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Abstract High-fidelity simulators that connect theoretical models with observations are indispensable tools in many sciences. If the likelihood is known, inference can proceed using standard techniques. However, when the likelihood is intractable or unknown, a simulator makes it possible to infer the parameters of a theoretical model directly from real and simulated observations when coupled with machine learning. We introduce an extension of the recently proposed likelihood-free frequentist inference (LF2I) approach that makes it possible to construct confidence sets with thep-value function and to use the same function to check the coverage explicitly at any given parameter point. LikeLF2I, this extension yields provably valid confidence sets in parameter inference problems for which a high-fidelity simulator is available. The utility of our algorithm is illustrated by applying it to three pedagogically interesting examples: the first is from cosmology, the second from high-energy physics and astronomy, both with tractable likelihoods, while the third, with an intractable likelihood, is from epidemiology³3Code to reproduce all of our results is available onhttps://github.com/AliAlkadhim/ALFFI.. 

Identifiability of a mathematical model plays a crucial role in the parameterization of the model. In this study, we established the structural identifiability of a susceptible-exposed-infected-recovered (SEIR) model given different combinations of input data and investigated practical identifiability with respect to different observable data, data frequency, and noise distributions. The practical identifiability was explored by both Monte Carlo simulations and a correlation matrix approach. Our results showed that practical identifiability benefits from higher data frequency and data from the peak of an outbreak. The incidence data gave the best practical identifiability results compared to prevalence and cumulative data. In addition, we compared and distinguished the practical identifiability by Monte Carlo simulations and a correlation matrix approach, providing insights into when to use which method for other applications. 

Increasing temperatures have raised concerns over the potential effect on disease spread. Temperature is a well known factor affecting mosquito population dynamics and the development rate of the malaria parasite within the mosquito, and consequently, malaria transmission. A sinusoidal wave is commonly used to incorporate temperature effects in malaria models, however, we introduce a seasonal malaria framework that links data on temperature-dependent mosquito and parasite demographic traits to average monthly regional temperature data, without forcing a sinusoidal fit to the data. We introduce a spline methodology that maps temperature-dependent mosquito traits to time-varying model parameters. The resulting non-autonomous system of differential equations is used to study the impact of seasonality on malaria transmission dynamics and burden in a high and low malaria transmission region in Malawi. We present numerical simulations illustrating how temperature shifts alter the entomological inoculation rate and the number of malaria infections in these regions.