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Language development can be framed as the process of learning how to mean (Halliday, 1975). From this perspective, the role of communicative function is central to the language-learning process with development being guided by interaction with experienced others. In the current study, we present a detailed analysis of the communicative functions used in interaction with prelinguistic infants aged 10-12 months from three cultural groups living in the United Kingdom. The findings indicate that caregivers from all three groups used a wide range of communicative acts when interacting with their infants, ranging from directives to discussions of inner thoughts and feelings. In addition, we identified significant differences in the frequency with which different communicative acts were used across our three groups. The study complements the positive contributions made by pivotal studies on language socialisation by highlighting the diversity and variation of caregiver speech at the functional level.

Many Western industrialized nations have high levels of ethnic diversity but to date there are very few studies which investigate prelinguistic and early language development in infants from ethnic minority backgrounds. This study tracked the development of infant communicative gestures from 10 to 12 months (n = 59) in three culturally distinct groups in the United Kingdom and measured their relationship, along with maternal utterance frequency and responsiveness, to vocabulary development at 12 and 18 months. No significant differences were found in infant gesture development and maternal responsiveness across the groups, but relationships were identified between gesture, maternal responsiveness, and vocabulary development.

Introduction: Thermoregulation refers to the ability to maintain a stable internal body temperature regardless of external conditions. In neonates, particularly preterm infants, thermoregulation is critical due to several factors. Objective: To assess the knowledge on thermoregulation among the mothers of under five children in selected hospitals, Dehradun (UK),To assess the practise of thermoregulation among the mothers of under five children in selected hospitals, Dehradun (UK),To assess the Effectiveness of planned teaching programme on knowledge and practice regarding thermoregulation among the mothers of under five children in selected hospitals, Dehradun (UK). Methodology-The researchers have used A Quasi Experimental Research Design (One group Pre-test and Post-test).Non Probability Purposive sampling technique was used.80 Mothers who fullfill the inclusion criteria were included in the study In the present study the below scales were used to collect the data. Structured Questionnaire and observational checklist was used to assess the Effectiveness of planned teaching programme on knowledge and practice regarding thermoregulation among the mothers of under five children in selected hospitals, Dehradun (UK). Conclusion: The planned teaching programme significantly improved the knowledge and practices of thermoregulation among mothers of under-five children. Educating mothers on thermoregulation techniques is crucial for reducing temperature-related health issues in children, thereby improving their overall health outcomes. [ABSTRACT FROM AUTHOR]

Simultaneous pancreas-kidney (SPK) transplantation improves quality of life and limits progression of diabetic complications. There is reluctance to accept pancreata from donors with abnormal blood tests, due to concern of inferior outcomes. We investigated whether donor amylase and liver blood tests (markers of visceral ischaemic injury) predict pancreas graft outcome using the UK Transplant Registry (2016-2021). 857 SPK recipients were included (619 following brainstem death, 238 following circulatory death). Peak donor amylase ranged from 8 to 3300 U/L (median = 70), and this had no impact on pancreas graft survival when adjusting for multiple confounders (aHR = 0.944, 95% CI = 0.754-1.81). Peak alanine transaminases also did not influence pancreas graft survival in multivariable models (aHR = 0.967, 95% CI = 0.848-1.102). Restricted cubic splines were used to assess associations between donor blood tests and pancreas graft survival without assuming linear relationships; these confirmed neither amylase, nor transaminases, significantly impact pancreas transplant outcome. This is the largest, most statistically robust study evaluating donor blood tests and transplant outcome. Provided other factors are acceptable, pancreata from donors with mild or moderately raised amylase and transaminases can be accepted with confidence. The use of pancreas grafts from such donors is therefore a safe, immediate, and simple approach to expand the donor pool to reach increasing demands. [ABSTRACT FROM AUTHOR]

Background: Overweight and obesity are well-established risk factors for COVID-19 severity; however, less is known about the role of sedentary behaviors such as television (TV) viewing. The purpose of this brief report was to determine whether lower TV viewing time may mitigate the risk of severe COVID-19 in individuals with excess weight. Methods: We analyzed 329,751 UK Biobank participants to investigate the independent and combined associations of BMI and self-reported TV viewing time with odds of severe COVID-19 (inpatient COVID-19 or COVID-19 death). Results: Between March 16 and December 8, 2020, there were 1648 instances of severe COVID-19. Per 1-unit (hours per day) increase in TV viewing time, the odds of severe COVID-19 increased by 5% (adjusted odds ratio = 1.05, 95% confidence interval = 1.02–1.08). Compared with normal-weight individuals with low (≤1 h/d) TV viewing time, the odds ratios for overweight individuals with low and high (≥4 h/d) TV viewing time were 1.17 (0.89–1.55) and 1.66 (1.31–2.11), respectively. For individuals with obesity, the respective ORs for low and high TV viewing time were 2.18 (1.61–2.95) and 2.14 (1.69–2.73). Conclusion: Higher TV viewing time was associated with higher odds of severe COVID-19 independent of BMI and moderate to vigorous physical activity. Additionally, low TV viewing time may partly attenuate the elevated odds associated with overweight, but not obesity. [ABSTRACT FROM AUTHOR]

Energy systems across the world are becoming localized, decarbonized, and digitalized. This is the era of local energy system integrating heat, power, and transport. Local energy system refers to arrangements that operate locally at a scale less than the traditional centralized model to maximize social, economic, environmental benefits for people or organization in a specific geographical area. Beyond decarbonization, local energy systems are expected to provide a wide range of other benefits such as alleviating fuel poverty, community income generation. The increase in the deployment of local energy systems has been the subject of intensive research and development in recent era. This article aims to review the recent local energy system developments in India and United Kingdom. Specifically, this will focus on local energy system taxonomy, landscape, challenges, pilot projects, policies, energy storage technologies in India and United Kingdom. Further, this work will also discuss how local energy system can be used for electrification of rural India. Thus, this work will put forward the latest developments of local energy system in a developed and developing country. This work will conclude by presenting the way forward for local energy system adoption and development in India and United Kingdom. It is expected that this work will help power and energy system researchers to track down the recent developments and landscape, and lessons of local energy system. This article is categorized under:Sustainable Energy > Other RenewablesClimate and Environment > Net Zero Planning and DecarbonizationEnergy and Power Systems > Energy Infrastructure [ABSTRACT FROM AUTHOR]

Technological advancements in computer science have started to bring artificial intelligence (AI) from the bench closer to the bedside. While there is still lots to do and improve, AI models in medical imaging and radiotherapy are rapidly being developed and increasingly deployed in clinical practice. At the same time, AI governance frameworks are still under development. Clinical practitioners involved with procuring, deploying, and adopting AI tools in the UK should be well-informed about these AI governance frameworks. This scoping review aimed to map out available literature on AI governance in the UK, focusing on medical imaging and radiotherapy. Searches were performed on Google Scholar, Pubmed, and the Cochrane Library, between June and July 2022. Of 4225 initially identified sources, 35 were finally included in this review. A comprehensive conceptual AI governance framework was proposed, guided by the need for rigorous AI validation and evaluation procedures, the accreditation rules and standards, and the fundamental ethical principles of AI. Fairness, transparency, trustworthiness, and explainability should be drivers of all AI models deployed in clinical practice. Appropriate staff education is also mandatory to ensure AI’s safe and responsible use. Multidisciplinary teams under robust leadership will facilitate AI adoption, and it is crucial to involve patients, the public, and practitioners in decision-making. Collaborative research should be encouraged to enhance and promote innovation, while caution should be paid to the ongoing auditing of AI tools to ensure safety and clinical effectiveness. [ABSTRACT FROM AUTHOR]

Objective: Endovascular treatment (EVT) of spinal dural arteriovenous fistulae (SDAVF) has become increasingly popular given its less invasive nature. This study aims to assess radiological obliteration rates after surgery and EVT for SDAVF in a major tertiary referral centre serving a population of 2.2 million. Method: A retrospective review of all patients diagnosed with SDAVF between February 2010 and February 2018 was undertaken, identifying baseline demographics, treatment modality and the final radiological outcome (i.e., persistence of the SDAVF). Patients were identified from the departmental neurovas-cular database, clinical notes and imaging reports. Results: Twenty patients were identified with an angiographically confirmed SDAVF. Two (10%) were managed conservatively. Nine patients (45%) underwent EVT. Obliteration was achieved in one patient (11%) after a single procedure, while one patient required two sessions. Further surgery was required in five patients (56%) to achieve complete obliteration. Nine patients (45%) underwent surgical disconnection as first treatment. Obliteration was radiologically confirmed in eight patients (89%). No radiological (MRI or angiographic) follow-up data was available for two patients (one from each group) and these were excluded from analysis. In this study, the obliteration rate of SDAVF after surgery was superior compared to EVT (p <0.01). Conclusion: Complete obliteration and recurrence rates after single treatment with EVT were inferior compared to surgical intervention. EVT may be better suited for specific presentations of SDAVF either in isolation or as an adjunct in multi-modality treatment. A national registry of outcomes may aid ongoing refinement of patient selection for EVT. [ABSTRACT FROM AUTHOR]

Autoimmune conditions have been reported among patients with cysteine-altering NOTCH3 variants and CADASIL. This study aimed to investigate the occurrence of autoimmune illnesses and markers of inflammation in such populations. Cases were identified who had a NOTCH3 cysteine-altering variant from the Geisinger MyCode® Community Health Initiative (MyCode®). We further performed external validation using the UK Biobank cohort. A cohort of 121 individuals with a NOTCH3 cysteine-altering variant from MyCode® was compared to a control group with no non-synonymous variation in NOTCH3 (n = 184). Medical records were evaluated for inflammatory markers and autoimmune conditions, which were grouped by the organ systems involved. A similar analysis was conducted using data from the UK Biobank (n~450,000). An overall increase in inflammatory markers among participants with a NOTCH3 cysteine-altering variant was observed when compared to an age- and sex-matched MyCode® control group (out of participants with laboratory testing: 50.9% versus 26.7%; p = 0.0047; out of total participants: 23.1% versus 10.9%; p = 0.004). Analysis of UK Biobank data indicated any autoimmune diagnosis (1.63 [1.14, 2.09], p= 2.665 × 10−3) and multiple sclerosis (3.42 [1.67, 6.02], p = 9.681 × 10−4) are associated with a NOTCH3 cysteine-altering variant in any domain. Our findings suggest a possible association between NOTCH3 cysteine-altering variants and autoimmune conditions. [ABSTRACT FROM AUTHOR]

Background: Decision-making in the management of patients with retroperitoneal sarcoma is complex and requires input from a number of different specialists. The aim of this study was to evaluate the levels of agreement in terms of resectability, treatment allocation, and organs proposed to be resected across different retroperitoneal sarcoma multidisciplinary team meetings. Methods: The CT scans and clinical information of 21 anonymized retroperitoneal sarcoma patients were sent to all of the retroperitoneal sarcoma multidisciplinary team meetings in Great Britain, which were asked to give an opinion about resectability, treatment allocation, and organs proposed to be resected. The main outcome was inter-centre reliability, which was quantified using overall agreement, as well as the chance-corrected Krippendorff's alpha statistic. Based on the latter, the level of agreement was classified as: 'slight' (0.00-0.20), 'fair' (0.21-0.40), 'moderate' (0.41-0.60), 'substantial' (0.61-0.80), or 'near-perfect' (>0.80). Results: Twenty-one patients were reviewed at 12 retroperitoneal sarcoma multidisciplinary team meetings, giving a total of 252 assessments for analysis. Consistency between centres was only 'slight' to 'fair', with rates of overall agreement and Krippendorff's alpha statistics of 85.4 per cent (211 of 247) and 0.37 (95 per cent c.i. 0.11 to 0.57) for resectability; 80.4 per cent (201 of 250) and 0.39 (95 per cent c.i. 0.33 to 0.45) for treatment allocation; and 53.0 per cent (131 of 247) and 0.20 (95 per cent c.i. 0.17 to 0.23) for the organs proposed to be resected. Depending on the centre that they had attended, 12 of 21 patients could either have been deemed resectable or unresectable, and 10 of 21 could have received either potentially curative or palliative treatment. Conclusions: Inter-centre agreement between retroperitoneal sarcoma multidisciplinary team meetings was low. Multidisciplinary team meetings may not provide the same standard of care for patients with retroperitoneal sarcoma across Great Britain. [ABSTRACT FROM AUTHOR]

Objective: Work Place-Based Assessments (WPBAs) were introduced into psychiatry along with the new curriculum in 2005. The Royal College of Psychiatrists decided to pilot several WPBAs to ascertain their suitability. Method: Eight types of assessments (Case-Based Discussion, Assessment of Clinical Expertise, Mini-Assessed Clinical Encounter, Mini-Peer Assessment Tool, Direct Observations of Procedural Skills, Patient Satisfaction Questionnaires, Case Conference, and Journal Club Presentation) were piloted, either singly or in combination, on 16 sites, with 600 psychiatric trainees. Results: Consultant psychiatrists carried out most of the assessments. Case-Based Discussion was the most popular, and high levels of correlation were obtained across several assessment tools. Conclusions: There is evidence that with suitable training of assessors and trainees, WPBAs can be introduced and are feasible in assessing some competencies.

The focus of this study is the nature and concomitants of pretend play among young children with autism. Age- and language-matched children with autism ("n"= 27), autism spectrum disorder ("n"= 14), and developmental disorders without autism ("n"= 16) were administered the Test of Pretend Play (ToPP; Lewis & Boucher, 1997), with an additional rating of "playful pretence". As predicted, children with autism showed less playful pretend than participants with developmental disorders who did not have autism. Across the groups, playful pretence was correlated with individual differences in communication and social interaction, even when scores on the ToPP were taken into account. Limitations in creative, playful pretend among children with autism relate to their restricted interpersonal communication and engagement. (Contains 2 tables and 2 figures.)

Salmonella is a food-borne pathogen often linked to poultry sources, causing gastrointestinal infections in humans, with the numbers of multidrug resistant (MDR) isolates increasing globally. To gain insight into the genomic diversity of common serovars and their potential contribution to disease, we characterized antimicrobial resistance genes, and virulence factors encoded in 88 UK and 55 Thai isolates from poultry; the presence of virulence genes was detected through an extensive virulence determinants database compiled in this study. Long-read sequencing of three MDR isolates, each from a different serovar, was used to explore the links between virulence and resistance. To augment current control methods, we determined the sensitivity of isolates to 22 previously characterized Salmonella bacteriophages. Of the 17 serovars included, Salmonella Typhimurium and its monophasic variants were the most common, followed by S. Enteritidis, S. Mbandaka, and S. Virchow. Phylogenetic analysis of Typhumurium and monophasic variants showed poultry isolates were generally distinct from pigs. Resistance to sulfamethoxazole and ciprofloxacin was highest in isolates from the UK and Thailand, respectively, with 14–15% of all isolates being MDR. We noted that >90% of MDR isolates were likely to carry virulence genes as diverse as the srjF, lpfD, fhuA, and etc operons. Long-read sequencing revealed the presence of global epidemic MDR clones in our dataset, indicating they are possibly widespread in poultry. The clones included MDR ST198 S. Kentucky, harboring a Salmonella Genomic Island-1 (SGI)-K, European ST34 S. 1,4,[5],12:i:-, harboring SGI-4 and mercury resistance genes, and a S. 1,4,12:i:- isolate from the Spanish clone harboring an MDR-plasmid. Testing of all isolates against a panel of bacteriophages showed variable sensitivity to phages, with STW-77 found to be the most effective. STW77 lysed 37.76% of the isolates, including serovars important for human clinical infections: S. Enteritidis (80.95%), S. Typhimurium (66.67%), S. 1,4,[5],12:i:- (83.3%), and S. 1,4,12: i:- (71.43%). Therefore, our study revealed that combining genomics and phage sensitivity assays is promising for accurately identifying and providing bio controls for Salmonella to prevent its dissemination in poultry flocks and through the food chain to cause infections in humans. [ABSTRACT FROM AUTHOR]

Background: For many years, universities have placed a strong emphasis on providing students with an internationalization experience through study-abroad programs; however, the recent pandemic led many universities to look for alternatives to continue offering students an international experience. Method: This article describes the implementation and evaluation of a collaborative online international learning (COIL) experience between nursing students in Australia and the United Kingdom. Results: Students explored community spirit in the recovery from COVID-19. Students positively rated the experience and shared insights and outcomes gained from the program. Conclusion: The COIL experience exposed nursing students from Australia and the United Kingdom to learn about public health issues and develop cultural awareness and a sense of global community. Future programs should evaluate the long-term effects on students' nursing practice and their careers. [J Nurs Educ. 2023;62(7):387–392.] [ABSTRACT FROM AUTHOR]

This paper presents an investigation into how students studying at university engage actively with learning technology in their self-directed study time. The case study surveyed 250 students studying at undergraduate and postgraduate level from a purposive sample of departments within one institution. The study has also conducted focus groups and a number of in-depth follow-up interviews with respondents to the survey. In this article we explore three emerging aspects of the learning experience, namely student expectations of the technology, their lecturers' engagement with technology and how the technology might support processes of transition in higher education. One key implication is that more academic guidance is needed on what and how to use the technology effectively for independent learning, even where ICT skills levels are high. The study also identifies the significant role that the lecturer plays in facilitating students' use of technology. The findings of this study will be of interest to those working to incorporate learning technologies more effectively in higher education, in particular for those who are looking to improve the engagement of students in self-directed learning. (Contains 1 table, 2 figures, and 2 notes.)

Background There is a paucity of data on anesthesia-related outcomes for endovascular treatment (EVT) in the extended window (>6 hours from ischemic stroke onset). We compared functional and safety outcomes between local anesthesia (LA) without sedation, conscious sedation (CS) and general anesthesia (GA). Methods Patients who underwent EVT in the early (<6 hours) and extended time windows using LA, CS, or GA between October 2015 and March 2020 were included from a UK national stroke registry. Multivariable analyses were performed, adjusted for age, sex, baseline stroke severity, pre-stroke disability, EVT technique, center, procedural time and IV thrombolysis. Results A total of 4337 patients were included, 3193 in the early window (1135 LA, 446 CS, 1612 GA) and 1144 in the extended window (357 LA, 134 CS, 653 GA). Compared with GA, patients treated under LA alone had increased odds of an improved modified Rankin Scale (mRS) score at discharge (early: adjusted common (ac) 0R=1.50, 95% CI 1.29 to 1.74, p=0.001; extended: acOR=1.29, 95% CI 1.01 to 1.66, p=0.043). Similar mRS scores at discharge were found in the LA and CS cohorts in the early and extended windows (p=0.21). Compared with CS, use of GA was associated with a worse mRS score at discharge in the early window (acOR=0.73, 95% CI 0.45 to 0.96, p=0.017) but not in the extended window (p=0.55). There were no significant differences in the rates of symptomatic intracranial hemorrhage or in-hospital mortality across the anesthesia modalities in the extended window. Conclusion LA without sedation during EVT was associated with improved functional outcomes compared with GA, but not CS, within and beyond 6 hours from stroke onset. Prospective studies assessing anesthesia-related outcomes in the extended time window are warranted. [ABSTRACT FROM AUTHOR]

Background: Artificial intelligence (AI)-enabled applications are increasingly being used in providing healthcare services, such as medical imaging support. Sufficient and appropriate education for medical imaging professionals is required for successful AI adoption. Although, currently, there are AI training programmes for radiologists, formal AI education for radiographers is lacking. Therefore, this study aimed to evaluate and discuss a postgraduate-level module on AI developed in the UK for radiographers. Methodology: A participatory action research methodology was applied, with participants recruited from the first cohort of students enrolled in this module and faculty members. Data were collected using online, semi-structured, individual interviews and focus group discussions. Textual data were processed using data-driven thematic analysis. Results: Seven students and six faculty members participated in this evaluation. Results can be summarised in the following four themes: a. participants' professional and educational backgrounds influenced their experiences, b. participants found the learning experience meaningful concerning module design, organisation, and pedagogical approaches, c. some module design and delivery aspects were identified as barriers to learning, and d. participants suggested how the ideal AI course could look like based on their experiences. Conclusions: The findings of our work show that an AI module can assist educators/academics in developing similar AI education provisions for radiographers and other medical imaging and radiation sciences professionals. A blended learning delivery format, combined with customisable and contextualised content, using an interprofessional faculty approach is recommended for future similar courses. Key points: A novel postgraduate module on AI for radiographers was developed and evaluated. Blended-learning delivery, customisable and contextualised course content, and interprofessional faculty are the ways forward for an ideal AI course for radiographers. Future courses could use this approach to develop their own AI training. [ABSTRACT FROM AUTHOR]

We examined the joint associations of BMI category and grip strength tertile with risk of severe COVID-19 (inpatient COVID-19 or COVID-19 mortality) in 327 500 UK Biobank participants. Compared to normal-weight males with high grip strength, the odds ratio (95 % confidence interval) for males with obesity with low grip strength was 2.39 (1.59–3.60), but 1.52 (0.98–2.35) for males with obesity with a high grip strength. A higher grip strength did not appear to be associated with lower risk of severe COVID-19 in females. Muscle mass and strength development should be considered as a means to reduce risk of severe COVID-19 for males with obesity. [ABSTRACT FROM AUTHOR]

The current corpus-based study investigates the frequency distributions of temporal and causal conjunctive relations in British and Pakistani research discourse by utilizing Halliday and Hassan (1976) framework of conjunctive relations. The study achieves its objectives by developing two corpora, British and Pakistani, each consisting of one million words. A mixed-methods approach (QUAN →qual) was employed to analyze the frequency distributions of temporal and causal conjunctions in both British and Pakistani corpora (Cresswell, 2007). The findings of the study show that temporal and causal conjunctions are less frequently used in the Pakistani corpus than in the British corpus. The study implies that Pakistani researchers' access to the native research discourse will enable them to widen their knowledge about the correct and variant use of temporal and causal conjunctive relations in their research discourse. [ABSTRACT FROM AUTHOR]

Objective: To assess the feasibility and preliminary efficacy of adding cetuximab to standard chemoradiotherapy for muscle‐invasive bladder cancer. Patients and Methods: TUXEDO was a prospective, single‐arm, open‐label, phase I/II trial conducted in six UK hospitals. Cetuximab was administered with an initial loading dose of 400 mg/m2 on Day 1 of Week −1, and then seven weekly doses of 250 mg/m2. The radiotherapy schedule was 64 Gy/32F with Day 1 mitomycin C (12 g/m2) and 5‐fluorouracil (500 mg/m2/day) over Days 1–5 and Days 22–26. Patients with T2‐4aN0M0 urothelial cancer and a performance status of 0–1 were eligible. Prior neoadjuvant therapy was permitted. The Phase I primary outcome was impact on radiotherapy treatment completion and toxicity experienced during treatment. The Phase II primary outcome was local control at 3 months post treatment. Results: Between September 2012 and October 2016, 33 patients were recruited; seven in Phase I, 26 in Phase II. Three patients in Phase II were subsequently deemed ineligible and received no trial therapy. Eight patients discontinued cetuximab due to adverse effects. The patients' median (range) age was 70.1 (60.6–75.1) years, 20 had a performance status of 0, 27 were male and 26 had already received neoadjuvant chemotherapy. In Phase I, all patients completed planned radiotherapy, with no delays or dose reductions. Of the 30 evaluable patients in Phase II, 25 had confirmed local control 3 months after treatment (77%, 95% confidence interval 58–90). During the trial there were 18 serious adverse events. The study was halted due to slow accrual. Conclusion: Phase I data demonstrate it is feasible and safe to add cetuximab to chemoradiotherapy. Exploratory analysis of Phase II data provides evidence to consider further clinical evaluation of cetuximab in this setting. [ABSTRACT FROM AUTHOR]

Marking a significant step aimed at making governance more transparent the UK requires audit committees (ACs) to publish a report on their activities. Although regulators continue to emphasise the roles of ACs, there is limited evidence on what the AC does in practice. This paper provides evidence on the nature of AC actions as reported in AC reports relating to external audit, internal audit and financial reporting. We use summative content analysis to analyze AC reports of UK FTSE 350 firms and find that AC actions mainly entail reviewing processes and reports and there is limited incidence of them reporting that they have undertaken investigations into auditing and reporting issues. Moreover, what is reported is mainly general and descriptive of process. Our findings highlight the importance of AC reports providing meaningful information rather than engaging in symbolism. ACs can use their reports to signal their substantive monitoring and how they have contributed to improving auditing and reporting quality. The findings also suggest that future research examining the reviewing, investigating and outsourcing activities of boards and ACs can contribute to a better understanding of the governance process and outcomes. [ABSTRACT FROM AUTHOR]

Background: End-stage ankle osteoarthritis causes severe pain and disability. There are no randomized trials comparing the 2 main surgical treatments: total ankle replacement (TAR) and ankle fusion (AF).Objective: To determine which treatment is superior in terms of clinical scores and adverse events.Design: A multicenter, parallel-group, open-label randomized trial. (ISRCTN registry number: 60672307).Setting: 17 National Health Service trusts across the United Kingdom.Patients: Patients with end-stage ankle osteoarthritis, aged 50 to 85 years, and suitable for either procedure.Intervention: Patients were randomly assigned to TAR or AF surgical treatment.Measurements: The primary outcome was change in Manchester-Oxford Foot Questionnaire walking/standing (MOXFQ-W/S) domain scores between baseline and 52 weeks after surgery. No blinding was possible.Results: Between 6 March 2015 and 10 January 2019, a total of 303 patients were randomly assigned; mean age was 68 years, and 71% were men. Twenty-one patients withdrew before surgery, and 281 clinical scores were analyzed. At 52 weeks, the mean MOXFQ-W/S scores improved for both groups. The adjusted difference in the change in MOXFQ-W/S scores from baseline was -5.6 (95% CI, -12.5 to 1.4), showing that TAR improved more than AF, but the difference was not considered clinically or statistically significant. The number of adverse events was similar between groups (109 vs. 104), but there were more wound healing issues in the TAR group and more thromboembolic events and nonunion in the AF group. The symptomatic nonunion rate for AF was 7%. A post hoc analysis suggested superiority of fixed-bearing TAR over AF (-11.1 [CI, -19.3 to -2.9]).Limitation: Only 52-week data; pragmatic design creates heterogeneity of implants and surgical techniques.Conclusion: Both TAR and AF improve MOXFQ-W/S and had similar clinical scores and number of harms. Total ankle replacement had greater wound healing complications and nerve injuries, whereas AF had greater thromboembolism and nonunion, with a symptomatic nonunion rate of 7%.Primary Funding Source: National Institute for Health and Care Research Heath Technology Assessment Programme. [ABSTRACT FROM AUTHOR]

Introduction: The effects of the COVID‐19 pandemic on mental health have been profound. Mental health and diabetes self‐care are inter‐related. We examined whether COVID‐19 anxiety, depressive symptoms and health anxiety were associated with domains of diabetes self‐management and investigated whether greater COVID‐19 anxiety syndrome would independently contribute to suboptimal diabetes self‐care. Research design and methods: Surveys were sent to people attending diabetes clinics of three London hospitals. Participants completed the Diabetes Self‐Management Questionnaire (DSMQ), the COVID‐19 Anxiety Syndrome Scale (C‐19 ASS), which measures perseveration and avoidant maladaptive coping behaviour, assessed with measures of co‐existent depressive symptoms and anxiety, controlling for age, gender and social deprivation. Clinical data, including pre‐ and post‐lockdown HbA1c measures, were obtained from hospital records for 369 respondents, a response rate of 12.8%. Results: Depressive symptom scores were high. Both pre‐existing health anxiety and depressive symptoms were independently linked to improvable measures of diabetes care, as was lower socio‐economic rank. However, avoidant COVID‐19 anxiety responses were independently associated with higher diabetes self‐care scores. HbA1c levels improved modestly over the year of UK lockdown in this cohort. Conclusion: During the height of lockdown, avoidant coping behaviours characteristic of the COVID‐19 anxiety syndrome may in fact work to improve diabetes self‐care, at least in the short term. We recommend screening for depressive symptoms and being aware of the significant minority of people with COVID‐19 anxiety syndrome who may now find it difficult to re‐engage with face‐to‐face clinic opportunities. [ABSTRACT FROM AUTHOR]

Deep learning has recently achieved best-in-class performance in several fields, including biomedical domains such as X-ray images. Yet, data scarcity poses a strict limit on training successful deep learning systems in many, if not most, biomedical applications, including those involving brain images. In this study, we translate state-of-the-art transfer learning techniques for single-subject prediction of simpler (sex and age) and more complex phenotypes (number of people in household, household income, fluid intelligence and smoking behavior). We fine-tuned 2D and 3D ResNet-18 convolutional neural networks for target phenotype predictions from brain images of ∼ 40,000 UK Biobank participants, after pretraining on YouTube videos from the Kinetics dataset and natural images from the ImageNet dataset. Transfer learning was effective on several phenotypes, especially sex and age classification. Additionally, transfer learning in particular outperformed deep learning models trained from scratch especially on smaller sample sizes. The out-of-sample performance using transfer learning from previously learned knowledge based on real-world images and videos could unlock the potential in many areas of imaging neuroscience where deep learning solutions are currently infeasible. • Neuroimaging faces challenges in effectively training DNNs due to data scarcity. • Transfer learning (TL) could aid in training DNNs in the data-scarce neuroimaging setting. • Using TL, we improved predictions on several phenotypes and smaller sample sizes. [ABSTRACT FROM AUTHOR]

Jammu and Kashmir is the seventh largest state (now a union territory) of India in terms of area, with about 1.25 crore inhabitants. It has 11 universities (Central and State) and 308 colleges affiliated with Jammu and Kashmir universities. With such a diverse higher educational structure, one presumes the region will have sufficient scientific output for scientometric analysis. The study tried to assess its research output and impact in science and technology by analysing 4,697 journal articles indexed in the Science Citation Index–Expanded database Web of Science. The examination of articles revealed that they are predominantly dealing with plant sciences, dairy and animal science, agriculture, and chemistry. All these articles have a mean of 7.24 authors and citation per publication of 6.43. The Jammu and Kashmir researchers' international collaboration is primarily with Saudi Arabia, the United Kingdom, and the United States. The most prolific institutions are the University of Kashmir, Sher-e-Kashmir University of Agricultural Sciences & Technology of Kashmir (SKUAST), and Sher-i-Kashmir Institute of Medical Sciences (SKIMS). The most productive researchers are Sheikh Javid Ahmad from Cluster University Srinagar, and Farooq Ahmad Masoodi and Aijaz Ahmad Dar from University of Kashmir. The study will serve as an index to assist researchers and organizations in Jammu and Kashmir and their publication profiles in the overall science and technology output of the state. [ABSTRACT FROM AUTHOR]

Background. Randomized studies of neoadjuvant (NA) trastuzumab and pertuzumab combined with chemotherapy for HER2-positive breast cancers (BC) have reported pathological complete response (pCR) rates of 39 to 61%. This study aimed to determine the real-world efficacy and toxicity of NA trastuzumab and pertuzumab combined with chemotherapy in a UK tertiary referral cancer centre. Methods. HER2-positive early BC patients given neoadjuvant chemotherapy with trastuzumab and pertuzumab between October 2016 and February 2018 at our tertiary referral cancer centre were identified via pharmacy records. Clinico-pathological information, treatment regimens, treatment-emergent toxicities, operative details, and pathological responses and outcomes were recorded. Results. 78 female patients were identified; 2 had bilateral diseases and 48 of 78 (62%) were node positive at presentation. 55 of 80 (71%) tumours were ER-positive. PCR occurred in 37 of 78 (46.3%; 95% CI: 35.3–57.2%) patients. 14 of 23 (60.8%) patients with ER-negative tumours achieved pCR; 23 of 55 (41.8%) were ER-positive and 6 of 19 (31.6%) were ER-positive and PgR-positive. No cardiac toxicity was documented. Diarrhoea occurred in 53 of 72 (74%) patients. Grade 3–4 toxicity occurred in ≥2% patients. These were diarrhoea, fatigue, and infection. The Median follow up period was 45.2 months (95% CI 43.8–46.3) with 71 of 78 (91.0%) remaining disease-free and 72 of 78 (92.3%) alive. Estimated OS at 2 years 86% (95% CI: 75–99%). Conclusion. This data confirms the efficacy of neoadjuvant chemotherapy combined with dual HER2 directed therapy. While no cardiac toxicity was observed, diarrhoea occurred frequently. The low pCR rate observed in ER and PgR-positive BCs warrants further investigation and consideration of strategies to increase the pCR rate. [ABSTRACT FROM AUTHOR]

Background: STAMPEDE has previously reported that radiotherapy (RT) to the prostate improved overall survival (OS) for patients with newly diagnosed prostate cancer with low metastatic burden, but not those with high-burden disease. In this final analysis, we report long-term findings on the primary outcome measure of OS and on the secondary outcome measures of symptomatic local events, RT toxicity events, and quality of life (QoL). Methods and findings: Patients were randomised at secondary care sites in the United Kingdom and Switzerland between January 2013 and September 2016, with 1:1 stratified allocation: 1,029 to standard of care (SOC) and 1,032 to SOC+RT. No masking of the treatment allocation was employed. A total of 1,939 had metastatic burden classifiable, with 42% low burden and 58% high burden, balanced by treatment allocation. Intention-to-treat (ITT) analyses used Cox regression and flexible parametric models (FPMs), adjusted for stratification factors age, nodal involvement, the World Health Organization (WHO) performance status, regular aspirin or nonsteroidal anti-inflammatory drug (NSAID) use, and planned docetaxel use. QoL in the first 2 years on trial was assessed using prospectively collected patient responses to QLQ-30 questionnaire. Patients were followed for a median of 61.3 months. Prostate RT improved OS in patients with low, but not high, metastatic burden (respectively: 202 deaths in SOC versus 156 in SOC+RT, hazard ratio (HR) = 0·64, 95% CI 0.52, 0.79, p < 0.001; 375 SOC versus 386 SOC+RT, HR = 1.11, 95% CI 0.96, 1.28, p = 0·164; interaction p < 0.001). No evidence of difference in time to symptomatic local events was found. There was no evidence of difference in Global QoL or QLQ-30 Summary Score. Long-term urinary toxicity of grade 3 or worse was reported for 10 SOC and 10 SOC+RT; long-term bowel toxicity of grade 3 or worse was reported for 15 and 11, respectively. Conclusions: Prostate RT improves OS, without detriment in QoL, in men with low-burden, newly diagnosed, metastatic prostate cancer, indicating that it should be recommended as a SOC. Trial registration: ClinicalTrials.gov NCT00268476, ISRCTN.com ISRCTN78818544. Chris C Parker and colleagues report long-term findings on overall survival and local complications in men with metastatic prostate cancer treated with radiotherapy. Author summary: Why was this study done?: Prostate cancer is the most common cancer in males. Radiotherapy (RT) to the prostate is widely used as a radical treatment for nonmetastatic prostate cancer. A comparison was added to the STAMPEDE protocol to assess whether RT to the prostate would also be helpful for males with metastatic prostate cancer. A benefit in survival was targeted. The trial previously reported a clinically relevant, statistically significant overall survival (OS) benefit for patients with a low metastatic burden but not for men with a high metastatic burden. This long-term analysis assesses survival with substantially longer follow-up and more events and looked also at complications of local disease. What did the researchers do and find?: A randomised controlled trial of adding RT to the prostate to standard of care (SOC) was incorporated into the STAMPEDE protocol. More than 2,000 patients joined the comparison between 2013 and 2016. The data set was frozen in 2021 and analysed using standard methods. There was a clear improvement in survival with prostate RT in the low metastatic burden group. There was no improvement in survival with prostate RT in the high metastatic burden group. Symptomatic local progression and the need for later local intervention were improved with RT in the low metastatic burden group. In the low metastatic burden group, the improvement with RT was similar whether the RT was given with a daily schedule (over 4.5 weeks) or a weekly schedule (over 6 weeks). The adverse effects of RT were manageable without any impact on long-term quality of life (QoL). What do these findings mean?: Prostate RT is a relatively cheap, widely accessible, and well-tolerated treatment. Prostate RT is indicated in patients with newly diagnosed prostate cancer with a low metastatic burden. RT to the prostate is not routinely indicated for patients with a high metastatic burden. [ABSTRACT FROM AUTHOR]

Few studies have investigated brain responses to different art media. Investigations into brain processes during art making have highlighted important structures. Neuroimaging tools have been used to investigate activation of brain areas whilst artmaking, but not in a therapeutic setting. This review highlights recent advancements in this area and encourages researchers to be the first to apply this in the UK. To understand how the principles of neuroscience are currently informing the literature to explain the effects of art media in art therapy practice. Review of published peer-reviewed research between years 2000 and 2020 on neuroscience and art therapy. Findings were summarised into categories discussing psychological/neurobiological issues, art media, neuroimaging technology, and models posited. Forty-six studies were found; majority discussed the structure and function of the brain to explain art therapy processes. The Expressive Therapies Continuum (ETC) model theorised that media properties stimulate different levels of visual and cognitive processing. The novel Mobile Brain/Body Imaging (MoBI) neuroimaging technology may be used as a means of quantifying data. Significant progress has been made in attempting to explain brain responses during the art therapy process. However empirical data is needed to prove theoretical models. The use of neuroimaging has started this process to lead research into evidence-based practice. Evidencing the ground-breaking ETC model, using neuroimaging and MoBI technology is needed through close collaboration between transdisciplinary departments. Art therapists should be encouraged to use the ETC to inform art therapy assessment, planning and treatment. Neuroscience is the study of the brain and its processes, and recently technology has been available to researchers to examine brain processes in detail. This systematic narrative review explores recent literature that uses the principles of neuroscience to investigate the effects of art therapy, with a specific interest in art media. A systematic narrative review is when the findings of the study rely on the use of words to summarise the data. Art media is an important part of art therapy, as it is through artistic expressions that the client communicates their inner troubles. Different art media has been shown to elicit different feelings and behavioural responses in clients. However, research showing brain responses to different art media is limited. This study highlights ways in which further research in this field can take place. Results show that significant advancements have already been made that identify important structures and functions of the brain accessed during art therapy. Important models which incorporate neuroscience principles and theorise the art therapy process are highlighted. A significant model is the Expressive Therapies Continuum. This model explains how the brain processes information when different art media is used. However empirical data is needed to substantiate the theory behind this model. The use of neuroimaging technology is one way to achieve this. Therefore, this paper encourages transdisciplinary research to further investigate the effects different art media has on the brain during the art therapy process. [ABSTRACT FROM AUTHOR]

Background: Hip fracture in elderly patients is associated with a significant mortality which may be worsened by COVID-19 infection. Objective: To undertake a systematic review and meta-analysis of studies assessing the effect of COVID-19 infection and mortality rates in hip fracture patients in the United Kingdom (UK) during the first surge of the pandemic. Design: A systematic literature search of 9 online databases was undertaken independently by 2 reviewers using the Cochrane methodology for systematic reviews. Eligibility criteria were any study of an adult population with a hip fracture that assessed the relationship between COVID-19 infection and 30-day mortality in the UK. Meta-analysis was conducted using a random-effects model. Results: Out of 309 identified articles, 10 studies reporting on 2448 hip fracture patients met the inclusion criteria. Meta-analysis showed that the estimated mortality rate in patients with laboratory confirmed COVID-19 infection was 32.5% (95% CI= 28.3 to 37.0) compared to 8.6% (95% CI= 6.3 to 11.6) in COVID-19 negative patients. Meta-analysis of 9 comparative studies showed a significantly higher mortality in patients with laboratory confirmed COVID-19 infection as compared to patients without (RR=3.937, 95% CI= 2.867 to 5.406, P<.001). Similar findings were obtained when comparing mortality in COVID-19 laboratory confirmed or clinically suspected infected vs non-infected patients (RR=4.576, 95% CI = 3.589 to 5.835, P <.001). Conclusions: COVID-19 infection is associated with a 4-fold increase in mortality risk in hip fracture patients. Every effort should be made to avoid COVID-19 infection and nosocomial exposure in this highly vulnerable patient group. [ABSTRACT FROM AUTHOR]

Background: Stroke in UK Biobank (UKB) is ascertained via linkages to coded administrative datasets and self-report. We studied the accuracy of these codes using genetic validation. Methods: We compiled stroke-specific and broad cerebrovascular disease (CVD) code lists (Read V2/V3, ICD-9/-10) for medical settings (hospital, death record, primary care) and self-report. Among 408,210 UKB participants, we identified all with a relevant code, creating 12 stroke definitions based on the code type and source. We performed genome-wide association studies (GWASs) for each definition, comparing summary results against the largest published stroke GWAS (MEGASTROKE), assessing genetic correlations, and replicating 32 stroke-associated loci. Results: The stroke case numbers identified varied widely from 3,976 (primary care stroke-specific codes) to 19,449 (all codes, all sources). All 12 UKB stroke definitions were significantly correlated with the MEGASTROKE summary GWAS results (rg.81-1) and each other (rg.4-1). However, Bonferroni-corrected confidence intervals were wide, suggesting limited precision of some results. Six previously reported stroke-associated loci were replicated using ≥1 UKB stroke definition. Conclusions: Stroke case numbers in UKB depend on the code source and type used, with a 5-fold difference in the maximum case-sample size. All stroke definitions are significantly genetically correlated with the largest stroke GWAS to date. [ABSTRACT FROM AUTHOR]

What explains the backlash against the liberal international order? Are its causes economic or cultural? We argue that while cultural values are central to understanding the backlash, those values are, in part, endogenous and shaped by long-run economic change. Using an original survey of the British population, we show that individuals living in regions where the local labor market was more substantially affected by imports from China have significantly more authoritarian values and that this relationship is driven by the effect of economic change on authoritarian aggression. This result is consistent with a frustration-aggression mechanism by which large economic shocks hinder individuals' expected attainment of their goals. This study provides a theoretical mechanism that helps to account for the opinions and behaviors of Leave voters in the 2016 UK referendum who in seeking the authoritarian values of order and conformity desired to reduce immigration and "take back control" of policymaking. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to test the performance of the new ACR and EULAR criteria, that include ANA positivity as entry criterion, in JSLE. Methods Performance of the ACR/EULAR-2019 criteria were compared with Systemic Lupus International Collaborating Clinics (SLICC-2012), using data from children and young people (CYP) in the UK JSLE Cohort Study (n  = 482), with the ACR-1997 criteria used as reference standard. An unselected cohort of CYP positive for ANA (n  = 129) was used to calculate positive/negative predictive values of the criteria. Results At both first and last visits, the number of patients fulfilling the different classification criteria varied significantly (P < 0.001). The sensitivity of the SLICC-2012 criteria was higher when compared with that of the ACR/EULAR-2019 criteria at first and last visits (98% vs 94% for first visit, and 98% vs 96% for last visit; P < 0.001), when all available CYP were considered. The ACR/EULAR-2019 criteria were more specific when compared with the SLICC-2012 criteria (77% vs 67% for first visit, and 81% vs 71% for last visit; P < 0.001). Significant differences between the classification criteria were mainly caused by the variation in ANA positivity across ages. In the unselected cohort of ANA-positive CYP, the ACR/EULAR-2019 criteria produced the highest false-positive classification (6/129, 5%). Conclusion In CYP, the ACR/EULAR-2019 criteria are not superior to those of the SLICC-2012 or ACR-1997 criteria. If classification criteria are designed to include CYP and adult populations, paediatric rheumatologists should be included in the consensus and evaluation process, as seemingly minor changes can significantly affect outcomes. [ABSTRACT FROM AUTHOR]

Background and purpose: The global COVID‐19 pandemic led many stroke centres worldwide to shift from in‐person to telemedicine consultations to assess patients with transient ischaemic attacks (TIAs). We aimed to investigate the impact of telemedicine during the COVID‐19 pandemic on the management and outcome of the patients with TIA. Methods: We retrospectively analysed data from a registry of consecutive TIA patients assessed at the Stroke Department, Imperial College Health Care Trust, London, during the national lockdown period (between March 23 2020 and 30 June 2020). As controls, we evaluated the clinical reports and stroke quality metrics of patients presenting to the TIA clinic in the same period of 2019. Results: Between 23 March 2020 and 30 June 2020, 136 patients were assessed using the telemedicine TIA clinic, compared to 180 patients evaluated with face‐to‐face consultation in the same period in 2019. Patients' characteristics were similar in both groups. At 3 months after the TIA, there were no significant differences in the proportion of patients admitted to the hospital for recurrent TIA/stroke or any other cardiovascular cause from the 2020 period compared to the same period in 2019. Conclusions: Our analysis showed that during the pandemic, our telemedicine consultations of TIA patients were not associated with an increased 3‐month rate of recurrent TIA/stroke or cardiovascular hospital admissions. More robust studies looking at this model of care will be needed to assess its long‐term effects on patients and health care systems. [ABSTRACT FROM AUTHOR]

White matter hyperintensities (WMH) are among the most common radiological abnormalities in the ageing population and an established risk factor for stroke and dementia. While common variant association studies have revealed multiple genetic loci with an influence on their volume, the contribution of rare variants to the WMH burden in the general population remains largely unexplored. We conducted a comprehensive analysis of this burden in the UK Biobank using publicly available whole-exome sequencing data (n up to 17 830) and found a splice-site variant in GBE1, encoding 1,4-alpha-glucan branching enzyme 1, to be associated with lower white matter burden on an exome-wide level [c.691+2T>C, β = -0.74, standard error (SE) = 0.13, P = 9.7 × 10-9]. Applying whole-exome gene-based burden tests, we found damaging missense and loss-of-function variants in HTRA1 (frequency of 1 in 275 in the UK Biobank population) to associate with an increased WMH volume (P = 5.5 × 10-6, false discovery rate = 0.04). HTRA1 encodes a secreted serine protease implicated in familial forms of small vessel disease. Domain-specific burden tests revealed that the association with WMH volume was restricted to rare variants in the protease domain (amino acids 204-364; β = 0.79, SE = 0.14, P = 9.4 × 10-8). The frequency of such variants in the UK Biobank population was 1 in 450. The WMH volume was brought forward by ∼11 years in carriers of a rare protease domain variant. A comparison with the effect size of established risk factors for WMH burden revealed that the presence of a rare variant in the HTRA1 protease domain corresponded to a larger effect than meeting the criteria for hypertension (β = 0.26, SE = 0.02, P = 2.9 × 10-59) or being in the upper 99.8% percentile of the distribution of a polygenic risk score based on common genetic variants (β = 0.44, SE = 0.14, P = 0.002). In biochemical experiments, most (6/9) of the identified protease domain variants resulted in markedly reduced protease activity. We further found EGFL8, which showed suggestive evidence for association with WMH volume (P = 1.5 × 10-4, false discovery rate = 0.22) in gene burden tests, to be a direct substrate of HTRA1 and to be preferentially expressed in cerebral arterioles and arteries. In a phenome-wide association study mapping ICD-10 diagnoses to 741 standardized Phecodes, rare variants in the HTRA1 protease domain were associated with multiple neurological and non-neurological conditions including migraine with aura (odds ratio = 12.24, 95%CI: 2.54-35.25; P = 8.3 × 10-5]. Collectively, these findings highlight an important role of rare genetic variation and the HTRA1 protease in determining WMH burden in the general population. [ABSTRACT FROM AUTHOR]

Introduction: The administration of medications targeting type 2 diabetes mellitus (T2D) has evolved over time. As injection delivery systems continue to evolve, it is necessary to understand patients' perceptions of currently available treatments. The objective of this study was to examine the patient perspective of injectable treatment for T2D and identify characteristics of these treatments that are most important to patients. Methods: Data were collected via an online survey study with a sample of individuals in the UK and US who were treated for T2D with injectable medication. The survey was designed to elicit perceptions of the treatment process for injectable glucagon-like peptide 1 (GLP-1) receptor agonists and insulin. Results: The sample included 504 participants (251 UK, 253 US). Approximately half (50.4%) were treated with a GLP-1 receptor agonist and half (49.6%) were treated with insulin. Respondents were presented with a list of 17 characteristics of injectable medication and asked to indicate which were most important to them. Respondents most frequently selected confidence in administering the correct dose (n = 300, 59.5%); ease of selecting the correct dose (n = 268, 53.2%); overall ease of using the injection device (n = 239, 47.4%); frequency of injections (n = 223, 44.2%); and ease of carrying the device when necessary to inject away from home (n = 190, 37.7%). Characteristics least frequently cited as important included dose escalation (n = 79, 15.7%); handling the needle (n = 74, 14.7%); connectivity to an electronic device (n = 70, 13.9%); and the time required to prepare and inject each dose (n = 62, 12.3%). Conclusion: Results of this survey suggest that patients prioritize some attributes of injectable treatments over others. These findings may have implications for clinical practice and development of injection devices. [ABSTRACT FROM AUTHOR]

Background. Infective endocarditis (IE) is challenging to manage in the COVID-19 lockdown period, in part given its reliance on echocardiography for diagnosis and management and the associated virus transmission risks to patients and healthcare workers. This study assesses utilisation of the endocarditis team (ET) in limiting routine echocardiography, especially transoesophageal echocardiography (TOE), in patients with suspected IE, and explores the effect on clinical outcomes. Methods. All patients discussed at the ET meeting at Imperial College Healthcare NHS Trust during the first lockdown in the UK (23 March to 8 July 2020) were prospectively included and analysed in this observational study. Results. In total, 38 patients were referred for ET review (71% male, median age 54 [interquartile range 48, 65.5] years). At the time of ET discussion, 21% had no echo imaging, 16% had point-of-care ultrasound only, and 63% had formal TTE. In total, only 16% underwent TOE. The ability of echocardiography, in those where it was performed, to affect IE diagnosis according to the Modified Duke Criteria was significant (p = 0.0099); however, sensitivity was not affected. All-cause mortality was 17% at 30 days and 25% at 12 months from ET discussion in those with confirmed IE. Conclusion. Limiting echocardiography in patients with a low pretest probability (not probable or definite IE according to the Modified Duke Criteria) did not affect the diagnostic ability of the Modified Duke Criteria to rule out IE in this small study. Moreover, restricting nonessential echocardiography, and importantly TOE, in patients with suspected IE through use of the ET did not impact all-cause mortality. [ABSTRACT FROM AUTHOR]

Orbital exenteration is a radical oncological surgery that is usually indicated for advanced primary orbital tumors or invasion from local malignancy. We report a 5-year series from a tertiary head and neck center with particular focus on our ablative and reconstructive approach. We performed a clinicopathological review of patients referred to Guy's and St Thomas' NHS Foundation Trust Head and Neck multidisciplinary team for management input of an orbital malignancy during the period of 2013 to 2018. Cases involving local invasion from sinonasal malignancy were excluded. The reconstructive approach, perioperative complications, disease-free and overall survival were analyzed. 27 patients were identified and of those treated surgically, a radical extended orbital exenteration was required in almost half (44.4%), with squamous cell carcinoma being the most common pathology (55.6%). A concurrent neck dissection and parotidectomy were commonly performed with confirmed or suspected regional disease, or in the presence of high-risk pathological features. This approach resulted in favourable 2-year overall survival in these advanced stage cases of 84.6% and disease-free survival of 73.2%, with 92% achieving a negative surgical margin. The majority of treated patients required a free flap reconstruction, especially when an extended exenteration defect or adjuvant treatment was anticipated. The anterolateral thigh flap was the most commonly used donor site, and we present our algorithm for reconstruction of these defects. A multidisciplinary approach to advanced orbital malignancy with a comprehensive approach to surgical resection and reconstruction results in favorable oncological outcomes and addresses functional and cosmetic patient rehabilitation. [ABSTRACT FROM AUTHOR]

Corporate criminal liability and piercing corporate veil are challenges of the criminal administration of justice. The company pleads lack of men's rea. The wrongdoers hide behind the corporate veil. However, justice and equity demand enforcement of criminal liability for crimes. The notions of corporate criminal liability piercing the corporate veil are duly recognized in statutes and precedents of Pakistan and the United Kingdom. However, some theoretical and procedural deficiencies ought to be addressed. The test to weigh corporate men's rea, the ambiguity of principles justifying piercing corporate veil, the multiplicity of forums, unregulated discretion of the court, and chances of double jeopardy are some of the important issues. The objectives of this research are to examine all the issues, identify the causes, and find out the remedial steps. The research methodology is mainly doctrinal and comparative through evaluation of statutes and precedents with the United Kingdom. This research has corporate and legal impacts. It shall aid expeditious and meritorious adjudication, development of positive corporate culture, and boosting public trust in the judiciary. The findings reveal that the major issues exist while the solution lies in the reformation of corporate criminal laws. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA) are sub-divided into intrahepatic (iCCA) or extrahepatic (eCCA). eCCA are further subdivided into perihilar (pCCA) and distal (dCCA). Current and previous versions of the WHO International Coding of Disease and Oncology classifications (ICD) have separate topography codes for iCCA and eCCA, but none for pCCA. Over recent decades, multiple studies report rising incidence rates of iCCA with declining rates of eCCA, without reference to pCCA. We hypothesised the lack of a specific code for pCCA has led to errors CCA coding, specifically with miscoding of pCCA as iCCA. Clinical notes of cases coded as hepatobiliary carcinoma using ICD-10 criteria (C22.1/Intrahepatic Bile Duct carcinoma, C24.0/Extrahepatic Bile Duct carcinoma, C23X/Malignant Neoplasm Gall Bladder, C22.0/Malignant Neoplasm Liver Cell Carcinoma) over a 2 year period (2015–2017), were reviewed by two independent clinicians at three independent UK regional HepatoPancreatoBiliary centres. The agreed final diagnosis was compared to the originally allocated ICD-10 code. Of the 625 CCA cases fully reviewed, 226 were coded as C22.1/iCCA. 98 (43%) of these were true iCCA and coded correctly, while 76 cases (34%) were actually pCCA. 92% all pCCA cases were incorrectly coded as iCCA. CCA coding misclassification in UK HPB centres is common, particularly the miscoding of pCCA, which is extrahepatic and the commonest form of CCA, as iCCA. This may be contributing to apparent rising incidence rates of iCCA. Our findings confirm the need to implement distinct topographical codes for iCCA, pCCA and dCCA in future iterations of ICD. [ABSTRACT FROM AUTHOR]

Introduction and objectives: The novel severe acute respiratory syndrome coronavirus 2 (COVID-19) pandemic has had drastic effects on global healthcare with the UK amongst the countries most severely impacted. The aim of this study was to examine how COVID-19 challenged the neurosurgical delivery of care in a busy tertiary unit serving a socio-economically diverse population. Methods: A prospective single-centre cohort study including all patients referred to the acute neurosurgical service or the subspecialty multidisciplinary teams (MDT) as well as all emergency and elective admissions during COVID-19 (18th March 2020–15th May 2020) compared to pre-COVID-19 (18th of January 2020–17th March 2020). Data on demographics, diagnosis, operation, and treatment recommendation/outcome were collected and analysed. Results: Overall, there was a reduction in neurosurgical emergency referrals by 33.6% and operations by 55.6% during the course of COVID-19. There was a significant increase in the proportion of emergency operations performed during COVID-19 (75.2% of total, n=155) when compared to pre-COVID-19 (n = 198, 43.7% of total, p < 0.00001). In contrast to other published series, the 30-day perioperative mortality remained low (2.0%) with the majority of post-operative COVID-19-infected patients (n = 13) having underlying medical co-morbidities and/or suffering from post-operative complications. Conclusion: The capacity to safely treat patients requiring urgent or emergency neurosurgical care was maintained at all times. Strategies adopted to enable this included proactively approaching the referrers to maintain lines of communications, incorporating modern technology to run clinics and MDTs, restructuring patient pathways/facilities, and initiating the delivery of NHS care within private sector hospitals. Through this multi-modal approach we were able to minimize service disruptions, the complications, and mortality. [ABSTRACT FROM AUTHOR]

Objectives: Problem bladder pain syndrome/interstitial cystitis (BPS/IC) is a heterogeneous disorder with variation in management worldwide. Phenotyping aims to personalize therapy and optimize outcomes. The most well‐described phenotype is Hunner lesion disease (HLD). The prevalence of HLD and outcome of phenotype‐directed management in the UK is not well‐studied. We describe the management of a contemporary cohort of patients with BPS/IC in the UK. Methods: Retrospective analysis of all patients with BPS/IC from January 2015‐November 2018. Outcomes of patients who underwent laser ablation to Hunner lesions were collected using the Global Response Assessment tool. Results: One hundred and sixty‐three patients (mean age of 43 years [20–85]) were included. 78% were female and patients had experienced symptoms for an average 6 years (1–30) prior to specialist assessment. Eighty‐three percent of patients had pelvic imaging (44% ultrasound, 42% magnetic resonance imaging and 14% computed tomography), and a relevant abnormality was found in five (4%). Twenty‐two patients (14%) had HLD (International Society for the Study of BPS [ESSIC] 3), with a mean bladder capacity of 373 mL (175‐650 mL); 77% were ESSIC C on histopathology. All patients with HLD underwent laser ablation, with 55% experiencing a moderate/marked improvement in symptoms, with a mean duration of effect of 10 months (3–36); 27% of patients had a repeat treatment. Conclusions: The presence of HLD in patients with BPS/IC is not uncommon. Pelvic imaging rarely identifies any cause for pain and so cystoscopy under anesthesia is essential for accurate phenotyping. Phenotype‐directed management with holmium laser ablation to Hunner lesions has good short‐term efficacy in improving pain, but re‐intervention is often required. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has altered the normal delivery of medical education globally. Following the cancelation of traditional course components such as elective placements, UK medical students have been able to carry out temporary roles within the NHS. We believe these events may have an effect on medical students' future choice of specialty. [ABSTRACT FROM AUTHOR]

This study aimed to compare the treatment pathway and 30-day outcomes of hip fracture patients admitted during the COVID-19 pandemic with the pre-pandemic period. Three periods were retrospectively analysed: period C = 23/03/2020–11/05/2020, period A = 23/03/2018–11/05/2018, period B = 23/03/2019–11/05/2019. No statistically significant differences in time to surgery, type of treatment, complications, and mortality rates were noted. A significant reduction (p = 0.021) in the time to orthogeriatric assessment and length of inpatient stay (p < 0.001) was found in period C. Institutional adaptions to facilitate prompt treatment in hip fractures during the pandemic resulted in favourable outcomes. [ABSTRACT FROM AUTHOR]

Patellar dislocations are a significant injury with the potential for long term problems. Little work has been done on establishing the mechanism by which this injury occurs. To determine the mechanism of injury of a patella dislocation based on the available published literature and compare them to already proposed theories. A systematic review of the literature was conducted following searches performed on MEDLINE, EMBASE and ProQuest from the earliest year of indexing using the following search terms in any combination: "patella", "dislocation", "mechanism of injury", "anatomy", "biomechanical" and "risk factor". A broad inclusion criteria was used that included studies that looked at patellar dislocations and instability with respect to the patellofemoral joint (PFJ) kinematics or altered kinematics of the PFJ. Studies that did not address the kinematics or biomechanics of the PFJ were excluded. Studies were appraised based on their methodology using a combination of the Critical Appraisal Skills Programme tool and the Quality Appraisal for Cadaveric Studies. 113 studies were identified from a search of MEDLINE, EMBASE and ProQuest databases. Following application of our inclusion criteria, a total of 23 studies were included in our review. 18 of these studies were cadaveric biomechanical studies. The remaining studies were anatomical, imaging based, and a computer simulation based study. These biomechanical and kinematic studies provide some evidence that a dislocation is likely to occur during early knee flexion with external rotation of the tibia and contraction of the quadriceps. There is limited evidence to support other elements of proposed mechanisms of dislocation. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is an inflammatory disorder of young children, associated with vasculitis of the coronary arteries with subsequent aneurysm formation in up to one-third of untreated patients. Those who develop aneurysms are at life-long risk of coronary thrombosis or the development of stenotic lesions, which may lead to myocardial ischaemia, infarction or death. The incidence of KD is increasing worldwide, and in more economically developed countries, KD is now the most common cause of acquired heart disease in children. However, many clinicians in the UK are unaware of the disorder and its long-term cardiac complications, potentially leading to late diagnosis, delayed treatment and poorer outcomes. Increasing numbers of patients who suffered KD in childhood are transitioning to the care of adult services where there is significantly less awareness and experience of the condition than in paediatric services. The aim of this document is to provide guidance on the long-term management of patients who have vascular complications of KD and guidance on the emergency management of acute coronary complications. Guidance on the management of acute KD is published elsewhere. [ABSTRACT FROM AUTHOR]

This paper investigates the dynamics of low income household (LIH) indebtedness under austerity in Britain. Building on a range of political economy studies on the role of the state in the process of financialisation, the paper discusses the transition in the nature of LIH indebtedness in connection to the recent welfare retrenchment. The analysis of survey data and semi-structured interviews establishes the fact that LIHs experienced the greatest growth in unsecured debt to income ratio under austerity. More importantly, unlike the pre-crisis period when LIHs' debt reflected a desire 'to keep-up with the Joneses', post crisis, a different form of indebtedness has emerged. There has been a notable rise in debt for essential needs such as rent, food and utility services. Liabilities are not only owed to banks and fringe providers (payday lenders, money shops, etc.) but also to non-financial companies and local authorities which have become de facto creditors. The evidence in this paper shows that these changes are directly related to the austerity measures, especially, to the cuts in welfare budgets and the intensified use of 'disciplinary techniques' in the form of sanctions and administrative / legal enforcement of debt collection by public sector entities. [ABSTRACT FROM AUTHOR]

Primary hepatobiliary cancer incidence in the UK is rising and survival rates are low. Surgery is the main curative option for these cancers, but multimodality therapies are expanding. The aim of our original study was to determine trends in survival, over an 8-year period, of patients treated for primary hepatobiliary cancers at our tertiary referral Centre. Patients treated for the most common types of primary hepatobiliary cancers, namely Hepatocellular carcinoma (HCC), Cholangiocarcinoma and Gallbladder cancer between January 2009 and December 2016 were retrospectively analysed from a prospective database linked to UK Hospital Episode Statistics data. A total of 1536 patients with primary hepatobiliary cancers were assessed and treatment plans formulated at our supra-regional specialist Hepatobiliary MDT. The primary hepatobiliary cancers treated were HCC (n = 836), Cholangiocarcinoma (n = 516), and Gallbladder cancer (n = 184). Survival for all the 3 cancers was significantly better with curative treatment. Overall median survival times were 350, 180, and 150 days respectively for HCC, Cholangiocarcinoma and Gallbladder cancer. Excluding best supportive care patients, the respective survival figures were 900, 600, and 400 days. Survival for HCC patients improved over time and was significantly increased in the final 3 years of the study (p ≤ 0.011 for all). Cholangiocarcinoma and Gallbladder cancer survivals were poor and did not change significantly over time. HCC outcome has improved in association with expanded multimodal therapies. Survivals for cholangiocarcinoma and gallbladder cancer remain poor in parallel with limited expansion of multimodal therapies highlighting an unmet therapeutic need for biliary tract cancers. [ABSTRACT FROM AUTHOR]

Aims: To assess the utility of corneal confocal microscopy in identifying small fiber damage in patients with burning mouth syndrome (BMS). Methods: A prospective cross-sectional cohort study was conducted at two United Kingdom dental hospitals between 2014 and 2017. A total of 17 consecutive patients with idiopathic BMS aged between 18 and 85 years and 14 healthy age-matched control subjects were enrolled in this study. Corneal subbasal nerve plexus measures were quantified in images acquired using a laser-scanning in vivo corneal confocal microscope. The main outcome measures were corneal nerve fiber density, nerve branch density, nerve fiber length, and Langerhans cell density. Results: Of the 17 patients with BMS, 15 (88%) were women, and the mean (standard deviation) age of the sample was 61.7 (6.5) years. Of the healthy controls, 7 (50%) were women, and the mean (standard deviation) age was 59.3 (8.68) years. Corneal nerve fiber density (no./mm2) (BMS: 29.27 ± 6.22 vs controls: 36.19 ± 5.9; median difference = 6.71; 95% CI: 1.56 to 11.56; P = .007) and corneal nerve fiber length (mm/mm2) (BMS: 21.06 ± 4.77 vs controls: 25.39 ± 3.91; median difference = 4.5; 95% CI: 1.22 to 6.81; P = .007) were significantly lower in BMS patients compared to controls, and Langerhans cell density (no./mm2) (BMS: 74.04 ± 83.37 vs controls: 29.17 ± 45.14; median difference = -21.27; 95% CI: -65.35 to -2.91; P = .02) was significantly higher. Conclusion: Using a rapid noninvasive ophthalmic imaging technique, this study provides further evidence for small fiber damage in BMS and has potential utility for monitoring disease progression and/or response. Furthermore, this technique shows a hitherto undocumented increased density of immune cells in this group of patients. [ABSTRACT FROM AUTHOR]

Aim: Colonoscopy certification in the UK is taken in two parts – provisional and full – mandating lifetime procedure counts of 200 or 300, respectively. The aim of this study was to determine the number of procedures performed by colorectal trainees by the end of training compared with their gastroenterology peers and to determine the factors associated with achieving the 300‐procedure target for full certification. Method: Dates of entry onto the specialist register were obtained from the General Medical Council. This list was cross‐referenced with procedure counts from the Joint Advisory Group on Gastrointestinal Endoscopy (JAG) Endoscopy Training System database to determine the number of colonoscopies and polypectomies performed during training. Factors associated with achieving 300 procedures were analysed by logistic regression. Results: Procedures numbers were obtained for 234 gastroenterology and 148 colorectal surgery trainees. Over the last 5 years, the number of colonoscopies performed during training has declined for colorectal surgery trainees but increased for gastroenterology trainees. Gastroenterology trainees are more likely to achieve provisional and full certification. For trainees completing training in 2017, 19% of colorectal surgery trainees compared with 88% of gastroenterology trainees were able to reach the threshold of 300 procedures for full certification. Conclusion: Colorectal surgery trainees lag behind their gastroenterology counterparts in accruing endoscopy experience. This affects the ability of colorectal surgery trainees to achieve certification prior to completion of training. An urgent debate is required to decide what endoscopy training is required of a colorectal surgeon and how a robust training system can be put in place to ensure this is achieved. [ABSTRACT FROM AUTHOR]

This study aimed to create a new prognostic score integrating the systemic inflammatory response to predict survival in patients treated with curative intent for colorectal liver metastases (CLM). We identified independent prognostic factors in patients who underwent liver surgery for CLM in a tertiary centre in the United Kingdom (UK) between 2010 and 2015. A pre- and a postoperative score (Liverpool score) were created by combining these factors to stratify patients into different risk groups. These new scores were validated in an international cohort of 219 patients from China and France. Multivariate cox regression analysis of the 364 patients of the UK cohort identified 6 preoperative and 1 postoperative prognostic factors for overall survival (OS): American society of anaesthesiologists (ASA) score, location and node status of the primary tumour, number and size of CLM, neutrophil-to-lymphocyte ratio (NLR) and resection margin. Both pre- and postoperative scores can be calculated with an online calculator at https://jscalc.io/calc/PXatrmjfrEFpYy2t. Using the pre-operative model on the UK cohort, median OS was 61.22 (50.23, not reached) months in the low-risk group (n = 162) and 30.36 (23.68, 35.95) months in the high-risk group (n = 162, p < 0.0001). The same difference was observed in the validation cohort. The Liverpool score outperformed previously published scoring system with a c-index of 0.619 pre-operatively and of 0.637 post-operatively. We developed a new prognostic score based on clinicopathologic characteristics including the site of the primary tumour location and on measurement of the systemic inflammatory response which could help to tailor patients' management. [ABSTRACT FROM AUTHOR]