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PubMed2004

Robust algorithm for estimation of time-varying transfer functions.

We introduce a new method to estimate reliable time-varying (TV) transfer functions (TFs) and TV impulse response functions. The method is based on TV autoregressive moving average models in which the TV parameters are accurately obtained using the optimal parameter search method which we have previously developed. The new method is more accurate than the recursive least-squares (RLS), and remains robust even in the case of significant noise contamination. Furthermore, the new method is able to track dynamics that change abruptly, which is certainly a deficiency of the RLS. Application of the new method to renal blood pressure and flow revealed that hypertensive rats undergo more complex and TV autoregulation in maintaining stable blood flow than do normotensive rats. This observation has not been previously revealed using time-invariant TF analyses. The newly developed approach may promote the broader use of TV system identification in studies of physiological systems and makes linear and nonlinear TV modeling possible in certain cases previously thought intractable.

Algorithms↗

PubMed1997

Dynamic contact stress and rolling resistance model for total knee arthroplasties.

Problems associated with premature failure of total knee replacements (TKR's) include: wear, creep, and oxidation of ultrahigh-molecular-weight polyethylene (UHMWPe) as well as adverse tissue reactions to polyethylene wear debris. These problems are associated in part with the mechanical behavior of UHMWPe. In TKR's, contact stress analyses have been performed on the UHMWPe tibial component; however, most have employed simplified material properties and not accounted for joint kinematics. A nonlinear viscoelastic rolling model was developed for TKR's to predict the contact stress and rolling friction for varying rolling speed, conformity, applied load, and tibial plateau thickness. Results indicated that the contact stress increased and rolling friction decreased with increasing rolling speed. Effects of conformity, applied load, and tibial plateau thickness were consistent with previous models. At large rolling speeds, predicted peak contact stresses were almost twice their static value, resulting in a compound fatigue problem in UHMWPe components due to normal cyclic loading, moving point of contact, and velocity-dependent stresses.

Elasticity↗

PubMed2004

Education and the course of cognitive decline in Alzheimer disease.

OBJECTIVE: To test the hypothesis that higher level of education is related to more rapid cognitive decline in Alzheimer disease (AD). METHODS: Participants are older persons with clinically diagnosed AD recruited from health care facilities in the Chicago area. At 6-month intervals for up to 4 years, they underwent uniform structured clinical evaluations that included administration of nine cognitive performance tests from which a composite measure of global cognition was derived. Analyses are based on 494 persons with follow-up data (89.3% of those eligible). In mixed models that allowed for linear and nonlinear decline, the authors first accounted for the effects of age on cognition and then tested the relation of education to rate of cognitive decline. RESULTS: Global cognitive decline had linear and nonlinear components, resulting in a gradually accelerating course of decline. Age was related to linear but not nonlinear decline, with more rapid decline observed in younger compared with older persons. Higher educational level was related to more rapid global cognitive decline, as hypothesized, with education related to the nonlinear but not the linear component of decline. CONCLUSION: Higher educational attainment is associated with a slightly accelerated rate of cognitive decline in Alzheimer disease.

Adult↗

PubMed1996

Determination of regional rate constants from dynamic FDG-PET studies in Parkinson's disease.

UNLABELLED: Dynamic [18F]fluorodeoxyglucose (FDG) PET was used in Parkinson's disease patients and normal controls to determine kinetic rate constants for FDG. The goal was to assess whether the metabolic decreases observed in Parkinson's disease are associated with transport or phosphorylation processes or both. METHODS: Fluorine-18-FDG was administered to 18 Parkinson's disease and 15 normal control subjects. Dynamic PET scanning was performed for 1 h and rate constants were obtained by nonlinear, least-squares analysis. Regional glucose metabolic rate was calculated from the individually fitted rate constants and by two standard static scan analyses. RESULTS: Global CMRglu was decreased in Parkinson's disease (mean reduction 22%), reaching statistical significance in all regions investigated. K1 was significantly reduced in parietal cortex, temporal cortex and striatum while k3 was significantly reduced only in parietal cortex. The rate constant k2 was unchanged. CONCLUSION: K1, k3 and CMRglu all demonstrated greater deficits across the brain with progression of disease and development of dementia, particularly in the parietal an occipital cortex. This suggested that the metabolic disturbance may be a global dysfunction throughout the brain. Because altered rate constants are specifically taken into account, dynamic measurements has shown to provide higher sensitivity for detecting diminished glucose utilization in Parkinson's disease than static approaches.

Adult↗

PubMed1994

Nonlinear input-output functions derived from the responses of guinea-pig cochlear nerve fibres: variations with characteristic frequency.

Rate-versus-level functions (RLFs) were recorded from individual cochlear nerve fibres in anaesthetised guinea-pigs. Variations in the shapes of these functions with frequency were used to derive input-output (IO) relationships for the mechanical preprocessing mechanisms in the cochlea. It was assumed that these preprocessing mechanisms operated linearly at frequencies well below each fibre's characteristic frequency (CF). The IO functions derived at each fibre's CF provided strong evidence of compressively nonlinear preprocessing in most regions of the cochlea. However, the apparent degree of compression depended on the fibre's CF, and hence on the presumed site of cochlear innervation. For fibres with CFs of between 1.5 and 3.6 kHz, the CF derived IO functions grew at rates of around 0.5 dB/dB. For fibres with CFs above 4 kHz, the IO functions were more compressive, with high-intensity asymptotic slopes of around 0.13 dB/dB. In the highest (> or = 10 kHz) CF fibres, the degree of compression depended on the physiological condition of the cochlea; the derived IO functions becoming more linear as the cochlea became less sensitive. The derived IO technique was not well suited to analyse responses evoked by very low frequency (e.g., < 500 Hz) tones. Nonetheless, the CF RLFs from fibres with CFs lower than approximately 1 kHz provided little evidence of mechanical nonlinearity near the apex of the cochlea. These findings imply a longitudinal variation in the mechanisms of cochlear preprocessing, and provide important new tests for functional models of the cochlea.

Acoustic Stimulation↗

PubMed1990

Pattern recognition analysis of high resolution 1H NMR spectra of urine. A nonlinear mapping approach to the classification of toxicological data.

A computer-based pattern recognition (PR) approach has been applied to the interpretation of 1H NMR generated urinalysis data in a variety of experimental toxicity states in the rat. 1H NMR signal intensities for each endogenous metabolite in urine were regarded as coordinates in multi-dimensional space and analysed using computer pattern recognition methods through which the dimensionality was reduced for display and categorization purposes. Initially 17 metabolic dimensions were used which were defined by the scored relative concentrations of a variety of urinary metabolites detected in 1H NMR spectra. By employing the unsupervised learning methods of 2- and 3-dimensional nonlinear mapping (NLM) different types of toxin (hepatotoxins, cortical and papillary nephrotoxins) could be classified according to NMR-detectable biochemical effects in the urine. The robustness of the classification methods, and the influence of the addition of new scored biochemical data reflecting dose response situations, nutritional effects on toxicity, sex differences in biochemical response to toxins and addition of a new toxin class (testicular toxin) to the pattern recognition analysis were also evaluated. We find that the initial training set maps are fundamentally stable to the addition of all data types and that the PR methods correctly 'predicted' the toxicological effects of the test compounds. These results confirm the power and wide applicability of linked PR and 1H NMR urinalysis as an approach to the generation and classification of acute toxicological data.

Animals↗

PubMed2005

Automated state analyses: proposed applications to neonatal neurointensive care.

The two principal challenges of neonatal physiologic monitoring device are: (1) the development of computational strategies that consider the rudimentary forms of neonatal sleep state especially for preterm infants and (2) any physiologic monitoring device for clinical applications in a neonatal intensive care setting must be small, portable, and user-friendly. Our multicenter neonatal sleep consortium has acquired more than 1,100 multihour EEG-sleep recordings on over 370 neonates, ranging from 24 to 44 weeks gestation. Each recording was visually-scored for state, arousals, movements, and rapid eye movements, which were used as templates when applying spectral analyses. The authors have defined a brain dysmaturity index to represent functional brain reorganization as the prenate matures to a full-term age; delayed or accelerated physiologic behaviors have been described for the preterm cohort when compared to the full-term group at the same postmenstrual age. Seven EEG-sleep measures comprise this index: quiet sleep percentage, sleep cycle length, rapid eye movements, arousals, spectral beta EEG energies, spectral EEG correlations, and a spectral measure of respiratory regularity. Linear and nonlinear computational algorithms are being developed to automate the computation of the dysmaturity index and to identify new feature types that correlate with dysmaturity. Automated neonatal sleep monitoring system can potentially improve neonatal neurointensive care by facilitating analyses of pervasive neonatal brain disorders expressed primarily as altered sleep state organization, and help predict altered developmental trajectories of children at higher risk for neurologic sequelae.

Brain↗

PubMed1990

Bifurcation analysis of nonlinear retinal horizontal cell models. II. Network properties.

1. We have previously presented a model of horizontal-cell soma isolated from fish retina. The model consists of a synaptic conductance representing input from photoreceptors in parallel with voltage-dependent membrane currents. Membrane-current models are based on I-V curves measured in isolated fish horizontal cells. Bifurcation theory was used to analyze model properties. The major findings of this study were 1) the inward Ca2+ current must be inactivated to account for horizontal-cell resting potentials and hyperpolarizing responses to light stimuli in a background of dark, and 2) the synaptic conductance controls the bifurcation structure of the model, with bistable behavior occurring at small and monostable behavior occurring at larger values of the synaptic conductance. The synaptic conductance at the point of transition from bistable to monostable behavior corresponds to the activation of as few as 100 synaptic channels. Thus tonic synaptic input from photoreceptors and inactivation of the inward Ca2+ current act to "linearize" responses of isolated horizontal-cell models. 2. The model described in this paper extends these analyses to large networks of horizontal cells in which each cell is coupled resistively to its nearest neighbors and is modeled with the use of the full complement of nonlinear membrane currents. Network responses to arbitrary patterns of conductance change (simulating inputs from photoreceptors), current-, or voltage-clamp stimuli are computed using the Newton iteration. The Newton descent direction is computed using either conjugate gradient (CG) or preconditioned CG algorithms. 3. An analysis of network stability properties is performed. Network I-V curves are computed by voltage-clamping the center node and computing the current required to maintain the clamp voltage. Computations are performed on networks of model cells in which the Ca2+ current is fully activated and the synaptic conductance is zero, thus making each cell as nonlinear as possible. Coupling conductance values slightly greater than 100 pS provide a current shunt sufficient to prevent the generation of Ca2+ action potentials in the network. This coupling conductance corresponds to the conductance of as few as two gap-junction channels and is more than two orders of magnitude less than the coupling known to exist between pairs of cultured horizontal cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2006

Nonlinear additive autoregressive model-based analysis of short-term heart rate variability.

In this contribution we test the hypothesis that nonlinear additive autoregressive model-based data analysis improves the diagnostic ability based on short-term heart rate variability. For this purpose, a nonlinear regression approach, namely, the maximal correlation method is applied to the data of 37 patients with dilated cardiomyopathy as well as of 37 age- and sex-matched healthy subjects. We find that this approach is a powerful tool in discriminating both groups and promising for further model-based analyses.

Algorithms↗

PubMed1998

The effects of muscular dystrophy on craniofacial growth in mice: a study of heterochrony and ontogenetic allometry.

Mechanical loading of muscles on bones at their sites of attachment can regulate skeletal morphology. The present study examined the effects of muscle degeneration on craniofacial growth, using two strains of muscular dystrophic mice, Mus musculus, differing in pathological severity. We collected radiographic and weight data longitudinally and digitized radiographs to obtain distances between anatomical landmarks in different functional regions of the skull. We then quantified heterochronic and allometric differences among genotypes and between sexes. Because growth is nonlinear with respect to time, we first used the Gompertz model to obtain heterochronic growth parameters, which were then tested with ANOVA. Ontogenetic allometric analyses examined the scaling relationships between various measurements with linear regressions. For most measurements the severely dystrophic mice are significantly smaller in final size than both the control and the mildly dystrophic mice, which are statistically indistinguishable. Measures of total growth and the neurocranium exhibit more differences among groups in heterochronic parameters of early ontogeny because growth in these regions is controlled primarily by brain expansion that ceases early in development. In contrast, the face and mandible exhibit more differences in later growth parameters possibly because of the increased influence of muscles on these regions as growth progresses. The severely dystrophic mice have flatter, more elongate skulls and mandibles than those of the other two genotypes, concurrent with an absence of muscular forces to stimulate growth in a superior-inferior direction.

Alleles↗

PubMed2006

Influence of femoral head size on impingement, dislocation and stress distribution in total hip replacement.

Dislocation remains a serious complication of total hip replacement. An insufficient range of motion can lead to impingement of the prosthetic neck on the acetabular cup. Together with the initiation of subluxation and dislocation, recurrent impingement can cause material failure in the liner. The objective of this study was to generate a validated finite element (FE) model capable of predicting the dislocation stability of different femoral head sizes with regard to impingement in different implant positions as well as the corresponding stress distribution in the liner. In order to cover posterior and anterior dislocation, two total hip dislocation associated manoeuvres were simulated using a three-dimensional nonlinear finite element model. The dislocation stability of two head sizes was determined numerically and experimentally. After validation, the FE model was used to analyse the dislocation stability of four different head sizes in variable implant positions. Range of motion (ROM) until impingement, the resisting moment that was developed and ROM until dislocation were evaluated. Additionally, stress distribution within the polyethylene liner during impingement and subluxation was determined. For both dislocation modes, a cup position of 45 degrees lateral abduction and 15 degrees up to 30 degrees anteversion resulted in appropriate ROM and dislocation stability. In general, larger head diameters revealed an increase in ROM and higher resisting moments. Stress analysis showed decreased contact pressures at the egress site of the liners with the larger inner diameters during subluxation. The analysis shows that an optimal implant position and a larger head diameter can reduce the risk of dislocation induced by impingement. The finite element model that was developed enables simplification of design variations compared to experimental studies since prototyping and assembling are replaced by prompt numerical simulation.

Arthroplasty, Replacement, Hip↗

PubMed2001

Investigation of surfactant-enhanced dissolution of entrapped nonaqueous phase liquid chemicals in a two-dimensional groundwater flow field.

Because of their low solubility, waste chemicals in the form of nonaqueous phase liquids (NAPLs) that are entrapped in subsurface formations act as long-term sources of groundwater contamination. In the design of remediation schemes that use surfactants, it is necessary to estimate the mass transfer rate coefficients under multi-dimensional flow fields that exit at field sites. In this study, we investigate mass transfer under a two-dimensional flow field to obtain an understanding of the basic mechanisms of surfactant-enhanced dissolution and to quantify the mass transfer rates. Enhanced dissolution experiments in a two-dimensional test cell were conducted to measure rates of mass depletion from entrapped NAPLs to a flowing aqueous phase containing a surfactant. In situ measurement of transient saturation changes using a gamma attenuation system revealed dissolution patterns that are affected by the dimensionality of the groundwater flow field. Numerical modeling of local flow fields that changed with time, due to depletion of NAPL sources, enabled the examination of the basic mechanisms of NAPL dissolution in complex groundwater systems. Through nonlinear regression analysis, mass transfer rates were correlated to porous media properties, NAPL saturation and aqueous phase velocity. Results from the experiments and numerical analyses were used to identify deficiencies in existing methods of analysis that uses assumptions of one-dimensional flow, homogeneity of aquifer properties, local equilibrium and idealized transient mass transfer.

Environmental Monitoring↗

PubMed2002

Clinical applications for change-point analysis of herpes zoster pain.

Pain is the most frequent and disabling complication of herpes zoster. The analysis of pain severity data is complicated by the nonlinear rate of resolution. Further, three distinct phases characterize pain resolution--acute, subacute, and chronic. Using two clinical trial datasets as the bases for analyses, the rates of baseline pain resolution were computed across each of three phases and compared for age, severity of pain at onset, and number of lesions at baseline. The results defined transition points of 24.4 +/- 3.34 for the subacute phase and 110.3 +/- 11.9 days for the chronic phase. The model demonstrated a treatment effect of valiciclovir (VACV) during the subacute phase as compared to acyclovir (ACV) (P = 0.006) and supports effects of age, baseline pain and number lesions on pain cessation rates in the acute phase. This model verifies three phases of zoster pain and delineates the impact of treatment and other factors on the phase-specific rates of pain cessation.

Adolescent↗

PubMed2006

3,3'-Diphosphoryl-1,1'-bi-2-naphthol-Zn(II) complexes as conjugate acid-base catalysts for enantioselective dialkylzinc addition to aldehydes.

A highly enantioselective dialkylzinc (R(2)(2)Zn) addition to a series of aromatic, aliphatic, and heteroaromatic aldehydes (5) was developed based on conjugate Lewis acid-Lewis base catalysis. Bifunctional BINOL ligands bearing phosphine oxides [P(=O)R(2)] (7), phosphonates [P(=O)(OR)(2)] (8 and 9), or phosphoramides [P(=O)(NR(2))(2)] (10) at the 3,3'-positions were prepared by using a phospho-Fries rearrangement as a key step. The coordination of a NaphO-Zn(II)-R(2) center as a Lewis acid to a carbonyl group in a substrate and the activation of R(2)(2)Zn(II) with a phosphoryl group (P=O) as a Lewis base in the 3,3'-diphosphoryl-BINOL-Zn(II) catalyst could promote carbon-carbon bond formation with high enantioselectivities (up to >99% ee). Mechanistic studies were performed by X-ray analyses of a free ligand (7) and a tetranuclear Zn(II) cluster (21), a 31P NMR experiment on Zn(II) complexes, an absence of nonlinear effect between the ligand (7) and Et-adduct of benzaldehyde, and stoichiometric reactions with some chiral or achiral Zn(II) complexes to propose a transition-state assembly including monomeric active intermediates.

Journal Article↗

PubMed2005

Vibration characteristics of the human spine under axial cyclic loads: effect of frequency and damping.

STUDY DESIGN: A nonlinear finite element model of lumbar spine segment L3-L5 was developed. The effects of upper body mass, nucleus injury, damping, and different vibration frequency loads were analyzed for the whole body vibration. OBJECTIVES: To analyze the influence of whole body vibration on facets of lumbar spine and to analyze the influence of nucleus injury, upper body mass, and damping on the dynamic characteristics of lumbar spine. SUMMARY OF BACKGROUND DATA: Many studies have investigated whole body vibration for lumbar spine. However, very few investigations analyzed the influence of whole body vibration on facets and vibration characteristics of the injured spine. METHODS: The nonlinear finite element model of the L3-L5 segment was constructed based on the embalmed vertebra geometry and validated. Besides static and modal analyses, transient dynamic analyses were also conducted on the model with an upper body mass under damping and different frequency cyclic loads. RESULTS: In the period of human spine vibration, the vibration effects of different regions of the lumbar spine are not the same. Anterior regions of the L3-L5 segment show small vibration amplitudes, but posterior regions show large amplitudes. The vibration amplitude of facet contact force is more than 2.0-fold as large as that of displacement and stress on vertebrae or discs. To decrease the weight of the upper body will increase the resonant frequency. To remove the nucleus will decrease the resonant frequencies. The vibration displacement, stress, and facet contact force will reduce generally by 50% using damping ratio 0.08. CONCLUSIONS: The posterior regions of intervertebral discs of the lumbar spine are easy to injure during long-term whole body vibration compared to anterior regions. The vibration of human spine is more dangerous to facets, especially during whole body vibration approximating a sympathetic vibration, which may lead to abnormal remodeling and disorder of the lumbar spine.

Cadaver↗

PubMed2000

A quantitative genetic model for analyzing species differences in outcrossing species.

A genetic model based on a two-level intra- and interspecific mating design is proposed to estimate the genetic architecture of species differences and heterosis for outcrossing species. The underlying genetic analyses make use of classical quantitative genetic theories and recent results from molecular genetic studies. Gene effects across different quantitative trait loci (QTL) can be approximated by a geometric series. Under natural selection, gene effects are often associated with allele frequencies in a particular way, which can be approximated by the gamma distribution. By incorporating these approximations into family structural analyses in the mating design, we are able to estimate a number of genetic parameters that contribute to quantitative genetic variation based on a nonlinear optimization approach. These parameters include the number of QTL, their gene effects, and their allele frequencies in the parental populations. We perform simulation studies and illustrate an example to demonstrate the statistical property and procedure of the method.

Alleles↗

PubMed1993

Population pharmacokinetics of theophylline. I: Intravenous infusion to children in the acute episode of asthma.

The population pharmacokinetics of theophylline during constant-rate intravenous infusion has been studied in 66 children (8.7 +/- 4.7 year of age; 26.0 +/- 12.8 kg, mean +/- S.D.) with an episode of acute asthma. One hundred and twelve theophylline serum concentrations (13.9 +/- 4.8 micrograms/ml) collected retrospectively were analyzed using a nonlinear mixed-effect model. The influence of hepatic dysfunction, age, gender, days after admission, blood gas measurements (PaO2, PaCO2, blood pH) and clinical analyses data (total serum protein, albumin concentration, haemoglobin concentration, haematocrit) on theophylline clearance was examined by the likelihood ratio test. A final estimate of population mean clearance was 58.6 ml/kg/h, which was decreased by 36% in patients with hepatic dysfunction. Other factors tested displayed no statistically significant effect on theophylline clearance. The inter-individual variability in clearance was 26% while the intra-individual variability in theophylline concentrations was 2.6 micrograms/ml as a standard deviation, which was almost double that observed for stable patients. Taking into account that the therapeutic window of this drug is 10-20 micrograms/ml, this value indicates a relatively large intra-individual variability and suggests that frequent (daily) monitoring of serum concentrations is necessary for patients with an episode of acute asthma.

Acute Disease↗

PubMed1979

Further evidence for four mechanisms mediating vision at threshold: sensitivities to complex gratings and aperiodic stimuli.

It is now generally accepted that several mechanisms mediate contrast detection at threshold. Many attempts to measure the bandwidths of these mechanisms using subthreshold summation have yielded estimates suggesting very narrow frequency tuning. We have measured thresholds for three classes of stimuli: gratings containing two sinusoidal components, sums of "difference of Gaussian" (DOG) patterns, and square waves. The results of the subthreshold summation experiments with gratings are consistent with those of other studies. All of these thresholds can be predicted by a model requiring only four center-surround-type mechanisms at each retinal locus. These mechanisms have a full bandwidth at a half-height of about 1.75 octaves. Quantitative prediction of sensitivities depends critically upon spatial probability summation. It is this spatial nonlinearity that yields these somewhat conterintuitive results. The much narrower bandwidths inferred by others are due to the assumption of linearity used in their analyses.

Computers↗