Design and implementation of a multisite data repository for pediatric epilepsy

This dissertation established a software-hardware integrated design for a multisite data repository in pediatric epilepsy. A total of 16 institutions formed a consortium for this web-based application. This innovative fully operational web application allows users to upload and retrieve information through a unique human-computer graphical interface that is remotely accessible to all users of the consortium. A solution based on a Linux platform with My-SQL and Personal Home Page scripts (PHP) has been selected. Research was conducted to evaluate mechanisms to electronically transfer diverse datasets from different hospitals and collect the clinical data in concert with their related functional magnetic resonance imaging (fMRI). What was unique in the approach considered is that all pertinent clinical information about patients is synthesized with input from clinical experts into 4 different forms, which were: Clinical, fMRI scoring, Image information, and Neuropsychological data entry forms. A first contribution of this dissertation was in proposing an integrated processing platform that was site and scanner independent in order to uniformly process the varied fMRI datasets and to generate comparative brain activation patterns. The data collection from the consortium complied with the IRB requirements and provides all the safeguards for security and confidentiality requirements. An 1-MR1-based software library was used to perform data processing and statistical analysis to obtain the brain activation maps. Lateralization Index (LI) of healthy control (HC) subjects in contrast to localization-related epilepsy (LRE) subjects were evaluated. Over 110 activation maps were generated, and their respective LIs were computed yielding the following groups: (a) strong right lateralization: (HC=0%, LRE=18%), (b) right lateralization: (HC=2%, LRE=10%), (c) bilateral: (HC=20%, LRE=15%), (d) left lateralization: (HC=42%, LRE=26%), e) strong left lateralization: (HC=36%, LRE=31%). Moreover, nonlinear-multidimensional decision functions were used to seek an optimal separation between typical and atypical brain activations on the basis of the demographics as well as the extent and intensity of these brain activations. The intent was not to seek the highest output measures given the inherent overlap of the data, but rather to assess which of the many dimensions were critical in the overall assessment of typical and atypical language activations with the freedom to select any number of dimensions and impose any degree of complexity in the nonlinearity of the decision space.

A mathematical resolution to log transformations and the binning effect in applied processing of data in flow cytometry

This dissertation develops a new mathematical approach that overcomes the effect of a data processing phenomenon known as “histogram binning” inherent to flow cytometry data. A real-time procedure is introduced to prove the effectiveness and fast implementation of such an approach on real-world data. The histogram binning effect is a dilemma posed by two seemingly antagonistic developments: (1) flow cytometry data in its histogram form is extended in its dynamic range to improve its analysis and interpretation, and (2) the inevitable dynamic range extension introduces an unwelcome side effect, the binning effect, which skews the statistics of the data, undermining as a consequence the accuracy of the analysis and the eventual interpretation of the data. ^ Researchers in the field contended with such a dilemma for many years, resorting either to hardware approaches that are rather costly with inherent calibration and noise effects; or have developed software techniques based on filtering the binning effect but without successfully preserving the statistical content of the original data. ^ The mathematical approach introduced in this dissertation is so appealing that a patent application has been filed. The contribution of this dissertation is an incremental scientific innovation based on a mathematical framework that will allow researchers in the field of flow cytometry to improve the interpretation of data knowing that its statistical meaning has been faithfully preserved for its optimized analysis. Furthermore, with the same mathematical foundation, proof of the origin of such an inherent artifact is provided. ^ These results are unique in that new mathematical derivations are established to define and solve the critical problem of the binning effect faced at the experimental assessment level, providing a data platform that preserves its statistical content. ^ In addition, a novel method for accumulating the log-transformed data was developed. This new method uses the properties of the transformation of statistical distributions to accumulate the output histogram in a non-integer and multi-channel fashion. Although the mathematics of this new mapping technique seem intricate, the concise nature of the derivations allow for an implementation procedure that lends itself to a real-time implementation using lookup tables, a task that is also introduced in this dissertation. ^

A mathematical resolution to log transformations and the binning effect in applied processing of data in flow cytometry

This dissertation develops a new mathematical approach that overcomes the effect of a data processing phenomenon known as "histogram binning" inherent to flow cytometry data. A real-time procedure is introduced to prove the effectiveness and fast implementation of such an approach on real-world data. The histogram binning effect is a dilemma posed by two seemingly antagonistic developments: (1) flow cytometry data in its histogram form is extended in its dynamic range to improve its analysis and interpretation, and (2) the inevitable dynamic range extension introduces an unwelcome side effect, the binning effect, which skews the statistics of the data, undermining as a consequence the accuracy of the analysis and the eventual interpretation of the data. Researchers in the field contended with such a dilemma for many years, resorting either to hardware approaches that are rather costly with inherent calibration and noise effects; or have developed software techniques based on filtering the binning effect but without successfully preserving the statistical content of the original data. The mathematical approach introduced in this dissertation is so appealing that a patent application has been filed. The contribution of this dissertation is an incremental scientific innovation based on a mathematical framework that will allow researchers in the field of flow cytometry to improve the interpretation of data knowing that its statistical meaning has been faithfully preserved for its optimized analysis. Furthermore, with the same mathematical foundation, proof of the origin of such an inherent artifact is provided. These results are unique in that new mathematical derivations are established to define and solve the critical problem of the binning effect faced at the experimental assessment level, providing a data platform that preserves its statistical content. In addition, a novel method for accumulating the log-transformed data was developed. This new method uses the properties of the transformation of statistical distributions to accumulate the output histogram in a non-integer and multi-channel fashion. Although the mathematics of this new mapping technique seem intricate, the concise nature of the derivations allow for an implementation procedure that lends itself to a real-time implementation using lookup tables, a task that is also introduced in this dissertation.