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PubMed2000

Stochastic epidemics in dynamic populations: quasi-stationarity and extinction.

Empirical evidence shows that childhood diseases persist in large communities whereas in smaller communities the epidemic goes extinct (and is later reintroduced by immigration). The present paper treats a stochastic model describing the spread of an infectious disease giving life-long immunity, in a community where individuals die and new individuals are born. The time to extinction of the disease starting in quasi-stationarity (conditional on non-extinction) is exponentially distributed. As the population size grows the epidemic process converges to a diffusion process. Properties of the limiting diffusion are used to obtain an approximate expression for tau, the mean-parameter in the exponential distribution of the time to extinction for the finite population. The expression is used to study how tau depends on the community size but also on certain properties of the disease/community: the basic reproduction number and the means and variances of the latency period, infectious period and life-length. Effects of introducing a vaccination program are also discussed as is the notion of the critical community size, defined as the size which distinguishes between the two qualitatively different behaviours.

Child↗
PubMed2006

[Measurement of peripapillary nerve fiber layer thickness at different distances from the optic nerve head with OCT].

PURPOSE: The aim of this study was to assess which distance to the optic nerve head is most favorable for circular measurements of retinal nerve fiber layer thickness (RNFLT) with OCT to detect differences between glaucoma and normal subjects. METHODS: A total of 98 eyes of 67 subjects (normal subjects and POAG patients) were examined by Stratus OCT (Zeiss, Model 3000, Software Version 2.0). Images were scanned in the "proportional circle" mode and analyzed with the "RNFL thickness analysis" protocol. For statistical analysis the Friedman test and the Mann-Whitney U test with Bonferroni correction were used. RESULTS: For 23 normal and 19 eyes of POAG patients a complete set of scans could be analyzed by the OCT software. RNFLT was statistically significantly different in scan diameters in both groups (P=0.000). Differences between the groups were statistically significant for the 1.0-fold (P=0.003), for the 1.4-fold (P=0.01), and for the 1.8-fold (P=0.002) disc diameter. CONCLUSION: Circular scans with a 1-fold and with a 1.8-fold disc diameter seem to be able to differentiate best between glaucoma and normal subjects.

Adolescent↗
PubMed2006

Volumetric brain imaging studies in the elderly with mood disorders.

Volumetric neuroimaging studies of the elderly with affective disorders provide important insights into the underlying physiology of the illnesses. Advantages of studying the elderly include the ability to make various assessments and obtain a history differentiating subtypes of illness. However, challenges to studying the elderly include the heterogeneity of affective illnesses and confounds of medical comorbidity and medications. Volumetric assessments have provided important information in the neural mechanisms of mood regulation, especially in the overlap of cognitive disorders. This article reviews articles describing findings of volumetric analyses in elderly with unipolar depression and bipolar disorders, and compares and contrasts these findings with the larger volumetric research in affective disorders.

Aged↗
PubMed1987

Simulating failure times when the event of interest is unobservable with emphasis on animal carcinogenicity studies.

This paper discusses and summarizes the methods which can be used to simulate failure times when an intermediate event of interest is unobservable. Data from animal carcinogenicity experiments are typically of this form. The simulation of time-to-event data where cause of failure is known and the case where cause of failure is unknown are discussed. The methods proposed for simulating failure times use identifiable hazard functions and allow for random sampling of functioning experimental units at fixed times. Some useful design and programming tools are also given.

Algorithms↗
PubMed1990

Conducting a matched-pairs historical cohort study with a computer-based ambulatory medical record system.

We describe techniques for using the Computer-Stored Ambulatory Record (COSTAR) at the Massachusetts General Hospital to conduct a historical cohort study of the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on blood pressure control. A query language was used to identify patients satisfying clinical and data-availability criteria, to match these patients with clinically similar patients not exposed to NSAIDs, and to collect data from the COSTAR records of both groups of patients to determine any differences in outcome. We analyzed over 30,000 patient records to select 90 pairs of patients used in the study. This approach to clinical research uses data collected for purpose of patient care and so does not require the separate recording of patient data for clinical research. Using computer-based medical record systems with a query language allows selection and matching of patients using detailed demographic and clinical criteria. The ability to conduct such studies is an advantage of computer-based medical record systems over the paper record system.

Ambulatory Care↗
PubMed1990

An algorithm for approximating conditional probabilities.

When diagnostic programs are constructed within a probabilistic framework, it is often the case that computation of joint probabilities of exhaustive combinations of events is easy, but computation of the kind of conditional probabilities the user wishes to know, is hard. This paper describes a simple algorithm for computing the required values, and then suggests several heuristic optimizations that may enable suitable approximations to be obtained in a feasible time when the task is otherwise intractable. An account is given of a specific application of the method in the construction of a medical diagnostic program, which is described in more detail elsewhere.

Algorithms↗
PubMed1995

Time-frequency analysis of postural sway.

Postural sway during quiet stance has been used to characterize the postural control system. Most studies have used center of pressure (COP) measurements and have assumed stationarity, however, recent research has indicated that COP is not stationary. The purpose of this study is to introduce and demonstrate a nonstationary spectral estimation technique to examine the time-varying nature of postural sway. Data from two experiments were used to verify the usefulness of the spectral estimator for the analysis of COP. The first data set contains COP recorded from normal subjects swaying about their ankles in response to a metronome as it was gradually changed from 2 to 1 Hz. The time-frequency distribution reveals time-varying spectral changes corresponding to frequency changes made by the subjects. The second set consists of COP from normal subjects and vestibularly impaired patients standing quietly on a force plate with eyes closed for 100 s. The time-frequency distributions for the COP were estimated for both sets of data. The COP's appear to be nonstationary with the energies at a given frequency modulating through time.

Computer Simulation↗
PubMed1995

The accuracy of CT-based inhomogeneity corrections and in vivo dosimetry for the treatment of lung cancer.

PURPOSE: To determine the accuracy of dose calculations based on CT-densities for lung cancer patients irradiated with an anterio posterior parallel-opposed treatment technique and to evaluate, for this technique, the use of diodes and an Electronic Portal Imaging Device (EPID) for absolute exit dose and relative transmission dose verification, respectively. MATERIALS AND METHODS: Dose calculations were performed using a 3-dimensional treatment planning system, using CT-densities or assuming the patient to be water-equivalent. A simple inhomogeneity correction model was used to take CT-densities into account. For 22 patients, entrance and exit dose calculations at the central beam axis and at several off-axis positions were compared with diode measurements. For 12 patients, diode exit dose measurements and exit dose calculations were compared with EPID transmission dose values. RESULTS: Using water-equivalent calculations, the actual exit dose value under lung was, on average, underestimated by 30%, with an overall spread of 10% (1 SD) in the ratio of measurement and calculation. Using inhomogeneity corrections, the exit dose was, on average, overestimated by 4%, with an overall spread of 6% (1 SD). Only 2% of the average deviation was due to the inhomogeneity correction model. The other 2% resulted from a small inaccuracy in beam fit parameters and the fact that lack of backscatter is not taken into account by the calculation model. Organ motion, resulting from the ventilatory or cardiac cycle, caused an estimated uncertainty in calculated exit dose of 2.5% (1 SD). The most important reason for the large overall spread was, however, the inaccuracy involved in point measurements, of about 4% (1 SD), which resulted from the systematic and random deviation in patient set-up and therefore in the diode position with respect to patient anatomy. Transmission and exit dose values agreed with an average difference of 1.1%. Transmission dose profiles also showed good agreement with calculated exit dose profiles. CONCLUSIONS: The study shows that, for this treatment technique, the dose in the thorax region is quite accurately predicted using CT-based dose calculations and a simple heterogeneity correction model. Point detectors such as diodes are not suitable for exit dose verification in regions with inhomogeneities. The EPID has the advantage that the dose can be measured in the entire irradiation field, thus allowing an accurate verification of the dose delivered to regions with large dose gradients.

Female↗
PubMedDate not supplied

Simulation of linear compartment models with application to nuclear medicine kinetic modeling.

Several techniques are evaluated for solving the linear ordinary differential equations arising from compartment models. The methods involve approximating the matrix exponential of the state matrix (i.e. the transition matrix). The computational efficiencies of these techniques, together with that of a general purpose differential equation solver, are compared for several models arising from radiopharmacokinetic studies. The matrix exponential calculations are performed using both Ward's Padé approximation method and an eigenvalue-eigenvector decomposition (QR factorization) of the matrix A. These two algorithms have been incorporated as simulation options into the programs of the ADAPT package. ADAPT consists of a set of high-level programs for simulation, parameter estimation and experiment design, developed primarily for basic and clinical research modeling and data analysis applications involving pharmacokinetic and pharmacodynamic processes. The advantages and disadvantages of these simulation strategies for solving linear kinetic models within a parameter estimation setting are illustrated and discussed.

Algorithms↗
PubMed1995

Computer simulation of the temperature- and hydration-dependent lateral diffusion of phosphatidylcholine in lipid bilayers.

A lattice model of a lipid bilayer near the so-called main phase transition between the liquid crystalline (L alpha) and the gel (L beta) phase is presented. It is based on a two-state model. Jump dynamics are defined for the lattice molecules to simulate lateral diffusion. The temperature and hydration dependence of the lateral diffusion coefficients of the model are calculated for the L alpha phase using Monte Carlo simulation techniques. The results obtained allow the estimation of the hydration dependent part of the lateral diffusion activation energy by thermodynamical quantities. We compare these results with measured activation energies of dipalmitoylphosphatidylcholine (DPPC) and propose a model to describe the total lateral diffusion activation energy of such systems.

Chemical Phenomena↗
PubMed2004

Determination of accurate KI values for tight-binding enzyme inhibitors: an in silico study of experimental error and assay design.

Determination of accurate K(I) values for tight-binding enzyme inhibitors is important from both a basic biochemistry point of view (understanding the differences in affinity of related molecules) and a medicinal chemistry vantage (developing structure-activity relationships (SAR)). It is advantageous to directly fit the quadratic equation describing tight-binding behavior, known commonly as the Morrison equation, to obtain these K(I) values. The results of simulated experiments that examine the effect of assay design and experimental error on the ability to accurately determine K(I) values at several [E]0/K(I-app) ratios are described. Input ("true") values of the uninhibited velocity, inhibition constant, and total enzyme concentration were used to calculate the velocity at various inhibitor concentrations. Gaussian error was introduced into the velocities and the simulated reactions were fit to estimate upsilon0, K(I), and [E]0. Recommendations for optimizing the inhibitor dilutions within the context of a 96-well-plate format and simple serial dilution steps are made. These include using three points to determine the enzyme concentration ([I]=0, 0.5[E]0, and [E]0), using a narrow dilution series with only two or three points to determine the asymptote at high inhibitor concentration, and avoiding fixing [E]0 to a constant value in the fitting if at all possible. The risks and rewards of fixing [E]0 to a constant value, especially the effect on SAR, are also examined.

Computer Simulation↗
PubMed2004

Non-linear mixed-effects pharmacokinetic/pharmacodynamic modelling in NLME using differential equations.

The standard software for non-linear mixed-effect analysis of pharmacokinetic/pharmacodynamic (PK/PD) data is NONMEM while the non-linear mixed-effects package NLME is an alternative as long as the models are fairly simple. We present the nlmeODE package which combines the ordinary differential equation (ODE) solver package odesolve and the non-linear mixed effects package NLME thereby enabling the analysis of complicated systems of ODEs by non-linear mixed-effects modelling. The pharmacokinetics of the anti-asthmatic drug theophylline is used to illustrate the applicability of the nlmeODE package for population PK/PD analysis using the available data analysis tools in R for model inspection and validation. The nlmeODE package is numerically stable and provides accurate parameter estimates which are consistent with NONMEM estimates.

Algorithms↗
PubMed2006

Nonlinear analysis of wheezes using wavelet bicoherence.

Wheezes, as being abnormal breath sounds, are observed in patients with obstructive pulmonary diseases, such as asthma. The aim of this study was to capture and analyze the nonlinear characteristics of asthmatic wheezes, reflected in the quadrature phase coupling of their harmonics, as they evolve over time within the breathing cycle. To achieve this, the continuous wavelet transform (CWT) was combined with third-order statistics/spectra. Wheezes from patients with diagnosed asthma were drawn from a lung sound database and analyzed in the time-bi-frequency domain. The analysis results justified the efficient performance of this combinatory approach to reveal and quantify the evolution of the nonlinearities of wheezes with time.

Algorithms↗
PubMed2005

Unraveling the electrically evoked compound action potential.

With the advent of eCAP recording tools such as NRT and NRI for cochlear implants, neural monitoring has become widely used to ascertain the integrity of the neural/electrode interface as well as for assisting in the setting of program levels. The basic concepts of eCAP recordings are deduced from the acoustical equivalent of the electrocochleogram. There are, however, indications that under electrical stimulation some of these do not hold, like the unitary response concept (i.e., the principle that every fiber produces the same contribution to the eCAP). Computer modeling has proven to be a valuable tool for gaining insight into the functioning of electrical stimulation. In this study the extension of a three-dimensional human cochlea, incorporating back-measuring capabilities, is described. Using this new model, the contribution of single fiber action potentials (SFAPs) to the measured eCAP is investigated. The model predicts that contrary to common belief--the compound action potential as measured by the cochlear implant system does not necessarily reflect the propagated action potential along the auditory nerve.

Action Potentials↗
PubMed2004

Trend detection via temporal difference model predicts inferior prefrontal cortex activation during acquisition of advantageous action selection.

The process of accurately predicting which actions are associated with advantageous versus disadvantageous outcomes is an important function of daily life. An integral part of this process is being able to detect when the association between an action and an outcome changes. This investigation examined the hypothesis that the inferior prefrontal cortex is critical for the detection of trends and that a trend process derived from the temporal difference model accomplishes this detection. Nineteen normal right-handed volunteers completed 120 4-s trials of a Rock Paper Scissors (RPS) task during functional magnetic resonance imaging. Subjects acquired the selection of advantageous actions during the RPS task. Activations in the medial frontal gyrus (BA 10), left ventrolateral frontal gyrus (BA 11/47), and left pallidum were significantly higher during trials in which subjects acquired the advantageous action. The time course of individually derived trend detection functions was found to be time-locked to the hemodynamic changes in the inferior frontal gyrus. These findings are consistent with the hypothesis that the inferior prefrontal cortex computes a trend from previously experienced action-outcome sequences based on a value function derived from the temporal difference model.

Association Learning↗
PubMed2004

Cognitive conjunction and cognitive functions.

We argue that conjunction analysis does not solve the problems with subtraction analyses that it sets out to solve and that it has additional problems of its own. We argue that detailed analyses of the tasks set to identify cognitive functions are required for both conjunction and subtraction analyses to achieve their goals of localizing cognitive operations using functional neuroimaging techniques.

Attention↗
PubMed2004

Fast and robust parameter estimation for statistical partial volume models in brain MRI.

Due to the finite spatial resolution of imaging devices, a single voxel in a medical image may be composed of mixture of tissue types, an effect known as partial volume effect (PVE). Partial volume estimation, that is, the estimation of the amount of each tissue type within each voxel, has received considerable interest in recent years. Much of this work has been focused on the mixel model, a statistical model of PVE. We propose a novel trimmed minimum covariance determinant (TMCD) method for the estimation of the parameters of the mixel PVE model. In this method, each voxel is first labeled according to the most dominant tissue type. Voxels that are prone to PVE are removed from this labeled set, following which robust location estimators with high breakdown points are used to estimate the mean and the covariance of each tissue class. Comparisons between different methods for parameter estimation based on classified images as well as expectation--maximization-like (EM-like) procedure for simultaneous parameter and partial volume estimation are reported. The robust estimators based on a pruned classification as presented here are shown to perform well even if the initial classification is of poor quality. The results obtained are comparable to those obtained using the EM-like procedure, but require considerably less computation time. Segmentation results of real data based on partial volume estimation are also reported. In addition to considering the parameter estimation problem, we discuss differences between different approximations to the complete mixel model. In summary, the proposed TMCD method allows for the accurate, robust, and efficient estimation of partial volume model parameters, which is crucial to a variety of brain MRI data analysis procedures such as the accurate estimation of tissue volumes and the accurate delineation of the cortical surface.

Artifacts↗
PubMed2004

Combinatorial codes in ventral temporal lobe for object recognition: Haxby (2001) revisited: is there a "face" area?

Haxby et al. [Science 293 (2001) 2425] recently argued that category-related responses in the ventral temporal (VT) lobe during visual object identification were overlapping and distributed in topography. This observation contrasts with prevailing views that object codes are focal and localized to specific areas such as the fusiform and parahippocampal gyri. We provide a critical test of Haxby's hypothesis using a neural network (NN) classifier that can detect more general topographic representations and achieves 83% correct generalization performance on patterns of voxel responses in out-of-sample tests. Using voxel-wise sensitivity analysis we show that substantially the same VT lobe voxels contribute to the classification of all object categories, suggesting the code is combinatorial. Moreover, we found no evidence for local single category representations. The neural network representations of the voxel codes were sensitive to both category and superordinate level features that were only available implicitly in the object categories.

Adult↗