Resonant Thickening of Disks by Small Satellite Galaxies

We study the vertical heating and thickening of galaxy disks due to accretion of small satellites. Our simulations are restricted to axial symmetry, which largely eliminates numerical evolution of the target galaxy but requires the trajectory of the satellite to be along the symmetry axis of the target. We find that direct heating of disk stars by the satellite is not important because the satellite's gravitational perturbation has little power at frequencies resonant with the vertical stellar orbits. The satellite does little damage to the disk until its decaying orbit resonantly excites large-scale disk bending waves. Bending waves can damp through dynamical friction from the halo or internal wave-particle resonances; we find that wave-particle resonances dominate the damping. The principal vertical heating mechanism is therefore dissipation of bending waves at resonances with stellar orbits in the disk. Energy can thus be deposited some distance from the point of impact of the satellite. The net heating from a tightly bound satellite can be substantial, but satellites that are tidally disrupted before they are able to excite bending waves do not thicken the disk.Comment: 13 pages, 8 figures, to appear in ApJ, latex (aaspp4.sty

Relaxation to thermal equilibrium in the self-gravitating sheet model

We revisit the issue of relaxation to thermal equilibrium in the so-called "sheet model", i.e., particles in one dimension interacting by attractive forces independent of their separation. We show that this relaxation may be very clearly detected and characterized by following the evolution of order parameters defined by appropriately normalized moments of the phase space distribution which probe its entanglement in space and velocity coordinates. For a class of quasi-stationary states which result from the violent relaxation of rectangular waterbag initial conditions, characterized by their virial ratio R_0, we show that relaxation occurs on a time scale which (i) scales approximately linearly in the particle number N, and (ii) shows also a strong dependence on R_0, with quasi-stationary states from colder initial conditions relaxing much more rapidly. The temporal evolution of the order parameter may be well described by a stretched exponential function. We study finally the correlation of the relaxation times with the amplitude of fluctuations in the relaxing quasi-stationary states, as well as the relation between temporal and ensemble averages.Comment: 37 pages, 24 figures; some additional discussion of previous literature and other minor modifications, final published versio

The Cardiovascular Effects of a Meal: J-Tpeak and Tpeak -Tend Assessment and Further Insights Into the Physiological Effects.

Meal intake leads to a significant and prolonged increase in cardiac output to supply the splanchnic vasculature. A meal is associated with sympathetic activation of the cardiovascular system, and food ingestion is correlated with an increase in heart rate, an increase in cardiac stroke volume, and QTc interval shortening for up to 7 hours. Given the complexity of the system, one or several of many mechanisms could explain this observation. The shortening of the QTc interval was correlated with a rise of C-peptide following food ingestion, but the mechanisms by which C-peptide may be involved in the modulation of cardiac repolarization are still unknown. This shortening of the myocardial action potential caused by the ingestion of food was further investigated in the present study by measuring the QRS, J-Tpeak , and Tpeak -Tend intervals in search of further clues to better understand the underlying mechanisms. A retrospective analysis was conducted based on data collected in a formal thorough QT/QTc study in which 32 subjects received a carbohydrate-rich "continental" breakfast, moxifloxacin without food, and moxifloxacin with food. We assessed the effect of food on T-wave morphology using validated algorithms for measurement of J-Tpeak and Tpeak -Tend intervals. Our findings demonstrate that a standardized meal significantly shortened J-Tpeak for 4 hours after a meal and to a much lesser extent and shorter duration (up to 1 hour) prolonged the Tpeak -Tend and QRS intervals. This suggests that the QTc shortening occurs mainly during phase 2 of the cardiac action potential. As there was no corresponding effect on Tpeak -Tend beyond the first hour, we conclude that a meal does not interfere with the outward correcting potassium channels but possibly with Ca2+ currents. An effect on mainly Ca2+ aligns well with our understanding of physiology whereby an increase in stroke volume, as observed after a meal, is associated with changes in Ca2+ cycling in and out of the sarcoplasmic reticulum during cardiac myocyte contraction

Starcounts Redivivus. IV. Density Laws Through Photometric Parallaxes

In an effort to more precisely define the spatial distribution of Galactic field stars, we present an analysis of the photometric parallaxes of 70,000 stars covering nearly 15 square degrees in seven Kapteyn Selected Areas. We address the affects of Malmquist Bias, subgiant/giant contamination, metallicity and binary stars upon the derived density laws. The affect of binary stars is the most significant. We find that while the disk-like populations of the Milky Way are easily constrained in a simultaneous analysis of all seven fields, no good simultaneous solution for the halo is found. We have applied halo density laws taken from other studies and find that the Besancon flattened power law halo model (c/a=0.6, r^-2.75) produces the best fit to our data. With this halo, the thick disk has a scale height of 750 pc with an 8.5% normalization to the old disk. The old disk scale height is 280-300 pc. Corrected for a binary fraction of 50%, these scale heights are 940 pc and 350-375 pc, respectively. Even with this model, there are systematic discrepancies between the observed and predicted density distributions. Our model produces density overpredictions in the inner Galaxy and density underpredictions in the outer Galaxy. A possible solution is modeling the stellar halo as a two-component system in which the halo has a flattened inner distribution and a roughly spherical, but substructured outer distribution. Further reconciliation could be provided by a flared thick disk, a structure consistent with a merger origin for that population. (Abridged)Comment: 66 pages, accepted to Astrophysical journal, some figures compresse

Safety and efficacy of dronedarone from clinical trials to real-world evidence: implications for its use in atrial fibrillation.

Efficacy and safety of dronedarone was shown in the ATHENA trial for paroxysmal or persistent atrial fibrillation (AF) patients. Further trials revealed safety concerns in patients with heart failure and permanent AF. This review summarizes insights from recent real-world studies and meta-analyses, including reports on efficacy, with focus on liver safety, mortality risk in patients with paroxysmal/persistent AF, and interactions of dronedarone with direct oral anticoagulants. Reports of rapidly progressing liver failure in dronedarone-prescribed patients in 2011 led to regulatory cautions about potential liver toxicity. Recent real-world evidence suggests dronedarone liver safety profile is similar to other antiarrhythmics and liver toxicity could be equally common with many Class III antiarrhythmics. Dronedarone safety concerns (increased mortality in patients with permanent AF) were raised based on randomized controlled trials (RCT) (ANDROMEDA and PALLAS), but comedication with digoxin may have increased the mortality rates in PALLAS, considering the dronedarone-digoxin pharmacokinetic (PK) interaction. Real-world data on apixaban-dronedarone interactions and edoxaban RCT observations suggest no significant safety risks for these drug combinations. Median trough plasma concentrations of dabigatran 110 mg during concomitant use with dronedarone are at acceptable levels, while PK data on the rivaroxaban-dronedarone interaction are unavailable. In RCTs and real-world studies, dronedarone significantly reduces AF burden and cardiovascular hospitalizations, and demonstrates a low risk for proarrhythmia in patients with paroxysmal or persistent AF. The concerns on liver safety must be balanced against the significant reduction in hospitalizations in patients with non-permanent AF and low risk for proarrhythmias following dronedarone treatment

Assessment of OMT-28, a synthetic analog of omega-3 epoxyeicosanoids, in patients with persistent atrial fibrillation: Rationale and design of the PROMISE-AF phase II study.

We designed a placebo controlled, double-blind, randomized, dose-finding phase II study on OMT-28 in the maintenance of sinus rhythm after electrical cardioversion (DCC) in patients with persistent atrial fibrillation (PROMISE-AF). OMT-28 is a first-in-class, synthetic analog of 17,18-epoxyeicosatetetraenoic acid, a bioactive lipid mediator generated by cytochrome P450 enzymes from the omega-3 fatty acid eicosapentaenoic acid. OMT-28 improves Ca2+-handling and mitochondrial function in cardiomyocytes and reduces pro-inflammatory signaling. This unique mode of action may provide a novel approach to target key mechanism contributing to AF pathophysiology. In a recent phase I study, OMT-28 was safe and well tolerated and showed favorable pharmacokinetics. The PROMISE-AF study (NCT03906799) is designed to assess the efficacy (primary objective), safety, and population pharmacokinetics (secondary objectives) of three different doses of OMT-28, administered once daily, versus placebo until the end of the follow-up period. Recruitment started in March 2019 and the study will include a total of 120 patients. The primary efficacy endpoint is the AF burden (% time with any AF), evaluated over a 13-week treatment period after DCC. AF burden is calculated based on continuous ECG monitoring using an insertable cardiac monitor (ICM). The primary efficacy analysis will be conducted on the modified intention-to-treat (mITT) population, whereas the safety analysis will be done on the safety population. Although ICMs have been used in other interventional studies to assess arrhythmia, PROMISE-AF will be the first study to assess antiarrhythmic efficacy and safety of a novel rhythm-stabilizing drug after DCC by using ICMs

Phase transitions in self-gravitating systems and bacterial populations with a screened attractive potential

We consider a system of particles interacting via a screened Newtonian potential and study phase transitions between homogeneous and inhomogeneous states in the microcanonical and canonical ensembles. Like for other systems with long-range interactions, we obtain a great diversity of microcanonical and canonical phase transitions depending on the dimension of space and on the importance of the screening length. We also consider a system of particles in Newtonian interaction in the presence of a ``neutralizing background''. By a proper interpretation of the parameters, our study describes (i) self-gravitating systems in a cosmological setting, and (ii) chemotaxis of bacterial populations in the original Keller-Segel model

The European Network for Translational Research in Atrial Fibrillation (EUTRAF): objectives and initial results.

Atrial fibrillation (AF) is the most common sustained arrhythmia in the general population. As an age-related arrhythmia AF is becoming a huge socio-economic burden for European healthcare systems. Despite significant progress in our understanding of the pathophysiology of AF, therapeutic strategies for AF have not changed substantially and the major challenges in the management of AF are still unmet. This lack of progress may be related to the multifactorial pathogenesis of atrial remodelling and AF that hampers the identification of causative pathophysiological alterations in individual patients. Also, again new mechanisms have been identified and the relative contribution of these mechanisms still has to be established. In November 2010, the European Union launched the large collaborative project EUTRAF (European Network of Translational Research in Atrial Fibrillation) to address these challenges. The main aims of EUTRAF are to study the main mechanisms of initiation and perpetuation of AF, to identify the molecular alterations underlying atrial remodelling, to develop markers allowing to monitor this processes, and suggest strategies to treat AF based on insights in newly defined disease mechanisms. This article reports on the objectives, the structure, and initial results of this network

Real-world utilization of the pill-in-the-pocket method for terminating episodes of atrial fibrillation: data from the multinational Antiarrhythmic Interventions for Managing Atrial Fibrillation (AIM-AF) survey

AIMS: Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. Episodes may stop spontaneously (paroxysmal AF); may terminate only via intervention (persistent AF); or may persist indefinitely (permanent AF) (see European and American guidelines, referenced below, for more precise definitions). Recently, there has been renewed interest in an approach to terminate AF acutely referred to as 'pill-in-the-pocket' (PITP). The PITP is recognized in both the US and European guidelines as an effective option using an oral antiarrhythmic drug for acute conversion of acute/recent-onset AF. However, how PITP is currently used has not been systematically evaluated. METHODS AND RESULTS: The recently published Antiarrhythmic Interventions for Managing Atrial Fibrillation (AIM-AF) survey included questions regarding current PITP usage, stratified by US vs. European countries surveyed, by representative countries within Europe, and by cardiologists vs. electrophysiologists. This manuscript presents the data from this planned sub-study. Our survey revealed that clinicians in both the USA and Europe consider PITP in about a quarter of their patients, mostly for recent-onset AF with minimal or no structural heart disease (guideline appropriate). However, significant deviations exist. See the Graphical abstract for a summary of the data. CONCLUSION: Our findings highlight the frequent use of PITP and the need for further physician education about appropriate and optimal use of this strategy

Critical dynamics of self-gravitating Langevin particles and bacterial populations

We study the critical dynamics of the generalized Smoluchowski-Poisson system (for self-gravitating Langevin particles) or generalized Keller-Segel model (for the chemotaxis of bacterial populations). These models [Chavanis & Sire, PRE, 69, 016116 (2004)] are based on generalized stochastic processes leading to the Tsallis statistics. The equilibrium states correspond to polytropic configurations with index $n$ similar to polytropic stars in astrophysics. At the critical index $n_{3}=d/(d-2)$ (where $d\ge 2$ is the dimension of space), there exists a critical temperature $\Theta_{c}$ (for a given mass) or a critical mass $M_{c}$ (for a given temperature). For $\Theta>\Theta_{c}$ or $M<M_{c}$ the system tends to an incomplete polytrope confined by the box (in a bounded domain) or evaporates (in an unbounded domain). For $\Theta<\Theta_{c}$ or $M>M_{c}$ the system collapses and forms, in a finite time, a Dirac peak containing a finite fraction $M_c$ of the total mass surrounded by a halo. This study extends the critical dynamics of the ordinary Smoluchowski-Poisson system and Keller-Segel model in $d=2$ corresponding to isothermal configurations with $n_{3}\to +\infty$. We also stress the analogy between the limiting mass of white dwarf stars (Chandrasekhar's limit) and the critical mass of bacterial populations in the generalized Keller-Segel model of chemotaxis