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The degrees to which transtrochanteric rotational osteotomy moves the region of osteonecrotic femoral head out of the weight-bearing area as evaluated by computer simulation.

BACKGROUND: Transtrochanteric rotational osteotomy is a technical demanding procedure. Currently, the pre-operative planning of the transtrochanteric rotational osteotomy is mostly based on X-ray images. The surgeons would need to reconstruct the three-dimensional structure of the femoral head and the necrosis in their mind. This study develops a simulation platform using computer models based on the computed tomography images of the femoral head to evaluate the degree to which transtrochanteric rotational osteotomy moves the region of osteonecrotic femoral head out of the weight-bearing area in stance and gait cycle conditions. Based on this simulation procedure, the surgeons would be better informed before the surgery and the indication can be carefully assessed. METHOD: A case with osteonecrosis involving 15% of the femoral head was recruited. Virtual models with the same size lesion but at different locations were devised. Computer models were created using SolidWorks 2000 CAD software. The area ratio of weight-bearing zone occupied by the necrotic lesion on two conditions, stance and gait cycle, were measured after surgery simulations. FINDINGS: For the specific case and virtual models devised in this study, computer simulation showed the following two findings: (1) The degrees needed to move the necrosis out of the weight-bearing zone in stance were less by anterior rotational osteotomy as compared to that of posterior rotational osteotomy. However, the necrotic region would still overlap with the weight-bearing area during gait cycle. (2) Because the degrees allowed for posterior rotation were less restricted than anterior rotation, posterior rotational osteotomies were often more effective to move the necrotic region out of the weight-bearing area during gait cycle. INTERPRETATION: The computer simulation platform by registering actual CT images is a useful tool to assess the direction and degrees needed for transtrochanteric rotational osteotomy. Although the results indicated that anterior rotational osteotomy was more effective to move the necrosis out of the weight-bearing zone in stance for models devised in this study, in circumstances where the necrotic region located at various locale, considering the limitation of anterior rotation inherited with the risk of vascular compromise, it might be more beneficial to perform posterior rotation osteotomy in taking account of gait cycle.

Computer Simulation↗

Reversed-phase liquid chromatographic separation of complex samples by optimizing temperature and gradient time III. Improving the accuracy of computer simulation.

Previous studies have shown that four experimental runs, where both temperature T and gradient time tG are varied, can be used for the reliable prediction of separation as a function of these two variables (two-dimensional optimization). Computer simulation (e.g., DryLab) can then be used to predict "optimized" conditions for maximum sample resolution using either isocratic or gradient elution. Samples that contain a large number of components (e.g., n>15-20) present a greater challenge. Resolution for these more complex samples is often quite sensitive to small changes in T or tG in turn requiring greater accuracy in predictions that result from computer simulation. In the present study of several samples, we have examined computer simulation errors that can arise from inexact expressions for retention time as a function of T, tG or isocratic %B. Resulting conclusions are applicable to both complex and simpler samples, in either one- or two-dimensional optimization. Means to anticipate and minimize the impact of these predictive errors are examined.

Chromatography, Liquid↗

The coefficient of error of optical fractionator population size estimates: a computer simulation comparing three estimators.

The optical fractionator is a design-based two-stage systematic sampling method that is used to estimate the number of cells in a specified region of an organ when the population is too large to count exhaustively. The fractionator counts the cells found in optical disectors that have been systematically sampled in serial sections. Heretofore, evaluations of optical fractionator performance have been made by performing tests on actual tissue sections, but it is difficult to evaluate the coefficient of error (CE), i.e. the precision of a population size estimate, by using biological tissue samples because they do not permit a comparison of an estimated CE with the true CE. However, computer simulation does permit making such comparisons while avoiding the observational biases inherent in working with biological tissue. This study is the first instance in which computer simulation has been applied to population size estimation by the optical fractionator. We used computer simulation to evaluate the performance of three CE estimators. The estimated CEs were evaluated in tests of three types of non-random cell population distribution and one random cell population distribution. The non-random population distributions varied by differences in 'intensity', i.e. the expected cell counts per disector, according to both section and disector location within the section. Two distributions were sinusoidal and one was linearly increasing; in all three there was a six-fold difference between the high and low intensities. The sinusoidal distributions produced either a peak or a depression of cell intensity at the centre of the simulated region. The linear cell intensity gradually increased from the beginning to the end of the region that contained the cells. The random population distribution had a constant intensity over the region. A 'test condition' was defined by its population distribution, the period between consecutive sampled sections and the spacing between consecutive sampled disectors. There were 1000 independently simulated cell populations for each test condition, and a 'trial' was conducted for each of these cell populations. In each trial we calculated the (unique) true CE of the population size estimate and the three CE estimates obtained by applying the Scheaffer-Mendenhall-Ott (SMO) and both Gundersen-Jensen (GJ) estimators. We compared the estimated CEs with the true CEs for each population distribution. We found that the CE estimates obtained by the SMO estimator were closer to the true CEs and had less scatter than those of the nugget-modified GJ estimator. Both had small positive bias. The CE estimates obtained by the unmodified GJ estimator exhibited widely varying bias and large scatter. In all the population distributions we tested, the average true CE was very nearly proportional to 1/square root of QT, where QT is the average number of cells counted in the two-stage systematic sample.

Cell Count↗

Computer simulation and spatial modelling in heart surgery.

In this work, three dimensional modelling and computer simulation of heat transfer on generally-shaped nonhomogeneous bodies is proposed and described. The complexity of the calculation is estimated and the potential use of high performance parallel computers is discussed. The method is focused on applications in medicine. As an example, a numerical algorithm for the parallel computer simulation of heart cooling procedures during surgery is presented. On the basis of simulated results, two different methods of cooling are compared.

Algorithms↗

RF tumour ablation: computer simulation and mathematical modelling of the effects of electrical and thermal conductivity.

This study determined the effects of thermal conductivity on RF ablation tissue heating using mathematical modelling and computer simulations of RF heating coupled to thermal transport. Computer simulation of the Bio-Heat equation coupled with temperature-dependent solutions for RF electric fields (ETherm) was used to generate temperature profiles 2 cm away from a 3 cm internally-cooled electrode. Multiple conditions of clinically relevant electrical conductivities (0.07-12 S m-1) and 'tumour' radius (5-30 mm) at a given background electrical conductivity (0.12 S m-1) were studied. Temperature response surfaces were plotted for six thermal conductivities, ranging from 0.3-2 W m-1 degrees C (the range of anticipated clinical and experimental systems). A temperature response surface was obtained for each thermal conductivity at 25 electrical conductivities and 17 radii (n=425 temperature data points). The simulated temperature response was fit to a mathematical model derived from prior phantom data. This mathematical model is of the form (T=a+bRc exp(dR) s(f) exp(g)(s)) for RF generator-energy dependent situations and (T=h+k exp(mR)+n?exp(p)(s)) for RF generator-current limited situations, where T is the temperature (degrees C) 2 cm from the electrode and a, b, c, d, f, g, h, k, m, n and p are fitting parameters. For each of the thermal conductivity temperature profiles generated, the mathematical model fit the response surface to an r2 of 0.97-0.99. Parameters a, b, c, d, f, k and m were highly correlated to thermal conductivity (r2=0.96-0.99). The monotonic progression of fitting parameters permitted their mathematical expression using simple functions. Additionally, the effect of thermal conductivity simplified the above equation to the extent that g, h, n and p were found to be invariant. Thus, representation of the temperature response surface could be accurately expressed as a function of electrical conductivity, radius and thermal conductivity. As a result, the non-linear temperature response of RF induced heating can be adequately expressed mathematically as a function of electrical conductivity, radius and thermal conductivity. Hence, thermal conductivity accounts for some of the previously unexplained variance. Furthermore, the addition of this variable into the mathematical model substantially simplifies the equations and, as such, it is expected that this will permit improved prediction of RF ablation induced temperatures in clinical practice.

Catheter Ablation↗

Computer simulation of bulk mechanical properties and surface hydration of biomaterials.

Some intrinsic properties of biomaterials are calculated with atomistic computer simulations through energy minimizations and molecular dynamics methods. The mechanical properties of bulk polymers such as poly(vinyl alcohol) and poly(ethylene terephthalate) are obtained in terms of the Young's modulus, the bulk and shear moduli, and the Poisson ratio below the glass transition temperature. The calculated values apply to an ideal, defect-free sample, and therefore, they correspond to the theoretical upper limit for the mechanical behavior of these materials. The surface hydration of the same polymers and of graphite is analyzed in terms of the statistical distribution of the water molecules near the surfaces of these materials that range from hydrophilic to strongly hydrophobic. Consistent with recent spectroscopic evidence, it is found that water forms relatively ordered hydration shells driven by hydrogen bonds above the hydrophilic surface, but is highly disordered over the hydrophobic one. Therefore, it is suggested that computer simulations provide a new useful tool to investigate various aspects of biomaterials.

Biocompatible Materials↗

Thermodynamic cycle integration by computer simulation as a tool for obtaining free energy differences in molecular chemistry.

A new and promising development in the field of computer simulation of molecular systems is the so-called thermodynamic cycle integration technique, which combines well-known results from statistical thermodynamics with powerful computer simulation methods. The basic formulas, the development and the applications in the areas of drug design, protein engineering and conformational analysis of this elegant technique are discussed.

Computer Simulation↗

Computer simulation of flagellar movement. VI. Simple curvature-controlled models are incompletely specified.

Computer simulation is used to examine a simple flagellar model that will initiate and propagate bending waves in the absence of viscous resistances. The model contains only an elastic bending resistance and an active sliding mechanism that generates reduced active shear moment with increasing sliding velocity. Oscillation results from a distributed control mechanism that reverses the direction of operation of the active sliding mechanism when the curvature reaches critical magnitudes in either direction. Bend propagation by curvature-controlled flagellar models therefore does not require interaction with the viscous resistance of an external fluid. An analytical examination of moment balance during bend propagation by this model yields a solution curve giving values of frequency and wavelength that satisfy the moment balance equation and give uniform bend propagation, suggesting that the model is underdetermined. At 0 viscosity, the boundary condition of 0 shear rate at the basal end of the flagellum during the development of new bends selects the particular solution that is obtained by computer simulations. Therefore, the details of the pattern of bend initiation at the basal end of a flagellum can be of major significance in determining the properties of propagated bending waves in the distal portion of a flagellum. At high values of external viscosity, the model oscillates at frequencies and wavelengths that give approximately integral numbers of waves on the flagellum. These operating points are selected because they facilitate the balance of bending moments at the ends of the model, where the external viscous moment approaches 0. These mode preferences can be overridden by forcing the model to operate at a predetermined frequency. The strong mode preferences shown by curvature-controlled flagellar models, in contrast to the weak or absent mode preferences shown by real flagella, therefore do not demonstrate the inapplicability of the moment-balance approach to real flagella. Instead, they indicate a need to specify additional properties of real flagella that are responsible for selecting particular operating points.

Flagella↗

Computer simulation of selection in a hypothetical crop species.

A computer simulation model demonstrating the effect of directional selection upon a simplified quantitative genetic character, is presented. Complementary homozygous parents were crossed to generate a fully heterozygous F1 population. Phenotypic truncation selection was effected upon the F2 and subsequent generations, and genotypic and phenotypic response to selection, as well as the change in population heterozygosity, was monitored to generation F9. The model simulates selection for alternative breeding regimes, modes of allelic interaction, selection pressure, population size and levels of environmental variation. Three alternative methods for the simulation of the environmental component of phenotypic variance are incorporated, and mechanisms and relative merits of the rival methods are discussed. Data generated by the model conformed closely to theoretical expectation, lending support to the use of the model as a platform for development of more comprehensive simulation models. Potential improvements to the model are discussed.

Algorithms↗

Computer simulation of MRS localization techniques: an analysis of ISIS.

Computer simulations were used to evaluate the ISIS localization technique as implemented with both head and surface coils. The effects of chemical shift, B1 inhomogeneity, repetition time, T2 relaxation, a postacquisition saturation pulse, and a B1 insensitive observation pulse were examined. Integrals of ISIS signals over the sample volume showed that significant signal loss from the volume of interest (VOI) and contamination from outside the VOI can occur for both head and surface coil ISIS experiments. The results showed that the saturation pulse, order of the various ISIS acquisitions, and repetition time affect contamination but not signal loss. In addition, short T2 and high RF power can combine synergistically to degrade the selective inversion pulses, causing further contamination and signal loss.

Computer Simulation↗

Computer simulation of clinical irradiation schemes applied to in vitro tumor spheroids.

In this contribution the attempt is made to study the effect of irradiation on in vitro tumor spheroids by computer simulation applying clinical treatment schedules. The starting point is a computer model stimulating the spatial (three-dimensional) growth of a tumor spheroid, developed by our group previously. In the present paper, this model is extended by creating a comfortable data input with a graphical interface. This expansion includes characteristic features of radiotherapy (sensitivity, repair capacity, reoxygenation, repopulation) and therapy schedules. In this way, it is possible to test different clinical irradiation schemes on in vitro tumor spheroids by computer experiments (standard and non-standard fractionations). In the long run the aim of our work is to optimize irradiation schedules by computer simulation prior to clinical therapy.

Adenocarcinoma↗

The association of memory complaint with computer-simulated everyday memory performance.

The relationship of memory self-report to self-rated depression and to actual performance on computer-simulated everyday memory tasks was investigated in 125 normal adults. Canonical correlation analyses demonstrated that self-rated memory performance and objective computer-simulated everyday memory performance shared from 27.9% to 29.4% of common variance. These data provide initial concurrent validity for a new memory self-report scale, the MAC-S. Results are discussed in relation to psychometric factors important in the design and validation of self-report memory scales.

Adolescent↗

Are the current bioequivalence standards sufficient for the acceptance of narrow therapeutic index drugs? Utilization of a computer simulated warfarin bioequivalence model.

PURPOSE: The purpose of this computer simulation was to determine the likelihood of two bioequivalent (vs. reference) generic warfarin formulations (with varying bioavailability) passing current bioequivalence criteria against each other at varying bioavailability. Methods. A bioequivalence simulation program generated 100 warfarin bioequivalence (BE) studies with 24 patients/study. The reference formulation (R) was assigned a bioavailability of 90%. In these simulations the first generic (G(1)) had a bioavailability that was incrementally decreased from 90%. The second generic (G(2)) had a bioavailability that was incrementally increased from 90%. The bioequivalence testing was performed initially as G(1 )vs. R, then G(2) vs. R, and finally G(2) vs. G(1). The tests were performed according to current criteria for therapeutic index drugs. RESULTS: 5400 BE studies with a total of 129,600 subjects and 2,462,400 sampling times were simulated. When G(1) vs. R was compared, fewer than 80% of studies passed when the relative AUC(0-t )ratios were 88% or less. When G(2) vs. R were compared, fewer than 80% of studies passed when the relative AUC(0-t )ratios were 113% or greater. When Generic 2 and Generic 1 were compared fewer than 80% of studies passed when the relative AUC(0-t) ratios deviated from the reference by 7% or more. DISCUSSION Despite limitations this simulation indicates that two bioequivalent (vs. reference) generic warfarin products may not be bioequivalent to each other. Alternative methods of assessing bioequivalence are needed when more than one generic of narrow therapeutic index drug exists on the market.

Anticoagulants↗

Computer simulation of the reentrant cardiac arrhythmias in ischemic myocardium.

Computer simulation was performed to determine how reentrant activity could occur due to the spatial heterogeneity in refractoriness induced by the regional ischemia. Two regional ischemic models were developed by decreasing the intracellular ATP concentration, reducing conductance of the inward Na+ current and increasing the extracellular K+ concentration on the two-dimensional sheet. Operator splitting method was used to integrate the models. The vulnerability to reentry was estimated from the timings of premature stimuli on the constructed models, which could result in unidirectionally propagating action potentials. Two kinds of sustained spiral waves and their Pseudo-Electroscardiograms were observed in numerical simulation. The results showed that the dispersion of refractory period increased with ischemic aggravation, and led to augment of the vulnerable window. A permature stimulation within the vulnerable window could easily induce spiral reentry. The Pseudo-Electrocardiograms of the spiral waves exhibited monomorphic tachycardiac waveforms. Thus, the spatial heterogeneity in refractoriness could be a substrate for reentrant ventricular tachyarrhythmias on the regional ischemic tissue.

Computer Simulation↗

Resource reallocation in an emergency medical service system using computer simulation.

Emergency medical service (EMS) policy makers must seek to achieve maximum effectiveness with finite resources. This research establishes an EMS computer simulation model using eM-Plant software. The simulation model is based on Taipei city's EMS system with input data from prehospital care records from December 2000; it manipulates resource allocation levels and rates of idle errands. Presently, EMS ambulance utilization is about 8.78%. On average, 20.89 minutes are required to transport a patient to the hospital. Computer simulations showed that reducing the number of ambulances to one at each of the 36 response units increases the utilization rate to 15.47% but does not compromise the current service quality level. Thus, ambulance utilization improves, times of patients waiting for pre-hospital care and arrival at hospitals are only slightly affected, and considerable cost savings result. This study provides a research methodology and suggests specific policy directions for resource allocation in EMS. Limiting the number of ambulances to one per response unit reduces costs, increases efficiency, and yet maintains the same operational pattern of medical service.

Ambulances↗

[Deformation of brain and stress distribution caused by putaminal hemorrhage--numerical computer simulation by finite element method].

Deformation and stress distribution caused by putaminal hemorrhage in two-dimensional model brain were analyzed by computer simulation using finite element method. The model brain was composed of cerebral cortex, white matter, caudate nucleus, lenticular nucleus, thalamus and lateral ventricle. Young's modulus of gray and white matter was assumed to be 0.08 and 0.04 kgf/cm2, respectively, and Poisson's ratio was 0.47 for both of them. Bleeding of 100 mmHg pressure was represented by 4 vectors of force directing anterior, lateral, posterior and medial direction from the middle portion of putamen. Calculation of finite element method was carried out by a 16-bit personal computer. The calculated deformation of brain presented a hematoma cavity elongated from anterior to posterior direction at the lenticular nucleus. Mass effect of hematoma was noted from displacement of the anterior horn of the lateral ventricle and the internal capsule. Distribution of stress vector revealed the stress concentration at the lenticular nucleus while small stress was noted all over the model brain. Strength of principal stress was presented by contour-line and took the shape of concentric circles with a center at the putamen. This study suggested that the computer simulation by finite element method would be a useful technique to analyze the physical phenomenon of brain suffered from intracerebral hemorrhage.

Basal Ganglia Diseases↗

Operations research survey and computer simulation of waiting times in two medical outpatient clinic structures.

Outpatient services are increasingly recognised as an important component of health care provision and may be improved through the application of modern management techniques. We have performed a time and role audit of consultation and waiting times in two medical clinics using different queuing systems: namely, a serial processing clinic where patients wait in a single queue and a quasi-parallel processing clinic where patients are directed to the shortest queue to maintain clinic flow. Data collected were used to construct a computer simulation of patient flows in clinic. Assessment of patient satisfaction in the clinic process was determined using a self-administered questionnaire. Mean waiting time was shorter in the quasi-parallel processing clinic: 26 (SD 17) minutes compared with 36(24) minutes in the serial processing clinic. In the serial processing clinic 61% of patients waited more than 30 minutes compared with 41% in the quasi-parallel processing clinic. In the serial processing clinic 8% of 142 patients surveyed complained of the time spent waiting. The computer simulation we produced was able to determine waiting times with different clinic structures. The simulation showed that reductions in waiting time up to 30% might be achieved by changing our serial processing clinic to a quasi-parallel processing one. Performance of medical outpatient clinics can be improved by examining and changing clinic management. Computer simulation of outpatient clinics offers a means of assessing the impact of such changes on waiting time in clinic and on waiting lists.

Algorithms↗

Mechanism and computer simulation of immune complex formation, opsonization, and clearance.

A computer simulation of immune complex formation, opsonization, and clearance has been developed (ICMODEL) that uses equations describing the kinetics of known immunologic processes and an additional pathologic process of immune complex-mediated tissue damage and antigen production. ICMODEL was used to (1) compare simulated with reported immune response kinetics, (2) evaluate the relative stability of the immune system described by the simulation, and (3) determine the conditions required to produce high immune complex levels as found in patients with immune complex-mediated disease. ICMODEL simulated primary and secondary immune responses as well as short- and long-term immunity. ICMODEL also depicted a relatively stable immune response system. Under certain conditions, however, the system could be perturbed, resulting in an unstable response. For example, when the rate constant regulating Fc gamma-mediated phagocytosis was decreased and the rate constant regulating immune complex-mediated tissue damage/antigen production was increased, immune complex concentrations oscillated with time and increased exponentially. These data suggest that ICMODEL can be used to define the specific parameters that, when perturbed, will give rise to increased immune complex concentrations. As such, this model has direct implications for studies of immune complex-mediated disease in human patients.

Animals↗