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PubMed1981

Sensitivity analysis and optimization for a head movement model.

A sixth order nonlinear model for horizontal head rotations in humans is analyzed using an extended parameter sensitivity analysis and a global optimization algorithm. The sensitivity analysis is used in both the direct sense, as a model fitting tool, and in the indirect sense, as a guide to experimental design. Resolution is defined in terms of the sensitivity table, and is used to interpret the sensitivity results. Using sensitivity analyses, the head and eye movement systems are compared and contrasted. Controller signal parameters are the most influential. Their variations and effects on head movement trajectories and accelerations are investigated, and the conclusions are compared with clinical neurological findings. The global optimization algorithm, in addition to automating the fitting of various types of data, is combined with time optimality theory to give theoretical time-optimal inputs to the model.

Computers↗

PubMed2003

Antidepressant prescribing in community cancer care.

GOALS: To describe patterns of antidepressant (ADs) prescribing in community oncology practice. PATIENTS AND METHODS: Data were collected using an electronic medical record on all staged breast, colon, and lung cancer patients in three community-based oncology practices. The data were analyzed retrospectively, using descriptive and bivariate analyses and multivariate logistic regression modeling. There were 850 breast, 299 colon, and 473 lung cancer patients identified in this analysis. MAIN RESULTS: Overall, 19.2% of breast, 11% of colon, and 13.7% of lung cancer patients had been prescribed ADs during the 2-year period. The clinic in which cancer treatment was received predicted AD prescribing. The relationship between AD administration and age proved to be nonlinear; the pattern exhibited an "inverted U" shape. Patients with comorbidities and on pain medications were more likely to be administered ADs. Colon cancer patients on pain medications were five times more likely to be administered ADs than those not on pain medications. CONCLUSIONS: While some predictors of AD prescribing appear to be consistent with other studies, such as being on pain medication, there is still a great amount of variability in prescribing patterns across community practices, age groups, and cancer diagnoses. This study demonstrates that prescriptions of ADs seem to be influenced by parameters other than psychopathology. Given the importance of major depression in oncology care, diagnosis of psychiatric disorders and prescription patterns of psychotropics should be part of the routine monitoring and quality management in oncology patient care.

Adult↗

PubMed2004

Population pharmacokinetics of gentamicin in hospitalized patients receiving once-daily dosing.

The purpose of this study was to describe the population pharmacokinetics of gentamicin in a group of 939 adult hospitalized patients receiving once-daily administration of gentamicin and to evaluate the potential influence of patient covariates on gentamicin disposition. Data comprising 1294 serum concentrations from 939 patients, were analyzed using a nonlinear mixed-effect model (NONMEM). The patients had an average age of 55 and an average weight of 70 kg, 431 of the patients were female. The patient covariates including body weight, gender, age, and creatinine clearance (CL(CR)) were analyzed in a stepwise fashion to identify their potential influences on gentamicin pharmacokinetics. The data were best described with a two-compartment model. NONMEM analyses showed that gentamicin clearance (CL, l/h) was linearly correlated with CLcR with proportionality constant: 0.047 (S.E.: 0.0035) x CL(CR) (ml/min). Volume of the central compartment (V1, 1) was linearly related to body weight with proportionality constant: 0.28 (S.E.: 0.021) x body weight (kg). The mean population estimates of CL and V1 were 4.32 l/h and 19.61. respectively. The inter-individual variability in CL and V1 were 29.6 and 5.8%, respectively. Residual errors were 0.23 mg/l and 23.7%. The mean population values of CL and V1 of gentamicin dosed once daily are in agreement with those described by others. This analysis indicates that once-daily dosing (7 mg/kg) of gentamicin should achieve satisfactory concentration in patients with normal renal function although serum concentration monitoring is required to confirm the optimal dosing interval in patients with impaired renal function.

Adolescent↗

PubMed2004

Expeditious implementation of two new methods for analysing the pigment composition of photosynthetic specimens.

Two new methods for analysing the pigment composition of photosynthetic samples have been developed during the last few years. One, called the spectral reconstruction method, uses linear least-squares fitting, while the other, named the Gauss-peak spectra method, entails non-linear optimisation; each has some advantages over the other, but both use a large number of data points and surpass the traditional method which uses absorbance at a few wavelengths. In order to make the new methods transparent to experimentalists who are not well versed in statistical analysis, curve fitting and interpolation, simple procedures are described for implementing the methods with the aid of a spreadsheet. The problem of analysing a sample containing chlorophyll c, which is difficult to isolate in a form sufficiently pure to serve as an analytical standard, is also briefly addressed.

Avena↗

PubMed2003

Rectification and non-linear pre-processing of EMG signals for cortico-muscular analysis.

Rectification of the electromyographic (EMG) signal is a commonly used pre-processing procedure that allows detection of significant coherence between EMG and measured cortical signals. However, despite its accepted and wide-spread use, no detailed analysis has been presented to offer insight into the precise function of rectification. We begin this paper with arguments based on single motor unit action potential (AP) trains to demonstrate that rectification effectively enhances the firing rate information of the signal. Enhancement is achieved by shifting the peak of the AP spectrum toward the lower firing rate frequencies, whilst maintaining the firing rate spectra. A similar result is obtained using the analytic envelope of the signal extracted using the Hilbert transform. This argument is extended to simulated EMG signals generated using a published EMG model. Detection of firing rate frequencies is obtained using phase randomised surrogate data, where the original EMG power spectrum exceeds the averaged rectified surrogate spectra at integer multiples of firing rate frequencies. Model simulations demonstrate that this technique accurately determines grouped firing rate frequencies. Extraction of grouped firing rate frequencies prior to coherency analyses may further aid interpretation of significant cortico-muscular coherence findings.

Action Potentials↗

PubMed2005

Core genetic module: the mixed feedback loop.

The so-called mixed feedback loop (MFL) is a small two-gene network where protein A regulates the transcription of protein B and the two proteins form a heterodimer. It has been found to be statistically over-represented in statistical analyses of gene and protein interaction databases and to lie at the core of several computer-generated genetic networks. Here, we propose and mathematically study a model of the MFL and show that, by itself, it can serve both as a bistable switch and as a clock (an oscillator) depending on kinetic parameters. The MFL phase diagram as well as a detailed description of the nonlinear oscillation regime are presented and some biological examples are discussed. The results emphasize the role of protein interactions in the function of genetic modules and the usefulness of modeling RNA dynamics explicitly.

Cell Physiological Phenomena↗

PubMedDate not supplied

[Induction of chromosome aberrations and micronuclei in human peripheral blood lymphocytes at low dose of radiation].

The chromosome damage induced by the doses of y-irradiation 6)Co in peripheral blood lymphocytes was studied using different cytogenetic assays. Isolated lymphocytes were exposed to 0.01-1.0 Gy, stimulated by PHA, and analysed for chromosome aberrations at 48 h postirradiation by metaphase method, at 49 h--by the anaphase method, at 58 h by micronucleus assay with cytochalasin B and, additionally, micronuclei were counted at 48 h on the slides prepared for the metaphase analysis without cytochalasin B. Despite of the quantitative differences in the amount of chromosome damage revealed by different methods all of them demonstrated complex nonlinear dose dependence of the frequency of aberrant cells and aberrations. At the dose range from 0.01 Gy to 0.05-0.07 Gy the cells had the highest radiosensitivity mainly due to chromatid-type aberration induction. With dose increasing the frequency of the aberrant cells and aberrations decreased significantly (in some cases to the control level). At the doses up to 0.5-0.7 Gy the dose-effect curves have become linear with the decreased slope compare to initial one (by factor of 5 to 10 for different criteria) reflecting the higher radioresistance of cells. These data confirm the idea that the direct linear extrapolation of high dose effect to low dose range--the procedure routinelly used to estimate genetic risk of low dose irradiation--cannot be effective and may lead to underestimation of chromosome damage produced by low radiation doses. Preferences and disadvantages of used cytogenetic assays and possible mechanisms of low ionising radiation doses action were discussed.

Cells, Cultured↗

PubMed1993

Pattern association and retrieval in a continuous neural system.

This paper studies the behavior of a large body of neurons in the continuum limit. A mathematical characterization of such systems is obtained by approximating the inverse input-output nonlinearity of a cell (or an assembly of cells) by three adjustable linearized sections. The associative spatio-temporal patterns for storage in the neural system are obtained by using approaches analogous to solving space-time field equations in physics. A noise-reducing equation is also derived from this neural model. In addition, conditions that make a noisy pattern retrievable are identified. Based on these analyses, a visual cortex model is proposed and an exact characterization of the patterns that are storable in this cortex is obtained. Furthermore, we show that this model achieves pattern association that is invariant to scaling, translation, rotation and mirror-reflection.

Animals↗

PubMed2006

A viscoelastic traction layer model of muco-ciliary transport.

A new mathematical model of the transport of mucus and periciliary liquid (PCL) in the airways by cilia is presented. Mucus is represented by a linearly viscoelastic fluid, the mat of cilia is modelled as an 'active porous medium.' The propulsive effect of the cilia is modelled by a time-dependent force acting in a shear-thinned 'traction layer' between the mucus and the PCL. The effects of surface and interface tension are modelled by constraining the mucus free surface and mucus-PCL interface to be flat. It is assumed that the epithelium is impermeable to fluid. Using Fourier series, the system is converted into ODEs and solved numerically. We calculate values for mean mucus speed close to those observed by Matsui et al. [J. Clin. Invest., 102(6):1125-1131, 1998], (approximately 40 microm s(-1)). We obtain more detail regarding the dynamics of the flow and the nonlinear relationships between physical parameters in healthy and diseased states than in previously published models. Pressure gradients in the PCL caused by interface and surface tension are vital to ensuring efficient transport of mucus, and the role of the mucus-PCL interface appears to be to support such pressure gradients, ensuring efficient transport. Mean transport of PCL is found to be very small, consistent with previous analyses, providing insight into theories regarding the normal tonicity of PCL.

Cilia↗

PubMed2026

Axial Length Adjustment and AL/R Ratio Optimization of IOL Power Calculation in Extremely Long Eyes.

PURPOSE: To evaluate the accuracy of modern intraocular lens (IOL) power calculation formulas and axial length (AL) adjustment methods in eyes with AL ≥ 30.0 mm. DESIGN: Retrospective consecutive cross-sectional study. PARTICIPANTS AND CONTROLS: A total of 308 eyes (308 patients) with AL ≥ 30.00 mm were included. METHODS: Accuracy of modern online formulas, alone or with established AL adjustments methods, was analyzed. Subgroup analyses were performed based on AL, keratometry (K), anterior chamber depth (ACD), lens thickness (LT), and AL-to-corneal radius (AL/R) ratio. MAIN OUTCOME MEASURES: Predictive accuracy was evaluated using the formula performance index (FPI), root mean square absolute prediction error (RMSAE), standard deviation (SD) of prediction error (PE), and percentage of eyes within ±0.25 and ±0.50 diopters (D). RESULTS: Overall, Holladay 1 combined with the nonlinear polynomial Wang-Koch axial length adjustment (H1-PWK) demonstrated the best overall performance, achieving the lowest SD (0.40), RMSAE (0.40), and highest FPI (0.494). A tendency toward hyperopic error was observed in eyes with AL ≥ 32.0 mm, K ≥ 46.0 D. The AL/R ratio showed a significant positive correlation with PE in the Ladas Super formula, Barrett Universal II, EVO, PEARL-DGS, and Hoffer QST formulas. Spline-based regression analysis indicated that the transition point of AL/R from myopic to hyperopic PE varied across different formulas. CONCLUSIONS: H1-PWK provides robust refractive accuracy in extremely long eyes. The AL/R ratio may provide a useful composite biometric stratification parameter compared to AL alone.

Humans↗

PubMed1998

Body mass index as a measure of adiposity among children and adolescents: a validation study.

OBJECTIVES: To test the hypothesis that in a healthy pediatric population body mass index (BMI) (kilograms per meter square) is a valid measure of fatness that is independent of age for both sexes. METHODS: Total body fat (TBF) (in kilograms) and percent of body weight as fat (PBF) were estimated by dual energy x-ray absorptiometry (DXA) in 198 healthy Italian children and adolescents between 5 and 19 years of age. We developed multiple regression analysis models with TBF and percent body fat as dependent variables and BMI, age, and interaction terms as independent variables. Separate analyses were conducted for boys and girls. RESULTS: BMI was strongly associated with TBF (R2 = 0.85 and 0.89 for boys and girls, respectively) and PBF (R2 =0.63 and 0.69 for boys and girls, respectively). Confidence limits on BMI-fatness association were wide, with individuals of similar BMI showing large differences in TBF and in PBF. Age was a significant covariate in all regression models. Addition of nonlinear terms for BMI did not substantially increase the R2 for TBF and PBF models in boys and girls. CONCLUSION: Our results support the use of BMI as a fatness measure in groups of children and adolescents, although interpretation should be cautious when comparing BMI across groups that differ in age or when predicting a specific individual's TBF or PBF.

Absorptiometry, Photon↗

PubMed2003

The charge-transfer motif in crystal engineering. Self-assembly of acentric (diamondoid) networks from halide salts and carbon tetrabromide as electron-donor/acceptor synthons.

Unusual strength and directionality for the charge-transfer motif (established in solution) are shown to carry over into the solid state by the facile synthesis of a series of robust crystals of the [1:1] donor/acceptor complexes of carbon tetrabromide with the electron-rich halide anions (chloride, bromide, and iodide). X-ray crystallographic analyses identify the consistent formation of diamondoid networks, the dimensionality of which is dictated by the size of the tetraalkylammonium counterion. For the tetraethylammonium bromide/carbon tetrabromide dyad, the three-dimensional (diamondoid) network consists of donor (bromide) and acceptor (CBr(4)) nodes alternately populated to result in the effective annihilation of centers of symmetry in agreement with the sphaleroid structural subclass. Such inherently acentric networks exhibit intensive nonlinear optical properties in which the second harmonics generation in the extended charge-transfer system is augmented by the effective electronic (HOMO-LUMO) coupling between contiguous CBr(4)/halide centers.

Journal Article↗

PubMedDate not supplied

Chromium and nickel in roadside grapes.

Chromium and nickel concentration in roadside unwashed wine grapes and leaves is considered as a function of the distance from the suspected source, an isolated straight road. The analyses were performed with electrothermal atomization in a graphite furnace. The decrease in the concentration of the element can be described by means of a three-parameter exponential function c = A + (B - A)exp(-Cd), which allows the determination of the asymptotic level far from the emitting source (C infinity) and the pollution level (C0) at the edge of the road (d = 0). Least-squares nonlinear regression gives the estimation of the parameters A, B, and C. The results indicate that an effect is detectable up to a distance of about 50 m.

Chromium↗

PubMed2005

Asymptotic approach to combustion instability.

This paper presents an asymptotic approach to combustion instability in premixed flames under the assumptions of large activation energy and small Mach number. The entire flow consists of four distinct yet fully interactive sub-regions, which accommodate the chemical reaction, heat transport, hydrodynamics and acoustics, respectively. A reduced system was derived to describe the intricate coupling between the flame and acoustics that underlies the combustion instability. The asymptotically reduced system was employed to study the weakly nonlinear interaction between the Darrieus-Landau instability and the longitudinal acoustic mode of the combustion chamber. The general asymptotic formulation includes the influence of enthalpy fluctuation in the oncoming mixture. It is shown that one-dimensional enthalpy fluctuation, through its interaction with flame, produces sound waves, and may cause parametric instability of the flame. The mutual coupling between the sound wave and parametric instability is analysed at the instability thresholds.

Journal Article↗

PubMedDate not supplied

Human frequency-following responses to two-tone approximations of steady-state vowels.

Auditory nerve single-unit population studies have demonstrated that phase-locking plays a dominant role in the neural encoding of the spectrum of speech sounds. Since the scalp-recorded human frequency-following response (FFR) reflects synchronous, phase-locked activity in a population of neurons in the rostral auditory brainstem, it was reasoned that the human FFR might preserve information about certain acoustic features of speech sounds. FFRs to three different two-tone approximations of vowels (symbols, see text) were obtained from 10 normal-hearing human adults at 85, 75, 65 and 55 dB nHL. Spectrum analyses of the FFRs revealed distinct peaks at frequencies corresponding to the first and the second formants across all levels suggesting that phase-locked activity among two distinct populations of neurons are indeed preserved in the FFR. Also, the FFR spectrum for vowels (symbols, see text) revealed a robust component at 2F1-F2 frequency suggesting that the human FFR contains a neural representation of cochlear nonlinearity. Finally, comparison of FFRs to the vowel approximations and the individual components at F1 and F2 revealed effects that may be suggestive of two-tone synchrony suppression and/or lateral inhibition. These results suggest that the scalp-recorded FFR may be used to evaluate not only neural encoding of speech sounds but also processes associated with cochlear nonlinearity.

Adolescent↗

PubMed1996

Linear and non-linear properties of heart rate in postnatal maturation.

OBJECTIVE: An investigation was made of how postnatal maturation of cardiac control can be described by linear and non-linear methods of time series analysis. METHODS: Sixteen healthy and term newborns were studied during their first 6 months of life. Power spectrum analysis including total power (TP), low frequency power (LF), high frequency power (HF) and LF/HF ratio were performed on the instantaneous heart rate (IHR) time series and mean heart rate (HR) was derived. The largest Lyapunov exponent (LLE) was calculated using a modified Wolf algorithm and checked by means of the surrogate-data test. RESULTS: There is an age dependency for the parameters LLE, HR, TP, HF, LF, LF/HF for active and LLE, HR, TP, HF, LF/HF for quiet sleep. HR is characterised by a steep increase between the 5th and 7th day. HF demonstrates a distinct development with high values around the first week and 90-180th day and low values around the 10-60th day. TP, LF and LF/HF show significantly higher values in active sleep in comparison to quiet sleep. For all ages and sleep stages, positive LLE were found, indicating sensitivity to initial conditions, a hall-mark of chaos. For the period between the 7 and 90th days of life, the LLE for active sleep took on larger values compared with the LLE of quiet sleep. CONCLUSIONS: This study shows that by linear as well as non-linear analysis one can reveal the complexity of the IHR development in humans and may gain insight into the system controlling the heart during the period considered. The positive LLE indicate that there is a non-linear component in the heart rate control. There is no "straight line" development for the parameters analysed within the first 6 months. This may result from manifold influences on the autonomic system, due to structural and functional maturation in this period of life.

Heart↗

PubMed1990

Reference data for ambulatory blood pressure monitoring: what results are equivalent to the established limits of office blood pressure?

In 1039 subjects ambulatory blood pressure monitoring was performed to define threshold values, which are equivalent to the established limits of the office blood pressure. Mean values and proportions of elevated single readings were correlated to office blood pressure by regression analyses. To avoid impact of varying sleeping periods on 24 h blood pressure, only daytime readings were considered. Correlations between average daytime blood pressure and office blood pressure were linear: Mean daytime values of 135 mmHg (systolic) and of 84 mmHg (diastolic) were equivalent to the casual blood pressure limits of 140 mmHg and 90 mmHg. Correlations between percentages of elevated single readings and office blood pressure were nonlinear: Proportions of 25% systolic readings greater than 140 mmHg and of 17% diastolic readings greater than 90 mmHg were equivalent to casual blood pressure limits of 140 mmHg and 90 mmHg. On the basis of the regression equations, any result of ambulatory blood pressure recording during daytime can now be evaluated in terms of the established standards of office blood pressure.

Blood Pressure Monitors↗

PubMed2001

Speciation, introgressive hybridization and nonlinear rate of molecular evolution in flycatchers.

Evolutionary history of Muscicapidae flycatchers is inferred from nuclear and mitochondrial DNA (mtDNA) sequence comparisons and population genetic analysis of nuclear and mtDNA markers. Phylogenetic reconstruction based on sequences from the two genomes yielded similar trees with respect to the order at which the species split off. However, the genetic distances fitted a nonlinear, polynomial model reflecting diminishing divergence rate of the mtDNA sequences compared to the nuclear DNA sequences. This could be explained by Haldane's rule because genetic isolation might evolve more rapidly on the mitochondrial rather than the nuclear genome in birds. This is because hybrid sterility of the heterogametic sex (females) would predate that of the homogametic sex (males), leading to sex biased introgression of nuclear genes. Analyses of present hybrid zones of pied (Ficedula hypoleuca) and collared flycatchers (F. albicollis) may indicate a slight sexual bias in rate of introgression, but the introgression rates were too low to allow proper statistical analyses. It is suggested, however, that the observed deviation from linearity can be explained by a more rapid mutational saturation of the mtDNA sequences than of the nuclear DNA sequences, as supported by analyses of third codon position transversions at two protein coding mtDNA genes. A phylogeographic scenario for the black and white flycatcher species is suggested based on interpretation of the genetic data obtained. Four species appear to have diverged from a common ancestor relatively simultaneously during the Pleistocene. After the last glaciation period, pied and collared flycatchers expanded their breeding ranges and eventually came into secondary contact in Central and Eastern Europe and on the Baltic Isles.

Animals↗