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Results for “hypothesis testing”

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At least 217 records · Page 12Linked to original sources
PubMed1999

A physiological model for tert-amyl methyl ether and tert-amyl alcohol: hypothesis testing of model structures.

The oxygenate tert-amyl methyl ether (TAME) is a gasoline fuel additive used to reduce carbon monoxide in automobile emissions. To evaluate the relative health risk of TAME as a gasoline additive, information is needed on its pharmacokinetics and toxicity. The objective of this study was to use a physiologically-based pharmacokinetic (PBPK) model to describe the disposition of TAME and its major metabolite, tert-amyl alcohol (TAA), in male Fischer-344 rats. The model compartments for TAME and TAA were flow-limited. The TAME physiological model had 6 compartments: lung, liver, rapidly perfused tissues, slowly perfused tissues, fat, and kidney. The TAA model had 3 compartments: lung, liver, and total-body water. The 2 models were linked through metabolism of TAME to TAA in the liver. Model simulations were compared with data on blood concentrations of TAME and TAA taken from male Fischer-344 rats during and after a 6-hour inhalation exposure to 2500, 500, or 100 ppm TAME. The PBPK model predicted TAME pharmacokinetics when 2 saturable pathways for TAME oxidation were included. The TAA model, which included pathways for oxidation and glucuronide conjugation of TAA, underpredicted the experimental data collected at later times postexposure. To account for biological processes occurring during this time, three hypotheses were developed: nonspecific binding of TAA, diffusion-limited transport of TAA, and enterohepatic circulation of TAA glucuronide. These hypotheses were tested using three different model structures. Visual inspection and statistical evaluation involving maximum likelihood techniques indicated that the model incorporating nonspecific binding of TAA provided the best fit to the data. A correct model structure, based upon experimental data, statistical analyses, and biological interpretation, will allow a more accurate extrapolation to humans and, consequently, a greater understanding of human risk from exposure to TAME.

Administration, Inhalation↗
PubMed1991

Problem of between-eye correlation for statistical hypothesis testing: rabbit corneal thickness.

The two eyes of a subject often yield correlated data. Statistical analysis which treats correlated data as if it were independent is most likely to be biased toward statistical significance; that is, the probability of a type I error is likely to be inflated. To illustrate the importance of lack of independence to the inferential process, data from an experimental design commonly used in optometric research are used to demonstrate (1) the potential magnitude of between-eye correlation, (2) the statistical bias toward a significant outcome when the between-eye correlation is ignored via inappropriate analysis, and (3) simple ways by which the bias can be avoided. The researcher must be aware of the between-eye correlation which exists for the particular effect under study, and the statistical bias that ensues from the correlation when the data are not handled correctly.

Animals↗
PubMed2004

Comparative analysis of gene sets in the Gene Ontology space under the multiple hypothesis testing framework.

The Gene Ontology (GO) resource can be used as a powerful tool to uncover the properties shared among, and specific to, a list of genes produced by high-throughput functional genomics studies, such as microarray studies. In the comparative analysis of several gene lists, researchers maybe interested in knowing which GO terms are enriched in one list of genes but relatively depleted in another. Statistical tests such as Fisher's exact test or Chi-square test can be performed to search for such GO terms. However, because multiple GO terms are tested simultaneously, individual p-values from individual tests do not serve as good indicators for picking GO terms. Furthermore, these multiple tests are highly correlated, usual multiple testing procedures that work under an independence assumption are not applicable. In this paper we introduce a procedure, based on False Discovery Rate (FDR), to treat this correlated multiple testing problem. This procedure calculates a moderately conserved estimator of q-value for every GO term. We identify the GO terms with q-values that satisfy a desired level as the significant GO terms. This procedure has been implemented into the GoSurfer software. GoSurfer is a windows based graphical data mining tool. It is freely available at http://www.gosurfer.org.

Algorithms↗
PubMed2003

A generally robust approach to hypothesis testing in independent and correlated groups designs.

Standard least squares analysis of variance methods suffer from poor power under arbitrarily small departures from normality and fail to control the probability of a Type I error when standard assumptions are violated. These problems are vastly reduced when using a robust measure of location; incorporating bootstrap methods can result in additional benefits. This paper illustrates the use of trimmed means with an approximate degrees of freedom heteroskedastic statistic for independent and correlated groups designs in order to achieve robustness to the biasing effects of nonnormality and variance heterogeneity. As well, we indicate when a boostrap methodology can be effectively employed to provide improved Type I error control. We also illustrate, with examples from the psychophysiological literature, the use of a new computer program to obtain numerical results for these solutions.

Algorithms↗
PubMed1990

Statistical inference on mean dioptric power: hypothesis testing and confidence regions.

It has not hitherto been possible to apply formal methods of statistical analysis to data on dioptric powers. The solution to the basic statistical problem is now provided in this paper. Recognition of the matric-variate nature of dioptric power allows calculation of sample means and variance-covariances. These in turn can be used to calculate a statistic for testing hypotheses on population means and for obtaining confidence regions for those means. In a graphical representation of dioptric power the confidence region turns out to be an ellipsoid centred on the mean of the sample of dioptric powers. The theory is illustrated by means of numerical examples. Singularity of the variance-covariance matrix may occur especially when the sample is small. When it does occur it is the cause of some difficulty in applying the statistics. Nevertheless singularity is rare in practical situations and can usually be avoided simply by increasing the size of the sample. Singularity, therefore, is not treated fully in this paper. Dioptric power is essentially four-dimensional in character but in practice a three-dimensional subspace is almost always sufficient. To avoid the difficulty of having to represent four-dimensional shapes and to avoid the complication of singularity (which is the rule rather than the exception in practice in four-space) only the common three-dimensional problem is considered in detail.

Analysis of Variance↗
PubMed1991

Hypothesis testing as an approach to the analysis of complex tachycardias--an illustrative case of a preexcitation variant.

The correct elucidation of the electrophysiological substrate and mechanism(s) responsible for a complex arrhythmia requires a systematic approach to the analysis of the electrophysiological data. One approach calls for the formulation of a set of hypotheses that could explain the data obtained during the study. The hypotheses are then tested for compatibility with phenomena observed and the one that agrees with the majority of the findings would represent the most tenable explanation. We present the case of a young girl with a wide QRS complex tachycardia and a history of ventricular preexcitation that illustrates this approach. The complexities were resolved only after intraoperative analysis and surgical ablation of a right-sided accessory pathway with decremental properties, and provides further insight into our understanding of the nodoventricular Mahaim fiber.

Anti-Arrhythmia Agents↗
PubMed1999

Rapid hypothesis testing with Candida albicans through gene disruption with short homology regions.

Disruption of newly identified genes in the pathogen Candida albicans is a vital step in determination of gene function. Several gene disruption methods described previously employ long regions of homology flanking a selectable marker. Here, we describe disruption of C. albicans genes with PCR products that have 50 to 60 bp of homology to a genomic sequence on each end of a selectable marker. We used the method to disrupt two known genes, ARG5 and ADE2, and two sequences newly identified through the Candida genome project, HRM101 and ENX3. HRM101 and ENX3 are homologous to genes in the conserved RIM101 (previously called RIM1) and PacC pathways of Saccharomyces cerevisiae and Aspergillus nidulans. We show that three independent hrm101/hrm101 mutants and two independent enx3/enx3 mutants are defective in filamentation on Spider medium. These observations argue that HRM101 and ENX3 sequences are indeed portions of genes and that the respective gene products have related functions.

Alleles↗