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PubMed1981

Determinants of ridge counts in MZ twin kinships.

The inheritance of total ridge count (TRC) was studied in 967 individuals from the families of 111 pairs of MZ twins. The sample included data on 47 male half-sibships with 227 offspring and 64 female half-sibships with 306 offspring. The males in this sample had a mean ridge count of 135 +/- 2 and the females a mean ridge count of 124 +/- 2. The distribution of scores for females showed evidence for significant skewness. For this reason, prior to the analysis, the data were corrected for sex and adjusted to normality using a power transformation. Nested analyses of variance were performed on the ridge counts from male and female half-sibships separately to derive estimates of among, between, and within-variance components. These estimates were then used in a nonlinear least squares program to estimate genetic and environmental parameters and to determine the goodness of fit of various models. A model which included additive genetic and dominance effects could not be rejected (P = 0.67) but did not fit the data as well as a simple additive genetic-random environmental model (P = 0.81). The addition of maternal effects to the later model also provided a satisfactory fit (P = 0.68). However, there were no improvement in the goodness of fit over the simple model, and estimated magnitude of the maternal effect was not significantly different from zero.

Analysis of Variance↗
PubMed2002

Biomechanical response of retrodiscal tissue in the temporomandibular joint under compression.

PURPOSE: The present study was conducted to investigate the biomechanical response of bovine retrodiscal tissue of the temporomandibular joint (TMJ) in compression. PATIENTS AND METHODS: Using 10 retrodiscal tissues obtained from 10 cattle, the viscoelastic response of the retrodiscal tissue was evaluated by means of stress-strain analyses. These compressive strains were produced at a high strain rate and were kept constant during 5 minutes for stress-relaxation. RESULTS: Although the stress-strain relationship in the retrodiscal tissue was essentially nonlinear represented by a quadratic or power function of strain, a linear model could reasonably represent its elastic property. In this case, the instantaneous and relaxed moduli were 1.54 and 0.21 MPa, respectively. The stress-relaxation curve showed a marked drop in load during the initial 10 seconds, and the stress reached a steady nonzero level. Furthermore, when using Kelvin's model, a satisfactory agreement can be obtained between the experimental and theoretical stress-relaxation curves. CONCLUSION: It is concluded that bovine retrodiscal tissue has a great capacity for energy dissipation during stress-relaxation, although it has little or no function to pull the articular disc back.

Animals↗
PubMed1996

Heart rate variations during sleep in preadolescents.

Heart rate variations during sleep have been documented for infant and adult populations, but not for children and adolescents. To provide normative data for the preadolescent age group, this investigation used a combination of time-domain measures and nonlinear procedures (Poincare plots) to describe heart rate variations during two consecutive nights of undisturbed baseline sleep in 14 normal 8- to 10-year-old males. Heart rate variables, based on all-night analyses of computer-determined beat-to-beat (RR) intervals, were related to sleep stage and sleep cycle measures within and across nights. Time-domain summary statistics revealed a tendency for higher mean heart rates in rapid eye movement (REM) compared to slow-wave (SW) and stage 2 sleep, but the differences were not significant. Heart rate variability, as measured by average RR interval standard deviation, was greatest in stage 2 and least in SW sleep, but it did not vary significantly across sleep stages. Analyses of heart rate variables across the initial four sleep cycles showed a significant heart rate decrease (quadratic trend) and a significant increase (linear trend) for heart rate variability. All effects replicated across nights. Poincare plots revealed wide-ranging individual differences, generally characterized by greater dispersion at longer RR intervals and a remarkable night-to-night consistency in whole-night as well as stage-specific patterns. The sleep-stage plots uniformly indicated reduced overall range and variability in SW relative to REM and stage 2 and a general equivalence of stage 2 and REM patterns. The results indicate several features of sleep-related heart rate variations in preadolescents that differ from those in adults. The differences can be attributed to developmental variations in autonomic cardiac control and are consistent with increased parasympathetic influences reported to occur at this time.

Autonomic Nervous System↗
PubMed2000

Rotating machinery dynamics simulation. I. Rigid systems with ball bearing nonlinearities and outer ring ovality under rotating unbalance excitation

The radial clearance in rolling bearing systems, required to compensate for dimensional changes associated with thermal expansion of the various parts during operation, may cause dimensional attrition and comprise bearing life, if unloaded operation occurs and balls skid [D. Childs and D. Moyer, ASME J. Eng. Gas Turb. Power 107, 152-159 (1985)]. Also, it can cause jumps in the response to unbalance excitation. These undesirable effects may be eliminated by introducing two or more loops into one of the bearing races so that at least two points of the ring circumference provide a positive zero clearance [D. Childs, Handbook of Rotordynamics, edited by F. Ehrich (McGraw-Hill, NY, 1992)]. The deviation of the outer ring with two loops, known as ovality, is one of the bearing distributed defects. Although this class of imperfections has received much work, none of the available studies has simulated the effect of the outer ring ovality on the dynamic behavior of rotating machinery under rotating unbalance with consideration of ball bearing nonlinearities, shaft elasticity, and speed of rotation. To fill this gap, the equations of motion of a rotor-ball bearing system are formulated using finite-elements (FE) discretization and Lagrange's equations. The analyses are specialized to a rigid-rotor system, by retaining the rigid body modes only in the FE solution. Samples of the results are presented in both time domain and frequency domain for a system with and without outer ring ovality. It is found that with ideal bearings (no ovality), the vibration spectrum is qualitatively and quantitatively the same in both the horizontal and vertical directions. When the ring ovality is introduced, however, the spectrum in both orthogonal planes is no longer similar. And magnitude of the bearing load has increased in the form of repeated random impacts, between balls and rings, in the horizontal direction (direction of maximum clearance) compared to a continuous contact along the vertical direction (direction of positive zero clearance). This underlines the importance of the vibration measuring probe's direction, with respect to the outer ring axes, to capture impact-induced vibrations. Moreover, when the harmonic excitation is increased for a system with ideal bearings, the spectral peaks above forcing frequency have shifted to a higher-frequency region, indicating some sort of a hard spring mechanism inherent in the system. Another observation, is that for the same external excitation, vibration amplitude at forcing frequency in the bearing force spectrum is the same for systems with or without outer ring ovality.

Journal Article↗
PubMed1979

Flux of labeled compounds in biochemical oscillations.

If a labeled compound (e.g., a radioisotopically or chemically labeled metabolite) is introduced into any biochemical reaction system, the label will be removed by catabolic reactions and replaced by unlabeled compound through anagolic reactions. It is shown that the removal of labeled compounds is particularly efficient if the rates of the catabolic steps are able to oscillate. This is demonstrated by comparing reaction schemes that maintain the same mean fluxes and concentrations of metabolites and the same overall chemical affinity but which differe in that the rate of catabolism is either constant or oscillates as a function of time. Simple analyses are presented for both small and large oscillations of undefined wave form and for sinusoidal oscillations. The enhanced removal of labeled compounds from oscillating reaction systems is also documented by numerical computation on a nonlinear model system. It is suggested that this ability to remove labeled compounds may have provided a selective advantage for the evolution of some biological oscillations.

Kinetics↗
PubMed2006

Alterations in memory networks in mild cognitive impairment and Alzheimer's disease: an independent component analysis.

Memory function is likely subserved by multiple distributed neural networks, which are disrupted by the pathophysiological process of Alzheimer's disease (AD). In this study, we used multivariate analytic techniques to investigate memory-related functional magnetic resonance imaging (fMRI) activity in 52 individuals across the continuum of normal aging, mild cognitive impairment (MCI), and mild AD. Independent component analyses revealed specific memory-related networks that activated or deactivated during an associative memory paradigm. Across all subjects, hippocampal activation and parietal deactivation demonstrated a strong reciprocal relationship. Furthermore, we found evidence of a nonlinear trajectory of fMRI activation across the continuum of impairment. Less impaired MCI subjects showed paradoxical hyperactivation in the hippocampus compared with controls, whereas more impaired MCI subjects demonstrated significant hypoactivation, similar to the levels observed in the mild AD subjects. We found a remarkably parallel curve in the pattern of memory-related deactivation in medial and lateral parietal regions with greater deactivation in less-impaired MCI and loss of deactivation in more impaired MCI and mild AD subjects. Interestingly, the failure of deactivation in these regions was also associated with increased positive activity in a neocortical attentional network in MCI and AD. Our findings suggest that loss of functional integrity of the hippocampal-based memory systems is directly related to alterations of neural activity in parietal regions seen over the course of MCI and AD. These data may also provide functional evidence of the interaction between neocortical and medial temporal lobe pathology in early AD.

Aged↗
PubMed2006

Optimization analysis of decentralised sanitation and re-use system.

With the application of system dynamics, a dynamic nonlinear model reflecting the relationship between decentralised water use and reclaimed water supply and demand has been established. Through a system analysis, the model has been applied to a small residential district to predict and analyse the situation of future use of fresh water, demand and supply of re-used water, and treatment scale of reclaimed water. It is illustrated in this paper that wastewater decentralised treatment and re-use can decrease the consumption of fresh water without lowering the standard of living water for the district residents. On this basis, a rational scale and construction time of the decentralised sanitation and re-use system have been determined. Also, the paper predicts the influencing factors of the increasing water cost and changes in consumers' acceptability to re-use water in the decentralised sanitation and re-use system.

China↗
PubMed1999

Population pharmacokinetics of lamivudine in adult human immunodeficiency virus-infected patients enrolled in two phase III clinical trials.

Lamivudine population pharmacokinetics were investigated by using nonlinear mixed-effect modelling (NONMEM) analysis of data from 394 human immunodeficiency virus (HIV)-infected patients treated with lamivudine (150 to 300 mg every 12 h) in two large, phase III clinical efficacy-safety trials, NUCA3001 and NUCA3002. Analyses of 1,477 serum lamivudine concentration determinations showed that population estimates for lamivudine oral clearance (CL/F; 25.1 liters/h) and volume of distribution (V/F; 128 liters) were similar to values previously reported for HIV-infected patients in phase I pharmacokinetic studies. Lamivudine CL/F was significantly influenced by the covariates creatinine clearance and weight and not affected by age, Centers for Disease Control and Prevention (CDC) classification, CD4(+) cell count, HIV type 1 (HIV-1) RNA PCR, or gender and race when CL/F was corrected for differences in patient weight. The population estimate for lamivudine V/F was not significantly influenced by the covariates gender, race, age, weight, renal function, HIV-1 RNA PCR, or CDC classification and CD4(+) cell count when creatinine clearance was included with CL/F in the model. Lamivudine disposition was significantly influenced by renal function. However, as only three patients had an estimated creatinine clearance of <60 ml/min, dosage adjustments for patients with impaired renal function should not be determined based on the population parameters derived in this analysis.

Adult↗
PubMed2001

Evaluation of novel PET ligands (+)N-[11C]methyl-3-piperidyl benzilate ([11C](+)3-MPB) and its stereoisomer [11C](-)3-MPB for muscarinic cholinergic receptors in the conscious monkey brain: a PET study in comparison with.

The novel muscarinic cholinergic ligands (+)N-[11C]methyl-3-piperidyl benzilate ([11C](+)3-MPB) and its stereoisomer [11C](-)3-MPB were evaluated in comparison with [11C]4-MPB in the brains of conscious monkeys (Macaca mulatta) using high-resolution positron emission tomography (PET). The regional distribution patterns of [11C](+)3-MPB and [11C]4-MPB at 60-91 min postinjection were almost identical: highest in the striatum and occipital cortex; intermediate in the temporal and frontal cortices, cingulate gyrus, hippocampus, and thalamus; lower in the pons; and lowest in the cerebellum. The uptake of [11C](+)3-MPB in all regions was higher and the dynamic range of regional uptake differences of [11C](+)3-MPB was better than those of [11C]4-MPB. The levels of [11C](-)3-MPB were much lower in all regions of the brain than [11C](+)3-MPB and [11C]4-MPB. Administration of scopolamine, a muscarinic cholinergic antagonist, at a dose of 50 microg/kg reduced the radioactivity of [11C](+)3-MPB and [11C]4-MPB in all regions except the cerebellum. Time-activity curves of [11C](+)3-MPB peaked in all regions, while those of [11C]4-MPB showed gradual increases with time in all regions except the thalamus, pons, and cerebellum. Two graphical analyses (Logan plot and Patlak plot) with plasma radioactivity as an input function into the brain were applied to evaluate receptor binding in vivo. [11C](+)3-MPB showed linear regression curves on Logan plot analysis and nonlinear curves on Patlak plot in all regions, suggesting that [11C](+)3-MPB bound reversibly to the muscarinic receptors. The in vivo binding parameters as well as uptake at 60-91 min postinjection of [11C](+)3-MPB were consistent with muscarinic receptor density in the brain as reported in vitro.

Animals↗
PubMed1992

Behavioral economics of drug self-administration. III. A reanalysis of the nicotine regulation hypothesis.

The maintenance of a characteristic level of nicotine in a smoker's body is referred to as nicotine regulation. Considerable research has examined this question of whether smokers regulate nicotine intake. This is because nicotine regulation raises the question of whether smokers who, to decrease their intake of tar, switch to low tar/low nicotine cigarettes will increase the number and/or intensity of cigarettes smoked. Although the results of studies examining nicotine regulation are reported as generally consistent, considerable variability exists across these analyses such that the health hazards of smoking low tar/nicotine cigarettes remains uncertain. In the present analysis, these studies were analyzed to ascertain whether a behavioral-economic interpretation could better quantify the effects of changing nicotine yield on individuals' nicotine and smoke consumption. Specifically, 17 nicotine-regulation studies were reanalyzed using a unit-price analysis (i.e., cost-benefit analysis). The reanalysis showed less variability across regulation studies than previously reported; a positively-decelerating demand curve was found across most studies, consistent with previous unit-price analyses of food- and drug-maintained behavior. The benefits of this reanalysis versus the traditional regulation interpretation are that the behavioral economics approach: 1) brings unity to a variable set of data, 2) shows a nonlinear relationship, previously considered to be linear, between nicotine consumption and nicotine yield, 3) shows that nicotine yields higher, and not lower, than the smoker's usual brand decrease smoke consumption and thus decreases consumption of the harmful agents in tobacco, 4) better quantifies the data and provides a more parsimonious interpretation that generalizes to other drugs and food-maintained behavior in humans and nonhumans and, 5) integrates behavioral and pharmacological factors that control the consumption of reinforcers. These results suggest the value of behavioral economics in the study of consumptive behaviors and clinically suggest, in agreement with the studies contained herein, that decreasing the smoker's usual nicotine yield can have potential health risks for smokers who are unable to stop smoking.

Behavior↗
PubMed2002

Comparison of the mechanical behavior of the lumbar spine following mono- and bisegmental stabilization.

OBJECTIVE: To determine whether the mechanical behavior of the entire lumbar spine differs following mono- and bisegmental stabilization. DESIGN: The mechanical behavior of the lumbar spine was studied using the finite element method. BACKGROUND: Nonunion is somewhat more frequent after bi- than after monosegmental stabilization of the spine. Little is known about differences between the mechanical behavior associated with these procedures. METHODS: A three-dimensional nonlinear finite element model of the lumbar spine with internal spinal fixators and bone grafts was used to study mechanical behavior after mono- and bisegmental fixation with and without stabilization of the bridged vertebra. Finite element analyses were performed to determine the influence of four different graft positions, five loading conditions, and six different pretensions in the longitudinal fixator rod. The following parameters were considered: the maximum contact pressure at the interface between the bone graft and vertebral body, the force transmitted by the bone graft, and the size of the contact area between the graft and the vertebral body. RESULTS: Our model shows no clear differences between mono- and bisegmental fixation. Additional stabilization of the bridged vertebra exerts a partly adverse influence on the parameters studied. Pretension in the bridged region has a strong effect on the mechanical behavior. CONCLUSIONS: The mechanical behavior of the lumbar spine after mono- and bisegmental stabilization is similar. Thus biological factors and the surgical procedure are probably decisive in determining the fusion rate. RELEVANCE: Knowledge of the mechanical behavior after stabilization of the spine may help to improve the fusion rate. Our results suggest that the mechanical factors studied have only a minor influence on fusion rate and that other factors, such as incomplete resection of cartilage plate and poor local blood supply, are more decisive.

Biomechanical Phenomena↗
PubMed2001

In vivo finite element model-based image analysis of pacemaker lead mechanics.

BACKGROUND: Fractures of implanted pacemaker leads are currently identified by inspecting radiographic images without making full use of a priori known material and structural information. Moreover, lead designers are unable to incorporate clinical image data into analyses of lead mechanics. METHODS: A novel finite element/active contour method was developed to quantify the in vivo mechanics of implanted leads by estimating the distributions of stress, strain, and traction using biplane videoradiographic images. The nonlinear equilibrium equations governing a thin elastic beam undergoing 3-D large rotation were solved using one-dimensional isoparametric finite elements. External forces based on local image greyscale values were computed from each pair of images using a perspective transformation governing the relationship between the image planes. RESULTS: Cantilever beam forward solution results were within 0.2% of the analytic solution for a wide range of applied loads. The finite element/active contour model was able to reproduce the principal curvatures of a synthetic helix within 3% of the analytic solution and estimates of the helix's geometric torsion were within 20% of the analytic solution. Applying the method to biplane videoradiographic images of a lead acutely implanted in an anesthetized dog resulted in expected variations in curvature and bending stress between compliant and rigid segments of the lead. CONCLUSIONS: By incorporating knowledge about lead geometric and material properties, the 3-D finite element/active contour method regularizes the image reconstruction problem and allows for more quantitative and automatic assessment of implanted lead mechanics.

Algorithms↗
PubMedDate not supplied

Quality control data for low blood lead concentrations by three methods used in clinical studies.

During several clinical studies of blood lead (BPb) concentrations from environmental exposure, quality control data for three different methods of BPb analysis were compiled. Anodic stripping voltammetry by a commercial method (cASV), a modified method (mASV), and graphite furnace atomic absorption spectrophotometry (GFAA) were compared for precision at low BPb concentrations (less than 25 micrograms/dL) analyses. Both duplicate and interassay precision, as well as direct determinations of intraassay precision, were less for GFAA. The mASV incorporated calibration with lower BPb standards than used in the commercial protocol. This appeared to correct nonlinearity in response at lower BPb and reduced the bias between ASV and GFAA at BPb concentrations typical of environmental exposure levels.

Electrochemistry↗
PubMed1990

Mortality and air pollution in London: a time series analysis.

The relation between air pollution and mortality in London was examined for the winters of 1958-1972. The data exhibited a high degree of autocorrelation, requiring analyses using autoregressive models. There was a highly significant relation between mortality and either particulate matter or sulfur dioxide (after controlling for temperature and humidity), both overall and in each individual year. Graphic analysis revealed a nonlinear relation with no threshold, and a steeper exposure-response curve at lower air pollution levels. In models with both pollutants, particulate matter remained a significant predictor with about a 10% reduction in its estimated coefficients, while sulfur dioxide was insignificant, with a large drop in its estimated coefficient. The authors conclude that particulates are strongly associated with mortality rates in London, and the relation is likely causal.

Air Pollution↗
PubMed1988

Cyclosporine pharmacokinetics in pancreas transplant recipients.

Ten CsA pharmacokinetic studies were performed on five pancreas transplant recipients to determine proper doses and dosing intervals. These cadaver pancreas transplants were performed with exocrine ductal drainage into the urinary tract through a bladder anastomosis in four cases and into the bowel in one case. Four CsA pharmacokinetic studies were performed on diabetic renal transplant recipients and an additional six studies were performed while with pancreas transplant patients taking metoclopramide in an effort to enhance absorption of CsA. Mean CsA dose was 3.7 mg/kg/dose (range 2.1 to 7.5 mg/kg/dose). All patients but one were on twice daily dosing intervals yielding an average daily dose of 7.4 mg/kg/d. Noncompartmental pharmacokinetic analyses were used. The adequacy of a 1-, 2-, or 3-exponential model was determined by breakpoint analysis of the log concentration v time curve using the F statistic. The terminal rate constant was calculated by nonlinear regression analysis. The AUC and AUMC were calculated by the trapezoidal method with exponential extrapolation and these were used to calculate the MRT and Vdss. The unknown fractional absorption, F, was used to correct the oral data. The average CsA concentration maximum (Cmax) was 528 ng/mL with an average time to maximum concentration (Tmax) of 4.7 hours, a mean residence time of 7.75 hours, with a Vdss/%F of 9.61 L/kg in the pancreas transplant recipients. Additional studies of six patients receiving metoclopramide with CsA revealed an average Cmax of 723 ng/mL, an average Tmax of 2.3 hours, an average MRT of 6.08 hours, and an average Vdss/%F of 5.7% L/kg. These results indicate that coexistent gastroparesis in diabetic recipients of either pancreatic or renal transplants may result in reduced bioavailability of CsA.

Adult↗
PubMedDate not supplied

Stages of change in physical exercise: a test of stage discrimination and nonlinearity.

OBJECTIVES: To investigate the utility of the protection motivation theory (PMT), social-cognitive theory (SCT) and transtheoretical model's (TTM) processes of change (POC) by (1) discriminating between TTM's stages with planned comparisons and (2) examining higher-ordered trends across stages. METHODS: 1582 individuals were included in the analyses that tested severity, vulnerability, response-efficacy, self-efficacy, POC, pros and cons, social and environmental support. RESULTS: The findings provide evidence for the utility of the PMT and TTM's POC for stage discrimination; stage discontinuity patterns are supported. CONCLUSIONS: Promotion of health behavior should target stage-specific variables, such as threat appraisals for early stage movements.

Adult↗
PubMed1997

Sample-Induced RF Perturbations in High-Field, High-Resolution NMR Spectroscopy

Conducting dielectric samples are often used in high-resolution experiments at high field. It is shown that significant amplitude and phase distortions of the RF magnetic field may result from perturbations caused by such samples. Theoretical analyses demonstrate the spatial variation of the RF field amplitude and phase across the sample, and comparisons of the effect are made for a variety of sample properties and operating field strengths. Although the effect is highly nonlinear, it tends to increase with increasing field strength, permittivity, conductivity, and sample size. There are cases, however, in which increasing the conductivity of the sample improves the homogeneity of the amplitude of the RF field across the sample at the expense of distorted RF phase. It is important that the perturbation effects be calculated for the experimental conditions used, as they have the potential to reduce the signal-to-noise ratio of NMR experiments and may increase the generation of spurious coherences. The effect of RF-coil geometry on the coherences is also modeled, with the use of homogeneous resonators such as the birdcage design being preferred. Recommendations are made concerning methods of reducing sample-induced perturbations. Experimental high-field imaging and high-resolution studies demonstrate the effect.

Journal Article↗