SPC Applications in Syndromic Surveillance

2007 Proceedings of the American Statistical Association [CD-ROM], Alexandria, VA: American Statistical Association, 4035-4044.syndromic surveillance, biosurveillance, terrorism, disease, detection, statistical process control, CUSUM (MCUSUM) and the multivariate exponentially weighted moving average (MEWMA). Based on our analyses, we found that the CUSUM performed better than the EARS' methods across all of the scenarios we evaluated and, similar to results for the univariate CUSUM and EWMA in classical SPC applications, the directionally sensitive MCUSUM and MEWMA perform very similarly

Comparing Directionally Sensitive MCUSUM and MEWMA Procedures with Application to Biosurveillance

This paper compares the performance of two new directionally-sensitive multivariate methods, based on the multivariate CUSUM (MCUSUM) and the multivariate exponentially weighted moving average (MEWMA), for syndromic surveillance. While neither of these methods is currently in use in a biosurveillance system, they are among the most promising multivariate methods for this application. Our analysis is based on a detailed series of simulations using synthetic syndromic surveillance data that mimics various types of disease background incidence and outbreaks. We apply the MCUSUM and the MEWMA to residuals from an adaptive regression that accounts for the systematic effects normally present in syndromic surveillance data. We find that, similar to results for the univariate CUSUM and EWMA in classical statistical process control applications, the directionallysensitive MCUSUM and MEWMA perform very similarly.

Evidence for proton transfer in the rate-limiting step of a fast-cleaving Varkud satellite ribozyme

A fast-cleaving version of the Varkud satellite ribozyme, called RG, shows an apparent cis-cleavage rate constant of 5 sec(−1), similar to the rates of protein enzymes that catalyze similar reactions. Here, we describe mutational, pH-rate, and kinetic solvent isotope experiments that investigate the identity and rate constant of the rate-limiting step in this reaction. Self-cleavage of RG exhibits a bell-shaped rate vs. pH profile with apparent pK(a)s of 5.8 and 8.3, consistent with the protonation state of two nucleotides being important for the rate of cleavage. Cleavage experiments in heavy water (D(2)O) revealed a kinetic solvent isotope effect consistent with proton transfer in the rate-limiting step. A mutant RNA that disrupts a peripheral loop–loop interaction involved in RNA folding exhibits pH- and D(2)O-independent cleavage ≈10(3)-fold slower than wild type, suggesting that this mutant is limited by a different step than wild type. Substitution of adenosine 756 in the putative active-site loop with cytosine also decreases the cleavage rate ≈10(3)-fold, but the A756C mutant retains pH- and D(2)O-sensitivity similar to wild type, consistent with this mutant and wild type being limited by the chemical step of the reaction. These results suggest that the RG ribozyme provides a good experimental system to investigate the nature of fast, rate-limiting steps in a ribozyme cleavage reaction