Bridging that gap: a qualitative study of perceptions of equality, diversity and inclusivity in colorectal surgery in the UK and Ireland.

BACKGROUND: There is a growing recognition on the importance of equality, diversity and inclusion (EDI) within surgery and the need to diversify the surgical community and its various organisations, in a bidto reflect the diverse populations they serve. To create, sustain and encourage a diverse surgical workforce requires an in-depth understanding of the current makeup of key surgical institutions, relevant issues pertaining to EDI and appropriate solutions and strategies to ensure tangible change. OBJECTIVES: Following on from the recent Kennedy Review into Diversity and Inclusion commissioned by the Royal College of Surgeons of England, the aim of this qualitative study was to understand the EDI issues which affected the membership of the Association of Coloproctology of Great Britain and Ireland, while seeking appropriate solutions to address them. DESIGN: Dedicated, online and qualitative focus groups. PARTICIPANTS: Colorectal surgeons, trainees and nurse specialists were recruited using a volunteer sampling strategy. METHODS: A series of online, dedicated, qualitative focus groups across the 20 chapter regions were held. Each focus group was run informed by a structured topic guide. All participants who were given the opportunity to remain anonymous were offered a debriefing at the end. This study has been reported in keeping with the Standards for Reporting Qualitative Research. RESULTS: Between April and May 2021, a total number of 20 focus groups were conducted, with a total of 260 participants across 19 chapter regions. Seven themes and one standalone code pertaining to EDI were identified: support, unconscious behaviours, psychological consequences, bystander behaviour, preconceptions, inclusivity and meritocracy and the one standalone code was institutional accountability. Five themes were identified pertaining to potential strategies and solutions: education, affirmative action, transparency, professional support and mentorship. CONCLUSION: The evidence presented here is of a range of EDI issues which affect the working lives of those within colorectal surgery in the UK and Ireland, and of potential strategies and solutions which can help build a more inclusive, equitable and diverse colorectal community.

Agrobacterium-mediated direct transformation of wheat mature embryos through organogenesis.

Transgenic plant production in monocotyledonous species has primarily relied on embryogenic callus induction from both immature and mature embryos as the pathway for plant regeneration. We have efficiently regenerated fertile transgenic wheat plants through organogenesis after Agrobacterium-mediated direct transformation of mechanically isolated mature embryos from field-grown seed. Centrifugation of the mature embryos in the presence of Agrobacterium was found to be essential for efficient T-DNA delivery to the relevant regenerable cells. The inoculated mature embryos formed multiple buds/shoots on high-cytokinin medium, which directly regenerated into transgenic shoots on hormone-free medium containing glyphosate for selection. Rooted transgenic plantlets were obtained within 10-12 weeks after inoculation. Further optimization of this transformation protocol resulted in significant reduction of chimeric plants to below 5%, as indicated by leaf GUS staining and T1 transgene segregation analysis. Direct transformation of wheat mature embryos has substantial advantages over traditional immature embryo-based transformation systems, including long-term storability of the mature dry explants, scalability, and greatly improved flexibility and consistency in transformation experiments.

Commercial scale genetic transformation of mature seed embryo explants in maize.

A novel, efficient maize genetic transformation system was developed using Agrobacterium-mediated transformation of embryo explants from mature seeds. Seeds from field grown plants were sterilized and crushed to isolate embryo explants consisting of the coleoptile, leaf primordia, and shoot apical meristem which were then purified from the ground seed bulk preparation. The infection of relevant tissues of seed embryo explants (SEEs) by Agrobacterium was improved by the centrifugation of the explants. Transgenic plants were obtained by multiple bud induction on high cytokinin media, followed by plant regeneration on hormone-free medium. Three different selectable markers (cp4 epsps, aadA, and nptII) were successfully used for producing transgenic plants. Stable integration of transgenes in the maize genome was demonstrated by molecular analyses and germline transmission of the inserted transgenes to the next generation was confirmed by pollen segregation and progeny analysis. Phenotypic evidence for chimeric transgenic tissue was frequently observed in initial experiments but was significantly reduced by including a second bud induction step with optimized cytokinin concentration. Additional improvements, including culturing explants at an elevated temperature during bud induction led to the development of a revolutionary system for efficient transgenic plant production and genome editing. To our knowledge, this is the first report of successful transgenic plant regeneration through Agrobacterium-mediated transformation of maize mature SEEs. This system starts with mature seed that can be produced in large volumes and the SEEs explants are storable. It has significant advantages in terms of scalability and flexibility over methods that rely on immature explants.

The development of a minimum dataset for MRI reporting of anorectal fistula: a multi-disciplinary, expert consensus process.

There are a range of sphincter-preserving procedures available to treat anorectal fistula, some of which can be precluded, or rendered more optimal by specific features of fistula anatomy. Magnetic resonance imaging (MRI) is the gold standard modality for assessing anorectal fistula. To maximise clinical utility, the MRI report should accurately describe these clinically relevant features. We aimed to develop a minimum dataset for reporting MRI of anorectal fistula, in order to improve the assessment and management of these patients. A longlist of 70 potential items for the minimum dataset was generated through systematic review of the literature. This longlist was presented to radiologists, surgeons and gastroenterologists in an online survey to understand the features that shape current clinical practice. The longlist and survey results were then presented to an expert consensus panel to generate the final minimum dataset through discussion and anonymous voting. The final minimum dataset details the general characteristics, features of the internal and external openings, path of the fistula through the sphincters and any associated extensions and collections that should be described in all MRI reports for anal fistula. Additional surgical and perianal Crohn's disease subsets were developed to indicate the features that aid decision-making for these patients, in addition to a minimum dataset for the clinical request. This study represents a multi-disciplinary approach to developing a minimum dataset for MRI reporting of anal fistula, highlighting the most important features to report that can assist in clinical decision-making. KEY POINTS: • This paper recommends the minimum features that should be included in all MRI reports for the assessment of anal fistula, including Parks classification, number of tracts, features of the internal and external opening, path of the tract through the sphincters, the presence and features of extensions and collections. • Additional features that aid decision-making for surgery or in the presence of Crohn's disease have been identified. • The items that should be included when requesting an MRI are specified.

Demonstration of targeted crossovers in hybrid maize using CRISPR technology.

Naturally occurring chromosomal crossovers (CO) during meiosis are a key driver of genetic diversity. The ability to target CO at specific allelic loci in hybrid plants would provide an advantage to the plant breeding process by facilitating trait introgression, and potentially increasing the rate of genetic gain. We present the first demonstration of targeted CO in hybrid maize utilizing the CRISPR Cas12a system. Our experiments showed that stable and heritable targeted CO can be produced in F1 somatic cells using Cas12a at a significantly higher rate than the natural CO in the same interval. Molecular characterization of the recombinant plants demonstrated that the targeted CO were driven by the non-homologous end joining (NHEJ) or HDR repair pathways, presumably during the mitotic cell cycle. These results are a step towards the use of RNA-guided nuclease technology to simplify the creation of targeted genome combinations in progeny and accelerate breeding.

Laparoscopic Colorectal Surgery Outcomes Improved After National Training Program (LAPCO) for Specialists in England.

OBJECTIVE: To examine the impact of The National Training Program for Lapco on the rate of laparoscopic surgery and clinical outcomes of cases performed by Lapco surgeons after completion of training. SUMMARY OF BACKGROUND DATA: Lapco provided competency-based supervised clinical training for specialist colorectal surgeons in England. METHODS: We compared the rate of laparoscopic surgery, mortality, and morbidity for colorectal cancer resections by Lapco delegates and non-Lapco surgeons in 3-year periods preceding and following Lapco using difference in differences analysis. The changes in the rate of post-Lapco laparoscopic surgery with the Lapco sign-off competency assessment and in-training global assessment scores were examined using risk-adjusted cumulative sum to determine their predictive clinical validity with predefined competent scores of 3 and 5 respectively. RESULTS: One hundred eight Lapco delegates performed 4586 elective colo-rectal resections pre-Lapco and 5115 post-Lapco while non-Lapco surgeons performed 72,930 matched cases. Lapco delegates had a 37.8% increase in laparoscopic surgery which was greater than non-Lapco surgeons by 20.9% [95% confidence interval (CI), 18.5-23.3, P < 0.001) with a relative decrease in 30-day mortality by -1.6% (95% CI, -3.4 to -0.2, P = 0.039) and 90-day mortality by -2.3% (95% CI, -4.3 to -0.4, P = 0.018). The change point of risk-adjusted cumulative sum was 3.12 for competency assessment tool and 4.74 for global assessment score whereas laparoscopic rate increased from 44% to 66% and 40% to 56%, respectively. CONCLUSIONS: Lapco increased the rate of laparoscopic colorectal cancer surgery and reduced mortality and morbidity in England. In-training competency assessment tools predicted clinical performance after training.

Numerical simulations of capsule deformation using a dual time-stepping lattice Boltzmann method.

In this work a quasisteady, dual time-stepping lattice Boltzmann method is proposed for simulation of capsule deformation. At each time step the steady-state lattice Boltzmann equation is solved using the full approximation storage multigrid scheme for nonlinear equations. The capsule membrane is modeled as an infinitely thin shell suspended in an ambient fluid domain with the fluid structure interaction computed using the immersed boundary method. A finite element method is used to compute the elastic forces exerted by the capsule membrane. Results for a wide range of parameters and initial configurations are presented. The proposed method is found to reduce the computational time by a factor of ten.

Influence of Anticipation and Motor-Motor Task Performance on Cutting Biomechanics in Healthy Men.

CONTEXT: Biomechanical analyses of cutting tasks have demonstrated kinematic differences associated with the noncontact knee-injury risk when the movement direction is unanticipated. Motor-motor dual tasks occur within dynamic environments and change the demand for attentional resources needed to complete athletic maneuvers, which may contribute to injury risk. OBJECTIVE: To investigate the influence of anticipation and motor-motor task performance on cutting biomechanics. DESIGN: Cross-sectional study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: A total of 32 healthy, recreationally active men (age = 23.1 ± 3.6 years, height = 180.0 ± 7.0 cm, mass = 81.3 ± 17.3 kg) who self-reported regular participation in cutting sports. INTERVENTION(S): Participants performed a 45° side-step cut on the dominant limb in a random order of conditions: anticipation (anticipated, unanticipated) and task (no ball throw, ball fake, ball throw). MAIN OUTCOME MEASURE(S): Triplanar trunk, hip, and knee angles were assessed throughout the stance phase using 3-dimensional motion capture. Data were analyzed using a time series of means calculated from initial contact to toe-off (0%-100%) with 90% confidence intervals. Mean differences between conditions were identified as regions of nonoverlapping confidence intervals, and those that occurred during the region of peak vertical ground reaction force (0%-25%) are presented. RESULTS: Regardless of anticipation, attending to a ball (ball throw) resulted in more trunk extension (range = 2.9°-3.7°) and less lateral trunk flexion toward the cutting direction (range = 5.2°-5.9°). Planning to attend to a ball (ball fake) resulted in less lateral trunk flexion toward the cutting direction (4.7°). During unanticipated cutting, more trunk rotation away from the cutting direction was observed when attending to a ball (range = 5.3°-7.1°). The interaction of anticipation and task had a similar influence on sagittal- and frontal-plane trunk position. CONCLUSIONS: Motor-motor task performance and its interaction with anticipation induced an upright, neutral trunk position during side-step cutting, which has been associated with the risk for noncontact knee injury. Promoting task complexity during rehabilitation and injury-prevention programs may better prepare individuals to succeed when performing high-risk athletic maneuvers.

External ankle taping does not alter lower extremity side-step cut and straight sprint biomechanics in young adult males.

Lateral ankle sprains (LAS) are one of the most common musculoskeletal injuries and as a response, clinicians often use external ankle taping prophylactically to reduce the prevalence of injuries. External ankle taping techniques have been shown to significantly reduce passive ankle range of motion; however, there is limited research on the effects of external ankle taping on lower extremity kinematics or kinetics during sport specific tasks. Therefore, our objective was to compare the effects of external ankle taping on ankle, knee and hip kinematics and kinetics compared to no taping during an anticipated sidestep cutting task and a straight sprint task. We conducted a cross-over laboratory study with 16 healthy males. Three-dimensional kinematics and kinetics were collected with a motion capture system and in-ground force plate during 5 trials of a sprint and anticipated side-step cut with or without external ankle taping. Group means and associated 90% confidence intervals were plotted across 100 data points for each task, significance being identified when the confidence intervals did not overlap for three consecutive data points. No significant kinetic or kinematic differences were identified between conditions for the tasks. External ankle taping does not influence lower extremity biomechanics during a control cutting task.

A-Kinase Anchoring Protein 13 (AKAP13) Augments Progesterone Signaling in Uterine Fibroid Cells.

Context: Uterine leiomyomata (fibroids) are prevalent sex hormone‒dependent tumors with an altered response to mechanical stress. Ulipristal acetate, a selective progesterone receptor (PR) modulator, significantly reduces fibroid size in patients. However, PR signaling in fibroids and its relationship to mechanical signaling are incompletely understood. Objective: Our prior studies revealed that A-kinase anchoring protein 13 (AKAP13) was overexpressed in fibroids and contributed to altered mechanotransduction in fibroids. Because AKAP13 augmented nuclear receptor signaling in other tissues, we sought to determine whether AKAP13 might influence PR signaling in fibroids. Methods and Results: Fibroid samples from patients treated with ulipristal acetate or placebo were examined for AKAP13 expression by using immunohistochemistry. In immortalized uterine fibroid cell lines and COS-7 cells, we observed that AKAP13 increased ligand-dependent PR activation of luciferase reporters and endogenous progesterone-responsive genes for PR-B but not PR-A. Inhibition of ERK reduced activation of PR-dependent signaling by AKAP13, but inhibition of p38 MAPK had no effect. In addition, glutathione S-transferase‒binding assays revealed that AKAP13 was bound to PR-B through its carboxyl terminus. Conclusion: These data suggest an intersection of mechanical signaling and PR signaling involving AKAP13 through ERK. Further elucidation of the integration of mechanical and hormonal signaling pathways in fibroids may provide insight into fibroid development and suggest new therapeutic strategies for treatment.

The Trendelenburg Position and Cognitive Decline: A Case-Control Interventional Study Involving Healthy Volunteers.

BACKGROUND: Postoperative cognitive decline (POCD) is defined as a new cognitive impairment arising after a surgical intervention. Aspects of cognitive function can be assessed using various validated cognitive function tests including the N-back task, the Stroop task, and the lexical decision-making task (LDT). There is some concern that prolonged Trendelenburg positioning during laparoscopic colorectal surgery may cause POCD. OBJECTIVE: The objective of this study was to assess the effect of time spent in the Trendelenburg position on cognitive function. METHODS: Volunteers were placed in the Trendelenburg position for 3 hours and, then, supine for 30 minutes. Validated cognitive function tests including 1-, 2-, and 3-back tasks, Stroop test, and LDT were performed at baseline and every 30 minutes after Trendelenburg positioning. Cognitive decline was defined per the International Study of Postoperative Cognitive Dysfunction trial: a decrease in accuracy from the volunteers' baseline or an increase in response time from the volunteers' baseline by >2 control group SDs. RESULTS: We recruited 15 healthy volunteers (8 males, 7 females) with an average age of 69 years (range 57-81) and average body mass index of 27.7 kg/m2 (range 20.9-33). Accuracy remained within 2 SDs at all time points. An increase in response time did occur, and of 15 participants, 3 (20%) showed cognitive decline in the Trendelenburg position after 30 minutes, 4 (27%) after 1 hour, 5 (33%) after 90 minutes, 4 (27%) after 120 and 150 minutes, and 6 (40%) after 180 minutes. On moving to a supine position, 33% (5/15) participants showed cognitive decline. CONCLUSIONS: The results of this study indicate that Trendelenburg positioning leads to cognitive decline. This may have implications for patients undergoing prolonged Trendelenburg positioning during laparoscopic colorectal surgery.

Surface electromyography of the forearm musculature during an overhead throwing rehabilitation progression program.

OBJECTIVE: The flexor carpi ulnaris (FCU) and flexor digitorum superficialis (FDS) provide dynamic stabilization to the medial elbow. It remains unclear how these muscles function during progressive throwing exercises. Our objective was to compare FCU and FDS surface electromyography (sEMG) during a throwing progression. DESIGN: Crossover. SETTING: Laboratory. PARTICIPANTS: Sixteen healthy males. MAIN OUTCOME MEASURES: Participants completed a plyometric throw (PLYO), long-toss 50% (LT50), long-toss 75% (LT75), and pitch (PITCH). sEMG was synchronized with three-dimensional kinematics to assess the acceleration phase of each exercise. Peak sEMG amplitude (%MVIC) and percentage change between progressive exercises was measured. Continuous sEMG data were assessed to determine when peak activation occurred during acceleration. RESULTS: FCU activity was greater during PITCH than LT50, and during LT75 than LT50. Percentage change was greater from LT50-to-LT75 than PLYO-to-LT50 for both muscles. PLYO and PITCH increased most during late acceleration, whereas LT50 and LT75 increased most during mid-acceleration. CONCLUSIONS: FCU activity did not increase in a stepwise manner, and FDS remained unchanged. Each muscle demonstrated a disproportionate increase in activation during the second exercise progression (LT50-to-LT75) compared to the first (PLYO-to-LT50), suggesting that additional exercises may be required to achieve a stepwise progression relative to forearm muscle activation.

Effect of public reporting of surgeons' outcomes on patient selection, "gaming," and mortality in colorectal cancer surgery in England: population based cohort study.

OBJECTIVE: To determine the effect of surgeon specific outcome reporting in colorectal cancer surgery on risk averse clinical practice, "gaming" of clinical data, and 90 day postoperative mortality. DESIGN: National cohort study. SETTING: English National Health Service hospital trusts. POPULATION: 111 431 patients diagnosed as having colorectal cancer from 1 April 2011 to 31 March 2015 included in the National Bowel Cancer Audit. INTERVENTION: Public reporting of surgeon specific 90 day mortality in elective colorectal cancer surgery in England introduced in June 2013. MAIN OUTCOME MEASURES: Proportion of patients with colorectal cancer who had an elective major resection, predicted 90 day mortality based on characteristics of patients and tumours, and observed 90 day mortality adjusted for differences in characteristics of patients and tumours, comparing patients who had surgery between April 2011 and June 2013 and between July 2013 and March 2015. RESULTS: The proportion of patients with colorectal cancer undergoing major resection did not change after the introduction of surgeon specific public outcome reporting (39 792/62 854 (63.3%) before versus 30 706/48 577 (63.2%) after; P=0.8). The proportion of these major resections categorised as elective or scheduled also did not change (33 638/39 792 (84.5%) before versus 25 905/30 706 (84.4%) after; P=0.5). The predicted 90 day mortality remained the same (2.7% v 2.7%; P=0.3), but the observed 90 day mortality fell (952/33 638 (2.8%) v 552/25 905 (2.1%)). Change point analysis showed that this reduction was over and above the existing downward trend in mortality before the introduction of public outcome reporting (P=0.03). CONCLUSIONS: This study did not find evidence that the introduction of public reporting of surgeon specific 90 day postoperative mortality in elective colorectal cancer surgery has led to risk averse clinical practice behaviour or "gaming" of data. However, its introduction coincided with a significant reduction in 90 day mortality.

"Cell grafting": a new approach for transferring cytoplasmic or nuclear genome between plants.

KEY MESSAGE: A new method based on mixing and wounding of callus tissue was used to transfer plastid or nuclear DNA between cells. Methods alternative to sexual hybridization can be powerful tools for crop improvement. We have developed a new hybridization technology based on wounding a mixed population of cells of two parents growing in vitro as callus ("cell grafting"), and have demonstrated the utility of this system for plastid or nuclear genome transfer. In our proof-of concept experiments, non-organized growing tissue (callus) from tobacco var. Samsun, carrying the nuclear marker genes nptII and uidA (GUS), and tobacco var. Petit Havana, carrying aadA and gfp genes in the plastid genome, were mixed together, wounded with a razor blade and placed for regeneration on selection medium containing both spectinomycin (aadA) and paromomycin (nptII). Plants with aadA and gfp positive plastids and nptII plus uidA positive nuclear background were produced. Molecular analysis confirmed the presence of all four genes in these plants. Morphology and ploidy level analysis confirmed the production of "diploid" plants similar to var. Samsun possessing transformed plastids from var. Petit Havana. Reciprocal crosses between the experimentally produced plants and wild type tobacco confirmed maternal inheritance of aadA and gfp and Mendelian inheritance of nptII and uidA. For transfer of nuclear traits between plants we used two nuclear-transformed parents with different selectable markers; one with nptII (paromomycin resistant), and another with aadA (spectinomycin resistant). Plants resistant to both antibiotics which also had different visible markers were produced.

Mice deficient in AKAP13 (BRX) develop compulsive-like behavior and increased body weight.

OBJECTIVE: Hormonal contributions to the sex-dependent development of both obsessive-compulsive disorder (OCD) and obesity have been described, but the underlying mechanisms are incompletely understood. A-kinase anchoring protein 13 (AKAP13) significantly augments ligand-dependent activation of estrogen receptors alpha and beta. The hypothalamus and pituitary gland are implicated in the development and exacerbation of OCD and obesity and have strong AKAP13 expression. The AKAP13 localization pattern observed in these key brain regions together with its effects on sex steroid action suggest a potential role for AKAP13 in compulsive-like behaviors. Here we tested the role of AKAP13 in compulsive-like behavior and body weight using an Akap13 haploinsufficient murine model. MATERIALS AND METHODS: Targeted deletion of the Akap13 gene generated haploinsufficient (Akap13+/-) mice in a C57BL6/J genetic background. Established behavioral assays were conducted, video recorded, and scored blindly to assess compulsive-like behavior based on genotype and gender. Tests included: marble-burying, grooming, open- field and elevated plus-maze. Brain and body weights were also obtained. Mean levels of test outcomes were compared using multi-way ANOVA to test for genotype, sex, genotype*sex, and genotype*sex*age interaction effects with Bonferroni adjustment for multiple comparisons, to further explain any significant interactions. RESULTS: The marble-burying and grooming assays revealed significant sex-dependent increases in perseverative, compulsive-like behaviors in female Akap13 haploinsufficient mice compared to female wild type (WT) mice by demonstrating increased marble-burying activity (p = .0025) and a trend towards increased grooming behavior (p = .06). Male Akap13 haploinsufficient mice exhibited no behavioral changes (p > 0.05). Elevated plus-maze and open-field test results showed no overt anxiety-like behavior in Akap13 haploinsufficient mice irrespective of sex (p > 0.05, both). No differences in brain weight were found in Akap13 haploinsufficient mice compared to WT mice (p > 0.05). However, female Akap13 haploinsufficient mice weighed more than female WT mice in the 4 to <7 months age range (p = .0051). Male Akap13 haploinsufficient mice showed no differences in weight compared to male WT mice (p = >0.05) at any age range examined. CONCLUSION: Akap13 haploinsufficiency led to sex-dependent, compulsive-like behavioral changes in a murine model. Interestingly, Akap13 haploinsufficiency also led to a sex-dependent increase in body weight. These results revealed a requirement for AKAP13 in murine behavior, particularly in female mice, and is the first report of AKAP13 involvement in murine behavior. Future studies may examine the involvement of AKAP13 in the pathophysiology of OCD in female humans and may contribute to a better understanding of the role of AKAP13 and sex hormones in the development and exacerbation of OCD.