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Daily physical activity and the use of a walking aid in relation to falls in elderly people in a residential care setting.

Physical activity is usually considered as an important component of a healthy lifestyle, including a preventive effect on the risk of falls in the elderly. The relationship between physical activity and falls is complex: physical activity is a prerequisite to maintain neuromuscular functioning, necessary to keep balance and to react to a fall, but a higher level of physical activity also implies a greater exposure to environmental threats, possibly leading to a fall. Related to this greater exposure to threats, the use of a walking aid may protect against falls in those who have impaired mobility. In this cross-sectional study we investigated the relationship between daily physical activity and falls and the use of a walking aid in elderly subjects. Participants were 131 men and 563 women, aged 70 years and over (mean age and standard deviation: 82+/-6 years), living in homes for the elderly (n=335) and apartment houses for elderly (n=359). Data on baseline characteristics and falls in the previous year were obtained using a questionnaire. The level of daily physical activity in the previous year was obtained by means of a questionnaire regarding household and leisure activities. Subjects with a lower extremity fracture in the previous year were excluded from the analyses. Data were analysed using multiple logistic regression, adjusted for age, gender, and residence. In the past year, 40% of the participants fell at least one time, and 19% of the participants fell two times or more. Since falls and recurrent falls were nonlinearly related to the level of daily physical activity, the physical activity score was grouped into quartiles: the highest quartile corresponding to the highest activity level. Odds ratios (and 95% confidence intervals) for falls and recurrent falls for subjects in the highest quartile contrasted with those in the lowest quartile were 0.5 (0.3-0.9) and 0.3 (0.2-0.6), respectively. The risk of falls and recurrent falls was not lower for those with intermediate levels of daily physical activity. The use of a walking aid protected against falls in those with intermediate high activity levels (third quartile). It was suggested that the exposure to environmental hazards, due to some degree of physical activity may have been responsible for the nonlinear relationship between daily physical activity and falling. We conclude that a high activity level and the use of a walking aid may protect against falls.

Accidental Falls↗

Inherent correlation between dose and clearance in therapeutic drug monitoring settings: possible misinterpretation in population pharmacokinetic analyses.

During the course of therapeutic drug monitoring (TDM), doses are adjusted to attain a target concentration range and a correlation between clearance (CL) and dose is introduced. In population pharmacokinetic analyses of such TDM data, CL has frequently been modeled as a function of dose. This paper demonstrates by simulation methodology that the TDM process does indeed introduce a correlation between dose and CL which can be interpreted as a nonlinearity. Using literature values of carbamazepine pharmacokinetics, three steady-state concentrations were simulated following a standard 1000 mg total daily dose (TDD) regimen in 100 in silico subjects. A set of clinical rules was established to adjust the TDD based on these three concentrations, as might be done in the clinical setting. Another set of concentrations using these TDM-derived TDDs for each subject (600-1600 mg) was simulated. A standard population pharmacokinetic analysis of the post-TDM data was conducted using NONMEM. This process was replicated 100 times to estimate the type II error rate. When CL was modeled without TDD, plots of WRES versus PRED demonstrated a clear pattern, as did the delta plots of CL (CL minus TVCL) versus TDD, suggesting the covariate TDD should be incorporated into the model. After TDD was included in the model for CL, the objective function value decreased by an average of 75.7 (p < 0.001). In addition, the inter-individual variability in CL expressed as a coefficient of variation decreased by an average of 9.9% and the diagnostic plots improved. Although CL was simulated to be independent of TDD, it was identified as an important covariate using standard approaches in a simulated TDM setting in 100% of the replicated simulation studies. The TDM process introduces a correlation between CL and TDD that can be misinterpreted as nonlinearity in the system.

Analgesics, Non-Narcotic↗

Steady-state two-dimensional maps of very alkaline proteins in an immobilized pH 10-12 gradient, as exemplified by histone types.

Two-dimensional steady-state patterns of histones are here reported for the first time. The first dimension run consists in nonlinear immobilized pH gradients, spanning the pH 10-12 range. The second dimension run is a standard SDS-PAGE in a constant concentration (15% T) gel slab, in presence of a 6% T stacking gel. All the histone fractions analysed (II-AS, VI-S, VII-S and VIII-S) exhibit pI values between pH 11 and 12. The M(r) values range from 13 to 32 kDa, with the heaviest distribution around 18 kDa. When running all different histone fractions in a single mixture, and analysing the 2-D gel by computerized image data acquisition, a total of 35 individual spots is detected.

Electrophoresis, Agar Gel↗

Interconversion of metarhodopsins I and II: a branched photointermediate decay model.

Flash photolysis experiments designed to monitor the establishment of the metarhodopsin I to metarhodopsin II equilibrium are interpreted according to a branched model in which two spectrally indistinguishable but kinetically distinguishable forms of metarhodopsin II are postulated to exist in equilibrium with a common pool of metarhodopsin I. This interpretation arises from the consistent requirement for at least three exponentials for a valid description of the observed growth of absorbance at 380 nm following bleaching of bovine rhodopsin in rod outer segment disk membranes. Analysis of the 380-nm transient absorbance data permitted direct determination of the five physically interpretable individual rate constants of the model. This analysis represents a more explicit interpretation of kinetic data than that employed in earlier experiments of this kind, which involved estimating only apparent rates and apparent amplitudes of discrete multiexponential functions. The 380-nm absorbance contributions of all relevant species contributing to the observed dynamic absorbance change were accounted for simultaneously during nonlinear least-squares estimation of the model rate parameters. Analysis of deconvoluted equilibrium spectra acquired from samples identical with those used in the kinetics experiments confirmed the metarhodopsin I-metarhodopsin II equilibrium constants, Keq, derived from the dynamic analyses. It is shown that Keq varies from 1.28 at 10 degrees C to 7.3 at 37 degrees C and that approximately 90% of the metarhodopsin II present is in the form of metarhodopsin IIslow over the temperature range 10-37 degrees C. A physical interpretation of this decay model is discussed in the context of a distribution of metarhodopsin II structural and energetic states.

Cell Membrane↗

Employing simulated data to illustrate an important cause of the 'steepling' effect in breath alcohol analysis.

The 'steepling' effect (large excursions in analytical data over time) is a debated issue in forensic breath alcohol analysis with various explanations being postulated. Simulated breath alcohol data was generated according to a hypothetical kinetic model where single random samples as well as means of duplicate random samples were plotted with respect to time at 0.2 hour intervals. In addition, the simulated data was compared when both two or more digit treatment was employed. Results showed the occurrence of significant noise or 'steepling' when single, two-digit breath alcohol samples were employed as compared to a four-digit mean computed from three-digit duplicates. The magnitude of variability was quantified by means of nonlinear regression resulting in the residual sum of squares (RSS) = 0.00202 for the single analysis and RSS = 0.00053 for the mean of duplicates. The method of data collection and treatment appears to contribute significantly to the 'steepling' phenomenon. Intuitively, replicate analyses reduce variability and allow for more accurate kinetic modelling employing breath alcohol analysis.

Alcoholic Intoxication↗

Testing the fit of a regression model via score tests in random effects models.

This paper considers testing the goodness-of-fit of regression models. Emphasis is on a goodness-of-fit test for generalized linear models with canonical link function and known dispersion parameter. The test is based on the score test for extra variation in a random effects model. By choosing a suitable form for the dispersion matrix, a goodness-of-fit test statistic is obtained which is quite similar to test statistics based on non-parametric kernel methods. We consider the distribution of the test statistic and discuss the choice of the dispersion matrix. The testing method can handle models with continuous and discrete covariates. Corrections for bias when parameters are estimated are available and extensions to models with unknown dispersion parameters, and more general nonlinear models are discussed. The proposed goodness-of-fit method is demonstrated in a simulation study and on real data of bone marrow transplant patients. The individual contributions of observations to the test statistic are used to perform residual analyses.

Age Factors↗

Deterministic and stochastic features of rhythmic human movement.

The dynamics of rhythmic movement has both deterministic and stochastic features. We advocate a recently established analysis method that allows for an unbiased identification of both types of system components. The deterministic components are revealed in terms of drift coefficients and vector fields, while the stochastic components are assessed in terms of diffusion coefficients and ellipse fields. The general principles of the procedure and its application are explained and illustrated using simulated data from known dynamical systems. Subsequently, we exemplify the method's merits in extracting deterministic and stochastic aspects of various instances of rhythmic movement, including tapping, wrist cycling and forearm oscillations. In particular, it is shown how the extracted numerical forms can be analysed to gain insight into the dependence of dynamical properties on experimental conditions.

Forearm↗

[Time variant bispectral analysis based on adaptive recursive Fourier transformation].

An appropriate investigation of quadratic phase couplings (QPC) in non-stationary signals requires time-variant methods of bispectral analysis. A new approach for time-variant estimation of power spectrum and bispectrum based on an adaptively, recursively estimated Fourier transform (ADFT) is presented in this paper. A reduced calculation effort and the possibility of the calculation of the bispectrum for selected frequency triples are important advantages of this method. Because of the recursive calculation, the ADFT is convenient for analysing ongoing signals. This will be demonstrated for simulated and real biomedical signals.

Electroencephalography↗

Alpha rhythms: noise, dynamics and models.

Alpha rhythms appear as sinusoidal-like oscillations in the electroencephalogram (EEG) within the frequency range 8-12 Hz that waxe and wane in a more or less irregular way. The irregularity may have various origins. It may be due to noise or the oscillations may have an intrinsic irregular character, e.g. they may be generated by chaotic processes [Jansen (1991) Quantitative analysis of electroencephalograms: is there chaos in the future? Int. J. Biomed. Comput., 27: 95-123; Pradham, N. and Dutt, D.N. (1993) A nonlinear perspective in understanding the neurodynamics of EEG. Comput. Biol. Med., 23: 425-442; Pritchard et al. (1995) Dimensional analysis of resting human EEG II: Surrogate-data testing indicates nonlinearily but not low-dimensional chaos. Psychophysiology. 32: 486]. The term noise is often used in neurophysiology with different connotations as pointed out by Bullock (1990), either meaning an unwanted signal from the point of view of the receiver of a message, or a signal with intrinsic random fluctuations, i.e. with a stochastic character. Here we consider noise in this sense, as random or quasi-random neural activity. In this overview, we concentrate on the question of whether alpha rhythms should be considered generated in neuronal networks (1) as forms of filtered noise, (2) as deterministic oscillations influenced by noise or (3) as the result of chaotic dynamics. A clear answer to this question can have theoretical value because it may lead to a general model of the generation of this important EEG signal. Such a model, of course, would be a macroscopic one, since it would primarily account for the properties of the alpha rhythms at the neuronal network level. A translation of these properties to the microscopic, i.e. neuronal, level will not be easy to achieve without more direct knowledge of the membrane and synaptic basic properties of the neurons involved. Here we consider the question formulated above by presenting some relevant experimental evidence and theoretical arguments. The consideration whether alpha rhythms may have noise or chaotic sources implies examining how and where such sources can occur in the neuronal networks of the brain. Therefore we present, first, some basic data regarding the possible origin of noise and of chaos in neuronal networks. Second, the signal analysis methods that have to be applied in order to discriminate between filtered noise activities and chaotic oscillations are introduced. Third, the implications of these signal analyses regarding the possible answer to the initial question are discussed.

Alpha Rhythm↗

Integral equation models for endemic infectious diseases.

Endemic infectious diseases for which infection confers permanent immunity are described by a system of nonlinear Volterra integral equations of convolution type. These constant-parameter models include vital dynamics (birth and deaths), immunization and distributed infectious period. The models are shown to be well posed, the threshold criteria are determined and the asymptotic behavior is analysed. It is concluded that distributed delays do not change the thresholds and the asymptotic behaviors of the models.

Communicable Diseases↗

Receptor-recycling model of clearance and distribution of insulin in the perfused mouse liver.

After perfusion of mouse livers with A14-125I-insulin for designated intervals, an acid-wash technique was employed to separately measure the surface-bound (Xs) and intracellular (Xi) A14-125I-insulin, as well as intracellular degradation products (Xdeg) of labelled insulin. From the perfusate concentrations (Cp) of A14-125I-insulin, the apparent intrinsic hepatic clearance of labelled insulin at a high dose (0.2 nmol/l) was shown to be 60% smaller than that at a low dose (0.018 nmol/l), indicating that the cellular uptake of insulin is remarkably nonlinear at the concentration range examined. From the time courses of Cp, Xs, Xi and Xdeg, the hepatic insulin disposition was shown to be largely accounted for by the receptor-mediated endocytosis. The observed data at the low dose were analysed to estimate biochemical parameters, (i.e., total receptor number, endocytotic rate constant and intracellular degradation rate constant) according to "receptor-recycling" and "non-receptor-recycling" models, using a computer-aided optimization procedure. The "receptor-recycling" model could not only adequately explain the Cp, Xs, Xi and Xdeg at the low dose, but also predict the Cp at the high dose. On the other hand, a "non-receptor-recycling" model, in which recycling of receptors was not assumed, could also explain the observed data at the low dose, but failed to predict the Cp at the high dose, indicating that the receptor recycling process is necessary to explain the hepatic insulin clearance at high insulin concentrations, at which hepatic insulin clearance should be limited by the rate of receptor recycling.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Risk assessment for benefits analysis: framework for analysis of a thyroid-disrupting chemical.

Benefit-cost analysis is of growing importance in developing policies to reduce exposures to environmental contaminants. To quantify health benefits of reduced exposures, economists generally rely on dose-response relationships estimated by risk assessors. Further, to be useful for benefits analysis, the endpoints that are quantified must be expressed as changes in incidence of illnesses or symptoms that are readily understood by and perceptible to the layperson. For most noncancer health effects and for nonlinear carcinogens, risk assessments generally do not provide the dose-response functions necessary for economic benefits analysis. This article presents the framework for a case study that addresses these issues through a combination of toxicology, epidemiology, statistics, and economics. The case study assesses a chemical that disrupts proper functioning of the thyroid gland, and considers the benefits of reducing exposures in terms of both noncancer health effects (hypothyroidism) and thyroid cancers. The effects are presumed to be due to a mode of action involving interference with thyroid-pituitary functioning that would lead to nonlinear dose response. The framework integrates data from animal testing, statistical modeling, human data from the medical and epidemiological literature, and economic methodologies and valuation studies. This interdisciplinary collaboration differs from the more typical approach in which risk assessments and economic analyses are prepared independently of one another. This framework illustrates particular approaches that may be useful for expanded quantification of adverse health effects, and demonstrates the potential of such interdisciplinary approaches. Detailed implementation of the case study framework will be presented in future publications.

Animals↗

Influence of source geometry and materials on the transverse axis dosimetry of 192Ir brachytherapy sources.

Monte Carlo dose rates on the transverse axis in water and air kerma strengths normalized to unit source activity were calculated for a low dose rate steel-clad 192Ir source. MicroSelectron high dose rate and pulsed dose rate 192Ir sources, and a VariSource high dose rate 192Ir source, as well as five other hypothetical cylindrical 192Ir source designs. Based on these results, the dependence of dose rate and air kerma strength on source geometry and materials was analysed. Source geometry and attenuation in the core material are the important factors determining basic dosimetric characteristics. Core length, h, only affects the dose rate on the transverse axis at radial distances r < 4 h, over which the dose rate decreases nonlinearly with increasing core length. By comparison, core diameter, d, influences the air kerma strength and dose rate at all radial distances; these decrease linearly with increasing core diameter. Based on their dosimetric characteristics, pertinent dosimetry modelling for four actual 192Ir sources is suggested, and similarities and differences in the dose rate constant and radial dose function between these sources are explained.

Air↗

Overview of quantitative measurement methods. Equivalence, invariance, and differential item functioning in health applications.

BACKGROUND: Reviewed in this article are issues relating to the study of invariance and differential item functioning (DIF). The aim of factor analyses and DIF, in the context of invariance testing, is the examination of group differences in item response conditional on an estimate of disability. Discussed are parameters and statistics that are not invariant and cannot be compared validly in crosscultural studies with varying distributions of disability in contrast to those that can be compared (if the model assumptions are met) because they are produced by models such as linear and nonlinear regression. OBJECTIVES: The purpose of this overview is to provide an integrated approach to the quantitative methods used in this special issue to examine measurement equivalence. The methods include classical test theory (CTT), factor analytic, and parametric and nonparametric approaches to DIF detection. Also included in the quantitative section is a discussion of item banking and computerized adaptive testing (CAT). METHODS: Factorial invariance and the articles discussing this topic are introduced. A brief overview of the DIF methods presented in the quantitative section of the special issue is provided together with a discussion of ways in which DIF analyses and examination of invariance using factor models may be complementary. CONCLUSIONS: Although factor analytic and DIF detection methods share features, they provide unique information and can be viewed as complementary in informing about measurement equivalence.

Cross-Cultural Comparison↗

The Langmuir two-surface equation as a model for cadmium adsorption on peat: a new method of the calculation of equation constants.

The Langmuir isotherm equation is often used to describe the adsorption of cadmium on peat. If the total surface consists of two or more populations of sites with different bonding energies, it is proposed that the Langmuir two-surface equation be used. The effects of the contact time and pH on adsorption were investigated in batch experiments. Adsorption batch isotherm studies were carried out by using 12 solutions with initial concentrations of 5-110 mg/l. The samples were analysed by using axial ICP-AES. Adsorption data were compared using four different linearizations (Lineweaver-Burk, Eadie-Hofstee, Scatchard and Langmuir linearizations). Better results among linearizations were found with the Langmuir linearization, but the results obtained by using the nonlinear regression were still the best. A new, nonlinear regression method for the calculation of the equation constants was created by using the system of equations and these findings were compared to the results found using earlier methods.

Adsorption↗

Initiated chemical vapor deposition of linear and cross-linked poly(2-hydroxyethyl methacrylate) for use as thin-film hydrogels.

Initiated chemical vapor deposition (iCVD) is able to synthesize linear and cross-linked poly(2-hydroxyethyl methacrylate) (PHEMA) thin films, in one step, from vapors of 2-hydroxyethyl methacrylate (HEMA), ethylene glycol diacrylate (EGDA), and tert-butyl peroxide (TBPO) without using any solvents. This all-dry technique also allows control of the cross-link density by adjusting the partial pressure of the cross-linking agent EGDA in the vapor phase. Films with specific cross-link densities and hence thermal, wetting, and swelling properties can be created in one single vacuum processing step. Through selective thermal decomposition of the initiator TBPO, films with well-defined chemical structures and full functionality retention can be deposited, which is evident in the Fourier transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses. These spectroscopic methods also facilitate determination of EGDA incorporation in the cross-linked films based on the fact that HEMA contains a hydroxyl group but EGDA does not. For the linear PHEMA depositions, the growth rate was found to be nonlinear in the partial pressure of HEMA, possibly due to nonlinear multilayer adsorption and/or primary termination. The EGDA/HEMA ratio in the films systematically increased from 0.00 to 0.46 as the EGDA partial pressure was raised. The onset temperatures of decomposition were between 270 and 302 degrees C for the linear and the most cross-linked films, respectively. Thermal annealing at approximately 430 degrees C resulted in minuscule amounts of residue for all films, linear or cross-linked. The most cross-linked film had approximately 99.50% thickness removed after annealing. The contact angle was found to increase with increasing cross-link density. Significant contact-angle hysteresis was observed, indicating surface reconfiguration, and the lowest receding angle was 17 degrees for the linear film. Swelling measurements using spectroscopic ellipsometry showed that the degree of swelling decreased with increasing EGDA incorporation. The water content decreased from 35% (v/v) for the linear film to below 10% (v/v) for the most cross-linked film. These results show that iCVD is able to produce PHEMA thin films that function as hydrogels when soaked in water. The spectroscopic results, the contact-angle results, and the swelling analysis altogether prove the retention of the hydrophilic pendant groups in the iCVD process.

Journal Article↗

Tooth-implant connection: some biomechanical aspects based on finite element analyses.

This study investigated, with the use of two- and three-dimensional finite element analysis, the peri-implant stress that occurred during loading of a tooth that was rigidly connected to a distally placed implant. A fixed bond between the bone and the implant was assumed, while the periodontal ligament was represented by means of three-dimensional nonlinear visco-elastic spring elements. Two different loading conditions were compared in the study: i) an axially directed static load of 50 kg that was applied to the tooth for 10 s, and ii) a transitional load of 50 kg that was applied for 5 milliseconds. Load duration appeared to have a greater influence than load intensity on the stress distribution in the bone around an implant and a rigidly connected tooth. Static load is, therefore, potentially more harmful for peri-implant bone than transitional load. The periodontal ligament seems to play a key role in the stress distribution between a tooth and a rigidly connected implant.

Alveolar Process↗

Medical disease and alcohol use among veterans with human immunodeficiency infection: A comparison of disease measurement strategies.

BACKGROUND: Many people with human immunodeficiency (HIV) infection drink alcohol. We asked whether level of exposure to alcohol is associated with medical disease in a linear or nonlinear manner, whether the association depends upon the proximity of alcohol use, and whether it varies by source used to measure disease (chart review vs. ICD-9 Diagnostic Codes). METHODS: The Veterans Aging 3 Site Cohort Study (VACS 3) enrolled 881 veterans, 86% of all HIV-positive patients seen, at 3 VA sites from June 23, 1999, to July 28, 2000. To maximize the sensitivity for alcohol exposure, alcohol use was measured combining data from patient self-report, chart review, and ICD-9 codes. We assigned the greatest exposure level reported from any source. Alcohol use within the past 12 months was considered current. Data on comorbid and AIDS-defining medical diseases were collected via chart review and ICD-9 diagnostic codes. The association of alcohol use (level and timing) and disease was modeled only for diseases demonstrating > or =10% prevalence. Linearity was compared with nonlinearity of association using nested multivariate models and the likelihood ratio test. All multivariate models were adjusted for age, CD4 cell count, viral load, intravenous drug use, exercise, and smoking. RESULTS: Of 881 subjects enrolled, 866 (98%) had sufficient data for multivariate analyses, and 876 (99%) had sufficient data for comparison of chart review with ICD-9 Diagnostic Codes. Of the 866, 42 (5%) were lifetime abstainers; 247 (29%) were past drinkers; and 577 (67%) were current users. Among the 824 reporting past or current alcohol use, 341 (41%) drank in moderation, 192 (23%) drank hazardously, and 291 (35%) carried a diagnosis of abuse or dependence. ICD-9 codes showed limited sensitivity, but overall agreement with chart review was good for 15 of 20 diseases (kappa > 0.4). The following diseases demonstrated a > or =10% prevalence with both measures (hepatitis C, hypertension, diabetes, obstructive lung disease, candidiasis, and bacterial pneumonia). All of these were associated with alcohol use (P < 0.05). Hepatitis C, hypertension, obstructive lung disease, candidiasis, and bacterial pneumonia demonstrated linear associations with level of alcohol use (P < 0.03). Past alcohol use increased the risk of hepatitis C and diabetes after adjustment for level of exposure (P < 0.01). With the exception of candidiasis, the associations between level and timing of alcohol use were similar when measured by ICD-9 codes or by chart review. CONCLUSIONS: Past and current use of alcohol is common among those with HIV infection. Estimates of disease risk associated with alcohol use based upon ICD-9 Diagnostic Codes appear similar to those based upon chart review. After adjustment for level of alcohol exposure, past use is associated with similar (or higher) prevalence of disease as among current drinkers. Finally, level of alcohol use is linearly associated with medical disease. We find no evidence of a "safe" level of consumption among those with HIV infection.

Alcohol Drinking↗