Growing evidence suggests that impaired gut permeability and gut microbiota alterations are involved in the pathogenesis of Inflammatory Bowel Diseases (IBDs), which include Ulcerative Colitis (UC) and Crohn\'s Disease (CD). Vedolizumab is an anti-α4β7 antibody approved for IBD treatment, used as the first treatment or second-line therapy when the first line results in inadequate effectiveness. The aim of this study is to develop a mathematical model capable of describing the pathophysiological mechanisms of Vedolizumab treatment in IBD patients. In particular, the relationship between drug concentration in the blood, colonic mucosal permeability and fecal microbiota composition was investigated and modeled to detect and predict trends in order to support and tailor Vedolizumab therapies. To pursue this aim, clinical data from a pilot study on a cluster of 11 IBD patients were analyzed. Enrolled patients underwent colonoscopy in three phases (before (t0), after 24 weeks of (t1) and after 52 weeks of (t2 ) Vedolizumab treatment) to collect mucosal biopsies for transepithelial electrical resistance (TEER) evaluation (permeability to ions), intestinal permeability measurement and histological analysis. Moreover, fecal samples were collected for the intestinal microbiota analysis at the three time points. The collected data were compared to those of 11 healthy subjects at t0, who underwent colonoscopy for screening surveillance, and used to implement a three-compartmental mathematical model (comprising central blood, peripheral blood and the intestine). The latter extends previous evidence from the literature, based on the regression of experimental data, to link drug concentration in the peripheral blood compartment with Roseburia abundance and intestinal permeability. The clinical data showed that Vedolizumab treatment leads to an increase in TEER and a reduction in intestinal permeability to a paracellular probe, improving tissue inflammation status. Microbiota analysis showed increasing values of Roseburia, albeit not statistically significant. This trend was adequately reproduced by the mathematical model, which offers a useful tool to describe the pathophysiological effects of Vedolizumab therapy on colonic mucosal permeability and fecal microbiota composition. The model\'s satisfactory predictive capabilities and simplicity shed light on the relationship between the drug, the microbiota and permeability and allow for its straightforward extension to diverse therapeutic conditions.

OBJECTIVE: Evaluation of distribution kinetics is a neglected aspect of pharmacokinetics. This study examines the utility of the model-independent parameter whole body distribution clearance (CLD) in this respect.
METHODS: Since mammillary compartmental models are widely used, CLD was calculated in terms of parameters of this model for 15 drugs. The underlying distribution processes were explored by assessment of relationships to pharmacokinetic parameters and covariates.
RESULTS: The model-independence of the definition of the parameter CLD allowed a comparison of distributional properties of different drugs and provided physiological insight. Significant changes in CLD were observed as a result of drug-drug interactions, transporter polymorphisms and a diseased state.
CONCLUSIONS: Total distribution clearance CLD is a useful parameter to evaluate distribution kinetics of drugs. Its estimation as an adjunct to the model-independent parameters clearance and steady-state volume of distribution is advocated.

We propose a versatile model with a flexible choice of control for an early-pandemic outbreak prevention when vaccine/drug is not yet available. At that stage, control is often limited to non-medical interventions like social distancing and other behavioral changes. For the SIR optimal control problem, we show that the running cost of control satisfying mild, practically justified conditions generates an optimal strategy, u(t), t ∈ [0, T], that is sustainable up until some moment τ ∈ [0, T). However, for any t ∈ [τ, T], the function u(t) will decline as t approaches T, which may cause the number of newly infected people to increase. So, the window from 0 to τ is the time for public health officials to prepare alternative mitigation measures, such as vaccines, testing, antiviral medications, and others. In addition to theoretical study, we develop a fast and stable computational method for solving the proposed optimal control problem. The efficiency of the new method is illustrated with numerical examples of optimal control trajectories for various cost functions and weights. Simulation results provide a comprehensive demonstration of the effects of control on the epidemic spread and mitigation expenses, which can serve as invaluable references for public health officials.

In this work, we introduce a compartmental model of ovarian follicle development all along lifespan, based on ordinary differential equations. The model predicts the changes in the follicle numbers in different maturation stages with aging. Ovarian follicles may either move forward to the next compartment (unidirectional migration) or degenerate and disappear (death). The migration from the first follicle compartment corresponds to the activation of quiescent follicles, which is responsible for the progressive exhaustion of the follicle reserve (ovarian aging) until cessation of reproductive activity. The model consists of a data-driven layer embedded into a more comprehensive, knowledge-driven layer encompassing the earliest events in follicle development. The data-driven layer is designed according to the most densely sampled experimental dataset available on follicle numbers in the mouse. Its salient feature is the nonlinear formulation of the activation rate, whose formulation includes a feedback term from growing follicles. The knowledge-based, coating layer accounts for cutting-edge studies on the initiation of follicle development around birth. Its salient feature is the co-existence of two follicle subpopulations of different embryonic origins. We then setup a complete estimation strategy, including the study of structural identifiability, the elaboration of a relevant optimization criterion combining different sources of data (the initial dataset on follicle numbers, together with data in conditions of perturbed activation, and data discriminating the subpopulations) with appropriate error models, and a model selection step. We finally illustrate the model potential for experimental design (suggestion of targeted new data acquisition) and in silico experiments.

This paper simulates a hypothetical pan-coronavirus vaccine that confers immediate sterilizing immunity against all SARS-CoV-2 variants. Simulations used a SEIIS (susceptible, exposed, infective, immune, susceptible) spreadsheet model that ran two parallel subpopulations: one that accepted vaccination and another that refused it. The two subpopulations could transmit infections to one another. Using data from the United States (US), the simulated vaccine was tested against limiting factors such as vaccine hesitancy, slow vaccination distribution, and the development of high-transmission variants. The vaccine was often successful at reducing cases, but high-transmission variants and discontinuation of non-pharmaceutical interventions (NPIs) such as masking greatly elevated cases. A puzzling outcome was that if NPIs were discontinued and high-transmission variants became common, the model predicted consistently higher rates of disease than are actually observed in the US in 2024. However, if cumulative exposure to virus antigens increased the duration of immunity or decreased the infectivity of the virus, the model predictions were brought back into a more realistic range. The major finding was that even when a COVID-19 vaccine always produces sterilizing immunity against every SARS-CoV-2 variant, its ability to control the epidemic can be compromised by multiple common conditions.

Human travel plays a crucial role in the spread of infectious disease between regions. Travel of infected individuals from one region to another can transport a virus to places that were previously unaffected or may accelerate the spread of disease in places where the disease is not yet well established. We develop and apply models and metrics to analyze the role of inter-regional travel relative to the spread of disease, drawing from data on COVID-19 in the United States. To better understand how transportation affects disease transmission, we established a multi-regional time-varying compartmental disease model with spatial interaction. The compartmental model was integrated with statistical estimates of travel between regions. From the integrated model, we derived a transmission import index to assess the risk of COVID-19 transmission between states. Based on the index, we determined states with high risk for disease spreading to other states at the scale of months, and we analyzed how the index changed over time during 2020. Our model provides a tool for policymakers to evaluate the influence of travel between regions on disease transmission in support of strategies for epidemic control.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infections in children worldwide. The highest incidence of severe disease is in the first 6 months of life, with infants born preterm at greatest risk for severe RSV infections. The licensure of new RSV therapeutics (a long-acting monoclonal antibody and a maternal vaccine) in Europe, USA, UK and most recently in Australia, has driven the need for strategic decision making on the implementation of RSV immunisation programs. Data driven approaches, considering the local RSV epidemiology, are critical to advise on the optimal use of these therapeutics for effective RSV control.
METHODS: We developed a dynamic compartmental model of RSV transmission fitted to individually-linked population-based laboratory, perinatal and hospitalisation data for 2000-2012 from metropolitan Western Australia (WA), stratified by age and prior exposure. We account for the differential risk of RSV-hospitalisation in full-term and preterm infants (defined as < 37 weeks gestation). We formulated a function relating age, RSV exposure history, and preterm status to the risk of RSV-hospitalisation given infection.
RESULTS: The age-to-risk function shows that risk of hospitalisation, given RSV infection, declines quickly in the first 12 months of life for all infants and is 2.6 times higher in preterm compared with term infants. The hospitalisation risk, given infection, declines to < 10% of the risk at birth by age 7 months for term infants and by 9 months for preterm infants.
CONCLUSIONS: The dynamic model, using the age-to-risk function, characterises RSV epidemiology for metropolitan WA and can now be extended to predict the impact of prevention measures. The stratification of the model by preterm status will enable the comparative assessment of potential strategies in the extended model that target this RSV risk group relative to all-population approaches. Furthermore, the age-to-risk function developed in this work has wider relevance to the epidemiological characterisation of RSV.

OBJECTIVE: To investigate the optimal dual-time-point (DTP) approaches using dynamic 68Ga-PSMA-11 PET/CT imaging to generate parametric images for prostate cancer patients.
METHODS: Fifteen patients with prostate cancer were intravenously administered 68Ga-PSMA-11 of 181.9 ± 47.2 MBq, followed by an immediate 60 min dynamic PET/CT scan. List-mode data were reconstructed into 25 timeframes (6 × 10 s, 8 × 30 s, and 11 × 300 s) and corrected for motion and partial volume effect. DTP parametric images were generated using different interval time points of 5 min and 10 min, with a minimum of 30 min time interval. Net influx rates (Ki) were calculated through the fitting of a single irreversible two-tissue compartmental model. Intraclass correlation coefficient (ICC) values between DTP protocols and 60 min Ki were obtained. Lesion-to-background ratios (LBRs) of Ki and standardized uptake value (SUV) images in each DTP protocol were determined.
RESULTS: The DTP protocol of 5-10 min with a 40-45 min interval showed the highest ICC of 0.988 compared with the 60 min Ki, whereas the ICC values for the intervals of 0-5 min with 55-60 min and 0-10 min with 50-60 min were 0.941. The LBRs of the 60 min Ki, 5-10 min with 40-45 min Ki, 0-5 min with 55-60 min Ki, 0-10 min with 50-60 min Ki, SUVmean, and SUVmax images were 29.53 ± 27.33, 13.05 ± 15.28, 45.15 ± 53.11, 45.52 ± 70.31, 19.77 ± 23.43, and 25.06 ± 30.07, respectively.
CONCLUSIONS: The 0-5 min with 55-60 min DTP parametric imaging exhibits a comparable Ki to 60 min parametric imaging and remarkable image quality and contrast than SUV imaging, enhancing prostate cancer diagnosis while maintaining time efficiency.

BACKGROUND: The use of temephos, the most common intervention for the chemical control of Aedes aegypti over the last half century, has disappointing results in control of the infection. The footprint of Aedes and the diseases it carries have spread relentlessly despite massive volumes of temephos. Recent advances in community participation show this might be more effective and sustainable for the control of the dengue vector.
METHODS: Using data from the Camino Verde cluster randomized controlled trial, a compartmental mathematical model examines the dynamics of dengue infection with different levels of community participation, taking account of gender of respondent and exposure to temephos.
RESULTS: Simulation of dengue endemicity showed community participation affected the basic reproductive number of infected people. The greatest short-term effect, in terms of people infected with the virus, was the combination of temephos intervention and community participation. There was no evidence of a protective effect of temephos 220 days after the onset of the spread of dengue.
CONCLUSIONS: Male responses about community participation did not significantly affect modelled numbers of infected people and infectious mosquitoes. Our model suggests that, in the long term, community participation alone may have the best results. Adding temephos to community participation does not improve the effect of community participation alone.

This study aims to examine the development trend of COVID-19 in China and propose a model to assess the impacts of various prevention and control measures in combating the COVID-19 pandemic. Using COVID-19 cases reported by the National Health Commission of China from January 2, 2020, to January 2, 2022, we established a Susceptible-Exposed-Infected-Asymptomatic-Quarantined-Vaccinated-Hospitalized-Removed (SEIAQVHR) model to calculate the COVID-19 transmission rate and Rt effective reproduction number, and assess prevention and control measures. Additionally, we built a stochastic model to explore the development of the COVID-19 epidemic. We modeled the incidence trends in five outbreaks between 2020 and 2022. Some important features of the COVID-19 epidemic are mirrored in the estimates based on our SEIAQVHR model. Our model indicates that an infected index case entering the community has a 50%-60% chance to cause a COVID-19 outbreak. Wearing masks and getting vaccinated were the most effective measures among all the prevention and control measures. Specifically targeting asymptomatic individuals had no significant impact on the spread of COVID-19. By adjusting prevention and control parameters, we suggest that increasing the rates of effective vaccination and mask-wearing can significantly reduce COVID-19 cases in China. Our stochastic model analysis provides a useful tool for understanding the COVID-19 epidemic in China.