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.

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.

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.

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".

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.

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.

Efficiency of translation initiation by non-AUG codons in Saccharomyces cerevisiae.

The quantitative levels of initiation of protein synthesis at codons other than AUG were determined with a CYC7-lacZ fused gene in the yeast Saccharomyces cerevisiae. AUG was the only codon which efficiently initiated translation, although some non-AUG codons allowed initiation at very low efficiency, below 1% of the normal level. Since translation initiates at codons other than AUG in at least two wild-type genes from eucaryotes, other factors presumably play a role in enhancing the activity of non-AUG codons.

Respirable dust concentrations in equine stables. Part 2: the benefits of soaking hay and optimising the environment in a neighbouring stable.

The effect of soaking hay to minimise equine breathing zone respirable dust concentration (RDC) is unknown, as is the duration of soaking required. Additionally, the influence of the bedding and forage used in one stable on the mean and maximum RDC in a neighbouring stable within a common airspace is unknown. Consequently, in the management of equine environmental respiratory disease uncertainty remains about the necessity for optimising conditions in neighbouring stables. Investigations using a real-time continuous particle monitor revealed that when feeding hay, horses' mean breathing zone RDC was significantly reduced if the hay was immersed or soaked for a prolonged time, prior to feeding. There was no advantage in soaking for an extended time period. Implementing management changes in one stable (changing from straw bedding and hay feeding to wood shavings bedding and haylage feeding) significantly reduced mean and maximum background RDC in a neighbouring stable within a common airspace.

Respirable dust concentrations in equine stables. Part 1: validation of equipment and effect of various management systems.

Traditional methods of measuring airborne dust concentrations (ADC) in animal housing have included the collection of dust onto pre-weighed filters permitting the calculation of mean, not maximum, ADC. However real-time continuous particle monitors are advantageous in identifying short duration elevations in ADC which may be detrimental to equine respiratory health in the face of a relatively low mean ADC. These monitors have not previously been used to measure ADC in equine stables. Comparisons of a filter-based sampler and a real-time continuous particle monitor revealed no significant difference (P=0.079) and good agreement (>or=95% of the points fell within two standard deviations of the mean of the differences and the mean of the differences approximated zero) between the devices, with respect to mean respirable dust concentration (RDC) measurements. Investigations of the influence of various equine management systems on RDC revealed that both mean and maximum breathing zone RDC were significantly reduced (P<0.05) in equine stables by changing the environment from hay feed and straw bedding, to haylage feed and wood shavings bedding (reduction in mean - 0.0867mg/m(3) to 0.0260mg/m(3); reduction in maximum - 4.0758mg/m(3) to 0.2182mg/m(3), respectively).

Applying dynamic data collection to improve dry electrode system performance for a P300-based brain-computer interface.

OBJECTIVE: Dry electrodes have an advantage over gel-based 'wet' electrodes by providing quicker set-up time for electroencephalography recording; however, the potentially poorer contact can result in noisier recordings. We examine the impact that this may have on brain-computer interface communication and potential approaches for mitigation. APPROACH: We present a performance comparison of wet and dry electrodes for use with the P300 speller system in both healthy participants and participants with communication disabilities (ALS and PLS), and investigate the potential for a data-driven dynamic data collection algorithm to compensate for the lower signal-to-noise ratio (SNR) in dry systems. MAIN RESULTS: Performance results from sixteen healthy participants obtained in the standard static data collection environment demonstrate a substantial loss in accuracy with the dry system. Using a dynamic stopping algorithm, performance may have been improved by collecting more data in the dry system for ten healthy participants and eight participants with communication disabilities; however, the algorithm did not fully compensate for the lower SNR of the dry system. An analysis of the wet and dry system recordings revealed that delta and theta frequency band power (0.1-4 Hz and 4-8 Hz, respectively) are consistently higher in dry system recordings across participants, indicating that transient and drift artifacts may be an issue for dry systems. SIGNIFICANCE: Using dry electrodes is desirable for reduced set-up time; however, this study demonstrates that online performance is significantly poorer than for wet electrodes for users with and without disabilities. We test a new application of dynamic stopping algorithms to compensate for poorer SNR. Dynamic stopping improved dry system performance; however, further signal processing efforts are likely necessary for full mitigation.

Crystallization and preliminary X-ray diffraction characterisation of both a native and selenomethionyl VLA-4 binding fragment of VCAM-1.

Soluble fragments of the extracellular region of vascular cell adhesion molecule 1 (VCAM-1) expressed in Escherichia coli retain functional adhesive activity. An integrin (VLA-4) binding fragment consisting of the N-terminal two immunoglobulin-like domains (VCAM-d1,2) has been crystallized. The crystals belong to space group P2(1)2(1)2(1) with cell dimensions of a = 52.7 A, b = 66.5 A, c = 113.2 A and contain two molecules in the crystallographic asymmetric unit. A batch of protein produced in the standard E. coli strain (HW1110), but grown in the presence of selenomethionine enriched media, showed 85% incorporation of selenium in place of sulphur at methionine residues. The selenomethionyl VCAM-d1,2 was crystallized by microseeding techniques initially using the native crystals for nucleation. Both native and selenomethionyl crystals diffract X-rays to a minimum Bragg spacing of 1.8 A.

Matrix metalloproteinases and processing of pro-TNF-alpha.

Tumor necrosis factor-alpha (TNF-alpha) is released from a cell membrane-anchored precursor by proteolytic cleavage. We have shown that broad spectrum synthetic inhibitors of matrix metalloproteinases (MMPs) prevent the processing of the TNF precursor but do not inhibit the release of other cytokines. Purified MMPs, stromelysin, matrilysin, collagenase, and the gelatinases can all cleave a recombinant pro-TNF substrate to yield mature TNF. MMP inhibitors prevent the rise in blood levels of TNF after endotoxin administration in rats and are effective in animal models of inflammatory disease such as adjuvant arthritis. Drugs that inhibit MMP action and TNF release show great promise for the treatment of autoimmune inflammatory diseases.

Transcription and processing signals in the 3-phosphoglycerate kinase (PGK) gene from Aspergillus nidulans.

The 3-phosphoglycerate kinase gene from Aspergillus nidulans contains two 57-bp introns and codes for a 421-amino acid (aa) protein with considerable homology to the Saccharomyces cerevisiae (68%) and mammalian (64%) proteins. Almost total conservation is found in Aspergillus of residues thought to be important to the structure and function of the yeast enzyme, and the introns fall between coding sequences for postulated structures in the N-domain. The strong codon preference found is more similar to that in other filamentous fungi than in yeast. The transcription start point (+1) has been mapped 32 bp upstream from the start codon, and the promoter region contains potential homologies for CAAT (-80 bp) and TATA (-30 bp) sequences, and certain other features common to other highly expressed genes in ascomycetes. There are three major termini 23, 83 and 115 bp beyond the stop codon and two of these are preceded by the polyadenylation consensus sequence and contain potential secondary structure.

Expression and activity of a gene encoding rat cytochrome c in the yeast Saccharomyces cerevisiae.

A rat-processed pseudogene, which encodes normal rat cytochrome c, has been expressed in the yeast, Saccharomyces cerevisiae. The translated region of the chromosomal CYC1+ locus, which encodes yeast iso-1-cytochrome c, was replaced by the translated region of the gene encoding rat cytochrome c (CYC1-RAT), thus preserving the proper CYC1 transcription initiation and termination signals. Although the levels of transcription of the normal CYC1+ gene and the CYC1-RAT gene in yeast were equivalent, rat cytochrome c was produced at approx. 40% of the level of iso-1-cytochrome c. In addition, the specific activity in vivo was estimated to be approx. 60% that of the yeast iso-1-cytochrome c. N-terminal processing of indigenous rat cytochrome c, in which the N-terminal methionine residue is cleaved and the penultimate glycine residue is acetylated, also occurred in yeast. Methionine cleavage was complete, while acetylation proceeded to only 70% completion. Lys-72 was trimethylated to 66% completion in the rat cytochrome c produced in yeast. The near normal expression (40%) and specific activity (60%) in vivo indicates that the 40% difference in amino acid sequence is not critical for mitochondrial import, heme attachment and interactions with redox partners.

Secretion of human epidermal growth factor from Saccharomyces cerevisiae using synthetic leader sequences.

We have investigated different leader sequences for their ability to direct the efficient secretion of human epidermal growth factor (hEGF) from Saccharomyces cerevisiae. We designed a consensus signal sequence which directs secretion of hEGF from yeast as efficiently as the yeast invertase signal sequence. However, secretion is increased over fivefold by the introduction, after the signal sequence, of a synthetic 19-amino acid (aa) pro-sequence containing a cleavage recognition site for the KEX2 protease. Even in the absence of an Asn-linked glycosylation site, secretion of hEGF using the synthetic prepro-leader was as efficient as that directed by the alpha-factor leader. The role of the KEX2 protease cleavage site was investigated by mutation of the yeast alpha-factor KEX2 site (cleavage after Lys-Arg). Cleavage was obtained with the following order of efficiency, Lys-Arg greater than Pro-Arg greater than Asp-Arg, although the sequence context was also found to affect efficiency.

Synthesis and expression of genes encoding tuna, pigeon, and horse cytochromes c in the yeast Saccharomyces cerevisiae.

Genes encoding tuna, pigeon, and horse cytochromes c were constructed with synthetic oligodeoxyribonucleotides having preferred codons and portions of the iso-1-cytochrome c-encoding gene from the yeast Saccharomyces cerevisiae. The genes were ligated into an expression vector, which contains the normal 5'- and 3'-untranslated regions of the yeast iso-1-cytochrome c gene, and were integrated in single copy into the chromosome. Yeast strains were also constructed with multiple integrated copies of the pigeon gene. The heterologous and normal mRNA levels of the single-copy strains were equivalent. Although the N-terminal methionines were completely cleaved in the heterospecific proteins, the levels of trimethylation of Lys72 and acetylation of N-terminal glycines ranged from 39-78% and 10-70%, respectively. Horse cytochrome c was produced at a nearly normal level, whereas the pigeon and tuna cytochromes c were produced at approx. 40% of the normal levels. The levels of the cytochromes c and growth of the mutant yeast strains indicated that the heterospecific cytochromes c had approx. 50% specific activity in vivo.

Cloning and characterization of a gene encoding pig epidermal growth factor.

A portion of the pig epidermal growth factor (EGF) gene has been isolated and characterized. The nucleotide sequencies of exons 20 and 21, which encode the EGF region of the precursor protein, show 85% similarity with the human EGF gene sequence. In addition, conservation of the intron-exon boundaries between the two species was generally observed. Although the pig exon 21 appeared to lack a single nucleotide at its 5' end relative to the human gene, sequences obtained by direct amplification of the genomic DNA around the 5' end of this exon using the polymerase chain reaction, and from a pig EGF cDNA recombinant isolated from a kidney library, indicated that the deletion was probably a cloning artifact. Comparison of the predicted amino acid sequence of pig EGF with that of EGF from other species, as well as with several other polypeptides which bind to the EGF receptor, indicated conservation of Gly18, Tyr37, Gly39 and Arg41 in addition to all six cysteine residues and Leu47, which are known to be critical for biological activity. A synthetic gene encoding the predicted amino acid sequence of pig EGF was expressed in yeast. The recombinant polypeptide was shown to compete with 125I-labelled mouse EGF for binding to cells and to stimulate DNA synthesis in quiescent monolayers of Swiss 3T3 cells.