Identification of High Platelet Reactivity Despite ADP P2Y12 Inhibitor Treatment: Two Populations in the Vasodilator-Stimulated Phosphoprotein Assay and Variable PFA-P2Y Shapes of Curve.

Introduction Response to ADP P2Y <sub>12</sub> receptor inhibition by clopidogrel can be evaluated by various techniques. Here, we compared a functional rapid point-of-care technique (PFA-P2Y) with the degree of biochemical inhibition assessed by the VASP/P2Y <sub>12</sub> assay. Methods Platelet response to clopidogrel was investigated in 173 patients undergoing elective intracerebral stenting (derivation cohort n = 117; validation cohort n = 56). High platelet reactivity (HPR) was defined as PFA-P2Y occlusion time <106 seconds or VASP/P2Y <sub>12</sub> platelet reactivity index (PRI) >50%. Results In the derivation cohort, receiver operator characteristics analysis for the ability of PFA-P2Y to detect biochemical HPR showed high specificity (98.4%) but poor sensitivity (20.0%) and a very low area under the curve (0.59). The VASP/P2Y <sub>12</sub> assay revealed two coexisting platelet populations with different levels of vasodilator-stimulated phosphoprotein (VASP) phosphorylation: a fraction of highly phosphorylated, inhibited platelets and another of poorly phosphorylated, reactive platelets. Analysis of the PFA-P2Y curve shape revealed different types, categorized by time of occlusion (<106 seconds, 106 to 300 seconds, >300 seconds), and pattern (regular, irregular, and atypical). Noteworthy, curves with late occlusion and permeable curves with an irregular or atypical pattern correlated with VASP-PRI >50% and smaller sizes of the inhibited platelet subpopulation. Considering the PFA-P2Y shape of the curve for the detection of HPR improved sensitivity (72.7%) and preserved specificity (91.9%), with a rather high AUC (0.823). The validation cohort confirmed the VASP/P2Y <sub>12</sub> assay data and the usefulness of considering the PFA-P2Y curve shape. Conclusion In patients treated with acetylsalicylic acid and clopidogrel for 7-10 days, the VASP/P2Y <sub>12</sub> assay reveals two coexisting subpopulations of differentially inhibited platelets, whose relative sizes predict global PRI and distinct PFA-P2Y curve patterns, indicating incomplete clopidogrel efficacy. The detailed analysis of both VASP/P2Y <sub>12</sub> and PFA-P2Y is necessary for optimal detection of HPR

Metabolic syndrome before puberty: Myth or reality?

Metabolic syndrome (MetS) is defined as a cluster of alterations related with insulin resistance (obesity, dyslipidemia, hypertension, and impaired glucose metabolism), which are associated with a higher risk of cardiovascular disease in adults. Several definitions have been proposed for older children and adolescents. However, no definitions have been made in accordance with pubertal status, and those in prepubertal state have not received attention enough, despite there are data suggesting the early presence of risk factors. The new insights concerning healthy and unhealthy metabolic status or the addition of novel metabolic risk biomarkers, may contribute to the knowledge about the development of MetS in children. This manuscript reviews the available evidence on MetS during childhood, focusing on the prepubertal period

Numerical model of the inhomogeneous scattering by the human lens

We present in this work a numerical model for characterizing the scattering properties of the human lens. After analyzing the scattering properties of two main scattering particles actually described in the literature through FEM (finite element method) simulations, we have modified a Monte Carlo''s bulk scattering algorithm for computing ray scattering in non-sequential ray tracing. We have implemented this ray scattering algorithm in a layered model of the human lens in order to calculate the scattering properties of the whole lens. We have tested our algorithm by simulating the classic experiment carried out by Van der Berg et al for measuring "in vitro" the angular distribution of forward scattered light by the human lens. The results show the ability of our model to simulate accurately the scattering properties of the human lens. (C) 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreemen

Estudio del Comportamiento en Fractura de Vainas de Combustible Nuclear fragilizadas por Hidruros

En este artículo se ha estudiado, mediante el ensayo de compresión diametral (RCT), el comportamiento mecánico y en rotura de vainas de combustible nuclear de ZIRLO TM hidruradas. El hidrógeno se introdujo en las muestras mediante carga catódica y se precipitó en forma de hidruros circunferenciales mediante un tratamiento térmico. Los ensayos de compresión diametral se realizaron para concentraciones de hidrógeno de 150 a 2000 ppm. Los resultados experimentales obtenidos muestran que este ensayo es particularmente útil para el estudio del comportamiento en fractura de las vainas. Con este fin, se desarrolló un modelo de elementos finitos en el que se implemento la teoría de la fisura cohesiva. Aplicando dicho modelo se ha logrado calcular la energía de fractura de las vainas de combustible nuclear en dirección circunferencial para los distintos contenidos de hidrógeno estudiados a partir de los registros experimentales carga-desplazamiento del ensay

Open-Ended Evolutionary Robotics: an Information Theoretic Approach

This paper is concerned with designing self-driven fitness functions for Embedded Evolutionary Robotics. The proposed approach considers the entropy of the sensori-motor stream generated by the robot controller. This entropy is computed using unsupervised learning; its maximization, achieved by an on-board evolutionary algorithm, implements a "curiosity instinct", favouring controllers visiting many diverse sensori-motor states (sms). Further, the set of sms discovered by an individual can be transmitted to its offspring, making a cultural evolution mode possible. Cumulative entropy (computed from ancestors and current individual visits to the sms) defines another self-driven fitness; its optimization implements a "discovery instinct", as it favours controllers visiting new or rare sensori-motor states. Empirical results on the benchmark problems proposed by Lehman and Stanley (2008) comparatively demonstrate the merits of the approach

Characterization of Procoagulant COAT Platelets in Patients with Glanzmann Thrombasthenia.

Patients affected by the rare Glanzmann thrombasthenia (GT) suffer from defective or low levels of the platelet-associated glycoprotein (GP) IIb/IIIa, which acts as a fibrinogen receptor, and have therefore an impaired ability to aggregate platelets. Because the procoagulant activity is a dichotomous facet of platelet activation, diverging from the aggregation endpoint, we were interested in characterizing the ability to generate procoagulant platelets in GT patients. Therefore, we investigated, by flow cytometry analysis, platelet functions in three GT patients as well as their ability to generate procoagulant collagen-and-thrombin (COAT) platelets upon combined activation with convulxin-plus-thrombin. In addition, we further characterized intracellular ion fluxes during the procoagulant response, using specific probes to monitor by flow cytometry kinetics of cytosolic calcium, sodium, and potassium ion fluxes. GT patients generated higher percentages of procoagulant COAT platelets compared to healthy donors. Moreover, they were able to mobilize higher levels of cytosolic calcium following convulxin-plus-thrombin activation, which is congruent with the greater procoagulant activity. Further investigations will dissect the role of GPIIb/IIIa outside-in signalling possibly implicated in the regulation of platelet procoagulant activity

Illuminating shadows: introducing shadow interaction in spatial augmented reality

Computer Systems, Imagery and Medi

Estudios previos y redacción del proyecto de recuperación de la Playa de Poniente; T.M. de la Línea de la Concepción (Cádiz)

Entre 1992 y 1993, durante la construcción del Puerto de la Atunara por parte de la Consejería de Obras Publicas de la Junta de Andalucía, se aprovechó parte del dragado efectuado para crear una nueva playa en la parte de poniente (dentro de la Bahía de Algeciras) frente al casco urbano de la ciudad y satisfacer así una gran demanda existente. En aquella época, esa parte de costa caía dentro de la zona de competencia de la Autoridad Portuaria. Gracias a la colaboración prestada entre los distintos organismos(Puerto de Algeciras, Ayuntamiento de La Línea de la Concepción y Demarcación de Costas de Andalucía-Atlántico) pudo abordarse la ejecución de las obras, consistentes en la construcción de un espigón y el transporte y extendido de 132.000 m3 de arena. Una vez transcurridos 14 años desde entonces, se ha acometido este trabajo, en elque se ha estudiado por un lado el comportamiento de la playa durante este lapso de tiempo, y que por otro, ha permitido la redacción de un proyecto que posibilita el aprovechamiento de las obras ya contempladas por la Autoridad Portuaria para mejorar o ampliar la zona de servicio de la playa

Maternal Oral Bacterial Levels Predict Early Childhood Caries Development

Objective: To calculate the association of maternal salivary bacterial challenge (mutans streptococci [MS] and lactobacilli [LB]) from pregnancy through 24 months’ postpartum with child caries incidence (≥1 cavitated or restored teeth) at 36 months. Materials & Methods: Dental, salivary bacterial, sociodemographic, and behavioral measures were collected at three- to six-month intervals from a birth cohort of low-income Hispanic mother-child dyads (N = 243). We calculated the relative child caries incidence, adjusted for confounding, following higher maternal challenge of MS (>4500 colony-forming units per milliliter of saliva [CFU/mL]) and LB (>50 CFU/mL) based on multivariable models. Results: Salivary MS and LB levels were greater among mothers of caries-affected children versus caries-free children. Mothers with higher salivary MS challenge were more likely to have MS-positive children (>0 CFU/mL), but maternal LB challenge was not a statistically significant predictor of child LB-positive status. Adjusting for sociodemographics, feeding and care practices, and maternal dental status, higher maternal salivary challenge of both MS and LB over the study period predicted nearly double the child caries incidence versus lower MS and LB (cumulative incidence ratio: 1.9; 95% confidence interval: 1.1, 3.8). Conclusion: Maternal salivary bacterial challenge not only is associated with oral infection among children but also predicts increased early childhood caries occurrence