Intermittent atrial tachycardia facilitates atrial fibrillation by a shortening of activation recovery interval

Introduction: We recently observed in a chronic ovine model that a shortening of action potential duration (APD) as assessed by the activation recovery interval (ARI) may be a mechanism whereby pacing-induced atrial tachycardia (PIAT) facilitates atrial fibrillation (AF), mediated by a return to 1:1 atrial capture after the effective refractory period has been reached. The aim of the present study is to evaluate the effect of long term intermittent burst pacing on ARI before induction of AF.Methods: We specifically developed a chronic ovine model of PIAT using two pacemakers (PM) each with a right atrial (RA) lead separated by ∼2cm. The 1st PM (Vitatron T70) was used to record a broadband unipolar RA EGM (800 Hz, 0.4 Hz high pass filter). The 2nd was used to deliver PIAT during electrophysiological protocols at decremental pacing CL (400 beats, from 400 to 110ms) and long term intermittent RA burst pacing to promote electrical remodeling (5s of burst followed by 2s of sinus rhythm) until onset of sustained AF. ARI was defined as the time difference between the peak of the atrial repolarization wave and the first atrial depolarization. The mean ARIs of paired sequences (before and after remodeling), each consisting of 20 beats were compared.Results: As shown in the figure, ARIs (n=4 sheep, 46 recordings) decreased post remodeling compared to baseline (86±19 vs 103±12 ms, p<0.05). There was no difference in atrial structure as assessed by light microscopy between control and remodeled sheep.Conclusions: Using standard pacemaker technology, atrial ARIs as a surrogate of APDs were successfully measured in vivo during the electrical remodeling process leading to AF. The facilitation of AF by PIAT mimicking salvos from pulmonary veins is heralded by a significant shortening of ARI

AltitudeOmics: Baroreflex Sensitivity During Acclimatization to 5,260 m.

<b>Introduction:</b> Baroreflex sensitivity (BRS) is essential to ensure rapid adjustment to variations in blood pressure (BP). Little is known concerning the adaptive responses of BRS during acclimatization to high altitude at rest and during exercise. <b>Methods:</b> Twenty-one healthy sea-level residents were tested near sea level (SL, 130 m), the 1st (ALT1) and 16th day (ALT16) at 5,260 m using radial artery catheterization. BRS was calculated using the sequence method (direct interpretation of causal link between BP and heartrate). At rest, subjects breathed a hyperoxic mixture (250 mmHg O <sub>2</sub> , end tidal) to isolate the preponderance of CO <sub>2</sub> chemoreceptors. End-tidal CO <sub>2</sub> varied from 20 to 50 mmHg to assess peripheral chemoreflex. Rebreathing provoked incremental increase in CO <sub>2</sub> , increasing BP to assess baroreflex. During incremental cycling exercise to exhaustion, subjects breathed room air. <b>Results:</b> Resting BRS decreased in ALT1 which was exacerbated in ALT16. This decrease in ALT1 was reversible upon additional inspired CO <sub>2</sub> , but not in ALT16. BRS decrease during exercise was greater and occurred at lower workloads in ALT1 compared to SL. At ALT16, this decrease returned toward SL values. <b>Discussion/Conclusion:</b> This study is the first to report attenuated BRS in acute hypoxia, exacerbated in chronic hypoxia. In ALT1, hypocapnia triggered BRS reduction whilst in ALT16 resetting of chemoreceptor triggered BRS reduction. The exercise BRS resetting was impaired in ALT1 but normalized in ALT16. These BRS decreases indicate decreased control of BP and may explain deteriorations of cardiovascular status during exposure to high altitude

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

AltitudeOmics: Spontaneous Baroreflex Sensitivity During Acclimatization to 5,260 m: A Comparison of Methods

Baroreflex sensitivity (BRS) is essential to ensure rapid adjustment to variations in blood pressure (BP). Spontaneous baroreflex function can be assessed using continuous recordings of blood pressure. The goal of this study was to compare four methods for BRS quantification [the sequence, Bernardi's (BER), frequency and transfer function methods] to identify the most consistent method across an extreme range of conditions: rest and exercise, in normoxia, hypoxia, hypocapnia, and hypercapnia. Using intra-radial artery BP in young healthy participants, BRS was calculated and compared using the four methods in normoxia, acute and chronic hypoxia (terrestrial altitude of 5,260 m) in hypocapnia (hyperventilation), hypercapnia (rebreathing) and during ramp exercise to exhaustion. The sequence and BER methods for BRS estimation showed good agreement during the resting and exercise protocols, whilst the ultra- and very-low frequency bands of the frequency and transfer function methods were more discrepant. Removing respiratory frequency from the blood pressure traces affected primarily the sequence and BER methods and occasionally the frequency and transfer function methods. The sequence and BER methods contained more respiratory related information than the frequency and transfer function methods, indicating that the former two methods predominantly rely on respiratory effects of BRS. BER method is recommended because it is the easiest to compute and even though it tends to overestimate BRS compared to the sequence method, it is consistent with the other methods, whilst its interquartile range is the smallest

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

Fragile histidine triad gene inactivation in lung cancer: the European Early Lung Cancer project.

Rationale: Fragile histidine triad (FHIT) is a tumor suppressor gene involved in the pathogenesis of lung cancer. Objectives: The purpose of this study was to investigate the different molecular alterations leading to the inactivation of FHIT gene function and to validate their use as biomarkers of risk for progression of the disease in patients belonging to the multicentric European study for the Early detection of Lung Cancer (EUELC) who were resected for early-stage lung tumors. Methods: FHIT immunostaining was performed on 305 tumor samples. Themethylation status of FHIT promoterwas assessed by nested methylation-specific polymerase chain reaction (MSP-PCR) in 232 tumor and 225 normal lung samples ofwhich a subset of 187 patients had available normal/tumorDNA pairs. Loss of heterozygosity (LOH) at the FHIT locus was analyzed in 202 informative cases by D3S1300 and D3S1234 microsatellite markers. Measurements and Main Results: Lost or reduced FHIT expression was found in 36.7 and 75.7% of the tumor samples, respectively. Methylation of the FHIT promoter was found in 36.7%of tumor and 32.7% of normal lung samples, whereas LOH was detected in 61.9% of the tumors. A strong association with complete loss of FHIT expression was presentwhenmethylation and LOHwere analyzed together (P5 0.0064). Loss of FHIT protein expression was significantly more frequent in squamous cell carcinoma histotype (P , 0.0001) and in smokers (P5 0.008). FHIT methylation in normal lung was associated with an increased risk of progressive disease (OR, 2.27; P 5 0.0415). Conclusions:Our results indicate thatdifferentmolecularmechanisms interplay to inactivate FHIT expression and support the proposition that FHIT methylation in normal lung tissue could represent a prognostic marker for progressive disease

Membrane-Bound TNF Induces Protective Immune Responses to M. bovis BCG Infection: Regulation of memTNF and TNF Receptors Comparing Two memTNF Molecules

Several activities of the transmembrane form of TNF (memTNF) in immune responses to intracellular bacterial infection have been shown to be different from those exerted by soluble TNF. Evidence is based largely on studies in transgenic mice expressing memTNF, but precise cellular mechanisms are not well defined and the importance of TNF receptor regulation is unknown. In addition, memTNF activities are defined for a particular modification of the extracellular domain of TNF but a direct comparison of different mutant memTNF molecules has not been done in vivo

Charge Asymmetries for D, D_s and Lambda_c Production in Sigma- - Nucleus Interactions at 340 GeV/c

CERN experiment WA89 has studied charmed particles produced by a Sigma^- beam at 340 GeV/c on nuclear targets. Production of particles which have light quarks in common with the beam is compared to production of those which do not. Considerable production asymmetries between D^- and D^p, D_s^ and D_s^+ and Lambda_c and Antilambda_c are observed. The results are compared with pion beam data and with theoretical calculations.Comment: LaTeX ; 16 pages including 4 ps figure

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