Search

The ability of epidemiologic evidence to inform regulatory decisions is largely dependent on the coherence and quality of the published literature. This systematic review examines the quality and consistency of studies assessing health outcomes associated with exposure to triclosan (TCS), an antimicrobial chemical with a short physiologic half-life. We used elements of the Biomonitoring, Environmental Epidemiology, and Short-Lived Chemicals instrument to evaluate aspects of study quality. Each methodological domain – overall design, exposure assessment, and data analysis – was categorized according to three tiers where Tier 1 indicated the highest quality. We also examined consistency of methods, results and reporting as considerations for weight of evidence (WOE) assessment. Studies were considered sufficiently comparable if they addressed the same or similar research questions. Forty-two studies met the criteria for inclusion. Only one randomized cross-over clinical trial of TCS was assigned to Tier 1 for all three domains. Most other studies were assigned to Tier 3 for at least one domain. Although the available literature examined more than 100 different health endpoints and reported hundreds of different measures of association, few studies were considered comparable. For reported measures of association, most were not significantly different from the null; the few statistically significant results represented isolated findings without a discernable across- or within-study pattern. We conclude that the current body of epidemiologic literature does not allow a meaningful WOE assessment due to methodological limitations of individual studies and lack of inter-study consistency. On the other hand, methodologically stronger studies may be used to inform future research. [ABSTRACT FROM PUBLISHER]

As the complexity and heterogeneity of cancer is being increasingly appreciated through genomic analyses, microarray-based cancer classification comprising multiple discriminatory molecular markers is an emerging trend. Such multiclass classification problems pose new methodological and computational challenges for developing novel and effective statistical approaches. In this paper, we introduce a new approach for classifying multiple disease states associated with cancer based on gene expression profiles. Our method focuses on detecting small sets of genes in which the relative comparison of their expression values leads to class discrimination. For an m-class problem, the classification rule typically depends on a small number of m-gene sets, which provide transparent decision boundaries and allow for potential biological interpretations. We first test our approach on seven common gene expression datasets and compare it with popular classification methods including support vector machines and random forests. We then consider an extremely large cohort of leukemia cancer patients to further assess its effectiveness. In both experiments, our method yields comparable or even better results to benchmark classifiers. In addition, we demonstrate that our approach can integrate pathway analysis of gene expression to provide accurate and biological meaningful classification. [ABSTRACT FROM AUTHOR]

An iterative position-specific score matrix (PSSM)-based approach was used to predict σ28 promoters in 11 Shewanella genomes. The Shewanella Correlation Browser was used to distinguish true-positive predictions from false-positive predictions in Shewanella oneidensis MR-1 by generating a σ28-regulated transcriptional network from transcriptional profiling data. This dual-pronged approach identified several genes that have σ28 promoters and that may be involved with motility or chemotaxis in Shewanella. [ABSTRACT FROM AUTHOR]

A two-step approach was used to predict σ28 promoter sequences in a number of Gammaproteobacteria. Putative promoters were initially identified upstream of motility and chemotaxis genes in test species based on their similarity to the Escherichia coliσ28 promoter consensus. These sequences were then used to generate position specific score matrices that were used iteratively during whole-genome analyses. The consistent identification of promoter sequences upstream of orthologous genes suggested that the predictions were biologically relevant. [ABSTRACT FROM AUTHOR]

In shotgun proteomics, tandem mass spectrometry is used to identify peptides derived from proteins. After the peptides are detected, proteins are reassembled via a reference database of protein or gene information. Redundancy and homology between protein records in databases make it challenging to assign peptides to proteins that may or may not be in an experimental sample. Here, a probability model is introduced for determining the likelihood that peptides are correctly assigned to proteins. This model derives consistent probability estimates for assembled proteins. The probability scores make it easier to confidently identify proteins in complex samples and to accurately estimate false-positive rates. The algorithm based on this model is robust in creating protein complements from peptides from bovine protein standards, yeast, Ustilago maydis cell lysates, and Arabidopsis thaliana leaves. It also eliminates the side effects of redundancy and homology from the reference databases by employing a new concept of peptide grouping and by coherently distinguishing distinct peptides from unique records and shared peptides from homologous proteins. The software that runs the algorithm, called PANORAMICS, provides a tool to help analyze the data based on a researcher's knowledge about the sample. The software operates efficiently and quickly compared to other software platforms. [ABSTRACT FROM AUTHOR]

A standard approach to calculation of critical values for affected sib pair multiple testing is based on: (a) fully informative markers, (b) Haldane map function assumptions leading to a Markov chain model for inheritance vectors, (c) central limit approximation to averages of sampled inheritance vectors leading to an Ornstein-Uhlenbeck process approximation, and (d) simple approximations to the maximum of such a process. Under these assumptions, assuming equispaced or close to equispaced markers, if the sample size is large, an approximation is available that is easy to calculate and performs well. However, for small sample sizes, a large number of markers, and for small p-values, there is good reason to be cautious about the use of the Gaussian approximation. We develop an algorithm for calculation of multiple testing p-values based on the standard Markov chain model, avoiding the use of Gaussian (large sample) approximation. We illustrate the use of this algorithm by demonstrating some inadequacies of the Gaussian approximation. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We find that students in the big mathematics service courses at the Johns Hopkins University who were encouraged to use calculators in K-12 have somewhat lower grades than those who weren't. [ABSTRACT FROM AUTHOR]

Using the Genetic Analysis Workshop 13 simulated data set, we compared the technique of importance sampling to several other methods designed to adjust p-values for multiple testing: the Bonferroni correction, the method proposed by Feingold et al., and naïve Monte Carlo simulation. We performed affected sib-pair linkage analysis for each of the 100 replicates for each of five binary traits and adjusted the derived p-values using each of the correction methods. The type I error rates for each correction method and the ability of each of the methods to detect loci known to influence trait values were compared. All of the methods considered were conservative with respect to type I error, especially the Bonferroni method. The ability of these methods to detect trait loci was also low. However, this may be partially due to a limitation inherent in our binary trait definitions. [ABSTRACT FROM AUTHOR]

There is a close mathematical relationship between integer grids of a particular echelon form and coherent systems in reliability in the case of states coded as integer grid points. This paper shows that such an integer representation is the link between abstract tube theory, which gives improved inclusion-exclusion bounds, and an algebraic method, Gröbner bases, based on the polynomial ideal of the failure event. [ABSTRACT FROM AUTHOR]

Presents an importance sampling method for deciding, based on an observed random field, if a scan statistic provides evidence of increased activity in some localized region of time or space. Applications of the method to genetics and medical image analysis; Overview of molecular genetics; Information on spatial point processes.

A clear picture of ranges of doses of breast-milk contaminants experienced by nursing infants in North America has not yet been described, resulting in a significant gap in our understanding of potential health risks to infants from those contaminants. While point estimates of incremental dose have appeared in the published literature, these do not account for the wide variability in exposures experienced by nursing infants. This research expands on the current state of understanding of breast-milk contaminant exposure by characterizing distributions, rather than point estimates, of dose. Distributions of milk intake by nursing infants were characterized to exam ine intake of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and dichlorodiphenyl dichloroethane (DDE). The results indicate that, despite the uncertainties inherent in modeling incremental body burdens of chemicals from nursing, estimating incremental infant body burdens of lipophilic chemicals from breastfeeding using point estimates may result in overly conservative estimates of the contribution of breastfeeding to long-term body burdens of those chemicals in children. To develop reliable estimates of incremental body burden from nursing, depuration via lactation and half-life in the infant should be considered. Further, incremental infant body burdens of lipophilic chemicals increase rapidly at the start of lactation, but decrease after approximately 5 to 6 mo; by 2 yr postpartum, incremental body burdens have decreased substantially. Given the benefits afforded to infants who breastfeed, and because breastfeeding does not necessarily lead to significantly increased long-term body burdens in infants, breastfeeding should be encouraged and promoted. [ABSTRACT FROM AUTHOR]