arXiv subjects
Publications and source records attributed to Irina V. Biktasheva.
Transient local over-dry environment might be a contributor and an explanation for the observed asynchronous local rises in Covid-19 mortality. We propose that a habitat's air humidity negatively correlate with Covid-19 morbidity and mortality, and support this hypothesis on the example of publicly available data from German federal states.
In many oscillatory or excitable systems, dynamical patterns emerge which are stationary or periodic up in a moving frame of reference. Examples include traveling waves or spiral waves in chemical systems or cardiac tissue. We present a unified theoretical framework for the drift of such patterns under small external perturbations, in terms of overlap integrals between the perturbation and the adjoint critical eigenfunctions of the linearised operator (i.e. `response functions'). For spiral waves, the finite radius of the spiral tip trajectory as well as spiral wave meander are taken into account. Different coordinates systems can be chosen, depending on whether one wants to predict the motion of the spiral wave tip, the time-averaged tip path, or the center of the meander flower. The framework is applied to analyse the drift of a meandering spiral wave in a constant external field in different regimes.
Cardiac re-entry regime of self-organised abnormal synchronisation underlie dangerous arrhythmias and fatal fibrillation. Recent advances in the theory of dissipative vortices, experimental studies, and anatomically realistic computer simulations, elucidated the role of cardiac re-entry interaction with fine anatomical features in the heart, and anatomy induced drift. The fact that anatomy and structural anisotropy of the heart is consistent within a species suggested its possible functional effect on spontaneous drift of cardiac re-entry. A comparative study of the anatomy induced drift could be used in order to predict evolution of atrial arrhythmia, and improve low-voltage defibrillation protocols and ablation strategies. Here, in micro-CT based model of rat pulmonary vein wall, and in sheep atria models based on high resolution serial histological sections, we demonstrate effects of heart geometry and anisotropy on cardiac re-entry anatomy induced drift, its pinning to fluctuations of thickness in the layer. The data sets of sheep atria and rat pulmonary vein wall are incorporated into the BeatBox High Performance Computing simulation environment. Re-entry is initiated at prescribed locations in the spatially homogeneous mono-domain models of cardiac tissue. Excitation is described by FitzHugh-Nagumo kinetics. In the in-silico models, isotropic and anisotropic conduction show specific anatomy effects and the interplay between anatomy and anisotropy of the heart. The main objectives are to demonstrate the functional role of the species hearts geometry and anisotropy on cardiac re-entry anatomy induced drift. In case of the rat pulmonary vein wall with ~90 degree transmural fibre rotation, it is shown that the joint effect of the PV wall geometry and anisotropy turns a plane excitation wave into a re-entry pinned to a small fluctuation of thickness in the wall.
Rotating scroll waves are self-organising patterns which are found in many oscillating or excitable systems. Here we show that quasi-periodic (meandering) scroll waves, which include the rotors that organise cardiac arrhythmias, exhibit filament tension when averaged over the meander cycle. With strong filament curvature or medium thickness gradients, however, scroll wave dynamics are governed by phase-locked drift instead of filament tension. Our results are validated in computational models of cycloidal meander and a cardiac tissue model with linear core.
The effect of heart geometry and anisotropy on cardiac re-entry dynamics and self-termination is studied here in anatomically realistic computer simulations of human foetal heart. 20 weeks of gestational age human foetal heart isotropic and anisotropic anatomy models from diffusion tensor MRI data sets are used in the computer simulations. The fibre orientation angles of the heart were obtained from the DT-MRI primary eigenvalues. In a spatially homogeneous electrophysiological mono domain model with the DT-MRI based heart geometries, we initiate simplified Fitz-Hugh-Nagumo kinetics cardiac re-entry at a prescribed location in a 2D slice, and in the full 3D anatomy model. In a slice of the heart, the MRI based fibre anisotropy changes the re-entry dynamics from pinned to anatomical re-entry. In the full 3D MRI based model, the foetal heart fibre anisotropy changes the re-entry dynamics from a persistent re-entry to the re-entry self-termination.
The BeatBox simulation environment combines flexible script language user interface with the robust computational tools, in order to setup cardiac electrophysiology in-silico experiments without re-coding at low-level, so that cell excitation, tissue/anatomy models, stimulation protocols may be included into a BeatBox script, and simulation run either sequentially or in parallel (MPI) without re-compilation. BeatBox is a free software written in C language to be run on a Unix-based platform. It provides the whole spectrum of multi scale tissue modelling from 0-dimensional individual cell simulation, 1-dimensional fibre, 2-dimensional sheet and 3-dimensional slab of tissue, up to anatomically realistic whole heart simulations, with run time measurements including cardiac re-entry tip/filament tracing, ECG, local/global samples of any variables, etc. BeatBox solvers, cell, and tissue/anatomy models repositories are extended via robust and flexible interfaces, thus providing an open framework for new developments in the field. In this paper we give an overview of the BeatBox current state, together with a description of the main computational methods and MPI parallelisation approaches.
This has been written as a chapter for "Engineering Chemical Complexity II", and as such does not have an abstract.
The dose regimen of Warfarin is separated into two phases. Firstly a loading dose is given, which is designed to bring the International Normalisation Ratio (INR) to within therapeutic range. Then a stable maintenance dose is given to maintain the INR within therapeutic range. In the United Kingdom (UK) the loading dose is usually given as three individual daily doses, the standard loading dose being 10mg on days one and two and 5mgs on day three, which can be varied at the discretion of the clinician. However, due to the large inter-individual variation in the response to Warfarin therapy, it is difficult to identify which patients will reach the narrow therapeutic window for target INR, and which will be above or below the therapeutic window. The aim of this research was to develop a methodology using a neural networks classification algorithm and data mining techniques to predict for a given loading dose and patient characteristics if the patient is more likely to achieve target INR or more likely to be above or below therapeutic range. Multilayer perceptron (MLP) and 10-fold stratified cross validation algorithms were used to determine an artificial neural network to classify patients' response to their initial Warfarin loading dose. The resulting neural network model correctly classifies an individual's response to their Warfarin loading dose over 80% of the time. As well as taking into account the initial loading dose, the final model also includes demographic, genetic and a number of other potential confounding factors. With this model clinicians can predetermine whether a given loading regimen, along with specific patient characteristics will achieve a therapeutic response for a particular patient. Thus tailoring the loading dose regimen to meet the individual needs of the patient and reducing the risk of adverse drug reactions associated with Warfarin.
Abnormal electrical activity from the boundaries of ischemic cardiac tissue is recognized as one of the major causes in generation of ischemia-reperfusion arrhythmias. Here we present theoretical analysis of the waves of electrical activity that can rise on the boundary of cardiac cell network upon its recovery from ischaemia-like conditions. The main factors included in our analysis are macroscopic gradients of the cell-to-cell coupling and cell excitability and microscopic heterogeneity of individual cells. The interplay between these factors allows one to explain how spirals form, drift together with the moving boundary, get transiently pinned to local inhomogeneities, and finally penetrate into the bulk of the well-coupled tissue where they reach macroscopic scale. The asymptotic theory of the drift of spiral and scroll waves based on response functions provides explanation of the drifts involved in this mechanism, with the exception of effects due to the discreteness of cardiac tissue. In particular, this asymptotic theory allows an extrapolation of 2D events into 3D, which has shown that cells within the border zone can give rise to 3D analogues of spirals, the scroll waves. When and if such scroll waves escape into a better coupled tissue, they are likely to collapse due to the positive filament tension. However, our simulations have shown that such collapse of newly generated scrolls is not inevitable and that under certain conditions filament tension becomes negative, leading to scroll filaments to expand and multiply leading to a fibrillation-like state within small areas of cardiac tissue.
Rotating spiral and scroll waves (vortices) are investigated in the FitzHugh-Nagumo model of excitable media. The focus is on a parameter region in which there exists bistability between alternative stable vortices with distinct periods. Response Functions are used to predict the filament tension of the alternative scrolls and it is shown that the slow-period scroll has negative filament tension, while the filament tension of the fast-period scroll changes sign within a hysteresis loop. The predictions are confirmed by direct simulations. Further investigations show that the slow-period scrolls display features similar to delayed after-depolarisation (DAD) and tend to develop into turbulence similar to Ventricular Fibrillation (VF). Scrolls with positive filament tension collapse or stabilize, similar to monomorphic Ventricular Tachycardia (VT). Perturbations, such as boundary interaction or shock stimulus, can convert the vortex with negative filament tension into the vortex with positive filament tension. This may correspond to transition from VF to VT unrelated to pinning.