Rapidly progressive post-transplant lymphoproliferative disease following withdrawal of sirolimus

Sirolimus, a potent inhibitor of B- and T-cell activation, is a commonly used immunosuppressant after renal transplantation. Withdrawal of sirolimus from the immunosuppression regimen may reduce B-cell surveillance. We present a case of rapidly progressive central nervous system (CNS) polymorphic Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disorder following the withdrawal of sirolimus

Understanding stakeholder interactions in urban partnerships

This paper aims to better understand urban partnerships through the nature of the interactions between their stakeholders. Following a review of approaches to stakeholder arrangements in urban partnerships, which draws on a variety of literatures, including strategic management, public administration, urban studies and geography, the paper presents results of an action-case study undertaken in an urban partnership context – namely, Houldsworth Village Partnership (HVP) – within the Greater Manchester region of the UK. The findings begin by classifying HVP stakeholders along broad sectoral lines, before moving to examine, through a thematic analysis of data, the influences on their interactions in terms of ‘process enablers’ and ‘inhibitors’. This leads to a schema, whereby HVP stakeholder interactions are conceptualized on the dual continua of attitude and behavior. The schema provides a theoretical contribution by offering an understanding of stakeholders' dynamic interplay within an urban partnership context, and a means of classifying such stakeholders beyond their individual/organizational characteristics or sectoral affiliations

Sheep Updates 2005 - Part 7

This session covers eight papers from different authors: POSTERS 1. Sulpher in wool and its implications for fleece weight and sheep health, SM Liu, AC Schlink, JR Williams, CSIRO Livestock Industries Wembley WA, ME Dowling,JCGreef, Department of Agriculture Western Australia. 2. Stubbles for sheep: a reality check, Roy Butler, Keith Croker, Department of Agriculture Western Australia. 3. Genetic benchmarking using artificial insemination, LC Butler, JC Greeff, Department of Agriculture Western Australia. 4. The potential lambing performances of ewes in mixed age flocks, Kieth Croker, Department of Agriculture Western Australia, Rob Davidson, WAMMCO International, formally University of Western Australia, Ken Hart, Department of Agriculture Western Australia,Doug Harrington Cowcher Farms Narrogin, Mario D\u27Antuono, Department of Agriculture Western Australia. 5. National Livestock Identification System (Sheep) in Western Australia, Julian Gardner, Department of Agriculture Western Australia. DISPLAYS - TOOLS 6. To Feed or Not to Feed - I Only Hamlet had the Calculator!, Geoff Duddy, Livestock Officer(Sheep & Wool) Yanco. 7. WormBoss - a national Australian computer-based sheep worm control tool, RG Woodgate, Department of Agriculture Western Australia, A LeFeuvre, Queensland Department of Primary Industries and Fisheries, and Genie Pty Ltd, Warwick Qld, A Bailey, Department of Primary Industries, Water and Environment, Kings Meadow Tas, RB Besier, Department of Agriculture Western Australia, N. Campbell, Department of Primary Industries Victoria, Attwood Vic, I Carmichael, South Australian Research and Development Institute, Glenside SA, S. Love, NSW Department of Primary Industries, Armidale NSW. 8. \u27Eye in the sky\u27 takes guesswork out of farmers pasture decisions, Richard Stovold, Department of Land Informatio

Subsurface morphology and scaling of lunar impact basins

Impact bombardment during the first billion years after the formation of the Moon produced at least several tens of basins. The Gravity Recovery and Interior Laboratory (GRAIL) mission mapped the gravity field of these impact structures at significantly higher spatial resolution than previous missions, allowing for detailed subsurface and morphological analyses to be made across the entire globe. GRAIL-derived crustal thickness maps were used to define the regions of crustal thinning observed in centers of lunar impact basins, which represents a less unambiguous measure of a basin size than those based on topographic features. The formation of lunar impact basins was modeled numerically by using the iSALE-2D hydrocode, with a large range of impact and target conditions typical for the first billion years of lunar evolution. In the investigated range of impactor and target conditions, the target temperature had the dominant effect on the basin subsurface morphology. Model results were also used to update current impact scaling relationships applicable to the lunar setting (based on assumed target temperature). Our new temperature-dependent impact-scaling relationships provide estimates of impact conditions and transient crater diameters for the majority of impact basins mapped by GRAIL. As the formation of lunar impact basins is associated with the first ~700 Myr of the solar system evolution when the impact flux was considerably larger than the present day, our revised impact scaling relationships can aid further analyses and understanding of the extent of impact bombardment on the Moon and terrestrial planets in the early solar system

The P2 Receptor Antagonist PPADS Supports Recovery from Experimental Stroke In Vivo

BACKGROUND: After ischemia of the CNS, extracellular adenosine 5'-triphosphate (ATP) can reach high concentrations due to cell damage and subsequent increase of membrane permeability. ATP may cause cellular degeneration and death, mediated by P2X and P2Y receptors. METHODOLOGY/PRINCIPAL FINDINGS: The effects of inhibition of P2 receptors by pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) on electrophysiological, functional and morphological alterations in an ischemia model with permanent middle cerebral artery occlusion (MCAO) were investigated up to day 28. Spontaneously hypertensive rats received PPADS or vehicle intracerebroventricularly 15 minutes prior MCAO for up to 7 days. The functional recovery monitored by qEEG was improved by PPADS indicated by an accelerated recovery of ischemia-induced qEEG changes in the delta and alpha frequency bands along with a faster and sustained recovery of motor impairments. Whereas the functional improvements by PPADS were persistent at day 28, the infarct volume measured by magnetic resonance imaging and the amount of TUNEL-positive cells were significantly reduced by PPADS only until day 7. Further, by immunohistochemistry and confocal laser scanning microscopy, we identified both neurons and astrocytes as TUNEL-positive after MCAO. CONCLUSION: The persistent beneficial effect of PPADS on the functional parameters without differences in the late (day 28) infarct size and apoptosis suggests that the early inhibition of P2 receptors might be favourable for the maintenance or early reconstruction of neuronal connectivity in the periinfarct area after ischemic incidents

Enhanced tonic GABAA inhibition in typical absence epilepsy

The cellular mechanisms underlying typical absence seizures, which characterize various idiopathic generalized epilepsies, are not fully understood, but impaired GABAergic inhibition remains an attractive hypothesis. In contrast, we show here that extrasynaptic GABAA receptor–dependent ‘tonic’ inhibition is increased in thalamocortical neurons from diverse genetic and pharmacological models of absence seizures. Increased tonic inhibition is due to compromised GABA uptake by the GABA transporter GAT–1 in the genetic models tested, and GAT–1 is critical in governing seizure genesis. Extrasynaptic GABAA receptors are a requirement for seizures in two of the best characterized models of absence epilepsy, and the selective activation of thalamic extrasynaptic GABAA receptors is sufficient to elicit both electrographic and behavioural correlates of seizures in normal animals. These results identify an apparently common cellular pathology in typical absence seizures that may have epileptogenic significance, and highlight novel therapeutic targets for the treatment of absence epilepsy.peer-reviewe

Rod and Cone Pathway Signalling Is Altered in the P2X7 Receptor Knock Out Mouse

The P2X7 receptor (P2X7-R) is expressed in the retina and brain and has been implicated in neurodegenerative diseases. However, whether it is expressed by neurons and plays a role as a neurotransmitter receptor has been the subject of controversy. In this study, we first show that the novel vesicular transporter for ATP, VNUT, is expressed in the retina, verifying the presence of the molecular machinery for ATP to act as neurotransmitter at P2X7-Rs. Secondly we show the presence of P2X7-R mRNA and protein in the retina and cortex and absence of the full length variant 1 of the receptor in the P2X7-R knock out (P2X7-KO) mouse. The role of the P2X7-R in neuronal function of the retina was assessed by comparing the electroretinogram response of P2X7-KO with WT mice. The rod photoreceptor response was found to be similar, while both rod and cone pathway post-photoreceptor responses were significantly larger in P2X7-KO mice. This suggests that activation of P2X7-Rs modulates output of second order retinal neurons. In line with this finding, P2X7-Rs were found in the outer plexiform layer and on inner retinal cell classes, including horizontal, amacrine and ganglion cells. The receptor co-localized with conventional synapses in the IPL and was expressed on amacrine cells post-synaptic to rod bipolar ribbon synapses. In view of the changes in visual function in the P2X7-KO mouse and the immunocytochemical location of the receptor in the normal retina, it is likely the P2X7-R provides excitatory input to photoreceptor terminals or to inhibitory cells that shape both the rod and cone pathway response

Systematic review and meta-analysis of the efficacy of interleukin-1 receptor antagonist in animal models of stroke: an update

Interleukin-1 receptor antagonist (IL-1 RA) is an anti-inflammatory protein used clinically to treat rheumatoid arthritis and is considered a promising candidate therapy for stroke. Here, we sought to update the existing systematic review and meta-analysis of IL-1 RA in models of ischaemic stroke, published in 2009, to assess efficacy, the range of circumstances in which efficacy has been tested and whether the data appear to be confounded due to reported study quality and publication bias. We included 25 sources of data, 11 of which were additional to the original review. Overall, IL-1 RA reduced infarct volume by 36.2 % (95 % confidence interval 31.6–40.7, n = 76 comparisons from 1283 animals). Assessments for publication bias suggest 30 theoretically missing studies which reduce efficacy to 21.9 % (17.3–26.4). Efficacy was higher where IL-1 RA was administered directly into the ventricles rather than peripherally, and studies not reporting allocation concealment during the induction of ischaemia reported larger treatment effects. The preclinical data supporting IL-1 RA as a candidate therapy for ischaemic stroke have improved. The reporting of measures to reduce the risk of bias has improved substantially in this update, and studies now include the use of animals with relevant co-morbidities. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12975-016-0489-z) contains supplementary material, which is available to authorized users