Publications by authors named "Simon Wells"

The electrophysiological properties of the hearts of women and men are different. These differences are at least partly mediated by the actions of circulating estrogens and androgens on the cardiomyocytes. Experimentally, much of our understanding in this field is based on studies focusing on ventricular tissue, with considerably less known in the context of atrial electrophysiology.

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Transmural action potential duration differences and transmural conduction gradients aid the synchronization of left ventricular repolarization, reducing vulnerability to transmural reentry and arrhythmias. A high-fat diet and the associated accumulation of pericardial adipose tissue are linked with conduction slowing and greater arrhythmia vulnerability. It is predicted that cardiac adiposity may more readily influence epicardial conduction (versus endocardial) and disrupt normal transmural activation/repolarization gradients.

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Optical mapping of animal models is a widely used technique in pre-clinical cardiac research. It has several advantages over other methods, including higher spatial resolution, contactless recording and direct visualisation of action potentials and calcium transients. Optical mapping enables simultaneous study of action potential and calcium transient morphology, conduction dynamics, regional heterogeneity, restitution and arrhythmogenesis.

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Purpose: We sought to evaluate the factors associated with better outcomes for emergency department (ED) patients treated for primary headache.

Methods: This was a health records review of consecutive patients over a 3-month period presenting to two tertiary EDs and discharged with a diagnosis of primary headache. The primary outcome was the need for second round medications, defined as medications received > 1 h after the initial physician-ordered medications were administered.

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Background: Clinical studies have reported that epicardial adipose tissue (EpAT) accumulation associates with the progression of atrial fibrillation (AF) pathology and adversely affects AF management. The role of local cardiac EpAT deposition in disease progression is unclear, and the electrophysiological, cellular, and molecular mechanisms involved remain poorly defined.

Objectives: The purpose of this study was to identify the underlying mechanisms by which EpAT influences the atrial substrate for AF.

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Cardiac arrhythmias of both atrial and ventricular origin are an important feature of cardiovascular disease. Novel antiarrhythmic therapies are required to overcome current drug limitations related to effectiveness and pro-arrhythmia risk in some contexts. Cardiomyocyte culture models provide a high-throughput platform for screening antiarrhythmic compounds, but comparative information about electrophysiological properties of commonly used types of cardiomyocyte preparations is lacking.

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Optical mapping is an established technique for high spatio-temporal resolution study of cardiac electrophysiology in multi-cellular preparations. Here we present, in a step-by-step guide, the use of ElectroMap for analysis, quantification, and mapping of high-resolution voltage and calcium datasets acquired by optical mapping. ElectroMap analysis options cover a wide variety of key electrophysiological parameters, and the graphical user interface allows straightforward modification of pre-processing and parameter definitions, making ElectroMap applicable to a wide range of experimental models.

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The ability to record and analyse electrical behaviour across the heart using optical and electrode mapping has revolutionised cardiac research. However, wider uptake of these technologies is constrained by the lack of multi-functional and robustly characterised analysis and mapping software. We present ElectroMap, an adaptable, high-throughput, open-source software for processing, analysis and mapping of complex electrophysiology datasets from diverse experimental models and acquisition modalities.

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Background: Healthcare-associated Clostridium difficile infection (CDI) in pregnant/postpartum women is underreported, especially outside of North America. We report a cluster of cases in 2 neighboring secondary care hospitals in South-East England. The objective of this study was to identify the epidemiology and risk factors for infection.

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Identifying the biological origin of forensic traces can provide crucial evidence to aid criminal investigations. Current forensic practice for the identification of body fluids mostly uses protein-based presumptive tests. Such tests cannot identify all of the forensically relevant fluids and have issues of cross-reactivity.

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HyBeacons are linear oligonucleotides which incorporate fluorescent dyes covalently linked to internal nucleotides. They have previously been used with PCR and isothermal amplification to interrogate SNPs and STRs in fields as diverse as clinical diagnostics, food authentication, and forensic DNA profiling. This work explores their use for the identification of expressed gene sequences through mRNA profiling.

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A combined study of the vibrational spectroscopy of iodopentafluorobenzene by new Raman and Fourier transform infrared (FTIR) spectroscopies, over the spectral range 300 to 3200 cm (Raman) and 50 to 3400 cm (FTIR), with a state-of-the-art theoretical investigation is reported. This has enabled reliable identification of numerous fundamental, overtone, and combination band transitions in unprecedented detail. The theoretical analysis, beyond the double-harmonic approximation, is based on generalized second-order vibrational perturbation theory (GVPT2) with a hybrid coupled cluster/density functional theory (CC/DFT) approach.

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Objective: The purpose of this study was to perform a systematic review and meta-analysis to determine whether a difference exists in hematoma rates following thyroidectomy for any of the following subgroups of patients: Graves disease, toxic nodular goiter (TNG), and malignancy.

Study Design: Systematic review and meta-analysis.

Methods: A systematic literature search was performed for all relevant English and French language studies (1946-2015) using Ovid MEDLINE, EMBASE, and PubMed.

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Article Synopsis
  • DNA profiling using STR analysis is essential for human identification, but traditional methods are often slow and costly, leading to challenges in investigations.
  • The ParaDNA(®) Intelligence System offers a faster, user-friendly solution for DNA profiling, requiring minimal training and able to analyze samples directly in about 75 minutes.
  • Developed following established guidelines, the system has proven effective across various biological samples, indicating its potential utility in forensic, military, and disaster victim identification applications.
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The PRESENILIN1 and PRESENILIN2 genes encode structurally related proteases essential for γ-secretase activity. Of nearly 200 PRESENILIN mutations causing early onset, familial Alzheimer's disease (FAD) only the K115Efx10 mutation of PSEN2 causes truncation of the open reading frame. If translated, the truncated product would resemble a naturally occurring isoform of PSEN2 named PS2V that is induced by hypoxia and found at elevated levels in late onset Alzheimer's disease (AD) brains.

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Current assessment of whether a forensic evidence item should be submitted for STR profiling is largely based on the personal experience of the Crime Scene Investigator (CSI) and the submissions policy of the law enforcement authority involved. While there are chemical tests that can infer the presence of DNA through the detection of biological stains, the process remains mostly subjective and leads to many samples being submitted that give no profile or not being submitted although DNA is present. The ParaDNA(®) Screening System was developed to address this issue.

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We describe the creation of a transgenic zebrafish expressing GFP driven by a 7.5 kb promoter region of the tbx16 gene. This promoter segment is sufficient to recapitulate early embryonic expression of endogenous tbx16 in the presomitic mesoderm, the polster and, subsequently, in the hatching gland.

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The molecules and mechanisms involved in patterning the dorsoventral axis of the developing vertebrate spinal cord have been investigated extensively and many are well known. Conversely, knowledge of mechanisms patterning cellular distributions along the rostrocaudal axis is relatively more restricted. Much is known about the rostrocaudal distribution of motoneurons and spinal cord cells derived from neural crest but there is little known about the rostrocaudal patterning of most of the other spinal cord neurons.

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Presenilin1 (PSEN1) and presenilin2 (PSEN2) are involved in the processing of type-1 transmembrane proteins including the amyloid precursor protein (APP), Notch and several others. PSEN1 has been shown to be crucial for proteolytic cleavage of Notch in developing animal embryos. Mouse embryos lacking Psen1 function show disturbed neurogenesis and somite formation, resembling Notch pathway mutants.

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Missense mutations in the PRESENILIN1 (PSEN1) gene frequently underlie familial Alzheimer's disease (FAD). Nonsense and most splicing mutations result in the synthesis of truncated peptides, and it has been assumed that truncated PSEN1 protein is functionless so that heterozygotes for these mutations are unaffected. Some FAD mutations affecting PSEN1 mRNA splicing cause loss of exon 8 or 9 sequences while maintaining the reading frame.

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Background: The spadetail (spt) gene of zebrafish is expressed in presomitic mesoderm and in neural cells previously suggested to be Rohon-Beard neurons. The mechanism(s) generating the apparently irregular rostrocaudal distribution of spt-expressing cells in the developing CNS is unknown.

Results: spt-expressing neural cells co-express huC, a marker of neurons.

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