Amplitude-weighted mean velocity: Clinical utilization for quantitation of mitral regurgitation

AbstractObjectives. The purpose of this study was to determine the clinical usefulness of the amplitude-weighted mean velocity method for quantitation of mitral regurgitation.Background. Amplitude-weighted mean velocity is a nonvolumetric method for calculating the mitral regurgitant fraction. Its previous validation at one center mandated an independent assessment of its usefulness and limitations.Methods. In 56 patients with and 16 patients without mitral regugitation, the regurgitant fraction was measured simultaneously by amplitude-weighted mean velocity, quantitative Doppler study and quantitative two-dimensional echocardiography. In 16 patients, multiple gain settings were used to determine the influence of this variable on amplitude-weighted mean velocity.Results. In ptients without regurgitation, amplitude-weighted mean velocity showed more scattering of regurgitant fraction (−18% to 23%) than Doppler (p = 0.016) or two-dimensional echocardiography (p = 0.022). The absolute value of regurgitant fraction was (mean ± SD) 8 ± 6%, 4 ± 2% and 4 ± 3%, respectively (p = NS). With increasing gain, the amplitudeweighted mean velocity mitral and aortic integrals increased, but the calculated regurgitant fraction remained unchanged. In patients with mitral regurgitation, significant correlation was found between amplitude-weighted mean velocity and Doppler study (r = 0.79, p = 0.0001) and between implitude-weighted mean velocity and two-dimensional echocardiography (r = 0.76, p = 0.0001) for calculated regurgitant fraction, but the standard error of the estimate (12%) was large.Conclusions. The amplitude-weighted mean velocitycalculated regurgitant fraction is gain independent, whereas the aortic and mitral integrals are gain dependent. Compared with Doppler and two-dimensional echocardiography, It shows more scattering of values in patients without regurgitation, but the methods correlate significantly in patients with mitral regurgitation. Amplitude-weighted mean velocity can be used as a simple adjunctive tool for comprehensive, noninvasive quantitation of mitral regurgitation

Mechanical Response and Decomposition of Thermally Degraded Energetic Materials: Experiments and Model Simulations

We report progress of a continuing effort to characterize and simulate the response of energetic materials (EMs), primarily HMX-based, under conditions leading to cookoff. Our experiments include mechanical-effects testing of HMX and FIMX with binder at temperatures nearing decomposition thresholds. Additional experiments have focused on decomposition of these EMs under confinement, measuring evolution of gas products and observing the effect of pressurization on the solid. Real-time measurements on HMX show abrupt changes that maybe due to sudden void collapse under increasing load. Postmortem examination shows significant internal damage to the pellets, including voids and cracks. These experiments have been used to help develop a constitutive model for pure HMX. Unconfined uniaxial compression tests were performed on HMX and LX-14 to examine the effect of binders on the deviatoric strength of EM pellets, and to assess the need of including deviatoric terms in the model. A scale-up experiment will be described that is being developed to validate the model and provide additional diagnostics

Relayed signaling between mesenchymal progenitors and muscle stem cells ensures adaptive stem cell response to increased mechanical load

Adaptation to mechanical load, leading to enhanced force and power output, is a characteristic feature of skeletal muscle. Formation of new myonuclei required for efficient muscle hypertrophy relies on prior activation and proliferation of muscle stem cells (MuSCs). However, the mechanisms controlling MuSC expansion under conditions of increased load are not fully understood. Here we demonstrate that interstitial mesenchymal progenitors respond to mechanical load and stimulate MuSC proliferation in a surgical mouse model of increased muscle load. Mechanistically, transcriptional activation of Yes-associated protein 1 (Yap1)/transcriptional coactivator with PDZ-binding motif (Taz) in mesenchymal progenitors results in local production of thrombospondin-1 (Thbs1), which, in turn, drives MuSC proliferation through CD47 signaling. Under homeostatic conditions, however, CD47 signaling is insufficient to promote MuSC proliferation and instead depends on prior downregulation of the Calcitonin receptor. Our results suggest that relayed signaling between mesenchymal progenitors and MuSCs through a Yap1/Taz-Thbs1-CD47 pathway is critical to establish the supply of MuSCs during muscle hypertrophy

High Yield Production Process for Shigella Outer Membrane Particles

Gram-negative bacteria naturally shed particles that consist of outer membrane lipids, outer membrane proteins, and soluble periplasmic components. These particles have been proposed for use as vaccines but the yield has been problematic. We developed a high yielding production process of genetically derived outer membrane particles from the human pathogen Shigella sonnei. Yields of approximately 100 milligrams of membrane-associated proteins per liter of fermentation were obtained from cultures of S. sonnei ΔtolR ΔgalU at optical densities of 30–45 in a 5 L fermenter. Proteomic analysis of the purified particles showed the preparation to primarily contain predicted outer membrane and periplasmic proteins. These were highly immunogenic in mice. The production of these outer membrane particles from high density cultivation of bacteria supports the feasibility of scaling up this approach as an affordable manufacturing process. Furthermore, we demonstrate the feasibility of using this process with other genetic manipulations e.g. abolition of O antigen synthesis and modification of the lipopolysaccharide structure in order to modify the immunogenicity or reactogenicity of the particles. This work provides the basis for a large scale manufacturing process of Generalized Modules of Membrane Antigens (GMMA) for production of vaccines from Gram-negative bacteria

New CC0\pi\ GENIE Model Tune for MicroBooNE

A novel tune has been made for the MicroBooNE experiment. The fit uses 4 new parameters within the GENIE v3.0.6 Monte Carlo program. Charged current pionless data from the T2K experiment was used. New uncertainties were obtained. These results will be used in future MicroBooNE analyses.Comment: 24 pages, 14 figure