Role of word-of-mouth for programs of voluntary vaccination: A game-theoretic approach

We propose a model describing the synergetic feedback between word-of-mouth (WoM) and epidemic dynamics controlled by voluntary vaccination. We combine a game-theoretic model for the spread of WoM and a compartmental model describing $SIR$ disease dynamics in the presence of a program of voluntary vaccination. We evaluate and compare two scenarios, depending on what WoM disseminates: (1) vaccine advertising, which may occur whether or not an epidemic is ongoing and (2) epidemic status, notably disease prevalence. Understanding the synergy between the two strategies could be particularly important for organizing voluntary vaccination campaigns. We find that, in the initial phase of an epidemic, vaccination uptake is determined more by vaccine advertising than the epidemic status. As the epidemic progresses, epidemic status become increasingly important for vaccination uptake, considerably accelerating vaccination uptake toward a stable vaccination coverage.Comment: 10 pages, 2 figure

Affordable Development and Qualification Strategy for Nuclear Thermal Propulsion

Nuclear Thermal Propulsion (NTP) is a concept which uses a nuclear reactor to heat a propellant to high temperatures without combustion and can achieve significantly greater specific impulse than chemical engines. NTP has been considered many times for human and cargo missions beyond low earth orbit. A lot of development and technical maturation of NTP components took place during the Rover/NERVA program of the 60's and early 70's. Other NTP programs and studies followed attempting to further mature the NTP concept and identify a champion customer willing to devote the funds and support the development schedule to a demonstration mission. Budgetary constraints require the use of an affordable development and qualification strategy that takes into account all the previous work performed on NTP to construct an existing database, and include lessons learned and past guidelines followed. Current guidelines and standards NASA uses for human rating chemical rocket engines is referenced. The long lead items for NTP development involve the fuel elements of the reactor and ground testing the engine system, subsystem, and components. Other considerations which greatly impact the development plans includes the National Space Policy, National Environmental Policy Act, Presidential Directive/National Security Council Memorandum #25 (Scientific or Technological Experiments with Possible Large-Scale Adverse Environmental Effects and Launch of Nuclear Systems into Space), and Safeguards and Security. Ground testing will utilize non-nuclear test capabilities to help down select components and subsystems before testing in a nuclear environment to save time and cost. Existing test facilities with minor modifications will be considered to the maximum extent practical. New facilities will be designed to meet minimum requirements. Engine and test facility requirements are based on the driving mission requirements with added factors of safety for better assurance and reliability. Emphasis will be placed on small engines, since the smaller the NTP engine, the easier it is to transport, assemble/disassemble, and filter the exhaust during tests. A new ground test concept using underground bore holes (modeled after the underground nuclear test program) to filter the NTP engine exhaust is being considered. The NTP engine system design, development, test, and evaluation plan includes many engine components and subsystems, which are very similar to those used in chemical engines, and can be developed in conjunction with them Other less mature NTP engine components and subsystems (e.g., reactor) will be thoroughly analyzed and tested to acceptable levels recommended by the referenced standards and guidelines. The affordable development strategy also considers a prototype flight test, as a final step in the development process. Preliminary development schedule estimates show that an aggressive development schedule (without much margin) will be required to be flight ready for a 2033 human mission to Mars

“Wait and see” vaccinating behavior

The final publication is available at Elsevier via http://dx.doi.org/10.1016/j.vaccine.2011.05.028. © 2011. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/During the 2009 H1N1 pandemic, many individuals adopted a “wait and see” approach to vaccinating until further information was available on the course of the pandemic and emerging vaccine risks. This behaviour implies two sources of strategic interactions between individuals: both perceived vaccine risk and the probability of becoming infected decline as more individuals become vaccinated. Here we analyze the outcome of these two strategic interactions by combining game theory with a mathematical model of disease transmission during an outbreak of a novel influenza strain. We include a case where perceived vaccine risk declines according to the cumulative number of individuals vaccinated. A common Nash equilibrium strategy exhibited by this model is a “wait and see” strategy where some individuals delay the decision to vaccinate, relying on the herd immunity provided by early vaccinators who also act as “guinea pigs” that validate the safety of the vaccine. The occurrence of “wait and see” strategies leads to a higher disease burden than occurs under socially optimal vaccine coverage. The model also exhibits both feedback and feed-forward processes. Feedback takes the form of individuals adjusting their vaccinating behaviour to accommodate changing transmissibility or risk parameters. Among other effects, this causes in the epidemic peak to occur at approximately the same time across a broad range of R0 values. Feedforward takes the form of high initial perceived vaccine risk perpetuating high perceived vaccine risks (and lower vaccine coverage) throughout the remainder of the outbreak, when perceived risk declines with the cumulative number vaccinated. This suggests that any effect of risk communication efforts at the start of a pandemic outbreak will be amplified compared to the same level of risk communication effort distributed throughout the outbreak, since any reductions in initial perceived risk will also result in reduced perceived risk throughout the outbreak.Canadian Institutes of Health Research. S. Bhattacharyya was supported through an internship from the CIHR Pandemic Outbreak Team Leader Grant (PTL-97126), Divi- sion of Mathematical Modeling, British Columbia Center for Disease Control (BCCDC) and through grants from the Ontario Ministry of Research and Innovation and the Natural Sciences and Engineering Research Council of Canada to C.T. Bauc

Affordable Development and Qualification Strategy for Nuclear Thermal Propulsion

A number of recent assessments have confirmed the results of several earlier studies that Nuclear Thermal Propulsion (NTP) is a leading technology for human exploration of Mars. It is generally acknowledged that NTP provides the best prospects for the transportation of humans to Mars in the 2030's. Its high Isp coupled with the high thrusts achievable, allow reasonable trip times, thereby alleviating concerns about space radiation and "claustrophobia" effects. NASA has embarked on the latest phase of the development of NTP systems, and is adopting an affordable approach in response to the pressure of the times. The affordable strategy is built on maximizing the use of the large NTP technology base developed in the 1950's and 60's. The fact that the NTP engines were actually demonstrated to work as planned, is a great risk reduction feature in its development. The strategy utilizes non-nuclear testing to the fullest extent possible, and uses focused nuclear tests for the essential qualification and certification tests. The perceived cost risk of conducting the ground tests is being addressed by considering novel testing approaches. This includes the use of boreholes to contain radioactive effluents, and use of fuel with very high retention capability for fission products. The use of prototype flight tests is being considered as final steps in the development prior to undertaking human flight missions. In addition to the technical issues, plans are being prepared to address the institutional and political issues that need to be considered in this major venture. While the development and deployment of NTP system is not expected to be cheap, the value of the system will be very high, and amortized over the many missions that it enables and enhances, the imputed costs will be very reasonable. Using the approach outlined, NASA and its partners, currently the DOE, and subsequently industry, have a good chance of creating a sustained development program leading to human missions to Mars within the next few decades

Allosteric regulation of tRNA import: interactions between tRNA domains at the inner membrane of Leishmania mitochondria

Import of nucleus‐encoded tRNAs into the mitochondria of the kinetoplastid protozoon Leishmania involves recognition of specific import signals by the membrane‐bound import machinery. Multiple signals on different tRNA domains may be present, and further, importable RNAs interact positively (Type I) or negatively (Type II) with one another at the inner membrane in vitro. By co‐transfection assays, it is shown here that tRNATyr (Type I) transiently stimulates the rate of entry of tRNAIle (Type II) into Leishmania mitochondria in transfected cells, and conversely, is inhibited by tRNAIle. Truncation and mutagenesis experiments led to the co‐localization of the effector and import activities of tRNATyr to the D domain and those of tRNAIle to the variable region–T domain (V‐T region), indicating that both activities originate from a single RNA–receptor interaction. A third tRNA, human tRNALys, is imported into Leishmania mitochondria in vitro as well as in vivo. This tRNA has Type I and Type II motifs in the D domain and the V‐T region, respectively, and shows both Type I and Type II effector activities. Such dual‐type tRNAs may interact simultaneously with the Type I and Type II binding sites of the inner membrane import machinery

Human Cultural Dimensions and Behavior during COVID-19 Can Lead to Policy Resistance and Economic Losses: A Perspective from Game Theory Analysis

The recent COVID-19 pandemic has caused significant societal impacts. Besides loss of life there were large additional costs incurred by every country including the treatment of patients and costs to implement response plans. The pandemic resulted in major economic disruptions and stalled growth worldwide due to travel bans, lockdowns, social distancing, and non-essential business closures. Public health officials in almost every country implemented and encouraged Nonpharmaceutical Interventions (NPIs) such as contact tracing, social distancing, masks, and isolation. Human behavioral decision-making concerning social isolation was a major hindrance to the success in curbing the pandemic worldwide. In many developing countries individuals’ choices were motivated by the competing risk of losing jobs, and daily income. In this chapter we focus on human behavior concerning social isolation in the context of decision-making during the pandemic. We developed a conceptual framework and deterministic model that integrated evolutionary game theory within our disease transmission model. We illustrate scenarios numerically simulating the model. This study highlights the idea that human behavior is an important component in successful disease control strategies. Economic resilience, especially in low-income countries, can improve public understanding and uptake of NPIs

Disparity in socio-economic status explains the pattern of self-medication of antibiotics in India: Understanding from game-theoretic perspective

The emergence of antimicrobial resistance has raised great concern for public health in many lower-income countries including India. Socio-economic determinants like poverty, health expenditure and awareness accelerate this emergence by influencing individuals' attitudes and healthcare practices such as self-medication. This self-medication practice is highly prevalent in many countries, where antibiotics are available without prescriptions. Thus, complex dynamics of drug- resistance driven by economy, human behaviour, and disease epidemiology poses a serious threat to the community, which has been less emphasized in prior studies. Here, we formulate a game-theoretic model of human choices in self-medication integrating economic growth and disease transmission processes. We show that this adaptive behaviour emerges spontaneously in the population through a self-reinforcing process and continual feedback from the economy, resulting in the emergence of resistance as externalities of human choice under resource constraints situations. We identify that the disparity between social-optimum and individual interest in self-medication is primarily driven by the effectiveness of treatment, health awareness and public health interventions. Frequent multiple-peaks of resistant strains are also observed when individuals imitate others more readily and self-medication is more likely. Our model exemplifies that timely public health intervention for financial risk protection, and antibiotic stewardship policies can improve the epidemiological situation and prevent economic collapse.S.B. thanks Science and Engineering Research Board (SERB), DST, India for financial support (ECR/2016/ 000591) to conduct this researc

A mosaic of RNA binding and protein interaction motifs in a bifunctional mitochondrial tRNA import factor from Leishmania tropica

Proteins that participate in the import of cytosolic tRNAs into mitochondria have been identified in several eukaryotic species, but the details of their interactions with tRNA and other proteins are unknown. In the kinetoplastid protozoon Leishmania tropica, multiple proteins are organized into a functional import complex. RIC8A, a tRNA-binding subunit of this complex, has a C-terminal domain that functions as subunit 6b of ubiquinol cytochrome c reductase (complex III). We show that the N-terminal domain, unique to kinetoplastid protozoa, is structurally similar to the appended S15/NS1 RNA-binding domain of aminoacyl tRNA synthetases, with a helix–turn–helix motif. Structure-guided mutagenesis coupled with in vitro assays showed that helix α1 contacts tRNA whereas helix α2 targets the protein for assembly into the import complex. Inducible expression of a helix 1-deleted variant in L. tropica resulted in formation of an inactive import complex, while the helix 2-deleted variant was unable to assemble in vivo. Moreover, a protein-interaction assay showed that the C-terminal domain makes allosteric contacts with import receptor RIC1 complexed with tRNA. These results help explain the origin of the bifunctionality of RIC8A, and the allosteric changes accompanying docking and release of tRNA during import