Brain glucose sensing, glucokinase and neural control of metabolism and islet function.

It is increasingly apparent that the brain plays a central role in metabolic homeostasis, including the maintenance of blood glucose. This is achieved by various efferent pathways from the brain to periphery, which help control hepatic glucose flux and perhaps insulin-stimulated insulin secretion. Also, critically important for the brain given its dependence on a constant supply of glucose as a fuel--emergency counter-regulatory responses are triggered by the brain if blood glucose starts to fall. To exert these control functions, the brain needs to detect rapidly and accurately changes in blood glucose. In this review, we summarize some of the mechanisms postulated to play a role in this and examine the potential role of the low-affinity hexokinase, glucokinase, in the brain as a key part of some of this sensing. We also discuss how these processes may become altered in diabetes and related metabolic diseases.Funding and support from Wellcome Trust, Medical Research Council including the Cambridge MRC Centre for Study of Obesity and Related Disorders (MRC-CORD), NIHR Cambridge Biomedical Research Centre, Diabetes UK (RD05/003059) and Yousef Jameel Fund).This is the final version published version. It first appeared at http://onlinelibrary.wiley.com/doi/10.1111/dom.12334/abstract

The bright optical afterglow of the nearby gamma-ray burst of 29 March 2003

Many past studies of cosmological gamma-ray bursts (GRBs) have been limited because of the large distance to typical GRBs, resulting in faint afterglows. There has long been a recognition that a nearby GRB would shed light on the origin of these mysterious cosmic explosions, as well as the physics of their fireballs. However, GRBs nearer than z=0.2 are extremely rare, with an estimated rate of localisation of one every decade. Here, we report the discovery of bright optical afterglow emission from GRB 030329. Our prompt dissemination and the brilliance of the afterglow resulted in extensive followup (more than 65 telescopes) from radio through X-ray bands, as well as measurement of the redshift, z=0.169. The gamma-ray and afterglow properties of GRB 030329 are similar to those of cosmological GRBs (after accounting for the small distance), making this the nearest known cosmological GRB. Observations have already securely identified the progenitor as a massive star that exploded as a supernova, and we anticipate futher revelations of the GRB phenomenon from studies of this source.Comment: 13 pages, 4 figures. Original tex

A contemporaneous infrared flash from a long gamma-ray burst: an echo from the central engine

The explosion that results in a cosmic gamma-ray burst (GRB) is thought to produce emission from two physical processes -- the activity of the central engine gives rise to the high-energy emission of the burst through internal shocking and the subsequent interaction of the flow with the external environment produces long-wavelength afterglow. While afterglow observations continue to refine our understanding of GRB progenitors and relativistic shocks, gamma-ray observations alone have not yielded a clear picture of the origin of the prompt emission nor details of the central engine. Only one concurrent visible-light transient has been found and was associated with emission from an external shock. Here we report the discovery of infrared (IR) emission contemporaneous with a GRB, beginning 7.2 minutes after the onset of GRB 041219a. Our robotic telescope acquired 21 images during the active phase of the burst, yielding the earliest multi-colour observations of any long-wavelength emission associated with a GRB. Analysis of an initial IR pulse suggests an origin consistent with internal shocks. This opens a new possibility to study the central engine of GRBs with ground-based observations at long wavelengths.Comment: Accepted to Nature on March 1, 2005. 9 pages, 4 figures, nature12.cls and nature1.cls files included. This paper is under press embargo until print publicatio

Cost-effectiveness of HBV and HCV screening strategies:a systematic review of existing modelling techniques

Introduction: Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. Methods: A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. Results: The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. Conclusion: When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers

Impact of the California Lead Ammunition Ban on Reducing Lead Exposure in Golden Eagles and Turkey Vultures

Predatory and scavenging birds may be exposed to high levels of lead when they ingest shot or bullet fragments embedded in the tissues of animals injured or killed with lead ammunition. Lead poisoning was a contributing factor in the decline of the endangered California condor population in the 1980s, and remains one of the primary factors threatening species recovery. In response to this threat, a ban on the use of lead ammunition for most hunting activities in the range of the condor in California was implemented in 2008. Monitoring of lead exposure in predatory and scavenging birds is essential for assessing the effectiveness of the lead ammunition ban in reducing lead exposure in these species. In this study, we assessed the effectiveness of the regulation in decreasing blood lead concentration in two avian sentinels, golden eagles and turkey vultures, within the condor range in California. We compared blood lead concentration in golden eagles and turkey vultures prior to the lead ammunition ban and one year following implementation of the ban. Lead exposure in both golden eagles and turkey vultures declined significantly post-ban. Our findings provide evidence that hunter compliance with lead ammunition regulations was sufficient to reduce lead exposure in predatory and scavenging birds at our study sites

Technology enhanced assessment in complex collaborative settings

Building upon discussions by the Assessment Working Group at EDUsummIT 2013, this article reviews recent developments in technology enabled assessments of collaborative problem solving in order to point out where computerised assessments are particularly useful (and where non-computerised assessments need to be retained or developed) while assuring that the purposes and designs are transparent and empowering for teachers and learners. Technology enabled assessments of higher order critical thinking in a collaborative social context can provide data about the actions, communications and products created by a learner in a designed task space. Principled assessment design is required in order for such a space to provide trustworthy evidence of learning, and the design must incorporate and take account of the engagement of the audiences for the assessment as well as vary with the purposes and contexts of the assessment. Technology enhanced assessment enables in-depth unobtrusive documentation or ‘quiet assessment’ of the many layers and dynamics of authentic performance and allows greater flexibility and dynamic interactions in and among the design features. Most important for assessment FOR learning, are interactive features that allow the learner to turn up or down the intensity, amount and sharpness of the information needed for self-absorption and adoption of the feedback. Most important in assessment OF learning, are features that compare the learner with external standards of performance. Most important in assessment AS learning, are features that allow multiple performances and a wide array of affordances for authentic action, communication and the production of artefacts

Mink Farms Predict Aleutian Disease Exposure in Wild American Mink

BACKGROUND: Infectious diseases can often be of conservation importance for wildlife. Spillover, when infectious disease is transmitted from a reservoir population to sympatric wildlife, is a particular threat. American mink (Neovison vison) populations across Canada appear to be declining, but factors thus far explored have not fully explained this population trend. Recent research has shown, however, that domestic mink are escaping from mink farms and hybridizing with wild mink. Domestic mink may also be spreading Aleutian disease (AD), a highly pathogenic parvovirus prevalent in mink farms, to wild mink populations. AD could reduce fitness in wild mink by reducing both the productivity of adult females and survivorship of juveniles and adults. METHODS: To assess the seroprevalence and geographic distribution of AD infection in free-ranging mink in relation to the presence of mink farms, we conducted both a large-scale serological survey, across the province of Ontario, and a smaller-scale survey, at the interface between a mink farm and wild mink. CONCLUSIONS/SIGNIFICANCE: Antibodies to AD were detected in 29% of mink (60 of 208 mink sampled); however, seroprevalence was significantly higher in areas closer to mink farms than in areas farther from farms, at both large and small spatial scales. Our results indicate that mink farms act as sources of AD transmission to the wild. As such, it is likely that wild mink across North America may be experiencing increased exposure to AD, via disease transmission from mink farms, which may be affecting wild mink demographics across their range. In light of declining mink populations, high AD seroprevalence within some mink farms, and the large number of mink farms situated across North America, improved biosecurity measures on farms are warranted to prevent continued disease transmission at the interface between mink farms and wild mink populations