Cryogenic Fluid Management Technology and Nuclear Thermal Propulsion

Cryogenic fluid management (CFM) is critical to the success of future nuclear thermal propulsion powered vehicles. While this is an issue for any propulsion system utilizing cryogenic propellants, this is made more challenging by the radiation flux produced by the reactor in a nuclear thermal rocket (NTR). Managing the cryogenic fuel to prevent propellant loss to boil off and leakage is needed to limit the required quantity of propellant to a reasonable level. Analysis shows deposition of energy into liquid hydrogen fuel tanks in the vicinity of the nuclear thermal engine. This is on top of ambient environment sources of heat. Investments in cryogenic/thermal management systems (some of which are ongoing at various organizations) are needed in parallel to nuclear thermal engine development in order to one day see the successful operation of an entire stage. High durability, low thermal conductivity insulation is one developmental need. Light weight cryocoolers capable of removing heat from large fluid volumes at temperatures as low as approx. 20 K are needed to remove heat leak from the propellant of an NTR. Valve leakage is an additional CFM issue of great importance. Leakage rates of state of the art, launch vehicle size valves (which is approximately the size valves needed for a Mars transfer vehicle) are quite high and would result in large quantities of lost propellant over a long duration mission. Additionally, the liquid acquisition system inside the propellant tank must deliver properly conditioned propellant to the feed line for successful engine operation and avoid intake of warm or gaseous propellant. Analysis of the thermal environment and the CFM technology development are discussed in the accompanying presentation

Risk Factors Associated with Mupirocin Resistance in Methicillin-Resistant Staphylococcus aureus

Implementation of meticillin-resistant Staphylococcus aureus (MRSA) decolonisation programmes has been increasing and the emergence of mupirocin resistance has been reported. However, the patient-level risk factors associated with mupirocin resistance are not clear. In this study, independent predictors of mupirocin resistance in MRSA among Providence Veterans Affairs Medical Center patients with MRSA-positive culture dates between 1 July 2004 and 30 June 2008 were identified using a frequency-matched case–control study. Forty cases (mupirocin-resistant) were matched on culture date quarter and year to 270 controls (mupirocin-susceptible). The adjusted conditional logistic regression model identified three significant independent predictors associated with mupirocin resistance in MRSA: (1) exposure to mupirocin in the year prior to the culture date [odds ratio (OR): 9.84; 95% confidence interval (CI): 2.93–33.09]; (2) Pseudomonas aeruginosa infection in the year before the culture-related admission (4.85; 1.20–19.61); and (3) cefepime use in the year prior to culture (2.80; 1.03–7.58). In sensitivity analyses, previous mupirocin exposure was associated with low-level [minimum inhibitory concentration (MIC) 8–128 mg/L; 23 cases, 202 controls; OR: 6.32; 95% CI: 1.58–25.33] and high-level (MIC ≥256 mg/L; 17 cases, 151 controls; OR: 11.18; 95% CI: 1.89–66.30) mupirocin resistance. To our knowledge, this is the first case–control study to reveal a strong association between previous mupirocin exposure and subsequent mupirocin resistance in MRSA, with demonstrated robustness in low- and high-level mupirocin resistance. Mupirocin susceptibility monitoring is critical for facilities instituting decolonisation with mupirocin as increased use may reduce effectiveness through resistance

An Investigation Into Human-centred Peer-support Education Systems for Students with Learning Difficulties

This research investigates the potential application and use of ICT in the development of peersupport networks centered on learners with Specific Learning Difficulties at third level education. Utilising a theoretical model based on both the social and medical models of disability, it is intended to develop a system that will allow learners to develop through interaction with their peers actionable education frameworks, adaptive learning strategies and reusable learning resources in a safe and contextualised learning environment. Primary research will be performed with the student population of Waterford Institute of Technology as a case study. The longitudinal goal is the improved retention, resilience and performance of the target population

Linker histone H1.2 and H1.4 affect the neutrophil lineage determination

Neutrophils are important innate immune cells that tackle invading pathogens with different effector mechanisms. They acquire this antimicrobial potential during their maturation in the bone marrow, where they differentiate from hematopoietic stem cells in a process called granulopoiesis. Mature neutrophils are terminally differentiated and short-lived with a high turnover rate. Here, we show a critical role for linker histone H1 on the differentiation and function of neutrophils using a genome-wide CRISPR/Cas9 screen in the human cell line PLB-985. We systematically disrupted expression of somatic H1 subtypes to show that individual H1 subtypes affect PLB-985 maturation in opposite ways. Loss of H1.2 and H1.4 induced an eosinophil-like transcriptional program, thereby negatively regulating the differentiation into the neutrophil lineage. Importantly, H1 subtypes also affect neutrophil differentiation and the eosinophil-directed bias of murine bone marrow stem cells, demonstrating an unexpected subtype-specific role for H1 in granulopoiesis

Liquid Phase Electron Microscopy of Bacterial Ultrastructure

Recent advances in liquid phase scanning transmission electron microscopy (LP‐STEM) have enabled the study of dynamic biological processes at nanometer resolutions, paving the way for live‐cell imaging using electron microscopy. However, this technique is often hampered by the inherent thickness of whole cell samples and damage from electron beam irradiation. These restrictions degrade image quality and resolution, impeding biological interpretation. Using graphene encapsulation, scanning transmission electron microscopy (STEM), and energy‐dispersive X‐ray (EDX) spectroscopy to mitigate these issues provides unprecedented levels of intracellular detail in aqueous specimens. This study demonstrates the potential of LP‐STEM to examine and identify internal cellular structures in thick biological samples. Specifically, it highlights the use of LP‐STEM to investigate the radiation resistant, gram‐positive bacterium, Deinococcus radiodurans using various imaging techniques

The Risk of Hepatotoxicity with Fluoroquinolones: A National Case-Control Safety Study

Purpose. Fluoroquinolones are generally considered safe and well-tolerated. However, suspected fluoroquinolone induced hepatotoxicity has been increasingly reported, but data are lacking. Thus, the objective of this study was to assess the risk of hepatotoxicity in patients using fluoroquinolones compared to non-users. Methods. National Veterans Affairs (VA) hospital admissions were assessed between January 1, 2002 and December 31, 2008. Our case-control study matched patients with a primary diagnosis of hepatotoxicity (cases) to those with myocardial infarction (controls) on admission date (matched up to 1:6). Conditional logistic regression was used to compute adjusted odds ratios (OR) and 95% confidence intervals (CI) of hepatotoxicity associated with fluoroquinolone exposure. Results. Our study included 7,862 cases and 45,512 matched controls. The majority of study patients were white (63.4%), males (97.7%), with a mean age of 61 years. After adjusting for confounders, fluoroquinolone use was significantly associated with a 20% increased risk of hepatotoxicity development (OR 1.20, 95% CI 1.04-1.38) compared to non-users. A statistically significant increased risk of hepatotoxicity was associated with ciprofloxacin use individually (OR 1.29, 95% CI 1.05-1.58), but not with levofloxacin or moxifloxacin use. Conclusion. The use of fluoroquinolones was associated with an increased risk of hepatotoxicity relative to non-users in our national VA study population

Bioactivity of Farnesyltransferase Inhibitors Against Entamoeba histolytica and Schistosoma mansoni.

The protozoan parasite Entamoeba histolytica can induce amebic colitis and amebic liver abscess. First-line drugs for the treatment of amebiasis are nitroimidazoles, particularly metronidazole. Metronidazole has side effects and potential drug resistance is a concern. Schistosomiasis, a chronic and painful infection, is caused by various species of the Schistosoma flatworm. There is only one partially effective drug, praziquantel, a worrisome situation should drug resistance emerge. As many essential metabolic pathways and enzymes are shared between eukaryotic organisms, it is possible to conceive of small molecule interventions that target more than one organism or target, particularly when chemical matter is already available. Farnesyltransferase (FT), the last common enzyme for products derived from the mevalonate pathway, is vital for diverse functions, including cell differentiation and growth. Both E. histolytica and Schistosoma mansoni genomes encode FT genes. In this study, we phenotypically screened E. histolytica and S. mansoni in vitro with the established FT inhibitors, lonafarnib and tipifarnib, and with 125 tipifarnib analogs previously screened against both the whole organism and/or the FT of Trypanosoma brucei and Trypanosoma cruzi. For E. histolytica, we also explored whether synergy arises by combining lonafarnib and metronidazole or lonafarnib with statins that modulate protein prenylation. We demonstrate the anti-amebic and anti-schistosomal activities of lonafarnib and tipifarnib, and identify 17 tipifarnib analogs with more than 75% growth inhibition at 50 μM against E. histolytica. Apart from five analogs of tipifarnib exhibiting activity against both E. histolytica and S. mansoni, 10 additional analogs demonstrated anti-schistosomal activity (severe degenerative changes at 10 μM after 24 h). Analysis of the structure-activity relationship available for the T. brucei FT suggests that FT may not be the relevant target in E. histolytica and S. mansoni. For E. histolytica, combination of metronidazole and lonafarnib resulted in synergism for growth inhibition. Also, of a number of statins tested, simvastatin exhibited moderate anti-amebic activity which, when combined with lonafarnib, resulted in slight synergism. Even in the absence of a definitive molecular target, identification of potent anti-parasitic tipifarnib analogs encourages further exploration while the synergistic combination of metronidazole and lonafarnib offers a promising treatment strategy for amebiasis

1437. Family Duty and Safety Linked to Overcoming Attitudinal Barriers to Adult Pneumococcal Vaccination in Disparate Populations

Background: Minority adult populations are at a higher risk for invasive pneumococcal disease and also have significantly lower vaccination rates when compared with the general population. Ingrained attitudes are a significant barrier to receipt of pneumococcal vaccine in these disparate populations, and therefore we tested targeted informational messaging to overcome these. Methods: A survey instrument of attitudinal questions related to pneumococcal vaccination was administered via YouGov, an online public national survey house in 2017. Socioeconomic information was captured and linked to baseline Likert scale attitudinal question responses. Respondents were randomly assigned into subsamples that received different science-based messages that included information on pneumococcal vaccines related to: pneumonia prevention, fatality/consequences, vaccine safety information, family duty/safety, and a combined vignette including all of these. Because of the random assignment, any differences observed in the respondents’ outcomes across subsamples can be attributed to the messages. Descriptive statistics were used to compare the persuasive effectiveness of these messages to conventional vaccine information across racial and ethnic groups. Results: A total of 2,608 respondents, 1,327 (51%) white and 1,281 (49%) non-white (over-sampled) were represented. Of the total respondents as well as in white, and non-white respondents, the combined vignette was associated with positive coefficients of b = 0.26, b = 0.24, and b = 0.32, respectively (P-values all \u3c0.05). In whites, the vaccine safety information and family duty/safety also had significant coefficients b = 0.24 ( = P = 0.012) and b = 0.24 (P = 0016), respectively. In non-Whites, family duty/safety was the only additional message with a significant coefficient b = 0.25 (P = 0.007). Conclusion: In this survey assessing attitudes toward pneumococcal vaccination across racial and ethnic subpopulations, the disparate population was persuaded to receive the vaccine only when family duty and safety were linked within the informational messages. Future studies implementing this informational messaging strategy should be performed to validate this finding