Energy-transport effects can alter the structure that develops as a supernova evolves into a supernova remnant. The Rayleigh-Taylor instability is thought to produce structure at the interface ...between the stellar ejecta and the circumstellar matter, based on simple models and hydrodynamic simulations. Here we report experimental results from the National Ignition Facility to explore how large energy fluxes, which are present in supernovae, affect this structure. We observed a reduction in Rayleigh-Taylor growth. In analyzing the comparison with supernova SN1993J, a Type II supernova, we found that the energy fluxes produced by heat conduction appear to be larger than the radiative energy fluxes, and large enough to have dramatic consequences. No reported astrophysical simulations have included radiation and heat conduction self-consistently in modeling supernova remnants and these dynamics should be noted in the understanding of young supernova remnants.
Fusion "scientific breakeven" (i.e., unity target gain G_{target}, total fusion energy out > laser energy input) has been achieved for the first time (here, G_{target}∼1.5). This Letter reports on ...the physics principles of the design changes that led to the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce target gain greater than unity and exceeded the previously obtained conditions needed for ignition by the Lawson criterion. Key elements of the success came from reducing "coast time" (the time duration between the end of the laser pulse and implosion peak compression) and maximizing the internal energy delivered to the "hot spot" (the yield producing part of the fusion fuel). The link between coast time and maximally efficient conversion of kinetic energy into internal energy is explained. The energetics consequences of asymmetry and hydrodynamic-induced mixing were part of high-yield big radius implosion design experimental and design strategy. Herein, it is shown how asymmetry and mixing consolidate into one key relationship. It is shown that mixing distills into a kinetic energy cost similar to the impact of implosion asymmetry, shifting the threshold for ignition to higher implosion kinetic energy-a factor not normally included in most statements of the generalized Lawson criterion, but the key needed modifications clearly emerge.
•Weight of evidence (WoE) method to evaluate key events in adverse outcome pathways.•Biological plausibility, empirical evidence and essentiality are WoE determinants.•Application to human health and ...ecological AOPs is illustrated with six examples.•A prototype quantitative decision analysis (MCDA) WoE model for AOPs is described.
Systematic consideration of scientific support is a critical element in developing and, ultimately, using adverse outcome pathways (AOPs) for various regulatory applications. Though weight of evidence (WoE) analysis has been proposed as a basis for assessment of the maturity and level of confidence in an AOP, methodologies and tools are still being formalized. The Organization for Economic Co-operation and Development (OECD) Users’ Handbook Supplement to the Guidance Document for Developing and Assessing AOPs (OECD 2014a; hereafter referred to as the OECD AOP Handbook) provides tailored Bradford-Hill (BH) considerations for systematic assessment of confidence in a given AOP. These considerations include (1) biological plausibility and (2) empirical support (dose-response, temporality, and incidence) for Key Event Relationships (KERs), and (3) essentiality of key events (KEs). Here, we test the application of these tailored BH considerations and the guidance outlined in the OECD AOP Handbook using a number of case examples to increase experience in more transparently documenting rationales for assigned levels of confidence to KEs and KERs, and to promote consistency in evaluation within and across AOPs. The major lessons learned from experience are documented, and taken together with the case examples, should contribute to better common understanding of the nature and form of documentation required to increase confidence in the application of AOPs for specific uses. Based on the tailored BH considerations and defining questions, a prototype quantitative model for assessing the WoE of an AOP using tools of multi-criteria decision analysis (MCDA) is described. The applicability of the approach is also demonstrated using the case example aromatase inhibition leading to reproductive dysfunction in fish. Following the acquisition of additional experience in the development and assessment of AOPs, further refinement of parameterization of the model through expert elicitation is recommended. Overall, the application of quantitative WoE approaches hold promise to enhance the rigor, transparency and reproducibility for AOP WoE determinations and may play an important role in delineating areas where research would have the greatest impact on improving the overall confidence in the AOP.
Indirect drive experiments at the National Ignition Facility are designed to achieve fusion by imploding a fuel capsule with x rays from a laser-driven hohlraum. Previous experiments have been unable ...to determine whether a deficit in measured ablator implosion velocity relative to simulations is due to inadequate models of the hohlraum or ablator physics. ViewFactor experiments allow for the first time a direct measure of the x-ray drive from the capsule point of view. The experiments show a 15%-25% deficit relative to simulations and thus explain nearly all of the disagreement with the velocity data. In addition, the data from this open geometry provide much greater constraints on a predictive model of laser-driven hohlraum performance than the nominal ignition target.
New approach methodologies (NAMs) are increasingly being used for regulatory decision making by agencies worldwide because of their potential to reliably and efficiently produce information that is ...fit for purpose while reducing animal use. This article summarizes the ability to use NAMs for the assessment of human health effects of industrial chemicals and pesticides within the United States, Canada, and European Union regulatory frameworks. While all regulations include some flexibility to allow for the use of NAMs, the implementation of this flexibility varies across product type and regulatory scheme. This article provides an overview of various agencies’ guidelines and strategic plans on the use of NAMs, and specific examples of the successful application of NAMs to meet regulatory requirements. It also summarizes intra- and inter-agency collaborations that strengthen scientific, regulatory, and public confidence in NAMs, thereby fostering their global use as reliable and relevant tools for toxicological evaluations. Ultimately, understanding the current regulatory landscape helps inform the scientific community on the steps needed to further advance timely uptake of approaches that best protect human health and the environment.
Recruitment and retention of medical practitioners is a challenging contemporary policy issue for rural areas. In this paper we explore this issue in the context of doctors in rural and remote ...Scotland, drawing on findings from a service mapping exercise into the recruitment and retention of doctors in rural areas, conducted by interviewing key stakeholders in the delivery of healthcare in rural and remote Scotland, most of whom combine clinical and organisational responsibilities. The aim of this paper is to understand the key issues, drawing on what the stakeholders see across the day‐to‐day delivery of their clinical roles and within the varied levels of the organisational structure of Scottish healthcare to which they contribute. Our findings build on a review of key literature of contemporary issues in rural Scotland, healthcare delivery in rural areas and wider international literature on recruitment and retention of medical practitioners. Our findings focus around three key themes: power of place; how people make place; and place and policy. In our conclusion, we argue that the importance of this stakeholder research is three‐fold. First, that such insights from stakeholders are important in shaping and preparing for future research on the topic, particularly interviewing those currently working. Second, it adds to and echoes the growing body of literature globally focused on recruitment and retention by expanding on the Scottish context. Finally, it proposes that appropriate and effective rural proofing is important in the implementation of new policies where place‐based challenges or differences can emerge.
Recruitment and retention of medical practitioners is a challenging contemporary policy issue for rural areas. The aim of this paper is to understand the key issues, drawing on what the stakeholders see across the day‐to‐day delivery of their clinical roles and within the varied levels of the organisational structure of Scottish healthcare to which they contribute.
Internationally, there are thousands of existing and newly introduced chemicals in commerce, highlighting the ongoing importance of innovative approaches to identify emerging chemicals of concern. ...For many chemicals, there is a paucity of hazard and exposure data. Thus, there is a crucial need for efficient and robust approaches to address data gaps and support risk-based prioritization. Several studies have demonstrated the utility of in vitro bioactivity data from the ToxCast program in deriving points of departure (PODs). ToxCast contains data for nearly 1,400 endpoints per chemical, and the bioactivity concentrations, indicative of potential adverse outcomes, can be converted to human-equivalent PODs using high-throughput toxicokinetics (HTTK) modeling. However, data gaps need to be addressed for broader application: the limited chemical space of HTTK and quantitative high-throughput screening data. Here we explore the applicability of in silico models to address these data needs. Specifically, we used ADMET predictor for HTTK predictions and a generalized read-across approach to predict ToxCast bioactivity potency. We applied these models to profile 5,801 chemicals on Canada’s Domestic Substances List (DSL). To evaluate the approach’s performance, bioactivity PODs were compared with in vivo results from the EPA Toxicity Values database for 1,042 DSL chemicals. Comparisons demonstrated that the bioactivity PODs, based on ToxCast data or read-across, were conservative for 95% of the chemicals. Comparing bioactivity PODs to human exposure estimates supports the identification of chemicals of potential interest for further work. The bioactivity workflow shows promise as a powerful screening tool to support effective triaging of chemical inventories.
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