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 1,477 records · Page 82Linked to original sources
PubMed1991

Limiting-laws of polyelectrolyte solutions. Ionic distribution in mixed-valency counterions systems. I: The model.

An extension of the counterion-condensation (CC) theory of linear polyelectrolytes has been developed for the case of a system containing a mixture of counterions of different valency, i and j. The main assumption in the derivation of the model is that the relative amount of the condensed counterions of the type i and j is strongly correlated and it is determined by the overall physical bounds of the system. The results predicted by the model are consistent, in the limiting cases of single species component, with those of the original CC theory. The most striking results are obtained for the cases of low charge density and excess of counterion species: in particular, an apparent positive "binding" cooperativity of divalent ions is revealed for small, increasing additions of M2+ ions to a solution containing a swamping amount of monovalent salt and a polyelectrolyte of low charge density. Apparent "competitive binding" of mono- and divalent ions derives as a bare consequence of the electrostatic interactions. Theoretical calculations of experimentally accessible quantities, namely single-(counter) ion activity coefficients, confirm the surprising predictions at low charge density, which qualitatively agree with the measured quantities.

Journal Article↗
PubMed1987

Time course adaptations in rat skeletal muscle isomyosins during compensatory growth and regression.

The purpose of this study was to ascertain the time course of change during both compensatory growth (hypertrophy) and subsequent growth regression on myosin isoform expression in rodent fast-twitch plantaris muscle in response to functional overload (induced by removal of synergists). Peak hypertrophy of the plantaris muscle (92%) occurred after 9 wk of overload. After 7 wk of overload regression (induced by a model of hindlimb unweighting), muscle weight returned to within 30% of control values. Myofibril protein content (mg/g muscle) remained relatively constant throughout the overload period but became significantly depressed relative to control values after 7 wk of regression. However, when expressed on a per muscle basis (mg/muscle) no differences existed at this time point (t = 7 wk regression). The distribution of native myosin isoforms in the myofibril protein pool of the overloaded plantaris muscle reflected a progressive increase (23% at t = 9 wk; P less than 0.001) in the relative proportion of slow myosin (Sm). This change was also accompanied by increases in intermediate myosin (Im) as well as the repression of the fast myosin one (Fm1) isoform (P less than 0.001). These shifts in Sm and Fm1 isoform expression were gradually reversed during the regression period, whereas Im remained elevated relative to control values. These adaptive changes in myosin isoform expression during both hypertrophy and regression were further supported by concomitant shifts in both myosin adenosinetriphosphatase (ATPase) activity (decreased during overload) and slow myosin light chain (SLC) expression. However, during regression the changes in myosin isoform expression and myosin ATPase were not as synchronous as they were during overload. Estimation of the mixed myosin heavy chain (MHC) half-life (t 1/2), using a linear model that assumes zero-order synthesis and first-order degradation kinetics, revealed t 1/2 values of approximately 19 and 10 days for the overload and regression periods, respectively. Collectively these data suggest that 1) skeletal muscle myosin isoforms and corresponding ATPase activity are in a dynamic state of change, although not completely synchronous, in response to altered muscle stress, and 2) the kinetics of change in the mixed MHC protein pool are slower during compensatory growth compared with regression of growth.

Adaptation, Physiological↗
PubMed1984

Linear regression analysis of binary response data with mixed covariates - a simulation study.

In a clinical trial with binary outcome, analyses are required for treatment or study group comparisons adjusted for covariate effects. A special problem arises with "mixed binary and Gaussian covariates", i.e., when some covariates are binary and some are continuous and may be assumed to be Gaussian. The correct model for such a data structure is of the logistic form. In the past, analyses of such data have been carried out by linear regression as well as by logistic regression methods. In this article, computer simulation was used to study the type I error level of linear regression analysis tests for treatment comparisons, when applied to a binary outcome variate obeying a logistic model with mixed binary and Gaussian covariates. It was found that the true type I error level depends on the distribution of covariates among treatment groups and on the magnitudes of the actual covariate effects, and can differ importantly from that assumed under Gaussian theory. Some recommendations are made for developing computer package programs for this problem.

Clinical Trials as Topic↗
PubMed1998

Development of adjustment factors for backfat and loin muscle area from serial real-time ultrasonic measurements on purebred lines of swine.

We recorded serial real-time ultrasonic measurements of backfat and loin muscle area to assess the rate of change per unit of live weight and growth rate measured as the change in weight per day of age during the finishing stage of production. Barrows (648) and gilts (459) representing eight major U.S. pure breeds of swine were evaluated in the study. Real-time ultrasonic measurements of backfat and loin muscle area were collected at average live weights (LW) of 67.4, 80.3, 93.4, and 104.9 kg. Backfat was measured at the midline over the last rib (LR) and last lumbar vertebra (LL) and off the midline at the 3/4 point (BF10) over the 10th rib. Loin muscle area (LMA) images were collected from the right-hand side of each pig at the 10th rib. Deposition rates were calculated on an intrapig basis for the dependent scan variables BF10, LMA, LR, and LL in models that included the independent variables LW and LW2. For growth rate (WDA), LW was regressed on age and age. Intrapig linear regression coefficients and y-intercepts were further analyzed as dependent variables in a mixed model that included the fixed effects test group, sex, and breed and random effects of sire and dam nested within breed. Significant breed effects were present for deposition rates of BF10, LMA, LR, LL, and WDA. Across the eight breeds, BF10 was deposited at a mean of .271 +/- .008 mm/kg, a rate faster than the average for LR (.201 mm/kg) and LL (.206 mm/kg). The LMA deposition rate across breeds averaged .304 cm2/kg. Average WDA across the breeds was .774 kg. Barrows deposited fat faster at all locations, deposited muscle slower, and grew faster than gilts in this study (P < .001). The results of this study indicate a need for breed- and sex-specific adjustment factors for rates of backfat and loin muscle deposition and for weight per day of age in swine.

Adipose Tissue↗
PubMed1998

Effects of demographic variables on vorozole pharmacokinetics in healthy volunteers and in breast cancer patients.

PURPOSE: Vorozole (VOR) is a selective nonsteroidal inhibitor of the cytochrome P450-dependent aromatase that catalyzes the conversion of androgens to estrogens. It is currently being developed as a therapeutic agent in the endocrine treatment of postmenopausal women with breast cancer. This work was aimed to explore the effects of demographic and other variables on VOR pharmacokinetics. METHODS: VOR plasma concentration-time data were obtained in healthy volunteers and in breast cancer patients after the oral administration of 2.5 mg of VOR as a single dose or once daily. The data obtained in 6 formal pharmacokinetics (PK) studies with frequent plasma sampling were included in the data base (84 healthy male and female volunteers and 13 breast cancer patients). Also included were data from 2 clinical efficacy trials involving 286 breast cancer patients who were treated for several months (1 sample per visit, up to 14 samples/patient). The nonlinear mixed-effect modeling (NONMEM) approach was applied. The two-compartment linear PK model with first-order absorption parameterized in terms of apparent clearance (CL), apparent central and peripheral volumes of distribution (Vc and Vp, respectively), apparent distributional flow (Q), and absorption constant (ka) was used. A population model was developed using data from formal PK studies. The final estimates of fixed and random effect parameters were obtained using both formal study data and clinical-efficacy trial data. RESULTS: The typical CL value obtained after a single dose was lower in patients (4.8 l/h) as compared with healthy volunteers (8.6 l/h) and did not depend on gender. The multiple- to single-dose ratio was 0.76. CL was constant over ages of up to 50 years and then decreased slightly (0.047 l/h per year). The typical CL value did not depend on any demographic variable related to body size (total body weight, WT; body surface area; lean body mass). Q and Vc were proportional to WT (0.17 l h(-1) kg(-1) and 0.43 l/kg, respectively). Vp was also proportional to WT and was higher in women as compared with men (0.64 and 0.40 l/kg, respectively). The same was true for the apparent steady-state volume of distribution. No effect of race or the duration of therapy (0.5-28 months) was seen. The unexplained variability in CL and the residual variability in VOR plasma concentrations were 39% and 28% (coefficient of variation), respectively. CONCLUSIONS: Healthy volunteer/patient, single/multiple dosing differences, and age were identified as the fixed effects influencing the CL of VOR. WT was the main determinant of distributional PK parameters. The peripheral and steady-state volumes of distribution were gender-dependent. In view of the relatively high degree of residual interpatient variability in CL, the slight effect of age on it is unlikely to be clinically significant.

Adult↗
PubMed2005

Assessment of orthodontic treatment outcomes: early treatment versus late treatment.

This investigation compares the treatment outcome of early treatment (in the mixed dentition) with that of late treatment (early permanent dentition) using objective evaluation criteria. Pretreatment and post-treatment records of all patients (n = 512) completed from 1998 to 2000 in the graduate orthodontics clinic at the Indiana University School of Dentistry (IUSD) were evaluated by the American Board of Orthodontics Objective Grading System (ABO OGS) and Comprehensive Clinical Assessment (CCA) method developed at IUSD. Two definitions of early treatment were used in this study: (1) all patients started in the mixed dentition with early-treatment objectives and (2) female individuals were <10 years and male individuals were <10.5 years of age when treatment began. Comparison of the final results between early- vs late-treatment groups showed that the early-treatment group had significantly longer treatment time and worse CCA scores than the late-treatment group, regardless of the definition of the early-treatment group or whether the early-debond (premature treatment termination) cases were included or not. There was no significant difference between early- and late-treatment groups regarding the ABO OGS score, which indicated that the CCA method is more sensitive in detecting compromised outcomes for patients with long treatment times. Prematurely terminated treatment was more prevalent in the early-treatment group than in the late-treatment group. In this large sample of consecutive patients (n = 512), the disadvantages of early treatment was prolonged treatment time, worse CCA score, and a higher incidence of premature termination of treatment, which was attributed to patient/parent "burn-out."

Age Factors↗
PubMed2005

Are the lower incisors the best predictors for the unerupted canine and premolars sums? an analysis of a Peruvian sample.

The lower permanent incisor tooth width sum has been proposed as the best predictor for the tooth width sums of the unerupted canine and premolars (SPCP) for populations from different ethnic origins. Only two previous studies have refuted it. The purpose of the present study was to determine which sum or combination of sums of permanent tooth widths presented the best prediction capability for the SPCP in a Peruvian sample, to calculate a specific linear regression equation for this population, and to evaluate the clinical significance. A total of 150 children with complete permanent dentitions were selected. Fifty more children were used as a validation sample for the application of a multiple linear regression equation (MLRE). They did not present clinically visible dental caries or proximal restorations and no active or previous orthodontic treatment. Their dental casts were measured to 0.1 mm with a sliding caliper with a Vernier scale. Three-way analysis of variance, Pearson Correlation Test, Fisher Z values and a MLRE were used for the statistical analysis. The combination of the sums of permanent upper and lower central incisors and upper first molars was the best predictor for the SPCP in this sample. A MLRE was calculated including sex and arch as additional predictor variables. The MLRE determination coefficient was 60% with a standard error of 0.8 mm. This new MLRE underestimates (less than 1 mm discrepancy) the actual SPCP in only 7% of the cases on the basis of a validation sample.

Adolescent↗
PubMed2002

Level and pattern of HIV-1-RNA viral load over age: differences between girls and boys?

OBJECTIVE: To estimate RNA viral load patterns over age in vertically infected children that account for between- and within-individual variation, treatment and assay cut-off detection level. To investigate possible sex-based differences. DESIGN: A total of 118 infected children with 894 RNA viral load measurements enrolled in the European Collaborative Study were prospectively followed from birth for up to 15 years. METHODS: Fractional polynomial and mixed effects models with censored data to assess the non-linear pattern of viral load over age, allowing for repeated measures. RESULTS: The RNA viral load peaked at approximately 3 months of age, and gradually declined thereafter. The sex by age interaction was significant (chi2 = 19.7, P < 0.001); viral load peaked higher for girls than boys, but after 4 years the RNA load was consistently 0.25-0.5 log10 lower for girls than boys. The effects of sex and treatment on viral load vary over age (chi2 = 6.31, P = 0.043). Sex differences in RNA viral load relating to measurement without treatment were more pronounced than those under treatment. Disease progression was more rapid for girls than for boys up to the age of 4 years, and less rapid thereafter; the overall difference was not statistically significant. CONCLUSION: Differences in RNA viral load over age between untreated boys and girls may have implications for policies for the initiation of antiretroviral therapy, but do not seem to translate into differences in progression to serious disease. The findings would suggest underlying biological explanations, which need further investigation.

Adolescent↗
PubMed2000

Depressive syndromes and functional disability in dementia.

The goals of this study were to assess (1) the prevalence of major and minor depression in Alzheimer's disease (AD), ischemic vascular dementia (IVD), and mixed dementia (AD/IVD); (2) demographic and clinical variables that may be associated with depression; and (3) the relationship between depression severity and the level of functional impairment and cognitive decline. Demographic variables, depression diagnoses, Mini-Mental State Examination scores, and Blessed Roth Dementia Rating Scale scores were compared in patients with AD (N = 582), IVD (N = 48), and mixed dementia (N = 61) using analysis of variance and linear regression models. Data were collected using standardized rating instruments at the time of the patients' initial evaluations at the University dementia clinics. The results were that (1) depression was related to lower education, (2) major depression was more prevalent in IVD compared to probable AD, and (3) functional impairment was greater in patients with minor or major depression compared to patients without depression. Our data suggest that the level of functional disability in dementia may be related to severity of depression. Additional studies are needed to validate our results and examine the contribution of additional neurobiologic factors to the pathophysiology of depression in dementia.

Aged↗
PubMed2002

Effect of radiation dose on the height of atomic bomb survivors: a longitudinal study.

We conducted a longitudinal analysis of height after age 20 for atomic bomb survivors in the Adult Health Study (AHS) cohort. The measurements we used were made from July 1958 to June 1998 (AHS examination cycles 1-20). We analyzed only the subjects with known atomic bomb radiation doses, excluding those who were not in the city at the time of bombing (ATB) and those exposed in utero. We also excluded from the analysis measurements made after the occurrence of vertebral fracture. The total number of subjects was 11,862, and the total number of measurements was 109,770; the mean number of measurements per subject was 9.25. Assuming that stature after age 20 is approximately constant, a simple mixed-effects model was fitted to stature after age 20, and linear dose effects for young ATB subjects were modeled for both sexes. The estimated mean heights for subjects born in 1945 in Hiroshima were 166.0 cm for men and 155.4 cm for women. The sex difference in height was 10.6 cm, with men significantly taller than women (P < 0.001). The difference between the cities was not significant (P = 0.162). The birth cohort effects per decade were -1.7 cm for men (P < 0.001) and -2.1 cm for women (P < 0.001). A reduction of stature due to radiation exposure was observed for individuals of both sexes who were below 19 years of age ATB (95% confidence interval, 17-21 years), and the dose effect was larger for women than for men (P = 0.028). The estimated effects per gray for those who were age 0 ATB were -1.2 cm for men and -2.0 cm for women and for those who were age 10 ATB were-0.57 cm for men and -0.96 cm for women.

Adolescent↗
PubMed2005

A linear programming approach for identifying a consensus sequence on DNA sequences.

MOTIVATION: Maximum-likelihood methods for solving the consensus sequence identification (CSI) problem on DNA sequences may only find a local optimum rather than the global optimum. Additionally, such methods do not allow logical constraints to be imposed on their models. This study develops a linear programming technique to solve CSI problems by finding an optimum consensus sequence. This method is computationally more efficient and is guaranteed to reach the global optimum. The developed method can also be extended to treat more complicated CSI problems with ambiguous conserved patterns. RESULTS: A CSI problem is first formulated as a non-linear mixed 0-1 optimization program, which is then converted into a linear mixed 0-1 program. The proposed method provides the following advantages over maximum-likelihood methods: (1) It is guaranteed to find the global optimum. (2) It can embed various logical constraints into the corresponding model. (3) It is applicable to problems with many long sequences. (4) It can find the second and the third best solutions. An extension of the proposed linear mixed 0-1 program is also designed to solve CSI problems with an unknown spacer length between conserved regions. Two examples of searching for CRP-binding sites and for FNR-binding sites in the Escherichia coli genome are used to illustrate and test the proposed method. AVAILABILITY: A software package, Global Site Seer for the Microsoft Windows operating system is available by http://www.iim.nctu.edu.tw/~cjfu/gss.htm

Algorithms↗
PubMed2005

A robustified modeling approach to analyze pediatric length of stay.

PURPOSE: Length of stay (LOS) is an important measure of the cost of pediatric hospitalizations, but the guidelines developed so far are not rigorously evidence-based. This study demonstrates a robust gamma mixed regression approach to analyze the positively skewed LOS variable, which has implications for future studies of pediatric health care management. METHODS: The robustified approach is applied to analyze hospital discharge data on childhood gastroenteritis in Western Australia (n=514). The model accounts for demographic characteristics and co-morbidities of the patients, as well as the dependency of LOS outcomes nested within the 58 hospitals in the State. The method is compared with the standard linear mixed regression with trimming of extreme observations. RESULTS: For the empirical application, the linear mixed regression results are sensitive to the magnitude of trimming. The identified significant factors from the robust regression model, namely infection, failure to thrive, and iron deficiency anemia are resistant to high-LOS outliers. CONCLUSIONS: Robust gamma mixed regression appears to be a suitable alternative to analyze the clustered and positively skewed pediatric LOS, without transforming and trimming the data arbitrarily.

Child, Hospitalized↗
PubMed1996

Pharmacokinetics and pharmacodynamics of AC137 (25,28,29 tripro-amylin, human) after intravenous bolus and infusion doses in patients with insulin-dependent diabetes.

A study was conducted to evaluate the effect of 30-mug, 100-mug, and 300-mug 2-minute bolus doses and 2-hour infusion doses of AC137 (25,28,29 tripro-amylin, human) on plasma AC137 concentrations and plasma glucose and lactate responses in patients with insulin-dependent diabetes mellitus (IDDM). The study design was an imbedded two-way cross-over wherein patients received placebo and active boluses in one period and placebo and active infusions in the other period. Two patients in each dose group received placebo throughout the two periods. Pharmacokinetics and pharmacodynamics (PK/PD) were determined during the 6-hour period after initiation of dosing. Data were fitted with a linked PK/PD model. Pharmacokinetics were linear over the dose range studied, and attenuation of glucose and lactate responses to a mixed meal was dose and concentration dependent. The results of the PK/PD model indicate that the attenuation of glucose and lactate responses was greater after AC137 infusion doses than after the same doses given as a bolus. Glucose and lactate responses to a mixed meal were essentially negated by the 300-mug infusion dose.

Adult↗
PubMed1980

A method of sire evaluation for dichotomies.

In this paper, the following problems associated with genetic evaluation of categorical traits by linear models are discussed: (1) Scores are arbitrarily assigned to response categories. (2) Mixed model solutions do not incorporate the restriction in the estimation space that the sum of response probabilities must total 1 across categories (3) The variance in the observed scale is not constant and depends on the genotypic value of the candidates for selection. (4) The additive genetic variance in the observed scale depends on the mean incidence of the character in the subpopulations considered in the model. (5) Nonadditive genetic variation is present in the observed scale. (6) Linear relationships fail outside a restricted range of the data. (7) Ranking optimality of best linear predictors is lacking when the conditional expectation of the predictand given the data is not linear. A method of sire evaluation of dichotomies based on a log-linear model is introduced, its properties are discussed and examples are presented.

Animals↗
PubMed2003

Congener-based Aroclor quantification and speciation techniques: a comparison of the strengths, weaknesses, and proper use of two alternative approaches.

This paper compares two previously published methods, an Aroclor estimation method and a mixing model method, that relate Aroclor contamination to congener specific data in environmental samples. The Aroclor estimation method, which is consistent with U.S. EPA Method 8082, uses a limited set of congener specific data to estimate Aroclor contributions to the sample, while the mixing model method uses the full congener data to model sample compositions as linear combinations of Aroclors. The performance of these methods are compared, using 181 samples at a variety of trophic levels, in terms of (a) total PCB concentrations, (b) compositional modification levels from original Aroclors, and (c) determination of the Aroclor mixture or mixtures best describing the sample (Aroclor speciation). We find that the two methods agree in all three terms for samples of low trophic level, but disagree for samples of higher tropic levels. Most significantly, the comparison reveals systematic overestimation of total PCB content by the Aroclor estimation method for samples at high trophic levels. The implication is that Aroclor determinations using persistent congeners cannot reliably be used as surrogates for total PCB concentration. The strengths and weaknesses of each method are detailed.

Animals↗
PubMed2000

The use of case-parent triads to study joint effects of genotype and exposure.

Most noninfectious disease is caused by low-penetrance alleles interacting with other genes and environmental factors. Consider the simple setting where a diallelic autosomal candidate gene and a binary exposure together affect disease susceptibility. Suppose that one has genotyped affected probands and their parents and has determined each proband's exposure status. One proposed method for assessment of etiologic interaction of genotype and exposure, an extension of the transmission/disequilibrium test, tests for differences in transmission of the variant allele from heterozygous parents to exposed versus unexposed probands. We show that this test is not generally valid. An alternative approach compares the conditional genotype distribution of unexposed cases, given parental genotypes, versus that of exposed cases. This approach provides maximum-likelihood estimators for genetic relative-risk parameters and genotype-exposure-interaction parameters, as well as a likelihood-ratio test (LRT) of the no-interaction null hypothesis. We show how to apply this approach, using log-linear models. When a genotype-exposure association arises solely through incomplete mixing of subpopulations that differ in both exposure prevalence and allele frequency, the LRT remains valid. The LRT becomes invalid, however, if offspring genotypes do not follow Mendelian proportions in each parental mating type-for example, because of genotypic differences in survival-or if a genotype-exposure association reflects an influence of genotype on propensity for exposure-for example, through behavioral mechanisms. Because the needed assumptions likely hold in many situations, the likelihood-based approach should be broadly applicable for diseases in which probands commonly have living parents.

Disease Susceptibility↗
PubMed1994

A characterization of the blood lead concentrations in Saudi Arabian children.

The results presented in this paper are those derived from an extensive analysis of lead in 1047 children aged 2 months to 16 years attending as outpatients at a reference hospital, taking cases from all parts of the Kingdom of Saudi Arabia. Since the distribution of blood lead data in the sample suggested the existence of two mixed sub groups among the studied children, a non-linear mathematical model was used fit to the data. More than 20% of the children had blood lead concentrations above 0.608 mumol/L (12.59 micrograms/dL).

Adolescent↗
PubMed1998

Evaluation of the accuracy of solid implant casts.

PURPOSE: Materials used to fabricate the most dimensionally accurate implant casts have not been identified experimentally. The purpose of this investigation was to examine the dimensional accuracy of implant casts fabricated with different materials. Measurements of linear horizontal dimensional change and strain produced on a master framework were evaluated and correlated. MATERIALS AND METHODS: A master framework was fabricated to fit an aluminum five-implant model. Forty polyether implant impressions of the aluminium model were randomly grouped and poured in either Vel-mix, Die Keen, Resin Rock, or Low Fusing Alloy. A digital veneer caliper was used to measure linear distance between the most distal abutments on each of the experimental implant casts and the master model. In addition, strain values were recorded from strain gauges bonded in the mesiodistal axis of the framework, which was secured by prosthetic retaining screws torqued to 10 Ncm. RESULTS: A one-way ANOVA showed a significant difference among the four die materials in dimensional change of the experimental casts (p = .0001). A post-hoc Duncan's multiple-range test (p < .05) showed that casts fabricated with Low Fusing Alloy had the least linear dimensional change from the master cast, but the material exhibited the greatest dimensional variability. A MANOVA (Wilks' Lambda) showed significant differences in strain on the framework based upon die material (p = .015). A post-hoc Duncan's multiple-range test (p < .05) showed that Resin Rock casts induced significantly less strain on the framework than the other materials. Negligible correlation was found between the linear horizontal dimensional change and the total absolute strain on the framework. CONCLUSION: Experimental implant casts made of Resin Rock minimized strain on the master framework and decreased the amount of framework distortion on casts of this material. Low Fusing Alloy yielded accurate casts, but highly variable linear dimensional changes in the horizontal dimension may preclude its clinical benefit.

Analysis of Variance↗