Evolution of spiral and scroll waves of excitation in a mathematical model of ischaemic border zone

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.Comment: 26 pages, 13 figures, appendix and 2 movies, as accepted to PLoS ONE 2011/08/0

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Gravitational-wave research as an emerging field in the Max Planck Society. The long roots of GEO600 and of the Albert Einstein Institute

On the occasion of the 50th anniversary since the beginning of the search for gravitational waves at the Max Planck Society, and in coincidence with the 25th anniversary of the foundation of the Albert Einstein Institute, we explore the interplay between the renaissance of general relativity and the advent of relativistic astrophysics following the German early involvement in gravitational-wave research, to the point when gravitational-wave detection became established by the appearance of full-scale detectors and international collaborations. On the background of the spectacular astrophysical discoveries of the 1960s and the growing role of relativistic astrophysics, Ludwig Biermann and his collaborators at the Max Planck Institute for Astrophysics in Munich became deeply involved in research related to such new horizons. At the end of the 1960s, Joseph Weber's announcements claiming detection of gravitational waves sparked the decisive entry of this group into the field, in parallel with the appointment of the renowned relativist Juergen Ehlers. The Munich area group of Max Planck institutes provided the fertile ground for acquiring a leading position in the 1970s, facilitating the experimental transition from resonant bars towards laser interferometry and its innovation at increasingly large scales, eventually moving to a dedicated site in Hannover in the early 1990s. The Hannover group emphasized perfecting experimental systems at pilot scales, and never developed a full-sized detector, rather joining the LIGO Scientific Collaboration at the end of the century. In parallel, the Max Planck Institute for Gravitational Physics (Albert Einstein Institute) had been founded in Potsdam, and both sites, in Hannover and Potsdam, became a unified entity in the early 2000s and were central contributors to the first detection of gravitational waves in 2015.Comment: 94 pages. Enlarged version including new results from further archival research. A previous version appears as a chapter in the volume The Renaissance of General Relativity in Context, edited by A. Blum, R. Lalli and J. Renn (Boston: Birkhauser, 2020

The antenna phase center motion effect in high-accuracy spacecraft tracking experiments

We present an improved model for the antenna phase center motion effect for high-gain mechanically steerable ground-based and spacecraft-mounted antennas that takes into account non-perfect antenna pointing. Using tracking data of the RadioAstron spacecraft we show that our model can result in a correction of the computed value of the effect of up to 2 x 10(-14) in terms of the fractional frequency shift, which is significant for high-accuracy spacecraft tracking experiments. The total fractional frequency shift due to the phase center motion effect can exceed 1 x 10(-11) both for the ground and space antennas depending on the spacecraft orbit and antenna parameters. We also analyze the error in the computed value of the effect and find that it can be as large as 4 x 10(-14) due to uncertainties in the spacecraft antenna axis position, ground antenna axis offset and misalignment, and others. Finally, we present a way to reduce both the ground and space antenna phase center motion effects by several orders of magnitude, e.g. for RadioAstron to below 1 x 10(-16), by tracking the spacecraft simultaneously in the one-way downlink and two-way phase-locked loop modes, i.e. using the Gravity Probe A configuration of the communications links.</p

Probing the gravitational redshift with an Earth-orbiting satellite

We present an approach to testing the gravitational redshift effect using the RadioAstron satellite. The experiment is based on a modification of the Gravity Probe A scheme of nonrelativistic Doppler compensation and benefits from the highly eccentric orbit and ultra-stable atomic hydrogen maser frequency standard of the RadioAstron satellite. Using the presented techniques we expect to reach an accuracy of the gravitational redshift test of order 10-5, a magnitude better than that of Gravity Probe A. Data processing is ongoing, our preliminary results agree with the validity of the Einstein Equivalence Principle