A Comparison of the Bidomain and EMI Models in Refractory Cardiac Tissue

Computational cardiac modelling has made incredible strides over the past 40 years toward becoming an integral component of healthcare. The majority of cardiac modelling is accomplished using the bidomain or monodomain models, equations describing electrical conduction in cardiac tissue. These models use a volume averaging approach in which the structure of individual cells is disregarded; instead, cells are treated homogeneously as a continuum. Although this approach often provides an adequate view of cardiac activity at the macro level, there are situations where this approximation is insufficient, such as when discontinuities at the cellular level are implicated in a given disease or phenomenon. To address this, a more detailed tissue model has recently been developed: the extracellular-membrane-intracellular (EMI) model. The EMI model explicitly defines the extracellular, membrane, and intracellular compartments to form a highly detailed model of cardiac tissue. However, this additional level of detail also poses a high computational cost. This thesis investigates the trade-off that exists between the conventional bidomain model and the EMI model. To do this, we carry out a comparison study. This constitutes the first EMI comparison study that has been conducted outside of the research group that developed the model. Using both models, we find the currents required to trigger consecutive action potentials at varying time intervals. We then use these data points to construct refractory profiles for each model and compare these profiles against available experimental data. Our findings demonstrate that within the framework of this study, the behaviour of the EMI model is noticeably closer to experimental data than the behaviour of the bidomain model. These results have implications on the way we approach tissue model selection in the future, as well as for our general understanding of the refractory properties of cardiac tissue

Physiological accuracy in simulating refractory cardiac tissue: the volume-averaged bidomain model vs. the cell-based EMI model

The refractory period of cardiac tissue can be quantitatively described using strength-interval (SI) curves. The information captured in SI curves is pertinent to the design of anti-arrhythmic devices including pacemakers and implantable cardioverter defibrillators. As computational cardiac modelling becomes more prevalent, it is feasible to consider the generation of computationally derived SI curves as a supplement or precursor to curves that are experimentally derived. It is beneficial, therefore, to examine the profiles of the SI curves produced by different cardiac tissue models to determine whether some models capture the refractory period more accurately than others. In this study, we compare the unipolar SI curves of two tissue models: the current state-of-the-art bidomain model and the recently developed extracellular-membrane-intracellular (EMI) model. The EMI model's resolution of individual cell structure makes it a more detailed model than the bidomain model, which forgoes the structure of individual cardiac cells in favour of treating them homogeneously as a continuum. We find that the resulting SI curves elucidate differences between the models, including that the behaviour of the EMI model is noticeably closer to the refractory behaviour of experimental data compared to that of the bidomain model. These results hold implications for future computational pacemaker simulations and shed light on the predicted refractory properties of cardiac tissue from each model.Comment: 30 pages, 12 figures, 3 table

Plenary Session III – Policy Track: Focus on Innovation

Dr. Cicchini will describe the Insurance Institute for Highway Safety and how its work can inform efforts in Massachusetts to promote older driver road safety. Dr. Reimer will describe innovations in research and the implications for policy. Nora Moreno Cargie will discuss how corporate and philanthropic partners can support innovative policy developments. Meghan Verona Joyce will describe Uber’s innovative partnership with government partners as a model for other entities to consider as they face regulatory challenges. Betsey Crimmins will discuss the legal and elder justice innovations needed to keep older MA adults safe and mobile

Electron microscopy of quantum dots

This brief review describes the different types of semiconductor quantum dost systems, their main applications and which types of microscopy methods are used to characterize them. Emphasis is put on the need for a comprehensive investigation of their size distribution, microstructure, chemical composition, strain state and electronic properties, all of which influence the optical properties and can be measured by different types of imaging, diffraction and spectroscopy methods in an electron microscope

Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics

In December 2016, a panel of experts in microbiology, nutrition and clinical research was convened by the International Scientific Association for Probiotics and Prebiotics to review the definition and scope of prebiotics. Consistent with the original embodiment of prebiotics, but aware of the latest scientific and clinical developments, the panel updated the definition of a prebiotic: a substrate that is selectively utilized by host microorganisms conferring a health benefit. This definition expands the concept of prebiotics to possibly include non-carbohydrate substances, applications to body sites other than the gastrointestinal tract, and diverse categories other than food. The requirement for selective microbiota-mediated mechanisms was retained. Beneficial health effects must be documented for a substance to be considered a prebiotic. The consensus definition applies also to prebiotics for use by animals, in which microbiota-focused strategies to maintain health and prevent disease is as relevant as for humans. Ultimately, the goal of this Consensus Statement is to engender appropriate use of the term ‘prebiotic’ by relevant stakeholders so that consistency and clarity can be achieved in research reports, product marketing and regulatory oversight of the category. To this end, we have reviewed several aspects of prebiotic science including its development, health benefits and legislation

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570