A two-year participatory intervention project with owners to reduce lameness and limb abnormalities in working horses in Jaipur, India

Participatory methods are increasingly used in international human development, but scientific evaluation of their efficacy versus a control group is rare. Working horses support families in impoverished communities. Lameness and limb abnormalities are highly prevalent in these animals and a cause for welfare concern. We aimed to stimulate and evaluate improvements in lameness and limb abnormalities in horses whose owners took part in a 2-year participatory intervention project to reduce lameness (PI) versus a control group (C) in Jaipur, India.In total, 439 owners of 862 horses participated in the study. PI group owners from 21 communities were encouraged to meet regularly to discuss management and work practices influencing lameness and poor welfare and to track their own progress in improving these. Lameness examinations (41 parameters) were conducted at the start of the study (Baseline), and after 1 year and 2 years. Results were compared with control horses from a further 21 communities outside the intervention. Of the 149 horses assessed on all three occasions, PI horses showed significantly (P<0.05) greater improvement than C horses in 20 parameters, most notably overall lameness score, measures of sole pain and range of movement on limb flexion. Control horses showed slight but significantly greater improvements in four parameters, including frog quality in fore and hindlimbs.This participatory intervention succeeded in improving lameness and some limb abnormalities in working horses, by encouraging changes in management and work practices which were feasible within owners’ socioeconomic and environmental constraints. Demonstration of the potentially sustainable improvements achieved here should encourage further development of participatory intervention approaches to benefit humans and animals in other contexts

Metabolic disorders and the risk of head and neck cancer: a protocol for a systematic review and meta-analysis

Introduction Head and neck cancer squamous cell carcinoma (HNSCC) is the sixth most common cancer internationally. Established risk factors include smoking, alcohol and presence of human papillomavirus (HPV). The incidence rate of new disease continues to rise, despite falls in alcohol consumption and a reduction in smoking, the rising rates are unlikely to be solely attributed to HPV status alone. Obesity and its associated conditions such as type 2 diabetes (T2D) are implicated in the risk and progression of a variety of cancers, but there is paucity of evidence regarding its role in HNSCC. Methods and analysis A systematic review of cohort studies, reporting a risk of incident HNSCC, will be included. A systematic search strategy has been developed, multiple databases will be searched from January 1966 to November 2021, including Cochrane Library, OVID SP versions of Medline and EMBASE. The primary outcome will be incident HNSCC based on exposures of T2D, obesity, dyslipidaemia and hypertension as defined by the WHO. A combined risk effect across studies will be calculated using meta-analysis, although depending on the heterogeneity in study design, exposure and outcome reporting this may not be possible. Ethics and dissemination No ethical approval is required for this systematic review. The review will be published in a relevant peer-review journal and findings will be presented at scientific meetings in both poster and oral presentation form. PROSPERO registration number details This study has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) with study registration number CRD42021250520. This protocol has been developed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidance statement

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

More than one way of being a moa: differences in leg bone robustness map divergent evolutionary trajectories in Dinornithidae and Emeidae (Dinornithiformes).

The extinct moa of New Zealand included three families (Megalapterygidae; Dinornithidae; Emeidae) of flightless palaeognath bird, ranging in mass from 200 kg. They are perceived to have evolved extremely robust leg bones, yet current estimates of body mass have very wide confidence intervals. Without reliable estimators of mass, the extent to which dinornithid and emeid hindlimbs were more robust than modern species remains unclear. Using the convex hull volumetric-based method on CT-scanned skeletons, we estimate the mass of a female Dinornis robustus (Dinornithidae) at 196 kg (range 155-245 kg) and of a female Pachyornis australis (Emeidae) as 50 kg (range 33-68 kg). Finite element analysis of CT-scanned femora and tibiotarsi of two moa and six species of modern palaeognath showed that P. australis experienced the lowest values for stress under all loading conditions, confirming it to be highly robust. In contrast, stress values in the femur of D. robustus were similar to those of modern flightless birds, whereas the tibiotarsus experienced the highest level of stress of any palaeognath. We consider that these two families of Dinornithiformes diverged in their biomechanical responses to selection for robustness and mobility, and exaggerated hindlimb strength was not the only successful evolutionary pathway

On the fate of plumes from deep-sea oil well blowouts, and their effects on sediment communities

Little is known about the fate of subsurface hydrocarbon plumes from prolonged oil well blowouts, and their effects on deep-sea sediment communities. As deepwater drilling expands in the Faroe-Shetland Channel (FSC), oil well blowouts are a possibility, and the complex ocean circulation of this region presents challenges to understanding possible subsurface oil pathways. Here, questions on the fate and effects of subsurface oil plumes were addressed with experiments and modelling. Experiments were performed on uncontaminated deep-sea sediments from a site remote from the FSC. A three dimensional ocean general circulation model (GCM) was used with a Lagrangian particle tracking algorithm to study patterns of subsurface oil distribution from a release in the FSC for the period 1994 – 2009.Deep-sea sediment microcosms were incubated in the presence of water accommodated fraction of crude oil (WAF) at low to high (5 % to 50 % by water volume) treatment levels, with sediment community oxygen consumption (SCOC) measured and compared to controls. Sediment macrofauna and bacteria were studied using measures of biomass. The microbial community was further studied using relative abundance and stable carbon isotope ratios (?13C values) of phospholipid fatty acids (PLFAs).Oxygen demand increased significantly at higher treatment levels (25% to 50% WAF). Treatment effects on macrofauna biomass were non-significant. However, there was significant WAF-driven reduction in bacteria biomass, and clear changes in microbial community composition. There were non-significant shifts in the ?13C values of PLFAs.Release depth of modelled subsurface plumes affected both the direction and extent of their transport and there was both seasonal and interannual variability. Plumes that were advected into overflow water were carried the furthest (&gt;2500 km in June 2008); westwards through the Faroe Bank Channel towards the Iceland basin, reaching as far as southern Greenland, the Labrador Sea and the Northwest Atlantic. An index of temperature-controlled oxygen consumption rate (simulating oil respiration) indicated that large areas of the subsurface ocean (&gt;50,000 km2 in 300 m depth water after one month) would be impacted by increased oxygen consumption in the event of a prolonged oil well blowout and the seafloor footprint beneath the plumes could be up to 100,000 km2. Quantifying impacts of any potential future spill in the FSC will benefit from these investigations on the distribution and effects of subsurface oil in this region