Selective COX-2 inhibitors and risk of myocardial infarction

Selective inhibitors of cyclooxygenase- 2 ( COX- 2, ` coxibs') are highly effective anti-inflammatory and analgesic drugs that exert their action by preventing the formation of prostanoids. Recently some coxibs, which were designed to exploit the advantageous effects of non- steroidal anti-inflammatory drugs while evading their side effects, have been reported to increase the risk of myocardial infarction and atherothrombotic events. This has led to the withdrawal of rofecoxib from global markets, and warnings have been issued by drug authorities about similar events during the use of celecoxib or valdecoxib/ parecoxib, bringing about questions of an inherent atherothrombotic risk of all coxibs and consequences that should be drawn by health care professionals. These questions need to be addressed in light of the known effects of selective inhibition of COX- 2 on the cardiovascular system. Although COX- 2, in contrast to the cyclooxygenase-1 ( COX- 1) isoform, is regarded as an inducible enzyme that only has a role in pathophysiological processes like pain and inflammation, experimental and clinical studies have shown that COX- 2 is constitutively expressed in tissues like the kidney or vascular endothelium, where it executes important physiological functions. COX- 2- dependent formation of prostanoids not only results in the mediation of pain or inflammatory signals but also in the maintenance of vascular integrity. Especially prostacyclin ( PGI(2)), which exerts vasodilatory and antiplatelet properties, is formed to a significant extent by COX- 2, and its levels are reduced to less than half of normal when COX- 2 is inhibited. This review outlines the rationale for the development of selective COX- 2 inhibitors and the pathophysiological consequences of selective inhibition of COX- 2 with special regard to vasoactive prostaglandins. It describes coxibs that are currently available, evaluates the current knowledge on the risk of atherothrombotic events associated with their intake and critically discusses the consequences that should be drawn from these insights. Copyright (C) 2005 S. Karger AG, Basel

Mesoscopic Capacitance Oscillations

We examine oscillations as a function of Fermi energy in the capacitance of a mesoscopic cavity connected via a single quantum channel to a metallic contact and capacitively coupled to a back gate. The oscillations depend on the distribution of single levels in the cavity, the interaction strength and the transmission probability through the quantum channel. We use a Hartree-Fock approach to exclude self-interaction. The sample specific capacitance oscillations are in marked contrast to the charge relaxation resistance, which together with the capacitance defines the RC-time, and which for spin polarized electrons is quantized at half a resistance quantum. Both the capacitance oscillations and the quantized charge relaxation resistance are seen in a strikingly clear manner in a recent experiment.Comment: 9 pages, 2 figure

Application of computer-aided dispatch in law enforcement: An introductory planning guide

A set of planning guidelines for the application of computer-aided dispatching (CAD) to law enforcement is presented. Some essential characteristics and applications of CAD are outlined; the results of a survey of systems in the operational or planning phases are summarized. Requirements analysis, system concept design, implementation planning, and performance and cost modeling are described and demonstrated with numerous examples. Detailed descriptions of typical law enforcement CAD systems, and a list of vendor sources, are given in appendixes

Mass accretion rates of clusters of galaxies: CIRS and HeCS

We use a new spherical accretion recipe tested on N-body simulations to measure the observed mass accretion rate (MAR) of 129 clusters in the Cluster Infall Regions in the Sloan Digital Sky Survey (CIRS) and in the Hectospec Cluster Survey (HeCS). The observed clusters cover the redshift range of $0.01<z<0.30$ and the mass range of $\sim 10^{14}-10^{15} {h^{-1}~\rm{M_\odot}}$. Based on three-dimensional mass profiles of simulated clusters reaching beyond the virial radius, our recipe returns MARs that agree with MARs based on merger trees. We adopt this recipe to estimate the MAR of real clusters based on measurements of the mass profile out to $\sim 3R_{200}$. We use the caustic method to measure the mass profiles to these large radii. We demonstrate the validity of our estimates by applying the same approach to a set of mock redshift surveys of a sample of 2000 simulated clusters with a median mass of $M_{200}= 10^{14} {h^{-1}~\rm{M_{\odot}}}$ as well as a sample of 50 simulated clusters with a median mass of $M_{200}= 10^{15} {h^{-1}~\rm{M_{\odot}}}$: the median MARs based on the caustic mass profiles of the simulated clusters are unbiased and agree within $19\%$ with the median MARs based on the real mass profile of the clusters. The MAR of the CIRS and HeCS clusters increases with the mass and the redshift of the accreting cluster, which is in excellent agreement with the growth of clusters in the $\Lambda$CDM model.Comment: 25 pages, 19 figures, 7 table

Experimental study of boundary layer transition on a heated flat plate

A detailed investigation to the document momentum and thermal development of boundary layers undergoing natural transition on a heated flat plate was performed. Experimental results of both overall and conditionally sampled characteristics of laminar, transitional, and low Reynolds number turbulent boundary layers are presented. Measurements were done in a low-speed, closed-loop wind tunnel with a freestream velocity of 100 ft/s and zero pressure gradient over a range of freestream turbulence intensities from 0.4 to 6 percent. The distributions of skin friction, heat transfer rate, and Reynolds shear stress were all consistent with previously published data. Reynolds analogy factors for momentum thickness Reynolds number, Re(sub theta) less than 2300 were found to be well predicted by laminar and turbulent correlations which accounted for an unheated starting length and uniform heat flux. A small dependence of turbulence results on the freestream turbulence intensity was observed

Crucial role of local peroxynitrite formation in neutrophil-induced endothelial cell activation

Introduction and methods: The reaction of superoxide anions and NO not only results in a decreased availability of NO, but also leads to the formation of peroxynitrite, the role of which in the cardiovascular system is still discussed controversially. In cultured human endothelial cells, we studied whether there is a significant interaction between endothelial NO and neutrophil-derived superoxide anions in terms of endothelial peroxynitrite formation. We particularly studied whether a significantly higher redox-stress can be found in those endothelial cells directly adjacent to an activated neutrophil. Results: A considerable part of the 2,7-dihydrodichlorofluoresceine signal in endothelial cells was due to oxidation by peroxynitrite. Providing superoxide radicals by enzymatic source or by the neutrophil respiratory burst increased the fluorescence, which was attenuated by blockade of endothelial NO-synthase, suggesting that peroxynitrite was formed from neutrophil- or extracellular enzyme-derived superoxide and endothelial NO. Considerably higher fluorescence intensity was observed in endothelial cells in direct neighborhood to a neutrophil. This was particularly pronounced in the presence of a NO-donor and was accompanied by a strong activation of NF-κB and increased expression of E-selectin in these cells. Conclusion: Endothelial cells adjacent to neutrophils may have elevated levels of peroxynitrite that result in an increased expression of adhesion molecules. Such cells might represent a preferential site for adhesion and migration of additional neutrophils when simultaneously high concentrations of NO and neutrophil-derived superoxide are present

Gentrification and Displacement in the San Francisco Bay Area: A Comparison of Measurement Approaches.

Gentrification may play an important role in influencing health outcomes, but few studies have examined these associations. One major barrier to producing empirical evidence to establish this link is that there is little consensus on how to measure gentrification. To address this barrier, we compared three gentrification classification methodologies in relation to their ability to identify neighborhood gentrification in nine San Francisco Bay Area counties: the Freeman method, the Landis method, and the Urban Displacement Project (UDP) Regional Early Warning System. In the 1580 census tracts, 43% of the population had a bachelor's degree or higher. The average median household income was $79,671 in 2013. A comparison of gentrification methodologies revealed that the Landis and Freeman methodologies characterized the vast majority of census tracts as stable, and only 5.2% and 6.1% of tracts as gentrifying. UDP characterized 46.7% of tracts at risk, undergoing, or experiencing advanced stages of gentrification and displacement. There was substantial variation in the geographic location of tracts identified as gentrifying across methods. Given the variation in characterizations of gentrification across measures, studies evaluating associations between gentrification and health should consider using multiple measures of gentrification to examine the robustness of the study findings across measures

Significance of low energy impact damage on modal parameters of composite beams by design of experiments

This paper presents an experimental study on the effects of multi-site damage on the vibration response of composite beams damaged by low energy impacts around the barely visible impact damage limit (BVID). The variation of the modal parameters with different levels of impact energy and density of damage is studied. Vibration tests have been carried out with both burst random and classical sine dwell excitations in order to compare that which of the methods among Polymax and Half Bandwidth Method is more suitable for damping estimation in the presence of damage. Design of experiments (DOE) performed on the experimental data show that natural frequency is a more sensitive parameter for damage detection than the damping ratio. It also highlighted energy of impact as the factor having a more significant effect on the modal parameters. Half Bandwidth Method is found to be unsuitable for damping estimation in the presence of damage

Turbulent heat flux measurements in a transitional boundary layer

During an experimental investigation of the transitional boundary layer over a heated flat plate, an unexpected result was encountered for the turbulent heat flux (bar-v't'). This quantity, representing the correlation between the fluctuating normal velocity and the temperature, was measured to be negative near the wall under certain conditions. The result was unexpected as it implied a counter-gradient heat transfer by the turbulent fluctuations. Possible reasons for this anomalous result were further investigated. The possible causes considered for this negative bar-v't' were: (1) plausible measurement error and peculiarity of the flow facility, (2) large probe size effect, (3) 'streaky structure' in the near wall boundary layer, and (4) contributions from other terms usually assumed negligible in the energy equation including the Reynolds heat flux in the streamwise direction (bar-u't'). Even though the energy balance has remained inconclusive, none of the items (1) to (3) appear to be contributing directly to the anomaly