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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]

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]