Modeling tumor size dynamics based on real-world electronic health records and image data in advanced melanoma patients receiving immunotherapy.

The development of immune checkpoint inhibitors (ICIs) has revolutionized cancer therapy but only a fraction of patients benefits from this therapy. Model-informed drug development can be used to assess prognostic and predictive clinical factors or biomarkers associated with treatment response. Most pharmacometric models have thus far been developed using data from randomized clinical trials, and further studies are needed to translate their findings into the real-world setting. We developed a tumor growth inhibition model based on real-world clinical and imaging data in a population of 91 advanced melanoma patients receiving ICIs (i.e., ipilimumab, nivolumab, and pembrolizumab). Drug effect was modeled as an ON/OFF treatment effect, with a tumor killing rate constant identical for the three drugs. Significant and clinically relevant covariate effects of albumin, neutrophil to lymphocyte ratio, and Eastern Cooperative Oncology Group (ECOG) performance status were identified on the baseline tumor volume parameter, as well as NRAS mutation on tumor growth rate constant using standard pharmacometric approaches. In a population subgroup (n = 38), we had the opportunity to conduct an exploratory analysis of image-based covariates (i.e., radiomics features), by combining machine learning and conventional pharmacometric covariate selection approaches. Overall, we demonstrated an innovative pipeline for longitudinal analyses of clinical and imaging RWD with a high-dimensional covariate selection method that enabled the identification of factors associated with tumor dynamics. This study also provides a proof of concept for using radiomics features as model covariates.

Spatio-temporal estimation of wind speed and wind power using extreme learning machines: predictions, uncertainty and technical potential.

With wind power providing an increasing amount of electricity worldwide, the quantification of its spatio-temporal variations and the related uncertainty is crucial for energy planners and policy-makers. Here, we propose a methodological framework which (1) uses machine learning to reconstruct a spatio-temporal field of wind speed on a regular grid from spatially irregularly distributed measurements and (2) transforms the wind speed to wind power estimates. Estimates of both model and prediction uncertainties, and of their propagation after transforming wind speed to power, are provided without any assumptions on data distributions. The methodology is applied to study hourly wind power potential on a grid of 250 × 250  m 2 for turbines of 100 m hub height in Switzerland, generating the first dataset of its type for the country. We show that the average annual power generation per turbine is 4.4 GWh. Results suggest that around 12,000 wind turbines could be installed on all 19,617 km 2 of available area in Switzerland resulting in a maximum technical wind potential of 53 TWh. To achieve the Swiss expansion goals of wind power for 2050, around 1000 turbines would be sufficient, corresponding to only 8% of the maximum estimated potential. Supplementary Information: The online version contains supplementary material available at 10.1007/s00477-022-02219-w.

A novel framework for spatio-temporal prediction of environmental data using deep learning.

As the role played by statistical and computational sciences in climate and environmental modelling and prediction becomes more important, Machine Learning researchers are becoming more aware of the relevance of their work to help tackle the climate crisis. Indeed, being universal nonlinear function approximation tools, Machine Learning algorithms are efficient in analysing and modelling spatially and temporally variable environmental data. While Deep Learning models have proved to be able to capture spatial, temporal, and spatio-temporal dependencies through their automatic feature representation learning, the problem of the interpolation of continuous spatio-temporal fields measured on a set of irregular points in space is still under-investigated. To fill this gap, we introduce here a framework for spatio-temporal prediction of climate and environmental data using deep learning. Specifically, we show how spatio-temporal processes can be decomposed in terms of a sum of products of temporally referenced basis functions, and of stochastic spatial coefficients which can be spatially modelled and mapped on a regular grid, allowing the reconstruction of the complete spatio-temporal signal. Applications on two case studies based on simulated and real-world data will show the effectiveness of the proposed framework in modelling coherent spatio-temporal fields.