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Simultaneous liquid chromatographic determination of seventeen of the major monoamine neurotransmitters, precursors and metabolites. I. Optimization of the mobile phase using factorial designs and a computer program to predict chromatograms.

Utilizing reversed-phase high-performance liquid chromatography (HPLC) with electrochemical detection and optimization of the mobile phase using factorial designs and a constructed computer program to predict chromatograms, it has been possible to obtain a satisfactory resolution of seventeen of the major monoamine neurotransmitters, precursors and metabolites. A rapid (less than 25 min) isocratic system for the simultaneous determination of 3,4-dihydroxyphenylalanine, dopamine, dihydroxyphenylacetic acid, 3-methoxytyramine, homovanillic acid, norepinephrine, normetanephrine, 3,4-dihydroxyphenylethylene glycol, 3-methoxy-4-hydroxyphenylethylene glycol, epinephrine, metanephrine, vanillylmandelic acid, 5-hydroxytryptophan, serotonin, 5-hydroxytryptophol and 5-hydroxyindoleacetic acid in addition to the internal standard isoproterenol is presented. The optimization strategy included selection of variables to optimize by a reduced factorial design a detailed study of these variables by a complete factorial design, theoretical predictions of chromatograms by a constructed computer program and test on the HPLC system. This optimization strategy can easily be applied to any problem of solute separation by liquid chromatography.

Chromatography, High Pressure Liquid

An interactive computer program to teach and investigate diagnostic processing.

An interactive computer program designed to present information about a patient taken from a history, physical examination and investigations is described. The application and advantages of the technique for the purposes of teaching and investigating medical (diagnostic) problem-solving are briefly discussed.

Computer-Assisted Instruction

A computer program to prepare and answer multiple choice questions.

A computer program to develop files of multiple choice questions for examination and teaching purposes is described. The program enables an examiner to prepare and modify up to 50 short answer questions with either a single or multiple correct answer format, and allows one to review the students answers individually or collectively, updating the item discrimination and difficulty indices each time a student performs the test. It also provides the option of answering the question file with or without review of the correct answer and reference.

Computers

A computer program for the morphometric analysis of cell profiles.

A computer program which yields values for the volumes, surface areas, and volume/surface area ratios of cell profiles is described for use on a desktop calculator (minicomputer). This program uses standard morphometric procedures, and incorporates data obtained from electron micrographs at two levels of sampling. The main program yields values for the 'average cell volume' at the tissue level of sampling. Two options at the cellular level of sampling are also included which yield values for the volumes, surface areas and volume/surface area ratios for the organelles. The first option allows an analysis of 'whole cells' containing equatorial profiles through the nucleus, while the second option permits a 'fractional' approach using segments of the cells. Finally, some of the advantages of the two options are discussed.

Cell Count

Bound and determined: a computer program for making buffers of defined ion concentrations.

A computer program that allows the preparation of buffers containing known concentrations of metal-ligand complexes at defined pH values and temperatures is described. Ligands are defined as compounds that bind metals and may include AMP, ADP, ATP, GMP, GDP, GTP, EGTA, EDTA, BAPTA, phosphate, sulfate, chloride, monocarboxylic acids, dicarboxylic acids, organophosphates, and/or citric acid. Metals may include sodium, potassium, magnesium, calcium, and/or manganese. The program uses association constants corrected for temperature and ionic strength so that solutions between 0 and 40 degrees C and between pH values of 4 and 10 can be defined. The program can perform the following: (i) calculate the concentration of all metal-ligand complexes when total metal and total ligand concentrations are known, (ii) calculate the concentration of metal ion required to make a solution of known free metal ion concentration when total ligand concentrations are known, (iii) calculate the concentration of ligand required to make a solution of known free metal ion concentration when total metal concentrations are known, and (iv) calculate the total concentrations of metal and ligand required to make a buffer of known metal-ligand concentration. Options i-iii are useful for making buffers of defined free metal ion concentrations; option iv is useful for making buffers of defined metal-nucleotide concentrations.

Adenosine Triphosphate

A computer program for the statistical analysis of cancer inhibition/promotion experiments.

The computer program discussed and presented in this paper is designed for the statistical analysis of data from cancer inhibition/promotion experiments that involve Type I censoring. The theoretical derivation of the method is described in Biometrics 43 (1987) 525-534 and Appl. Math. Lett. 1 (1988) 197-201. Turbo Pascal is used to compute maximum likelihood estimates of the parameters of interest: the mean number of induced tumors per animal, and the mean time to tumor detection. The program conducts a likelihood ratio test to determine if there is an overall experiment effect, and allows the user to select options to isolate the pair(s) of groups contributing to the experiments effect, to isolate group differences in terms of tumor number and growth rate, and to graph 95% confidence regions for the vector parameter of interest.

Animals

Sympmed I: computer program for primary health care.

Sympmed I is an experimental computer program that identifies and offers treatment to outpatients whose symptoms can be effectively and safely treated. To verify the safety of using such a package an evaluation of Sympmed I was carried out. The patients' symptoms were entered into the computer by a junior doctor and then by a non-medical person, an engineer. The prescriptions offered by the program were compared with those given by a general practitioner after examining the patient. It was found that 390 of 500 (78%) patients in the first group and 276 of 400 (69%) patients in the second group were offered prescriptions comparable to the ones given by the general practitioner, and the rest were advised to see a doctor. In no case was a patient offered treatment when he or she needed to see a doctor. The results of the evaluation confirm that most problems seen by first level medical personnel in developing countries are simple, repetitive, and treatable at home or by a paramedical worker with a few safe, essential drugs, thus avoiding unnecessary visits to a doctor.

Developing Countries

Computational analysis and dosimetric evaluation of a commercial irregular-fields computer program.

The proper evaluation of the accuracy of a new computer program for radiation-therapy dosimetry requires consideration of both the mathematical algorithm used in the program and the performance required in clinical applications. As an example, our evaluation of the irregular-fields dosimetry program currently marketed by SHM for their Rad-8 system is described. The evaluation begins with an explanation of the mathematical computation described. The evaluation begins with an explanation of the mathematical computation method, with emphasis on the points where the calculation differs from previous methods. Next, the procedure for setting up the beam data file is discussed. Finally, a step-by-step procedure is described in which calculated doses are compared with measured doses, using a Varian Clinac-4 with lead flattening filter, and the limits within which a +/- 5% accuracy is attainable are estimated. Some sources of error and areas for possible improvements are mentioned.

Computers

Assessment of the performance of electrocardiographic computer programs with the use of a reference data base.

To allow an exchange of measurements and criteria between different electrocardiographic (ECG) computer programs, an international cooperative project has been initiated aimed at standardization of computer-derived ECG measurements. To this end an ECG reference library of 250 ECGs with selected abnormalities was established and a comprehensive reviewing scheme was devised for the visual determination of the onsets and offsets of P, QRS, and T waves. This task was performed by a group of cardiologists on highly amplified, selected complexes from the library of ECGs. With use of a modified Delphi approach, individual outlying point estimates were eliminated in four successive rounds. In this way final referee estimates were obtained that proved to be highly reproducible and precise. This reference data base was used to study measurement results obtained with nine vectorcardiographic and 10 standard 12-lead ECG analysis programs. The medians of program determinations of P, QRS, and T wave onsets and offsets were close to the final referee estimates. However, an important variability could be demonstrated between measurements from individual programs and mean differences from the referee estimates amounted to 10 msec for QRS for certain programs. In addition, the variances of all programs with respect to the referee point estimates were variable. Some programs proved to be more accurate and stable when the data from high- vs low-noise recordings were analyzed. Average Q wave durations calculated from ECGs for which programs agreed on the presence of a Q or QS wave differed by more than 8 msec in several program-to-program comparisons. Such differences may have important consequences with respect to diagnostic performance. Various factors that might explain these differences have been determined. The present study demonstrates that to allow an exchange of results and diagnostic criteria between different ECG computer programs, definitions, minimum wave requirements, and measurement procedures urgently need to be standardized.

Computers

A computer program for multivariate ratio analysis (MISCAT).

Analysts must deal frequently with missing data in multivariate analysis. In such cases, estimating the covariance maxtrix V of the dependent variables usually involves initial estimation and iterative adjustment of imputed missing data values, and/or smoothing of an estimate V which is not necessarily positive semi-definite. This paper presents an alternative procedure for computing estimates of relevant multivariate parameters in situations where missing data occur at random and with small probability. MISCAT is a computer program which computes multivariate ratio estimates of the means and a corresponding positive semi-definite estimate of the covariance matrix. It is an extension of GENCAT, which is a program for the generalizaed least squares analysis of categorical data. Thus, one advantage of dealing with missing data in this manner is that variation among the ratio estimates may be conveniently analyzed within MISCAT using asymptotic regression methodology, provided that sample sizes are sufficiently large. An example is given to illustrate such analysis for longitudinal data from a multicenter clinical trial.

Computers

A computer program for stepwise logistic regression using maximum likelihood estimation.

A computer program has been written which performs a stepwise selection of variables for logistic regression using maximum likelihood estimation. The selection procedure is based on likelihood ratio tests for the coefficients. These tests are used in a forward selection and a backward elimination at each step. The use of the program is illustrated by several examples.

Computers

Development of a computer program to analyze the parameters of platelet-vessel wall interaction.

The use of the Baumgartner perfusion system allows the morphometric quantification of platelets interacting with vessel wall, however it presents the basic difficulties of morphometrical measurements. In order to facilitate the procedure of evaluation we developed a semiautomated method to avoid the complexity of the classical evaluation. Our system consists on an optical picture analysis system connected with a specially developed computer program which allows fast quantification. Simultaneously to the outlining of interacting platelets the computer program recognizes, corrects, selects and stores the information, in order to perform the final calculations as previously established. This system has been demonstrated to be as effective as the classical morphometric evaluation in the measure of platelets interacting with subendothelium. Potential sources of error such as subjectivity of the observers in selecting the class of interacting platelets are avoided. The use of this combined method opens the possibility to adapt the Baumgartner perfusion system to clinical routine and to the screening of drugs that modify platelet adherence.

Animals

The AAHA Computer Program. American Animal Hospital Association.

The American Animal Hospital Association Computer Program should benefit all small animal practitioners. Through the availability of well-researched and well-developed certified software, veterinarians will have increased confidence in their purchase decisions. With the expansion of computer applications to improve practice management efficiency, veterinary computer systems will further justify their initial expense. The development of the Association's veterinary computer network will provide a variety of important services to the profession.

Animals

Reduction of the limitations for the calculations of shielding effects with Van de Geijn's computer program.

The possibilities for reducing in Van de Geijn's computer program the original limitations for the size and the position within the field of shielding blocks are explored. New methods are presented which are based on experimental measurements as well as more theoretical approaches, without need for any change in the program itself. Two typical clinical examples are presented and the precision obtained critically investigated.

Cobalt Radioisotopes

A simple computer program for optimization of source loading in cervical intracavitary applicators.

A computer program has been developed to aid in the brachytherapy of cancer of the cervix. Using a least-squares minimization algorithm, the program will optimize the source loading in intracavitary applicators so as to reproduce, as nearly as physical considerations allow, the dose distribution requested by the user. Applicator geometry and the relative positions of anatomical points of interest must be supplied to the program, as well as an inventory of available source strengths. Output from the computer includes the optimized source loading, time of application, and the resulting relative doses to the various user-selected points of interest.

Computers

A computer program for multiple decrement life table analyses.

Life table analysis has traditionally been the tool of choice in analyzing distribution of "survival" times when a parametric form for the survival curve could not be reasonably assumed. Chiang, in two papers [1,2] formalized the theory of life table analyses in a Markov chain framework and derived maximum likelihood estimates of the relevant parameters for the analyses. He also discussed how the techniques could be generalized to consider competing risks and follow-up studies. Although various computer programs exist for doing different types of life table analysis [3] to date, there has not been a generally available, well documented computer program to carry out multiple decrement analyses, either by Chiang's or any other method. This paper describes such a program developed by Research Triangle Institute. A user's manual is available at printing costs which supplements the contents of this paper with a discussion of the formula used in the program listing.

Computers