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Biomedical subjects

Molin Wang

Publications and source records attributed to Molin Wang.

5 recordsLinked to original sources

A simple imputation method for longitudinal studies with non-ignorable non-responses.

Missing data are a common problem in longitudinal studies in the health sciences. Motivated by data from the Muscatine Coronary Risk Factor (MCRF) study, a longitudinal study of obesity, we propose a simple imputation method for handling non-ignorable non-responses (i.e., when non-response is related to the specific values that should have been obtained) in longitudinal studies with either discrete or continuous outcomes. In the proposed approach, two regression models are specified; one for the marginal mean of the response, the other for the conditional mean of the response given non-response patterns. Statistical inference for the model parameters is based on the generalized estimating equations (GEE) approach. An appealing feature of the proposed method is that it can be readily implemented using existing, widely-available statistical software. The method is illustrated using longitudinal data on obesity from the MCRF study.

Algorithms↗

Plasma matrix metalloproteinases 7 and 9 in patients with metastatic breast cancer treated with marimastat or placebo: Eastern Cooperative Oncology Group trial E2196.

BACKGROUND: The purpose of this study was to evaluate the prognostic and predictive utility of measuring plasma levels of matrix metalloproteinase (MMP)-7 and MMP-9 in patients with metastatic breast cancer (MBC) treated with the oral MMP inhibitor (MMPI) marimastat or a placebo. PATIENTS AND METHODS: We measured plasma levels of MMP-7 and MMP-9 using an enzyme-linked immunoassay method in 140 evaluable patients with MBC enrolled on a multicenter clinical trial that compared the MMPI marimastat with placebo. Specimens were collected after completion of first-line chemotherapy in patients who had responding or stable disease and 3, 6, and 12 months after initiation of marimastat (10 mg orally twice daily) or placebo. RESULTS: Baseline plasma MMP-7 and MMP-9 levels did not correlate with each other or with progression-free or overall survival. In addition, serial evaluation of plasma MMP-7 and MMP-9 levels revealed no significant changes over time in the marimastat or placebo groups or any correlation with trough plasma marimastat level. CONCLUSION: We conclude that measurement of plasma MMP-7 or MMP-9 levels, as performed in our trial, was not a useful prognostic or predictive factor in patients with MBC or in patients treated with an MMPI.

Administration, Oral↗

Generalization of the Mantel-Haenszel estimating function for sparse clustered binary data.

We extend the Mantel-Haenszel estimating function to estimate both the intra-cluster pairwise correlation and the main effects for sparse clustered binary data. We propose both a composite likelihood approach and an estimating function approach for the analysis of such data. The proposed estimators are consistent and asymptotically normally distributed. Simulation results demonstrate that the two approaches are comparable in terms of bias and efficiency; however, the estimating equation approach is computationally simpler. Analysis of the Georgia High Blood Pressure survey is used for illustration.

Cluster Analysis↗

A semiparametric method for analyzing matched case-control family studies with a continuous outcome and proband sampling.

We consider matched case-control familial studies which match a group of patients, called "case probands," with a group of disease-free subjects, called "control probands," using a set of family-level matching variables. Family members of each proband are then recruited into the study. Of interest here is the familial aggregation of the response variable and the effects of subject-specific covariates on the response. We propose an estimating equation approach to jointly estimate the main effects and intrafamilial correlations for matched family studies with a continuous outcome. Only knowledge of the first two joint moments of the response variable is required. The induced estimators for the main effects and intrafamilial correlations are consistent and asymptotically normally distributed. We apply the proposed method to sleep apnea data. A simulation study demonstrates the usefulness of our approach.

Biometry↗

Rapid transcriptional suppression of rat cytochrome P450 genes by endotoxin treatment and its inhibition by curcumin.

Down-regulation of constitutive hepatic cytochrome P450 (P450) mRNAs by bacterial endotoxin (lipopolysaccharide, LPS) or other inflammatory stimuli has been documented extensively, but the contribution of transcriptional suppression to this effect is poorly understood. Here, we demonstrate that the rates of transcription of the CYP2C11, CYP3A2, and CYP2E1 genes are reduced to 20, 30, and 10% of control levels, respectively, in rat liver within 1 to 2 h of injection of LPS (1 mg/kg). The magnitude and rapidity of these effects indicate that transcriptional suppression is a primary reason for the decline in P450 mRNAs. Injection of curcumin significantly inhibited the rapid transcriptional suppression of CYP2E1, and blocked that of CYP3A2. These effects seemed to be independent of inhibition of nuclear factor-kappaB (NF-kappaB) activation by curcumin, because induction of known NF-kappaB-regulated genes was not attenuated. One hour after LPS injection, the DNA-binding activities of hepatocyte nuclear factor (HNF)1alpha, HNF3beta, and HNF4alpha were reduced to 73, 72, and 53%, respectively, of control values. The nuclear abundances of Sp1, liver-enriched transcriptional inhibitory protein (LIP), HNF1alpha, and HNF3beta were unchanged, whereas the abundance of HNF4alpha was reduced to 87% of control levels. We conclude that changes in Sp1 or LIP do not contribute significantly to the early suppression of P450 transcription in the acute phase rat liver. Although changes in DNA-binding activities of HNF1alpha, HNF3beta, and HNF4alpha are too small individually to explain the observed changes in P450 transcription, the role of each factor in concert with other factors remains to be determined.

Animals↗