Incidence de la source de pollution sur la dissolution et la rétention sélective d'hydrocarbures en milieu poreux saturé en eau

Des expérimentations menées sur des modèles-colonnes de milieu poreux, se localisant sur des études de lessivage du corps d'imprégnation formé par des mélanges d'hydrocarbures et sur des essais de propagation de leurs parties solubles, ont été réalisées au laboratoire. Il est montré que le comportement des hydrocarbures en solution pendant le lessivage est fonction de la nature de la source de pollution, et que le transport des traces solubles d'alcanes est fortement freiné par les effets de l'échange liquide-gaz masquant les propriétés adsorbantes de la matrice solide, ou pouvant entraîner une modification du processus de sorption des hydrocarbures par la phase solide.La solubilité n'est pas un critère suffisant pour expliquer la dissolution sélective et progressive des constituants d'un corps d'imprégnation formé par un mélange de plusieurs espèces d'hydrocarbures, et lors du transport des parties solubles d'une telle source de contamination, l'influence des paramètres solubilité, constante de Henry et coefficient de distribution doivent être pris en compte simultanément pour étudier leur rétention sélective.In the case of groundwater contamination hy petroleum products, the constituents of the immiscible pollutant source will be selectively solubilized and transporled over large distances by the water movement. Then, long-term pollution of aquifers is essentially due to the transfer and transport of dissolved hydrocarbon traces. The behaviour of soluble hydrocarbons and the extent of pollution depend on hydrodynamical conditions of the infiltration area and phase partitioning between water, oil, gas and solid in the aquifer.This article deals with some aspects linked to the transfer mechanisms which take place during the selective dissolution of hydrocarbons and those relating to physico-chemicai exchanges accompanying the transport of soluble substances of the pollution source through saturated porous media. The experiments have been conducted with physical models constituted of glass columns : The glass column source of pollution (L = 75 cm, Ф = 10.4 cm) contained both natural quartz land and a motionless oil phase uniformly distributed in quantifies below residual saturation; it allows to study the selective dissolution of the constituents of the impregnation body. The exchange phenomena between phases were examined in a second glass column (L = 70 cm, Ф = 9.3 cm) which received the water charged with dissolved hydrocarbons coming from the glass column source, and filled with solid matrixes which were not contaminated at the beginning. The solid phase in the second glass column consisted of quartz sand or a mixture of agricultural soil and sand. The soil contained an average of 1.3 % of organic materials, 6.7 % of clay minerals and 27 % of limestone. The influence of the adsorbing properties of the solid material and the role of residual air on the transport and retention of soluble hydrocarbons were investigated. The variation of residual air content was obtained according to the filling method of the second glass column : “dry filling” favours the presence of the gaseous phase (water introduced by imbibition); “lifting by sedimentation” can reduce or partially avoid it (the second column is filled with the porous medium under water).For a pollutant source made of a mixture of hydrocarbons at equal fractions and belonging to a same homologous series (alkanes and aromatics), the experimental results allowed to establish the importance of solubility parameter as well on the mode of selective leaching of the impregnation body, as on the selective retention of soluble elements of the pollutant source.The behaviour of the constituents of the pollution source made of several hydrocarbon species appears differently and then, the solubility dues not constitute, for such a source, a sufficient criterion to apprehend the observed transfer and exchange mechanisms.- Selective dissolution : the modifications of behaviour especially result to the fact that some components of the pollution source are represented at very low proportions then, they can’t respect, during the partition phenomenon, the gradation of solubility values as well at the beginning of the leaching of the impregnation body, as at the decreasing stages of concentrations. This situation must be regarded for studying the transfer of soluble hydrocarbons after accidental spill of petroleum products because it will affect the transport and the contamination prediction.- Exchange phenomena : we observed that the liquid/gas exchange is the major factor of retention of soluble alkanes masking the effects of adsorbing materials. The influence of adsorbing character of the solid material appears clearly, only when the air content of the porous matrix is low. On the other band, the residual air content has no influence on the transport of soluble monoaromatics but the main phenomenon observed is in that case the liquid/solid exchange.Moreover, the impact of the gaseous phase on the alkanes involves a modification of sorption process of hydrocarbons by the solid phase : the selective retention of various constituents of a pollution source made of several hydrocarbon species should be interpreted by the knowledge at their respective distribution coefficient Kd as it was admitted by several authors, when the air content of the porous matrix is low. The sorption process should be more complex when the residual air content is great because the gaseous phase plays a preponderant role for the alkanes; in that case, the simultaneous effects of the solubility, the Henry's constant and the distribution coefficient must be taken into account together for getting a best understanding of each component behaviour of the pollution source and assessing their fate in the case of alluvial aquifer contamination

Cutaneous Burn Injury Modulates Urinary Antimicrobial Peptide Responses and the Urinary Microbiome

OBJECTIVES: Characterization of urinary bacterial microbiome and antimicrobial peptides after burn injury to identify potential mechanisms leading to urinary tract infections and associated morbidities in burn patients. DESIGN: Retrospective cohort study using human urine from control and burn subjects. SETTING: University research laboratory. PATIENTS: Burn patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Urine samples from catheterized burn patients were collected hourly for up to 40 hours. Control urine was collected from "healthy" volunteers. The urinary bacterial microbiome and antimicrobial peptide levels and activity were compared with patient outcomes. We observed a significant increase in urinary microbial diversity in burn patients versus controls, which positively correlated with a larger percent burn and with the development of urinary tract infection and sepsis postadmission, regardless of age or gender. Urinary psoriasin and β-defensin antimicrobial peptide levels were significantly reduced in burn patients at 1 and 40 hours postadmission. We observed a shift in antimicrobial peptide hydrophobicity and activity between control and burn patients when urinary fractions were tested against Escherichia coli and Enterococcus faecalis urinary tract infection isolates. Furthermore, the antimicrobial peptide activity in burn patients was more effective against E. coli than E. faecalis. Urinary tract infection-positive burn patients with altered urinary antimicrobial peptide activity developed either an E. faecalis or Pseudomonas aeruginosa urinary tract infection, suggesting a role for urinary antimicrobial peptides in susceptibility to select uropathogens. CONCLUSIONS: Our data reveal potential links for urinary tract infection development and several morbidities in burn patients through alterations in the urinary microbiome and antimicrobial peptides. Overall, this study supports the concept that early assessment of urinary antimicrobial peptide responses and the bacterial microbiome may be used to predict susceptibility to urinary tract infections and sepsis in burn patients

A Prominent Role for DC-SIGN+ Dendritic Cells in Initiation and Dissemination of Measles Virus Infection in Non-Human Primates

Measles virus (MV) is a highly contagious virus that is transmitted by aerosols. During systemic infection, CD150+T and B lymphocytes in blood and lymphoid tissues are the main cells infected by pathogenic MV. However, it is unclear which cell types are the primary targets for MV in the lungs and how the virus reaches the lymphoid tissues. In vitro studies have shown that dendritic cell (DC) C-type lectin DC-SIGN captures MV, leading to infection of DCs as well as transmission to lymphocytes. However, evidence of DC-SIGN-mediated transmission in vivo has not been established. Here we identified DC-SIGNhiDCs as first target cells in vivo and demonstrate that macaque DC-SIGN functions as an attachment receptor for MV. Notably, DC-SIGNhicells from macaque broncho-alveolar lavage and lymph nodes transmit MV to B lymphocytes, providing in vivo support for an important role for DCs in both initiation and dissemination of MV infection

Minimising Immunohistochemical False Negative ER Classification Using a Complementary 23 Gene Expression Signature of ER Status

BACKGROUND: Expression of the oestrogen receptor (ER) in breast cancer predicts benefit from endocrine therapy. Minimising the frequency of false negative ER status classification is essential to identify all patients with ER positive breast cancers who should be offered endocrine therapies in order to improve clinical outcome. In routine oncological practice ER status is determined by semi-quantitative methods such as immunohistochemistry (IHC) or other immunoassays in which the ER expression level is compared to an empirical threshold. The clinical relevance of gene expression-based ER subtypes as compared to IHC-based determination has not been systematically evaluated. Here we attempt to reduce the frequency of false negative ER status classification using two gene expression approaches and compare these methods to IHC based ER status in terms of predictive and prognostic concordance with clinical outcome. METHODOLOGY/PRINCIPAL FINDINGS: Firstly, ER status was discriminated by fitting the bimodal expression of ESR1 to a mixed Gaussian model. The discriminative power of ESR1 suggested bimodal expression as an efficient way to stratify breast cancer; therefore we identified a set of genes whose expression was both strongly bimodal, mimicking ESR expression status, and highly expressed in breast epithelial cell lines, to derive a 23-gene ER expression signature-based classifier. We assessed our classifiers in seven published breast cancer cohorts by comparing the gene expression-based ER status to IHC-based ER status as a predictor of clinical outcome in both untreated and tamoxifen treated cohorts. In untreated breast cancer cohorts, the 23 gene signature-based ER status provided significantly improved prognostic power compared to IHC-based ER status (P = 0.006). In tamoxifen-treated cohorts, the 23 gene ER expression signature predicted clinical outcome (HR = 2.20, P = 0.00035). These complementary ER signature-based strategies estimated that between 15.1% and 21.8% patients of IHC-based negative ER status would be classified with ER positive breast cancer. CONCLUSION/SIGNIFICANCE: Expression-based ER status classification may complement IHC to minimise false negative ER status classification and optimise patient stratification for endocrine therapies

Cell-Type Independent MYC Target Genes Reveal a Primordial Signature Involved in Biomass Accumulation

The functions of key oncogenic transcription factors independent of context have not been fully delineated despite our richer understanding of the genetic alterations in human cancers. The MYC oncogene, which produces the Myc transcription factor, is frequently altered in human cancer and is a major regulatory hub for many cancers. In this regard, we sought to unravel the primordial signature of Myc function by using high-throughput genomic approaches to identify the cell-type independent core Myc target gene signature. Using a model of human B lymphoma cells bearing inducible MYC, we identified a stringent set of direct Myc target genes via chromatin immunoprecipitation (ChIP), global nuclear run-on assay, and changes in mRNA levels. We also identified direct Myc targets in human embryonic stem cells (ESCs). We further document that a Myc core signature (MCS) set of target genes is shared in mouse and human ESCs as well as in four other human cancer cell types. Remarkably, the expression of the MCS correlates with MYC expression in a cell-type independent manner across 8,129 microarray samples, which include 312 cell and tissue types. Furthermore, the expression of the MCS is elevated in vivo in Eμ-Myc transgenic murine lymphoma cells as compared with premalignant or normal B lymphocytes. Expression of the MCS in human B cell lymphomas, acute leukemia, lung cancers or Ewing sarcomas has the highest correlation with MYC expression. Annotation of this gene signature reveals Myc's primordial function in RNA processing, ribosome biogenesis and biomass accumulation as its key roles in cancer and stem cells

Pediatric Measles Vaccine Expressing a Dengue Antigen Induces Durable Serotype-specific Neutralizing Antibodies to Dengue Virus

Dengue disease is an increasing global health problem that threatens one-third of the world's population. Despite decades of efforts, no licensed vaccine against dengue is available. With the aim to develop an affordable vaccine that could be used in young populations living in tropical areas, we evaluated a new strategy based on the expression of a minimal dengue antigen by a vector derived from pediatric live-attenuated Schwarz measles vaccine (MV). As a proof-of-concept, we inserted into the MV vector a sequence encoding a minimal combined dengue antigen composed of the envelope domain III (EDIII) fused to the ectodomain of the membrane protein (ectoM) from DV serotype-1. Immunization of mice susceptible to MV resulted in a long-term production of DV1 serotype-specific neutralizing antibodies. The presence of ectoM was critical to the immunogenicity of inserted EDIII. The adjuvant capacity of ectoM correlated with its ability to promote the maturation of dendritic cells and the secretion of proinflammatory and antiviral cytokines and chemokines involved in adaptive immunity. The protective efficacy of this vaccine should be studied in non-human primates. A combined measles–dengue vaccine might provide a one-shot approach to immunize children against both diseases where they co-exist

Temporal Dynamics of Host Molecular Responses Differentiate Symptomatic and Asymptomatic Influenza A Infection

Exposure to influenza viruses is necessary, but not sufficient, for healthy human hosts to develop symptomatic illness. The host response is an important determinant of disease progression. In order to delineate host molecular responses that differentiate symptomatic and asymptomatic Influenza A infection, we inoculated 17 healthy adults with live influenza (H3N2/Wisconsin) and examined changes in host peripheral blood gene expression at 16 timepoints over 132 hours. Here we present distinct transcriptional dynamics of host responses unique to asymptomatic and symptomatic infections. We show that symptomatic hosts invoke, simultaneously, multiple pattern recognition receptors-mediated antiviral and inflammatory responses that may relate to virus-induced oxidative stress. In contrast, asymptomatic subjects tightly regulate these responses and exhibit elevated expression of genes that function in antioxidant responses and cell-mediated responses. We reveal an ab initio molecular signature that strongly correlates to symptomatic clinical disease and biomarkers whose expression patterns best discriminate early from late phases of infection. Our results establish a temporal pattern of host molecular responses that differentiates symptomatic from asymptomatic infections and reveals an asymptomatic host-unique non-passive response signature, suggesting novel putative molecular targets for both prognostic assessment and ameliorative therapeutic intervention in seasonal and pandemic influenza

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo