Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “linear mixed model”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,567 records · Page 87Linked to original sources
PubMed1995

Linearity of pharmacokinetics and model estimation of sufentanil.

BACKGROUND: The pharmacokinetic profiles of sufentanil available in the literature are conflicting because of methodologic differences. Length of sampling and assay sensitivity are key factors involved in accurately estimating the volumes of distribution, clearances, and elimination phase. The unit disposition function of increasing doses of sufentanil were investigated and the influence of dose administered on the linearity of pharmacokinetics was assessed. METHODS: The pharmacokinetics of sufentanil were investigated in 23 patients, aged 14-68 yr, scheduled for surgery with postoperative ventilation. After induction of anesthesia, sufentanil was administered as a short infusion (10-20 min) in doses ranging from 250 micrograms to 1,500 micrograms. Frequent arterial blood samples were gathered during and at the end of infusion, then at specific intervals up to 48 h after infusion. Plasma concentrations of sufentanil were measured by radioimmunoassay (limit of sensitivity 0.02 ng.ml-1). The data were analyzed with the standard two-stage, naive pooled-data and the mixed effect pharmacokinetic approaches. RESULTS: The pharmacokinetics of sufentanil were adequately described by a linear three-compartmental mamillary model with the following parameters, expressed as log mean values with 95% confidence intervals: the central volume of distribution = 14.3 l (13.1-15.41), the rapidly equilibrating volume = 63.1 l (61.9-64.3 l), the slowly equilibrating volume = 261.6 l (260.2-262.9 l), the steady-state distribution volume = 339 l (335-343 l), metabolic clearance = 0.92 l.min-1 (0.84-1.05 l.min-1), rapid distribution clearance = 1.55 l.min-1 (1.34-2.14 l.min-1), slow distribution clearance = 0.33 l.min-1 (0.27-0.49 l.min-1), and elimination half-life = 769 min (690-1011 min). No relation to age, weight, or lean body mass was found for any of the parameters. CONCLUSIONS: Sufentanil pharmacokinetics were linear within the dose range studied. Drug detection up to 24 h after dosing was necessary to define the terminal elimination phase. The metabolic clearance approached liver blood flow and a large volume of distribution was identified, consistent with the long terminal elimination half-life. Simulations predicted that plasma sufentanil steady-state concentrations would rapidly decline after termination of an infusion despite the long half-lives.

Adolescent↗
PubMed1993

Identification and simulation of new non-random statistical properties common to different populations of eukaryotic non-coding genes.

The autocorrelation function analysing the occurrence probability of the i-motif YRY(N)iYRY in genes allows the identification of mainly two periodicities modulo 2, 3 and the preferential occurrence of the motif YRY(N)6YRY (R = purine = adenine or guanine, Y = pyrimidine = cytosine or thymine, N = R or Y). These non-random genetic statistical properties can be simulated by an independent mixing of the three oligonucleotides YRYRYR, YRYYRY and YRY(N)6 (Arquès & Michel, 1990b). The problem investigated in this study is whether new properties can be identified in genes with other autocorrelation functions and also simulated with an oligonucleotide mixing model. The two autocorrelation functions analysing the occurrence probability of the i-motifs RRR(N)iRRR and YYY(N)iYYY simultaneously identify three new non-random genetic statistical properties: a short linear decrease, local maxima for i identical to 3[6] (i = 3, 9, etc) and a large exponential decrease. Furthermore, these properties are common to three different populations of eukaryotic non-coding genes: 5' regions, introns and 3' regions (see section 2). These three non-random properties can also be simulated by an independent mixing of the four oligonucleotides R8, Y8, RRRYRYRRR, YYYRYRYYY and large alternating R/Y series. The short linear decrease is a result of R8 and Y8, the local maxima for i identical to 3[6], of RRRYRYRRR and YYYRYRYYY, and the large exponential decrease, of large alternating R/Y series (section 3). The biological meaning of these results and their relation to the previous oligonucleotide mixing model are presented in the Discussion.

Animals↗
PubMed2007

Evaluation of uncertainty parameters estimated by different population PK software and methods.

The uncertainty associated with parameter estimations is essential for population model building, evaluation, and simulation. Summarized by the standard error (SE), its estimation is sometimes questionable. Herein, we evaluate SEs provided by different non linear mixed-effect estimation methods associated with their estimation performances. Methods based on maximum likelihood (FO and FOCE in NONMEM, nlme in Splus, and SAEM in MONOLIX) and Bayesian theory (WinBUGS) were evaluated on datasets obtained by simulations of a one-compartment PK model using 9 different designs. Bootstrap techniques were applied to FO, FOCE, and nlme. We compared SE estimations, parameter estimations, convergence, and computation time. Regarding SE estimations, methods provided concordant results for fixed effects. On random effects, SAEM and WinBUGS, tended respectively to under or over-estimate them. With sparse data, FO provided biased estimations of SE and discordant results between bootstrapped and original datasets. Regarding parameter estimations, FO showed a systematic bias on fixed and random effects. WinBUGS provided biased estimations, but only with sparse data. SAEM and WinBUGS converged systematically while FOCE failed in half of the cases. Applying bootstrap with FOCE yielded CPU times too large for routine application and bootstrap with nlme resulted in frequent crashes. In conclusion, FO provided bias on parameter estimations and on SE estimations of random effects. Methods like FOCE provided unbiased results but convergence was the biggest issue. Bootstrap did not improve SEs for FOCE methods, except when confidence interval of random effects is needed. WinBUGS gave consistent results but required long computation times. SAEM was in-between, showing few under-estimated SE but unbiased parameter estimations.

Bayes Theorem↗
PubMed1983

Computer simulation of transport phenomena during dialysis deglycerolization of red blood cells.

A computer simulation model has been developed to aid in the understanding, parameter prediction, and performance optimization of a unique dialysis process where glycerol is removed from cryopreserved red blood cells using a semipermeable membrane pouch fixed in a mildly agitated transport cell. The dynamic system considered here consists of flow channels and the membrane blood pouch which contains the red blood cells, extracellular fluid, and cryopreservatives. Dialysate flows over the membrane surfaces while salt enters the pouch preventing osmotic hemolysis. The glycerol diffuses rapidly from the red cells and plasma across the membrane into the dialysate which carries it out of the transport cell. The system is discretized into completely mixed subdomains. Constituent transport and solvent flux are modeled with the transient convection-diffusion equation and linear equations of nonequilibrium thermodynamics, respectively. The integrated compartment method was used to solve for the principal variables, that is, salt and glycerol concentrations, water flow rates, and pressure in space and time. The computer simulation model, calibrated and verified with in-house data sets, is a reliable, cost-effective and flexible tool for dialysis system investigations, prediction, and optimal design.

Biological Transport↗
PubMed2004

Cardiac surgery risk models: a position article.

Differences in medical outcomes may result from disease severity, treatment effectiveness, or chance. Because most outcome studies are observational rather than randomized, risk adjustment is necessary to account for case mix. This has usually been accomplished through the use of standard logistic regression models, although Bayesian models, hierarchical linear models, and machine-learning techniques such as neural networks have also been used. Many factors are essential to insuring the accuracy and usefulness of such models, including selection of an appropriate clinical database, inclusion of critical core variables, precise definitions for predictor variables and endpoints, proper model development, validation, and audit. Risk models may be used to assess the impact of specific predictors on outcome, to aid in patient counseling and treatment selection, to profile provider quality, and to serve as the basis of continuous quality improvement activities.

Bayes Theorem↗
PubMed1998

Genes and environment have gender-independent influences on the eating and drinking of free-living humans.

Males and females differ in the amounts of food and fluids they ingest. Previous studies suggest that this may be due to differences in genetic influences on intake. Gender differences in the heritability of food and fluid intake were investigated with 110 identical and 102 fraternal same-sex and 53 fraternal mixed-gender adult twin pairs who were paid to maintain 7-day food intake diaries. Linear structural modeling revealed significant genetic influences on the overall and meal intakes of foods and fluids and specific beverage and food types. No gender differences were found in the genes that influence intake or, for the most part, in the magnitude of the genetic influences on intake. However, gender differences were found for the between-meal intakes of fluids, being influenced by heredity for males but by common, familial, environment for females. The data suggest that intakes are equivalently influenced by inheritance and individual environment for both males and females and that most gender differences are due to a simple multiplicative difference between intakes possibly due to body size and/or caloric expenditure differences.

Adult↗
PubMed1993

Prediction of the size of unerupted canines and premolars in a Saudi Arab population.

The estimation of the size of unerupted permanent teeth is an essential aspect in treatment planning in the mixed dentition. The commonly used prediction methods of Moyers and Tanaka and Johnston are based on data from a sample of children of Northern European descent. The accuracy of these methods when applied to a different population is questionable. When we applied the Moyers probability tables to a limited sample of a Saudi Arab population, we found that the 35% level was a more accurate determinant than the commonly used 75% confidence level. Likewise, the prediction equations of Tanaka and Johnston overestimated the size of buccal segments in this population. The data illustrate the limitations of these methods when applied to a sample population of other than European descent. From this data, two linear regression equations were developed for tooth size prediction in Saudi Arab children.

Adolescent↗
PubMed2006

Is body surface area still the best way to determine pump flow rate during cardiopulmonary bypass?

For over four decades, pump flow rate during cardiopulmonary bypass (CPB) has been estimated using body surface area (BSA). As patients presenting for heart surgery are increasingly obese, this approach may no longer be appropriate and other estimates of systemic metabolism should be used, such as body mass index and lean body mass. Mixed venous oxygen saturation (SvO2) is a robust and independent estimate of the global efficacy of CPB. The aim of this study was to determine which factors, including body surface area, body mass index and lean body mass, best predict SvO2 during CPB. Forty-eight patients undergoing elective cardiac surgery requiring CPB were studied. Patients' height, weight and skinfold thickness at four sites (biceps, triceps, subscapularis and suprailiac) were measured. Body surface area, lean body mass and body mass index were then calculated. Pump flow rate was maintained at 2.4 L/min/ m2 during CPB as per standard unit protocol. Arterial and mixed venous blood samples were taken during the cooling, stable hypothermia and rewarming phases of CPB. Nasopharyngeal temperatures and flow rates were recorded contemporaneously. The blood samples were analysed for oxygen saturation, haemoglobin concentration and partial pressures of oxygen and carbon dioxide. The values of the three time points were meaned. All potential predictor variables were then univariately correlated with mixed venous oxygen saturation (SvO2). Those correlating significantly (p < 0.1) were entered into a multivariate linear regression model. Nasopharyngeal temperature (beta = 0.615, p < 0.001) and lean body mass (beta = 0.256, p < 0.028) were the only significant predictors of SvO2 (r2 = 0.433, p2 < 0.001). Pump flow rates maintained at 2.4 L/min/m2 throughout CPB results in relative over-perfusion during hypothermia. Lean body mass may be a more sensitive estimate of systemic metabolism and, therefore, may provide a more accurate means of determining pump flow rate than body surface area in patients undergoing heart surgery.

Body Mass Index↗
PubMed1996

A modified EM algorithm for estimation in generalized mixed models.

Application of the EM algorithm for estimation in the generalized mixed model has been largely unsuccessful because the E-step cannot be determined in most instances. The E-step computes the conditional expectation of the complete data log-likelihood and when the random effect distribution is normal, this expectation remains an intractable integral. The problem can be approached by numerical or analytic approximations; however, the computational burden imposed by numerical integration methods and the absence of an accurate analytic approximation have limited the use of the EM algorithm. In this paper, Laplace's method is adapted for analytic approximation within the E-step. The proposed algorithm is computationally straightforward and retains much of the conceptual simplicity of the conventional EM algorithm, although the usual convergence properties are not guaranteed. The proposed algorithm accommodates multiple random factors and random effect distributions besides the normal, e.g., the log-gamma distribution. Parameter estimates obtained for several data sets and through simulation show that this modified EM algorithm compares favorably with other generalized mixed model methods.

Algorithms↗
PubMed2005

The Academic Medical Center Linear Disability Score (ALDS) item bank: item response theory analysis in a mixed patient population.

BACKGROUND: Currently, there is a lot of interest in the flexible framework offered by item banks for measuring patient relevant outcomes. However, there are few item banks, which have been developed to quantify functional status, as expressed by the ability to perform activities of daily life. This paper examines the measurement properties of the Academic Medical Center linear disability score item bank in a mixed population. METHODS: This paper uses item response theory to analyse data on 115 of 170 items from a total of 1002 respondents. These were: 551 (55%) residents of supported housing, residential care or nursing homes; 235 (23%) patients with chronic pain; 127 (13%) inpatients on a neurology ward following a stroke; and 89 (9%) patients suffering from Parkinson's disease. RESULTS: Of the 170 items, 115 were judged to be clinically relevant. Of these 115 items, 77 were retained in the item bank following the item response theory analysis. Of the 38 items that were excluded from the item bank, 24 had either been presented to fewer than 200 respondents or had fewer than 10% or more than 90% of responses in the category 'can carry out'. A further 11 items had different measurement properties for younger and older or for male and female respondents. Finally, 3 items were excluded because the item response theory model did not fit the data. CONCLUSION: The Academic Medical Center linear disability score item bank has promising measurement characteristics for the mixed patient population described in this paper. Further studies will be needed to examine the measurement properties of the item bank in other populations.

Academic Medical Centers↗
PubMed2006

Analysis of longitudinal multinomial outcome data.

Analysis of categorical outcomes in a longitudinal study has been an important statistical issue. Continuous outcome in a similar study design is commonly handled by the mixed effects model. The longitudinal binary or Poisson-like outcome analysis is often handled by the generalized estimation equation (GEE) method. Neither method is appropriate for analyzing a multinomial outcome in a longitudinal study, although the cross-sectional multinomial outcome is often analyzed by generalized linear models. One reason that these methods are not used is that the correlation structure of two multinomial variables can not be easily specified. In addition, methods that rely upon GEE or mixed effects models are unsuitable in instances when the focus of a longitudinal study is on the rate of moving from one category to another. In this research, a longitudinal model that has three categories in the outcome variable will be examined. A continuous-time Markov chain model will be used to examine the transition from one category to another. This model permits an unbalanced number of measurements collected on individuals and an uneven duration between pairs of consecutive measurements. In this study, the explicit expression for the transition probability is derived that provides an algebraic form of the likelihood function and hence allows the implementation of the maximum likelihood method. Using this approach, the instantaneous transition rate that is assumed to be a function of the linear combination of independent variables can be estimated. For a comparison between two groups, the odds ratios of occurrence at a particular category and their confidence intervals can be calculated. Empirical studies will be performed to compare the goodness of fit of the proposed method with other available methods. An example will also be used to demonstrate the application of this method.

Biometry↗
PubMed1995

Comparing non-nested regression models.

A method for comparing the fits of two non-nested models, based on a suggestion of Davidson and MacKinnon (1981), is developed in the context of linear and nonlinear regression with normal errors. Each model is regarded as a special case of an artificial "supermodel" and is obtained by restricting the value of a mixing parameter gamma to 0 or 1. To enable estimation and hypothesis testing for gamma, an approximate supermodel is used in which the fitted values from the individual models appear in place of the original parametrization. In the case of nested linear models, the proposed test essentially reproduces the standard F test. The calculations required are for the most part straight-forward (basically, linear regression through the origin). The test is extended to cover situations in which serious bias in the maximum likelihood estimate of gamma occurs, simple approximate bounds for the bias being given. Two real datasets are used illustratively throughout.

Biometry↗
PubMedDate not supplied

A computational procedure for optimal engineering interventions using kinetic models of metabolism.

The identification of optimal intervention strategies is a key step in designing microbial strains with enhanced capabilities. In this paper, we propose a general computational procedure to determine which genes/enzymes should be eliminated, repressed or overexpressed to maximize the flux through a product of interest for general kinetic models. The procedure relies on the generalized linearization of a kinetic description of the investigated metabolic system and the iterative application of mixed-integer linear programming (MILP) optimization to hierarchically identify all engineering interventions allowing for reaction eliminations and/or enzyme level modulations. The effect of the magnitude of the allowed changes in concentrations and enzyme levels is investigated, and a variant of the method to explore high-fold changes in enzyme levels is also analyzed. The proposed framework is demonstrated using a kinetic model modeling part of the central carbon metabolism of E. coli for serine overproduction. The proposed computational procedure is a general approach that can be applied to any metabolic system for which a kinetic description is provided.

Computer Simulation↗
PubMed2002

Models for mixed irradiation with a 'reciprocal-time' pattern of the repair function.

Suzuki presented models for mixed irradiation with two and multiple types of radiation by extending the Zaider and Rossi model, which is based on the theory of dual radiation action. In these models, the repair function was simply assumed to be semi-logarithmically linear (i.e., monoexponential), or a first-order process, which has been experimentally contradicted. Fowler, however, suggested that the repair of radiation damage might be largely a second-order process rather than a first-order one, and presented data in support of this hypothesis. In addition, a second-order repair function is preferred to an n-exponential repair function for the reason that only one parameter is used in the former instead of 2n-1 parameters for the latter, although both repair functions show a good fit to the experimental data. However, according to a second-order repair function, the repair rate depends on the dose, which is incompatible with the experimental data. We, therefore, revised the models for mixed irradiation by Zaider and Rossi and by Suzuki, by substituting a 'reciprocal-time' pattern of the repair function, which is derived from the assumption that the repair rate is independent of the dose in a second-order repair function, for a first-order one in reduction and interaction factors of the models, although the underlying mechanism for this assumption cannot be well-explained. The reduction factor, which reduces the contribution of the square of a dose to cell killing in the linear-quadratic model and its derivatives, and the interaction factor, which also reduces the contribution of the interaction of two or more doses of different types of radiation, were formulated by using a 'reciprocal-time' pattern of the repair function. Cell survivals calculated from the older and the newly modified models were compared in terms of the dose-rate by assuming various types of single and mixed irradiation. The result implies that the newly modified models for mixed irradiation can express or predict cell survival more accurately than the older ones, especially when irradiation is prolonged at low dose rates.

Animals↗
PubMed2003

Stable spatiotemporal spinning solitons in a bimodal cubic-quintic medium.

We investigate the formation of stable spatiotemporal three-dimensional (3D) solitons ("light bullets") with internal vorticity ("spin") in a bimodal system described by coupled cubic-quintic nonlinear Schrödinger equations. Two relevant versions of the model, for the linear and circular polarizations, are considered. In the former case, an important ingredient of the model are four-wave-mixing terms, which give rise to a phase-sensitive nonlinear coupling between two polarization components. Thresholds for the formation of both spinning and nonspinning 3D solitons are found. Instability growth rates of perturbation eigenmodes with different azimuthal indices are calculated as functions of the solitons' propagation constant. As a result, stability domains in the model's parameter plane are identified for solitons with the values of the spins of their components s=0 and s=1, while all the solitons with s> or =2 are unstable. The solitons with s=1 are stable only if their energy exceeds a certain critical value, so that, in typical cases, the stability region occupies approximately 25% of their existence domain. Direct simulations of the full system produce results that are in perfect agreement with the linear-stability analysis: stable 3D spinning solitons readily self-trap from initial Gaussian pulses with embedded vorticity, and easily heal themselves if strong perturbations are imposed, while unstable spinning solitons quickly split into a set of separating zero-spin fragments whose number is exactly equal to the azimuthal index of the strongest unstable perturbation eigenmode.

Journal Article↗
PubMed1990

Smooth muscle energetics: testing theories of crossbridge regulation.

Our results indicate that the kinetic "latch" model of Hai & Murphy is not very sensitive to the proportion of ATP assigned to crossbridges relative to that ascribed to MLC phosphorylation/dephosphorylation. Thus the basis for the relatively low efficiency of smooth muscle, attributed to high MLC phosphorylation/dephosphorylation in this model, remains open to question. Moreover, this model, or any model with mixed populations of crossbridges with differing cycle rates and/or high MLC phosphorylation/dephosphorylation rates is unlikely to account for the observed linearity of JATP and stress reported for many smooth muscles. Our studies comparing the heat production of intact and skinned smooth muscle indicate that the ATPase associated with myosin phosphorylation/dephosphorylation is unlikely to be a major factor in the tension cost of intact smooth muscle. Thus it would appear that energetics places considerable constraints on current theories of crossbridge regulation. Our modelling (Paul, 1989) suggests that it may be time to reevaluate Bozler's original hypothesis that a high attachment:detachment rate ratio for smooth muscle actin-myosin interaction may be sufficient to explain the energetics of smooth muscle.

Adenosine Triphosphate↗
PubMed2005

Population balance modeling of aggregation kinetics of recombinant human interleukin-1 receptor antagonist.

The kinetics of benzyl alcohol-induced nonnative aggregation of recombinant human interleukin-1 receptor antagonist (rhIL-1ra) were investigated using a population balance model. Steady-state size distributions of rhIL-1ra aggregates formed in a continuous mixed suspension, mixed product removal (MSMPR) reactor were measured and used to extrapolate aggregate nucleation and growth rates parameters. Aggregate growth rate was size-dependent and a linear growth rate model was used to derive a population density function. Addition of 0.9 wt/v% benzyl alcohol increased the nucleation rate by approximately four orders of magnitude. The growth rate for aggregates, however, changed little as a function of benzyl alcohol concentration in the range of 0-0.9%. The addition of sucrose to buffer containing 0.9% benzyl alcohol decreased rhIL1-ra nucleation rate by orders of magnitude and had little impact on growth rate kinetics. The simplicity of the population balance model and the physical relevance of the information obtained from this model render it a useful tool to study protein aggregation kinetics and the effects of excipients on this process.

Benzyl Alcohol↗
PubMed2001

Patterns of sperm precedence and predictors of paternity in the Trinidadian guppy.

Despite its widespread occurrence in animals, sperm competition has been studied in a limited range of taxa. Among the most neglected groups in this respect are internally fertilizing fish in which virtually nothing is known about the dynamics of sperm competition. In this study, we examined the outcome of sperm competition when virgin female guppies mated with two males. Behavioural cues were used to ensure that each male mated once (with female cooperation) and that sperm were successfully inseminated at copulation. Two polymorphic microsatellite loci were used to estimate the proportion of offspring sired by the second male (P2) and the results revealed a bimodal distribution with either first or (more often) second male priority The observed P2 distribution differed from that expected under the 'fair raffle' model of sperm competition. Random sperm mixing is therefore unlikely to account for the observed variance in P2 in this study. A further aim of our study was to identify predictors of male reproductive success. Using logistic linear modelling, we found that the best predictors of paternity were time to remating and the difference in courtship display rate between first and second males. Males that mated quickly and performed relatively high numbers of sigmoid displays obtained greater parentage than their slower and less vigorous counterparts. Since females are attracted to high-displaying males, our results suggest that female choice may facilitate sperm competition and/or sperm choice in guppies.

Animals↗