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A growing literature shows an improvement of chronic hepatitis C virus (HCV)-related depression after successful treatment with direct-acting antivirals. However, depression after HCV cure remains insufficiently documented in people living with HIV (PLWH) and HCV, a population with specific mental health challenges. This study aimed to (i) document the prevalence of moderate-to-severe depression (PHQ-9 score ≥10) across different age classes in HCV-cured PLWH; (ii) identify associated socio-behavioral correlates.Descriptive analyses were performed on data collected during a cross-sectional survey (February 2018 - May 2019) nested in a prospective, multicenter cohort of individuals living with HIV and HCV (ANRS CO13 HEPAVIH). Socio-behavioral correlates of moderate-to-severe depression were identified using logistic regression.Among the 398 HCV-cured individuals in the study sample (median age [IQR]: 56 [53-59] years; 73.1% men), 23.9% presented with moderate-to-severe depression (PHQ-9 score ≥10). Depressive symptom prevalence rates were as follows: anhedonia: 52.3%; feeling 'down' or feelings of hopelessness: 48.3%; sleeping problems: 65.7%; lack of energy: 70.3%; eating disorders: 51.2%; lack of self-esteem: 34.3%; difficulty concentrating: 34.9%; sluggishness (in movement and voice) or restlessness: 24.6%; suicidal ideation: 17.1%. No significant difference was detected across age classes. Female sex, unhealthy alcohol use, sedentary lifestyle, and unhealthy eating behaviors were associated with increased odds of moderate-to-severe depression.Depressive symptoms were common in this sample of HCV-cured PLWH. Unlike findings for the French general population, the prevalence of depression did not decrease with age class. Mental health remains a key issue for HIV-HCV-coinfected individuals, even after HCV cure, especially in women and in individuals with unhealthy behaviors.Despite potential improvements in mental health after successful treatment with direct-acting antivirals, many people living with HIV (PLWH) and hepatitis C virus (HCV) - even in older age classes - still face depressive symptoms after HCV cure. In this population, women and people reporting unhealthy alcohol use, sedentary lifestyle, or unhealthy eating behaviors are more prone to report depressive symptoms after HCV cure. Mental health and lifestyle-related issues should be integrated in a global care model for PLWH living with or having a history of hepatitis C.

International audience; No abstract available

Impaired type I interferons (IFNs) production or signaling have been associated with severe COVID-19, further promoting the evaluation of recombinant type I IFNs as therapeutics against SARS-CoV-2 infection. In the Syrian hamster model, we show that intranasal administration of IFN-α starting one day pre-infection or one day post-infection limited weight loss and decreased viral lung titers. By contrast, intranasal administration of IFN-α starting at the onset of symptoms three days post-infection had no impact on the clinical course of SARS-CoV-2 infection. Our results provide evidence that early type I IFN treatment is beneficial, while late interventions are ineffective, although not associated with signs of enhanced disease., Author summary Type I interferons are major antiviral effectors produced by the host in response to viral infections. Importantly, delayed or impaired type I IFN signalling response has been shown to correlate with severe COVID-19. These observations provided further impetus to test the administration of exogenous type I IFN as a treatment against SARS-CoV-2 infection in patients. However, studies using MERS-CoV or SARS-CoV infected mice demonstrated that type I interferon treatment was beneficial when administered early, but was ineffective and even caused deleterious immunopathology when administered at later stages of infection. It is therefore crucial to understand how the timing of the type I IFN treatments modulates their efficacy and safety against SARS-CoV-2. In this preclinical study using the SARS-CoV-2-infected Syrian hamster model, we showed that intranasal type I IFN treatment was beneficial only when administered before the onset of symptoms. Importantly, late treatment was ineffective but was not associated with deleterious effects. This study provides important information to interpret clinical trials showing no to modest effects of type I IFNs in COVID-19 patients.

Background We investigated the association between socioclinical, inflammatory, and metabolic markers and weight gain in people with human immunodeficiency virus (HIV) on combination antiretroviral therapy (cART). Methods Individuals from the COPANA cohort of normal weight (body mass index [BMI], 18.5–24.9 [ calculated as weight in kilograms divided by height in meters squared) at cART initiation who achieved virological suppression (viral load, Results After 36 months of cART, 32 of 158 people with HIV (20%) became overweight or obese (21% female; 65% born in France and 23% born in sub-Saharan Africa; median BMI at cART initiation, 22 [interquartile range, 21–23]). After adjustment, higher BMI, originating from sub-Saharan Africa, living in a couple, and higher soluble tumor necrosis factor receptor 2 and lower adiponectin concentrations at cART initiation were associated with becoming overweight or obese. Conclusion Weight gain on cART is multifactorial. Special attention should be given to migrants from sub-Saharan Africa. Monocyte activation and adipocyte dysfunction at cART initiation affect weight regulation.

International audience; BackgroundOral vaccination with Mycobacterium bovis Bacille of Calmette and Guerin (BCG) has provided protection against M. bovis to badgers both experimentally and in the field. There is also evidence suggesting that the persistence of live BCG within the host is important for maintaining protection against TB. Here we investigated the capacity of badger inductive mucosal sites to absorb and maintain live BCG. The targeted mucosae were the oropharyngeal cavity (tonsils and sublingual area) and the small intestine (ileum).ResultsWe showed that significant quantities of live BCG persisted within badger in tissues of vaccinated badgers for at least 8 weeks following oral vaccination with only very mild pathological features and induced the circulation of IFNγ-producing mononuclear cells. The uptake of live BCG by tonsils and drainage to retro-pharyngeal lymph nodes was repeatable in the animal group vaccinated by oropharyngeal instillation whereas those vaccinated directly in the ileum displayed a lower frequency of BCG detection in the enteric wall or draining mesenteric lymph nodes. No faecal excretion of live BCG was observed, including when BCG was delivered directly in the ileum.ConclusionsThe apparent local loss of BCG viability suggests an unfavorable gastro-enteric environment for BCG in badgers, which should be taken in consideration when developing an oral vaccine for use in this species.

Summary Background In 2013, the interim analysis of the Protocol for Herceptin as Adjuvant therapy with Reduced Exposure (PHARE) trial could not show that 6 months of adjuvant trastuzumab was non-inferior to 12 months. Here, we report the planned final analysis based on the prespecified number of occurring events. Methods PHARE is an open-label, phase 3, non-inferiority randomised trial of patients with HER2-positive early breast cancer comparing 6 months versus 12 months of trastuzumab treatment concomitant with or following standard neoadjuvant or adjuvant chemotherapy. The study was undertaken in 156 centres in France. Eligible patients were women aged 18 years or older with non-metastatic, operable, histologically confirmed adenocarcinoma of the breast and either positive axillary nodes or negative axillary nodes but a tumour of at least 10 mm. Participants must have received at least four cycles of a chemotherapy for this breast cancer and have started receiving adjuvant trastuzumab-treatment. Eligible patients were randomly assigned to either 6 months or 12 months of trastuzumab therapy duration between the third and sixth months of adjuvant trastuzumab. The randomisation was stratified by concomitant or sequential treatment with chemotherapy, oestrogen receptor status, and centre. The primary objective was non-inferiority in the intention-to-treat population in the 6-month group in terms of disease-free survival with a prespecified hazard margin of 1·15. This trial is registered with ClinicalTrials.gov, number NCT00381901. Findings 3384 patients were enrolled and randomly assigned to either 12 months (n=1691) or 6 months (n=1693) of adjuvant trastuzumab. One patient in the 12-month group and three patients in the 6-month group were excluded, so 1690 patients in each group were included in the intention-to-treat analysis. At a median follow-up of 7·5 years (IQR 5·3–8·8), 704 events relevant to disease-free survival were observed (345 [20·4%] in the 12-month group and 359 [21·2%] in the 6-month group). The adjusted hazard ratio for disease-free survival in the 12-month group versus the 6-month group was 1·08 (95% CI 0·93–1·25; p=0·39). The non-inferiority margin was included in the 95% CI. No differences in effects pertaining to trastuzumab duration were found in any of the subgroups. After the completion of trastuzumab treatment, rare adverse events occurred over time and the safety analysis remained similar to the previously published report. In particular, we found no change in the cardiac safety comparison, and only three additional cases in which the left ventricular ejection fraction decreased to less than 50% have been reported in the 12-month group. Interpretation The PHARE study did not show the non-inferiority of 6 months versus 12 months of adjuvant trastuzumab. Hence, adjuvant trastuzumab standard duration should remain 12 months. Funding The French National Cancer Institute.

Preventing foodborne pathogen contamination of raw fruit and vegetables in the field is critically important for public health. Specifically, it involves preventing faecal deposit by wildlife or domestic animals in fields of crops and kitchen gardens. The present study aims to identify the drivers of fox, dog and cat faecal deposits in kitchen gardens in order to mitigate the risk of contamination of raw produce with parasites shed in carnivore faeces. The focus was on Echinococcus multilocularis, ranked highest in the importance of foodborne parasites in Europe, but attention was also paid to other parasites of major concern - Toxoplasma gondii and Toxocara spp. During the winters of 2014 to 2016, faecal samples were collected from 192 kitchen gardens located in north-eastern France. From these samples, 77% contained scat of carnivores. Molecular analyses revealed that 59% of the 1016 faeces collected were from cats, 31% from foxes, and 10% from dogs. The ease of accessibility to kitchen gardens, the presence of food in the vicinity, and the composition of the surrounding vegetation were used to explain the distribution of fox and cat faeces. Generalized Linear Mixed Effects modelling showed that: i) fencing was not efficient in reducing cat faecal deposits, but drastically decreases those of foxes; ii) the abundance of Microtus sp. indicates a reason for the presence of both fox and cat faecal deposits, iii) the abundance of Arvicola terrestris, the proximity of fruit trees or farms and the predominance of forest and grassland around the village are all drivers of fox faecal deposits. These results point to the importance of fencing around kitchen gardens located in E. multilocularis endemic areas, particularly those surrounded by forest and grassland or close to fruit trees or farms., Highlights • 192 kitchen gardens sampled 6 times over 2 winters, 1016 carnivore faeces collected. • Fencing, food and vegetation cover tested as explanatory factors for faeces location. • Numerous cat faeces, even in enclosed gardens. Microtus sp. drives their deposit. • Garden accessibility, food and vegetation cover drive the faecal deposits of foxes. • Fencing off kitchen gardens should be encouraged in E. multilocularis endemic areas.

International audience; TMT (2,5-dihydro-2,4,5-trimethylthiazoline) is known as a component of fox feces inducing fear in rodents. However, no recent chemical analyses of fox feces are available, and few studies make direct comparisons between TMT and fox feces. Fox feces from 3 individuals were used to prepare 24 samples to be analyzed for the presence of TMT using gas chromatography-mass spectrometry (GC-MS). When TMT was added in low amounts (50–2000 nmol/g), TMT was detected in 10 out of 11 samples. When no TMT was added, TMT was detected in only 1 out of 13 samples. In a second experiment, we tested the behavioral response of male Brown Norway (BN) and Wistar rats to either fox feces, a low amount of TMT (0.6 nmol) or 1-hexanol. TMT induced freezing in the rats, but fox feces induced significantly more freezing episodes and longer total duration of freezing in both rat strains. In experiment 3, male BN rats were exposed over several days to fox feces, rat feces, 1-hexanol, cadaverine, 2-phenylethylamine, and TMT, one odor at a time. Fox feces induced significantly more freezing episodes of a longer total duration than any of the other odors, with rat feces and 1-hexanol giving rise to the lowest amount of freezing. This finding, together with our inability to verify the presence of TMT in fox feces, indicates that the concentration of TMT in our fox feces samples was below 50 nmol/g. It may also be that other compounds in fox feces play a role in its fear-inducing properties.

Recent studies have independently implicated the chemokine CXCL12 and its receptors, CXCR4 and CXCR7, in the pathophysiology of Kaposi sarcoma (KS).We investigated whether the CXCL12/CXCR4-CXCR7 protein trio could constitute KS biomarkers.Endothelial and spindle cells positive for CXCL12/CXCR4-CXCR7, human herpesvirus-8 latency-associated nuclear antigen (LANA), Ki67 antigen (proliferation) and vascular endothelial growth factor (VEGF) were quantitated in skin lesions from patients with AIDS-associated KS, patients with classic KS and patients with angiomas, using immunohistochemistry and quantitative image analysis (16, 21 and 20 skin lesions, respectively). Plasma CXCL12 concentrations were measured by enzyme-linked immunosorbent assay from 20 patients with AIDS-KS, 12 HIV-infected patients without KS and 13 healthy donors' samples.Cells positive for CXCL12, CXCR4, CXCR7, LANA, Ki67 and VEGF were significantly enriched in patients with AIDS-associated KS and classic KS vs. angiomas (P0·001), and in nodular vs. macular/papular KS lesions (P0·05). CXCL12, CXCR4 and CXCR7 detection correlated with LANA, Ki67 and VEGF detection (r0·4; P0·05). However, plasma CXCL12 concentrations did not differ between patients with AIDS-associated KS, HIV-infected patients without KS, and healthy donors.The CXCL12/CXCR4-CXCR7 trio is upregulated in KS and correlates with KS pathophysiological markers and the severity of skin lesions. Histological assessment of the CXCL12 axis could serve as a valuable biomarker for KS diagnosis and progression.

The Echinococcus granulosus tapeworm is responsible for cystic echinococcosis (CE), a zoonotic disease with worldwide distribution. The life cycle of the parasite is mainly domestic and takes place between dogs and livestock species. A slaughterhouse survey was conducted in 2012 in the Republic of Moldova in order to estimate the prevalence of CE. A total of 1525 cattle, 5580 sheep and 12,700 pigs were surveyed. No CE infection was observed in pigs, while prevalence was estimated at 59.3% in cattle and 61.9% in sheep. Infection was significantly higher in animals raised in private households than in those from collective farms. The frequency of infection increased with age in both species. In cattle and in sheep, infection of both the liver and lungs was the most common, while infection in the lungs only was much less frequent. Farm type appears to be an important factor in CE infection in Moldova, due to the extensive farming and the home-slaughtering undertaken in the majority private sector, despite a high prevalence of CE also recorded in the public sector. The low fertility of cysts in cattle (1.1%) compared to sheep (47.6%) confirmed the maintenance of E. granulosussensu stricto in a dog–sheep life cycle which excludes cattle. Further studies are needed to obtain a complete overview of the parasite's epidemiology in its intermediate and definitive hosts, in order to implement control and preventive measures, with specific attention given to farms in the private sector.

Human cystic echinococcosis (hydatid disease) caused by the Echinococcus granulosus tapeworm continues to be a substantial cause of morbidity and mortality in many parts of the world. France is still considered as endemic area, but the current infestation by E. granulosus of intermediate hosts in France remains currently unknown due to the absence of official data reporting for the last 20 years. A 1-year prevalence survey was conducted in the 24 slaughterhouses of ten departments of the South of France. We demonstrate that the E. granulosus parasite is still currently present at low prevalence at slaughterhouses in the study area (4 cases for 100,000 sheep and 3 cases for 100,000 cattle). In addition, we assess the presence of genotype G1 in infected animals and identify for the first time in France genotypes G2 and G3 of E. granulosus sensu stricto.

Introduction Le consentement eclaire est au cœur de la demarche de soin moderne. Il est obligatoire sous forme ecrite pour toute inclusion dans un essai clinique, apres information du patient. Cependant peu de donnees sont disponibles sur les criteres de decision qui menent les patients a participer a un essai clinique. Afin d’explorer le processus de consentement, nous avons realise une etude qualitative descriptive retrospective aupres de patients inclus dans un essai clinique en oncohematologie. Patients et methodes Un questionnaire a ete adresse aux patients ayant accepte d’etre inclus dans un essai clinique. Etaient inclus les patients majeurs ayant ete inclus dans un essai clinique entre 3 mois et 2 ans avant le debut de notre etude. Etaient exclus les incapables majeurs et les patients dont l’esperance de vie etait estimee inferieure a 3 mois. Des entretiens semi-directifs etaient proposes dans un second temps aux patients ayant renvoye le questionnaire. Resultats Soixante-deux patients repondaient aux criteres d’inclusion, 31 ont retourne le questionnaire (15 hommes et 16 femmes, âge moyen 54 ans), dont 10 ont participe a un entretien. Les patients etaient atteints de lymphomes, de leucemies aigues ou de leucemies chroniques. Le modele de relation medecin/patient allegue par les patients etait paternaliste pour 23 %, autonomiste pour 19 % et le modele de decision partagee pour 52 %. Tous les patients sauf un estimaient avoir beneficie de consultations suffisamment longues pour apprehender l’essai clinique (temps necessaire estime en moyenne a 42 minutes). Deux tiers des patients etaient accompagnes a la consultation, dont 76 % par leur conjoint, 12 % par leurs parents, et 12 % par un ami. La premiere source d’information citee etait la consultation avec le specialiste qui propose l’essai (94 % de patients), suivie par le medecin traitant (39 %), internet (26 %) et les proches exercant une profession de sante (16 %). La fiche d’information remise etait jugee adaptee pour 97 % des patients et complete pour 85 % des patients. Seuls 14 % des patients estimaient avoir assez peu compris l’essai. Les avis recueillis en vue de la decision de consentement etaient en premier lieu celui du specialiste (45 %), puis de la famille (37 %) et du medecin traitant (26 %). Le delai de reflexion etait de 1 a 15 jours. Les motivations alleguees etaient la confiance dans le medecin (74 %), l’altruisme – faire progresser la connaissance pour en faire beneficier les patients des annees a venir (58 %), recevoir un traitement nouveau (32 %), etre mieux soigne (29 %), montrer au medecin qu’on lui fait confiance (3 %). Discussion Le role du specialiste proposant l’essai est central : il est souvent a la fois celui qui a etabli le diagnostic, celui qui va mettre en œuvre le traitement, celui qui informe, et celui dont l’avis compte le plus. Le medecin traitant joue egalement un role important, beneficiant d’une relation tissee de plus longue date. Le conjoint tient enfin un role central, notamment dans la reception de l’information lorsqu’il assiste a la consultation. La notion d’equivalence (« equipoise » en anglais) des deux bras de l’essai (le plus souvent traitement de reference contre traitement de reference + nouvelle molecule) est difficile a apprehender par les patients qui acceptent l’inclusion. La plupart sont influences par trois mythes irrationnels : l’aura de la recherche, la reconnaissance envers le medecin qui a diagnostique leur pathologie, l’urgence ressentie du traitement. La recherche de benefice personnel apparait dans les entretiens comme le principal determinant de la decision, dans un mecanisme de double pari : celui de ne pas avoir d’effet secondaire lie a la nouvelle molecule et celui que cette molecule conferera un benefice de survie. Ainsi les patients sont-ils « decus » lorsqu’ils sont randomises dans le bras placebo. Sans doute une meilleure information du grand public pourrait-elle ameliorer la comprehension de la randomisation et de l’equivalence a priori des deux bras d’un essai clinique. Conclusion Le processus de consentement eclaire en recherche clinique est imparfait, notamment car il suit souvent de peu l’annonce diagnostique d’une maladie grave qui destabilise le patient. Le specialiste joue un role majeur dans l’information du patient et sa decision d’etre inclus dans l’essai clinique. Ce dernier s’appuie egalement sur son medecin traitant et sur son conjoint pour etablir sa decision.

Laser-induced breakdown spectroscopy (LIBS) measurements were performed on a steel sample to investigate the feasibility for obtaining fast information on cleanness. A calibration approach was considered to enable the quantification of the elemental composition of nonmetallic inclusions. The same data was also used to estimate the size of the inclusions. Preliminary results for the determination of inclusion populations by LIBS were very encouraging and compared very well with scanning electron microscopy energy dispersive X-ray (SEM-EDX) results, which is the conventional method used for steel cleanness assessment. Due to the speed of analysis and the systematic recording of signal on the scanned area, LIBS enables the analysis of larger areas of sample and in significantly shorter time than with automated SEM-EDX. This paper summarizes the results obtained up until now for the fast analysis of inclusions in steel by LIBS.

We study here the phase behavior of colloidal dispersions, which are constituted of almost monodisperse γ-Fe2O3 magnetic nanoparticles dispersed in water at pH 7. Those electrostatically stabilized dispersions present, if the interparticle repulsion is decreased, gas−liquid transitions, a phase behavior scarcely reported for such charged nanoparticles. Small-angle neutron scattering experiments prove that there is no chaining of the particles and that, from the point of view of interparticle interactions, increasing ionic strength (through addition of NaCl) is equivalent to decreasing temperature. A phenomenological expression of the osmotic pressure π is determined and shown to be in agreement with direct π measurements. The scattering experiments associated to optical microscopy determinations of phase diagrams lead to a general π−Φ diagram. Gas−solid transitions may exist even if their observation is disturbed by metastability phenomena. The results are in qualitative agreement with theoretical predict...

We have measured the Coulomb dissociation of ${}^{8}\mathrm{B}$ into ${}^{7}\mathrm{Be}$ and a proton at 254 MeV/nucleon using a large-acceptance focusing spectrometer. The astrophysical ${S}_{17}$-factor for the ${}^{7}\mathrm{Be}(p,\ensuremath{\gamma}{)}^{8}\mathrm{B}$ reaction at ${E}_{\mathrm{c}.\mathrm{m}.}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}0.25--2.78\mathrm{MeV}$ is deduced yielding ${S}_{17}(0)\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}20.6\ifmmode\pm\else\textpm\fi{}1.2$ (expt) $\ifmmode\pm\else\textpm\fi{}1.0(\mathrm{theor})\phantom{\rule{0ex}{0ex}}\mathrm{eV}\mathrm{b}$. This result agrees with the presently adopted zero-energy ${S}_{17}$-factor obtained in direct-reaction measurements and with the results of other Coulomb-dissociation studies performed at 46.5 and 51.2 MeV/nucleon.

Two new isomeric states in the self-conjugate nucleus 66As have been observed at the final focus of the LISE3 spectrometer at GANIL. The nucleus has been produced in a fragmentation reaction of 78Kr at 73A MeV. The 66m1,m2As isomeric levels are placed at excitation energies of E ∗m1 =3023.9 keV and E ∗m2 =1356.7 keV. Half-lives of T1/2m1=17.5(15) μs and T1/2m2=1.9(5) μs have been measured for the isomers and a decay scheme has been established.

In an experiment at the LISE3 facility of GANIL, we used the projectile fragmentation of a 36 Ar primary beam at 95 MeV/nucleon to produce the isotope 24 Si. The beta decay half-life of 24 Si has been determined to be T 1/2 = (140 ± 8) ms, in agreement with earlier measurements. In addition to the decay of the isobaric analog state, several proton peaks are observed for the first time allowing to identify most of the Gamow-Teller transitions to unbound states and to present a partial decay scheme for 24 Si. These results are compared with shell-model predictions.

International audience; : Alveolar echinococcosis, caused by the cestode Echinococcus multilocularis, is the most serious parasitic disease for humans in Europe, with a sylvatic life cycle generally between small rodents and red foxes. General expansion of the range of E. multilocularis has been observed across Europe over the last 15years. In France, a westward spread of the known endemic areas of the parasite was described recently. For genotyping, the microsatellite EmsB was used to trace expansion in five French areas. A total of 22 EmsB profiles were identified, with five similar to those previously described in other parts of Europe. An imbalance of genetic diversity was observed between the five areas which also revealed their interconnection with the presence of common profiles, notably the two main profiles both present in all regions except one in the North. These two findings are similar to those described at the European level, highlighting transmission of the parasite by a mainland-island system. A spatio-temporal scenario of the expansion of E. multilocularis can be proposed with spread from the French historical focus in eastern France to the Lorraine, the Champagne-Ardenne and finally the North, while simultaneously another expansion has occurred from the historical focus into the West. The colonization by the parasite into the West and North areas from the historical focus was probably due to the migration of foxes several decades ago. Recent detection of the parasite in new endemic "départements" may be due to more active research rather than a recent spread of the parasite. Regarding the numerous data obtained by the different EmsB analyses, principally across Europe, centralization of all the profiles described in a public databank appears necessary in order to obtain a precise understanding of transmission of the parasite from one country to another.

23Si isotopes have been produced as projectile fragments of a 36Ar primary beam at 95 MeV/nucleon at the LISE3 spectrometer of GANIL. After implantation in a detector telescope, β-delayed one-proton and β-delayed two-proton emission has been observed. The main one-proton peaks are at (1.32±0.04)MeV, (2.40±0.04)MeV, and (2.83±0.06)MeV. The total decay energy for the β2p decay is (6.18±0.10)MeV for the decay to the ground state and (5.86±0.10)MeV for the decay to the first excited state in the daughter nucleus. However, energetically possible decays via βpα and β3p emission have not been identified. The spectra allowed us to determine the excitation energy of the isobaric analogue state in 23Al. This enabled us to calculate the coefficients of the T = 5/2 isobaric multiplet mass equation for A = 23. The mass excess of the 23Si ground state was deduced. This value is compared to different theoretical predictions. Additionally, we determined the branching ratios for the different decay branches. A half-life measurement yielded T1/2 = (40.7±0.4)ms.

In an experiment at the LISE3 facility of GANIL, we produced the proton-rich isotope 22Al by the fragmentation of a 36Ar primary beam at 95 MeV/nucleon. After implantation in a detector telescope, the decay of 22Al via β-delayed proton emission, β-delayed two-proton emission as well as, for the first time, via β-delayed α emission has been studied. An α peak has been observed at (3.27 ± 0.04) MeV with a branching ratio of (0.31 ± 0.09) %. The comparison of the different decay channels to those of the mirror nucleus 22F and to shell-model calculations favor a 3+ state as being the ground state of 22Al. A half life of T1/2 = (59 ± 3) ms has been measured.

We present the experimental method conceived to measure high energy neutrons in the range (200 ≤ E ≤ 1600 MeV). The neutrons produce recoil protons in a liquid hydrogen converter. Momentum evaluation and identification of these protons are made by using a magnetic spectrometer equipped with plastic scintillators and three double-plane ( X - Y ) wire chambers. The response functions of the apparatus are determined using quasi-monoenergetic neutron beams produced by the break-up of deuterons or 3 He on a Be target. The performance of the apparatus is illustrated in the form of a preliminary neutron spectrum.

We present an experimental method based on a time-of-flight technique between the tagged incident particles and a thick liquid NE213 scintillator to measure neutron energy spectra from 3 to 400 MeV at the Saturne synchrotron of Saclay. Efficiency measurements are made using a pulsed neutron source from the Tandem Van de Graaff of Bruyeres-le-Châtel at low energies and a quasi-monoenergetic neutron beam at Saturne up to 50 MeV.

A primary beam of ${}^{58}$Ni at 600 MeV/nucleon from the SIS synchrotron at GSI was used to produce proton-rich isotopes in the titanium-to-nickel region by projectile fragmention on a beryllium target. The fragments were separated by a projectile-fragement separator and unambiguously identified. We report here the first observation of the ${T}_{z}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}\ensuremath{-}7/2$ nuclei ${}^{45}$Fe and ${}^{49}$Ni, the most proton-rich nuclei ever synthesized with an excess of seven protons. In addition, the new isotope ${}^{42}$Cr $({T}_{z}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}\ensuremath{-}3)$ was identified. According to commonly used mass predictions, these isotopes are all unbound with respect to two-proton emission from their ground states. From the nonobservation of ${}^{38}$Ti $({T}_{z}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}\ensuremath{-}3)$ in this experiment, an upper limit of 120 ns is deduced for the half-life of this isotope.

A sixty-year old female was referred to the Internal Medicine Department for the treatment of a diffuse high-grade non Hodgkin's lymphoma. She presented episodes of fever in context of neutropenia (neutrophils 0.35 x 10(9)/1 from 1.6 x 10(9)/1 white blood cells). Hemoglobin level was 8.2 g/dl and platelets 132 x 10(12)/1. A monoclonal IgM-Kappa protein (48 g/l) was detected in her serum. A direct antiglobulin test on the red cells proved positive with anti-C3d but not with anti-IgG antiglobulin, due to the presence of an IgM cold antibody with a serological anti-i specificity. The IgM antibody was found on the patient's neutrophils as well as in her serum. The antibody recognized all neutrophils tested in conventional serological tests whether the neutrophil phenotypes in systems NA, NB, and 5. It was demonstrated that it recognized the i antigen expressed on the neutrophils. These results suggest that a cold agglutinin anti-i might be responsible for neutropenia in some patients.

To evaluate the potential of (18)F-fluoro-deoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) for early therapeutic intervention in patients with probable or confirmed tuberculosis (TB).Twenty-one consecutive human immunodeficiency virus negative patients were prospectively included. All patients underwent (18)F-FDG PET/CT before and after 1 month of anti-tuberculosis treatment. The maximum standardised uptake value (SUV(max)) of the most (18)F-FDG avid lesions was recorded.The median age of patients was 36 years (range 18-84); 33.3% were male, 80.9% were born in endemic countries, and 23.8% had a past history of TB. TB was confirmed on culture in 8, on histology in 9 and on the basis of clinical symptoms in 4 patients. (18)F-FDG PET/CT detected active pulmonary TB (n = 1), extra-pulmonary (n = 10) or both (n = 10). The second (18)F-FDG PET/CT showed reduced radiotracer uptake intensity in 19 of 21 patients, with a median percentage decrease of SUV(max) of 31% (range 2-84). Two patients showed no improvement. TB was ruled out in one patient during follow-up; the final diagnosis was a non-Hodgkin's lymphoma. The other patient was smear-positive for 3 months.(18)F-FDG PET/CT allows an easy evaluation of early therapeutic response in patients with TB, particularly extra-pulmonary TB.

Small-angle neutron scattering (SANS) experiments have been performed on a semi-dilute polymer solution at rest and in laminar shear flow under a constant shear gradient in the range ? ?c > 1, with ?c being the longest relaxation time of the system. Temperature was varied from T = 13-55?C at rest and chosen at T = 25, 30 and 50?C for the measurements under shear, hence the theta solvent regime as well as the good-solvent regime are explored. An anisotropy of the two-dimensional scattering pattern is observed under shear at all temperatures, with an increase of the low q scattering in the direction parallel to the flow. The corresponding double winged shape of the pattern resembles the butterfly shapes found for the interchain scattering in deformed gels and rubbers. Spontaneous fluctuation as well as frozen fluctuation models may both be compared with the results.

The hantaviruses (genus Hantavirus, family Bunyaviridae) include human pathogens and occur worldwide. In Western and Central Europe, the predominant serotype is Puumala (PUU) virus, which causes epidemic nephropathy. Voles are considered to be the main reservoir and the vector of PUU virus. A total of 719 rodents (mainly Clethrionomys glareolus, Apodemus sp.) trapped by capture-mark-recapture (CMR) in four sites in Ardennes department (France) between April 2004 and October 2005 were tested for the presence of PUU virus antibodies by enzyme-linked immunosorbent assay (ELISA). The predominant species, C. glareolus (86.5% [622 of 719]), also had the highest antibody prevalence (37.6% [291 of 773]). In C. glareolus, the antibody prevalence rate increased with age (weight) in site A, B and D, reaching more than 50% in the heaviest weight, and suggesting that horizontal infection may be important.

The regularity of medical followup of HIVinfected patients greatly influences the effectiveness of antiretroviral treatments and of prophylaxis of opportunistic infections.To identify potential barriers to a regular followup, a retrospective study was conducted among the adult AIDS patients diagnosed between July 1993 and May 1995 in two French districts (Gironde and HautsdeSeine). Medical followup was described based on the frequency of CD4 counts in the medical file and on a confidential interview among patients whose HIV infection had been diagnosed at least 6 months before AIDS. Irregular followup (less than one CD4 count per year when CD4500/ mm(3), and per 6months when CD4500/ mm(3)) within the two years preceding AIDS diagnosis was analysed according to socioeconomic status and to social and behavioral factors.Among 290 patients, followup was irregular in 51% of the patients (injecting drug users: 66%, homo/bisexual men: 41%, patients infected through heterosexual contact: 49%, p0.01). Factors independently associated with irregular followup were low income level (adjusted odds ratio (aOR)= 2.4; 95% confidence interval (CI), 1.44.1); absence of regular practitioner at HIV diagnosis (aOR= 1.9; 95% CI 1.13.3); imprisonment between HIV diagnosis and AIDS (aOR= 3.8; 95% CI 1.310. 9), and being non homo/bisexual male (aOR= 2.4; 95% CI 1.15.1) versus homo/bisexual male (aOR= 1.3; 95% CI 0.72.7) and female (reference).Results of this study show that several socioeconomic, psychological and cultural barriers to a regular preAIDS medical followup still exist. Impact of new antiretroviral therapy may only be optimal if these barriers are overcome.

To estimate the change in survival of patients with AIDS-related progressive multifocal leukoencephalopathy (PML), in relation to the introduction of protease inhibitors (PI).The French Hospital Database on HIV (FHDH) is a prospective cohort of 70 224 HIV-infected subjects. This study included the patients diagnosed with PML between 1 July 1995 and 30 June 1997. PML diagnosis was both presumptive and confirmed. We compared the survival probability according to the diagnosis period (period 1 or 2, before or after introduction of PI in France on 1 April 1996). Cox's model was used to calculate the relative hazards of death according to the antiretroviral regimen.The study included 246 patients, 109 diagnosed during period 1 and 137 during period 2. In all, 131 patients received an antiretroviral combination that included PI. By 31 December 1997, a total of 131 deaths had been reported. The probability of survival at 6 months for patients from period 2 was nearly twice as high as for patients from period 1 (60.5 versus 34.5%). In comparison with patients receiving no treatment, the risk of death in patients on combination therapy not including PI was reduced by 38% [relative hazard (RH) 0.62, 95% confidence interval (CI) (0.41; 0.95), P = 0.026] and in patients on combination therapy with PI, by 63% [RH 0.37, 95% CI (0.22; 0.64), P = 0.0004].This study of a large cohort of patients diagnosed with PML (n = 246), provides evidence that a combination antiretroviral regimen, especially one including PI, confers marked survival benefits.

Little is known about the complex stepwise process of giving up intravenous (i.v.) drugs. However, HIV risk reduction programs directed towards i.v. drug users have been accused by some opponents to encourage users to continue. In order to better assess the relationships between risk reduction and abstinence, we studied factors associated with abstinence in HIV-infected patients using i.v. drugs at enrollment in the SEROCO cohort (1988-1994).63 HIV-infected patients injecting i.v. drugs at enrollment were followed-up every 6 months with a clinical examination and a questionnaire concerning sexual and drugs practices since last consultation. Abstinence was defined as non injecting for at least 6 months. The 30 patients who became abstinent during a follow-up period of 3 years were compared to the 33 remaining.Abstinence during follow-up was not related to age at inclusion, duration of i.v. drug use, gender or marital status. However, patients who became abstinent were more likely to have a professional activity at inclusion than the remaining (70% vs 42%, p = 0.03). Before knowledge of HIV infection, frequency of injections, needle sharing and use of condoms did not differ between the 2 groups. During follow-up, behavioural changes occurred in the two groups, but were more marked in those who lately became abstinent. These latter were more likely to always inject with new needles/syringes (57% vs 18%, p = 0.003), and to use condoms with HIV-negative partners or of unknown status (73% vs 39%, p = 0.06). Professional activity and systematic use of new needles/syringes remained independently associated with abstinence in multivariate analysis.In this cohort, abstinence appeared as a stepwise process in which risk reduction preceded abstinence. This confirms that risk reduction programs do not work against those messages aimed at stopping i.v. drug use. Since this analysis selected particular subjects, enrolled in a cohort of HIV-infected patients, results should be confirmed in other samples of i.v. drugs users.Few prospective studies have described the stepwise process of giving up intravenous drug (IV) use. In an effort to deepen the understanding of the relationship between risk reduction related to IV drug use and giving up such drug use, the authors studied factors associated with IV drug abstinence among HIV-infected patients using IV drugs at their enrollment in the multicenter French cohort SEROCO between 1988 and 1994. 63 HIV-infected patients injecting IV drugs at enrollment were followed clinically every 6 months and with a questionnaire on their sexual practices and drug use since their most recent consultations. The termination of drug use was defined as not using drugs for a period of at least 6 months. The 30 subjects who gave up IV drug use over the 3-year follow-up were compared to the 33 subjects who continued using IV drugs. Those who gave up IV drugs were more likely to be professionally active at enrollment than those who kept injecting, they more often used during the follow-up period new injection materials for each injection, and more often used condoms with HIV-negative partners and those of unknown serostatus. The abandonment of IV drug use in this study followed a stepwise process in which the reduction of risks preceded the eventual cessation of drug use.

A relativistic primary beam of 58Ni from the SIS synchrotron at GSI was used to produce proton-rich isotopes in the titanium-to-nickel region by projectile fragmention at the FRS. We report here on the first observation of the Tz=−7/2 nuclei 45Fe and 49Ni. In addition, the new isotope 42Cr (Tz=−3) was identified. This opens the route to the yet unobserved doubly-magic nucleus 48Ni.

We have measured the Coulomb-dissociation cross section for 8B→7Be+p in the field of 208Pb for a wide range of 0.15–2.95 MeV at Ein=254 MeV/u. The preliminary results agree with Monte Carlo simulations that used the 7Be(p,γ)8B cross sections measured by Filippone et al., and Vaughn et al. and assuming E1 (+M1) Coulomb dissociation process. Further analysis is in progress.

β-delayed one- and two-proton and α spectroscopic studies of the neutron-deficient nuclei 22,23,24Si and 22Al produced in projectile fragmentation of a 36Ar primary beam at 95 MeV/u have been performed at GANIL. Isotopes of interest were analyzed using the LISE3 spectrometer and were implanted in a telescope made of silicon detectors and a micro-strip gaseous counter where decay particles were detected.

In an experiment at the LISE3 facility of GANIL, we used the projectile fragmentation of a 36 Ar primary beam at 95 MeV/nucleon to produce neutron-deficient isotopes in the Al-Si region. The selected isotopes were implanted in a detector telescope, where their decay particles were observed. We report here on the study of the βp, β2p, and βα decay of the isotopes 22,23,24 Si and 22 Al. Beta-decay half-lives have been measured. The ground-state mass excess of 23 Si has been determined. Partial decay schemes are presented on the basis of the transitions associated with the observed decay peaks.

In an experiment performed at the FRS of GSI, we measured total interaction cross sections for 7 Be, 8 B, and 9 C, one-proton-removal cross sections for 8 B and 9 C as well as two-proton-removal cross sections for 9 C on targets ranging from carbon to lead at an energy of 285 MeV/nucleon. In addition, we performed measurements at 142 MeV/nucleon for 8 B. The experimental results are compared to different calculations. Glauber-type calculations with different model·density distributions show that, down to incident energies of about 50 MeV/nucleon, total interaction cross-section measurements with light targets are not sensitive to an extended proton distribution in 8 B. However, at lower incident energies, a tail in the proton density distribution is needed to explain the total interaction cross sections. Total interaction cross-section measurements with high-Z targets in the present experiment show a significant increase of the cross sections due to low-lying electromagnetic strength.

The interaction of spermatozoa with the zona pellucida is a critical step of fertilization. Specific sperm surface proteins involved in this process can be added or modified during epididymal transit. We have previously described a 34-kDa human epididymal sperm protein (P34H) that we proposed to be involved in sperm-zona pellucida interaction. In this study, Western blot analysis were performed to determine the level of P34H protein present on the spermatozoa of 16 men with idiopathic infertility. These levels were compared with the amount of P34H protein found in men of proven fertility. In addition, a sperm-zona pellucida binding assay was performed with spermatozoa from fertile and infertile men. Spermatozoa obtained from different semen samples from a given individual had similar P34H levels. However, the amount of P34H varied from one man to another. Nine of 16 infertile men had a P34H level that was less than 30% of the normal value based on a population of fertile men, while the remaining 7 males were in the normal range. Sperm from infertile subjects with a normal P43H determination bound to zonae pellucidae as efficiently as those from controls. However, spermatozoa from subjects with a low amount of P34H exhibited a dramatic diminution in their ability to interact with zonae pellucidae. Our results show that the quantity of the epididymal protein P34H varied from one male to another and that low levels of this epididymal sperm protein are associated with certain cases of idiopathic infertility. Results are discussed with regard to the function of human epididymis in sperm maturation.

During epididymal transit, spermatozoa acquire new surface antigens that are involved in the acquisition of their fertilizing ability. We have previously described a 34-kDa (P34H) human epididymal sperm protein that shows antigenic and functional homologies with the hamster P26h. P34H is localized on the acrosomal cap of human spermatozoa and has been proposed to be involved in the interaction with the zona pellucida. The aim of this study was to document the expression of P34H on the sperm surface during transit along the male and female genital tracts. Immunohistochemical techniques were performed on human testes and epididymides by means of an antiserum specific for P34H. No labelling was detected on those spermatozoa found within the seminiferous tubules or in the vasa efferentia. P34H first appeared in the caput epididymidis and was restricted to the acrosomal cap. Signal intensity then increased considerably from the proximal corpus to the cauda region of the epididymis. After ejaculation, the same pattern of P34H distribution was observed, but the intensity was much lower than that characterizing the cauda epididymal spermatozoa. Strong labeling was restored after incubation in B2 medium and was maximal after 5 h of capacitation. After acrosomal exocytosis induced by a Ca2+ ionophore, the percentage of P34H-labeled spermatozoa decreased proportionally to the number of acrosome-reacted spermatozoa as determined by Pisum sativum-fluorescein isothiocyanate (FITC) labeling. P34H appeared to be strongly anchored to the sperm plasma membrane during epididymal transit as indicated by the requirement for detergent to extract this surface antigen from ejaculated spermatozoa. This confirms the importance of P34H binding to the sperm plasma membrane during epididymal maturation. We have previously proposed that P34H is involved in sperm-zone pellucida interaction. The appearance and accumulation of P34H on the sperm plasma membrane during epididymal maturation, followed by its inaccessibility associated with ejaculation, its unmasking during capacitation, and finally its elimination after the acrosome reaction, are in agreement with te proposed function of this sperm antigen.

The binding of the spermatozoon to the zona pellucida is a species-specific phenomenon. We have previously shown that the binding of hamster sperm to the homologous zona pellucida involves a sperm 26-kDa glycoprotein, the P26h, originating in the epididymis. In order to establish to what extent this sperm protein is involved in the species-specific recognition of the egg's extracellular coat, we have compared the inhibitory properties of anti-P26h antibodies in a sperm-zona pellucida assay using hamster and mouse gametes. Anti-P26h IgGs inhibit, in a dose-dependent manner, gamete interactions in both species, although in a less efficient manner in the mouse than in the hamster. While anti-26kDa Fab fragments are as efficient as the intact IgG to inhibit hamster sperm-zona pellucida binding, they have no effect on mouse gamete interaction. ELISA, Western blot, and immunohistochemical experiments have been performed in order to characterize the mouse antigen(s) recognized by the anti-P26h antiserum. ELISA and Western blots showed that this antiserum recognized two proteins on mouse spermatozoa that are less reactive than the hamster P26h. These antigens are localized in the acrosomal region of epididymal spermatozoa of both species. These results indicate that the hamster P26H involved in zona pellucida interaction has certain unique epitopes, while others are common to the sperm of both species.

During epididymal transit, mammalian spermatozoa acquire new surface antigens that may participate in gamete interaction. We have previously described a 26-kDa (P26h) epididymal hamster sperm protein that we propose to be involved in fertilization. In this study, we have searched for an antigenically related protein in the human, and have found that an anti-P26h antiserum recognizes a 34-kDa (P34H) protein on Western blot of human sperm proteins. Immunostaining showed that this protein is localized on the acrosomal cap of human epididymal spermatozoa but not on testicular gametes. The effect of the anti-P26h antiserum on the fertilizing ability of human spermatozoa was evaluated by use of a human zona pellucida binding assay. Compared to the preimmune serum, the antiserum caused a highly significant decrease in the number of sperm bound per zona pellucida. This inhibition was not due to the induction of a premature acrosomal reaction nor to an effect on the motility of the spermatozoa. The antiserum recognizing the P34H human sperm protein had no effect on gamete fusion as determined by the zona-free hamster test. Our results suggest that the human spermatozoon acquires an epididymal protein that shares a common epitope(s) with the P26h hamster sperm protein. The possible involvement of this human sperm antigen in the binding to the zona pellucida is discussed.

Pneumocystis carinii pneumonia and toxoplasmic encephalitis are frequent life-threatening opportunistic infections in patients with human immunodeficiency virus (HIV) infection. Primary prophylaxis against P. carinii pneumonia is now common, but there are few data on regimens for primary prophylaxis against toxoplasmosis.We conducted a randomized trial that compared two prophylactic regimens: dapsone (50 mg per day) plus pyrimethamine (50 mg per week) was compared with aerosolized pentamidine (300 mg per month). The patients had symptomatic HIV infection, no history of P. carinii pneumonia or symptomatic toxoplasmosis, and CD4+ counts below 200 per cubic millimeter (0.2 x 10(9) per liter).In an intention-to-treat analysis, after a median follow-up of 539 days P. carinii pneumonia developed in 10 patients in each group, whereas toxoplasmosis developed in 32 of 176 patients in the pentamidine group and 19 of 173 patients in the dapsone-pyrimethamine group. Those assigned to pentamidine had a risk of P. carinii pneumonia that was similar to the risk in those assigned to dapsone-pyrimethamine (adjusted relative risk, 1.13; 95 percent confidence interval, 0.44 to 2.92; P = 0.79), but a higher risk of toxoplasmosis (adjusted relative risk, 1.81; 95 percent confidence interval, 1.12 to 2.94; P = 0.02). Among the 262 patients with serologic evidence of past exposure to Toxoplasma gondii, the relative risk of symptomatic toxoplasmosis was 2.37 times higher in those assigned to pentamidine (95 percent confidence interval, 1.3 to 4.4; P = 0.006). More patients discontinued dapsone-pyrimethamine than pentamidine because of toxicity (42 vs. 3; P0.001). Survival was similar in the two groups.For primary prevention of P. carinii pneumonia, dapsone-pyrimethamine is as effective, though not as well tolerated, as aerosolized pentamidine. Dapsone-pyrimethamine also prevents first episodes of toxoplasmosis.