Numerical simulations in the development of the French radioactive waste vitrification processes using induction furnace

International audienceFor many years, the CEA (Commissariat à l’Énergie Atomique et aux Énergies Alternatives) Marcoule France has developed various processes dedicated to radioactive waste confinement, especially vitrification processes for HLLW. For 15 years now, the numerical simulation has become an important tool for research and developement projects held in the CEA-AREVA Joint Vitrification Laboratory (LCV). Induction heating, fluid mechanics and thermal simulations take part of all new R&D projects. The apports of such simulations are, first, the enhancement of the working knowledge of existing process. Those data are very useful to define optimisation choices, for example upgrades made on the hot metallic melter used since the 90s at LaHague facility. Second, the simulations are, of course, also used at the conception stage of new processes as a tool allowing wide ranges parametric tests. This has been extensively used in the design of the cold crucible inductive melter (CCIM) commissioned in 2010 at La Hague plant. Finally, it is a powerful and relatively cheap tool for prospective studies for processes of the future. Whatever the purpose, the potential benefits are gains on the reliability, the output capacity and the life time

Mise en cohérence spatiale et temporelle de données TEP-TDM acquises en respiration libre pour l'évaluation du cancer pulmonaire

Les mouvements respiratoires associés à une durée d'acquisition longue entraînent un flou des images TEP/TDM, altérant l'interprétation du médecin, l'évaluation de la réponse thérapeutique et la mise en place de traitements de radiothérapie avancés. L'objectif de la recherche est une revue et une optimisation des techniques permettant la limitation du mouvement respiratoire et la détection de la trajectoire des tumeurs pulmonaires sur les images TEP/TDM. Dans un premier temps, le dispositif de référence permettant la synchronisation de l'examen TEP/TDM à la respiration a été caractérisé. Plusieurs méthodes de tri rétrospectif des données TEP/TDM à partir de ce dispositif, permettant l'amélioration de la quantification des images et une réduction de moitié de la durée d'acquisition, sont présentées et évaluées sur des données cliniques. Un nouveau dispositif de synchronisation respiratoire spirométrique, créé au sein d'un consortium, a également été caractérisé à partir d'expériences sur fantôme respiratoire pour permettre une synchronisation temps réel performante des images TEP/TDM. Ce dispositif est dorénavant en phase d'étude clinique de phase I. Une synthèse finale résume les principaux travaux réalisés montrant l'optimisation de la synchronisation respiratoire en TEP/TDM. Les intérêts de l'examen TEP/TDM synchronisé à la respiration sont discutés en fonction de ses indications pour la prise en charge des patients atteints de cancer pulmonaire. Quelques perspectives sont également proposées dans l'objectif d'améliorer la quantification des tumeurs en TEP/TDM.The respiratory movements associated with a long acquisition duration cause blurred images PET/CT, leading to misinterpretation of physician, inaccurate assessment of therapeutic response or radiation therapy. The objective of the research is a review and an optimization of techniques limiting the impact of respiratory motion and detecting the trajectory of lung tumors on PET/CT images (4D PET/CT). First, the gold standard respiratory gating device for 4D PET/CT was characterized. Several PET/CT retrospective binning methods to improve the image quantification and halving the acquisition duration are presented and evaluated on clinical data. A new spirometric gating device, created by a consortium, was also characterized from experiments on respiratory phantom to allow real-time synchronization of PET/CT images. This system is now under Phase I clinical trial. A conclusion summarizes the main results showing the optimization of respiratory gating in PET/CT. The interests of the 4D PET/CT examination are discussed according to the indications for the treatment of patients with lung cancer. Some prospects are also proposed with the aim to improve the quantification of tumors in PET/CT

Down selecting adjuvanted vaccine formulations: a comparative method for harmonized evaluation.

The need for rapid and accurate comparison of panels of adjuvanted vaccine formulations and subsequent rational down selection, presents several challenges for modern vaccine development. Here we describe a method which may enable vaccine and adjuvant developers to compare antigen/adjuvant combinations in a harmonized fashion. Three reference antigens: Plasmodium falciparum apical membrane antigen 1 (AMA1), hepatitis B virus surface antigen (HBsAg), and Mycobacterium tuberculosis antigen 85A (Ag85A), were selected as model antigens and were each formulated with three adjuvants: aluminium oxyhydroxide, squalene-in-water emulsion, and a liposome formulation mixed with the purified saponin fraction QS21. The nine antigen/adjuvant formulations were assessed for stability and immunogenicity in mice in order to provide benchmarks against which other formulations could be compared, in order to assist subsequent down selection of adjuvanted vaccines. Furthermore, mouse cellular immune responses were analyzed by measuring IFN-γ and IL-5 production in splenocytes by ELISPOT, and humoral responses were determined by antigen-specific ELISA, where levels of total IgG, IgG1, IgG2b and IgG2c in serum samples were determined. The reference antigens and adjuvants described in this study, which span a spectrum of immune responses, are of potential use as tools to act as points of reference in vaccine development studies. The harmonized methodology described herein may be used as a tool for adjuvant/antigen comparison studies

Disordered microbial communities in asthmatic airways.

A rich microbial environment in infancy protects against asthma [1], [2] and infections precipitate asthma exacerbations [3]. We compared the airway microbiota at three levels in adult patients with asthma, the related condition of COPD, and controls. We also studied bronchial lavage from asthmatic children and controls.We identified 5,054 16S rRNA bacterial sequences from 43 subjects, detecting >70% of species present. The bronchial tree was not sterile, and contained a mean of 2,000 bacterial genomes per cm(2) surface sampled. Pathogenic Proteobacteria, particularly Haemophilus spp., were much more frequent in bronchi of adult asthmatics or patients with COPD than controls. We found similar highly significant increases in Proteobacteria in asthmatic children. Conversely, Bacteroidetes, particularly Prevotella spp., were more frequent in controls than adult or child asthmatics or COPD patients.The results show the bronchial tree to contain a characteristic microbiota, and suggest that this microbiota is disturbed in asthmatic airways

IL-1β Suppresses Innate IL-25 and IL-33 Production and Maintains Helminth Chronicity.

Approximately 2 billion people currently suffer from intestinal helminth infections, which are typically chronic in nature and result in growth retardation, vitamin A deficiency, anemia and poor cognitive function. Such chronicity results from co-evolution between helminths and their mammalian hosts; however, the molecular mechanisms by which these organisms avert immune rejection are not clear. We have found that the natural murine helminth, Heligmosomoides polygyrus bakeri (Hp) elicits the secretion of IL-1β in vivo and in vitro and that this cytokine is critical for shaping a mucosal environment suited to helminth chronicity. Indeed in mice deficient for IL-1β (IL-1β(-/-)), or treated with the soluble IL-1βR antagonist, Anakinra, helminth infection results in enhanced type 2 immunity and accelerated parasite expulsion. IL-1β acts to decrease production of IL-25 and IL-33 at early time points following infection and parasite rejection was determined to require IL-25. Taken together, these data indicate that Hp promotes the release of host-derived IL-1β that suppresses the release of innate cytokines, resulting in suboptimal type 2 immunity and allowing pathogen chronicity

Successive influenza virus infection and Streptococcus pneumoniae stimulation alter human dendritic cell function

Background: Influenza virus is a major cause of respiratory disease worldwide and Streptococcus pneumoniae infection associated with influenza often leads to severe complications. Dendritic cells are key antigen presenting cells but its role in such co-infection is unclear.Methods: In this study, human monocyte derived-dentritic cells were either concurrently or successively challenged with the combination of live influenza virus and heat killed pneumococcus to mimic the viral pneumococcal infection. Dendritic cell viability, phenotypic maturation and cytokine production were then examined.Results: The challenge of influenza virus and pneumococcus altered dendritic cell functions dependent on the time interval between the successive challenge of influenza virus and pneumococcus, as well as the doses of pneumococcus. When dendritic cells were exposed to pneumococcus at 6 hr, but not 0 hr nor 24 hr after influenza virus infection, both virus and pneumococcus treated dendritic cells had greater cell apoptosis and expressed higher CD83 and CD86 than dendritic cells infected with influenza virus alone. Dendritic cells produced pro-inflammatory cytokines: TNF-α, IL-12 and IFN-γ synergistically to the successive viral and pneumococcal challenge. Whereas prior influenza virus infection suppressed the IL-10 response independent of the timing of the subsequent pneumococcal stimulation.Conclusions: Our results demonstrated that successive challenge of dendritic cells with influenza virus and pneumococcus resulted in synergistic up-regulation of pro-inflammatory cytokines with simultaneous down-regulation of anti-inflammatory cytokine, which may explain the immuno-pathogenesis of this important co-infection. © 2011 Wu et al; licensee BioMed Central Ltd.published_or_final_versio

A novel outbred mouse model of 2009 pandemic influenza and bacterial co-infection severity

Influenza viruses pose a significant health risk and annually impose a great cost to patients and the health care system. The molecular determinants of influenza severity, often exacerbated by secondary bacterial infection, are largely unclear. We generated a novel outbred mouse model of influenza virus, Staphylococcus aureus, and coinfection utilizing influenza A/CA/07/2009 virus and S. aureus (USA300). Outbred mice displayed a wide range of pathologic phenotypes following influenza virus or co-infection ranging broadly in severity. Influenza viral burden positively correlated with weight loss although lung histopathology did not. Inflammatory cytokines including IL-6, TNF-α, G-CSF, and CXCL10 positively correlated with both weight loss and viral burden. In S. aureus infection, IL-1β, G-CSF, TNF-α, and IL-6 positively correlated with weight loss and bacterial burden. In co-infection, IL-1β production correlated with decreased weight loss suggesting a protective role. The data demonstrate an approach to identify biomarkers of severe disease and to understand pathogenic mechanisms in pneumonia. © 2013 McHugh et al

An antiinflammatory role for IKKβ through the inhibition of “classical” macrophage activation

The nuclear factor κB (NF-κB) pathway plays a central role in inflammation and immunity. In response to proinflammatory cytokines and pathogen-associated molecular patterns, NF-κB activation is controlled by IκB kinase (IKK)β. Using Cre/lox-mediated gene targeting of IKKβ, we have uncovered a tissue-specific role for IKKβ during infection with group B streptococcus. Although deletion of IKKβ in airway epithelial cells had the predicted effect of inhibiting inflammation and reducing innate immunity, deletion of IKKβ in the myeloid lineage unexpectedly conferred resistance to infection that was associated with increased expression of interleukin (IL)-12, inducible nitric oxide synthase (NOS2), and major histocompatibility complex (MHC) class II by macrophages. We also describe a previously unknown role for IKKβ in the inhibition of signal transducer and activator of transcription (Stat)1 signaling in macrophages, which is critical for IL-12, NOS2, and MHC class II expression. These studies suggest that IKKβ inhibits the “classically” activated or M1 macrophage phenotype during infection through negative cross talk with the Stat1 pathway. This may represent a mechanism to prevent the over-exuberant activation of macrophages during infection and contribute to the resolution of inflammation. This establishes a new role for IKKβ in the regulation of macrophage activation with important implications in chronic inflammatory disease, infection, and cancer