Publications by authors named "David Hutchings"

Ventricular arrhythmias can cause death in heart failure (HF). A trigger is the occurrence of Ca waves which activate a Na -Ca exchange (NCX) current, leading to delayed after-depolarisations and triggered action potentials. Waves arise when sarcoplasmic reticulum (SR) Ca content reaches a threshold and are commonly induced experimentally by raising external Ca , although the mechanism by which this causes waves is unclear and was the focus of this study.

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Cardiovascular magnetic resonance (CMR) is used to investigate suspected acute myocarditis, however most supporting data is retrospective and few studies have included parametric mapping. We aimed to investigate the utility of contemporary multiparametric CMR in a large prospective cohort of patients with suspected acute myocarditis, the impact of real-world variations in practice, the relationship between clinical characteristics and CMR findings and factors predicting outcome. 540 consecutive patients we recruited.

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Normal cardiac function requires that intracellular Ca concentration be reduced to low levels in diastole so that the ventricle can relax and refill with blood. Heart failure is often associated with impaired cardiac relaxation. Little, however, is known about how diastolic intracellular Ca concentration is regulated.

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Heart failure (HF) is characterized by poor survival, a loss of catecholamine reserve and cellular structural remodeling in the form of disorganization and loss of the transverse tubule network. Indeed, survival rates for HF are worse than many common cancers and have not improved over time. Tadalafil is a clinically relevant drug that blocks phosphodiesterase 5 with high specificity and is used to treat erectile dysfunction.

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The lung is the entry site for Bacillus anthracis in inhalation anthrax, the most deadly form of the disease. Spores must escape through the alveolar epithelial cell (AEC) barrier and migrate to regional lymph nodes, germinate and enter the circulatory system to cause disease. Several mechanisms to explain alveolar escape have been postulated, and all these tacitly involve the AEC barrier.

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Novel cardioprotective agents are needed in both heart failure (HF) and myocardial infarction. Increasing evidence from cellular studies and animal models indicate protective effects of phosphodiesterase-5 (PDE5) inhibitors, drugs usually reserved as treatments of erectile dysfunction and pulmonary arterial hypertension. PDE5 inhibitors have been shown to improve contractile function in systolic HF, regress left ventricular hypertrophy, reduce myocardial infarct size and suppress ischaemia-induced ventricular arrhythmias.

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The first experimental TE-mode silicon-on-insulator (SOI) isolators using Faraday Rotation are here realized to fill the 'missing link' in source-integrated near infrared photonic circuits. The isolators are simple 1D 2-element waveguides, where garnet claddings and longitudinal magnetic fields produce nonreciprocal mode conversion, the waveguide equivalent of Faraday Rotation (FR). Quasi-phase matched claddings are used to overcome the limitations of birefringence.

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The respiratory system is a complex network of many cell types, including subsets of macrophages and dendritic cells that work together to maintain steady-state respiration. Owing to limitations in acquiring cells from healthy human lung, these subsets remain poorly characterized transcriptionally and phenotypically. We set out to systematically identify these subsets in human airways by developing a schema of isolating large numbers of cells by whole-lung bronchoalveolar lavage.

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Background: Cigarette smoking (CS) is the main risk factor for the development of chronic obstructive pulmonary disease (COPD) and most COPD exacerbations are caused by respiratory infections including influenza. Influenza infections are more severe in smokers. The mechanism of the increased risk and severity of infections in smokers is likely multifactorial, but certainly includes changes in immunologic host defenses.

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Objective: Experimental evidence has shown potential cardioprotective actions of phosphodiesterase type-5 inhibitors (PDE5is). We investigated whether PDE5i use in patients with type 2 diabetes, with high-attendant cardiovascular risk, was associated with altered mortality in a retrospective cohort study.

Research Design And Methods: Between January 2007 and May 2015, 5956 men aged 40-89 years diagnosed with type 2 diabetes before 2007 were identified from anonymised electronic health records of 42 general practices in Cheshire, UK, and were followed for 7.

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Background: Femoral artery closure device use following percutaneous cannulation allows earlier mobilization, reduced staff burden, and improved comfort for patients compared with manual compression. The Mynx device (Access Closure, Inc), a novel extravascular closure device, uses a water-soluble non-thrombogenic polyethylene glycol plug.

Methods: We report retrospective analysis of success, complication rates, and associated factors in 432 consecutive patients undergoing elective outpatient coronary angiography in a single United Kingdom center.

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Hypertrophic cardiomyopathy is the most common genetic cardiovascular disorder and the leading cause of sudden cardiac death in the young. This article reviews the ventricular arrhythmias associated with hypertrophic cardiomyopathy, the difficulties in risk stratification, and current and future therapeutic strategies.

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Objectives: To investigate rates of and reasons for second and subsequent stent procedures in an unselected, "real-world" population.

Background: Repeat stenting is the primary difference reported in clinical trials of alternative revascularization strategies. The incidence, indication, and outcome for repeat stenting in contemporary practice outside the more selective populations of trials and registries has not been described.

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Intravascular imaging with optical coherence tomography (OCT) can produce high-resolution images (10-20 μm) of the coronary vessel wall and is being increasingly used to provide insight into coronary pathology and neointima formation following coronary stenting. Fourier domain OCT (FD-OCT) permits a greater scan diameter than time domain OCT and enables larger-caliber coronary structures to be effectively imaged. We present a case of a large, symptomatic and expanding right coronary artery aneurysm treated with FD-OCT-guided pericardial covered stenting and describe the OCT findings immediately after stent deployment and at 6 months.

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Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by increased type I interferons (IFNs) and multiorgan inflammation frequently targeting the skin. IFN-kappa is a type I IFN expressed in skin. A pooled genome-wide scan implicated the IFNK locus in SLE susceptibility.

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Second-harmonic generation using the type-II polarization configuration is demonstrated in quasi-phase-matched GaAs radicalAlGaAs superlattice waveguides. Phase-matching wavelengths and conversion efficiencies were determined for several quasi-phase-matching periods using 1.9 ps pulses.

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Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common congenital facial defects, with an incidence of 1 in 700-1,000 live births among individuals of European descent. Several linkage and association studies of NSCL/P have suggested numerous candidate genes and genomic regions. A genomewide linkage analysis of a large multigenerational family (UR410) with NSCL/P was performed using a single-nucleotide-polymorphism array.

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Split-hand/foot malformation with long-bone deficiency (SHFLD) is a rare, severe limb deformity characterized by tibia aplasia with or without split-hand/split-foot deformity. Identification of genetic susceptibility loci for SHFLD has been unsuccessful because of its rare incidence, variable phenotypic expression and associated anomalies, and uncertain inheritance pattern. SHFLD is usually inherited as an autosomal dominant trait with reduced penetrance, although recessive inheritance has also been postulated.

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Nonsyndromic cleft lip with or without cleft palate (CL-P) is a common congenital anomaly with incidence ranging from 1 in 300 to 1 in 2,500 live births. We analyzed two Indian pedigrees (UR017 and UR019) with isolated, nonsyndromic CL-P, in which the anomaly segregates as an autosomal dominant trait. The phenotype was variable, ranging from unilateral to bilateral CL-P.

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The potential role of the plastidial oxidative pentose phosphate pathway (OPPP) in providing the NADPH for fatty acid synthesis in plastids from developing embryos of Brassica napus (L.) has been investigated. Measurements of distributions of enzyme activities in fractions obtained from homogenates of isolated embryos have revealed that the glucose 6-phosphate and 6-phosphogluconate dehydrogenases are present in both cytosol and plastid, as is ribose 5-phosphate isomerase.

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