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In the framework of the NEWGAIN project, which aims to build a second injector with a mass to charge-state ratio A/q = 7 for the SPIRAL2 linear accelerator at GANIL, CEA is developing in collaboration with LPSC and GANIL a new superconducting 28 GHz ECR Ion Source Magnet named ASTERICS. The magnetic design is based on an advanced concept of the VENUS ECR ion source operating at Berkeley and the FRIB source under commisionning at MSU. The ion source superconducting magnet consists of a sextupole inside three solenoids to confine the plasma and a shell-based support structure to apply a preload to the sextupole coils. The confinement coils will be made in Nb-Ti and will be operated at 4.2 K. The cryogenic environment will be ensured by liquid helium thermosiphon closed loop thanks to six in-situ cryocoolers. Specific HTS current leads are being designed to power the magnet. A cold integrated He buffer will also allow He almost-lossless quenches. The preliminary design choices of the ASTERICS superconducting magnet are presented here from the magnetic, mechanical and protection design to the cryogenic definition emphasizing the global approach used to obtain the final magnet configuration.

Le traitement du DRESS repose sur la corticothérapie (CT), de modalités mal codifiées. Alors que l’expertise préconise la CT locale très forte (CTL) dans le DRESS mineur et la CT générale (CTG) 1mg/kg/j dans le DRESS grave, le choix entre CTL et CTG n’est pas consensuel dans le DRESS modéré. Le but de l’essai DRESSCODE était de comparer CTL et CTG dans le DRESS modéré.

Le traitement de la gale sévère, mal codifié et parfois sous-optimal, n’a jamais fait l’objet d’un essai contrôlé randomisé (ECR). Les experts préconisent l’association traitement local – ivermectine orale à dose standard et administrée de façon répétée. Des doses plus élevées d’ivermectine ont permis d’accroître son efficacité dans certaines parasitoses (pédiculose du cuir chevelu notamment). Le but de l’essai était de comparer 2 doses d’ivermectine, 400 vs 200μg/kg, dans la gale sévère.

The cause of a rapid change in Atlantic Ocean circulation and northern cooling at the onset of Heinrich Stadial 1 ~18.5 ka is unclear. Previous studies have simulated the event using ice sheet and/or iceberg meltwater forcing, but these idealized freshwater fluxes have been unrealistically large. Here we use a different approach, driving a high‐resolution drainage network model with a recent time‐resolved global paleo‐ice sheet reconstruction to generate a realistic meltwater forcing. We input this flux to the Hadley Centre Coupled Model version 3 (HadCM3) climate model without adjusting the timing or amplitude and find that an acceleration in northern ice sheet melting (up to ~7.5 m/kyr global mean sea level rise equivalent) triggers a 20% reduction in the Atlantic Meridional Overturning Circulation. The simulated pattern of ocean circulation and climate change matches an array of paleoclimate and ocean circulation reconstructions for the onset of Heinrich Stadial 1, in terms of both rates and magnitude of change. This is achieved with a meltwater flux that matches constraints on sea level changes and ice sheet evolution around 19–18 ka. Since the rates of melting are similar to those projected for Greenland by 2200, constraining the melt rates and magnitude of climate change during Heinrich Stadial 1 would provide an important test of climate model sensitivity to future ice sheet melt. Atlantic Ocean circulation plays a key role in redistributing heat around Earth's surface, and thus has an important influence on our climate. Because of this, sudden shifts in Atlantic Ocean circulation can drive rapid climate changes. One such example is at the onset of “Heinrich Stadial 1”, 18.5 thousand years ago, when geological records show that Atlantic circulation weakened and the Northern Hemisphere cooled while the Southern Hemisphere warmed. At the time, huge ice sheets (several kilometers thick) covered much of North America and northern Europe. Climate model results suggest that the freshwater produced by these melting ice sheets is responsible for weakening the Atlantic Ocean circulation and triggering the abrupt climate changes captured in the geological records. This result helps to elucidate the complex interaction between ice sheets, ocean circulation, and climate, and how these interactions can lead to sudden shifts in climates of the past and, potentially, the future. Indeed, the rate of melting we adopt in the present model is comparable to the melting projected for the Greenland Ice Sheet by 2200. The simulated pattern of ocean circulation and climate change matches records of the transition to Heinrich Stadial 1 ~18.5 kaThe rate of meltwater needed to drive this change (<7.5 mm/year global mean sea level rise equivalent) is much less than previously usedThe forcing is consistent with accelerated Eurasian ice sheet melting 19–18 ka, providing the likely cause of Heinrich Stadial 1

Records indicate that 14,500 years ago, sea level rose by 12–22 m in under 340 years. However, the source of the sea level rise remains contentious, partly due to the competing climatic impact of different hemispheric contributions. Antarctic meltwater could indirectly strengthen the Atlantic Meridional Overturning Circulation (AMOC), causing northern warming, whereas Northern Hemisphere ice sheet meltwater has the opposite effect. This story has recently become more intriguing, due to increasing evidence for sea level contributions from both hemispheres. Using a coupled climate model with freshwater forcing, we demonstrate that the climatic influence of southern‐sourced meltwater is overridden by northern sources even when the Antarctic flux is double the North American contribution. This is because the Southern Ocean is quickly resalinized by Antarctic Circumpolar water. These results imply that the pattern of surface climate changes caused by ice sheet melting cannot be used to fingerprint the hemispheric source of the meltwater. The fastest major sea level rise ever recorded took place 14,500 years ago, when sea level rose by 12–22 m in under 340 years. The extra water came from melting ice sheets, which stretched across North America and northern Europe as well as Greenland and Antarctica. We ran a climate model to test the impact of different meltwater contributions from Antarctica and the Northern Hemisphere ice sheets (North America, Greenland, and Eurasia). Our simulations demonstrate that northern meltwater has a much stronger and longer lasting effect on ocean circulation and climate than Southern Hemisphere melt. Consequently, northern melting overrides the impact of southern melting even when the flux of water from North America is only half the magnitude of the Antarctic flux. This means that past climate records cannot be used to identify the contribution of meltwater from different ice sheets: the northern signal can override the southern signal. The simulated impact of Northern Hemisphere sources of Meltwater Pulse 1a overwhelms the climatic influence of Antarctic sourcesThis is because Antarctic meltwater is rapidly dissipated and the Southern Ocean is quickly resalinized by Antarctic Circumpolar waterTherefore, surface climate signals cannot be used to fingerprint the hemispheric source of ice sheet meltwater

The Last Glacial Maximum extent of the North American Ice Sheets is well constrained empirically but has proven to be challenging to simulate with coupled Climate‐Ice Sheet models. Coupled Climate‐Ice Sheet models are often too computationally expensive to sufficiently explore uncertainty in input parameters, and it is unlikely that values calibrated to reproduce modern ice sheets will reproduce the known extent of the ice at the Last Glacial Maximum. To address this, we run an ensemble with a coupled Climate‐Ice Sheet model (FAMOUS‐ice), simulating the final stages of growth of the last North American Ice Sheets' maximum extent. Using this large ensemble approach, we explore the influence of numerous uncertain ice sheet albedo, ice sheet dynamics, atmospheric, and oceanic parameters on the ice sheet extent. We find that ice sheet albedo parameters determine the majority of uncertainty when simulating the Last Glacial Maximum North American Ice Sheets. Importantly, different albedo parameters are needed to produce a good match to the Last Glacial Maximum North American Ice Sheets than have previously been used to model the contemporary Greenland Ice Sheet due to differences in cloud cover over ablation zones. Thus, calibrating coupled climate‐ice sheet models on one ice sheet may produce strong biases when the model is applied to a new domain. At the peak of the last ice age, an ice sheet covered much of North America. The extent of this ice sheet is well‐understood after decades of intensive data collection, but producing a computer simulation of the ice sheet which matches our observations has been a challenge. This is partly because of uncertainty about the “correct” model set‐up to create the best simulation, and partly because the computer models used in the simulations require large computing resources. In this paper, we present a series of simulations of the North American Ice Sheet at the peak of the last ice age using a fast‐running computer model in which the atmosphere and ice sheets interact. We run hundreds of simulations to tackle the uncertainty about the optimum values for unknown input parameters. We find that the model's representation of how reflective the ice sheet surface is has the most impact on the size and shape of the simulated ice sheet. Importantly, the parameter values that produce the best simulations of modern‐day Greenland produce poor simulations of the North American Ice Sheets during the last ice age, calling into question whether the parameters chosen for modern Greenland are appropriate from simulating ice sheets under different conditions. Simulating the Last Glacial Maximum North American Ice Sheets successfully requires de‐tuning the coupled Climate‐Ice Sheet model FAMOUS‐iceAfter running a large ensemble, we identify multiple acceptable simulations of the LGM North American Ice SheetThe LGM North American cloud cover revealed overtuned albedo parameters to compensate for modern Greenland cloud biases Simulating the Last Glacial Maximum North American Ice Sheets successfully requires de‐tuning the coupled Climate‐Ice Sheet model FAMOUS‐ice After running a large ensemble, we identify multiple acceptable simulations of the LGM North American Ice Sheet The LGM North American cloud cover revealed overtuned albedo parameters to compensate for modern Greenland cloud biases

The source or sources of meltwater pulse 1A (MWP‐1A) at ~14.5 ka, recorded at widely distributed sites as a sea level rise of ~10–20 m in less than 500 years, is uncertain. A recent ice modeling study of North America and Greenland has suggested that the collapse of an ice saddle between the Laurentide and Cordilleran ice sheets, with a eustatic sea level equivalent (ESLE) of ~10 m, may have been the dominant contributor to MWP‐1A. To test this suggestion, we predict gravitationally self‐consistent sea level changes from the Last Glacial Maximum to the present day associated with the ice model. We find that a combination of the saddle collapse scenario and melting outside North America and Greenland with an ESLE of ~3 m yields sea level changes across MWP‐1A that are consistent with far‐field sea level records at Barbados, Tahiti, and Sunda Shelf. We predict sea level changes associated with a model of North American deglaciationA North American ice saddle collapse may have been the dominant source of MWP‐1AWe draw our conclusions on the basis of fits to far‐field sea level records

Abstract: The aim of this study was to determine whether viral type (HPV-6 vs. HPV-11) could predict the clinical course of recurrent respiratory papillomatosis in children. Viral typing, using the polymerase chain reaction, was performed on laryngeal biopsies of 61 patients treated at Children's Hospital of Michigan. HPV-6 was detected in 29 of the patients' biopsies and HPV-11 in 32 biopsies. HPV-11 was more common among the African-American patients than among Caucasians (P = 0.001). Patients with HPV-11 were diagnosed at a younger age (36.2 vs. 48.2 months; P = 0.04) and were more likely to have active disease (P = 0.0311) at the time of this study. They tended to have longer periods of disease activity (8 years vs. 5 years; P = 0.026), required more surgical procedures (42 procedures/patient vs. 13.6; P = 0.02), and more procedures per patient, per year (2.9 vs. 5.3; P = 0.0164). Three of the patients infected with HPV-11 developed invasive papillomatosis and bronchogenic squamous cell carcinoma, and two of these patients died of disease. Our findings suggest that HPV-11 infection confers a more aggressive course to recurrent respiratory papillomatosis.

The originally embryonic γ-globin locus duplicated and acquired a novel (fetal) pattern of expression in a defined time period (55–40 million years ago) during primate phylogeny. The objective of this study was to determine some of the factors that led to first the emergence of fetal γ specificity and then the maintenance of different fetal γ expression patterns in extant simian primates (e.g., human, capuchin monkey). Analyses focused on two platyrrhine (New World monkey) species: the common marmoset (Callithrix jacchus) and the brown capuchin monkey (Cebus apella), each of which has paired, non-allelic γ loci (5'-γ1–γ2-3'). Quantitation of β-type globin mRNAs expressed in a 4.5 week old embryo of Callithrix jacchus revealed that in addition to its primary ε-globin message, considerable amounts of γ1 message and just trace levels of γ2 message are present. In contrast, analyses of γ-globin messenger RNAs expressed in a Cebus apella fetal liver indicated that γ2 expression is at least 120 times greater than γ1 expression. Using a luciferase reporter and a transient assay system, the strengths of γ1 and γ2 promoter fragments of Cebus apella were compared in erythroid (K562) and non-erythroid (HeLa) cell lines. Due to the lack of chromatin repression in a transient expression system, the results do not fully recapitulate globin expression. However, the results suggest that sequences contained within the Cebus γ1 and γ2 proximal promoter regions (−200 to +1 bp) can direct γ transcription in both cell lines. In K562 and, to a lesser extent, in HeLa cells Cebus γ2 promoter fragments were significantly stronger (P &lt; 0.01) than γ1 promoter fragments. This is consistent with the fact that the Cebus γ1 promoter contains several mutations, including a proximal CCAAT box mutation (CCAAT→CCAAc). The εγ-1 intergenic distances in these platyrrhines (5.4 kb in Cebus apella and 6.9 kb in Callithrix jacchus) are short, supporting the inference that it was also short in the stem simian primates. The results suggest that immediately following the γ duplication, the γ1 gene of the stem simians was still embryonic and the downstream γ2 gene was largely silent. A further inference is that once γ2 accumulated regulatory mutations that disrupted binding of fetal repressors, γ2 was expressed fetally and, through gene conversion, passed these characteristics to the γ1 gene. The fetal expression of γ1 is most evident in catarrhines (Old World monkeys and hominoids), which preferentially express the γ1 locus during fetal life. J. Exp. Zool. (Mol. Dev. Evol.) 285:27–40, 1999. © 1999 Wiley-Liss, Inc.

Endocervical adenocarcinoma in situ (AIS) is believed to be a precursor of invasive disease; however, the biologic behavior of endocervical glandular “atypias” (GAs) is unclear. The purpose of this study was to evaluate the potential role of GA as a precursor of adenocarcinoma by assessment of the human papillomavirus (HPV) status of glandular lesions. We analyzed by polymerase chain reaction (PCR) 69 cases within a spectrum of endocervical glandular lesions encompassing invasive adenocarcinoma (IACA: 20 cases), AIS (21 cases), adenosquamous carcinoma (ASqCA: eight cases) and GA (20 cases) for HPV DNA sequences. Cervical adenocarcinoma is often associated with neoplastic squamous lesions (SL). In this study, after exclusion of ASqCA, 29 (47.5) of 61 cases of endocervical glandular lesions were associated with an SL. The rate of HPV detection was not statistically different in adenocarcinoma with or without an SL (73.3 vs. 61.5, respectively). In contrast, 64.3 of GAs with an SL (nine of 14 cases) were HPV positive, while only 16.7 of GAs without an SL (one of six cases) were positive. These findings suggest that HPV was preferentially associated with the concomitant SL rather than the GA. To localize the HPV sequences within the lesions, eight of the nine HPV-positive GAs with an SL were analyzed by in situ hybridization (ISH). Four cases were positive by ISH and showed hybridization of the probe only in the nuclei of squamous epithelial cells; in no lesion did the probe localize to the glandular epithelium. In our study, HPV infection of the glandular epithelium of GAs unassociated with an SL appeared to be an uncommon event. None of the GAs were associated with low- or intermediate-risk HPV, and only the GA (which was high grade) unassociated with an SL contained a high-risk virus type. The possibility must be considered that pathogenetic mechanisms for squamous intraepithelial lesions may be different from those responsible for intraepithelial glandular lesions.

The polymerase chain reaction has potential for use in the detection of small amounts of human papillomavirus (HPV) viral nucleic acids present in clinical specimens. However, new HPV types for which no probes exist would remain undetected by using type-specific primers for the polymerase chain reaction before hybridization. Primers corresponding to highly conserved HPV sequences may be useful for detecting low amounts of known HPV DNA as well as new HPV types. Here we analyze a pair of primers derived from conserved sequences within the E1 open reading frame for HPV sequence amplification by using the polymerase chain reaction. The longest perfect homology among HPV sequences is a 12-mer within the first exon of E1M. A region of conserved amino acids coded by the E1 open reading frame allowed the detection of another highly conserved region about 850 base pairs downstream. Two 21-mers derived from these conserved regions were used to amplify sequences from all HPV DNAs used as templates. The amplified DNA was shown to be specific for HPV sequences within the E1 open reading frame. DNA from HPVs whose sequences were not available were amplified by using these two primers. HPV DNA sequences in clinical specimens could also be amplified with the primers.

The relationships among 65 basidiomycetous yeast strains were determined by one-dimensional electrophoresis of SDS-solubilized whole-cell proteins. Protein profiles were compared by the Pearson product moment correlation coefficient (r). The strains investigated represented species from the generaCystofilobasidium, Filobasidium, Filobasidiella, Kondoa, Leucosporidium, Mrakia andRhodosporidium. Except for the genusMrakia, all species constituted separate protein electrophoretic clusters. The species of the genusMrakia (M. frigida, M. gelida, M. nivalis andM. stokesii) show highly similar protein patterns, suggesting that these four species may be synonymous. Strains of two varieties ofFilobasidiella neoformans, F. neoformans var.neoformans andF. neoformans var.bacillispora, could not be differentiated by protein electrophoresis.

Propenlap (projet IC061626, STIC) est une étude multicentrique (n=13) prospective avec lecture centralisée des pièces opératoires, comparant la voie rétropubienne à la voie mini-invasive (laparoscopique sans et avec robot assistance) en termes carcinologiques, fonctionnels et économiques. Nous rapportons ici les résultats fonctionnels.