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Results for “parameter estimation”

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PubMed2006

Ultraviolet spectrophotometry as an index parameter for estimating the biochemical oxygen demand of domestic wastewater.

The relationship between ultraviolet absorbance at 280 nm (UV280) and the 5-day Biochemical Oxygen Demand (BOD5) test was evaluated using wastewater samples collected during March - December 1998 from the Fort Meade wastewater treatment plant (Maryland, U.S.A.). Three types of samples were collected: raw influent wastewater, primary effluent, and the effluent from the nitrification settling basin. A regression of BOD5 on UV280 was obtained using half of the data, with the other half of the data used to test application of the equation. The presence of NO3 and NO2, did not interfere with the BOD5/UV relationship. However, the relative fraction of organic compounds that absorb at UV280 and are biodegradable did appear to decrease across the treatment plant, thereby reducing the strength of the association between BOD5 and UV280 further along the treatment train. Interestingly, the exclusion of solids > 1 microm from the BOD5 test did not strengthen the association between BOD5 and UV280. These results suggest that simple UV absorbance measurements may be a useful analytical tool for wastewater treatment personnel, allowing them to quickly monitor for changes in the BOD5 during the treatment process and to quickly estimate the BOD5 when determining what dilutions to use in the standard BOD5 test. However, such relationships are likely to be wastewater and treatment plant specific and variable with time and treatment.

Bioreactors↗

PubMed2002

Models for microarray gene expression data.

This paper describes a general methodology for the analysis of differential gene expression based on microarray data. First, we characterize the data by a linear statistical model that accounts for relevant sources of variation in the data and then we consider estimation of the model parameters. Because microarray studies typically involve thousands of genes, we propose a two-stage method for parameter estimation. The interaction terms for genes and experimental conditions in this model capture all relevant information about differential gene expression in the microarray data. We propose a mixture distribution model for a summary statistic of differential expression that consists of null and alternative component distributions. The mixture model suggests two methods for identifying genes exhibiting differential expression. One is a frequentist method that identifies distinguished genes and the other an empirical Bayes procedure that yields estimated posterior probabilities of differential expression, conditional on observed microarray readings.

Animals↗

PubMed2005

Joint modeling of linkage and association: identifying SNPs responsible for a linkage signal.

Once genetic linkage has been identified for a complex disease, the next step is often association analysis, in which single-nucleotide polymorphisms (SNPs) within the linkage region are genotyped and tested for association with the disease. If a SNP shows evidence of association, it is useful to know whether the linkage result can be explained, in part or in full, by the candidate SNP. We propose a novel approach that quantifies the degree of linkage disequilibrium (LD) between the candidate SNP and the putative disease locus through joint modeling of linkage and association. We describe a simple likelihood of the marker data conditional on the trait data for a sample of affected sib pairs, with disease penetrances and disease-SNP haplotype frequencies as parameters. We estimate model parameters by maximum likelihood and propose two likelihood-ratio tests to characterize the relationship of the candidate SNP and the disease locus. The first test assesses whether the candidate SNP and the disease locus are in linkage equilibrium so that the SNP plays no causal role in the linkage signal. The second test assesses whether the candidate SNP and the disease locus are in complete LD so that the SNP or a marker in complete LD with it may account fully for the linkage signal. Our method also yields a genetic model that includes parameter estimates for disease-SNP haplotype frequencies and the degree of disease-SNP LD. Our method provides a new tool for detecting linkage and association and can be extended to study designs that include unaffected family members.

Alleles↗

PubMed1990

Pharmacokinetics of atracurium during continuous infusion.

The pharmacokinetics of atracurium were investigated by a model-independent method during continuous infusion under propofol anaesthesia. Following an intubating dose of suxamethonium, atracurium was infused according to a predetermined profile which continually set the infusion rate to maintain stable muscle paralysis and a target steady state plasma concentration when equilibrium between the biophase and plasma had occurred. Atracurium was infused for the first 1 h to maintain a target steady state plasma concentration of 1.0 microgram ml-1. Thereafter, the target plasma concentration was adjusted to maintain 90% muscle paralysis. The maintenance infusion rate required to maintain 90% paralysis was 4.25 (SD) 1.11 micrograms kg-1 min-1, with an estimated steady state plasma concentration of atracurium required to maintain 90% paralysis (Cpss90) of 1.13 (0.24) microgram ml-1. The clearances of atracurium, estimated by the constant infusion rate required to maintain the steady state plasma concentration, at 50-60 min and during estimation of Cpss90 were 3.8 (1.0) and 3.9 (1.1) ml kg-1 min-1 (ns), respectively. The volume of distribution at steady state of atracurium after 1 h of infusion, calculated using the clearance and the area under the plasma concentration-time curve to 1 h, was 130 (50) ml kg-1. These estimates of the pharmacokinetic parameters of atracurium are markedly different from those derived from pharmacokinetic analysis of single bolus dose data. Normalization of the pharmacokinetic parameter estimates by lean body mass decreased interpatient variability and improved precision in comparison with the un-weighted data and normalization by total body weight.

Anesthesia, Intravenous↗

PubMed1998

EMS-induced polygenic mutation rates for nine quantitative characters in Drosophila melanogaster.

Polygenic mutations were induced by treating Drosophila melanogaster adult males with 2.5 mM EMS. The treated second chromosomes, along with untreated controls, were then made homozygous, and five life history, two behavioral, and two morphological traits were measured. EMS mutagenesis led to reduced performance for life history traits. Changes in means and increments in genetic variance were relatively much higher for life history than for morphological traits, implying large differences in mutational target size. Maximum likelihood was used to estimate mutation rates and parameters of distributions of mutation effects, but parameters were strongly confounded with one another. Several traits showed evidence of leptokurtic distributions of effects and mean effects smaller than a few percent of trait means. Distributions of effects for all traits were strongly asymmetrical, and most mutations were deleterious. Correlations between life history mutation effects were positive. Mutation parameters for one generation of spontaneous mutation were predicted by scaling parameter estimates from the EMS experiment, extrapolated to the whole genome. Predicted mutational coefficients of variation were in good agreement with published estimates. Predicted changes in means were up to 0.14% or 0.6% for life history traits, depending on the model of scaling assumed.

Analysis of Variance↗

PubMed2001

Distinguishing migration from isolation: a Markov chain Monte Carlo approach.

A Markov chain Monte Carlo method for estimating the relative effects of migration and isolation on genetic diversity in a pair of populations from DNA sequence data is developed and tested using simulations. The two populations are assumed to be descended from a panmictic ancestral population at some time in the past and may (or may not) after that be connected by migration. The use of a Markov chain Monte Carlo method allows the joint estimation of multiple demographic parameters in either a Bayesian or a likelihood framework. The parameters estimated include the migration rate for each population, the time since the two populations diverged from a common ancestral population, and the relative size of each of the two current populations and of the common ancestral population. The results show that even a single nonrecombining genetic locus can provide substantial power to test the hypothesis of no ongoing migration and/or to test models of symmetric migration between the two populations. The use of the method is illustrated in an application to mitochondrial DNA sequence data from a fish species: the threespine stickleback (Gasterosteus aculeatus).

Animals↗

PubMed2001

Modeling linkage disequilibrium between a polymorphic marker locus and a locus affecting complex dichotomous traits in natural populations.

Linkage disequilibrium is an important topic in evolutionary and population genetics. An issue yet to be settled is the theory required to extend the linkage disequilibrium analysis to complex traits. In this study, we present theoretical analysis and methods for detecting or estimating linkage disequilibrium (LD) between a polymorphic marker locus and any one of the loci affecting a complex dichotomous trait on the basis of samples randomly or selectively collected from natural populations. Statistical properties of these methods were investigated and their powers were compared analytically or by use of Monte Carlo simulations. The results show that the disequilibrium may be detected with a power of 80% by using phenotypic records and marker genotype when both the trait and marker variants are common (30%) and the LD is relatively high (40-100% of the theoretical maximum). The maximum-likelihood approach provides accurate estimates of the model parameters as well as detection of linkage disequilibrium. The likelihood method is preferred for its higher power and reliability in parameter estimation. The approaches developed in this article are also compared to those for analyzing a continuously distributed quantitative trait. It is shown that a larger sample size is required for the dichotomous trait model to obtain the same level of power in detecting linkage disequilibrium as the continuous trait analysis. Potential use of these estimates in mapping the trait locus is also discussed.

Alleles↗

PubMed1988

Statistical analysis of DNA sequences.

Developments in the statistical analysis of DNA sequence data since 1984 are reviewed. Mathematical methods employing dynamic programming or incorporating Markov chain theory have been developed to search sequences for regions of similarity and to align sequences. When the biological forces of mutation and genetic drift are included in models, distances between aligned sequences allow the construction of evolutionary trees. Theory based on models may lead to estimates of variation of parameter estimates and so give a means of assessing the statistical significance of observed patterns and relationships. The complexity of DNA sequences, however, suggests that most statistical inferences will rest on random permutations of sequences.

Base Sequence↗

PubMed1999

Perioperative pharmacodynamics of acetaminophen analgesia in children.

BACKGROUND: There are no adequate pharmacodynamic data relating concentrations of acetaminophen in serum to analgesia. METHODS: Children undergoing outpatient tonsillectomy were administered acetaminophen either orally, 0.5-1.0 h preoperatively (n = 20), or per rectum at induction of anesthesia (n = 100). No other analgesic agents were administered. Individual concentrations of acetaminophen in serum and pain scores (0-10) measured over a 4-h postoperative period were analyzed using a nonlinear mixed-effects model (NONMEM). RESULTS: Mean (% CV) estimates of population pharmacokinetic parameters with percent coefficient of variation, standardized to a 70-kg person, for a one-compartment model with first-order input, lag time, and first order-elimination were a volume of distribution of 60 (21) 1 and a clearance of 13.5 (46) 1/h. Rectally administered acetaminophen had an absorption half-life of 35 (63) min with a lag time of 40 min. The absorption half-life for the oral preparation was 4.5 (63) min without a detectable lag time. The relative bioavailability of the rectal compared with the oral formulation was 0.54. The equilibration half-time of an effect compartment was 1.6 (131) h. Pharmacodynamic population parameter estimates (percent coefficient of variation) for a fractional sigmoidal Emax model, in which the greatest possible pain relief equates to an Emax of 1, were Emax = 1, EC50 (the concentration producing 50% of Emax) = 3.4 (94) mg/l, and Hill coefficient = 0.54 (42). CONCLUSIONS: The pharmacodynamics of acetaminophen can be described using a sigmoidal Emax model with a low Hill coefficient. To achieve a mean posttonsillectomy pain score of 3.6 of 10, an effect compartment concentration of 10 mg/l is necessary.

Acetaminophen↗

PubMed1993