Simulating the Simultaneous Impact of Medication for Opioid Use Disorder and Naloxone on Opioid Overdose Death in Eight New York Counties.

BACKGROUND: The United States is in the midst of an opioid overdose epidemic; 28.3 per 100,000 people died of opioid overdose in 2020. Simulation models can help understand and address this complex, dynamic, and nonlinear social phenomenon. Using the HEALing Communities Study, aimed at reducing opioid overdoses, and an agent-based model, Simulation of Community-Level Overdose Prevention Strategy, we simulated increases in buprenorphine initiation and retention and naloxone distribution aimed at reducing overdose deaths by 40% in New York Counties. METHODS: Our simulations covered 2020-2022. The eight counties contrasted urban or rural and high and low baseline rates of opioid use disorder treatment. The model calibrated agent characteristics for opioid use and use disorder, treatments and treatment access, and fatal and nonfatal overdose. Modeled interventions included increased buprenorphine initiation and retention, and naloxone distribution. We predicted a decrease in the rate of fatal opioid overdose 1 year after intervention, given various modeled intervention scenarios. RESULTS: Counties required unique combinations of modeled interventions to achieve a 40% reduction in overdose deaths. Assuming a 200% increase in naloxone from current levels, high baseline treatment counties achieved a 40% reduction in overdose deaths with a simultaneous 150% increase in buprenorphine initiation. In comparison, low baseline treatment counties required 250-300% increases in buprenorphine initiation coupled with 200-1000% increases in naloxone, depending on the county. CONCLUSIONS: Results demonstrate the need for tailored county-level interventions to increase service utilization and reduce overdose deaths, as the modeled impact of interventions depended on the county's experience with past and current interventions.

Inverse Generative Social Science: Backward to the Future.

The agent-based model is the principal scientific instrument of generative social science. Typically, we design completed agents-fully endowed with rules and parameters-to grow macroscopic target patterns from the bottom up. Inverse generative science (iGSS) stands this approach on its head: Rather than handcrafting completed agents to grow a target-the forward problem-we start with the macro-target and evolve micro-agents that generate it, stipulating only primitive agent-rule constituents and permissible combinators. Rather than specific agents as designed inputs, we are interested in agents-indeed, families of agents-as evolved outputs. This is the backward problem and tools from Evolutionary Computing can help us solve it. In this overarching essay of the current JASSS Special Section, Part 1 discusses the motivation for iGSS. Part 2 discusses its goals, as distinct from other approaches. Part 3 discusses how to do it concretely, previewing the five iGSS applications that follow. Part 4 discusses several foundational issues for agent-based modeling and economics. Part 5 proposes a central future application of iGSS: to evolve explicit formal alternatives to the Rational Actor, with Agent_Zero as one possible point of evolutionary departure. Conclusions and future research directions are offered in Part 6. Looking 'backward to the future,' I also include, as Appendices, a pair of 1992 memoranda to the then President of the Santa Fe Institute on the forward (growing artificial societies from the bottom up) and backward (iGSS) problems.

Can Social Norms Explain Long-Term Trends in Alcohol Use? Insights from Inverse Generative Social Science.

Social psychological theory posits entities and mechanisms that attempt to explain observable differences in behavior. For example, dual process theory suggests that an agent's behavior is influenced by intentional (arising from reasoning involving attitudes and perceived norms) and unintentional (i.e., habitual) processes. In order to pass the generative sufficiency test as an explanation of alcohol use, we argue that the theory should be able to explain notable patterns in alcohol use that exist in the population, e.g., the distinct differences in drinking prevalence and average quantities consumed by males and females. In this study, we further develop and apply inverse generative social science (iGSS) methods to an existing agent-based model of dual process theory of alcohol use. Using iGSS, implemented within a multi-objective grammar-based genetic program, we search through the space of model structures to identify whether a single parsimonious model can best explain both male and female drinking, or whether separate and more complex models are needed. Focusing on alcohol use trends in New York State, we identify an interpretable model structure that achieves high goodness-of-fit for both male and female drinking patterns simultaneously, and which also validates successfully against reserved trend data. This structure offers a novel interpretation of the role of norms in formulating drinking intentions, but the structure's theoretical validity is questioned by its suggestion that individuals with low autonomy would act against perceived descriptive norms. Improved evidence on the distribution of autonomy in the population is needed to understand whether this finding is substantive or is a modeling artefact.

Privacy and contact tracing efficacy.

As the COVID-19 pandemic emerged, public health authorities and software designers considered the possibility that smartphones could be used for contact tracing to control disease spread. Smartphone-based contact tracing was attractive in part because it promised to allow the tracing of contacts that might not be reported using traditional contact tracing methods. Comprehensive contact tracing raises distinctive privacy concerns, however, that have not been previously explored. Contacts outside of an individual's ordinary social network are more likely to be privacy-sensitive, making fear that such contacts will be disclosed a potential disincentive to adoption of smartphone contact tracing. Here, we modify the standard SEIR infectious disease transmission model to incorporate contact tracing and perform a series of simulations aimed at studying the importance of tracing socially distant (and potentially privacy-sensitive) contacts. We find that, for a simple model network, ensuring that distant contacts are traced is surprisingly unimportant as long as contact tracing adoption is sufficiently high. These results suggest that policy-makers designing contact tracing systems should be willing to trade off comprehensiveness for more widespread adoption.

Triple contagion: a two-fears epidemic model.

We present a differential equations model in which contagious disease transmission is affected by contagious fear of the disease and contagious fear of the control, in this case vaccine. The three contagions are coupled. The two fears evolve and interact in ways that shape distancing behaviour, vaccine uptake, and their relaxation. These behavioural dynamics in turn can amplify or suppress disease transmission, which feeds back to affect behaviour. The model reveals several coupled contagion mechanisms for multiple epidemic waves. Methodologically, the paper advances infectious disease modelling by including human behavioural adaptation, drawing on the neuroscience of fear learning, extinction and transmission.

A review and agenda for integrated disease models including social and behavioural factors.

Social and behavioural factors are critical to the emergence, spread and containment of human disease, and are key determinants of the course, duration and outcomes of disease outbreaks. Recent epidemics of Ebola in West Africa and coronavirus disease 2019 (COVID-19) globally have reinforced the importance of developing infectious disease models that better integrate social and behavioural dynamics and theories. Meanwhile, the growth in capacity, coordination and prioritization of social science research and of risk communication and community engagement (RCCE) practice within the current pandemic response provides an opportunity for collaboration among epidemiological modellers, social scientists and RCCE practitioners towards a mutually beneficial research and practice agenda. Here, we provide a review of the current modelling methodologies and describe the challenges and opportunities for integrating them with social science research and RCCE practice. Finally, we set out an agenda for advancing transdisciplinary collaboration for integrated disease modelling and for more robust policy and practice for reducing disease transmission.

Data analysis and modeling pipelines for controlled networked social science experiments.

There is large interest in networked social science experiments for understanding human behavior at-scale. Significant effort is required to perform data analytics on experimental outputs and for computational modeling of custom experiments. Moreover, experiments and modeling are often performed in a cycle, enabling iterative experimental refinement and data modeling to uncover interesting insights and to generate/refute hypotheses about social behaviors. The current practice for social analysts is to develop tailor-made computer programs and analytical scripts for experiments and modeling. This often leads to inefficiencies and duplication of effort. In this work, we propose a pipeline framework to take a significant step towards overcoming these challenges. Our contribution is to describe the design and implementation of a software system to automate many of the steps involved in analyzing social science experimental data, building models to capture the behavior of human subjects, and providing data to test hypotheses. The proposed pipeline framework consists of formal models, formal algorithms, and theoretical models as the basis for the design and implementation. We propose a formal data model, such that if an experiment can be described in terms of this model, then our pipeline software can be used to analyze data efficiently. The merits of the proposed pipeline framework is elaborated by several case studies of networked social science experiments.

The Normative Underpinnings of Population-Level Alcohol Use: An Individual-Level Simulation Model.

Background. By defining what is "normal," appropriate, expected, and unacceptable, social norms shape human behavior. However, the individual-level mechanisms through which social norms impact population-level trends in health-relevant behaviors are not well understood. Aims. To test the ability of social norms mechanisms to predict changes in population-level drinking patterns. Method. An individual-level model was developed to simulate dynamic normative mechanisms and behavioral rules underlying drinking behavior over time. The model encompassed descriptive and injunctive drinking norms and their impact on frequency and quantity of alcohol use. A microsynthesis initialized in 1979 was used as a demographically representative synthetic U.S. population. Three experiments were performed in order to test the modelled normative mechanisms. Results. Overall, the experiments showed limited influence of normative interventions on population-level alcohol use. An increase in the desire to drink led to the most meaningful changes in the population's drinking behavior. The findings of the experiments underline the importance of autonomy, that is, the degree to which an individual is susceptible to normative influence. Conclusion. The model was able to predict theoretically plausible changes in drinking patterns at the population level through the impact of social mechanisms. Future applications of the model could be used to plan norms interventions pertaining to alcohol use as well as other health behaviors.

Toward inverse generative social science using multi-objective genetic programming.

Generative mechanism-based models of social systems, such as those represented by agent-based simulations, require that intra-agent equations (or rules) be specified. However there are often many different choices available for specifying these equations, which can still be interpreted as falling within a particular class of mechanisms. Whilst it is important for a generative model to reproduce historically observed dynamics, it is also important for the model to be theoretically enlightening. Genetic programs (our own included) often produce concatenations that are highly predictive but are complex and hard to interpret theoretically. Here, we develop a new method - based on multi-objective genetic programming - for automating the exploration of both objectives simultaneously. We demonstrate the method by evolving the equations for an existing agent-based simulation of alcohol use behaviors based on social norms theory, the initial model structure for which was developed by a team of human modelers. We discover a trade-off between empirical fit and theoretical interpretability that offers insight into the social norms processes that influence the change and stasis in alcohol use behaviors over time.

Social conformity despite individual preferences for distinctiveness.

We demonstrate that individual behaviours directed at the attainment of distinctiveness can in fact produce complete social conformity. We thus offer an unexpected generative mechanism for this central social phenomenon. Specifically, we establish that agents who have fixed needs to be distinct and adapt their positions to achieve distinctiveness goals, can nevertheless self-organize to a limiting state of absolute conformity. This seemingly paradoxical result is deduced formally from a small number of natural assumptions and is then explored at length computationally. Interesting departures from this conformity equilibrium are also possible, including divergence in positions. The effect of extremist minorities on these dynamics is discussed. A simple extension is then introduced, which allows the model to generate and maintain social diversity, including multimodal distinctiveness distributions. The paper contributes formal definitions, analytical deductions and counterintuitive findings to the literature on individual distinctiveness and social conformity.

Modeling the regional spread and control of vancomycin-resistant enterococci.

BACKGROUND: Because patients can remain colonized with vancomycin-resistant enterococci (VRE) for long periods of time, VRE may spread from one health care facility to another. METHODS: Using the Regional Healthcare Ecosystem Analyst, an agent-based model of patient flow among all Orange County, California, hospitals and communities, we quantified the degree and speed at which changes in VRE colonization prevalence in a hospital may affect prevalence in other Orange County hospitals. RESULTS: A sustained 10% increase in VRE colonization prevalence in any 1 hospital caused a 2.8% (none to 62%) average relative increase in VRE prevalence in all other hospitals. Effects took from 1.5 to >10 years to fully manifest. Larger hospitals tended to have greater affect on other hospitals. CONCLUSIONS: When monitoring and controlling VRE, decision makers may want to account for regional effects. Knowing a hospital's connections with other health care facilities via patient sharing can help determine which hospitals to include in a surveillance or control program.

Combining Computational Fluid Dynamics and Agent-Based Modeling: a new approach to evacuation planning.

We introduce a novel hybrid of two fields-Computational Fluid Dynamics (CFD) and Agent-Based Modeling (ABM)-as a powerful new technique for urban evacuation planning. CFD is a predominant technique for modeling airborne transport of contaminants, while ABM is a powerful approach for modeling social dynamics in populations of adaptive individuals. The hybrid CFD-ABM method is capable of simulating how large, spatially-distributed populations might respond to a physically realistic contaminant plume. We demonstrate the overall feasibility of CFD-ABM evacuation design, using the case of a hypothetical aerosol release in Los Angeles to explore potential effectiveness of various policy regimes. We conclude by arguing that this new approach can be powerfully applied to arbitrary population centers, offering an unprecedented preparedness and catastrophic event response tool.

Modeling the spread of methicillin-resistant Staphylococcus aureus (MRSA) outbreaks throughout the hospitals in Orange County, California.

BACKGROUND: Since hospitals in a region often share patients, an outbreak of methicillin-resistant Staphylococcus aureus (MRSA) infection in one hospital could affect other hospitals. METHODS: Using extensive data collected from Orange County (OC), California, we developed a detailed agent-based model to represent patient movement among all OC hospitals. Experiments simulated MRSA outbreaks in various wards, institutions, and regions. Sensitivity analysis varied lengths of stay, intraward transmission coefficients (ß), MRSA loss rate, probability of patient transfer or readmission, and time to readmission. RESULTS: Each simulated outbreak eventually affected all of the hospitals in the network, with effects depending on the outbreak size and location. Increasing MRSA prevalence at a single hospital (from 5% to 15%) resulted in a 2.9% average increase in relative prevalence at all other hospitals (ranging from no effect to 46.4%). Single-hospital intensive care unit outbreaks (modeled increase from 5% to 15%) caused a 1.4% average relative increase in all other OC hospitals (ranging from no effect to 12.7%). CONCLUSION: MRSA outbreaks may rarely be confined to a single hospital but instead may affect all of the hospitals in a region. This suggests that prevention and control strategies and policies should account for the interconnectedness of health care facilities.

A Distributed Platform for Global-Scale Agent-Based Models of Disease Transmission.

The Global-Scale Agent Model (GSAM) is presented. The GSAM is a high-performance distributed platform for agent-based epidemic modeling capable of simulating a disease outbreak in a population of several billion agents. It is unprecedented in its scale, its speed, and its use of Java. Solutions to multiple challenges inherent in distributing massive agent-based models are presented. Communication, synchronization, and memory usage are among the topics covered in detail. The memory usage discussion is Java specific. However, the communication and synchronization discussions apply broadly. We provide benchmarks illustrating the GSAM's speed and scalability.

Economic cost and health care workforce effects of school closures in the U.S.

School closure is an important component of U.S. pandemic flu mitigation strategy, but has important costs. We give estimates of both the direct economic and health care impacts for school closure durations of 2, 4, 6, and 12 weeks under a range of assumptions. We find that closing all schools in the U.S. for four weeks could cost between $10 and $47 billion dollars (0.1-0.3% of GDP) and lead to a reduction of 6% to 19% in key health care personnel.

Modelling to contain pandemics.

Agent-based computational models can capture irrational behaviour, complex social networks and global scale--all essential in confronting H1N1, says Joshua M. Epstein.

Coupled contagion dynamics of fear and disease: mathematical and computational explorations.

BACKGROUND: In classical mathematical epidemiology, individuals do not adapt their contact behavior during epidemics. They do not endogenously engage, for example, in social distancing based on fear. Yet, adaptive behavior is well-documented in true epidemics. We explore the effect of including such behavior in models of epidemic dynamics. METHODOLOGY/PRINCIPAL FINDINGS: Using both nonlinear dynamical systems and agent-based computation, we model two interacting contagion processes: one of disease and one of fear of the disease. Individuals can "contract" fear through contact with individuals who are infected with the disease (the sick), infected with fear only (the scared), and infected with both fear and disease (the sick and scared). Scared individuals--whether sick or not--may remove themselves from circulation with some probability, which affects the contact dynamic, and thus the disease epidemic proper. If we allow individuals to recover from fear and return to circulation, the coupled dynamics become quite rich, and can include multiple waves of infection. We also study flight as a behavioral response. CONCLUSIONS/SIGNIFICANCE: In a spatially extended setting, even relatively small levels of fear-inspired flight can have a dramatic impact on spatio-temporal epidemic dynamics. Self-isolation and spatial flight are only two of many possible actions that fear-infected individuals may take. Our main point is that behavioral adaptation of some sort must be considered.

Controlling pandemic flu: the value of international air travel restrictions.

BACKGROUND: Planning for a possible influenza pandemic is an extremely high priority, as social and economic effects of an unmitigated pandemic would be devastating. Mathematical models can be used to explore different scenarios and provide insight into potential costs, benefits, and effectiveness of prevention and control strategies under consideration. METHODS AND FINDINGS: A stochastic, equation-based epidemic model is used to study global transmission of pandemic flu, including the effects of travel restrictions and vaccination. Economic costs of intervention are also considered. The distribution of First Passage Times (FPT) to the United States and the numbers of infected persons in metropolitan areas worldwide are studied assuming various times and locations of the initial outbreak. International air travel restrictions alone provide a small delay in FPT to the U.S. When other containment measures are applied at the source in conjunction with travel restrictions, delays could be much longer. If in addition, control measures are instituted worldwide, there is a significant reduction in cases worldwide and specifically in the U.S. However, if travel restrictions are not combined with other measures, local epidemic severity may increase, because restriction-induced delays can push local outbreaks into high epidemic season. The per annum cost to the U.S. economy of international and major domestic air passenger travel restrictions is minimal: on the order of 0.8% of Gross National Product. CONCLUSIONS: International air travel restrictions may provide a small but important delay in the spread of a pandemic, especially if other disease control measures are implemented during the afforded time. However, if other measures are not instituted, delays may worsen regional epidemics by pushing the outbreak into high epidemic season. This important interaction between policy and seasonality is only evident with a global-scale model. Since the benefit of travel restrictions can be substantial while their costs are minimal, dismissal of travel restrictions as an aid in dealing with a global pandemic seems premature.

Containing a large bioterrorist smallpox attack: a computer simulation approach.

BACKGROUND: A bioterrorist release of smallpox is a constant threat to the population of the USA and other countries. DESIGN: A stochastic simulation model of the spread of smallpox due to a large bioterrorist attack in a structured population was constructed. Disease natural history parameter estimates, time lines of behavioral activities, and control scenarios were based on the literature and on the consensus opinion of a panel of smallpox experts. RESULTS: The authors found that surveillance and containment, i.e., isolation of known cases and vaccination of their close contacts, would be sufficient to effectively contain a large intentional smallpox release. Given that surveillance and containment measures are in place, preemptive vaccination of hospital workers would further reduce the number of smallpox cases and deaths but would require large numbers of prevaccinations. High levels of reactive mass vaccination after the outbreak begins would further reduce smallpox cases and deaths to a minimum, but would require even larger numbers of vaccinations. Reactive closure of schools would have a minimal effect. CONCLUSION: A rapid and well-organized response to a bioterrorist attack would be necessary for effective surveillance and containment to control spread. Preemptive vaccination of hospital workers and reactive vaccination of the target population would further limit spread, but at a cost of many more vaccinated. This cost in resources and potential harm due to vaccination will have to be weighed against the potential benefits should an attack occur. Prevaccination of the general population is not necessary.