Mathematical Modeling to Investigate Antiarrhythmic Drug Side Effects: Rate-Dependence Role in Ionic Currents and Action Potentials Shape in the O’Hara Model

Sudden cardiac death due to ventricular arrhythmia is one of the leading causes of mortality in the world. In the last decades, it has proven that anti-arrhythmic drugs, which prolong the refractory period by means of prolongation of the cardiac action potential duration (APD), play a good role in preventing of relevant human arrhythmias. However, it has long been observed that the “class III antiarrhythmic effect” diminish at faster heart rates and that this phenomenon represent a big weakness, since it is the precise situation when arrhythmias are most prone to occur. It is well known that mathematical modeling is a useful tool for investigating cardiac cell behavior. In the last 60 years, a multitude of cardiac models has been created; from the pioneering work of Hodgkin and Huxley (1952), who first described the ionic currents of the squid giant axon quantitatively, mathematical modeling has made great strides. The O’Hara model, that I employed in this research work, is one of the modern computational models of ventricular myocyte, a new generation began in 1991 with ventricular cell model by Noble et al. Successful of these models is that you can generate novel predictions, suggest experiments and provide a quantitative understanding of underlying mechanism. Obviously, the drawback is that they remain simple models, they don’t represent the real system. The overall goal of this research is to give an additional tool, through mathematical modeling, to understand the behavior of the main ionic currents involved during the action potential (AP), especially underlining the differences between slower and faster heart rates. In particular to evaluate the rate-dependence role on the action potential duration, to implement a new method for interpreting ionic currents behavior after a perturbation effect and to verify the validity of the work proposed by Antonio Zaza using an injected current as a perturbing effect.

Deterministic and probabilistic verification of multi-model meteorological forecasts on the subseasonal timescale

In questo studio, un multi-model ensemble è stato implementato e verificato, seguendo una delle priorità di ricerca del Subseasonal to Seasonal Prediction Project (S2S). Una regressione lineare è stata applicata ad un insieme di previsioni di ensemble su date passate, prodotte dai centri di previsione mensile del CNR-ISAC e ECMWF-IFS. Ognuna di queste contiene un membro di controllo e quattro elementi perturbati. Le variabili scelte per l'analisi sono l'altezza geopotenziale a 500 hPa, la temperatura a 850 hPa e la temperatura a 2 metri, la griglia spaziale ha risoluzione 1 ◦ × 1 ◦ lat-lon e sono stati utilizzati gli inverni dal 1990 al 2010. Le rianalisi di ERA-Interim sono utilizzate sia per realizzare la regressione, sia nella validazione dei risultati, mediante stimatori nonprobabilistici come lo scarto quadratico medio (RMSE) e la correlazione delle anomalie. Successivamente, tecniche di Model Output Statistics (MOS) e Direct Model Output (DMO) sono applicate al multi-model ensemble per ottenere previsioni probabilistiche per la media settimanale delle anomalie di temperatura a 2 metri. I metodi MOS utilizzati sono la regressione logistica e la regressione Gaussiana non-omogenea, mentre quelli DMO sono il democratic voting e il Tukey plotting position. Queste tecniche sono applicate anche ai singoli modelli in modo da effettuare confronti basati su stimatori probabilistici, come il ranked probability skill score, il discrete ranked probability skill score e il reliability diagram. Entrambe le tipologie di stimatori mostrano come il multi-model abbia migliori performance rispetto ai singoli modelli. Inoltre, i valori più alti di stimatori probabilistici sono ottenuti usando una regressione logistica sulla sola media di ensemble. Applicando la regressione a dataset di dimensione ridotta, abbiamo realizzato una curva di apprendimento che mostra come un aumento del numero di date nella fase di addestramento non produrrebbe ulteriori miglioramenti.

Bayesian Linear Regression for estimation of the Fractal Dimension of the Cerebral Cortex

The cerebral cortex presents self-similarity in a proper interval of spatial scales, a property typical of natural objects exhibiting fractal geometry. Its complexity therefore can be characterized by the value of its fractal dimension (FD). In the computation of this metric, it has usually been employed a frequentist approach to probability, with point estimator methods yielding only the optimal values of the FD. In our study, we aimed at retrieving a more complete evaluation of the FD by utilizing a Bayesian model for the linear regression analysis of the box-counting algorithm. We used T1-weighted MRI data of 86 healthy subjects (age 44.2 ± 17.1 years, mean ± standard deviation, 48% males) in order to gain insights into the confidence of our measure and investigate the relationship between mean Bayesian FD and age. Our approach yielded a stronger and significant (P < .001) correlation between mean Bayesian FD and age as compared to the previous implementation. Thus, our results make us suppose that the Bayesian FD is a more truthful estimation for the fractal dimension of the cerebral cortex compared to the frequentist FD.

Meta-learning for informed model searches in Automated Machine Learning

Day by day, machine learning is changing our lives in ways we could not have imagined just 5 years ago. ML expertise is more and more requested and needed, though just a limited number of ML engineers are available on the job market, and their knowledge is always limited by an inherent characteristic of theirs: they are humans. This thesis explores the possibilities offered by meta-learning, a new field in ML that takes learning a level higher: models are trained on other models' training data, starting from features of the dataset they were trained on, inference times, obtained performances, to try to understand the relationship between a good model and the way it was obtained. The so-called metamodel was trained on data collected by OpenML, the largest ML metadata platform that's publicly available today. Datasets were analyzed to obtain meta-features that describe them, which were then tied to model performances in a regression task. The obtained metamodel predicts the expected performances of a given model type (e.g., a random forest) on a given ML task (e.g., classification on the UCI census dataset). This research was then integrated into a custom-made AutoML framework, to show how meta-learning is not an end in itself, but it can be used to further progress our ML research. Encoding ML engineering expertise in a model allows better, faster, and more impactful ML applications across the whole world, while reducing the cost that is inevitably tied to human engineers.