Mechanisms Underlying the Morning Increase in Platelet Aggregation: A Flow Cytometry Study

ObjectivesMechanisms underlying the morning increase in platelet aggregation produced by arising and assuming the upright posture were studied by examining 1) the expression on the platelet surface of activation-dependent markers; 2) platelet aggregation in whole blood; and 3) hematologic factors likely to influence aggregation.BackgroundThe morning increase in thrombotic cardiovascular events has been attributed, in part, to the morning surge in platelet aggregability, but its mechanisms are poorly understood.MethodsExpression of seven platelet surface antigens (including P-selectin, activated GPIIb-IIIa and GPIb-IX), whole-blood platelet aggregation, platelet count and hematocrit were measured before and after arising in 17 normal volunteers. The fibrinolytic variables, tissue-type plasminogen activator, plasminogen activator inhibitor 1 and catecholamine levels were also measured.ResultsOn arising and standing, platelet aggregation increased by 71% (p ≤ 0.01) and 27% (p ≤ 0.03) in response to collagen and adenosine diphosphate, respectively. However, there was no change in any of the activation-dependent platelet surface markers. Whole-blood platelet count and hematocrit increased by 15% and 7% (both p < 0.0001), respectively. Norepinephrine and epinephrine levels increased by 189% (p < 0.0001) and 130% (p < 0.01), respectively. Tissue-type plasminogen activator antigen increased (31%, p < 0.01), but there was no significant increase in plasminogen activator inhibitor 1, suggesting an overall increase in fibrinolysis on standing. Prothrombin fragment 1.2 increased by 28% (p < 0.02), indicating a small increase in thrombin generation. The increases in hematocrit and platelet count that occurred on standing were carefully mimicked in vitro and resulted in a 115% (p < 0.05) increase in platelet aggregation in response to adenosine diphosphate.ConclusionsThese data demonstrate that the morning increase in platelet aggregation is not accompanied by expression of activation-dependent platelet surface receptors and suggest that the increase in whole-blood aggregation may be primarily due to the increases in catecholamine levels, platelet count and hemocon-centration

Contemporary Tendencies in Mediation

Editors: Humberto dalla Bernardina de Pinho, Juliana Loss de AndradePresentation / Humberto Dalla Bernardina de Pinho, Juliana Loss de Andrade. -- Mediation in England / Neil Andrews. -- Un Reto para la Mediación: el Diseño de su Código Deontológico / Nuria Belloso Martín. -- Alternative Dispute Resolution and Aboriginal-Crown Reconciliation in Canada / Roshan Danesh, Jessica Dickson. -- A False ‘Prince Charming’ Keeps ‘Sleeping Beauty’ in a Coma: On Voluntary Mediation Being the True Oxymoron of Dispute Resolution Policy / Giuseppe De Palo. -- Programa de Derivación Judicial en Puerto Rico Desde la Perspectiva de la Mediación / Jacqueline N. Font-Guzmán. -- Mediation in Switzerland / Isabelle Hering. -- Reconocimiento y eficacia de los acuerdos de mediación mercantil internacional / Juliana Loss de Andrade. -- The Uses of Mediation / Lela P. Love, Joseph B. Stulberg. -- Multi-Dimensional Mediation / Paul E. Mason. -- “Italy Is Doing It – Should We Be?” Civil and Commercial Mediation in Italy / Giovanni Matteucci. -- Limites dos Meios Alternativos de Conflito / José Marinho Paulo Junior. -- New Perspectives of Civil and Commercial Mediation in Brazil / Humberto Dalla Bernardina de Pinho. -- Practical Impacts of Theoretical Lenses / Elton Simoes, Andrea Maia. -- Development and Resistance in South Europe Justice Systems to Restorative Justice / Helena Soleto Muño

Caustic Formation in Tachyon Effective Field Theories

Certain configurations of D-branes, for example wrong dimensional branes or the brane-antibrane system, are unstable to decay. This instability is described by the appearance of a tachyonic mode in the spectrum of open strings ending on the brane(s). The decay of these unstable systems is described by the rolling of the tachyon field from the unstable maximum to the minimum of its potential. We analytically study the dynamics of the inhomogeneous tachyon field as it rolls towards the true vacuum of the theory in the context of several different tachyon effective actions. We find that the vacuum dynamics of these theories is remarkably similar and in particular we show that in all cases the tachyon field forms caustics where second and higher derivatives of the field blow up. The formation of caustics signals a pathology in the evolution since each of the effective actions considered is not reliable in the vicinity of a caustic. We speculate that the formation of caustics is an artifact of truncating the tachyon action, which should contain all orders of derivatives acting on the field, to a finite number of derivatives. Finally, we consider inhomogeneous solutions in p-adic string theory, a toy model of the bosonic tachyon which contains derivatives of all orders acting on the field. For a large class of initial conditions we conclusively show that the evolution is well behaved in this case. It is unclear if these caustics are a genuine prediction of string theory or not.Comment: 23 pages, 5 figures; accepted for publication in JHEP. Revised derivation of eikonal equation for the DBI action. Added comments concerning the relationship between p-adic string theory and tachyon matter. Added second example of inhomogeneous evolution in p-adic string theory. Misleading statements concerning caustic-free evolution removed, references adde

The Late Stages of Protoplanetary Disk Evolution: A Millimeter Survey of Upper Scorpius

We present deep 1.2 millimeter photometry of 37 stars in the young (5 Myr) Upper Scorpius OB association, sensitive to ~4 x 10^-3 Mjup of cool millimeter dust. Disks around four low- and solar-mass stars are detected, as well as one debris disk around an intermediate mass star, with dust masses ranging from 3.6 x 10^-3 -- 1.0 x 10^-1 Mjup. The source with the most massive disk exhibits a transition-disk spectral energy distribution. Combining our results with previous studies, we find the millimeter-detection fraction of Class II sources has significantly decreased from younger ages, and comparison with near-infrared and Halpha measurements indicates the present disks have undergone significant evolution in composition or structure at all radii. The disks of Upper Scorpius represent the tail-end of the depletion of primordial disks; while a few near-solar mass stars may still sustain giant planet formation, this process has finished around higher mass starsComment: Accepted by ApJ. 8 pages, 5 figures, 4 table

Smc5/6 coordinates formation and resolution of joint molecules with chromosome morphology to ensure meiotic divisions

During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and the regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of a subset of joint-molecule intermediates. In this regard, Smc5/6 functions independently of the major crossover pathway defined by the MutLγ complex. Furthermore, we show that Smc5/6 is required for stable chromosomal localization of the XPF-family endonuclease, Mus81-Mms4Eme1. Our data suggest that the Smc5/6 complex is required for specific recombination and chromosomal processes throughout meiosis and that in its absence, attempts at cell division with unresolved joint molecules and residual cohesin lead to severe recombination-induced meiotic catastroph

IL-21 conditions antigen-presenting human γδ T-cells to promote IL-10 expression in naïve and memory CD4+ T-cells

Direct interaction between T-cells exerts a major influence on tissue immunity and inflammation across multiple body sites including the human gut, which is highly enriched in ‘unconventional’ lymphocytes such as γδ T-cells. We previously reported that microbial activation of human Vγ9/Vδ2+ γδ T-cells in the presence of the mucosal damage-associated cytokine IL-15 confers the ability to promote epithelial barrier defence, specifically via induction of IL-22 expression in conventional CD4+ T-cells. In the current report, we assessed whether other cytokines enriched in the gut milieu also functionally influence microbe-responsive Vγ9/Vδ2 T-cells. When cultured in the presence of IL-21, Vγ9/Vδ2 T-cells acquired the ability to induce expression of the immunoregulatory cytokine IL-10 in both naïve and memory CD4+ T-cells, at levels surpassing those induced by monocytes or monocyte-derived DCs. These findings identify an unexpected influence of IL-21 on Vγ9/Vδ2 T-cell modulation of CD4+ T-cell responses. Further analyses suggested a possible role for CD30L and/or CD40L reverse signalling in mediating IL-10 induction by IL-21 conditioned Vγ9/Vδ2 T-cells. Our findings indicate that the local microenvironment exerts a profound influence on Vγ9/Vδ2 T-cell responses to microbial challenge, leading to induction of distinct functional profiles among CD4+ T-cells that may influence inflammatory events at mucosal surfaces. Targeting these novel pathways may offer therapeutic benefit in disorders such as inflammatory bowel disease

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Evaluation of the performance of five diagnostic tests for Fasciola hepatica infection in naturally infected cattle using a Bayesian no gold standard approach

The clinical and economic importance of fasciolosis has been recognised for centuries, yet diagnostic tests available for cattle are far from perfect. Test evaluation has mainly been carried out using gold standard approaches or under experimental settings, the limitations of which are well known. In this study, a Bayesian no gold standard approach was used to estimate the diagnostic sensitivity and specificity of five tests for fasciolosis in cattle. These included detailed liver necropsy including gall bladder egg count, faecal egg counting, a commercially available copro-antigen ELISA, an in-house serum excretory/secretory antibody ELISA and routine abattoir liver inspection. In total 619 cattle slaughtered at one of Scotland’s biggest abattoirs were sampled, during three sampling periods spanning summer 2013, winter 2014 and autumn 2014. Test sensitivities and specificities were estimated using an extension of the Hui Walter no gold standard model, where estimates were allowed to vary between seasons if tests were a priori believed to perform differently for any reason. The results of this analysis provide novel information on the performance of these tests in a naturally infected cattle population and at different times of the year where different levels of acute or chronic infection are expected. Accurate estimates of sensitivity and specificity will allow for routine abattoir liver inspection to be used as a tool for monitoring the epidemiology of F. hepatica as well as evaluating herd health planning. Furthermore, the results provide evidence to suggest that the copro-antigen ELISA does not cross-react with Calicophoron daubneyi rumen fluke parasites, while the serum antibody ELISA does

Veterinary students' usage and perception of video teaching resources

<p>Abstract</p> <p>Background</p> <p>The purpose of our study was to use a student-centred approach to develop an online video learning resource (called 'Moo Tube') at the School of Veterinary Medicine and Science, University of Nottingham, UK and also to provide guidance for other academics in the School wishing to develop a similar resource in the future.</p> <p>Methods</p> <p>A focus group in the format of the nominal group technique was used to garner the opinions of 12 undergraduate students (3 from year-1, 4 from year-2 and 5 from year-3). Students generated lists of items in response to key questions, these responses were thematically analysed to generate key themes which were compared between the different year groups. The number of visits to 'Moo Tube' before and after an objective structured practical examination (OSPE) was also analysed to provide data on video usage.</p> <p>Results</p> <p>Students highlighted a number of strengths of video resources which can be grouped into four overarching themes: (1) teaching enhancement, (2) accessibility, (3) technical quality and (4) video content. Of these themes, students rated teaching enhancement and accessibility most highly. Video usage was seen to significantly increase (P < 0.05) prior to an examination and significantly decrease (P < 0.05) following the examination.</p> <p>Conclusions</p> <p>The students had a positive perception of video usage in higher education. Video usage increases prior to practical examinations. Image quality was a greater concern with year-3 students than with either year-1 or 2 students but all groups highlighted the following as important issues: i) good sound quality, ii) accessibility, including location of videos within electronic libraries, and iii) video content. Based on the findings from this study, guidelines are suggested for those developing undergraduate veterinary videos. We believe that many aspects of our list will have resonance in other areas of medicine education and higher education.</p