SEARCH · PubMed Health

Results for “computational modelling”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources

PubMed1977

A Monte Carlo computer model to investigate patient scheduling.

A Monte Carlo computer model was developed to investigate various types of patient appointment schedules for a single channel queue. Input parameters included the incidence of no-shows, the rate of unscheduled walk-ins, the frequency distribution of physician examination times, and the string of appointment times. The results included the frequency distributions of physician utilization rates and the total waiting time of all patients. Five hospital clinics were simulated. Even increment schedules yielded the best trade-off between physician utilization and patient waiting.

Appointments and Schedules↗

PubMed1989

Computer model of cardiac repolarization processes and of the recovery sequence.

A computer model simulating both excitation and recovery processes within a block of heart muscle tissue has been developed and implemented on different IBM PC AT compatible computers. The model incorporates blocks of tissue consisting of several thousand elements and introduces phenomena which are completely or partly omitted in other existing cardiac electrophysiology models. These phenomena include the electric anisotropy of the tissue, different durations of repolarization in different layers of tissue, and the different shapes of action potential which correspond to cells excited when not fully recovered. Implementation of the model on small personal computers requires the use of a special data structure management and an effective algorithmic background. The program of the model is written in PASCAL and uses dynamically allocated data structures and the asynchronous simulation technique of event planing. These techniques are described in detail. The model has been used in various experiments. Results of simulation studies are presented in the form of modeled three-lead electrocardiographic records. The experimental series which are described include basic patterns of regular activation sequences, modeling of premature beats, simulation of effects due to fast pacing, models of ischemia and infarction, simulation of reentry mechanisms with a special reference to the initiation of ventricular fibrillation, and models of late potentials. The future development of more realistic models of the cardiac recovery process is also discussed.

Action Potentials↗

PubMed1987

A computer model of hemorrhagic shock in domestic swine.

We used a modified version of the computer model of the circulation developed by C.V. Greenway (Pharmacol Rev 33:213-251, 1982) to study the volume-pressure relationship of the systemic venous circulation during and immediately after massive blood loss. Our theoretical predictions were based on experimental measurements performed in conscious, chronically instrumented swine subjected to massive and rapid loss of a predetermined amount of blood. These animals were subjected to an exponential removal of either 50% of their calculated blood volume in 1 hour or a linear removal of 60% in 15 minutes. Our computer model indicates a hysteresis effect between the volume-pressure curves during and immediately following hemorrhage. The results emphasize the importance of venous capacitance changes as a compensatory response to blood loss.

Animals↗

PubMed1996

Sensory gating in a computer model of the CA3 neural network of the hippocampus.

We have developed a unique computer model of the CA3 region of the hippocampus that simulates the P50 auditory evoked potential response to repeated stimuli in order to study the neuronal circuits involved in a sensory processing deficit associated with schizophrenia. Our computer model of the CA3 hippocampal network includes recurrent activation from within the CA3 region as well as input from the entorhinal cortex and the medial septal nucleus. We used the model to help us determine if the cortical and septal inputs to the CA3 hippocampus alone are responsible for the gating of auditory evoked activity, or if the strong recurrent activity within the CA3 region contributes to this phenomenon. The model suggests that the medial septal input is critical for normal gating; however, to a large extent the activity of the medial septal input can be replaced by simulated stimulation of the hippocampal neurons by a nicotinic agonist. The model is thus consistent with experimental data that show that nicotine restores gating of the N40 evoked potential in fimbria-fornix lesioned rats and of the P50 evoked potential in schizophrenic patients.

Animals↗

PubMed1985

Shell computer model of cardiac electropotential changes.

A discrete process computer model has been developed to simulate the electropotential changes of heart musculature and the operation of the cardiac conduction system. The model is implemented on an ICL-4/72 computer and is oriented to cardiac rhythm studies, allowing practically all rhythm pathologies, including pacemaker applications, to be simulated. The paper describes in detail the principles on which the model is based, compares the model with other models of the same system and shows concisely some results of simulation experiments in the form of computer generated ECG records.

Atrioventricular Node↗

PubMed1986

Computer modeling of actinomycin D interactions with double-helical DNA.

We have performed molecular mechanical calculations on intercalation complexes of actinomycin D with a series of base-paired hexanucleoside pentaphosphates; d(GCGCGC)2, d(GCCGGC)2, d(GCATGC)2, d(GCTAGC)2 and d(ATGCAT)2. Our results are in good agreement with previous experimental work on sequence selectivity. The results provide a rationalization for the strong preference of actinomycin D to intercalate on the 3' side of guanine residues, consistent with previously proposed models. Finally, the computed structures for d(ATGCAT)2-actinomycin D complexes have been compared with two-dimensional nuclear magnetic resonance nuclear Overhauser effect experimental results. To our knowledge, this is the first extensive comparison of molecular mechanical model structures for a drug-DNA complex with experimental solution phase data. We find generally good agreement between our computational models and the experimental solution phase structures.

Computers↗

PubMed1995

Validation of a computer model of haemorrhage and transcapillary refill.

A computer model is described which uses blood volume deficit and its duration to simulate the first two hours of haemorrhage, including an estimation of the blood volume added by Starlings transcapillary refill mechanism. Computer prediction of the haematocrit was compared with published data on haemorrhage in animals. There was close correlation with data on the haemodilution caused by Starling's transcapillary refill mechanism in conscious swine (r = 0.84).

Animals↗

PubMed1989

Three-dimensional computer model of the heart: fibrillation induced by extrastimulation.

We present a three-dimensional (3D) computer model that simulates electrical activity in the heart during fibrillation. A real dog heart is discretized to form 1473 interconnected cubic elements. The model exhibits normal activation and recovery from pacing. Five or more extrastimuli induce a self-sustaining tachyarrhythmia that soon degenerates into a fibrillatory rhythm. The extrastimuli increase the excitability of the myocardial cell population. The result is a rapid re-excitation of cells that allows for only a partial recovery of cell action potential. This suggests that a dispersion of refractory states of the cell population is the cause of fibrillation in this computer model.

Animals↗

PubMed1991

An evaluation of eight computer models of mammalian inner hair-cell function.

Eight computer models of auditory inner hair cells have been evaluated. From an extensive literature on mammalian species, a subset of well-reported auditory-nerve properties in response to tone-burst stimuli were selected and tested for in the models. This subset included tests for: (a) rate-level functions for onset and steady-state responses; (b) two-component adaptation; (c) recovery of spontaneous activity; (d) physiological forward masking; (e) additivity; and (f) frequency-limited phase locking. As models of hair-cell functioning are increasingly used as the front end of speech-recognition devices, the computational efficiency of each model was also considered. The evaluation shows that no single model completely replicates the subset of tests. Reasons are given for our favoring the Meddis model [R. Meddis, J. Acoust. Soc. Am. 83, 1056-1063 (1988)] both in terms of its good agreement with physiological data and its computational efficiency. It is concluded that this model is well suited to provide the primary input to speech recognition devices and models of central auditory processing.

Animals↗

PubMed1995

Computer models: killing mosquitoes with information.

This paper looks at the relationship between man and mosquitoes from the perspective of coevolution. From this perspective, the primacy of information processing in vector control programs becomes acutely evident. A composite mosquito control program is developed and illustrated to show the benefits derived from incremental increases in information. The use of computer modeling is seen as the next logical step to be taken by vector control personnel to add the next increment of efficiency and effectiveness. This step could well lead to significant reductions or perhaps the elimination of the need for pesticide use. The author encourages the use of computer modeling in teams as the means to learn across disciplines. The feasibility of this approach has been greatly enhanced by the availability of off-the-shelf modeling programs. The author appeals to university and vector control professionals to support students and staff in learning computer modeling techniques.

Animals↗

PubMed1987

A computational model of reasoning from the clinical literature.

This paper explores the premise that a formalized representation of empirical studies can play a central role in computer-based decision support. The specific motivations underlying this research include the following propositions: Reasoning from experimental evidence contained in the clinical literature is central to the decisions physicians make in patient care. A computational model, based upon a declarative representation for published reports of clinical studies, can drive a computer program that selectively tailors knowledge of the clinical literature as it is applied to a particular case. The development of such a computational model is an important first step toward filling a void in computer-based decision support systems. Furthermore, the model may help us better understand the general principles of reasoning from experimental evidence both in medicine and other domains. Roundsman is a developmental computer system which draws upon structured representations of the clinical literature in order to critique plans for the management of primary breast cancer. Roundsman is able to produce patient-specific analyses of breast cancer management options based on the 24 clinical studies currently encoded in its knowledge base. The Roundsman system is a first step in exploring how the computer can help to bring a critical analysis of the relevant literature to the physician, structured around a particular patient and treatment decision.

Artificial Intelligence↗

PubMed1993

Regularity of cochlear nucleus stellate cells: a computational modeling study.

This article reports on a computational modeling study designed to investigate the generation of the transient chopper response of cochlear nucleus stellate cells. The model is based on a simulation of the auditory periphery which feeds a generic stellate-cell model. Physiological recordings of transient chopper units in response to short, best frequency, tone bursts show a brief initial period (typically < 10 ms) of rapid rate adaptation as evidenced by a rapid rise in mean interspike interval. Associated with this rate adaptation is a significant increase in firing irregularity. The changes in rate and irregularity have recently been attributed to the activation of noisy inhibitory inputs on the cell [e.g., Banks and Sachs, J. Neurophysiol. 65, 606-629 (1991)]. However, the results show that the transient chopper response pattern can be generated without the need for inhibitory inputs. The transience of the initial chopping pattern is sensitive to the following model parameters: (a) the firing threshold of the cell, (b) the number of excitatory inputs that converge on the cell, and (c) the magnitude of the current delivered to the cell for each active input. The response was also found to be relatively insensitive to changes in the degree of dendritic filtering imposed on the auditory-nerve input. The results of each simulation can be explained by considering the pattern of depolarization the cell receives during the course of a tone burst.

Acoustic Stimulation↗

PubMed1990

The use of selective inhibitors and computer modelling to evaluate the role of specific high affinity cyclic AMP phosphodiesterases in the hormonal regulation of hepatocyte intracellular cyclic AMP concentrations.

Using experimentally derived data for the activities and kinetic constants of hepatocyte cyclic AMP phosphodiesterase isoenzymes together with the derived changes in adenylate cyclase activity, due to stimulation and subsequent desensitization by glucagon, a computer model was established to simulate hepatocyte cyclic AMP metabolism. The established ability of glucagon to activate the 'dense-vesicle' cyclic AMP phosphodiesterase by eliciting its cyclic AMP-dependent phosphorylation was shown on the model to be capable of eliciting a profound reduction in the glucagon-stimulated increase in intracellular cyclic AMP. This was consistent with experimentally derived observations using the compound ICI 118233 which was used to inactivate the 'dense-vesicle' enzyme selectively. The non-hydrolysable adenosine agonist N6 (phenylisopropyl)-adenosine (PIA), which prevents glucagon pre-treatment of hepatocytes blocking the ability of insulin to stimulate the peripheral plasma membrane cyclic AMP phosphodiesterase, is shown here to accentuate the ability of insulin to decrease glucagon-elevated intracellular cyclic AMP concentrations. This effect was obliterated using the compound ICI 63197, a selective inhibitor of the peripheral plasma membrane phosphodiesterase. Computer modelling studies, taking into account experimentally derived actions in insulin in activating the peripheral plasma membrane phosphodiesterase, confirmed the potential of this enzyme to decrease intracellular cyclic AMP concentrations. Modelling of the putative effect of an insulin 'mediator' in activating the two cyclic GMP-stimulated cyclic AMP phosphodiesterase isoenzymes was shown to elicit a decrease in intracellular cyclic AMP concentrations which was comparable to that caused by insulin's action on intact hepatocytes. The relative contribution of each phosphodiesterase form to the metabolism of hepatocyte intracellular cyclic AMP, together with an assessment of the potential effect of inhibition and activation of specific species, was evaluated using the computer model. These experimental and stimulation studies indicate that alterations in the phosphodiesterase activity of the 'dense-vesicle' enzyme, the peripheral plasma membrane enzyme, the cyclic GMP-stimulated cyclic AMP isoforms and the IBMX-insensitive PDE-MQ-II can elicit profound effects upon hepatocyte intracellular cyclic AMP concentrations.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1994

Coupling of spinal locomotor networks in larval lamprey revealed by receptor blockers for inhibitory amino acids: neurophysiology and computer modeling.

1. Receptor blockers for inhibitory amino acids were applied to part or all of the spinal cord of larval lamprey during brain stem-initiated locomotor activity. Blocking glycinergic inhibition with strychnine applied to the entire spinal cord converted the locomotor pattern from left-right alternation to synchronous left-right bursting. The results suggest that left and right oscillators are connected by relatively strong reciprocal inhibitory (glycinergic) connections in parallel with weaker reciprocal excitatory connections. This possible organization was supported by results from a computer model consisting of left and right oscillators connected by reciprocal inhibition and excitation in parallel. In addition, the results suggest that reciprocal inhibition is not required for left-right rhythmicity but rather is involved primarily with phasing of left-right activity. 2. Locally blocking glycinergic inhibition with strychnine in the rostral spinal cord resulted in synchronous left-right burst activity in that region of the cord as well as in more caudal areas of the cord in which reciprocal inhibition should still be functional. 3. Blocking glycinergic inhibition in the caudal spinal cord converted the pattern in that region of the cord to left-right synchronous activity. The effects in the ascending direction on the burst patterns in more rostral areas of the spinal cord were less than those mentioned above in the descending direction with application of strychnine to the rostral spinal cord. 4. With glycinergic inhibition or GABAergic inhibition blocked in the entire spinal cord, stable longitudinal coupling along the spinal cord persisted. This and the neurophysiology results mentioned above suggest that the main mechanism for longitudinal coupling between locomotor networks in adjacent regions of the spinal cord is ipsilateral excitatory connections and not crossed inhibitory connections. This possible organization was supported by results from a computer model, which consisted of a pair of oscillators in the more rostral and more caudal spinal cord that could be connected by various types of coupling schemes. 5. The neurophysiological data above suggest that ipsilateral, excitatory coupling is stronger in the descending direction than in the ascending direction. In the computer model, a dominant descending coupling is a necessary requirement to produce positive longitudinal phase lags.

Animals↗

PubMed1976

Subsite mapping of enzymes. Application of the depolymerase computer model to two alpha-amylases.

In the preceding paper (Allen and Thoma, 1976) we developed a depolymerase computer model, which uses a minimization routine to establish a subsite map for a depolymerase. In the present paper we show how the model is applied to experimental data for two alpha-amylases. Michaelis parameters and bond-cleavage frequencies for substrates of chain lengths up to twelve glucosyl units have been reported for Bacillus amyloliquefaciens, and a subsite map has been proposed for this enzyme [Thoma et al. (1971) J. Biol. Chem. 246, 5621-5635]. By applying the computer model to the experimental data, we have arrived at a ten-subsite map. We find that a significant improvement in this map is achieved by allowing the hydrolytic rate coefficient to vary as a function of the number of occupied subsites comprising the enzyme-binding region. The bond-cleavage frequencies, the enzyme is found to have eight subsites. A partial subsite map is arrived at, but the entire binding region cannot be mapped because Michaelis parameters are complicated by transglycosylation reactions. The hydrolytic rate coefficients for this enzyme are not constant.

Amino Acid Sequence↗

PubMed1991

3-D computer model of subcortical structures of human brain.

Three-dimensional computer model of thalamus and adjacent formations of human brain has been elaborated on the basis of sagittal slices from the Schaltenbrand-Bailey stereotactic atlas. The model includes 120 morphologically distinguishable structures and consists of more than 16 million points (volume elements) each of them being associated with the particular structure in the brain. The model is stored in the long-term computer memory. A special software has been developed to facilitate utilizing the model obtained. The software facilitates synthesizing arbitrary cross-sections through the brain and provides the correspondence between the stereotactic coordinates of any point and its position on the screen of monitor. The coordinates of the point in the system of stereotactic atlas and the name of the structure, the point belongs to, are also supplied. It is also possible to get magnified images of cross-sections and to get isometrical images. The system enables the neurosurgeon to improve the planning and execution of stereotactic operations, and will also be helpful for education.

Brain↗

PubMed1991

Three-dimensional model of Escherichia coli ribosomal 5 S RNA as deduced from structure probing in solution and computer modeling.

The conformation of Escherichia coli 5 S rRNA was investigated using chemical and enzymatic probes. The four bases were monitored at one of their Watson-Crick positions with dimethylsulfate (at C(N-3) and A(N-1], with a carbodiimide derivative (at G(N-1) and U(N-3] and with kethoxal (at G(N-1, N-2]. Position N-7 of purine was probed with diethylpyrocarbonate (at A(N-7] and dimethylsulfate (at G(N-7]. Double-stranded or stacked regions were tested with RNase V1 and unpaired guanine residues with RNase T1. We also used lead(II) that has a preferential affinity for interhelical and loop regions and a high sensitivity for flexible regions. Particular care was taken to use uniform conditions of salt, magnesium, pH and temperature for the different enzymatic chemical probes. Derived from these experimental data, a three dimensional model of the 5 S rRNA was built using computer modeling which integrates stereochemical constraints and phylogenetic data. The three domains of 5 S rRNA secondary structure fold into a Y-shaped structure that does not accommodate long-range tertiary interactions between domains. The three domains have distinct structural and dynamic features as revealed by the chemical reactivity and the lead(II)-induced hydrolysis: domain 2 (loop B/helix III/loop C) displays a rather weak structure and possesses dynamic properties while domain 3 (helix V/region E/helix IV/loop D) adopts a highly structured and overall helical conformation. Conserved nucleotides are not crucial for the tertiary folding but maintain an intrinsic structure in the loop regions, especially via non-canonical pairing (A.G, G.U, G.G, A.C, C.C), which can close the loops in a highly specific fashion. In particular, nucleotides in the large external loop C fold into an organized conformation leading to the formation of a five-membered loop motif. Finally, nucleotides at the hinge region of the Y-shape are involved in a precise array of hydrogen bonds based on a triple interaction between U14, G69 and G107 stabilizing the quasi-colinearity of helices II and V. The proposed tertiary model is consistent with the localization of the ribosomal protein binding sites and possesses strong analogy with the model proposed for Xenopus laevis 5 S rRNA, indicating that the Y-shape model can be generalized to all 5 S rRNAs.

Base Sequence↗

PubMed1988

Computer modelling antibiotic therapy costs. Impact of therapeutic range.

Computer modelling techniques were used to examine the economic consequences of intravenous chemotherapy of serious infection. Acquisition cost of the drug was found to be a poor predictor of global cost, since inclusion of the preparation and administration costs and projected laboratory and drug complication costs narrow, or even reverse, apparent cost differentials between drugs. Thus, the cost per day for acquisition/total treatment (in US dollars) are: penicillin $5/$30, gentamicin $1/$46, amikacin $26/$63, clindamycin $38/$57, metronidazole $12/$20 and cefotaxime $47/$60. 'Triple therapy' involving gentamicin ($0.40/dose) resulted in higher hospital costs than the equivalent regimen involving cefotaxime ($16/dose). Even when the purchase price is high, humanitarian considerations advocate the use of safe, predictable, efficacious drugs. Fortunately, the present analysis suggests that such drugs frequently result in the lowest total treatment cost. Current cost containment efforts that are based on acquisition costs only are flawed and may result in both suboptimal care and higher actual costs.

Anti-Bacterial Agents↗