Monica Betta

Perspectives on optimal control of varicella and herpes zoster by mass routine varicella vaccination

Herpes zoster arises from reactivation of the varicella–zoster virus (VZV), causing varicella in children. As reactivation occurs when cell-mediated immunity (CMI) declines, and there is evidence that re-exposure to VZV boosts CMI, mass varicella immunization might increase the zoster burden, at least for some decades. Fear of this natural zoster boom is the main reason for the paralysis of varicella immunization in Europe. We apply optimal control to a realistically parametrized age-structured model for VZV transmission and reactivation to investigate whether feasible varicella immunization paths that are optimal in controlling both varicella and zoster exist. We analyse the optimality system numerically focusing on the role of the cost functional, of the relative zoster–varicella cost and of the planning horizon length. We show that optimal programmes will mostly be unfeasible for public health owing to their complex temporal profiles. This complexity is the consequence of the intrinsically antagonistic nature of varicella immunization programmes when aiming to control both varicella and zoster. However, we show that gradually increasing—hence feasible—vaccination schedules can perform better than routine programmes with constant vaccine uptake. Finally, we show the optimal profiles of feasible programmes targeting mitigation of the post-immunization natural zoster boom with priority.

Detection and removal of ocular artifacts from EEG signals for an automated REM sleep analysis

Rapid eye movements (REMs) are a prominent feature of REM sleep, and their distribution and time density over the night represent important physiological and clinical parameters. At the same time, REMs produce substantial distortions on the electroencephalographic (EEG) signals, which strongly affect the significance of normal REM sleep quantitative study. In this work a new procedure for a complete and automated analysis of REM sleep is proposed, which includes both a REMs detection algorithm and an ocular artifact removal system. The two steps, based respectively on Wavelet Transform and adaptive filtering, are fully integrated and their performance is evaluated using REM simulated signals. Thanks to the integration with the detection algorithm, the proposed artifact removal system shows an enhanced accuracy in the recovering of the true EEG signal, compared to a system based on the adaptive filtering only. Finally the artifact removal system is applied to physiological data and an estimation of the actual distortion induced by REMs on EEG signals is supplied.

Combining pharmacological therapy and vaccination in Chronic Myeloid Leukemia via model predictive control

This paper describes a simulation study which aims at optimizing the therapy for the control of Chronic Myeloid Leukemia according to the following objectives: the reduction of the administered drug and vaccine amounts, the establishment of a auto-immune response and the long-term control of disease without reducing the effective of therapy with respect to the full treatment. A therapy optimization method is developed defining and solving a Model Predictive Control algorithm, preceded by an accurate Initial Guess search based on Monte-Carlo like approach. Simulation results show that the suggested procedure achieves the proposed goals.

Regional low-frequency oscillations in human rapid-eye movement sleep

Although the EEG slow wave of sleep is typically considered to be a hallmark of Non Rapid Eye Movement (NREM) sleep, recent work in mice has shown that slow waves can also occur in REM sleep. Here we investigated the presence and cortical distribution of low-frequency (1-4 Hz) oscillations in human REM sleep by analyzing high-density EEG sleep recordings obtained in 28 healthy subjects. We identified two clusters of low-frequency oscillations with distinctive properties: 1) a fronto-central cluster characterized by ∼2.5-3.0 Hz, relatively large, notched delta waves (so-called ‘sawtooth waves’) that tended to occur in bursts, were associated with increased gamma activity and rapid eye movements, and upon source modeling, displayed an occipito-temporal and a fronto-central component; and 2) a medial occipital cluster characterized by more isolated, slower (<2 Hz) and smaller waves that were not associated with rapid eye movements, displayed a negative correlation with gamma activity and were also found in NREM sleep. Thus, low-frequency oscillations are an integral part of REM sleep in humans, and the two identified subtypes (sawtooth and medial-occipital slow waves) may reflect distinct generation mechanisms and functional roles. Sawtooth waves, which are exclusive to REM sleep, share many characteristics with ponto-geniculo-occipital (PGO) waves described in animals and may represent the human equivalent or a closely related event while medio-occipital slow waves appear similar to NREM sleep slow waves.

Procoagulant control strategies for the human blood clotting process

This paper describes the comparison between two drug control strategies to hemophilia A. To emulate blood clotting and the pathological condition of hemophilia, a mathematical model composed by 14 ordinary differential equations is considered. We adopt a variable structure non-linear PID approach and a Model Predictive Control in order to control the dosage of procoagulant factor used in the treatment of hemophiliac patient. The two control actions are sampled for a practical application. Finally, we discuss and compare the results of the two control approaches, introducing a suited control index (eINR).

A Classification method for eye movements direction during REM sleep trained on wake electro-oculographic recordings

Rapid eye movements (REMs) are a peculiar and intriguing aspect of REM sleep, even if their physiological function still remains unclear. During this work, a new automatic tool was developed, aimed at a complete description of REMs activity during the night, both in terms of their timing of occurrence that in term of their directional properties. A classification stage of each singular movement detected during the night according to its main direction, was in fact added to our procedure of REMs detection and ocular artifact removal. A supervised classifier was constructed, using as training and validation set EOG data recorded during voluntary saccades of five healthy volunteers. Different classification methods were tested and compared. The further information about REMs directional characteristic provided by the procedure would represent a valuable tool for a deeper investigation into REMs physiological origin and functional meaning.