UK utility data integration: overcoming schematic heterogeneity

In this paper we discuss syntactic, semantic and schematic issues which inhibit the integration of utility data in the UK. We then focus on the techniques employed within the VISTA project to overcome schematic heterogeneity. A Global Schema based architecture is employed. Although automated approaches to Global Schema definition were attempted the heterogeneities of the sector were too great. A manual approach to Global Schema definition was employed. The techniques used to define and subsequently map source utility data models to this schema are discussed in detail. In order to ensure a coherent integrated model, sub and cross domain validation issues are then highlighted. Finally the proposed framework and data flow for schematic integration is introduced

REFORM: Rotor Estimation From Object Resampling and Matching

Abstract: In this paper we tackle the problem of correspondence and rotor estimation between models composed of geometric primitives of different types. We frame this problem as searching for the rotor that takes a query model to a reference model. The situations that we consider are those in which our query model: contains additional primitives not present in the reference; is missing primitives that are present in the reference. We will also look at cases in which there are a large number of primitives per model. These are all common issues facing any SLAM-type (simultaneous localisation and mapping) systems. To overcome these problems we introduce an inter-object rotor magnitude-based matching function and a subsampled iterative rotor estimation and matching algorithm. We title the finished algorithm: Rotor Estimation From Object Resampling and Matching—REFORM. REFORM builds on ideas from the RANSAC (RAndom SAmple Consensus) [7] and ICP (Iterative Closest Point) [3, 11] algorithms and extends these to multivector correspondence. It is easily parallelisable and designed for good convergence performance with models of real objects

Biofilm formation is a risk factor for mortality in patients with Candida albicans bloodstream infection-Scotland, 2012-2013

Acknowledgements This work was supported by the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377/Z/11/Z. Data collection was supported by a grant from Pfizer. G. Ramage was also supported by a research fellowship grant from Gilead Sciences. We are grateful to microbiology colleagues throughout Scotland for submitting isolates.Peer reviewedPublisher PD

Data Portraits and Intermediary Topics: Encouraging Exploration of Politically Diverse Profiles

In micro-blogging platforms, people connect and interact with others. However, due to cognitive biases, they tend to interact with like-minded people and read agreeable information only. Many efforts to make people connect with those who think differently have not worked well. In this paper, we hypothesize, first, that previous approaches have not worked because they have been direct -- they have tried to explicitly connect people with those having opposing views on sensitive issues. Second, that neither recommendation or presentation of information by themselves are enough to encourage behavioral change. We propose a platform that mixes a recommender algorithm and a visualization-based user interface to explore recommendations. It recommends politically diverse profiles in terms of distance of latent topics, and displays those recommendations in a visual representation of each user's personal content. We performed an "in the wild" evaluation of this platform, and found that people explored more recommendations when using a biased algorithm instead of ours. In line with our hypothesis, we also found that the mixture of our recommender algorithm and our user interface, allowed politically interested users to exhibit an unbiased exploration of the recommended profiles. Finally, our results contribute insights in two aspects: first, which individual differences are important when designing platforms aimed at behavioral change; and second, which algorithms and user interfaces should be mixed to help users avoid cognitive mechanisms that lead to biased behavior.Comment: 12 pages, 7 figures. To be presented at ACM Intelligent User Interfaces 201

Hsp90 governs dispersion and drug resistance of fungal biofilms

Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving clinical outcome in the treatment of biofilm infections

Candida albicans forms biofilms on the vaginal mucosa

Current understanding of resistance and susceptibility to vulvovaginal candidiasis challenges existing paradigms of host defence against fungal infection. While abiotic biofilm formation has a clearly established role during systemic Candida infections, it is not known whether C. albicans forms biofilms on the vaginal mucosa and the possible role of biofilms in disease. In vivo and ex vivo murine vaginitis models were employed to examine biofilm formation by scanning electron and confocal microscopy. C. albicans strains included 3153A (lab strain), DAY185 (parental control strain), and mutants defective in morphogenesis and/or biofilm formation in vitro (efg1/efg1 and bcr1/bcr1). Both 3153A and DAY815 formed biofilms on the vaginal mucosa in vivo and ex vivo as indicated by high fungal burden and microscopic analysis demonstrating typical biofilm architecture and presence of extracellular matrix (ECM) co-localized with the presence of fungi. In contrast, efg1/efg1 and bcr1/bcr1 mutant strains exhibited weak or no biofilm formation/ECM production in both models compared to wild-type strains and complemented mutants despite comparable colonization levels. These data show for the first time that C. albicans forms biofilms in vivo on vaginal epithelium, and that in vivo biotic biofilm formation requires regulators of biofilm formation (BCR1) and morphogenesis (EFG1)

The impact of capital structure on the decision to outsource with long term contracts

This paper analyzes how capital structure affects the firms’ strategic choice between outsourcing with long term contracts and outsourcing to the spot market. When outsourcing to the spot market firms are exposed to price uncertainty, whereas a long term contract allows them to set in advance the outsourcing price. We show that, to the extent that leverage and uncertainty can lead to financial distress costs in bad states of nature, firms may use long term contracts as a risk management device to hedge input price uncertainty.N/

The novel mTOR inhibitor RAD001 (Everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells

Background/Aim: Tumors exhibiting constitutively activated PI(3) K/Akt/mTOR signaling are hypersensitive to mTOR inhibitors such as RAD001 (everolimus) which is presently being investigated in clinical phase II trials in various tumor entities, including neuroendocrine tumors (NETs). However, no preclinical data about the effects of RAD001 on NET cells have been published. In this study, we aimed to evaluate the effects of RAD001 on BON cells, a human pancreatic NET cell line that exhibits constitutively activated PI(3) K/Akt/mTOR signaling. Methods: BON cells were treated with different concentrations of RAD001 to analyze its effect on cell growth using proliferation assays. Apoptosis was examined by Western blot analysis of caspase-3/PARP cleavage and by FACS analysis of DNA fragmentation. Results: RAD001 potently inhibited BON cell growth in a dose-dependent manner which was dependent on the serum concentration in the medium. RAD001-induced growth inhibition involved G0/G1-phase arrest as well as induction of apoptosis. Conclusion: In summary, our data demonstrate antiproliferative and apoptotic effects of RAD001 in NET cells in vitro supporting its clinical use in current phase II trials in NET patients. Copyright (c) 2007 S. Karger AG, Basel

Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat diet

Glucocorticoid hormones are critical to respond and adapt to stress. Genetic variations in the glucocorticoid receptor (GR) gene alter hypothalamic-pituitary-adrenal (HPA) axis activity and associate with hypertension and susceptibility to metabolic disease. Here we test the hypothesis that reduced GR density alters blood pressure and glucose and lipid homeostasis and limits adaption to obesogenic diet. Heterozygous GR βgeo/+ mice were generated from embryonic stem (ES) cells with a gene trap integration of a β-galactosidase-neomycin phosphotransferase (βgeo) cassette into the GR gene creating a transcriptionally inactive GR fusion protein. Although GRβgeo/+ mice have 50% less functional GR, they have normal lipid and glucose homeostasis due to compensatory HPA axis activation but are hypertensive due to activation of the renin-angiotensin- aldosterone system (RAAS). When challenged with a high-fat diet, weight gain, adiposity, and glucose intolerance were similarly increased in control and GRβgeo/+ mice, suggesting preserved control of intermediary metabolism and energy balance. However, whereas a high-fat diet caused HPA activation and increased blood pressure in control mice, these adaptions were attenuated or abolished in GRβgeo/+ mice. Thus, reduced GR density balanced by HPA activation leaves glucocorticoid functions unaffected but mineralocorticoid functions increased, causing hypertension. Importantly, reduced GR limits HPA and blood pressure adaptions to obesogenic diet

Thresholds for clinical importance were defined for the European Organisation for Research and Treatment of Cancer Computer Adaptive Testing Core-an adaptive measure of core quality of life domains in oncology clinical practice and research

Objectives The aim of this article was to establish thresholds for clinical importance (TCIs) for the European Organisation for Research and Treatment of Cancer (EORTC) Computer Adaptive Testing (CAT) Core measure, the new adaptive version of the EORTC QLQ-C30. Study Design and Setting For our diagnostic study, we recruited cancer patients with mixed diagnoses and treatments from six European countries. Patients completed the EORTC CAT Core and a questionnaire with anchor items assessing criteria for clinical importance (limitations in everyday life, need for help/care, and worries by the patient/family/partner) for each EORTC CAT Core domain. We used a binary variable summarizing the anchor items for determining TCIs and for calculating the area under the curve (AUC) in receiving operator characteristic analysis as a measure of diagnostic accuracy. Results Using data from 498 cancer patients (mean age 60.4 years, 55.2% women), we established TCIs for the 14 domains of the EORTC CAT Core. Median AUC across domains was 0.93 (range 0.84–0.94). Median sensitivity and specificity of the TCIs were 0.91 (range 0.80–0.96) and 0.77 (range 0.66–0.84), respectively. TCIs and AUCs were largely consistent across patient groups. Conclusion We have generated TCIs for the 14 functional health and symptom domains of the EORTC CAT Core. The EORTC CAT Core showed high diagnostic accuracy in identifying clinically important symptoms and functional impairments