SEARCH · PubMed Health

Results for “nonlinear analyses”

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 307 records · Page 17Linked to original sources

PubMed1996

The effects of epoprostenol on drug disposition. II: A pilot study of the pharmacokinetics of furosemide with and without epoprostenol in patients with congestive heart failure.

The effect of epoprostenol on the pharmacokinetics of furosemide was investigated in 23 patients with end-stage congestive heart failure (CHF) receiving conventional therapy alone or conventional therapy plus epoprostenol. Estimates of the apparent oral clearance, volume of distribution, and absorption rate constant for furosemide were generated from 198 serum furosemide concentrations using nonlinear mixed effects modeling (NONMEM). Univariate analyses were performed to assess the effects of patient factors on the apparent oral clearance of furosemide. The final multivariate model determined by backwards elimination included concomitant digoxin therapy. When concomitant epoprostenol therapy was included in the final model, there was a 13% decrease in the apparent oral clearance of furosemide in response to short-term administration of epoprostenol. However, the effect of concomitant epoprostenol therapy was not statistically significant and was no longer apparent by the end of the 12-week study. These data suggest that epoprostenol may have a slight short-term effect on the pharmacokinetics of furosemide; the interaction between epoprostenol and furosemide is not clinically significant, however.

Diuretics↗

PubMedDate not supplied

Variational approaches toward nonlinear time-series analysis.

Linear autoregressive models (AR) have broad applications toward spectral analyses and digital filtering of signals, as well as identification, prediction, and control of dynamical systems. However, the symmetric Gaussian properties of linear AR presume independence between the first and second order moments of system outputs. Using nonlinear AR to quantify interactions between the mean and autocovariance of a signal, analysts can discriminate asymmetric frequency components, estimate the relative contribution of system nonlinearities toward mean output, evaluate relative structural stability of a system, and predict critical regions where bifurcations in its dynamics might occur. Quadratic analyses are performed on simulated outputs from a nonlinear model and various experimental time series (Canadian lynx population, respiratory volume dynamics in rat, Cheyne-Stokes respiration in patients with congestive heart failure, intracranial pressures in patient with cerebral hematoma). These case studies demonstrate the utility of the techniques for evaluating the qualitative behaviors of dynamical systems in the presence of slowly varying inputs.

Adult↗

PubMed1997

Genetic analysis of discrete reproductive traits in sheep using linear and nonlinear models: II. Goodness of fit and predictive ability.

The performance of linear and nonlinear sire and animal models in the analyses of reproductive traits (fertility, litter size, and ovulation rate) in two sheep populations (Rambouillet and Finnsheep) was compared in terms of goodness of fit and predictive ability. Linear sire (LSM) and animal (LAM) models were used with all traits. Nonlinear models were the threshold, Poisson, and negative binomial. Threshold sire (TSM) and animal (TAM) models were also used with all traits. Litter size and ovulation rate were analyzed also with Poisson and negative binomial sire (PSM and NBSM, respectively) and animal (PAM and NBAM, respectively) models. Variance components were those reported in the companion article. For PAM a new set of variance components derived from estimates found with the linear animal model also was used (PAM-L). Mean squares error (MSE) and correlations between fitted and observed values were used to assess goodness of fit. Predictive ability was assessed by partitioning the data sets for the different traits into two subsets with the restriction that all levels of fixed effects were represented in each subset. Parameters from one subset were employed to predict observations in the other, and then MSE and correlations between observed and predicted values were used as criteria for model comparison. Within estimation procedure, breed, and trait, goodness of fit of sire and animal models was similar. Linear and threshold models resulted in similar fit, and both outperformed Poisson and negative binomial models. In terms of predictive ability, linear and threshold models performed only slightly better than Poisson and negative binomial models. Goodness of fit and predictive ability generally were better when models included permanent environmental effects.

Animals↗

PubMed1982

A quantitative analysis of glucagon binding to isolated intact neonatal and adult rat hepatocytes on the basis of two different binding models.

The interaction of glucagon with specific receptors has been studied in isolated intact neonatal and adult rat hepatocytes. The hormone binding measured directly with 125I-labelled glucagon was saturable and reversible. The 125I-labelled glucagon binding was inhibited by unlabelled homologous hormone at concentrations ranging from 0.5 nM to 50 microM. Two different binding models were assumed to analyse the binding data by a nonlinear least-squares procedure: (I) a single class of independent sites and (II) two classes of independent sites. The comparison of the fitted theoretical curves reveals that both binding models are in fact compatible with these data. Adult hepatocytes have a considerably higher affinity for glucagon than neonatal hepatocytes; the binding capacity of neonatal liver cells from 1-7-days-old rats proved to be markedly reduced compared with the cells from adult rats. The glucagon-induced intracellular cyclic AMP production was measured at various hormone concentrations under conditions identical to those for the determination of extracellular hormone binding. The correlation of both parameters indicates a direct connection between receptor-occupancy and adenylate cyclase stimulation of both parameters indicates a direct connection between receptor-occupancy and adenylate cyclase stimulation. These results suggest that a decreased receptor concentration in neonatal hepatocytes is responsible for the decreased cyclic AMP production.

Age Factors↗

PubMed1984

Cooperative association of plasminogen with fibrinogen.

We have examined the association of both Glu- and Lys-plasminogen to fibrinogen by ultracentrifugal sedimentation equilibrium in neutral isotonic buffer in the presence of aprotinin. The fibrinogen and plasminogens, which were homogenous, did not exhibit any self-association. In each association study, five different molar ratios of plasminogen to fibrinogen were examined. The data were analyzed by mathematical modeling using nonlinear least-squares curve fitting. Analyses of molecular species present showed that up to 4 mol of either Glu- or Lys-plasminogen was associated with each mol of fibrinogen. For the binding of Glu-plasminogen, the values of the successive changes of the standard free energy of association were found to be -5.48, -7.73, -8.88, and -11.41 kcal/mol (Ka = 2.16 X 10(4), 1.32 X 10(6), 1.06 X 10(7), and 1.08 X 10(9) M-1). For the experimental conditions used here, the association of Lys-plasminogen appears to be described by virtually the same fitting parameters. The very marked cooperativity of association found here would appear to imply that there are significant alterations of the structure of fibrinogen as a result of each successive molecule of plasminogen bound.

Binding Sites↗

PubMed1999

Testing the generalized slowing hypothesis in specific language impairment.

This study investigated the proposition that children with specific language impairment (SLI) show a generalized slowing of response time (RT) across tasks compared to chronological-age (CA) peers. Three different theoretical models consistent with the hypothesis of generalized slowing--a proportional, linear, and nonlinear model--were examined using regression analyses of group RT data. Each model was an excellent fit with the RT data. The most parsimonious model indicated that the SLI group was proportionally slower than the CA group. Mean RTs of the SLI group were about one fifth slower across tasks than the CA group's mean RTs. Less slowing was evident for a subgroup of young children with expressive SLI than for children with mixed (expressive and receptive) SLI. Although the mean RT data reflected many individual SLI children's RT performance, not all SLI children showed generalized slowing.

Age Factors↗

PubMed2003

Population pharmacokinetics of netilmicin in short-term prophylactic treatment.

AIMS: To characterize the population pharmacokinetics of netilmicin, an aminoglycoside antibiotic, in adult urology patients and to develop a covariate model for improved dose titration. METHODS: Data from 62 adult patients (55 male, seven female), undergoing urological surgery and treated with netilmicin for short-term prophylaxis, were evaluated retrospectively. The group had (median, range) ages 68, 31-92 years, weights 72, 43-106 kg and heights 167, 148-182 cm. No patient showed renal impairment before netilmicin treatment (serum creatinine </=1.9 mg dl-1). Netilmicin (100 mg) was administered as a maximum of four successive intravenous infusions of 30 min, at 8-h intervals. A total of five blood samples were collected from each patient. Prior to analysis, the dataset was divided into 'index' (n = 44) and 'validation' (n = 18) groups at random. The time courses of netilmicin concentrations from all subjects were analysed using a mixed effects, population, nonlinear modelling package (WinNonMix). For covariate model development, a stepwise procedure was used with backward elimination followed by forward inclusion based on age, sex, weight, height, creatinine clearance and type of surgery. The final covariate model parameters from the index group were used to simulate concentrations in the validation group and the bias and precision were compared with the observations. RESULTS: A bi-compartmental open model with a proportional residual error best described the data. The population parameters for central and peripheral volumes of distribution were (typical population value [interindividual CV%]) Vc = 14.5 l [56%] and Vp = 10.2 l [not estimated], and the systemic and intercompartmental clearances were CL = 3.9 l h-1[42%] and CLQ = 10.1 l h-1[not estimated], respectively. The final population covariate relationships were based on sex (SEX) and creatinine clearance (CrCL): (Vc, l) = 18.9 - 5.9 x SEX [29%] and (CL, l h-1) = 0.06 x CrCL [33%]. Compared with the observations in the validation group, this model showed a bias (95% confidence interval) of -0.028 (-0.28, 0.25) and precision of 1.22 (0.78, 1.34). CONCLUSION: Bi-compartmental pharmacokinetic parameters of netilmicin have been estimated from clinical data in urological surgery patients using a population approach. A given single dose results in large variability in plasma concentrations and thus the population covariate final model can be used for direct estimation of initial dosing in patients.

Adult↗

PubMedDate not supplied

Damage in trabecular bone at small strains.

Evidence that damage decreases bone quality, increases fracture susceptibility, and serves as a remodeling stimulus motivates further study of what loading magnitudes induce damage in trabecular bone. In particular, whether damage occurs at the smaller strains characteristic of habitual, as opposed to traumatic, loading is not known. The overall goal of this study was to characterize damage accumulation in trabecular bone at small strains (0.20 - 0.45% strain). A continuum damage mechanics approach was taken whereby damage was quantified by changes in modulus and residual strain. Human vertebral specimens (n = 7) were tested in compression using a multi-cycle load - unload protocol in which the maximum applied strain for each cycle, epsilonmax, was increased incrementally from epsilonmax = 0.20% on the first loading cycle to epsilonmax = 0.45% on the last cycle. Modulus and residual strain were measured for each cycle. Both changes in modulus and residual strains commenced at small strains, beginning as early as 0.24 and 0.20% strain, respectively. Strong correlations between changes in modulus and residual strains were observed (r = 0.51 - 0.98). Fully nonlinear, high-resolution finite element analyses indicated that even at small apparent strains, tissue-level strains were sufficiently high to cause local yielding. These results demonstrate that damage in trabecular bone occurs at apparent strains less than half the apparent compressive yield strain reported previously for human vertebral trabecular bone. Further, these findings imply that, as a consequence of the highly porous trabecular structure, tissue yielding can initiate at very low apparent strains and that this local failure has detectable and negative consequences on the apparent mechanical properties of trabecular bone.

Biomechanical Phenomena↗

PubMed2003

Self-similar optical wave collapse: observation of the Townes profile.

Analyses of many different types of nonlinear wave equations indicate that a collapsing wave will transform into a universal blowup profile regardless of its initial shape; that is, the amplitude of the wave increases as the spatial extent decreases in a self-similar fashion. We show experimentally that the spatial profile of a collapsing optical wave evolves to a specific circularly symmetric shape, known as the Townes profile, for elliptically shaped or randomly distorted input beams. These results represent the first experimental confirmation of this universal collapsing behavior and provide deeper insight into the high-power filamentation of femtosecond laser pulses in air.

Journal Article↗

PubMed2006

Hyperglycaemia acutely decreases circulating dehydroepiandrosterone levels in healthy men.

OBJECTIVE: This study was conducted in order to evaluate the effect of glucose-insulin homeostasis on adrenal steroids and was designed to separate the effects of hyperglycaemia from those of insulin. DESIGN: Eight healthy men aged 22.6 +/- 3.4 (SD) underwent an 80 mU/m2/min hyperinsulinaemic euglycaemic 100-min clamp, a 200-min graded glucose infusion at 2-16 mg/kg/min and a measurement of fat mass. MEASUREMENTS: Circulating glucose, insulin and adrenal steroid levels including dehydroepiandrosterone (DHEA) were determined before and during both infusion tests. Steroid variations in relation to insulinaemia and glycaemia were analysed using univariate, multivariate tests and nonlinear mixed models. RESULTS: Hyperinsulinaemia induced no significant modification of adrenal steroid levels. By contrast, hyperglycaemia decreased all adrenal steroids except DHEA-sulphate by 47-66%. The drop occurred early, averaging 51% for 17OH pregnenolone and 57% for DHEA at the 80th minute of glucose infusion, whereas blood glucose was 7.1 +/- 1.2 mmol/1. This effect was independent of insulinaemia, fat mass and waist circumference. Thus, we estimated models that could best predict steroid variations according to blood glucose. At thresholds defining impaired fasting glycaemia and diabetes, the estimated decrease in DHEA was 40% and 45%, respectively, culminating at 60% at 9.3 mmol/1 glycaemia, with no detectable further decrease. CONCLUSIONS: Our data suggest that hyperglycaemia dramatically decreases adrenal androgen levels in men, possibly by acting at early steps of synthesis, independently of insulinaemia and fat mass.

17-alpha-Hydroxypregnenolone↗

PubMed2000

Contributions of suppression and excitation to simultaneous masking: effects of signal frequency and masker-signal frequency relation.

This study investigated the contributions of suppression and excitation to simultaneous masking for a range of masker frequencies both below and above three different signal frequencies (750, 2000, and 4850 Hz). A two-stage experiment was employed. In stage I, the level of each off-frequency simultaneous masker necessary to mask a signal at 10 or 30 dB sensation level was determined. In stage II, three different forward-masking conditions were tested: (1) an on-frequency condition, in which the signals in stage I were used to mask probes of the same frequency; (2) an off-frequency condition, in which the off-frequency maskers (at the levels determined in stage I) were used to mask the probes; and (3) a combined condition, in which the on- and off-frequency maskers were combined to mask the probes. If the off-frequency maskers simultaneously masked the signal via spread of excitation in stage I, then the off-frequency and combined maskers should produce considerable forward masking in stage II. If, on the other hand, they masked via suppression, they should produce little or no forward masking. The contribution of suppression was found to increase with increasing signal frequency; it was absent at 750 Hz, but dominant at 4850 Hz. These results have implications for excitation pattern analyses and are consistent with stronger nonlinear processing at high rather than at low frequencies.

Acoustic Stimulation↗

PubMed1996

Acute baroreflex resetting: differential control of pressure and nerve activity.

This study evaluated acute resetting of carotid baroreflex control of arterial blood pressure and renal or thoracic sympathetic nerve activity in thiopental-anesthetized mongrel dogs with the use of a vascularly isolated carotid sinus preparation, the experimental model used previously to characterize acute resetting in carotid baroreceptor afferent fibers. Carotid baroreceptors were conditioned with a pulsatile pressure for 20 minutes at three pressure ranges: low (50 to 75 mm Hg), mid (100 to 125), or high (150 to 175). Blood pressure and nerve activity were recorded in response to slow ramp increases in sinus pressure; nonlinear regression and best-fit analyses were used for determination of curve fit parameters of the blood pressure and nerve activity versus sinus pressure response curves. Carotid sinus pressure thresholds for blood pressure and renal nerve activity responses at all conditioning pressures were significantly different; however, only the pressure threshold for thoracic nerve activity at the low conditioning pressure was significantly different from the responses at other conditioning pressures. Average renal activity resetting (0.506 +/- 0.072) was significantly greater than blood pressure resetting (0.335 +/- 0.046) in the same dogs, and thoracic activity (0.200 +/- 0.057) was not different from blood pressure resetting (0.194 +/- 0.031) in the same dogs. In a previous investigation, our laboratory had demonstrated that type 1 carotid baroreceptors acutely reset at a value of about 0.15. These results indicate that (1) renal and thoracic nerve activities and blood pressure acutely reset to a greater degree than type 1 carotid baroreceptors and that (2) renal activity acutely resets to a greater degree than blood pressure and thoracic nerve activity.

Animals↗

PubMed2001

Forced spirometry reference values for Norwegian adults: the Bronchial Obstruction in Nord-Trøndelag Study.

The purpose of this study was to develop new prediction equations for flow/volume spirometry parameters in asymptomatic, never-smoking adults in Norway, and to assess any differences of these parameters when applying the new and most commonly used equation sets. Flow/volume spirometry was measured according to the American Thoracic Society criteria in 2,792 subjects aged > or = 20 yrs, randomly selected from participants in the Nord-Trøndelag Health Study. Ever-smokers and subjects with respiratory symptoms and/or diseases reported in this questionnaire were excluded. A total of 546 females and 362 males met the inclusion criteria and were included in the analyses. Most lung function variables were nonlinear by age and had to be transformed. After a plateau in younger adults, the variables declined by age. The reference values for forced expiratory volume in one second and forced vital capacity from the present study, were higher than those given by prediction equations from the European Community for Coal and Steel, but in closer agreement with later studies from Europe, Australia and the USA. Healthcare providers should be encouraged to reconsider their choice of prediction equations of spirometry in order to improve management of obstructive lung diseases.

Adult↗

PubMed2026

Human-Centered Workspace Optimization: A 2 × 2 Factorial Study of Adjustable Furniture and Indoor Environmental Quality.

Small workspaces function as integrated systems, yet ergonomic furniture and indoor environmental conditions are usually evaluated separately. A six-site, assessor-blinded, randomized 2 × 2 factorial controlled study was conducted of two multicomponent packages-adjustable furniture and optimized indoor environmental quality (IEQ)-among 240 office workers for four weeks. Each group included 60 participants. Overall comfort in week 4 was highest for both packages (5.62 ± 0.53 versus 3.99 ± 0.60 with fixed furniture and basic IEQ). In a site-adjusted factorial model with HC3 robust standard errors, the adjustable-furniture effect was 0.86 points (95% confidence interval [CI], 0.62-1.09), the optimized-IEQ effect was 0.34 points (95% CI, 0.12-0.55), and their interaction was 0.44 points (95% CI, 0.14-0.74). Adjustable furniture improved postural comfort and reduced neck and lower back discomfort; optimized IEQ improved environmental comfort; both packages improved perceived productivity, satisfaction, and fatigue. The task-accuracy interaction did not remain significant after false-discovery-rate adjustment, and exploratory mediation and spline analyses did not support indirect or nonlinear effects. These results support coordinated ergonomic and environmental implementation while preserving distinct outcome pathways.

Interior Design and Furnishings↗

PubMed1999

Catastrophic forgetting in simple networks: an analysis of the pseudorehearsal solution.

Catastrophic forgetting is a major problem for sequential learning in neural networks. One very general solution to this problem, known as 'pseudorehearsal', works well in practice for nonlinear networks but has not been analysed before. This paper formalizes pseudorehearsal in linear networks. We show that the method can fail in low dimensions but is guaranteed to succeed in high dimensions under fairly general conditions. In this case an optimal version of the method is equivalent to a simple modification of the 'delta rule'.

Algorithms↗

PubMed1995

[A study of acquisition time using compartment analysis with 99mTc-GSA liver scintigraphy].

99mTc-galactosyl human serum albumin (99mTc-GSA) is a newly developed receptor-binding agent specific for the asialoglycoprotein receptor, which resides exclusively on the plasma membrane of mammalian hepatocytes. Liver scintigraphy using 99mTc-GSA was performed on 13 patients with liver disease. Dynamic data were obtained by gamma camera during 40 min after the intravenous injection of 3 mg (185 MBq) of 99mTc-GSA. Heart and liver time activity curves with acquisition times of 40,30 and 20 min were created, and two different compartment analyses were examined. One was a nonlinear five-compartment model adopting the Michaelis-Menten type for the transfer of 99mTc-GSA from hepatic blood to receptor, and the other was a linear five-compartment model assuming a linear rate constant (P(2)*) for the transfer of 99mTc-GSA. The maximum removal rate obtained by the nonlinear model, P(2), was found to be independent of the change in acquisition time, while the maximum removal rate obtained by the linear model, P(2)*.Km, which was given by the product of P(2)* and the Michaelis constant Km, increased with shortening acquisition times from 40 to 20 min. For both models, the liver blood flow rate decreased with shortening acquisition time. The maximum removal rate and liver blood flow rate obtained by the linear model were significantly correlated with those obtained by the nonlinear model. It was concluded that linear model with an acquisition time of 20 min was applicable to liver scintigraphy with 99mTc-GSA.

Adolescent↗

PubMed2005

The linear and nonlinear stability of thread-annular flow.

The surgical technique of thread injection of medical implants is modelled by the axial pressure-gradient-driven flow between concentric cylinders with a moving core. The linear stability of the flow to both axisymmetric and asymmetric perturbations is analysed asymptotically at large Reynolds number, and computationally at finite Reynolds number. The existence of multiple regions of instability is predicted and their dependence upon radius ratio and thread velocity is determined. A discrepancy in critical Reynolds numbers and cut-off velocity is found to exist between experimental results and the predictions of the linear theory. In order to account for this discrepancy, the high Reynolds number, nonlinear stability properties of the flow are analysed and a nonlinear, equilibrium critical layer structure is found, which leads to an enhanced correction to the basic flow. The predictions of the nonlinear theory are found to be in good agreement with the experimental data.

Humans↗

PubMed2003

Fibril reinforced poroelastic model predicts specifically mechanical behavior of normal, proteoglycan depleted and collagen degraded articular cartilage.

Degradation of collagen network and proteoglycan (PG) macromolecules are signs of articular cartilage degeneration. These changes impair cartilage mechanical function. Effects of collagen degradation and PG depletion on the time-dependent mechanical behavior of cartilage are different. In this study, numerical analyses, which take the compression-tension nonlinearity of the tissue into account, were carried out using a fibril reinforced poroelastic finite element model. The study aimed at improving our understanding of the stress-relaxation behavior of normal and degenerated cartilage in unconfined compression. PG and collagen degradations were simulated by decreasing the Young's modulus of the drained porous (nonfibrillar) matrix and the fibril network, respectively. Numerical analyses were compared to results from experimental tests with chondroitinase ABC (PG depletion) or collagenase (collagen degradation) digested samples. Fibril reinforced poroelastic model predicted the experimental behavior of cartilage after chondroitinase ABC digestion by a major decrease of the drained porous matrix modulus (-64+/-28%) and a minor decrease of the fibril network modulus (-11+/-9%). After collagenase digestion, in contrast, the numerical analyses predicted the experimental behavior of cartilage by a major decrease of the fibril network modulus (-69+/-5%) and a decrease of the drained porous matrix modulus (-44+/-18%). The reduction of the drained porous matrix modulus after collagenase digestion was consistent with the microscopically observed secondary PG loss from the tissue. The present results indicate that the fibril reinforced poroelastic model is able to predict specifically characteristic alterations in the stress-relaxation behavior of cartilage after enzymatic modifications of the tissue. We conclude that the compression-tension nonlinearity of the tissue is needed to capture realistically the mechanical behavior of normal and degenerated articular cartilage.

Animals↗