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Results for “parameter identification”

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PubMed1990

Michaelis-Menten metabolite formation kinetics: equations relating area under the curve and metabolite recovery to the administered dose.

A computational approach which concomitantly determines the capacity-limited rate constants of parent drug elimination and metabolite formation is presented. The approach applies both the presently derived total excretory recovery versus dose relationships of the metabolite and the AUC versus dose relationships of the parent drug to identify the parameters. Three parent drug elimination conditions were assessed: pooled first-order, pooled Michaelis-Menten, and parallel first-order and pooled Michaelis-Menten kinetics. Model and parameter identification criteria are discussed. Literature data for theophylline and two of its metabolites in rats were examined to reveal pooled Michaelis-Menten elimination kinetics of theophylline and capacity-limited formation of the metabolites. The proposed technique is useful for quantitating commonly obtained nonlinear drug disposition data such as AUC and amount of metabolites excreted.

Animals↗

PubMed1997

Measurement of rigidity in Parkinson's disease.

Clinical assessment of rigidity in parkinsonian patients is largely qualitative. The reliability and validity of the assessments are sometimes in doubt. Several "engineering" methods of quantifying rigidity have been described, but none has been adopted into general clinical practice. A possible reason is that these methods differ in crucial aspects from the clinical exam. We therefore tackled the problem by monitoring the clinical exam itself, using small sensors to measure the forces and displacements applied. Limb impedance (Z) was computed using parameter identification methods and compared to raters' verbalized ratings of rigidity based on a 5-point scale: the Unified Parkinson's Disease Rating System. The qualitative and quantitative estimates of impedance covaried over a fourfold range, depending on the forces imposed and the subject's motor set. Raters differed by up to 1 full point in their mean qualitative ratings and sometimes disagreed on whether levodopa reduced rigidity. This was not due to any significant differences in the overall range of rigidity they evoked, but rather to the way they scored this range [the ratio of mean rating to mean impedance (R/Z) varied between raters and subjects]. On the other hand, the R/Z ratio was reproducible over separate sets of ratings and may therefore serve to convert measured impedance into a standardized rating. Our results indicate that the current clinical exam may be too abbreviated to detect the sometimes quite small reductions in rigidity after levodopa. We conclude that a device that conveniently quantifies the clinical assessment of rigidity is now available and will lead to more standardized protocols for rating rigidity in the near future.

Antiparkinson Agents↗

PubMed1985

Phase alterations of spin echoes by motion along magnetic field gradients.

Using a Taylor series expansion of the phase shift of a moving isochromatic spin group in the presence of a magnetic field gradient, the refocusing effects of the Carr-Purcell-Meiboom-Gill pulse sequence on stationary nuclei and those with constant, rectilinear velocity are readily demonstrated. Continuing the analysis to higher orders of motion reveals that nuclei with a constant, rectilinear acceleration have a phase shift at the spin echoes which increases linearly with echo number. Constant, rectilinear jerk (the time rate of change of acceleration) leads to an increase in phase shift from echo to echo which is quadratic in nature with an overlying reduction of the odd-numbered echoes by a constant amount. Motion parameters may be measured by parameter identification techniques. These principles may be applied to phase-sensitive NMR imaging.

Magnetic Resonance Spectroscopy↗

PubMed2002

A mathematical model that predicts the force-frequency relationship of human skeletal muscle.

In previous work we developed and validated a mathematical model that predicted force output from skeletal muscles subjected to six-pulse stimulation trains under isometric condition. The current study investigated the model's ability to predict force responses to longer stimulation trains under both nonfatigued and fatigued conditions. Using the six-pulse train model to predict the force produced by longer stimulation trains showed that the model was successful, but a modified parameter identification scheme was required. For most of the trains tested the model accounted for 95% of the variance in the experimental forces produced by stimulation trains, with mean frequencies from 12.5 to 100 HZ, train durations from 485 to 1000 ms, and number of pulses from 14 to 50 for both nonfatigued and fatigued muscles. The success of our mathematical model in predicting forces produced by stimulations with a wide range of frequencies, durations, and number of pulses implies great potential of the model for the identification of optimal activation patterns that should be used during functional electrical stimulation.

Actins↗

PubMed1997

Visualization-based analysis of multiparameter models using environment for N-dimensional model analysis.

We present a methodology, based on N-dimensional computer visualization, for analyzing multiparameter models. This approach originally consisted of three steps: behavior analysis, sensitivity analysis, identifiability analysis. We have now developed a new way of calculating sensitivity based on the statistical measure of the coefficient of variation. Furthermore, we extended the methodology through the addition of an extra step, visual regression. Visual regression allows the user to visualize the process of actual parameter identification and presents a combined, empirical view of the first three steps in a single image. Next we applied this methodology to pulmonary capillary-transport models. Finally, we implemented the model analysis process as a stand-alone program. EN-DIMAN, the resulting software, allows researchers to carry out model analysis in a graphical user interface (GUI)-based environment.

Algorithms↗

PubMed1994

Spatial and space-time correlations in systems of subpopulations with stochastic migration.

The great majority of models of the population genetics of subdivided populations have made the simplifying assumption that the gene frequencies in migrant groups are deterministic. The present paper examines models which more closely mimic natural conditions, in which the gene frequencies in migrant groups are subject to stochastic effects. It is shown that some types of stochastic migration can cause dramatic changes in spatial correlations and variance. These changes depend on how the stochastic migration effects in the gene frequency recursion equations are shared among nearby subpopulations during the same generation. Only for cases where the effects are completely unshared are the equilibrium spatial and space-time correlations among adult subpopulations unaffected, but the variance is always inflated. The analyses here use novel methods, by recasting population genetic migration-drift models as space-time autoregressive moving average (STARMA) processes. Recent theorems for STARMA processes are employed for finding the spatial correlations, and for the first time in population genetics theory the complete set of space-time correlations, for systems with general patterns of migration rates and numbers of spatial dimensions. The space-time correlations provide a uniquely detailed description of a system, and thus form a link between observed spatial autocorrelation statistics and the underlying space-time population genetic process. STARMA theoretical processes have direct statistical analogues that can be applied for process identification, parameter estimation, model fitting, and forecasting in real systems.

Animals↗

PubMed1987

Computer-operated microspectrofluorimetry to identify formaldehyde-induced fluorophores of biogenic monoamines and precursor substances in models and tissue sections.

By means of a histochemical reaction using formaldehyde vapour (Falck and Owman 1965), biogenic monoamines and precursor substances, i.e., L-DOPA, dopamine, noradrenaline, adrenaline, 5-hydroxytryptophan and 5-hydroxytryptamine, may be converted into fluorophores with specific spectral characteristics, i.e., the emission spectrum, excitation spectrum and fading curve. The registration and correction of the spectral properties and changes induced by acidification with hydrochloric acid vapour or treatment with ammonia vapour, of these formaldehyde-induced fluorophores, are performed by an automated microspectrofluorimeter, developed by modification of a Leitz MPV 2 system. This work deals with the instrumental configuration and certain methodological features in order to identify the fluorogenic biogenic monoamines and precursor substances in models and tissue sections. Registrations of excitation peak values, for the first time extended to a wavelength range from 240-460 nm, are discussed, which enable the calculation of peak ratio values 410/260, 380/320, 320/260 or 385/315, suitable as identification parameters for formaldehyde-induced fluorophores of biogenic monoamines and precursor amino acids.

5-Hydroxytryptophan↗

PubMed1987

Distribution of transvascular pathway sizes through the pulmonary microvascular barrier.

Mathematical models of solute and water exchange in the lung have been helpful in understanding factors governing the volume flow rate and composition of pulmonary lymph. As experimental data and models become more encompassing, parameter identification becomes more difficult. Pore sizes in these models should approach and eventually become equivalent to actual physiological pathway sizes as more complex and accurate models are tried. However, pore sizes and numbers vary from model to model as new pathway sizes are added. This apparent inconsistency of pore sizes can be explained if it is assumed that the pulmonary blood-lymph barrier is widely heteroporous, for example, being composed of a continuous distribution of pathway sizes. The sieving characteristics of the pulmonary barrier are reproduced by a log normal distribution of pathway sizes (log mean = -0.20, log s.d. = 1.05). A log normal distribution of pathways in the microvascular barrier is shown to follow from a rather general assumption about the nature of the pulmonary endothelial junction.

Animals↗

PubMed2004

A survey of computational and physical methods applied to solid-state fermentation.

During the last decade, significant effort has been made to apply computational and physical methods to solid-state fermentation (SSF). This had positive impact both on our understanding of the basic principles underlying this old technology, and on the latest progress made in industrial bioengineering. Guidelines on bioreactor design and operation including scale-up, new methods for biomonitoring and advanced control strategies are among the most important outcomes of practical use. Nevertheless, there still is a lack of experimental data, which hampers parameter identification and thus broader use of mathematical modeling. More attention should therefore be paid to combining and concentrating modern physical techniques and computational approaches in order to allow better model validation and thus further progress in rational bioengineering of SSF.

Bioreactors↗

PubMed1999

Numerical fourier transform spectroscopy of EMG half-waves: fragmentary-decomposition-based approach to nonstationary signal analysis.

A nonstationary signal analysis technique is introduced, which regards an oscillatory physiological signal as a sum of its fragments, presented in the form of a fragmentary decomposition (FD). The virtue of FD is that it is free of the necessity to choose a priori the basis functions intended for signal analysis or synthesis. FD uses an unchanged signal fragment between adjacent zero-crossings, as a natural basis function called the half-wave function (HWF). To show that such a function is a physically meaningful object, Fourier transform methods were employed, supported by the similar basis function (SBF) algorithm, which provides the means for numerical Fourier transform spectroscopy of separate half-waves and their frequency domain description in terms of both amplitude and phase. The application of this method to parameter identification of 751 EMG half-waves from the eye blink EMG records of ten normal subjects showed that HWF's frequency domain image represents a Gaussian distribution, which applies over a defined range of relative frequencies. This empirical evidence shows that HWFs are produced by a specific system of first-order nonlinear differential equations, whose dependency on a number of random factors is characteristic of deterministic chaos. The particular form of solutions indicates that statistical regularities relevant to the central limit theorem are likely to underlie the genesis of the mass potentials studied. FD shows potential utility in a range of nonstationary physiological signals.

Adolescent↗

PubMed2002

Model-based optimization of viral capsid protein production in fed-batch culture of recombinant Escherichia coli.

An optimized fed-batch cultivation process for the production of the polyoma virus capsid protein VP1 in recombinant Escherichia coli BL21 bacteria is presented. The optimization procedure maximizing the amount of desired protein is based on a mathematical model. The model distinguishes an initial cell growth phase from a protein production phase initiated by inducer injection. A new approach to model the target protein formation rate was elaborated, where product formation is primarily dependent on the specific biomass growth rate. Lower growth rates led to higher specific protein concentrations. The model was identified from a series of fed-batch experiments designed for parameter identification purposes and possesses good prediction quality. Then the model was used to determine optimal open-loop control profiles by manipulating the substrate feed rates in both phases as well as the induction time. Feed-rate optimization has been solved using Pontryagin's maximum principle. The solution was validated experimentally. A significant improvement of the process performance index was achieved.

Journal Article↗

PubMed2005

Simultaneous estimation of sludge biological activity and influent nitrogen load using ORP and DO dynamics.

This paper proposes a new optimization strategy to estimate nitrifiable nitrogen concentration in wastewater, nitrification rate, denitrification rate and/or COD available for denitrification of an activated sludge process submitted to intermittent aeration. The approach uses the oxydo-reduction potential and dissolved oxygen measurements only. The parameter identification is based on a Simplex optimization of a cost function related to the error between an experimental cycle (an aerobic period followed by an anoxic one) and a simulation of a reduced model derived from ASM1. Results show very good prediction of experimental oxygen, ammonium and nitrate profiles. The estimation of nitrifiable nitrogen and removal rates has been validated both on simulated data obtained from COST action 624 benchmark and on experimental data.

Algorithms↗

PubMed1993

Determination of renal clearance of neopterin by a pharmacokinetic approach.

Pharmacokinetic modelling was used to determine the glomerular filtration rate and tubular secretion of neopterin, a marker for cellular immune activation. The method involves parameter identification employing the transient venous plasma concentration profiles of marker substances. By combined i.v. injection of neopterin and inulin which is excreted exclusively via glomerular filtration, neopterin was shown to be excreted in addition to glomerular filtration, by tubular secretion: clearance of inulin, 112 (S.D. 2.2) ml/liter; clearance of neopterin, 499 (S.D. 79.7) ml/min. A pilot experiment using in addition p-amino hippuric acid suggests that neopterin and p-amino hippuric acid may employ the same carrier system for tubular secretion.

Adult↗

PubMed1990

Control of functional electrical stimulation with extended physiological proprioception.

The use of functional electrical stimulation (FES) of muscle for paraplegic locomotion, or grasp augmentation in tetraplegia, is limited by the variability in muscle response to stimulation as a result of several external and internal factors. Previous approaches to this problem have used position-servo controllers, which have been shown to function satisfactorily in the laboratory. However, such systems will fail should obstacles be encountered or should the stimulation hardware develop a fault. To prevent such potentially dangerous failures some form of sensory feedback is required. This paper describes the first application of a technique known as extended physiological proprioception (EPP) to the control of FES to compensate for muscle response variability and provide proprioceptive feedback via the appropriate sensory pathways. In the experimental system described, a paraplegic subject controlled the extension of his paralysed knee by shoulder protraction. A Bowden cable linked the two joints, and a dynamometer in this cable was used to derive the control signal for a computer-controlled stimulator which delivered surface stimulation to the quadriceps muscle group. Modelling and parameter identification were performed by analysis of the step response, and the controller was designed from consideration of the root locus. The advantages of the system, in terms of improved proprioceptive feedback and reduced limb-positioning error were assessed in a test of joint positioning accuracy with vision occluded. The EPP system showed improvements over both open and closed-loop position-servo controllers.

Artificial Limbs↗

PubMedDate not supplied

Modelling, simulation and control in a data-rich environment.

This paper describes the use and potential use of mathematical modelling, computer simulation, real-time parameter identification and adaptive feedback control techniques in data-rich clinical environments. We consider a system to be operating in a data-rich environment when measurements of system inputs and outputs are frequently available. Two particular application examples which illustrate the power of these techniques will be examined. The first example that will be described involves the development and testing of a real-time adaptive controller for simultaneous regulation of mean arterial pressure and cardiac output using two drugs. The second application of these techniques involves the real-time control of electrical stimulation for the functional use of paralyzed muscles in neuroprosthetic devices.

Computer Simulation↗

PubMed2006

Integral-based filtering of continuous glucose sensor measurements for glycaemic control in critical care.

Hyperglycaemia is prevalent in critical illness and increases the risk of further complications and mortality, while tight control can reduce mortality up to 43%. Adaptive control methods are capable of highly accurate, targeted blood glucose regulation using limited numbers of manual measurements due to patient discomfort and labour intensity. Therefore, the option to obtain greater data density using emerging continuous glucose sensing devices is attractive. However, the few such systems currently available can have errors in excess of 20-30%. In contrast, typical bedside testing kits have errors of approximately 7-10%. Despite greater measurement frequency larger errors significantly impact the resulting glucose and patient specific parameter estimates, and thus the control actions determined creating an important safety and performance issue. This paper models the impact of the continuous glucose monitoring system (CGMS, Medtronic, Northridge, CA) on model-based parameter identification and glucose prediction. An integral-based fitting and filtering method is developed to reduce the effect of these errors. A noise model is developed based on CGMS data reported in the literature, and is slightly conservative with a mean Clarke Error Grid (CEG) correlation of R=0.81 (range: 0.68-0.88) as compared to a reported value of R=0.82 in a critical care study. Using 17 virtual patient profiles developed from retrospective clinical data, this noise model was used to test the methods developed. Monte-Carlo simulation for each patient resulted in an average absolute 1-h glucose prediction error of 6.20% (range: 4.97-8.06%) with an average standard deviation per patient of 5.22% (range: 3.26-8.55%). Note that all the methods and results are generalizable to similar applications outside of critical care, such as less acute wards and eventually ambulatory individuals. Clinically, the results show one possible computational method for managing the larger errors encountered in emerging continuous blood glucose sensors, thus enabling their more effective use in clinical glucose regulation studies.

Adult↗

PubMed2005

Mathematical modeling of arterial pressure response to hemodialysis-induced hypovolemia.

A computer model of pressure response to hemodialysis-induced hypovolemia is reported. Heart rate and hematocrit, measured in the course of hemodialysis, are imposed as computer model inputs and the model computes the arterial pressure response after tuning model parameters representative of patient's cardiovascular reactivity. Computer model reproduced with good accuracy experimental data (arterial pressure, cardiac output and total peripherical resistance). Parameter identification over successive sessions of the same patients revealed satisfactory reliability, providing a physiological interpretative key to patient's hemodynamic behavior during hemodialysis.

Blood Pressure↗

PubMed2006

Effects of different tissue loads on high power ultrasonic surgery scalpel.

The objective of this study is to investigate the influence of various tissue loads on the working characteristic of the ultrasonic scalpel, including working frequency, input admittance and reflection factor. Ex vivo animal experiments are carried out and relevant discussions of experimental results are provided. Admittance measurement results show that different tissue loads have different effects on a scalpel's working ability. Soft tissue makes the working frequency decrease and bone tissue makes it increase. Radius of admittance circles and reflection factor are also different. Equivalent circuit model is found and with a least-square parameter identification method, input admittance of ultrasonic scalpel with different tissue loads is solved. Results show that admittance circle radius is determined by the value of R1. Changes in L1 and C1 contribute to the shift of working frequency. This study will help decrease the sensitivity of ultrasonic scalpel to loads and greatly increase surgery efficiency.

Adipose Tissue↗