Despite the progress in medical data collection the actual burden of SARS-CoV-2 remains unknown due to under-ascertainment of cases. This was apparent in the acute phase of the pandemic and the use of reported deaths has been pointed out as a more reliable source of information, likely less prone to under-reporting. Since daily deaths occur from past infections weighted by their probability of death, one may infer the total number of infections accounting for their age distribution, using the data on reported deaths. We adopt this framework and assume that the dynamics generating the total number of infections can be described by a continuous time transmission model expressed through a system of nonlinear ordinary differential equations where the transmission rate is modeled as a diffusion process allowing to reveal both the effect of control strategies and the changes in individuals behavior. We develop this flexible Bayesian tool in Stan and study 3 pairs of European countries, estimating the time-varying reproduction number ( R t $$ {R}_t $$ ) as well as the true cumulative number of infected individuals. As we estimate the true number of infections we offer a more accurate estimate of R t $$ {R}_t $$ . We also provide an estimate of the daily reporting ratio and discuss the effects of changes in mobility and testing on the inferred quantities.

Concentrations of pathogen genomes measured in wastewater have recently become available as a new data source to use when modeling the spread of infectious diseases. One promising use for this data source is inference of the effective reproduction number, the average number of individuals a newly infected person will infect. We propose a model where new infections arrive according to a time-varying immigration rate which can be interpreted as an average number of secondary infections produced by one infectious individual per unit time. This model allows us to estimate the effective reproduction number from concentrations of pathogen genomes, while avoiding difficulty to verify assumptions about the dynamics of the susceptible population. As a byproduct of our primary goal, we also produce a new model for estimating the effective reproduction number from case data using the same framework. We test this modeling framework in an agent-based simulation study with a realistic data generating mechanism which accounts for the time-varying dynamics of pathogen shedding. Finally, we apply our new model to estimating the effective reproduction number of SARS-CoV-2, the causative agent of COVID-19, in Los Angeles, CA, using pathogen RNA concentrations collected from a large wastewater treatment facility.

We propose a compartmental model for investigating smoking dynamics in an Italian region (Tuscany). Calibrating the model on local data from 1993 to 2019, we estimate the probabilities of starting and quitting smoking and the probability of smoking relapse. Then, we forecast the evolution of smoking prevalence until 2043 and assess the impact on mortality in terms of attributable deaths. We introduce elements of novelty with respect to previous studies in this field, including a formal definition of the equations governing the model dynamics and a flexible modelling of smoking probabilities based on cubic regression splines. We estimate model parameters by defining a two-step procedure and quantify the sampling variability via a parametric bootstrap. We propose the implementation of cross-validation on a rolling basis and variance-based Global Sensitivity Analysis to check the robustness of the results and support our findings. Our results suggest a decrease in smoking prevalence among males and stability among females, over the next two decades. We estimate that, in 2023, 18% of deaths among males and 8% among females are due to smoking. We test the use of the model in assessing the impact on smoking prevalence and mortality of different tobacco control policies, including the tobacco-free generation ban recently introduced in New Zealand.

The COVID-19 pandemic emerged in late December 2019. In the first six months of the global outbreak, the U.S. reported more cases and deaths than any other country in the world. Effective modeling of the course of the pandemic can help assist with public health resource planning, intervention efforts, and vaccine clinical trials. However, building applied forecasting models presents unique challenges during a pandemic. First, case data available to models in real time represent a nonstationary fraction of the true case incidence due to changes in available diagnostic tests and test-seeking behavior. Second, interventions varied across time and geography leading to large changes in transmissibility over the course of the pandemic. We propose a mechanistic Bayesian model that builds upon the classic compartmental susceptible-exposed-infected-recovered (SEIR) model to operationalize COVID-19 forecasting in real time. This framework includes nonparametric modeling of varying transmission rates, nonparametric modeling of case and death discrepancies due to testing and reporting issues, and a joint observation likelihood on new case counts and new deaths; it is implemented in a probabilistic programming language to automate the use of Bayesian reasoning for quantifying uncertainty in probabilistic forecasts. The model has been used to submit forecasts to the U.S. Centers for Disease Control through the COVID-19 Forecast Hub under the name MechBayes. We examine the performance relative to a baseline model as well as alternate models submitted to the forecast hub. Additionally, we include an ablation test of our extensions to the classic SEIR model. We demonstrate a significant gain in both point and probabilistic forecast scoring measures using MechBayes, when compared to a baseline model, and show that MechBayes ranks as one of the top two models out of nine which regularly submitted to the COVID-19 Forecast Hub for the duration of the pandemic, trailing only the COVID-19 Forecast Hub ensemble model of which which MechBayes is a part.

During the COVID-19 pandemic, several forecasting models were released to predict the spread of the virus along variables vital for public health policymaking. Of these, the susceptible-infected-recovered (SIR) compartmental model was the most common. In this paper, we investigated the forecasting performance of The University of Texas COVID-19 Modeling Consortium SIR model. We considered the following daily outcomes: hospitalizations, ICU patients, and deaths. We evaluated the overall forecasting performance, highlighted some stark forecast biases, and considered forecast errors conditional on different pandemic regimes. We found that this model tends to overforecast over the longer horizons and when there is a surge in viral spread. We bolstered these findings by linking them to faults with the SIR framework itself.

Life history traits have been studied under various environmental factors, but the ability to combine them into a simple function to assess pest response to climate is still lacking complete understanding. This study proposed a risk index derived by combining development, mortality, and fertility rates from a stage-structured dynamic mathematical model. The first part presents the theoretical framework behind the risk index. The second part of the study is concerned with the application of the index in two case studies of major economic pest: the brown planthopper (Nilaparvata lugens) and the spotted wing drosophila (Drosophila suzukii), pests of rice crops and soft fruits, respectively. The mathematical calculations provided a single function composed of the main thermal biodemographic rates. This function has a threshold value that determines the possibility of population increase as a function of temperature. The tests carried out on the two pest species showed the capability of the index to describe the range of favourable conditions. With this approach, we were able to identify areas where pests are tolerant to climatic conditions and to project them on a geospatial risk map. The theoretical background developed here provided a tool for understanding the biogeography of Nilaparvata lugens and Drosophila suzukii. It is flexible enough to deal with mathematically simple (N. lugens) and complex (D. Suzukii) case studies of crop insect pests. It produces biologically sound indices that behave like thermal performance curves. These theoretical results also provide a reasonable basis for addressing the challenge of pest management in the context of seasonal weather variations and climate change. This may help to improve monitoring and design management strategies to limit the spread of pests in invaded areas, as some non-invaded areas may be suitable for the species to develop.

OBJECTIVE: The ability to measure specific molecules at multiple sites within the body simultaneously, and with a time resolution of seconds, could greatly advance our understanding of drug transport and elimination.
METHODS: As a proof-of-principle demonstration, here we describe the use of electrochemical aptamer-based (EAB) sensors to measure transport of the antibiotic vancomycin from the plasma (measured in the jugular vein) to the cerebrospinal fluid (measured in the lateral ventricle) of live rats with temporal resolution of a few seconds.
RESULTS: In our first efforts, we made measurements solely in the ventricle. Doing so we find that, although the collection of hundreds of concentration values over a single drug lifetime enables high-precision estimates of the parameters describing intracranial transport, due to a mathematical equivalence, the data produce two divergent descriptions of the drug\'s plasma pharmacokinetics that fit the in-brain observations equally well. The simultaneous collection of intravenous measurements, however, resolves this ambiguity, enabling high-precision (typically of ±5 to ±20% at 95% confidence levels) estimates of the key pharmacokinetic parameters describing transport from the blood to the cerebrospinal fluid in individual animals.
CONCLUSIONS: The availability of simultaneous, high-density \'in-vein\' (plasma) and \'in-brain\' (cerebrospinal fluid) measurements provides unique opportunities to explore the assumptions almost universally employed in earlier compartmental models of drug transport, allowing the quantitative assessment of, for example, the pharmacokinetic effects of physiological processes such as the bulk transport of the drug out of the CNS via the dural venous sinuses.

We consider compartmental models of communicable disease with uncertain contact rates. Stochastic fluctuations are often added to the contact rate to account for uncertainties. White noise, which is the typical choice for the fluctuations, leads to significant underestimation of the disease severity. Here, starting from reasonable assumptions on the social behavior of individuals, we model the contacts as a Markov process which takes into account the temporal correlations present in human social activities. Consequently, we show that the mean-reverting Ornstein-Uhlenbeck (OU) process is the correct model for the stochastic contact rate. We demonstrate the implication of our model on two examples: a Susceptibles-Infected-Susceptibles (SIS) model and a Susceptibles-Exposed-Infected-Removed (SEIR) model of the COVID-19 pandemic and compare the results to the available US data from the Johns Hopkins University database. In particular, we observe that both compartmental models with white noise uncertainties undergo transitions that lead to the systematic underestimation of the spread of the disease. In contrast, modeling the contact rate with the OU process significantly hinders such unrealistic noise-induced transitions. For the SIS model, we derive its stationary probability density analytically, for both white and correlated noise. This allows us to give a complete description of the model\'s asymptotic behavior as a function of its bifurcation parameters, i.e., the basic reproduction number, noise intensity, and correlation time. For the SEIR model, where the probability density is not available in closed form, we study the transitions using Monte Carlo simulations. Our modeling approach can be used to quantify uncertain parameters in a broad range of biological systems.

The aim of this article is to give a better understanding of the dynamics of the SARS-CoV-2 pandemic in the Bergamo province (Italy), one of the most hit areas of the world, between February and April 2020. A new compartmental model, called SIAT3HE, was designed and fitted on accurate data about the pandemic provided by ATS Bergamo, the health protection agency of the Bergamo province. Our results show that SARS-CoV-2 reached Bergamo in January and infected 318,000 people, the 28.8% of the province population. The 43.1% of the infected individuals stayed asymptomatic. As 6,028 people died due to COVID-19 till April 30th, the infection fatality ratio of SARS-CoV-2 in the Bergamo province was 1.9%. These results are in very good agreement with available information: the number of infections is consistent with the results of recent serological surveys and the number of deaths due to COVID-19 is close to the excess mortality of the considered period.

Screening programs that pre-emptively and routinely test population groups for disease at a massive scale were first implemented during the COVID-19 pandemic in a handful of countries. One of these countries was Greece, which implemented a mass self-testing program during 2021. In contrast to most other non-pharmaceutical interventions (NPIs), mass self-testing programs are particularly attractive for their relatively small financial and social burden, and it is therefore important to understand their effectiveness to inform policy makers and public health officials responding to future pandemics. This study aimed to estimate the number of deaths and hospitalizations averted by the program implemented in Greece and evaluate the impact of several operational decisions.
Granular data from the mass self-testing program deployed by the Greek government between April and December 2021 were obtained. The data were used to fit a novel compartmental model that was developed to describe the dynamics of the COVID-19 pandemic in Greece in the presence of self-testing. The fitted model provided estimates on the effectiveness of the program in averting deaths and hospitalizations. Sensitivity analyses were used to evaluate the impact of operational decisions, including the scale of the program, targeting of sub-populations, and sensitivity (i.e., true positive rate) of tests.
Conservative estimates show that the program reduced the reproduction number by 4%, hospitalizations by 25%, and deaths by 20%, translating into approximately 20,000 averted hospitalizations and 2,000 averted deaths in Greece between April and December 2021.
Mass self-testing programs are efficient NPIs with minimal social and financial burden; therefore, they are invaluable tools to be considered in pandemic preparedness and response.