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 919 records · Page 51Linked to original sources

PubMed2007

HPLC determinations of enantiomeric ratios.

Evaporative light-scattering detection (ELSD) is widely applied in the HPLC analysis of organic compounds lacking a UV chromophore. However, this detection method is generally unsuitable for determination of enantiomeric ratios (er). The er calculated from a UV trace and an ELS trace of the same compound differs significantly. Because of the nonlinear concentration response of the ELS detector, a compound with an er of 95:5 appears to be enantiomerically pure by ELS detection. It is possible to obtain a calibration curve and to calculate a correction factor, but this procedure is time consuming and therefore not very practical for routine analyses. In contrast, a charged aerosol detector allows a very accurate determination of the enantiomeric ratios. Like the ELS detection, the CA detection is independent of the chromophore properties of the substrate. Therefore, we recommend the use of CA instead of ELS detection for determination of the enantiomeric ratios of non-UV active compounds.

Chromatography, High Pressure Liquid↗

PubMedDate not supplied

Numerical inverse interpretation of single-hole pneumatic tests in unsaturated fractured tuff.

A numerical inverse method was used to interpret simultaneously multirate injection and recovery data from single-hole pneumatic tests in unsaturated fractured tuff at the Apache Leap Research Site near Superior, Arizona. Our model represents faithfully the three-dimensional geometry of boreholes at the site, and accounts directly for their storage and conductance properties by treating them as high-permeability and high-porosity cylinders of finite length and radius. It solves the airflow equations in their original nonlinear form and yields information about air permeability, air-filled porosity and dimensionless borehole storage coefficient. Some of this is difficult to accomplish with analytical type-curves. Air permeability values obtained by our inverse method agree well with those obtained by steady-state and type-curve analyses.

Air↗

PubMed1992

Phenobarbitone population pharmacokinetics from routine clinical data: role of patient characteristics for estimating dosing regimens.

Routine clinical pharmacokinetic data collected from patients receiving phenobarbitone have been analysed to evaluate the role of patient characteristics for estimating dosing regimens. The data were analysed using NONMEM, a computer program designed for population pharmacokinetic analysis that allows pooling of data. The pharmacokinetic model of phenobarbitone was described using a one-compartment steady-state model. The effect of a variety of developmental and demographic factors on clearance was investigated. NONMEM estimates indicated a nonlinear function of total body weight as the optimum adjustment of phenobarbitone clearance. Concomitant administration of phenobarbitone and other antiepileptic drugs showed a decrease of phenobarbitone clearance in young children. The dosing method based on clearance values obtained by NONMEM analysis allowed the prediction of the steady-state concentration as a function of maintenance dose with acceptable error for therapeutic drug monitoring.

Adolescent↗

PubMed2005

Challenges for the identification of biological systems from in vivo time series data.

Modern methods of high-throughput molecular biology render it possible to generate time series of metabolite concentrations and the expression of genes and proteins in vivo. These time profiles contain valuable information about the structure and dynamics of the underlying biological system. This information is implicit and its extraction is a challenging but ultimately very rewarding task for the mathematical modeler. Using a well-suited modeling framework, such as Biochemical Systems Theory (BST), it is possible to formulate the extraction of information as an inverse problem that in principle may be solved with a genetic algorithm or nonlinear regression. However, two types of issues associated with this inverse problem make the extraction task difficult. One type pertains to the algorithmic difficulties encountered in nonlinear regressions with moderate and large systems. The other type is of an entirely different nature. It is a consequence of assumptions that are often taken for granted in the design and analysis of mathematical models of biological systems and that need to be revisited in the context of inverse analyses. The article describes the extraction process and some of its challenges and proposes partial solutions.

Linear Models↗

PubMed2005

Population pharmacokinetics of delavirdine and N-delavirdine in HIV-infected individuals.

OBJECTIVE: Delavirdine is a non-nucleoside reverse transcriptase inhibitor used in combination regimens for the treatment of HIV-1 infection. Our objective was to characterise the population pharmacokinetics of delavirdine in HIV-infected patients who participated in the adult AIDS Clinical Trials Group (ACTG) 260 and 261 studies. METHODS: ACTG 261 was a randomised, double-blind study of delavirdine 400mg three times daily, in various combination regimens; ACTG 260 was a concentration-targeted monotherapy study. Two hundred and thirty-four patients, and 1254 and 1251 plasma concentrations for delavirdine and N-delavirdine, respectively, were available for population pharmacokinetic analysis. The pharmacokinetic model (and initial parameters), based on previous studies, included two compartments for delavirdine (peripheral and central) and parallel clearance pathways (nonlinear conversion to N-delavirdine and first order clearance from the body). The model was one compartment for N-delavirdine with first order clearance. Diurnal variation of delavirdine and N-delavirdine oral clearance was modelled as a cosine function, with amplitude variation a fitted parameter. Pharmacokinetic parameter estimates were derived from iterative two-stage analysis; observed delavirdine and N-delavirdine concentrations fit with weighting by the inverse observation variance. Covariates were analysed by multiple general linear modelling. RESULTS: The mean (percent coefficient of variation [%CV]) CD4 count was 315 (109) cells/mm(3), weight 76.9 (14.7) kg, age 37 (8.5) years, and 15% of the population were women. Mean (%CV) population pharmacokinetic parameter estimates for delavirdine were: volume of distribution at steady state 67.6 (100) L, intrinsic oral clearance 19.8 (64) L/h, concentration at half the maximum velocity of metabolism (V(max)) 6.3 (69) micromol/L and first order oral clearance 0.57 (86) L/h. For N-delavirdine, the mean (%CV) apparent volume of distribution was 24.7 (75) L and apparent clearance 29.7 (42) L/h. The mean V(max) was 1376 (68) mg/day. The final model for average intrinsic clearance of delavirdine included race, sex, weight and age as significant covariates (p < 0.05); however, these covariates do not explain a significant proportion of the overall variability in the population. CONCLUSIONS: Delavirdine disposition exhibits nonlinear pharmacokinetics and large interpatient variability, and is significantly altered by time of day (impacting potential therapeutic drug monitoring and future pharmacokinetic study designs). Although race and sex appear to influence delavirdine pharmacokinetics, men and women and patients of different races should receive similar mg/kg dosage regimens. The presence of large interpatient variability supports the further investigation of the utility of therapeutic drug monitoring for delavirdine, if target drug concentrations can be better defined.

Adolescent↗

PubMed2005

Characterization of female breast lesions from multi-wavelength time-resolved optical mammography.

Characterization of both malignant and benign lesions in the female breast is presented as the result of a clinical study that involved more than 190 subjects in the framework of the OPTIMAMM European project. All the subjects underwent optical mammography, by means of a multi-wavelength time-resolved mammograph, in the range 637-985 nm. Optical images were processed by applying a perturbation model, relying on a nonlinear approximation of time-resolved transmittance curves in the presence of an inclusion, with the aim of estimating the major tissue constituents (i.e. oxy- and deoxy-haemoglobin, lipid and water) and structural parameters (linked to dimension and density of the scatterer centres) for both the lesion area and the surrounding tissue. The critical factors for the application of the perturbation model on in vivo data are also discussed. Forty-six malignant and 68 benign lesions were analysed. A subset of 32 cancers, 40 cysts and 14 fibroadenomas were found reliable for the perturbation analysis. For cancers, we show a higher blood content with respect to the surrounding tissue, while cysts are characterized by a lower concentration of scattering centres with respect to the surrounding tissue. For fibroadenomas, the low number of cases does not allow any definite conclusions.

Breast Cyst↗

PubMed1997

Decrease of cardiac chaos in congestive heart failure.

The electrical properties of the mammalian heart undergo many complex transitions in normal and diseased states. It has been proposed that the normal heartbeat may display complex nonlinear dynamics, including deterministic chaos, and that such cardiac chaos may be a useful physiological marker for the diagnosis and management of certain heart trouble. However, it is not clear whether the heartbeat series of healthy and diseased hearts are chaotic or stochastic, or whether cardiac chaos represents normal or abnormal behaviour. Here we have used a highly sensitive technique, which is robust to random noise, to detect chaos. We analysed the electrocardiograms from a group of healthy subjects and those with severe congestive heart failure (CHF), a clinical condition associated with a high risk of sudden death. The short-term variations of beat-to-beat interval exhibited strongly and consistently chaotic behaviour in all healthy subjects, but were frequently interrupted by periods of seemingly non-chaotic fluctuations in patients with CHF. Chaotic dynamics in the CHF data, even when discernible, exhibited a high degree of random variability over time, suggesting a weaker form of chaos. These findings suggest that cardiac chaos is prevalent in healthy heart, and a decrease in such chaos may be indicative of CHF.

Adult↗

PubMed2004

Efficient use of nonequilibrium measurement to estimate free energy differences for molecular systems.

A promising method for calculating free energy differences DeltaF is to generate nonequilibrium data via "fast-growth" simulations or by experiments--and then use Jarzynski's equality. However, a difficulty with using Jarzynski's equality is that DeltaF estimates converge very slowly and unreliably due to the nonlinear nature of the calculation--thus requiring large, costly data sets. The purpose of the work presented here is to determine the best estimate for DeltaF given a (finite) set of work values previously generated by simulation or experiment. Exploiting statistical properties of Jarzynski's equality, we present two fully automated analyses of nonequilibrium data from a toy model, and various simulated molecular systems. Both schemes remove at least several k(B)T of bias from DeltaF estimates, compared to direct application of Jarzynski's equality, for modest sized data sets (100 work values), in all tested systems. Results from one of the new methods suggest that good estimates of DeltaF can be obtained using 5-40-fold less data than was previously possible. Extending previous work, the new results exploit the systematic behavior of bias due to finite sample size. A key innovation is better use of the more statistically reliable information available from the raw data.

Algorithms↗

PubMed2003

Prediction of human pharmacokinetics from animal data and molecular structural parameters using multivariate regression analysis: oral clearance.

The aim of the study reported here was to develop a regression equation for predicting oral clearance of various kinds of drugs in humans using experimental data from rats and dogs and molecular structural parameters. The data concerning the oral clearance of 87 drugs from rats, dogs, and humans were obtained from literature. The compounds have various structures, pharmacological activities, and pharmacokinetic characteristics. In addition, the molecular weight, calculated partition coefficient (c log P), and the number of hydrogen bond acceptors were used as possible descriptors related to oral clearance in human. Multivariate regression analyses, multiple linear regression analysis, and the partial least squares (PLS) method were used to predict oral clearance in human, and the predictive performances of these techniques were compared by allometric approaches, which have been used in interspecies scaling. Interaction terms were also introduced into the regression analysis to evaluate the nonlinear relationship. For the data set used in this study, the PLS model with the tertiary term descriptors gave the best predictive performance, and the value of the squared cross-validated correlation coefficient (q(2)) was 0.694. This PLS model, using animal oral clearance data for only two species and easily calculated molecular structural parameters, can generally predict oral clearance in human better than the allometric approaches. In addition, the molecular structural parameters and the interaction term descriptors were useful for predicting oral clearance in human by PLS. Another advantage of this PLS model is that it can be applied to drugs with various characteristics.

Administration, Oral↗

PubMed2007

Transformation of an alpha-helix peptide into a beta-hairpin induced by addition of a fragment results in creation of a coexisting state.

Intrinsic rules of determining the tertiary structure of a protein have been unknown partly because physicochemical factors that contribute to stabilization of a protein structure cannot be represented as a linear combination of local interactions. To clarify the rules on the nonlinear term caused by nonlocal interaction in a protein, we tried to transform a peptide that has a fully helical structure (Target Peptide or TP) into a peptide that has a beta-hairpin structure (Designed Peptide or DP) by adding seven residues to the C terminus of TP. According to analyses of nuclear magnetic resonance measurements, while the beta-hairpin structure is stabilized in some DPs, it is evident that the helical structure observed in TP is also persistent and even extended throughout the length of the molecule. As a result, we have produced a peptide molecule that contains both the alpha-helix and beta-hairpin conformation at an almost equally populated level. The helical structures contained in these DPs were more stable than the helix in TP, suggesting that stabilizing one conformation does not result in destabilizing the other conformation. These DPs can thus be regarded as an isolated peptide version of the chameleon sequence, which has the capability of changing the secondary structure depending on the context of the surrounding environment in a protein structure. The fact that the transformation of one secondary structure caused stabilization of both the original and the induced structure would shed light on the mechanism of protein folding.

Amino Acid Sequence↗

PubMed2001

Utility of health belief model as a guide for explaining or predicting breast cancer screening behaviours.

AIM: The purpose of this study was to assess the utility of HBM as a theoretical guide for predicting breast cancer screening and therefore for guiding intervention studies. BACKGROUND: Breast cancer is the leading cause of death for middle age women (35-50) and the second leading cause of cancer deaths in all women in the United States (US). Early detection of breast cancer through screening is the only option available to women. However, less than half of all women in the US participate in screening. The health belief model (HBM), which specifies interactions of values and beliefs about health and their influence on choices, has been widely used to explain screening behaviour. METHODS: An integrative research review analysed 16 published descriptive studies employing HBM. Literature was located through a search of research based studies listed in Cumulative Index of Nursing and Allied Health (CINAHL), Medline, and cancer literature databases and studies cited in other references between 1990 and 1999. FINDINGS: Application of HBM was inconsistent. No study tested nonlinear relationships between variables as specified in the model. At best, the model explained 47% of the variance in screening behaviour when socioeconomic status was included. Otherwise predictive power was low, ranging from 15 to 27%. CONCLUSIONS: While the model provides some description of the values, beliefs and behaviours of middle-aged women primarily, HBM does not appear to have the power to consistently predict behaviours. Further research is needed to provide more thorough depiction of the social, nonhealth care meaning of breast cancer.

Adult↗

PubMed2003

Statistics and graphs for heart rate variability: pNN50 or pNN20?

Two measures of heart rate variability, pNN50 and pNN20, are compared. A non-linear transformation of these measures is proposed, that is helpful in understanding their interrelationship. Provided a valid statistical test is employed, results from analysing pNN20 are likely to be equivalent to those from analysing pNN50. Arguments recently made by Mietus et al (2002 Heart 88 378-80) against the commonly used pNN50 are unconvincing.

Data Interpretation, Statistical↗

PubMed1996

Association of transient ischemic attack/stroke symptoms assessed by standardized questionnaire and algorithm with cerebrovascular risk factors and carotid artery wall thickness. The ARIC Study, 1987-1989.

The baseline examination (1987-1989) for the Atherosclerosis Risk in Communities (ARIC) Study was conducted in 15,792 free-living residents aged 45-64 years in four geographically dispersed US communities. A questionnaire on symptoms of transient ischemic attack (TIA) and stroke was evaluated by computer algorithm for 12,205 of these participants. Data were also collected on lipoprotein levels, hemostasis, hematology, anthropometry, blood pressure, medical history, lifestyle, socioeconomic status, and medication use. Noninvasive high resolution B-mode ultrasonographic imaging was used to determine carotid arterial intimal-medial wall thickness (IMT). The cross-sectional relation between the prevalence of TIA/stroke symptoms and putative risk factors was assessed by logistic regression, controlling for age and community. Odds ratios for TIA/stroke symptoms were significantly elevated (p < or = 0.01) for diabetes mellitus, current smoking, hypertension, lower levels of education, income, and work activity, and higher levels of lipoprotein(a), IMT, hemostasis factor VIII, and von Willebrand factor. However, the relations with education and carotid IMT were not present for black Americans. In whites, the relations of TIA/stroke symptoms to IMT were nonlinear. Only at extreme levels of IMT were symptoms substantially more frequent: For example, men with an IMT greater than 1.17 mm or women with an IMT greater than 0.85 mm had approximately twice the odds of having positive TIA/stroke symptoms as those with lower IMTs. The authors plan in future analyses to address the issue prospectively, as well as to examine the relation with magnetic resonance imaging-defined outcomes and clinically defined incident stroke.

Algorithms↗

PubMed1998

Phase- and density-dependent population dynamics in Norwegian lemmings: interaction between deterministic and stochastic processes.

We analysed two 26-year long (1970-1995) time-series on annual population growth rates of Norwegian lemmings (Lemmus lemmus) from Finse, south Norway, using a threshold autoregressive (TAR) approach. We demonstrate that the population dynamics is both phase- and density-dependent. The phase-dependence accounts for the observed nonlinearity. We used the deduced stochastic model structure as a basis for evaluating the dynamic properties of this system. The dynamics is characterized either by limit cycles or chaos (the latter with a strong semi-periodic component). Stochasticity is seen to play an important role in the determination of the periodicity. The ecological implications of these statistical and mathematical results are discussed.

Animals↗

PubMed1998

Imaging of LED arrays for BLSS.

Arrays of light-emitting diodes (LEDS) are being used in life science plant flight experiments and show promise for use in Bioregenerative Life Support Systems (BLSS). However, the small volume available for the systems and the short distances from the LED array necessary in these applications create several unique problems. The discrete LEDS are small and the spacing between the lamps results in significant irradiance variation on surfaces near the array. These irradiance variations make it difficult to use traditional hand-held sensors to measure light levels under the array accurately. The usefulness of rear projection video camera imaging is investigated for the analysis of uniformity of irradiance from an LED array. Irradiance measurements were taken at a high mounting height from the array using both a 400-700-nm quantum sensor and a video camera. Additionally, video images were recorded at different mounting heights from the array. The rear projection imaging technique was suitable for analyzing the irradiance from LED arrays. Comparison of the readings from the video image and the sensor suggests that there is a nonlinear relationship between video image reading and sensor value (R(2) = 0.884). These data also show that the average photosynthetically active radiation level (PAR) does not change as mounting height varies, but that the spatial uniformity of the PAR does increase as mounting height increases. These results are consistent with geometrical analyses of the system.

Ecological Systems, Closed↗

PubMed2000

Morphometric analysis of dendritic tree of cerebellar Purkinje-cells.

Basic neural processes of sensorimotor adaptation can be observed by cellular-level studies on cerebellar cortex, both by electrophysiological and morphological means. In earlier studies we demonstrated double (sometimes triple or quadruple) rhythmic prespike activity patterns in dendritic microelectrode records taken from cerebellar Pc. By their active and passive interactions, the actual input pattern will turn into an arrhythmic output spiking, realizing a nonlinear and phase-sensitive integration. This curious complex spike-generating process can give rise to novel cerebellar functional models. The acting membrane dynamics rely not just upon the ionic current machinery but also upon the specific micromorphology of the dendritic tree, especially that of the branching areas. Although, statistical analyses on Pc dendrites generally followed the graph-theory, elaborated abstract parameters for complexity and hierarchy, and denied realistic geometry. Thus a novel specific morphometric study should be carried out, first applied to the main branching sites.

Animals↗

PubMed1986

Convergence in a distributed nervous system: parallel processing and self-organization.

The present findings show that the motor system of the carnivorous sea slug Pleurobranchaea californica consists of parallel, distributed, and interconnected neuronal channels by which motor activity may emerge from the dynamics of the system rather than from "switchboard" circuitry. The findings are shown primarily through the properties of the buccal-cerebral neurons (BCNs) that extensively converge and diverge monosynaptically and polysynaptically onto brain motoneurons, providing them with drive and patterned activity. The motoneurons, some of which are electrically coupled, feed back onto the BCNs. The BCNs are functionally heterogeneous both as a group and individually. Many are multifunctional in that they take part in the generation of different behaviors, and some also appear to change their timing with respect to the phase of the pattern generator in the different motor patterns. In the buccal ganglion, the BCNs affect the characteristics of the pattern generator and may be part of the pattern generator itself. By sending axons to buccal roots and to the brain, some BCNs may act as motoneurons and also integrate the activity of brain motoneurons. Because of the effects produced by the extensive interconnections among such functionally heterogeneous and nonlinear elements, and because the "history" of activity in the system can bias subsequent activity, there is ambiguity in assessing the response properties of neurons by examining them individually or in pairs. Such an assessment requires, first, an understanding of the context of activity in which a neuron becomes coactive, and, second, because of inherent variability in the system, it is necessary to consider the temporal, nonlinear computations of the system as a whole. We discuss the findings with regard to the attractor theory that has been used to study complex mammalian systems but that does not rely on modeling of any neuronal activity. The Pleurobranchaea nervous system may provide the means for studying individual neurons within such analyses of global activity.

Animals↗

PubMed1998

Resonant population cycles in temporally fluctuating habitats.

Experiments with the flour beetle Tribolium have revealed that animal numbers were larger in cultures grown in a periodically fluctuating volume of medium than in cultures grown in a constant volume of the same average size. In this paper we derive and analyze a discrete stage-structured mathematical model that explains this phenomenon as a kind of resonance effect. Habitat volume is incorporated into the model by the assumption that all rates of cannibalism (larvae on eggs, adults on eggs and pupae) are inversely proportional to the volume of the culture medium. We tested this modeling assumption by conducting and statistically analyzing laboratory experiments. For parameter estimates derived from experimental data, our model indeed predicts, under certain circumstances, a larger (cycle-average) total population abundance when the habitat volume periodically fluctuates than when the habitat volume is held constant at the average volume. The model also correctly predicts certain phase relationships and transient dynamics observed in data. The analyses involve a thorough integration of mathematics, statistical methods, biological details and experimental data.

Animals↗