74 research outputs found

    Effect of preoperative administration of atenolol to dogs with pulmonic stenosis undergoing interventional procedures

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    BACKGROUND: Beta‐blockade is sometimes used in dogs with pulmonic stenosis with the intent of reducing frequency of ventricular arrhythmias during right heart catheterization. OBJECTIVES: To evaluate if pretreatment with atenolol reduces frequency of ventricular arrhythmias, anesthetist interventions, or shortens procedure time. ANIMALS: Thirty dogs with pulmonic stenosis scheduled for interventional procedures. METHODS: Single center, prospective, randomized, open‐label study. Dogs were randomized to treatment with atenolol or no treatment preoperatively for a minimum of 10 days. Variables recorded included heart rate, arrhythmias and complexity, total procedure time and administration of antiarrhythmic treatment, vasopressors, positive chronotropes, or fluid boluses. RESULTS: Fifteen dogs were enrolled in each group. Dogs receiving atenolol had lower mean heart rates during the procedure (atenolol 100 ± 11 bpm vs untreated 115 ± 19 bpm, P = .01). There were no significant differences between the atenolol and untreated groups in the frequency of ventricular ectopic complexes (535 [6‐5296] vs 553 [79‐2863], P = .9), ventricular couplets (46 [0‐481] vs 29 [3‐121], P = .59), ventricular triplets (20 [0‐265] vs 16 [1‐82], P = .67), ventricular tachycardia (8 [0‐224] vs 8 [1‐118], P = .99), proportion exhibiting R‐on‐T phenomenon (11/15 vs 14/15, P = .33), proportion receiving intraoperative lidocaine (1/15 vs 3/15, P = .6), vasopressors/positive chronotropes (11/15 vs 5/15, P = .06), or fluid boluses (12/15 vs 7/15, P = .13). The procedure time was similar (atenolol 41 [23‐68] min vs untreated 35 [18‐98] min, P = .91). CONCLUSIONS AND CLINICAL IMPORTANCE: No benefit of preoperative atenolol treatment was identified in this small group of dogs

    Magnetic resonance imaging of the rheology of ionic liquid colloidal suspensions

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    The rheology, and underpinning colloidal interactions, of ionic liquid (IL) dispersions of colloidal silica have been investigated using bulk rheological measurements with magnetic resonance (MR) velocity and relaxation measurements. Two ionic liquids were investigated: tetradecyl(trihexyl)phosphonium bistriflamide ([P6,6,6,14][NTf2]) and 1-butyl-methylimidizolium tetrafluoroborate ([C4mim][BF4]), in the absence and presence of hydrophilic silica nanoparticles (Aerosil 200). Bulk rheology was probed using measurements of shear stress and viscosity as a function of shear rate in a cone-and-plate rheometer. Local rheology was probed using MR velocity imaging of flow in Couette and cone-and-plate cells. Velocity profiles were extracted from the Couette measurements and fitted using a power-law model. Newtonian rheology was observed for both ILs in the absence of dispersed silica. For the dispersion of 15% silica in [C4mim][BF4], bulk rheology and MR velocity imaging measurements showed Newtonian behaviour at low shear rates (10 s−1). For the dispersion of 5% silica in [P6,6,6,14][NTf2], more complex rheology was observed in the flow curve, which was suggestive of shear-banding. This was investigated further using the MR velocity profiles in a Couette cell and velocity images in a cone-and-plate cell, which both showed the coexistence of regions of sheared and unsheared fluid. The sheared fluid was found to be highly shear-thinning and close inspection of the flow profile at the interface between sheared and unsheared fluid suggested that the behaviour was shear-banding rather than shear-localisation. This was further confirmed by the velocity images in the cone-and-plate rheometer, which showed sheared and unsheared fluid in a uniform shear stress environment

    Characterisation of faecal protease activity in irritable bowel syndrome with diarrhoea: origin and effect of gut transit

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    OBJECTIVES: Faecal serine proteases (FSPs) may play a role in irritable bowel syndrome with diarrhoea (IBS-D), but their origin is unclear. We aimed to structurally characterise them and define the impact of colonic cleansing and transit time. DESIGN: Faecal samples were obtained from 30 healthy volunteers (HV) and 79 patients with IBS-D participating in a trial of ondansetron versus placebo. Colonic transit was measured using radio-opaque markers. Samples were also obtained from 24 HV before and after colonic cleansing with the osmotic laxative MoviPrep. FSPs were purified from faecal extracts using benzamidine-Sepharose affinity chromatography. SDS-PAGE profiled components were identified using trypsinolysis and tandem mass spectrometry. Functional protease activity in faecal extracts was measured using a colorimetric assay based on the proteolysis of azo-casein. RESULTS: Protein analysis identified the most abundant FSPs as being of human origin and probably derived from pancreatic juice. Functional assays showed increased faecal protease (FP) and amylase in patients with IBS-D compared with HV. Those with higher amylase had significantly higher FP and greater anxiety. FP activity correlated negatively with whole gut transit in patients with IBS-D (Spearman r=−0.32, p=0.005) and HV (r=−0.55, p=0.014). Colon cleansing caused a significant rise in FP activity in HV from a baseline of median (IQR) 253 (140–426) to 1031 (435–2296), levels similar to those seen in patients with IBS-D. FSP activity correlated positively with days/week with urgency. CONCLUSIONS: The most abundant FSPs are of human origin. Rapid transit through the colon and/or decreased (possibly bacterial) proteolytic degradation increases their faecal concentration and could contribute to visceral hypersensitivity in patients with IBS-D. CLINICALTRIALS.GOV: NCT00745004

    What you see is not always what you get: A qualitative, comparative analysis of ex ante visualizations with ex post photography of landscape and architectural projects

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    This study presents a qualitative, comparative analysis of ex ante visualizations, created during planning and design phases, with ex post photography of landscape and architectural projects. Visualizations play an increasingly important role as decision-making tools in the planning process and are expected to successfully communicate proposals to both experts and laypersons. Outside of the wind farm industry there is a lack of detailed guidance for those creating landscape visualizations and currently no method of analyzing the accuracy of visualizations exists. In a world where we increasingly rely on information communicated in a visual manner itis imperative that potential viewers are provided with clues to enable them to distinguish between what is real and what is not. This study analyses a selection of visualizations from a cross section of landscape and architectural projects and reveals reoccurring patterns of inconsistencies in the depiction of content elements. The control of production through agreed guidelines proposed by previously published research could have both positive and negative effects for the future of visualization production. This research proposes that the starting point for honest communication lies in transparency, in both production techniques and presentation to clients, stakeholders and the public. There is scope for more in depth image analysis of a larger body of projects that may reveal more detailed findings that could contribute to future guideline discussions

    How do NHS organisations plan research capacity development? Strategies, strengths, and opportunities for improvement

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    Research that is integral into a 'learning healthcare system' can promote cost effective services and knowledge creation. As such, research is defined as a 'core function' in UK health service organisations, and is often planned through research and development (R&D) strategies that aim to promote research activity and research capacity development (RCD). The discussion focuses around the content of ten R&D strategies for healthcare organisations in England and Scotland, with respect to RCD. These organisations were engaged with a research interest network called ACORN (Addressing Organisational Capacity to do Research Network) that included two Scottish Health Boards, four community and mental health trusts, two provincial district hospitals, and two teaching hospitals. We undertook a thematic documentary analysis of the R&D strategies which identified 11 'core activities' of RCD. The potential for building research capacity in these 'core activities' was established by reviewing them through the lens of a RCD framework. Core activities aimed to 'hard wire' RCD into health organisations. They demonstrated a complex interplay between developing a strong internal organisational infrastructure, and supporting individual career planning and skills development, in turn enabled by organisational processes. They also included activities to build stronger inter-organisational relationships and networks. Practitioner, manager and patient involvement was a cross cutting theme. The potential to demonstrate progress was included in plans through monitoring activity across all RCD principles. Strategies were primarily aimed at research production rather than research use. Developing 'actionable dissemination' was poorly addressed in the strategies, and represents an area for improvement. We describe strengths of RCD planning activities, and opportunities for improvement. We explore how national policy and research funders can influence health systems' engagement in research

    Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

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    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∌8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

    Change in physical activity level and clinical outcomes in older adults with knee pain: a secondary analysis from a randomised controlled trial

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    BACKGROUND: Exercise interventions improve clinical outcomes of pain and function in adults with knee pain due to osteoarthritis and higher levels of physical activity are associated with lower severity of pain and higher levels of physical functioning in older adults with knee osteoarthritis in cross-sectional studies. However, to date no studies have investigated if change in physical activity level during exercise interventions can explain clinical outcomes of pain and function. This study aimed to investigate if change in physical activity during exercise interventions is associated with future pain and physical function in older adults with knee pain. METHODS: Secondary longitudinal data analyses of a three armed exercise intervention randomised controlled trial. Participants were adults with knee pain attributed to osteoarthritis, over the age of 45 years old (n = 514) from Primary Care Services in the Midlands and Northwest regions of England. Crude and adjusted associations between absolute change in physical activity from baseline to 3 months (measured by the self-report Physical Activity Scale for the Elderly (PASE)) and i) pain ii) physical function (Western Ontario and McMaster Universities Osteoarthritis Index) and iii) treatment response (OMERACT-OARSI responder criteria) at 3 and 6 months follow-up were investigated using linear and logistic regression. RESULTS: Change in physical activity level was not associated with future pain, function or treatment response outcomes in crude or adjusted models at 3 or 6 months (P > 0.05). A 10 point increase in PASE was not associated with pain ÎČ = - 0.01 (- 0.05, 0.02), physical function ÎČ = - 0.09 (- 0.19, 0.02) or likelihood (odds ratio) of treatment response 1.02 (0.99, 1.04) at 3 months adjusting for sociodemographics, clinical covariates and the trial intervention arm. Findings were similar for 6 month outcome models. CONCLUSIONS: Change in physical activity did not explain future clinical outcomes of pain and function in this study. Other factors may be responsible for clinical improvements following exercise interventions. However, the PASE may not be sufficiently responsive to measure change in physical activity level. We also recommend further investigation into the responsiveness of commonly used physical activity measures. TRIAL REGISTRATION: ( ISRCTN93634563 ). Registered 29th September 2011

    Gene-gene Interaction Analyses for Atrial Fibrillation

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    Atrial fibrillation (AF) is a heritable disease that affects more than thirty million individuals worldwide. Extensive efforts have been devoted to the study of genetic determinants of AF. The objective of our study is to examine the effect of gene-gene interaction on AF susceptibility. We performed a large-scale association analysis of gene-gene interactions with AF in 8,173 AF cases, and 65,237 AF-free referents collected from 15 studies for discovery. We examined putative interactions between genome-wide SNPs and 17 known AF-related SNPs. The top interactions were then tested for association in a
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