The phenomenon of jet quenching provides essential information about the properties of hot and dense matter created in ultra-relativistic heavy-ion collisions. Recent results from experiments at the ...Large Hadron Collider (LHC) show evidence for an unexpectedly similar suppression of both light and heavy flavor jets. Furthermore, the role of radiative energy loss of heavy quarks is still under active discussion within the theoretical community. By employing the parton cascade Boltzmann Approach to Multi-Parton Scatterings (BAMPS), which numerically solves the 3+1 D Boltzmann equation both for light and heavy flavor partons, we calculate the nuclear modification factor of inclusive and b-tagged reconstructed jets in 0–10% central sLHC=2.76 A TeV Pb + Pb collisions. Based on perturbative QCD cross sections we find a suppression of both light and heavy flavor jets. While the inclusive jets are slightly too strong suppressed within Bamps in comparison with data, both elastic + radiative and only elastic interactions lead to a realistic b-tagged jet suppression. To further investigate light and heavy flavor energy loss we predict the R dependence of inclusive and b-tagged jet suppression. Furthermore, we propose the medium modification of b-tagged jet shapes as an observable for discriminating between different heavy quark energy loss scenarios.
The Statistical Hadronization Model can be extended to include hadrons which are produced far away from chemical equilibrium or in an earlier phase of the evolution of a heavy ion collision. The ...effects of J ψ production above the critical temperature are explored, with special focus on the mass shift for the thermal dressed mass of the charm quarks in the quark-gluon plasma.
Between 1997 and 2000, an outbreak of skin lesions and observations of emaciated striped bass, Morone saxatilis (Walbaum), in upper Chesapeake Bay were attributed to a perceived shortage of its main ...prey, Atlantic menhaden, Brevoortia tyrannus Latrobe. Abundance estimates, Atlantic menhaden consumption per recruit analysis (modified yield‐per‐recruit), bioenergetics analysis and predator–prey theory were combined to explore whether an imbalance between striped bass and Atlantic menhaden in upper Chesapeake Bay was plausible. Reduced fishing mortality and higher size limits that underpinned the effort to restore striped bass during the 1980s and 1990s lead to more abundant and larger striped bass in upper Chesapeake Bay, increasing predatory demand for forage‐sized Atlantic menhaden, the abundance of which declined to a historic low. Nominal losses of age 0–2 Atlantic menhaden to harvest and potential striped bass predation exceeded supply after 1998. The outbreak of lesions in upper Chesapeake Bay striped bass coincided with increased variation in weight‐at‐length, decreased length‐at‐age, and decreased presence of Atlantic menhaden in diets. Decreased attack success, inferred from a 97% decline in ratios of forage‐sized Atlantic menhaden to striped bass between 1983 and 1998, would have expected to have been followed by a deterioration of striped bass nutritional state. Transmission of disease would have been aided by high density of striped bass in poor nutritional condition residing in degraded habitat (Chesapeake Bay was the most hypoxic estuary in the mid‐Atlantic region in the late 1990s). These problems suggest that striped bass exceeded their carrying capacity in Chesapeake Bay during the late 1990s.
Abstract
Background
The SGLT2-inhibitors dapagliflozin and empagliflozin have emerged as standard therapy for the treatment of heart failure with reduced ejection fraction. However, experimental data ...on the electrophysiologic safety is sparse.
Purpose
Aim of this study was to characterize the safety profile of the SGLT2 inhibitors dapagliflozin and empagliflozin in a sensitive whole-heart model.
Methods
26 rabbit hearts of New Zealand white rabbits were excised and mounted to a Langendorff-apparatus. Hearts were divided up into two groups. The first group (n=12) was perfused with dapagliflozin in ascending concentrations (3, 5 and 10 μM). Further 14 hearts were treated with empagliflozin (1, 3 and 5 μM). Ventricular vulnerability was assessed by a predefined pacing protocol consisting of premature extra stimuli and burst stimulation.
Results
Dapagliflozin led to a significant reduction of the QT interval (3 μM: −27 ms, p<0.01; 5 μM: −47 ms, p<0.01; 10 μM: - 42 ms, p<0.01), action potential duration (APD90; 3 μM: −21 ms, p<0.01; 5 μM: −37 ms, p<0.01; 10 μM: −24 ms, p<0.01) and effective refractory periods (ERP; 3 μM: −34 ms, p<0.01.; 5 μM: −49 ms, p<0.01; 10 μM: −52 ms, p<0.01). Spatial dispersion of repolarization was not increased after dapagliflozin treatment (3 μM: −4 ms, p=ns; 5 μM: −4 ms, p<0.05; 10 μM: −8 ms, p=ns). Empagliflozin also led to a pronounced abbreviation of cardiac repolarization duration (QT: 1 μM: −28 ms, p<0.01.; 3 μM: −47 ms, p<0.01; 5 μM: −69 ms, p<0.01; APD90: 1 μM: −27 ms, p<0.01; 3 μM: −46 ms, p<0.01; 5 μM: −51 ms, p<0.01) and ERP (1 μM: −28 ms, p<0.05; 3 μM: −40 ms, p<0.01; 5 μM: −56 ms, p<0.01). In contrast to dapagliflozin, empagliflozin amplified spatial dispersion of repolarization (1 μM: −3 ms, p=ns.; 3 μM: +4 ms, p<0.05; 5 μM: +9 ms, p=ns). Dapagliflozin infusion did not provoke more ventricular arrhythmias (VA) compared to baseline conditions (baseline: 2 episodes; 3 μM: 6 episodes, p=ns.; 5 μM: 11 episodes, p=ns; 10 μM: 18 episodes, p=ns). In contrast, empagliflozin treatment significantly increased the occurrence of VA (baseline: 4 episodes; 1 μM: 12 episodes, p<0.05.; 3 μM: 8 episodes, p=ns; 5 μM: 29 episodes, p<0.05). Of note, none of the drugs provoked arrhythmias of the torsade de pointes type after lowering the potassium concentration.
Conclusion
The SGLT2 inhibitors dapagliflozin and empagliflozin shorten cardiac repolarization and effective refractory periods. While spatial dispersion remains stable after administration of dapagliflozin, empagliflozin amplifies spatial dispersion of repolarization. As a result, significantly more ventricular arrhythmias were inducible after empagliflozin treatment.
Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Hans and Gertie Fischer-Foundation (to C.E.)
Abstract
Background
The SGLT2 inhibitors dapagliflozin and empagliflozin have an evolving role in heart failure therapy. Observational data suggest a lower risk of atrial fibrillation (AF) for ...patients on SGLT2 inhibitors. So far, it is unclear whether this is related to a direct antiarrhythmic potential of SGLT2 inhibitors or just a marker of improved heart function. Experimental data on the impact of SGTL2 inhibitors on atrial electrophysiology is scarce.
Purpose
This study aimed at evaluating the effects of the two SGLT2 inhibitors dapagliflozin and empagliflozin on atrial electrophysiology.
Methods
25 rabbit hearts were explanted and retrogradely perfused employing the Langendorff-setup. Two catheters were placed on both atria to record monophasic action potentials. Hearts were paced at three different cycle lengths (350ms, 250ms, 150ms), thereby obtaining cycle-length dependent atrial action potential durations (aAPD90) and effective refractory periods (aERP). Atrial post-repolarization (aPRR) refractoriness was determined by the difference between aERP and aAPD90. AF was induced in the presence of acetylcholine (ACh, 1μM) and isoproterenol (Iso, 1μM). Thereafter, hearts were treated with dapagliflozin (n=13, 3 μM) or empagliflozin (n=12, 3 μM).
Results
Ach/Iso abbreviated aAPD90, aERP and prolonged aPRR in both groups (dapagliflozin group: aAPD90: −49 ms, p<0.01; aERP: −33 ms, p<0.01; aPRR: +18 ms, p=0.06; empagliflozin group: aAPD90: −40 ms, p<0.01; aERP: −25 ms, p<0.05; aPRR: +18 ms, p=0.05). Further treatment with dapagliflozin increased aAPD90 (+13 ms, p<0.01), aERP (+34 ms, p<0.05) and aPRR (+6 ms, p=ns). Additional administration of empagliflozin had no significant effect on aAPD90 (−8 ms, p=ns), aERP (−1 ms, p=ns) or aPRR (+9 ms, p=ns). Vulnerability to AF was assessed by a standardized protocol consisting of several trains of burst pacing. Ach/Iso increased the vulnerability to AF episodes in both groups (dapagliflozin group: 71 episodes vs. 1 under baseline conditions, p<0.01; empagliflozin group: 27 episodes vs. 2 under baseline conditions, p=0.08). Additional perfusion of dapagliflozin significantly reduced the occurrence of AF (to 30 episodes, p<0.05) while additional empagliflozin treatment had no significant antiarrhythmic effect (32 episodes, p=ns).
Conclusion
Dapagliflozin and empagliflozin had opposing effects on atrial electrophysiology. Dapagliflozin prolonged aAPD90 and aERP, thereby preventing AF. In contrast, empagliflozin did not change aAPD90 or aERP, resulting in no antiarrhythmic effect. Our findings hint at a potential antiarrhythmic benefit of dapagliflozin.
Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Hans and Gertie Fischer-Foundation (to C.E.)
This report reviews the study of open heavy-flavour and quarkonium production in high-energy hadronic collisions, as tools to investigate fundamental aspects of Quantum Chromodynamics, from the ...proton and nucleus structure at high energy to deconfinement and the properties of the Quark–Gluon Plasma. Emphasis is given to the lessons learnt from LHC Run 1 results, which are reviewed in a global picture with the results from SPS and RHIC at lower energies, as well as to the questions to be addressed in the future. The report covers heavy flavour and quarkonium production in proton–proton, proton–nucleus and nucleus–nucleus collisions. This includes discussion of the effects of hot and cold strongly interacting matter, quarkonium photoproduction in nucleus–nucleus collisions and perspectives on the study of heavy flavour and quarkonium with upgrades of existing experiments and new experiments. The report results from the activity of the SaporeGravis network of the I3 Hadron Physics programme of the European Union 7
th
Framework Programme.
Chlamydia pneumoniae is an intracellular bacterium responsible for respiratory tract infections. Recent studies have implicated this organism in the pathogenesis of atherosclerosis.
To address how ...the organism is transported from lungs to cardiac vessels, we characterized the cell population within peripheral blood mononuclear cells (PBMCs) that harbor C pneumoniae DNA. Adherent and nonadherent PBMCs from 28 patients with coronary artery disease (CAD) and 19 healthy blood donors were evaluated for the presence of C pneumoniae DNA by touchdown nested polymerase chain reaction (nPCR). Of the 28 patients, 10 (36%) had detectable PCR product in their nonadherent and 3 (10%) in their adherent PBMC population. C pneumoniae-specific PCR results were positive for 5 of 19 (26%) healthy blood donors. PCR positivity was detected only in the nonadherent cell population among this group of individuals. Fractionation of nonadherent PBMCs identified C pneumoniae-specific PCR signal among the CD3+ T-cell population exclusively. Of the 18 PCR-positive subjects (13 patients and 5 healthy control subjects), 67% (8 patients and 4 healthy blood donors) tested positive for C pneumoniae-specific IgG serology. Interestingly, 2 patients became PCR negative on a repeated blood draw 5 months after initial detection of C pneumoniae DNA despite retaining C pneumoniae-specific antibodies.
Our results demonstrate marginally significant prevalence of C pneumoniae DNA in patients with CAD compared with healthy subjects (P=0.082). In contrast, the prevalence of IgG seropositivity among the 2 groups did not reach statistical significance (P=0.306). We also provide unequivocal evidence for the presence of C pneumoniae DNA predominantly among the circulating CD3+ T-cell population.
We discuss recent applications of the partonic perturbative QCD based cascade model DAMPS with focus on heavy-ion phenomenology in the hard and soft momentum range. First, the elliptic flow and ...suppression of charm and bottom quarks are studied at LFIC energies. Thereafter, we compare in a detailed study the standard Gunion-Bertsch approximation of the matrix elements for inelastic processes to the exact results in leading order perturbative QCD. Since a disagreement is found, we propose an improved Gunion-Bertsch matrix element, which agrees with the exact result in all phase space regions.
We discuss recent applications of the partonic perturbative QCD based cascade model BAMPS with focus on heavy-ion phenomeneology in hard and soft momentum range. First, the elliptic flow and ...suppression of charm and bottom quarks are studied at LHC energies. Thereafter, we compare in a detailed study the standard Gunion-Bertsch approximation of the matrix elements for inelastic processes to the exact results at leading order perturbative QCD. Since a disagreement is found, we propose an improved Gunion-Bertsch matrix element, which agrees with the exact result in all phase space regions. In addition to recent jet-quenching investigations we present results on the application of jet reconstruction algorithms in BAMPS. Finally, jet phenomena inducing collective effects such as Mach cones, are demonstrated in an expanding medium at relativistic heavy-ion collisions. We address the question, whether the signal of a Mach cones is the origin for a double peak structure in extracted two-particle correlations.
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