Impact des nouveaux médias sur la jeunesse (l\u27)

Rapport d\u27information n° 46 (2008-2009) du 22 octobre 2008 par M. David ASSOULINE, fait au nom de la commission des Affaires culturelles portant sur l\u27inpact des nouveaux médias pour la jeunesse. Après être revenu sur ces derniers comme chance, puis comme menace, le rapport insiste sur l\u27impératif éducatif. Une synthèse du document est disponible à l\u27adresse : http://www.senat.fr/rap/r08-046/r08-046-syn.pd

Quantum confinement effects in Pb Nanocrystals grown on InAs

In the recent work of Ref.\cite{Vlaic2017-bs}, it has been shown that Pb nanocrystals grown on the electron accumulation layer at the (110) surface of InAs are in the regime of Coulomb blockade. This enabled the first scanning tunneling spectroscopy study of the superconducting parity effect across the Anderson limit. The nature of the tunnel barrier between the nanocrystals and the substrate has been attributed to a quantum constriction of the electronic wave-function at the interface due to the large Fermi wavelength of the electron accumulation layer in InAs. In this manuscript, we detail and review the arguments leading to this conclusion. Furthermore, we show that, thanks to this highly clean tunnel barrier, this system is remarkably suited for the study of discrete electronic levels induced by quantum confinement effects in the Pb nanocrystals. We identified three distinct regimes of quantum confinement. For the largest nanocrystals, quantum confinement effects appear through the formation of quantum well states regularly organized in energy and in space. For the smallest nanocrystals, only atomic-like electronic levels separated by a large energy scale are observed. Finally, in the intermediate size regime, discrete electronic levels associated to electronic wave-functions with a random spatial structure are observed, as expected from Random Matrix Theory.Comment: Main 12 pages, Supp: 6 page

Efficient generation of spin currents by the Orbital Hall effect in pure Cu and Al and their measurement by a Ferris-wheel ferromagnetic resonance technique at the wafer level

We present a new ferromagnetic resonance (FMR) method that we term the Ferris FMR. It is wideband, has significantly higher sensitivity as compared to conventional FMR systems, and measures the absorption line rather than its derivative. It is based on large-amplitude modulation of the externally applied magnetic field that effectively magnifies signatures of the spin-transfer torque making its measurement possible even at the wafer-level. Using the Ferris FMR, we report on the generation of spin currents from the orbital Hall effect taking place in pure Cu and Al. To this end, we use the spin-orbit coupling of a thin Pt layer introduced at the interface that converts the orbital current to a measurable spin current. While Cu reveals a large effective spin Hall angle exceeding that of Pt, Al possesses an orbital Hall effect of opposite polarity in agreement with the theoretical predictions. Our results demonstrate additional spin- and orbit- functionality for two important metals in the semiconductor industry beyond their primary use as interconnects with all the advantages in power, scaling, and cost

Budesonide Oral Suspension Improves Symptomatic, Endoscopic, and Histologic Parameters Compared With Placebo in Patients With Eosinophilic Esophagitis

BACKGROUND & AIMS: Pharmacologic treatment of eosinophilic esophagitis (EoE) is limited to off-label use of corticosteroids not optimized for esophageal delivery. We performed a randomized, controlled phase 2 trial to assess the ability of budesonide oral suspension (BOS), a novel muco-adherent topical steroid formulation, to reduce symptoms and esophageal eosinophilia in adolescents and adults with EoE. METHODS: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group trial, 93 EoE patients between the ages of 11 and 40 years with dysphagia and active esophageal eosinophilia were randomized to receive either BOS 2 mg or placebo twice daily for 12 weeks. Co-primary outcomes were change in Dysphagia Symptom Questionnaire (DSQ) score from baseline, and proportion of patients with a histologic response (≤6 eosinophils/high-power field) after treatment. Endoscopic severity scores and safety parameters were assessed. RESULTS: At baseline, mean DSQ scores were 29.3 and 29.0, and mean peak eosinophil counts were 156 and 130 per hpf in the BOS and placebo groups, respectively. After treatment, DSQ scores were 15.0 and 21.5, and mean peak eosinophil counts were 39 and 113 per high-power field, respectively (P < .05 for all). For BOS vs placebo, change in DSQ score was -14.3 vs -7.5 (P = .0096), histologic response rates were 39% vs 3% (P < .0001), and change in endoscopic severity score was -3.8 vs 0.4 (P < .0001). Adverse events were similar between groups. CONCLUSIONS: Treatment with BOS was well tolerated in adolescent and young adult patients with EoE and resulted in improvement in symptomatic, endoscopic, and histologic parameters using validated outcome instruments. ClinicalTrials.gov ID NCT01642212

DYNAMO: A Phase II Study of Duvelisib (IPI-145) in Patients With Refractory Indolent Non-Hodgkin Lymphoma

PURPOSE Indolent non-Hodgkin lymphoma (iNHL) remains largely incurable and often requires multiple lines of treatment after becoming refractory to standard therapies. Duvelisib was approved by the Food and Drug Administration for relapsed or refractory (RR) chronic lymphocytic leukemia or small lymphocytic lymphoma (SLL) and RR follicular lymphoma (FL) after two or more prior systemic therapies. On the basis of the activity of duvelisib, a first-in-class oral dual inhibitor of phosphoinositide 3-kinase-δ,-γ, in RR iNHL in a phase I study, the safety and efficacy of duvelisib monotherapy was evaluated in iNHL refractory to rituximab and either chemotherapy or radioimmunotherapy. PATIENTS AND METHODS Eligible patients had measurable iNHL (FL, SLL, or marginal zone B-cell lymphoma) double refractory to rituximab (monotherapy or in combination) and to either chemotherapy or radioimmunotherapy. All were treated with duvelisib 25 mg orally twice daily in 28-day cycles until progression, unacceptable toxicity, or death. The primary end point was overall response rate (ORR) using the revised International Working Group criteria for malignant lymphoma. RESULTS This open-label, global phase II trial enrolled 129 patients (median age, 65 years; median of three prior lines of therapy) with an ORR of 47.3% (SLL, 67.9%; FL, 42.2%; MZL, 38.9%). The estimated median duration of response was 10 months, and the estimated median progression-free survival was 9.5 months. The most frequent any-grade treatment-emergent adverse events (TEAEs) were diarrhea (48.8%), nausea (29.5%), neutropenia (28.7%), fatigue (27.9%), and cough (27.1%). Among the 88.4% of patients with at least one grade 3 or greater TEAE, the most common TEAEs were neutropenia (24.8%), diarrhea (14.7%), anemia (14.7%), and thrombocytopenia (11.6%). CONCLUSION In the DYNAMO study, oral duvelisib monotherapy demonstrated clinically meaningful activity and a manageable safety profile in heavily pretreated, double-refractory iNHL, consistent with previous observations. Duvelisib may provide a new oral treatment option for this patient population of which many are elderly and in need of additional therapies

GWAS in the SIGNAL/PHARE clinical cohort restricts the association between the FGFR2 locus and estrogen receptor status to HER2-negative breast cancer patients

International audienceGenetic polymorphisms are associated with breast cancer risk. Clinical and epidemiological observations suggest that clinical characteristics of breast cancer, such as estrogen receptor or HER2 status, are also influenced by hereditary factors. To identify genetic variants associated with pathological characteristics of breast cancer patients, a Genome Wide Association Study was performed in a cohort of 9365 women from the French nationwide SIGNAL/PHARE studies (NCT00381901/RECF1098). Strong association between the FGFR2 locus and ER status of breast cancer patients was observed (ER-positive n=6211, ER-negative n=2516; rs3135718 OR=1.34 p=5.46x10-12). This association was limited to patients with HER2-negative tumors (ER-positive n=4267, ER-negative n=1185; rs3135724 OR=1.85 p=1.16x10-11). The FGFR2 locus is known to be associated with breast cancer risk. This study provides sound evidence for an association between variants in the FGFR2 locus and ER status among breast cancer patients, particularly among patients with HER2-negative disease. This refinement of the association between FGFR2 variants and ER-status to HER2-negative disease provides novel insight to potential biological and clinical influence of genetic polymorphisms on breast tumors

Infiltration from the pedon to global grid scales: an overview and outlook for land surface modelling

Infiltration in soils is a key process that partitions precipitation at the land surface in surface runoff and water that enters the soil profile. We reviewed the basic principles of water infiltration in soils and we analyzed approaches commonly used in Land Surface Models (LSMs) to quantify infiltration as well as its numerical implementation and sensitivity to model parameters. We reviewed methods to upscale infiltration from the point to the field, hill slope, and grid cell scale of LSMs. Despite the progress that has been made, upscaling of local scale infiltration processes to the grid scale used in LSMs is still far from being treated rigorously. We still lack a consistent theoretical framework to predict effective fluxes and parameters that control infiltration in LSMs. Our analysis shows, that there is a large variety in approaches used to estimate soil hydraulic properties. Novel, highly resolved soil information at higher resolutions than the grid scale of LSMs may help in better quantifying subgrid variability of key infiltration parameters. Currently, only a few land surface models consider the impact of soil structure on soil hydraulic properties. Finally, we identified several processes not yet considered in LSMs that are known to strongly influence infiltration. Especially, the impact of soil structure on infiltration requires further research. In order to tackle the above challenges and integrate current knowledge on soil processes affecting infiltration processes on land surface models, we advocate a stronger exchange and scientific interaction between the soil and the land surface modelling communities

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue