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PubMed2000

The finite element analysis of stresses in atherosclerotic arteries during balloon angioplasty.

Finite element models of diseased arteries subject to balloon dilation are used to study the stresses in the arterial wall and plaque at peak balloon pressures. These models incorporate large strain, simulate contact between the balloon and the inner artery, and the constituent materials are modeled as nonlinear elastic. In these analyses, balloon dilation pressures range from 300 to 450 kPa. The stress in the diseased artery is recorded under different stenosis levels dilated using different balloons and possible causes of restenosis and plaque rupture are discussed.

Angioplasty, Balloon↗

PubMed1992

Autoradiographic characterization of beta-adrenergic receptor subtype in the canine conduction system.

It has been hypothesized, based on physiological evidence, that there is a greater proportion of beta 2-adrenergic receptors on the myocytes of the conduction system when compared with the working myocardium. The purpose of these studies was to examine beta-adrenergic receptor subtype in the conduction system of the dog by using the technique of coverslip autoradiography. Scintillation studies of [125I]pindolol binding to ventricular sections demonstrated that binding was saturable (dissociation constant of 116 pM), had the correct order of potency for a beta-receptor, and was stereoselective. Both betaxolol (beta 1-selective) and ICI-118,551 (beta 2-selective) competition curves fit a two-site model in nonlinear curve-fitting analyses (78% beta 1-receptors). Autoradiographic studies determined that the myocytes of the sinoatrial node had approximately twice as many autoradiographic grains as the surrounding atrial myocytes. The myocytes of the atrioventricular bundle had a number of grains similar to the number in surrounding septal myocytes. Autoradiographic inhibition curves with betaxolol or ICI-118,551 demonstrated that both the sinoatrial node and the atrioventricular bundle had inhibition profiles similar to the surrounding myocytes (predominantly beta 1) but unlike the inhibition profiles of arterioles (predominantly beta 2). Calculations using the dissociation constants derived from the nonlinear curve-fitting analysis and the percent specific binding in the presence of 4 x 10(-7) M betaxolol or ICI-118,551 determined that the proportion of beta 1- to beta 2-receptors was the same (70-80% beta 1) when comparing the sinoatrial node and the surrounding atrial myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

PubMed2026

Association of Age at Menarche With Depression in Adulthood in NHANES 2015-2023: A Cross-Sectional Study.

PURPOSE: The primary objective of this study is to elucidate the role of age at menarche in depression in adulthood and explore the implications of this association. METHODS: We conducted a study involving 9,826 adult female participants from the National Health and Nutrition Examination Survey (NHANES) between 2015 and August 2023. Age at menarche was categorized as early (<12 years), normal (12-14 years), or late (≥15 years). Depression was assessed using the 9-item Patient Health Questionnaire (PHQ-9) and clinical diagnoses. Logistic regression and restricted cubic spline analyses were performed to address the study objectives. In addition, subgroup analyses were conducted based on demographic, lifestyle, and clinical characteristics. RESULTS: The depression group had a significantly higher proportion of young adults (aged 18-30 years) compared to the nondepression group (26.46% vs. 20.52%, p < .001). Conversely, the nondepression group included a greater proportion of older adults (over 60 years) than the depression group (29.53% vs. 23.98%, p < .001). After comprehensive adjustments, early menarche was significantly associated with increased depression risk (adjusted odds ratio [aOR] = 1.224, 95% confidence interval [CI]: 1.003-1.493, p = .047). Restricted cubic spline analyses revealed an L-shaped nonlinear pattern (p for nonlinearity = 0.006), with optimal age at menarche around 12 years. Subgroup analyses confirmed consistent associations without significant interactions. DISCUSSION: Early menarche is linked to increased depression risk, especially among women aged 18-30 years. Menarche at 12 years may serve as a key point for early intervention to prevent depression in young women.

Humans↗

PubMed1999

Nonlinearity in the lung cancer dose-response for airborne arsenic: apparent confounding by year of hire in evaluating lung cancer risks from arsenic exposure in Tacoma smelter workers.

Most analytic studies of human epidemiologic data have affirmed the linear association between excess lung cancer risk and airborne arsenic exposure. Recent Canadian analyses, however, based on the mortality follow-up of Tacoma smelter workers from 1940-1976, provided strong evidence of a nonlinear dose-response when lung cancer risk was expressed in terms of the standardized mortality ratio. Using recently updated data covering ten additional years of mortality experience among Tacoma workers (1940-1986), new analyses were undertaken to further explore nonlinearity in the lung cancer dose-response in this worker cohort. Lung cancer risk was expressed in terms of both the standardized mortality ratio (SMR) and the excess mortality rate (EMR). As in Canadian analyses, nonlinearity was assessed through a three parameter model containing both linear and negative exponential terms for dose. Dropping the negative-exponential dose-term lead to the standard suite of linear dose-response models, with and without intercept, used for comparative purposes. Analyses were undertaken by subcohort as there was strong evidence of confounding by year of initial hire, which largely explained the nonlinearity in the dose-response observed in Canadian analyses. Subcohort analyses based on initial employment, prior to 1940 or thereafter, showed that the nonlinearity in the dose-response was strongly influenced by date of initial hire. whether the cohort risk was measured by either the SMR or EMR, a nonlinear dose-response was evident only among workers hired prior to 1940. This, however, was strongly related to the artifactually low lung cancer mortality seen among workers hired between 1930 and 1939. Among workers hired after 1940, analyses showed that a linear dose-response provided a clearly superior fit. While analyses showed comparable goodness of fit when models were fitted to the SMR and EMR. Only those based on the EMR provided strong evidence of a dose-response. Overall, nonlinearity as observed in Canadian analyses was likely the result of several sources of bias not taken into account by Canadian investigators.

Adult↗

PubMed2006

Selecting a battery of bioassays for ecotoxicological characterization of wastes.

This study was conducted in France within the context of waste classification (Hazardous Waste Council Directive 91/689/EEC), and focused on "ecotoxic" property (H14). In 1998, an experimental test strategy was developed to assess ecotoxicological properties of wastes using a battery of six standardized bioassays. This combined direct and indirect approaches integrating two solid-phase tests: emergence and growth inhibition of Lactuca sativa (14 days), mortality of Eisenia fetida (14 days) and four standardized tests performed on water extracts from wastes: growth inhibition of Pseudokirchneriella subcapitata (3 days), inhibition of mobility of Daphnia magna (48 h), inhibition of reproduction of Ceriodaphnia dubia (7 days), inhibition of light emission of Vibrio fischeri (30 min). This study aimed to set up preliminary conclusions on relevancy of this experimental test strategy, based on data obtained since 1998. Results were analyzed from the combined use of Hierarchical Cluster Analysis, Principal Component Analysis and Nonlinear Mapping. These multivariate analyses clearly showed that it was possible to reduce this number of tests without changing the typology of the wastes. A battery of bioassays including one solid phase test and two tests performed on water extracts (L. sativa, V. fischeri and C. dubia) was found as an optimal solution for characterizing the toxicity of the studied wastes. This optimal battery represents a good basis for determining the H14 property.

Aliivibrio fischeri↗

PubMed2000

Nonlinear mechanisms of cortical oscillations.

Not only theoretical consideration but also analyses of MEG or EEG recordings prove the nonlinear character of cortical dynamics. For instance, an averaged local Lyapunov Exponents (ILE) have positive value that is characteristic for chaotic dynamics. Also a test for nonlinearity (or determinism)--so called surrogate data test distinguishes between original- and randomized-phase time-series proving that recorded signals are nonlinear. These facts are a very strong experimental evidence to support the hypothesis that brain oscillators are governed by the deterministic, nonlinear, low-dimensional dynamics. The experimental manifestations of nonlinear cortical oscillations in the healthy and pathologically altered human brain and their deterministic character seems to be an important step in the understanding brain dynamics in the language of nonlinear systems theory. Clinical application may use nonlinear measures (especially ILE, and PD2i) for classification of pathologies and rough localization of the functional disturbance in the brain.

Cerebral Cortex↗

PubMed2004

Spinal muscle forces, internal loads and stability in standing under various postures and loads--application of kinematics-based algorithm.

This work aimed to evaluate trunk muscle forces, internal loads and stability margin under some simulated standing postures, with and without external loads, using a nonlinear finite element model of the T1-S1 spine with realistic nonlinear load-displacement properties. A novel kinematics-based algorithm was applied that exploited a set of spinal sagittal rotations, initially calculated to minimize balancing moments, to solve the redundant active-passive system. The loads consisted of upper body gravity distributed along the spine with or without 200 N held in the hands, either in the front of the body or on the sides. Nonlinear and linear stability/perturbation analyses at deformed, stressed configurations with a linear stiffness-force relationship for muscles identified the system stability and critical muscle stiffness coefficient. Predictions were in good agreement with reported measurements of posture, muscle EMG and intradiscal pressure. Minimal changes in posture (posterior pelvic tilt and lumbar flattening) substantially influenced muscle forces, internal loads and stability margin. Addition of 200 N load in front of the body markedly increased the system stability, global muscle forces, and internal loads, which reached anterior shear and compression forces of approximately 500 N and approximately 1,200 N, respectively, at lower lumbar levels. Co-activation in abdominal muscles (up to 3% maximum force) substantially increased extensor muscle forces, internal loads and stability margin, allowing a smaller critical muscle coefficient. A tradeoff existed between lower internal loads in passive tissues and higher stability margins, as both increased with greater muscle activation. The strength of the proposed model is in accounting for the synergy by simultaneous consideration of passive structure and muscle forces under applied postures and loads.

Algorithms↗

PubMed2006

A new calibration method that compensates for the effects of O2 and N2 on infrared CO2 analysers.

OBJECTIVE: This study evaluates a method for calibrating mainstream CO(2) analysers in which CO(2) partial pressure (P (CO2)) is calculated as a function of the outputs of CO(2) and O(2) analysers. METHODS: Three mass flow controllers were used to generate 25 different reference mixtures of O(2), N(2) and CO(2). Reference gas mixtures were combinations of P (CO2) = 2, 4, 6, 8, 10 kPa and O(2) partial pressure (P (O2)) = 10, 20, 40, 60, 80 kPa (balance N(2)). CO(2) and O(2) analyser data were fitted by a calibration equation which took into account the effects of oxygen partial pressure and nonlinearity of the CO(2) analyser. The calibration coefficients were tested in a separate validation data set with a variety of combinations of CO(2) and O(2). RESULTS: Our new calibration method yields a standard deviation of CO(2) measurement error that is significantly lower than a CO(2)-only calibration method in the validation data set (0.54% versus 2.72%, P < 0.05). P (CO2) measurement errors produced by the single gas calibration equation are significantly correlated with P (O2) in both the calibration (R = -0.9906, P < 0.05) and validation data sets (R = -0.9642, P < 0.05), but the errors given by our new calibration equation are independent of P (O2) (R = -0.0364, NS, and R = -0.0305, NS, for calibration and validation data sets respectively). Calibration with only CO(2) cannot eliminate the error related to the collision broadening effect of O(2), which in our CO(2) analyser is approximately a 1% underestimation of P (CO2) for every 10 kPa (75 mmHg) increase in P (O2). CONCLUSIONS: This study shows that non-dispersive infrared CO(2) analyser readings can be substantially affected by background oxygen. This effect can be corrected for by calibrating the CO(2) analyser with gases containing known proportions of both CO(2) and O(2).

Blood Gas Analysis↗

PubMed1995

Within-herd genetic analyses of stayability of beef females.

Nonlinear mixed-model procedures for analysis of binary data were used to estimate heritability (h2), predict individual genetic merit, and determine genetic and environmental trends for four measures of stayability of beef females. Traits considered were probabilities of a female having 2 [S(2/1)], 5 [S(5/1)], 8 [S(8/1)] and 11 [S(11/1)] calves, given that she calved once. Colorado State University Beef Improvement Center (BIC) and Beckton Stock Farm (BSF) provided data for the analyses. Heritability was estimated using animal model marginal maximum likelihood (AM MML), sire model marginal maximum likelihood (SM MML), and animal model Method R (AM MR). Individual genetic merit was predicted using single-trait animal models with each h2 estimate. Birth year was treated as fixed in all analyses. Only AM MML yielded h2 estimates for all traits in both herds. The AM MML h2 estimates for S(2/1), S(5/1), S(8/1), and S(11/1) were .09, .11, .07, and .20, respectively, for BSF data and .02, .14, .09, and .07, respectively, for BIC data. Differing h2 estimates did not substantially influence rank of individual predictions. Genetic trends in stayability were positive in both herds, although birth year solutions indicated variable or negative environmental trends. Genetic improvement of stayability may be accelerated by incorporating predictions of genetic merit for stayability in selection criteria. S(5/1) may be the most useful trait for consideration in national cattle evaluations.

Animals↗

PubMed1988

Effects of ingrowth, geometry, and material on stress transfer under porous-coated hip surface replacements.

Three different interface geometries for porous ingrowth surface replacements of the hip were examined using two-dimensional linear and nonlinear contact finite element analyses. The results indicate that incorporation of a nearly flat prosthesis interface between the surface replacement and the underlying cancellous bone may reduce stress shielding and improve stress transfer from the component. For all designs analyzed, the bone stress shielding was insensitive to component material stiffness when the elastic modulus was greater than 30 MPa. The use of titanium instead of cobalt-chrome (Co--Cr) as the prosthesis material therefore had a negligible effect on stress shielding.

Hip Joint↗

PubMed1997

Implementation of EPA Revised Cancer Assessment Guidelines: Incorporation of Mechanistic and Pharmacokinetic Data.

A workshop entitled "Implementation of EPA Revised Cancer Assessment Guidelines: Incorporation of Mechanistic and Pharmacokinetic Data" was held in Anaheim, California, in 1996 at the 35th Annual Meeting of the Society of Toxicology (SOT). This workshop was jointly sponsored by the Carcinogenesis, Risk Assessment, and Veterinary Specialty Sections of the SOT. The thrust of the workshop was to discuss the scientific basis for the revisions to the EPA Guidelines for cancer assessment and EPA's plans for their implementation. This is the first revision to the original EPA guidelines which have been in use by EPA since 1986. The principal revisions are intended to provide a framework for an increased ability to incorporate biological data into the risk assessment process. Two cases were presented, for chloroform and triclioroethylene, that demonstrated the use of the revised guidelines for specific cancer risk assessments. Using these new guidelines, nonlinear margin of exposure analyses were proposed for these chemicals instead of the linearized multistage model previously used by the EPA as the default method. The workshop participants generally applauded the planned revisions to the EPA guidelines. For the most part, they considered that the revised guidelines represented a positive step which should allow for and encourage the use of biological information in the conduct of cancer risk assessments. Several participants cautioned however that the major problem with cancer risk assessments would continue to be the inadequacy of available data on which to conduct more scientific risk assessments.

Animals↗

PubMed1993

Allosterism and Na(+)-D-glucose cotransport kinetics in rabbit jejunal vesicles: compatibility with mixed positive and negative cooperativities in a homo- dimeric or tetrameric structure and experimental evidence for only one transport protein involved.

We first present two simple dimeric models of cotransport that may account for all of the kinetics of Na(+)-D-glucose cotransport published so far in the small intestine. Both the sigmoidicity in the Na+ activation of transport (positive cooperativity) and the upward deviations from linearity in the Eadie-Hofstee plots relative to glucose concentrations (negative cooperativity) can be rationalized within the concept of allosteric kinetic mechanisms corresponding to either of two models involving sequential or mixed concerted and sequential conformational changes. Such models also allow for 2 Na+: 1 S and 1 Na+: 1 S stoichiometries of cotransport at low and high substrate concentrations, respectively, and for partial inhibition by inhibitors or substrate analogues. Moreover, it is shown that the dimeric models may present physiological advantages over the seemingly admitted hypothesis of two different cotransporters in that tissue. We next address the reevaluation of Na(+)-D-glucose cotransport kinetics in rabbit intestinal brush border membrane vesicles using stable membrane preparations, a dynamic approach with the Fast Sampling Rapid Filtration Apparatus (FSRFA), and both nonlinear regression and statistical analyses. Under different conditions of temperatures, Na+ concentrations, and membrane potentials clamped using two different techniques, we demonstrate that our data can be fully accounted for by the presence of only one carrier in rabbit jejunal brush border membranes since transport kinetics relative to glucose concentrations satisfy simple Michaelis-Menten kinetics. Although supporting a monomeric structure of the cotransporter, such a conclusion would conflict with previous kinetic data and more recent studies implying a polymeric structure of the carrier protein. We thus consider a number of alternatives trying to reconcile the observation of Michaelis-Menten kinetics with allosteric mechanisms of cotransport associated with both positive and negative cooperativities for Na+ and glucose binding, respectively. Such models, implying energy storage and release steps through conformational changes associated with ligand binding to an allosteric protein, provide a rational hypothesis to understand the long-time debated question of energy transduction from the Na+ electrochemical gradient to the transporter.

Allosteric Regulation↗

PubMed1989

An epidemiological model with a delay and a nonlinear incidence rate.

An epidemiological model with both a time delay in the removed class and a nonlinear incidence rate is analysed to determine the equilibria and their stability. This model is for diseases where individuals are first susceptible, then infected, then removed with temporary immunity and then susceptible again when they lose their immunity. There are multiple equilibria for some parameter values, and, for certain of these, periodic solutions arise by Hopf bifurcation from the large nontrivial equilibrium state.

Epidemiologic Methods↗

PubMed1989

Information theory and the analysis of ligand-binding data.

The phenomenological principles of information theory are used in the analysis of ligand-binding phenomena in biological macromolecules. Information maps are constructed to visualize regions of ligand chemical potential with maximum amount of information and to devise suitable experimental strategies therefrom. Extensive simulation studies and analysis of experimental data also point out the properties of information used as a weighting procedure in nonlinear least-squares analyses.

Carbon Monoxide↗

PubMed2005

Data reduction in headspace analysis of blood and urine samples for robust bacterial identification.

This paper demonstrates the application of chemical headspace analysis to the problem of classifying the presence of bacteria in biomedical samples by using computational tools. Blood and urine samples of disparate forms were analysed using a Cyrano Sciences C320 electronic nose together with an Agilent 4440 Chemosensor. The high dimensional data sets resulting from these devices present computational problems for parameter estimation of discriminant models. A variety of data reduction and pattern recognition techniques were employed in an attempt to optimise the classification process. A 100% successful classification rate for the blood data from the Agilent 4440 was achieved by combining a Sammon mapping with a radial basis function neural network. In comparison a successful classification rate of 80% was achieved for the urine data from the C320 which were analysed using a novel nonlinear time series model.

Bacteremia↗

PubMed1995

Analysis of saturation transfer electron paramagnetic resonance spectra of a spin-labeled integral membrane protein, band 3, in terms of the uniaxial rotational diffusion model.

Algorithms have been developed for the calculation of saturation transfer electron paramagnetic resonance (ST-EPR) spectra of a nitroxide spin-label assuming uniaxial rotational diffusion, a model that is frequently used to describe the global rotational dynamics of large integral membrane proteins. One algorithm explicitly includes terms describing Zeeman overmodulation effects, whereas the second more rapid algorithm treats these effects approximately using modified electron spin-lattice and spin-spin relaxation times. Simulations are presented to demonstrate the sensitivity of X-band ST-EPR spectra to the rate of uniaxial rotational diffusion and the orientation of the nitroxide probe with respect to the diffusion axis. Results obtained by using the algorithms presented, which are based on the transition-rate formalism, are in close agreement with those obtained by using an eigenfunction expansion approach. The effects of various approximations used in the simulation algorithms are considered in detail. Optimizing the transition-rate formalism to model uniaxial rotational diffusion results in over an order of magnitude reduction in computation time while allowing treatment of nonaxial A- and g-tensors. The algorithms presented here are used to perform nonlinear least-squares analyses of ST-EPR spectra of the anion exchange protein of the human erythrocyte membrane, band 3, which has been affinity spin-labeled with a recently developed dihydrostilbene disulfonate derivative, [15N,2H13]-SL-H2DADS-MAL. These results suggest that all copies of band 3 present in intact erythrocytes undergo rotational diffusion about the membrane normal axis at a rate consistent with a band 3 dimer.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗

PubMed2002

Nonlinear analysis of dynamic binding in affinity capillary electrophoresis demonstrated for inclusion complexes of beta-cyclodextrin.

The stability of the molecular host-guest inclusion complexes of beta-cyclodextrin with benzoate and four different hydroxybenzoates is investigated. For the measurement of the binding constants an experimental method is devised that is based on affinity capillary electrophoresis (ACE) with indirect UV absorbance detection. We derive an explicit equation for effective mobilities in ACE experiments without violation of rigorous mass balance. This equation is employed in the nonlinear least-squares analyses of the experimental data yielding binding constants of 48+/-2 M(-1) for benzoate, 299+/-38 M(-1) for 2-hydroxybenzoate, 37+/-1 M(-1) for 3-hydroxybenzoate, 228+/-9 M(-1) for 4-hydroxybenzoate, and 895+/-110 M(-1) in the case of 2,4-dihydroxybenzoate.

Cyclodextrins↗

PubMed2002

Kinetic assessment of the effects of task difficulty, microencephaly, and a response manipulandum alteration on the rate of fixed-ratio discrimination acquisition.

Fixed-ratio discrimination (FRD) training session-accuracy curves were constructed using first-order, nonlinear regression and probit analyses to determine maximal (asymptotic) accuracy and the number of sessions required to reach half-maximal accuracy. Increased FRD difficulty (reductions in the differences between the 2 fixed-ratio values to be discriminated) and a training parameter change each increased the number of sessions required to reach half-maximal accuracy and decreased maximal FRD accuracy (i.e., session-accuracy curves were shifted down and to the right) regardless of analysis procedure. These findings indicate that the above manipulations induced mixed competitive-noncompetitive inhibition of the rate of FRD learning. Microencephalic rats were more sensitive to increases in FRD difficulty, whereas control rats were more sensitive to the training parameter change.

Animals↗