Mechanisms of opsonized HIV entry in normal B lymphocytes

AbstractUsing our in vitro model of normal B cell infection that functions with low doses of HIV but requires virus opsonization by seropositive patient serum, and complement, we analyzed what receptors allowed virus entry. Here, we show that HIV infection of B cells occurs through 2 major receptors: the CD4 antigen and the CR1/CR2 complex. These 2 pathways work independently since a complete inhibition of virus entry requires both CD4 and CD21/CD35 blockade on CD4dim tonsillar B cells whereas only the latter is critical on CD4-negative B cells

0432: Impact of early complications on outcomes among patients with implantable cardioverter defibrillator in primary prevention

BackgroundThe life-saving benefit of implantable cardioverter defibrillators (ICD) has been well demonstrated, and therefore their utilization has considerably grown in the last 10 years. At the same time, complications have become an increasingly important concern.ObjectivesThis study aimed to assess the prevalence and impact on outcomes (late complications and overall mortality) of early complications after ICD implantation for primary prevention in a large French population.MethodsFrom a multicentric French registry (DAI-PP Registry, 2002-2012), 5547 consecutive patients, with coronary artery disease or dilated cardiomyopathy, were implanted with an ICD in the setting of primary prevention. From 5338 (96%) patients with full information, we determined prevalence, independent associated factors and prognosis of the occurrence of early (within 30 days post implantation) complications.ResultsEarly complications occurred in 709 patients (13.5%), mainly related to lead dysfunction or hematoma (56%). Independent associated factors to early complications were renla impairment (clearance <30ml/min, OR=1.69, 95% CI 1.19-2.41, P<0.001), cardiac resynchronization therapy (OR=1.61, 95% CI 1.17-2.21, P=0.004), anticoagulant therapy (OR=1.30, 95% CI 1.04-1.63, P=0.02) and older age (OR=1.02, 95% CI 1.01-1.02, P=0.03). During a mean follow-up of 3.1±2.3 years, 834 patients experienced ≥1 complication (15.6%), mainly inappropriate therapies and/or lead dysfunction (75%). After consideration of potential confounding factors, early complications were significantly associated with the occurrence of late complications (OR=2.15, 95% CI 1.73-2.66, P<0.0001) and a higher risk of overall mortality (OR=1.48, 95% CI 1.17-1.88, P=0.001).ConclusionsEarly complication is a frequent event after ICD implantation occurring in one out of six patients. These events are associated with a significant increase of late complications and overall mortality

A review of multisite pacing to achieve cardiac resynchronization therapy

Non-response to cardiac resynchronization therapy remains a significant problem in up to 30% of patients. Multisite stimulation has emerged as a way of potentially overcoming non-response. This may be achieved by the use of multiple leads placed within the coronary sinus and its tributaries (dual-vein pacing) or more recently by the use of multipolar (quadripolar) left ventricular pacing leads which can deliver pacing stimuli at multiple sites within the same vein. This review covers the role of multisite pacing including the interaction with the underlying pathophysiology, the current and planned studies, and the potential pitfalls of this technolog

The CMS Electromagnetic Calorimeter Data Acquisition System at the 2006 Test Beam

The Electromagnetic Calorimeter of the CMS experiment at the CERN LHC is an homogeneous calorimeter made of about 80000 Lead Tungstate crystals. From June to November 2006, eleven barrel Supermodules (1700 crystals each) were exposed to beam at CERN SPS, both in stand-alone and in association with portions of the Hadron Calorimeter. We present the description of the system used to configure and readout the calorimeter during this period. The full set of final readout electronics boards was employed, together with the pre-series version of the data acquisition software. During this testbeam, the hardware and software concepts for the final system were validated and the successfull operation of all the ten supermodules was ensured

eLife

The functions of the TAF subunits of mammalian TFIID in physiological processes remain poorly characterised. In this study, we describe a novel function of TAFs in directing genomic occupancy of a transcriptional activator. Using liver-specific inactivation in mice, we show that the TAF4 subunit of TFIID is required for post-natal hepatocyte maturation. TAF4 promotes pre-initiation complex (PIC) formation at post-natal expressed liver function genes and down-regulates a subset of embryonic expressed genes by increased RNA polymerase II pausing. The TAF4-TAF12 heterodimer interacts directly with HNF4A and in vivo TAF4 is necessary to maintain HNF4A-directed embryonic gene expression at post-natal stages and promotes HNF4A occupancy of functional cis-regulatory elements adjacent to the transcription start sites of post-natal expressed genes. Stable HNF4A occupancy of these regulatory elements requires TAF4-dependent PIC formation highlighting that these are mutually dependent events. Local promoter-proximal HNF4A-TFIID interactions therefore act as instructive signals for post-natal hepatocyte differentiation

Laser monitoring system for the CMS lead tungstate crystal calorimeter

We report on the multiple wavelength laser monitoring system designed for the CMS lead tungstate crystal calorimeter read-out with avalanche photodiodes (Barrel calorimeters) and vacuum phototriodes (End Cap calorimeters). Results are presented for the test beam performance of the system designed to achieve 0.5% relative inter-calibration of the optical transmittance for lead tungstate scintillation emission over nearly 80 000 channels. The system operates in continuous measurement cycles to follow each crystal?s evolution under irradiation and recovery periods foreseen during operation at the LHC

Viral Load Levels Measured at Set-Point Have Risen Over the Last Decade of the HIV Epidemic in the Netherlands

HIV-1 RNA plasma concentration at viral set-point is associated not only with disease outcome but also with the transmission dynamics of HIV-1. We investigated whether plasma HIV-1 RNA concentration and CD4 cell count at viral set-point have changed over time in the HIV epidemic in the Netherlands.We selected 906 therapy-naïve patients with at least one plasma HIV-1 RNA concentration measured 9 to 27 months after estimated seroconversion. Changes in HIV-1 RNA and CD4 cell count at viral set-point over time were analysed using linear regression models. The ATHENA national observational cohort contributed all patients who seroconverted in or after 1996; the Amsterdam Cohort Studies (ACS) contributed seroconverters before 1996. The mean of the first HIV-1 RNA concentration measured 9-27 months after seroconversion was 4.30 log(10) copies/ml (95% CI 4.17-4.42) for seroconverters from 1984 through 1995 (n = 163); 4.27 (4.16-4.37) for seroconverters 1996-2002 (n = 232), and 4.59 (4.52-4.66) for seroconverters 2003-2007 (n = 511). Compared to patients seroconverting between 2003-2007, the adjusted mean HIV-1 RNA concentration at set-point was 0.28 log(10) copies/ml (95% CI 0.16-0.40; p<0.0001) and 0.26 (0.11-0.41; p = 0.0006) lower for those seroconverting between 1996-2002 and 1984-1995, respectively. Results were robust regardless of type of HIV-1 RNA assay, HIV-1 subtype, and interval between measurement and seroconversion. CD4 cell count at viral set-point declined over calendar time at approximately 5 cells/mm(3)/year.The HIV-1 RNA plasma concentration at viral set-point has increased over the last decade of the HIV epidemic in the Netherlands. This is accompanied by a decreasing CD4 cell count over the period 1984-2007 and may have implications for both the course of the HIV infection and the epidemic

Impact of early complications on outcomes in patients with implantable cardioverter-defibrillator for primary prevention

International audienceBackground - The lifesaving benefit of implantable cardioverter-defibrillators (ICDs) has been demonstrated. Their use has increased considerably in the past decade, but related complications have become a major concern. Objective - The purpose of this study was to assess the incidence and effect on outcomes of early (≤30 days) complications after ICD implantation for primary prevention in a large French population. Methods - We analyzed data from 5539 patients from the multicenter French DAI-PP (Défibrillateur Automatique Implantable-Prévention Primaire) registry (2002-2012) who had coronary artery disease or dilated cardiomyopathy and were implanted with an ICD for primary prevention. Results - Overall, early complications occurred in 707 patients (13.5%), mainly related to lead dislodgment or hematoma (57%). Independent factors associated with occurrence of early complications were severe renal impairment (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.17-2.37, P = .02), age ≥75 years (OR 1.01, 95% CI 1.00-1.02, P = .03), cardiac resynchronization therapy (OR 1.58, 95% CI 1.16-2.17, P = .01), and anticoagulant therapy (OR 1.28, 95% CI 1.02-1.61, P = .03). During a mean ± SD follow-up of 3.1 ± 2.3 years, 824 (15.8%) patients experienced ≥1 late complication (>30 days), and 782 (14.9%) patients died. After adjustment, early complications remained associated with occurrence of late complications (OR 2.15, 95% CI 1.73-2.66, P < .0001) and mortality (OR 1.70, 95% CI 1.34-2.17, P = .003). Conclusion - Early complications are common after ICD implantation for primary prevention, occurring in 1 in 7 patients, and are associated with an increased risk of late complications and overall mortality. Further studies are needed to investigate the underlying mechanisms of such associations

Transmission Selects for HIV-1 Strains of Intermediate Virulence: A Modelling Approach

Recent data shows that HIV-1 is characterised by variation in viral virulence factors that is heritable between infections, which suggests that viral virulence can be naturally selected at the population level. A trade-off between transmissibility and duration of infection appears to favour viruses of intermediate virulence. We developed a mathematical model to simulate the dynamics of putative viral genotypes that differ in their virulence. As a proxy for virulence, we use set-point viral load (SPVL), which is the steady density of viral particles in blood during asymptomatic infection. Mutation, the dependency of survival and transmissibility on SPVL, and host effects were incorporated into the model. The model was fitted to data to estimate unknown parameters, and was found to fit existing data well. The maximum likelihood estimates of the parameters produced a model in which SPVL converged from any initial conditions to observed values within 100–150 years of first emergence of HIV-1. We estimated the 1) host effect and 2) the extent to which the viral virulence genotype mutates from one infection to the next, and found a trade-off between these two parameters in explaining the variation in SPVL. The model confirms that evolution of virulence towards intermediate levels is sufficiently rapid for it to have happened in the early stages of the HIV epidemic, and confirms that existing viral loads are nearly optimal given the assumed constraints on evolution. The model provides a useful framework under which to examine the future evolution of HIV-1 virulence

LʼOccident grec de Marseille à Mégara Hyblaea

La recherche sur l’expansion grecque en Méditerranée occidentale à l’époque archaïque a largement progressé en France pendant les quarante dernières années grâce aux travaux d’Henri Tréziny et aux pistes qu’il a lancées dans l’interprétation des découvertes archéologiques de Sicile et du Sud de la Gaule. En présentant ces études sur l’urbanisme, l’architecture et divers artefacts de la vie matérielle dans ces régions occupées par les Grecs à partir du VIIIe siècle av. J.-C., ses amis, collègues et élèves ont voulu lui rendre hommage en centrant en particulier leurs réflexions sur les deux sites qui ont constitué les piliers de sa carrière, Marseille et Mégara Hyblaea. Vingt-trois contributions dues à quelques-uns des meilleurs spécialistes de ces questions, français, italiens et espagnols, mettent ici en évidence le dynamisme de la recherche dans ces régions périphériques du monde grec où populations locales et Grecs ont constitué une culture spécifique, faite de brassages et d’emprunts respectifs dans les domaines de la ville, de la religion ou des pratiques culturelles. Le volume s’ouvre sur la publication de découvertes récentes des chercheurs turcs à Phocée, la métropole de Marseille et une des cités grecques les plus actives dans cette expansion vers l’Ouest