Numerical integration rules with improved accuracy close to singularities

Sometimes it is necessary to obtain a numerical integration using only discretised data. In some cases, the data contains singularities which position is known but does not coincide with a discretisation point, and the jumps in the function and its derivatives are available at these positions. The motivation of this paper is to use the previous information to obtain numerical quadrature formulas that allow approximating the integral of the discrete data over certain intervals accurately. This work is devoted to the construction and analysis of a new nonlinear technique that allows to obtain accurate numerical integrations of any order using data that contains singularities, and when the integrand is only known at grid points. The novelty of the technique consists in the inclusion of correction terms with a closed expression that depends on the size of the jumps of the function and its derivatives at the singularities, that are supposed to be known. The addition of these terms allows recovering the accuracy of classical numerical integration formulas even close to the singularities, as these correction terms account for the error that the classical integration formulas commit up to their accuracy at smooth zones. Thus, the correction terms can be added during the integration or as post-processing, which is useful if the main calculation of the integral has been already done using classical formulas. The numerical experiments performed allow us to confirm the theoretical conclusions reached in this paper.Comment: 23 pages, 5 Figures, 3 Table

Dually sensitive dextran-based micelles for methotrexate delivery

Temperature-sensitive polymeric micelles were prepared from dextran grafted with poly(N-isopropylacrylamide) (PNIPAAm) or polyethylene glycol methyl ether (PEGMA) via controlled radical polymerization and evaluated as delivery systems of the anticancer drug methotrexate (MTX). Polymer-grafting was carried out after introduction of initiating groups onto the polysaccharide backbone, without the need for protection of hydroxyl groups and avoiding the use of toxic solvents. Temperature-responsive dextran-based copolymers were designed to exhibit self-aggregation behaviour, affinity for MTX and high cellular internalization. In addition, some grafted polymers incorporated 2-aminoethyl methacrylate to reinforce MTX encapsulation in the micelles by means of ionic interactions. Dextran-based micelles were cytocompatible and had an appropriate size to be used as drug carriers. MTX release was dependent on the pH and temperature. The combination of poly(2-aminoethylmethacrylate) and PNIPAAm with the dextran backbone permitted the complete release of MTX at normal physiological temperature. Co-polymer micelles were highly internalized by tumour cells (CHO-K1) and, when loaded with MTX, led to enhanced cytotoxicity compared to the free drug

"Assessment of effectiveness and security in high pressure postdilatation of bioresorbable vascular scaffolds during percutaneous coronary intervention. Study in a contemporary, non-selected cohort of Spanish patients"

OBJECTIVES: To determine security and benefits of high pressure postdilatation (HPP) of bioresorbable vascular scaffolds (BVS) in percutaneous coronary intervention (PCI) of complex lesions whatever its indication is. BACKGROUND: Acute scaffold disruption has been proposed as the main limitation of BVS when they are overexpanded. However, clinical implications of this disarray are not yet clear and more evidence is needed. METHODS: A total of 25 BVS were deployed during PCI of 14 complex lesions after mandatory predilatation. In all cases HPP was performed with NC balloon in a 1:1 relation to the artery. After that, optical coherence tomography (OCT) analyses were performed. RESULTS: Mean and maximal postdilatation pressure were 17±3.80 and 20 atmospheres (atm) respectively. Postdilatation balloon/scaffold diameter ratio was 1.01. A total of 39,590 struts were analyzed. Mean, minimal and maximal scaffold diameter were respectively: 3.09±0.34mm, 2.88±0.31mm and 3.31±0.40mm. Mean eccentricity index was 0.13±0.05. ISA percentage was 1.42% with a total of 564 malapposed struts. 89 struts were identified as disrupted, which represents a percentage of disrupted struts of 0.22%. At 30days, none of our patients died, suffered from stroke, stent thrombosis or needed target lesion revascularization (TLR). CONCLUSIONS: NC balloon HPP of BVS at more than 17atm (up to 20atm) is safe during PCI and allows to achieve better angiographic and clinical results

Non-productive angiogenesis disassembles Aß plaque-associated blood vessels

The human Alzheimer’s disease (AD) brain accumulates angiogenic markers but paradoxically, the cerebral microvasculature is reduced around Aß plaques. Here we demonstrate that angiogenesis is started near Aß plaques in both AD mouse models and human AD samples. However, endothelial cells express the molecular signature of non-productive angiogenesis (NPA) and accumulate, around Aß plaques, a tip cell marker and IB4 reactive vascular anomalies with reduced NOTCH activity. Notably, NPA induction by endothelial loss of presenilin, whose mutations cause familial AD and which activity has been shown to decrease with age, produced a similar vascular phenotype in the absence of Aß pathology. We also show that Aß plaque-associated NPA locally disassembles blood vessels, leaving behind vascular scars, and that microglial phagocytosis contributes to the local loss of endothelial cells. These results define the role of NPA and microglia in local blood vessel disassembly and highlight the vascular component of presenilin loss of function in AD

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics