ROC Surfaces in the Presence of Verification Bias

In diagnostic medicine, the Receiver Operating Characteristic (ROC) surface is one of the established tools for assessing the accuracy of a diagnostic test in discriminating three disease states, and the volume under the ROC surface has served as a summary index for diagnostic accuracy. In practice, the selection for definitive disease examination may be based on initial test measurements, and induces verification bias in the assessment. We propose here a nonparametric likelihood-based approach to construct the empirical ROC surface in the presence of differential verification, and to estimate the volume under the ROC surface. Estimators of the standard deviation are derived by both the Fisher\u27s Information and Jack-knife method, and their relative accuracy is evaluated in an extensive simulation study. The methodology is further extended to incorporate discrete baseline covariates in the selection process, and to compare the accuracy of a pair of diagnostic tests. We apply the proposed method to compare the diagnostic accuracy between Mini-Mental State Examination and clinical evaluation of dementia, in discriminating among three disease states of Alzheimer\u27s disease

Black Box Modeling of Hydrocarbon Physiochemical Properties and its Approach to Fuel Optimization

An energy pathway of great interest is gas-to-liquid (GTL) technologies, which converts natural gas to valuable chemicals and fuels. Three powerful regression methods were implemented, to create models for accurate predictions of physical properties– density, freezing point, flash point, and heat content. With the use of experimental training data, three distinct techniques were performed and analyzed: artificial neural networks, support vector machine (SVM) and Kriging modeling. For further accuracy, optimal simulation settings were elucidated through repeated runs and rigorous testing, with substantial increases in performance in low performing models. Most models generated were accurate with good trends, except freezing point. A formulation package called DataMine, coded in R, was created for current work and future endeavors

RIPK3 restricts viral pathogenesis via cell death-independent neuroinflammation

Receptor-interacting protein kinase-3 (RIPK3) is an activator of necroptotic cell death, but recent work has implicated additional roles for RIPK3 in inflammatory signaling independent of cell death. However, while necroptosis has been shown to contribute to antiviral immunity, death-independent roles for RIPK3 in host defense have not been demonstrated. Using a mouse model of West Nile virus (WNV) encephalitis, we show that RIPK3 restricts WNV pathogenesis independently of cell death. Ripk3(-/-) mice exhibited enhanced mortality compared to wild-type (WT) controls, while mice lacking the necroptotic effector MLKL, or both MLKL and caspase-8, were unaffected. The enhanced susceptibility of Ripk3(-/-) mice arose from suppressed neuronal chemokine expression and decreased central nervous system (CNS) recruitment of T lymphocytes and inflammatory myeloid cells, while peripheral immunity remained intact. These data identify pleiotropic functions for RIPK3 in the restriction of viral pathogenesis and implicate RIPK3 as a key coordinator of immune responses within the CNS

The rational design of polymeric EUV resist materials by QSPR modelling

We present the initial results of the development of a qualitative structure property relationship (QSPR) model to guide in the design and synthesis of high-sensitivity, non-CAR materials for EUV lithography. The model was developed using the fragmentation data of low molecular weight species at 70 eV using a mass spectrometer (MS) with an electron ionization source as the input parameter. The preliminary model has highlighted a number of structural elements which will be important in the future design of resists, however, limitations with the current set of input data for molecules which fragment readily have been identified and these are currently being addressed. Additionally, a correlation between gamma (1 MeV) and EUV (92 eV) radiolysis of selected polymers has been established and it is proposed that the higher energy (1 MeV) irradiation source is a suitable model process for EUV and can, therefore, be used in the future screening of polymeric materials