204 Overdrive ventricular pacing in patients with permanent atrial arrhythmias and sleep apnea

BackgroundIn contrast to its efficacy in patients with heart failure (HF) and central (C) sleep apnea (SA), cardiac pacing is ineffective in obstructive SA. We examined whether overdrive ventricular pacing (OVP) has an effect on SA in pacemaker recipients with permanent atrial arrhythmias.MethodsAn apnea-hypopnea index (AHI) ≥ 15 was confirmed in 28 of 38 patients screened by finger oximetry during ventricular pacing at a backup rate of 40 bpm (BUV40). These 28 patients were randomly assigned in a crossover design to BUV40 versus OVP at 20 bpm above the mean heart rate measured during screening oximetry.ResultsAHI ≥ 30 and CSA were observed in 61% and 79% of patients, respectively. In 21 patients (19 with CSA) with a ≥ 5 OVP-induced decrease or no change in AHI, left ventricular ejection fraction (LVEF) was 40±16%, versus 55±18% (p=0.04) in 7 patients (3 with CSA, p=0.02) with a ≥ 5 OVP-induced increase in AHI. In 13 patients with histories of HF decompensation, AHI decreased from 32.8±12.9 during BUV40 to 24.9±16.5 during OVP, versus increased from 37.6±11.0 to 39.0±11.5 in 15 patients without histories of HF decompensation (p=0.02 vs. patients with histories of decompensated HF). In 9 patients with LVEF ≤ 35%, AHI decreased from 37.3±14.7 during BUV40 to 28.4±17.9 during OVP, versus from 34.5±10.7 to 34.4±14.3 in 19 patients with LVEF >35%, (p=0.04 vs. patients with LVEF ≤ 35%).ConclusionsIn patients with permanent atrial tachyarrhythmias, AHI decreased significantly during OVP in patients with a) histories of decompensated HF and CSA, or b) LVEF ≤ 35%, and increased or was unchanged by OVP in patients without these characteristics

A Thermodynamic Approach to Predict the Metallic and Oxide Phases Precipitations in Nuclear Waste Glass Melts

AbstractAmong the large number of matrixes explored as hosts for high-level nuclear wastes, conditioning of fission products and minor actinides into a homogeneous borosilicate glass is the most promising technique already implemented at the industrial scale. The advantage of this vitrification process is the volume reduction of the high level waste coming from the spent fuel reprocessing and its stability for the long-term storage. Nevertheless, some fission products are poorly soluble in molten glasses:•Platinoids (Pd, Ru, Rh) which precipitate as (Pd-Te, Ru-Rh) metallic particles and (Rh,Ru)O2 oxide phases with acicular or polyhedral shapes during the vitrification process.•Molybdenum oxide (MoO3) which can form complex molybdates.In order to point out the chemical interactions between the glass and these precipitated phases issuing from the calcinated waste, a thermodynamic approach is developed using the Calphad method. The objective of this work is to calculate thermodynamic properties for complex fission product systems in order to predict the precipitation of platinoids or molybdate phases.This thermodynamic database is being developed on the Mo-Pd-Rh-Ru-Se-Te-O complex system. This flexible tool enables to predict phase diagrams, composition and relative stability of the metallic or oxide precipitated phases as a function of both temperature and oxygen potential in the glass melt

Effects of deletion of the Streptococcus pneumoniae lipoprotein diacylglyceryl transferase gene lgt on ABC transporter function and on growth in vivo

Lipoproteins are an important class of surface associated proteins that have diverse roles and frequently are involved in the virulence of bacterial pathogens. As prolipoproteins are attached to the cell membrane by a single enzyme, prolipoprotein diacylglyceryl transferase (Lgt), deletion of the corresponding gene potentially allows the characterisation of the overall importance of lipoproteins for specific bacterial functions. We have used a Δlgt mutant strain of Streptococcus pneumoniae to investigate the effects of loss of lipoprotein attachment on cation acquisition, growth in media containing specific carbon sources, and virulence in different infection models. Immunoblots of triton X-114 extracts, flow cytometry and immuno-fluorescence microscopy confirmed the Δlgt mutant had markedly reduced lipoprotein expression on the cell surface. The Δlgt mutant had reduced growth in cation depleted medium, increased sensitivity to oxidative stress, reduced zinc uptake, and reduced intracellular levels of several cations. Doubling time of the Δlgt mutant was also increased slightly when grown in medium with glucose, raffinose and maltotriose as sole carbon sources. These multiple defects in cation and sugar ABC transporter function for the Δlgt mutant were associated with only slightly delayed growth in complete medium. However the Δlgt mutant had significantly reduced growth in blood or bronchoalveolar lavage fluid and a marked impairment in virulence in mouse models of nasopharyngeal colonisation, sepsis and pneumonia. These data suggest that for S. pneumoniae loss of surface localisation of lipoproteins has widespread effects on ABC transporter functions that collectively prevent the Δlgt mutant from establishing invasive infection

QUBIC: The QU Bolometric Interferometer for Cosmology

One of the major challenges of modern cosmology is the detection of B-mode polarization anisotropies in the CMB. These originate from tensor fluctuations of the metric produced during the inflationary phase. Their detection would therefore constitute a major step towards understanding the primordial Universe. The expected level of these anisotropies is however so small that it requires a new generation of instruments with high sensitivity and extremely good control of systematic effects. We propose the QUBIC instrument based on the novel concept of bolometric interferometry, bringing together the sensitivity advantages of bolometric detectors with the systematics effects advantages of interferometry. Methods: The instrument will directly observe the sky through an array of entry horns whose signals will be combined together using an optical combiner. The whole set-up is located inside a cryostat. Polarization modulation will be achieved using a rotating half-wave plate and interference fringes will be imaged on two focal planes (separated by a polarizing grid) tiled with bolometers. We show that QUBIC can be considered as a synthetic imager, exactly similar to a usual imager but with a synthesized beam formed by the array of entry horns. Scanning the sky provides an additional modulation of the signal and improve the sky coverage shape. The usual techniques of map-making and power spectrum estimation can then be applied. We show that the sensitivity of such an instrument is comparable with that of an imager with the same number of horns. We anticipate a low level of beam-related systematics thanks to the fact that the synthesized beam is determined by the location of the primary horns. Other systematics should be under good control thanks to an autocalibration technique, specific to our concept, that will permit the accurate determination of most of the systematics parameters.Comment: 12 pages, 10 figures, submitted to Astronomy and Astrophysic

Cholinesterase Inhibitors and Hospitalization for Bradycardia: A Population-Based Study

Laura Park-Wyllie and colleagues examined the health records of more than 1.4 million older adults and show that initiation of cholinesterase inhibitor therapy is associated with a more than doubling of the risk of hospitalization for bradycardia

In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus

Hepatitis delta virus (HDV) can dramatically worsen liver disease in patients coinfected with hepatitis B virus (HBV). No effective medical therapy exists for HDV. The HDV envelope requires HBV surface antigen proteins provided by HBV. Once inside a cell, however, HDV can replicate its genome in the absence of any HBV gene products. In vitro, HDV virion assembly is critically dependent on prenyl lipid modification, or prenylation, of its nucleocapsid-like protein large delta antigen. To overcome limitations of current animal models and to test the hypothesis that pharmacologic prenylation inhibition can prevent the production of HDV virions in vivo, we established a convenient mouse-based model of HDV infection capable of yielding viremia. Such mice were then treated with the prenylation inhibitors FTI-277 and FTI-2153. Both agents were highly effective at clearing HDV viremia. As expected, HDV inhibition exhibited duration-of-treatment dependence. These results provide the first preclinical data supporting the in vivo efficacy of prenylation inhibition as a novel antiviral therapy with potential application to HDV and a wide variety of other viruses

Interferon Impedes an Early Step of Hepatitis Delta Virus Infection

Hepatitis delta virus (HDV) infects hepatocytes, the major cell type of the liver. Infection of the liver may be either transient or chronic. The prognosis for patients with chronic HDV infection is poor, with a high risk of cirrhosis and hepatocellular carcinoma. The best antiviral therapy is weekly administration for at least one year of high doses of interferon alpha. This efficacy of interferon therapy has been puzzling in that HDV replication in transfected cell lines is reported as insensitive to administration of interferon alpha or gamma. Similarly, this study shows that even when an interferon response was induced by transfection of poly(IC) into a cell line, HDV RNA accumulation was only modestly inhibited. However, when the HDV replication was initiated by infection of primary human hepatocytes, simultaneous addition of interferons alpha or gamma at 600 units/ml, a concentration comparable to that achieved in treated patients, the subsequent HDV RNA accumulation was inhibited by at least 80%. These interferon treatments were shown to produce significant time-dependent increases of host response proteins such as for Stat-1, phosphoStat-1, Mx1/2/3 and PKR, and yet interferon pretreatment of hepatocytes did not confer an increased inhibition of HDV replication over interferon treatment at the time of (or after) infection. These and other data support the interpretation that interferon action against HDV replication can occur and is largely mediated at the level of entry into primary human hepatocytes. Thus in vivo, the success of long-term interferon therapy for chronic HDV, may likewise involve blocking HDV spread by interfering with the initiation of productive infection of naïve hepatocytes

QUBIC: The Q&U Bolometric Interferometer for Cosmology - A novel way to look at the polarized Cosmic Microwave Background

In this paper we describe QUBIC, an experiment that takes up the challenge posed by the detection of primordial gravitational waves with a novel approach, that combines the sensitivity of state-of-the art bolometric detectors with the systematic effects control typical of interferometers. The so-called "self-calibration" is a technique deeply rooted in the interferometric nature of the instrument and allows us to clean the measured data from instrumental effects. The first module of QUBIC is a dual band instrument (150 GHz and 220 GHz) that will be deployed in Argentina during the Fall 2018.Fil: Mennella, Aniello. University of Milan; ItaliaFil: Ade, P. A. R.. Cardiff University; Reino UnidoFil: Aumont, J.. Institut d'Astrophysique Spatiale; FranciaFil: Banfie, S.. Istituto Nazionale Di Fisica Nucleare; ItaliaFil: Battaglia, P.. Università degli Studi di Trieste; ItaliaFil: Battistelli, E. S.. Università degli Studi di Roma "La Sapienza"; ItaliaFil: Baùe, F.. Istituto Nazionale Di Fisica Nucleare; ItaliaFil: Buzi, D.. Università degli Studi di Roma "La Sapienza"; ItaliaFil: Columbro, F.. Università degli Studi di Roma "La Sapienza"; ItaliaFil: Bélie, B.. Institute of Fundamental Electronics; FranciaFil: Bennett, D.. Maynooth University; IrlandaFil: Bergé, L.. Centre de Sciences Nucléaires et de Sciences de la Matière; FranciaFil: Bernard, J. Ph.. Institut de Recherche en Astrophysique et Planétologie; FranciaFil: Bersanelli, M.. University of Milan; ItaliaFil: Bigot Sazy, M. A.. APC; FranciaFil: Bleurvacq, N.. APC; FranciaFil: Bordier, G.. APC; FranciaFil: Brossard, J.. APC; FranciaFil: Bunn, E. F.. Richmond University; Estados UnidosFil: Burke, D. P.. Maynooth University; IrlandaFil: Buzi, D.. Università degli Studi di Roma "La Sapienza"; ItaliaFil: Buzzelli, A.. Universita Tor Vergata; ItaliaFil: Cammilleri, D.. APC; FranciaFil: Cavaliere, F.. University of Milan; ItaliaFil: Chanial, P.. APC; FranciaFil: Etchegoyen, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Harari, Diego Dario. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Medina, Maria Clementina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Romero, Gustavo Esteban. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Argentino de Radioastronomía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Argentino de Radioastronomía; ArgentinaFil: Suarez, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaThe European Physical Society Conference on High Energy PhysicsVeneciaItaliaEuropean Physical Societ