Standard cost model: three different paths and their common problems

Red tape is not desirable as it impedes business growth. Relief from the administrative burdens that businesses face due to legislation can benefit the whole economy, especially at times of recession. However, recent governmental initiatives aimed at reducing administrative burdens have encountered some success, but also failures. This article compares three national initiatives - in the Netherlands, UK and Italy - aimed at cutting red tape by using the Standard Cost Model. Findings highlight the factors affecting the outcomes of measurement and reduction plans and ways to improve the Standard Cost Model methodology.

Stephen Martin Leake: a Victorian's view of the Common Law

This article considers the life and work of Stephen Martin Leake and seeks to locate his work within the wider context of the procedural and substantive transformation of the mid-to-late Victorian legal world. In particular, the article attempts to rescue Leake from obscurity and emphasise his importance in this process. It is argued that Leake’s work began the process whereby common lawyers conceived of their law as organised in a principled rather than procedural manner. Later common law jurists built upon this work. Consideration is also given to the philosophical and jurisprudential sources upon which Leake drew in constructing his treatises.

Error, reproducibility and sensitivity: a pipeline for data processing of Agilent oligonucleotide expression arrays

Background: Expression microarrays are increasingly used to obtain large scale transcriptomic information on a wide range of biological samples. Nevertheless, there is still much debate on the best ways to process data, to design experiments and analyse the output. Furthermore, many of the more sophisticated mathematical approaches to data analysis in the literature remain inaccessible to much of the biological research community. In this study we examine ways of extracting and analysing a large data set obtained using the Agilent long oligonucleotide transcriptomics platform, applied to a set of human macrophage and dendritic cell samples. Results: We describe and validate a series of data extraction, transformation and normalisation steps which are implemented via a new R function. Analysis of replicate normalised reference data demonstrate that intrarray variability is small (only around 2 of the mean log signal), while interarray variability from replicate array measurements has a standard deviation (SD) of around 0.5 log(2) units (6 of mean). The common practise of working with ratios of Cy5/Cy3 signal offers little further improvement in terms of reducing error. Comparison to expression data obtained using Arabidopsis samples demonstrates that the large number of genes in each sample showing a low level of transcription reflect the real complexity of the cellular transcriptome. Multidimensional scaling is used to show that the processed data identifies an underlying structure which reflect some of the key biological variables which define the data set. This structure is robust, allowing reliable comparison of samples collected over a number of years and collected by a variety of operators. Conclusions: This study outlines a robust and easily implemented pipeline for extracting, transforming normalising and visualising transcriptomic array data from Agilent expression platform. The analysis is used to obtain quantitative estimates of the SD arising from experimental (non biological) intra- and interarray variability, and for a lower threshold for determining whether an individual gene is expressed. The study provides a reliable basis for further more extensive studies of the systems biology of eukaryotic cells.

Within-host evolution of Staphylococcus aureus during asymptomatic carriage

Background Staphylococcus aureus is a major cause of healthcare associated mortality, but like many important bacterial pathogens, it is a common constituent of the normal human body flora. Around a third of healthy adults are carriers. Recent evidence suggests that evolution of S. aureus during nasal carriage may be associated with progression to invasive disease. However, a more detailed understanding of within-host evolution under natural conditions is required to appreciate the evolutionary and mechanistic reasons why commensal bacteria such as S. aureus cause disease. Therefore we examined in detail the evolutionary dynamics of normal, asymptomatic carriage. Sequencing a total of 131 genomes across 13 singly colonized hosts using the Illumina platform, we investigated diversity, selection, population dynamics and transmission during the short-term evolution of S. aureus. Principal Findings We characterized the processes by which the raw material for evolution is generated: micro-mutation (point mutation and small insertions/deletions), macro-mutation (large insertions/deletions) and the loss or acquisition of mobile elements (plasmids and bacteriophages). Through an analysis of synonymous, non-synonymous and intergenic mutations we discovered a fitness landscape dominated by purifying selection, with rare examples of adaptive change in genes encoding surface-anchored proteins and an enterotoxin. We found evidence for dramatic, hundred-fold fluctuations in the size of the within-host population over time, which we related to the cycle of colonization and clearance. Using a newly-developed population genetics approach to detect recent transmission among hosts, we revealed evidence for recent transmission between some of our subjects, including a husband and wife both carrying populations of methicillin-resistant S. aureus (MRSA). Significance This investigation begins to paint a picture of the within-host evolution of an important bacterial pathogen during its prevailing natural state, asymptomatic carriage. These results also have wider significance as a benchmark for future systematic studies of evolution during invasive S. aureus disease.

WCSC 2013: the 3rd World Chess Software Championship

The 3rd World Chess Software Championship took place in Yokohama, Japan during August 2013. It pits chess engines against each other on a common hardware platform - in this instance, the Intel i7 2740 Ivy Bridge with 16GB RAM supporting a potential eight processing threads. It was narrowly won by HIARCS from JUNIOR and PANDIX with JONNY, SHREDDER and MERLIN taking the remaining places. Games, occasionally annotated, are available here.

A self-calibrating electrometer for atmospheric charge measurements from a balloon platform

Charged aerosol particles and water droplets are abundant throughout the lower atmosphere, and may influence interactions between small cloud droplets. This note describes a small, disposable sensor for the measurement of charge in non-thunderstorm cloud, which is an improvement of an earlier sensor [K. A. Nicoll and R. G. Harrison, Rev. Sci. Instrum. 80, 014501 (2009)]. The sensor utilizes a self-calibrating current measurement method. It is designed for use on a free balloon platform alongside a standard meteorological radiosonde, measuring currents from 2 fA to 15 pA and is stable to within 5 fA over a temperature range of 5 °C to −60 °C. During a balloon flight with the charge sensor through a stratocumulus cloud, charge layers up to 40 pC m−3 were detected on the cloud edges.

Progress in the genetics of common obesity and type 2 diabetes

The prevalence of obesity and diabetes, which are heritable traits that arise from the interactions of multiple genes and lifestyle factors, continues to rise worldwide, causing serious health problems and imposing a substantial economic burden on societies. For the past 15 years, candidate gene and genome-wide linkage studies have been the main genetic epidemiological approaches to identify genetic loci for obesity and diabetes, yet progress has been slow and success limited. The genome-wide association approach, which has become available in recent years, has dramatically changed the pace of gene discoveries. Genome-wide association is a hypothesis-generating approach that aims to identify new loci associated with the disease or trait of interest. So far, three waves of large-scale genome-wide association studies have identified 19 loci for common obesity and 18 for common type 2 diabetes. Although the combined contribution of these loci to the variation in obesity and diabetes risk is small and their predictive value is typically low, these recently identified loci are set to substantially improve our insights into the pathophysiology of obesity and diabetes. This will require integration of genetic epidemiological methods with functional genomics and proteomics. However, the use of these novel insights for genetic screening and personalised treatment lies some way off in the future.

Studying economics reduces overexploitation in a common resource experiment

This paper studies the economic behavior of agents, who make decisions regarding the sustainability of Common-Pool Resources (CPR). For this purpose, economic experiments are applied to simulate the yield of a CPR, taking into account the influence of economics training on the learning process of individuals, regarding their decisions for sustainability. Based on a non-cooperative game with simultaneous choices, the results of experiments show that after several rounds the existence of economics knowledge reflects a better learning process for making decisions regarding sustainability of CPR.

Note: Active optical detection of cloud from a balloon platform

A disposable backscatter instrument is described for optical detection of cloud in the atmosphere from a balloon-carried platform. It uses an ultra-bright light emitting diode (LED) illumination source with a photodiode detector. Scattering of the LED light by cloud droplets generates a small optical signal which is separated from background light fluctuations using a lock-in technique. The signal to noise obtained permits cloud detection using the scattered LED light, even in daytime. The response is interpreted in terms of the equivalent visual range within the cloud. The device is lightweight (150 g) and low power (∼30 mA), for use alongside a conventional meteorological radiosonde.