Stratification bias in low signal microarray studies

BACKGROUND: When analysing microarray and other small sample size biological datasets, care is needed to avoid various biases. We analyse a form of bias, stratification bias, that can substantially affect analyses using sample-reuse validation techniques and lead to inaccurate results. This bias is due to imperfect stratification of samples in the training and test sets and the dependency between these stratification errors, i.e. the variations in class proportions in the training and test sets are negatively correlated. RESULTS: We show that when estimating the performance of classifiers on low signal datasets (i.e. those which are difficult to classify), which are typical of many prognostic microarray studies, commonly used performance measures can suffer from a substantial negative bias. For error rate this bias is only severe in quite restricted situations, but can be much larger and more frequent when using ranking measures such as the receiver operating characteristic (ROC) curve and area under the ROC (AUC). Substantial biases are shown in simulations and on the van 't Veer breast cancer dataset. The classification error rate can have large negative biases for balanced datasets, whereas the AUC shows substantial pessimistic biases even for imbalanced datasets. In simulation studies using 10-fold cross-validation, AUC values of less than 0.3 can be observed on random datasets rather than the expected 0.5. Further experiments on the van 't Veer breast cancer dataset show these biases exist in practice. CONCLUSION: Stratification bias can substantially affect several performance measures. In computing the AUC, the strategy of pooling the test samples from the various folds of cross-validation can lead to large biases; computing it as the average of per-fold estimates avoids this bias and is thus the recommended approach. As a more general solution applicable to other performance measures, we show that stratified repeated holdout and a modified version of k-fold cross-validation, balanced, stratified cross-validation and balanced leave-one-out cross-validation, avoids the bias. Therefore for model selection and evaluation of microarray and other small biological datasets, these methods should be used and unstratified versions avoided. In particular, the commonly used (unbalanced) leave-one-out cross-validation should not be used to estimate AUC for small datasets

Utilizing Stable Isotopes and Isotopic Anomalies to Study Early Solar System Formation Processes

Chondritic meteorites contain a diversity of particle components, i.e., chondrules and calcium-, aluminum-rich refractory inclusions (CAIs), that have survived since the formation of the Solar System. The chemical and isotopic compositions of these materials provide a record of the conditions present in the protoplanetary disk where they formed and can aid our understanding of the processes and reservoirs in which solids formed in the solar nebula, an important step leading to the accretion of planetesimals. Isotopic anomalies associated with nucleosynthetic processes are observed in these discrete materials, and can be compared to astronomical observations and astrophysical formation models of stars and more recently proplyds. The existence and size of these isotopic anomalies are typically thought to reflect a significant state of isotopic heterogeneity in the earliest Solar System, likely left over from molecular cloud heterogeneities on the grain scale, but some could also be due to late stellar injection. The homogenization of these isotopic anomalies towards planetary values can be used to track the efficiency and timescales of disk wide mixing

The Life and Times of Supervolcanoes: Inferences from Long Valley Caldera

Cataclysmic eruptions of silicic magma from "supervolcanoes" are among the most awe-inspiring natural phenomena found in the geologic record, in terms of size, power, and potential hazard. Based on the repose intervals between eruptions of this magnitude, the magmas responsible for them could accumulate gradually in the shallow crust over time scales that may be in excess of a million years (Smith, 1979; Spera and Crisp, 1981; Shaw, 1985). Pre-eruption magma residence time scales can also be inferred from the age difference between eruption (i.e., using 40Ar/39Ar dating to determine the time when hot erupted material cools to below its Ar closure temperature, 200 to 600 degC) and early pre-eruption crystallization (i.e., zircon saturation temperatures; Reid et al., 1997). I will discuss observations from Long Valley a Quaternary volcanic center in California. Long Valley is a voluminous, dominantly silicic caldera system. Based on extensive dating of accessory minerals (e.g., U-Th-Pb dating of zircon and allanite) along with geochemical and isotopic data we find that silicic magmas begin to crystallize 10's to 100's of thousands of years prior to their eruption and that rhyolites record episodes of punctuated and independent evolution rather than the periodic tapping of a long-lived magma. The more punctuated versus more gradual magma accumulation rates required by the absolute and model ages, respectively, imply important differences in the mass and heat fluxes associated with the generation, differentiation, and storage of voluminous rhyolites and emphasize the need to reconcile the magmatic age differences

Longitudinal and transverse meson correlators in the deconfined phase from the lattice

It has long been known that QCD undergoes a deconfining phase transition at high temperature. One of the consequent features of this new, quark-gluon phase is that hadrons become unbounded. In this talk meson correlation functions at non-zero momentum are studied in the deconfined phase using the Maximum Entropy Method.Comment: 6 pages. Prepared for Achievements and New Directions in Subatomic Physics: Workshop in Honour of Tony Thomas' 60th Birthday, Adelaide, Australia, 15-19 Feb 201

An Experimental test of the endowment effect

Thesis (M. Com. (Economics))--University of the Witwatersrand, Faculty of Commerce, Law and Management, School of Economic & Business Sciences, 2017In this study, I use a computer game based lab experiment to investigate the existence of the Endowment Effect. Previous empirical evidence has been criticised for failing to adequately account for the effects of transactions costs and other frictions. The structure of the game used in this study allows me to control for these effects, and the results provide evidence in support of the existence of an Endowment Effect. The effect is found to be stronger when transactions costs are present.GR201

Chemical and Thermodynamic Constraints on the Thermal Evolution of Eucrites

Vesta is the only differentiated asteroid with a nearly intact crust, making it the candidate for studying early planetary differentiation. It is commonly thought that the howardite, eucrite, and diogenite (HED) clan of meteorites derive from Vesta, and thus the study of HEDs is important for understanding the evolution of primitive bodies in the early solar system [1]. Of particular interest are the unusual trace element abundances in Stannern group eucrites, which have been interpreted as partial melting and melt contamination events that occurred on the parent body during thermal metamorphism[2]. However, some samples that contain evidence of high temperature metamorphism, such as Elephant Moraine (EET) 90020, have anomalous REE patterns that have been interpret-ed multiple ways. For example [3] concluded that the loss of small degrees of partial melt depleted the sample in LREEs while [4] concluded that subsolidus diffusion better explained why depletion of only some highly incompatible elements is observed. The heterogeneous nature of this sample makes reconstructing its petrologic history challenging. Here, we conduct further petrographic and chemical studies on polished thin sections of EET 90020 and compare results to previous studies [3-5]. Additionally, we combine chemical analyses with thermodynamic models in order to refine the constraints on the post-crystallization thermal history of EET 90020. We additionally include studies of Graves Nunataks (GRA) 98098, which also contains evidence of high temperature metamorphism and anomalous geochemical signatures, as well as evidence of solid state diffusion at lower temperatures [6]

From boundary object to boundary subject; the role of the patient in coordination across complex systems of care during hospital discharge

From boundary object to boundary subject; the role of 1 the patient in coordination across complex systems of 2 care during hospital discharge 3 4 Abstract 5 Advocates for patient involvement argue that seeking the active contribution of 6 patients and families in the coordination of care can help mitigate system 7 complexity, and lead to improvements in quality. However, sociological and 8 organisational research has identified barriers to involving patients in care 9 planning, not least the power of, and boundaries between, multiple professional 10 groups. This study draws on literature from Science and Technology Studies (STS) 11 to explore the patients' role in coordinating care across professional-practice 12 boundaries in complex care systems. Findings are drawn from a two-year 13 ethnographic study (including 69 qualitative interviews) of hospital discharge 14 following hip-fracture care, and describe the changing role of the patient as they 15 move out of hospital into community settings. Findings describe how 'the patient' 16 plays a relatively passive role as boundary object while recovering from surgery 17 within hospital, where inter-professional coordination was prescribed by 18 evidence-based guidelines, leaving little space for patient voice. As discharge 19 planning begins, patient involvement is both encouraged and contested by 20 different professional groups, with varying commitment to include patient 21 subjectivities in care. As patients move into home and community settings, they, 2