Biomedical subjects

Chap T Le

Publications and source records attributed to Chap T Le.

8 recordsLinked to original sources

PubMed2003

Quality control and the identification of vaccine responders using ELISA-derived antibody data.

First vaccines are traditionally licensed after showing favourable results from phase III efficacy trials. Subsequent competing vaccines, however, have been licensed primarily on the basis of immunogenicity data rather than clinical efficacy. Focusing on pneumococcal vaccines where optical densities are measured and serum antibody concentrations are 'estimated' (from a statistical model) using an immunoglobulin (IgG) enzyme-linked immunosorbent assay (ELISA), the focus of this paper will centre on two highly related issues: the determination of an upper limit for quality control used in the assay methodology (let us call it the maximum tolerated limit or MTL) and the identification of vaccine responders. The goal is to show that these two issues are inter-related, so that investigators could reduce misclassification which would interfere with the eventual comparison of immunogenicity results.

Antibodies, Bacterial↗

PubMed2003

Some statistical methods for investigating the date of birth as a disease indicator.

Some methods of temporal statistics are presented and proposed for investigating the date of birth as a disease predictor. A subject's birthday is proposed to be used as a continuous variable with a circular distribution, a special type of interval scale without a true zero point. Three types of endpoints are then considered: a dichotomous endpoint; a continuous endpoint; and time-to-event. A study of otitis media is used for illustration. We found, for example, that children born in late winter to early spring tend to have higher cord blood pneumococcal antibody concentration and lower risk of disease as compared to those born in summer to early fall perhaps due largely to exposure to indoor pollution by pregnant mothers.

Antibodies, Bacterial↗

PubMed2003

A mixture model approach to detecting differentially expressed genes with microarray data.

An exciting biological advancement over the past few years is the use of microarray technologies to measure simultaneously the expression levels of thousands of genes. The bottleneck now is how to extract useful information from the resulting large amounts of data. An important and common task in analyzing microarray data is to identify genes with altered expression under two experimental conditions. We propose a nonparametric statistical approach, called the mixture model method (MMM), to handle the problem when there are a small number of replicates under each experimental condition. Specifically, we propose estimating the distributions of a t -type test statistic and its null statistic using finite normal mixture models. A comparison of these two distributions by means of a likelihood ratio test, or simply using the tail distribution of the null statistic, can identify genes with significantly changed expression. Several methods are proposed to effectively control the false positives. The methodology is applied to a data set containing expression levels of 1,176 genes of rats with and without pneumococcal middle ear infection.

Animals↗

PubMed2003

Preliminary study on reducing oral moist snuff use.

BACKGROUND: Tobacco exposure reduction may be an alternative treatment approach for those tobacco users who are unwilling or unable to quit tobacco use. However, very little information is available on the feasibility of this type of intervention, especially in the area of oral moist snuff tobacco (ST). This pilot study examined whether reducing ST use using various methods can be achieved and whether this reduction results in lower exposure to carcinogens. METHODS: Moist snuff users (N=40 males) were randomly assigned to 4 mg nicotine gum, non-tobacco mint snuff, brand switching, or elimination of ST use in specific situations. These approaches were used to reduce ST use or nicotine exposure by at least 25% for the first 2 weeks and 50% the subsequent 6 weeks of treatment. Follow-up sessions occurred at 12 and 26 weeks. RESULTS: Significant reductions were observed in tins per week and cotinine levels across all conditions. Among the intent-to-treat population, the abstinence rate was 15% at 26 weeks. Reduction in nicotine exposure was associated with reduction in exposure to nitrosamines. CONCLUSION: Reduction in ST use may be a viable approach for those oral moist ST users with no immediate quit plans. Future research in this area is needed.

Administration, Oral↗

PubMed2002

How many replicates of arrays are required to detect gene expression changes in microarray experiments? A mixture model approach.

BACKGROUND: It has been recognized that replicates of arrays (or spots) may be necessary for reliably detecting differentially expressed genes in microarray experiments. However, the often-asked question of how many replicates are required has barely been addressed in the literature. In general, the answer depends on several factors: a given magnitude of expression change, a desired statistical power (that is, probability) to detect it, a specified Type I error rate, and the statistical method being used to detect the change. Here, we discuss how to calculate the number of replicates in the context of applying a nonparametric statistical method, the normal mixture model approach, to detect changes in gene expression. RESULTS: The methodology is applied to a data set containing expression levels of 1,176 genes in rats with and without pneumococcal middle-ear infection. We illustrate how to calculate the power functions for 2, 4, 6 and 8 replicates. CONCLUSIONS: The proposed method is potentially useful in designing microarray experiments to discover differentially expressed genes. The same idea can be applied to other statistical methods.

Animals↗

PubMed2002

Model-based cluster analysis of microarray gene-expression data.

BACKGROUND: Microarray technologies are emerging as a promising tool for genomic studies. The challenge now is how to analyze the resulting large amounts of data. Clustering techniques have been widely applied in analyzing microarray gene-expression data. However, normal mixture model-based cluster analysis has not been widely used for such data, although it has a solid probabilistic foundation. Here, we introduce and illustrate its use in detecting differentially expressed genes. In particular, we do not cluster gene-expression patterns but a summary statistic, the t-statistic. RESULTS: The method is applied to a data set containing expression levels of 1,176 genes of rats with and without pneumococcal middle-ear infection. Three clusters were found, two of which contain more than 95% genes with almost no altered gene-expression levels, whereas the third one has 30 genes with more or less differential gene-expression levels. CONCLUSIONS: Our results indicate that model-based clustering of t-statistics (and possibly other summary statistics) can be a useful statistical tool to exploit differential gene expression for microarray data.

Animals↗

PubMed2002

Purulent otitis media in children and adults.

This study was designed to compare tympanic membrane (TM) and middle ear (ME) pathologies of temporal bones from children and adults with purulent otitis media (POM). Thirty-four temporal bones were used from 22 subjects ages 2 days to 76 years with histopathologic evidence of POM. There were 55 age-matched controls. Histopathologic findings of the TM and ME in children and adults with POM were compared. Clinical histories and the presence of complications were recorded. The incidence of POM was more common in male children than in females. There was a significant increase in the thickness of the posterosuperior and posteroinferior quadrants in children with POM compared to non-OM children. In adults with POM, there was a significant decrease in the thickness of the posteroinferior and anteroinferior quadrants compared to non-OM adults. Children with POM showed a significant increase in the anterioinferior and posteroinferior quadrants and the umbo compared to adults with POM. Pathology of the TM and ME occurred in adults and children, but severity was greater in children. Residual mesenchyme was frequently observed in temporal bones of children. Serious complications such as labyrinthtis and meningitis were observed more frequently in children. All cases with meningitis had labyrinthitis, previous histories of otitis media and had been treated with antibiotics. Although POM occurs in both children and adults, pathologic changes of the middle ear are more severe, and complications (labyrinthitis and meningitis) occur more often in children. Our findings suggest the need to monitor children carefully under the age of 2 years who have POM.

Adolescent↗

PubMed2002

Results of treatment for metastatic osteosarcoma with neoadjuvant chemotherapy and surgery.

The purpose of the current study was to define the survival outcome variables for the 85 patients with Stage IIB osteosarcoma treated with neoadjuvant chemotherapy at the authors' institution from 1982 to 1997. A minimum 4-year followup or death was a requisite for inclusion. Forty-three patients were relapse-free survivors and 14 had no evidence of disease at followup for an overall survival of 67%. Twenty-nine patients had thoracotomy and nine have no evidence of disease with a minimum 4-year followup from last thoracotomy. The mean time to metastasis after diagnosis for patients presenting with Stage IIB disease was 12.8 months. There was no difference in the survival for any of the three chemotherapy protocols, used during the 15 years included in this analysis. There was a significant relation between length of time to relapse and survival. For each additional year without relapse, there is an 18% increase in chance of survival. In patients who were treated with thoracotomy, the number of metastatic nodules was a significant predictor of survival; specifically, each nodule increased the risk of death by 43%. A favorable outcome in this cohort of patients is related to the length of time between initiation of therapy and diagnosis of metastasis, and the number of metastatic foci.

Adolescent↗