Metabolism of ticagrelor in patients with acute coronary syndromes.

© The Author(s) 2018Ticagrelor is a state-of-the-art antiplatelet agent used for the treatment of patients with acute coronary syndromes (ACS). Unlike remaining oral P2Y12 receptor inhibitors ticagrelor does not require metabolic activation to exert its antiplatelet action. Still, ticagrelor is extensively metabolized by hepatic CYP3A enzymes, and AR-C124910XX is its only active metabolite. A post hoc analysis of patient-level (n = 117) pharmacokinetic data pooled from two prospective studies was performed to identify clinical characteristics affecting the degree of AR-C124910XX formation during the first six hours after 180 mg ticagrelor loading dose in the setting of ACS. Both linear and multiple regression analyses indicated that ACS patients presenting with ST-elevation myocardial infarction or suffering from diabetes mellitus are more likely to have decreased rate of ticagrelor metabolism during the acute phase of ACS. Administration of morphine during ACS was found to negatively influence transformation of ticagrelor into AR-C124910XX when assessed with linear regression analysis, but not with multiple regression analysis. On the other hand, smoking appears to increase the degree of ticagrelor transformation in ACS patients. Mechanisms underlying our findings and their clinical significance warrant further research.Peer reviewedFinal Published versio

Shape Synthesis in Mechanical Design

The shaping of structural elements in the area of mechanical design is a recurrent problem. The mechanical designer, as a rule, chooses what is believed to be the “simplest” shapes, such as the geometric primitives: lines, circles and, occasionally, conics. The use of higher-order curves is usually not even considered, not to speak of other curves than polynomials. However, the simplest geometric shapes are not necessarily the most suitable when the designed element must withstand loads that can lead to failure-prone stress concentrations. Indeed, as mechanical designers have known for a while, stress concentrations occur, first and foremost, by virtue of either dramatic changes in curvature or extremely high values thereof. As an alternative, we propose here the use of smooth curves that can be simply generated using standard concepts such as non-parametric cubic splines. These curves can be readily used to produce either extruded surfaces or surfaces of revolution.

Legal considerations for using digital twins in additive manufacture a review of the literature

Rapid technological change presents new opportunities and reveals new risks, challenging existing governance arrangements. The fusion of Industry 4.0 technologies combines with Additive Manufacturing (AM) to create new business solutions. Legal issues with AM are well documented, for example Daly[1] explores the interaction of 3D printing with the law, identifying Intellectual Property, Product Liability and Data Privacy as areas of importance. However, this technology fusion has also enabled improved real-time digital representation, monitoring, simulation and control of the physical delivered through applications of Digital Twin. Such Digital Twins are prevalent in manufacturing and in AM can potentially provide assurance that a printed item meets specified requirements. However, additional legal considerations are emerging. This paper illustrates these by examining the attributes of "Digital Twins in Additive Manufacture Use Cases" revealed through literature

Gambaran Histopatologi Lambung Tikus Wistar Yang Diberi Cabe Rawit (Capsicum Frutescens)

Background: Capsaicin is one of the active substantial that can be found in Chili pepper and one of the irritant for mammal that causing the burning sensation. The discomfort sensation in the gastric by capsaicin can be caused because the Transient receptor potential vanilloid-1 that can be found in gastric is stimulated.Objective: To demonstrate the gastric that was administered with Chili pepper.Method: The study conducted on Integrated Research Laboratory Faculty of Medicine Sam Ratulangi University Manado from October 2012 to January 2013. The study used 17 wistars, which divided to 5 groups and last to 7 days. This study was using Chili pepper in 45mg, 90mg, 135mg, and 180mg to study the histological changes of wistar rat's gastric.Results: The result showed that the administration of 180mg dose of Chili pepper did not cause a meaningful damage. The administration in 90mg of Chili pepper did cause a great damage with many inflammation signs occurring.Conclusions: The administration of Chili pepper in little to moderate dose causing a greater damage than the administration of Chili pepper in high dose

Comparative bactericidal activities of daptomycin, glycopeptides, linezolid and tigecycline against blood isolates of Gram-positive bacteria in Taiwan

ABSTRACTIn-vitro MICs and minimum bactericidal concentrations (MBCs) of daptomycin, linezolid, tigecycline, vancomycin and teicoplanin against Gram-positive bacteria were determined using the broth microdilution method for ten blood isolates each of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), including two vancomycin-intermediate S. aureus (VISA), vancomycin-resistant Enterococcus faecium and Enterococcus faecalis. One strain of VISA was tested in a time-kill synergism assay of daptomycin combined with oxacillin, imipenem, rifampicin and isepamicin. Daptomycin showed excellent in-vitro bactericidal activity against all the isolates tested, with no tolerance or synergism effects when combined with other agents, except with rifampicin against VISA. Vancomycin had better bactericidal activity against MRSA and MSSA than did teicoplanin. Linezolid had the poorest bactericidal activity against the isolates tested, with 100% tolerance by the MSSA and VRE isolates, and 80% tolerance by the MRSA isolates. Tolerance towards tigecycline was exhibited by 40% of the MRSA isolates, 100% of the MSSA and vancomycin-resistant E. faecalis isolates, and 90% of the vancomycin-resistant E. faecium isolates

A New Viscosity Equation For Bin Aqueous Solutions.

An equation for the viscosity of binary aqueous solutions has been derived based on the Power law equation and Erying's absolute rate theory. The concentration dependent equation for viscosities of binary aqueous systems is derived using additive contribution from water and solute component. The equation has sufficient degree of freedom to represent the' whole range of concentration. The equation has been applied to 12 nonelectrolyte aqueous systems and 10 electrolyte systems at various temperatures. An average absolute deviation percentage error' (AAD%) of 0.2856% is reported for electrolyte systems: For non-electrolyte systems an average AAD% of 0.7843% is reported. Overall, the equation is found to have yielded an AAD% of 0.5576%

Famine Early Warning Systems Network (FEWS NET) Land Data Assimilation System (LDAS) and Other Assimilated Hydrological Data at NASA GES DISC

The NASA Goddard Earth Sciences Data and Information Services Center (GES DISC) provides science support for several data sets relevant to agriculture and food security, including the Famine Early Warning Systems Network (FEWS NET) Land Data Assimilation System (LDAS), or FLDAS data set. The GES DISC is one of twelve NASA Earth Observing System (EOS) data centers that process, archive, document, and distribute data from Earth science missions and related projects. The GES DISC hosts a wide range of remote sensing and model data, and provides reliable and robust data access and other services to users worldwide. Beyond data archive and access, the GES DISC offers many services to visualize and analyze the data. This presentation provides a summary of the hydrological data available at the GES DISC, along with an overview of related data services. Specifically, the FLDAS data set has been adapted to work with domains, data streams, and monitoring and forecast requirements associated with food security assessment in data-sparse, developing country settings. The FLDAS global monthly data have a 0.1 x 0.1 degree spatial resolution covering the period from January 1982 to present. Global FLDAS monthly anomaly and monthly climatology data are also available at the GES DISC to evaluate how current conditions compare to averages over the FLDAS 35-year period. Several case studies using the FLDAS soil moisture, evapotranspiration, rainfall, runoff, and surface temperature data will be presented

Search for the Lepton-Number-Violating Decay Ξ−→pμ−μ−\Xi^- \to p \mu^- \mu^-

A sensitive search for the lepton-number-violating decay $\Xi^-\to p \mu^-\mu^-$ has been performed using a sample of $\sim10^9$ $\Xi^-$ hyperons produced in 800 GeV/$c$ $p$-Cu collisions. We obtain $\mathcal{B}(\Xi^-\to p \mu^-\mu^-)< 4.0\times 10^{-8}$ at 90% confidence, improving on the best previous limit by four orders of magnitude.Comment: 9 pages, 5 figures, to be published in Phys. Rev. Let