RESUMEN
Mathematical models of a cellular action potential (AP) in cardiac modelling have become increasingly complex, particularly in gating kinetics, which control the opening and closing of individual ion channel currents. As cardiac models advance towards use in personalized medicine to inform clinical decision-making, it is critical to understand the uncertainty hidden in parameter estimates from their calibration to experimental data. This study applies approximate Bayesian computation to re-calibrate the gating kinetics of four ion channels in two existing human atrial cell models to their original datasets, providing a measure of uncertainty and indication of potential issues with selecting a single unique value given the available experimental data. Two approaches are investigated to reduce the uncertainty present: re-calibrating the models to a more complete dataset and using a less complex formulation with fewer parameters to constrain. The re-calibrated models are inserted back into the full cell model to study the overall effect on the AP. The use of more complete datasets does not eliminate uncertainty present in parameter estimates. The less complex model, particularly for the fast sodium current, gave a better fit to experimental data alongside lower parameter uncertainty and improved computational speed. This article is part of the theme issue 'Uncertainty quantification in cardiac and cardiovascular modelling and simulation'.
Asunto(s)
Atrios Cardíacos/citología , Modelos Cardiovasculares , Incertidumbre , Potenciales de Acción , Calibración , Atrios Cardíacos/metabolismo , Humanos , Canales Iónicos/metabolismoRESUMEN
Patient-specific cardiac models are now being used to guide therapies. The increased use of patient-specific cardiac simulations in clinical care will give rise to the development of virtual cohorts of cardiac models. These cohorts will allow cardiac simulations to capture and quantify inter-patient variability. However, the development of virtual cohorts of cardiac models will require the transformation of cardiac modelling from small numbers of bespoke models to robust and rapid workflows that can create large numbers of models. In this review, we describe the state of the art in virtual cohorts of cardiac models, the process of creating virtual cohorts of cardiac models, and how to generate the individual cohort member models, followed by a discussion of the potential and future applications of virtual cohorts of cardiac models. This article is part of the theme issue 'Uncertainty quantification in cardiac and cardiovascular modelling and simulation'.
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Modelos Cardiovasculares , Modelación Específica para el Paciente , Estudios de Cohortes , Biología Computacional , Humanos , Aprendizaje Automático , Interfaz Usuario-ComputadorRESUMEN
A hybrid parallelisation technique for distributed memory systems is investigated for a coupled Fourier-spectral/hp element discretisation of domains characterised by geometric homogeneity in one or more directions. The performance of the approach is mathematically modelled in terms of operation count and communication costs for identifying the most efficient parameter choices. The model is calibrated to target a specific hardware platform after which it is shown to accurately predict the performance in the hybrid regime. The method is applied to modelling turbulent flow using the incompressible Navier-Stokes equations in an axisymmetric pipe and square channel. The hybrid method extends the practical limitations of the discretisation, allowing greater parallelism and reduced wall times. Performance is shown to continue to scale when both parallelisation strategies are used.
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Measurements of cardiac conduction velocity provide valuable functional and structural insight into the initiation and perpetuation of cardiac arrhythmias, in both a clinical and laboratory context. The interpretation of activation wavefronts and their propagation can identify mechanistic properties of a broad range of electrophysiological pathologies. However, the sparsity, distribution and uncertainty of recorded data make accurate conduction velocity calculation difficult. A wide range of mathematical approaches have been proposed for addressing this challenge, often targeted towards specific data modalities, species or recording environments. Many of these algorithms require identification of activation times from electrogram recordings which themselves may have complex morphology or low signal-to-noise ratio. This paper surveys algorithms designed for identifying local activation times and computing conduction direction and speed. Their suitability for use in different recording contexts and applications is assessed.
Asunto(s)
Algoritmos , Arritmias Cardíacas/fisiopatología , Electrocardiografía , Sistema de Conducción Cardíaco/fisiopatología , Modelos Cardiovasculares , Procesamiento de Señales Asistido por Computador , Femenino , Humanos , MasculinoRESUMEN
We investigate the relative performance of a second-order Adams-Bashforth scheme and second-order and fourth-order Runge-Kutta schemes when time stepping a 2D linear advection problem discretised using a spectral/hp element technique for a range of different mesh sizes and polynomial orders. Numerical experiments explore the effects of short (two wavelengths) and long (32 wavelengths) time integration for sets of uniform and non-uniform meshes. The choice of time-integration scheme and discretisation together fixes a CFL limit that imposes a restriction on the maximum time step, which can be taken to ensure numerical stability. The number of steps, together with the order of the scheme, affects not only the runtime but also the accuracy of the solution. Through numerical experiments, we systematically highlight the relative effects of spatial resolution and choice of time integration on performance and provide general guidelines on how best to achieve the minimal execution time in order to obtain a prescribed solution accuracy. The significant role played by higher polynomial orders in reducing CPU time while preserving accuracy becomes more evident, especially for uniform meshes, compared with what has been typically considered when studying this type of problem.© 2014. The Authors. International Journal for Numerical Methods in Fluids published by John Wiley & Sons, Ltd.
RESUMEN
Flow past a circular cylinder is investigated in the subcritical regime, below the onset of Bénard-von Kármán vortex shedding at Reynolds number Re(c)≃47 . The transient response of infinitesimal perturbations is computed. The domain requirements for obtaining converged results is discussed at length. It is shown that energy amplification occurs as low as Re=2.2 . Throughout much of the subcritical regime the maximum energy amplification increases approximately exponentially in the square of Re reaching 6800 at Re(c). The spatiotemporal structure of the optimal transient dynamics is shown to be transitory Bénard-von Kármán vortex streets. At Re≃42 the long-time structure switches from exponentially increasing downstream to exponentially decaying downstream. Three-dimensional computations show that two-dimensional structures dominate the energy growth except at short times.