arXiv subjects

Jonathan Dushoff

Publications and source records attributed to Jonathan Dushoff.

15 recordsLinked to original sources

arXiv2024

Best practices for estimating and reporting epidemiological delay distributions of infectious diseases using public health surveillance and healthcare data

Epidemiological delays, such as incubation periods, serial intervals, and hospital lengths of stay, are among key quantities in infectious disease epidemiology that inform public health policy and clinical practice. This information is used to inform mathematical and statistical models, which in turn can inform control strategies. There are three main challenges that make delay distributions difficult to estimate. First, the data are commonly censored (e.g., symptom onset may only be reported by date instead of the exact time of day). Second, delays are often right truncated when being estimated in real time (not all events that have occurred have been observed yet). Third, during a rapidly growing or declining outbreak, overrepresentation or underrepresentation, respectively, of recently infected cases in the data can lead to bias in estimates. Studies that estimate delays rarely address all these factors and sometimes report several estimates using different combinations of adjustments, which can lead to conflicting answers and confusion about which estimates are most accurate. In this work, we formulate a checklist of best practices for estimating and reporting epidemiological delays with a focus on the incubation period and serial interval. We also propose strategies for handling common biases and identify areas where more work is needed. Our recommendations can help improve the robustness and utility of reported estimates and provide guidance for the evaluation of estimates for downstream use in transmission models or other analyses.

stat.ME↗

arXiv2023

Toward a comprehensive system for constructing compartmental epidemic models

Compartmental models are valuable tools for investigating infectious diseases. Researchers building such models typically begin with a simple structure where compartments correspond to individuals with different epidemiological statuses, e.g., the classic SIR model which splits the population into susceptible, infected, and recovered compartments. However, as more information about a specific pathogen is discovered, or as a means to investigate the effects of heterogeneities, it becomes useful to stratify models further -- for example by age, geographic location, or pathogen strain. The operation of constructing stratified compartmental models from a pair of simpler models resembles the Cartesian product used in graph theory, but several key differences complicate matters. In this article we give explicit mathematical definitions for several so-called ``model products'' and provide examples where each is suitable. We also provide examples of model stratification where no existing model product will generate the desired result.

q-bio.PE↗

arXiv2022

Evaluating undercounts in epidemics: response to Maruotti et al. 2022

Maruotti et al. 2022 used a mark-recapture approach to estimate bounds on the true number of monkeypox infections in various countries. These approaches are fundamentally flawed; it is impossible to estimate undercounting based solely on a single stream of reported cases. Simulations based on a Richards curve for cumulative incidence show that, for reasonable epidemic parameters, the proposed methods estimate bounds on the ascertainment ratio of $\approx 0.2-0.5$ roughly independently of the true ascertainment ratio. These methods should not be used.

q-bio.PE↗

arXiv2021

Testing and Isolation Efficacy: Insights from a Simple Epidemic Model

Testing individuals for pathogens can affect the spread of epidemics. Understanding how individual-level processes of sampling and reporting test results can affect community- or population-level spread is a dynamical modeling question. The effect of testing processes on epidemic dynamics depends on factors underlying implementation, particularly testing intensity and on whom testing is focused. Here, we use a simple model to explore how the individual-level effects of testing might directly impact population-level spread. Our model development was motivated by the COVID-19 epidemic, but has generic epidemiological and testing structures. To the classic SIR framework we have added a per capita testing intensity, and compartment-specific testing weights, which can be adjusted to reflect different testing emphases -- surveillance, diagnosis, or control. We derive an analytic expression for the relative reduction in the basic reproductive number due to testing, test-reporting and related isolation behaviours. Intensive testing and fast test reporting are expected to be beneficial at the community level because they can provide a rapid assessment of the situation, identify hot spots, and may enable rapid contact-tracing. Direct effects of fast testing at the individual level are less clear, and may depend on how individuals' behaviour is affected by testing information. Our simple model shows that under some circumstances both increased testing intensity and faster test reporting can reduce the effectiveness of control, and allows us to explore the conditions under which this occurs. Conversely, we find that focusing testing on infected individuals always acts to increase effectiveness of control.

q-bio.PE↗

arXiv2021

pcoxtime: Penalized Cox Proportional Hazard Model for Time-dependent Covariates

The penalized Cox proportional hazard model is a popular analytical approach for survival data with a large number of covariates. Such problems are especially challenging when covariates vary over follow-up time (i.e., the covariates are time-dependent). The standard R packages for fully penalized Cox models cannot currently incorporate time-dependent covariates. To address this gap, we implement a variant of gradient descent algorithm (proximal gradient descent) for fitting penalized Cox models. We apply our implementation to real and simulated data sets.

stat.ME↗

arXiv2018

I can see clearly now: reinterpreting statistical significance

Null hypothesis significance testing remains popular despite decades of concern about misuse and misinterpretation. We believe that much of the problem is due to language: significance testing has little to do with other meanings of the word "significance". Despite the limitations of null-hypothesis tests, we argue here that they remain useful in many contexts as a guide to whether a certain effect can be seen clearly in that context (e.g. whether we can clearly see that a correlation or between-group difference is positive or negative). We therefore suggest that researchers describe the conclusions of null-hypothesis tests in terms of statistical "clarity" rather than statistical "significance". This simple semantic change could substantially enhance clarity in statistical communication.

stat.OT↗

arXiv2017

Patterns of Influenza Vaccination Coverage in the United States from 2009 to 2015

Background: Globally, influenza is a major cause of morbidity, hospitalization and mortality. Influenza vaccination has shown substantial protective effectiveness in the United States. We investigated state-level patterns of coverage rates of seasonal and pandemic influenza vaccination, among the overall population in the U.S. and specifically among children and the elderly, from 2009/10 to 2014/15, and associations with ecological factors. Methods and Findings: We obtained state-level influenza vaccination coverage rates from national surveys, and state-level socio-demographic and health data from a variety of sources. We employed a retrospective ecological study design, and used mixed-model regression to determine the levels of ecological association of the state-level vaccinations rates with these factors, both with and without region as a factor for the three populations. We found that health-care access is positively and significantly associated with mean influenza vaccination coverage rates across all populations and models. We also found that prevalence of asthma in adults are negatively and significantly associated with mean influenza vaccination coverage rates in the elderly populations. Conclusions: Health-care access has a robust, positive association with state-level vaccination rates across different populations. This highlights a potential population-level advantage of expanding health-care access.

q-bio.PE↗

arXiv2016

Relatedness of the Incidence Decay with Exponential Adjustment (IDEA) Model, "Farr's Law" and Compartmental Difference Equation SIR Models

Mathematical models are often regarded as recent innovations in the description and analysis of infectious disease outbreaks and epidemics, but simple models have been in use for projection of epidemic trajectories for more than a century. We recently described a single equation model (the incidence decay with exponential adjustment, or IDEA, model) that can be used for short term forecasting. In the mid-19th century, Dr. William Farr developed a single equation approach (Farr's law) for epidemic forecasting. We show here that the two models are in fact identical, and can be expressed in terms of one another, and also in terms of a susceptible-infectious-removed (SIR) compartmental model with improving control. This demonstrates that the concept of the reproduction number, R0, is implicit to Farr's (pre-microbial era) work, and also suggests that control of epidemics, whether via behavior change or intervention, is as integral to the natural history of epidemics as is the dynamics of disease transmission.

stat.AP↗

arXiv2016

Stochasticity and the limits to confidence when estimating R_0 of Ebola and other emerging infectious diseases

Dynamic models - often deterministic in nature - were used to estimate the basic reproductive number, R_0, of the 2014-5 Ebola virus disease (EVD) epidemic outbreak in West Africa. Estimates of R_0 were then used to project the likelihood for large outbreak sizes, e.g., exceeding hundreds of thousands of cases. Yet fitting deterministic models can lead to over-confidence in the confidence intervals of the fitted R_0, and, in turn, the type and scope of necessary interventions. In this manuscript we propose a hybrid stochastic-deterministic method to estimate R_0 and associated confidence intervals (CIs). The core idea is that stochastic realizations of an underlying deterministic model can be used to evaluate the compatibility of candidate values of R_0 with observed epidemic curves. The compatibility is based on comparing the distribution of expected epidemic growth rates with the observed epidemic growth rate given "process noise", i.e., arising due to stochastic transmission, recovery and death events. By applying our method to reported EVD case counts from Guinea, Liberia and Sierra Leone, we show that prior estimates of R_0 based on deterministic fits appear to be more confident than analysis of stochastic trajectories suggests should be possible. Moving forward, we recommend including a hybrid stochastic-deterministic fitting procedure when quantifying the full R_0 CI at the onset of an epidemic due to multiple sources of noise.

q-bio.PE↗

arXiv2014

Post-death Transmission of Ebola: Challenges for Inference and Opportunities for Control

Multiple epidemiological models have been proposed to predict the spread of Ebola in West Africa. These models include consideration of counter-measures meant to slow and, eventually, stop the spread of the disease. Here, we examine one component of Ebola dynamics that is of growing concern -- the transmission of Ebola from the dead to the living. We do so by applying the toolkit of mathematical epidemiology to analyze the consequences of post-death transmission. We show that underlying disease parameters cannot be inferred with confidence from early-stage incidence data (that is, they are not "identifiable") because different parameter combinations can produce virtually the same epidemic trajectory. Despite this identifiability problem, we find robustly that inferences that don't account for post-death transmission tend to underestimate the basic reproductive number -- thus, given the observed rate of epidemic growth, larger amounts of post-death transmission imply larger reproductive numbers. From a control perspective, we explain how improvements in reducing post-death transmission of Ebola may reduce the overall epidemic spread and scope substantially. Increased attention to the proportion of post-death transmission has the potential to aid both in projecting the course of the epidemic and in evaluating a portfolio of control strategies.

q-bio.PE↗

arXiv2013

Effects of mixing in threshold models of social behavior

We consider the dynamics of an extension of the influential Granovetter model of social behavior, where individuals are affected by their personal preferences and observation of the neighbors' behavior. Individuals are arranged in a network (usually, the square lattice) and each has a state and a fixed threshold for behavior changes. We simulate the system asynchronously either by picking a random individual and either update its state or exchange it with another randomly chosen individual (mixing). We describe the dynamics analytically in the fast-mixing limit by using the mean-field approximation and investigate it mainly numerically in case of a finite mixing. We show that the dynamics converge to a manifold in state space, which determines the possible equilibria, and show how to estimate the projection of manifold by using simulated trajectories, emitted from different initial points. We show that the effects of considering the network can be decomposed into finite-neighborhood effects, and finite-mixing-rate effects, which have qualitatively similar effects. Both of these effects increase the tendency of the system to move from a less-desired equilibrium to the "ground state". Our findings can be used to probe shifts in behavioral norms and have implications for the role of information flow in determining when social norms that have become unpopular (such as foot binding or female genital cutting) persist or vanish.

physics.soc-ph↗

arXiv2013

Robust estimation of microbial diversity in theory and in practice

Quantifying diversity is of central importance for the study of structure, function and evolution of microbial communities. The estimation of microbial diversity has received renewed attention with the advent of large-scale metagenomic studies. Here, we consider what the diversity observed in a sample tells us about the diversity of the community being sampled. First, we argue that one cannot reliably estimate the absolute and relative number of microbial species present in a community without making unsupported assumptions about species abundance distributions. The reason for this is that sample data do not contain information about the number of rare species in the tail of species abundance distributions. We illustrate the difficulty in comparing species richness estimates by applying Chao's estimator of species richness to a set of in silico communities: they are ranked incorrectly in the presence of large numbers of rare species. Next, we extend our analysis to a general family of diversity metrics ("Hill diversities"), and construct lower and upper estimates of diversity values consistent with the sample data. The theory generalizes Chao's estimator, which we retrieve as the lower estimate of species richness. We show that Shannon and Simpson diversity can be robustly estimated for the in silico communities. We analyze nine metagenomic data sets from a wide range of environments, and show that our findings are relevant for empirically-sampled communities. Hence, we recommend the use of Shannon and Simpson diversity rather than species richness in efforts to quantify and compare microbial diversity.

q-bio.PE↗

arXiv2010

Fluctuation Domains in Adaptive Evolution

We derive an expression for the variation between parallel trajectories in phenotypic evolution, extending the well known result that predicts the mean evolutionary path in adaptive dynamics or quantitative genetics. We show how this expression gives rise to the notion of fluctuation domains - parts of the fitness landscape where the rate of evolution is very predictable (due to fluctuation dissipation) and parts where it is highly variable (due to fluctuation enhancement). These fluctuation domains are determined by the curvature of the fitness landscape. Regions of the fitness landscape with positive curvature, such as adaptive valleys or branching points, experience enhancement. Regions with negative curvature, such as adaptive peaks, experience dissipation. We explore these dynamics in the ecological scenarios of implicit and explicit competition for a limiting resource.

q-bio.PE↗

arXiv2009

On the accessibility of adaptive phenotypes of a bacterial metabolic network

The mechanisms by which adaptive phenotypes spread within an evolving population after their emergence are understood fairly well. Much less is known about the factors that influence the evolutionary accessibility of such phenotypes, a pre-requisite for their emergence in a population. Here, we investigate the influence of environmental quality on the accessibility of adaptive phenotypes of Escherichia coli's central metabolic network. We used an established flux-balance model of metabolism as the basis for a genotype-phenotype map (GPM). We quantified the effects of seven qualitatively different environments (corresponding to both carbohydrate and gluconeogenic metabolic substrates) on the structure of this GPM. We found that the GPM has a more rugged structure in qualitatively poorer environments, suggesting that adaptive phenotypes could be intrinsically less accessible in such environments. Nevertheless, on average ~74% of the genotype can be altered by neutral drift, in the environment where the GPM is most rugged; this could allow evolving populations to circumvent such ruggedness. Furthermore, we found that the normalized mutual information (NMI) of genotype differences relative to phenotype differences, which measures the GPM's capacity to transmit information about phenotype differences, is positively correlated with (simulation-based) estimates of the accessibility of adaptive phenotypes in different environments. These results are consistent with the predictions of a simple analytic theory and they suggest an intuitive information-theoretic principle for evolutionary adaptation; adaptation could be faster in environments where the GPM has a greater capacity to transmit information about phenotype differences.

q-bio.PE↗

arXiv2004

Synonymous codon usage and selection on proteins

Selection pressures on proteins are usually measured by comparing homologous nucleotide sequences (Zuckerkandl and Pauling 1965). Recently we introduced a novel method, termed `volatility', to estimate selection pressures on protein sequences from their synonymous codon usage (Plotkin and Dushoff 2003, Plotkin et al 2004a). Here we provide a theoretical foundation for this approach. We derive the expected frequencies of synonymous codons as a function of the strength of selection, the mutation rate, and the effective population size. We analyze the conditions under which we can expect to draw inferences from biased codon usage, and we estimate the time scales required to establish and maintain such a signal. Our results indicate that, over a broad range of parameters, synonymous codon usage can reliably distinguish between negative selection, positive selection, and neutrality. While the power of volatility to detect negative selection depends on the population size, there is no such dependence for the detection of positive selection. Furthermore, we show that phenomena such as transient hyper-mutators in microbes can improve the power of volatility to detect negative selection, even when the typical observed neutral site heterozygosity is low.

q-bio.PE↗