A multi-objective evolutionary algorithm fitness function for case-base maintenance.

Case-Base Maintenance (CBM) has two important goals. On the one hand, it aims to reduce the size of the case-base. On the other hand, it has to improve the accuracy of the CBR system. CBM can be represented as a multi-objective optimization problem to achieve both goals. Multi-Objective Evolutionary Algorithms (MOEAs) have been recognised as appropriate techniques for multi-objective optimisation because they perform a search for multiple solutions in parallel. In the present paper we introduce a fitness function based on the Complexity Profiling model to perform CBM with MOEA, and we compare its results against other known CBM approaches. From the experimental results, CBM with MOEA shows regularly good results in many case-bases, despite the amount of redundant and noisy cases, and with a significant potential for improvement

What lies beneath? The role of informal and hidden networks in the management of crises

Crisis management research traditionally focuses on the role of formal communication networks in the escalation and management of organisational crises. Here, we consider instead informal and unobservable networks. The paper explores how hidden informal exchanges can impact upon organisational decision-making and performance, particularly around inter-agency working, as knowledge distributed across organisations and shared between organisations is often shared through informal means and not captured effectively through the formal decision-making processes. Early warnings and weak signals about potential risks and crises are therefore often missed. We consider the implications of these dynamics in terms of crisis avoidance and crisis management

Serpentinization, Carbonation, and Metasomatism of Ultramafic Sequences in the Northern Apennine Ophiolite (NW Italy)

Fluid-rock interaction in ultramafic rocks considerably affects the chemical and isotopic composition of the oceanic lithosphere. We present a geochemical and petrological study of serpentinites and ophicalcites of the Northern Apennine ophiolite, Italy. This ophiolite sequence represents fragments of Jurassic oceanic lithosphere that have been denuded by low angle detachment faults, exposing peridotites on the ocean floor and triggering hydrothermal alteration. Seawater circulation is documented by (Jurassic) seawater-like 87Sr/86Sr values and δ13C values of 1.1–3.0‰ in carbonate veins of the ophicalcites. Bulk rock ophicalcites have low 87Sr/86Sr values of 0.70489–0.70599, elevated SiO2 contents, and talc druses filling calcite veins that record Si-metasomatism. In contrast, underlying serpentinites have 87Sr/86Sr values above Jurassic seawater values. Bulk rock δD and δ18O values of ophicalcites and serpentinites suggest interaction with an evolved seawater-derived and/or magmatic fluid. These chemical signatures result from a complex history of serpentinization, carbonation, and metasomatism. Multiphase water-rock interaction includes infiltration of basement-derived fluids during initial mantle upwelling within an opening ocean basin, followed by localized high-temperature fluid infiltration, extensive seawater circulation resulting in carbonation, and oxidation near the seawater-exposed surface, and finally, fluid-rock interaction with overlying mafic lithologies leading to Si-metasomatism. The studied sequence represents an excellent example of the evolution from serpentinite to ophicalcite during continuous uplift and exposure of ultramafic rocks on the seafloor and documents the complex hydrothermal evolution of ultramafic rocks associated with this process. The extensive chemical transformation of mantle peridotites likely has an impact on geochemical cycles and subduction zone processes

Human skeletal muscle drug transporters determine local exposure and toxicity of statins

Rationale: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, are important drugs used in the treatment and prevention of cardiovascular disease. Although statins are well tolerated, many patients develop myopathy manifesting as muscle aches and pain. Rhabdomyolysis is a rare but severe toxicity of statins. Interindividual differences in the activities of hepatic membrane drug transporters and metabolic enzymes are known to influence statin plasma pharmacokinetics and risk for myopathy. Interestingly, little is known regarding the molecular determinants of statin distribution into skeletal muscle and its relevance to toxicity. Objective: We sought to identify statin transporters in human skeletal muscle and determine their impact on statin toxicity in vitro. Methods and Results: We demonstrate that the uptake transporter OATP2B1 (human organic anion transporting polypeptide 2B1) and the efflux transporters, multidrug resistance-associated protein (MRP)1, MRP4, and MRP5 are expressed on the sarcolemmal membrane of human skeletal muscle fibers and that atorvastatin and rosuvastatin are substrates of these transporters when assessed using a heterologous expression system. In an in vitro model of differentiated, primary human skeletal muscle myoblast cells, we demonstrate basal membrane expression and drug efflux activity of MRP1, which contributes to reducing intracellular statin accumulation. Furthermore, we show that expression of human OATP2B1 in human skeletal muscle myoblast cells by adenoviral vectors increases intracellular accumulation and toxicity of statins and such effects were abrogated when cells overexpressed MRP1. Conclusions: These results identify key membrane transporters as modulators of skeletal muscle statin exposure and toxicity. © 2010 American Heart Association, Inc

The effects of graded motor imagery and its components on chronic pain: A systematic review and meta-analysis

This is the post-print version of the final paper published in The Journal of Pain. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2013 The American Pain Society.Graded motor imagery (GMI) is becoming increasingly used in the treatment of chronic pain conditions. The objective of this systematic review was to synthesize all evidence concerning the effects of GMI and its constituent components on chronic pain. Systematic searches were conducted in 10 electronic databases. All randomized controlled trials (RCTs) of GMI, left/right judgment training, motor imagery, and mirror therapy used as a treatment for chronic pain were included. Methodological quality was assessed using the Cochrane risk of bias tool. Six RCTs met our inclusion criteria, and the methodological quality was generally low. No effect was seen for left/right judgment training, and conflicting results were found for motor imagery used as stand-alone techniques, but positive effects were observed for both mirror therapy and GMI. A meta-analysis of GMI versus usual physiotherapy care favored GMI in reducing pain (2 studies, n = 63; effect size, 1.06 [95% confidence interval, .41, 1.71]; heterogeneity, I2 = 15%). Our results suggest that GMI and mirror therapy alone may be effective, although this conclusion is based on limited evidence. Further rigorous studies are needed to investigate the effects of GMI and its components on a wider chronic pain population.NHMR

The beginnings of geography teaching and research in the University of Glasgow: the impact of J.W. Gregory

J.W. Gregory arrived in Glasgow from Melbourne in 1904 to take up the post of foundation Professor of Geology in the University of Glasgow. Soon after his arrival in Glasgow he began to push for the setting up of teaching in Geography in Glasgow, which came to pass in 1909 with the appointment of a Lecturer in Geography. This lecturer was based in the Department of Geology in the University's East Quad. Gregory's active promotion of Geography in the University was matched by his extensive writing in the area, in textbooks, journal articles and popular books. His prodigious output across a wide range of subject areas is variably accepted today, with much of his geomorphological work being judged as misguided to varying degrees. His 'social science' publications - in the areas of race, migration, colonisation and economic development of Africa and Australia - espouse a viewpoint that is unacceptable in the twenty-first century. Nonetheless, that viewpoint sits squarely within the social and economic traditions of Gregory's era, and he was clearly a key 'Establishment' figure in natural and social sciences research in the first half of the twentieth century. The establishment of Geography in the University of Glasgow remains enduring testimony of J.W. Gregory's energy, dedication and foresight

The Green Bank Northern Celestial Cap Pulsar Survey II: The Discovery and Timing of Ten Pulsars

We present timing solutions for ten pulsars discovered in 350 MHz searches with the Green Bank Telescope. Nine of these were discovered in the Green Bank Northern Celestial Cap survey and one was discovered by students in the Pulsar Search Collaboratory program in analysis of drift-scan data. Following discovery and confirmation with the Green Bank Telescope, timing has yielded phase-connected solutions with high precision measurements of rotational and astrometric parameters. Eight of the pulsars are slow and isolated, including PSR J0930$-$2301, a pulsar with nulling fraction lower limit of $\sim$30\% and nulling timescale of seconds to minutes. This pulsar also shows evidence of mode changing. The remaining two pulsars have undergone recycling, accreting material from binary companions, resulting in higher spin frequencies. PSR J0557$-$2948 is an isolated, 44 \rm{ms} pulsar that has been partially recycled and is likely a former member of a binary system which was disrupted by a second supernova. The paucity of such so-called `disrupted binary pulsars' (DRPs) compared to double neutron star (DNS) binaries can be used to test current evolutionary scenarios, especially the kicks imparted on the neutron stars in the second supernova. There is some evidence that DRPs have larger space velocities, which could explain their small numbers. PSR J1806+2819 is a 15 \rm{ms} pulsar in a 44 day orbit with a low mass white dwarf companion. We did not detect the companion in archival optical data, indicating that it must be older than 1200 Myr.Comment: 9 pages, 5 figure

Identification and Characterization of Trimethylamine-N-oxide Uptake and Efflux Transporters

Trimethylamine-N-oxide (TMAO) is a recently identified predictor of cardiovascular and chronic kidney disease. TMAO is primarily generated through gut-microbiome mediated conversion of dietary choline and carnitine to TMA, which is converted to TMAO by hepatic flavin monooxygenase 3 (FMO3) and subsequently undergoes renal elimination. We investigated the role of uptake and efflux drug transporters in TMAO disposition in vitro and in vivo. After screening a large array of uptake transporters, we show organic cation transporter 2 (OCT2) is the key transporter for TMAO cellular uptake. In Oct1/2 knockout mice, we observed increased plasma TMAO levels with reduced renal retention, suggesting the importance of Oct2 in facilitating the uptake of TMAO into renal tubular cells in vivo. Multiple transporters of the ATP-binding cassette (ABC) family, including ABCG2 (BCRP) and ABCB1 (MDR1), were capable of TMAO efflux. In human subjects, clinical, dietary, and pharmacogenetic covariates were evaluated for contribution to TMAO levels in a cohort of dyslipidemic patients (n = 405). Interestingly, genetic variation in ABCG2, but not other transporters, appeared to play a role in modulating TMAO exposure