Development of an acute ovine model of polycystic ovaries to assess the effect of ovarian denervation

Introduction: Polycystic ovary syndrome (PCOS) seems to be associated with increased ovarian sympathetic nerve activity and in rodent models of PCOS reducing the sympathetic drive to the ovary, through denervation or neuromodulation, improves ovulation rate. We hypothesised that sympathetic nerves work with gonadotropins to promote development and survival of small antral follicles to develop a polycystic ovary phenotype.Methods: Using a clinically realistic ovine model we showed a rich sympathetic innervation to the normal ovary and reinnervation after ovarian transplantation. Using needlepoint diathermy to the nerve plexus in the ovarian vascular pedicle we were able to denervate the ovary resulting in reduced intraovarian noradrenaline and tyrosine hydroxylase immunostained sympathetic nerves. We developed an acute polycystic ovary (PCO) model using gonadotrophin releasing hormone (GnRH) agonist followed infusion of follicle stimulating hormone (FSH) with increased pulsatile luteinising hormone (LH). This resulted in increased numbers of smaller antral follicles in the ovary when compared to FSH infusion suggesting a polycystic ovary.Results: Denervation had no effect of the survival or numbers of follicles in the acute PCO model and did not impact on ovulation, follicular and luteal hormone profiles in a normal cycle.Discussion: Although the ovary is richly inervated we did not find evidence for a role of sympathetic nerves in ovarian function or small follicle growth and surviva

Responsibility-sharing in the giving and receiving of assessment feedback

Many argue that effective learning requires students to take a substantial share of responsibility for their academic development, complementing the responsibilities taken by their educators. Yet this notion of responsibility-sharing receives minimal discussion in the context of assessment feedback, where responsibility for enhancing learning is often framed as lying principally with educators. Developing discussion on this issue is critical: many barriers can prevent students from engaging meaningfully with feedback, but neither educators nor students are fully empowered to remove these barriers without collaboration. In this discussion paper we argue that a culture of responsibility-sharing in the giving and receiving of feedback is essential, both for ensuring that feedback genuinely benefits students by virtue of their skilled and proactive engagement, and also for ensuring the sustainability of educators’ effective feedback practices. We propose some assumptions that should underpin such a culture, and we consider the practicalities of engendering this cultural shift within modern higher education

Natural and hybrid immunity following four COVID-19 waves: A prospective cohort study of mothers in South Africa

BACKGROUND: More than half the global population has been exposed to SARS-CoV-2. Naturally induced immunity influences the outcome of subsequent exposure to variants and vaccine responses. We measured anti-spike IgG responses to explore the basis for this enhanced immunity. METHODS: A prospective cohort study of mothers in a South African community through ancestral/beta/delta/omicron SARS-CoV-2 waves (March 2020-February 2022). Health seeking behaviour/illness were recorded and post-wave serum samples probed for IgG to Spike (CoV2-S-IgG) by ECLISA. To estimate protective CoV2-S-IgG threshold levels, logistic functions were fit to describe the correlation of CoV2-S-IgG measured before a wave and the probability for seroconversion/boosting thereafter for unvaccinated and vaccinated adults. FINDINGS: Despite little disease, 176/339 (51·9%) participants were seropositive following wave 1, rising to 74%, 89·8% and 97·3% after waves 2, 3 and 4 respectively. CoV2-S-IgG induced by natural exposure protected against subsequent SARS-CoV-2 infection with the greatest protection for beta and least for omicron. Vaccination induced higher CoV2-S-IgG in seropositive compared to naïve vaccinees. Amongst seropositive participants, proportions above the 50% protection against infection threshold were 69% (95% CrI: 62, 72) following 1 vaccine dose, 63% (95% CrI: 63, 75) following 2 doses and only 11% (95% CrI: 7, 14) in unvaccinated during the omicron wave. INTERPRETATION: Naturally induced CoV2-S-IgG do not achieve high enough levels to prevent omicron infection in most exposed individuals but are substantially boosted by vaccination leading to significant protection. A single vaccination in those with prior immunity is more immunogenic than 2 doses in a naïve vaccinee and may provide adequate protection. FUNDING: UK NIH GECO award (GEC111), Wellcome Trust Centre for Infectious Disease Research in Africa (CIDRI), Bill & Melinda Gates Foundation, USA (OPP1017641, OPP1017579) and NIH H3 Africa (U54HG009824, U01AI110466]. HZ is supported by the SA-MRC. MPN is supported by an Australian National Health and Medical Research Council Investigator Grant (APP1174455). BJQ is supported by a grant from the Bill and Melinda Gates Foundation (OPP1139859). Stefan Flasche is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant number 208812/Z/17/Z)

Ocean ecosystem-based management mandates and implementation in the North Atlantic

Ecosystem-based management (EBM) necessarily requires a degree of coordination across countries that share ocean ecosystems, and among national agencies and departments that have responsibilities relating to ocean health and marine resource utilization. This requires political direction, legal input, stakeholder consultation and engagement, and complex negotiations. Currently there is a common perception that within and across national jurisdictions there is excessive legislative complexity, a relatively low level of policy coherence or alignment with regards to ocean and coastal EBM, and that more aligned legislation is needed to accelerate EBM adoption. Our Atlantic Ocean Research Alliance (AORA) task group was comprised of a small, focused and interdisciplinary mix of lawyers, social scientists, and natural scientists from Canada, the USA, and the EU. We characterized, compared, and synthesized the mandates that govern marine activities and ocean stressors relative to facilitating EBM in national and international waters of the North Atlantic, and identified formal mandates across jurisdictions and, where possible, policy and other non-regulatory mandates. We found that irrespective of the detailed requirements of legislation or policy across AORA jurisdictions, or the efficacy of their actual implementation, most of the major ocean pressures and uses posing threats to ocean sustainability have some form of coverage by national or regional legislation. The coverage is, in fact, rather comprehensive. Still, numerous impediments to effective EBM implementation arise, potentially relating to the lack of integration between agencies and departments, a lack of adequate policy alignment, and a variety of other socio-political factors. We note with concern that if challenges regarding EBM implementation exist in the North Atlantic, we can expect that in less developed regions where financial and governance capacity may be lower, that implementation of EBM could be even more challenging

Vulnerability to fuel price increases in the UK: A household level analysis

In highly motorised countries, some sectors of the population own and use cars despite struggling to afford their running costs, and so may be particularly vulnerable to motor fuel prices increases, whether market-led or policy-driven. This paper proposes a novel, disaggregated approach to investigating vulnerability to such increases at the household level. We propose a set of indicators of ‘car-related economic stress’ (CRES), based on individual household level expenditure data for the UK, to identify which low-income households spend disproportionately on running motor vehicles, and to assess the depth of their economic stress. By subsequently linking the dataset to local fuel price data, we are able to model the disaggregated price elasticities of car fuel demand. This provides us with an indicator of each households’ adaptive capacity to fuel price increases. The findings show that ‘Low-Income, High Cost’ households (LIHC) account for 9% of UK households and have distinct socio-demographic characteristics. Interestingly, they are characterised by very low responses to fuel price increases, which may cause them to compromise on other important areas of their household expenditures. Simulations suggest that a 20% increase in fuel prices would substantially increase the depth, but not the incidence of CRES. Overall, the study sheds light on a sector of the population with high levels of vulnerability to fuel price increases, owing to high exposure, high sensitivity and low adaptive capacity. This raises challenges for social, environmental and resilience policy in the transport sector

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care