Stabilizing role of platelet P2Y(12) receptors in shear-dependent thrombus formation on ruptured plaques

Background: In most models of experimental thrombosis, healthy blood vessels are damaged. This results in the formation of a platelet thrombus that is stabilized by ADP signaling via P2Y(12) receptors. However, such models do not predict involvement of P2Y(12) in the clinically relevant situation of thrombosis upon rupture of atherosclerotic plaques. We investigated the role of P2Y(12) in thrombus formation on (collagen-containing) atherosclerotic plaques in vitro and in vivo, by using a novel mouse model of atherothrombosis. Methodology: Plaques in the carotid arteries from Apoe(-/-) mice were acutely ruptured by ultrasound treatment, and the thrombotic process was monitored via intravital fluorescence microscopy. Thrombus formation in vitro was assessed in mouse and human blood perfused over collagen or plaque material under variable conditions of shear rate and coagulation. Effects of two reversible P2Y(12) blockers, ticagrelor (AZD6140) and cangrelor (AR-C69931MX), were investigated. Principal Findings: Acute plaque rupture by ultrasound treatment provoked rapid formation of non-occlusive thrombi, which were smaller in size and unstable in the presence of P2Y(12) blockers. In vitro, when mouse or human blood was perfused over collagen or atherosclerotic plaque material, blockage or deficiency of P2Y(12) reduced the thrombi and increased embolization events. These P2Y(12) effects were present at shear rates >500 s(-1), and they persisted in the presence of coagulation. P2Y(12)-dependent thrombus stabilization was accompanied by increased fibrin(ogen) binding. Conclusions/Significance: Platelet P2Y(12) receptors play a crucial role in the stabilization of thrombi formed on atherosclerotic plaques. This P2Y(12) function is restricted to high shear flow conditions, and is preserved in the presence of coagulation

Evaluation of Phenotypic Carbapenemase Production in blaOXA-48 positive K. pneumoniae Isolates by Modified Hodge and Carbapenemase Inactivation Tests

Aim:In recent years, increasing colonization rates of K. pneumoniae in patients with immunosuppression, long hospital stay, invasive devices and treated with broad spectrum antibiotics lead to resistant infections. In this investigate, we aimed to investigate carbapenem resistance in multiresistant K. pneumoniae isolates derived from clinical specimens by phenotypic and genotypic methods.Materials and Methods:In July 2014, 51 K. pneumoniae isolates which were derived from clinical specimens were evaluated. Identification and antibiotic susceptibility tests of isolates were studied with automatized system. Verification of carbapenem resistance were studied with with gradient strip tests. Identification of carbapenemase resistant genes were studied with with “in house” PCR. Phenotypic tests including Modified Hodge test (MHT) and Carbapenemase Inactivation Method (CIM) were applied to all isolates. We re-studied all carbapenems for the isolates with incompatible results.Results:Resistance rates of all isolates to imipenem, meropenem and ertapenem were 78.43%, 60.78% and 96.08%, respectively. 42 of 51 isolates were positive with MHT and 43 of 51 isolates were positive with CIM. blaOXA-48 gene was identified in 42 isolates with PCR. nine isolates which were negative for blaOXA-48 and other carbapenemases gene were negative with MHT and eight isolates which were negative for blaOXA-48 gene were negative with CIM.Conclusion:MHT and CIM are fast and easy methods for the identification of carbapenemase presence. CIM is an easy screening test, but one should be cautious for false negative and positive results. We suggest that modification of the test with carbapenem discs should decrease false negative results

Low Q^2 measurements of the proton form factor ratio mupGE/GMmu_p G_E / G_M

We present an updated extraction of the proton electromagnetic form factor ratio, mu_p G_E/G_M, at low Q^2. The form factors are sensitive to the spatial distribution of the proton, and precise measurements can be used to constrain models of the proton. An improved selection of the elastic events and reduced background contributions yielded a small systematic reduction in the ratio mu_p G_E/G_M compared to the original analysis.Comment: 12 pages, 5 figures, archival paper for proton form factor extraction from Jefferson Lab "LEDEX" experimen

The Proton Elastic Form Factor Ratio at Low Momentum Transfer

High precision measurements of the proton elastic form factor ratio have been made at four-momentum transfers, Q^2, between 0.2 and 0.5 GeV^2. The new data, while consistent with previous results, clearly show a ratio less than unity and significant differences from the central values of several recent phenomenological fits. By combining the new form-factor ratio data with an existing cross-section measurement, one finds that in this Q^2 range the deviation from unity is primarily due to GEp being smaller than the dipole parameterization.Comment: 5 pages, 2 figure

Reconstruction of computer generated holograms by spatial light modulators

Computer generated holograms generated by using three different numerical techniques are reconstructed optically by spatial light modulators. Liquid crystal spatial light modulators (SLM) on transmission and on reflection modes with different resolutions were investigated. A good match between numerical simulation and optically reconstructed holograms on both SLMs was observed. The resolution of the optically reconstructed images was comparable to the resolution of the SLMs. © Springer-Verlag Berlin Heidelberg 2006

Collateral Circulation and Outcome in Atherosclerotic Versus Cardioembolic Cerebral Large Vessel Occlusion

Background and Purpose- Due to chronic hypoperfusion, cervical atherosclerosis may promote cerebral collateral circulation. We hypothesized that patients with ischemic stroke due to cervical carotid atherosclerosis have a more extensive collateral circulation and better outcomes than patients with cardioembolism. We tested this hypothesis in a population of patients who underwent endovascular treatment for large vessel occlusion. Methods- From the MR-CLEAN Registry (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), we selected consecutive adult endovascular treatment patients (March 2014 to June 2016) with acute ischemic stroke due to anterior circulation large vessel occlusion and compared patients with cervical carotid artery stenosis >50% to those with cardioembolic etiology. The primary outcome was collateral score, graded on a 4-point scale. Secondary outcomes included the modified Rankin Scale (mRS) score and mortality at 90 days. We performed multivariable regression analyses and adjusted for potential confounders. Results- Of 1627 patients in the Registry, 190 patients with cervical carotid atherosclerosis and 476 with cardioembolism were included. Patients with cervical carotid atherosclerosis were younger (median 69 versus 76 years, P<0.001), more often male (67% versus 47%, P<0.001), more often had an internal carotid artery terminus occlusion (33% versus 18%, P<0.001), and a lower prestroke mRS (mRS score, 0-2; 96% versus 85%, P<0.001), than patients with cardioembolism. Stroke due to cervical carotid atherosclerosis was associated with higher collateral score (adjusted common odds ratio, 1.67 [95% CI, 1.17-2.39]) and lower median mRS at 90 days (adjusted common odds ratio, 1.45 [95% CI, 1.03-2.05]) compared with cardioembolic stroke. There was no statistically significant difference in proportion of mRS 0-2 (aOR, 1.36 [95% CI, 0.90-2.07]) or mortality at 90 days (aOR, 0.80 [95% CI, 0.48-1.34]). Conclusions- Patients with stroke due to cervical carotid atherosclerosis had a more extensive cerebral collateral circulation and a slightly better median mRS at 90 days than patients with cardioembolic stroke

Prognostic value of gross tumor volume delineated by FDG-PET-CT based radiotherapy treatment planning in patients with locally advanced pancreatic cancer treated with chemoradiotherapy

<p>Abstract</p> <p>Background</p> <p>We aimed to assess whether gross tumor volume (GTV) determined by fusion of contrast-enhanced computerized tomography (CT) and 18F-fluoro-deoxy-D-glucose positron emission tomography-CT (FDG-PET-CT) based radiotherapy planning could predict outcomes, namely overall survival (OS), local-regional progression-free survival (LRPFS), and progression-free survival (PFS) in cases with locally advanced pancreas cancer (LAPC) treated with definitive concurrent chemoradiotherapy.</p> <p>Methods</p> <p>A total of 30 patients with histological proof of LAPC underwent 50.4 Gy (1.8 Gy/28 fractions) of radiotherapy concurrent with continuously infused 5-FU followed by 4 to 6 courses of maintenance gemcitabine. Target volume delineations were performed on FDG-PET-CT-based RTP. Patients were stratified into 2 groups: GTV lesser (GTV_L) versus greater (GTV_G) than cut off value determined by receiver operating characteristic (ROC) analysis, and compared in terms of OS, LRPFS and PFS.</p> <p>Results</p> <p>Median GTV delineated according to the FDG-PET-CT data was 100.0 cm³. Cut off GTV value determined from ROC curves was 91.1 cm³. At a median follow up of 11.2 months, median OS, LRPFS and PFS for the entire population were 10.3, 7.8 and 5.7 months, respectively. Median OS, LRPFS and PFS for GTV_Land GTV_Gcohorts were 16.3 vs. 9.5 (<it>p </it>= 0.005), 11.0 vs. 6.0 (<it>p </it>= 0.013), and 9.0 vs. 4.8 months (<it>p </it>= 0.008), respectively.</p> <p>Conclusions</p> <p>The superior OS, LRPFS and PFS observed in GTV_Lpatients over GTV_Gones suggests a potential for FDG-PET-CT-defined GTV size in predicting outcomes of LAPC patients treated with definitive C-CRT, which needs to be validated by further studies with larger cohorts.</p

Deafening silence? Marxism, international historical sociology and the spectre of Eurocentrism

Approaching the centenary of its establishment as a formal discipline, International Relations today challenges the ahistorical and aspatial frameworks advanced by the theories of earlier luminaries. Yet, despite a burgeoning body of literature built on the transdisciplinary efforts bridging International Relations and its long-separated nomothetic relatives, the new and emerging conceptual frameworks have not been able to effectively overcome the challenge posed by the ‘non-West’. The recent wave of international historical sociology has highlighted possible trajectories to problematise the myopic and unipolar conceptions of the international system; however, the question of Eurocentrism still lingers in the developing research programmes. This article interjects into the ongoing historical materialist debate in international historical sociology by: (1) conceptually and empirically challenging the rigid boundaries of the extant approaches; and (2) critically assessing the postulations of recent theorising on ‘the international’, capitalist states-system/geopolitics and uneven and combined development. While the significance of the present contributions in international historical sociology should not be understated, it is argued that the ‘Eurocentric cage’ still occupies a dominant ontological position which essentially silences ‘connected histories’ and conceals the role of inter-societal relations in the making of the modern states-system and capitalist geopolitics