Challenges in cybersecurity: Lessons from biological defense systems.

Defending against novel, repeated, or unpredictable attacks, while avoiding attacks on the 'self', are the central problems of both mammalian immune systems and computer systems. Both systems have been studied in great detail, but with little exchange of information across the different disciplines. Here, we present a conceptual framework for structured comparisons across the fields of biological immunity and cybersecurity, by framing the context of defense, considering different (combinations of) defensive strategies, and evaluating defensive performance. Throughout this paper, we pose open questions for further exploration. We hope to spark the interdisciplinary discovery of general principles of optimal defense, which can be understood and applied in biological immunity, cybersecurity, and other defensive realms.

Mobility restrictions for the control of epidemics: When do they work?

BACKGROUND: Mobility restrictions-trade and travel bans, border closures and, in extreme cases, area quarantines or cordons sanitaires-are among the most widely used measures to control infectious diseases. Restrictions of this kind were important in the response to epidemics of SARS (2003), H1N1 influenza (2009), Ebola (2014) and, currently in the containment of the ongoing COVID-19 pandemic. However, they do not always work as expected. METHODS: To determine when mobility restrictions reduce the size of an epidemic, we use a model of disease transmission within and between economically heterogeneous locally connected communities. One community comprises a low-risk, low-density population with access to effective medical resources. The other comprises a high-risk, high-density population without access to effective medical resources. FINDINGS: Unrestricted mobility between the two risk communities increases the number of secondary cases in the low-risk community but reduces the overall epidemic size. By contrast, the imposition of a cordon sanitaire around the high-risk community reduces the number of secondary infections in the low-risk community but increases the overall epidemic size. INTERPRETATION: Mobility restrictions may not be an effective policy for controlling the spread of an infectious disease if it is assessed by the overall final epidemic size. Patterns of mobility established through the independent mobility and trade decisions of people in both communities may be sufficient to contain epidemics.

Epidemics on networks: Reducing disease transmission using health emergency declarations and peer communication.

Understanding individual decisions in a world where communications and information move instantly via cell phones and the internet, contributes to the development and implementation of policies aimed at stopping or ameliorating the spread of diseases. In this manuscript, the role of official social network perturbations generated by public health officials to slow down or stop a disease outbreak are studied over distinct classes of static social networks. The dynamics are stochastic in nature with individuals (nodes) being assigned fixed levels of education or wealth. Nodes may change their epidemiological status from susceptible, to infected and to recovered. Most importantly, it is assumed that when the prevalence reaches a pre-determined threshold level, P * , information, called awareness in our framework, starts to spread, a process triggered by public health authorities. Information is assumed to spread over the same static network and whether or not one becomes a temporary informer, is a function of his/her level of education or wealth and epidemiological status. Stochastic simulations show that threshold selection P * and the value of the average basic reproduction number impact the final epidemic size differentially. For the Erdos-Rényi and Small-world networks, an optimal choice for P * that minimize the final epidemic size can be identified under some conditions while for Scale-free networks this is not case.

Modeling the dynamics of glucose, insulin, and free fatty acids with time delay: The impact of bariatric surgery on type 2 diabetes mellitus.

The role of free fatty acids (FFA) on Type 2 diabetes mellitus (T2DM) progression has been studied extensively with prior studies suggesting that individuals with shared familial genetic predisposition to metabolic-related diseases may be vulnerable to dysfunctional plasma FFA regulation. A harmful cycle arises when FFA are not properly regulated by insulin contributing to the development of insulin resistance, a key indicator for T2DM, since prolonged insulin resistance may lead to hyperglycemia. We introduce a hypothesis-driven dynamical model and use it to evaluate the role of FFA on insulin resistance progression that is mathematically constructed within the context of individuals that have genetic predisposition to dysfunctional plasma FFA. The dynamics of the nonlinear interactions that involve glucose, insulin, and FFA are modeled by incorporating a fixed-time delay with the corresponding delay-differential equations being studied numerically. The results of computational studies, that is, extensive simulations, are compared to the known minimal ordinary differential equations model. Parameter estimation and model validation are carried out using clinical data of patients who underwent bariatric surgery. These estimates provide a quantitative measure that is used to evaluate the regulation of lipolysis by insulin action measured by insulin sensitivity, within a metabolically heterogeneous population (non-diabetic to diabetic). Results show that key metabolic factors improve after surgery, such as the effect of insulin inhibition of FFA on insulin and glucose regulation, results that do match prior clinical studies. These findings indicate that the reduction in weight or body mass due to surgery improve insulin action for the regulation of glucose, FFA, and insulin levels. This reinforces what we know, namely, that insulin action is essential for regulating FFA and glucose levels and is a robust effect that can be observed not only in the long-term, but also in the short-term; thereby preventing the manifestation of T2DM.

Building matrix population models when individuals are non-identifiable.

Matrix Population Models (MPM) are among the most widely used tools in ecology and evolution. These models consider the life cycle of an individual as composed by states to construct a matrix containing the likelihood of transitions between these states as well as sexual and/or asexual per-capita offspring contributions. When individuals are identifiable one can parametrize an MPM based on survival and fertility data and average development times for every state, but some of this information is absent or incomplete for non-cohort data, or for cohort data when individuals are not identifiable. Here we introduce a simple procedure for the parameterization of an MPM that can be used with cohort data when individuals are non-identifiable; among other aspects our procedure is a novelty in that it does not require information on stage development (or stage residence) times, which current procedures require to be estimated externally, and it is a frequent source of error. We exemplify the procedure with a laboratory cohort dataset from Eratyrus mucronatus (Reduviidae, Triatominae). We also show that even if individuals are identifiable and the duration of each stage is externally estimated with no error, our procedure is simpler to use and yields the same MPM parameter estimates.

Dynamics of a stochastic delayed Harrison-type predation model: Effects of delay and stochastic components.

This paper investigates the complex dynamics of a Harrison-type predator-prey model that incorporating: (1) A constant time delay in the functional response term of the predator growth equation; and (2) environmental noise in both prey and predator equations. We provide the rigorous results of our model including the dynamical behaviors of a positive solution and Hopf bifurcation. We also perform numerical simulations on the effects of delay or/and noise when the corresponding ODE model has an interior solution. Our theoretical and numerical results show that delay can either remain stability or destabilize the model; large noise could destabilize the model; and the combination of delay and noise could intensify the periodic instability of the model. Our results may provide us useful biological insights into population managements for prey-predator interaction models.

Detecting the contagion effect in mass killings; a constructive example of the statistical advantages of unbinned likelihood methods.

BACKGROUND: When attempting to statistically distinguish between a null and an alternative hypothesis, many researchers in the life and social sciences turn to binned statistical analysis methods, or methods that are simply based on the moments of a distribution (such as the mean, and variance). These methods have the advantage of simplicity of implementation, and simplicity of explanation. However, when null and alternative hypotheses manifest themselves in subtle differences in patterns in the data, binned analysis methods may be insensitive to these differences, and researchers may erroneously fail to reject the null hypothesis when in fact more sensitive statistical analysis methods might produce a different result when the null hypothesis is actually false. Here, with a focus on two recent conflicting studies of contagion in mass killings as instructive examples, we discuss how the use of unbinned likelihood methods makes optimal use of the information in the data; a fact that has been long known in statistical theory, but perhaps is not as widely appreciated amongst general researchers in the life and social sciences. METHODS: In 2015, Towers et al published a paper that quantified the long-suspected contagion effect in mass killings. However, in 2017, Lankford & Tomek subsequently published a paper, based upon the same data, that claimed to contradict the results of the earlier study. The former used unbinned likelihood methods, and the latter used binned methods, and comparison of distribution moments. Using these analyses, we also discuss how visualization of the data can aid in determination of the most appropriate statistical analysis methods to distinguish between a null and alternate hypothesis. We also discuss the importance of assessment of the robustness of analysis results to methodological assumptions made (for example, arbitrary choices of number of bins and bin widths when using binned methods); an issue that is widely overlooked in the literature, but is critical to analysis reproducibility and robustness. CONCLUSIONS: When an analysis cannot distinguish between a null and alternate hypothesis, care must be taken to ensure that the analysis methodology itself maximizes the use of information in the data that can distinguish between the two hypotheses. The use of binned methods by Lankford & Tomek (2017), that examined how many mass killings fell within a 14 day window from a previous mass killing, substantially reduced the sensitivity of their analysis to contagion effects. The unbinned likelihood methods used by Towers et al (2015) did not suffer from this problem. While a binned analysis might be favorable for simplicity and clarity of presentation, unbinned likelihood methods are preferable when effects might be somewhat subtle.

Modeling the Diet Dynamics of Children: the Roles of Socialization and the School Environment.

Childhood obesity is a health emergency in many parts of the world including the U.S. and, consequently, identifying local, regional or national intervention models capable, of altering the dynamics of obesity at scales that make a difference remains a challenge. The fact that consumption of healthful foods among most youth has yet to meet recommended nutritional standards highlights a lack of effective policies aimed at addressing the epidemic of obesity. Mathematical models are used to evaluate the roles of socialization and school environment on the diet dynamics of children. Data suggest that standard nutrition education programs may have, at best, minimal impact in altering diet dynamics at the population-level. Inclusion of peer influence (model as contagion) reinforced by the use of culturally-sensitive school menus (environmental disruption) may prove capable of modifying obesity enhancing diet dynamics; altering the diets of a significant (critical) proportion of youngsters. A framework is introduced to explore the value of behavior-based interventions and policies that account for the sociocultural environments of at risk communities. These models capture carefully choreographed scenarios to account for the fact that when dealing with diet-dynamics systems, thinking additively is not enough as it cannot account for the power of nonlinear effects.

Mathematical Analysis of an SIQR Influenza Model with Imperfect Quarantine.

The identification of mechanisms responsible for recurrent epidemic outbreaks, such as age structure, cross-immunity and variable delays in the infective classes, has challenged and fascinated epidemiologists and mathematicians alike. This paper addresses, motivated by mathematical work on influenza models, the impact of imperfect quarantine on the dynamics of SIR-type models. A susceptible-infectious-quarantine-recovered (SIQR) model is formulated with quarantined individuals altering the transmission dynamics process through their possibly reduced ability to generate secondary cases of infection. Mathematical and numerical analyses of the model of the equilibria and their stability have been carried out. Uniform persistence of the model has been established. Numerical simulations show that the model supports Hopf bifurcation as a function of the values of the quarantine effectiveness and other parameters. The upshot of this work is somewhat surprising since it is shown that SIQR model oscillatory behavior, as shown by multiple researchers, is in fact not robust to perturbations in the quarantine regime.

The role of mobility and health disparities on the transmission dynamics of Tuberculosis.

BACKGROUND: The transmission dynamics of Tuberculosis (TB) involve complex epidemiological and socio-economical interactions between individuals living in highly distinct regional conditions. The level of exogenous reinfection and first time infection rates within high-incidence settings may influence the impact of control programs on TB prevalence. The impact that effective population size and the distribution of individuals' residence times in different patches have on TB transmission and control are studied using selected scenarios where risk is defined by the estimated or perceive first time infection and/or exogenous re-infection rates. METHODS: This study aims at enhancing the understanding of TB dynamics, within simplified, two patch, risk-defined environments, in the presence of short term mobility and variations in reinfection and infection rates via a mathematical model. The modeling framework captures the role of individuals' 'daily' dynamics within and between places of residency, work or business via the average proportion of time spent in residence and as visitors to TB-risk environments (patches). As a result, the effective population size of Patch i (home of i-residents) at time t must account for visitors and residents of Patch i, at time t. RESULTS: The study identifies critical social behaviors mechanisms that can facilitate or eliminate TB infection in vulnerable populations. The results suggest that short-term mobility between heterogeneous patches contributes to significant overall increases in TB prevalence when risk is considered only in terms of direct new infection transmission, compared to the effect of exogenous reinfection. Although, the role of exogenous reinfection increases the risk that come from large movement of individuals, due to catastrophes or conflict, to TB-free areas. CONCLUSIONS: The study highlights that allowing infected individuals to move from high to low TB prevalence areas (for example via the sharing of treatment and isolation facilities) may lead to a reduction in the total TB prevalence in the overall population. The higher the population size heterogeneity between distinct risk patches, the larger the benefit (low overall prevalence) under the same "traveling" patterns. Policies need to account for population specific factors (such as risks that are inherent with high levels of migration, local and regional mobility patterns, and first time infection rates) in order to be long lasting, effective and results in low number of drug resistant cases.

Role of short-term dispersal on the dynamics of Zika virus in an extreme idealized environment.

In November 2015, El Salvador reported their first case of Zika virus (ZIKV) infection, an event followed by an explosive outbreak that generated over 6000 suspected cases in a period of two months. National agencies began implementing control measures that included vector control and recommending an increased use of repellents. Further, in response to the alarming and growing number of microcephaly cases in Brazil, the importance of avoiding pregnancies for two years was stressed. In this paper, we explore the role of mobility within communities characterized by extreme poverty, crime and violence. Specifically, the role of short term mobility between two idealized interconnected highly distinct communities is explored in the context of ZIKV outbreaks. We make use of a Lagrangian modeling approach within a two-patch setting in order to highlight the possible effects that short-term mobility, within highly distinct environments, may have on the dynamics of ZIKV outbreak when the overall goal is to reduce the number of cases not just in the most affluent areas but everywhere. Outcomes depend on existing mobility patterns, levels of disease risk, and the ability of federal or state public health services to invest in resource limited areas, particularly in those where violence is systemic. The results of simulations in highly polarized and simplified scenarios are used to assess the role of mobility. It quickly became evident that matching observed patterns of ZIKV outbreaks could not be captured without incorporating increasing levels of heterogeneity. The number of distinct patches and variations on patch connectivity structure required to match ZIKV patterns could not be met within the highly aggregated model that is used in the simulations.

Perspectives on the role of mobility, behavior, and time scales in the spread of diseases.

The dynamics, control, and evolution of communicable and vector-borne diseases are intimately connected to the joint dynamics of epidemiological, behavioral, and mobility processes that operate across multiple spatial, temporal, and organizational scales. The identification of a theoretical explanatory framework that accounts for the pattern regularity exhibited by a large number of host-parasite systems, including those sustained by host-vector epidemiological dynamics, is but one of the challenges facing the coevolving fields of computational, evolutionary, and theoretical epidemiology. Host-parasite epidemiological patterns, including epidemic outbreaks and endemic recurrent dynamics, are characteristic to well-identified regions of the world; the result of processes and constraints such as strain competition, host and vector mobility, and population structure operating over multiple scales in response to recurrent disturbances (like El Niño) and climatological and environmental perturbations over thousands of years. It is therefore important to identify and quantify the processes responsible for observed epidemiological macroscopic patterns: the result of individual interactions in changing social and ecological landscapes. In this perspective, we touch on some of the issues calling for the identification of an encompassing theoretical explanatory framework by identifying some of the limitations of existing theory, in the context of particular epidemiological systems. Fostering the reenergizing of research that aims at disentangling the role of epidemiological and socioeconomic forces on disease dynamics, better understood as complex adaptive systems, is a key aim of this perspective.

Estimate of the reproduction number of the 2015 Zika virus outbreak in Barranquilla, Colombia, and estimation of the relative role of sexual transmission.

BACKGROUND: In 2015, the Zika arbovirus (ZIKV) began circulating in the Americas, rapidly expanding its global geographic range in explosive outbreaks. Unusual among mosquito-borne diseases, ZIKV has been shown to also be sexually transmitted, although sustained autochthonous transmission due to sexual transmission alone has not been observed, indicating the reproduction number (R0) for sexual transmission alone is less than 1. Critical to the assessment of outbreak risk, estimation of the potential attack rates, and assessment of control measures, are estimates of the basic reproduction number, R0. METHODS: We estimated the R0 of the 2015 ZIKV outbreak in Barranquilla, Colombia, through an analysis of the exponential rise in clinically identified ZIKV cases (n=359 to the end of November, 2015). FINDINGS: The rate of exponential rise in cases was ρ=0.076days-1, with 95% CI [0.066,0.087] days-1. We used a vector-borne disease model with additional direct transmission to estimate the R0; assuming the R0 of sexual transmission alone is less than 1, we estimated the total R0=3.8 [2.4,5.6], and that the fraction of cases due to sexual transmission was 0.23 [0.01,0.47] with 95% confidence. INTERPRETATION: This is among the first estimates of R0 for a ZIKV outbreak in the Americas, and also among the first quantifications of the relative impact of sexual transmission.

A two-strain TB model with multiple latent stages.

A two-strain tuberculosis (TB) transmission model incorporating antibiotic-generated TB resistant strains and long and variable waiting periods within the latently infected class is introduced. The mathematical analysis is carried out when the waiting periods are modeled via parametrically friendly gamma distributions, a reasonable alternative to the use of exponential distributed waiting periods or to integral equations involving ``arbitrary'' distributions. The model supports a globally-asymptotically stable disease-free equilibrium when the reproduction number is less than one and an endemic equilibriums, shown to be locally asymptotically stable, or l.a.s., whenever the basic reproduction number is greater than one. Conditions for the existence and maintenance of TB resistant strains are discussed. The possibility of exogenous re-infection is added and shown to be capable of supporting multiple equilibria; a situation that increases the challenges faced by public health experts. We show that exogenous re-infection may help established resilient communities of actively-TB infected individuals that cannot be eliminated using approaches based exclusively on the ability to bring the control reproductive number just below 1.

Modeling eating behaviors: The role of environment and positive food association learning via a Ratatouille effect.

Eating behaviors among a large population of children are studied as a dynamic process driven by nonlinear interactions in the sociocultural school environment. The impact of food association learning on diet dynamics, inspired by a pilot study conducted among Arizona children in Pre-Kindergarten to 8th grades, is used to build simple population-level learning models. Qualitatively, mathematical studies are used to highlight the possible ramifications of instruction, learning in nutrition, and health at the community level. Model results suggest that nutrition education programs at the population-level have minimal impact on improving eating behaviors, findings that agree with prior field studies. Hence, the incorporation of food association learning may be a better strategy for creating resilient communities of healthy and non-healthy eaters. A Ratatouille effect can be observed when food association learners become food preference learners, a potential sustainable behavioral change, which in turn, may impact the overall distribution of healthy eaters. In short, this work evaluates the effectiveness of population-level intervention strategies and the importance of institutionalizing nutrition programs that factor in economical, social, cultural, and environmental elements that mesh well with the norms and values in the community.

Vector-borne diseases models with residence times - A Lagrangian perspective.

A multi-patch and multi-group modeling framework describing the dynamics of a class of diseases driven by the interactions between vectors and hosts structured by groups is formulated. Hosts' dispersal is modeled in terms of patch-residence times with the nonlinear dynamics taking into account the effective patch-host size. The residence times basic reproduction number R0 is computed and shown to depend on the relative environmental risk of infection. The model is robust, that is, the disease free equilibrium is globally asymptotically stable (GAS) if R0≤1 and a unique interior endemic equilibrium is shown to exist that is GAS whenever R0>1 whenever the configuration of host-vector interactions is irreducible. The effects of patchiness and groupness, a measure of host-vector heterogeneous structure, on the basic reproduction number R0, are explored. Numerical simulations are carried out to highlight the effects of residence times on disease prevalence.

Some models for epidemics of vector-transmitted diseases.

Vector-transmitted diseases such as dengue fever and chikungunya have been spreading rapidly in many parts of the world. The Zika virus has been known since 1947 and invaded South America in 2013. It can be transmitted not only by (mosquito) vectors but also directly through sexual contact. Zika has developed into a serious global health problem because, while most cases are asymptomatic or very light, babies born to Zika - infected mothers may develop microcephaly and other very serious birth defects. We formulate and analyze two epidemic models for vector-transmitted diseases, one appropriate for dengue and chikungunya fever outbreaks and one that includes direct transmission appropriate for Zika virus outbreaks. This is especially important because the Zika virus is the first example of a disease that can be spread both indirectly through a vector and directly (through sexual contact). In both cases, we obtain expressions for the basic reproduction number and show how to use the initial exponential growth rate to estimate the basic reproduction number. However, for the model that includes direct transmission some additional data would be needed to identify the fraction of cases transmitted directly. Data for the 2015 Zika virus outbreak in Barranquilla, Colombia has been used to fit parameters to the model developed here and to estimate the basic reproduction number.

SIS and SIR Epidemic Models Under Virtual Dispersal.

We develop a multi-group epidemic framework via virtual dispersal where the risk of infection is a function of the residence time and local environmental risk. This novel approach eliminates the need to define and measure contact rates that are used in the traditional multi-group epidemic models with heterogeneous mixing. We apply this approach to a general n-patch SIS model whose basic reproduction number [Formula: see text] is computed as a function of a patch residence-time matrix [Formula: see text]. Our analysis implies that the resulting n-patch SIS model has robust dynamics when patches are strongly connected: There is a unique globally stable endemic equilibrium when [Formula: see text], while the disease-free equilibrium is globally stable when [Formula: see text]. Our further analysis indicates that the dispersal behavior described by the residence-time matrix [Formula: see text] has profound effects on the disease dynamics at the single patch level with consequences that proper dispersal behavior along with the local environmental risk can either promote or eliminate the endemic in particular patches. Our work highlights the impact of residence-time matrix if the patches are not strongly connected. Our framework can be generalized in other endemic and disease outbreak models. As an illustration, we apply our framework to a two-patch SIR single-outbreak epidemic model where the process of disease invasion is connected to the final epidemic size relationship. We also explore the impact of disease-prevalence-driven decision using a phenomenological modeling approach in order to contrast the role of constant versus state-dependent [Formula: see text] on disease dynamics.

Contagion in Mass Killings and School Shootings.

BACKGROUND: Several past studies have found that media reports of suicides and homicides appear to subsequently increase the incidence of similar events in the community, apparently due to the coverage planting the seeds of ideation in at-risk individuals to commit similar acts. METHODS: Here we explore whether or not contagion is evident in more high-profile incidents, such as school shootings and mass killings (incidents with four or more people killed). We fit a contagion model to recent data sets related to such incidents in the US, with terms that take into account the fact that a school shooting or mass murder may temporarily increase the probability of a similar event in the immediate future, by assuming an exponential decay in contagiousness after an event. CONCLUSIONS: We find significant evidence that mass killings involving firearms are incented by similar events in the immediate past. On average, this temporary increase in probability lasts 13 days, and each incident incites at least 0.30 new incidents (p = 0.0015). We also find significant evidence of contagion in school shootings, for which an incident is contagious for an average of 13 days, and incites an average of at least 0.22 new incidents (p = 0.0001). All p-values are assessed based on a likelihood ratio test comparing the likelihood of a contagion model to that of a null model with no contagion. On average, mass killings involving firearms occur approximately every two weeks in the US, while school shootings occur on average monthly. We find that state prevalence of firearm ownership is significantly associated with the state incidence of mass killings with firearms, school shootings, and mass shootings.