The work presented in this thesis focuses on methods for the construction of diagnostic rules based on clinical mass spectrometry proteomic data. Mass spectrometry has become one of the key... Show moreThe work presented in this thesis focuses on methods for the construction of diagnostic rules based on clinical mass spectrometry proteomic data. Mass spectrometry has become one of the key technologies for jointly measuring the expression of thousands of proteins in biological samples. However, the development of MS instrumentation gave rise to new statistical challenges in the processing and analysis of the acquired data. This is due to the complex nature of the spectral proteomic signal which is measured, as it consists of high-dimensional functions representing the within-patient proteome expression. This work considers new methods to respond to these challenges. Our main interest focuses on the comparison of mass spectral proteomic profiles collected from healthy individuals and cancer patients in the context of distinct case-control studies. A key objective in such studies is the construction of discriminant rules for distinguishing between individuals as to the presence or absence of the disease as well as for predicting the health status of future patients. We present a series of data analyses for distinct case-control cancer studies where we address these questions through the use of methodology specific for the type of data considered in each of the studies. Show less
Major advances have been made in the treatment of rheumatoid arthritis, a potentially chronic disabling disease which poses a large burden on both patients and society. By early start of disease... Show moreMajor advances have been made in the treatment of rheumatoid arthritis, a potentially chronic disabling disease which poses a large burden on both patients and society. By early start of disease-modifying antirheumatic drugs, including methotrexate as a prominent drug, the use of combination therapies including prednisone or biologicals, and tight control of disease activity, many patients are able to reach a state of clinical remission and some can even taper and stop antirheumatic therapy. Challenges lie in correctly identifying the earliest manifestations of the disease, starting the right treatment sufficiently early, tailored to the individual patient, and setting the optimal treatment goal at which to steer therapy adjustments. This thesis has made a start towards tackling several of these challenges and discusses further necessary steps that may lead to a fundamental change in the outlook of patients with rheumatoid arthritis. Show less
As the de facto industry standard for software modeling, the Unified Modeling Language (UML) is used widely across various IT domains. UML__s wide acceptance is partly because the language offers... Show moreAs the de facto industry standard for software modeling, the Unified Modeling Language (UML) is used widely across various IT domains. UML__s wide acceptance is partly because the language offers flexibility and freedom in modeling software systems: 1) UML provides an extensive set of modeling notations that can be used to model various concepts; 2) UML can be used both in a casual and formal manners. In the context of model-driven software development, the degree of freedom in which UML is used raises an important issue related to model quality. Different styles and rigors in using UML affect the quality of the resulting models. It is then logical to think that the level of quality of the UML model may affect the quality of the resulting software. This thesis reports on a series of empirical studies performed to address a pivotal question concerning the benefits of UML modeling in software development, particularly from a quality perspective. The results of these empirical studies show that the use of UML provides benefits in terms of increased quality and productivity in software development. The availability of UML models also allows early prediction of defects in software systems. Such prediction is potentially useful for identifying and fixing defects early during software development, and for prioritizing testing. Show less
