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 271 records · Page 15Linked to original sources

PubMed2005

Pharmacokinetic/pharmacodynamic relationships of asparaginase formulations: the past, the present and recommendations for the future.

The discovery of the tumour-inhibitory properties of asparaginase began 50 years ago with the observation that guinea-pig serum-treated lymphoma-bearing mice underwent rapid and often complete regression. Soon afterwards, the asparaginase of bacterial origin was isolated. The asparaginases of bacterial origin induce anti-asparaginase neutralising antibodies in a large proportion of patients (44-60%), thus negating the specific enzymatic activity and resulting in failure of the target amino acid deamination in serum. There is immunological cross-reaction between the antibodies against various formulations of native Escherichia coli-asparaginase and polyethylene glycol (PEG)-asparaginases, but not to Erwinia asparaginase, as suggested by laboratory preclinical findings. This evidence was strongly inferred from the interim analyses in the Children's Cancer Group (CCG)-1961 study. Thus, anti-E. coli or PEG-asparaginase antibodies seropositive patients may benefit from the Erwinia asparaginase. The inter-relationships between asparaginase activity, asparagine (ASN) and glutamine deamination remain largely unexplored in patients. Studies have shown that ASN depletion is insufficient to induce apoptosis in T lymphoblasts in vitro and that the inhibitory concentration of CEM T-cell line is correlated with the asparaginase concentration responsible for 50% glutamine deamination. The optimal catalysis of ASN and glutamine deamination in serum by asparaginase induces apoptosis of leukaemic lymphoblasts. The percentage of ASN and glutamine deamination was predicted by asparaginase activity. Asparaginase activity of 0.1 IU/mL provided insufficient depletion of both amino acids in high-risk acute lymphoblastic leukaemia (ALL) patients. With increasing glutamine deamination, mean asparaginase activities and percentages of post-treatment samples with effective ASN depletion (<3 micromol/L) increase. Both glutamine and ASN deamination are predicted by asparaginase activity. Further population analyses resulted in identification of sigmoid relationships between asparaginase levels and post-treatment glutamine and ASN deamination.Furthermore, pharmacodynamic analyses strongly suggested that >/=90% deamination of glutamine must occur before optimal ASN deamination takes place, due to the de novo ASN biosynthesis by the liver. These pharmacodynamic results from the best-fit population pharmacokinetic/pharmacodynamic model obtained from nonlinear mixed effects model pharmacodynamic analyses for standard-risk ALL patients are similar. These analyses produced the following results: (i) asparaginase activity </=0.4 IU/mL provided insufficient deamination of ASN, whereas >0.4-0.7 IU/mL was required for optimal (90%) ASN and glutamine deamination; and (ii) deamination of glutamine is dependent on asparaginase activity and it correlates with enhanced serum ASN deamination. Thus, glutamine deamination enhances asparaginase efficacy in ALL patients. Deamination of ASN >/=90% of control or ASN concentration <3 micromol/L may be associated with improved survival in this subset of patients. Our findings support the pharmacodynamic mechanism of PEG-asparaginase for disease control in ALL patients. These results taken together strongly support new experimental approaches for application of population pharmacokinetic/pharmacodynamic analyses to further enhance survival of leukaemia patients.

Animals↗

PubMed2005

Phonatory impairment in Parkinson's disease: evidence from nonlinear dynamic analysis and perturbation analysis.

Many persons with Parkinson's disease (PD) will eventually experience vocal impairment as their condition advances. Using standard perturbation analyses (parameters like jitter and shimmer) to measure fluctuations in phonatory signal may inhibit researchers from recognizing severely disordered patterns that seem to be present in the voices of some PD patients. Nonlinear dynamic analysis can quantify these aperiodic patterns, which indicate severe pathology that is usually characterized perceptually by hoarseness. Here, sustained vowel phonations of a heterogeneous group of PD subjects (20 women and 21 men) were compared with those of a control group (22 women and 18 men) based on results of nonlinear dynamic analyses (D(2)) and perturbation analyses. Results showed PD subjects as a whole to have significantly higher D(2) values than control subjects (P = 0.016), which indicates increased signal complexity in PD vocal pathology. Differences in the comparison of these two groups were significant in jitter (P = 0.014) but nonsignificant in shimmer (P = 0.695). Furthermore, the performance on these three measures was affected by subject sex. Nonlinear dynamic analysis showed significantly higher D(2) in the female PD group than in the female control group (P = 0.001), but jitter and shimmer did not show such a difference. The male PD group had statistically higher jitter than the male control group (P = 0.036), but these groups did not differ in D(2) or shimmer. Overall, nonlinear dynamic analysis may be a valuable method for the diagnosis of Parkinsonian laryngeal pathology.

Female↗

PubMedDate not supplied

'Derived nonlinear' versus 'linear' click-evoked otoacoustic emissions.

Recordings of emission evoked in response to transient stimuli (TEOAE) are partially contaminated by the initial stimulus artifact. For this reason, a nonlinear estimation method is widely used (derived nonlinear response, DNLR). The aims of this paper are: (1) to analyse some very basic properties of the derived nonlinear emissions such as the short-time input/output relationships; and (2) to show similarities and differences between the classical averaging (linear) and the derived nonlinear recording techniques, in the same ears, both in time and in the frequency domain. At latencies greater than about 6 ms, responses which are recorded using the derived nonlinear technique exhibit no additional features in comparison with linear recordings, at all stimulus levels. At latencies less than 6 ms, the derived nonlinear technique greatly reduces the linear content of the acoustic artifact, and the response may be considered as the initial part of the emission. However, the derived nonlinear responses tend to be considerably noisier than the linear emissions, thus reducing the effectiveness of the technique. The linear responses show a strikingly similar frequency content with respect to the derived nonlinear responses, at least at a high stimulus level and around the main peaks of the spectrum.

Acoustic Stimulation↗

PubMedDate not supplied

Nonlinear growth curve analysis: estimating the population parameters.

A model for analysing longitudinal growth data with covariates is proposed. It assumes that the data for each individual follow a nonlinear growth model, with parameters unique to that individual. The parameters of individuals are assumed to vary in the population, with the population mean of each parameter dependent upon covariates. Several simple, two-stage methods of estimation are described and compared for making inferences about the effects of covariates upon growth. We also present a method of model validation for nonlinear models. These two-stage methods solve the inference problem we encounter when performing multiple cross-sectional analyses of the effects of covariates along the age scale. In addition, these two-stage methods permit us to study the effects of covariates upon growth rate, or other, possibly nonlinear, growth parameters. We find that some methods are better than others at reproducing the covariate effects observed in a series of age-specific analyses of the data.

Age Factors↗

PubMed2006

A simple method for the estimation of peritoneal fluid transport.

BACKGROUND: Evaluating peritoneal fluid kinetics is of great value to the adjustment of peritoneal dialysis prescription. Therefore, in the present study, we developed a simple method, based on a membrane transport model, to evaluate the fluid transport characteristics of the peritoneal membrane in continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: Patients' peritoneal ultrafiltration (UF) volume was collected for 2 consecutive months. Membrane transport model and nonlinear least-squares regression analyses were applied to the pooled UF volume for the first month for fluid kinetic simulation and the data from the second month were used to evaluate the reliability and precision of simulated UF values. RESULTS: Seventeen chronic peritoneal dialysis (PD) patients were selected for the present study. Simulated UF values based on the pooled UF volume in the first month correlated significantly with the actual measured UF values in the second month. By Bland-Atman plot, the width between the 95% limits of agreement fell within -133.3 to 154.2 ml with a mean difference of 10.5 ml. CONCLUSION: Our study showed that applying the fluid transport model and nonlinear least-squares regression analysis to the pooled actual UF value might be a good and simple way to predict peritoneal UF.

Aged↗

PubMed1997

Meta-analyses of age-cognition relations in adulthood: estimates of linear and nonlinear age effects and structural models.

A meta-analysis was conducted on 91 studies to derive a correlation matrix for adult age, speed of processing, primary-working memory, episodic memory, reasoning, and spatial ability. Structural equation modeling with a single latent common cognitive factor showed that all cognitive measures shared substantial portions of age-related variance. A mediational model revealed that speed of processing and primary-working memory appear to be important mediators of age-related differences in the other measures. However, not all of the age-related influences were mediated. An examination of quadratic age effects and correlational patterns for subsamples under and over 50 years of age revealed that (a) negative age-cognition relations were significant for the 18- to 50-year-old sample and (b) the age-related decline accelerated significantly over the adult life span for variables assessing speed, reasoning, and episodic memory.

Adult↗

PubMed2007

Time preferences for health in northern Tanzania: an empirical analysis of alternative discounting models.

AIM: The discounted utility (DU) model has dominated economic evaluation for almost 7 decades, despite the fact that important assumptions of the model are commonly found to be violated. This paper formally explores whether the key assumption of stationarity is violated in a sample of the general population of Northern Tanzania. Furthermore, three hyperbolic discounting models are fitted to the data, and whether they perform better than the DU model in predicting individuals' time preferences is tested using nonlinear least squares regression. METHOD: The data were collected from 450 households by trained enumerators. The individual data on time preferences were collected by structured interviews using an open-ended stated preference methodology. Respondents marked a rating scale to indicate the maximum number of days they would be willing to suffer a nonfatal disease if the outbreak of the disease could be delayed to a point further into the future. Households were randomised to answer questions framed to elicit either a private or social time preference. RESULTS: Hypothesis testing confirmed decreasing time aversion and a magnitude effect, suggesting that the DU model is inappropriate as a descriptive tool. When the DU model was compared with the three hyperbolic discounting models by analysing the discount factor using nonlinear least squares regression, the most important findings were that a variable for starting point was nonsignificant only for the Loewenstein and Prelec (L&P) and the Mazur models, and that people in this setting generally discounted future health far more than suggested by current discounting practice in economic evaluations. CONCLUSION: The time preferences of our sample are better represented by the L&P and the Mazur models (which allow relaxation of the stationarity assumption through a modification of the expression for the discount factor) and less well reflected by the Harvey (a modification of the L&P model that assigns more importance to the future than standard utility discounting) and DU models. This implies that, from the point of view of a consumer sovereignty-friendly economist, the Mazur and the L&P models are preferable for discounting of future health in economic evaluations. However, from the point of view of other value bases for discounting the choice of discounting model is of less importance.

Aged↗

PubMed2002

Effects of a limited class of nonlinearities on estimates of relative weights.

Perturbation analyses have been applied in recent years to determine the relative contribution of individual stimulus components in detection and discrimination tasks. Responses to stimulus samples are compared to stimulus parameters to determine the details of the decision rule. Often, a linear model is assumed and it is of interest to determine the relative contribution of different stimulus elements to the decision. Here, biases in estimated relative weights are considered for the case where the decision variable is given by D = (sigma(alphaiXn(i))k)m and the stimulus components, the Xi, are normally distributed, of equal variance, and mutually independent. The alphai are the "true" combination weights, and n, k, and m are positive reals. The method used to estimate relative weights is the correlation coefficient between the Xi and the observer's responses. Estimates of relative alphai do not depend on m but may depend on the mean values of the Xi and the values of n and k (a dependence on the variance, sigmai2, holds even for linear transformations).

Computer Simulation↗

PubMed1991

Nonlinear dynamic behavior of the human knee joint--Part II: Time-domain analyses: effects of structural damage in postmortem experiments.

A description is given of the results obtained for step excitation for two human knee joint specimens using a time-domain analysis technique. As was expected from the results of a previous study, the magnitude of the dynamic load applied has a marked influence upon the stiffness and damping values for the two observed vibration modes. Deliberate damaging of selected joint elements also yields a well observable change in the dynamic behavior of the joint although these changes are difficult to interpret. Here the use of a nonlinear dynamic numerical model of the knee joint seems indispensable. An important observation is, however, that the experimental method discussed here enables to quantify the behavior of the joint and therefore may provide a valuable tool for validation of such a model.

Anterior Cruciate Ligament↗

PubMed1991

Nonlinear dynamic behavior of the human knee joint--Part I: Postmortem frequency domain analyses.

Characteristics results of postmortem experiments on five knee-joint specimens are reported. The experiments were performed to investigate the applicability of a local linearization technique that would make it possible to describe the dynamic behavior of the joint in terms of transfer functions. The results indicate that the stiffness of the bracing wires, attached to muscle tendons to create a static equilibrium position, can be accounted for when determining the stiffness of the joint. Besides the static equilibrium configuration, the magnitude of the dynamic load and the type of dynamic load applied to the joint can be shown to have their influence. As the influence of the dynamic load is significant, it has to be concluded that in essence the knee joint has to be regarded as a nonlinear system, making application of a Local Linearization Technique questionable. However, when the magnitude of the dynamic load is included as an additional measurement parameter, an indication can be obtained about the behavior of the joint and the degree of nonlinearity.

Biomechanical Phenomena↗

PubMed1993

Stresses at the meniscofemoral joint: elastostatic investigations on the applicability of interface elements.

Stress distributions at the meniscofemoral joint were analysed and the applicability of nonlinear interface elements in a finite element model (FEM) were tested. Centred and 70% off-centre load cases with a complete, a partially removed or a totally removed medial meniscus were evaluated in two dimensions. Interface width was assumed to increase linearly from almost zero to 1 mm at the inner and outer border of the femoral condyles. Maximum interface forces were found at the centre of the condyles, decreasing to zero at the peripherical and intercondylar femoral border. Simulation data concerning a removed medial meniscus or medial 70% off-centre load with complete meniscus indicated higher medial contact forces in the first case. A decrease in the elastic modulus of the articular surface tissues caused two small force transfer peaks (femoral centre and intercondylar border), which were strongly influenced by the predefined gap width.

Adult↗

PubMed2006

Model and in vivo studies on human trunk load partitioning and stability in isometric forward flexions.

To resolve the trunk redundancy to determine muscle forces, spinal loads, and stability margin in isometric forward flexion tasks, combined in vivo-numerical model studies was undertaken. It was hypothesized that the passive resistance of both the ligamentous spine and the trunk musculature plays a crucial role in equilibrium and stability of the system. Fifteen healthy males performed free isometric trunk flexions of approximately 40 degrees and approximately 65 degrees +/- loads in hands while kinematics by skin markers and EMG activity of trunk muscles by surface electrodes were measured. A novel kinematics-based approach along with a nonlinear finite element model were iteratively used to calculate muscle forces and internal loads under prescribed measured postures and loads considered in vivo. Stability margin was investigated using nonlinear, linear buckling, and perturbation analyses under various postures, loads and alterations in ligamentous stiffness. Flexion postures significantly increased activity in extensor muscles when compared with standing postures while no significant change was detected in between flexed postures. Compression at the L5-S1 substantially increased from 570 and 771 N in upright posture, respectively, for +/-180 N, to 1912 and 3308 N at approximately 40 degrees flexion, and furthermore to 2332 and 3850 N at approximately 65 degrees flexion. Passive ligamentous/muscle components resisted up to 77% of the net moment. In flexion postures, the spinal stability substantially improved due both to greater passive stiffness and extensor muscle activities so that, under 180 N, no muscle stiffness was required to maintain stability. The co-activity of abdominal muscles and the muscle stiffness were of lesser concern to maintain stability in forward flexion tasks as compared with upright tasks. An injury to the passive system, on one hand, required a substantial compensatory increase in active muscle forces which further increased passive loads and, hence, the risk of injury and fatigue. On the other hand, it deteriorated the system stability which in turn could require greater additional muscle activation. This chain of events would place the entire trunk active-passive system at higher risks of injury, fatigue and instability.

Abdomen↗

PubMed1998

Comparison of fluconazole pharmacokinetics in serum, aqueous humor, vitreous humor, and cerebrospinal fluid following a single dose and at steady state.

The objective of this study was to characterize the pharmacokinetic parameters and penetration of fluconazole following a single dose in the serum, aqueous humor, vitreous humor and cerebrospinal fluid (CSF) of non pigmented rabbits using serial sampling techniques and to determine if the pharmacokinetic parameters in the eye and CSF are similar. Twenty healthy male rabbits received intravenous fluconazole 20 mg/kg as a single dose or 20 mg/kg every 12 hours for 4 doses. Serum, aqueous humor, vitreous humor and CSF samples were taken 15 minutes after the initial intravenous injection and hourly thereafter for six hours. Fluconazole concentrations were determined by microbiological assay. Pharmacokinetic analyses were performed using a nonlinear least-square regression program. Fluconazole's penetration in all anatomical compartments was > 70% than in the serum. Similar elimination half-lives and time to reach maximum concentrations were noted in all compartments. While mean concentrations in each anatomical compartment were similar in animals receiving a single dose or among those at serum steady state, the mean concentrations achieved in the serum, aqueous and vitreous humors and CSF were between 1.82 and 2.17 times higher at serum steady state than following a single dose. At serum concentrations that are comparable to those in humans, the penetration of fluconazole into the noninflamed aqueous and vitreous humors and CSF were > or = 70%. The CSF and ocular pharmacokinetic parameters closely resembled each other, so that either could be used as a surrogate for the other.

Animals↗

PubMed2006

Environmental forcing as a main determinant of bloom dynamics of the Chrysochromulina algae.

In this paper, we demonstrate that the seasonal dynamics in the abiotic factors, without including seasonal changes in the biological relationships, can appropriately account for the seasonal dynamics of Chrysochromulina spp. This is through the analysis of data on the population dynamics of Chrysochromulina spp. off southern Norway that is evaluated in relation to environmental factors and season by the analyses of 12 year monthly time-series. Chrysochromulina spp. abundance, nutrient concentrations, hydrographical properties, as well as current and wind data were analysed on a monthly scale by means of autoregressive moving average models, principal component analyses (PCA), and linear and nonlinear regression models. Seasonal development of the Chrysochromulina assemblage was well predicted from regression models forced with two PCA components representing seasonal variation in nutrient and chlorophyll a levels and ratios, inflow of North Seawater to the Skagerrak and northeasterly wind along the Norwegian coast. Assuming these to be general results, we might hypothesis that marine algal communities are governed by seasonally varying abiotic factors to a large extent.

Chlorophyll↗

PubMed2005

Low-density lipoprotein cholesterol and mortality in older people.

OBJECTIVES: To investigate the role of low-density lipoprotein cholesterol (LDL-C) as a predictor of mortality in elderly subjects. DESIGN: Population-based prospective cohort study. SETTING: Two communities in northern Italy. PARTICIPANTS: Three thousand one hundred twenty Caucasian subjects aged 65 and older recruited in for the Cardiovascular Study in the Elderly and followed up for 12 years. MEASUREMENTS: Anthropometric measures: fasting plasma total cholesterol, triglyceride, high-density lipoprotein cholesterol, LDL-C, glucose, creatinine, and body mass index. Clinical measures: medical assessment, diabetes mellitus, hypertension, stroke, coronary disease, heart failure, and smoking and drinking habits. Vital status measures: death certificates from the Registry Office and causes of death according to the International Classification of Diseases. After plotting mortality rates using quartiles of LDL-C, relative hazard rates (RHRs) were calculated using multivariate Cox regression analyses. When the trend was nonlinear, the RHRs were further calculated for the 25th, 50th, and 75th percentiles of the distribution to confirm curvilinearity. RESULTS: The distribution of risk of total mortality in women and of fatal heart failure in all subjects was curvilinear (non J-shaped), decreasing nonlinearly with LDL-C. For total mortality in men and cardiovascular mortality in both sexes, the relationship with LDL-C was J-shaped. The risk of fatal myocardial infarction was J-shaped in men, whereas it increased linearly with higher LDL-C in women. In both sexes, the association between stroke mortality and LDL-C was not significant. CONCLUSION: This study adds to the uncertainty of the role of elevated levels of LDL-C as a risk factor for mortality in old people.

Aged↗

PubMed1996

A poroelastic finite element formulation including transport and swelling in soft tissue structures.

A field theory is presented for the study of swelling in soft tissue structures that are modeled as poroelastic materials. As a first approximation, soft tissues are assumed to be linear isotropic materials undergoing infinitesimal strains. Material properties are identified that are necessary for the solution of initial boundary value problems where swelling and convection are significant. A finite element model is developed that includes the solid displacements, the relative fluid displacements, and a representative concentration as the primary unknowns. A numerical example is presented based on a triphasic model. The finite model simulates a typical experimental protocol for soft tissue testing and demonstrates the interaction and coupling associated with relative fluid motion and swelling in a deforming poroelastic materiaL The theory and finite element model provide a starting point for nonlinear porohyperelastic transport-swelling analyses of soft tissue structures that include finite strains in anisotropic materials.

Algorithms↗

PubMed2000

Ventilator-induced overdistension in children: dynamic versus low-flow inflation volume-pressure curves.

We applied to 20 paralyzed ventilated children (0.15 to 14.3 yr, six with acute respiratory distress syndrome [ARDS]) the low-flow inflation (LFI) technique providing quasi-static volume-pressure (V-P) curves and compared the assessment of overdistension (OD) on dynamic and LFI (reference) inspiratory V-P curves. Dynamic curves were obtained at the airway opening during regular constant flow ventilation (Servo 300). Then LFI curves were obtained. Two analyses were performed: First, the nonlinear coefficient c of a second order polynomial equation (SOPE) fitted to dynamic data obtained during constant flow was compared with the c of SOPE fitted to LFI curve (within tidal volume [VT]). Second, the dynamic C20/C (ratio of compliance of the last 20% of the curve (C20) to total compliance [C]) was compared with the determination of the upper inflection point (UIP) on the LFI curve. OD was defined as a negative value of c, a C20/C < 0.80, an UIP included within the VT range for that child during regular ventilation. Using LFI V-P curves as reference, SOPE offered a better detection of OD than dynamic C20/C or the determination of the UIP by graphical means. Indeed the first analysis showed a substantial agreement (kappa 0.75) between dynamic c and LFI c detection of OD whereas the second analysis showed a poor agreement (kappa 0.22) between C20/ C and LFI detection of the UIP. In conclusion, quasi-static V-P curves can easily be obtained in children with the LFI technique. SOPE offers a good detection of OD on dynamic and LFI V-P curves but the C20/C index seems to be an inadequate measure of OD.

Adolescent↗

PubMed2004

Hormesis, hotspots and emissions trading.

Instrument choice--the comparison of technology standards, performance standards, taxes and tradable permits--has been a major topic in environmental law and environmental economics. Most analyses assume that emissions and health effects are positively and linearly related. If they are not, this complicates the instrument choice analysis. This article analyses the effects of a nonlinear dose-response function on instrument choice. In particular, it examines the effects of hormesis (high-dose harm but low-dose benefit) on the choice between fixed performance standards and tradable emissions permits. First, the article distinguishes the effects of hormesis from the effects of local emissions. Hormesis is an attribute of the dose-response or exposure-response relationship. Hotspots are an attribute of the emissions-exposure relationship. Some pollutants may be hormetic and cause local emissions-exposure effects; others may be hormetic without causing local emissions-exposure effects. It is only the local exposure effects of emissions that pose a problem for emissions trading. Secondly, the article shows that the conditions under which emissions trading would perform less well or even perversely under hormesis, depend on how stringent a level of protection is set. Only when the regulatory standard is set at the nadir of the hormetic curve would emissions trading be seriously perverse (assuming other restrictive conditions as well), and such a standard is unlikely. Moreover, the benefits of the overall programme may justify the risk of small perverse effects around this nadir. Thirdly, the article argues that hotspots can be of concern for two distinct reasons, harmfulness and fairness. Lastly, the paper argues that the solution to these problems may not be to abandon market-based incentive instruments and their cost-effectiveness gains, but to improve them further by moving from emissions trading and emissions taxes to risk trading and risk taxes. In short, the article argues that hormesis does not pose a general obstacle to emissions trading or emissions taxes, but that in those cases where hormesis does pose such a problem, a shift toward risk trading or risk taxes would be the superior route.

Air Pollutants↗