All Outputs (90)

Cardiac TdP risk stratification modelling of anti-infective compounds including chloroquine and hydroxychloroquine (2021)
Journal Article

Hydroxychloroquine (HCQ), the hydroxyl derivative of chloroquine (CQ), is widely used in the treatment of rheumatological conditions (systemic lupus erythematosus, rheumatoid arthritis) and is being studied for the treatment and prevention of COVID-1... Read More about Cardiac TdP risk stratification modelling of anti-infective compounds including chloroquine and hydroxychloroquine.

Use of Patient Health Records to Quantify Drug-Related Pro-arrhythmic Risk (2020)
Journal Article

There is an increasing expectation that computational approaches may supplement existing human decision-making. Frontloading of models for cardiac safety prediction is no exception to this trend, and ongoing regulatory initiatives propose use of high... Read More about Use of Patient Health Records to Quantify Drug-Related Pro-arrhythmic Risk.

A nonlinear and time-dependent leak current in the presence of calcium fluoride patch-clamp seal enhancer [version 1; peer review: 2 approved with reservations] (2020)
Journal Article

Automated patch-clamp platforms are widely used and vital tools in both academia and industry to enable high-throughput studies such as drug screening. A leak current to ground occurs whenever the seal between a pipette and cell (or internal solution... Read More about A nonlinear and time-dependent leak current in the presence of calcium fluoride patch-clamp seal enhancer [version 1; peer review: 2 approved with reservations].

Accounting for variability in ion current recordings using a mathematical model of artefacts in voltage-clamp experiments (2020)
Journal Article

Mathematical models of ion channels, which constitute indispensable components of action potential models, are commonly constructed by fitting to whole-cell patch-clamp data. In a previous study, we fitted cell-specific models to hERG1a (Kv11.1) reco... Read More about Accounting for variability in ion current recordings using a mathematical model of artefacts in voltage-clamp experiments.

Considering discrepancy when calibrating a mechanistic electrophysiology model (2020)
Journal Article

Uncertainty quantification (UQ) is a vital step in using mathematical models and simulations to take decisions. The field of cardiac simulation has begun to explore and adopt UQ methods to characterize uncertainty in model inputs and how that propaga... Read More about Considering discrepancy when calibrating a mechanistic electrophysiology model.

The fickle heart: uncertainty quantification in cardiac and cardiovascular modelling and simulation (2020)
Journal Article

Corrigendum to “A systematic strategy for estimating hERG block potency and its implications in a new cardiac safety paradigm” [Toxicology and Applied Pharmacology volume 394C (2020) 114961] (2020)
Journal Article

© 2020 The Author(s) The authors regret that one affiliation address is mistaken in the published paper. Matthew Bridgland-Taylor's affiliation was incorrectly listed as Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Cambridge, United Kin... Read More about Corrigendum to “A systematic strategy for estimating hERG block potency and its implications in a new cardiac safety paradigm” [Toxicology and Applied Pharmacology volume 394C (2020) 114961].

A systematic strategy for estimating hERG block potency and its implications in a new cardiac safety paradigm (2020)
Journal Article

© 2020 Introduction: hERG block potency is widely used to calculate a drug's safety margin against its torsadogenic potential. Previous studies are confounded by use of different patch clamp electrophysiology protocols and a lack of statistical quant... Read More about A systematic strategy for estimating hERG block potency and its implications in a new cardiac safety paradigm.

Chaste: Cancer, Heart and Soft Tissue Environment (2020)
Journal Article

Calibration of ionic and cellular cardiac electrophysiology models (2020)
Journal Article

© 2020 The Authors. WIREs Systems Biology and Medicine published by Wiley Periodicals, Inc. Cardiac electrophysiology models are among the most mature and well-studied mathematical models of biological systems. This maturity is bringing new challenge... Read More about Calibration of ionic and cellular cardiac electrophysiology models.

Rapid characterisation of hERG channel kinetics II: temperature dependence (2019)
Journal Article

Ion channel behavior can depend strongly on temperature, with faster kinetics at physiological temperatures leading to considerable changes in currents relative to room temperature. These temperature-dependent changes in voltage-dependent ion channel... Read More about Rapid characterisation of hERG channel kinetics II: temperature dependence.

General Principles for the Validation of Proarrhythmia Risk Prediction Models: An Extension of the CiPA In Silico Strategy (2019)
Journal Article

This white paper presents principles for validating proarrhythmia risk prediction models for regulatory use as discussed at the In Silico Breakout Session of a Cardiac Safety Research Consortium/Health and Environmental Sciences Institute/US Food and... Read More about General Principles for the Validation of Proarrhythmia Risk Prediction Models: An Extension of the CiPA In Silico Strategy.

High-throughput measurement and modeling of hERG kinetics using an automated platform (2019)
Journal Article

Four Ways to Fit an Ion Channel Model (2019)
Journal Article

© 2019 Biophysical Society Mathematical models of ionic currents are used to study the electrophysiology of the heart, brain, gut, and several other organs. Increasingly, these models are being used predictively in the clinic, for example, to predict... Read More about Four Ways to Fit an Ion Channel Model.

Rapid Characterization of hERG Channel Kinetics I: Using an Automated High-Throughput System (2019)
Journal Article

Predicting how pharmaceuticals may affect heart rhythm is a crucial step in drug-development, and requires a deep understanding of a compound’s action on ion channels. In vitro hERG-channel current recordings are an important step in evaluating the p... Read More about Rapid Characterization of hERG Channel Kinetics I: Using an Automated High-Throughput System.

Rapid Characterization of hERG Channel Kinetics II: Temperature Dependence (2019)
Journal Article

© 2019 Biophysical Society Ion channel behavior can depend strongly on temperature, with faster kinetics at physiological temperatures leading to considerable changes in currents relative to room temperature. These temperature-dependent changes in vo... Read More about Rapid Characterization of hERG Channel Kinetics II: Temperature Dependence.

Probabilistic Inference on Noisy Time Series (PINTS) (2019)
Journal Article

Time series models are ubiquitous in science, arising in any situation where researchers seek to understand how a system’s behaviour changes over time. A key problem in time series modelling is inference; determining properties of the underlying syst... Read More about Probabilistic Inference on Noisy Time Series (PINTS).

Selective recruitment of different Ca2+-dependent transcription factors by STIM1-Orai1 channel clusters (2019)
Journal Article

© 2019, The Author(s). Store-operated Ca2+ entry, involving endoplasmic reticulum Ca2+ sensing STIM proteins and plasma membrane Orai1 channels, is a widespread and evolutionary conserved Ca2+ influx pathway. This form of Ca2+ influx occurs at discre... Read More about Selective recruitment of different Ca2+-dependent transcription factors by STIM1-Orai1 channel clusters.

Defining vitamin D status using multi-metabolite mathematical modelling: a pregnancy perspective (2019)
Journal Article

Vitamin D deficiency is linked to adverse pregnancy outcomes such as pre-eclampsia (PET) but remains defined by serum measurement of 25-hydroxyvitamin D3 (25(OH)D3) alone. To identify broader changes in vitamin D metabolism during normal and PET preg... Read More about Defining vitamin D status using multi-metabolite mathematical modelling: a pregnancy perspective.

Response to “CiPA's Complexity Bias” (2019)
Journal Article