A numerical study of the statistics of roughness parameters for fluctuating interfaces.

Self-affine rough interfaces are ubiquitous in experimental systems, and display characteristic scaling properties as a signature of the nature of disorder in their supporting medium, i.e. of the statistical features of its heterogeneities. Different methods have been used to extract roughness information from such self-affine structures, and in particular their scaling exponents and associated prefactors. Notably, for an experimental characterization of roughness features, it is of paramount importance to properly assess sample-to-sample fluctuations of roughness parameters. Here, by performing scaling analysis based on displacement correlation functions in real and reciprocal space, we compute statistical properties of the roughness parameters. As an ideal, artifact-free reference case study and particularly targeting finite-size systems, we consider three cases of numerically simulated one-dimensional interfaces: (i) elastic lines under thermal fluctuations and free of disorder, (ii) directed polymers in equilibrium with a disordered energy landscape, and (iii) elastic lines in the critical depinning state when the external applied driving force equals the depinning force set by disorder. Our results show that sample-to-sample fluctuations are rather large when measuring the roughness exponent. These fluctuations are also relevant for roughness amplitudes. Therefore a minimum of independent interface realizations (at least a few tens in our numerical simulations) should be used to guarantee sufficient statistical averaging, an issue often overlooked in experimental reports.

Pharmacokinetics of tiludronate in horses: A field population study.

BACKGROUND: Tiludronate is a bisphosphonate drug marketed to treat different bone conditions in horses. OBJECTIVES: The goal of this study was to measure the plasma concentrations of tiludronate in a population of race and sport horses under field conditions, and using pharmacokinetic population modelling, to estimate detection times for doping control. STUDY DESIGN: Prospective cohort. METHODS: This study was conducted under field conditions on 39 race or sport horses diagnosed with bone conditions based on a lameness examination and treated with tiludronate. Each horse received 1 mg/kg of tiludronate (Tildren® ) intravenously (i.v.). Blood samples (from 1 to 4 per horse with a total of 93 samples) were collected around 10, 20, 30, 40 and 50 days after tiludronate administration. Tiludronate was quantified by HPLC/ESI-MSn . Tiludronate concentrations were analysed using nonlinear mixed-effects modelling (population approach). Monte Carlo simulations were then used to compute a prediction interval to estimate the corresponding quantile of horses predicted to have concentrations below some potential screening limits. RESULTS: This study highlighted pharmacokinetic differences between healthy experimental horses and the population of horses being treated in the field as well as the effect of level of training on plasma tiludronate. Different detection times were computed corresponding to different possible screening limits. MAIN LIMITATIONS: The number of horses in each group was limited, and the specific disease being treated with tiludronate is unknown. CONCLUSIONS: This population pharmacokinetic study on tiludronate will enable racing and other sports authorities to provide a detection time reflecting field conditions for the medication control of tiludronate. More generally, our study design and the data modelling serve as an example of how to generate detection times directly from the target horse population rather than from experimental horses.

HPLC/ESI-MS(n) method for non-amino bisphosphonates: application to the detection of tiludronate in equine plasma.

Tiludronate is a non-nitrogen-containing biphosphonate drug approved in equine veterinary medicine for the treatment of navicular disease and bone sparvin in horse. Its hydrophilic properties and its strong affinity for the bone have made the control of its use quite difficult. After an initial step of method development in plasma and urine, due to a strong matrix effect and erratic detection in urine, the final method development was conducted in plasma. After addition of (3-trifluoromethylphenyl) thiomethylene biphosphonic acid as internal standard, automated sample preparation consisted of a filtration on a Nexus cartridge followed by a Solid Phase Extraction on an Oasis WAX cartridge with weak anion exchange properties. After methylation of the residue with trimethyl orthoacetate (TMOA), analysis was conducted by HPLC/ESI-MS(n) on a LTQ mass spectrometer. The method has been validated with a LOD and LOQ of respectively 1 and 2.5ng/mL. Using a weighting factor of 1/concentration(2), a linear model was suitable in the range of 2.5 up to 500ng/mL. Precision and accuracy data determined at two concentrations were satisfactory (i.e. less than 15%). Carryover would have been a problem but this has finally been fixed using the additional steps of washing during robotised SPE extraction and analysis on both the autosampler and the analytical column. The method was successfully employed for the first time to the quantification of tiludronate in plasma samples collected from horses treated with Tildren™ (Intravenous administration at the dose of 0.1mg/kg/day for 10 days).

Multiscaling analysis of ferroelectric domain wall roughness.

Using multiscaling analysis, we compare the characteristic roughening of ferroelectric domain walls in Pb(Zr0.2Ti0.8)O3 thin films with numerical simulations of weakly pinned one-dimensional interfaces. Although at length scales up to L(MA)≥5 µm the ferroelectric domain walls behave similarly to the numerical interfaces, showing a simple monoaffine scaling (with a well-defined roughness exponent ζ), we demonstrate more complex scaling at higher length scales, making the walls globally multiaffine (varying ζ at different observation length scales). The dominant contributions to this multiaffine scaling appear to be very localized variations in the disorder potential, possibly related to dislocation defects present in the substrate.

A preclinical pharmacokinetic and pharmacodynamic approach to determine a dose of spironolactone for treatment of congestive heart failure in dog.

Fifteen Beagle dogs were used to describe the anti-aldosterone effect of spironolactone (0, 0.8, 2 and 8 mg/kg) in a hyperaldosteronism model. The magnitude of the aldosterone response observed in this model was very similar to the one described in a dog with congestive heart failure (CHF). Each dog was allocated to a treatment group according to a 5 x 5 Latin square crossover design for five periods with a washout period of 7 days between each period. A maximal possible effect (E(max)) model was employed to determine the basic pharmacodynamic parameters of spironolactone, measured by high-performance liquid chromatography, in antagonizing the renal effects of aldosterone. The change in urinary sodium/potassium ratio in response to a single dose of aldosterone was calculated. The inhibition of this response by oral spironolactone administration was assessed. Aldosterone alone decreased sodium excretion by approximately 35% and urinary potassium concentrations increased by 25%, whereas the urine volume decreased, as expected. The effect of aldosterone on the Na(+)/K(+) ratio was completely reversed (88% inhibition) at a dose of 2 mg spironolactone/kg, while at the dose of 0.8 mg/kg, partial reversal was seen (27.5% inhibition). Urine flow rate was not significantly modified by either aldosterone treatment or aldosterone with spironolactone. The dose of spironolactone required to inhibit the action of aldosterone by 50% (ED(50)) was estimated to be 1.08 +/- 0.28 mg/kg. The E(max) was a ratio of 1.089 +/- 0.085, close to the observed value in negative control group (1.00 +/- 0.18). The proposed spironolactone dose using this E(max) model was 2 mg/kg b.w. once daily for the management.

Determination of a dosage regimen of colistin by pharmacokinetic/pharmacodynamic integration and modeling for treatment of G.I.T. disease in pigs.

Colistin is an antimicrobial drug of the polymyxin group and COLIVET SOLUTION is an aqueous solution containing colistin sulphate (2 x 10(6) IU/mL), formulated for oral administration. The target species is the pig, particularly the suckling and post weaning animal. This investigation was undertaken to provide pharmacokinetic and pharmacodynamic data on which to base the selection of dosage rate and interval of the solution for the treatment of porcine colibacillosis. Colistin absorption from the gastrointestinal tract of young pigs, when administered at dosage rates of 25,000, 50,000 and 100,000 IU/kg, was slight or absent. The drug was therefore restricted almost entirely to the required site of action. The colistin concentration-time profile within the jejunum and ileum was established, and this enabled determination of the pharmacokinetic variables, maximum concentration (C(max)) and area under curve (AUC) and derivation of the surrogate indices of antibacterial activity, C(max)/minimum inhibitory concentration (MIC) and AUC/MIC through integration of in vivo data with the results of in vitro potency studies for four strains of Escherichia coli. In the in vitro bacterial growth inhibition studies colistin acted by a concentration-dependent killing mechanism. Numerical values for the surrogate parameter AUC/MIC producing bactericidal and eradication effects of colistin against four strains of E. coli were established by PK-PD modeling based on the sigmoidal E(max) equation. These data were used to predict a daily dosage regimen for colistin.

Comparative pharmacokinetics of two intravenous administration regimens of tiludronate in healthy adult horses and effects on the bone resorption marker CTX-1.

Bioavailability and pharmacological effects of tiludronate were compared when administered as an intravenous (i.v.) bolus at a dosage of 0.1 mg/kg body weight (b.w.) once daily for 10 consecutive days (group 1, n = 6) and as a single constant rate infusion (CRI) at a total dose of 1 mg/kg b.w. (group 2, n = 6) in healthy adult horses. Tiludronate and carboxy-terminal cross-linking telopeptide of type I collagen (CTX-1) were measured in plasma and urine. There was no statistically significant difference in area under the curve (AUC) and clearance (Cl) between the two groups. Bioavailability of the CRI was 103% (not significantly different) that of the 10 daily i.v. bolus doses. Cumulative urine tiludronate excretion could not be compared between groups because of poor sensitivity of the assay in urine. Plasma and urine CTX-1 levels were not different between groups throughout the study. However, interindividual variations were greater in group 1 than in group 2. A significant decrease in CTX-1 levels was observed in plasma after the first administration in group 1, but not in urine; while in group 2, a significant decrease in CTX-1 concentrations was observed after treatment in both plasma and urine. In conclusion, both dosage regimens of tiludronate produced similar plasma exposure and pharmacological effects in adult healthy horses.

[Axillary lymph node recurrence after sentinel lymph node biopsy for breast cancer]. / Récidives ganglionnaires axillaires après lymphadénectomie sentinelle pour cancer du sein.

OBJECTIVE: The aim of this review is to summarize the current knowledge about axillary recurrences after sentinel lymph node (SLN) biopsy for breast cancer. METHODS: A Pubmed search for publications (in English or French) related to breast cancer, SLN and axillary recurrence was carried out from 1995 to 2006. RESULTS: Under controlled conditions (notably after a learning curve concerning the multidisciplinary team), the SLN procedure proved to be a reliable method for evaluation of axillary nodal status in selected patients with early-stage invasive breast cancer. When the SLN is free of cancer cells, the rate of axillary recurrence varies from 0% to 2% with a follow-up ranging from 14 to 57 months. Recurrence after axillary lymph node dissection is similar. When isolated cancer cells or micrometastases invaded the SLN, the rate of axillary recurrence remains low, but a complete axillary lymph node dissection must be performed to reduce this rate significantly. The use of intraoperative miniaturized gamma cameras could contribute to the optimization of the SLN procedure and to reduce axillary recurrences.

[Development of technologies for sentinel lymph node biopsy in case of breast cancer]. / Technologies en développement pour l'identification des ganglions sentinelles en chirurgie mammaire.

Sentinel lymph node (SLN) biopsy is now routinely used in breast cancer multidisciplinary management. The combined use of blue dye and lymphoscintigraphy gives the best SLN identification rate. Two different types of probes are available for the SLN procedure: semi-conductor probes and scintillator ones. Moreover, to increase the performances of the SLN procedure, intra-operative gamma cameras have recently been developed. The objectives of our review are to describe these materials to highlight their advantages and drawbacks from the point of view of the surgeon and the physicist.

[Comparative study between medieval (12th -14th c.) and modern skulls samples of five cranio-facial measures]. / Etude comparative de cinq mesures crânio-faciales entre un échantillon de cranes médiévaux (XIIe-XIVe siècles) et un échantillon contemporain.

OBJECTIVES: The aim of this study was to compare cephalometric norms of complete medieval skulls (n=35) with contemporary skulls (n=41), all from the same region, taking five craniofacial measures. MATERIAL AND METHOD: The medieval skulls were from different sites and tombs from southwestern France and contemporary skulls were those of students from the Faculty of Dental Surgery, Toulouse. A lateral cephalometric radiograph of each skull was obtained. All the skulls had to contain teeth and all anatomical reference points required for inclusion in the study. Cephalometric points were selected by inspection. The angles were chosen to evaluate the sagittal maxillo-mandibular relation, the cranial base flexion and the vertical dimension. RESULTS: Results showed that the ANB angle was wider in the medieval skulls (4.11 degrees vs 2.41 degrees ) but no significant difference for the cranial base flexion and the vertical dimension could be found between the two populations. DISCUSSION: We suggest there is no significant change in cephalometric norms over a period of approximately 800 years. Changes in lifestyle, diet, environment and populations intermixing do not appear to significantly affect cephalometric norms, although such factors are thought to affect dental occlusion.

Performances of a new prototype handheld scintillating probe for the search of sentinel lymph nodes in breast cancer.

AIM: The aim of this study is to evaluate the performances of a new prototype handheld gamma probe in a series of patients with infiltrative breast cancer justifying sentinel lymph node (SLN) excision. METHODS AND PATIENTS: SLN excision was performed on nine patients being treated for infiltrative breast cancer. After preoperative radio-isotope injection and lymphoscintigraphy, individual removal of all radioactive nodes was performed after their localisation using a novel new prototype handheld gamma intraoperative probe named CarolIReS. The activity of SLN following resection has been measured by a gamma ray counter. The mean geometrical detection efficiency of this gamma ray counter has been obtained by Monte Carlo simulation. RESULTS: With respect to the total number of SLNs identified by the CarolIReS probe, the detection probability was 80% for the lymphoscintigraphy. A mean number of 2.2 (1-5) SLNs per patient was detected after the complete SLN procedure. Among the removed SLNs, 19 were axillary SLN, 17 were located in the level I of Berg, two were located in the Rotter area and one was an intramammary SLN (ISLN) located in the lower inner area of the breast. The detection efficiency of the CarolIReS probe ranged from 2.1 to 100.0cpskBq(-1) referred to the activity of the SLN at the time of the surgery. CONCLUSION: This study shows that the CarolIReS probe is well adapted to the SLN detection and allows an efficient identification of both axillary and intramammary lymph nodes.

First results of the search for neutrinoless double-beta decay with the NEMO 3 detector.

The NEMO 3 detector, which has been operating in the Fréjus underground laboratory since February 2003, is devoted to the search for neutrinoless double-beta decay (beta beta 0v). The half-lives of the two neutrino double-beta decay (beta beta 2v) have been measured for 100Mo and 82Se. After 389 effective days of data collection from February 2003 until September 2004 (phase I), no evidence for neutrinoless double-beta decay was found from approximately 7 kg of 100Mo and approximately 1 kg of 82Se. The corresponding limits are T1/2(beta beta0v) > 4.6 x 10(23) yr for 100Mo and T1/2(beta beta 0v) > 1.0 x 10(23) yr for 82Se (90% C.L.). Depending on the nuclear matrix element calculation, the limits for the effective Majorana neutrino mass are < 0.7-2.8 e/v for 100Mo and < 1.7-4.9 eV for 82Se.

Development of a high-performance liquid chromatography-tandem mass spectrometry method for the determination of flurogestone acetate in ovine plasma.

Flurogestone (FGA) is a synthetic progesterone, with a progestational action higher than that of progesterone itself. It is intended for vaginal use in large animals to induce oestrus synchronization. A quantitative method for the analysis of flurogestone acetate (FGA) in ovine plasma by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has been developed. After the incorporation of megestrol acetate (MGA) as internal standard (IS) and followed by a liquid-liquid extraction from plasma, FGA and MGA were chromatographed using a reverse-phase HPLC column and detected by tandem mass spectrometry with a TurboIonSpray source. Multiple reaction-monitoring (MRM) mode was used for the quantitative determination of FGA in ovine plasma. The precursor ions [M+H](+) at m/z 407.2 and 385.1 for FGA and MGA, respectively, produced product ions at m/z 267.1/285.1 for FGA and m/z 267.1/224.0 for MGA. The validated concentration range was 0.2-5.0 ng/ml based on 500 microl plasma aliquots. The lower limit of quantitation was 0.2 ng/ml. Fully validated selectivity, accuracy, precision and reproducibility criteria for routine use in pharmacokinetic studies were demonstrated.

The "Sym'Previus" software, a tool to support decisions to the foodstuff safety.

Describing the Sym'Previus project, the software and its deliverable facilities is the aim of this present paper. This software concerns all the partners of the food industry who are involved in the management of food safety and allows food-borne pathogen behaviour in food to be predicted, as function of the environment (nature of the food, manufacturing process, conditions of conservation). This analysis of microbial behaviour has been possible thanks to the progress made in predictive microbiology since the 1980s. Sym'Previus offers to food industry professionals and their partners the possibility of applying this progress, by giving access to a database, to simulation systems and expertise.

A preclinical pharmacokinetic/pharmacodynamic approach to determine a dose of GnRH, for treatment of ovarian follicular cyst in cattle.

The objective of this study was to explore the value of a preclinical PK/PD approach to determine a gonadotropin-releasing hormone (GnRH) dose in cows using the pituitary LH response as a surrogate endpoint. Using an indirect effect model with stimulation of the LH entry rate, the in vivo basic pharmacodynamic parameters of GnRH were determined. The EC(50) of GnRH was 51 +/- 16 pg/mL, the EC(50) being the GnRH plasma concentration able to produce 50% of the maximum possible stimulation (S(max)) of the hypophysis (S(max) = 48 +/- 13). From individual PK/PD parameters, the ED(50) of GnRH, i.e. the estimated dose of GnRH required to determine half the maximum possible stimulating effect on LH release, was calculated to 62 microg/h per cow. Using the PK/PD model, the GnRH dose required to achieve a selected breakpoint value of 5 ng/mL for maximum LH concentration (surrogate value for LH concentration predicting clinical efficacy for cystic conditions), was 52 +/- 18 microg and for a standard GnRH dose of 100 microg, the mean maximum plasma LH concentration predicted by the model was 7.22 +/- 0.98 ng/mL.

Modelling the growth kinetics of Listeria as a function of temperature, pH and organic acid concentration.

The combined effects of temperature, pH and organic acids (lactic, acetic and propionic) on the growth kinetics of Listeria innocua ATCC 33090 were studied. First, a multiplicative model was built assuming independent effects of all environmental factors. Thus, the model was expanded by the inclusion of a novel term describing the effects of interactions on the growth/no growth limits. The proposed approach allows an accurate description of the boundary between growth and no growth of Listeria.

Chernobyl post-accident management: the ETHOS project.

ETHOS is a pilot research project supported by the radiation protection research program of the European Commission (DG XII). The project provides an alternative approach to the rehabilitation of living conditions in the contaminated territories of the CIS in the post-accident context of Chernobyl. Initiated at the beginning of 1996, this 3-y project is currently being implemented in the Republic of Belarus. The ETHOS project involves an interdisciplinary team of European researchers from the following institutions: the Centre d'etude sur l'Evaluation de la Protection dans le domaine Nucleaire CEPN (radiological protection, economics), the Institute National d'Agronomie de Paris-Grignon INAPG (agronomy, nature & life management), the Compiegne University of Technology (technological and industrial safety, social trust), and the Mutadis Research Group (sociology, social risk management), which is in charge of the scientific co-ordination of the project. The Belarussian partners in the ETHOS project include the Ministry of Emergencies of Belarus as well as the various local authorities involved with the implementation site. The ETHOS project relies on a strong involvement of the local population in the rehabilitation process. Its main goal is to create conditions for the inhabitants of the contaminated territories to reconstruct their overall quality of life. This reconstruction deals with all the day-to-day aspects that have been affected or threatened by the contamination. The project aims at creating a dynamic process whereby acceptable living conditions can be rebuilt. Radiological security is developed in the ETHOS project as part of a general improvement in the quality of life. The approach does not dissociate the social and the technical dimensions of post-accident management. This is so as to avoid radiological risk assessment and management being reduced purely to a problem for scientific experts, from which local people are excluded, and to take into consideration the problems of acceptability of decisions and the distrust of the population towards experts. These cannot be solved merely by a better communication strategy. This paper presents the main features of the methodological approach of the ETHOS project. It also explains how it is being implemented in the village of Olmany in the district of Stolyn (Brest region) in Belarus since March 1996, as well as its initial achievements.

Routine determination of flumequine in kidney tissue of pig using automated liquid chromatography.

A high-performance liquid chromatographic assay is described as a routine analytical method for the determination of flumequine (FLU) and its hydroxylated metabolite (OH-FLU) in pig kidney tissue. Kidney samples (2 g) containing FLU and OH-FLU were extracted by liquid-liquid extraction with ethyl acetate (10 ml). Analytical separations were performed by reversed-phase HPLC with fluorometric detection at 252 nm excitation and 356 nm emission under gradient conditions. The mobile phase was acetonitrile-2.7.10(-3) M oxalic acid in water (pH 2.5). The assay is specific and reproducible within the flumequine range of 0.050-2.5 micrograms/g and recovery at 0.050 microgram/g was 94.8%.

Determination of fumagillin in muscle tissue of rainbow trout using automated ion-pairing liquid chromatography.

A high-performance liquid chromatographic assay is described as a routine analytical method for the determination of fumagillin in rainbow trout muscle tissue. Muscle tissue samples (1 g) containing fumagillin were deproteinized with 8 ml of an acetonitrile-water mixture (2:6, v/v). The extracts were purified with a Bond Elut Octyl C8 cartridge column, washed with a water-methanol mixture (95:5, v/v; 4 ml) and fumagillin was eluted with acetonitrile (1 ml). Analytical separations were performed by reversed-phase HPLC with UV detection at 351 nm under gradient conditions. The mobile phase was acetonitrile-0.005 M tetrabutyl ammonium phosphate in water (pH 7.8). The assay is specific and reproducible within the fumagillin range of 20-1000 ng/g and recovery at 20 ng/g was 69.2%. Sample preparation involves the use of a robotic sample preparation system. Gravimetric validation of all operations enabled Good Laboratory Practices to be observed.