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PubMed2001

The relation of glycaemia to the risk of development and progression of retinopathy in the Diabetic Control and Complications Trial.

AIMS/HYPOTHESIS: We have assessed the relation between the quarterly capillary glucose profile and the risk of the development and progression of retinopathy in the DCCT. METHODS: Seven point (preprandial and 90-min postprandial for each meal and bedtime) capillary glucose data were analysed from volunteers whose collections were complete in 80 %, or more, of quarterly periods and who were in the study longer than 4 years (n = 296, conventional therapy; n = 269, intensive therapy). The study cohort differed from excluded patients in having more women and lower HbA(1c) at baseline and fewer adolescents, older age and lower baseline mean blood glucose in the intensive therapy group. RESULTS: Univariate analysis showed significant (p < 0.01) associations to sustained 3-step change in retinopathy of each updated glycaemic parameter: mean blood glucose, mean preprandial glucose, mean postprandial glucose, each preprandial, postprandial and bedtime glucose; range glucose, standard deviation glucose; M-value of Schlichtkrull and mean amplitude of glycaemic excursions, albeit with relatively small hazard ratios. Multivariate analyses showed updated mean blood glucose to be the primary risk factor (p < 0.001) with a weak contribution of mean amplitude of glycaemic excursions at baseline (p < 0.005); no other variables added significantly to the model. The association between updated mean blood glucose and risk for retinopathy was nonlinear: risk progressively increased above updated mean blood glucose of 8.3 mmol/l. A gradient of risk could not be determined below this level because events were few. CONCLUSION/INTERPRETATION: Within the limitations provided by quarterly 7-point capillary glucose measurements as an expression of overall glycaemic behaviour, the major risk for progression of retinopathy is conveyed by updated mean blood glucose especially above 8.3 mmol/l.

Adolescent↗

PubMed1985

Leukocyte distribution to arteriolar branches: dependence on microvascular blood flow.

Leukocyte distribution to arteriolar branches in the hamster cheek pouch microvasculature was studied by rendering the cells fluorescent via a constant intravenous infusion of acridine orange. A principal objective was to determine the major factors influencing the partitioning of the cellular flux between daughter branches at arteriolar branch points with internal diameters permitting single-file leukocyte flow. Leukocyte flux determinations (cells/sec) and individual cell velocities were made for over 8000 cells at 13 branch sites in 10 animals. The results indicate that for the branch flow ratios of 0.3 to 0.7 encountered in the present experiments, the predominant factor influencing the average leukocyte flux is the branch blood flow. Branch fractional flux dependence on fractional blood flow was analyzed using linear and nonlinear models. A linear characterization provided an excellent fit and description of the functional relationship but a slight nonlinear component was also predicted by the nonlinear sigmoidal model which also fit the data well. Because of the small degree of predicted nonlinearity and the overlap of the standard deviations of the parameter estimates, we were not able to statistically decide on which model, and hence which functional relationship, is operative. Thus, the answer to the question regarding the presence of any preferential distribution is inconclusive. However, the data and analyses suggest that if preferential distribution is operative, its magnitude over the flow range and conditions here studied is small, and that for many purposes the relationship between the in vivo average fractional cell flux and blood flow may be viewed as linear.

Animals↗

PubMed1994

Biomechanics of small bowel motility.

A biomechanical model and results of numerical simulation of the propagation of electromechanical waves of deformation along the small bowel are presented. The organ is modelled as a soft orthotropic cylindrical biological shell reinforced by orthogonally interwoven smooth muscle elements, embedded in a connective tissue network. The dynamic reaction starts as a response to the propagation of a depolarization wave along the smooth muscle layers. The muscle layers contract independently but in a coordinated way with the generation of active forces. The mechanical properties of the wall are assumed to be nonlinear. Deformations of the bioshell are finite. The governing system of equations is obtained and solved numerically. The finite-difference method of the second order accuracy over the time and space variables was used. The dynamics of strain distribution in the biological shell and shape changes are analysed.

Biomechanical Phenomena↗

PubMed2004

Model development and numerical simulation of electric-stimulus-responsive hydrogels subject to an externally applied electric field.

Based on a multi-phasic mixture theory with consideration of ionic diffusion and convection, a multi-physic model, called the multi-effect-coupling electric-stimulus (MECe) model, is developed for simulation of responsive behavior of the electric-sensitive hydrogels when they are immersed into a bathing solution subject to an externally applied electric field. In the developed model, with chemo-electro-mechanical coupling effects, the convection-diffusion equations for concentration distribution of diffusive ions incorporate the influence of electric potential. The electroneutrality condition is replaced by the Poisson equation for distribution of electric potential. The steady and transient analyses of hydrogel deformation are easily carried out by the continuity and momentum equations of the mixture phase. Further, the computational domain of the present model covers both the hydrogel and the surrounding solution. In order to solve the present mathematical model consisting of multi-field coupled nonlinear partial differential governing equations, a hierarchical iteration technique is proposed and a meshless Hermite-Cloud method (HCM) is employed. The steady-state simulation of the electric-stimulus responsive hydrogel is numerically conducted when it is subjected to an externally applied electric field. The hydrogel deformation and the ionic concentrations as well as electric potentials of both the hydrogel and external solution are investigated. The parameter influences on the swelling behaviors of the hydrogel are also discussed in detail. The simulating results are in good agreement with the experimental data and they validate the presently developed model.

Biosensing Techniques↗

PubMed2005

A distributed computing system for multivariate time series analyses of multichannel neurophysiological data.

We present a client-server application for the distributed multivariate analysis of time series using standard PCs. We here concentrate on analyses of multichannel EEG/MEG data, but our method can easily be adapted to other time series. Due to the rapid development of new analysis techniques, the focus in the design of our application was not only on computational performance, but also on high flexibility and expandability of both the client and the server programs. For this purpose, the communication between the server and the clients as well as the building of the computational tasks has been realized via the Extensible Markup Language (XML). Running our newly developed method in an asynchronous distributed environment with random availability of remote and heterogeneous resources, we tested the system's performance for a number of different univariate and bivariate analysis techniques. Results indicate that for most of the currently available analysis techniques, calculations can be performed in real time, which, in principle, allows on-line analyses at relatively low cost.

Algorithms↗

PubMed2000

Peripheral blood stem cell collection: the interaction of technology, procedure, and biological factors.

Centrifugal technology, continuous flow and discontinuous flow, has served as the technology platform for extracting cell concentrates of interest from peripheral blood (PB) for patient therapy for the past 35-40 yr. Models for procedure outcome exist for collection of normal donor (ND) platelet and granulocyte concentrates that integrate: (1) biological variables (pre-procedure PB cell concentration, the total circulating quantity of cells, donor/patient blood volume (BV)), (2) device efficiency, and (3) procedure parameters such as total blood processed (TBP), and in the case of cytoreductions - the volume collected. (cf. Hester J, Kellogg R, Mulzet A, et al., Blood (54) (1979) 254; Hester J, Ventura G, J Clin Apheresis (4) (1988) 188.) To date, no predictive CD34+ yield algorithm integrating these three variables has been formulated that could be applied prospectively for individual ND or patients (PT). There are economic, toxicity and statistical comparison benefits to be derived from generating such an algorithm.A small pilot study is presented with a brief review of current publications that suggest the circulating quantity of CD34+ cells available to be collected and the quantity mobilized during leukapheresis are the major contributing factors to CD34+ yield, somewhat obscuring the role of the total blood processed (TBP). Intraprocedure CD34+ cell mobilization, incompletely characterized to date, appears to be a dynamic nonlinear process, as the harvested yield does not rise proportionally as the fraction of BV processed increases. And, like the pre-procedure PB CD34+ concentration and total circulating quantity, CD34+ mobilization during leukapheresis probably relates to prior treatment and the priming regimen. Studies that provide: (1) separate analyses of PT populations divided according to chemotherapy toxicity factors; (2) design and implementation of optimal priming regimens with respect to dose 'intensity' of both growth factors and chemotherapy; and (3) standardization of laboratory assays of CD34+ enumeration seem essential to generating a predictive algorithm.

Algorithms↗

PubMed1999

Methodology for pharmacokinetic/pharmacodynamic data analysis.

This review will highlight the role of exploratory data analysis and nonlinear regression software in pharmacokinetic-pharmacodynamic (PK/PD) data analysis. Kinetic and dynamic modelling situations typical to the pharmacokineticist in the drug industry will be addressed, and two case studies, including single-dose intravenous bolus plasma data and multiple-dose response-time data will be analysed. Approaches to assessing the suitability of model fit to the observed data will be discussed, and a summary of the key features of available commercial PK software will be given. Specific emphasis will be placed on the application of WinNonlin.

Journal Article↗

PubMed2006

Self-assembled monolayers of dipolar nonlinear optical nickel(II) molecules on the Si(100) surface with nanoscale uniformity.

The synthesis and structure of a dipolar nonlinear optical bis(salicylaldiminato)Ni(II)-derivatized Schiff base complex chemisorbed on H-terminated Si(100) surfaces is reported. The existence of a monolayer of the derivatized complex chemisorbed on the Si(100) surface is unambiguously confirmed by high-resolution core-level XPS and AFM/SNOM analyses. The comparison between the optical SNOM images highlights the contribution of the monolayer to the local reflectivity of the sample. Angle-resolved XPS data indicate the presence of chlorine head atoms on the monolayer surface. Altogether, XPS and AFM/SNOM data suggest the formation of a nanoscale uniform, homogeneous, complete, ordered monolayer self-assembled on the Si(100) surface.

Journal Article↗

PubMed1995

A two-step iterative algorithm for estimation in nonlinear mixed-effect models with an evaluation in population pharmacokinetics.

This article proposes an EM-like algorithm for estimating, by maximum likelihood, the population parameters of a nonlinear mixed-effect model given sparse individual data. The first step involves Bayesian estimation of the individual parameters. During the second step, population parameters are estimated using a linearization about those Bayesian estimates. This algorithm (implemented in P-PHARM) is evaluated on simulated data, mimicking pharmacokinetic analyses and compared to the First-Order method and the First-Order Conditional Estimates method (both implemented in NONMEM). The accuracy of the results, within few iterations, shows the estimation capabilities of the proposed approach.

Algorithms↗

PubMed2000

Dynamics of pulsed holmium:YAG laser photocoagulation of albumen.

The pulsed holmium:YAG laser (lambda = 2.12 microm, tau(p) = 250 micros) has been investigated as a method for inducing localized coagulation for medical procedures, yet the dynamics of this process are not well understood. In this study, photocoagulation of albumen (egg white) was analysed experimentally and results compared with optical-thermal simulations to investigate a rate process approach to thermal damage and the role of heat conduction and dynamic changes in absorption. The coagulation threshold was determined using probit analysis, and coagulum dynamics were documented with fast flash photography. The nonlinear computational model, which included a Beer's law optical component, a finite difference heat transfer component and an Arrhenius equation-based damage calculation, was verified against data from the literature. Moderate discrepancies between simulation results and our experimental data probably resulted from the use of a laser beam with an irregular spatial profile. This profile produced a lower than expected coagulation threshold and an irregular damage distribution within a millisecond after laser onset. After 1 ms, heat conduction led to smoothing of the coagulum. Simulations indicated that dynamic changes in absorption led to a reduction in surface temperatures. The Arrhenius equation was shown to be effective for simulating transient albumen coagulation during pulsed holmium:YAG laser irradiation. Greater understanding of pulsed laser-tissue interactions may lead to improved treatment outcome and optimization of laser parameters for a variety of medical procedures.

Albumins↗

PubMed1989

Development of the convenient and direct numerical analytical method of the pharmacokinetics of phenytoin by an ordinary and/or the Bayesian weighted least-squares method using the program MULTI2(BAYES).

A Simple and convenient numerical integration method was developed for the purpose of analyzing the pharmacokinetics of phenytoin not only at steady state but also at non-steady state. The algorithm was linked on a nonlinear least-squares method program MULTI2(BAYES). The computing time was significantly decreased compared to Runge-Kutta-Gill Method at analysis by the Simplex algorithm and calculating precision was higher, especially at a large integration interval. This method was found to be sufficiently applicable to the analyses of the serum concentrations of phenytoin at non-steady state as well as at steady state and the dosage adjustment by simulation. The flexibility of analyzed parameters on a microcomputer can be overcome by analyzing at the integration subinterval smaller than 0.25 h with the appropriate initial values of parameters, although very time consuming, or by using the Bayesian method with appropriate population parameters.

Bayes Theorem↗

PubMed1993

Acculturation and hypertension in Mexican Americans.

In this analysis, we employ data from the Hispanic Health and Nutrition Examination Survey to examine the association between level of acculturation into the larger society and rates of hypertension in Mexican Americans. Analyses conducted separately by gender in three broad age groups (ages 20 to 39, 40 to 59, and 60 to 74 years) fail to indicate a linear effect of acculturation on hypertension after controlling for age, education, marital status, employment, smoking, alcohol consumption, and body mass index. A nonlinear hypothesis was subsequently examined and found partial support among middle-aged men. Other things equal, middle-aged men at the middle of the acculturation continuum have significantly higher rates of hypertension than persons at the low end of the continuum. Lower rates are also observed among men at the high end of the acculturation continuum, but these rates are not significantly lower than those among men in the middle acculturation group when other variables are controlled. These findings for middle-aged men support an "acculturative stress" model that suggests that stress is higher at the middle of the acculturation continuum. Research on the influence of acculturation on health outcomes should go beyond simply examining linear effects to investigate the viability of nonlinear effects.

Acculturation↗

PubMed1996

Wealth Accumulation across the Adult Life Course: Stability and Change in Sociodemographic Covariate Structures of Net Worth Data in the Survey of Income and Program Participation, 1984-1991

This paper reports microlevel Tobit regression analyses of sociodemographic covariates of the life course accumulation of total household net worth data in eight waves of five distinct panels-spanning over 6 years from late 1984 through early 1991-of the Survey of Income and Program Participation (SIPP). It is found that the quadratic age-wealth relationship predicted by Modigliani's Life Cycle Hypothesis is evident in aggregate age-median wealth profiles as well as in the micro data for households with positive net worth. However, when adult status attainment variables are entered into the regression models either by themselves or in combination with marital/family status variables, the age of household head at which net worth begins to decline is far beyond the typical retirement age. In addition, the traditional criterion variables of sociological status attainment theory-educational attainment, occupational status, and earnings-are found to be positively associated with household net worth, although the net effect of occupational status generally is not statistically significant and the earnings effect is nonlinear. Further, consistent with status attainment theory, householder minority status (black, Hispanic) is negatively associated with the accumulation of net worth. It is found that both single male and single female householder status are negatively associated with the accumulation of household net worth (relative to married couple households) as is the size of the household (measured by the number of children under age 18 present). Separate logistic regression analyses show that households with zero and negative net worth are more likely than households with positive net worth to be black and have low earnings. Higher levels of educational and occupational status attainment reduce the probability of zero net worth but not the probability of negative net worth. Male- and female-headed households and households headed by Hispanics also are more likely to have zero net worth, but not negative net worth. The estimated sociodemographic covariate structures of household net worth are found to exhibit substantial stability across both waves and panels in the SIPP-although effects of the 1990-1991 recession are detectable in estimates for the 1990 panel. Possible applications of the estimated models in demographic projections of household net worth are suggested.

Journal Article↗

PubMed1995

Bootstrap estimated uncertainty of the dominant Lyapunov exponent for Holarctic microtine rodents.

The dominant Lyapunov exponent, as estimated from time series using the Jacobian-based method, is often used for indicating whether the underlying dynamic system is chaotic or not. The Jacobian-based method together with Response Surface Methodology has been suggested as a method for detecting chaotic dynamics in ecological time series. Besides pointing out that this may not be an appropriate method, we report on estimates of the uncertainty in the estimates of the dominant Lyapunov exponent. For this purpose, we have used time series data on Holarctic microtines. On the basis of our analyses, we are unable to find general evidence for chaotic dynamics in northern microtine populations (north of 60 degrees N) as recently suggested in the ecological literature. It seems, however, that the dynamic properties of the northern and southern populations are different. These patterns are supported by testing for nonlinearity.

Animals↗

PubMed1997

New approach to studies on ECG dynamics: extraction and analyses of QRS complex irregularity time series.

How to extract information intensively from ECGs for the diagnosis of cardiovascular diseases and assessment of heart function is a topical subject. Using a method based on the wavelet transform to calculate the irregularity of the QRS complex, which may relate to inotropy, the QRS complex irregularity time series is successfully extracted from original ECG signals. This provides a new approach to studies of ECG dynamics. With the help of non-linear dynamics theory, the QRS complex irregularity time series of eight subjects from the MIT/BIH arrhythmia database are studied qualitatively and quantitatively, and the characteristics of ECG dynamics are analysed extensively. The power spectrum, phase portrait, correlation dimension, largest Lyapunov exponent, time-dependent divergence exponent and complexity measure all verify the fact that ECG dynamics are dominated by an underlying 5-6-dimensional non-linear chaotic system, whose complexity measure is about 0.7. The QRS complex irregularity time series contains abundant information about all parts of the heart and the regulation of the autonomic nervous system, and so further analyses are of great potential theoretical and clinical significance to patho-physiology studies and ambulatory monitoring.

Cardiovascular Diseases↗

PubMed1998

Non-linear dynamic complexity of the human EEG during evoked emotions.

The present study examined EEG dimensional complexity (estimated correlation dimension) in 76 healthy volunteers in response to emotionally valenced (i.e. neutral, positive and negative) film clip stimulation. EEG was recorded from 18 sites (10-20 system). We estimated the dimensional complexity by the Grassberger and Procaccia and Skinner's point-wise dimension (PD2i) methods. The results were compared to spectral measures of the EEG. Only the PD2i algorithm (i.e. the one that did not require data stationarity) discriminated among all the three film categories. The main results showed that both negative and positive emotions occurred with higher values (at some posterior locations) of EEG DCx estimates compared to the neutral viewing condition. The topographical differences (frontal vs. posterior temporal) between positive and negative evoked emotions were obtained. There were also some significant direct relationships between dynamic complexity estimates and intensities of subjective emotional feelings. It is concluded that dimensional complexity estimates turned out to be sensitive to subtle aspects of emotional processing not accessible by linear EEG analyses.

Adolescent↗

PubMed2003

[To understand blood pressure and heart rate variability].

OBJECTIVES: To review current data on the heart rate and blood pressure variability. DATA SOURCES: Search through Medline databases of articles in french or english. DATA SELECTION: Original articles and case reports were selected according to their quality and main advances. The articles were analysed in order to obtain current data about the methods of study and clinical application of blood pressure and heart rate variability. DATA SYNTHESIS: Various regulatory systems in the cardiovascular system play crucial roles in controlling and assuring adequate perfusion of the peripheral tissues. Among them the baroreceptor reflex is the most important regulatory mechanism in the short-term control of the heart rate and blood pressure, and operates through the autonomic nervous system. The gain of the cardiac baroreflex further referred to, as baroreflex sensitivity is an interesting way to study this system. Unfortunately, with our current knowledge, it is not possible to predict the instantaneous output of the baroreceptor in response to instantaneous changes in input within a frequency range of physiological importance. The fast Fourier transform can describe variables as the sum of elementary oscillatory components and it has been established as practical clinical methods for detecting abnormalities in cardiovascular control. A time-frequency distribution provides an indication of how the spectral energy distribution varies with time and it is an interesting tool in non-stationary data. One of the major motivations behind spectral analysis is the hope that the combination of time-domain and frequency-domain analyses will provide dynamical informations about the relation between blood pressure and heart rate.

Animals↗

PubMed2004

Dendritic oligoguanidines as intracellular translocators.

A series of polyguanidylated dendritic structures that can be used as molecular translocators have been designed and synthesized based on nonpeptide units. The dendritic oligoguanidines conjugated with fluorescein or with a green fluorescent protein (GFP) mutant as cargos were isolated and characterized. Quantification and time-course analyses of the cellular uptake of the conjugates using HeLa S3 and human cervical carcinoma cells reveal that the polyguanidylated dendrimers have comparable translocation efficiency to the Tat(49-57) peptide. Furthermore, the deconvolution microscopy image analysis shows that they are located inside the cells. These results clearly show that nonlinear, branched dendritic oligoguanidines are capable of translocation through the cell membrane. This work also demonstrates the potential of these nonpeptidic dendritic oligoguanidines as carriers for intracellular delivery of small molecule drugs, bioactive peptides, and proteins.

Biopolymers↗