Experimental design approach for deposition optimization of RF sputtered chalcogenide thin films devoted to environmental optical sensors.

The development of the optical bio-chemical sensing technology is an extremely important scientific and technological issue for diagnosis and monitoring of diseases, control of industrial processes, environmental detection of air and water pollutants. Owing to their distinctive features, chalcogenide amorphous thin films represent a keystone in the manufacture of middle infrared integrated optical devices for a sensitive detection of biological or environmental variations. Since the chalcogenide thin films characteristics, i.e. stoichiometric conformity, structure, roughness or optical properties can be affected by the growth process, the choice and control of the deposition method is crucial. An approach based on the experimental design is undoubtedly a way to be explored allowing fast optimization of chalcogenide film deposition by means of radio frequency sputtering process. Argon (Ar) pressure, working power and deposition time were selected as potentially the most influential factors among all possible. The experimental design analysis confirms the great influence of the Ar pressure on studied responses: chemical composition, refractive index in near-IR (1.55 µm) and middle infrared (6.3 and 7.7 µm), band-gap energy, deposition rate and surface roughness. Depending on the intended application and therefore desired thin film characteristics, mappings of the experimental design meaningfully help to select suitable deposition parameters.

Drug loading of foldable commercial intraocular lenses using supercritical impregnation.

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 show deep 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 µg CIP/mg IOL 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 µg DXP/mg IOL). 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.

Parameters optimization using experimental design for headspace solid phase micro-extraction analysis of short-chain chlorinated paraffins in waters under the European water framework directive.

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 C10-C13 (SCCPs), still represent an analytical challenge, because few laboratories are nowadays able to analyze them. Moreover, an annual average quality standards as low as 0.4µgL(-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 3×2(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°C, extraction time 80min, with the PDMS 100µm fiber and desorption at 250°C during 2min. Linear response from 0.2ngmL(-1) to 10ngmL(-1) with r(2)=0.99 and limits of detection and quantification, respectively of 4pgmL(-1) and 120pgmL(-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.

Fractions of Rechtschaffner matrices as supersaturated designs in screening experiments aimed at evaluating main and two-factor interaction effects.

Optimal fractions of resolution V design matrices proposed by Rechtschaffner in 1967 are developed and applied as supersaturated designs in screening experiments. Rechtschaffner matrices allow evaluation of all main factors and two-factor interactions, which in many real-world studies are of practical significance. However, the number of experimental runs increases rapidly with the number of factors in the matrices, which are therefore impractical for more than 5-6 factors. On the contrary, saturated fractions based on Hadamard matrices, which are commonly applied in screening studies, cannot evaluate the interaction effects. Here, a procedure for selecting the optimum fractions of Rechtschaffner matrices is presented and provides supersaturated matrices that are well adapted to a variety of problems, thus allowing the development of screening studies with a relatively small number of experiments. The procedures developed to derive the size-reduced matrices and to evaluate the active factors are discussed and compared in terms of efficiency and reliability, by means of simulation studies and application to a real problem. These fractions are the first supersaturated design matrices capable of estimating interaction effects. Additionally, one important advantage of these supersaturated matrices is that they enable development of follow-up procedures in cases of inconclusive results, by enlarging the matrix and eventually resolving the full Rechtschaffner matrix of departure when it is necessary to evaluate the active factors and their interactions.

Investigation of gamma radiation effect on the anion exchange resin Amberlite IRA-400 in hydroxide form by Fourier transformed infrared and 13C nuclear magnetic resonance spectroscopies.

Radiation-induced decomposition of the anion exchange resin Amberlite IRA-400 in hydroxide form by gamma radiolysis has been studied under different irradiation doses and irradiation atmospheres. In this work, we focused on the degradation of the solid part of the resin by Fourier transformed infrared (FTIR) and (13)C nuclear magnetic resonance (NMR) spectroscopies associated with chemometric treatments. FTIR and (13)C NMR techniques showed that only -CH(2)N(+)(CH(3))(3) groups were detached from the resin whereas the polystyrene divinylbenzene backbone remains intact. The quaternary ammonium groups were replaced by amine or carbonyl groups according to the irradiation atmosphere (with or without water or oxygen). Principal components analysis (PCA) was used to classify the degraded resins according to their irradiation conditions by separating the effect of the dose or the environment. The PCA loadings have shown spectral regions which discriminate the irradiated resins whereas SIMPLe-to-use Interactive Self-modeling Mixture Analysis (SIMPLISMA) allows to identify families of component characterizing the chemical structure of resins and estimate their relative contributions according to the irradiation atmospheres.

A starch-based microparticulate system dedicated to diagnostic and therapeutic nuclear medicine applications.

The aim of this work was to develop a new microparticulate system able to form a complex with radionuclides with a high yield of purity for diagnostic or therapeutic applications. Owing to its properties potato starch was chosen as starting material and modified by oxidization and coupling of a ligand (polyamine) enabling modified starch to chelate radionuclides. The choice of suitable experiments was based on a combination of a Rechtschaffner experimental design and a surface response design to determine the influence of experimental parameters and to optimize the final product. Starch-based microparticle formulations from the experimental plans were compared and characterized through particle size analysis, scanning electron microscopy, elemental analysis and, for the most promising formulations, by in vitro labeling stability studies and determination of free polyamine content or in vivo imaging studies. The mechanism of starch-based microparticle degradation was identified by means of size measurements. The results of the Rechtschaffner design showed the positive qualitative effect of the temperature and the duration of coupling reaction whereas surface response analysis clearly showed that, by increasing the oxidization level and starch concentration, the nitrogen content in the final product is increased. In vitro and in vivo characterization led to identification of the best formulation. With a size around 30 µm, high radiochemical purity (over 95%) and a high signal-to-noise ratio (over 600), the new starch-based microparticulate system could be prepared as ready-to-use kits and sterilized without modification of its characteristics, and thus meet the requirement for in vivo diagnostic and therapeutic applications.

Optimization of a culture medium for the differentiation of preadipocytes into adipocytes in a monolayer.

UNLABELLED: Our objective was to optimize a medium for preadipocyte differentiation into adipocytes. METHODS: The differentiation medium contains fixed components as well as 7 variable ones. To perform this study, different experiments were designed and the study was carried out in 4 stages. The first two stages tested the influence of serum, dexamethasone, hydrocortisone and an cAMP activator. In the third stage, two new variables were added: rosiglitazone and insulin. In the final stage, the medium selected in stage 3 was validated. The differentiation selection criteria consisted of the number of mature adipocytes and adiponectin secretion. RESULTS: We have shown that each variable was indispensable and that positive interactions occurred between some variables. No negative interactions were found and it was possible to optimize the concentration of each variable. CONCLUSIONS: We selected the following medium, which provides optimal adipocyte size and adiponectin secretion: DMEM/HAMF12+10% Foetal Clone Serum (FCS)+2 nM triiodothyronine+10 nM hydrocortisone +0.5 mM IsoButyl Methyl Xanthine (IBMX)+500 nM dexamethasone+1 microM rosiglitazone+0.15 UI/ml insulin+antibiotics.

Multivariate optimization of solid-phase extraction applied to iron determination in finished waters.

In this work, Amberlite XAD-4 resin functionalized with salicylic acid was synthetized, characterized and applied as a new packing material for an on-line system to iron determination in aqueous samples. The detection method is based on the sorption of Fe(III) ions in a minicolumn containing the synthesized resin, followed by a desorption step using an acid solution and measurement of iron by vis-spectrophotometry (CAS method). The optimization of the solid-phase extraction system was performed using factorial design and Doehlert matrix considering six variables: sample percolation rate (0.5-9 ml min(-1)), sample metal concentration (20-200 microg l(-1)), flow-through sample volume (0-5 ml) (all three directly linked to the extraction step), elution flow-rate (0.5-9 ml min(-1)), concentration and volume of eluent (HCl 0.1-0.5M) (all three directly linked to the elution step). The aim of this study was to obtain a set of operating ranges for the six variables tested in order to obtain--by means of a mathematical function allowing maximisation of each response (desirability function)--at least 90% of iron recovery rates. Using the experimental conditions defined in the optimization, the method allowed iron determination with achieved detection limit of 2.3 microgl(-1) and precision (assessed as the relative standard deviation) of 9.3-2.8% for iron solutions of 10.0-150 microgl(-1). Real samples (coming from a water treatment unit) were used successfully when evaluating potentialities of the developed SPE procedure coupled to a spectrophotometric determination.

An experimental design approach for optimizing polycyclic aromatic hydrocarbon analysis in contaminated soil by pyrolyser-gas chromatography-mass spectrometry.

Pyrolyser-gas chromatography-mass spectrometry was used to analyze polycyclic aromatic hydrocarbons in contaminated soil without preliminary extraction. Experimental research methodology was used to obtain optimal performance of the system. After determination of the main factors (desorption time, Curie point temperature, carrier gas flow), modeling was done using a Box-Behnken matrix. Study of the response surface led to factor values that optimize the experimental response and achieve better chromatographic results.

An experimental design to optimize the flow extraction parameters for the selective removal of Fe(III) and Al(III) in aqueous samples using salicylic acid grafted on Amberlite XAD-4 and final determination by GF-AAS.

In this paper, a multivariable approach has been applied for the selective removing of Fe(III) and Al(III), in the range 0-200 microg l(-1), in water samples onto a modified organic support (salicylic acid grafted on XAD-4). An empirical mathematical model was designed which establishes the relationship between the variation of the responses (extraction yields), and the variation of three factors (sample volume, sample percolation flow rate and amount of metallic ions present in the sample). To estimate the coefficients of the developed model, an uniform shell Doehlert design has been applied; these experiments consisted in GF-AAS determination of aluminium and iron amounts in eluates after percolation of samples through modified support. Results show a similar behaviour of the resin towards aluminium and iron with a preponderant effect of the percolation flow rate value; however this one is crucial for aluminium extraction and should be maintained below to 0.55 ml min(-1) to reach a 95% Al3+ extraction yield (versus 2.25 ml min(-1) for Fe3+). The optima determined by this experimental design approach have been further applied to the selective extraction of aluminium and iron from multielement synthetic samples and from real samples at the outlet of potable water treatment units.

Experimental design approach for the solid-phase extraction of residual aluminium coagulants in treated waters.

Solid-phase extraction (SPE) of trace elements before their analysis has become a conventional pretreatment step of analytes because of their frequent low concentrations in numerous samples. Additionally, interfering compounds often accompagny analytes of interest, thus requiring a clean-up step. The preconcentration step and/or matrix removal can be efficiently improved by chemometric approaches allowing obtention of reliable results. Single variable approach is often used but is time and cost consuming, and may be the source of mistakes; multivariable approach allows to overcome these problems and increases the probability of global optimum finding. In order to obtain a set of experimental conditions for the selective extraction of Al(III) in water samples, onto a modified organic support (salicylic acid grafted on XAD-4), a multicriteria approach (response surface methodology) has been applied. The extraction method was optimized by the aid of a factorial design and a uniform shell Doehlert design for six variables: sample percolation flow rate, trace metal amount, sample volume, concentration and volume of HCl used for elution of aluminium. Results demonstrate the synergic effects of four factors and allow us to define working ranges for each parameter tested. The designed SPE procedure was then sucessfully applied to synthetic and real samples, issued from a potable water treatment unit.

Oxygen-related band gap state in single crystal rubrene.

A molecular exciton signature is established and investigated under different ambient conditions in rubrene single crystals. An oxygen-related band gap state is found to form in the ambient atmosphere. This state acts as an acceptor center and assists in the fast dissociation of excitons, resulting in a higher dark and photoconductivity of oxidized rubrene. The band gap state produces a well-defined photoluminescence band at an energy 0.25 eV below the energy of the 0-0 molecular exciton transition. Two-photon excitation spectroscopy shows that the states are concentrated near the surface of naturally oxidized rubrene.

Texture optimization of water-in-oil emulsions.

The aim of this research is to demonstrate the effect of variations in certain parameters of the oily phase (OP) in water-in-oil (W/O) emulsions on rheological and texture properties of finished products. The formulated emulsions were selected according to an optimal experimental procedure. The applied variations were nature of the OP, its volume fraction, the hydrophilic-lipophilic balance (HLB) value, and the surfactant proportion. Results are presented for the followed tests carried out on the emulsions: texture analysis, rheology, and particle size analysis. The oils used in the study were sweet almond oil, liquid paraffin, maize oil, cyclomethicone, dimethicone, and wheat germ oil. The resulting data demonstrate a notable influence of the volume fraction oil on hardness, viscosity, adhesiveness, and cohesiveness of W/O emulsions. Emulsion hardness and viscosity increased as the OP percentage increased; this effect being even more pronounced for the vegetable oils. In contrast, emulsion adhesiveness and cohesiveness decreased as the volume fraction oil increased. The HLB value of the surfactant mixture of the emulsion also influenced hardness, adhesiveness, and elasticity, increasing or decreasing as HLB value did.

How experimental design can improve the validation process. Studies in pharmaceutical analysis.

A critical discussion about the possibility of improving the method validation process by means of experimental design is presented. The reported multivariate strategies concern the evaluation of the performance parameters robustness and intermediate precision, and the optimisation of bias and repeatability. In particular, accuracy and precision improvement constitutes a special subset of experimental design in which the bias and the relative standard deviation of the assay are optimised. D-optimal design was used in order to plan experiments for this aim. The analytical methods considered were capillary electrophoresis, HPLC, adsorptive stripping voltammetry and differential pulse polarography. All methods were applied to real pharmaceutical analysis problems.

TQI in the Albuquerque Veterans Affairs Medical Center's long-term oxygen therapy program.

BACKGROUND: Long-term oxygen therapy (LTOT) is the only treatment demonstrated to prolong the life of patients with chronic obstructive pulmonary disease. In November 1994, a multidisciplinary total quality improvement (TQI) team composed of the involved hospital services was established to reorganize and improve the LTOT program at the Albuquerque Veterans Affairs Medical Center (AVAMC), Albuquerque. FROM THE OLD TO THE NEW PROCESS: The LTOT team used a process map to analyze the current process and gather information from patients and staff regarding their satisfaction with the program. It then began working on the identified problems and streamlining the LTOT referral process. A respiratory therapy position with the specific responsibility of serving as the home oxygen (O2) coordinator (HOC) was established and filled. The evaluation process was to be initiated by the AVAMC physicians, following which the HOC would perform a newly standardized evaluation that would establish the patient's need for O2 and result in a specific prescription. RESULTS: Quality indicators were selected to monitor changes in the program. Data from chart reviews, the Veterans Affairs National Cost Containment Center, and patient surveys were used to evaluate the indicators. Timeliness of referral to the program before inpatient discharge improved, O2 prescriptions in the new program more frequently addressed activity, and the cost per patient was reduced by 37.1%. Patient satisfaction rates also improved. DISCUSSION: A motivated team with representatives of the services involved was able to analyze and dramatically improve an important but complicated program.

[Early, severe, neonatal infections due to streptococcus group B. Multicenter retrospective study on the incidence and risk factors]. / Infections néonatales précoces graves à streptocoque du groupe B. Etude multicentrique rétrospective de l'incidence et des facteurs de risque.

UNLABELLED: Streptococcus group B is often the causal agent in maternofetal infections occurring early. The prevention of fatal fulminant forms is much controversial. POPULATION AND METHODS: A retrospective multicentric study (10 maternity wards, 5 years, 96.243 live births) was conducted. All cases of early (<48 th) infection due to Streptococcus group B were collected and divided into two groups for comparison: group 1: infant death, and group 2: surviving infants requiring ventilatory assistance for > or = 12 hours. The aim of this study was to determine the incidence of fatal infections and to ascertain he clinical features and laboratory data correlated with death. RESULTS: The incidence of fatal early maternofetal infection due to Streptococcus group B (group 1) was 14 cases in 96,243 live births (0.14%) or 1 case in 7,143 live births. All newborns who died were symptomatic at 8 hours of life. The factors significantly correlated with death were: lack of antibiotics per partum, which did not [correction of no] altogether prevent severe forms (2/14 deaths and 14/28 survivals had had antibiotic per partum); prematurity; impaired adaptation to birth, early clinical signs and sudden aggravation; lack of an inflammatory syndrome at first work-up; a chest X-ray suggesting hyalin membrane disease; and major non-infectious associated disease. CONCLUSION: These findings underscore the importance of antibiotic prophylaxy per partum and the need for immediate paediatric care in case of risk factors.

Hyaline membrane disease in black newborns: does fetal lung maturation occur earlier?

Debate has developed among several authors about possible accelerated maturation of black fetuses in comparison with whites. In Guadeloupe, French West Indies, where 85% of the population is of black African-American origin, it has been noted that the incidence of hyaline membrane disease (HMD) represents a significant drop beginning after the 32nd week of gestation. Over a 3-year period, 419 black low-birthweight singleton newborns were admitted in the University Hospital's Neonatal Department covering 70% of all births of the island. The incidence of HMD was 50% among very low birthweight (< 1500 g) and 8.3% among moderate low birthweight (> or = 1500 g; P < 0.001). The incidence of HMD was 48.8% among the very preterm (< 32 weeks) and 7.8% (26/331) among the moderate preterm (> or = 32 weeks; P < 0.001). These differences were similar for appropriate for gestational age and small for gestational age infants. Significant differences remained after controlling for several maternal risk factors. These results suggest that the 32nd week of gestation represents a significant drop in the risk for respiratory distress syndrome in black premature compared with that reported in literature on European infants (34th week) and therefore may implicate different obstetrical decisions in the management of critical pregnancies in this population.

Neonatal bacterial septicemia in a tropical area. Four-year experience in Guadeloupe (French West Indies).

During a four-year study (1987-1990) at the Neonatal Department, University Hospital Pointe-à-Pitre (French West Indies), blood culture was systematically performed on all admitted newborns. The incidence of septicemia was 48 of 1000 admissions and 8.9 of 1000 inborn live births. Among the 107 neonatal positive blood cultures, group B streptococcus accounted for 37% of blood culture isolates and was the most frequent cause of septicemia. The overall mortality rate was 8.4%. The incidence of neonatal bacterial septicemia was among the high rates reported in the literature. The incidence of neonatal bacterial septicemia is discussed as a public health problem in perinatology in Guadeloupe in spite of good medical care. A review of the literature on bacterial septicemia in tropical or developing countries compared to the Guadeloupean experience allows speculation that this problem might be underestimated in third world countries.

Image quality study in 3D X-ray angiography: a first approach using the experimental design strategy.

The visual detection of fine structures and the accuracy of the quantitation of geometric and densitometric features, are closely related to the quality of the images available in two-dimensional (2D) and three-dimensional (3D) X-ray angiography. In this context, we propose to analyze all the parameters influencing this accuracy using an experimental design strategy. Preliminary tests of this procedure, applied to 2D and 3D angiographic data obtained from a dedicated phantom, yield encouraging results. We show that the detection of small arteries in a 3D angiogram is more sensitive to the number of projections than to the X-ray dose.