (70%, 36%, and 47%, respectively, all P

Measurement(s) Transcriptomics • Hemagglutination Inhibition Assay • IgG IgM IgA Total Measurement • Virus-neutralizing Antibody • ELISA Technology Type(s) Microarray • RNA sequencing • Hemagglutination Inhibition Assay • ELISA • Microneutralization Assay • serum neutralization of viral infectivity assay Sample Characteristic - Organism Homo sapiens

Abstract Background The e-coachER trial aimed to determine whether adding web-based behavioural support to exercise referral schemes (ERS) increased long-term device-measured physical activity (PA) for patients with chronic conditions, compared to ERS alone, within a randomised controlled trial. This study explores the mechanisms of action of the e-coachER intervention using measures of the behaviour change processes integral to the intervention’s logic model. Methods Four hundred fifty adults with obesity, diabetes, hypertension, osteoarthritis or history of depression referred to an ERS were recruited in Plymouth, Birmingham and Glasgow. The e-coachER intervention comprising 7-Steps to Health was aligned with Self-Determination Theory and mapped against evidence-based behaviour change techniques (BCTs). Participants completed questionnaires at 0, 4, and 12 months to assess PA and self-reported offline engagement with core BCTs in day-to-day life (including action planning and self-monitoring) and beliefs relating to PA (including perceived importance, confidence, competence, autonomy and support). We compared groups at 4 and 12 months, controlling for baseline measures and other covariates. Mediation analysis using the product of coefficients method was used to determine if changes in process variables mediated intervention effects on moderate to vigorous physical activity (MVPA) recorded by accelerometer and self-report at 4- and 12-months. Results The internal reliability (Cronbach’s alpha) for all multi-item scales was > 0.77. At 4-months, those randomised to e-coachER reported higher levels of PA beliefs relating to importance (1.01, 95% confidence interval (CI): 0.42 to 1.61, p = 0.001), confidence (1.28, 95% CI: 0.57 to 1.98, p

INTRODUCTION Peer learning and near-peer teaching have been described in many specialties, less so in Radiology. We present near-peer teaching whereby residents present a series of didactic sessions at the course outset in the form of “symposia” and perform a scholarly activity in the form of teaching. We aim to demonstrate how near-peer teaching in symposia front-loaded within an introductory radiology course can improve medical student satisfaction. METHOD A total of 169 students were enrolled over a period of 3 years, 55 before (2017-2018) and 114 (2018-2020) after the introduction of the symposium. Anonymous course evaluations were collected from all students. In addition, 240 fourth-year medical students who also attended symposium lectures received satisfaction surveys in 2019 and 2020. RESULTS All (169/169, 100%) students taking the course evaluated it. Overall evaluation scores rose from 8.3/10 to 9.0/10 post-symposia. Among student satisfaction surveys, 89/240 (37%) specifically commented on symposia; 91% (80/89) of those found symposia very or extremely informative. 29/71 (41%) of all residents were able to participate in the symposia, 20/29 in multiple years throughout residency, allowing them to fulfill the Accreditation Council for Graduate Medical Education interpersonal and communication skills core competencies and meet scholarly activity requirements. CONCLUSION Near-peer teaching in the form of resident-taught interactive didactics grouped in symposia can have a positive outcome on medical student satisfaction.

In the secondary metals refining processes, vacuum arc remelting (VAR) and electroslag remelting (ESR), the consumable electrode is commonly produced by vacuum induction melting (VIM) which employs the regrettably primitive casting technique of simply pouring into the open top of the mold. Despite the vacuum, the resulting oxidizing conditions and the immensely powerful turbulence accompanying the top-pouring of the electrode is now known to create a substantial density of serious cracks. The cracks in the cast electrode are bifilms (double oxide films), which in turn are proposed to be responsible for the major faults of the VAR ingot, including undetectable, horizontal macroscopic cracks, white spots (clean and dirty varieties) and in-fallen crown. The remedial action to solve all these issues at a stroke is the provision of a counter-gravity cast electrode, cast in air or vacuum, or provision of any similar electrode substantially free from bifilm defects. The ESR process is also described, explaining the reasons for its significantly reduced sensitivity to the top-poured VIM electrode, but indicating that with an improved electrode, this already nearly reliable process has the potential for perfect reliability. The target of this critical overview is an assessment of the potential of these secondary refining processes to produce, for the first time, effectively defect-free metals, metals we can trust.

In 2010, Kh. Hessami Pilehrood and T. Hessami Pilehrood introduced generating function identities used to obtain series accelerations for values of Dirichlet's $\beta$ function, via the Markov--Wilf--Zeilberger method. Inspired by these past results, together with related results introduced by Chu et al., we introduce a variety of hypergeometric recurrences. We prove these recurrences using the WZ method, and we apply these recurrences to obtain series acceleration identities. We introduce a family of summations generalizing a Ramanujan-type series for $\frac{1}{\pi^2}$ due to Guillera, and a family of summations generalizing an accelerated series for Catalan's constant due to Lupa\c{s}, and many related results.

Introduction: Rural General Practice (GP) surgeries often struggle to employ and retain multidisciplinary team members. Existing research into rural recruitment and retention issues is limited, and usually focussed on doctors. Rural practices often rely on income from dispensing medications; little is known about how maintaining dispensing services contributes to the recruitment and retention of staff. This study aimed to understand the barriers and facilitators to working and remaining in rural dispensing practices, and to explore how the primary care team value dispensing services.Methods: We undertook semi-structured interviews with multidisciplinary team members of rural dispensing practices across England. Interviews were audio-recorded, transcribed and anonymised. Framework analysis was conducted using Nvivo 12.Results: Seventeen staff members (including GPs, practice nurses, practice managers, dispensers and administrative staff) from 12 rural dispensing practices across England were interviewed. Personal and professional reasons for taking up a role in a rural dispensing practice included perceived career autonomy and development opportunities, and preference for working and living in a rural setting. Key factors impacting retention of staff included revenue generated by dispensing, opportunities for staff development, job satisfaction and the positive work environment. Perceived challenges to retention were the balancing of the required skillset of dispensing with the wages available for the role, lack of skilled job applicants, travel difficulties and negative perceptions of rural primary care practice.Discussion: These findings will inform national policy and practice with the aim of providing further understanding of the drivers and challenges of working in rural dispensing primary care in England.

Johne's disease is an insidious infectious disease of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). Johne's disease can have important implications for animal welfare and risks causing economic losses in affected herds due to reduced productivity, premature culling and replacement, and veterinary costs. Despite the limited accuracy of diagnostic tools, testing and culling is the primary option for controlling Johne's disease in beef herds. However, evidence to inform specific test and cull strategies is lacking. In this study, a stochastic, continuous-time agent-based model was developed to investigate Johne's disease and potential control options in a typical western Canadian cow-calf herd. The objective of this study was to compare different testing and culling scenarios that included varying the testing method and frequency as well as the number and risk profile of animals targeted for testing using the model. The relative effectiveness of each testing scenario was determined by the simulated prevalence of cattle shedding MAP after a 10-year testing period. A second objective was to compare the direct testing costs of each scenario to identify least-cost options that are the most effective at reducing within-herd disease prevalence. Whole herd testing with individual PCR at frequencies of 6 or 12 months were the most effective options for reducing disease prevalence. Scenarios that were also effective at reducing prevalence but with the lowest total testing costs included testing the whole herd with individual PCR every 24 months and testing the whole herd with pooled PCR every 12 months. The most effective method with the lowest annual testing cost per unit of prevalence reduction was individual PCR on the whole herd every 24 months. Individual PCR testing only cows that had not already been tested 4 times also ranked well when considering both final estimated prevalence at 10 years and cost per unit of gain. A more in-depth economic analysis is needed to compare the cost of testing to the cost of disease, taking into account costs of culling, replacements and impacts on calf crops, and to determine if testing is an economically attractive option for commercial cow-calf operations.

BackgroundThe use of web-based services within primary care (PC) in the National Health Service in England is increasing, with medically underserved populations being less likely to engage with web-based services than other patient groups. Digital facilitation—referring to a range of processes, procedures, and personnel that seek to support patients in the uptake and use of web-based services—may be a way of addressing these challenges. However, the models and impact of digital facilitation currently in use are unclear. ObjectiveThis study aimed to identify, characterize, and differentiate between different approaches to digital facilitation in PC; establish what is known about the effectiveness of different approaches; and understand the enablers of digital facilitation. MethodsAdopting scoping review methodology, we searched academic databases (PubMed, EMBASE, CINAHL, Web of Science, and Cochrane Library) and gray literature published between 2015 and 2020. We conducted snowball searches of reference lists of included articles and articles identified during screening as relevant to digital facilitation, but which did not meet the inclusion criteria because of article type restrictions. Titles and abstracts were independently screened by 2 reviewers. Data from eligible studies were analyzed using a narrative synthesis approach. ResultsA total of 85 publications were included. Most (71/85, 84%) were concerned with digital facilitation approaches targeted at patients (promotion of services, training patients to improve their technical skills, or other guidance and support). Further identified approaches targeted PC staff to help patients (eg, improving staff knowledge of web-based services and enhancing their technical or communication skills). Qualitative evidence suggests that some digital facilitation may be effective in promoting the uptake and use of web-based services by patients (eg, recommendation of web-based services by practice staff and coaching). We found little evidence that providing patients with initial assistance in registering for or accessing web-based services leads to increased long-term use. Few studies have addressed the effects of digital facilitation on health care inequalities. Those that addressed this suggested that providing technical training for patients could be effective, at least in part, in reducing inequalities, although not entirely. Factors affecting the success of digital facilitation include perceptions of the usefulness of the web-based service, trust in the service, patients’ trust in providers, the capacity of PC staff, guidelines or regulations supporting facilitation efforts, and staff buy-in and motivation. ConclusionsDigital facilitation has the potential to increase the uptake and use of web-based services by PC patients. Understanding the approaches that are most effective and cost-effective, for whom, and under what circumstances requires further research, including rigorous evaluations of longer-term impacts. As efforts continue to increase the use of web-based services in PC in England and elsewhere, we offer an early typology to inform conceptual development and evaluations. Trial RegistrationPROSPERO International Prospective Register of Systematic Reviews CRD42020189019; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=189019

While Johne's disease (JD) is less common in beef than in dairy herds, consolidation is increasing transmission risk. Estimates of Mycobacterium avium spp. paratuberculosis (MAP) prevalence and test performance in cow-calf herds are needed to inform control programs. Objectives of this study included describing the prevalence of MAP in Canadian cow-calf herds and comparing the relative performance of a serum ELISA, pooled fecal PCR and individual fecal PCR using Bayesian latent class models, and to investigate factors associated with positive MAP tests. Blood and fecal samples (n = 3,171) were collected from 159 Canadian cow-calf herds. All samples were analyzed using serum ELISA and fecal PCR (pools of five samples) and a subset of 913 fecal samples were also tested with individual PCR. Based on latent class analysis, MAP prevalence was higher in eastern compared to western Canada for both animals {East, 3% [95% Credible Interval (CrI) 1–7%]; West, 1% [95% CrI 0.2–2%]} and herds [East, 15% (95% CrI 2–35%); West, 10% (95% CrI 1–26%), based on one or more positive results]. Sensitivity (Se) and specificity (Sp) for animal level individual PCR were 96% (95% CrI 80–100%) and 98% (95% CrI 96–100%), respectively followed by pooled PCR [Se = 54% (95% CrI 36–72%), Sp > 99.9% (95% CrI 99.8–100%)] and ELISA [Se = 36% (95% CrI 22–52%), Sp = 98% (95% CrI 96–99%)]. Based on 20 samples per herd, the herd level Se of ELISA was 79% (95% CrI 47–100%) (at least one positive sample) compared to 43% (95% CrI 14–94%) for pooled PCR. Herd-level Sp was 99% (95% CrI 96–100%) for pooled PCR and 90% (95% CrI 83–100%) for ELISA. Cows from herds with dairy cattle on farm and cows with symptoms of JD in the past 3 years were more likely to be MAP positive. Herds that had animals with JD symptoms in the previous 3 years and those with more breeding females were most likely to test positive for MAP. While serum ELISA can be effective for herd screening, PCR performed better for animal testing. Pooled PCR testing could be a less costly option; however, determining the most cost-effective approach will require further economic analysis.

Abstract We present a calculation of t-channel single-top-quark production and decay in the five-flavor scheme at NNLO. Our results resolve a disagreement between two previous calculations of this process that found a difference in the inclusive cross section at the level of the NNLO coefficient itself. We compare in detail with the previous calculations at the inclusive, differential and fiducial level including b-quark tagging at a fixed scale μ = m t . In addition, we advocate the use of double deep inelastic scattering (DDIS) scales (μ 2 = Q 2 for the light-quark line and μ 2 = Q 2 + m t 2 $$ {m}_t^2 $$ for the heavy-quark line) that maximize perturbative stability and allow for robust scale uncertainties. All NNLO and NLO⊗NLO contributions for production and decay are included in the on-shell and vertex-function approximation. We present fiducial and differential results for a variety of observables used in Standard Model and Beyond Standard Model analyses, and find an important difference between the NLO and NNLO predictions of exclusive t + n-jet cross sections. Overall we find that NNLO corrections are crucial for a precise identification of the t-channel process.

Technology is disrupting the practice of law and revolutionizing how lawyers work. This revolution is made more powerful because it is increasingly coupled with a rigorous and scientific approach to the law. In some ways, law is looking more like a Silicon Valley startup and less like the oak-paneled law firms of the last 200 years. As law, technology, and science merge, the implications for the profession are wide-sweeping. This article explores persuasive legal writing, offering new thoughts on what the future will hold. Specifically, this article pilots a method for applying technology and science to measure, analyze and improve persuasive legal writing, offering it as a proof of concept that anchors the article’s broader, and perhaps more controversial assertion. Namely, more powerful and refined persuasive legal writing software tools, fueled by artificial intelligence, should and will disrupt and reshape significant portions of the legal space, including how legal writing is taught and how it is produced. The effect will be to view legal writing as more science, and less art. The next set of luminaries won’t rely on anecdote or intuition to teach or create legal writing; they will rely on software and data.

Objectives: We aimed to evaluate the quality of currently available health apps for prevention of type 2 diabetes among Asian Indians using validated rating scales. Materials and Methods: Using the keywords, “diabetes prevention,” “healthy lifestyle,” and “fitness,” a total of 1486 apps available in India via Google Play were assessed for eligibility by two independent reviewers. After initial screening using specific inclusion and exclusion criteria, 50 apps underwent a pre-specified rating based on user reviews, number of downloads, and app size. Sixteen apps that scored ≥ 9 were shortlisted for further review using the Mobile App Rating Scale (MARS). The mean MARS scores (for categories I and II) were used to identify the top ranked apps. Results: The mean score for Category I of MARS rating was highest for “Google Fit: Health and Activity Tracking” (4.55/5). This was followed by “Healthifyme—Diet Plan, Health, and Weight Loss” (4.45/5). For Category II of MARS, “Diabetes M,” “Google Fit: Health and Activity Tracking,” “Calorie Counter—My Fitness Pal,” and “Healthifyme—Diet Plan, Health, and Weight Loss” all scored equally well. On comparing the advantages and disadvantages of each of these applications, “Google Fit: Health and Activity Tracking” and “Healthifyme—Diet Plan, Health, and Weight Loss” again ranked the best. Conclusion: Our review identifies two commercially available apps “Google Fit: Health and Activity Tracking” and “Healthifyme—Diet Plan, Health, and Weight Loss” as being user friendly and good quality. Although encouraging, further research is needed to evaluate the efficacy of these apps for the prevention of diabetes.

Introduction: Point of care testing (POCT) for total cholesterol (TC) is invaluable in non-communicable disease (NCD) surveillance programs, as it may permit rapid risk stratification for efficient channeling of limited finances in resource constrained settings. Nevertheless, one needs to be aware of some caveats to the dependability of POCT results for TC in high load situations. Aims & Objectives: To evaluate the analytical performance of POCT for TC in a population-based NCD surveillance study, by comparing its results with a laboratory assay, and to identify sources of error. Place and duration of study: Mangamandi, Lahore (sampling); Services Institute of Medical Sciences, Lahore (laboratory), from December 2019 to March 2020. Material & Methods: POCT for TC was done as part of CVD risk stratification in a large NCD surveillance project. Lower than expected readings of TC on POCT were flagged during routine data quality checking, and this prospective study was designed to determine accuracy of POCT readings by testing the same sample in a laboratory. Mean ±SD of two methods were compared in overall sample and in subgroups. Linear regression analysis was done to determine correlation between the two methods. After a significant disparity was confirmed, POCT process was scrutinized to identify its cause, and re -testing after its correction confirmed the source of interference. Results: Mean TC level in overall sample (n= 699) by POCT was significantly lower than that of laboratory method: 2.80 (±0.30 SD) mmol/l vs. 5.28 (±1.27 SD) mmol/l (p

Abstract Background The number of older people with multiple health problems is increasing worldwide. This creates a strain on clinicians and the health service when delivering clinical care to this patient group, who themselves carry a large treatment burden. Despite shared decision-making being acknowledged by healthcare organisations as a priority feature of clinical care, older patients with multimorbidity are less often involved in decision-making when compared with younger patients, with some evidence suggesting associated health inequalities. Interventions aimed at facilitating shared decision-making between doctors and patients are outdated in their assessments of today’s older patient population who need support in prioritising complex care needs in order to maximise quality of life and day-to-day function. Aims To undertake feasibility testing of an intervention (‘VOLITION’) aimed at facilitating the involvement of older patients with more than one long-term health problem in shared decision-making about their healthcare during GP consultations. To inform the design of a fully powered trial to assess intervention effectiveness. Methods This study is a cluster randomised controlled feasibility trial with qualitative process evaluation interviews. Participants are patients, aged 65 years and above with more than one long-term health problem (multimorbidity), and the GPs that they consult with. This study aims to recruit 6 GP practices, 18 GPs and 180 patients. The intervention comprises two components: (i) a half-day training workshop for GPs in shared decision-making; and (ii) a leaflet for patients that facilitate their engagement with shared decision-making. Intervention implementation will take 2 weeks (to complete delivery of both patient and GP components), and follow-up duration will be 12 weeks (from index consultation and commencement of data collection to final case note review and process evaluation interview). The trial will run from 01/01/20 to 31/01/21; 1 year 31 days. Discussion Shared decision-making for older people with multimorbidity in general practice is under-researched. Emerging clinical guidelines advise a patient-centred approach, to reduce treatment burden and focus on quality of life alongside disease control. The systematic development, testing and evaluation of an intervention is warranted and timely. This study will test the feasibility of implementing a new intervention in UK general practice for future evaluation as a part of routine care. Trial registration CLINICAL TRIALS.GOV registration number NCT03786315 , registered 24/12/18

Abstract Without proper control of numerical and methodological errors in theoretical predictions at the per mille level it is not possible to study the effect of input parameters in current hadron-collider measurements at the required precision. We present the new version of the parton-level code MCFM-9.0 that achieves this requirement through its highly-parallelized nature, significant performance improvements and new features. An automatic differential jettiness slicing cutoff extrapolation is introduced to assess the cutoff dependence of all results, thus ensuring their reliability and potentially improving fixed- cutoff results by an order of magnitude. The efficient differential study of PDF uncertainties and PDF set differences at NNLO, for multiple PDF sets simultaneously, is achieved by exploiting correlations. We use these improvements to study uncertainties and PDF sensitivity at NNLO, using 371 PDF set members. The work described here permits NNLO studies that were previously prohibitively expensive, and lays the groundwork necessary for a future implementation of NNLO calculations with a jet at Born level in MCFM.

There is significant evidence from light metals that turbulence in casting leads to bifilm defects; enfolded, doubled-over oxide films which act like cracks in the liquid, and are inherited as cracks by the solid. This population of introduced cracks is now known to significantly influence the tensile failure behaviour of light alloys. There is evidence that analogous defects exist in steels. This paper examines the possibility that bifilms may control the hot ductility of TWIP and TRIP steels, and therefore the problems of straightening during continuous casting. Techniques for overcoming these problems are indicated.

Introduction BCG vaccination modulates immune responses to unrelated pathogens. This off-target effect could reduce the impact of emerging pathogens. As a readily available, inexpensive intervention that has a well-established safety profile, BCG is a good candidate for protecting healthcare workers (HCWs) and other vulnerable groups against COVID-19.Methods and analysis This international multicentre phase III randomised controlled trial aims to determine if BCG vaccination reduces the incidence of symptomatic and severe COVID-19 at 6 months (co-primary outcomes) compared with no BCG vaccination. We plan to randomise 10 078 HCWs from Australia, The Netherlands, Spain, the UK and Brazil in a 1:1 ratio to BCG vaccination or no BCG (control group). The participants will be followed for 1 year with questionnaires and collection of blood samples. For any episode of illness, clinical details will be collected daily, and the participant will be tested for SARS-CoV-2 infection. The secondary objectives are to determine if BCG vaccination reduces the rate, incidence, and severity of any febrile or respiratory illness (including SARS-CoV-2), as well as work absenteeism. The safety of BCG vaccination in HCWs will also be evaluated. Immunological analyses will assess changes in the immune system following vaccination, and identify factors associated with susceptibility to or protection against SARS-CoV-2 and other infections.Ethics and dissemination Ethical and governance approval will be obtained from participating sites. Results will be published in peer-reviewed open-access journals. The final cleaned and locked database will be deposited in a data sharing repository archiving system.Trial registration ClinicalTrials.gov NCT04327206