Heat pipe cooled heat rejection subsystem modelling for nuclear electric propulsion

NASA LeRC is currently developing a FORTRAN based computer model of a complete nuclear electric propulsion (NEP) vehicle that can be used for piloted and cargo missions to the Moon or Mars. Proposed designs feature either a Brayton or a K-Rankine power conversion cycle to drive a turbine coupled with rotary alternators. Both ion and magnetoplasmodynamic (MPD) thrusters will be considered in the model. In support of the NEP model, Rocketdyne is developing power conversion, heat rejection, and power management and distribution (PMAD) subroutines. The subroutines will be incorporated into the NEP vehicle model which will be written by NASA LeRC. The purpose is to document the heat pipe cooled heat rejection subsystem model and its supporting subroutines. The heat pipe cooled heat rejection subsystem model is designed to provide estimate of the mass and performance of the equipment used to reject heat from Brayton and Rankine cycle power conversion systems. The subroutine models the ductwork and heat pipe cooled manifold for a gas cooled Brayton; the heat sink heat exchanger, liquid loop piping, expansion compensator, pump and manifold for a liquid loop cooled Brayton; and a shear flow condenser for a K-Rankine system. In each case, the final heat rejection is made by way of a heat pipe radiator. The radiator is sized to reject the amount of heat necessary

Estimating the recharge properties of the deep ocean using noble gases and helium isotopes

The distribution of noble gases and helium isotopes in the dense shelf waters of Antarctica reflect the boundary conditions near the ocean surface: air-sea exchange, sea ice formation and subsurface ice melt. We use a non-linear least-squares solution to determine the value of the recharge temperature and salinity, as well as the excess air injection and glacial meltwater content throughout the water column and in the precursor to Antarctic Bottom Water. The noble gas-derived recharge temperature and salinity in the Weddell Gyre are -1.95 °C and 34.95 psu near 5500 m; these cold, salty recharge values are a result of surface cooling as well as brine rejection during sea ice formation in Antarctic polynyas. In comparison, the global value for deep water recharge temperature is -0.44 °C at 5500 m, which is 1.5 °C warmer than the southern hemisphere deep water recharge temperature, reflecting the contribution from the north Atlantic. The contrast between northern and southern hemisphere recharge properties highlight the impact of sea ice formation on setting the gas properties in southern sourced deep water. Below 1000 m, glacial meltwater averages 3.5 ‰ by volume and represents greater than 50% of the excess neon and argon found in the water column. These results indicate glacial melt has a non-negligible impact on the atmospheric gas content of Antarctic Bottom Water

A retrospective analysis of clinical use of alirocumab in lipoprotein apheresis patients

BACKGROUND: The previously published ODYSSEY ESCAPE trial demonstrated a significant reduction in the use of lipoprotein apheresis for heterozygous familial hypercholesterolemia (HeFH) patients when placed on alirocumab 150 mg every 2 weeks. In patients with HeFH who have consistently elevated levels of low-density lipoprotein cholesterol (LDL-C) despite maximally tolerated statin therapy, current lipid guidelines recommend apheresis. Although apheresis reduces LDL-C levels by 50%-75%, it must be repeated, as frequently as every 1-2 weeks. OBJECTIVE: To assess clinical experience with apheresis and alirocumab for patients in a real-world practice setting. METHODS: This retrospective review included patients from 5 apheresis centers who were treated with apheresis and had started alirocumab therapy. In addition to LDL-C levels, total cholesterol, high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides, and particle numbers were evaluated if data were available. RESULTS: Eleven of the 25 (44%) patients discontinued apheresis completely after initiation of alirocumab therapy, having achieved LDL-C \u3c70 mg/dL or \u3e50% reduction from baseline levels. Among the 14 patients who remained on apheresis, seven decreased the frequency of apheresis sessions. No significant safety problems were reported. CONCLUSION: Alirocumab lowered LDL-C levels by an average of 55.5% in patients receiving apheresis for elevated LDL-C. Seventy-two percent of patients on alirocumab therapy discontinued or reduced the frequency of apheresis treatment. However, some patients continued to require apheresis due to elevated lipoprotein(a), extremely elevated LDL-C, or if alirocumab therapy was discontinued due to less than anticipated LDL-C reduction

Tildacerfont in Adults With Classic Congenital Adrenal Hyperplasia: Results from Two Phase 2 Studies

Context: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) is typically treated with lifelong supraphysiologic doses of glucocorticoids (GCs). Tildacerfont, a corticotropin-releasing factor type-1 receptor antagonist, may reduce excess androgen production, allowing for GC dose reduction. Objective: Assess tildacerfont safety and efficacy. Design and setting: Two Phase 2 open-label studies. Patients: Adults with 21OHD. Intervention: Oral tildacerfont 200 to 1000 mg once daily (QD) (n = 10) or 100 to 200 mg twice daily (n = 9 and 7) for 2 weeks (Study 1), and 400 mg QD (n = 11) for 12 weeks (Study 2). Main outcome measure: Efficacy was evaluated by changes from baseline at 8 am in adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), and androstenedione (A4) according to baseline A4 ≤ 2× upper limit of normal (ULN) or A4 > 2× ULN. Safety was evaluated using adverse events (AEs) and laboratory assessments. Results: In Study 1, evaluable participants with baseline A4 > 2× ULN (n = 11; 19-67 years, 55% female) had reductions from baseline in ACTH (-59.4% to -28.4%), 17-OHP (-38.3% to 0.3%), and A4 (-24.2% to -18.1%), with no clear dose response. In Study 2, participants with baseline A4 > 2× ULN (n = 5; 26-63 years, 40% female) had ~80% maximum mean reductions in biomarker levels. ACTH and A4 were normalized for 60% and 40%, respectively. In both studies, participants with baseline A4 ≤ 2× ULN maintained biomarker levels. AEs (in 53.6% of patients overall) included headache (7.1%) and upper respiratory tract infection (7.1%). Conclusions: For patients with 21OHD, up to 12 weeks of oral tildacerfont reduced or maintained key hormone biomarkers toward normal

Spent Culture Medium from Virulent Borrelia burgdorferi Increases Permeability of Individually Perfused Microvessels of Rat Mesentery

Lyme disease is a common vector-borne disease caused by the spirochete Borrelia burgdorferi (Bb), which manifests as systemic and targeted tissue inflammation. Both in vitro and in vivo studies have shown that Bb-induced inflammation is primarily host-mediated, via cytokine or chemokine production that promotes leukocyte adhesion/migration. Whether Bb produces mediators that can directly alter the vascular permeability in vivo has not been investigated. The objective of the present study was to investigate if Bb produces a mediator(s) that can directly activate endothelial cells resulting in increases in permeability in intact microvessels in the absence of blood cells.The effects of cell-free, spent culture medium from virulent (B31-A3) and avirulent (B31-A) B. burgdorferi on microvessel permeability and endothelial calcium concentration, [Ca(2+)](i), were examined in individually perfused rat mesenteric venules. Microvessel permeability was determined by measuring hydraulic conductivity (Lp). Endothelial [Ca(2+)](i), a necessary signal initiating hyperpermeability, was measured in Fura-2 loaded microvessels. B31-A3 spent medium caused a rapid and transient increase in Lp and endothelial [Ca(2+)](i). Within 2-5 min, the mean peak Lp increased to 5.6+/-0.9 times the control, and endothelial [Ca(2+)](i) increased from 113+/-11 nM to a mean peak value of 324+/-35 nM. In contrast, neither endothelial [Ca(2+)](i) nor Lp was altered by B31-A spent medium.A mediator(s) produced by virulent Bb under culture conditions directly activates endothelial cells, resulting in increases in microvessel permeability. Most importantly, the production of this mediator is associated with Bb virulence and is likely produced by one or more of the 8 plasmid(s) missing from strain B31-A

Financing U.S. Graduate Medical Education: A Policy Position Paper of the Alliance for Academic Internal Medicine and the American College of Physicians

In this position paper, the Alliance for Academic Internal Medicine and the American College of Physicians examine the state of graduate medical education (GME) financing in the United States and recent proposals to reform GME funding. They make a series of recommendations to reform the current funding system to better align GME with the needs of the nation's health care workforce. These recommendations include using Medicare GME funds to meet policy goals and to ensure an adequate supply of physicians, a proper specialty mix, and appropriate training sites; spreading the costs of financing GME across the health care system; evaluating the true cost of training a resident and establishing a single per-resident amount; increasing transparency and innovation; and ensuring that primary care residents receive training in well-functioning ambulatory settings that are financially supported for their training roles

AMI radio continuum observations of young stellar objects with known outflows

We present 16 GHz (1.9 cm) deep radio continuum observations made with the Arcminute Microkelvin Imager (AMI) of a sample of low-mass young stars driving jets. We combine these new data with archival information from an extensive literature search to examine spectral energy distributions (SEDs) for each source and calculate both the radio and sub-mm spectral indices in two different scenarios: (1) fixing the dust temperature (Td) according to evolutionary class; and (2) allowing Td to vary. We use the results of this analysis to place constraints on the physical mechanisms responsible for the radio emission. From AMI data alone, as well as from model fitting to the full SED in both scenarios, we find that 80 per cent of the objects in this sample have spectral indices consistent with freefree emission. We find an average spectral index in both Td scenarios, consistent with freefree emission. We examine correlations of the radio luminosity with bolometric luminosity, envelope mass and outflow force, and find that these data are consistent with the strong correlation with envelope mass seen in lower luminosity samples. We examine the errors associated with determining the radio luminosity and find that the dominant source of error is the uncertainty on the opacity index, beta. We examine the SEDs for variability in these young objects, and find evidence for possible radio flare events in the histories of L1551 IRS 5 and Serpens SMM 1

The JCMT Gould Belt Survey: evidence for dust grain evolution in Perseus star-forming clumps

The dust emissivity spectral index, β, is a critical parameter for deriving the mass and temperature of star-forming structures and, consequently, their gravitational stability. The β value is dependent on various dust grain properties, such as size, porosity, and surface composition, and is expected to vary as dust grains evolve. Here we present β, dust temperature, and optical depth maps of the star-forming clumps in the Perseus Molecular Cloud determined from fitting spectral energy distributions to combined Herschel and JCMT observations in the 160, 250, 350, 500, and 850 μm bands. Most of the derived β and dust temperature values fall within the ranges of 1.0-2.7 and 8-20 K, respectively. In Perseus, we find the β distribution differs significantly from clump to clump, indicative of grain growth. Furthermore, we also see significant localized β variations within individual clumps and find low-β regions correlate with local temperature peaks, hinting at the possible origins of low-β grains. Throughout Perseus, we also see indications of heating from B stars and embedded protostars, as well evidence of outflows shaping the local landscape