Development and implementation of the population Fisher information matrix for the evaluation of population pharmacokinetic designs.

In population pharmacokinetic studies, the precision of parameter estimates is dependent on the population design. Methods based on the Fisher information matrix have been developed and extended to population studies to evaluate and optimize designs. In this paper we propose simple programming tools to evaluate population pharmacokinetic designs. This involved the development of an expression for the Fisher information matrix for nonlinear mixed-effects models, including estimation of the variance of the residual error. We implemented this expression as a generic function for two software applications: S-PLUS and MATLAB. The evaluation of population designs based on two pharmacokinetic examples from the literature is shown to illustrate the efficiency and the simplicity of this theoretic approach. Although no optimization method of the design is provided, these functions can be used to select and compare population designs among a large set of possible designs, avoiding a lot of simulations.

Light guiding light: Nonlinear refraction in rubidium vapor

Recently there has been experimental and theoretical interest in cross-dispersion effects in rubidium vapor, which allows one beam of light to be guided by another. We present theoretical results which account for the complications created by the D line hyperfine structure of rubidium as well as the presence of the two major isotopes of rubidium. This allows the complex frequency dependence of the effects observed in our experiments to be understood and lays the foundation for future studies of nonlinear propagation.

Mathematical methods for spatially cohesive reserve design

The problem of designing spatially cohesive nature reserve systems that meet biodiversity objectives is formulated as a nonlinear integer programming problem. The multiobjective function minimises a combination of boundary length, area and failed representation of the biological attributes we are trying to conserve. The task is to reserve a subset of sites that best meet this objective. We use data on the distribution of habitats in the Northern Territory, Australia, to show how simulated annealing and a greedy heuristic algorithm can be used to generate good solutions to such large reserve design problems, and to compare the effectiveness of these methods.

On positive solutions of nonlinear elliptic equations involving concave and critical nonlinearities

We study the existence of nonnegative solutions of elliptic equations involving concave and critical Sobolev nonlinearities. Applying various variational principles we obtain the existence of at least two nonnegative solutions.

Difference equations associated with fully nonlinear boundary value problems for second order ordinary differential equations

We study the continuous problem y"=f(x,y,y'), xc[0,1], 0=G((y(0),y(1)),(y'(0), y'(1))), and its discrete approximation (y(k+1)-2y(k)+y(k-1))/h(2) =f(t(k), y(k), v(k)), k = 1,..., n-1, 0 = G((y(0), y(n)), (v(1), v(n))), where f and G = (g(0), g(1)) are continuous and fully nonlinear, h = 1/n, v(k) = (y(k) - y(k-1))/h, for k =1,..., n, and t(k) = kh, for k = 0,...,n. We assume there exist strict lower and strict upper solutions and impose additional conditions on f and G which are known to yield a priori bounds on, and to guarantee the existence of solutions of the continuous problem. We show that the discrete approximation also has solutions which approximate solutions of the continuous problem and converge to the solution of the continuous problem when it is unique, as the grid size goes to 0. Homotopy methods can be used to compute the solution of the discrete approximation. Our results were motivated by those of Gaines.

Probing the time course of nonlinear discriminations during human electrodermal conditioning

Animal-based theories of Pavlovian conditioning propose that patterning discriminations are solved using unique cues or immediate configuring. Recent studies with humans, however, provided evidence that in positive and negative patterning two different rules are utilized. The present experiment was designed to provide further support for this proposal by tracking the time course of the allocation of cognitive resources. One group was trained in a positive patterning; schedule (A-, B-, AB+) and a second in a negative patterning schedule (A+, B+, AB-). Electrodermal responses and secondary task probe reaction time were measured. In negative patterning, reaction times were slower during reinforced stimuli than during non-reinforced stimuli at both probe positions while there were no differences in positive patterning. These results support the assumption that negative patterning is solved using a rule that is more complex and requires more resources than does the rule employed to solve positive patterning. (C) 2001 Elsevier Science (USA).

Interval training program optimization in highly trained endurance cyclists

Purpose: The purpose of this study was to examine the influence of three different high-intensity interval training (HIT) regimens on endurance performance in highly trained endurance athletes. Methods: Before, and after 2 and 4 wk of training, 38 cyclists and triathletes (mean +/- SD; age = 25 +/- 6 yr; mass = 75 +/- 7 kg; (V)over dot O-2peak = 64.5 +/- 5.2 mL.kg(-1).min(-1)) performed: 1) a progressive cycle test to measure peak oxygen consumption ((V)over dotO(2peak)) and peak aerobic power output (PPO), 2) a time to exhaustion test (T-max) at their (V)over dotO(2peak) power output (P-max), as well as 3) a 40-kin time-trial (TT40). Subjects were matched and assigned to one of four training groups (G(1), N = 8, 8 X 60% T-max P-max, 1:2 work:recovery ratio; G(2), N = 9, 8 X 60% T-max at P-max, recovery at 65% HRmax; G(3), N = 10, 12 X 30 s at 175% PPO, 4.5-min recovery; G(CON), N = 11). In addition to G(1) G(2), and G(3) performing HIT twice per week, all athletes maintained their regular low-intensity training throughout the experimental period. Results: All HIT groups improved TT40 performance (+4.4 to +5.8%) and PPO (+3.0 to +6.2%) significantly more than G(CON) (-0.9 to + 1.1 %; P < 0.05). Furthermore, G(1) (+5.4%) and G(2) (+8.1%) improved their (V)over dot O-2peak significantly more than G(CON) (+ 1.0%; P < 0.05). Conclusion: The present study has shown that when HIT incorporates P-max as the interval intensity and 60% of T-max as the interval duration, already highly trained cyclists can significantly improve their 40-km time trial performance. Moreover, the present data confirm prior research, in that repeated supramaximal HIT can significantly improve 40-km time trial performance.

A genetic algorithm/method of moments approach to the optimization of an RF coil for MRI applications - Theoretical considerations - Abstract

A Combined Genetic Algorithm and Method of Moments design methods is presented for the design of unusual near-field antennas for use in Magnetic Resonance Imaging systems. The method is successfully applied to the design of an asymmetric coil structure for use at 190MHz and demonstrates excellent radiofrequency field homogeneity.

Geometric nonlinear analysis of thin plates by a refined nonlinear non-conforming triangular plate element

Based on the refined non-conforming element method for geometric nonlinear analysis, a refined nonlinear non-conforming triangular plate element is constructed using the Total Lagrangian (T.L.) and the Updated Lagrangian (U.L.) approach. The refined nonlinear non-conforming triangular plate element is based on the Allman's triangular plane element with drilling degrees of freedom [1] and the refined non-conforming triangular plate element RT9 [2]. The element is used to analyze the geometric nonlinear behavior of plates and the numerical examples show that the refined non-conforming triangular plate element by the T.L. and U.L. approach can give satisfactory results. The computed results obtained from the T.L. and U.L. approach for the same numerical examples are somewhat different and the reasons for the difference of the computed results are given in detail in this paper. © 2003 Elsevier Science Ltd. All rights reserved.