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A FORTRAN computer program written to perform a multivariate analysis of growth and response curves is described. The underlying statistical methodology is particularly applicable with incomplete observations, and may offer improved power performance to the distribution-free methods described previously.
Many observations encountered in biological and medical research are randomly distributed in bivariate scales, and thus not susceptible to simple regression analyses. Since such data are depicted by ellipses in scatter diagrams, a computer program to calculate the confidence regions for the means or the total data of bivariate samples was written in BASIC for correlational analyses. The program, based on the principal axes algorithm, plots the calculated confidence regions as an elliptic area, using the fitted equations for its major and minor axes. The program displays the sample parameters required to perform comparisons between different groups of experimental conditions.
BOOMER is an improved version of an earlier non-linear regression program, MULTI-FORTE. Rather than the user writing a FORTRAN subroutine, models are defined by means of the parameters which make up the model. Models based on differential equations are specified by means of zero-order, first-order, or Michaelis-Menten-type rate constants. Doses (in units of mass) are translated into the usually observed concentration units by a reciprocal volume parameter. Integrated equation models are specified in terms of baseline terms, exponential terms, or the emax function with slope term as described by the Hill equation. Time points can be specified as parameters to specify dose times, infusion start/stop times, or lag times. With careful selection of parameters quite complex models can be specified. The user has a choice of differential equation solvers and fitting algorithms.
This paper describes a program for summarizing scatter plots with robust ellipses. The program is written in BASIC and is designed for interactive use on a microcomputer graphics terminal to enable quick redesigns of the graph.
Generating random variables from a specific distribution, whether symmetric or asymmetric, is a concern of investigators involved in Monte Carlo studies. Of particular interest to those concerned with robustness is the generation of contaminated symmetric distributions such as those used in the Princeton Robustness Study. A reliable composite uniform U(0,1) generator is described and algorithms for transforming U(0,1) to symmetric long-tailed and contaminated symmetric distributions are given. Goodness-of-fit tests and graphical illustrations demonstrate the adequacy of the empirical distributions.
An updated version of the computer program EXCAD [1] allows the user to optimize experimental design to estimate parameters of particular semi-parametric models. The semi-parametric models take the general form of a function of time (t): Y(t) = NL (c(t,alpha),beta). The function NL(C(t,alpha),beta), is, in general, a non-linear transformation of a function, C(t,alpha), that in turn is the convolution of two others. One of these two functions is expressed in a non-parametric form, and is not of direct interest to the experimenter. The other is of direct interest: it is a parametric function depending on a set of parameters alpha. This semi-parametric model applies to numerous kinds of biological experiments, such as pharmacokinetic/pharmacodynamic, physiological, circulatory flow experiments. This paper presents a new method for determining an optimal experimental design to estimate the parameters alpha and beta. The new approach adopts the D-optimal criterion, and is illustrated using real thiopental data.
The need for a knowledge based expert system for efficient decision making in the field of pathology has been well accepted. To build the knowledge-base for such an expert system is a painstaking task. This work is an attempt to provide the pathologists a powerful and user-friendly tool that will help them in the process of building the knowledge-base for medical diagnosis by closely looking at the specimen images and their extracted feature values. The tool is based on multi-media relational database and software like VAX Rally (4GL), ILIAD and SAS to provide a wide-range comparative study between feature data and image data; and also their statistical analysis.
A recently described method for speed of sound estimation in tissues in pulse-echo mode involves reception of echoes generated by an ultrasonic pulse by means of a linearly tracking transducer. When the peaks of echo amplitudes are used as markers of arrival time, stairstep-like artifacts appear in the echo arrival time vs. transducer position plots. We postulate that these artifacts are a consequence of the speckle phenomenon commonly encountered in ultrasonic imaging. To test this hypothesis, we report computer simulations and water tank experiments which demonstrate similarities between the behavior of the stairsteps and the properties of ultrasonic speckle. Additionally, equations describing the precision of the speed of sound estimation in terms of the second order statistical properties of the stairstep artifact are derived.
Helical macromolecular assemblies are particularly difficult to study by X-ray diffraction but are quite well suited to analysis by electron microscopy. Most of our information about helical macromolecular assemblies has come from the electron microscope but has been limited to about 25 A resolution. With the use of low-dose electron cryomicroscopy, one can obtain structural data to near atomic resolution on two-dimensional crystals, but the problem is to extract the information from the noise. In this paper we present methods to extract signal from low-dose electron cryomicrographs of helically symmetric structures. We apply these methods to extract 10 A data from the bacterial flagellar filament.
A methodology able to derive spatial geometric models from input sequences of sonographic slices is proposed. The developed modeling procedure can be utilized to perform computer-assisted anatomic 3D analysis both on all echo space and selected subregions. The modeling procedure is mainly composed of three sequential phases: a) automatic acquisition and preprocessing of time sequences of 2D echotomograms; b) 3D reconstruction of images and computing of discrete distance maps of selected echoes according to predefined projective laws; and c) generation of a spatial geometric model of the examined object starting from the previously computed maps.
Either length measurements or area measurements may be made on a sample of profiles for the purpose of estimating the mean volume of a population of convex particles. Diameters of spheres, caliper diameters of ellipsoids and intercept lengths are available length measurements. Profile areas can be evaluated by planimetry or point counting. Either all the available profiles in random sections or point sampled profiles can be utilized. We have applied a Monte Carlo simulation to compare several of the stereologic methods for the estimation of the mean volumes of spheres and ellipsoids. Populations of spherical, prolate ellipsoidal and oblate ellipsoidal particles were subjected to random sectioning and measurement. Diameter, point sampled intercept length, area and point sampled area were measured in the case of the spherical particles. With the ellipsoids, the same measurement excepting diameters were performed. The measurements were converted to volumes by the appropriate equations, and the means, the standard deviations of the means and the 95% confidence intervals were determined for increasing sample sizes. All the methods provide estimates that converge on their theoretical mean volumes. The area measurements and particularly the point sampled area measurement show some advantage over the length measurements, but differences among the methods are small, not entirely consistent over the different cases and unlikely to be significant in most real applications.
Points of degenerate Hopf bifurcation in the Hodgkin-Huxley model are found as parameters temperature T and voltage level of sodium VNa are varied. Local techniques of degenerate Hopf bifurcation analysis are used to show the existence of families of periodic solutions of the model: isolated branches of periodic solutions (i.e. branches not connected to the stationary branch) are found in addition to Hopf branches. Purely numerical techniques are used to show that the isolas persist for VNa up to a value slightly greater than 114 mV. Under some conditions there are multiple stable periodic solutions, so "jumping" between action potentials of different amplitudes might be observed.
We analyzed the relationship between several morphonuclear parameters related to nuclear size, densitometry (deoxyribonucleic acid content and ploidy) and the chromatin pattern versus the histopathological grading of 46 bladder cancer samples graded according to the World Health Organization classification. We used a SAMBA 200 cell image processor with software allowing for the discrimination of 15 different parameters on Feulgen-stained imprint smears. In addition, we set up preliminary data banks that enable objective and reproducible grading of unknown cases. This approach must be validated in a large series of cases to create an expert system for bladder malignancy diagnosis.
We developed a sample size estimation program (SSEP) with which medical researchers can easily estimate the appropriate sample size for a specific significance level and statistical power using their favorite WWW browsers. SSEP can estimate the sample sizes for six statistical methods by Monte-Carlo simulation: Student's t-test, Welch's t-test, Analysis of variance, Wilcoxon's rank sum test, Kruskal-Wallis test, and the Cochran-Armitage test for linear trends. The SSEP simulation programs were created using the SAS software macro language. Medical researchers can interactively use this program and determine reliable sample sizes when planning new prospective clinical studies and animal experiments.
Analysis of longitudinal data is one of the most challenging tasks in statistical modeling. In the analysis, it is often necessary to take into account nonlinear response to a set of parameters of interest and correlation between measurements taken from the same individual. In addition, between- and within-subject variation has to be handled properly. An example of addressing these issues is the hierarchical nonlinear model, where parameter estimation can be performed using linearization method. In this paper a new NLMEM SAS/IML macro for hierarchical nonlinear models is proposed. The program uses a portion of the code developed earlier in NLINMIX. NLMEM retains all the benefits of NLINMIX while allowing the systematic part of the model structure to be specified using IML syntax. Consequently, NLMEM allows estimation of models which are not tractable using NLINMIX. In particular, it allows us to address advanced population pharmacokinetics and pharmacodynamics models specified by ordinary differential equations.
OBJECTIVES: Biometrical comparison procedures for cardiac imaging methods with continuous outcome are reviewed mainly concentrating on assessment and design adequate comparison of accuracy and precision. Univariate graphical and numerical representation of corresponding deviations is outlined to derive a 'check list' of minimum information necessary to compare the measurement methods. DATA: The methods reviewed here are illustrated by the comparison of standard 2DE bidimensional cardial volumetry versus assessment using TDE colour imaging in 28 normal probands. SOURCES: The paired t-test and the corresponding confidence interval approach are used to assess deviations in location of two imaging methods; the test procedures of Maloney and Rastogi Hahn and Nelson and Grubbs are surveyed as proposals for the comparison of precisions in paired data. The Krippendorff coefficient and the Bradley/Blackwood test are illustrated as surrogate measures for method concordance. CONCLUSIONS: Since these methods can be performed by simple modification of standard options available in most statistics software packages, this review intends to enable cardiologists to choose appropriate methods for statistical data analysis and representation on their own.
In 1995, the MedView project, based on a co-operation between computing science and clinical medicine was initiated. The overall goal of the project was to develop models, methods and tools to support clinicians in their daily diagnostic work. As part of MedView, two information visualisation tools were developed and tested as solutions to the problem of visualising clinical experience derived from large amounts of clinical data. The first tool (The Cube) was based on the idea of dynamic three-dimensional (3D) parallel diagrams, an idea similar to the notion of 3D parallel co-ordinates. The Cube was developed to enhance the clinician's ability to intelligibly analyse existing patient material and to allow for pattern recognition and statistical analysis. The second tool (SimVis) was based on a similarity assessment-based interaction model for exploring data, and was designed to help clinicians to classify and cluster clinical examination data. User interaction was supported by 3D visualisation of clusters and similarity measures. Both tools were tested on a knowledge base containing about 1500 examinations obtained from different clinics. Clinical practice indicated that the basic ideas are conceptually appealing to the involved clinicians as the tools can be used for generating and testing of hypotheses.
A computer program called LAURA has been developed to predict the production rates of any member of a nuclei network undergoing spontaneous decay and/or induced neutron transformation in a nuclear reactor. The theoretical bases for the development of LAURA were discussed in Part I. In particular, in Part I, we described how an expression based on the Rubinson (1949) approach is used to evaluate the depletion function. In this paper (Part II), we describe the full simulation of radionuclide production including the decomposition of a reaction network into independent linear chains, provisions for periodic reactor shutdown and restart, and implementation of an approximate solution given by Raykin and Shlyakhter (1989) to account for the effect of feedback due to alpha decay. Also included are some examples which demonstrate possible uses for LAURA.