Rapport sur "i2010 : Vers une bibliothèque numérique européenne" (2006/2040(INI))

RAPPORT de la Commission de la culture et de l\u27éducation sur l\u27initiativer de la Commission européenne "i2010 : Vers une bibliothèque numérique européenne" (2006/2040(INI)) Rapporteur: Marie-Hélène Descamp

"Du proche au lointain : essais de restitution de l'espace vécu à Paris à la fin du Moyen Âge"

Cet article est la synthèse d'une journée d'études organisée dans le cadre du séminaire sur l'histoire de Paris. Elle visait à tenter de cerner la perception de l'espace au Moyen Âge à travers différentes sources. Il se dégage de la confrontation des dossiers l'impression qu'il y a des usages sociaux très sélectifs de l'espace urbain, même si il faut compter aussi avec un effet de source, puisque chacune met en avant une dimension de la vie et que l'existence en comporte plusieurs. Les parcours individuels découpent des zones plus ou moins linéaires qui dessinent un espace en étoile coïncidant mal avec le périmètre urbain défini par les remparts ou les cartes des historiens. Les pérégrinations des demandeurs de lettres de rémission sont à ce titre éclairantes. Il est probablement exagéré d'évoquer un usage exclusivement nodal, en archipel, de l'espace urbain comme dans la ville contemporaine, mais la notion rassurante de quartier entendu comme village urbain qui serait caractéristique de l'Ancien Régime mériterait d'être questionnée. Des quartiers existent certainement, mais forment-ils la trame de tout l'espace urbain ? Rien n'est moins sûr : il faudrait s'assurer d'abord que toutes les zones ont une identité, et ensuite que leurs habitants n'ont pas d'intérêts significatifs en dehors. Sous cet angle, le Paris de la fin du Moyen Âge pourrait peut-être se rapprocher d'une ville contemporaine. Les réseaux s'inscrivent-ils dans un espace dominé par des contraintes physiques ou par l'horizon interpersonnel de chacun, c'est-à-dire la géographie humaine de la ville ? Il y a une dialectique temporelle complexe entre ces deux données, puisque la répartition des artisans est fonction des ressources naturelles et humaines dont ils ont besoin, mais des circonstances exceptionnelles montrent qu'ils peuvent surmonter l'éloignement physique avec leurs collaborateurs ou leurs ressources. Pour eux, la Seine est un obstacle surmontable ; tandis que pour tous ceux qui en vivent, marchands, propriétaires de vignes rurales ou bateliers, elle est un axe de circulation et une mère nourricière. D'une manière générale, il est fort probable que la Seine a le même statut ambigu à l'époque médiévale qu'à l'époque moderne, où elle est tout à la fois une frontière et un pôle d'attraction dont l'influence se fait sentir loin dans l'espace parisien . L'espace vécu est donc très fragmentaire, mais l'espace imaginaire semble être plus vaste et plus cohérent : les éloges de Paris ou les farces le dessinent à l'échelle de la rive, voire même de la ville entière. L'étude des itinéraires des processions pourrait aller dans ce sens, car il semble qu'un certain nombre d'entre elles traversent le fleuve et sortent même des murs, contribuant ainsi à ressouder les morceaux de la ville . La circulation officielle du roi, qui entre dans Paris par la porte Saint-Denis mais en sort par la porte Saint-Antoine , participe du même phénomène. Tout se passe comme si les rituels politiques et religieux ou les cérémonies ludiques qui unifient l'espace parisien étaient les contrepoints nécessaires à l'éclatement de l'espace vécu réel

CVD and CVI of pyrocarbon from various precursors

International audienceThe control of pyrocarbon (pyC) chemical vapor infiltration (CVI) is a key issue in the processing of high-performance C/C composites with applications in aerospace parts and braking technology. For years, the precise investigation of deposition kinetics and pyC nanometerscale anisotropy has been rehearsed in chemical vapor deposition (CVD) and several variants of CVI with various pore sizes, and using mostly propane, propylene, and methane as source precursors. A literature survey and the analysis of recent experimental data have helped to understand better the role of gas-phase intermediate species in the various nanotextural transitions; a coherent modeling frame, which is suitable for propane, propylene, and methane—the latter having a neatly lower reactivity—has been set up and tested against experimental results from independent teams. The relation between nanotexture and processing conditions is then explained

Fetal tachycardia: A role for amiodarone as first- or second-line therapy?

SummaryBackgroundFetal tachycardias result in serious prenatal and postnatal morbidity and mortality. Intrauterine treatment can improve prognosis dramatically and the therapeutic protocol is well defined. Currently, amiodarone is used as third-line therapy and is reserved for refractory cases.AimsOur aim was to review the management and outcome of fetal tachycardia, giving particular consideration to the efficacy and safety of amiodarone therapy.MethodsThis was a retrospective study of 24 consecutive cases of sustained fetal tachycardia, treated mainly with digoxin and/or amiodarone administered by the transplacental route.ResultsThe 24 fetal tachycardias comprised 16 supraventricular tachycardias with 1:1 atrioventricular conduction, seven atrial flutters and one ventricular tachycardia. Seven fetuses were hydropic and eight experienced less severe cardiac failure. Digoxin monotherapy converted 5/12 non-hydropic fetuses and 0/2 hydropic fetuses, with one intrauterine death. Amiodarone monotherapy converted 5/5 fetuses, including two hydropic fetuses: one ventricular tachycardia, two atrial flutters and two supraventricular tachycardias. When administered with digoxin, amiodarone converted all but two fetuses (7/9). No deaths were associated with amiodarone, but there was moderate morbidity, with six transient elevations of thyroid stimulating hormone at birth, two of which required short-term thyroid hormonal substitution therapy.ConclusionMaternal oral amiodarone seems to be effective and relatively safe, even in hydropic fetuses. We suggest that this treatment could be used earlier than is currently advised

IL-27, but not IL-35, inhibits neuroinflammation through modulating GM-CSF expression

IL-27 and IL-35 are heterodimeric cytokines, members of the IL-12 family and considered to have immunomodulatory properties. Their role during neuroinflammation had been investigated using mutant mice devoid of either one of their subunits or lacking components of their receptors, yielding conflicting results. We sought to understand the therapeutic potential of IL-27 and IL-35 delivered by gene therapy in neuroinflammation. We constructed lentiviral vectors expressing IL-27 and IL-35 from a single polypeptide chain, and we validated in vitro their biological activity. We injected IL-27 and IL-35-expressing lentiviral vectors into the cerebrospinal fluid (CSF) of mice affected by experimental neuroinflammation (EAE), and performed clinical, neuropathological and immunological analyses. Both cytokines interfere with neuroinflammation, but only IL-27 significantly modulates disease development, both clinically and neuropathologically. IL-27 protects from autoimmune inflammation by inhibiting granulocyte macrophages colony-stimulating factor (GM-CSF) expression in CD4+ T cells and by inducing program death-ligand 1 (PD-L1) expression in both CNS-resident and CNS-infiltrating myeloid cells. We demonstrate here that IL-27 holds therapeutic potential during neuroinflammation and that IL-27 inhibits GM-CSF and induces pd-l1 mRNA in vivo

IFN-γ/IL-27 axis induces PD-L1 expression in monocyte-derived dendritic cells and restores immune tolerance in CNS autoimmunity

Antigen (Ag)-specific tolerance induction by intravenous (i.v.) injection of high-dose auto-Ags has been explored for therapy of autoimmune diseases, including multiple sclerosis (MS). It is thought that the advantage of such Ag-specific therapy over non-specific immunomodulatory treatments would be selective suppression of a pathogenic immune response without impairing systemic immunity, thus avoiding adverse effects of immunosuppression. Auto-Ag i.v. tolerance induction has been extensively studied in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and limited clinical trials demonstrated that it is safe and beneficial to a subset of MS patients. Nonetheless, mechanisms of i.v. tolerance induction are incompletely understood, hampering the development of better approaches and their clinical application. Here, we describe a pathway whereby auto-Ag i.v. injected into mice with ongoing clinical EAE induces IFN-γ secretion by auto-Ag-specific CD4+ T cells, triggering IL-27 production by conventional dendritic cells type 1 (cDC1). IL-27 then, via STAT3 activation, induces PD-L1 expression by monocyte-derived DCs (moDCs) in the CNS of mice with EAE. PD-L1 interaction with PD-1 on pathogenic CD4+ T cells leads to their apoptosis/anergy, resulting in disease amelioration. These findings identify a key role of the IFN-γ/IL-27/PD-L1 axis, involving T cells/cDC1/moDCs in the induction of i.v. tolerance

Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma

Objectives The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study. Methods Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were >50 copies/mL in both compartments and bulk genotypic tests were realized. Results On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P = 0.0455) and T215Y (P = 0.0455). Conclusions In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performe

« Bronzes grecs et romains, recherches récentes » — Hommage à Claude Rolley

Philologue, archéologue, historien, spécialiste des bronzes, Claude Rolley, disparu en 2007, occupa une place originale parmi les spécialistes du monde méditerranéen antique. Marqué par la découverte du cratère de Vix (en 1953) qu’il ne cessa d’étudier tout au long de sa carrière, il sut croiser recherches et approches sur les périodes à la fois classique et proto-historique, de la Laconie à la Bourgogne jusqu’à la Grande Grèce. Les bronzes, de toutes dimensions ou origines, dont il tint la chronique pendant près de 25 ans dans la Revue archéologique, étaient pour lui une source de réflexion multiple : stylistique, technique – il prenait en compte aussi bien les questions d’assemblage ou de fonte que la composition chimique des objets –, ou culturelle – ses travaux ont apporté des éclairages décisifs sur la formation des ateliers et la circulation des objets d’un centre de production à l’autre. À l’initiative de plusieurs de ses disciples, un colloque lui a rendu hommage (INHA, 16-17 juin 2009) : les textes qui suivent en sont le fruit

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

Serotonin Reduction in Post-acute Sequelae of Viral Infection

Post-acute sequelae of COVID-19 (PASC, Long COVID ) pose a significant global health challenge. The pathophysiology is unknown, and no effective treatments have been found to date. Several hypotheses have been formulated to explain the etiology of PASC, including viral persistence, chronic inflammation, hypercoagulability, and autonomic dysfunction. Here, we propose a mechanism that links all four hypotheses in a single pathway and provides actionable insights for therapeutic interventions. We find that PASC are associated with serotonin reduction. Viral infection and type I interferon-driven inflammation reduce serotonin through three mechanisms: diminished intestinal absorption of the serotonin precursor tryptophan; platelet hyperactivation and thrombocytopenia, which impacts serotonin storage; and enhanced MAO-mediated serotonin turnover. Peripheral serotonin reduction, in turn, impedes the activity of the vagus nerve and thereby impairs hippocampal responses and memory. These findings provide a possible explanation for neurocognitive symptoms associated with viral persistence in Long COVID, which may extend to other post-viral syndromes