Simulation of ectopic pacemakers in the heart: multiple ectopic beats generated by reentry inside fibrotic regions

The inclusion of nonconducting media, mimicking cardiac fibrosis, in two models of cardiac tissue produces the formation of ectopic beats. The fraction of nonconducting media in comparison with the fraction of healthy myocytes and the topological distribution of cells determines the probability of ectopic beat generation. First, a detailed subcellular microscopic model that accounts for the microstructure of the cardiac tissue is constructed and employed for the numerical simulation of action potential propagation. Next, an equivalent discrete model is implemented, which permits a faster integration of the equations. This discrete model is a simplified version of the microscopic model that maintains the distribution of connections between cells. Both models produce similar results when describing action potential propagation in homogeneous tissue; however, they slightly differ in the generation of ectopic beats in heterogeneous tissue. Nevertheless, both models present the generation of reentry inside fibrotic tissues. This kind of reentry restricted to microfibrosis regions can result in the formation of ectopic pacemakers, that is, regions that will generate a series of ectopic stimulus at a fast pacing rate. In turn, such activity has been related to trigger fibrillation in the atria and in the ventricles in clinical and animal studies.Peer ReviewedPostprint (published version

Expectativa e realidade: efeitos de uma intervenção pedagógica com estratégias autorregulatórias de atividade física

This study, a Doctorate Research excerpt, aimed to map the effects of an on-line pedagogical intervention guided on physical activity (PA) self-regulatory strategies during the pandemic at a public school. This is qualitative Research, of the pedagogical intervention type using an educational tool. 35 high school students (14 to 17 years old) were interviewed in 8 on-line focus groups. The software IRaMuTeQ was employed to interpret data. The results were organized in six classes: “Diary as in incentive to PA”, “Strategies to increase motivation”, “Choices and PA sociostructural factors”, “How preferences and social support influences PA”, “Goals and self-assessment reflections”, “PA monitoring”. Previously inactive, insufficiently active students (who identified themselves with the educational tool´s character) felt more confident to engage in PA (positive effect) using strategies taught in the intervention (PA diary). Previously physically active students rated the intervention effects as neutral, but praised critical debates on social inequalities and PA. During the intervention, some students employed simple self-regulatory strategies (graded goals), while others did not employ any due to not being something intuitive, lack of motivation, forgetting. This pedagogical intervention seems to be effective to teach the conceptual interfaces between PA, psychology, and society.En este estudio, que forma parte de una investigación de Doctorado, nos propusimos mapear los efectos de una intervención pedagógica en línea anclada en estrategias autorreguladoras de actividad física (AF) durante la pandemia en un instituto público. Se trata de una investigación cualitativa, del tipo intervención pedagógica con ayuda de recurso didáctico. Se realizaron 8 entrevistas semiestructuradas en grupo en línea con 35 alumnos (14 a 17 años) de la enseñanza secundaria. Se utilizó el software IRaMuTeQ para interpretar los datos. Los resultados se organizaron en seis clases: "Diario como estímulo para AF", "Estrategias para aumentar la motivación", "Elecciones y factores socioestructurales para AF", "Influencia del gusto y del incentivo para AF", "Reflexiones sobre metas y autoevaluación", "Monitoreo de la AF". Alumnos anteriormente inactivos o poco activos (identificados con el personaje del recurso didáctico) se sintieron más seguros para practicar AF (efecto positivo) con estrategias enseñadas en la intervención (diario de AF). Los estudiantes físicamente activos atribuyeron un efecto neutro a la intervención, pero valoraron las reflexiones críticas sobre las desigualdades sociales y la AF. Algunos estudiantes emplearon estrategias sencillas de autorregulación (metas graduales) de forma más consistente durante la intervención, mientras que otros no las emplearon porque: no eran intuitivas; les faltó motivación; se olvidaron de hacerlo. La intervención pedagógica parece ser eficaz para la enseñanza conceptual de las interfaces entre AF, psicología y sociedad.Neste estudo, recorte de uma pesquisa de Doutorado, objetivou-se mapear os efeitos de uma intervenção pedagógica on-line ancorada em estratégias autorregulatórias de atividade física (AF) durante a pandemia em um colégio público. Trata-se de uma pesquisa qualitativa, do tipo intervenção pedagógica com auxílio de recurso didático. Foram realizadas 8 entrevistas semiestruturadas em grupo on-line com 35 estudantes (14 a 17 anos) do Ensino Médio. Utilizou-se o software IRaMuTeQ para interpretar os dados. Os resultados foram organizados em seis classes: “Diário como estímulo para AF”, “Estratégias para aumentar a motivação”, “Escolhas e fatores socioestruturais para AF”, “Influência do gosto e do incentivo para AF”, “Reflexões sobre metas e autoavaliação”, “Monitoramento da AF”. Estudantes previamente inativos ou pouco ativos (identificados com o personagem do recurso didático) sentiram-se mais confiantes para praticar AF (efeito positivo) com estratégias ensinadas na intervenção (diário de AF). Estudantes ativos fisicamente atribuíram efeito neutro à intervenção, mas valorizaram as reflexões críticas sobre as desigualdades sociais e a AF. Alguns estudantes empregaram estratégias autorregulatórias simples (metas graduais) mais consistentemente durante a intervenção, enquanto outros não as empregaram por: não ser algo intuitivo; falta de motivação; esquecimento. A intervenção pedagógica parece ser eficaz para o ensino conceitual das interfaces entre AF, psicologia e sociedade

A Next-Generation Liquid Xenon Observatory for Dark Matter and Neutrino Physics

The nature of dark matter and properties of neutrinos are among the mostpressing issues in contemporary particle physics. The dual-phase xenontime-projection chamber is the leading technology to cover the availableparameter space for Weakly Interacting Massive Particles (WIMPs), whilefeaturing extensive sensitivity to many alternative dark matter candidates.These detectors can also study neutrinos through neutrinoless double-beta decayand through a variety of astrophysical sources. A next-generation xenon-baseddetector will therefore be a true multi-purpose observatory to significantlyadvance particle physics, nuclear physics, astrophysics, solar physics, andcosmology. This review article presents the science cases for such a detector.<br

A next-generation liquid xenon observatory for dark matter and neutrino physics

The nature of dark matter and properties of neutrinos are among the most pressing issues in contemporary particle physics. The dual-phase xenon time-projection chamber is the leading technology to cover the available parameter space for weakly interacting massive particles, while featuring extensive sensitivity to many alternative dark matter candidates. These detectors can also study neutrinos through neutrinoless double-beta decay and through a variety of astrophysical sources. A next-generation xenon-based detector will therefore be a true multi-purpose observatory to significantly advance particle physics, nuclear physics, astrophysics, solar physics, and cosmology. This review article presents the science cases for such a detector

Simulation of ectopic pacemakers in the heart: multiple ectopic beats generated by reentry inside fibrotic regions

The inclusion of nonconducting media, mimicking cardiac fibrosis, in two models of cardiac tissue produces the formation of ectopic beats. The fraction of nonconducting media in comparison with the fraction of healthy myocytes and the topological distribution of cells determines the probability of ectopic beat generation. First, a detailed subcellular microscopic model that accounts for the microstructure of the cardiac tissue is constructed and employed for the numerical simulation of action potential propagation. Next, an equivalent discrete model is implemented, which permits a faster integration of the equations. This discrete model is a simplified version of the microscopic model that maintains the distribution of connections between cells. Both models produce similar results when describing action potential propagation in homogeneous tissue; however, they slightly differ in the generation of ectopic beats in heterogeneous tissue. Nevertheless, both models present the generation of reentry inside fibrotic tissues. This kind of reentry restricted to microfibrosis regions can result in the formation of ectopic pacemakers, that is, regions that will generate a series of ectopic stimulus at a fast pacing rate. In turn, such activity has been related to trigger fibrillation in the atria and in the ventricles in clinical and animal studies.Peer Reviewe

Simulations of Complex and Microscopic Models of Cardiac Electrophysiology Powered by Multi-GPU Platforms

Key aspects of cardiac electrophysiology, such as slow conduction, conduction block, and saltatory effects have been the research topic of many studies since they are strongly related to cardiac arrhythmia, reentry, fibrillation, or defibrillation. However, to reproduce these phenomena the numerical models need to use subcellular discretization for the solution of the PDEs and nonuniform, heterogeneous tissue electric conductivity. Due to the high computational costs of simulations that reproduce the fine microstructure of cardiac tissue, previous studies have considered tissue experiments of small or moderate sizes and used simple cardiac cell models. In this paper, we develop a cardiac electrophysiology model that captures the microstructure of cardiac tissue by using a very fine spatial discretization (8 μm) and uses a very modern and complex cell model based on Markov chains for the characterization of ion channel’s structure and dynamics. To cope with the computational challenges, the model was parallelized using a hybrid approach: cluster computing and GPGPUs (general-purpose computing on graphics processing units). Our parallel implementation of this model using a multi-GPU platform was able to reduce the execution times of the simulations from more than 6 days (on a single processor) to 21 minutes (on a small 8-node cluster equipped with 16 GPUs, i.e., 2 GPUs per node)

Reactive interstitial and reparative fibrosis as substrates for cardiac ectopic pacemakers and reentries

This book constitutes the refereed proceedings of the 4th International Conference on Bioinformatics and Biomedical Engineering, IWBBIO 2016, held in Granada, Spain, in April 2016. The 69 papers presented were carefully reviewed and selected from 286 submissions. The scope of the conference spans the following areas: bioinformatics for healthcare and diseases; biomedical image analysis; biomedical signal analysis; computational systems for modeling biological processes; eHealth; tools for next generation sequencing data analysis; assistive technology for people with neuromotor disorders; fundamentals of biological dynamics and maximization of the information extraction from the experiments in the biological systems; high performance computing in bioinformatics, computational biology and computational chemistry; human behavior monitoring, analysis and understanding; pattern recognition and machine learning in the -omics sciences; and resources for bioinformatics.Dangerous cardiac arrhythmias have been frequently associated with focal sources of fast pulses, i.e. ectopic pacemakers. However, there is a lack of experimental evidences that could explain how ectopic pacemakers could be formed in cardiac tissue. In recent studies, we have proposed a new theory for the genesis of ectopic pacemakers in pathological cardiac tissues: reentry inside microfbrosis, i.e., a small region where excitable myocytes and non-conductive material coexist. In this work, we continue this investigation by comparing different types of fibrosis, reparative and reactive interstitial fibrosis. We use detailed and modern models of cardiac electrophysiology that account for the micro-structure of cardiac tissue. In addition, for the solution of our models we use, for the first time, a new numerical algorithm based on the Uniformization method. Our simulation results suggest that both types of fibrosis can support reentries, and therefore can generate in-silico ectopic pacemakers. However, the probability of reentries differs quantitatively for the different types of fibrosis. In addition, the new Uniformization method yields 20-fold increase in cardiac tissue simulation speed and, therefore, was an essential technique that allowed the execution of over a thousand of simulations.Peer Reviewe