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PubMed1996

Computerization of Fujimori's method of waveform recognition. A review and methodological considerations for its application to all-night sleep EEG.

This article critically reviews 8 computer implementations of Fujimori's method for EEG waveform recognition, with methodological considerations for the application of this method to the analysis of all-night sleep EEG. Fujimori's method has been considered one of the most appropriate waveform analyses for EEG. This kind of analysis is advantageous for measuring frequency and amplitude of each EEG wave separately. However, current implementations have drawbacks which must be resolved before they can be used on all-night sleep EEG. An optimal sampling rate should be determined which is appropriate to the purpose of analysis. Amplitude thresholds for wave recognition, which are now set arbitrarily, should also be improved. Measurement of waves in higher orders of superimposition is also necessary, although existing systems are limited to the second order. Additional algorithms, such as for the separate detection of sleep slow waves, may be useful. Further applications for Fujimori's method are suggested.

Electroencephalography↗
PubMed1995

Functional brain imaging with SPECT in normal aging and dementia. Methodological, pathophysiological, and diagnostic aspects.

New developments in instrumentation, radiochemistry, and data analysis, particularly the introduction of 99M TC-labeled brain-retained tracers for perfusion studies, have opened up a new era of single photon emission computed tomography (SPECT). In this review critical methodological issues relating to the SPECT instrument, the radioactive tracers, the scanning procedure, the data analysis and interpretation of data, and subject selection are discussed together with the changes in regional cerebral blood flow (rCBF) observed in normal aging. An overview is given of the topography and the pathophysiological and diagnostic significance of focal rCBF deficits in Alzheimer's disease and in other dementia disorders, in which SPECT is capable of early or preclinical disease detection. In Alzheimer's disease, the diagnostic sensitivity and specificity of focal rCBF deficits measured with SPECT and brain-retained tracers are very high, in particular when combined with medial temporal lobe atrophy on CT. Together with neuropsychological testing, SPECT serves to map the topography of brain dysfunction. Thus, in the clinical setting, SPECT provides information that is supplemental to that obtained in other studies. Future applications include neuroreceptor studies and treatment studies, in which SPECT may serve as a diagnostic aid in the selection of patients and as a potential mean for monitoring treatment effects. Although positron emission tomography is the best characterized tool for addressing some of these clinical and research issues in dementia, only the less expensive and technically simpler SPECT technique will have the potential of being available as a screening diagnostic instrument in the clinical setting. It is concluded that, properly approached, functional brain imaging with SPECT represents an important tool in the diagnosis, management, and research of dementia disorders.

Aging↗
PubMed2004

Period analysis for 'up-to-date' cancer survival data: theory, empirical evaluation, computational realisation and applications.

Long-term survival rates are the most commonly used outcome measures for patients with cancer. However, traditional long-term survival statistics, which are derived by cohort-based types of analysis, essentially reflect the survival expectations of patients diagnosed many years ago. They are therefore often severely outdated at the time they become available. A couple of years ago, a new method of survival analysis, denoted period analysis, has been introduced to derive more 'up-to-date' estimates of long-term survival rates. We give a comprehensive review of the new methodology, its statistical background, empirical evaluation, computational realisation and applications. We conclude that period analysis is a powerful tool to provide more 'up-to-date' cancer survival rates. More widespread use by cancer registries should help to increase the use of cancer survival statistics for patients, clinicians, and public health authorities.

Cohort Studies↗
PubMed1995

The use of physiologically-based pharmacokinetic/pharmacodynamic dosimetry models for chemical mixtures.

Human exposure to chemicals is rarely, if ever, limited to a single chemical. Therefore, it is essential that we consider multiple chemical effects and interactions in our risk assessment process. However, with the almost infinitely large number of chemical mixtures in the environment, systematic studies of the toxicology of these chemical mixtures with conventional methodologies and approaches are impossible because of the immense resources and unrealistically long durations required. Thus, the development of 'Predictive and Alternative Toxicology' is imperative. At Colorado State University (CSU), our research effort is entirely devoted to this challenge. In order to have a reasonable chance to deal with the complex issue of toxicology of chemical mixtures, we believe that the following concepts must be considered: (1) the utilization of computer, (2) the exploitation of mathematical/statistical methodologies; (3) developing very focused, mechanistically based, and short-term toxicology studies; (4) coupling computer/mathematical modeling with mechanistically-based toxicology. Our strategy therefore the utilization of physiologically-based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling, coupled with very focused, model-directed toxicology experiments as well as other statistical/mathematical methodologies such as Monte Carlo simulation, isobolographic analysis, and response surface methodology. We believe that 'Predictive and Alternative Toxicology' in terms of tissue dosimetry at the pharmacokinetic and pharmacodynamic levels is achievable with simple and complex but chemically defined mixtures. In this presentation, we describe two ongoing research projects as an illustration of our 'Bottom-Up' and 'Top-Down' approaches for handling the chemical mixtures: (1) PBPK/PD modeling of toxicologic interactions between Kepone and carbon tetrachloride (CCl4) and the coupling of Monte Carlo simulation for the prediction of acute toxicity; (2) the conceptual development of PBPK/PD modeling for a more complex chemical mixture of seven groundwater contaminants from hazardous waste sites and the consideration of subfractionation of this chemical mixture.

Animals↗
PubMed1998

Measuring departures from Hardy-Weinberg: a Markov chain Monte Carlo method for estimating the inbreeding coefficient.

Many well-established statistical methods in genetics were developed in a climate of severe constraints on computational power. Recent advances in simulation methodology now bring modern, flexible statistical methods within the reach of scientists having access to a desktop workstation. We illustrate the potential advantages now available by considering the problem of assessing departures from Hardy-Weinberg (HW) equilibrium. Several hypothesis tests of HW have been established, as well as a variety of point estimation methods for the parameter which measures departures from HW under the inbreeding model. We propose a computational, Bayesian method for assessing departures from HW, which has a number of important advantages over existing approaches. The method incorporates the effects-of uncertainty about the nuisance parameters--the allele frequencies--as well as the boundary constraints on f (which are functions of the nuisance parameters). Results are naturally presented visually, exploiting the graphics capabilities of modern computer environments to allow straightforward interpretation. Perhaps most importantly, the method is founded on a flexible, likelihood-based modelling framework, which can incorporate the inbreeding model if appropriate, but also allows the assumptions of the model to he investigated and, if necessary, relaxed. Under appropriate conditions, information can be shared across loci and, possibly, across populations, leading to more precise estimation. The advantages of the method are illustrated by application both to simulated data and to data analysed by alternative methods in the recent literature.

Algorithms↗
PubMed1981

Real time computerization of two-dimensional echocardiography.

A computerized system was developed for real time acquisition, enhanced processing, analysis, and display of cross-sectional images of the left ventricle derived by two-dimensional echocardiography (2DE). The new methodology couples a standard medical imaging computer system to the video output of any current 2DE unit, uses a 128 x 128 or 64 x 64 matrix window and stores the real time 30 frames/sec digitized images on a magnetic disk. Computerized beat-to-beat and frame-by-frame processing employs space-time smoothing the automatic detection of endocardial interfaces by standard threshold and second derivative techniques. Multiple views are displayed in real time with 256 levels of gray and color. The methodology was used to analyze and graphically display frame-by-frame changes throughout the cardiac cycle. In addition, regional wall motion and thickness were analyzed in 12 sectors of individual cross-sections using a standardized angular subdivision originating at the center of area and indexed by an external reference point. An algorithm was developed to correct cross-sectional interference definition from the commonly used trailing-to-leading edge to the more valid leading-to-leading outline technique. Computerized analysis of spatial and temporal variations of cardiac contraction were demonstrated in several clinical and experimental applications, including bicycle exercise testing, investigation of acute myocardial infarction, and assessment of interventions. Initial evaluation indicates that the new real time computerized digital acquisition and data analysis represents a major advances toward quantitation of left ventricular function using 2DE.

Animals↗
PubMed1995

Computational flow optimization of rotary blood pump components.

In an effort to improve and automate the fluid dynamic design of rotary blood pumps, a coupled computational fluid dynamics (CFD) shape optimization methodology has been developed and implemented. This program couples a finite element flow simulation with a gradient-based optimization routine to modify automatically the shape of an initial candidate blood path, according to a variety of desired fluid dynamic criteria, including shear stress, vorticity/circulation, and viscous dissipation. Preliminary results have led to both intuitive and nonintuitive transformations of the initial blood flow paths for both internal and external flows. This application of computer design optimization offers the ability to explore a much broader design space much more efficiently than would be possible with traditional parametric methods. It is believed that this computer tool can assist developers of rotary blood pumps in designing blood-wetted components that minimize thrombosis and hemolysis while simultaneously providing maximum flow performance.

Biomechanical Phenomena↗
PubMed2003

A general gel layer model for the transport of colloids and macroions in dilute solution.

A general boundary element methodology for studying the dilute solution transport of rigid macroions that contain gel layers on their outer surfaces is developed and applied to several model systems. The methodology can be applied to particles of arbitrary size, shape, charge distribution, and gel layer geometry. Account is also taken of the steady state distortion of the ion atmosphere from equilibrium, which makes it applicable to the transport of highly charged structures. The coupled field equations (Poisson, ion-transport, low-Reynolds-number Navier-Stokes, and Brinkman) are solved numerically and from this, transport properties (diffusion constants, electrophoretic mobilities, excess viscosities) can be computed. In the present work, the methodology is first applied to a gel sphere model over a wide range of particle charge and the resulting transport properties are found to be in excellent agreement with independent theory under those conditions where independent theory is available. It is then applied to several prolate spheroidal models of a particular silica sol sample in an attempt to identify possible solution structures. A single model, that is able to account simultaneously for all of the transport behavior, which does not undergo significant conformational change with salt concentration, could not be found. A model with a thin (</=1-nm) gel layer at high salt content that expands on going to low salt content is able to explain the salt dependence of the intrinsic viscosity, but not the electrophoretic mobility. However, a model with a fairly thick (2-nm) gel layer at high salt content, which expands slightly (2.5-nm) at low salt content, is in fairly good agreement with experiment. In addition, the influence of particle charge and the presence of a gel layer on the Scheraga-Mandelkern parameter are examined. This parameter is proportional to the product of the translational diffusion constant and the cube root of the intrinsic viscosity. It is found to be very robust with regard to net particle charge as well as properties of the gel layer.

Journal Article↗
PubMed2002

A comparison of transient dose model predictions and experimental measurements.

The RADTRAN and RISKIND transportation risk analysis computer codes are the primary tools used to estimate dose consequences and risks associated with the transport of radioactive material. Over the years, some of the mathematical models used within the two computer codes have been updated and the methodologies to calculate input parameters have been improved. In addition, both codes have been evaluated for ease of use and appropriateness of application and verified against other computer codes that perform similar calculations. However, neither code has been validated against experimental data. This report discusses the results of five sets of experimental measurements used to partially validate the specific mathematical models used to predict the dose to an individual due to a passing shipment of radioactive material within the RADTRAN and RISKIND computer codes. Based on the comparisons it was found that RISKIND most closely predicted the measured dose in the majority of the investigated scenarios and that 12 out of 14 cases demonstrate the expected inverse relationship between the measured dose and the distance of closest approach. Only half of the data demonstrated the expected inverse relationship between dose and speed of travel.

Algorithms↗
PubMed2006

Accommodating space, time and randomness in network simulation.

Interest in the possibility of dynamically simulating complex cellular processes has escalated markedly in recent years. This interest has been fuelled by three factors: the generally accepted value in understanding living processes as integrated systems; the dramatic increase in computational capability; and the availability of new or improved technology for making the quantitative measurements that are needed to drive and validate cellular simulations. Between the extremes of atom-scale and organism-scale simulation is a vast middle-ground requiring simulation strategies that are capable of dealing with a range of spatial, temporal and molecular abundance scales that are crucial for a comprehensive understanding of integrative cell biology. Although at an early stage, methodological improvements and the development of computational platforms provide some hope that simulations will emerge that can bridge the gap between network models and the true operation of the cell as a complex machine.

Animals↗
PubMed2006

Is the bare spot a consistent landmark for shoulder arthroscopy? A study of 20 embalmed glenoids with 3-dimensional computed tomographic reconstruction.

PURPOSE: Our aim was to test a published methodology for arthroscopically quantifying glenoid bone loss for its dependability in a cadaver-based anatomic study with 3-dimensional (3-D) computed tomographic (CT) reconstructions of 20 embalmed glenoids. METHODS: Manual macroscopic measurements were made in a standardized fashion. In addition, we marked the center of the visible bare spot in 20 embalmed glenoids with a titanium pin. The shoulder joints were carefully selected for intact rotator cuff, missing capsule-labral deficiency, and absence of severe cartilage degeneration. 3-D reconstructed CT scans were evaluated for consistency of the bare spot. RESULTS: The mean distance from the bare spot to the anterior margin measured manually was 10.9 mm (CT-based, 13.9 mm), to the posterior margin 13.7 mm (CT-based, 16.4 mm), and to the inferior margin 9.7 mm (CT-based, 15.1 mm). Distances were significantly different. CONCLUSIONS: The bare spot did not prove its consistency in 20 carefully selected specimens. Therefore, we conclude that this methodology is not a reliable way to intraoperatively determine bony glenoid deficiency. CLINICAL RELEVANCE: We recommend preoperative bilateral CT scans for evaluation of bony glenoid deficiency for exact quantification of the bone loss.

Aged↗
PubMed1993

Application of computational fluid dynamics to regional dosimetry of inhaled chemicals in the upper respiratory tract of the rat.

For certain inhaled air pollutants, such as reactive, water soluble gases, the distribution of nasal lesions observed in F344 rats may be closely related to regional gas uptake patterns in the nose. These uptake patterns can be influenced by the currents of air flowing through the upper respiratory tract during the breathing cycle. Since data on respiratory tract lesions in F344 rats are extrapolated to humans to make predictions of risk to human health, a better understanding of the factors affecting these responses is needed. To assess potential effects of nasal airflow on lesion location and severity, a methodology was developed for creation of computer simulations of steady-state airflow and gas transport using a three-dimensional finite element grid reconstructed from serial step-sections of the nasal passages of a male F344 rat. Simulations on a supercomputer used the computational fluid dynamics package FIDAP (FDI, Evanston, IL). Distinct streams of bulk flow evident in the simulations matched inspiratory streams reported for the F344 rat. Moreover, simulated regional flow velocities matched measured velocities in concurrent laboratory experiments with a hollow nasal mold. Computer-predicted flows were used in simulations of gas transport to nasal passage walls, with formaldehyde as a test case. Results from the uptake simulations were compared with the reported distribution of formaldehyde-induced nasal lesions observed in the F344 rat, and indicated that airflow-driven uptake patterns probably play an important role in determining the location of certain nasal lesions induced by formaldehyde. This work demonstrated the feasibility of applying computational fluid dynamics to airflow-driven dosimetry of inhaled chemicals in the upper respiratory tract.

Administration, Inhalation↗
PubMed2001

How to be a gray box: dynamic semi-physical modeling.

A general methodology for gray-box, or semi-physical, modeling is presented. This technique is intended to combine the best of two worlds: knowledge-based modeling, whereby mathematical equations are derived in order to describe a process, based on a physical (or chemical, biological, etc.) analysis, and black-box modeling, whereby a parameterized model is designed, whose parameters are estimated solely from measurements made on the process. The gray-box modeling technique is very valuable whenever a knowledge-based model exists, but is not fully satisfactory and cannot be improved by further analysis (or can only be improved at a very large computational cost). We describe the design methodology of a gray-box model, and illustrate it on a didactic example. We emphasize the importance of the choice of the discretization scheme used for transforming the differential equations of the knowledge-based model into a set of discrete-time recurrent equations. Finally, an application to a real, complex industrial process is presented.

Algorithms↗
PubMedDate not supplied

International nifedipine trial on anti-atherosclerotic therapy (INTACT)--methodologic implications and results of a coronary angiographic follow-up study using computer-assisted film analysis.

Animal experiments demonstrated a significant suppressive effect of various calcium channel blockers on the formation of atherosclerotic lesions. Therefore, a prospective, placebo-controlled, randomized, double blind multicenter study was performed to investigate the inhibitory influence of the calcium channel blocker nifedipine (80 mg/day) on the progression of coronary artery disease in man. Study endpoints were changes of coronary morphology documented by coronary angiography with particular respect to the formation of new coronary stenoses. In 348 out of 425 patients included in the study, coronary angiograms were repeated after three years. The angiograms were standardized by induction of a maximal coronary vasodilation with high doses of nitrates and by using absolutely identical angiographic projections. Quantitative analysis of coronary cineangiograms was performed with the computer-assisted contour detection system CAAS. Parameters were mean and minimal diameter of all segments and minimal stenosis diameter, percent diameter stenosis, length and plaque area of all stenoses. Continuous intake of study medication was registered in 282 patients, 134 on nifedipine and 148 patients on placebo. In these patients, a total of 3808 coronary segments with 893 stenoses (greater than or equal to 20% diameter reduction in at least one angiographic projection) were compared on the baseline and follow-up cineangiograms. The changes in all angiographic parameters analyzed averaged over all patients by considering all angiographic projections analyzed, indicated significant progression of the disease (p less than 0.006). The average changes in all parameters were even about three times more profound, when in the individual patients only the respective projections indicating the maximal changes were considered for the calculation (p less than 0.001). However, with neither of these two analysis modes, the differences in progression between the treatment groups were statistically significant. In the follow-up angiograms, a total of 196 new coronary lesions (185 stenoses, 11 occlusions) were found at previously normal arterial sites. In patients on nifedipine, an average of only 0.58 new lesions per patient were detected versus 0.80 lesions per patient on placebo (-27%; p = 0.031). INTACT is the first prospective angiographic trial on the progression of coronary artery disease using computer-assisted quantitative coronary angiography in such a high number of patients. All parameters analyzed indicated significant progression of coronary artery sclerosis. Nifedipine had no influence on the progression of preexisting coronary stenoses, but inhibited significantly the formation of new angiographically recognizable lesions. Further prospective coronary angiographic trials with calcium channel blockers using a comparably exact method are needed to confirm the results of this study.

Cineangiography↗
PubMed1984

Sex differences in blood protein patterns: a computer-assisted electrophoretic analysis of mid-molecular weight range proteins of human serum.

We have studied the sexual dimorphism of human serum proteins between the ranges of approximately 60,000 and 150,000 daltons using computerized imaging and densitometry. Methodology is presented, based on the TEXAC computer system for the detection, segmentation and integration of protein bands. The results are discussed in terms of potential future applications in computerized medical diagnosis.

Adolescent↗
PubMed1999

Size effect in resin/glass composite flexure strengths.

The objective of this study was to test the hypothesis that composite restorative materials possess an elastic-brittle nature and therefore will exhibit a size effect for flexure strength data. The experimental material consisted of 20 wt% 60:40 BISGMA:TEGDMA, 10 wt% colloidal silica, and 70 wt% Sr glass and was cured by light irradiation. Two sizes of flexure specimens were fabricated: 3.2x1.6x35 mm, and 6.25x3.1x35 mm. Half of the specimens made were soaked to equilibrium weight gain in 50:50 ethanol:water. The fracture strengths were measured in four-point bending tests. The beams under load were modelled by the finite element package ABAQUS. A statistical fracture mechanics methodology embodied in a public domain computer program called CARES/LIFE, developed by NASA, utilized the ABAQUS input and the fracture strengths of the smaller specimens to predict the fracture strengths of the larger specimens. In making the computation it used an approach that combines a Weibull distribution of flaw size with Batdorf's fracture mechanical model for failure at a material flaw. Both the soaked and unsoaked specimens exhibited Weibull behaviour, with shape parameters ranging from 4.04 to 8.15. Soaking had a clearly detrimental effect on the strengths of specimens of both sizes, and produced a comparable percentage reduction in the estimated scale parameter of the fracture strength distribution. Both the soaked and unsoaked specimens also exhibited a clear and comparable size effect, i.e. the larger specimens had a fracture strength that was lower than that of the smaller specimens by roughly the same percentage. Moreover, the magnitude of the size effect was well predicted by the CARES/LIFE methodology for both the soaked and the dry specimens. The elastic-brittle character of both soaked and unsoaked composite specimens was validated by load-deflection data, the magnitude of the Weibull shape parameters of the observed fracture strength data (<10), and the observed effect of specimen size. The accuracy of CARES/LIFE in predicting the magnitude of the observed size effect in beams of two different sizes strongly suggests that CARES/LIFE will be useful for computation of failure probabilities for clinically relevant structures.

Bisphenol A-Glycidyl Methacrylate↗
PubMed2002

Development of a simple computer program for spirometry interpretation.

OBJECTIVES: To develop and evaluate a computer program for interpretation of spirometry. METHODOLOGY: The spirometry programme was constructed in Epi Info software using a previously defined algorithm for interpretation. The programme incorporated current American Thoracic Society guidelines on interpretation of spirometry and was based on regression equations for healthy North Indians previously derived by us. The programme was pretested for two months before being put to routine use. RESULTS: Use of this spirometry programme led to consistent interpretation of spirometry results. There was significant saving of time while preparing reports, without any additional expenditure. CONCLUSION: The use of such computer programmes accelerate the reporting of pulmonary function test results at little extra cost, and all interpretations are performed in a consistent fashion.

Female↗
PubMed1991

Cardiac electrophysiological experiments in numero, Part II: Models of electrophysiological processes.

This article is the second part of a three article series reviewing computer simulation models of the heart, in particular of cardiac electrophysiology. The previous section of the review discussed the methodological principles of the construction and application of computer models. This article overviews the development of mathematical and computer modeling studies applied to cardiology. The models are classified according to the physiological processes that were simulated; this article distinguishes models oriented to cardiac mechanics, hemodynamics, and electrophysiology. The electrophysiology models are discussed in more detail and the review classifies them into four main categories: models of cellular processes, models of tissue behavior, models of the ventricular electric field, and models of macroconduction disturbances. In each category, the historical development of the models and their key achievements are described.

Animals↗