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PURPOSE This phase I, first-in-human study evaluated the safety, maximum-tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and preliminary efficacy of SAR245409, an inhibitor of pan-Class I phosphoinositide 3-kinase (PI3K) and mTOR, administered orally once or twice daily in patients with advanced solid tumors. EXPERIMENTAL DESIGN Eighty-three(More)
The LASSO-Patternsearch algorithm is proposed to efficiently identify patterns of multiple dichotomous risk factors for outcomes of interest in demographic and genomic studies. The patterns considered are those that arise naturally from the log linear expansion of the multivariate Bernoulli density. The method is designed for the case where there is a(More)
The maximum tolerated dose of SAR245409 (voxtalisib), a pan-class I phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor, was determined in a phase 1 dose-escalation study in advanced solid tumors. We report safety, pharmacokinetics (PK), pharmacodynamics and preliminary efficacy of SAR245409 capsules 50 mg twice daily in an(More)
The Genetic Analysis Workshop 15 Problem 3 simulated rheumatoid arthritis data set provided 100 replicates of simulated single-nucleotide polymorphism (SNP) and covariate data sets for 1500 families with an affected sib pair and 2000 controls, modeled after real rheumatoid arthritis data. The data generation model included nine unobserved trait loci, most(More)
The LASSO-Patternsearch is proposed, as a two-stage procedure to identify clusters of multiple risk factors for outcomes of interest in large demographic studies, when the predictor variables are dichotomous or take on values in a small finite set. Many diseases are suspected of having multiple interacting risk factors acting in concert, and it is of much(More)
In systems biology, the task of reverse engineering gene pathways from data has been limited not just by the curse of dimensionality (the interaction space is huge) but also by systematic error in the data. The gene expression barcode reduces spurious association driven by batch effects and probe effects. The binary nature of the resulting expression calls(More)
Acknowledgments First and most importantly, I would like to express my deepest gratitude toward my advisor Professor Grace Wahba. Her guidance and encouragement through my PhD study into various statistical machine learning methods is the key factor to the success of this dissertation. Grace is a brilliant and passionate statistician, and her insightful(More)
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