The T-wave of an electrocardiogram (ECG) represents the ventricular repolarization that is critical in restoration of the heart muscle to a pre-contractile state prior to the next beat. Alterations in the T-wave reflect various cardiac conditions; and links between abnormal (prolonged) ventricular repolarization and malignant arrhythmias have been documented. Cardiac safety testing prior to approval of any new drug currently relies on two points of the ECG waveform: onset of the Q-wave and termination of the T-wave; and only a few beats are measured. Using functional data analysis, a statistical approach extracts a common shape for each subject (reference curve) from a sequence of beats, and then models the deviation of each curve in the sequence from that reference curve as a four-dimensional vector. The representation can be used to distinguish differences between beats or to model shape changes in a subjectâ€™s T-wave over time. This model provides physically interpretable parameters characterizing T-wave shape, and is robust to the determination of the endpoint of the T-wave. Thus, this dimension reduction methodology offers the strong potential for definition of more robust and more informative biomarkers of cardiac abnormalities than the QT (or QT corrected) interval in current use.

%B Annals of Applied Statistics %V 3 %P 1382-1402 %G eng %R 10.1214/09-AOAS273 %0 Journal Article %J Annals of Applied Statistics %D 2009 %T Functional Data Analytic Approach of Modeling ECG T-wave shape to Measure Cardiovascular Behavior %A Zhou, Y-C. %A Sedransk, N. %K cardiac safety %K ECG T-wave %K Functional data analysis %K QT interval %K T-wave morphology %XThe T-wave of an electrocardiogram (ECG) represents the ventricular repolarization that is critical in restoration of the heart muscle to a pre-contractile state prior to the next beat. Alterations in the T-wave reflect various cardiac conditions; and links between abnormal (prolonged) ventricular repolarization and malignant arrhythmias have been documented. Cardiac safety testing prior to approval of any new drug currently relies on two points of the ECG waveform: onset of the Q-wave and termination of the T-wave; and only a few beats are measured. Using functional data analysis, a statistical approach extracts a common shape for each subject (reference curve) from a sequence of beats, and then models the deviation of each curve in the sequence from that reference curve as a four-dimensional vector. The representation can be used to distinguish differences between beats or to model shape changes in a subjectâ€™s T-wave over time. This model provides physically interpretable parameters characterizing T-wave shape, and is robust to the determination of the endpoint of the T-wave. Thus, this dimension reduction methodology offers the strong potential for definition of more robust and more informative biomarkers of cardiac abnormalities than the QT (or QT corrected) interval in current use.

%B Annals of Applied Statistics %V 3 %P 1382-1402 %G eng %R 10.1214/09-AOAS273 %0 Journal Article %J The American Statistician %D 2006 %T A framework for evaluating the utility of data altered to protect confidentiality %A A. F. Karr %A C. N. Kohnen %A A. Oganyan %A J. P. Reiter %A A. P. Sanil %B The American Statistician %V 60 %P 224-232 %G eng %0 Conference Proceedings %B Workshop on Foundations for Modeling and Simulation %D 2002 %T A Framework for Validating Computer Models %A M.J. Bayarri %A J. Berger %A D. Higdon %A M. Kottas %A R. Paulo %A J. Sacks %A J. Cafeo %A J. Cavendish %A C. Lin %A J. Tu %B Workshop on Foundations for Modeling and Simulation %I Society for Computer Simulation %8 2002 %G eng %0 Conference Paper %B 2001 International Symposium on Advanced Highway Technology %D 2001 %T A Framework for Traffic Simulation Model Validation Procedure Using CORSIM as a Test-Bed %A Park, B. %A N. M. Rouphail %A J. Sacks %B 2001 International Symposium on Advanced Highway Technology %8 2001 %G eng %0 Journal Article %J Journal of Transportation Engineering, ASCE %D 1997 %T Frequency of probe vehicle reports and variances of link travel time estimates %A A. Sen %A P. Thakuriah %A X. Zhu %A A. F. Karr %XAn important design issue relating to probe-based Advanced Traveler Information Systems (ATISs) and Advanced Traffic Management Systems is the sample size of probes (or the number of link traversals by probe vehicles) per unit time used in order to obtain reliable network information in terms of link travel time estimates. The variance of the mean of travel times obtained from n probes for the same link over a fixed time period may be shown to be of the form a+b/n where a and b are link-specific parameters. Using probe travel time data from a set of signalized arterials, it is shown that a is positive for well-traveled signalized links. This implies that the variance does not go to zero with increasing n. Consequences of this fact for probe-based systems are explored. While the results presented are for a specific set of links, we argue that because of the nature of the underlying travel time process, the broad conclusions would hold for most well-traveled links with signal control.

%B Journal of Transportation Engineering, ASCE %V 123 %P 290?297 %G eng %R http://dx.doi.org/10.1061/(ASCE)0733-947X(1997)123:4(290)