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Analysis of the Effect of C3 Transferase on Behavioral Outcomes with Informative Right-Censoring

Catevenis, Katherine Antigone (2012)
Master's Thesis (56 pages)
Committee Chair / Thesis Adviser: Hanfelt, John
Committee Members:
Research Fields: Statistics; Health Sciences, Public Health
Partnering Agencies: Emory University schools, faculty or affiliated programs
Keywords: Amyotrophic Lateral Sclerosis; Informative Right Censoring; C3 Transferase
Program: Rollins School of Public Health, Biostatistics and Bioinformatics (Biostatistics)
Permanent url: http://pid.emory.edu/ark:/25593/bqs88

Abstract

This study aimed to slow the degradation rates of the motor functions of mice with Amyotrophic Lateral Sclerosis (ALS). Two treatment groups, high titer AAV2 C3 and low titer AAV2 C3, were investigated to determine their effect on the degradation of the SOD1 mice, measured through the Basso-Beattie-Bresnahan (BBB) locomotor rating. In this experiment each mouse served as its own control through one side being treated and the other side used as a control. An analysis that adjusted for the correlation between the sides of each animal and the presence of informative right censoring was used. This method used an Empirical Bayes approach and was an extension of the method used by PAK[1999]. Twenty SOD1 gene mice were injected with their treatment on one side. Eight mice received the high titer treatment, eight mice received the low titer treatment, and four mice received a control GFP treatment. The BBB score was measured once before the injection and then on specific days after the injection. A test of informative right censoring was performed for each side of the mice for each treatment group. None of the treatment groups were found to have informative right censoring. Three types of slope estimates were compared for each animal, ordinary least squares, Empirical Bayes assuming no informative right censoring, and Empirical Bayes adjusted for informative right censoring. None of the treatment groups showed a significant difference between the decline of function in the treated versus the untreated side (p > 0.70).

Table of Contents

1. Introduction

2. Methods

2.1 Basic Model and Assumptions

2.2 Implications of the Model

2.2.1 Distribution of OLS Estimates of Slope

2.2.2 Posterior Distribution of the True Slopes

2.3 Inference

3. Results

3.1 Checking Assumptions

3.2 Model Based Results

4. Discussion

5. Appendices

A. Figures

B. R Code

Files

application/pdf Dissertation/Thesis 56 pages (1.2 MB) [Access copy of Dissertation/Thesis]
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