Impact of changes in protective behaviors and out-of-household activities by age on COVID-19 transmission and hospitalization in Chicago, Illinois.

PURPOSE: Even with an efficacious vaccine, protective behaviors (social distancing, masking) are essential for preventing COVID-19 transmission and could become even more important if current or future variants evade immunity from vaccines or prior infection. METHODS: We created an agent-based model representing the Chicago population and conducted experiments to determine the effects of varying adult out-of-household activities (OOHA), school reopening, and protective behaviors across age groups on COVID-19 transmission and hospitalizations. RESULTS: From September-November 2020, decreasing adult protective behaviors and increasing adult OOHA both substantially impacted COVID-19 outcomes; school reopening had relatively little impact when adult protective behaviors and OOHA were maintained. As of November 1, 2020, a 50% reduction in young adult (age 18-40) protective behaviors resulted in increased latent infection prevalence per 100,000 from 15.93 (IQR 6.18, 36.23) to 40.06 (IQR 14.65, 85.21) and 19.87 (IQR 6.83, 46.83) to 47.74 (IQR 18.89, 118.77) with 15% and 45% school reopening. Increasing adult (age ≥18) OOHA from 65% to 80% of prepandemic levels resulted in increased latent infection prevalence per 100,000 from 35.18 (IQR 13.59, 75.00) to 69.84 (IQR 33.27, 145.89) and 38.17 (IQR 15.84, 91.16) to 80.02 (IQR 30.91, 186.63) with 15% and 45% school reopening. Similar patterns were observed for hospitalizations. CONCLUSIONS: In areas without widespread vaccination coverage, interventions to maintain adherence to protective behaviors, particularly among younger adults and in out-of-household settings, remain a priority for preventing COVID-19 transmission.

Uncertainty-Informed Deep Transfer Learning of Perfluoroalkyl and Polyfluoroalkyl Substance Toxicity.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) pose a significant hazard because of their widespread industrial uses, environmental persistence, and bioaccumulation. A growing, increasingly diverse inventory of PFAS, including 8163 chemicals, has recently been updated by the U.S. Environmental Protection Agency. However, with the exception of a handful of well-studied examples, little is known about their human toxicity potential because of the substantial resources required for in vivo toxicity experiments. We tackle the problem of expensive in vivo experiments by evaluating multiple machine learning (ML) methods, including random forests, deep neural networks (DNN), graph convolutional networks, and Gaussian processes, for predicting acute toxicity (e.g., median lethal dose, or LD50) of PFAS compounds. To address the scarcity of toxicity information for PFAS, publicly available datasets of oral rat LD50 for all organic compounds are aggregated and used to develop state-of-the-art ML source models for transfer learning. A total of 519 fluorinated compounds containing two or more C-F bonds with known toxicity are used for knowledge transfer to ensembles of the best-performing source model, DNN, to generate the target models for the PFAS domain with access to uncertainty. This study predicts toxicity for PFAS with a defined chemical structure. To further inform prediction confidence, the transfer-learned model is embedded within a SelectiveNet architecture, where the model is allowed to identify regions of prediction with greater confidence and abstain from those with high uncertainty using a calibrated cutoff rate.

Characterizing Risk for Cumulative Risk Assessments.

In assessing environmental health risks, the risk characterization step synthesizes information gathered in evaluating exposures to stressors together with dose-response relationships, characteristics of the exposed population, and external environmental conditions. This article summarizes key steps of a cumulative risk assessment (CRA) followed by a discussion of considerations for characterizing cumulative risks. Cumulative risk characterizations differ considerably from single chemical- or single source-based risk characterization. CRAs typically focus on a specific population instead of a pollutant or pollutant source and should include an evaluation of all relevant sources contributing to the exposures in the population and other factors that influence dose-response relationships. Second, CRAs may include influential environmental and population-specific conditions, involving multiple chemical and nonchemical stressors. Third, a CRA could examine multiple health effects, reflecting joint toxicity and the potential for toxicological interactions. Fourth, the complexities often necessitate simplifying methods, including judgment-based and semi-quantitative indices that collapse disparate data into numerical scores. Fifth, because of the higher dimensionality and potentially large number of interactions, information needed to quantify risk is typically incomplete, necessitating an uncertainty analysis. Three approaches that could be used for characterizing risks in a CRA are presented: the multiroute hazard index, stressor grouping by exposure and toxicity, and indices for screening multiple factors and conditions. Other key roles of the risk characterization in CRAs are also described, mainly the translational aspect of including a characterization summary for lay readers (in addition to the technical analysis), and placing the results in the context of the likely risk-based decisions.

Advancing Risk Analysis for Nanoscale Materials: Report from an International Workshop on the Role of Alternative Testing Strategies for Advancement.

The Society for Risk Analysis (SRA) has a history of bringing thought leadership to topics of emerging risk. In September 2014, the SRA Emerging Nanoscale Materials Specialty Group convened an international workshop to examine the use of alternative testing strategies (ATS) for manufactured nanomaterials (NM) from a risk analysis perspective. Experts in NM environmental health and safety, human health, ecotoxicology, regulatory compliance, risk analysis, and ATS evaluated and discussed the state of the science for in vitro and other alternatives to traditional toxicology testing for NM. Based on this review, experts recommended immediate and near-term actions that would advance ATS use in NM risk assessment. Three focal areas-human health, ecological health, and exposure considerations-shaped deliberations about information needs, priorities, and the next steps required to increase confidence in and use of ATS in NM risk assessment. The deliberations revealed that ATS are now being used for screening, and that, in the near term, ATS could be developed for use in read-across or categorization decision making within certain regulatory frameworks. Participants recognized that leadership is required from within the scientific community to address basic challenges, including standardizing materials, protocols, techniques and reporting, and designing experiments relevant to real-world conditions, as well as coordination and sharing of large-scale collaborations and data. Experts agreed that it will be critical to include experimental parameters that can support the development of adverse outcome pathways. Numerous other insightful ideas for investment in ATS emerged throughout the discussions and are further highlighted in this article.

Cumulative risk assessment toolbox: methods and approaches for the practitioner.

The historical approach to assessing health risks of environmental chemicals has been to evaluate them one at a time. In fact, we are exposed every day to a wide variety of chemicals and are increasingly aware of potential health implications. Although considerable progress has been made in the science underlying risk assessments for real-world exposures, implementation has lagged because many practitioners are unaware of methods and tools available to support these analyses. To address this issue, the US Environmental Protection Agency developed a toolbox of cumulative risk resources for contaminated sites, as part of a resource document that was published in 2007. This paper highlights information for nearly 80 resources from the toolbox and provides selected updates, with practical notes for cumulative risk applications. Resources are organized according to the main elements of the assessment process: (1) planning, scoping, and problem formulation; (2) environmental fate and transport; (3) exposure analysis extending to human factors; (4) toxicity analysis; and (5) risk and uncertainty characterization, including presentation of results. In addition to providing online access, plans for the toolbox include addressing nonchemical stressors and applications beyond contaminated sites and further strengthening resource accessibility to support evolving analyses for cumulative risk and sustainable communities.

Nano risk analysis: advancing the science for nanomaterials risk management.

Scientists, activists, industry, and governments have raised concerns about health and environmental risks of nanoscale materials. The Society for Risk Analysis convened experts in September 2008 in Washington, DC to deliberate on issues relating to the unique attributes of nanoscale materials that raise novel concerns about health risks. This article reports on the overall themes and findings of the workshop, uncovering the underlying issues for each of these topics that become recurring themes. The attributes of nanoscale particles and other nanomaterials that present novel issues for risk analysis are evaluated in a risk analysis framework, identifying challenges and opportunities for risk analysts and others seeking to assess and manage the risks from emerging nanoscale materials and nanotechnologies. Workshop deliberations and recommendations for advancing the risk analysis and management of nanotechnologies are presented.

An approach for assessing human exposures to chemical mixtures in the environment.

Humans are exposed daily to multiple chemicals, including incidental exposures to complex chemical mixtures released into the environment and to combinations of chemicals that already co-exist in the environment because of previous releases from various sources. Exposures to chemical mixtures can occur through multiple pathways and across multiple routes. In this paper, we propose an iterative approach for assessing exposures to environmental chemical mixtures; it is similar to single-chemical approaches. Our approach encompasses two elements of the Risk Assessment Paradigm: Problem Formulation and Exposure Assessment. Multiple phases of the assessment occur in each element of the paradigm. During Problem Formulation, analysts identify and characterize the source(s) of the chemical mixture, ensure that dose-response and exposure assessment measures are concordant, and develop a preliminary evaluation of the mixture's fate. During Exposure Assessment, analysts evaluate the fate of the chemicals comprising the mixture using appropriate models and measurement data, characterize the exposure scenario, and estimate human exposure to the mixture. We also describe the utility of grouping the chemicals to be analyzed based on both physical-chemical properties and an understanding of environmental fate. In the article, we also highlight the need for understanding of changes in the mixture composition in the environment due to differential transport, differential degradation, and differential partitioning to other media. The Results section describes the application of the method to various chemical mixtures, highlighting issues associated with assessing exposures to chemical mixtures in the environment.

Regulating under uncertainty: newsboy for exposure limits.

Setting action levels or limits for health protection is complicated by uncertainty in the dose-response relation across a range of hazards and exposures. To address this issue, we consider the classic newsboy problem. The principles used to manage uncertainty for that case are applied to two stylized exposure examples, one for high dose and high dose rate radiation and the other for ammonia. Both incorporate expert judgment on uncertainty quantification in the dose-response relationship. The mathematical technique of probabilistic inversion also plays a key role. We propose a coupled approach, whereby scientists quantify the dose-response uncertainty using techniques such as structured expert judgment with performance weights and probabilistic inversion, and stakeholders quantify associated loss rates.

A phased approach for assessing combined effects from multiple stressors.

We present a phased approach for evaluating the effects of physical, biological, chemical, and psychosocial stressors that may act in combination. Although a phased concept is common to many risk-based approaches, it has not been explicitly outlined for the assessment of combined effects of multiple stressors. The approach begins with the development of appropriate conceptual models and assessment end points. The approach then proceeds through a screening stage wherein stressors are evaluated with respect to their potential importance as contributors to risk. Stressors are considered individually or as a combination of independent factors with respect to one or more common assessment end points. As necessary, the approach then proceeds to consider interactions among stressors. We make a distinction between applications that begin with effects of concern (effects based) or with specific stressors (stressor based). We describe a number of tools for use within the phased approach. The methods profiled are ones that have been applied to yield results that can be communicated to a wide audience. The latter characteristic is considered especially important because multiple stressor problems usually involve exposures to communities or to ecologic regions with many stakeholders.

Engineered containment and control systems: nurturing nature.

The development of engineered containment and control systems for contaminated sites must consider the environmental setting of each site. The behaviors of both contaminated materials and engineered systems are affected by environmental conditions that will continue to evolve over time as a result of such natural processes as climate change, ecological succession, pedogenesis, and landform changes. Understanding these processes is crucial to designing, implementing, and maintaining effective systems for sustained health and environmental protection. Traditional engineered systems such as landfill liners and caps are designed to resist natural processes rather than working with them. These systems cannot be expected to provide long-term isolation without continued maintenance. In some cases, full-scale replacement and remediation may be required within 50 years, at an effort and cost much higher than for the original cleanup. Approaches are being developed to define smarter containment and control systems for stewardship sites, considering lessons learned from implementing prescriptive waste disposal regulations enacted since the 1970s. These approaches more effectively involve integrating natural and engineered systems; enhancing sensors and predictive tools for evaluating performance; and incorporating information on failure events, including precursors and consequences, into system design and maintenance. An important feature is using natural analogs to predict environmental conditions and system responses over the long term, to accommodate environmental change in the design process, and, as possible, to engineer containment systems that mimic favorable natural systems. The key emphasis is harmony with the environment, so systems will work with and rely on natural processes rather than resisting them. Implementing these new integrated systems will reduce current requirements for active management, which are resource-intensive and expensive.

Priorities for mixtures health effects research.

In order to better inform scientific decision making in the occupational environment, we need a better understanding of the toxicology of mixed exposures. In particular, we need an understanding of the dose-response relationship from the level of individual or population exposure down to the molecular level (and then back up again from the molecular level to the specific health-related response of the organism as a whole). Mixtures toxicology is proving to be different from single-chemical toxicology in several fundamental but barely recognized ways: Knowledge gained in mixtures research should be able to improve current risk assessment and mitigation or intervention methods. In NIOSH's National Occupational Research Agenda (NORA) three priority areas have been identified:

Synergy and other ineffective mixture risk definitions.

A substantial effort has been spent over the past few decades to label toxicologic interaction outcomes as synergistic, antagonistic, or additive. Although useful in influencing the emotions of the public and the press, these labels have contributed fairly little to our understanding of joint toxic action. Part of the difficulty is that their underlying toxicological concepts are only defined for two chemical mixtures, while most environmental and occupational exposures are to mixtures of many more chemicals. Furthermore, the mathematical characterizations of synergism and antagonism are inextricably linked to the prevailing definition of 'no interaction,' instead of some intrinsic toxicological property. For example, the US EPA has selected dose addition as the no-interaction definition for mixture risk assessment, so that synergism would represent toxic effects that exceed those predicted from dose addition. For now, labels such as synergism are useful to regulatory agencies, both for qualitative indications of public health risk as well as numerical decision tools for mixture risk characterization. Efforts to quantify interaction designations for use in risk assessment formulas, however, are highly simplified and carry large uncertainties. Several research directions, such as pharmacokinetic measurements and models, and toxicogenomics, should promote significant improvements by providing multi-component data that will allow biologically based mathematical models of joint toxicity to replace these pairwise interaction labels in mixture risk assessment procedures.

Volume and activity of buried transuranic-contaminated wastes at U.S. Department of Energy facilities.

From the 1940's through the 1970's, radioactive wastes meeting the current definition of transuranic wastes were disposed of by shallow land burial and other techniques at a number of sites owned and operated by the federal government in support of the nuclear weapons program. After transuranic wastes were identified as a separate category of radioactive wastes (distinct from low-level wastes) in 1970 by the U.S. Atomic Energy Commission, they were generally segregated and placed in retrievable storage pending the availability of a geologic repository. Updated information on buried transuranic wastes was recently developed to support future decisions on how to manage these materials. This paper summarizes the approach used to develop this information for U.S. Department of Energy facilities and presents the volumes and transuranic activities of these wastes. The total volume of buried transuranic wastes at DOE sites is approximately 126,000 m3 with a much smaller volume (about 11,000 m3) disposed of at intermediate depths. The reported transuranic activity in these previously disposed of wastes is about 28,000 TBq.

Integrating information for better environmental decisions.

As more is learned about the complex nature and extent of environmental impacts from progressive human disturbance, scientists, policy analysts, decision makers, educators, and communicators are increasingly joining forces to develop strategies for preserving and protecting the environment. The Eco-Informa Foundation is an educational scientific organization dedicated to promoting the collaborative development and sharing of scientific information. The Foundation participated in a recent international conference on environmental informatics through a special symposium on integrating information for better environmental decisions. Presentations focused on four general themes: (1) remote sensing and data interpretation, including through new knowledge management tools; (2) risk assessment and communication, including for radioactively contaminated facilities, introduced biological hazards, and food safety; (3) community involvement in cleanup projects; and (4) environmental education. The general context for related issues, methods and applications, and results and recommendations from those discussions are highlighted here.