In vivo measurements of atrial repolarization alternans based on standard pacemaker technology

It has been shown that repolarization alternans, a beat-to-beat alternation in action potential duration, enhances dispersion of repolarization above a critical heart rate and promotes susceptibility to ventricular arrhythmias. It is unknown whether repolarization alternans is measurable in the atria using standard pacemakers and whether it plays a role in promoting atrial fibrillation. In this work, atrial repolarization alternans amplitude and periodicity are studied in a sheep model of pacing-induced atrial fibrillation. Two pacemakers, each with one right atrial and ventricular lead, were implanted in 4 male sheep after ablation of the atrioventricular junction. The first one was used to deliver rapid pacing for measurements of right atrial repolarization alternans and the second one to record a unipolar electrogram. Atrial repolarization alternans appeared rate-dependent and its amplitude increased as a function of pacing rate. Repolarization alternans was intermittent but no periodicity was detected. An increase of repolarization alternans preceding episodes of non-sustained atrial fibrillation suggests that repolarization alternans is a promising parameter for assessment of atrial fibrillation susceptibility

Dominant-Negative Tumor Necrosis Factor Protects from Mycobacterium bovis Bacillus Calmette-Guérin (BCG) and Endotoxin-Induced Liver Injury without Compromising Host Immunity to BCG and Mycobacterium tuberculosis

BackgroundTumor necrosis factor (TNF) is associated with the development of inflammatory pathologies. Antibodies and soluble TNF (solTNF) receptors that neutralize excessive TNF are effective therapies for inflammatory and autoimmune diseases. However, clinical use of TNF inhibitors is associated with an increased risk of infections MethodsA novel dominant-negative (DN) strategy of selective TNF neutralization, consisting of blocking solTNF while sparing transmembrane TNF (tmTNF), was tested in mouse models of mycobacterial infection and acute liver inflammation. XENP1595, a DN-TNF biologic, was compared with etanercept, a TNF receptor 2 (TNFR2)-IgG1 Fc fusion protein that inhibits murine solTNF and tmTNF ResultsXENP1595 protected mice from acute liver inflammation induced by endotoxin challenge in Mycobacterium bovis bacillus Calmette-Guérin (BCG)-infected mice, but, in contrast to etanercept, it did not compromise host immunity to acute M. bovis BCG and Mycobacterium tuberculosis infections in terms of bacterial burden, granuloma formation, and innate immune responses ConclusionsA selective inhibitor of solTNF efficiently protected mice from acute liver inflammation yet maintained immunity to mycobacterial infections. In contrast, nonselective inhibition of solTNF and tmTNF suppressed immunity to M. bovis BCG and M. tuberculosis. Therefore, selective inhibition of solTNF by DN-TNF biologics may represent a new therapeutic strategy for the treatment of inflammatory diseases without compromising host immunit

Measurement of the Omega_c Lifetime

We present the measurement of the lifetime of the Omega_c we have performed using three independent data samples from two different decay modes. Using a Sigma- beam of 340 GeV/c we have obtained clean signals for the Omega_c decaying into Xi- K- pi+ pi+ and Omega- pi+ pi- pi+, avoiding topological cuts normally used in charm analysis. The short but measurable lifetime of the Omega_c is demonstrated by a clear enhancement of the signals at short but finite decay lengths. Using a continuous maximum likelihood method we determined the lifetime to be tau(Omega_c) = 55 +13-11(stat) +18-23(syst) fs. This makes the Omega_c the shortest living weakly decaying particle observed so far. The short value of the lifetime confirms the predicted pattern of the charmed baryon lifetimes and demonstrates that the strong interaction plays a vital role in the lifetimes of charmed hadrons.Comment: 15 pages, including 7 figures; gzipped, uuencoded postscrip

Search for the exotic Ξ−−(1860)\Xi^{--}(1860) Resonance in 340GeV/c Σ−\Sigma^--Nucleus Interactions

We report on a high statistics search for the $\Xi^{--}(1860)$ resonance in $\Sigma^-$-nucleus collisions at 340GeV/c. No evidence for this resonance is found in our data sample which contains 676000 $\Xi^-$ candidates above background. For the decay channel $\Xi^{--}(1860) \to \Xi^-\pi^-$ and the kinematic range 0.15$<x_F<$0.9 we find a 3$\sigma$ upper limit for the production cross section of 3.1 and 3.5 $\mu$b per nucleon for reactions with carbon and copper, respectively.Comment: 5 pages, 4 figures, modification of ref. 43 and 4

Search for the pentaquark candidate Θ+\Theta^+(1540) in the hyperon beam experiment WA89

We report on a high-statistics search for the \t1540 resonance in $\Sigma^-$-nucleus collisions at 340 \gevc1 . No evidence for this resonance was found in our data sample which contains 13 millions $K^0_s \to \pi^+\pi^-$ decays above background. For the decay channel $\Theta^+ \to K^0_s p$ and the kinematic range $x_F>$ 0.05 we find the production cross section to be $BR(\Theta^+ \to K^0_s p)\cdot \sigma_0 <$ 1.8 $\mu$b per nucleon at 99% CL.Comment: 5 pages, 4 figure

Tracking of Stepwise Ablation of Persistent Atrial Fibrillation using Synchronization of nearby Electrogams

Intracardiac organization indices such as atrial fibril- lation (AF) cycle length (AFCL) have been used to track the efficiency of stepwise catheter ablation (step-CA) of long-standing persistent AF (pers-AF), however, with lim- ited success. The timing between nearby bipolar intracar- diac electrograms (EGMs) reflects the spatial dynamics of wavelets during AF. The extent of synchronization between EGMs is an indirect measure of AF spatial organization. The synchronization between nearby EGMs during step- CA of pers-AF was evaluated using new indices based on the cross-correlation. The first one (spar(W)) quantifies the sparseness of the cross-correlation of local activation times. The second one (OI(W)) reflects the local concen- tration around the largest peak of the cross-correlation. By computing their relative evolution during step-CA until AF termination (AF-term), we found that OI(W) appeared su- perior to AFCL and spar(W) to track the effect of step-CA "en route" to AF-term