Using the Traditional Ex Vivo Whole Blood Model to Discriminate Bacteria by Their Inducible Host Responses

Whole blood models are rapid and versatile for determining immune responses to inflammatory and infectious stimuli, but they have not been used for bacterial discrimination. Staphylococcus aureus, S. epidermidis and Escherichia coli are the most common causes of invasive disease, and rapid testing strategies utilising host responses remain elusive. Currently, immune responses can only discriminate between bacterial ‘domains’ (fungi, bacteria and viruses), and very few studies can use immune responses to discriminate bacteria at the species and strain level. Here, whole blood was used to investigate the relationship between host responses and bacterial strains. Results confirmed unique temporal profiles for the 10 parameters studied: IL-6, MIP-1α, MIP-3α, IL-10, resistin, phagocytosis, S100A8, S100A8/A9, C5a and TF3. Pairwise analysis confirmed that IL-6, resistin, phagocytosis, C5a and S100A8/A9 could be used in a discrimination scheme to identify to the strain level. Linear discriminant analysis (LDA) confirmed that (i) IL-6, MIP-3α and TF3 could predict genera with 95% accuracy; (ii) IL-6, phagocytosis, resistin and TF3 could predict species at 90% accuracy and (iii) phagocytosis, S100A8 and IL-10 predicted strain at 40% accuracy. These data are important because they confirm the proof of concept that host biomarker panels could be used to identify bacterial pathogens

Graduate Entry Medicine: Selection Criteria and Student Performance

Background: Graduate entry medicine raises new questions about the suitability of students with different backgrounds. We examine this, and the broader issue of effectiveness of selection and assessment procedures. Methods: The data included background characteristics, academic record, interview score and performance in pre-clinical modular assessment for two years intake of graduate entry medical students. Exploratory factor analysis is a powerful method for reducing a large number of measures to a smaller group of underlying factors. It was used here to identify patterns within and between the selection and performance data. Principal Findings: Basic background characteristics were of little importance in predicting exam success. However, easily interpreted components were detected within variables comprising the ‘selection ’ and ‘assessment ’ criteria. Three selection components were identified (‘Academic’, ‘GAMSAT’, ‘Interview’) and four assessment components (‘General Exam’, ‘Oncology’, ‘OSCE’, ‘Family Case Study’). There was a striking lack of relationships between most selection and performance factors. Only ‘General Exam ’ and ‘Academic ’ showed a correlation (Pearson’s r = 0.55, p,0.001). Conclusions: This study raises questions about methods of student selection and their effectiveness in predicting performance and assessing suitability for a medical career. Admissions tests and most exams only confirmed previous academic achievement, while interview scores were not correlated with any consequent assessment

The Euclid Science Ground Segment Distributed Infrastructure: System Integration and Challenges

The Science Ground Segment (SGS) of the Euclid mission provides distributed and redundant data storage and processing, federating nine Science Data Centres (SDCs) and a Science Operations Centre. The SGS reference architecture is based on loosely coupled systems and services, broadly organized into a common infrastructure of transverse software components and the scientific data Processing Functions. The SGS common infrastructure includes: 1) the Euclid Archive System (EAS), a central metadata repository which inventories, indexes and localizes the huge amount of distributed data; 2) a Distributed Storage System of EAS, providing a unified view of the SDCs storage systems and supporting several transfer protocols; 3) an Infrastructure Abstraction Layer, isolating the scientific data processing software from the underlying IT infrastructure and providing a common, lightweight workflow management system; 4) a Common Orchestration System, performing a balanced distribution of data and processing among the SDCs. Virtualization is another key element of the SGS infrastructure. We present the status of the Euclid SGS software infrastructure, the prototypes developed and the continuous system integration and testing performed through the Euclid “SGS Challenges”

Genetic risk for schizophrenia and developmental delay is associated with shape and microstructure of midline white-matter structures

Genomic copy number variants (CNVs) are amongst the most highly penetrant genetic risk factors for neuropsychiatric disorders. The scarcity of carriers of individual CNVs and their phenotypical heterogeneity limits investigations of the associated neural mechanisms and endophenotypes. We applied a novel design based on CNV penetrance for schizophrenia (Sz) and developmental delay (DD) that allows us to identify structural sequelae that are most relevant to neuropsychiatric disorders. Our focus on brain structural abnormalities was based on the hypothesis that convergent mechanisms contributing to neurodevelopmental disorders would likely manifest in the macro- and microstructure of white matter and cortical and subcortical grey matter. Twenty one adult participants carrying neuropsychiatric risk CNVs (including those located at 22q11.2, 15q11.2, 1q21.1, 16p11.2 and 17q12) and 15 age- and gender-matched controls underwent T1-weighted structural, diffusion and relaxometry MRI. The macro- and microstructural properties of the cingulum bundles were associated with penetrance for both developmental delay and schizophrenia, in particular curvature along the anterior-posterior axis (Sz: pcorr = 0.026; DD: pcorr = 0.035) and intracellular volume fraction (Sz: pcorr = 0.019; DD: pcorr = 0.064). Further principal component analysis showed alterations in the interrelationships between the volumes of several midline white-matter structures (Sz: pcorr = 0.055; DD: pcorr = 0.027). In particular, the ratio of volumes in the splenium and body of the corpus callosum was significantly associated with both penetrance scores (Sz: p = 0.037; DD; p = 0.006). Our results are consistent with the notion that a significant alteration in developmental trajectories of midline white-matter structures constitutes a common neurodevelopmental aberration contributing to risk for schizophrenia and intellectual disability

Copy number variation in bipolar disorder.

Large (>100 kb), rare (500 kb) CNVs in BD compared with SZ, most notably for deletions >1 Mb (P=9 × 10(-4))

The stories we tell: uncanny encounters in Mr Straw’s house

During my first visit to Mr Straw’s House, a National Trust Property in the North of England, I was intrigued by the discrepancies between the narrative framework provided by the National Trust – its exclusions, silences and invisibilities – and the far more complex stories the house seemed to tantalisingly hint at. As a scholar I am drawn to certain sites and affectively engage with them and yet I usually keep silent about my investment which informs not only my interest but also how I read these heritage sites. My aim here is not primarily to interrogate my own investment, but to ask how productive it is, what it enables me to see and to describe and where its limits are. This case study explores a particular tourist attraction from the perspective of storytelling and asks what narratives can be constructed around, and generated through, the spatial-emotional dimensions of this heritage site. I am interested in the hold sites have over people, why and how they provoke imaginative and empathic investment that generates a network of stories and triggers processes of unravelling which have the potential to transform silences and unmetabolised affect into empathy and emotional thought

Extragalactic Radio Continuum Surveys and the Transformation of Radio Astronomy

Next-generation radio surveys are about to transform radio astronomy by discovering and studying tens of millions of previously unknown radio sources. These surveys will provide new insights to understand the evolution of galaxies, measuring the evolution of the cosmic star formation rate, and rivalling traditional techniques in the measurement of fundamental cosmological parameters. By observing a new volume of observational parameter space, they are also likely to discover unexpected new phenomena. This review traces the evolution of extragalactic radio continuum surveys from the earliest days of radio astronomy to the present, and identifies the challenges that must be overcome to achieve this transformational change.Comment: To be published in Nature Astronomy 18 Sept 201