Harold M. Hastings

Bio: Harold M. Hastings is an academic researcher from Hofstra University. The author has contributed to research in topics: Cofibration & Homotopy. The author has an hindex of 21, co-authored 96 publications receiving 2955 citations. Previous affiliations of Harold M. Hastings include Long Island Jewish Medical Center & Bard College at Simon's Rock.

Multiple mechanisms of spiral wave breakup in a model of cardiac electrical activity

Abstract: It has become widely accepted that the most dangerous cardiac arrhythmias are due to reentrant waves, i.e., electrical wave(s) that recirculate repeatedly throughout the tissue at a higher frequency than the waves produced by the heart's natural pacemaker (sinoatrial node). However, the complicated structure of cardiac tissue, as well as the complex ionic currents in the cell, have made it extremely difficult to pinpoint the detailed dynamics of these life-threatening reentrant arrhythmias. A simplified ionic model of the cardiac action potential (AP), which can be fitted to a wide variety of experimentally and numerically obtained mesoscopic characteristics of cardiac tissue such as AP shape and restitution of AP duration and conduction velocity, is used to explain many different mechanisms of spiral wave breakup which in principle can occur in cardiac tissue. Some, but not all, of these mechanisms have been observed before using other models; therefore, the purpose of this paper is to demonstrate them using just one framework model and to explain the different parameter regimes or physiological properties necessary for each mechanism (such as high or low excitability, corresponding to normal or ischemic tissue, spiral tip trajectory types, and tissue structures such as rotational anisotropy and periodic boundary conditions). Each mechanism is compared with data from other ionic models or experiments to illustrate that they are not model-specific phenomena. Movies showing all the breakup mechanisms are available at http://arrhythmia.hofstra.edu/breakup and at ftp://ftp.aip.org/epaps/chaos/E-CHAOEH-12-039203/ INDEX.html. The fact that many different breakup mechanisms exist has important implications for antiarrhythmic drug design and for comparisons of fibrillation experiments using different species, electromechanical uncoupling drugs, and initiation protocols. (c) 2002 American Institute of Physics.

Multiple mechanisms of spiral wave breakup in a model of cardiac electrical activity

Abstract: It has become widely accepted that the most dangerous cardiac arrhythmias are due to re- entrant waves, i.e., electrical wave(s) that re-circulate repeatedly throughout the tissue at a higher frequency than the waves produced by the heart's natural pacemaker (sinoatrial node). However, the complicated structure of cardiac tissue, as well as the complex ionic currents in the cell, has made it extremely difficult to pinpoint the detailed mechanisms of these life-threatening reentrant arrhythmias. A simplified ionic model of the cardiac action potential (AP), which can be fitted to a wide variety of experimentally and numerically obtained mesoscopic characteristics of cardiac tissue such as AP shape and restitution of AP duration and conduction velocity, is used to explain many different mechanisms of spiral wave breakup which in principle can occur in cardiac tissue. Some, but not all, of these mechanisms have been observed before using other models; therefore, the purpose of this paper is to demonstrate them using just one framework model and to explain the different parameter regimes or physiological properties necessary for each mechanism (such as high or low excitability, corresponding to normal or ischemic tissue, spiral tip trajectory types, and tissue structures such as rotational anisotropy and periodic boundary conditions). Each mechanism is compared with data from other ionic models or experiments to illustrate that they are not model-specific phenomena. The fact that many different breakup mechanisms exist has important implications for antiarrhythmic drug design and for comparisons of fibrillation experiments using different species, electromechanical uncoupling drugs, and initiation protocols.

Mechanisms for discordant alternans.

Abstract: Discordant Alternans Mechanism.Introduction: Discordant alternans has the potential to produce larger alternans of the ECG T wave than concordant alternans, but its mechanism is unknown. Methods and Results: We demonstrate by one- and two-dimensional simulation of action potential propagation models that discordant alternans can form spontaneously in spatially homogeneous tissue through one of two mechanisms, due to the interaction of conduction velocity and action potential duration restitution at high pacing frequencies or through the dispersion of diastolic interval produced by ectopic foci. In discordant alternans due to the first mechanism, the boundaries marking regions of alternans with opposite phase arise far from the stimulus site, move toward the stimulus site, and stabilize. Dynamic splitting of action potential duration restitution curves due to electrotonic coupling plays a crucial role in this stability. Larger tissues and faster pacing rates are conducive to multiple boundaries, and inhomogeneities of tissue properties facilitate or inhibit formation of boundaries. Conclusion: Spatial inhomogeneities of electrical restitution properties are not required to produce discordant alternans.

Cech and Steenrod Homotopy Theories with Applications to Geometric Topology

Abstract: Background.- The model structure on pro-spaces.- The homotopy inverse limit and its applications to homological algebra.- The algebraic topology of pro-C.- Proper homotopy theory.- Group actions on infinite dimensional manifolds.- Steenrod homotopy theory.- Some open questions.

Expression of interleukin‐1β in human breast carcinoma

Abstract: BACKGROUND Interleukin 1β (IL-1β) is a multifunctional cytokine that up-regulates the inflammatory response It is not known whether IL-1β plays a major role in human malignancy To determine whether IL-1β might be involved in breast carcinoma progression, the authors measured the IL-1β content in tissue extracts from >200 invasive breast carcinomas and smaller numbers of ductal carcinoma in situ (DCIS) and benign lesions METHODS IL-1β content was measured by an enzyme-linked immunoadsorbent assay and analyzed to determine whether these values were correlated with the contents of scatter factor (SF) (an invasogenic and angiogenic cytokine), von Willebrand's factor (VWF) (a marker of endothelium), thrombospondin-1 (TSP1) (an antiadhesive and antiangiogenic glycoprotein), and tumor necrosis factor-α (TNFα) (another proinflammatory cytokine) Studies were also performed to determine whether IL-1β content was correlated with other pathologic and immunochemical variables that have been utilized or proposed as prognostic indicators for breast carcinoma RESULTS The most important findings of these studies were: 1) immunoreactive IL-1β was detected in approximately 90% of invasive breast carcinomas; 2) IL-1β levels were significantly higher in invasive carcinomas than in a group of DCIS and benign lesions; 3) high IL-1β content in invasive carcinomas was significantly associated with higher contents of SF, VWF, and TSP1, but not TNFα; and 4) there was a trend toward higher IL-1β content in invasive carcinomas with a group of other parameters that suggest a biologically more aggressive tumor (estrogen receptor negativity, high tumor grade, p53 positivity, and bcl-2 negativity); and the proportion of invasive tumors with these characteristics was significantly increased in a subgroup of tumors having very high IL-1β content The authors also found a correlation between high IL-1β content and CD68 positivity, suggesting that macrophages may account for some of the IL-1β present in human breast carcinoma tissue CONCLUSIONS These findings suggest that significant titers of IL-1β are present within the microenvironment of most breast carcinomas and that a high IL-1β content is often associated with tumor invasiveness and with other pathologic features suggestive of an aggressive tumor biology Cancer 1997; 80:421-34 ©; 1997 American Cancer Society

The geometry of biological time , by A. T. Winfree. Pp 544. DM68. Corrected Second Printing 1990. ISBN 3-540-52528-9 (Springer)

Abstract: 1980 Preface * 1999 Preface * 1999 Acknowledgements * Introduction * 1 Circular Logic * 2 Phase Singularities (Screwy Results of Circular Logic) * 3 The Rules of the Ring * 4 Ring Populations * 5 Getting Off the Ring * 6 Attracting Cycles and Isochrons * 7 Measuring the Trajectories of a Circadian Clock * 8 Populations of Attractor Cycle Oscillators * 9 Excitable Kinetics and Excitable Media * 10 The Varieties of Phaseless Experience: In Which the Geometrical Orderliness of Rhythmic Organization Breaks Down in Diverse Ways * 11 The Firefly Machine 12 Energy Metabolism in Cells * 13 The Malonic Acid Reagent ('Sodium Geometrate') * 14 Electrical Rhythmicity and Excitability in Cell Membranes * 15 The Aggregation of Slime Mold Amoebae * 16 Numerical Organizing Centers * 17 Electrical Singular Filaments in the Heart Wall * 18 Pattern Formation in the Fungi * 19 Circadian Rhythms in General * 20 The Circadian Clocks of Insect Eclosion * 21 The Flower of Kalanchoe * 22 The Cell Mitotic Cycle * 23 The Female Cycle * References * Index of Names * Index of Subjects

Higher Topos Theory

Abstract: This purpose of this book is twofold: to provide a general introduction to higher category theory (using the formalism of "quasicategories" or "weak Kan complexes"), and to apply this theory to the study of higher versions of Grothendieck topoi. A few applications to classical topology are included.

Automatic classification of heartbeats using ECG morphology and heartbeat interval features

Abstract: A method for the automatic processing of the electrocardiogram (ECG) for the classification of heartbeats is presented. The method allocates manually detected heartbeats to one of the five beat classes recommended by ANSI/AAMI EC57:1998 standard, i.e., normal beat, ventricular ectopic beat (VEB), supraventricular ectopic beat (SVEB), fusion of a normal and a VEB, or unknown beat type. Data was obtained from the 44 nonpacemaker recordings of the MIT-BIH arrhythmia database. The data was split into two datasets with each dataset containing approximately 50 000 beats from 22 recordings. The first dataset was used to select a classifier configuration from candidate configurations. Twelve configurations processing feature sets derived from two ECG leads were compared. Feature sets were based on ECG morphology, heartbeat intervals, and RR-intervals. All configurations adopted a statistical classifier model utilizing supervised learning. The second dataset was used to provide an independent performance assessment of the selected configuration. This assessment resulted in a sensitivity of 75.9%, a positive predictivity of 38.5%, and a false positive rate of 4.7% for the SVEB class. For the VEB class, the sensitivity was 77.7%, the positive predictivity was 81.9%, and the false positive rate was 1.2%. These results are an improvement on previously reported results for automated heartbeat classification systems.

A model for human ventricular tissue

Abstract: The experimental and clinical possibilities for studying cardiac arrhythmias in human ventricular myocardium are very limited. Therefore, the use of alternative methods such as computer simulations is of great importance. In this article we introduce a mathematical model of the action potential of human ventricular cells that, while including a high level of electrophysiological detail, is computationally cost-effective enough to be applied in large-scale spatial simulations for the study of reentrant arrhythmias. The model is based on recent experimental data on most of the major ionic currents: the fast sodium, L-type calcium, transient outward, rapid and slow delayed rectifier, and inward rectifier currents. The model includes a basic calcium dynamics, allowing for the realistic modeling of calcium transients, calcium current inactivation, and the contraction staircase. We are able to reproduce human epicardial, endocardial, and M cell action potentials and show that differences can be explained by differences in the transient outward and slow delayed rectifier currents. Our model reproduces the experimentally observed data on action potential duration restitution, which is an important characteristic for reentrant arrhythmias. The conduction velocity restitution of our model is broader than in other models and agrees better with available data. Finally, we model the dynamics of spiral wave rotation in a two-dimensional sheet of human ventricular tissue and show that the spiral wave follows a complex meandering pattern and has a period of 265 ms. We conclude that the proposed model reproduces a variety of electrophysiological behaviors and provides a basis for studies of reentrant arrhythmias in human ventricular tissue.