Removing batch effects for prediction problems with frozen surrogate variable analysis

Batch effects are responsible for the failure of promising genomic prognos- tic signatures, major ambiguities in published genomic results, and retractions of widely-publicized findings. Batch effect corrections have been developed to re- move these artifacts, but they are designed to be used in population studies. But genomic technologies are beginning to be used in clinical applications where sam- ples are analyzed one at a time for diagnostic, prognostic, and predictive applica- tions. There are currently no batch correction methods that have been developed specifically for prediction. In this paper, we propose an new method called frozen surrogate variable analysis (fSVA) that borrows strength from a training set for individual sample batch correction. We show that fSVA improves prediction ac- curacy in simulations and in public genomic studies. fSVA is available as part of the sva Bioconductor package

Towards a dephasing diode: asymmetric and geometric dephasing

We study the effect of a noisy environment on spin and charge transport in ballistic quantum wires with spin-orbit coupling (Rashba coupling). We find that the wire then acts as a ``dephasing diode'', inducing very different dephasing of the spins of right and left movers. We also show how Berry phase (geometric phase) in a curved wire can induce such asymmetric dephasing, in addition to purely geometric dephasing. We propose ways to measure these effects through spin detectors, spin-echo techniques, and Aharanov-Bohm interferometry.Comment: 4 pages (2 fig) v2: extensive improvements to "readability" & references adde

Cavity QED with separate photon storage and qubit readout modes

We present the realization of a cavity quantum electrodynamics setup in which photons of strongly different lifetimes are engineered in different harmonic modes of the same cavity. We achieve this in a superconducting transmission line resonator with superconducting qubits coupled to the different modes. One cavity mode is strongly coupled to a detection line for qubit state readout, while a second long lifetime mode is used for photon storage and coherent quantum operations. We demonstrate sideband based measurement of photon coherence, generation of n photon Fock states and the scaling of the sideband Rabi frequency with the square root of n using a scheme that may be extended to realize sideband based two-qubit logic gates.Comment: 4 pages, 5 figures, version with high resolution figures available at http://qudev.ethz.ch/content/science/PubsPapers.htm

Using Sideband Transitions for Two-Qubit Operations in Superconducting Circuits

We demonstrate time resolved driving of two-photon blue sideband transitions between superconducting qubits and a transmission line resonator. Using the sidebands, we implement a pulse sequence that first entangles one qubit with the resonator, and subsequently distributes the entanglement between two qubits. We show generation of 75% fidelity Bell states by this method. The full density matrix of the two qubit system is extracted using joint measurement and quantum state tomography, and shows close agreement with numerical simulation. The scheme is potentially extendable to a scalable universal gate for quantum computation.Comment: 4 pages, 5 figures, version with high resolution figures available at http://qudev.ethz.ch/content/science/PubsPapers.htm

Thermal Excitation of Multi-Photon Dressed States in Circuit Quantum Electrodynamics

The exceptionally strong coupling realizable between superconducting qubits and photons stored in an on-chip microwave resonator allows for the detailed study of matter-light interactions in the realm of circuit quantum electrodynamics (QED). Here we investigate the resonant interaction between a single transmon-type multilevel artificial atom and weak thermal and coherent fields. We explore up to three photon dressed states of the coupled system in a linear response heterodyne transmission measurement. The results are in good quantitative agreement with a generalized Jaynes-Cummings model. Our data indicates that the role of thermal fields in resonant cavity QED can be studied in detail using superconducting circuits.Comment: ArXiv version of manuscript to be published in the Physica Scripta topical issue on the Nobel Symposium 141: Qubits for Future Quantum Computers(2009), 13 pages, 6 figures, hi-res version at http://qudev.ethz.ch/content/science/PubsPapers.htm

Quantum-to-Classical Transition in Cavity Quantum Electrodynamics

The quantum properties of electromagnetic, mechanical or other harmonic oscillators can be revealed by investigating their strong coherent coupling to a single quantum two level system in an approach known as cavity quantum electrodynamics (QED). At temperatures much lower than the characteristic energy level spacing the observation of vacuum Rabi oscillations or mode splittings with one or a few quanta asserts the quantum nature of the oscillator. Here, we study how the classical response of a cavity QED system emerges from the quantum one when its thermal occupation -- or effective temperature -- is raised gradually over 5 orders of magnitude. In this way we explore in detail the continuous quantum-to-classical crossover and demonstrate how to extract effective cavity field temperatures from both spectroscopic and time-resolved vacuum Rabi measurements.Comment: revised version: improved analysis, 4 pages, 4 figures, hi-res version available at http://qudev.ethz.ch/content/science/PubsPapers.htm

A scoping investigation of eye-tracking in Electronic Gambling Machine (EGM) play

The nature of the association between Electronic Gambling Machines (EGMs) and gambling problems remains uncertain. Eye-tracking offers a potentially powerful method to understand how individuals attend to the visual displays and features of machine games as a function of machine experience, use of other commercial gambling products, the degree to which some game features capture players attention and, critically, vulnerability to problematic patterns of machine play. Characterizing machine players' attention to machine games may aid the design of harm-minimization measures such as, but not limited to, pop-up messages and visible clocks; and provide an important ancillary measure for testing their efficacy. Here, we conducted the first study to use eye-tracking to improve our understanding of how machine players attend to EGM displays in local bookmaker offices (LBOs) situated across North West England, as well as North East and North Wales. Through liaison with 4 bookmaker operators, we recruited a sample of 118 LBO customers who, first, completed a small number of questionnaires about their gambling history and other gambling activities and, then, completed a typical machine gambling session with their own money while wearing eye-tracking glasses to capture eye-movement pattern. The protocol captured regions of gaze fixation while playing (B2) roulette or (B3) slots on B category machines (Gambling Commission, 2012). The final dataset consisted of 91 eye-tracking recordings: 59 games of roulette and 57 slots games. Our principle dependent measure was the percentage of fixations of visual features and machine display locations (as areas of interest; AOIs) as an objective indicator of overt visual attention and their importance to machine players. Our data analysis included statistical correction for differences in the relative size (display area) and display duration across AOIs. To summarise, our main findings are as follows: In roulette, 56.3% of LBO machine players fixations were distributed over the chip-placement area while placing bets (in the stationary states of the game), rising to 75.1% while the roulette wheel Eye-tracking & machines Rogers & Leek; main text v2; 24th March 2017 3 spun in the moving states of the games). Machine players looked at their credit balance 7.2% of the time while placing bets, only slightly more frequently than the previous winning number at 6.8%. In slots games, the slot-reels dominated machine players' visual attention: accounting for 53.6% of fixations while placing bets, rising to 91.7% while spinning. Players' fixations of their credit-balances amounted to 14% of the total while placing bets but only 5.1% while the slot-reels spun. Fixations away from the machine were more frequent while placing bets in both roulette and slots games: 13.5% and 13.4% respectively, dropping to 2.4% and 1.1% while the wheel/slot-reels spun. Players' age and years of education were only weakly related to fixation patterns while playing roulette or slots games. Unemployed players allocated fewer fixations over the chip-placement area (both while the roulette wheel was stationary and while it spun) and over the slot-reels while placing bets; they also tended to look away from the machine more while placing bets in roulette. Frequent machine players tended to look at the roulette wheel less frequently than infrequent users while playing roulette games; involvement in other forms of gambling tended to increase attention towards credit balance but was not otherwise linked to particular patterns of fixations. Finally, problems gamblers allocated fewer fixations to the roulette wheel while placing bets and while it spun compared to non-problem gamblers; and tended to look away from the machine more frequently; in slots games, problem gamblers looked more frequently at amount-won messages. These data describe, for the first time, the distributions of machine players overt attention while navigating roulette and slots games in a commercial settings. In general, fixation counts showed the least variability for moving visual features and events that are likely to capture attention automatically, such as spinning Eye-tracking & machines Rogers & Leek; main text v2; 24th March 2017 4 roulette wheels or spinning slot-reels. However, fixations were also concentrated upon visual features and elements with relatively less attentional capture such as the chip-placement-area while placing bets in roulette and looking at credit balances in both games. Associations between patterns of fixation and both frequency of past-month expenditure on B category machines and broader gambling involvement were modest, suggesting that most of the variability in eye-movements and fixations reflects players navigation through the sequenced behaviours of placing bets and monitoring spinning roulette wheels or slot-reels in anticipation of game outcomes. Players with extensive machine experience tended to discount slightly the roulette wheel as a visual feature; while players with broader patterns of gambling activity looked at credit balances frequently, suggesting that such individuals are mindful of available credits. Players with gambling problems allocated fewer fixations over the chip-placement-area while placing bets and while watching the wheel spun compared to non-problem gamblers, suggesting that placing of bets can be accomplished with less attentional focus. These individuals were also more likely to look away from the machine altogether, suggesting that, in roulette play, gambling problems might be associated with a loosened attentional focus to events elsewhere in the shop. However, in slots games, problems gamblers' attended to the reward signals of previous games (amount-won) when placing the next bets. So far as we are aware, these data are the first to show that eye-tracking methodology has some potential to offer insights into machine-player interactions, and to provide a bias-free measure of individual differences in attention to games visual features and events as a function of their experience with gambling machines, gambling background and vulnerability to gambling-related harms. This study offers a methodology for studying and optimizing the timing, placement and content of harm-minimization messaging

MLP: a MATLAB toolbox for rapid and reliable auditory threshold estimation

In this paper, we present MLP, a MATLAB toolbox enabling auditory thresholds estimation via the adaptive Maximum Likelihood procedure proposed by David Green (1990, 1993). This adaptive procedure is particularly appealing for those psychologists that need to estimate thresholds with a good degree of accuracy and in a short time. Together with a description of the toolbox, the current text provides an introduction to the threshold estimation theory and a theoretical explanation of the maximum likelihood adaptive procedure. MLP comes with a graphical interface and it is provided with several built-in, classic psychoacoustics experiments ready to use at a mouse click

Association of tumour necrosis factor alpha and its receptors with thymidine phosphorylase expression in invasive breast carcinoma.

Angiogenesis is an essential requirement for tumour growth and metastasis and is regulated by a complex network of factors produced by both stromal cells and neoplastic cells within solid tumours. The cytokine tumour necrosis factor alpha (TNF-alpha) and the enzyme thymidine phosphorylase (TP) are two factors known to promote tumour angiogenesis. We have demonstrated recently that high numbers of tumour-associated macrophages (TAMs) are significantly associated with increased tumour angiogenesis and poor prognosis in invasive carcinoma of the breast. We have also shown that TAMs are a major source of TNF-alpha in invasive breast carcinomas, and that macrophage-like stromal cells as well as tumour cells synthesize TP in such tumours. However, little is known of the factors that regulate the production or activity of these factors in the tumour microenvironment. As TNF-alpha has been shown to up-regulate TP expression in tumour cells in vitro we performed an immunohistochemical study to investigate the possibility that TNF-alpha may be involved in the regulation of TP expression by malignant breast epithelial cells in vivo. To do this, we used a cocktail of non-neutralizing monoclonal anti-TNF-alpha antibodies to visualize both TNF-alpha-expressing macrophages and TNF-alpha bound to its receptors on tumour cells and endothelial cells in a series of 93 invasive carcinomas of the breast. A semiquantitative grading system was then used to compare these staining patterns with that for TP in the same biopsies. TNF-alpha immunoreactivity was also compared with various important tumour variables known to relate to outcome in this disease (microvessel density, node status, grade, stage, receptor status and macrophage infiltration), as well as relapse-free and overall survival data for these patients. Our data show significant positive correlations between TNF-alpha bound to its receptors on tumour cells and: (1) TP protein production by tumour cells, and (2) axillary lymph node status (i.e. metastasis). These results suggest that tumour cell responsiveness to TNF-alpha produced by neighbouring TAMs may play a part in the regulation of TP expression by tumour cells as well as their metastatic behaviour. This may explain, in part, the relationship between increased macrophage infiltration and angiogenesis in breast cancer, and further supports the contention that TAMs may represent an important target for future anti-angiogenic therapies

A Demonstration of STIR-GATE-Connection

We present the first open-source version of STIR-GATE-Connection, a project that aims to provide an easy-to-use pipeline to simulate realistic PET data using GATE, followed by quantitative reconstruction using STIR. Monte Carlo simulations and image reconstruction are powerful research tools for emission tomography that can assist with the design of new medical imaging devices as well as the evaluation of novel image reconstruction algorithms and various correction techniques. STIR-GATE-Connection is a collection of scripts that aid with the: (i) setup of a realistic GATE simulation of a voxelised phantom using a user selected scanner configuration, (ii) conversion of the output list mode data into STIR compatible sinograms, and (iii) computation of additive and multiplicative data corrections for Poisson image reconstruction using STIR. In this work, we demonstrate example usage of these steps. A public release of STIR-GATE-Connection, licensed under the Apache 2.0 License, can be downloaded at: http://www.github.com/UCL/STIR-GATE-Connection