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PubMed1993

[Energy requirements for walking].

The energy requirement of walking, expressed indirectly by the oxygen consumption per kg body weight was assessed during different speeds of walking on a treadmill within the range of 3-12 km.h-1 in 87 untrained healthy men aged 17.5 to 60 years. The dependence of VO2.kg-1 on the speed of walking is non-linear in the mentioned range. Most suitable is the two-component linear model which in the range of 3-7 km.h-1 has the shape of VO2.kg-1 (ml.kg-1.min-1 = 3.207.v/km.h-1 - 1.777, r = 0.932 with a mean predicting error of 1.5.ml.kg-1.min-1, in the range of load of 7-12 km.h-1 VO2 = 7.120.v - 29.168, r = 0.941 with a error predicting of 3.73. The polynomic model of relations in the entire range of 3-12 km.h-1 is VO2 = 4.503 - 0.108.v + 0.379.v2, r = 0.922 with a predicting error of 4.43 ml.kg-1.min-1, and finally the exponential model has the shape VO2 = 4.360 exp (0.223.v), r = 0.861 with a mean predicting error of 6.84 ml.kg-1.min-1 in the entire range of load intensities. The justification to express the relationship between the oxygen consumption and the rate of walking by a two-component linear model as well as by non-linear models is confirmed also by the high correlation coefficient (p < 0.001 in all instances). The error of assessment of VO2.kg-1 from the speed of walking is 10% or less in all models. The mentioned models, in particular the linear one, can be used for evaluation of physical activities involving walking outdoors.

Adolescent↗

PubMed2003

Alternative approaches to predicting methane emissions from dairy cows.

Previous attempts to apply statistical models, which correlate nutrient intake with methane production, have been of limited value where predictions are obtained for nutrient intakes and diet types outside those used in model construction. Dynamic mechanistic models have proved more suitable for extrapolation, but they remain computationally expensive and are not applied easily in practical situations. The first objective of this research focused on employing conventional techniques to generate statistical models of methane production appropriate to United Kingdom dairy systems. The second objective was to evaluate these models and a model published previously using both United Kingdom and North American data sets. Thirdly, nonlinear models were considered as alternatives to the conventional linear regressions. The United Kingdom calorimetry data used to construct the linear models also were used to develop the three nonlinear alternatives that were all of modified Mitscherlich (monomolecular) form. Of the linear models tested, an equation from the literature proved most reliable across the full range of evaluation data (root mean square prediction error = 21.3%). However, the Mitscherlich models demonstrated the greatest degree of adaptability across diet types and intake level. The most successful model for simulating the independent data was a modified Mitscherlich equation with the steepness parameter set to represent dietary starch-to-ADF ratio (root mean square prediction error = 20.6%). However, when such data were unavailable, simpler Mitscherlich forms relating dry matter or metabolizable energy intake to methane production remained better alternatives relative to their linear counterparts.

Animal Feed↗

PubMed2002

A Monte Carlo EM algorithm for generalized linear mixed models with flexible random effects distribution.

A popular way to represent clustered binary, count, or other data is via the generalized linear mixed model framework, which accommodates correlation through incorporation of random effects. A standard assumption is that the random effects follow a parametric family such as the normal distribution; however, this may be unrealistic or too restrictive to represent the data. We relax this assumption and require only that the distribution of random effects belong to a class of 'smooth' densities and approximate the density by the seminonparametric (SNP) approach of Gallant and Nychka (1987). This representation allows the density to be skewed, multi-modal, fat- or thin-tailed relative to the normal and includes the normal as a special case. Because an efficient algorithm to sample from an SNP density is available, we propose a Monte Carlo EM algorithm using a rejection sampling scheme to estimate the fixed parameters of the linear predictor, variance components and the SNP density. The approach is illustrated by application to a data set and via simulation.

Journal Article↗

PubMedDate not supplied

Analysis using a linear viscoelastic model of the in vitro osmotic kinetics of polydisperse synthetic colloids.

This study clarifies the contribution to overall osmotic kinetics of colloid osmotic pressure (Pi) and the interaction of synthetic colloids with the membrane. Solutions (6%) of dextran with weight average molecular weight (MW(w)) 68 800 (DEX 70), dextran with MW(w) 40 000 (DEX 40), hydroxyethyl starch with MW(w) 70 000 (HES 70), gelatin with MW(w) 60 000 and albumin were tested. An osmotic flow cell fitted with membranes of molecular weight cutoff size 30 000 or 50 000 was used to measure time-dependent changes in Pi for each of these solutions. A linear viscoelastic model was fitted to the curve describing changes to Pi as a function of time. Values of total effective Pi for DEX 40 and DEX 70 were larger than those for HES 70, gelatin, and albumin. As an index of solute-solvent exchange rate at the membrane surface, these values were in the order DEX 40 > DEX 70, HES 70 > gelatin, albumin. The findings suggest that DEX 40 may be preferable for the temporary restoration of plasma volume because of a heightened initial osmotic force. In contrast, the osmotic force exerted by gelatin is slower to increase but is likely to be longer lasting in vivo as a result of the inhibition of gelatin from penetrating the capillary membrane due to its interaction with negatively charged groups in the endothelial glycocalyx.

Colloids↗

PubMed2006

Dosimetric characteristics of a newly designed grid block for megavoltage photon radiation and its therapeutic advantage using a linear quadratic model.

Grid radiation therapy with megavoltage x-ray beam has been proven to be an effective technique for management of large, bulky malignant tumors. The clinical advantage of GRID therapy, combined with conventional radiation therapy, has been demonstrated using a prototype GRID block [Mohiuddin, Curtis, Grizos, and Komarnicky, Cancer 66, 114-118 (1990)]. Recently, a new GRID block design with improved dosimetric properties has become commercially available from Radiation Product Design, Inc. (Albertive, MN). This GRID collimator consists of an array of focused apertures in a cerrobend block arranged in a hexagonal pattern having a circular cross-section with a diameter and center-to-center spacing of 14.3 and 21.1 mm, respectively, in the plane of isocenter. In this project, dosimetric characteristics of the newly redesigned GRID block have been investigated for a Varian 21EX linear accelerator (Varian Associates, Palo Alto, CA). These determinations were performed using radiographic films, thermoluminescent dosimeters in Solid Water phantom materials, and an ionization chamber in water. The output factor, percentage depth dose, beam profiles, and isodose distributions of the GRID radiation as a function of field size and beam energy have been measured using both 6 and 18 MV x-ray beams. In addition, the therapeutic advantage obtained from this treatment modality with the new GRID block design for a high, single fraction of dose has been calculated using the linear quadratic model with alpha/beta ratios for typical tumor and normal cells. These biological characteristics of the new GRID block design will also be presented.

Cell Survival↗

PubMed2006

Linear regression modeling to compare fluoride release profiles of various restorative materials.

OBJECTIVES: The aim of this study was to compare the released fluoride profiles of various restorative materials by using linear regression analysis. METHODS: Specimens were prepared using a cylindrical Teflon mold with a height of 2 mm and a radius of 8 mm. After being prepared, specimens were immediately placed into artificial saliva which was replaced at various times during 6 weeks. These released intrinsic fluoride amounts were measured by using an ion selective electrode. Then, data obtained cumulatively were statistically analyzed, and the released profiles were compared. RESULTS: It was observed that the materials released fluoride at different levels of concentration and the largest fluoride release was obtained from the conventional glass ionomer cement. This was followed by resin modified glass ionomer cement, polyacid modified composite resin, and fluoride releasing composite resin, respectively. Although the released fluoride amounts of the materials were different, their release profiles were found to be similar in that the release was initially fast and then it became steady as time passed. SIGNIFICANCE: The statistical modeling of the release profiles helps to compare the fluoride release behavior of materials and also to predict fluoride release amounts for the future. In literature, for these purposes, separate nonlinear statistical models have extensively been utilized. However, the single linear statistical modeling approach has numerous advantages such as providing estimators having good statistical properties, exact results, precise inference and simplicity in calculation. Therefore, this study was conducted to introduce the use of single linear regression modeling to compare release profiles statistically.

Compomers↗

PubMed1996

[Prevalence of porphyria cutanea tarda in Madrid and relationship between urine porphyrin and ethanol intake in a multiple linear regression model].

BACKGROUND: The application of a simple fluorometric analytical method enabled us to quantify the urinary porphyrin excretion and to establish the prevalence of porphyria cutanea tarda (PCT) in the town of Madrid, Spain, in a cross-sectional study. PATIENTS AND METHODS: The study assessed 1,613 subjects from three districts in Madrid, in whom further variables potentially related to porphyrinuria such as ethanol intake or -in women-oral contraceptive use were measured and recorded. RESULTS: The estimated prevalence of the disease was 1.24 cases per 1,000 inhabitants (95% confidence interval 0.15-4.47 per thousand). After excluding from the study sample all cases with existent disease, an analysis was performed to ascertain an unilateral tolerance interval for urinary porphyrin concentration in the adult population; this level was established at 181.2 micrograms/l. The effect of ethanol intake on porphyrinuria was considered significant using a multiple linear regression model adjusted for the control variables gender, age and body mass index. In fertile women, contraceptive use did not attain statistical significance when that variable was included in a multiple regression model. CONCLUSIONS: A high prevalence has been estimated for PCT in the Madrid population. A significant association was further found between alcohol intake and porphyrinuria in non-porphyric adults.

Adolescent↗

PubMedDate not supplied

A non-linear Maxwell model of biofluids: application to normal blood.

For transient shear stress responses at moderate shear rates, predictions of a Non-Linear Maxwell model, in which the viscosity coefficient is assumed to depend on the instantaneous structural state of the material, are compared to measurements on normal blood (McMillan et al., 1986). This is carried out on a modified viscometer which incorporates a dynamic balance torque monitoring, in order to eliminate apparatus inertia effects. Satisfactory agreement is obtained with model variables closely related to the structure kinetics.

Blood Viscosity↗

PubMed2002

A Bayesian space varying parameter model applied to estimating fertility schedules.

We propose a spatial generalized linear model (GLM) to analyse the vital rates for small areas. In each small area, we have a response vector and covariates to explain its variability. The statistical methodology is based on a spatial Bayesian approach and it allows the covariates' parameters of the generalized linear model to vary smoothly on space. Hence, the effect of a covariate on the response varies depending on the random variables measurement location. Our model is an extension of disease mapping models allowing the space-covariate interaction to be modelled in a natural way and giving space a position of intrinsic interest. We introduce the model in the context of fertility curve estimation. In each small area, we have a curve describing the variation of fertility rates by age modelled by Coale's fertility model, which implies a GLM in each area. A simulation shows the advantages of our approach. In addition, the paper applies the procedure to census data used to study the diffusion of low fertility behaviour in Brazil.

Adolescent↗

PubMed1991

The accelerated repopulation of a murine fibrosarcoma, FSA-II, during the fractionated irradiation and the linear-quadratic model.

Radiation response of a spontaneous mouse fibrosarcoma, FSa-II, to various fractionated doses was studied in vivo together with single dose cell survival curves. Early generation isotransplants were used. Animals were C3Hf/Sed mice derived from our defined flora mouse colony. Lung colony and TD50 assays were used to determine cell survival. Surviving fractions were determined following fractionated irradiations of 1.0 to 5.0 Gy each per fraction with interfractional time intervals of 4 hr. The alpha/beta ratio based on fractionated irradiations was 8.8 Gy for aerobic FSa-II tumor cells and flexure dose was less than 1.3 Gy. Multiple fractions of 5.0 Gy each given with 4, 12, and 24 hr intervals showed an increase in survival with increasing interfractional time interval, suggesting a rapid repopulation of tumor cells between fractions; namely, cell doubling time was shortened between fractions after the first 5.0 Gy doses. These results indicated that tumor cell repopulation is a critical factor in the fractionated radiotherapy. Linear-quadratic model was fitted to single dose survival data. Single dose survival curve of aerobic FSa-II tumor cells following lung colony assays which allowed determination of minimal survival of approximately 3.0 x 10(-3) showed that alpha, beta, and alpha/beta ratios were 0.25 Gy-1, 0.048 Gy-2, and 8.47 Gy, respectively. Single dose survival curve of the same aerobic cells determined by both lung colony and TD50 assays to a survival level of approximately 3.0 x 10(-6) demonstrated that alpha, beta, and alpha/beta ratios were 0.375, 0.0127, and 29.5, respectively. Similar determination for hypoxic FSa-II tumor cells showed that alpha, beta values were smaller whereas the alpha/beta ratio was much larger than for aerobic cells. The oxygen enhancement ratio calculated by the alpha/beta ratios was greater than 3.0.

Animals↗

PubMed1995

Biologically effective dose distribution based on the linear quadratic model and its clinical relevance.

PURPOSE: Radiotherapy plans based on physical dose distributions do not necessarily entirely reflect the biological effects under various fractionation schemes. Over the past decade, the linear-quadratic (LQ) model has emerged as a convenient tool to quantify biological effects for radiotherapy. In this work, we set out to construct a mechanism to display biologically oriented dose distribution based on the LQ model. METHODS AND MATERIALS: A computer program that converts a physical dose distribution calculated by a commercially available treatment planning system to a biologically effective dose (BED) distribution has been developed and verified against theoretical calculations. This software accepts a user's input of biological parameters for each structure of interest (linear and quadratic dose-response and repopulation kinetic parameters), as well as treatment scheme factors (number of fractions, fractional dose, and treatment time). It then presents a two-dimensional BED display in conjunction with anatomical structures. Furthermore, to facilitate clinicians' intuitive comparison with conventional fractionation regimen, a conversion of BED to normalized isoeffective dose (NID) is also allowed. RESULTS: Two sample cases serve to illustrate the application of our tool in clinical practice. (a) For an orthogonal wedged pair of x-ray beams treating a maxillary sinus tumor, the biological effect at the ipsilateral mandible can be quantified, thus illustrates the so-called "double-trouble" effects very well. (b) For a typical four-field, evenly weighted prostate treatment using 10 MV x-rays, physical dosimetry predicts a comparable dose at the femoral necks between an alternate two-fields/day and four-fields/day setups. However, our BED display reveals an approximate 21% higher BED for the two-fields/day scheme. This excessive dose to the femoral necks can be eliminated if the treatment is delivered with a 3:2 (anterio-posterior/posterio-anterior (AP/PA): bilaterally opposed (BLO)) dose weighting. With Co-60 beams, the increase of BED with alternate two-fields/day, 1:1 setup was even more pronounced (26%). CONCLUSION: We have demonstrated the feasibility of constructing a biologically oriented dose distribution for clinical practice of radiotherapy. The discordance between physical dose distributions and the biological counterparts based on the given treatment schemes was quantified. The computerized display of BED at nonprescription points greatly enhanced the versatility of this tool. Although the routine use of this implementation in clinical radiotherapy should be cautiously done, depending largely on the accuracy of the published biological parameters, it may, nevertheless, help the clinicians derive an optimal treatment plan with a particular fractionation scheme or use it as a quantitative tool for outcome analysis in clinical research.

Feasibility Studies↗

PubMed1998

Detection and utilization of single genes without DNA assays.

Quantitative traits are often assumed to be controlled by a large number of loci that each have a small effect. Under this assumption, the distribution of genotypic and phenotypic values can be adequately modeled by a multivariate normal distribution. Thus, most genetic analyses are based on mixed linear models. Evidence is accumulating, however, for the presence of loci that have large effects on traits of economic importance. If the genotypes for such loci can be observed without error, then--conditional on these observed genotypes--genotypic and phenotypic values follow a multivariate normal distribution, and data from very large pedigrees can be analyzed using a mixed linear model that includes the genotypic effects for these loci as fixed effects. However, when the major genotype is not observed, the genotypic and phenotypic values follow a mixture of multivariate normal distributions, and analyses based on fitting a mixed linear model may not be optimum, especially for populations undergoing selection and nonrandom mating. Several approaches are discussed for the genetic analysis of data when the major genotypes are not known.

Algorithms↗

PubMed2000

Parametric estimation of the continuous non-stationary spectrum and its dynamics in surface EMG studies.

Frequency spectrum of surface electromyographic signals (SEMGs) exhibit a non-stationary nature even in the case of constant level isometric muscle contractions due to changes related to muscle fatigue processes. These changes can be evaluated by methods for estimation of time-varying (TV) spectrum. The most widely adopted non-parametric approach is a short time Fourier transform (STFT), from which changes of mean frequency (MF) as well as other parameters for qualitative description of spectrum variation can be calculated. Similar idea of a sliding-window generalisation can also be used in case of parametric spectrum analysis methods. We applied such approach to obtain TV linear models of SEMGs, although its large variance due to independence of estimations in consequent windows represents a major drawback. This variance causes unrealistic abrupt changes in the curve of overall spectrum dynamics, calculated either as the second derivative of the MF or, as we propose, autoregressive moving average (ARMA) distance between subsequent linear models forming the TV parametric spectrum. A smoother estimation is therefore sought and another method shows to be superior over a simple sliding window technique. It supposes that trajectories of TV linear model coefficients can be described as linear combinations of known basis functions. We demonstrate that the later method is very appropriate for description of slowly changing spectra of SEMGs and that dynamics measures obtained from such estimations can be used as an additional indication of the fatigue process.

Electromyography↗

PubMed1996

Comparing non-hierarchical models: application to non-linear mixed effects modeling.

There is no method available to compare the fit of two non-hierarchical non-linear mixed effects models, although the common practice is to select the model with the lower objective function. Bootstrapping the log-likelihood differences (LLDs) of non-hierarchical models and constructing a bootstrap confidence interval on the LLDs is proposed for comparing the goodness-of-fit of such models. This is illustrated with different parameterizations of clearance models for an anti-infective agent in a longitudinal pharmacokinetic study which are compared. Additive and exponential models of creatinine clearance as a predictor of clearance are used as examples.

Adult↗

PubMed1996

Relationship between band sharing levels of DNA fingerprints and inbreeding coefficients and estimation of true inbreeding in turkey lines.

A regression analysis between band sharing of DNA fingerprints and calculated inbreeding coefficients was conducted using six experimental turkey lines. The DNA fingerprints were produced from 18 individual DNA samples per line representing different families. The DNA was digested with a HaeIII restriction enzyme and hybridized with Jeffreys' 33.6 probe. The band sharing within lines ranged from 0.42 to 0.62. The inbreeding coefficients of the lines were calculated based on population sizes and variation in family sizes. The inbreeding coefficients varied from 2.5 to 45%. Regression analysis between the two variables yielded a highly significant (P < or = 0.0001) linear model with a correlation coefficient of 0.992. The linear model was used to estimate the actual inbreeding in these lines.

Animals↗

PubMed2002

Identification of significant host factors for HIV dynamics modelled by non-linear mixed-effects models.

Non-linear mixed-effects models are powerful tools for modelling HIV viral dynamics. In AIDS clinical trials, the viral load measurements for each subject are often sparse. In such cases, linearization procedures are usually used for inferences. Under such linearization procedures, however, standard covariate selection methods based on the approximate likelihood, such as the likelihood ratio test, may not be reliable. In order to identify significant host factors for HIV dynamics, in this paper we consider two alternative approaches for covariate selection: one is based on individual non-linear least square estimates and the other is based on individual empirical Bayes estimates. Our simulation study shows that, if the within-individual data are sparse and the between-individual variation is large, the two alternative covariate selection methods are more reliable than the likelihood ratio test, and the more powerful method based on individual empirical Bayes estimates is especially preferable. We also consider the missing data in covariates. The commonly used missing data methods may lead to misleading results. We recommend a multiple imputation method to handle missing covariates. A real data set from an AIDS clinical trial is analysed based on various covariate selection methods and missing data methods.

Acquired Immunodeficiency Syndrome↗

PubMed1987

Fitting the linear-quadratic model using time of occurrence as the end-point for quantal response multifraction experiments.

A statistical technique is given for fitting the linear-quadratic model to experimental quantal response multifraction data using the time of the response as the end-point. The analysis used is based on the Cox Proportional Hazards model. The technique is useful for late effects where the time of occurrence of the response is dose dependent. The technique is compared to logistic regression analysis and the advantages and disadvantages are discussed. Both methods are applied to a lung pneumonitis experiment and a kidney experiment.

Animals↗

PubMed2005

A synthetic peptide based on the NS1 non-structural protein of tick-borne encephalitis virus induces a protective immune response against fatal encephalitis in an experimental animal model.

Linear immunogenic peptides corresponding to amino acid sequences from the NS1 non-structural protein from tick-borne encephalitis virus (strain Sophyin) were predicted using established algorithms and synthesized. Of the 12 peptides predicted, 11 were able to induce peptide-specific antibodies in BALB/c mice but only 1 of these 11 was able to induce antibodies, which reacted with the native protein in a radio-immune precipitation assay. This peptide corresponds to amino acids 37--55, and forms one of the predicted structurally conserved alpha helices of the virus NS1 protein. It was able to protect 60% of animals against lethal challenge with the homologous highly pathogenic tick-borne encephalitis virus strain, and adoptive transfer experiments indicated the involvement of the antibodies induced by this peptide in its protective activity in mice.

Amino Acid Sequence↗