Deriving chemosensitivity from cell lines: Forensic bioinformatics and reproducible research in high-throughput biology

High-throughput biological assays such as microarrays let us ask very detailed questions about how diseases operate, and promise to let us personalize therapy. Data processing, however, is often not described well enough to allow for exact reproduction of the results, leading to exercises in "forensic bioinformatics" where aspects of raw data and reported results are used to infer what methods must have been employed. Unfortunately, poor documentation can shift from an inconvenience to an active danger when it obscures not just methods but errors. In this report we examine several related papers purporting to use microarray-based signatures of drug sensitivity derived from cell lines to predict patient response. Patients in clinical trials are currently being allocated to treatment arms on the basis of these results. However, we show in five case studies that the results incorporate several simple errors that may be putting patients at risk. One theme that emerges is that the most common errors are simple (e.g., row or column offsets); conversely, it is our experience that the most simple errors are common. We then discuss steps we are taking to avoid such errors in our own investigations.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS291 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Blue-collar outlook not so blue in Texas

Employment (Economic theory) ; Texas

An investigation into the application of Claims Analysis to evaluate usability of a digital library interface

There is a need for tools that help developers evaluate the usability of digital library interfaces. The potential for using Claims Analysis to help developers in this way has been investigated in three linked case studies. The first explored the design rationale of an existing design with its developers. This showed that they had considered positive consequences for novice uses but that they found it difficult to identify negative effects. The second study explored the detailed design of an add-on feature. A scenario and sample claims were introduced to evaluate exploratory use within an action cycle of planning, execution and evaluation. This framework provided an effective stimulus to enable the developers to evaluate the design and explore opportunities for redesign. Finally, some novice users explored the digital library and the findings from this were used to validate a user scenario and claims

A qualitative analysis of factors influencing infant and young children feeding perceptions and practices, of working mothers, in London Borough of Ealing

Introduction: Optimum infant feeding practices, during the first 1000 days of life, are essential for children's health and development. The World Health Organization (WHO) recommends putting the infant to the breast within the first hour of life, and exclusively breastfeeding for six months. If every infant was exclusively breastfed 823,000 infant deaths could be avoided annually. Despite this fact only 41% of infants worldwide are exclusively breastfed. The Global Nutrition Target 5 seeks to increase this figure to 50% by 2025. In the UK, although there is widespread knowledge on the benefits of breastfeeding, with 81% mothers initiating breastfeeding, only 24% are exclusively breastfeeding at 6 weeks. By six months only 1% of mothers are still exclusively breastfeeding. This is the lowest rate in Europe. This research aimed to explore the infant feeding practices and perceptions of a small group of working mothers, with children under the age of five, in the London Borough of Ealing. Methodology: This study applied a qualitative methodology to gain a deeper understanding of factors influencing infant and young child feeding practices in a small group of working women. Two gatekeepers were used to recruit 14 participants through a mixture of convenience and snowball sampling. All mothers included were working and living in the Ealing Borough of London with children under five. Methods utilised for data collection included online interviews and open-ended surveys. Data were analysed using an inductive thematic approach, identifying four themes and eleven sub themes from the participants. Results: The study identified that mothers sought information on infant feeding from online sources, printed books, family and friends, and educational classes. However, most mothers expressed the need to have more information on different feeding methods and childbirth in general. Mothers highlighted that the main factors influencing their decision on how to feed their baby included the need to develop a strong connection with their baby, nutritional benefits for the infant and general knowledge about the benefits of breastfeeding. Most participants reported that they started breastfeeding at birth. Six mothers exclusively breastfed their baby until six months, followed by the introduction of complementary foods. Three of these mothers continued to breastfeed until nine months. Five mothers started formula feeding within two months due to personal challenges such as lack of support, perceived lack of milk supply and anatomical challenges such as tongue-tied infants. Mothers did not find work as a major barrier to breastfeeding. Conclusions: Increased information and support on all aspects of infant feeding could help the UK achieve their 2025 target. The timing of complementary feeding and clear advice on where to seek nutrition support could be included in an English Infant Feeding Strategy, like the strategy implemented in Scotland. More discussion on the small size of an infant’s stomach could reduce early breastfeeding cessation due to perceptions around lack of milk

Design of ternary signals for MIMO identification in the presence of noise and nonlinear distortion

A new approach to designing sets of ternary periodic signals with different periods for multi-input multi-output system identification is described. The signals are pseudo-random signals with uniform nonzero harmonics, generated from Galois field GF(q), where q is a prime or a power of a prime. The signals are designed to be uncorrelated, so that effects of different inputs can be easily decoupled. However, correlated harmonics can be included if necessary, for applications in the identification of ill-conditioned processes. A design table is given for q les 31. An example is presented for the design of five uncorrelated signals with a common period N = 168 . Three of these signals are applied to identify the transfer function matrix as well as the singular values of a simulated distillation column. Results obtained are compared with those achieved using two alternative methods

Cost-Effectiveness of Stronger Woodframe Buildings

We examine the cost-effectiveness of improvements in woodframe buildings. These include retrofits, redesign measures, and improved quality in 19 hypothetical woodframe dwellings. We estimated cost-effectiveness for each improvement and each zip code in California. The dwellings were designed under the CUREE-Caltech Woodframe Project. Costs and seismic vulnerability were determined on a component-by-component basis using the Assembly Based Vulnerability method, within a nonlinear time-history structural-analysis framework and using full-size test specimen data. Probabilistic site hazard was calculated by zip code, considering site soil classification, and integrated with vulnerability to determine expected annualized repair cost. The approach provides insight into uncertainty of loss at varying shaking levels. We calculated present value of benefit to determine cost-effectiveness in terms of benefit-cost ratio (BCR). We find that one retrofit exhibits BCRs as high as 8, and is in excess of 1 in half of California zip codes. Four retrofit or redesign measures are cost-effective in at least some locations. Higher quality is estimated to save thousands of dollars per house. Results are illustrated by maps for the Los Angeles and San Francisco regions and are available for every zip code in California

Phenomenological Constraints on Axion Models of Dynamical Dark Matter

In two recent papers (arXiv:1106.4546, arXiv:1107.0721), we introduced "dynamical dark matter" (DDM), a new framework for dark-matter physics in which the requirement of stability is replaced by a delicate balancing between lifetimes and cosmological abundances across a vast ensemble of individual dark-matter components whose collective behavior transcends that normally associated with traditional dark-matter candidates. We also presented an explicit model involving axions in large extra spacetime dimensions, and demonstrated that this model has all of the features necessary to constitute a viable realization of the general DDM framework. In this paper, we complete our study by performing a general analysis of all phenomenological constraints which are relevant to this bulk-axion DDM model. Although the analysis in this paper is primarily aimed at our specific DDM model, many of our findings have important implications for bulk axion theories in general. Our analysis can also serve as a prototype for phenomenological studies of theories in which there exist large numbers of interacting and decaying particles.Comment: 48 pages, LaTeX, 13 figures, 1 tabl

Modularity and 4D-2D spectral equivalences for large-N gauge theories with adjoint matter

In recent work, we demonstrated that the confined-phase spectrum of non-supersymmetric pure Yang-Mills theory coincides with the spectrum of the chiral sector of a two-dimensional conformal field theory in the large-$N$ limit. This was done within the tractable setting in which the gauge theory is compactified on a three-sphere whose radius is small compared to the strong length scale. In this paper, we generalize these observations by demonstrating that similar results continue to hold even when massless adjoint matter fields are introduced. These results hold for both thermal and $(-1)^F$-twisted partition functions, and collectively suggest that the spectra of large-$N$ confining gauge theories are organized by the symmetries of two-dimensional conformal field theories.Comment: 51 pages, LaTeX, 3 figure