UDP-sugars activate P2Y 14 receptors to mediate vasoconstriction of the porcine coronary artery

Aims UDP-sugars can act as extracellular signalling molecules, but relatively little is known about their cardiovascular actions. The P2Y14 receptor is a Gi/o-coupled receptor which is activated by UDP-glucose and related sugar nucleotides. In this study we sought to investigate whether P2Y14 receptors are functionally expressed in the porcine coronary artery using a selective P2Y14 receptor agonist, MRS2690, and a novel selective P2Y14 receptor antagonist, PPTN (4,7-disubstituted naphthoic acid derivative). Methods and results Isometric tension recordings were used to evaluate the effects of UDP-sugars in porcine isolated coronary artery segments. The effects of the P2 receptor antagonists suramin and PPADS, the P2Y14 receptor antagonist PPTN, and the P2Y6 receptor antagonist MRS2578, were investigated. Measurement of vasodilator-stimulated phosphoprotein (VASP) phosphorylation using flow cytometry was used to assess changes in cAMP levels. UDP-glucose, UDP-glucuronic acid UDP-N-acetylglucosamine (P2Y14 receptor agonists), elicited concentration-dependent contractions in the porcine coronary artery. MRS2690 was a more potent vasoconstrictor than the UDP-sugars. Concentration dependent contractile responses to MRS2690 and UDP-sugars were enhanced in the presence of forskolin (activator of cAMP), where the level of basal tone was maintained by addition of U46619, a thromboxane A2 mimetic. Contractile responses to MRS2690 were blocked by PPTN, but not by MRS2578. Contractile responses to UDP-glucose were also attenuated by PPTN and suramin, but not by MRS2578. Forskolin-induced VASP-phosphorylation was reduced in porcine coronary arteries exposed to UDP-glucose and MRS2690, consistent with P2Y14 receptor coupling to Gi/o proteins and inhibition of adenylyl cyclase activity. Conclusions Our data support a role of UDP-sugars as extracellular signalling molecules and show for the first time that they mediate contraction of porcine coronary arteries via P2Y14 receptors

Remote assessment of platelet function in patients with acute stroke or transient ischaemic attack

Background: Antiplatelets reduce recurrence after cerebral ischaemia. The international TARDIS trial assessed the safety and efficacy of intensive (combined aspirin, dipyridamole and clopidogrel) versus guideline (aspirin and dipyridamole, or clopidogrel alone) antiplatelet agents given for one month in patients with acute stroke or TIA. The aim of this substudy was to assess the effect of antiplatelet agents taken at baseline on platelet function reactivity and activation. Methods: In a substudy, platelet function, assessed by remotely measured surface expression of P-selectin (CD62P, Platelet Solutions Ltd), was assessed at baseline in patients who were and were not taking antiplatelet agents at the time of randomisation. Data are Median Fluorescence values (MF). Results: The aspirin P-selectin test demonstrated that platelet expression was lower in 485 patients taking aspirin than in 171 patients taking no aspirin: mean 209 (SD 188) vs. 552 (431), difference 343 (95% confidence intervals, CI 295.3, 390.7) (2p<0.001). Aspirin did not suppress P-selectin levels below 500 units in 22 (4.5%) patients. The clopidogrel P-selectin test showed that platelet reactivity was lower in 96 patients taking clopidogrel than in 586 patients taking no clopidogrel: 653 (297) vs. 969 (315), difference 316.1 (95% CI 248.6, 383.6) (2p<0.001). However, clopidogrel did not suppress P selectin level below 860 units in 24 (24.7%) patients. Conclusions: Aspirin and clopidogrel each suppress stimulated platelet P-selectin although one quarter of patients on clopidogrel have high on-treatment platelet reactivity. Platelet function testing, assessed as platelet P-selectin expression, may be performed remotely in the context of a large multicentre trial

The Vehicle, Spring 1993

Table of Contents The Shape of Things to Come.Peter F. Essigpage 6 SaxophoneWalt Howardpage 6 Gravity BedSue Songerpage 7 UntitledJennifer Gutowskipage 8 uncertaintyWalt Howardpage 9 Ruth Ann, et. al.Susan Eisenhourpage 9 Failed IndustryScott Langenpage 10 UntitledKaren Wisspage 10 wanted:Walt Howardpage 10 Dida; 1978Diana Matijaspage 11 UntitledJennifer Gutowskipage 12 The Lesson in NovemberSue Songerpage 13 Coal MinerJames P. Tangpage 16 Christmas CrueltySue Songerpage 17 Astral ProjectionSusan Eisenhourpage 18 UntitledBen Hausmannpage 19 Into Zagreb\u27s Evening*Diana Matjaspage 20 UntitledJennifer Gutowskipage 22 The AnniversaryJennifer Moropage 23 NudeDan Trutterpage 24 death for saleWalt Howardpage 24 JudgedKevin St. Angelpage 25 Nature\u27s RefugeeScott Langenpage 25 Arrowhead Hunting at TippecanoeJennifer Moropage 26 UntitledKimberly Foxpage 27 TAINTED LOVESarah C. Patiencepage 28 cemeteryWalt Howardpage 28 Cow GameSusan Eisenhourpage 29 UntitledJennifer Gutowskipage 31 ReflectionsPeter F. Essigpage 32 Destination U.S.A.Dan Trutterpage 33 UntitledMario Letopage 33 Authors\u27 Pagepage 34https://thekeep.eiu.edu/vehicle/1061/thumbnail.jp

The Vehicle, Spring 1993

Table of Contents The Shape of Things to Come.Peter F. Essigpage 6 SaxophoneWalt Howardpage 6 Gravity BedSue Songerpage 7 UntitledJennifer Gutowskipage 8 uncertaintyWalt Howardpage 9 Ruth Ann, et. al.Susan Eisenhourpage 9 Failed IndustryScott Langenpage 10 UntitledKaren Wisspage 10 wanted:Walt Howardpage 10 Dida; 1978Diana Matijaspage 11 UntitledJennifer Gutowskipage 12 The Lesson in NovemberSue Songerpage 13 Coal MinerJames P. Tangpage 16 Christmas CrueltySue Songerpage 17 Astral ProjectionSusan Eisenhourpage 18 UntitledBen Hausmannpage 19 Into Zagreb\u27s Evening*Diana Matjaspage 20 UntitledJennifer Gutowskipage 22 The AnniversaryJennifer Moropage 23 NudeDan Trutterpage 24 death for saleWalt Howardpage 24 JudgedKevin St. Angelpage 25 Nature\u27s RefugeeScott Langenpage 25 Arrowhead Hunting at TippecanoeJennifer Moropage 26 UntitledKimberly Foxpage 27 TAINTED LOVESarah C. Patiencepage 28 cemeteryWalt Howardpage 28 Cow GameSusan Eisenhourpage 29 UntitledJennifer Gutowskipage 31 ReflectionsPeter F. Essigpage 32 Destination U.S.A.Dan Trutterpage 33 UntitledMario Letopage 33 Authors\u27 Pagepage 34https://thekeep.eiu.edu/vehicle/1061/thumbnail.jp

Deweyan tools for inquiry and the epistemological context of critical pedagogy

This article develops the notion of resistance as articulated in the literature of critical pedagogy as being both culturally sponsored and cognitively manifested. To do so, the authors draw upon John Dewey\u27s conception of tools for inquiry. Dewey provides a way to conceptualize student resistance not as a form of willful disputation, but instead as a function of socialization into cultural models of thought that actively truncate inquiry. In other words, resistance can be construed as the cognitive and emotive dimensions of the ongoing failure of institutions to provide ideas that help individuals both recognize social problems and imagine possible solutions. Focusing on Dewey\u27s epistemological framework, specifically tools for inquiry, provides a way to grasp this problem. It also affords some innovative solutions; for instance, it helps conceive of possible links between the regular curriculum and the study of specific social justice issues, a relationship that is often under-examined. The aims of critical pedagogy depend upon students developing dexterity with the conceptual tools they use to make meaning of the evidence they confront; these are background skills that the regular curriculum can be made to serve even outside social justice-focused curricula. Furthermore, the article concludes that because such inquiry involves the exploration and potential revision of students\u27 world-ordering beliefs, developing flexibility in how one thinks may be better achieved within academic subjects and topics that are not so intimately connected to students\u27 current social lives, especially where students may be directly implicated

Simplified Models for LHC New Physics Searches

This document proposes a collection of simplified models relevant to the design of new-physics searches at the LHC and the characterization of their results. Both ATLAS and CMS have already presented some results in terms of simplified models, and we encourage them to continue and expand this effort, which supplements both signature-based results and benchmark model interpretations. A simplified model is defined by an effective Lagrangian describing the interactions of a small number of new particles. Simplified models can equally well be described by a small number of masses and cross-sections. These parameters are directly related to collider physics observables, making simplified models a particularly effective framework for evaluating searches and a useful starting point for characterizing positive signals of new physics. This document serves as an official summary of the results from the "Topologies for Early LHC Searches" workshop, held at SLAC in September of 2010, the purpose of which was to develop a set of representative models that can be used to cover all relevant phase space in experimental searches. Particular emphasis is placed on searches relevant for the first ~50-500 pb-1 of data and those motivated by supersymmetric models. This note largely summarizes material posted at http://lhcnewphysics.org/, which includes simplified model definitions, Monte Carlo material, and supporting contacts within the theory community. We also comment on future developments that may be useful as more data is gathered and analyzed by the experiments.Comment: 40 pages, 2 figures. This document is the official summary of results from "Topologies for Early LHC Searches" workshop (SLAC, September 2010). Supplementary material can be found at http://lhcnewphysics.or

Can You Hear us Now? Voices from the Margin: Using Indigenous Methodologies in Geographic Research

Indigenous methodologies are an alternative way of thinking about research processes. Although these methodologies vary according to the ways in which different Indigenous communities express their own unique knowledge systems, they do have common traits. This article argues that research on Indigenous issues should be carried out in a manner which is respectful and ethically sound from an Indigenous perspective. This naturally challenges Western research paradigms, yet it also affords opportunities to contribute to the body of knowledge about Indigenous peoples. It is further argued that providing a mechanism for Indigenous peoples to participate in and direct these research agendas ensures that their communal needs are met, and that geographers then learn how to build ethical research relationships with them. Indigenous methodologies do not privilege Indigenous researchers because of their Indigeneity, since there are many ‘insider’ views, and these are thus suitable for both Indigenous and non-Indigenous researchers. However, there is a difference between research done within an Indigenous context using Western methodologies and research done using Indig- enous methodologies which integrates Indigenous voices. This paper will discuss those differences while presenting a historical context of research on Indigenous peoples, providing further insights into what Indigenous methodologies entail, and proposing ways in which the academy can create space for this discourse

Comparable Ascertainment of Newly-Diagnosed Atrial Fibrillation Using Active Cohort Follow-Up versus Surveillance of Centers for Medicare and Medicaid Services in the Atherosclerosis Risk in Communities Study

Increasingly, epidemiologic studies use administrative data to identify atrial fibrillation (AF). Capture of incident AF is not well documented. We examined incidence rates and concordance of AF diagnosis based on active cohort follow-up versus surveillance of Centers for Medicare and Medicaid Services data in the Atherosclerosis Risk in Communities study

Multifactorial falls prevention programme compared with usual care in UK care homes for older people: Multicentre cluster randomised controlled trial with economic evaluation

Objectives: To determine the clinical and cost effectiveness of a multifactorial fall prevention programme compared with usual care in long term care homes. Design: Multicentre, parallel, cluster randomised controlled trial. Setting: Long term care homes in the UK, registered to care for older people or those with dementia. Participants: 1657 consenting residents and 84 care homes. 39 were randomised to the intervention group and 45 were randomised to usual care. Interventions: Guide to Action for Care Homes (GtACH): a multifactorial fall prevention programme or usual care. Main outcome measures: Primary outcome measure was fall rate at 91-180 days after randomisation. The economic evaluation measured health related quality of life using quality adjusted life years (QALYs) derived from the five domain five level version of the EuroQoL index (EQ-5D-5L) or proxy version (EQ-5D-5L-P) and the Dementia Quality of Life utility measure (DEMQOL-U), which were self-completed by competent residents and by a care home staff member proxy (DEMQOL-P-U) for all residents (in case the ability to complete changed during the study) until 12 months after randomisation. Secondary outcome measures were falls at 1-90, 181-270, and 271-360 days after randomisation, Barthel index score, and the Physical Activity Measure-Residential Care Homes (PAM-RC) score at 91, 180, 270, and 360 days after randomisation. Results: Mean age of residents was 85 years. 32% were men. GtACH training was delivered to 1051/1480 staff (71%). Primary outcome data were available for 630 participants in the GtACH group and 712 in the usual care group. The unadjusted incidence rate ratio for falls between 91 and 180 days was 0.57 (95% confidence interval 0.45 to 0.71, P<0.001) in favour of the GtACH programme (GtACH: six falls/1000 residents v usual care: 10 falls/1000). Barthel activities of daily living indices and PAM-RC scores were similar between groups at all time points. The incremental cost was £108 (95% confidence interval −£271.06 to 487.58), incremental QALYs gained for EQ-5D-5L-P was 0.024 (95% confidence interval 0.004 to 0.044) and for DEMQOL-P-U was 0.005 (−0.019 to 0.03). The incremental costs per EQ-5D-5L-P and DEMQOL-P-U based QALY were £4544 and £20 889, respectively. Conclusions: The GtACH programme was associated with a reduction in fall rate and cost effectiveness, without a decrease in activity or increase in dependency. Trial registration: ISRCTN34353836

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy