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Nonnegative matrix factorization can be used to automatically detect topics within a corpus in an unsupervised fashion. The technique amounts to an approximation of a nonnegative matrix as the product of two nonnegative matrices of lower rank. In certain applications it is desirable to extract topics and use them to predict quantitative outcomes. In this paper, we show Nonnegative Matrix Factorization can be combined with regression on a continuous response variable by minimizing a penalty function that adds a weighted regression error to a matrix factorization error. We show theoretically that as the weighting increases, the regression error in training decreases weakly. We test our method on synthetic data and real data coming from Rate My Professors reviews to predict an instructor's rating from the text in their reviews. In practice, when used as a dimensionality reduction method (when the number of topics chosen in the model is fewer than the true number of topics), the method performs better than doing regression after topics are identified—both during training and testing—and it retrains interpretability. [ABSTRACT FROM AUTHOR]

Oligomers of the amyloid β-protein (Aβ) have been implicated in the pathogenesis of Alzheimer's disease (AD) through their toxicity towards neurons. Understanding the process of oligomerization may contribute to the development of therapeutic agents, but this has been difficult due to the complexity of oligomerization and the metastability of the oligomers thus formed. To understand the kinetics of oligomer formation, and how that relates to the progression of AD, we developed models of the oligomerization process. Here, we use experimental data from cell viability assays and proxies for rate constants involved in monomer-dimer-trimer kinetics to develop a simple mathematical model linking Aβ assembly to oligomer-induced neuronal degeneration. This model recapitulates the rapid growth of disease incidence with age. It does so through incorporation of age-dependent changes in rates of Aβ monomer production and elimination. The model also describes clinical progression in genetic forms of AD (e.g., Down's syndrome), changes in hippocampal volume, AD risk after traumatic brain injury, and spatial spreading of the disease due to foci in which Aβ production is elevated. Continued incorporation of clinical and basic science data into the current model will make it an increasingly relevant model system for doing theoretical calculations that are not feasible in biological systems. In addition, terms in the model that have particularly large effects are likely to be especially useful therapeutic targets. Author summary: Oligomeric assemblies of Aβ are hypothesized to be seminal pathologic agents in Alzheimer's disease (AD). Mechanistic studies of oligomerization and neurotoxicity in humans are currently impossible, yet such studies promise to advance efforts toward target identification and drug development. To overcome this hurdle, we developed a simple, mathematical model parameterized using experimental data extant. The model couples the kinetics of oligomerization with oligomer toxicity and enables determination of age-related changes in AD risk and hippocampal volume, the effects of traumatic brain injury on lifetime AD risk, gene dosage effects, and the effects of spatial variation in Aβ monomer concentrations on millimeter scales. The model is easily interpretable and provides a foundation for development of more comprehensive models of AD development and progression. [ABSTRACT FROM AUTHOR]

In this paper, we develop a continuum model for the movement of agents on a lattice, taking into account location desirability, local and far-range migration, and localized entry and exit rates. Specifically, our motivation is to qualitatively describe the homeless population in Los Angeles. The model takes the form of a fully nonlinear, nonlocal, non-degenerate parabolic partial differential equation. We derive the model and prove useful properties of smooth solutions, including uniqueness and L 2 -stability under certain hypotheses. We also illustrate numerical solutions to the model and find that a simple model can be qualitatively similar in behavior to observed homeless encampments. [ABSTRACT FROM AUTHOR]

Many neurodegenerative diseases (NDs) are characterized by the slow spatial spread of toxic protein species in the brain. The toxic proteins can induce neuronal stress, triggering the Unfolded Protein Response (UPR), which slows or stops protein translation and can indirectly reduce the toxic load. However, the UPR may also trigger processes leading to apoptotic cell death and the UPR is implicated in the progression of several NDs. In this paper, we develop a novel mathematical model to describe the spatiotemporal dynamics of the UPR mechanism for prion diseases. Our model is centered around a single neuron, with representative proteins P (healthy) and S (toxic) interacting with heterodimer dynamics (S interacts with P to form two S’s). The model takes the form of a coupled system of nonlinear reaction–diffusion equations with a delayed, nonlinear flux for P (delay from the UPR). Through the delay, we find parameter regimes that exhibit oscillations in the P- and S-protein levels. We find that oscillations are more pronounced when the S-clearance rate and S-diffusivity are small in comparison to the P-clearance rate and P-diffusivity, respectively. The oscillations become more pronounced as delays in initiating the UPR increase. We also consider quasi-realistic clinical parameters to understand how possible drug therapies can alter the course of a prion disease. We find that decreasing the production of P, decreasing the recruitment rate, increasing the diffusivity of S, increasing the UPR S-threshold, and increasing the S clearance rate appear to be the most powerful modifications to reduce the mean UPR intensity and potentially moderate the disease progression. [ABSTRACT FROM AUTHOR]

We present an unsupervised method to detect anomalous time series among a collection of time series. To do so, we extend traditional Kernel Density Estimation for estimating probability distributions in Euclidean space to Hilbert spaces. The estimated probability densities we derive can be obtained formally through treating each series as a point in a Hilbert space, placing a kernel at those points, and summing the kernels (a "point approach"), or through using Kernel Density Estimation to approximate the distributions of Fourier mode coefficients to infer a probability density (a "Fourier approach"). We refer to these approaches as Functional Kernel Density Estimation for Anomaly Detection as they both yield functionals that can score a time series for how anomalous it is. Both methods naturally handle missing data and apply to a variety of settings, performing well when compared with an outlyingness score derived from a boxplot method for functional data, with a Principal Component Analysis approach for functional data, and with the Functional Isolation Forest method. We illustrate the use of the proposed methods with aviation safety report data from the International Air Transport Association (IATA). [ABSTRACT FROM AUTHOR]

In this paper, we use modified versions of the SIAR model for epidemics to propose two ways of understanding and quantifying the effect of non-compliance to non-pharmaceutical intervention measures on the spread of an infectious disease. The SIAR model distinguishes between symptomatic infected (I) and asymptomatic infected (A) populations. One modification, which is simpler, assumes a known proportion of the population does not comply with government mandates such as quarantining and social-distancing. In a more sophisticated approach, the modified model treats non-compliant behavior as a social contagion. We theoretically explore different scenarios such as the occurrence of multiple waves of infections. Local and asymptotic analyses for both models are also provided. [ABSTRACT FROM AUTHOR]

A major strategy to prevent the spread of COVID-19 is the limiting of in-person contacts. However, limiting contacts is impractical or impossible for the many disabled people who do not live in care facilities but still require caregivers to assist them with activities of daily living. We seek to determine which interventions can best prevent infections of disabled people and their caregivers. To accomplish this, we simulate COVID-19 transmission with a compartmental model that includes susceptible, exposed, asymptomatic, symptomatically ill, hospitalized, and removed/recovered individuals. The networks on which we simulate disease spread incorporate heterogeneity in the risk levels of different types of interactions, time-dependent lockdown and reopening measures, and interaction distributions for four different groups (caregivers, disabled people, essential workers, and the general population). Of these groups, we find that the probability of becoming infected is largest for caregivers and second largest for disabled people. Consistent with this finding, our analysis of network structure illustrates that caregivers have the largest modal eigenvector centrality of the four groups. We find that two interventions—contact-limiting by all groups and mask-wearing by disabled people and caregivers—most reduce the number of infections in disabled and caregiver populations. We also test which group of people spreads COVID-19 most readily by seeding infections in a subset of each group and comparing the total number of infections as the disease spreads. We find that caregivers are the most potent spreaders of COVID-19, particularly to other caregivers and to disabled people. We test where to use limited infection-blocking vaccine doses most effectively and find that (1) vaccinating caregivers better protects disabled people from infection than vaccinating the general population or essential workers and that (2) vaccinating caregivers protects disabled people from infection about as effectively as vaccinating disabled people themselves. Our results highlight the potential effectiveness of mask-wearing, contact-limiting throughout society, and strategic vaccination for limiting the exposure of disabled people and their caregivers to COVID-19. Author summary: Disabled people who need help with daily life tasks, such as dressing or bathing, have frequent close contacts with caregivers. This prevents disabled people and their caregivers from physically distancing from one another, and it also significantly increases the risk of both groups of contracting COVID-19. How can society help disabled people and caregivers avoid infections? To answer this question, we simulate infections on networks that we model based on a city of about one million people. We find that one good strategy is for both disabled people and their caregivers to use masks when they are together. We also find that if only disabled people limit their contacts while other people continue their lives normally, disabled people are not protected effectively. However, it helps disabled people substantially if the general population also limits their contacts. We also study which vaccination strategies can most efficiently protect disabled people. Our simulations suggest that vaccinating caregivers against COVID-19 protects the disabled subpopulation about equally effectively as vaccinating a similar number of disabled people. Our findings highlight both behavioral measures and vaccination strategies that society can take to protect disabled people and caregivers from COVID-19. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, conflicting opinions on physical distancing swept across social media, affecting both human behavior and the spread of COVID-19. Inspired by such phenomena, we construct a two-layer multiplex network for the coupled spread of a disease and conflicting opinions. We model each process as a contagion. On one layer, we consider the concurrent evolution of two opinions — pro-physical-distancing and anti-physical-distancing — that compete with each other and have mutual immunity to each other. The disease evolves on the other layer, and individuals are less likely (respectively, more likely) to become infected when they adopt the pro-physical-distancing (respectively, anti-physical-distancing) opinion. We develop approximations of mean-field type by generalizing monolayer pair approximations to multilayer networks; these approximations agree well with Monte Carlo simulations for a broad range of parameters and several network structures. Through numerical simulations, we illustrate the influence of opinion dynamics on the spread of the disease from complex interactions both between the two conflicting opinions and between the opinions and the disease. We find that lengthening the duration that individuals hold an opinion may help suppress disease transmission, and we demonstrate that increasing the cross-layer correlations or intra-layer correlations of node degrees may lead to fewer individuals becoming infected with the disease. [ABSTRACT FROM AUTHOR]