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Hybrid bonding or surface activated bonding is becoming a very attractive technology to manufacture higher performance CMOS by addressing pitch scaling difficulties of solder interconnects. One of the major challenges for dielectric bonding is to decrease the process temperature to be compatible with CMOS processing. Many investigations have demonstrated low bonding temperatures (annealing temperatures below 250°C) with either SiCN or SiN. In this paper, we focus on the dielectric layer deposition process. Both low temperature physical vapor deposition (PVD) of SiN and SiCN are investigated side by side. Film stress as function of film thickness is characterized to understand its potential impact on wafer warpage. Reliability of low temperature SiN film is tested on both inorganic and organic surfaces so it can be leveraged in a wide set of wafer level packaging applications.

[Objectives] To develop and validate baseline, perioperative and at-discharge risk-scoring systems for postsurgical prosthetic joint infection (PJI) in patients undergoing arthroplasty., [Methods] A multicentre prospective cohort study of patients undergoing hip and knee arthroplasty was performed. Patients were randomly assigned (2:1) to a derivation cohort (DC) or a validation cohort (VC). Multivariable predictive models of PJI were constructed at baseline (preoperative period), perioperative (adding perioperative variables) and at-discharge (adding wound state at discharge). The predictive ability of the models and scores was evaluated by area under the receiving operating characteristic curves (AUROC)., [Results] The DC and VC included 2324 and 1245 patients, respectively. Baseline model included total hip arthroplasty (THA), revision arthroplasty (RA), Charlson index and obesity. The AUROC for the score was 0.75 and 0.78 in the DC and VC, respectively. Perioperative model included THA, RA, obesity, National Nosocomial Infections Surveillance (NNIS) index ≥2, significant wound bleeding and superficial surgical site infection; the AUROC was 0.81 and 0.77 in the DC and VC, respectively. The at-discharge model included THA, RA, obesity, NNIS index ≥2, superficial surgical site infection and high-risk wound; the AUROC was 0.82 and 0.84 in the DC and VC, respectively. A score ≥8 points provided 99% negative predictive values for all models., [Conclusions] Simple scores for predicting PJI at three different moments of care in patients undergoing arthroplasty were developed and validated. The scores allow early and accurate identification of high-risk individuals in whom enhanced preventive measures and follow-up may be needed. Further external validation is needed.

Background To determine the prevalence of abdominal aortic aneurysm (AAA) (arterial diameter ≥30 mm), in patients with high or very high cardiovascular risk (CVR) and to evaluate their clinical features. Patients and methods Observational, cross-sectional and multicentric study conducted in Spanish Internal Medicine Services. We enrolled men with age >55 years and women >65 years who had a high or very high CVR. Results The study included 659 patients. The prevalence of AAA was 8% (53 patients). 76.9% were male with a mean age of 71 ± 8.7 years. The multivariate analysis showed an association between AAA and age (OR: 1.06; 95% CI: 1.02–1.1; P Conclusions The prevalence of AAA in patients with high CVR is high. Ultrasound screening can be performed by general practitioners. Men >65 years with elevated CVR could benefit, particularly in the presence of active smoking or peripheral arterial disease.

Resumen Objetivo Determinar la prevalencia de aneurisma de aorta abdominal (AAA), definido por un diametro arterial ≥ 30 mm, en pacientes con alto o muy alto riesgo cardiovascular (RCV) y evaluar sus caracteristicas clinicas. Pacientes y metodos Estudio observacional, transversal y multicentrico realizado en servicios de Medicina Interna del pais a varones con edad > 55 anos y mujeres > 65 anos que tenian un RCV alto o muy alto reclutados durante 24 meses. Resultados Se incluyeron 659 pacientes. La prevalencia de AAA fue del 8% (53 pacientes). El 76,9% fueron varones, con edad media de 71 ± 8,7 anos. El analisis multivariante demostro asociacion entre AAA y la edad (OR: 1,06; IC 95%: 1,02-1,1; p Conclusiones La prevalencia de AAA en pacientes de alto RCV es elevada. El cribado ecografico puede ser realizado por medicos generalistas. Pueden beneficiarse de un cribado oportunista los varones de mas de 65 anos, con RCV elevado, especialmente si presentan tabaquismo activo o arteriopatia periferica.

New challenges in packaging arise as the pitch of the first-level-interconnects shrinks below what can be achieved with solder joints. Hybrid bonding, including direct Cu-Cu bonding, is a promising solution but faces significant integration challenges.In this study, which is focused on potential use of direct bond technology for packaging applications, a model for quantifying the impact of wafer/substrate thickness to bond wave speed is presented and validated. Then, a low temperature deposited Silicon Nitride (SiN) surface is studied for both symmetrical and asymmetrical bonds. Guidance on densification needs, best surface preparation, and annealing condition to achieve sufficient bonding energy and void free bonding are reported for each interface type with low annealing temperature conditions (≤200°C). This ensures a solution can be leveraged for advance packaging applications.

Heterogeneous integration gained significant momentum in the semiconductor industry as it compliments lithographic scaling and offers alternative pathways to device improvement. Temporary bond debond technology (TBDB) with a glass carrier provides a manufacturing platform for this heterogeneous assembly on the wafer level. This paper describes the material development of a silicone-based temporary adhesive to enable robust bonding of the device wafer to glass carrier, as well as a thermoset polymer based laser release layer that enables stress-free glass debond upon receiving UV irradiation. We found that thermoset based temporary bond adhesive offers robust thermal stability, low outgassing, and excellent mechanical stability, making it suitable for wafer level assembly with a temporary glass carrier. An innovative, solvent-based cleaning solution was also identified to efficiently break down the crosslinked adhesive network, offering a robust wafer cleaning process, post laser debonding at room temperature. Some preliminary results of heterogeneous wafer level assembly using this novel temporary adhesive with laser debond will also be discussed.

A significant fraction of Czochralski (Cz) Silicon (Si) wafers suffer from oxygen-related bulk quality issues. The detection of such wafers in the as-cut state during incoming inspection has become a topic of attention as higher efficiency solar cell structures are developing. However such detection - for instance using photoluminescence images – has not yet proven successful due to a high risk of detection errors Shih et al. (2015) [1] . In this work, we tentatively introduce a material quality indicator referred to as “Thermal History Index” (THI) and investigate its ability, in conjunction with the interstitial oxygen concentration ([Oi]), to allow a better identification of low bulk quality wafers.

Background Measurement of left ventricular outflow tract (LVOT) diameter and area for estimation of aortic valve area (AVA) using transthoracic echocardiography (TTE) and the continuity equation assumes circular LVOT. The use of direct planimetric measurement of LVOT area by gated-CT can theoretically improve accuracy of AVA calculation. Purpose We aim to assess reproducibility of LVOT echo measurement and its correlation and agreement with Gated CT measurements. In the subgroup with aortic stenosis (AS) we secondarily assessed the potential change in AS severity using LVOT area by CT instead of TTE in the continuity equation. Methods We retrospectively studied 93 patients, 43 of whom with severe AS. LVOT Area was measured with 2D TTE by 2 expert echocardiographers and gated-CT by 2 expert radiologists; inter-reader agreement and inter-method (Echo vs gated CT) agreement and correlation were measured. Finally we used the measurement of CT scan in the continuity equation instead of TTE measurement to assess potential reclassification of AS severity. Results Mean age was 78±11. Table shows inter-reader and inter-method agreement and correlation. The correlation between 2 echocardiophers for LVOT measurements was good (rho = 0,77) although not perfect. Out of 43 severe AS, defined as AVA

Plasma drug-resistant minority human immunodeficiency virus type 1 variants (DRMVs) increase the risk of virological failure to first-line non-nucleoside reverse transcriptase inhibitor antiretroviral therapy (ART). The origin of DRMVs in ART-naive patients, however, remains unclear. In a large pan-European case-control study investigating the clinical relevance of pre-existing DRMVs using 454 pyrosequencing, the six most prevalent plasma DRMVs detected corresponded to G-to-A nucleotide mutations (V90I, V106I, V108I, E138K, M184I and M230I). Here, we evaluated if such DRMVs could have emerged from apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3G/F (APOBEC3G/F) activity. Out of 236 ART-naive subjects evaluated, APOBEC3G/F hypermutation signatures were detected in plasma viruses of 14 (5.9%) individuals. Samples with minority E138K, M184I, and M230I mutations, but not those with V90I, V106I or V108I, were significantly associated with APOBEC3G/F activity (Fisher's P0.005), defined as the presence of0.5% of sample sequences with an APOBEC3G/F signature. Mutations E138K, M184I and M230I co-occurred in the same sequence as APOBEC3G/F signatures in 3/9 (33%), 5/11 (45%) and 4/8 (50%) of samples, respectively; such linkage was not found for V90I, V106I or V108I. In-frame STOP codons were observed in 1.5% of all clonal sequences; 14.8% of them co-occurred with APOBEC3G/F signatures. APOBEC3G/F-associated E138K, M184I and M230I appeared within clonal sequences containing in-frame STOP codons in 2/3 (66%), 5/5 (100%) and 4/4 (100%) of the samples. In a re-analysis of the parent case control study, the presence of APOBEC3G/F signatures was not associated with virological failure. In conclusion, the contribution of APOBEC3G/F editing to the development of DRMVs is very limited and does not affect the efficacy of non-nucleoside reverse transcriptase inhibitor ART.

Resume But La loi du 5 mars 2007 a reforme la protection de l’enfance (PE). A compter de cette date, la saisine des services administratifs en charge de la PE est realisee par l’envoi d’une information preoccupante (IP). Objectif Evaluer l’etat des connaissances et des pratiques des medecins generalistes (MG) concernant la realisation et la transmission d’une IP. Methodes Une enquete epidemiologique descriptive a ete realisee aupres de l’ensemble des MG liberaux d’Ille-et-Vilaine en charge du suivi de la majorite de la population pediatrique dans ce departement. Le but de ce travail a consiste a evaluer leur connaissance sur les dispositions de la loi mars 2007. Resultats Deux cent quatre-vingt-dix-huit medecins (33,15 %) ont repondu au questionnaire, dont 113 femmes (37,9 %). Le profil de l’echantillon etudie et de la population des MG dans ce departement etait comparable. Seuls 25,5 % des MG avaient entendu parler de la loi du 5 mars 2007. Le terme d’IP etait inconnu de 70,1 % des MG et son destinataire de 77,2 % d’entre eux. La difference entre signalement et IP etait ignoree par 79,5 % des MG. De fait, seul 5 % des MG disaient avoir ete formes sur l’IP. L’obstacle majeur quant a la redaction d’un ecrit dans une suspicion d’enfant en danger etait le manque de formation. Parmi les MG, 91,9 % en etaient demandeurs. Conclusion L’IP et la nouvelle loi de PE sont tres mal connues des MG du departement d’Ille-et-Vilaine. Notre etude souligne l’importance et la qualite d’une formation medicale initiale et continue.

The PICARD microsatellite mission will provide 3 to 4 years simultaneous measurements of the solar diameter, differential rotation and solar constant to investigate the nature of their relations and variabilities. The major instrument, SODISM, is a whole Sun imaging telescope of O110 mm which will deliver an absolute measure (better than 4 mas) of the solar diameter and solar shape. Now in Phase B, PICARD is expected to be launched by 2005. We recall the scientific goals linked to the diameter measurement with interest for Earth Climate, Space Weather and Helioseismology, present the instrument optical concept and design, and give a brief overview of the program aspects.

Obesity is associated with reduced exercise maximal fat oxidation rate (FATmax), which is generally assessed by cardiopulmonary cycling test. The six-minute walking test (6MWT) presents an alternative method in patients.The aim of this study was to establish a practical reference equation facilitating the prediction of FATmax from the 6 MWT in obese children of both genders.This study is a cross-sectional study using mixed linear and multiple regression models.Anthropometric measurements were recorded and submaximal cycling test and 6 MWT conducted for 131 school-aged obese children, 68 boys and 63 girls. A multiple regression analysis for FATmax, including six-minute walking distance (6 MWD), anthropometric and cardiac parameters as the dependent variables, was performed for the two genders separately.Mean 6 MWD and FATmax were 564.9 ± 53.7 m and 126.5 ± 12.1 mg min(-1) for boys and 506.7 ± 55.0 m and 120.7 ± 10.0 mg min(-1) for girls, respectively. The 6MWD, body mass index, Z-score, fat-free mass, waist and hip circumferences (WC and HC), rest heart rate, and systolic and diastolic blood pressures were highly correlated with FATmax for both genders. There was a significant correlation between 6 MWD and FATmax in both boys and girls (r = 0.88 and r = 0.81, P0.001, respectively). Stepwise regression analyses revealed that the combinations of 6 MWD with HC for boys and 6MWD with WC for girls improved the predictability of the model (R(2) = 0.81 for boys and R(2) = 0.72 for girls; P0.001).In obese children, the 6MWT can be used to predict FATmax when formal test of exercise capacity and gas exchange analysis are unavailable or impractical. It is therefore possible to prescript targeted exercises at FATmax, without performing indirect calorimetry, just from a field test.

Objectives: To estimate the prevalence of transmitted drug resistance mutations and non-B subtype circulation in antiretroviral-naive chronically HIV-1-infected patients in France. Methods: Resistance mutations were sought in samples from 530 newly diagnosed HIV-1-infected patients from October 2006 to March 2007. Protease and reverse transcriptase mutations were identified from the 2007 Stanford Resistance Surveillance list. Results: Reverse transcriptase and protease resistance mutations were determined in 466 patients with duration of seropositivity

Aims. This article presents very-high-energy (VHE; E > 100 GeV) data from the $\gamma$-ray binary PSR B1259-63 as taken during the years 2005, 2006 and before as well as shortly after the 2007 periastron passage. These data extend the knowledge of the lightcurve of this object to all phases of the 3.4 year binary orbit. The lightcurve constrains physical mechanisms present in this TeV source. Methods. Observations of VHE $\gamma$-rays with the HESS telescope array using the Imaging Atmospheric Cherenkov Technique were performed. The HESS instrument features an angular resolution of < 0.1° and an energy resolution of < 20%. Gamma-ray events in an energy range of 0.5-70 TeV were recorded. From these data, energy spectra and lightcurve with a monthly time sampling were extracted. Results. VHE $\gamma$-ray emission from PSR B1259-63 was detected with an overall significance of 9.5 standard deviations using 55h of exposure, obtained from April to August 2007. The monthly flux of $\gamma$-rays during the observation period was measured, yielding VHE lightcurve data for the early pre-periastron phase of the system for the first time. No spectral variability was found on timescales of months. The spectrum is described by a power law with a photon index of $\Gamma$ = 2.8 $\pm$ 0.2stat $\pm$ 0.2sys and flux normalisation $\Phi_{0}$ = (1.1 $\pm$ 0.1stat $\pm$ 0.2sys) $\times$ 10-12 TeV-1 cm-2 s-1. PSR B1259-63 was also monitored in 2005 and 2006, far from periastron passage, comprising 8.9 h and 7.5 h of exposure, respectively. No significant excess of $\gamma$-rays is seen in those observations. Conclusions. PSR B1259-63 has been re-confirmed as a variable TeV $\gamma$-ray emitter. The firm detection of VHE photons emitted at a true anomaly $\theta$$\approx$-0.35 of the pulsar orbit, i.e. already ~50 days prior to the periastron passage, disfavors the stellar disc target scenario as a primary emission mechanism, based on current knowledge about the companion star's disc inclination, extension, and density profile. Results. VHE $\gamma$-ray emission from PSR B1259-63 was detected with an overall significance of 9.5 standard deviations using 55h of exposure, obtained from April to August 2007. The monthly flux of $\gamma$-rays during the observation period was measured, yielding VHE lightcurve data for the early pre-periastron phase of the system for the first time. No spectral variability was found on timescales of months. The spectrum is described by a power law with a photon index of $\Gamma$ = 2.8 $\pm$ 0.2stat $\pm$ 0.2sys and flux normalisation $\Phi_{0}$ = (1.1 $\pm$ 0.1stat $\pm$ 0.2sys) $\times$ 10-12 TeV-1 cm-2 s-1. PSR B1259-63 was also monitored in 2005 and 2006, far from periastron passage, comprising 8.9 h and 7.5 h of exposure, respectively. No significant excess of $\gamma$-rays is seen in those observations. Conclusions. PSR B1259-63 has been re-confirmed as a variable TeV $\gamma$-ray emitter. The firm detection of VHE photons emitted at a true anomaly $\theta$$\approx$-0.35 of the pulsar orbit, i.e. already ~50 days prior to the periastron passage, disfavors the stellar disc target scenario as a primary emission mechanism, based on current knowledge about the companion star's disc inclination, extension, and density profile.

A significant challenge in using thinner and larger crystalline silicon wafers for solar cell manufacture is the reduced yield due to higher wafer breakage rates. At a given process step, wafer/cell breakage depends on the stresses produced in the wafer/cell due to prior processing, handling and/or transport and on the presence of structural defects such as cracks. Specifically, analysis of wafer breakage requires knowledge of the total in-plane stress state produced in the wafer due to handling and residual stresses from prior processing. This paper presents a systematic approach to breakage analysis of crystalline silicon wafers during handling via analysis of the total stress state produced in the wafer. The total stress state is determined using a combination of wafer deformation measurements and non-linear finite element analysis. Knowledge of the total stress state in conjunction with the crack size and location enables the determination of wafer breakage and the associated fracture stress. This approach is experimentally validated through breakage tests performed on edge-defined film-fed growth (EFG) wafers with cracks introduced via indentation. The results show that the wafer breakage stress during handling is proportional to the inverse of the square root of the crack length, which is consistent with the linear elastic fracture mechanics theory. The work also confirms the capability of the proposed approach to determine the handling conditions under which wafer/cell breakage will occur.

SummaryThe objectives of this work were the analysis of the functional characteristics of circulating monocytes and T lymphocytes in patients with liver cirrhosis, and evaluation of the relationship with an increased exposure to antigens due to bacterial translocation. Forty patients with liver cirrhosis (20 with compensated cirrhosis and 20 with ascitic decompensation) and 20 healthy control subjects were studied. Bacterial translocation was evaluated by serum levels of lipopolysaccharide binding protein (LBP). Macrophage activation was studied by CD40 antigen expression. T lymphocytes were analysed for activation (CD25+, CD122+), effector function (CD8+CD45RO+CD57+), apoptosis (CD95+) and regulatory abilities, either by analysis of the membrane expression of co-stimulatory molecules CD80, CD86 and CD28, or by quantification of regulatory T cells CD4+CD25highforkhead box P3 (FoxP3). The percentage of activated monocytes and T lymphocytes in patients was increased significantly. The proportions of effector senescent cells and of those near to apoptosis were also significantly higher. With respect to these proportions, there were no significant differences between patients in function of the presence or absence of decompensation or in function of the increased or normal values of LBP. Conversely, those patients with elevated levels of LBP presented a significantly higher frequency of regulatory T cells than those with normal levels. In conclusion, patients with liver cirrhosis showed an intensive activation state with a higher percentage of cells committed to activation-induced death, even in non-advanced stages. It is possible that bacterial permeability and endotoxaemia contribute to the expansion of those lymphocyte populations implicated in the prevention of a more severe antigen-induced immunopathology.

Protecting the environment and the public from radioactive hazard is a top priority for all companies operating in the nuclear domain. In order to quantify dose impact on members of the public due to annual discharges of its nuclear installations, AREVA developed the COMODORE code in collaboration with Institute of Radiation Protection and Nuclear Safety (IRSN).COMODORE is a synthesis of 3 softwares validated by IRSN (ACADIE, COTRAM and AQUAREJ). ACADIE is a code elaborated by IRSN and the Treatment Business Unit of AREVA synthesizing the works of the GRNC (Nord-Cotentin Radioecology Group) created by the French government to deal with the estimation of exposure levels to ionizing radiation and associated risks of leukemia for populations in the Nord-Cotentin. COMODORE is a version of ACADIE designed to be adaptable to any other AREVA site. Thus, the operators of the south east of France (Pierrelatte, Marcoule and Romans sites) carried out the adaptation of COMODORE for theirs specificities (for instance, uranium in the terrestrial model).At the moment, COMODORE is used in routine by the AREVA operators to assess the annual dosimetric impact and is also being adapted with SGN to model the radiological impact of uranium ore treatment residues repositories.

Resume Le prelevement a coeur arrete a permis dans les sites pilotes des prelevements sur une nouvelle categorie de donneurs avec une bonne acceptation par la societe civile. Le nombre estime de prelevements supplementaires pour greffe de rein est de 20 %. Les problemes rencontres sont d’abord la formation des equipes et la synchronisation des soins avec la SAMU. Des problemes organisationnels sont en cours de reglement pour le financement, et en termes de mutualisation des equipes et de professionnalisation des competences. Un debat ethique en cours semble essentiellement lie a une meconnaissance et devrait rapidement s’eteindre.

This paper addresses the influence of the partial slip phenomenon on the dynamic motion of a spherical workpiece held in a fixture with application to machining fixture design. The model considers the effect of interfacial slip damping arising from partial slip at a spherical–planar frictional contact subjected to a constant normal load and oscillating tangential load. The model can be used in both single and multiple contact cases as long as the loading assumption for each contact is valid and harmonic balance can be applied. An experimental set up is designed to validate the model for the multiple contact case. Experimental results agree favorably with those predicted by the model. Under the conditions being studied, it is shown that the effect of the partial slip phenomenon on workpiece dynamic motion is significant and should not be ignored.

Resume Objectifs Ameliorer la prevention des troubles d’apprentissage. Population et methodes Les auteurs proposent une approche standardisee des competences langagieres et du developpement psychomoteur des enfants âges de 3 ans et 6 mois ½ a 4 ans et 6 mois ½ lors de l’examen systematique realise en ecole maternelle par les medecins de protection maternelle et infantile. L’exploitation statistique des resultats de 2 enquetes (enquete de prevalence conduite chez 2660 enfants et evaluation de performance des epreuves proposees chez 99 d’entre eux) ont permis de determiner des scores aidant a la decision d’une demande de bilan a visee diagnostique. Resultats La sensibilite et la specificite des epreuves proposees augmentent avec l’âge et sont meilleures dans le cadre des epreuves du langage. Ce nouveau bilan a recu un accueil tres positif de la part des medecins utilisateurs.

Las localizaciones pageticas aisladas en los huesos del pie corresponden al 1–3% de las enfermedades oseas de Paget, pero el 1–20% de los pageticos presenta, ademas, una afectacion podologica de la enfermedad. El calcaneo es el que con mayor frecuencia se afecta, seguido por los metatarsianos, el hueso cuboide y el astragalo. No suele encontrarse manifestacion clinica. Los signos mas frecuentes son el dolor y las deformidades locales. La alteracion radiologica es la del hueso pagetico, con hipertrofia osea y reorganizaciones estructurales asociadas. En las formas puramente podologicas, no hay anomalias de laboratorio definidas. En el caso de afectacion difusa, estas anomalias son detectables, sobre todo los marcadores de remodelado oseo. Nunca se han descrito complicaciones como fracturas. Las artropatias pageticas podologicas tienen un efecto significativo, y el pie se adapta notablemente a las deformidades subyacentes. Se ha descrito la degeneracion sarcomatosa tipica en el calcaneo. El tratamiento local, con asociacion de infiltraciones, fisioterapia, consejos relacionados con el calzado y ortesis plantares, es de sobra conocido. El tratamiento general va dirigido a las afecciones dolorosas y calcaneas.

In this paper a new characterization technique, the OXYMAP technology, allowing measurement of the interstitial oxygen concentration and the oxygen related defects in Czochralski grown silicon, is presented. We applied this technique to 8 inch industrial-like p-type ingots. Relevant information regarding the material quality (compositional and electrical properties) were extracted, and we demonstrated the ability of the developed technic to predict the impact of harmful oxygen-related defects on the solar cells performances.

Clinical data from the Ivory Coast indicate that infection with both human immunodeficiency virus (HIV)-1 and HIV-2 has reached the general population. In this study serologic testing for antibodies to HIV was performed on 3 study groups: 1) 42 confirmed acquired immunodeficiency syndrome (AIDS) cases at the Protestant Hospital of Dabou 2) 94 children aged 6 months-3 years of age who presented at Dabou Hospital with severe malnutrition and symptoms possibly indicative of AIDS and 3) 112 patients at a hospital in Abidjan with aggressive tuberculosis. Of the 42 AIDS patients 18 (43%) had antibodies to HIV-1 2 (5%) had antibodies to HIV-2 and 15 (35%) had antibodies to both infections; another 7 (17%) lacked detectable antibodies against either virus. Those patients with antibodies against both HIV-1 and HIV-2 exhibited a more progressive disease (46% died in the 2-5 months of follow-up) than those infected with HIV-1 alone or HIV-2 alone. 30% of the Dabou infants with severe malnutrition were seropositive for HIV infection; of these 63% had antibodies to HIV-1 30% had antibodies to HIV-1 and HIV-2 and 7% had antibodies against only HIV-2. Finally 51% of the tuberculosis patients were found to be seropositive for HIV infection. 44% of these had antibodies against HIV-1 16% had antibodies against HIV-2 and 40% had antibodies against HIV-1 and HIV-2. Again patients with antibodies to both viruses had a more unfavorable prognosis (66% died within 15 months) than those with antibodies to HIV-1 (48% mortality rate) or HIV-2 (33% mortality rate). Although the clinical symptoms of AIDS induced by HIV-1 and HIV-2 are indistinguishable it appears that the proportion of AIDS cases induced by HIV-2 alone--as well as the severity of the virus induced by this virus--is lower than the proportion and severity of disease induced by HIV-1 alone.

Interferon (IFN)-alpha induced CD4(+) T lymphopenia is a toxic effect of the treatment of chronic hepatitis C virus (HCV) in human immunodeficiency virus (HIV)-co-infected patients. To increase the knowledge about this secondary effect, we performed an analysis of the evolution of the T cell receptor excision circles (TRECs), CD4(+) and CD8(+) T cells and of their CD45RO(+) and CD45RA(+) subpopulations during the treatment of chronic hepatitis HCV with peginterferon alpha (pegIFN-alpha) + ribavirin. Twenty HCV/HIV-co-infected patients, with undetectable HIV load after highly active antiretroviral therapy (HAART), were treated with pegIFN-alpha + ribavirin. TRECs were determined using real-time polymerase chain reaction. CD4(+) and CD8(+) T cells and their CD45RO(+) and CD45RA(+) subpopulations were analysed by two-colour flow cytometry. Median baseline CD4(+) and CD8(+) T cells were 592 mm(3) and 874 mm(3), respectively. Median baseline CD45RO(+) subpopulation was 48% for CD4(+) T and 57% for CD8(+) T lymphocytes. A progressive decrease in both T cell populations, as well as of their CD45RO(+) and CD45RA(+) subpopulations, was detected, with a difference between the baseline and nadir levels approaching 50%. The evolution of T cell populations and TRECs was independent of the response to the treatment. T lymphocytes and their subpopulations returned to baseline levels at 24 weeks after the end of treatment, with the exception of the T CD4(+) CD45RA(+) subpopulation. The ratio of CD4(+) CD45RO(+)/CD4(+) CD45RA(+) increased from 0.89 (baseline) to 1.44 (24 weeks after the end of the therapy). TRECs/ml did not return to the basal values. In conclusion, a significant reduction of CD4(+) and CD8(+) T cells, and of their CD45RA(+) and CD45RO(+) subpopulations, in HIV/HCV co-infected patients treated with pegIFN-alpha was observed. Both subpopulations increased after the suppression of treatment, but the CD4(+) CD45RA subpopulation did not reach the basal levels as a consequence, at least in part, of a decrease in thymic production.

Objetivo Analizar la repercusion de la terapia antirretroviral de gran actividad (TARGA) sobre los ingresos y mortalidad de los pacientes con infeccion por el virus de la inmunodeficiencia humana (VIH) en particular y sobre un Servicio de Medicina Interna en general. Metodos Estudio retrospectivo que analiza los ingresos y exitus producidos en el Servicio de Medicina Interna de un hospital de especialidades entre enero de 1996 y diciembre de 2000. La TARGA se introdujo a partir de 1997. Se valoraron edad, genero, diagnostico principal al alta, peso del grupo relacionado con el diagnostico (GDR), causa de la muerte y estancia hospitalaria de forma global y distribuidas anualmente. Resultados Durante el periodo se produjeron 7.580 ingresos, de los cuales 939 estuvieron producidos por patologias relacionadas con la infeccion por el VIH. El numero de ingresos por VIH disminuyo en un 32,9% y la tasa de letalidad en un 67,8% entre 1996 y 2000, aumentando el volumen de pacientes con patologia respiratoria no infecciosa e infecciones en general. La estancia media de los pacientes ingresados en el servicio se mantuvo estable, disminuyendo la del grupo con infeccion por el VIH un 31,5% a partir de 1997. La complejidad de los GDR en este grupo disminuyo 0,56 puntos. Conclusiones La introduccion de la TARGA se ha relacionado con una disminucion en el numero de ingresos, complejidad de los diagnosticos y fallecimientos en el grupo de pacientes con infeccion por el VIH. Ese lugar ha sido ocupado por enfermos con patologia respiratoria e infecciosa diferente a la relacionada con el VIH.

Therapy with interferon and ribavirin for hepatitis C virus (HCV) infection induces a decrease in several haematological population counts. It is unclear whether haematological toxicity is more severe in patients co-infected with HCV and human immunodeficiency virus (HIV). This study analysed the evolution of haematological population counts during and after interferon and ribavirin therapy for chronic HCV infection. Eleven patients co-infected with HIV and HCV and treated with pegylated interferon plus ribavirin, and ten treated with standard interferon plus ribavirin, were analysed. With reference to baseline values, neutrophil counts decreased by an average of 45% (range 18–67%), total lymphocytes by 50% (16–63%), CD4 lymphocytes by 54% (16–61%), haemoglobin by 9% (5–16%) and platelets by 31% (16–45%). The nadir of the decrease was reached in the first weeks of therapy and was maintained while patients were receiving treatment. The reduction in all series was higher with pegylated interferon. Patients recovered their baseline counts after finishing the treatment. No cases of haemorrhage or outstanding infection were detected during follow-up.

Epidemiologia. La afectacion digestiva es una de las manifestaciones mas frecuentes de las enfermedades sistemicas inmunes. La incidencia varia mucho de unas a otras, oscilando entre la esclerosis sistemica, donde casi la totalidad de los pacientes presentaran sintomatologia durante la evolucion de la enfermedad, a la artritis reumatoide cuya afectacion gastrointestinal primaria suele ser anecdotica, ocurriendo con frecuencia de forma secundaria al tratamiento. Diagnostico diferencial. El diagnostico diferencial dependera de las manifestaciones extradigestivas de la enfermedad en cuestion, pudiendo convertirse en un proceso complejo en el caso de debut como afectacion digestiva. Dentro de los distintos cuadros clinicos, el dolor abdominal es el que representa el mayor reto diagnostico, por sus posibles implicaciones diagnosticas y terapeuticas. Evaluacion del paciente. Es fundamental la valoracion global del paciente, con una historia clinica detallada y dirigida a detectar semiologia subclinica sobre otros organos y aparatos, fundamentalmente el osteoarticular y la piel. Es importante tener en cuenta que la afectacion digestiva puede ser la mas sintomatica, pero que la implicacion de otros organos suele tener mayor repercusion sobre el pronostico. Tratamiento. Se puede dividir en dos grupos, aquellos farmacos dirigidos al alivio sintomatico, sobre todo antisecretores y procineticos; y aquellos otros modificadores de la evolucion de la enfermedad, que son los inmunosupresores, con los corticoides a la cabeza. Si bien los primeros deben usarse de forma generosa, la utilizacion de los inmunosupresores dependera del tipo de afectacion y del pronostico en funcion del organo implicado.

Resume Objectifs. – La possibilite de prendre en charge en assistance medicale a la procreation (AMP) des couples seropositifs, vis-a-vis du VIH-1 en particulier, a reactive la reflexion sur l'aspect securitaire de la conservation de tels gametes et des embryons issus de ceux-ci dans des cuves d'azote liquide. Ainsi nous avons voulu tester celui-ci vis-a-vis de la cryoconservation. Patients et methodes. – Nous avons evalue la securite de trois types de paillettes, polyvinyl chloride (PVC), polyethylene terephtalate glycol (PETG), et resine ionomere (RI) dites de « haute securite », contenant du VIH-1 dans les conditions de cryoconservation. La recherche de la contamination par le VIH a ete realisee par RT-PCR puis nested PCR. Resultats. – Cette etude, menee dans les conditions de cryoconservation, montre que l'extremite libre obturee des paillettes PVC et PETG n'est pas securitaire. Le systeme de fermeture par ultrasons semblerait etre le maillon faible pour l'etancheite parfaite des paillettes. A l'inverse, les paillettes RI pour leurs deux extremites sont securitaires vis-a-vis du VIH dans le cadre de leur utilisation en AMP. Conclusion. – Le systeme de fermeture par ultrasons pourrait constituer un risque concernant l'impermeabilite des paillettes. Les paillettes RI, thermosoudees apparaissent securitaires vis-a-vis du VIH dans les conditions de cryoconservation.

Aim. – To develop and to validate a simple system of evaluation of the syndrome of overtraining. Synthesis of facts. – The French questionnaire of the “Societe Francaise de Medecine du Sport” for detection of early signs of overtraining has undergone intensive methodological investigations, demonstrating its reproducibility and sensitivity. A multicentric study has been performed. It is easy to employ and the risk of misunderstanding is low. It can be used in follow-up studies and is correlated with biological markers. Actually its score is increased by both training and overtraining, so that the cut-off value between physiology and pathology remains elusive. However, values higher than 20–25 may reflect overreaching or overtraining or a situation at risk for them. Differential diagnosis with depression, eating disorders, of lack of sincerity due to external influences are not likely to induce misinterpretations if the clinician is aware of these possibilities. Conclusion. – This questionnaire remains a subject of research but appears to be suitable for clinical practice.

La infeccion por el VIH se ve frecuentemente complicada por la afectacion del sistema nervioso, habitualmente en fases tardias de la misma. La afectacion neurologica en la infeccion por el VIH se puede clasificar en complicaciones neurologicas en el sindrome retrovirico agudo, sindromes meningeos, afectacion encefalica, afectacion medular y del sistema nervioso periferico, toxicidad farmacologica y por drogas, y sindrome de reconstitucion inmune.

El sistema nervioso central tiene caracteristicas farmacocineticas que limitan el acceso de los farmacos de la circulacion sistemica. Para que un antibiotico sea eficaz, su concentracion en el LCR debe exceder en 10 o mas veces el valor de la concentracion minima bactericida in vitro, frente al microorganismo responsable de la infeccion. Los farmacos mas empleados habitualmente en este tipo de infecciones son betalactamicos, cefalosporinas y carbapenemas, vancomicina, aciclovir y anfotericina B. La administracion concomitante de corticoides ha demostrado en determinados tipos de meningitis una disminucion de la mortalidad en relacion con un control mas eficaz del proceso inflamatorio.

As part of the development of the European Space Agency Rosetta space mission to investigate a cometary nucleus, the selection of columns dedicated to the gas chromatographic subsystem of the Cometary Sampling and Composition (COSAC) experiment was achieved. Once the space probe launched, these columns will be exposed to the harsh environmental constraints of space missions: vibrations, radiation (by photons or energetic particles), space vacuum, and large temperature range. In order to test the resistance of the flight columns and their stationary phases, the columns were exposed to these rough conditions reproduced in the laboratory. The comparison of the analytical performances of the columns, evaluated prior and after the environmental tests, demonstrated that all the columns withstand space constraints, and that their analytical properties were preserved. Therefore, all the selected capillary columns, even having porous layer or chiral stationary phases, were qualified for space exploration.

Objective: Growth hormone (GH) has been shown to stimulate lipolysis and enhance lipid oxidation. We investigated whether GH could improve mitochondrial oxidative capacity. Method: Fourteen male Wistar rats received 14-day treatment with biosynthetic human GH (10 IU/kg/24 h) or placebo. Mitochondria were isolated from the total muscle of one hind limb of the rat. Mitochondrial oxygen consumption was measured in vitro using a Clark-type electrode with three substrates: palmitoyl-L-carnitine, pyruvate and succinate (+ rotenone). Results: Muscle mitochondrial yield was not significantly different in the GH-treated group from that in controls. Neither the basal nor ADP-stimulated respiratory state reached a significant difference between the 2 groups with palmitoyl-L-carnitine, pyruvate, and succinate. Conclusion: GH treatment did not improve the oxidative capacity of skeletal muscle mitochondria.

SummaryTo determine whether viral load rebounds during HAART impact on CD4+ T cell recovery and immune reconstitution, we studied a prospective cohort of 355 antiretroviral naive patients enrolled to be randomized in a trial of three strategies of induction/maintenance HAART. The extent of immune reconstitution in blood through 72 weeks of antiretroviral treatment was evaluated. Lymphocyte subset markers (CD4, CD8, CD45RA, CD62L, CD16, CD19), activation markers (HLA-DR, CD38, CD25) were performed by cytometry analysis. Our results showed that plasma HIV-1 RNA was suppressed to below 500 copies per ml through week 72 in 240 patients (group 1) while the remaining 115 patients experienced at least one viral rebound (group 2). At baseline, CD4 cell count was higher and HIV-1 RNA was lower in group 1 than in group 2. Over 72 weeks, mean increase in CD4+ T cell count was 0·32 cell/mm3/day in group 1 and only 0·14 cell/mm3/day in group 2 (P

The aim of this preliminary experimental study was to test the stability of cryopreservation straws to human immunodeficiency virus-1 (HIV-1). Three kinds of straws were tested: four polyvinyl chloride (PVC), four polyethylene terephthalate glycol (PETG) and 20 high-security ionomeric resin (IR). The PVC and PETG straws were sealed ultrasonically, and the IR straw by thermosoldering. Each sealed straw was cut in half to produce two demi-straws and then filled with 100 microl of HIV-1-containing supernatant (reverse transcriptase activity: 15 000 c.p.m./50 microl). The unsealed cotton end of PVC and PETG straws and the two halves of the IR straws (cotton and plastic plug ends) were tested. Each demi-straw was two- thirds submerged in RPMI medium at 37 degrees C, and RPMI samples were withdrawn on days 3, 7 and 11. Viral RNA was extracted from the medium and then amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) followed by nested PCR using primers specific to HIV-1 protease. On day 7, no HIV-1 RNA was detected in any of the different samples of medium that had surrounded the unsealed PVC and PETG straws with cotton ends, but three IR specimens were positive. On day 11, PVC and PETG remained negative but HIV-1 RNA was detected in RPMI samples for two more IR demi-straws (n = 5). In conclusion, under these experimental conditions (at 37 degrees C), the unsealed cotton end PVC, PETG and thermosoldered cotton end IR demi-straws appeared to be safe for HIV-1, while IR straws, sealed or unsealed with a plastic plug and with unsealed cotton ends, leaked.

We investigated metabolic and hormonal responses during repeated bouts of brief and intense exercise (a force-velocity test; Fv test) and examined the effect of glucose ingestion on these responses and on exercise performance. The test was performed twice by seven subjects [27 (2) years] according to a double-blind randomized crossover protocol. During the experimental trial (GLU), the subjects ingested 500 ml of glucose polymer solution containing 25 g glucose 15 min before starting the exercise. During the control trial (CON), the subjects received an equal volume of sweet placebo (aspartame). Exercise performance was assessed by calculating peak anaerobic power ( W˙ an,peak). Venous plasma lactate concentration increased significantly during the Fv test (P

At the end of 2011, UNAIDS estimated that 34 million (31.4 to 35.9) individuals were infected by HIV worldwide and that 2.5 million were newly infected during the year. Since 2001, we have observed an increased number of HIV-infected patients in the world, due to an expanded access to antiretroviral drugs. More than 23,5 million (22.1 to 24.8) HIV-infected patients live in Sub-Saharan Africa. The number of HIV-infected patients in France is estimated at 152,000. Two types of HIV cause AIDS: HIV-1 and HIV-2 that are subdivided in groups (M, N, O, P for HIV-1; A to H for HIV-2), subtypes (A-D, F-H, J-K for HIV-1 group M), sub-subtype (A1-A4 for subtype A, F1 and F2 for subtype F in HIV-1 group M), circulating recombinant forms (CRF), and unique recombinant forms in a small number of patients. Virological diagnostic and monitoring techniques have been constantly upgraded since HIV-1 was isolated in 1983 and the first serological tests became available in 1985. This is especially true for HIV-1, the most prevalent worldwide.

Varon de 65 anos que consulta por fiebre y alteracion del nivel de conciencia. Como antecedentes personales presenta habito enolico y tabaquico importante, con criterios clinicos de bronquitis cronica y varios ingresos por reagudizacion de la misma, cirrosis hepatica de etiologia etilica (diagnosticada dos anos antes mediante biopsia hepatica) sin episodios previos de descompensacion, y diverticulosis colonica diagnosticada hace tres anos mediante enema opaca ante estrenimiento de reciente aparicion. El paciente presentaba sindrome febril (38-39°C) de 24 horas de evolucion acompanado de alteracion del nivel de conciencia sin otra sintomatologia adicional. En una primera valoracion en el area de urgencias se objetivo temperatura de 39°C, frecuencia cardiaca 110 lpm, presion arterial 90/60 mmHg. Tinte icterico, obnubilacion, aleteo. La auscultacion cardiopulmonar no mostro datos de interes. La exploracion del abdomen revelo dolor a la palpacion de forma difusa, con dudosa contractura muscular en hemiabdomen inferior, ascitis no a tension, borde hepatico a 3-4 cm de reborde costal y ruidos intestinales disminuidos. En los miembros inferiores destacaba la presencia de edemas pretibiales con fovea a la presion. Tacto rectal: heces en ampolla rectal sin datos de sangrado digestivo. Los examenes complementarios iniciales mostraron los siguientes datos: Hemograma: hemoglobina 10 g/dl con volumen corpuscular medio (VCM) 105; leucocitos: 12.430 cel/mm , con desviacion a la izquierda; plaquetas 90.000 cels/mm . Bioquimica serica: GPT 44 UI/l; GOT 52 UI/l; bilirrubina total 4,3 mg/dl; bilirrubina directa 3,5 mg/dl; sodio 128 mEq/l; potasio 4 mEq/l; proteinas totales 5,3 g/l; LDH 210 UI/l; resto de determinaciones sin interes. Estudio de coagulacion: actividad de protrombina 55%, tiempo de cefalina 42 seg, fibrinogeno 650 mg/dl. Sistematico de orina normal. En la radiografia de torax se evidencian signos de broncopatia cronica. La radiografia simple de abdomen muestra dilatacion de asas intestinales, y la ecografia abdominal hepatoesplenomegalia con hipertension portal y ascitis moderada. Se realizo paracentesis diagnostica. El analisis del liquido revelo la presencia de 800 polimorfonucleares (PMN)/mm ; proteinas 6,4 g/dl; glucosa 40 mg/dl, LDH 450 UI/l. El liquido ascitico se envio a microbiologia y anatomia patologica.