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Species subject to predation and environmental threats commonly exhibit variable periods of population boom and bust over long timescales. Understanding and predicting such behavior, especially given the inherent heterogeneity and stochasticity of exogenous driving factors over short timescales, is an ongoing challenge. A modeling paradigm gaining popularity in the ecological sciences for such multi-scale effects is to couple short-term continuous dynamics to long-term discrete updates. We develop a data-driven method utilizing weak-form equation learning to extract such hybrid governing equations for population dynamics and to estimate the requisite parameters using sparse intermittent measurements of the discrete and continuous variables. The method produces a set of short-term continuous dynamical system equations parametrized by long-term variables, and long-term discrete equations parametrized by short-term variables, allowing direct assessment of interdependencies between the two time scales. We demonstrate the utility of the method on a variety of ecological scenarios and provide extensive tests using models previously derived for epizootics experienced by the North American spongy moth (Lymantria dispar dispar).

We introduce the Weak-form Estimation of Nonlinear Dynamics (WENDy) method for estimating model parameters for non-linear systems of ODEs. Without relying on any numerical differential equation solvers, WENDy computes accurate estimates and is robust to large (biologically relevant) levels of measurement noise. For low dimensional systems with modest amounts of data, WENDy is competitive with conventional forward solver-based nonlinear least squares methods in terms of speed and accuracy. For both higher dimensional systems and stiff systems, WENDy is typically both faster (often by orders of magnitude) and more accurate than forward solver-based approaches. The core mathematical idea involves an efficient conversion of the strong form representation of a model to its weak form, and then solving a regression problem to perform parameter inference. The core statistical idea rests on the Errors-In-Variables framework, which necessitates the use of the iteratively reweighted least squares algorithm. Further improvements are obtained by using orthonormal test functions, created from a set of C-infinity bump functions of varying support sizes. We demonstrate the high robustness and computational efficiency by applying WENDy to estimate parameters in some common models from population biology, neuroscience, and biochemistry, including logistic growth, Lotka-Volterra, FitzHugh-Nagumo, Hindmarsh-Rose, and a Protein Transduction Benchmark model. Software and code for reproducing the examples is available at (https://github.com/MathBioCU/WENDy)., Comment: 28 pages, 16 figures

The commonly observed negative correlation between the number of species in an ecological community and disease risk, typically referred to as "the dilution effect", has received a substantial amount of attention over the past decade. Attempts to test this relationship experimentally have revealed that, in addition to the mean disease risk decreasing with species number, so too does the variance of disease risk. This is referred to as the "variance reduction effect", and has received relatively little attention in the disease-diversity literature. Here, we set out to clarify and quantify some of these relationships in an idealized model of a randomly assembled multi-species community undergoing an epidemic. We specifically investigate the variance of the community disease reproductive ratio, a multi-species extension of the basic reproductive ratio R_0, for a family of random-parameter meta-community SIR models, and show how the variance of community $R_0$ varies depending on whether transmission is density or frequency-dependent. We finally outline areas of further research on how changes in variance affect transmission dynamics in other systems.

Biofilms are communities of bacteria that exhibit a multitude of multiscale biomechanical behaviors. Recent experimental advances have lead to characterizations of these behaviors in terms of measurements of the viscoelastic moduli of biofilms grown in bioreactors and the fracture and fragmentation properties of biofilms. These properties are macroscale features of biofilms; however, a previous work by our group has shown that heterogeneous microscale features are critical in predicting biofilm rheology. In this paper we use tools from statistical physics to develop a generative statistical model of the positions of bacteria in biofilms. We show through simulation that the macroscopic mechanical properties of biofilms depend on the choice of microscale spatial model. Our key finding is that a biologically inspired model of the locations of bacteria in a biofilm is critical to the simulation of biofilms with realistic in silico mechanical properties and statistical characteristics.

In this manuscript we demonstrate the analysis of right-censored survival outcomes using the MRH package in R. The MRH package implements the multi-resolution hazard (MRH) model, which is a Polya-tree based, Bayesian semi-parametric method for flexible estimation of the hazard rate and covariate effects. The package allows for covariates to be included under the proportional and non-proportional hazards assumption, and for robust estimation of the hazard rate in periods of sparsely observed failures via a "pruning" tool.

The "meningitis belt" is a region in sub-Saharan Africa where annual outbreaks of meningitis occur, with large epidemics observed cyclically. While we know that meningitis is heavily dependent on seasonal trends (in particular, weather), the exact pathways for contracting the disease are not fully understood and warrant further investigation. This manuscript examines meningitis trends in the context of survival analysis, quantifying underlying seasonal patterns in meningitis rates through the hazard rate for the population of Navrongo, Ghana. We compare three candidate models: the commonly used Poisson generalized linear model, the Bayesian multi-resolution hazard model, and the Poisson generalized additive model. We compare the accuracy and robustness of the models through the bias, RMSE, and the standard deviation. We provide a detailed case study of meningitis patterns for data collected in Navrongo, Ghana.

We give an overview of eight different software packages and functions available in R for semi- or non-parametric estimation of the hazard rate for right-censored survival data. Of particular interest is the accuracy of the estimation of the hazard rate in the presence of covariates, as well as the user-friendliness of the packages. In addition, we investigate the ability to incorporate covariates under both the proportional and the non-proportional hazards assumptions. We contrast the robustness, variability and precision of the functions through simulations, and then further compare differences between the functions by analyzing the "cancer" and "TRACE" survival data sets available in R, including covariates under the proportional and non-proportional hazards settings.

Analyzing outcomes in long-term cancer survivor studies can be complex. The effects of predictors on the failure process may be difficult to assess over longer periods of time, as the commonly used assumption of proportionality of hazards holding over an extended period is often questionable. In this manuscript, we compare seven different survival models that estimate the hazard rate and the effects of proportional and non-proportional covariates. In particular, we focus on an extension of the the multi-resolution hazard (MRH) estimator, combining a non-proportional hierarchical MRH approach with a data-driven pruning algorithm that allows for computational efficiency and produces robust estimates even in times of few observed failures. Using data from a large-scale randomized prostate cancer clinical trial, we examine patterns of biochemical failure and estimate the time-varying effects of androgen deprivation therapy treatment and other covariates. We compare the impact of different modeling strategies and smoothness assumptions on the estimated treatment effect. Our results show that the benefits of treatment diminish over time, possibly with implications for future treatment protocols.

In this paper we present a method for exact generation of multivariate samples with pre-specified marginal distributions and a given correlation matrix, based on a mixture of Fr\'echet-Hoeffding bounds and marginal products. The bivariate algorithm can accommodate any among the theoretically possible correlation coefficients, and explicitly provides a connection between simulation and the minimum correlation attainable for different distribution families. We calculate the minimum correlations in several common distributional examples, including in some that have not been looked at before. As an illustration, we provide the details and results of implementing the algorithm for generating three-dimensional negatively and positively correlated Beta random variables, making it the only non-copula algorithm for correlated Beta simulation in dimensions greater than two. This work has potential for impact in a variety of fields where simulation of multivariate stochastic components is desired., Comment: Major changes made compared to previous versions. Minimum correlations and Multivariate methods added. 10 pages, 5 figures