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International audience; In chlordecone (CLD)-contaminated soils of the French West Indies, if microbial remediation or a physicochemical remediation process, e.g., in situ chemical reduction, is implemented, concentrations of degradation byproducts, such as hydrochlordecones, are expected to increase in the ecosystems. To study their impact in mixtures with CLD, bioassays were carried out. They consisted in evaluating the regenerative capacity of hydra polyps, from a clone whose phylogenetic analysis confirmed that it belonged to the species Hydra vulgaris Pallas, 1766. Hydra gastric sections were exposed to CLD alone or CLD plus dechlorinated byproducts (CLD-BP) for 96 h to assess regeneration. Based on chromatographic analysis, the CLD-BP mix was composed of the 5-monohydrochlordecone isomer (CAS nomenclature), four dihydrochlordecone isomers, and one trihydrochlordecone isomer representing 50%, 47%, and 3% of the total chromatographic area, respectively. A total of 18 mixtures of CLD and CLD-BP were tested. Six environmental concentrations of CLD (2.10 −4 μM to 4.10 −2 μM) and a similar range of CLD-BP were used. Results from exposures to CLD alone showed the following: (i) a significant decrease in the regenerative capacity of hydra, except at the lowest concentration (2.10 −4 μM); (ii) a concentration-independent deleterious effect. The regeneration scores obtained after the exposure to the addition of CLD-BP were not significantly different from those obtained after exposure to CLD alone. Using an experimental design, a modeling of the regeneration scores of hydra exposed to mixtures is proposed. Interpreted carefully, since they are limited to only one type of bioassay, the present results suggest that the situation in the aquatic environments should not become worse in terms of toxicity, if soil remediation programs resulting in the formation of hydrochlordecones are put in place.; Dans les sols des Antilles françaises contaminés par la chlordécone (CLD), si une remédiation microbienne ou un processus de remédiation physico-chimique, par exemple une réduction chimique in situ, est mise en œuvre, on s'attend à ce que les concentrations de sous-produits de dégradation, tels que les hydrochlordécones, augmentent dans les écosystèmes. Pour étudier leur impact dans les mélanges avec la CLD, des bio-essais ont été réalisés. Ils ont consisté à évaluer la capacité de régénération de polypes d'hydre, à partir d'un clone dont l'analyse phylogénétique a confirmé l'appartenance à l'espèce Hydra vulgaris Pallas, 1766. Des sections gastriques d'hydres ont été exposées à la CLD seule ou à la CLD plus des sous-produits déchlorés (CLD-BP) pendant 96 h pour évaluer la régénération. D'après l'analyse chromatographique, le mélange CLD-BP était composé de l'isomère 5-monohydrochlordécone (nomenclature CAS), de quatre isomères dihydrochlordécone et d'un isomère trihydrochlordécone représentant respectivement 50 %, 47 % et 3 % de la surface chromatographique totale. Au total, 18 mélanges de CLD et de CLD-BP ont été testés. Six concentrations environnementales de CLD (2.10-4 μM à 4.10-2 μM) et une gamme similaire de CLD-BP ont été utilisées. Les résultats des expositions à la CLD seule ont montré ce qui suit : (i) une diminution significative de la capacité de régénération de l'hydre, sauf à la plus faible concentration (2.10-4 μM) ; (ii) un effet délétère indépendant de la concentration. Les scores de régénération obtenus après l'exposition à l'ajout de CLD-BP n'étaient pas significativement différents de ceux obtenus après l'exposition à la CLD seule. À l'aide d'un plan expérimental, une modélisation des scores de régénération des hydres exposés à des mélanges est proposée. Interprétés avec précaution, car limités à un seul type de bioessai, les présents résultats suggèrent que la situation des milieux aquatiques ne devrait pas s'aggraver en termes de toxicité, si des programmes de dépollution des sols entraînant la formation d'hydrochlordécones sont mis en place.

International audience; Prosthetic implants are widely used in dentistry and orthopedics and, as a result, infections can occur which cause their removal. Therefore, it is essential to propose methods of eradicating the bacteria that remain on the prosthesis during treatment. For this purpose, it is necessary to develop surfaces whose antibacterial activity can be controlled. Herein, we designed innovative and smart phosphonium self-assembled monolayer (SAM) interfaces that can be electrically activated on demand for controlling bacterial contaminations on solid surfaces. Upon electroactivation with a low potential (0.2 V for 60 min., conditions determined through a DOE), a successful stamping out of Gram-positive and Gram-negative bacterial strains was obtained with SAM-modified titanium surfaces, effectively killing 95% of Staphylococcus aureus and 90% Klebsiellapneumoniae. More importantly, no toxicity towards eukaryotic cells was observed which further enhances the biocompatible character of these novel surfaces for further implementation.

Chlordecone (CLD), an obsolete insecticide, used in the French West Indies between 1972 and 1993, is persistent in the environment but can be dechlorinated either chemically or under the action of microorganisms. Therefore, if soil remediation programs based on these processes are implemented in areas still contaminated today, those will see their concentrations of dechlorinated derivatives increase and these compounds will be also found in freshwater by streaming, leaching and erosion processes. The purpose of the present study was to evaluate, at environmental concentrations, the toxic effects of mixtures of chlordecone and a three-chlorine substituted byproduct. A hydra clone, which has been confirmed to be Hydra vulgaris Pallas, 1766 has been retained for bioassays where the toxicity has been evaluated by regeneration capacity during exposure. Exposure to mixtures is complex to investigate by classical methods, therefore, an experimental design associated to a mathematical model has been used to predict the effects of all the mixtures and to detect the toxic influence of each compound. The predictive model is discussed regarding the stochastic “endocrine disruptor effect” of CLD. At probable environmental concentrations of the compounds in the mixture, results show that impairment of regeneration capacity is explained mostly by the presence of CLD in the mixtures and support the implementation of remediation programs aimed at dechlorination of this persistent organochlorine pesticide.

International audience; La chlordécone (CLD) est un insecticide organochloré obsolète qui a été utilisé aux Antilles françaisesde 1972 à 1993. Elle est persistante dans l’environnement et se transforme très lentement pardéchloration. En conséquence, elle est encore présente dans les sols mais aussi dans les écosystèmesd’eau douce suite au lessivage, la lixiviation et l’érosion des sols sous l’action des pluies. Dans la mesureoù des programmes de remédiation des sols seraient mis en place dans des zones encore contaminéesaujourd’hui, la concentration des dérivés déchlorés augmenterait alors que celle en CLD diminuerait.L’objet du présent travail est d’évaluer la toxicité de mélanges de CLD et d’un dérivé déchloré, à desconcentrations susceptibles d’être retrouvées dans les eaux de surface, envers un invertébré d’eaudouce modèle. Le dérivé déchloré choisi ici correspond à une tri-hydrochlordécone (CLD-3Cl) qui seforme au cours du procédé de remédiation ISCR (In Situ Chemical Reduction) testé avec succès par leBRGM à l’échelle de la parcelle (Mouvet et al., 2020, https://doi.org/10.1007/s11356-020-07603-z).Pour les essais biologiques de toxicité, le cnidaire Hydra vulgaris a été choisi comme invertébrémodèle. Ces bioessais ont consisté à évaluer la capacité de régénération de cette hydre d’eau douceaprès 96 h d’exposition au mélange CLD + CLD-3Cl. L’impact des mélanges étant complexes à étudierpar les méthodes classiques, la méthode des plans d’expériences a été utilisée pour réduire le nombred’expériences à réaliser sur la plage de concentrations étudiées (0 à 20 μg/L équivalent CLD) sansperdre d’informations et de détecter d’éventuelles interactions entre les composés. Un modèleprédictif de la toxicité du mélange en fonction des différents niveaux de concentrations possibles estproposé ici. Celui-ci permet de conforter le fait que la molécule déchlorée est moins toxique que laCLD et que la présence de dérivés déchlorés en mélange avec cette dernière ne devrait pas engendrerune toxicité supérieure à la CLD seule. Nos résultats montrent que les plans d’expériences sont desoutils très utiles en écotoxicologie et toxicologie environnementale pour évaluer les effets de mélangescomplexes avec de faibles concentrations de xénobiotiques.

The global increase of multidrug resistant bacteria and the lack of new classes of antibiotic especially those targeting Gram-negative pathogens are leaving the clinicians disarmed to treat numerous bacterial infections. Recently, the design of adjuvants able to enhance antibiotics activities appears to be one of the most promising investigated solutions to circumvent this problem. In this context, we have recently identified a new polyamino-isoprenyl derivative NV716 able to potentiate, at a very low concentration the activity of doxycycline against resistant P. aeruginosa bacterial strains by increasing its intracellular concentration. In this study we will report an experimental protocol to optimize a dry powder for inhalation ensuring the simultaneous delivery of an antibiotic (doxycycline) and an adjuvant (the polyaminoisoprenyl derivative NV716 since aerosol therapy could allow a rapid drug administration and target the respiratory system by avoiding the first pass effect and minimizing undesirable systemic effects. Thus, an experimental design was carried out permitting to identify the influence of several factors on the aerosolization efficiency of our combination and allowing us to find the right composition and manufacture leading to the best optimization of the simultaneous delivery of the two compounds in the form of an inhalable powder. More precisely, the powders of the two active ingredients were prepared by freeze drying and their aerosolization was improved by the addition of carrier particles of lactose inhalation grade. Under these conditions, the best formulation was defined by combining the optimal factors leading to the best aerodynamic properties' values (the lowest MMAD (Mass Median Aerodynamic Diameter) and the highest FPF (Fraction of Fine Particles)) without even using sophisticated engineering techniques. Finally, our results suggest that these molecules could be successfully delivered at the requested concentration in the lungs and then able to decrease drug consumption as well as increase treatment efficacy.

International audience; Although the PIG-A gene mutation frequency (MF) is considered a good proxy to evaluate the somatic MF in animals, evidence remains scarce in humans. In this study, a granulocyte PIG-A-mutant assay was evaluated in patients undergoing radiation therapy (RT) for breast cancer. Breast cancer patients undergoing adjuvant RT were prospectively enrolled. RT involved the whole breast, with (WBNRT) or without (WBRT) nodal area irradiation. Blood samples were obtained from participants before (T0) RT, and T1, T2, and T3 samples were collected 3 weeks after the initiation of RT, at the end of RT, and at least 10 weeks after RT discontinuation, respectively. The MF was assessed using a flow cytometry protocol identifying PIG-A-mutant granulocytes. Cytokinesis-blocked micronucleated lymphocyte (CBML) frequencies were also evaluated. Thirty patients were included, and five of them had received chemotherapy prior to RT. The mean (±SD) PIG-A MFs were 7.7 (±12.1) per million at T0, 5.2 (±8.6) at T1, 6.4 (±8.0) at T2 and 3.8 (±36.0) at T3. No statistically significant increases were observed between the PIG-A MF at T0 and the MFs at other times. RT significantly increased the CBML frequencies: 7.9 ‰ (±3.1‰) versus 33.6‰ (±17.2‰) (p < .0001). By multivariate analysis, the CBML frequency was correlated with age at RT initiation (p = .043) and irradiation volume at RT discontinuation (p = .0001) but not with chemotherapy. RT for breast cancer therapy failed to induce an increase in the PIG-A MF. The PIG-A assay in humans needs further evaluation, in various genotoxic exposures and including various circulating human cells.

Enterotoxigenic E. coli (ETEC) is a leading cause of moderate-to-severe diarrhoea. ETEC colonizes the intestine through fimbrial tip adhesin colonization factors and produces heat-stable and/or heat-labile (LT) toxins, stimulating fluid and electrolyte release leading to watery diarrhoea. We reported that a vaccine containing recombinant colonization factor antigen (CfaEB) targeting fimbrial tip adhesin of the colonization factor antigen I (CFA/I) and an attenuated LT toxoid (dmLT) elicited mucosal and systemic immune responses against both targets. Additionally, the toll-like receptor 4 ligand second-generation lipid adjuvant (TLR4-SLA) induced a potent mucosal response, dependent on adjuvant formulation. However, a combination of vaccine components at their respective individual optimal doses may not achieve the optimal immune profile. We studied a subunit ETEC vaccine prototype in mice using a response surface design of experiments (DoE), consisting of 64 vaccine dose-combinations of CfaEB, dmLT and SLA in four formulations (aqueous, aluminium oxyhydroxide, squalene-in-water stable nanoemulsion [SE] or liposomes containing the saponin Quillaja saponaria-21 [LSQ]). Nine readouts focusing on antibody functionality and plasma cell response were selected to profile the immune response of parenterally administered ETEC vaccine prototype. The data were integrated in a model to identify the optimal dosage of each vaccine component and best formulation. Compared to maximal doses used in mouse models (10 µg CfaEB, 1 µg dmLT and 5 µg SLA), a reduction in the vaccine components up to 37%, 60% and 88% for CfaEB, dmLT and SLA, respectively, maintained or even maximized immune responses, with SE and LSQ the best formulations. The DoE approach can help determine the best vaccine composition with a limited number of experiments and may accelerate development of multi-antigen/component ETEC vaccines.

International audience; The efficiency of a versatile in vivo cascade involving a promiscuous alcohol dehydrogenase, obtained from a biodiversity search, and a Baeyer–Villiger monooxygenase was enhanced by the independent control of the production level of each enzyme to produce ε‐caprolactone and 3,4‐dihydrocoumarin. This goal was achieved by adjusting the copy number per cell of Escherichia coli plasmids. We started from the observation that this number generally correlates with the amount of produced enzyme and demonstrated that an in vivo multi‐enzymatic system can be improved by the judicious choice of plasmid, the lower activity of the enzyme that drives the limiting step being counter‐balanced by a higher concentration. Using a preconception‐free approach to the choice of the plasmid type, we observed positive and negative synergetic effects, sometimes unexpected and depending on the enzyme and plasmid combinations. Experimental optimization of the culture conditions allowed us to obtain the complete conversion of cyclohexanol (16 mM) and 1‐indanol (7.5 mM) at a 0.5‐L scale. The yield for the conversion of cyclohexanol was 80% (0.7 g ε‐caprolactone, for the productivity of 244 mg·L −1·h −1) and that for 1‐indanol 60% (0.3 g 3,4‐dihydrocoumarin, for the productivity of 140 mg·L −1·h −1).

Selection methods are commonly used to retain only the least correlated variables when data are described by a large number of variables. However, most of the currently available variable selection methods do not take the intrinsic quality of the subset retained into account. In this paper, we propose a new approach based on a multicriteria selection of variables. The intrinsic quality of the selected subset was assessed based on both criteria calculated from the model matrix and the procrustes analysis. This verification guarantees a good estimation of the coefficients for the model and a good representativity. This approach was applied to two cases: a benchmark dataset known as Coffee data and a real dataset produced by a study of quantitative structure–activity relationship. In both cases, the solutions were representative of the initial set and displayed good intrinsic quality, these solutions will therefore be useable in the modeling step.

Quality by Design is a recent concept from quality control which has led to new requirements demanded by the authorities, particularly in the pharmaceutical industry. Among these, the guideline ICHQ8 explains that quality cannot be tested into products but should be built in by design. Designs of Experiments have been used to establish the relationship between input and output parameters of a process or formula while minimizing the risk in the final decision. More precisely, modelling studies are carried out to better understand the process and to predict the outputs in the whole domain of interest. When there are many input and output parameters, the experimenter looks for a compromise zone in which all the output parameters comply with the specifications. In this area, we can define a region where all the inputs can vary without altering the quality of the product with a fixed probability that the objectives will be reached. This zone is called Design Space and the determination of their boundaries is recommended by the Food and Drug Administration. In this publication, we propose different methods such as Monte-Carlo method, Bootstrap technique, numerical approach and reliability method to determine the Design Space. A comparison study is achieved using a case study.

In the field of formulation, the behaviour of phenomena studied are often complex, including non-linear or chaotic zones which make classical strategies based on polynomial models inappropriate. In these situations, uniform experimental designs and kriging models are recommended. Nonetheless, when researchers have to set up an experimental strategy, they must choice the class of designs to be constructed, the number of experiments to be performed and the modeling kriging parameters to be used. To help with these choices, we propose a catalogue combining various uniform designs characterized by several intrinsic quality criteria and to establish decision-making rules linking these criteria to the quality of the information obtained from the design.

International audience; Solid-state fermentation (SSF) is a cultural method that holds tremendous potentials for the production of numerous microbial value-added compounds in various industries. As for every other process, experimental designs can provide tools to improve the product yields, diminish the production time and thus eventually decreasing the cost of the whole process. However, SSF, because of its solid nature, implies some constraints which consequently require specific tools to efficiently overcome them. The aim of this study was the improvement of the production of antioxidant naphtho-gamma-pyrones produced by Aspergillus niger G131 cultivated using SSF. Two experimental designs were presented, a combined design, taking into account two different types of variables to determine a proper solid medium, and a screening design with mixed-level factors to find solutes with significant positive effects on the output.

International audience; Uniform experimental designs (Space Filling Designs) are now widely used with independent variables, particularly in numerical simulation. A lot of construction methods have been developed to uniformly cover the domain of variables, but they remain rarely applied for the study of mixtures. In this article, we propose methods to build space-filling designs for mixtures that can be used to modelize complex phenomena in formulation. Various algorithms like Kennard and Stone, WSP, Strauss and Dmax algorithms, to construct these designs are detailed and compared with respect to uniformity criteria.

International audience; For the first time, Polyporus brumalis BRFM985 was cultivated on wheat straw to investigate the simultaneous effects of pretreatment parameters on anaerobic digestion: these include initial substrate humidity, temperature, duration, and metal supplementation. Surface response methodology was applied to quantify the importance of each parameter, as well as the synergistic effects between them. Firstly, metal addition and secondly, pretreatment duration, both resulted in a positive impact. According to calculations, the highest methane production (182 dm3 of methane per kilogram of initial Total Solids) is associated to pretreatment with metal addition during 20 days. In comparison with the least optimal conditions (118 dm3.kg−1 without metal addition, during 15 days), this result implies a 52% increase.

International audience; Drug/lense combinations have proven significant in the field of ocular therapeutics. The development of innovative systems and elaboration processes is an upcoming issue for ocular drug delivery. One challenging issue is the elaboration of drug loaded intraocular lenses (IOLs) to combine cataract surgery and post-operative treatments in a single procedure. In this work, we are studying the elaboration of such systems while using a green process using supercritical fluids for impregnating ophthalmic drugs on commercial IOLs. More particularly, rigid commercial intraocular lenses made from Poly (Methyl MethAcrylate) (PMMA), used in cataract surgery, are loaded with dexamethasone 21- phosphate disodium salt (DXP, an anti-inflammatory drug) and ciprofloxacin (CIP, an antibiotic) in order to prevent short- and mid-term postoperative complications.Supercritical impregnations were carried out in a batch mode and impregnation yields were determined through drug release kinetic studies in a solution simulating the aqueous humor. Before performing an experimental design, preliminary impregnation assays were conducted in order to delimit the operating domain. Transparent IOLs presenting an effective impregnation were obtained. The highest impregnation yields for DXP and CIP in PMMA IOLs were 18.3 and 2.8 μgdrug/mgIOL respectively. Despite the low solubility of each drug in the fluid phase, homogeneous and in-depth impregnations were successfully obtained with a prolonged drug delivery (about 40 days) for most impregnation experiments.

The purpose of this work was to optimize the pretreatment process of wheat straw by Polyporus brumalis_BRFM985 in order to improve carbohydrate accessibility for more efficient bioconversion. Indeed, there is growing demands to develop sustainable routes for lignocellulosic feedstocks valorization into value‐added products in energy, chemicals, materials, and animal feed fields. To be achieved, implementation of cheap and ecofriendly biomass pretreatment processes is necessary. In this frame, white rot basidiomycetes, well known for their ability to degrade lignin efficiently and selectively, are of great interest. The pretreatment of wheat straw by Polyporus brumalis_BRFM985 was performed in packed bed bioreactor and optimized using response surface methodology. The four pretreatment parameters optimized were metals addition (Cu, Mn, and Fe), time of culture, initial water content, and temperature. Multicriteria optimization highlighted that wheat straw pretreatment by Polyporus brumalis_ BRFM985 in the presence of metals with high initial water content of 3.6 g H2O/g at 27°C for 15–16 days led to an improvement of carbohydrate accessibility with minimal matter loss.

A high quality activated carbon has been obtained, by physical activation with steam, from a Moroccan agricultural by-product (Argan shells) and their characteristics were investigated. In order to optimize experimental conditions of the preparation, a combination of a fractional factorial design and a Doehlert design was applied. In the first step of this work, a two-level fractional factorial design 2 (5–1) was used to study effects and first order interactions of various factors such as atmosphere in carbonization step, carbonization time at 400 °C, activation temperature, activation time and steam flow. The results reveal that the most influential factors on the yield and the methylene blue adsorption are activation temperature, activation time, steam flow and the presence of a significant interaction between activation temperature and activation time in both cases. In the second step, activation temperature and activation time were optimized using Response Surface Methodology with a Doehlert design, and Desirability function. The optimal conditions for the preparation of activated carbon have been identified to be an activation temperature of 880 °C, an activation time of 96 min and steam flow fixed at this positive level of 0.2 cm 3 min − 1 . The characteristics of prepared activated carbon obtained at the optimal conditions were determined using adsorption capacity of methylene blue, iodine and phenol, BET surface area, pHpzc, and surface functions based on Boehm method. Those characteristics (MB adsorption: 608.9 mg g − 1 , iodine adsorption: 1026.4 mg g − 1 , phenol adsorption: 633.3 mg g − 1 , BET surface area: 1292 m 2 g − 1 ) were shown greater than those of a commercial activated carbon used in water treatment and those reported by other researchers studying activated carbon preparation from various solid wastes by steam activation method. On the other hand, this work showed that Argan shells are a good precursor for the production of activated carbon, by steam physical activation, with high performance to be used in water treatment applications.

International audience; We propose a new method to treat supersaturated designs which relies on the multivariate CCSWA (Common Components and Specific Weights Analysis), or ComDim, method. This method can be applied through two approaches. The first considers this method as a novel procedure to analyse supersaturated designs. This can reveal influential factors, and correctly identify the active factors even when the results do not fully comply with the standard hypotheses (sparsity). The second approach extracts the information common to the results obtained using a wide range of methods to analyse the designs. This could make it possible to overcome the errors specific to each of these methods.

International audience; The drug delivery through intraocular lenses (IOLs) allows the combination of cataract surgery act and postoperative treatment in a single procedure. In order to prepare such systems, “clean” supercritical CO2 processes are studied for loading commercial IOLs with ophthalmic drugs. Ciprofloxacin (CIP, an antibiotic) and dexamethasone 21-phosphate disodium (DXP, an anti-inflammatory drug) were impregnated into foldable IOLs made from poly-2-hydroxyethyl methacrylate (P-HEMA). A first pre-treatment step was conducted in order to remove absorbed conditioning physiological solution. Supercritical impregnations were then performed by varying the experimental conditions. In order to obtain transparent IOLs and avoid the appearance of undesirable foaming, it was necessary to couple slow pressurization and depressurization phases during supercritical treatments. The impregnation yields were determined through drug release studies. For both drugs, release studies showdeep and reproducible impregnation for different diopters.For the system P-HEMA/CIP, a series of impregnations was performed to delimit the experimental range at two pressures (80 and 200 bar) in the presence or absence of ethanol as a co-solvent for two diopters (+5.0 D and +21.0 D). Increase in pressure in the absence of a co-solvent resulted in improved CIP impregnation. The addition of ethanol (5 mol%) produced impregnation yields comparable to those obtained at 200 bar without co-solvent. A response surface methodology based on experimental designs was used to study the influence of operating conditions on impregnation of IOLs (+21.0 D) in the absence of co-solvent. Two input variables with 5 levels each were considered; the pressure (80–200 bar) and the impregnation duration (30–240 min). CIP impregnation yields ranging between 0.92 and 3.83 μgCIP/mgIOL were obtained from these experiments and response surface indicated the pressure as a key factor in the process.The DXP impregnation in P-HEMA was higher than CIP at all the tested conditions (8.50–14.53 μgDXP/mgIOL). Furthermore, unlike CIP, highest DXP impregnation yields were obtained in the presence of ethanol as a co-solvent (5 mol%). NMR spectroscopy was performed to confirm complete removal of ethanol in the co-solvent-treated IOLs

We report a numerical study on sunscreen design and optimization. Thanks to the combined use of electromagnetic modeling and design of experiments, we are able to screen the most relevant parameters of mineral filters and to optimize sunscreens. Several electromagnetic modeling methods are used depending on the type of particles, density of particles, etc. Both the sun protection factor (SPF) and the UVB/UVA ratio are considered. We show that the design of experiments' model should include interactions between materials and other parameters. We conclude that the material of the particles is a key parameter for the SPF and the UVB/UVA ratio. Among the materials considered, none is optimal for both. The SPF is also highly dependent on the size of the particles.

International audience; The water framework directives (WFD 2000/60/EC and 2013/39/EU) force European countries to monitor the quality of their aquatic environment. Among the priority hazardous substances targeted by the WFD, short chain chlorinated paraffins C-10-C-13 (SCCPs), still represent an analytical challenge, because few laboratories are nowadays able to analyze them. Moreover, an annual average quality standards as low as 0.4 mu g L-1 was set for SCCPs in surface water. Therefore, to test for compliance, the implementation of sensitive and reliable analysis method of SCCPs in water are required. The aim of this work was to address this issue by evaluating automated solid phase micro-extraction (SPME) combined on line with gas chromatography-electron capture negative ionization mass spectrometry (GC/ECNI-MS). Fiber polymer, extraction mode, ionic strength, extraction temperature and time were the most significant thermodynamic and kinetic parameters studied. To determine the suitable factors working ranges, the study of the extraction conditions was first carried out by using a classical one factor-at-a-time approach. Then a mixed level factorial 3 x 2(3) design was performed, in order to give rise to the most influent parameters and to estimate potential interactions effects between them. The most influent factors, i.e. extraction temperature and duration, were optimized by using a second experimental design, in order to maximize the chromatographic response. At the close of the study, a method involving headspace SPME (HS-SPME) coupled to GC/ECNI-MS is proposed. The optimum extraction conditions were sample temperature 90 degrees C, extraction time 80 min, with the PDMS 100 mu m fiber and desorption at 250 degrees C during 2 min. Linear response from 0.2 ng mL(-1) to 10 ng mL(-1) with r(2) = 0.99 and limits of detection and quantification, respectively of 4 pg mL(-1) and 120 pg mL(-1) in MilliQ water, were achieved. The method proved to be applicable in different types of waters and show key advantages, such as simplicity, automation and sensitivity, required for the monitoring programs linked to the WFD. (C) 2015 Elsevier B.V. All rights reserved.

International audience; In the field of keratoconus treatment, a lipid-based liquid crystal nanoparticles system has been developed to improve the preocular retention and ocular bioavailability of riboflavin, a water-soluble drug. The formulation of this ophthalmic drug delivery system was optimized by a simplex lattice experimental design. The delivery system is composed of three main components that are mono acyl glycerol (monoolein), poloxamer 407 and water and two secondary components that are riboflavin and glycerol (added to adjust the osmotic pressure). The amounts of these three main components were selected as the factors to systematically optimize the dependent variables that are the encapsulation efficiency and the particle size. In this way, 12 formulas describing experimental domain of interest were prepared. Results obtained using small angle X-rays scattering (SAXS) and cryo-transmission electron microscopy (cryo-TEM) evidenced the presence of nano-objects with either sponge or hexagonal inverted structure. In the zone of interest, the percentage of each component was determined to obtain both high encapsulation efficiency and small size of particles. Two optimized formulations were found: F7 and F1. They are very close in the ternary phase diagram as they contain 6.83% of poloxamer 407; 44.18% and 42.03% of monoolein; 46.29% and 48.44% of water for F7 and F11, respectively. These formulations displayed a good compromise between inputs and outputs investigated.

International audience; Various industrial processes and anthropogenic activities in urban areas induce a release of metals, metalloids and organic pollutants. Phytoremediation of co-contaminated waters in constructed wetlands is a promising solution for reducing the impact on natural environments. In order to improve the design and management of constructed wetlands, more knowledge is needed concerning the effect of organic pollutants on plant metal and metalloid uptake. In this study, the effects of a mixture of organic pollutants commonly found in industrial effluents (hydrocarbons, polycyclic aromatic hydrocarbons, anionic detergent) on the uptake of ten metals and metalloids (MM), i.e. Al, As, Cd, Cr, Cu, Fe, Mn, Ni, Pb, and Zn, by five helophytes having a wide European distribution were studied. Main effects of plant species and pollutant conditions on metal uptake and interactions between factors were determined by a statistical treatment of a microcosm experiment. Overall, the order of element uptake in plants was Fe > Al > Mn > Cr, Ni, Zn, > Cu > As, Cd, Pb, which was consistent with relative concentrations in the rhizosphere environment of microcosms. Larger amounts of metals were retained in belowground biomass of plants than in aboveground parts. Statistical analysis showed that organic pollutants enhanced the accumulation of Mn in whole plants and the retention of Fe in belowground parts, while they reduced the accumulation of Cd, Ni, and Zn in whole plants and the retention of Cu in belowground parts. For the other MM (Al, As, Cr, Pb), effects were variable, depending on the plant species. Among the five plants tested, Carex cuprina generally removed the highest quantities of MM, which was the result of both a high metal accumulation capacity and high biomass production. Nevertheless, no significant proportion of the MM total loading could be removed in plants aboveground parts. (C) 2014 Elsevier Ltd. All rights reserved.

International audience; To develop self-assembled liquid crystalline nanoparticles as a drug delivery system for keratoconus treatment, a formulation containing riboflavin a water-soluble drug, two surfactants (poloxamer 407 and mono acyl glycerol -monoolein-) and water was optimized and prepared by emulsification and a homogenization process. A fractional factorial design was applied to estimate the main effects and interaction effects of five parameters on two responses, namely particle size and encapsulation efficiency. The five parameters are the temperature of the two phases, the duration of emulsification, the presence of heating during homogenization, the number of passes and pressure. The most influent parameters are the presence of heating during the homogenization and the pressure that led to the production of nanoparticles with an average size of 145 nm and an average encapsulation efficiency of 46%.

In a context of global climate change, optimizing the management of agricultural resources, and in particular the mineral elements in soils, has become a major challenge. Mineral elements are at the same time indispensable resources for plant growth and carbon storage, potential pollutants in certain environmental compartments, and potentially toxic contaminants that can be transferred from plants to humans. Current methods for the determination of these elements are very costly in terms of time and money, and from an operational point of view, it is difficult in these conditions to carry out a frequent diagnosis in the field of a deficiency or contamination situation, or to characterize the spatio-temporal variability of the characteristics of an agricultural land.The recent emergence of portable sensors and systems has made it possible to develop new methods for measuring soil and plant properties and to complement or replace conventional laboratory techniques. This is the case of LIBS, a method of atomic emission spectroscopy from a laser-generated plasma, which is fast and green as it does not rely on the use of hazardous chemical reagents. The objective of this study is to evaluate the performance of the LIBS method, and more precisely of a portable instrument, applied to the quantitative multi-elemental analysis of plant and agricultural soil samples. The evaluation of this method takes into account the sample preparation and processing steps of LIBS spectra. It was implemented according to three axes: i. The characterization of plant samples of various species under ideal conditions, ii. The characterization of soil samples representative of the major French agricultural crops (wheat, corn, sunflower) always under ideal conditions and iii. The study of the impact of factors degrading the measurement conditions in order to evaluate the possibility of implementing the LIBS technique outside the laboratory.Our study, based on the use of the SciAps Z300 LIBS, allowed the detection of the elements C, Ca, Fe, K, Mg, Na, Si and P, concentrated in the g/kg range in soil and plant samples, both in laboratory conditions and in deliberately degraded conditions. On the other hand, neither nitrogen nor the elements Cd, Cu, Mn and Zn could be detected in these samples. For the analysis of plant samples, the elements Ca, Fe, Mg, Na, and P were quantified using univariate regression models coupled with an adapted normalization strategy. Quantitative soil analysis required the use of PLS models to account for matrix effects. As regards the analyses in degraded conditions, we established, using an experimental design, that the moisture content, higher than 40% in plants and 20% in soils was one of the main obstacles to LIBS field analyses. We also showed that the drop in LIBS signal observed when the moisture content increases could be corrected by applying a normalization step.The results of our study are partially satisfactory in terms of the quantitative performance of the regression models, even under ideal laboratory conditions. The diversity of physico-chemical conditions encountered in the field means that direct LIBS analyses are clearly not realistic. The principle of a field laboratory, with simplified sample preparation, could however be envisaged, in order to place the LIBS technique at the heart of new sampling strategies in the context of precision agriculture.; Dans un contexte de changement climatique mondial, l’optimisation de la gestion des ressources agricoles, et en particulier des éléments minéraux des sols, est devenue un enjeu majeur. Les éléments minéraux sont à la fois des ressources indispensables pour la croissance des végétaux et le stockage du carbone, des polluants potentiels de certains compartiments de l'environnement, et des contaminants potentiellement toxiques susceptibles d'être transférés depuis les végétaux jusqu'à l'homme. Les méthodes actuelles de dosage de ces éléments sont très coûteuses en temps et en argent et d’un point de vue opérationnel, il est difficile dans ces conditions de réaliser un diagnostic fréquent sur le terrain d’une situation de carence ou de contamination, ou encore de caractériser la variabilité spatio-temporelle des caractéristiques d’une parcelle agricole.L’émergence récente de capteurs et de systèmes portatifs a permis de développer de nouvelles méthodes pour mesurer les propriétés du sol et de la plante et compléter ou remplacer les techniques conventionnelles de laboratoire. C’est le cas de la LIBS, méthode de spectroscopie d’émission atomique à partir d’un plasma créé par laser, rapide et verte dans la mesure où elle ne s’appuie pas sur l’usage de réactifs chimiques dangereux. L’objectif de cette étude est d’évaluer les performances de la méthode LIBS, et plus précisément d’un instrument portable, appliquée à l’analyse multi-élémentaire quantitative d’échantillons de plantes et de sols agricoles. L’évaluation de cette méthode prend en compte la préparation des échantillons et les étapes de traitement des spectres LIBS. Elle a été mise en œuvre selon trois axes : i. La caractérisation des échantillons de plante d’espèces variées dans des conditions idéales, ii. La caractérisation des échantillons de sols représentatifs des grandes cultures françaises agricoles (blé, tournesol) toujours dans les conditions idéales et iii. L’étude de l’impact de facteurs dégradant les conditions de mesure afin d’évaluer la possibilité de mise en œuvre de la technique LIBS en dehors du laboratoire.Notre étude, basée sur l’utilisation du pistolet LIBS Z300 de SciAps, a permis de détecter les éléments C, Ca, Fe, K, Mg, Na, Si et P, concentrés dans la gamme du g/kg dans les échantillons de sols et de plantes, aussi bien en conditions de laboratoire qu’en conditions volontairement dégradées. En revanche, ni l’azote, ni les éléments Cd, Cu, Mn et Zn n’ont pu être détectés dans ces échantillons. En ce qui concerne l’analyse des échantillons de plantes, les éléments Ca, Fe, Mg, Na, et P, ont été quantifiés à l’aide de modèles de régression univariés couplés à une stratégie de normalisation adaptée. L’analyse quantitative des sols a nécessité quant à elle, l’emploi de modèles PLS, afin de prendre en compte les effets de matrice, et d’obtenir des modèles d’étalonnage satisfaisants pour les éléments Mg, Na et Fe. En ce qui concerne les analyses en conditions dégradées, nous avons établi, à l’aide d’un plan d’expériences, que le taux d’humidité, supérieur à 40% dans les plantes et à 20% dans les sols était l’un des principaux freins aux analyses LIBS de terrain. Nous avons aussi montré que la baisse de signal LIBS observée lorsque le taux d’humidité augmente pouvait être corrigée en appliquant une étape de normalisation.Le bilan de notre étude est partiellement satisfaisant sur le plan des performances quantitatives des modèles de régression, y compris dans les conditions idéales de laboratoire. La diversité des conditions physico-chimiques rencontrées sur le terrain fait que les analyses LIBS directes ne sont clairement pas réalistes. Le principe d’un laboratoire de campagne, avec une préparation simplifiée des échantillons, pourrait cependant être envisagé, afin de pouvoir placer la technique LIBS au cœur de nouvelles stratégies d’échantillonnage dans le contexte de l’agriculture de précision.

Technological progress has now made many experiments (or simulations) possible, along with taking into account a large number of parameters, which result in (very) high-dimensional matrix requiring the development of new tools to assess and visualize the data and, if necessary, to reduce the dimension. The quality of the information provided by all points of a database or an experimental design can be assessed using criteria based on distances that will inform about the uniformity of repartition in a multidimensional space. Among the visualization methods, Curvilinear Component Analysis has the advantage of projecting high-dimensional data in a two-dimensional space with respect to the local topology. This also enables the detection of clusters of points or gaps. The dimensional reduction is based on a judicious selection of subsets of points or variables, via accurate algorithms. The performance of these methods was assessed on case studies of QSAR, spectroscopy and numeric simulation.; L'évolution des technologies actuelles permet de traiter un grand nombre d'expériences (ou de simulations) et d'envisager un nombre important de paramètres. Cette situation conduit à des matrices de grande, voire très grande, dimension et nécessite le développement de nouveaux outils pour évaluer et visualiser ces données et, le cas échéant, en réduire la dimension. L'évaluation de la qualité de l'information apportée par l'ensemble de points constituant une base de données ou un plan d'expériences peut se faire au travers de critères basés sur des calculs de distance, qui renseigneront sur l'uniformité de la répartition dans l'espace multidimensionnel. Parmi les méthodes de visualisation, l'Analyse en Composantes Curvilignes a l'avantage de projeter des données en grande dimension dans un espace bidimensionnel en préservant la topologie locale, ce qui peut aider à détecter des amas de points ou des zones lacunaires. La réduction de dimension s'appuie sur une sélection judicieuse de sous-ensembles de points ou de variables, via des algorithmes. Les performances de ces méthodes ont été évaluées sur des cas d'étude issus des études QSAR, de la spectroscopie et de la simulation numérique.