166 research outputs found

    Serological markers of gluten sensitivity in Border terriers with gall bladder mucocoeles

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    Objectives To evaluate serological markers of gluten sensitivity in conjunction with cholecystokinin measurement in Border terriers with gall bladder mucocoeles. Materials and Methods Medical records from two referral hospitals were obtained between 2011 and 2019 to identify Border terriers with gall bladder mucocoeles, non‐Border terriers with gall bladder mucocoeles and control Border terriers with non‐biliary diseases. Enzyme‐linked immunosorbent assays were performed on stored fasted serum samples for anti‐gliadin IgG, anti‐canine transglutaminase‐2‐IgA autoantibodies and cholecystokinin. Statistical analysis was performed using the Kruskall‐Wallis test to identify differences between the groups. Results Fifteen Border terriers with gall bladder mucocoeles, 17 non‐Border terriers with gall bladder mucocoeles and 14 control Border terriers with non‐biliary diseases were recruited. Median transglutaminase‐2‐IgA autoantibodies in Border terriers with gall bladder mucocoeles was 0.73 (range: 0.18 to 1.67), which was significantly greater than in control Border terriers at 0.41 (0.07 to 1.14). Median cholecystokinin concentration in Border terriers with gall bladder mucocoeles was 13 pg/mL (6 to 45 pg/mL), which was significantly lower than in control Border terriers at 103 pg/mL (9 to 397 pg/mL). There was no difference in the anti‐gliadin IgG between these groups. There was no difference observed in the non‐Border terriers with gall bladder mucocoeles with either of the other groups. Clinical Significance Reduced cholecystokinin and increased transglutaminase‐2‐IgA autoantibodies was detected in Border terriers with gall bladder mucocoeles; which is in part homologous to gall bladder disease identified in human coeliac disease. The results suggest an immunological disease with impaired cholecystokinin release may be affecting gall bladder motility and possibly contributing to mucocoele formation in Border terriers

    0111i I ll III ACTUATOR PLACEMENT FOR ACTIVE SURGE CONTROL IN A MULTI-STAGE AXIAL COMPRESSOR

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    ABSTRACT. This paper describes an actuator placement methodology for the active control of purely onedimensional instabilities of a seven-stage axial compressor using an air bleeding strategy. In this theoretical study, using stage-by-stage non-linear modelling based on the conservation equations of mass, momentum, and energy, a scheduling LQR (Linear Quadratic Regulator) controller is designed for several actuator locations in a compressor from the first stage to the plenum. In this controller design, the LQR weighting matrices are selected so that the associated cost function includes only air bleeding mass flow leading to the minimisation of the air bleed. The LQR cost function represents a measure of the consumption of air bleeding and can be calculated analytically using the solution of an Algebraic Riccati Equation. From analysis of the cost at different compressor stages, the location of an air bleeding actuator is selected at the stage with the minimum cost. Finally, using an ACSL simulation program, the scheduling controller has been integrated with a non-lineat stage-by-stage model and the time response of the air bleeding mass flow at different locations has been obtained to confirm the results from the analytical approach. Results are presented to show actively stabilised compressor flow beyond the surge point where the air bleed is minimised. These results also indicate the preferred location of the actuator at the compressor downstream stages for both low and high compressor speeds

    Target trial emulation: Do antimicrobials or gastrointestinal nutraceuticals prescribed at first presentation for acute diarrhoea cause a better clinical outcome in dogs under primary veterinary care in the UK?

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    Target trial emulation applies design principles from randomised controlled trials to the analysis of observational data for causal inference and is increasingly used within human epidemiology. Veterinary electronic clinical records represent a potentially valuable source of information to estimate real-world causal effects for companion animal species. This study employed the target trial framework to evaluate the usefulness on veterinary observational data. Acute diarrhoea in dogs was used as a clinical exemplar. Inclusion required dogs aged ≥ 3 months and < 10 years, presenting for veterinary primary care with acute diarrhoea during 2019. Treatment strategies were: 1. antimicrobial prescription compared to no antimicrobial prescription and 2. gastrointestinal nutraceutical prescription compared to no gastrointestinal nutraceutical prescription. The primary outcome was clinical resolution (defined as no revisit with ongoing diarrhoea within 30 days from the date of first presentation). Informed from a directed acyclic graph, data on the following covariates were collected: age, breed, bodyweight, insurance status, comorbidities, vomiting, reduced appetite, haematochezia, pyrexia, duration, additional treatment prescription and veterinary group. Inverse probability of treatment weighting was used to balance covariates between the treatment groups for each of the two target trials. The risk difference (RD) of 0.4% (95% CI -4.5% to 5.3%) was non-significant for clinical resolution in dogs treated with antimicrobials compared with dogs not treated with antimicrobials. The risk difference (RD) of 0.3% (95% CI -4.5% to 5.0%) was non-significant for clinical resolution in dogs treated with gastrointestinal nutraceuticals compared with dogs not treated with gastrointestinal nutraceuticals. This study successfully applied the target trial framework to veterinary observational data. The findings show that antimicrobial or gastrointestinal prescription at first presentation of acute diarrhoea in dogs causes no difference in clinical resolution. The findings support the recommendation for veterinary professionals to limit antimicrobial use for acute diarrhoea in dogs

    Co-ingestion of whey protein with a carbohydrate-rich breakfast boes not affect glycemia, insulinemia or subjective appetite following a subsequent meal in healthy males

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    We aimed to assess postprandial metabolic and appetite responses to a mixed-macronutrient lunch following prior addition of whey protein to a carbohydrate-rich breakfast. Ten healthy males (age: 24 ± 1 y; body mass index (BMI): 24.5 ± 0.7 kg/m2) completed three trials in a non-isocaloric, crossover design. A carbohydrate-rich breakfast (93 g carbohydrate; 1799 kJ) was consumed with (CHO+WP) or without (CHO) 20 g whey protein isolate (373 kJ), or breakfast was omitted (NB). At 180 minutes, participants consumed a mixed-macronutrient lunch meal. Venous blood was sampled at 15 minute intervals following each meal and every 30 minutes thereafter, while subjective appetite sensations were collected every 30 minutes throughout. Post-breakfast insulinaemia was greater after CHO+WP (time-averaged area under the curve (AUC0-180 min): 193.1 ± 26.3 pmol/L), compared to CHO (154.7 ± 18.5 pmol/L) and NB (46.1 ± 8.0 pmol/L; p &lt; 0.05), with no difference in post breakfast (0-180 min) glycaemia (CHO+WP, 3.8 ± 0.2 mmol/L; CHO, 4.2 ± 0.2 mmol/L; NB, 4.2 ± 0.1 mmol/L; p = 0.247). There were no post lunch (0-180 min) effects of condition on glycaemia (p = 0.492), insulinaemia (p = 0.338) or subjective appetite (p &gt; 0.05). Adding whey protein to a carbohydrate-rich breakfast enhanced the acute postprandial insulin response, without influencing metabolic or appetite responses following a subsequent mixed-macronutrient meal

    Defining predictors of responsiveness to advanced therapies in Crohn’s disease and ulcerative colitis: protocol for the IBD-RESPONSE and nested CD-metaRESPONSE prospective, multicentre, observational cohort study in precision medicine

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    Introduction: Characterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can significantly impact patient’s quality of life. Therapeutic developments in the last 20 years have revolutionised treatment. However, clinical trials and real-world data show primary non-response rates up to 40%. A significant challenge is an inability to predict which treatment will benefit individual patients. Current understanding of IBD pathogenesis implicates complex interactions between host genetics and the gut microbiome. Most cohorts studying the gut microbiota to date have been underpowered, examined single treatments and produced heterogeneous results. Lack of cross-treatment comparisons and well-powered independent replication cohorts hampers the ability to infer real-world utility of predictive signatures. IBD-RESPONSE will use multi-omic data to create a predictive tool for treatment response. Future patient benefit may include development of biomarker-based treatment stratification or manipulation of intestinal microbial targets. IBD-RESPONSE and downstream studies have the potential to improve quality of life, reduce patient risk and reduce expenditure on ineffective treatments. Methods and analysis: This prospective, multicentre, observational study will identify and validate a predictive model for response to advanced IBD therapies, incorporating gut microbiome, metabolome, single-cell transcriptome, human genome, dietary and clinical data. 1325 participants commencing advanced therapies will be recruited from ~40 UK sites. Data will be collected at baseline, week 14 and week 54. The primary outcome is week 14 clinical response. Secondary outcomes include clinical remission, loss of response in week 14 responders, corticosteroid-free response/remission, time to treatment escalation and change in patient-reported outcome measures. Ethics and dissemination: Ethical approval was obtained from the Wales Research Ethics Committee 5 (ref: 21/WA/0228). Recruitment is ongoing. Following study completion, results will be submitted for publication in peer-reviewed journals and presented at scientific meetings. Publications will be summarised at www.ibd-response.co.uk. Trial registration number: ISRCTN96296121

    Efficacy of antimicrobial and nutraceutical treatment for canine acute diarrhoea: A systematic review and meta-analysis for European Network for Optimization of Antimicrobial Therapy (ENOVAT) guidelines

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    Systemic antimicrobial treatments are commonly prescribed to dogs with acute diarrhoea, while nutraceuticals (prebiotics, probiotics, and synbiotics) are frequently administered as an alternative treatment. The aim of this systematic review and meta-analysis was to assess the effectiveness of antimicrobials and nutraceutical preparations for treatment of canine acute diarrhoea (CAD). The results of this study will be used to create evidence-based treatment guidelines. PICOs (population, intervention, comparator, and outcome) were generated by a multidisciplinary expert panel taking into account opinions from stakeholders (general practitioners and dog owners). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to evaluate the certainty of the evidence. The systematic search yielded six randomised controlled trials (RCT) for antimicrobial treatment and six RCTs for nutraceutical treatment meeting the eligibility criteria. Categories of disease severity (mild, moderate, and severe) were created based on the presence of systemic signs and response to fluid therapy. Outcomes included duration of diarrhoea, duration of hospitalization, progression of disease, mortality, and adverse effects. High certainty evidence showed that antimicrobial treatment did not have a clinically relevant effect on any outcome in dogs with mild or moderate disease. Certainty of evidence was low for dogs with severe disease. Nutraceutical products did not show a clinically significant effect in shortening the duration of diarrhoea (based on very low to moderate certainty evidence). No adverse effects were reported in any of the studies
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