SPONTANEOUS-RECOVERY OF RATS FROM EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS IS DEPENDENT ON REGULATION OF THE IMMUNE-SYSTEM BY ENDOGENOUS ADRENAL CORTICOSTEROIDS

Experimental allergic encephalomyelitis (EAE) ' is a paralytic disease that can be induced in a number of animal species by evoking immune responses to antigens in central nervous system (CNS) myelin, and has been studied as a model for multiple sclerosis in man (1). In Lewis rats EAE can be induced either by immunization with guinea pig myelin basic protein (MBP) in CFA (active EAE) or by the intravenous injection into naive syngeneic recipients of spleen cells from animals with active EAE, after in vitro culture of the splenocytes with MBP (passive EAE). The ascending paralysis characteristic of EAE is caused by the action of CD4+ T lymphocytes that produce focal edema in the CNS by increasing vascular permeability (2-4). In both active and passive EAE, animals develop a transient paralysis, and recover completely within 4-5 d of its onset (5). The mechanisms responsible for this spontaneous recovery, which may be similar to the acute remissions occasionally seen in multiple sclerosis, are still poorly understood. Various mechanisms have been proposed, including: suppressor cells (T lymphocytes [6-9], B lymphocytes [10], and macrophages [11]), anti-T lymphocyte idiotype responses (12), serum suppressor factors (13-16), production ofimmunosuppressive factors by filial cells (17-19), regulation by IFN-'Y (20), and neuroendocrine-mediated immunoregulation (21, 22). None of these mechanisms has been shown directly to be necessary for spontaneous recovery from EAE. It has, however, been demonstrated that CD8+ T lymphocytes are not required (23-25). Here we demonstrate that endogenously produced corticosterone plays an essential role in the spontaneous recovery of rats from EAE. Downloaded from jem.rupress.org on February 21, 201

Frustrations of fur-farmed mink

Captive animals may suffer if strongly motivated to perform activities that their housing does not allow. We investigated this experimentally for caged mink, and found that they would pay high costs to perform a range of natural behaviours, and release cortisol if their most preferred activity, swimming, was prevented. Investigates the effect of limitations on caged mink. Popularity of fur farming; Research into the possible deprivation of mink, which result in their frustration; Details of the experiment; Impact of an access to water; Results which indicate that fur-farmed mink are still motivated to perform the same activities as their wild counterpart

MR-Clust: clustering of genetic variants in Mendelian randomization with similar causal estimates.

MOTIVATION: Mendelian randomization is an epidemiological technique that uses genetic variants as instrumental variables to estimate the causal effect of a risk factor on an outcome. We consider a scenario in which causal estimates based on each variant in turn differ more strongly than expected by chance alone, but the variants can be divided into distinct clusters, such that all variants in the cluster have similar causal estimates. This scenario is likely to occur when there are several distinct causal mechanisms by which a risk factor influences an outcome with different magnitudes of causal effect. We have developed an algorithm MR-Clust that finds such clusters of variants, and so can identify variants that reflect distinct causal mechanisms. Two features of our clustering algorithm are that it accounts for differential uncertainty in the causal estimates, and it includes 'null' and 'junk' clusters, to provide protection against the detection of spurious clusters. RESULTS: Our algorithm correctly detected the number of clusters in a simulation analysis, outperforming methods that either do not account for uncertainty or do not include null and junk clusters. In an applied example considering the effect of blood pressure on coronary artery disease risk, the method detected four clusters of genetic variants. A post hoc hypothesis-generating search suggested that variants in the cluster with a negative effect of blood pressure on coronary artery disease risk were more strongly related to trunk fat percentage and other adiposity measures than variants not in this cluster. AVAILABILITY AND IMPLEMENTATION: MR-Clust can be downloaded from https://github.com/cnfoley/mrclust. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online

MDI-GPU: accelerating integrative modelling for genomic-scale data using GP-GPU computing.

The integration of multi-dimensional datasets remains a key challenge in systems biology and genomic medicine. Modern high-throughput technologies generate a broad array of different data types, providing distinct--but often complementary--information. However, the large amount of data adds burden to any inference task. Flexible Bayesian methods may reduce the necessity for strong modelling assumptions, but can also increase the computational burden. We present an improved implementation of a Bayesian correlated clustering algorithm, that permits integrated clustering to be routinely performed across multiple datasets, each with tens of thousands of items. By exploiting GPU based computation, we are able to improve runtime performance of the algorithm by almost four orders of magnitude. This permits analysis across genomic-scale data sets, greatly expanding the range of applications over those originally possible. MDI is available here: http://www2.warwick.ac.uk/fac/sci/systemsbiology/research/software/

Prescribing practices of primary-care veterinary practitioners in dogs diagnosed with bacterial pyoderma

Concern has been raised regarding the potential contributions of veterinary antimicrobial use to increasing levels of resistance in bacteria critically important to human health. Canine pyoderma is a frequent, often recurrent diagnosis in pet dogs, usually attributable to secondary bacterial infection of the skin. Lesions can range in severity based on the location, total area and depth of tissue affected and antimicrobial therapy is recommended for resolution. This study aimed to describe patient signalment, disease characteristics and treatment prescribed in a large number of UK, primary-care canine pyoderma cases and to estimate pyoderma prevalence in the UK vet-visiting canine population

Collapse of superconductivity in a hybrid tin-graphene Josephson junction array

When a Josephson junction array is built with hybrid superconductor/metal/superconductor junctions, a quantum phase transition from a superconducting to a two-dimensional (2D) metallic ground state is predicted to happen upon increasing the junction normal state resistance. Owing to its surface-exposed 2D electron gas and its gate-tunable charge carrier density, graphene coupled to superconductors is the ideal platform to study the above-mentioned transition between ground states. Here we show that decorating graphene with a sparse and regular array of superconducting nanodisks enables to continuously gate-tune the quantum superconductor-to-metal transition of the Josephson junction array into a zero-temperature metallic state. The suppression of proximity-induced superconductivity is a direct consequence of the emergence of quantum fluctuations of the superconducting phase of the disks. Under perpendicular magnetic field, the competition between quantum fluctuations and disorder is responsible for the resilience at the lowest temperatures of a superconducting glassy state that persists above the upper critical field. Our results provide the entire phase diagram of the disorder and magnetic field-tuned transition and unveil the fundamental impact of quantum phase fluctuations in 2D superconducting systems.Comment: 25 pages, 6 figure

A Human Development Framework for CO2 Reductions

Although developing countries are called to participate in CO2 emission reduction efforts to avoid dangerous climate change, the implications of proposed reduction schemes in human development standards of developing countries remain a matter of debate. We show the existence of a positive and time-dependent correlation between the Human Development Index (HDI) and per capita CO2 emissions from fossil fuel combustion. Employing this empirical relation, extrapolating the HDI, and using three population scenarios, the cumulative CO2 emissions necessary for developing countries to achieve particular HDI thresholds are assessed following a Development As Usual approach (DAU). If current demographic and development trends are maintained, we estimate that by 2050 around 85% of the world's population will live in countries with high HDI (above 0.8). In particular, 300Gt of cumulative CO2 emissions between 2000 and 2050 are estimated to be necessary for the development of 104 developing countries in the year 2000. This value represents between 20% to 30% of previously calculated CO2 budgets limiting global warming to 2{\deg}C. These constraints and results are incorporated into a CO2 reduction framework involving four domains of climate action for individual countries. The framework reserves a fair emission path for developing countries to proceed with their development by indexing country-dependent reduction rates proportional to the HDI in order to preserve the 2{\deg}C target after a particular development threshold is reached. Under this approach, global cumulative emissions by 2050 are estimated to range from 850 up to 1100Gt of CO2. These values are within the uncertainty range of emissions to limit global temperatures to 2{\deg}C.Comment: 14 pages, 7 figures, 1 tabl

Quality of life among symptomatic compared to PSA-detected prostate cancer survivors - results from a UK wide patient-reported outcomes study

Background: Quality of life among prostate cancer survivors varies by socio-demographic factors and treatment type received; however, less in known about differences in functional outcomes by method of presentation. We investigate differences in reported urinary, bowel, sexual and hormone-related problems between symptomatic and PSA-detected prostate cancer survivors. Methods: A UK wide cross-sectional postal survey of prostate cancer survivors conducted 18-42 months post-diagnosis. Questions were included on presentation method and treatment. Functional outcome was determined using the EPIC-26 questionnaire. Reported outcomes were compared for symptomatic and PSA-detected survivors using ANOVA and multivariable log-linear regression. Results: Thirty-five thousand eight hundred twenty-three men responded (response rate: 60.8%). Of these, 31.3% reported presenting via PSA test and 59.7% symptomatically. In multivariable analysis, symptomatic men reported more difficulty with urinary incontinence (Adjusted mean ratio (AMR): 0.96, 95% CI: 0.96-0.97), urinary irritation (AMR: 0.95, 95% CI: 0.95-0.96), bowel function (AMR: 0.97, 95% CI: 0.97-0.98), sexual function (AMR: 0.90, 95% CI: 0.88-0.92), and vitality/hormonal function (AMR: 0.96, 95% CI: 0.96-0.96) than PSA-detected men. Differences were consistent across respondents of differing age, stage, Gleason score and treatment type. Conclusion: Prostate cancer survivors presenting symptomatically report poorer functional outcomes than PSA-detected survivors. Differences were not explained by socio-demographic or clinical factors. Clinicians should be aware that men presenting with symptoms are more likely to report functional difficulties after prostate cancer treatment and may need additional aftercare if these difficulties persist. Method of presentation should be considered as a covariate in patient-reported outcome studies of prostate cancer

Decision-making and referral processes for patients with motor neurone disease: a qualitative study of GP experiences and evaluation of a new decision-support tool

Background The diagnosis of motor neurone disease (MND) is known to be challenging and there may be delay in patients receiving a correct diagnosis. This study investigated the referral process for patients who had been diagnosed with MND, and whether a newly-developed tool (The Red Flags checklist) might help General Practitioners (GPs) in making referral decisions. Methods We carried out interviews with GPs who had recently referred a patient diagnosed with MND, and interviews/surveys with GPs who had not recently referred a patient with suspected MND. We collected data before the Red Flags checklist was introduced; and again one year later. We analysed the data to identify key recurring themes. Results Forty two GPs took part in the study. The presence of fasciculation was the clinical feature that most commonly led to consideration of a potential MND diagnosis. GPs perceived that their role was to make onward referrals rather than attempting to make a diagnosis, and delays in correct diagnosis tended to occur at the specialist level. A quarter of participants had some awareness of the newly-developed tool; most considered it useful, if incorporated into existing systems. Conclusions While fasciculation is the most common symptom associated with MND, other bulbar, limb or respiratory features, together with progression should be considered. There is a need for further research into how decision-support tools should be designed and provided, in order to best assist GPs with referral decisions. There is also a need for further work at the level of secondary care, in order that referrals made are re-directed appropriately