Experimental Validation of Stratified Flow Phenomena, Graphite Oxidation, and Mitigation Strategies of Air Ingress Accidents

The US Department of Energy is performing research and development (R&D) that focuses on key phenomena that are important during challenging scenarios that may occur in the Next Generation Nuclear Plant (NGNP) Program / GEN-IV Very High Temperature Reactor (VHTR). Phenomena identification and ranking studies (PIRT) to date have identified the air ingress event, following on the heels of a VHTR depressurization, as very important (Schultz et al., 2006). Consequently, the development of advanced air ingress-related models and verification and validation (V&V) are very high priority for the NGNP program. Following a loss of coolant and system depressurization, air will enter the core through the break. Air ingress leads to oxidation of the in-core graphite structure and fuel. The oxidation will accelerate heat-up of the bottom reflector and the reactor core and will cause the release of fission products eventually. The potential collapse of the bottom reflector because of burn-off and the release of CO lead to serious safety problems. For estimation of the proper safety margin we need experimental data and tools, including accurate multi-dimensional thermal-hydraulic and reactor physics models, a burn-off model, and a fracture model. We also need to develop effective strategies to mitigate the effects of oxidation. The results from this research will provide crucial inputs to the INL NGNP/VHTR Methods R&D project. This project is focused on (a) analytical and experimental study of air ingress caused by density-driven, stratified, countercurrent flow, (b) advanced graphite oxidation experiments, (c) experimental study of burn-off in the bottom reflector, (d) structural tests of the burnt-off bottom reflector, (e) implementation of advanced models developed during the previous tasks into the GAMMA code, (f) full air ingress and oxidation mitigation analyses, (g) development of core neutronic models, (h) coupling of the core neutronic and thermal hydraulic models, and (i) verification and validation of the coupled models

Evaluation of the transporter-mediated herb-drug interaction potential of DA-9801, a standardized dioscorea extract for diabetic neuropathy, in human in vitro and rat in vivo

BACKGROUND: Drug transporters play important roles in the absorption, distribution, and elimination of drugs and thereby, modulate drug efficacy and toxicity. With a growing use of poly pharmacy, concurrent administration of herbal extracts that modulate transporter activities with drugs can cause serious adverse reactions. Therefore, prediction and evaluation of drug-drug interaction potential is important in the clinic and in the drug development process. DA-9801, comprising a mixed extract of Dioscoreae rhizoma and Dioscorea nipponica Makino, is a new standardized extract currently being evaluated for diabetic peripheral neuropathy in a phase II clinical study. METHOD: The inhibitory effects of DA-9801 on the transport functions of organic cation transporter (OCT)1, OCT2, organic anion transporter (OAT)1, OAT3, organic anion transporting polypeptide (OATP)1B1, OATP1B3, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP) were investigated in HEK293 or LLC-PK1 cells. The effects of DA-9801 on the pharmacokinetics of relevant substrate drugs of these transporters were also examined in vivo in rats. RESULTS: DA-9801 inhibited the in vitro transport activities of OCT1, OCT2, OAT3, and OATP1B1, with IC(50) values of 106, 174, 48.1, and 273 μg/mL, respectively, while the other transporters were not inhibited by 300 μg/mL DA-9801. To investigate whether this inhibitory effect of DA-9801 on OCT1, OCT2, and OAT3 could change the pharmacokinetics of their substrates in vivo, we measured the pharmacokinetics of cimetidine, a substrate for OCT1, OCT2, and OAT3, and of furosemide, a substrate for OAT1 and OAT3, by co-administration of DA-9801 at a single oral dose of 1,000 mg/kg. Pre-dose of DA-9801 5 min or 2 h prior to cimetidine administration decreased the C(max) of cimetidine in rats. However, DA-9801 did not affect the elimination parameters such as half-life, clearance, or amount excreted in the urine, suggesting that it did not inhibit elimination process of cimetidine, which is governed by OCT1, OCT2, and OAT3. Moreover, DA-9801 did not affect the pharmacokinetic characteristics of furosemide, as evidenced by its unchanged pharmacokinetic parameters. CONCLUSION: Inhibitory effects of DA-9801 on OCT1, OCT2, and OAT3 observed in vitro may not necessarily translate into in vivo herb-drug interactions in rats even at its maximum effective dose

Utility of Parental Mediation Model on Youth’s Problematic Online Gaming

The Parental Mediation Model PMM) was initially designed to regulate children’s attitudes towards the traditional media. In the present era, because of prevalent online media there is a need for similar regulative measures. Spending long hours on social media and playing online games increase the risks of exposure to the negative outcomes of online gaming. This paper initially applied the PMM developed by European Kids Online to (i) test the reliability and validity of this model and (ii) identify the effectiveness of this model in controlling problematic online gaming (POG). The data were collected from 592 participants comprising 296 parents and 296 students of four foreign universities, aged 16 to 22 years in Kuala Lumpur (Malaysia). The study found that the modified model of the five-factor PMM (Technical mediation, Monitoring mediation, Restrictive mediation, Active Mediation of Internet Safety, and Active mediation of Internet Use) functions as a predictor for mitigating POG. The findings suggest the existence of a positive relation between ‘monitoring’ and ‘restrictive’ mediation strategies and exposure to POG while Active Mediation of Internet Safety and Active mediation of Internet use were insignificant predictors. Results showed a higher utility of ‘technical’ strategies by the parents led to less POG. The findings of this study do not support the literature suggesting active mediation is more effective for reducing youth’s risky behaviour. Instead, parents need to apply more technical mediations with their children and adolescents’ Internet use to minimize the negative effects of online gaming

Co-occurrence of Point Mutations in the Voltage-Gated Sodium Channel of Pyrethroid-Resistant Aedes aegypti Populations in Myanmar

Background:Single amino acid substitutions in the voltage-gated sodium channel associated with pyrethroid resistance constitute one of the main causative factors of knockdown resistance in insects. The kdr gene has been observed in several mosquito species; however, point mutations in the para gene of Aedes aegypti populations in Myanmar have not been fully characterized. The aim of the present study was to determine the types and frequencies of mutations in the para gene of Aedes aegypti collected from used tires in Yangon City, Myanmar.Methodology/Principal Findings:We determined high pyrethroid resistance in Aedes aegypti larvae at all collection sites in Yangon City, by using a simplified knockdown bioassay. We showed that V1016G and S989P mutations were widely distributed, with high frequencies (84.4% and 78.8%, respectively). By contrast, we were unable to detect I1011M (or I1011V) or L1014F mutations. F1534C mutations were also widely distributed, but with a lower frequency than the V1016G mutation (21.2%). High percentage of co-occurrence of the homozygous V1016G/S989P mutations was detected (65.7%). Additionally, co-occurrence of homozygous V1016G/F1534C mutations (2.9%) and homozygous V1016G/F1534C/S989P mutations (0.98%) were detected in the present study.Conclusions/Significance:Pyrethroid insecticides were first used for malaria control in 1992, and have since been constantly used in Myanmar. This intensive use may explain the strong selection pressure toward Aedes aegypti, because this mosquito is generally a domestic and endophagic species with a preference for indoor breeding. Extensive use of DDT for malaria control before the use of this chemical was banned may also explain the development of pyrethroid resistance in Aedes aegypti

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Acceleration of source convergence in Monte Carlo k-eigenvalue problems via anchoring with a p-CMFD deterministic method

a b s t r a c t The Monte Carlo method is widely used in neutron transport calculations, especially in complex geometry and continuous-energy problems. However, an extended application of the Monte Carlo method to large realistic eigenvalue problems remains a challenge due to its slow convergence and large fluctuations in the fission source distribution. In this paper, a deterministic partial current-based Coarse-Mesh Finite Difference (p-CMFD) method is proposed that achieves fast convergence in fission source distribution in Monte Carlo k-eigenvalue problems. In this method, the high-order Monte Carlo method provides homogenized and condensed cross section parameters while the low-order deterministic p-CMFD method provides anchoring of the fission source distribution. The proposed method is implemented in the MCNP5 code (version 1.30) and tested on realistic one-and two-dimensional heterogeneous continuous-energy large core problems, with encouraging results