The Use of Aerosolized Ribavirin in Respiratory Syncytial Virus Lower Respiratory Tract Infections in Adult Immunocompromised Patients: A Systematic Review

Introduction: Respiratory syncytial virus (RSV)–associated lower respiratory tract infection (LRTI) is a concern in immunocompromised patients. Aerosolized ribavirin (RBV AER) is used for treatment of RSV LRTI; however, adverse events and rising drug costs remain a challenge for patient management. The purpose of this systematic review is to summarize the efficacy and adverse event profile of RBV AER for the treatment of hospitalized RSV LRTI in immunocompromised adult patients. Methods: A Medline/PubMed, Embase, Google Scholar, Clinicaltrials.gov, and Cochrane Library database search was conducted from 1966 to January 2019 for the use of RBV AER. Search strategy: [(ribavirin OR ICN1229) AND (“administration, oral” OR “oral” OR “administration, inhalation” OR “inhalation)] AND (“respiratory tract infection” OR “pneumonia”). Studies were reviewed if adult patients were hospitalized, immunocompromised, had RSV LRTI, received RBV AER, and included the outcome of mortality and/or adverse reactions. Methodological quality was assessed using the Cochrane Collaboration GRADE approach. Results: A total of 1787 records were identified and 15 articles met inclusion criteria: hematopoietic stem cell transplant (HSCT)/bone marrow transplant (n = 8), other malignancy/neutropenic (n = 2), solid organ transplant (n = 5). All of the trials are observational with a low quality rating; therefore, a meta-analysis was not performed. The 30-day mortality in studies that contain \u3e10 patients with HSCT, malignancy, and transplant range from 0 to 15.4%, 6.3%, and 0 to 27%, respectively. Improved mortality was cited in 4 studies when RBV AER started before mechanical ventilation or within 2 weeks of symptom onset. Only 3 studies had comparative mortality data with RBV AER and RBV PO. Adverse reactions were reported in 5 studies and included psychiatric manifestations (anxiety, depression, feeling of isolation; n = 14), wheezing/bronchospasm (n = 6), snowflakes/hail blowing in face (n = 6), and precipitation in ventilator tubing (n = 5). Conclusion: There is a lack of high quality, comparative trials on the use of RBV AER for the treatment of RSV LRTI in adult hospitalized immunocompromised patients. There may be a mortality benefit when RBV AER is initiated early after diagnosis or prior to mechanical ventilation, but requires further study. Patient isolation and psychological effects must be weighed against the benefit of therapy

Gamma-Ray Bursts in Circumstellar Shells: A Possible Explanation for Flares

It is now generally accepted that long-duration gamma ray bursts (GRBs) are due to the collapse of massive rotating stars. The precise collapse process itself, however, is not yet fully understood. Strong winds, outbursts, and intense ionizing UV radiation from single stars or strongly interacting binaries are expected to destroy the molecular cloud cores that give birth to them and create highly complex circumburst environments for the explosion. Such environments might imprint features on GRB light curves that uniquely identify the nature of the progenitor and its collapse. We have performed numerical simulations of realistic environments for a variety of long-duration GRB progenitors with ZEUS-MP, and have developed an analytical method for calculating GRB light curves in these profiles. Though a full, three-dimensional, relativistic magnetohydrodynamical computational model is required to precisely describe the light curve from a GRB in complex environments, our method can provide a qualitative understanding of these phenomena. We find that, in the context of the standard afterglow model, massive shells around GRBs produce strong signatures in their light curves, and that this can distinguish them from those occurring in uniform media or steady winds. These features can constrain the mass of the shell and the properties of the wind before and after the ejection. Moreover, the interaction of the GRB with the circumburst shell is seen to produce features that are consistent with observed X-ray flares that are often attributed to delayed energy injection by the central engine. Our algorithm for computing light curves is also applicable to GRBs in a variety of environments such as those in high-redshift cosmological halos or protogalaxies, both of which will soon be targets of future surveys such as JANUS or Lobster.Comment: 12 pages, 5 figures, Accepted by Ap

Compatibility of grain-stabilized platinum with candidate propellants for resistojets

Resistojets are candidates for space station auxiliary propulsion, and should be characterized by both long life and multipropellant operations, requirements limited by available materials. Grain stabilized platinum is examined for use as a resistojet thruster material. Use of platinum in other applications indicates it can be used at moderately high temperatures for extended periods of time. Past results indicate that grain-stabilized platinum should be sufficiently inert in candidate propellant environments. Therefore, compatibility of platinum-yttria (P/Y2O3) and platinum-zirconia (Pt/ZrO2) with carbon dioxide, methane, hydrogen and ammonia is examined. A series of 1000 hr tests in CO2, H2, and NH3 is conducted at 1400 C and a series of 1000 hr tests in CH4 is conducted at about 500 C. Scanning electron microscopy, Auger electron spectroscopy and depth profiling analysis are then used to determine the effects of propellants on the material surface, to evaluate possible material contamination and to evaluate grain growth. The results indicate that there is carbon deposition on the surface of the Pt/Y2O3 and Pt/ZrO2 in both the CO2 and CH4 environments. In the H2 environment, the Pt/Y2O3 and Pt/ZrO2 specimen surfaces are roughened. After exposure to the NH3 environment, the Pt/Y2O3 and Pt/ZrO2 are roughened and pitted over the entire heated area with some pitted areas along the grain boundaries. SEM photos show grain growth in cross-sectional views of all the Pt/Y2O3 samples and the Pt/ZrO2 samples, except that tested in methane. Mass loss measurements indicate that Pt/Y2O3 and Pt/ZrO2 would last in excess of 200,000 hr in each propellant environment. However, in NH3 both Pt/Y2O3 and Pt/ZrO2 are severely pitted, with voids up to 50 percent into the material. Pt/Y2O3 and Pt/ZrO2 are not recommended for high temperature service in NH3

In-situ analysis of hydrazine decomposition products

A gas analyzer utilizing a nondispersive infrared (NDIR) detection system was used to monitor the ammonia and water vapor content of the products of a previously unused hydrazine gas generator. This provided an in-situ measurement of the generator's efficiency difficult to obtain by other means. The analyzer was easily installed in both the calibration and hydrazine systems, required no maintenance other than periodic zero adjustments, and performed well for extended periods in the operating range tested. The catalyst bed operated smoothly and repeatably during the 28 hr of testing. No major transients were observed on startup or during steady state operation. The amount of ammonia in the output stream of the gas generator was found to be a strong function of temperature at catalyst bed temperatures below 450 C. At temperatures above this, the efficiency remained nearly constant. On startup the gas generator efficiency was found to decrease with time until a steady state value was attained. Elevated catalyst bed temperatures in the periods before steady state operation was found to be responsible for this phenomenon

Radiation Hydrodynamical Instabilities in Cosmological and Galactic Ionization Fronts

Ionization fronts, the sharp radiation fronts behind which H/He ionizing photons from massive stars and galaxies propagate through space, were ubiquitous in the universe from its earliest times. The cosmic dark ages ended with the formation of the first primeval stars and galaxies a few hundred Myr after the Big Bang. Numerical simulations suggest that stars in this era were very massive, 25 - 500 solar masses, with H II regions of up to 30,000 light-years in diameter. We present three-dimensional radiation hydrodynamical calculations that reveal that the I-fronts of the first stars and galaxies were prone to violent instabilities, enhancing the escape of UV photons into the early intergalactic medium (IGM) and forming clumpy media in which supernovae later exploded. The enrichment of such clumps with metals by the first supernovae may have led to the prompt formation of a second generation of low-mass stars, profoundly transforming the nature of the first protogalaxies. Cosmological radiation hydrodynamics is unique because ionizing photons coupled strongly to both gas flows and primordial chemistry at early epochs, introducing a hierarchy of disparate characteristic timescales whose relative magnitudes can vary greatly throughout a given calculation. We describe the adaptive multistep integration scheme we have developed for the self-consistent transport of both cosmological and galactic ionization fronts.Comment: 6 pages, 4 figures, accepted for proceedings of HEDLA2010, Caltech, March 15 - 18, 201

SUPREM-II analysis of the phosphorus planar diffusion source PH 1000N

The phosphorus planar diffusion source, PH-1000N, was used to test the ability of the process simulation program SUPREM-H to accommodate solid source diffusion. Spreading resistance analysis and secondary ion mass spectrometry (SIMS) were used to determine the impurity concentration profiles of phosphorus diffused into p-type silicon. Sheet resistance and junction depth data, in addition to the impurity concentration profiles, were plotted against the respective data generated by SUPREM. The surface gas concentration, a parameter requested by SUPREM\u27s input file, was found to have the strongest influence on the program\u27s output. The solid solubility of phosphorus in silicon at process temperatures 950C, 975C, and 1000C was used as the initial surface gas concentration. The results given by SUPREM overestimated the sheet resistance by approximately 5 2/sq and underestimated the junction depth by .2 microns. A constant surface gas concentration of 8.5xl020 atoms/cm3 was used as input to improve the correlation between the predicted junction depth and the data obtain by the spreading resistance analysis. This improvement came at the expense of lost accuracy between the predicted and experimental concentration profiles. The best all around correlation between the theoretical output and the experimental data was obtained when the surface concentration parameter was extracted directly from the SIMS data

Dark Clouds Looming: The Uncertain Safety of Welfare Benefits for Probationers and Parolees

How much is thirty dollars per month worth to the average American? For many, it is not much—it can be the cost of a streaming subscription or a ticket to a baseball game. For others, however, thirty dollars is the cost of freedom from incarceration. In January 2019, Randall Graves failed to meet the conditions of his probation, which required that he pay a monthly intervention fee of thirty dollars to the Department of Corrections instead of serving his six-year prison sentence. To some, thirty dollars may not be worth much, but to Graves, it was a metric of freedom