Prediction of Infant Drug Exposure Through Breastfeeding: Population PK Modeling and Simulation of Fluoxetine Exposure.

The likelihood of significant exposure to drugs in infants through breast milk is poorly defined, given the difficulties of conducting pharmacokinetics (PK) studies. Using fluoxetine (FX) as an example, we conducted a proof-of-principle study applying population PK (popPK) modeling and simulation to estimate drug exposure in infants through breast milk. We simulated data for 1,000 mother-infant pairs, assuming conservatively that the FX clearance in an infant is 20% of the allometrically adjusted value in adults. The model-generated estimate of the milk-to-plasma ratio for FX (mean: 0.59) was consistent with those reported in other studies. The median infant-to-mother ratio of FX steady-state plasma concentrations predicted by the simulation was 8.5%. Although the disposition of the active metabolite, norfluoxetine, could not be modeled, popPK-informed simulation may be valid for other drugs, particularly those without active metabolites, thereby providing a practical alternative to conventional PK studies for exposure risk assessment in this population.

Dosage optimization of treatments using population pharmacokinetic modeling and simulation.

Pharmacokinetic variability in drug levels represent for some drugs a major determinant of treatment success, since sub-therapeutic concentrations might lead to toxic reactions, treatment discontinuation or inefficacy. This is true for most antiretroviral drugs, which exhibit high inter-patient variability in their pharmacokinetics that has been partially explained by some genetic and non-genetic factors. The population pharmacokinetic approach represents a very useful tool for the description of the dose-concentration relationship, the quantification of variability in the target population of patients and the identification of influencing factors. It can thus be used to make predictions and dosage adjustment optimization based on Bayesian therapeutic drug monitoring (TDM). This approach has been used to characterize the pharmacokinetics of nevirapine (NVP) in 137 HIV-positive patients followed within the frame of a TDM program. Among tested covariates, body weight, co-administration of a cytochrome (CYP) 3A4 inducer or boosted atazanavir as well as elevated aspartate transaminases showed an effect on NVP elimination. In addition, genetic polymorphism in the CYP2B6 was associated with reduced NVP clearance. Altogether, these factors could explain 26% in NVP variability. Model-based simulations were used to compare the adequacy of different dosage regimens in relation to the therapeutic target associated with treatment efficacy. In conclusion, the population approach is very useful to characterize the pharmacokinetic profile of drugs in a population of interest. The quantification and the identification of the sources of variability is a rational approach to making optimal dosage decision for certain drugs administered chronically.

Modeling and Simulation ofReal-Time System as a Tool to Improve Capacity Management - Case Fenix

Tämän tutkimustyön kohteena on TietoEnator Oy:n kehittämän Fenix-tietojärjestelmän kapasiteettitarpeen ennustaminen. Työn tavoitteena on tutustua Fenix-järjestelmän eri osa-alueisiin, löytää tapa eritellä ja mallintaa eri osa-alueiden vaikutus järjestelmän kuormitukseen ja selvittää alustavasti mitkä parametrit vaikuttavat kyseisten osa-alueiden luomaan kuormitukseen. Osa tätä työtä on tutkia eri vaihtoehtoja simuloinnille ja selvittää eri vaihtoehtojen soveltuvuus monimutkaisten järjestelmien mallintamiseen. Kerätyn tiedon pohjaltaluodaan järjestelmäntietovaraston kuormitusta kuvaava simulaatiomalli. Hyödyntämällä mallista saatua tietoa ja tuotantojärjestelmästä mitattua tietoa mallia kehitetään vastaamaan yhä lähemmin todellisen järjestelmän toimintaa. Mallista tarkastellaan esimerkiksi simuloitua järjestelmäkuormaa ja jonojen käyttäytymistä. Tuotantojärjestelmästä mitataan eri kuormalähteiden käytösmuutoksia esimerkiksi käyttäjämäärän ja kellonajan suhteessa. Tämän työn tulosten on tarkoitus toimia pohjana myöhemmin tehtävälle jatkotutkimukselle, jossa osa-alueiden parametrisointia tarkennetaan lisää, mallin kykyä kuvata todellista järjestelmää tehostetaanja mallin laajuutta kasvatetaan.

MODELING AND SIMULATION OF RELIEF INFLUENCE ON EUCALYPTUS FORESTS: INTERACTION BETWEEN SOLAR IRRADIANCE AND PRODUCTIVITY

ABSTRACT This study aimed to verify the differences in radiation intensity as a function of distinct relief exposure surfaces and to quantify these effects on the leaf area index (LAI) and other variables expressing eucalyptus forest productivity for simulations in a process-based growth model. The study was carried out at two contrasting edaphoclimatic locations in the Rio Doce basin in Minas Gerais, Brazil. Two stands with 32-year-old plantations were used, allocating fixed plots in locations with northern and southern exposure surfaces. The meteorological data were obtained from two automated weather stations located near the study sites. Solar radiation was corrected for terrain inclination and exposure surfaces, as it is measured based on the plane, perpendicularly to the vertical location. The LAI values collected in the field were used. For the comparative simulations in productivity variation, the mechanistic 3PG model was used, considering the relief exposure surfaces. It was verified that during most of the year, the southern surfaces showed lower availability of incident solar radiation, resulting in up to 66% losses, compared to the same surface considered plane, probably related to its geographical location and higher declivity. Higher values were obtained for the plantings located on the northern surface for the variables LAI, volume and mean annual wood increase, with this tendency being repeated in the 3PG model simulations.

Modeling and simulation of forced-air cooling of strawberries using variable convective coefficient

In the forced-air cooling process of fruits occurs, besides the convective heat transfer, the mass transfer by evaporation. The energy need in the evaporation is taken from fruit that has its temperature lowered. In this study it has been proposed the use of empirical correlations for calculating the convective heat transfer coefficient as a function of surface temperature of the strawberry during the cooling process. The aim of this variation of the convective coefficient is to compensate the effect of evaporation in the heat transfer process. Linear and exponential correlations are tested, both with two adjustable parameters. The simulations are performed using experimental conditions reported in the literature for the cooling of strawberries. The results confirm the suitability of the proposed methodology.

Dynamic modeling and simulation of the airflow cleaning device

The objective of the work is to study the flow behavior and to support the design of air cleaner by dynamic simulation.In a paper printing industry, it is necessary to monitor the quality of paper when the paper is being produced. During the production, the quality of the paper can be monitored by camera. Therefore, it is necessary to keep the camera lens clean as wood particles may fall from the paper and lie on the camera lens. In this work, the behavior of the air flow and effect of the airflow on the particles at different inlet angles are simulated. Geometries of a different inlet angles of single-channel and double-channel case were constructed using ANSYS CFD Software. All the simulations were performed in ANSYS Fluent. The simulation results of single-channel and double-channel case revealed significant differences in the behavior of the flow and the particle velocity. The main conclusion from this work are in following. 1) For the single channel case the best angle was 0 degree because in that case, the air flow can keep 60% of the particles away from the lens which would otherwise stay on lens. 2) For the double channel case, the best solution was found when the angle of the first inlet was 0 degree and the angle of second inlet was 45 degree . In that case, the airflow can keep 91% of particles away from the lens which would otherwise stay on lens.

Modeling premartensitic effects in Ni2MnGa: A mean-field and Monte Carlo simulation study

ic first-order transition line ending in a critical point. This critical point is responsible for the existence of large premartensitic fluctuations which manifest as broad peaks in the specific heat, not always associated with a true phase transition. The main conclusion is that premartensitic effects result from the interplay between the softness of the anomalous phonon driving the modulation and the magnetoelastic coupling. In particular, the premartensitic transition occurs when such coupling is strong enough to freeze the involved mode phonon. The implication of the results in relation to the available experimental data is discussed.

Some Aspects of Domain Specific Conceptual Modeling for Simulation of Logistic Terminal Operations

When simulation modeling is used for performance improvement studies of complex systems such as transport terminals, domain specific conceptual modeling constructs could be used by modelers to create structured models. A two stage procedure which includes identification of the problem characteristics/cluster - ‘knowledge acquisition’ and identification of standard models for the problem cluster – ‘model abstraction’ was found to be effective in creating structured models when applied to certain logistic terminal systems. In this paper we discuss some methods and examples related the knowledge acquisition and model abstraction stages for the development of three different types of model categories of terminal systems

Towards Grid-Wide Modeling and Simulation

Modeling and simulation permeate all areas of business, science and engineering. With the increase in the scale and complexity of simulations, large amounts of computational resources are required, and collaborative model development is needed, as multiple parties could be involved in the development process. The Grid provides a platform for coordinated resource sharing and application development and execution. In this paper, we survey existing technologies in modeling and simulation, and we focus on interoperability and composability of simulation components for both simulation development and execution. We also present our recent work on an HLA-based simulation framework on the Grid, and discuss the issues to achieve composability.

First structural analysis of a naphthalene-based poly(ether ketone): Crystal and molecular simulation from X-ray powder data and diffraction modeling

Polycondensation of 2,6-dihydroxynaphthalene with 4,4'-bis(4"-fluorobenzoyl)biphenyl affords a novel, semicrystalline poly(ether ketone) with a melting point of 406 degreesC and glass transition temperature (onset) of 168 degreesC. Molecular modeling and diffraction-simulation studies of this polymer, coupled with data from the single-crystal structure of an oligomer model, have enabled the crystal and molecular structure of the polymer to be determined from X-ray powder data. This structure-the first for any naphthalene-containing poly(ether ketone)-is fully ordered, in monoclinic space group P2(1)/b, with two chains per unit cell. Rietveld refinement against the experimental powder data gave a final agreement factor (R-wp) of 6.7%.

Multi-agent based modeling and simulation of complex system in hospital

This study puts forward a method to model and simulate the complex system of hospital on the basis of multi-agent technology. The formation of the agents of hospitals with intelligent and coordinative characteristics was designed, the message object was defined, and the model operating mechanism of autonomous activities and coordination mechanism was also designed. In addition, the Ontology library and Norm library etc. were introduced using semiotic method and theory, to enlarge the method of system modelling. Swarm was used to develop the multi-agent based simulation system, which is favorable for making guidelines for hospital's improving it's organization and management, optimizing the working procedure, improving the quality of medical care as well as reducing medical charge costs.

Modeling and simulation of the anode in direct ethanol fuels cells

Mathematical modeling has been extensively applied to the study and development of fuel cells. In this work, the objective is to characterize a mechanistic model for the anode of a direct ethanol fuel cell and perform appropriate simulations. The software Comsol Multiphysics (R) (and the Chemical Engineering Module) was used in this work. The software Comsol Multiphysics (R) is an interactive environment for modeling scientific and engineering applications using partial differential equations (PDEs). Based on the finite element method, it provides speed and accuracy for several applications. The mechanistic model developed here can supply details of the physical system, such as the concentration profiles of the components within the anode and the coverage of the adsorbed species on the electrode surface. Also, the anode overpotential-current relationship can be obtained. To validate the anode model presented in this paper, experimental data obtained with a single fuel cell operating with an ethanol solution at the anode were used. (C) 2008 Elsevier B.V. All rights reserved.