Memory effects in disease modelling through kernel estimates with oscillatory time history.

We design a linear chain trick algorithm for dynamical systems for which we have oscillatory time histories in the distributed time delay. We make use of this algorithmic framework to analyse memory effects in disease evolution in a population. The modelling is based on a susceptible-infected-recovered SIR-model and on a susceptible-exposed-infected-recovered SEIR-model through a kernel that dampens the activity based on the recent history of infectious individuals. This corresponds to adaptive behavior in the population or through governmental non-pharmaceutical interventions. We use the linear chain trick to show that such a model may be written in a Markovian way, and we analyze the stability of the system. We find that the adaptive behavior gives rise to either a stable equilibrium point or a stable limit cycle for a close to constant number of susceptibles, i.e. locally in time. We also show that the attack rate for this model is lower than it would be without the dampening, although the adaptive behavior disappears as time goes to infinity and the number of infected goes to zero.

The Dynamics of Pasture-Herbivores-Carnivores with Sigmoidal Density Dependent Harvesting.

We investigate biomass-herbivore-carnivore (top predator) interactions in terms of a tritrophic dynamical systems model. The harvesting rates of the herbivores and the top predators are described by means of a sigmoidal function of the herbivores density and the top predator density, respectively. The main focus in this study is on the dynamics as a function of the natural mortality and the maximal harvesting rate of the top predators. We identify parameter regimes for which we have non-existence of equilibrium points as well as necessary conditions for the existence of such states of the modelling framework. The system does not possess any finite equilibrium states in the regime of high herbivore mortality. In the regime of a high consumption rate of the herbivores and low mortality rates of the top predator, an asymptotically stable finite equilibrium state exists. For this positive equilibrium to exist the mortality of the top predator should not exceed a certain threshold level. We also detect regimes producing coexistence of equilibrium states and their respective stability properties. In the regime of negligible harvesting of the top predator level, we observe a finite window of the natural top predator mortality rates for which oscillations in the top predator-, the herbivore- and the biomass level take place. The lower and upper bound of this window correspond to two Hopf bifurcation points. We also identify a bifurcation diagram using the top predator harvesting rate as a control variable. Using this diagram we detect several saddle node- and Hopf bifurcation points as well as regimes for which we have coexistence of interior equilibrium states, bistability and relaxation type of oscillations.

Pattern formation in a 2-population homogenized neuronal network model.

We study pattern formation in a 2-population homogenized neural field model of the Hopfield type in one spatial dimension with periodic microstructure. The connectivity functions are periodically modulated in both the synaptic footprint and in the spatial scale. It is shown that the nonlocal synaptic interactions promote a finite band width instability. The stability method relies on a sequence of wave-number dependent invariants of [Formula: see text]-stability matrices representing the sequence of Fourier-transformed linearized evolution equations for the perturbation imposed on the homogeneous background. The generic picture of the instability structure consists of a finite set of well-separated gain bands. In the shallow firing rate regime the nonlinear development of the instability is determined by means of the translational invariant model with connectivity kernels replaced with the corresponding period averaged connectivity functions. In the steep firing rate regime the pattern formation process depends sensitively on the spatial localization of the connectivity kernels: For strongly localized kernels this process is determined by the translational invariant model with period averaged connectivity kernels, whereas in the complementary regime of weak and moderate localization requires the homogenized model as a starting point for the analysis. We follow the development of the instability numerically into the nonlinear regime for both steep and shallow firing rate functions when the connectivity kernels are modeled by means of an exponentially decaying function. We also study the pattern forming process numerically as a function of the heterogeneity parameters in four different regimes ranging from the weakly modulated case to the strongly heterogeneous case. For the weakly modulated regime, we observe that stable spatial oscillations are formed in the steep firing rate regime, whereas we get spatiotemporal oscillations in the shallow regime of the firing rate functions.

Ill-Posed Point Neuron Models.

We show that point-neuron models with a Heaviside firing rate function can be ill posed. More specifically, the initial-condition-to-solution map might become discontinuous in finite time. Consequently, if finite precision arithmetic is used, then it is virtually impossible to guarantee the accurate numerical solution of such models. If a smooth firing rate function is employed, then standard ODE theory implies that point-neuron models are well posed. Nevertheless, in the steep firing rate regime, the problem may become close to ill posed, and the error amplification, in finite time, can be very large. This observation is illuminated by numerical experiments. We conclude that, if a steep firing rate function is employed, then minor round-off errors can have a devastating effect on simulations, unless proper error-control schemes are used.

QMRA for Drinking Water: 1. Revisiting the Mathematical Structure of Single-Hit Dose-Response Models.

Dose-response models are essential to quantitative microbial risk assessment (QMRA), providing a link between levels of human exposure to pathogens and the probability of negative health outcomes. In drinking water studies, the class of semi-mechanistic models known as single-hit models, such as the exponential and the exact beta-Poisson, has seen widespread use. In this work, an attempt is made to carefully develop the general mathematical single-hit framework while explicitly accounting for variation in (1) host susceptibility and (2) pathogen infectivity. This allows a precise interpretation of the so-called single-hit probability and precise identification of a set of statistical independence assumptions that are sufficient to arrive at single-hit models. Further analysis of the model framework is facilitated by formulating the single-hit models compactly using probability generating and moment generating functions. Among the more practically relevant conclusions drawn are: (1) for any dose distribution, variation in host susceptibility always reduces the single-hit risk compared to a constant host susceptibility (assuming equal mean susceptibilities), (2) the model-consistent representation of complete host immunity is formally demonstrated to be a simple scaling of the response, (3) the model-consistent expression for the total risk from repeated exposures deviates (gives lower risk) from the conventional expression used in applications, and (4) a model-consistent expression for the mean per-exposure dose that produces the correct total risk from repeated exposures is developed.

QMRA for Drinking Water: 2. The Effect of Pathogen Clustering in Single-Hit Dose-Response Models.

Spatial and/or temporal clustering of pathogens will invalidate the commonly used assumption of Poisson-distributed pathogen counts (doses) in quantitative microbial risk assessment. In this work, the theoretically predicted effect of spatial clustering in conventional "single-hit" dose-response models is investigated by employing the stuttering Poisson distribution, a very general family of count distributions that naturally models pathogen clustering and contains the Poisson and negative binomial distributions as special cases. The analysis is facilitated by formulating the dose-response models in terms of probability generating functions. It is shown formally that the theoretical single-hit risk obtained with a stuttering Poisson distribution is lower than that obtained with a Poisson distribution, assuming identical mean doses. A similar result holds for mixed Poisson distributions. Numerical examples indicate that the theoretical single-hit risk is fairly insensitive to moderate clustering, though the effect tends to be more pronounced for low mean doses. Furthermore, using Jensen's inequality, an upper bound on risk is derived that tends to better approximate the exact theoretical single-hit risk for highly overdispersed dose distributions. The bound holds with any dose distribution (characterized by its mean and zero inflation index) and any conditional dose-response model that is concave in the dose variable. Its application is exemplified with published data from Norovirus feeding trials, for which some of the administered doses were prepared from an inoculum of aggregated viruses. The potential implications of clustering for dose-response assessment as well as practical risk characterization are discussed.

A minimal mechanistic model for temporal signal processing in the lateral geniculate nucleus.

The receptive fields of cells in the lateral geniculate nucleus (LGN) are shaped by their diverse set of impinging inputs: feedforward synaptic inputs stemming from retina, and feedback inputs stemming from the visual cortex and the thalamic reticular nucleus. To probe the possible roles of these feedforward and feedback inputs in shaping the temporal receptive-field structure of LGN relay cells, we here present and investigate a minimal mechanistic firing-rate model tailored to elucidate their disparate features. The model for LGN relay ON cells includes feedforward excitation and inhibition (via interneurons) from retinal ON cells and excitatory and inhibitory (via thalamic reticular nucleus cells and interneurons) feedback from cortical ON and OFF cells. From a general firing-rate model formulated in terms of Volterra integral equations, we derive a single delay differential equation with absolute delay governing the dynamics of the system. A freely available and easy-to-use GUI-based MATLAB version of this minimal mechanistic LGN circuit model is provided. We particularly investigate the LGN relay-cell impulse response and find through thorough explorations of the model's parameter space that both purely feedforward models and feedback models with feedforward excitation only, can account quantitatively for previously reported experimental results. We find, however, that the purely feedforward model predicts two impulse response measures, the time to first peak and the biphasic index (measuring the relative weight of the rebound phase) to be anticorrelated. In contrast, the models with feedback predict different correlations between these two measures. This suggests an experimental test assessing the relative importance of feedforward and feedback connections in shaping the impulse response of LGN relay cells.

Neural network firing-rate models on integral form: effects of temporal coupling kernels on equilibrium-state stability.

Firing-rate models describing neural-network activity can be formulated in terms of differential equations for the synaptic drive from neurons. Such models are typically derived from more general models based on Volterra integral equations assuming exponentially decaying temporal coupling kernels describing the coupling of pre- and postsynaptic activities. Here we study models with other choices of temporal coupling kernels. In particular, we investigate the stability properties of constant solutions of two-population Volterra models by studying the equilibrium solutions of the corresponding autonomous dynamical systems, derived using the linear chain trick, by means of the Routh-Hurwitz criterion. In the four investigated synaptic-drive models with identical equilibrium points we find that the choice of temporal coupling kernels significantly affects the equilibrium-point stability properties. A model with an alpha-function replacing the standard exponentially decaying function in the inhibitory coupling kernel is in most of our examples found to be most prone to instability, while the opposite situation with an alpha-function describing the excitatory kernel is found to be least prone to instability. The standard model with exponentially decaying coupling kernels is typically found to be an intermediate case. We further find that stability is promoted by increasing the weight of self-inhibition or shortening the time constant of the inhibition.

Nonlocal incoherent solitons.

We investigate the propagation of partially coherent beams in spatially nonlocal nonlinear media with a logarithmic type of nonlinearity. We derive analytical formulas for the evolution of the beam parameters and conditions for the formation of nonlocal incoherent solitons.

Collapse arrest and soliton stabilization in nonlocal nonlinear media.

We investigate the properties of localized waves in cubic nonlinear materials with a symmetric nonlocal nonlinear response of arbitrary shape and degree of nonlocality, described by a general nonlocal nonlinear Schrödinger type equation. We prove rigorously by bounding the Hamiltonian that nonlocality of the nonlinearity prevents collapse in, e.g., Bose-Einstein condensates and optical Kerr media in all physical dimensions. The nonlocal nonlinear response must be symmetric and have a positive definite Fourier spectrum, but can otherwise be of completely arbitrary shape and degree of nonlocality. We use variational techniques to find the soliton solutions and illustrate the stabilizing effect of nonlocality.

Generic features of modulational instability in nonlocal Kerr media.

The modulational instability (MI) of plane waves in nonlocal Kerr media is studied for a general response function. Several generic properties are proven mathematically, with emphasis on how new gain bands are formed through a bifurcation process when the degree of nonlocality, sigma, passes certain bifurcation values and how the bandwidth and maximum of each individual gain band depends on sigma. The generic properties of the MI gain spectrum, including the bifurcation phenomena, are then demonstrated for the exponential and rectangular response functions. For a focusing nonlinearity the nonlocality tends to suppress MI, but can never remove it completely, irrespectively of the shape of the response function. For a defocusing nonlinearity the stability properties depend sensitively on the profile of the response function. For response functions with a positive-definite spectrum, such as Gaussians and exponentials, plane waves are always stable, whereas response functions with spectra that are not positive definite (such as the rectangular) will lead to MI if sigma exceeds a certain threshold. For the square response function, in both the focusing and defocusing case, we show analytically and numerically how new gain bands that form at higher wave numbers when sigma increases will eventually dominate the existing gain bands at lower wave numbers and abruptly change the length scale of the periodic pattern that may be observed in experiments.