A role for dendritic cells in bleomycin-induced pulmonary fibrosis in mice?

RATIONALE: Lung dendritic cells (DCs) have been shown to accumulate in human fibrotic lung disease, but little is known concerning a role for DCs in the pathogenesis of fibrotic lung. OBJECTIVES: To characterize lung DCs in an in vivo model of bleomycin-induced pulmonary fibrosis in mice. METHODS: We characterized the kinetics and activation of pulmonary DCs during the course of bleomycin-induced lung injury by flow cytometry on lung single-cell suspensions. We also characterized the lymphocytes accumulating in bleomycin lung and the chemokines susceptible to favor the recruitment of immune cells. MEASUREMENTS AND MAIN RESULTS: We show, for the first time, that increased numbers of CD11c(+)/major histocompatibility complex class II(+) DCs, including CD11b(hi) monocyte-derived inflammatory DCs, infiltrate the lung of treated animals during the fibrotic phase of the response to bleomycin. These DCs are mature DCs expressing CD40, CD86, and CD83. They are associated with increased numbers of recently activated memory T cells expressing CD44, CD40L, and CD28, suggesting that fully mature DCs and Ag-experienced T cells can drive an efficient effector immune response within bleomycin lung. Most importantly, when DCs are inactivated with VAG539, a recently described new immunomodulator, VAG539 treatment attenuates the hallmarks of bleomycin lung injury. CONCLUSIONS: These findings identify lung DCs as key proinflammatory cells potentially able to sustain pulmonary inflammation and fibrosis in the bleomycin model

COSI6 : a Tool for Nuclear Transition Scenarios Studies

International audienceNuclear systems, composed of reactors with varied fuel and cycle facilities (enrichment plant, fabrication plant, reprocessing plant,) are complex and in constant evolution. Decision makers need to have all the technical elements, based on dynamic nuclear fleet transition scenarios studies. These scenarios are tools to compare different options of nuclear systems evolution, and identify strengths and drawbacks. To have a complete overview of nuclear systems, it is required to follow precisely material flows at each step of the fuel cycle front-end and back-end, and at each date of the operation period. The evolution in time and under flux of materials isotopic composition has also to be taken into account, which can give access to other interesting values (activity, decay heat, toxicity,).Since 1985, CEA has been developing the COSI software, simulating in detail the evolution in time of a nuclear reactors fleet and its associated fuel cycle facilities. It is designed to study different options for the introduction of various nuclear reactor types and the use of the associated nuclear materials.The general principle and the physical models of the current version in 2014 (COSI6 7.0) is described in the paper. The main physical models are the equivalence models in the fabrication plant, which determine the initial composition of mixed fuels in order to provide an equivalent efficiency whatever the isotopic composition of constitutive materials, and the depletion models for irradiated fuels in the core and cooling materials in storage the reference model is CESAR of which several versions are available. CESAR is the reference code at the AREVA NC La Hague reprocessing plant and is used to calculate the isotopic composition of spent fuel by solving Bateman equation, using one-group cross sections libraries coming from neutronic codes (APOLLO2 in thermal spectrum and ERANOS in fast spectrum). An exercise of validation of COSI6 previously carried out on the French PWR historic nuclear fleet until 2010 (and not presented in this paper) allows us to validate the essential phases of the fuel cycle computation and highlights the credibility of the results provided by the code. Otherwise, a methodology of propagation of inputs uncertainties on results has been developed and could be implemented to quantify the uncertainties associated to scenarios results.Finally, a methodology of optimization of scenarios is currently developed. It will consist in a module associated to COSI6, to find the appropriate input parameters defining the best scenarios for a given problem. Indeed COSI6 is a deterministic code in the sense that the scenario is simulated chronologically as function of the input parameters defined by the user, without any decision taken by the code. Nevertheless the user needs more and more often to identify solution scenarios to different problems (e.g. how to minimize natural resources consumption, waste production and toxicity) while respecting industrial constraints (maintaining the energy production, limiting the interim storages, stabilizing the plants capacities,...)

COSI6: A Tool for Nuclear Transition Scenario Studies and Application to SFR Deployment Scenarios with Minor Actinide Transmutation

International audienc

Lung function in Birt-Hogg-Dubé syndrome: a retrospective analysis of 96 patients.

Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder caused by mutations in the FLCN gene coding for folliculin. Its clinical expression includes cutaneous fibrofolliculomas, renal tumors, multiple pulmonary cysts, and recurrent spontaneous pneumothoraces. Data on lung function in BHD are scarce and it is not known whether lung function declines over time. We retrospectively assessed lung function at baseline and during follow-up in 96 patients with BHD. Ninety-five percent of BHD patients had multiple pulmonary cysts on computed tomography and 59% had experienced at least one pneumothorax. Mean values of forced expiratory volume in 1 second (FEV <sub>1</sub> ), forced vital capacity (FVC), FEV <sub>1</sub> /FVC ratio, and total lung capacity were normal at baseline. Mean (standard deviation) residual volume (RV) was moderately increased to 116 (36) %pred at baseline, and RV was elevated > 120%pred in 41% of cases. Mean (standard deviation) carbon monoxide transfer factor (DLco) was moderately decreased to 85 (18) %pred at baseline, and DLco was decreased < 80%pred in 33% of cases. When adjusted for age, gender, smoking and history of pleurodesis, lung function parameters did not significantly decline over a follow-up period of 6 years. Cystic lung disease in BHD does not affect respiratory function at baseline except for slightly increased RV and reduced DLco. No significant deterioration of lung function occurs in BHD over a follow-up period of 6 years

The Effects of Uncertainty of Input Parameters on Nuclear Fuel Cycle Scenario Studies

International audienceNuclear systems, composed of reactors and fuel cycle facilities, are complex and in constant evolution. Fuel cycle scenario studies aim at evaluating the consequences of decisions taken in the near term on the eventual outcomes of a chosen fuel cycle.Scenario studies require a large amount of data and hypotheses, such as the energy demand and its evolution or the performances and characteristics of existing and future technologies. Each hypothesis, represented by a parameter, is a potential source of uncertainty that can impact the scenario outcomes. The Nuclear Energy Agency's Expert Group on Advanced Fuel Cycle Scenarios (NEA/AFCS) recently completed an activity that used sensitivity studies to evaluate the impact of uncertainty of the primary scenario input parameters on scenario results.At the beginning of the study, a base case scenario was specified and evaluated. It considers a PWR UOX reactor fleet using low enriched uranium oxide fuel and its gradual replacement by a sodium fast reactor (SFR) fleet using uranium/plutonium mixed oxide fuel. Each member of the group evaluated this scenario with its own scenario code (COSI, COSAC, FAMILY, SITON, TR_EVOL or VISION). It is noteworthy that the different codes show a good consistency in the results and that the differences have been investigated and documented in order to ensure a strong basis for comparison in the sensitivity study.Then, 17 key input parameters and their range of variation as well as 22 scenario outputs were identified and sensitivity analyses were conducted. The key parameters were chosen amongst the general assumptions on the scenario (energy demand, introduction date of fast reactor), reactors and facilities characteristics (burn-ups, losses at reprocessing) and some minor actinides recycling parameters. As far as possible, each parameter was varied independently from the others. This sensitivity study shows the relative impact of each parameter on each output metric. In order to compare the large amount of results, two methods of summarization were adopted, as described in the paper. These comparisons have shown that some parameters, such as the energetic production or the introduction date of fast reactors, have a strong impact on the results whereas others, like the UOX fabrication time, have almost no impact on the studied scenario

Sarcoidosis, inorganic dust exposure and content of bronchoalveolar lavage fluid: the MINASARC pilot study

Inhalation of mineral dust was suggested to contribute to sarcoidosis. We compared the mineral exposome of 20 sarcoidosis and 20 matched healthy subjects. Bronchoalveolar lavage (BAL) samples were treated by digestion-filtration and analyzed by transmission electron microscopy. The chemical composition of inorganic particles was determined by energy-dispersive X-ray (EDX) spectroscopy. Dust exposure was also assessed by a specific questionnaire. Eight sarcoidosis patients and five healthy volunteers had a high dust load in their BAL. No significant difference was observed between the overall inorganic particle load of each group while a significant higher load for steel was observed in sarcoidosis patients (p=0.029). Moreover, the building activity sub-score was significantly higher in sarcoidosis patients (p=0.018). These results suggest that building work could be a risk factor for sarcoidosis which could be considered at least in some cases as a granulomatosis caused by airborne inorganic dust. The questionnaire should be validated in larger studies