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PubMed1999

Application and comparison of two modelling techniques for hospital bed management.

The use of the bed occupancy management and planning system (BOMPS) and the Sorensen multi-phased bed model were used to assess the implications of a hospital expanding its emergency facility. BOMPS flow modelling generates resource utilisation data dependent on the best visual and statistical fit between mixed exponential equations and time of bed occupancy; the Sorensen model creates models based on probabilities and length of stay distributions. Both models identified the presence of two streams of flow. However, there were differences in the number of beds identified as being short and longer stay. The advantage of flow modelling is that it enables decision-makers to pre-test their decisions.

Australia↗
PubMed2000

Appropriate tissue- and cell-specific expression of a single copy human angiotensinogen transgene specifically targeted upstream of the HPRT locus by homologous recombination.

Development of experimental models by genetic manipulation in mice has proven to be very useful in determining the significance of particular genes in the development of or susceptibility to hypertension. Advances in molecular genetics, transgenic mouse technology, and physiological measurements in mice provided an opportunity to go a step further and develop models to analyze the physiological significance of specific gene variants potentially causing hypertension. In this report, we describe the development of a human angiotensinogen transgenic mouse model generated by targeting the human angiotensinogen gene upstream of the mouse HPRT locus by homologous recombination. The main benefit of this transgenic mouse model is that the human angiotensinogen gene is inserted into the mouse genome as a single copy at a predefined locus and in a specific orientation-a process that can be repeated utilizing other variants of this gene. We establish the validity of this approach by showing that the hAGT(hprt) mice have normal tissue- and cell-specific expression of the human angiotensinogen gene and normally produce and process the hAGT protein at physiological levels.

Angiotensinogen↗
PubMed2003

Impact of antimicrobial resistance on health outcomes in the out-patient treatment of adult community-acquired pneumonia: a probability model.

Out-patient treatment of community-acquired pneumonia (CAP) is a major challenge in an era of increasing prevalence of antimicrobial resistance. However, data describing the clinical impact of such resistance are scarce. A probability model was developed to estimate the impact of antimicrobial resistance on clinical outcomes for adults with CAP, eligible for out-patient care. The model assumed patients would be evaluated at 48-72 h, with those failing to improve being either hospitalized or switched to a different antibiotic. Two strategies were considered: amoxicillin followed by erythromycin (amoxicillin/erythromycin) and erythromycin followed by levofloxacin (erythromycin/levofloxacin). Analyses were conducted based on susceptibility of the major pathogens in France and the UK. Primary model-generated outcome measures were the proportion of patients successfully treated with first-line therapy and the proportion of patients subsequently hospitalized. The model estimated that in France, the amoxicillin/erythromycin strategy would lead to 67.8% improving within 48-72 h and 12.7% subsequently being hospitalized, compared with 48.6% and 13.7% for erythromycin/levofloxacin. For the UK, first-line success and hospitalization rates were, respectively, 71.7% and 8.1% for amoxicillin/erythromycin, and 65.3% and 9.3% for erythromycin/levofloxacin. The model estimated that antimicrobial resistance was responsible for >40% of hospitalizations in France and 15% in the UK. These data suggest that in areas with substantially reduced levels of susceptibility, antimicrobial resistance may be a significant contributor to subsequent hospitalization in adults initially treated as out-patients for CAP. Choice of out-patient treatment strategy should consider local resistance rates in order to maximize the likelihood of early cure, thereby minimizing hospitalizations.

Adult↗
PubMed1988

Estimation of intramyocardial pressure and coronary blood flow distribution.

To characterize the intramyocardial pressure (IMP) and coronary blood flow distribution in a stenosed coronary circulation, we compared four analog circuits for modeling coronary impedance. The resistor (R)-diode (D) model simulates vascular collapse, and the capacitor (C) simulates compliance effect. Identification of the best model and magnitudes of the endocardial and epicardial IMPs (IMPendo and IMPepi) was done retrospectively using data from studies in 28 anesthetized swine. Performance evaluation was based on comparison of model predicted vs. observed coronary distal pressure (DP) waveforms and endocardial-to-epicardial (endo-epi) flow ratios as determined by radiolabeled microspheres. The R-D-C model gave the best performance at IMPendo = 1.1 times left ventricular pressure (LVP), and IMPepi = 0.1.LVP + 15 mmHg; with good fit to DP (r = 0.98, slope of regression line = 1.0) and estimates of endo-epi flow ratio (r = 0.78, slope = 1.01, P less than 0.02, SEE = 0.21, n = 139). The R-D model gave comparable results even though capacitance was omitted. Although R-C and R models predicted distal coronary pressure well, they failed to predict endo-epi flow ratios (r less than 0.50). The R-D-C and R-D models were applied in seven prospective studies. Both models generated reasonable estimates of endo-epi flow distribution (r = 0.78, n = 50). Thus the R-D-C or R-D models of the stenosed coronary circulation can be used to provide reliable estimates of transmural blood flow distribution.

Animals↗
PubMed1991

A tissue pressure model for palpatory perception of the cranial rhythmic impulse.

A tissue pressure model was developed to provide a possible physiologic basis for the manifestation of the cranial rhythmic impulse (CRI). The model assumes that the sensation described as the CRI is related to activation of slowly adapting cutaneous mechanoreceptors by tissue pressures of both the examiner and the subject, and that the sources of change in these tissue pressures are the combined respiratory and cardiovascular rhythms of both examiner and subject. The model generates rhythmic impulses with patterns similar to those reported for the CRI. Also, a significant correlation was found between frequencies calculated from the model and published values for CRI obtained by palpation. These comparisons suggest that the CRI may arise in soft tissues and represents a complex interaction of at least four different physiologic rhythms.

Humans↗
PubMed1986

Genetics of Darwinian fitness. III. A generalized approach to age structured selection and life history.

Most models in life history assume that maximization of lambda holds. Demographic genetic theory supports this assumption provided (i) the fecundity of each mating is determined solely by the age and genotype of the female, (ii) the two sexes experience the exact same selection intensities, and (iii) the two sexes are equal in their age specific schedules of survival and fecundity. But these assumptions will often not hold in nature: thus a more general means of analysis closely integrated with a broader genetic treatment is attempted here. First, operators are derived to map sex specific non-overlapping generation models into the more general case in which generations can overlap. Application of such operators then suggests a broader representation of age structured selection in which evolution acts according to a single composite Wrightian topography whose gradient is a weighted mean taken over selective gradients in all of the age classes. Application of this view is straightforward, showing, for example, that (i) the evolutionary maximization of lambda, which is the basis of present optimization theories for life history, is extremely fragile with biological deviation from mathematical assumptions used in its derivation, (ii) the cost of meiosis argument is shown not to conflict with traditional life history theory, although its correct application will depend critically and subtly upon how genic effects on fertility are measured, and (iii) correct weightings for age specific selection converge to those of Hamilton (1966) and Schaffer (1974) only when sex specific differences in fertility and survival are nonexistent or when selection occurs only in the demographically dominant sex. For life history problems beyond assumptions underlying tradition approaches the composite adaptive topography seems to provide a suitable alternate means for analysis.

Adaptation, Physiological↗
PubMed1996

Noninvasive visualization of blood flow in the choriocapillaris of the rat.

PURPOSE: The rat has been used to generate models of various eye diseases. However, methods to study the choriocapillaris noninvasively have been inadequate in this species. Laser-targeted angiography was applied to generate local, repetitive angiograms of the choriocapillaris in the rat and to assess the similarity between the choriocapillaris of the rat and that of the subhuman primate. METHODS: Carboxyfluorescein was encapsulated in heat-sensitive liposomes and injected intravenously in rats. The liposome contents were then released locally in the choroid by the application of a short, noncoagulating heat pulse provided by an argon laser. Videoangiograms of the downstream spread of the bolus of dye were generated with excitation illumination provided by another output from the argon laser. RESULTS: Laser-targeted angiography demonstrated that the bolus of dye perfused the choriocapillaris. Clusters of choriocapillaris lobules were observed and appeared similar to those described in the primate. Dynamic filling and emptying patterns also were similar to those of the primate. Lobules were filled by a central arteriole and drained by a venous annulus. CONCLUSIONS: This study demonstrates the feasibility of noninvasively studying the choriocapillaris of the living rat using the technique of laser-targeted angiography. It demonstrates as well the similarity between the rat and the primate choriocapillaris, thus indicating that the rat is an acceptable and convenient model for the study of physiological and pathologic changes in the choroidal vasculature.

Animals↗
PubMed2001

Disease model: dissecting the pathogenesis of the measles virus.

Host-pathogen interactions of measles virus (MV), a leading cause of childhood mortality worldwide, are still poorly understood. Using transgenic mice that express the human MV receptor CD46, we generated models to study the pathogenesis of MV infection of the central nervous system (CNS) and immune system. CNS infection in CD46 transgenic mice allows replication and spread throughout neurons, inflammation, and ultimately death of the animals. CD46-transgenic mice can also be used to study immunosuppression, a hallmark of measles. Together with mouse knockout technology and a system for generating recombinant MVs, CD46 transgenic mice will ultimately lead to a better understanding of both viral and host factors contributing to disease.

Animals↗
PubMed1993

The old-age security hypothesis revisited.

"Children's altruism toward parents is allowed in a two-overlapping-generations model with endogenous fertility. Parents raise children because, when retired, they expect gifts from their children who are essentially a capital good. Individuals' behavior between generations is examined by analyzing a Nash equilibrium, which is then compared with a social planner's optimal allocation. The pay-as-you-go public pension program is viewed as the optimal gifts from the optimal allocation when the latter is implemented. The effect on fertility of the introduction of a capital market is also analyzed. The validity of the old-age security hypothesis is shown to depend on the parameters of utility and cost functions."

Behavior↗
PubMed1990

Search for faster methods of fitting the regressive models to quantitative traits.

The regressive models describe familial patterns of dependence of quantitative measures by specifying regression relationships among a person's phenotype and genotype and the phenotypes and genotypes of antecedents. When the number of sibs in the pattern of dependence increases, as in the class D regressive model, computation of the likelihood becomes time consuming, since the Elston-Stewart algorithm cannot be used generally. On the other hand, the simpler class A regressive model, which imposes a restriction on the sib-sib correlation, may lead to inference of a spurious major gene, as already observed in some instances. A simulation study is performed to explore the robustness of class A model with respect to false inference of a major gene and to search for faster methods of computing the likelihood under class D model. The class A model is not robust against the presence of a sib-sib correlation exceeding that specified by the model, unless tests on transmission probabilities are performed carefully: false detection of a major gene is reduced from a number of 26-30 to between 0 and 4 data sets out of 30 replicates after testing both the Mendelian transmission and the absence of transmission of a major effect against the general transmission model. Among various approximations of the likelihood formulation of the class D model, approximations 6 and 8 are found to work appropriately in terms of both the estimation of all parameters and hypothesis testing, for each generating model. These approximations lessen the computer time by allowing use of the Elston-Stewart algorithm.

Computer Simulation↗
PubMed1995

Model-free association analysis of a rare disease.

Model-free methods of testing for association of a disease with alleles at a marker locus were used to analyze simulated data for a rare disease locus and 360 marker loci distributed at 2 cM intervals along six chromosomes. After adjustment for multiple tests, there was no evidence of significant heterogeneity of parental allele frequencies between a sample of parents with at least one affected child and a sample of parents with no affected children. Several significant deviations from Hardy-Weinberg equilibrium were detected after Bonferroni correction but these were Type I errors. After adjusting for multiple tests, the model-free test for association detected significant associations of alleles at two loci with the disease. These associations were in fact part of the generating model for the simulated data. However, these methods were unable to detect two other major loci contributing to the disease since these loci were not associated with any of the marker loci.

Alleles↗
PubMed1993

The Cascade Neural Network Model and a Speed-Accuracy Trade-Off of Arm Movement.

We propose a hybrid neural network model of aimed arm movements that consists of a feedforward controller and a postural controller. The cascade neural network of Kawato, Maeda, Uno, and Suzuki (1990) was employed as a computational implementation of the feedforward controller. This network computes feedforward motor commands based on a minimum torque-change criterion. If the weighting parameter of the smoothness criterion is fixed and the number of relaxation iterations is rather small, the cascade model cannot calculate the exact torque, and the hand does not reach the desired target by using the feedforward control alone. Thus, one observes an error between the final position and the desired target location. By using a fixed weighting parameter value and a limited iteration number to simulate target-directed arm movements, we found that the cascade model generated a planning time-accuracy trade-off, and a quasi-power-law type of speed-accuracy trade-off. The model provides a candidate neural mechanism to explain the stochastic variability of the time course of the feedforward motor command. Our approach also accounts for several invariant features of multijoint arm trajectories, such as roughly straight hand paths and bell-shaped speed profiles.

Journal Article↗
PubMed1991

A mathematical model describing the generation of oxygen radicals in mitochondria during ischemia-reperfusion.

A mathematical model for the generation of free radicals by mitochondria in ischemia-reperfusion is proposed. Computations show that normally two stable equilibrium states exist: the intact state, and the state characterized by damage to mitochondrial structures and a high rate of radical formation. Transition from one state to another occurs after hypoxia of a certain degree of severity and duration. The model also describes a number of phenomena observed during development of reperfusion injuries and drug therapy.

Free Radicals↗
PubMed2001

Using light scatter signal to estimate bacterial biovolume by flow cytometry.

BACKGROUND: In the past decade, flow cytometry has become a useful and precise alternative to microscopic bacterial cell counts in aquatic samples. However, little evidence of its usefulness for the evaluation of bacterial biovolumes has emerged in from the literature. METHODS: The light scattering and cell volume of starved bacterial strains and natural bacterial communities from the Black Sea were measured by flow cytometry and epifluorescence microscopy, respectively, in order to establish a relationship between light scattering and cell volume. RESULTS: With the arc-lamp flow cytometer, forward angle light scatter (FALS) was related to cell size in both the starved strains and natural communities, although regression parameters differed. We tested the predictive capacity of the FALS verous cell size relationship in a bacterial community from the North Sea. That analysis showed that a reliable bacterial biovolume prediction of a natural bacterial community can be obtained from FALS using a model generated from natural bacterial community data. CONCLUSIONS: Bacterial biovolume is likely to be related to FALS measurements. It is possible to establish a generally applicable model derived from natural bacterial assemblages for flow cytometric estimation of bacterial biovolumes by light scatter.

Aeromonas hydrophila↗
PubMed2000

Potential drugs and nondrugs: prediction and identification of important structural features

Using decision trees, a model to discriminate between potential drugs and nondrugs has been developed. Compounds from the Available Chemical Directory and the World Drug Index databases were used as training set; the molecular structures were represented using extended atom types. The error rate on an independent validation data set is 17.4%. The number of false negatives can be reduced by penalizing the misclassification of drugs so that 92 out of 100 potential drugs are correctly recognized. At the same time, 34 out of 100 nondrugs are classified as potential drugs. The predictions of the model can be used to guide the purchase or selection of compounds for biological screening or the design of combinatorial libraries. The visualization of the generated models in the form of colored trees allowed us to identify a few, surprisingly simple features that explain the most significant differences between drugs and nondrugs in the training set: Just by testing the presence of hydroxyl, tertiary or secondary amino, carboxyl, phenol, or enol groups, already three quarters of all drugs could be correctly recognized. The nondrugs, on the other hand, are characterized by their aromatic nature with a low content of functional groups besides halogens. The general applicability of the model is shown by the predictions made for several Organon databases.

Journal Article↗
PubMedDate not supplied

Ischemia-reperfusion injury in chronic pressure ulcer formation: a skin model in the rat.

Most animal models of chronic pressure ulcers were designed to study only the role of ischemic injury in wound formation, often using single applications of constant pressure. The purpose of this study was to develop and characterize a reproducible model of cyclic ischemia-reperfusion injury in the skin of small un-anesthetized animals using clinically relevant pressures and durations. Ischemia-reperfusion injury was created in a 9 cm2 region of dorsal skin in male rats by periodically compressing skin under a pressure of 50 mm Hg using an implanted metal plate and an overlying magnet. We varied the total number of ischemia-reperfusion cycles, examined the effect of varying the frequency and duration of ischemic insult, and compared ischemia-induced injury to ischemia-reperfusion-induced injury with this model. Tissue injury increased with an increasing number of total ischemia-reperfusion cycles, duration of ischemia, and frequency of ischemia-reperfusion cycles. This model generates reproducible ischemia-reperfusion skin injury as characterized by tissue necrosis, wound thickness, leukocyte infiltration, transcutaneous oxygen tension, and wound blood flow. Using this model, the biological markers of ischemia-reperfusion-induced wound development can be studied and therapeutic interventions can be evaluated in a cost-effective manner.

Animals↗
PubMedDate not supplied

Fabrication of titanium implant-retained restorations with nontraditional machining techniques.

Traditional laboratory techniques are being supplemented by modern precision technologies to solve complex restorative problems. Electrical discharge machining combined with laser scanning and computer aided design-computer aided manufacturing can create very precise restorations without the lost wax method. A laser scanner is used to create a three-dimensional polyline data model that can then be converted into a stereolithography file format for output to a stereolithography apparatus or other rapid prototyping device. A stereolithography-generated model is used to create an electric discharge machining electrode via copper electroforming. This electrode is used to machine dental restorations from an ingot of titanium, bypassing the conventional lost wax casting process. Retaining screw access holes are machined using conventional drilling procedures, but could be accomplished with electric discharge machining if desired. Other rapid prototyping technologies are briefly discussed.

Computer-Aided Design↗
PubMed1999

Pathophysiology of gene-targeted mouse models for cystic fibrosis.

Pathophysiology of Gene-Targeted Mouse Models for Cystic Fibrosis. Physiol. Rev. 79, Suppl.: S193-S214, 1999. - Mutations in the gene causing the fatal disease cystic fibrosis (CF) result in abnormal transport of several ions across a number of epithelial tissues. In just 3 years after this gene was cloned, the first CF mouse models were generated. The CF mouse models generated to date have provided a wealth of information on the pathophysiology of the disease in a variety of organs. Heterogeneity of disease in the mouse models is due to the variety of gene-targeting strategies used in the generation of the CF mouse models as well as the diversity of the murine genetic background. This paper reviews the pathophysiology in the tissues and organs (gastrointestinal, airway, hepatobiliary, pancreas, reproductive, and salivary tissue) involved in the disease in the various CF mouse models. Marked similarities to and differences from the human disease have been observed in the various murine models. Some of the CF mouse models accurately reflect the ion-transport abnormalities and disease phenotype seen in human CF patients, especially in gastrointestinal tissue. However, alterations in airway ion transport, which lead to the devastating lung disease in CF patients, appear to be largely absent in the CF mouse models. Reasons for these unexpected findings are discussed. This paper also reviews pharmacotherapeutic and gene therapeutic studies in the various mouse models.

Animals↗