A pharmacokinetic-pharmacodynamic model for duodenal levodopa infusion

Objective Levodopa in presence of decarboxylase inhibitors is following two-compartment kinetics and its effect is typically modelled using sigmoid Emax models. Pharmacokinetic modelling of the absorption phase of oral distributions is problematic because of irregular gastric emptying. The purpose of this work was to identify and estimate a population pharmacokinetic- pharmacodynamic model for duodenal infusion of levodopa/carbidopa (Duodopa®) that can be used for in numero simulation of treatment strategies. Methods The modelling involved pooling data from two studies and fixing some parameters to values found in literature (Chan et al. J Pharmacokinet Pharmacodyn. 2005 Aug;32(3-4):307-31). The first study involved 12 patients on 3 occasions and is described in Nyholm et al. Clinical Neuropharmacology 2003:26:156-63. The second study, PEDAL, involved 3 patients on 2 occasions. A bolus dose (normal morning dose plus 50%) was given after a washout during night. Plasma samples and motor ratings (clinical assessment of motor function from video recordings on a treatment response scale between -3 and 3, where -3 represents severe parkinsonism and 3 represents severe dyskinesia.) were repeatedly collected until the clinical effect was back at baseline. At this point, the usual infusion rate was started and sampling continued for another two hours. Different structural absorption models and effect models were evaluated using the value of the objective function in the NONMEM package. Population mean parameter values, standard error of estimates (SE) and if possible, interindividual/interoccasion variability (IIV/IOV) were estimated. Results Our results indicate that Duodopa absorption can be modelled with an absorption compartment with an added bioavailability fraction and a lag time. The most successful effect model was of sigmoid Emax type with a steep Hill coefficient and an effect compartment delay. Estimated parameter values are presented in the table. Conclusions The absorption and effect models were reasonably successful in fitting observed data and can be used in simulation experiments.

Constructing a Structural Macroeconomic Model Using Multiple Techniques

This project constructs a structural model of the United States Economy. This task is tackled in two separate ways: first econometric methods and then using a neural network, both with a structure that mimics the structure of the U.S. economy. The structural model tracks the performance of U.S. GDP rather well in a dynamic simulation, with an average error of just over 1 percent. The neural network performed well, but suffered from some theoretical, as well as some implementation issues.

Forecasting multivariate time series under present-value-model short- and long-run co-movement restrictions

It is well known that cointegration between the level of two variables (e.g. prices and dividends) is a necessary condition to assess the empirical validity of a present-value model (PVM) linking them. The work on cointegration,namelyon long-run co-movements, has been so prevalent that it is often over-looked that another necessary condition for the PVM to hold is that the forecast error entailed by the model is orthogonal to the past. This amounts to investigate whether short-run co-movememts steming from common cyclical feature restrictions are also present in such a system. In this paper we test for the presence of such co-movement on long- and short-term interest rates and on price and dividend for the U.S. economy. We focuss on the potential improvement in forecasting accuracies when imposing those two types of restrictions coming from economic theory.

Short-term temporal changes of soil carbon losses after tillage described by a first-order decay model

Tillage stimulates soil carbon (C) losses by increasing aeration, changing temperature and moisture conditions, and thus favoring microbial decomposition. In addition, soil aggregate disruption by tillage exposes once protected organic matter to decomposition. We propose a model to explain carbon dioxide (CO2) emission after tillage as a function of the no-till emission plus a correction due to the tillage disturbance. The model assumes that C in the readily decomposable organic matter follows a first-order reaction kinetics equation as: dC(sail)(t)/dt = -kC(soil)(t) and that soil C-CO2 emission is proportional to the C decay rate in soil, where C-soil(t) is the available labile soil C (g m(-2)) at any time (t). Emissions are modeled in terms soil C available to decomposition in the tilled and non-tilled plots, and a relationship is derived between no-till (F-NT) and tilled (F-Gamma) fluxes, which is: F-T = a1F(NT)e(-a2t), where t is time after tillage. Predicted and observed fluxes showed good agreement based on determination coefficient (R-2), index of agreement and model efficiency, with R-2 as high as 0.97. The two parameters included in the model are related to the difference between the decay constant (k factor) of tilled and no-till plots (a(2)) and also to the amount of labile carbon added to the readily decomposable soil organic matter due to tillage (a,). These two parameters were estimated in the model ranging from 1.27 and 2.60 (a(1)) and - 1.52 x 10(-2) and 2.2 x 10(-2) day(-1) (a(2)). The advantage is that temporal variability of tillage-induced emissions can be described by only one analytical function that includes the no-till emission plus an exponential term modulated by tillage and environmentally dependent parameters. (C) 2008 Elsevier B.V. All rights reserved.

A simple and non-destructive model for individual leaf area estimation in citrus

Introduction. Leaf area is often related to plant growth, development, physiology and yield. Many non-destructive models have been proposed for leaf area estimation of several plant genotypes, demonstrating that leaf length, leaf width and leaf area are closely correlated. Thus, the objective of our study was to develop a reliable model for leaf area estimation from linear measurements of leaf dimensions for citrus genotypes. Materials and methods. Leaves of citrus genotypes were harvested, and their dimensions (length, width and area) were measured. Values of leaf area were regressed against length, width, the square of length, the square of width and the product (length x width). The most accurate equations, either linear or second-order polynomial, were regressed again with a new data set; then the most reliable equation was defined. Results and discussion. The first analysis showed that the variables length, width and the square of length gave better results in second-order polynomial equations, while the linear equations were more suitable and accurate when the width and the product (length x width) were used. When these equations were regressed with the new data set, the coefficient of determination (R(2)) and the agreement index 'd' were higher for the one that used the variable product (length x width), while the Mean Absolute Percentage Error was lower. Conclusion. The product of the simple leaf dimensions (length x width) can provide a reliable and simple non-destructive model for leaf area estimation across citrus genotypes.

Estimates of correction factors for lactation length and genetic parameters for milk yield in buffaloes

Estimaram-se fatores de correção para produção de leite aos 90, 240, 270 e 305 dias de lactação e parâmetros genéticos e de ambiente da produção de leite ajustada para esses períodos de lactação, utilizando-se 3888 lactações de 1630 búfalas, controladas entre 1987 e 2001, em 10 rebanhos do Estado de São Paulo. Os parâmetros genéticos foram estimados por meio do método da máxima verossimilhança restrita, livre de derivadas, aplicado a um modelo animal com medidas repetidas. As estimativas de herdabilidade para produção de leite corrigida para 90, 240, 270 e 305 dias de lactação foram 0,17; 0,15; 0,14 e 0,14, respectivamente. Nessa mesma ordem de apresentação, as estimativas de repetibilidade foram 0,40; 0,44; 0,41 e 0,41. As estimativas de correlação genética entre essas produções de leite corrigidas variaram de 0,96 a 1,00. Os fatores de correção multiplicativos para as diferentes classes de duração da lactação foram eficientes para ajustar a produção de leite aos 90, 240, 270 e 305 dias de lactação.

Comparação de critérios de seleção para precocidade de crescimento em bovinos da raça Guzerá

Objetivou-se com este estudo comparar a seleção com base no ganho médio diário de peso na pré-desmama (GMD) e no número de dias para ganhar 160 kg nessa fase (D160), com e sem correção para efeitos de grupos de contemporâneos (GC), em bovinos da raça Guzerá. Utilizou-se o banco de dados de desenvolvimento ponderal da Associação Brasileira de Criadores de Zebu (ABCZ) para esta raça. A obtenção dos parâmetros e valores genéticos foi feita pelo método da máxima verossimilhança restrita utilizando-se modelo unicaracterístico com equações de modelos mistos. O modelo utilizado foi composto pelo efeito fixo de grupo genético e pelos efeitos aleatórios, genético aditivo direto e de ambiente permanente, além do erro residual. A média para D160 foi de 270,5 dias e para GMD, 642,3 g. As correlações de Spearman entre ganho médio diário e a precocidade em dias para ganhar 160 kg na pré-desmama (PD160), e GMD e PD160c (PD160 corrigido para o efeito de grupo de contemporâneo), foram iguais a 0,91 e 0,94, respectivamente. A seleção para PD160 favorece touros que produzem progênie com desempenho superior e menos variável e a padronização deste critério com base no grupo de contemporâneos melhorou sua eficiência. A classificação dos touros varia de acordo com o critério de seleção utilizado, GMD ou PD160, principalmente nos extremos, onde ocorrem seleção e descarte de reprodutores.

Improving the GNSS positioning stochastic model in the presence of ionospheric scintillation

Ionospheric scintillations are caused by time-varying electron density irregularities in the ionosphere, occurring more often at equatorial and high latitudes. This paper focuses exclusively on experiments undertaken in Europe, at geographic latitudes between similar to 50 degrees N and similar to 80 degrees N, where a network of GPS receivers capable of monitoring Total Electron Content and ionospheric scintillation parameters was deployed. The widely used ionospheric scintillation indices S4 and sigma(phi) represent a practical measure of the intensity of amplitude and phase scintillation affecting GNSS receivers. However, they do not provide sufficient information regarding the actual tracking errors that degrade GNSS receiver performance. Suitable receiver tracking models, sensitive to ionospheric scintillation, allow the computation of the variance of the output error of the receiver PLL (Phase Locked Loop) and DLL (Delay Locked Loop), which expresses the quality of the range measurements used by the receiver to calculate user position. The ability of such models of incorporating phase and amplitude scintillation effects into the variance of these tracking errors underpins our proposed method of applying relative weights to measurements from different satellites. That gives the least squares stochastic model used for position computation a more realistic representation, vis-a-vis the otherwise 'equal weights' model. For pseudorange processing, relative weights were computed, so that a 'scintillation-mitigated' solution could be performed and compared to the (non-mitigated) 'equal weights' solution. An improvement between 17 and 38% in height accuracy was achieved when an epoch by epoch differential solution was computed over baselines ranging from 1 to 750 km. The method was then compared with alternative approaches that can be used to improve the least squares stochastic model such as weighting according to satellite elevation angle and by the inverse of the square of the standard deviation of the code/carrier divergence (sigma CCDiv). The influence of multipath effects on the proposed mitigation approach is also discussed. With the use of high rate scintillation data in addition to the scintillation indices a carrier phase based mitigated solution was also implemented and compared with the conventional solution. During a period of occurrence of high phase scintillation it was observed that problems related to ambiguity resolution can be reduced by the use of the proposed mitigated solution.

GPS Satellite Kinematic Relative Positioning: Analyzing and Improving the Functional Mathematical Model Using Wavelets

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of measurement error and autocorrelation on the (X)over-bar chart

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Proposal of an alternative transmission line model for symmetrical and asymmetrical configurations

This article shows a transmission line model for simulation of fast and slow transients, applied to symmetrical or asymmetrical configurations. A transmission line model is developed based on lumped elements representation and state-space techniques. The proposed methodology represents a practical procedure to model three-phase transmission lines directly in time domain, without the explicit or implicit use of inverse transforms. In three-phase representation, analysis modal techniques are applied to decouple the phases in their respective propagation modes, using a correction procedure to set a real and constant matrix for untransposed lines with or without vertical symmetry plane. The proposed methodology takes into account the frequency-dependent parameters of the line and in order to include this effect in the state matrices, a fitting procedure is applied. To verify the accuracy of the proposed state-space model in frequency domain, a simple methodology is described based on line distributed parameters and transfer function associated with input/output signals of the lumped parameters representation. In addition, this article proposes the use of a fast and robust integration procedure to solve the state equations, enabling transient and steady-state simulations. The results obtained by the proposed methodology are compared with several established transmission line models in EMTP, taking into account an asymmetrical three-phase transmission line. The principal contribution of the proposed methodology is to handle a steady fundamental signal mixed with fast and slow transients, including impulsive and oscillatory behavior, by a practical procedure applied directly in time domain for symmetrical or asymmetrical representations. (C) 2011 Elsevier Ltd. All rights reserved.

Construção de modelos multivariados para determinação de lipídios totais e unidade em leite em pó comercial utilizando espectroscopia no infravermelho próximo

In this work calibration models were constructed to determine the content of total lipids and moisture in powdered milk samples. For this, used the near-infrared spectroscopy by diffuse reflectance, combined with multivariate calibration. Initially, the spectral data were submitted to correction of multiplicative light scattering (MSC) and Savitzsky-Golay smoothing. Then, the samples were divided into subgroups by application of hierarchical clustering analysis of the classes (HCA) and Ward Linkage criterion. Thus, it became possible to build regression models by partial least squares (PLS) that allowed the calibration and prediction of the content total lipid and moisture, based on the values obtained by the reference methods of Soxhlet and 105 ° C, respectively . Therefore, conclude that the NIR had a good performance for the quantification of samples of powdered milk, mainly by minimizing the analysis time, not destruction of the samples and not waste. Prediction models for determination of total lipids correlated (R) of 0.9955, RMSEP of 0.8952, therefore the average error between the Soxhlet and NIR was ± 0.70%, while the model prediction to content moisture correlated (R) of 0.9184, RMSEP, 0.3778 and error of ± 0.76%

Black hole entropy associated with the supersymmetric sigma model

By means of an identity that equates the elliptic genus partition function of a supersymmetric sigma model on the N-fold symmetric product (SX)-X-N of X ((SX)-X-N=X-N/S-N, where S-N is the symmetric group of N elements) to the partition function of a second-quantized string theory, we derive the asymptotic expansion of the partition function as well as the asymptotic for the degeneracy of spectrum in string theory. The asymptotic expansion for the state counting reproduces the logarithmic correction to the black hole entropy.

BORN-INFELD ELECTRODYNAMICS and EULER-HEISENBERG-LIKE MODEL: OUTSTANDING EXAMPLES of THE LACK of COMMUTATIVITY AMONG QUANTIZED TRUNCATED ACTIONS and TRUNCATED QUANTIZED ACTIONS

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Temperature and concentration dependence of heat capacity of model aqueous solutions

Heat capacities of binary aqueous solutions of different concentrations of sucrose, glucose, fructose, citric acid, malic acid, and inorganic salts were measured with a differential scanning calorimeter in the temperature range from 5degreesC to 65degreesC. Heat capacity increased with increasing water content and increasing temperature. At low concentrations, heat capacity approached that of pure water, with a less pronounced effect of temperature, and similar abnormal behavior of pure water with a minimum around 30degreesC-40degreesC. Literature data, when available agreed relatively well with experimental values. A correction factor, based on the assumption of chemical equilibrium between liquid and gas phase in the Differential Scanning Calorimeter, was proposed to correct for the water evaporation due to temperature rise. Experimental data were fitted to predictive models. Excess molar heat capacity was calculated using the Redlich-Kister equation to represent the deviation from the additive ideal model.