The Association of Surgeons in Training (ASiT) Consensus Statement on Major Trauma Training in the UK.

INTRODUCTION: Since the establishment of the Major Trauma Networks in 2012, it is estimated that an extra 1,600 lives have been saved across England. Although the delivery of trauma care has improved significantly, the provision of trauma training has not and remains fragmented. The Association of Surgeons in Training (ASiT), an independent organisation run by trainees, is dedicated to excellence in surgical training within the United Kingdom (UK) and Republic of Ireland (ROI). The aim of this study was to develop a consensus statement representing the views of the ASiT on the future of trauma surgery training. METHODS: A modified nominal group technique was used in five stages: 1, scoping exercise; 2, virtual consultation; 3, nominal group consensus meeting; 4, virtual feedback from stakeholders; and 5, virtual confirmation by the ASiT Council. The design and reporting of the consensus followed best practice methodology for consensus research. RESULTS: Overall, 62 participants gave 90 statements across stages 1-3. Eleven key themes were identified, all of which met the consensus of the ASiT Council. The key findings were widespread support for increased exposure to trauma for medical students and early surgical trainees as well as an increased use of simulation methods and improved focus on non-technical skills within trauma surgery. CONCLUSIONS: This study sets out the position of the ASiT on the future of trauma surgery training and how training in major trauma surgery in the UK and ROI could be improved.

'Factors influencing future career choices of Queen's University Belfast Medical students.'

INTRODUCTION: Decisions made by medical students on future career choice have demonstrated concordance with subsequent postgraduate career path. This study aimed to understand the factors that impact undergraduate career decision making. METHODS: An anonymous voluntary survey consisting of binominal, Likert and free text responses was distributed to all medical students registered at Queen's University Belfast (QUB). Data was collected over 6 weeks in April-May 2021. The primary outcome was future career aspirations. The secondary outcomes were the impact of mentorship on career choice, the likelihood of students completing their medical degree and practicing medicine upon graduation. Local ethical approval was obtained. RESULTS: 202 responses were received (response rate 15%). 67% (n = 135) were female. One third of respondents remained undecided about their future career choice. Surgery was both the most popular definite career choice (16.3%) of respondents, butalsothespecialtymarkedmostoftenas'Least preferred Specialty' (33%). Factors positively influencing career choice were academic interest and flexibility in working hours. Negative predictors of career choice were lack of interest in the area, perceived workload, and duration of training schemes. 71% (n=144) of respondents reported that a subspecialty mentor would positively influence their career choice and two-thirds of respondents reported that financial factors would influence their career decision. 11% (n= 22) of respondents were unsure or undecided if they would continue medicine as a career upon graduation. CONCLUSION: Uncertainty over future career intention remains common with surgery the least popular speciality. Mentorship, integrating flexibility in training and enhancing academic interest should be considered by educational stakeholders as mechanisms to generating undergraduate interest in a subspecialty. Furthermore, the reported rate of students intention to leave their medical degree prior to graduation by this cohort is concerning, warranting further investigation.

Quantitative Viral Outgrowth Assay to Measure the Functional SIV Reservoir in Myeloid Cells.

The role of CD4+ T cells in HIV infection and the latent reservoir, that is, latently infected cells that harbor replication competent virus, has been rigorously assessed. We have previously reported a quantitative viral outgrowth assay (QVOA) for SIV that demonstrated the frequency of latently infected CD4+ T cells is approximately 1 in a million cells, similar to that of HIV infected individuals on ART. However, the frequency of productively infected monocytes in blood and macrophages in tissues has not been similarly studied. Myeloid cells are infected during acute HIV and SIV infection; however, unlike lymphocytes, they are resistant to the cytopathic effects of the virus. Moreover, tissue-resident macrophages have the ability to self-renew and persist in the body for months to years. Thus, tissue macrophages, once infected, have the characteristics of a stable viral reservoir. A better understanding of the number of productively infected macrophages is critical to understanding the role of infected myeloid cells as a viral reservoir. In order to assess the functional latent reservoir. we have developed specific QVOAs for monocytes in blood, and macrophages in spleen, BAL and brain, which are described in detail in this chapter.

Recent advancements and application of in vitro models for predicting inhalation toxicity in humans.

Animals have been indispensable in testing chemicals that can pose a risk to human health, including those delivered by inhalation. In recent years, the combination of societal debate on the use of animals in research and testing, the drive to continually enhance testing methodologies, and technology advancements have prompted a range of initiatives to develop non-animal alternative approaches for toxicity testing. In this review, we discuss emerging in vitro techniques being developed for the testing of inhaled compounds. Advanced tissue models that are able to recreate the human response to toxic exposures alongside examples of their ability to complement in vivo techniques are described. Furthermore, technology being developed that can provide multi-organ toxicity assessments are discussed.

The quantitative impact of COVID-19 on surgical training in the United Kingdom.

BACKGROUND: COVID-19 has had a global impact on all aspects of healthcare including surgical training. This study aimed to quantify the impact of COVID-19 on operative case numbers recorded by surgeons in training, and annual review of competency progression (ARCP) outcomes in the UK. METHODS: Anonymized operative logbook numbers were collated from electronic logbook and ARCP outcome data from the Intercollegiate Surgical Curriculum Programme database for trainees in the 10 surgical specialty training specialties.Operative logbook numbers and awarded ARCP outcomes were compared between predefined dates. Effect sizes are reported as incident rate ratios (IRR) with 95 per cent confidence intervals. RESULTS: Some 5599 surgical trainees in 2019, and 5310 in surgical specialty training in 2020 were included. The IRR was reduced across all specialties as a result of the COVID-19 pandemic (0.62; 95 per cent c.i. 0.60 to 0.64). Elective surgery (0.53; 95 per cent c.i. 0.50 to 0.56) was affected more than emergency surgery (0.85; 95 per cent c.i. 0.84 to 0.87). Regional variation indicating reduced operative activity was demonstrated across all specialties. More than 1 in 8 trainees in the final year of training have had their training extended and more than a quarter of trainees entering their final year of training are behind their expected training trajectory. CONCLUSION: The COVID-19 pandemic has had a major effect on surgical training in the UK. Urgent, coordinated action is required to minimize the impacts from the reduction in training in 2020.

Adapting an emergency general surgery service in response to the COVID-19 pandemic.

INTRODUCTION: In response to the COVID-19 pandemic, our emergency general surgery (EGS) service underwent significant restructuring, including establishing an enhanced ambulatory service and undertaking nonoperative management of selected pathologies. The aim of this study was to compare the activity of our EGS service before and after these changes. METHODS: Patients referred by the emergency department were identified prospectively over a 4-week period beginning from the date our EGS service was reconfigured (COVID) and compared with patients identified retrospectively from the same period the previous year (Pre-COVID), and followed up for 30 days. Data were extracted from handover documents and electronic care records. The primary outcomes were the rate of admission, ambulation and discharge. RESULTS: There were 281 and 283 patients during the Pre-COVID and COVID periods respectively. Admission rate decreased from 78.7% to 41.7%, while there were increased rates of ambulation from 7.1% to 17.3% and discharge from 6% to 22.6% (all p<0.001). For inpatients, mean duration of admission decreased (6.9 to 4.8 days), and there were fewer operative or endoscopic interventions (78 to 40). There were increased ambulatory investigations (11 to 39) and telephone reviews (0 to 39), while early computed tomography scan was increasingly used to facilitate discharge (5% vs 34.7%). There were no differences in 30-day readmission or mortality. CONCLUSIONS: Restructuring of our EGS service in response to COVID-19 facilitated an increased use of ambulatory services and imaging, achieving a decrease of 952 inpatient bed days in this critical period, while maintaining patient safety.

Facing the Ethical Challenges: Consumer Involvement in COVID-19 Pandemic Research.

Consumer involvement in clinical research is an essential component of a comprehensive response during emergent health challenges. During the COVID-19 pandemic, the moderation of research policies and regulation to facilitate research may raise ethical issues. Meaningful, diverse consumer involvement can help to identify practical approaches to prioritize, design, and conduct rapidly developed clinical research amid current events. Consumer involvement might also elucidate the acceptability of flexible ethics review approaches that aim to protect participants whilst being sensitive to the challenging context in which research is taking place. This article describes the main ethical challenges arising from pandemic research and how involving consumers and the community could enable resolution of such issues.

An experimental aerosol air-agar interface mouse lymphoma assay methodology.

This work investigates a completely novel and experimental concept of exposing L5178Y cells at the air-agar-interface to mainstream cigarette smoke aerosol (Kentucky reference 3R4F). This study highlights the associated challenges of combining a suspension cell line alongside an in vitro aerosol exposure system. To achieve a monolayer, cells were 'seeded' in a concentrated cell super-mix suspension onto an RPMI/agar-matrix -base. The resulting cell suspension media was adsorbed into the agar base leaving the L5178Y cells lightly suspended on the agar surface, approximating a monolayer. Cells were deemed supportable on the agar-matrix, viable and recoverable. Using Vitrocell VC 10 exposure system and the Ames 4 exposure module, L5178Y cells were successfully exposed to a dynamic cigarette smoke aerosol, recovered and assessed for mutant frequencies, using standard assay procedures. Method development included assessment of flowing air conditions, plating efficiency and recovery of L5178Y cells from the agar-matrix surface. Positive controls MMS and B[a]P were successfully incorporated into the agar-matrix and metabolic activation was achieved by S-9 incorporation into the same agar-base-matrix. B[a]P demonstrated metabolic activation and positive response, suggesting a clear cellular interaction with the agar-matrix. Whole smoke exposed cells in the presence of metabolic activation showed a clear dose response and increasing mutant frequencies, well in excess of the controls (air and incubator) and the global evaluation factor following a 2 or 3 day expression period. This experimental concept demonstrates that L5178Y cells can be exposed to cigarette smoke aerosol, using a completely novel and a previously untested approach. Although this work successfully demonstrates the approach is viable and cells can be plated and maintained on an agar-matrix, more optimisation and robustness assessment is required before it can be considered fully adapted and used alongside other whole aerosol methodologies for the assessment of cigarette smoke and other inhaled aerosols.

Predicting the safety of medicines in pregnancy: A workshop report.

The framework for developmental toxicity testing has remained largely unchanged for over 50 years and although it remains invaluable in assessing potential risks in pregnancy, knowledge gaps exist, and some outcomes do not necessarily correlate with clinical experience. Advances in omics, in silico approaches and alternative assays are providing opportunities to enhance our understanding of embryo-fetal development and the prediction of potential risks associated with the use of medicines in pregnancy. A workshop organised by the Medicines and Healthcare products Regulatory Agency (MHRA), "Predicting the Safety of Medicines in Pregnancy - a New Era?", was attended by delegates representing regulatory authorities, academia, industry, patients, funding bodies and software developers to consider how to improve the quality of and access to nonclinical developmental toxicity data and how to use this data to better predict the safety of medicines in human pregnancy. The workshop delegates concluded that based on comparative data to date alternative methodologies are currently no more predictive than conventional methods and not qualified for use in regulatory submissions. To advance the development and qualification of alternative methodologies, there is a requirement for better coordinated multidisciplinary cross-sector interactions coupled with data sharing. Furthermore, a better understanding of human developmental biology and the incorporation of this knowledge into the development of alternative methodologies is essential to enhance the prediction of adverse outcomes for human development. The output of the workshop was a series of recommendations aimed at supporting multidisciplinary efforts to develop and validate these alternative methodologies.

Innovation in surgical practice: The Association of Surgeons in Training conference - Belfast 2019.

The Association of Surgeons in Training (ASiT) advocates for and represents surgical trainees throughout the United Kingdom and the Republic of Ireland. It promotes excellence in surgical training for the benefit of both surgeons and patients. Originally founded in 1976, ASiT is independent of the National Health Service (NHS), Surgical Royal Colleges, and Specialty Associations. The 2019 Annual Conference in Belfast hosted a record number of delegates (n = 855) over the 3-day educational weekend. The conference theme, "Innovation in Surgical Practice" focused on the latest educational and technological innovation to enhance trainee's knowledge and experience of surgical innovation to ultimately enhance patient care. A record number of technical and non-technical pre-conference courses (n = 13) covering a diverse range of topics was offered. A new feature, a 24-h Hackathon, was successfully delivered in parallel to the Conference. This opportunity generated productive, cross speciality collaboration, to address and solve current problems in healthcare. Over 1000 abstract submissions were received and there were over 30 poster and oral prizes on offer for winning submissions. The ASiT conference and the Association continues to grow annually and we look forward to welcoming delegates to Birmingham from the 6-8th March 2020 to enjoy another action packed weekend focused on "Optimising Performance".

Constraints to counting bioluminescence producing cells by a commonly used transgene promoter and its implications for experimental design.

It is routine to genetically modify cells to express fluorescent or bioluminescent reporter proteins to enable tracking or quantification of cells in vitro and in vivo. Herein, we characterized the stability of luciferase reporter systems in C4-2B prostate cancer cells in mono-culture and in co-culture with bone marrow-derived mesenchymal stem/stromal cells (BMSC). An assumption made when employing the luciferase reporter is that the luciferase expressing cell number and bioluminescence signal are linearly proportional. We observed instances where luciferase expression was significantly upregulated in C4-2B cell populations when co-cultured with BMSC, resulting in a significant disconnect between bioluminescence signal and cell number. We subsequently characterized luciferase reporter stability in a second C4-2B reporter cell line, and six other cancer cell lines. All but the single C4-2B reporter cell population had stable luciferase reporter expression in mono-culture and BMSC co-culture. Whole-genome sequencing revealed that relative number of luciferase gene insertions per genome in the unstable C4-2B reporter cell population was lesser than stable C4-2B, PC3 and MD-MBA-231 luciferase reporter cell lines. We reasoned that the low luciferase gene copy number and genome insertion locations likely contributed to the reporter gene expression being exquisitely sensitive BMSC paracrine signals. In this study, we show that it is possible to generate a range of stable and reliable luciferase reporter prostate- and breast- cancer cell populations but advise not to assume stability across different culture conditions. Reporter stability should be validated, on a case-by-case basis, for each cell line and culture condition.

Simulation in surgical training: Prospective cohort study of access, attitudes and experiences of surgical trainees in the UK and Ireland.

BACKGROUND: Surgical training is evolving, and simulation is becoming more important as a way to expedite the early learning curve and augment surgical techniques. With novel technology, and innovation, major changes are possible in how surgeons are trained. The integration of these concepts into the surgical curriculum may drive up educational standards and enhance patient safety. This survey sought to determine surgical trainees views on the current place of simulation in surgical training and explore their vision for the future. MATERIAL AND METHODS: This is a prospective, questionnaire-based cross-sectional study by *** and the ***, England. Surgical trainees were surveyed about their experiences of simulation during their training through an electronic questionnaire distributed in the UK and Republic of Ireland through mailing lists of RCS and ***. Quantitative and qualitative research methodology was used. RESULTS: Of 462 surveys submitted, a total of 323 were fully completed and included in the analysis. Core Surgical Trainees represented 28.4% of respondents. The vast majority of respondents (98.9%) considered that simulation training was important, however 55.0% felt it was delivered inadequately. 86.2% wanted greater access to simulation training: Less than half of respondents had access to simulation training at their current place of work or had simulation incorporated into their formal teaching programme (42.4% and 41.6% respectively). CONCLUSION: This study highlights the importance of simulation to trainees. Delivery and accessibility of simulation training varies widely. We highlight areas for improvement and best practice. In a culture of accountability, where patient safety is our highest priority, a "see one, do one, teach one" approach to training is no longer appropriate; instead we must utilise available simulation tools to augment learning.