Review of Nuclear Thermal Propulsion Ground Test Options

High efficiency rocket propulsion systems are essential for humanity to venture beyond the moon. Nuclear Thermal Propulsion (NTP) is a promising alternative to conventional chemical rockets with relatively high thrust and twice the efficiency of highest performing chemical propellant engines. NTP utilizes the coolant of a nuclear reactor to produce propulsive thrust. An NTP engine produces thrust by flowing hydrogen through a nuclear reactor to cool the reactor, heating the hydrogen and expelling it through a rocket nozzle. The hot gaseous hydrogen is nominally expected to be free of radioactive byproducts from the nuclear reactor; however, it has the potential to be contaminated due to off-nominal engine reactor performance. NTP ground testing is more difficult than chemical engine testing since current environmental regulations do not allow/permit open air testing of NTP as was done in the 1960's and 1970's for the Rover/NERVA program. A new and innovative approach to rocket engine ground test is required to mitigate the unique health and safety risks associated with the potential entrainment of radioactive waste from the NTP engine reactor core into the engine exhaust. Several studies have been conducted since the ROVER/NERVA program in the 1970's investigating NTP engine ground test options to understand the technical feasibility, identify technical challenges and associated risks and provide rough order of magnitude cost estimates for facility development and test operations. The options can be divided into two distinct schemes; (1) real-time filtering of the engine exhaust and its release to the environment or (2) capture and storage of engine exhaust for subsequent processing

Identification of Genes Implicated in Methapyrilene-Induced Hepatotoxicity by Comparing Differential Gene Expression in Target and Nontarget Tissue

BACKGROUND: Toxicogenomics experiments often reveal thousands of transcript alterations that are related to multiple processes, making it difficult to identify key gene changes that are related to the toxicity of interest. OBJECTIVES: The objective of this study was to compare gene expression changes in a nontarget tissue to the target tissue for toxicity to help identify toxicity-related genes. METHODS: Male rats were given the hepatotoxicant methapyrilene at two dose levels, with livers and kidneys removed 24 hr after one, three, and seven doses for gene expression analysis. To identify gene changes likely to be related to toxicity, we analyzed genes on the basis of their temporal pattern of change using a program developed at the National Institute of Environmental Health Sciences, termed “EPIG” (extracting gene expression patterns and identifying co-expressed genes). RESULTS: High-dose methapyrilene elicited hepatic damage that increased in severity with the number of doses, whereas no treatment-related lesions were observed in the kidney. High-dose methapyrilene elicited thousands of gene changes in the liver at each time point, whereas many fewer gene changes were observed in the kidney. EPIG analysis identified patterns of gene expression correlated to the observed toxicity, including genes associated with endoplasmic reticulum stress and the unfolded protein response. CONCLUSIONS: By factoring in dose level, number of doses, and tissue into the analysis of gene expression elicited by methapyrilene, we were able to identify genes likely to not be implicated in toxicity, thereby allowing us to focus on a subset of genes to identify toxicity-related processes

Loss of research and operational equipment in Antarctica: Balancing scientific advances with environmental impact

Antarctica has been subject to widespread, long-term and on-going human activity since the establishment of permanent research stations became common in the 1950s. Equipment may become intentionally or inadvertently lost in Antarctic marine and terrestrial environments as a result of scientific research and associated support activities, but this has been poorly quantified to date. Here we report the quantity and nature of equipment lost by the UK's national operator in Antarctica, the British Antarctic Survey (BAS). Over the 15-year study period (2005–2019), 125 incidents of loss were reported, with c. 23 tonnes of equipment lost of which 18% by mass was considered hazardous. The geographical distribution of lost equipment was widespread across the BAS operational footprint. However, impacts are considered low compared to those associated with research station infrastructure establishment and operation. To reduce environmental impact overall, we recommend that, where possible, better use is made of existing research station capacity to facilitate field research, thereby reducing the need for construction of new infrastructure and the generation of associated impacts. Furthermore, to facilitate reporting on the state of the Antarctic environment, we recommend that national Antarctic programmes reinvigorate efforts to comply with Antarctic Treaty System requirements to actively record the locations of past activities and make available details of lost equipment. In a wider context, analogous reporting is also encouraged in other pristine areas subject to new research activities, including in other remote Earth environments and on extra-terrestrial bodies

NASA's Nuclear Thermal Propulsion Project

The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation NTP system could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of a first generation NTP in the development of advanced nuclear propulsion systems could be analogous to the role of the DC- 3 in the development of advanced aviation. Progress made under the NTP project could also help enable high performance fission power systems and Nuclear Electric Propulsion (NEP)

The NASA Advanced Exploration Systems Nuclear Thermal Propulsion Project

The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation NTP system could provide high thrust at a specific impulse (Isp) above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of a first generation NTP in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation systems

The NASA Advanced Exploration Systems Nuclear Thermal Propulsion Project

No abstract availabl

Knowledge user survey and Delphi process to inform development of a new risk of bias tool to assess systematic reviews with network meta-analysis (RoB NMA tool)

Background: Network meta-analysis (NMA) is increasingly used in guideline development and other aspects of evidence-based decision-making. We aimed to develop a risk of bias (RoB) tool to assess NMAs (RoB NMA tool). An international steering committee recommended that the RoB NMA tool to be used in combination with the Risk of Bias in Systematic reviews (ROBIS) tool (i.e. because it was designed to assess biases only) or other similar quality appraisal tools (eg, A MeaSurement Tool to Assess systematic Reviews 2 [AMSTAR 2]) to assess quality of systematic reviews. The RoB NMA tool will assess NMA biases and limitations regarding how the analysis was planned, data were analysed and results were presented, including the way in which the evidence was assembled and interpreted. Objectives: Conduct (a) a Delphi process to determine expert opinion on an item's inclusion and (b) a knowledge user survey to widen its impact. Design: Cross-sectional survey and Delphi process. Methods: Delphi panellists were asked to rate whether items should be included. All agreed-upon item were included in a second round of the survey (defined as 70% agreement). We surveyed knowledge users' views and preferences about the importance, utility and willingness to use the RoB NMA tool to evaluate evidence in practice and in policymaking. We included 12 closed and 10 open-ended questions, and we followed a knowledge translation plan to disseminate the survey through social media and professional networks. Results: 22 items were entered into a Delphi survey of which 28 respondents completed round 1, and 22 completed round 2. Seven items did not reach consensus in round 2. A total of 298 knowledge users participated in the survey (14% respondent rate). 75% indicated that their organisation produced NMAs, and 78% showed high interest in the tool, especially if they had received adequate training (84%). Most knowledge users and Delphi panellists preferred a tool to assess both bias in individual NMA results and authors' conclusions. Response bias in our sample is a major limitation as knowledge users working in high-income countries were more represented. One of the limitations of the Delphi process is that it depends on the purposive selection of experts and their availability, thus limiting the variability in perspectives and scientific disciplines. Conclusions: This Delphi process and knowledge user survey informs the development of the RoB NMA tool

Gene expression response in target organ and whole blood varies as a function of target organ injury phenotype

Histopathology, clinical chemistry, hematology and gene expression data were collected from the rat liver and blood after treatment with eight known hepatotoxins

Acetaminophen dosing of humans results in blood transcriptome and metabolome changes consistent with impaired oxidative phosphorylation

The diagnosis and management of drug-induced liver injury (DILI) is hindered by the limited utility of traditional clinical chemistries. It has recently been shown that hepatotoxicants can produce compound-specific changes in the peripheral blood (PB) transcriptome in rodents, suggesting the blood transcriptome might provide new biomarkers of DILI. To investigate in humans, we used DNA microarrays as well as serum metabolomic methods to characterize changes in the transcriptome and metabolome in serial PB samples obtained from 6 healthy adults treated with a 4 g bolus dose of acetaminophen (APAP) and from 3 receiving placebo. Treatment did not cause liver injury as assessed by traditional liver chemistries. However, 48 hours after exposure, treated subjects showed marked down-regulation of genes involved in oxidative phosphorylation/mitochondrial function that was not observed in the placebos (p <1.66E-19). The magnitude of down-regulation was positively correlated with the percent of APAP converted to the reactive metabolite NAPQI (r = 0.739; p=0.058). In addition, unbiased analysis of the serum metabolome revealed an increase in serum lactate from 24 to 72 hours post dosing in the treated subjects alone (p<0.005). Similar PB transcriptome changes were observed in human overdose patients and rats receiving toxic doses

Mutation of HIV-1 Genomes in a Clinical Population Treated with the Mutagenic Nucleoside KP1461

The deoxycytidine analog KP1212, and its prodrug KP1461, are prototypes of a new class of antiretroviral drugs designed to increase viral mutation rates, with the goal of eventually causing the collapse of the viral population. Here we present an extensive analysis of viral sequences from HIV-1 infected volunteers from the first “mechanism validation” phase II clinical trial of a mutagenic base analog in which individuals previously treated with antiviral drugs received 1600 mg of KP1461 twice per day for 124 days. Plasma viral loads were not reduced, and overall levels of viral mutation were not increased during this short-term study, however, the mutation spectrum of HIV was altered. A large number (N = 105 per sample) of sequences were analyzed, each derived from individual HIV-1 RNA templates, after 0, 56 and 124 days of therapy from 10 treated and 10 untreated control individuals (>7.1 million base pairs of unique viral templates were sequenced). We found that private mutations, those not found in more than one viral sequence and likely to have occurred in the most recent rounds of replication, increased in treated individuals relative to controls after 56 (p = 0.038) and 124 (p = 0.002) days of drug treatment. The spectrum of mutations observed in the treated group showed an excess of A to G and G to A mutations (p = 0.01), and to a lesser extent T to C and C to T mutations (p = 0.09), as predicted by the mechanism of action of the drug. These results validate the proposed mechanism of action in humans and should spur development of this novel antiretroviral approach.Koronis Pharmaceutical