443 research outputs found

    Phosphodiesterase-5 inhibitors in management of pulmonary hypertension: safety, tolerability, and efficacy

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    Pulmonary arterial hypertension (PAH) is a progressive disease that causes severe disability and has no cure. Over the past 20 years, a variety of treatment options have evolved for the management of PAH. With an expanded therapeutic armamentarium come more complex decisions regarding treatment options. Agent selection depends upon several factors including efficacy, side effect profile, and cost, as well as convenience of administration. We have undertaken a review of phosphodiesterase-5 (PDE-5) inhibitors in PAH with a focus on efficacy and safety. A literature search was conducted using the Medline and Cochrane Central Register of Controlled Trials databases (1966–February 2010) for relevant randomized clinical studies. Overall, 10 studies met our inclusion criteria. Sildenafil was the most commonly studied agent, followed by tadalafil and vardenafil. Most trials found that the PDE-5 inhibitors significantly improved exercise capacity and lowered pulmonary pressures. However, there were conflicting results regarding these agents’ impact on improving cardiac function and functional class. Overall, these medications were effective and well tolerated with a relatively benign side effect profile. The PDE-5 inhibitors are an important option in treating PAH. While most of the published clinical data involved sildenafil, the other PDE-5 inhibitors show promise as well. Further studies are needed to determine the optimal doses of this therapeutic drug class, as well as its effects as adjunctive therapy with other agents in PAH

    Testing EUV/X-ray Atomic Data for the Solar Dynamics Observatory

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    The Atmospheric Imaging Assembly (AIA) and the Exteme-ultraviolet Variability Experiment (EVE) onboard the Solar Dynamics Observatory include spectral windows in the X-ray/EUV band. Accuracy and completeness of the atomic data in this wavelength range is essential for interpretation of the spectrum and irradiance of the solar corona, and of SDO observations made with the AIA and EVE instruments. Here we test the X-ray/EUV data in the CHIANTI database to assess their completeness and accuracy in the SDO bands, with particular focus on the 94A and 131A AIA passbands. Given the paucity of solar observations adequate for this purpose, we use high-resolution X-ray spectra of the low-activity solar-like corona of Procyon obtained with the Chandra Low Energy Transmission Grating Spectrometer (LETGS). We find that while spectral models overall can reproduce quite well the observed spectra in the soft X-ray range ll 130A, they significantly underestimate the observed flux in the 50-130A wavelength range. The model underestimates the observed flux by a variable factor ranging from \approx 1.5, at short wavelengths below \sim50A, up to \approx5-7 in the \sim 70-125A range. In the AIA bands covered by LETGS, i.e. 94A and 131A, we find that the observed flux can be underestimated by large factors (\sim 3 and \sim 1.9 respectively, for the case of Procyon presented here). We discuss the consequences for analysis of AIA data and possible empirical corrections to the AIA responses to model more realistically the coronal emission in these passbands.Comment: 11 pages, 9 figures, accepted for publication on Ap

    Development and Validation of a Novel Diagnostic Test for Human Brucellosis Using a Glyco-engineered Antigen Coupled to Magnetic Beads.

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    Brucellosis is a highly contagious zoonosis and still a major human health problem in endemic areas of the world. Although several diagnostic tools are available, most of them are difficult to implement especially in developing countries where complex health facilities are limited. Taking advantage of the identical structure and composition of the Brucella spp. and Yersinia enterocolitica O:9 O-polysaccharide, we explored the application of a recombinant Y. enterocolitica O:9-polysaccharide-protein conjugate (OAg-AcrA) as a novel antigen for diagnosis of human brucellosis. We have developed and validated an indirect immunoassay using OAg-AcrA coupled to magnetic beads. OAg-AcrA was produced and purified with high yields in Y. enterocolitica O:9 cells co-expressing the oligosaccharyltransferase PglB and the protein acceptor AcrA of Campylobacter jejuni without the need for culturing Brucella. Expression of PglB and AcrA in Y. enterocolitica resulted in the transfer of the host O-polysaccharide from its lipid carrier to AcrA. To validate the assay and determine the cutoff values a receiver-operating characteristic analysis was performed using a panel of characterized serum samples obtained from healthy individuals and patients of different clinical groups. Our results indicate that, using this assay, it is possible to detect infection caused by the three main human brucellosis agents (B. abortus, B. melitensis and B. suis) and select different cutoff points to adjust sensitivity and specificity levels as needed. A cutoff value of 13.20% gave a sensitivity of 100% and a specificity of 98.57%, and a cutoff value of 16.15% resulted in a test sensitivity and specificity of 93.48% and 100%, respectively. The high diagnostic accuracy, low cost, reduced assay time and simplicity of this new glycoconjugate-magnetic beads assay makes it an attractive diagnostic tool for using not only in clinics and brucellosis reference laboratories but also in locations with limited laboratory infrastructure and/or minimally trained community health workers.Fil: Ciocchini, Andres Eduardo. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús (San Martin); Argentina;Fil: Rey Serantes, Diego A.. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús (San Martin); Argentina;Fil: Melli, Luciano Jorge. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús (San Martin); Argentina;Fil: Iwashkiw, Jeremy A.. University of Alberta . Department of Biological Sciences . Alberta Glycomics Centre; Estados Unidos de América;Fil: Deodato, Bettina. Hospital Múñiz. Unidad de Enfermedades Infecciosas; Argentina;Fil: Wallach, Jorge. Hospital Múñiz. Unidad de Enfermedades Infecciosas; Argentina;Fil: Feldman, Mario F. University of Alberta . Department of Biological Sciences . Alberta Glycomics Centre; Estados Unidos de América;Fil: Ugalde, Juan E. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús (San Martin); Argentina;Fil: Comerci, Diego J. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús (San Martin); Argentina

    The "Solar Model Problem" Solved by the Abundance of Neon in Stars of the Local Cosmos

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    The interior structure of the Sun can be studied with great accuracy using observations of its oscillations, similar to seismology of the Earth. Precise agreement between helioseismological measurements and predictions of theoretical solar models has been a triumph of modern astrophysics (Bahcall et al. 2005). However, a recent downward revision by 25-35% of the solar abundances of light elements such as C, N, O and Ne (Asplund et al. 2004) has broken this accordance: models adopting the new abundances incorrectly predict the depth of the convection zone, the depth profiles of sound speed and density, and the helium abundance (Basu Antia 2004, Bahcall et al. 2005). The discrepancies are far beyond the uncertainties in either the data or the model predictions (Bahcall et al. 2005b). Here we report on neon abundances relative to oxygen measured in a sample of nearby solar-like stars from their X-ray spectra. They are all very similar and substantially larger than the recently revised solar value. The neon abundance in the Sun is quite poorly determined. If the Ne/O abundance in these stars is adopted for the Sun the models are brought back into agreement with helioseismology measurements (Antia Basu 2005, Bahcall et al. 2005c).Comment: 13 pages, 3 Figure

    SWIM: A Semi-Analytical Ocean Color Inversion Algorithm for Optically Shallow Waters

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    Ocean color remote sensing provides synoptic-scale, near-daily observations of marine inherent optical properties (IOPs). Whilst contemporary ocean color algorithms are known to perform well in deep oceanic waters, they have difficulty operating in optically clear, shallow marine environments where light reflected from the seafloor contributes to the water-leaving radiance. The effect of benthic reflectance in optically shallow waters is known to adversely affect algorithms developed for optically deep waters [1, 2]. Whilst adapted versions of optically deep ocean color algorithms have been applied to optically shallow regions with reasonable success [3], there is presently no approach that directly corrects for bottom reflectance using existing knowledge of bathymetry and benthic albedo.To address the issue of optically shallow waters, we have developed a semi-analytical ocean color inversion algorithm: the Shallow Water Inversion Model (SWIM). SWIM uses existing bathymetry and a derived benthic albedo map to correct for bottom reflectance using the semi-analytical model of Lee et al [4]. The algorithm was incorporated into the NASA Ocean Biology Processing Groups L2GEN program and tested in optically shallow waters of the Great Barrier Reef, Australia. In-lieu of readily available in situ matchup data, we present a comparison between SWIM and two contemporary ocean color algorithms, the Generalized Inherent Optical Property Algorithm (GIOP) and the Quasi-Analytical Algorithm (QAA)

    SWIM: A Semi-Analytical Ocean Color Inversion Algorithm for Optically Shallow Waters

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    In clear shallow waters, light that is transmitted downward through the water column can reflect off the sea floor and thereby influence the water-leaving radiance signal. This effect can confound contemporary ocean color algorithms designed for deep waters where the seafloor has little or no effect on the water-leaving radiance. Thus, inappropriate use of deep water ocean color algorithms in optically shallow regions can lead to inaccurate retrievals of inherent optical properties (IOPs) and therefore have a detrimental impact on IOP-based estimates of marine parameters, including chlorophyll-a and the diffuse attenuation coefficient. In order to improve IOP retrievals in optically shallow regions, a semi-analytical inversion algorithm, the Shallow Water Inversion Model (SWIM), has been developed. Unlike established ocean color algorithms, SWIM considers both the water column depth and the benthic albedo. A radiative transfer study was conducted that demonstrated how SWIM and two contemporary ocean color algorithms, the Generalized Inherent Optical Properties algorithm (GIOP) and Quasi-Analytical Algorithm (QAA), performed in optically deep and shallow scenarios. The results showed that SWIM performed well, whilst both GIOP and QAA showed distinct positive bias in IOP retrievals in optically shallow waters. The SWIM algorithm was also applied to a test region: the Great Barrier Reef, Australia. Using a single test scene and time series data collected by NASA's MODIS-Aqua sensor (2002-2013), a comparison of IOPs retrieved by SWIM, GIOP and QAA was conducted
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