2,144 research outputs found
Posaconazole-induced hypertension and hypokalemia due to inhibition of the 11b-hydroxylase enzyme
Seismic Performance Testing of Partially and Fully Anchored Wood-Frame Shear Walls
Earthquake performance of wood-frame shear walls was evaluated by comparing fully and partially anchored walls under monotonic, cyclic, and earthquake loads and comparing with code measures. Suitability of monotonic and cyclic testing to predict seismic performance was examined. Earthquake tests were conducted on 2440-mm-square walls with Douglas-fir studs. Two oriented strandboard panels were fastened to the frame with two gypsum wallboard panels on the opposite side. Partially anchored walls had two anchor bolts on the sill plate. Fully anchored walls had hold-downs at the ends. Four time histories were tested: three subduction zone ground motions and a strike-slip fault, all scaled to the Seattle design level. For fully anchored walls, subduction zone tests had capacities, energy dissipation, and failure modes most similar to cyclic tests. Wall displacement at maximum load was under-estimated by cyclic and overestimated by monotonic tests. For partially anchored walls, subduction zone and strike-slip earthquake tests had capacity, displacement at maximum load, initial stiffness, and ductility most similar to cyclic tests. Energy dissipation was most similar to monotonic tests, and failure modes were consistent with monotonic and cyclic tests. Partially anchored walls had lower capacity, displacement at maximum load, energy dissipation, and stiffness as compared with fully anchored walls
A library of infectious hepatitis C viruses with engineered mutations in the E2 gene reveals growth-adaptive mutations that modulate interactions with scavenger receptor class B type I
While natural hepatitis C virus (HCV) infection results in highly diverse quasispecies of related viruses over time, mutations accumulate more slowly in tissue culture, in part because of the inefficiency of replication in cells. To create a highly diverse population of HCV particles in cell culture and identify novel growth-enhancing mutations, we engineered a library of infectious HCV with all codons represented at most positions in the ectodomain of the E2 gene. We identified many putative growth-adaptive mutations and selected nine highly represented E2 mutants for further study: Q412R, T416R, S449P, T563V, A579R, L619T, V626S, K632T, and L644I. We evaluated these mutants for changes in particle-to-infectious-unit ratio, sensitivity to neutralizing antibody or CD81 large extracellular loop (CD81-LEL) inhibition, entry factor usage, and buoyant density profiles. Q412R, T416R, S449P, T563V, and L619T were neutralized more efficiently by anti-E2 antibodies and T416R, T563V, and L619T by CD81-LEL. Remarkably, all nine variants showed reduced dependence on scavenger receptor class B type I (SR-BI) for infection. This shift from SR-BI usage did not correlate with a change in the buoyant density profiles of the variants, suggesting an altered E2-SR-BI interaction rather than changes in the virus-associated lipoprotein-E2 interaction. Our results demonstrate that residues influencing SR-BI usage are distributed across E2 and support the development of large-scale mutagenesis studies to identify viral variants with unique functional properties. IMPORTANCE Characterizing variant viruses can reveal new information about the life cycle of HCV and the roles played by different viral genes. However, it is difficult to recapitulate high levels of diversity in the laboratory because of limitations in the HCV culture system. To overcome this limitation, we engineered a library of mutations into the E2 gene in the context of an infectious clone of the virus. We used this library of viruses to identify nine mutations that enhance the growth rate of HCV. These growth-enhancing mutations reduced the dependence on a key entry receptor, SR-BI. By generating a highly diverse library of infectious HCV, we mapped regions of the E2 protein that influence a key virus-host interaction and provide proof of principle for the generation of large-scale mutant libraries for the study of pathogens with great sequence variability
Diastereoselective Photoredox-Catalyzed [3 + 2] Cycloadditions of N-Sulfonyl Cyclopropylamines with Electron-Deficient Olefins
Healthcare Costs of Acute and Chronic Pain Associated with a Diagnosis of Herpes Zoster
To determine the healthcare costs of acute and chronic pain associated with herpes zoster. DESIGN : Retrospective cohort analysis. SETTING : Inpatient and outpatient care. PARTICIPANTS : Patients were selected from Medicare, commercial insurance, and Medicaid claims databases if they had a diagnosis of herpes zoster or postherpetic neuralgia (PHN) or were prescribed analgesics after a diagnosis of herpes zoster (possible PHN) and were matched to controls for demographic and clinical factors using propensity scores. MEASUREMENTS : One-year excess healthcare expenditures attributable to herpes zoster pain or PHN were calculated for inpatient, outpatient, and prescription drug services. RESULTS : For the Medicare cohort, the average excess cost per patient was 2,200 to $2,300 per patient with PHN or possible PHN. Patients with possible PHN were 53% more prevalent than patients with PHN in the Medicare cohort and accounted for half of all excess expenditures. Findings were similar in the younger cohorts with commercial insurance and Medicaid except that costs attributable to PHN and possible PHN were higher, and patients with possible PHN were three to five times as prevalent as patients with PHN. CONCLUSION : Healthcare costs associated with PHN were substantially greater than those associated with herpes zoster pain that resolved within 30 days. The data suggest that as many as 80% of patients with PHN may not be diagnosed with PHN and that these patients account for at least half of PHN expenditures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66349/1/j.1532-5415.2007.01231.x.pd
Measuring aortic pulse wave velocity using high-field cardiovascular magnetic resonance: comparison of techniques
<p>Abstract</p> <p>Background</p> <p>The assessment of arterial stiffness is increasingly used for evaluating patients with different cardiovascular diseases as the mechanical properties of major arteries are often altered. Aortic stiffness can be noninvasively estimated by measuring pulse wave velocity (PWV). Several methods have been proposed for measuring PWV using velocity-encoded cardiovascular magnetic resonance (CMR), including transit-time (TT), flow-area (QA), and cross-correlation (XC) methods. However, assessment and comparison of these techniques at high field strength has not yet been performed. In this work, the TT, QA, and XC techniques were clinically tested at 3 Tesla and compared to each other.</p> <p>Methods</p> <p>Fifty cardiovascular patients and six volunteers were scanned to acquire the necessary images. The six volunteer scans were performed twice to test inter-scan reproducibility. Patient images were analyzed using the TT, XC, and QA methods to determine PWV. Two observers analyzed the images to determine inter-observer and intra-observer variabilities. The PWV measurements by the three methods were compared to each other to test inter-method variability. To illustrate the importance of PWV using CMR, the degree of aortic stiffness was assessed using PWV and related to LV dysfunction in five patients with diastolic heart failure patients and five matched volunteers.</p> <p>Results</p> <p>The inter-observer and intra-observer variability results showed no bias between the different techniques. The TT and XC results were more reproducible than the QA; the mean (SD) inter-observer/intra-observer PWV differences were -0.12(1.3)/-0.04(0.4) for TT, 0.2(1.3)/0.09(0.9) for XC, and 0.6(1.6)/0.2(1.4) m/s for QA methods, respectively. The correlation coefficients (r) for the inter-observer/intra-observer comparisons were 0.94/0.99, 0.88/0.94, and 0.83/0.92 for the TT, XC, and QA methods, respectively. The inter-scan reproducibility results showed low variability between the repeated scans (mean (SD) PWV difference = -0.02(0.4) m/s and r = 0.96). The inter-method variability results showed strong correlation between the TT and XC measurements, but less correlation with QA: r = 0.95, 0.87, and 0.89, and mean (SD) PWV differences = -0.12(1.0), 0.8(1.7), and 0.65(1.6) m/s for TT-XC, TT-QA, and XC-QA, respectively. Finally, in the group of diastolic heart failure patient, PWV was significantly higher (6.3 ± 1.9 m/s) than in volunteers (3.5 ± 1.4 m/s), and the degree of LV diastolic dysfunction showed good correlation with aortic PWV.</p> <p>Conclusions</p> <p>In conclusion, while each of the studied methods has its own advantages and disadvantages, at high field strength, the TT and XC methods result in closer and more reproducible aortic PWV measurements, and the associated image processing requires less user interaction, than in the QA method. The choice of the analysis technique depends on the vessel segment geometry and available image quality.</p
CD4+ lymphocyte adenosine triphosphate determination in sepsis: a cohort study
INTRODUCTION: Patients suffering from sepsis are currently classified on a clinical basis (i.e., sepsis, severe sepsis, septic shock); however, this clinical classification may not accurately reflect the overall immune status of an individual patient. Our objective was to describe a cohort of patients with sepsis in terms of their measured immune status. METHODS: Fifty-two patients with sepsis (n = 13), severe sepsis (n = 21), or septic shock (n = 18) were studied. The immune status was determined by measuring the CD4+ lymphocyte adenosine triphosphate (ATP) content after mitogen stimulation in whole blood. RESULTS: The measured CD4+ lymphocyte ATP content at the time of ICU admission did not differ among the various groups defined by the sepsis classification system (sepsis = 454 ± 79 ng/ml; severe sepsis = 359 ± 54 ng/ml; septic shock = 371 ± 53 ng/ml; P = 0.44). Furthermore, survivors of sepsis had a significantly higher CD4+ lymphocyte ATP content at the time of ICU admission than did nonsurvivors of sepsis (431 ± 41 ng/mL vs. 266 ± 53 ng/mL, respectively; P = 0.04). CONCLUSIONS: The sepsis classification system that is currently used is not representative of the individual immune status as determined by measuring the CD4+ lymphocyte ATP content. Moreover, a lower CD4+ ATP content at the time of ICU admission is associated with a worse clinical outcome in those suffering from sepsis
Hypogene speleogenesis within the Central Basin Platform: Karst Porosity in the Yates Field, Pecos County, Texas, U.S.A.
The Yates Unit Oil Field is located on the southeastern tip of the Central Basin Platform in eastern Pecos County, Texas. It produces from Middle Permian strata, primarily the upper San Andres Formation. Locally, the productive upper San Andres Formation is comprised of successively vertically stacked progradational shelf carbonates. Stratigraphically overlying the Yates Field reservoir, the Toborg Field produces from the uppermost Triassic and Cretaceous units. Both fields are bounded on the north and east sides by the Pecos River, which has remained entrenched in its current location since the early Tertiary. As mapped, the top of the San Andres Formation is an unconformity representing erosional topography that does not truly reflect the subsurface structural configuration
Elevated calcitonin precursor levels are related to mortality in an animal model of sepsis
BACKGROUND: Increased serum levels of procalcitonin (ProCT) and its component peptides have been reported in humans with sepsis. Using a hamster model of bacterial peritonitis, we investigated whether serum ProCT levels are elevated and correlate with mortality and hypocalcemia. RESULTS: Incremental increases in doses of bacteria resulted in proportional increases in 72h mortality rates (0, 20, 70, and 100%) as well as increases in serum total immunoreactive calcitonin (iCT) levels at 12 h (250, 380, 1960, and 4020 pg/ml, respectively, vs control levels of 21 pg/ml). Gel filtration studies revealed that ProCT was the predominant (> 90%) molecular form of serum iCT secreted. In the metabolic experiments, total iCT peaked at 12 h concurrent with the maximal decrease in serum calcium. CONCLUSIONS: In this animal model, hyper-procalcitoninemia was an early systemic marker of sepsis which correlated closely with mortality and had an inverse correlation with serum calcium levels
One-way diffraction grating
Matthew J. Lockyear, Alastair P. Hibbins, Kevin R. White, and J. Roy Sambles, Physical Review E, Vol. 74, article 056611 (2006). "Copyright © 2006 by the American Physical Society."Diffraction gratings are elementary tools for much of optics and spectroscopy. Here, at microwave frequencies, we provide a new perspective on these fundamental structures. A transmission diffraction grating is presented that has diffracted beams emanating from one surface only. It can thus function either as a transmission grating with no reflected orders (other than zero) or, in the reverse configuration, as a partially transmitting structure with diffracted orders in reflection only
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