Mathematical modeling for estimating influenza vaccine efficacy: A case study of the Valencian Community, Spain.

Vaccine efficacy and its quantification is a crucial concept for the proper design of public health vaccination policies. In this work we proposed a mathematical model to estimate the efficacy of the influenza vaccine in a real-word scenario. In particular, our model is a SEIR-type epidemiological model, which distinguishes vaccinated and unvaccinated populations. Mathematically, its dynamics is governed by a nonlinear system of ordinary differential equations, where the non-linearity arises from the effective contacts between susceptible and infected individuals. Two key aspects of this study is that we use a vaccine distribution over time that is based on real data specific to the elderly people in the Valencian Community and the calibration process takes into account that over one influenza season a specific proportion of the population becomes infected with influenza. To consider the effectiveness of the vaccine, the model incorporates a parameter, the vaccine attenuation factor, which is related with the vaccine efficacy against the influenza virus. With this framework, in order to calibrate the model parameters and to obtain an influenza vaccine efficacy estimation, we considered the 2016-2017 influenza season in the Valencian Community, Spain, using the influenza reported cases of vaccinated and unvaccinated. In order to ensure the model identifiability, we choose to deterministically calibrate the parameters for different scenarios and we find the one with the minimum error in order to determine the vaccine efficacy. The calibration results suggest that the influenza vaccine developed for 2016-2017 influenza season has an efficacy of approximately 76.7%, and that the risk of becoming infected is five times higher for an unvaccinated individual in comparison with a vaccinated one. This estimation partially agrees with some previous studies related to the influenza vaccine. This study presents a new integrated mathematical approach to study the influenza vaccine efficacy and gives further insight into this important public health topic.

Analysis and prediction of long-term survival using a clinically applicable risk score based on the Electronic Health Record.

BACKGROUND: The long-term survival of a population assigned to a hospital can be essential to anticipate, manage, and provide appropriate hospital healthcare resources or lead preventive actions for high-risk mortality individuals. In this study, we discriminate which electronic health record variables are most relevant to predict the long-term survival of a population, and apply the results to identify high-risk mortality groups. MATERIALS AND METHODS: A prospective cohort study was conducted on a population of 113,403 individuals alive on July 1st, 2018 from the General Hospital of Castellón (Spain). Considering electronic health record patients' variables and survival days from the start date of the study, a Kaplan-Meier analysis and a multivariate Cox regression model were performed, and a risk score based on Cox coefficients was applied to predict survival over 3 years. RESULTS: All significant covariates from the Cox model (91.5% c-index) were associated with increased mortality risk. Using the proposed risk score, Kaplan-Meier curves show that survival probability in the 3rd year is 99.23% (95% confidence interval (CI) 99.18-99.29) for the low-risk, 91.21% (95% CI 90.67-91.76) for medium-risk, 76.52% (95% CI 75.59-77.46) for the high-risk, and 48.61 % (95% CI 46.85-50.36) for the very high-risk groups. DISCUSSION: The Cox model obtained is highly predictive, and it has been found that some electronic health record variables little studied to date, such as Clinical Risk Groups, have a strong impact on survival. Regarding clinical application, the proposed risk score is particularly useful for identifying high-risk subpopulations within a large population.

Characterization of Gene Circuit Parts Based on Multiobjective Optimization by Using Standard Calibrated Measurements.

Standardization and characterization of biological parts is necessary for the further development of bottom-up synthetic biology. Herein, an easy-to-use methodology that embodies both a calibration procedure and a multiobjective optimization approach is proposed to characterize biological parts. The calibration procedure generates values for specific fluorescence per cell expressed as standard units of molecules of equivalent fluorescein per particle. The use of absolute standard units enhances the characterization of model parameters for biological parts by bringing measurements and estimations results from different sources into a common domain, so they can be integrated and compared faithfully. The multiobjective optimization procedure exploits these concepts by estimating the values of the model parameters, which represent biological parts of interest, while considering a varied range of experimental and circuit contexts. Thus, multiobjective optimization provides a robust characterization of them. The proposed calibration and characterization methodology can be used as a guide for good practices in dry and wet laboratories; thus allowing not only portability between models, but is also useful for generating libraries of tested and well-characterized biological parts.