A5008693707- Cardiac electrophysiology and arrhythmias
- Radiation Dose and Imaging
- Neuroscience and Neural Engineering
- Receptor Mechanisms and Signaling
- Ion channel regulation and function
- Animal testing and alternatives
- Neuroscience and Neuropharmacology Research
- Air Quality and Health Impacts
- Cardiac Imaging and Diagnostics
- Wind and Air Flow Studies
- Anesthesia and Sedative Agents
- Advanced X-ray and CT Imaging
- Computational Drug Discovery Methods
- Cardiovascular Function and Risk Factors
- Aquatic Invertebrate Ecology and Behavior
- Cardiovascular Conditions and Treatments
- Fish Ecology and Management Studies
- 3D Printing in Biomedical Research
- Pluripotent Stem Cells Research
- Cardiac, Anesthesia and Surgical Outcomes
- Advanced Radiotherapy Techniques
- Meta-analysis and systematic reviews
- Veterinary Pharmacology and Anesthesia
- Freshwater macroinvertebrate diversity and ecology
- Cardiovascular Effects of Exercise
Guy's and St Thomas' NHS Foundation Trust
2007-2024
Janssen (Belgium)
2012-2021
The University of Sydney
2021
St Thomas' Hospital
1996-2020
University of Surrey
2020
Johnson & Johnson (United States)
2009-2012
King's College Hospital
2003
St. Thomas Hospital
1999
Royal Sussex County Hospital
1994
Johns Hopkins University
1985
Early prediction of cardiotoxicity is critical for drug development. Current animal models raise ethical and translational questions, have limited accuracy in clinical risk prediction. Human-based computer constitute a fast, cheap potentially effective alternative to experimental assays, also facilitating translation human. Key challenges include consideration inter-cellular variability responses integration computational methods safety pharmacology. Our aim evaluate the ability silico...
Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) are emerging as a powerful in vitro model for cardiac safety assessment which may allow better identification of compounds with poor arrhythmogenic liability profiles early the drug discovery process. Here, we describe our examination Kinetic Image Cytometer (KIC) system's ability to predict adverse compound effects using hiPS-CMs and library 53 compounds, majority known be cardioactive several negative controls. The KIC...
Advanced leads from a series of 1,2,4-triazolo[4,3-a]pyridines with mGlu2 receptor PAM activity are reported. By modification the analogous imidazo[1,2-a]pyridine series, newly reported have improved potency, in vitro ADMET, and hERG as well good vivo PK profile. The optimization focused on improving metabolic stability while controlling lipophilicity by introducing small modifications to scaffold substituents. Analysis this combined our previously PAMs showed how lipophilic ligand...
Over the last two decades, awareness of negative repercussions flaws in planning, conduct and reporting preclinical research involving experimental animals has been growing. Several initiatives have set out to increase transparency internal validity studies, mostly publishing expert consensus experience. While many points raised these various guidelines are identical or similar, they differ detail rigour. Most them focus on reporting, only few cover planning studies. The aim this systematic...
To measure the radiation exposure of operating team during endovascular aortic procedures, and to determine factors that predict high exposures.Electronic dosimeters placed over under protective lead garments, were used prospectively record repairs performed in a designated interventional radiology suite. Univariate multivariate linear regression analyses predictors performed.A total 26 infra-renal 10 thoracic cases studied. Median (IQR) patient age body mass index 76.0 (70.0-81.8) years...
We previously reported the discovery of 4-aryl-substituted pyridones with mGlu2 PAM activity starting from HTS hit 5. In this article, we describe a different exploration 5 that led to novel subseries phenylpiperidine-substituted pyridones. The optimization strategy involved introduction spacers between pyridone core and phenyl ring fine tuning metabolism hERG followed by differentiation advanced leads were identified on basis PK profiles in vivo potency converged lead compound 36...
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising cardiac safety platform, demonstrated by numerous validation studies using drugs with known adverse effects in humans. However, the challenge remains to implement hiPSC-CMs into de-risking of new chemical entities (NCEs) during preclinical drug development. Here, we used calcium transient screening assay develop hazard score system for electrical liabilities. Tolerance interval calculations and...
The objective of our study was to determine the relative sensitivity and lowest threshold bleeding detectable with digital subtraction angiography (DSA) MDCT using an in vitro physiologic system.A closed pulsatile cardiopulmonary bypass circuit connected tubes traversing a water bath simulate abdominal aorta inferior vena cava. Three smaller interconnecting acrylic plastic were as branches aortic tubing branch vessels. One three tubes, control, had no holes it, one 100-microm hole,...
Selected benign biliary strictures can be treated safely and successfully by percutaneous balloon dilatation. Primary appear to less responsive dilatation alone require stenting with large catheters (16-20 F) for several months permit scarring around the catheter. A long period of healing such a large-bore stent is crucial success treatment. The most important physiologic indicators successful are stricture challenge catheter placed proximal dilated segment allow bile drain internally across...
The goal of this research consortium including Janssen, MSD, Ncardia, FNCR/LBR, and Health Environmental Sciences Institute (HESI) was to evaluate the utility an additional in vitro assay technology detect potential drug-induced long QT torsade de pointes (TdP) risk by monitoring cytosolic free Ca2+ transients human stem-cell-derived cardiomyocytes (hSC-CMs). proarrhythmic risks 28 comprehensive proarrhythmia (CiPA) drugs linked low, intermediate, high clinical TdP were evaluated a blinded...
As an alternative to performing interventional radiology on inpatients under the care of internists and surgeons, authors have established a cardiovascular admitting service for well-screened, elective patients. The patients are admitted fellow staff physician. From April 1982 December 1983, 133 were service. Patients cared in surgical ward or intermediate unit, as determined by clinical situation. Advantages this approach include broader patient referral base, improved rapport with...
Drug-induced QTc interval prolongation (ΔQTc) is a main surrogate for proarrhythmic risk assessment. A higher in vivo than vitro potency hERG-mediated has been suggested. Also, between-species and patient populations’ sensitivity to drug-induced seems differ. Here, systems pharmacology model integrating preclinical (hERG binding) (conscious dog ΔQTc) data of three hERG blockers (dofetilide, sotalol, moxifloxacin) was applied (1) compare the operational efficacy drugs (2) quantify dog–human...
Background: An experimental imaging platform for longitudinal monitoring and evaluation of cardiac morphology-function changes has been long desired. We sought to establish such a by using rabbit model reperfused myocardial infarction (MI) that develops chronic left ventricle systolic dysfunction (LVSD) within 7 weeks. Methods: Fifty-five New Zeeland white (NZW) rabbits received sham-operated or 60-min circumflex coronary artery (LCx) ligation followed reperfusion. Cardiac magnetic resonance...
Recent years have seen the development of mobile CT units, designed for use in operating theatres, intensive care units and accident emergency departments. One such unit is Tomoscan M (Philips, Utrecht, The Netherlands). It operates with a maximum tube voltage 130 kV, current only 50 mA. This study tested whether acceptable quality images brain could be produced on these parameters. 44 consecutive normal head examinations performed scanner were compared 35 from two conventional units. Two...
The use of a single index to assist in quality control procedures X-ray television fluoroscopy systems was investigated. A devised incorporating measure threshold contrast detail detectability (TCDD) performance and taking into account image intensifier input kerma rate, field size, differences radiation beam quality, pulsed fluoroscopy. This applied number clinical investigate changes quantified over time. Accepted measurement protocols were used obtain these measurements. results show...
A radiological assessment was carried out on the release of positron-emitting radioactive gases from a roof-level stack at central London site. Different modelling approaches were performed to investigate range radiation doses representative persons. Contributions plume inhalation, gamma shine and immersion effective dose taken into account. Dry wet surface deposition roof, exposure contamination skin roof-workers, added only mean 4.7% neglected. 1:200 scale model, consisting surrounding...