SIMULIT : un modèle de simulation pour l'analyse et la planification de l'activité hospitalière

Le modèle développé à l'Institut universitaire de médecine sociale et préventive de Lausanne utilise un programme informatique pour simuler les mouvements d'entrées et de sorties des hôpitaux de soins généraux. Cette simulation se fonde sur les données récoltées de routine dans les hôpitaux; elle tient notamment compte de certaines variations journalières et saisonnières, du nombre d'entrées, ainsi que du "Case-Mix" de l'hôpital, c'est-à-dire de la répartition des cas selon les groupes cliniques et l'âge des patients.

Intravenous streptomycin dosing regimen in a patient undergoing hemodialysis: Plasma level monitoring and pharmacokinetic simulation

Introduction: Streptomycin, as other aminoglycosides, exhibits concentration-dependent bacterial killing but has a narrow therapeutic window. It is primarily eliminated unchanged by the kidneys. Data and dosing information to achieve a safe regimen in patients with chronic renal failure undergoing hemodialysis (HD) are scarce. Although main adverse reactions are related to prolonged, elevated serum concentrations, literature recommendation is to administer streptomycin after each HD. Patients (or Materials) and Methods: We report the case of a patient with end-stage renal failure, undergoing HD, who was successfully treated with streptomycin for gentamicin-resistant Enterococcus faecalis bacteremia with prosthetic arteriovenous fistula infection. Streptomycin was administered intravenously 7.5 mg/kg, 3 hours before each dialysis (3 times a week) during 6 weeks in combination with amoxicillin. Streptomycin plasma levels were monitored with repeated blood sampling before, after, and between HD sessions. A 2-compartment model was used to reconstruct the concentration time profile over days on and off HD. Results: Streptomycin trough plasma-concentration was 2.8 mg/L. It peaked to 21.4 mg/L 30 minutes after intravenous administration, decreased to 18.2 mg/L immediately before HD, and dropped to 4.5 mg/L at the end of a 4-hour HD session. Plasma level increased again to 5.7 mg/L 2 hours after the end of HD and was 2.8 mg/L 48 hours later, before the next administration and HD. The pharmacokinetics of streptomycin was best described with a 2-compartment model. The computer simulation fitted fairly well to the observed concentrations during or between HD sessions. Redistribution between the 2 compartments after the end of HD reproduced the rebound of plasma concentrations after HD. No significant toxicity was observed during treatment. The outcome of the infection was favorable, and no sign of relapse was observed after a follow-up of 3 months. Conclusion: Streptomycin administration of 7.5 mg/kg 3 hours before HD sessions in a patient with end-stage renal failure resulted in an effective and safe dosing regimen. Monitoring plasma levels along with pharmacokinetic simulation document the suitability of this dosing scheme, which should replace current dosage recommendations for streptomycin in HD.

A pseudo-spectral method for the simulation of poro-elastic seismic wave propagation in 2D polar coordinates using domain decomposition

We present a novel numerical approach for the comprehensive, flexible, and accurate simulation of poro-elastic wave propagation in 2D polar coordinates. An important application of this method and its extensions will be the modeling of complex seismic wave phenomena in fluid-filled boreholes, which represents a major, and as of yet largely unresolved, computational problem in exploration geophysics. In view of this, we consider a numerical mesh, which can be arbitrarily heterogeneous, consisting of two or more concentric rings representing the fluid in the center and the surrounding porous medium. The spatial discretization is based on a Chebyshev expansion in the radial direction and a Fourier expansion in the azimuthal direction and a Runge-Kutta integration scheme for the time evolution. A domain decomposition method is used to match the fluid-solid boundary conditions based on the method of characteristics. This multi-domain approach allows for significant reductions of the number of grid points in the azimuthal direction for the inner grid domain and thus for corresponding increases of the time step and enhancements of computational efficiency. The viability and accuracy of the proposed method has been rigorously tested and verified through comparisons with analytical solutions as well as with the results obtained with a corresponding, previously published, and independently bench-marked solution for 2D Cartesian coordinates. Finally, the proposed numerical solution also satisfies the reciprocity theorem, which indicates that the inherent singularity associated with the origin of the polar coordinate system is adequately handled.

Genome-Wide Prediction Methods in Highly Diverse and Heterozygous Species: Proof-of-Concept through Simulation in Grapevine.

Nowadays, genome-wide association studies (GWAS) and genomic selection (GS) methods which use genome-wide marker data for phenotype prediction are of much potential interest in plant breeding. However, to our knowledge, no studies have been performed yet on the predictive ability of these methods for structured traits when using training populations with high levels of genetic diversity. Such an example of a highly heterozygous, perennial species is grapevine. The present study compares the accuracy of models based on GWAS or GS alone, or in combination, for predicting simple or complex traits, linked or not with population structure. In order to explore the relevance of these methods in this context, we performed simulations using approx 90,000 SNPs on a population of 3,000 individuals structured into three groups and corresponding to published diversity grapevine data. To estimate the parameters of the prediction models, we defined four training populations of 1,000 individuals, corresponding to these three groups and a core collection. Finally, to estimate the accuracy of the models, we also simulated four breeding populations of 200 individuals. Although prediction accuracy was low when breeding populations were too distant from the training populations, high accuracy levels were obtained using the sole core-collection as training population. The highest prediction accuracy was obtained (up to 0.9) using the combined GWAS-GS model. We thus recommend using the combined prediction model and a core-collection as training population for grapevine breeding or for other important economic crops with the same characteristics.

Tax simulation in the SHP

This paper describes a simulation package designed to estimate the annual income taxes paid by respondents of the Swiss Household Panel (SHP). In Switzerland, the 26 cantons have their own tax system. Additionally, tax levels vary between the over 2000 municipalities and over time. The simulation package takes account of this complexity by building on existing tables on tax levels which are provided by the Swiss Federal Tax Administration Office. Because these are limited to a few types of households and only 812 municipalities, they have to be extended to cover all households and municipalities. A further drawback of these tables is that they neglect several deductions. The tax simulation package fills this gap by taking additionally account of deductions for children, double-earner couples, third pillar and support for dependent persons according to cantonal legislation. The resulting variable on direct taxes not only serves to calculate household income net of taxes, but can also be a variable for analysis by its own account.

Direct simulation of interface dynamics: linking capillary pressure, interfacial area and surface energy

We perform direct numerical simulations of drainage by solving Navier- Stokes equations in the pore space and employing the Volume Of Fluid (VOF) method to track the evolution of the fluid-fluid interface. After demonstrating that the method is able to deal with large viscosity contrasts and to model the transition from stable flow to viscous fingering, we focus on the definition of macroscopic capillary pressure. When the fluids are at rest, the difference between inlet and outlet pressures and the difference between the intrinsic phase average pressure coincide with the capillary pressure. However, when the fluids are in motion these quantities are dominated by viscous forces. In this case, only a definition based on the variation of the interfacial energy provides an accurate measure of the macroscopic capillary pressure and allows separating the viscous from the capillary pressure components.

Brownian dynamics simulation of DNA condensation.

DNA condensation observed in vitro with the addition of polyvalent counterions is due to intermolecular attractive forces. We introduce a quantitative model of these forces in a Brownian dynamics simulation in addition to a standard mean-field Poisson-Boltzmann repulsion. The comparison of a theoretical value of the effective diameter calculated from the second virial coefficient in cylindrical geometry with some experimental results allows a quantitative evaluation of the one-parameter attractive potential. We show afterward that with a sufficient concentration of divalent salt (typically approximately 20 mM MgCl(2)), supercoiled DNA adopts a collapsed form where opposing segments of interwound regions present zones of lateral contact. However, under the same conditions the same plasmid without torsional stress does not collapse. The condensed molecules present coexisting open and collapsed plectonemic regions. Furthermore, simulations show that circular DNA in 50% methanol solutions with 20 mM MgCl(2) aggregates without the requirement of torsional energy. This confirms known experimental results. Finally, a simulated DNA molecule confined in a box of variable size also presents some local collapsed zones in 20 mM MgCl(2) above a critical concentration of the DNA. Conformational entropy reduction obtained either by supercoiling or by confinement seems thus to play a crucial role in all forms of condensation of DNA.

Numerical simulation of ambient seismic wavefield modification caused by pore-fluid effects in an oil reservoir

We have modeled numerically the seismic response of a poroelastic inclusion with properties applicable to an oil reservoir that interacts with an ambient wavefield. The model includes wave-induced fluid flow caused by pressure differences between mesoscopic-scale (i.e., in the order of centimeters to meters) heterogeneities. We used a viscoelastic approximation on the macroscopic scale to implement the attenuation and dispersion resulting from this mesoscopic-scale theory in numerical simulations of wave propagation on the kilometer scale. This upscaling method includes finite-element modeling of wave-induced fluid flow to determine effective seismic properties of the poroelastic media, such as attenuation of P- and S-waves. The fitted, equivalent, viscoelastic behavior is implemented in finite-difference wave propagation simulations. With this two-stage process, we model numerically the quasi-poroelastic wave-propagation on the kilometer scale and study the impact of fluid properties and fluid saturation on the modeled seismic amplitudes. In particular, we addressed the question of whether poroelastic effects within an oil reservoir may be a plausible explanation for low-frequency ambient wavefield modifications observed at oil fields in recent years. Our results indicate that ambient wavefield modification is expected to occur for oil reservoirs exhibiting high attenuation. Whether or not such modifications can be detected in surface recordings, however, will depend on acquisition design and noise mitigation processing as well as site-specific conditions, such as the geologic complexity of the subsurface, the nature of the ambient wavefield, and the amount of surface noise.

Analysis, modelling and visualisation of spatiotemporal data for urban studies

The proportion of population living in or around cites is more important than ever. Urban sprawl and car dependence have taken over the pedestrian-friendly compact city. Environmental problems like air pollution, land waste or noise, and health problems are the result of this still continuing process. The urban planners have to find solutions to these complex problems, and at the same time insure the economic performance of the city and its surroundings. At the same time, an increasing quantity of socio-economic and environmental data is acquired. In order to get a better understanding of the processes and phenomena taking place in the complex urban environment, these data should be analysed. Numerous methods for modelling and simulating such a system exist and are still under development and can be exploited by the urban geographers for improving our understanding of the urban metabolism. Modern and innovative visualisation techniques help in communicating the results of such models and simulations. This thesis covers several methods for analysis, modelling, simulation and visualisation of problems related to urban geography. The analysis of high dimensional socio-economic data using artificial neural network techniques, especially self-organising maps, is showed using two examples at different scales. The problem of spatiotemporal modelling and data representation is treated and some possible solutions are shown. The simulation of urban dynamics and more specifically the traffic due to commuting to work is illustrated using multi-agent micro-simulation techniques. A section on visualisation methods presents cartograms for transforming the geographic space into a feature space, and the distance circle map, a centre-based map representation particularly useful for urban agglomerations. Some issues on the importance of scale in urban analysis and clustering of urban phenomena are exposed. A new approach on how to define urban areas at different scales is developed, and the link with percolation theory established. Fractal statistics, especially the lacunarity measure, and scale laws are used for characterising urban clusters. In a last section, the population evolution is modelled using a model close to the well-established gravity model. The work covers quite a wide range of methods useful in urban geography. Methods should still be developed further and at the same time find their way into the daily work and decision process of urban planners. La part de personnes vivant dans une région urbaine est plus élevé que jamais et continue à croître. L'étalement urbain et la dépendance automobile ont supplanté la ville compacte adaptée aux piétons. La pollution de l'air, le gaspillage du sol, le bruit, et des problèmes de santé pour les habitants en sont la conséquence. Les urbanistes doivent trouver, ensemble avec toute la société, des solutions à ces problèmes complexes. En même temps, il faut assurer la performance économique de la ville et de sa région. Actuellement, une quantité grandissante de données socio-économiques et environnementales est récoltée. Pour mieux comprendre les processus et phénomènes du système complexe "ville", ces données doivent être traitées et analysées. Des nombreuses méthodes pour modéliser et simuler un tel système existent et sont continuellement en développement. Elles peuvent être exploitées par le géographe urbain pour améliorer sa connaissance du métabolisme urbain. Des techniques modernes et innovatrices de visualisation aident dans la communication des résultats de tels modèles et simulations. Cette thèse décrit plusieurs méthodes permettant d'analyser, de modéliser, de simuler et de visualiser des phénomènes urbains. L'analyse de données socio-économiques à très haute dimension à l'aide de réseaux de neurones artificiels, notamment des cartes auto-organisatrices, est montré à travers deux exemples aux échelles différentes. Le problème de modélisation spatio-temporelle et de représentation des données est discuté et quelques ébauches de solutions esquissées. La simulation de la dynamique urbaine, et plus spécifiquement du trafic automobile engendré par les pendulaires est illustrée à l'aide d'une simulation multi-agents. Une section sur les méthodes de visualisation montre des cartes en anamorphoses permettant de transformer l'espace géographique en espace fonctionnel. Un autre type de carte, les cartes circulaires, est présenté. Ce type de carte est particulièrement utile pour les agglomérations urbaines. Quelques questions liées à l'importance de l'échelle dans l'analyse urbaine sont également discutées. Une nouvelle approche pour définir des clusters urbains à des échelles différentes est développée, et le lien avec la théorie de la percolation est établi. Des statistiques fractales, notamment la lacunarité, sont utilisées pour caractériser ces clusters urbains. L'évolution de la population est modélisée à l'aide d'un modèle proche du modèle gravitaire bien connu. Le travail couvre une large panoplie de méthodes utiles en géographie urbaine. Toutefois, il est toujours nécessaire de développer plus loin ces méthodes et en même temps, elles doivent trouver leur chemin dans la vie quotidienne des urbanistes et planificateurs.

Sex differences in urinary levels of several biological indicators of exposure: a simulation study using a compartmental based toxicokinetic model

Toxicokinetic modeling is a useful tool to describe or predict the behavior of a chemical agent in the human or animal organism. A general model based on four compartments was developed in a previous study in order to quantify the effect of human variability on a wide range of biological exposure indicators. The aim of this study was to adapt this existing general toxicokinetic model to three organic solvents, which were methyl ethyl ketone, 1-methoxy-2-propanol and 1,1,1,-trichloroethane, and to take into account sex differences. We assessed in a previous human volunteer study the impact of sex on different biomarkers of exposure corresponding to the three organic solvents mentioned above. Results from that study suggested that not only physiological differences between men and women but also differences due to sex hormones levels could influence the toxicokinetics of the solvents. In fact the use of hormonal contraceptive had an effect on the urinary levels of several biomarkers, suggesting that exogenous sex hormones could influence CYP2E1 enzyme activity. These experimental data were used to calibrate the toxicokinetic models developed in this study. Our results showed that it was possible to use an existing general toxicokinetic model for other compounds. In fact, most of the simulation results showed good agreement with the experimental data obtained for the studied solvents, with a percentage of model predictions that lies within the 95% confidence interval varying from 44.4 to 90%. Results pointed out that for same exposure conditions, men and women can show important differences in urinary levels of biological indicators of exposure. Moreover, when running the models by simulating industrial working conditions, these differences could even be more pronounced. In conclusion, a general and simple toxicokinetic model, adapted for three well known organic solvents, allowed us to show that metabolic parameters can have an important impact on the urinary levels of the corresponding biomarkers. These observations give evidence of an interindividual variablity, an aspect that should have its place in the approaches for setting limits of occupational exposure.

Numerical simulation of gel electrophoresis of DNA knots in weak and strong electric fields.

Gel electrophoresis allows one to separate knotted DNA (nicked circular) of equal length according to the knot type. At low electric fields, complex knots, being more compact, drift faster than simpler knots. Recent experiments have shown that the drift velocity dependence on the knot type is inverted when changing from low to high electric fields. We present a computer simulation on a lattice of a closed, knotted, charged DNA chain drifting in an external electric field in a topologically restricted medium. Using a Monte Carlo algorithm, the dependence of the electrophoretic migration of the DNA molecules on the knot type and on the electric field intensity is investigated. The results are in qualitative and quantitative agreement with electrophoretic experiments done under conditions of low and high electric fields.