Atherosclerosis of the ascending aorta is an independent predictor of long-term neurologic events and mortality

AbstractOBJECTIVESThis study was undertaken to determine whether atherosclerosis of the ascending aorta is a predictor of long-term neurologic events and mortality.BACKGROUNDAtherosclerosis of the thoracic aorta has been recently considered a significant predictor of neurologic events and peripheral embolism, but not of long-term mortality.METHODSLong-term follow-up (a total of 5,859 person-years) was conducted of 1,957 consecutive patients ≥50 years old who underwent cardiac surgery. Atherosclerosis of the ascending aorta was assessed intraoperatively (epiaortic ultrasound) and patients were divided into four groups according to severity (normal, mild, moderate or severe). Carotid artery disease was evaluated (carotid ultrasound) in 1,467 (75%) patients. Cox proportional-hazards regression analysis was performed to assess the independent effect of predictors on neurologic events and mortality.RESULTSA total of 491 events occurred in 472 patients (neurologic events 92, all-cause mortality 399). Independent predictors of long-term neurologic events were: hypertension (p = 0.009), ascending aorta atherosclerosis (p = 0.011) and diabetes mellitus (p = 0.015). The independent predictors of mortality were advanced age (p < 0.0001), left ventricular dysfunction (p < 0.0001), ascending aorta atherosclerosis (p < 0.0001), hypertension (p = 0.0001) and diabetes mellitus (p = 0.0002). There was >1.5-fold increase in the incidence of both neurologic events and mortality as the severity of atherosclerosis increased from normal-mild to moderate, and a greater than threefold increase in the incidence of both as the severity of atherosclerosis increased from normal-mild to severe.CONCLUSIONSAtherosclerosis of the ascending aorta is an independent predictor of long-term neurologic events and mortality. These results provide additional evidence that in addition to being a direct cause of cerebral atheroembolism, an atherosclerotic ascending aorta may be a marker of generalized atherosclerosis and thus of increased morbidity and mortality

Druse-Induced Morphology Evolution in Retinal Pigment Epithelium

The retinal pigment epithelium (RPE) is a key site of pathogenesis for many retina diseases. The formation of drusen in the retina is characteristic of retinal degeneration. We investigate morphological changes in the RPE in the presence of soft drusen using an integrated experimental and modeling approach. We collect RPE flat mount images from donated human eyes and develop 1) statistical tools to quantify the images and 2) a cell-based model to simulate the morphology evolution. We compare three different mechanisms of RPE repair evolution, cell apoptosis, cell fusion, and expansion, and Simulations of our RPE morphogenesis model quantitatively reproduce deformations of human RPE morphology due to drusen, suggesting that a purse-string mechanism is sufficient to explain how RPE heals cell loss caused by drusen-damage. We found that drusen beneath tissue promote cell death in a number that far exceeds the cell numbers covering the drusen. Tissue deformations are studied using area distributions, Voronoi domains and a texture tensor.Fil: Mazzitello, Karina Irma. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata; ArgentinaFil: Zhang, Qing. University of Emory; Estados UnidosFil: Chrenek, M. A.. University of Emory; Estados UnidosFil: Family, F.. University of Emory; Estados UnidosFil: Grossniklaus, H. E.. University of Emory; Estados UnidosFil: Nickerson, J. M.. University of Emory; Estados UnidosFil: Jiang, Y.. Georgia State University; Estados Unido

Three-dimensional organotypic co-culture model of intestinal epithelial cells and macrophages to study Salmonella enterica colonization patterns

Three-dimensional models of human intestinal epithelium mimic the differentiated form and function of parental tissues often not exhibited by two-dimensional monolayers and respond to Salmonella in key ways that reflect in vivo infections. To further enhance the physiological relevance of three-dimensional models to more closely approximate in vivo intestinal microenvironments encountered by Salmonella, we developed and validated a novel three-dimensional co-culture infection model of colonic epithelial cells and macrophages using the NASA Rotating Wall Vessel bioreactor. First, U937 cells were activated upon collagen-coated scaffolds. HT-29 epithelial cells were then added and the three-dimensional model was cultured in the bioreactor until optimal differentiation was reached, as assessed by immunohistochemical profiling and bead uptake assays. The new co-culture model exhibited in vivo-like structural and phenotypic characteristics, including three-dimensional architecture, apical-basolateral polarity, well-formed tight/adherens junctions, mucin, multiple epithelial cell types, and functional macrophages. Phagocytic activity of macrophages was confirmed by uptake of inert, bacteria-sized beads. Contribution of macrophages to infection was assessed by colonization studies of Salmonella pathovars with different host adaptations and disease phenotypes (Typhimurium ST19 strain SL1344 and ST313 strain D23580; Typhi Ty2). In addition, Salmonella were cultured aerobically or microaerobically, recapitulating environments encountered prior to and during intestinal infection, respectively. All Salmonella strains exhibited decreased colonization in co-culture (HT-29-U937) relative to epithelial (HT-29) models, indicating antimicrobial function of macrophages. Interestingly, D23580 exhibited enhanced replication/survival in both models following invasion. Pathovar-specific differences in colonization and intracellular co-localization patterns were observed. These findings emphasize the power of incorporating a series of related three-dimensional models within a study to identify microenvironmental factors important for regulating infection

Quantum error correction : an introductory guide

Quantum error correction protocols will play a central role in the realisation of quantum computing; the choice of error correction code will influence the full quantum computing stack, from the layout of qubits at the physical level to gate compilation strategies at the software level. As such, familiarity with quantum coding is an essential prerequisite for the understanding of current and future quantum computing architectures. In this review, we provide an introductory guide to the theory and implementation of quantum error correction codes. Where possible, fundamental concepts are described using the simplest examples of detection and correction codes, the working of which can be verified by hand. We outline the construction and operation of the surface code, the most widely pursued error correction protocol for experiment. Finally, we discuss issues that arise in the practical implementation of the surface code and other quantum error correction codes

Churn, Baby, Churn: Strategic Dynamics Among Dominant and Fringe Firms in a Segmented Industry

This paper integrates and extends the literatures on industry evolution and dominant firms to develop a dynamic theory of dominant and fringe competitive interaction in a segmented industry. It argues that a dominant firm, seeing contraction of growth in its current segment(s), enters new segments in which it can exploit its technological strengths, but that are sufficiently distant to avoid cannibalization. The dominant firm acts as a low-cost Stackelberg leader, driving down prices and triggering a sales takeoff in the new segment. We identify a “churn” effect associated with dominant firm entry: fringe firms that precede the dominant firm into the segment tend to exit the segment, while new fringe firms enter, causing a net increase in the number of firms in the segment. As the segment matures and sales decline in the segment, the process repeats itself. We examine the predictions of the theory with a study of price, quantity, entry, and exit across 24 product classes in the desktop laser printer industry from 1984 to 1996. Using descriptive statistics, hazard rate models, and panel data methods, we find empirical support for the theoretical predictions

The energy gap of intermediate-valent SmB6 studied by point-contact spectroscopy

We have investigated the intermediate valence narrow-gap semiconductor SmB6 at low temperatures using both conventional spear-anvil type point contacts as well as mechanically controllable break junctions. The zero-bias conductance varied between less than 0.01 mikrosiemens and up to 1 mS. The position of the spectral anomalies, which are related to the different activation energies and band gaps of SmB6, did not depend on the the contact size. Two different regimes of charge transport could be distinguished: Contacts with large zero - bias conductance are in the diffusive Maxwell regime. They had spectra with only small non-linearities. Contacts with small zero - bias conductance are in the tunnelling regime. They had larger anomalies, but still indicating a finite 45 % residual quasiparticle density of states at the Fermi level at low temperatures of T = 0.1 K. The density of states derived from the tunelling spectra can be decomposed into two energy-dependent parts with Eg = 21 meV and Ed = 4.5 meV wide gaps, respectively.Comment: 9 pages incl. 13 figure

Can disordered mobile phone use be considered a behavioral addiction? An update on current evidence and a comprehensive model for future research

Despite the many positive outcomes, excessive mobile phone use is now often associated with potentially harmful and/or disturbing behaviors (e.g., symptoms of deregulated use, negative impact on various aspects of daily life such as relationship problems, and work intrusion). Problematic mobile phone use (PMPU) has generally been considered as a behavioral addiction that shares many features with more established drug addictions. In light of the most recent data, the current paper reviews the validity of the behavioral addiction model when applied to PMPU. On the whole, it is argued that the evidence supporting PMPU as an addictive behavior is scarce. In particular, it lacks studies that definitively show behavioral and neurobiological similarities between mobile phone addiction and other types of legitimate addictive behaviors. Given this context, an integrative pathway model is proposed that aims to provide a theoretical framework to guide future research in the field of PMPU. This model highlights that PMPU is a heterogeneous and multi-faceted condition

Detection and Confirmation of Ractopamine and Its Metabolites in Horse Urine after Paylean® Administration

We have investigated the detection, confirmation, and metabolism of the beta-adrenergic agonist ractopamine administered as Paylean to the horse. A Testing Components Corporation enzyme-linked imunosorbent assay (ELISA) kit for ractopamine displayed linear response between 1.0 and 100 ng/ml, with an 1-50 of 10 ng/ml, and an effective screening limit of detection of 50 ng/mL. The kit was readily able to detect ractopamine equivalents in unhydrolyzed urine up to 24 h following a 300-mg oral dose. Gas chromatography-mass spectrometry (GC-MS) confirmation comprised glucuronidase treatment, solid-phase extraction, and trimethylsilyl derivatization, with selected-ion monitoring of ractopamine-tris(trimethylsilane) (TMS) m/z 267, 250, 179, and 502 ions. Quantitation was elaborated in comparison to a 445 Mw isoxsuprine-bis(TMS) internal standard monitored simultaneously. The instrumental limit of detection, defined as that number of ng on column for which signal-to-noise ratios for one or more diagnostic ions fell below a value of three, was 0.1 ng, corresponding to roughly 5 ng/mL in matrix. Based on the quantitation ions for ractopamine standards extracted from urine, standard curves showed a linear response for ractopamine concentrations between 10 and 100 ng/mL with a correlation coefficient r \u3e 0.99, whereas standards in the concentration range of 10-1000 ng/mL were fit to a second-order regression curve with r \u3e 0.99. The lower limit of detection for ractopamine in urine, defined as the lowest concentration at which the identity of ractopamine could be confirmed by comparison of diagnostic MS ion ratios, ranged between 25 and 50 ng/mL. Urine concentration of parent ractopamine 24 h post-dose was measured at 360 ng/mL by GC-MS after oral administration of 300 mg. Urinary metabolites were identified by electrospray ionization (+) tandem quadrupole mass spectrometry and were shown to include glucuronide, methyl, and mixed methyl-glucuronide conjugates. We also considered the possibility that an unusual conjugate added 113 amu to give an observed m/z 415 [M+H] species or two times 113 amu to give an m/z 528 [M+H] species with a daughter ion mass spectrum related to the previous one. Sulfate and mixed methyl-sulfate conjugates were revealed following glucuronidase treatment, suggesting that sulfation occurs in combination with glucuronidation. We noted a paired chromatographic peak phenomenon of apparent ractopamine metabolites appearing as doublets of equivalent intensity with nearly identical mass spectra on GC-MS and concluded that this phenomenon is consistent with Paylean being a mixture of RR, RS, SR, and SS diastereomers of ractopamine. The results suggest that ELISA-based screening followed by glucuronide hydrolysis, parent drug recovery, and TMS derivatization provide an effective pathway for detection and GC-MS confirmation of ractopamine in equine urine

A double-sided, shield-less stave prototype for the ATLAS upgrade strip tracker for the high luminosity LHC

A detailed description of the integration structures for the barrel region of the silicon strips tracker of the ATLAS Phase-II upgrade for the upgrade of the Large Hadron Collider, the so-called High Luminosity LHC (HL-LHC), is presented. This paper focuses on one of the latest demonstrator prototypes recently assembled, with numerous unique features. It consists of a shortened, shield-less, and double sided stave, with two candidate power distributions implemented. Thermal and electrical performances of the prototype are presented, as well as a description of the assembly procedures and tools

Detection of Potential Transit Signals in the First Three Quarters of Kepler Mission Data

We present the results of a search for potential transit signals in the first three quarters of photometry data acquired by the Kepler Mission. The targets of the search include 151,722 stars which were observed over the full interval and an additional 19,132 stars which were observed for only 1 or 2 quarters. From this set of targets we find a total of 5,392 detections which meet the Kepler detection criteria: those criteria are periodicity of the signal, an acceptable signal-to-noise ratio, and a composition test which rejects spurious detections which contain non-physical combinations of events. The detected signals are dominated by events with relatively low signal-to-noise ratio and by events with relatively short periods. The distribution of estimated transit depths appears to peak in the range between 40 and 100 parts per million, with a few detections down to fewer than 10 parts per million. The detected signals are compared to a set of known transit events in the Kepler field of view which were derived by a different method using a longer data interval; the comparison shows that the current search correctly identified 88.1% of the known events. A tabulation of the detected transit signals, examples which illustrate the analysis and detection process, a discussion of future plans and open, potentially fruitful, areas of further research are included