Fabricio Garelli

Universidad Nacional de La Plata | UNLP · Facultad de Ingeniería

Artificial pancreas (AP) algorithms can be divided into single-hormone (SH) and dual-hormone (DH). SH algorithms regulate glycemia using insulin as their control input. On the other hand, DH algorithms also use glucagon to counteract insulin. While SH-AP systems are already commercially available, DH-AP systems are still in an earlier research phas...

Introduction Artificial pancreas systems usually define an insulin-on-board constraint ([Formula: see text]) for safety schemes to limit the insulin infusion and avoid hypoglycemia during the closed-loop performance. Several methods have been proposed with impractical considerations requiring information from the prandial events or complex procedur...

Background: The first two studies of an artificial pancreas (AP) system carried out in Latin America took place in 2016 (phase 1) and 2017 (phase 2). They evaluated a hybrid algorithm from the University of Virginia (UVA) and the automatic regulation of glucose (ARG) algorithm in an inpatient setting using an AP platform developed by the UVA. The...

En este trabajo se presenta la experiencia argentina en el problema de regulación de los niveles de glucosa en sangre para pacientes con Diabetes Mellitus Tipo 1 (insulino-dependientes), denominado Páncreas Artificial. El grupo de trabajo ha realizado 3 pruebas clínicas, las primeras en Latinoamérica. Las dos primeras fueron concretadas en 2016 y 2...

This work presents an extended and age-band compartmentalised SEIR model that allows describing the spread evolution of SARS-CoV-2 and evaluating the effect of different detection rates, vaccination strategies or immunity periods. The model splits up the population into fifteen age groups of 5 years each, linked through a statistical interaction ma...

In recent years, closed-loop controllers for glucose regulation, also called Artificial Pancreas (AP) systems, have become an emblematic problem in the field of automatic control. Several closed-loop systems are in development around the world, such is the case of the Automatic Regulation of Glucose (ARG) algorithm developed in Argentina that has a...

This letter illustrates the potential of a new platform for simultaneous remote monitoring of multiple intensive care unit (ICU) and/or quarantined patients. To our best knowledge, this is the first multicenter, multisensor, multipatient, and potentially multitherapy platform for remote glucose monitoring employed in critically ill COVID patients....

Within the development of closed-loop glucose controllers, one of the major risks is insulin induced hypo-glycemia due to controller overreaction. In this paper, a novel strategy based on sliding mode control is proposed in order to reduce hypoglycemic events in glycemic closed-loop control via the subcutaneous route. This is achieved with the use...

Los pacientes en estado crítico con COVID-19 sufren hiperglucemias sostenidas de difícil manejo. A esto se suma el desafío de minimizar la exposición al contagio.En el presente artículo analizamos la evolución metabólica de dos pacientes pediátricos con COVID-19 admitidos en unidad de cuidados intensivos (UCI) para pacientes COVID-19 del Hospital “...

This work is focused on the multilevel control of the population confinement in the city of Buenos Aires and its surroundings due to the pandemic generated by the COVID-19 outbreak. The model used here is known as SEIRD and two objectives are sought: a time-varying identification of the infection rate and the inclusion of a controller. A control di...

In this work, global optimization techniques based on interval arithmetic are proposed to analyze and synthesize sliding mode (SM) controllers. The proposed methodology allows generating a series of maps, called subpavings, which put in evidence the required relationships among tuning parameters, disturbances and control amplitude to fulfill the su...

This work evaluates the potential of using sliding mode reference conditioning (SMRC) techniques as a guide for non-pharmaceutical intervention (NPI) to control the COVID-19 pandemic. In particular, for the epidemiological problem addressed here, it is used to compute the contact rate reduction requirement in order to limit the infectious populatio...

In this paper, a new glucose control strategy for patients with type 1 diabetes based on the dynamic simulation of an interval model is presented. Particularly, a safety scheme based on an interval insulin-on-board estimation model for artificial pancreas systems is designed, which includes a combination of soft and hard insulin-on-board constraint...

In this work, we review the figures used to characterize an epidemic outbreak most. Particular attention is drawn to epidemic spreading at time-varying transition rates. A time-varying SIR-like model is used to describe the epidemic dynamics, from which closed equations relating parameters and key quantities like reproduction ratio and doubling tim...

This work presents the second part of a study focused on the multilevel control of the population confinement for the AMBA region to mitigate the COVID-19 outbreak. With this aim, the model used throughout this study is known as SEIRD and two objectives are sought. Firstly, a time-varying identification of the infection rate and its relation with t...

This work presents the first part of a study focused on the multilevel control of the population confinement for the AMBA region to mitigate the COVID-19 outbreak. With this aim, the models used throughout this study are known as SEIR/SEIRD and two objectives are sought. Firstly, a timevarying identification of the infection rate and its relation w...

Ammonium removal is a key step in wastewater treatment which can be accomplished biologically. An interesting process option for this purpose is coupling partial nitritation with the Anammox process. The goal of the partial nitritation process is to convert half of the ammonium in the influent stream into nitrite, so both can be later converted int...

This work evaluates the potential of using sliding mode reference conditioning (SMRC) techniques as a guide for non-pharmaceutical interventions and population confinement to control the COVID-19 pandemic. SMRC technique allows robustly delimiting a given variable in dynamical systems. In particular, for the epidemiological problem addressed here,...

Artificial pancreas (AP) systems have shown to improve glucose regulation in type 1 diabetes (T1D) patients. However, full closed-loop performance remains a challenge particularly in children and adolescents, since these age groups often present the worst glycemic control. In this work, an algorithm based on switched control and time-varying IOB co...

In this paper, an adaptive proportional–integral (PI) control strategy for nonlinear systems with constrained actuators is discussed. In particular, a variable-structure anti-windup strategy that can be retrofitted onto different control structures is proposed and validated. Both the developed controller and anti-windup method are attuned to an aut...

In this work, a low-order model designed for glucose regulation in T1DM is obtained from the UVA/Padova metabolic simulator. It captures not only the nonlinear behavior of the glucose-insulin system, but also intra-patient variations related to daily insulin sensitivity ( ${S_{I}}$ ) changes. To overcome the large inter-subject variability, the mo...

Artificial pancreas (AP) systems have shown to improve glucose regulation in type 1 diabetes (T1D) patients. However, full closed-loop performance remains a challenge particularly in children and adolescents, since these age groups often present the worst glycemic control. In this work, a new algorithm based on switched control and time-varying ins...

In this paper, an interval simulator that considers different sources of uncertainty to estimate the blood glucose level of type 1 diabetes patients is presented. In particular, this study examines a model that includes the dynamics from the insulin delivery input to the subcutaneous-glucose concentration output, and a model that estimates the insu...

Background Either under standard basal-bolus treatment or hybrid closed-loop control, subjects with type 1 diabetes are required to count carbohydrates (CHOs). However, CHO counting is not only burdensome but also prone to errors. Recently, an artificial pancreas algorithm that does not require premeal insulin boluses—the so-called automatic regula...

One of the main challenges in automatic glycemic regulation in patients with type 1 diabetes (T1D) is to dispense with carbohydrate counting. In this context, we propose to equip a previously introduced switched Linear Quadratic Gaussian (LQG) controller-the so-called Automatic Regulation of Glucose (ARG) algorithm-with an automatic switching signa...

The objective of this work is to present a brief review on the international Artificial Pancreas project. In addition, the local project that led to the first Latin American clinical trials with an Artificial Pancreas will be described. These trials were performed in Buenos Aires during 2016 and 2017. The last trial used an algorithm developed in A...

Partial nitritation–anammox process is an interesting process option for biological nitrogen removal from wastewater. Partial nitritation needs to provide about equimolar ammonium and nitrite concentrations as required for the Anammox conversion. This study analyzes the equilibrium points of a stand-alone partial nitritation process as part of a tw...

Advances in genetic manipulation have allowed the overexpression of proteins and insertion of circuits in cells. However, the expected behaviour can be altered by the internal competition for the limited amount of cellular resources. In this work we analyse a feedback strategy based on transcription inhibition that aims to reduce the interaction in...

In wastewater treatment, ammonium removal is a key step which can be done biologically. One method is by coupling a partial nitritation with the Anammox process. The partial nitritation goal is to convert half of the ammonium into nitrite, so ammonium and nitrite can be later converted into dinitrogen gas by Anammox bacteria. To obtain a stable par...

• Abstract—In this work, we evaluate the potentials and limitations of Change-Point Analysis (CPA) tools for evaluating performance in Artificial Pancreas (AP) systems. In particular, we use Mood and Mann-Whitney’s non-parametric tests for detecting changes in scale and location in glucose data distributions. These tools are applied to the results...

This work explores both modeling and control of the experimental Ciscrea autonomous underwater vehicle. A 6-degree-of-freedom model is presented and validated for turn and emerge/sink maneuvers. Then, a constraint compensating algorithm is proposed based on quasi-sliding mode conditioning ideas and added to a pre-existing inaccessible proportional-...

Background: Emerging therapies such as closed-loop (CL) glucose control, also known as artificial pancreas (AP) systems, have shown significant improvement in type 1 diabetes mellitus (T1DM) management. However, demanding patient intervention is still required, particularly at meal times. To reduce treatment burden, the automatic regulation of glu...

A new approach to automatically regulate the glucose level in type 1 diabetes is presented in this work. This is the so-called Automatic Regulation of Glucose (ARG) algorithm, which is based on a switched Linear Quadratic Gaussian (LQG) inner controller, combined with an outer sliding mode safety loop with Insulin on Board (IOB) constraints. In sil...

The yeast Rhodosporidium toruloides has been extensively studied for its application in biolipid production. The knowledge of its metabolism capabilities and the application of constraint-based flux analysis methodology provide useful information for process prediction and optimization. The accuracy of the resulting predictions is highly dependent...

A novel extremum seeking scheme is proposed for the optimization of the specific growth rate in fed-batch processes with substrate inhibited kinetics. The proposed controller is based on a high order sliding mode algorithm, which uses the gradient of the specific growth rate as switching coordinate. A gradient estimation is obtained through a high...

This work revisits the dynamic behaviour of stirred continuous reactors in which a single bioreaction with unknown kinetics occurs. Conditions on the feeding strategy to avoid washing out the biomass and falling in batch operation are obtained. These conditions derive in a closed positively invariant region including the desired operating point. It...

Background and Objective: Although there has been significant progress towards closed-loop type 1 diabetes mellitus (T1DM) treatments, most diabetic patients still treat this metabolic disorder in an open-loop manner, based on insulin pump therapy (basal and bolus insulin infusion). This paper presents a method for automatic insulin bolus shaping b...

In this paper, we present a method to compute a control law for an Autonomous Underwater Vehicle (AUV) subject to external disturbances. The control law's design objectives are formulated as H∞ objectives used to synthesize a robust controller. Then, a robustness analysis of AUV model uncertainties is performed without conservatism with interval an...

The design of sliding mode (SM) comprises the selection of a sliding manifold on the state space and a switching logic. The sliding manifold design is associated with the desired dynamics and closed loop specifications, whereas the switching logic is designed to drive and keep the state on the prescribe manifold. The classical design can lead to ov...

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This article proposes a new adaptive control algorithm for active suspension systems of passenger cars. It combines a proportional–integral–derivative controller for suspension deflection together with a sliding mode reference conditioning outer loop that uses the vertical acceleration of the car body as a complementary source of control. The propo...

The �first clinical trials using an Artificial Pancreas (AP) in Latin America have been defined in 2 stages. The �first stage was carried out in November 2016 with the UVA controller (developed by the Center for Diabetes Technology and already clinically tested), and the second will be performed during the �first semester of 2017 with the ARG (Auto...

The first clinical trials using an Artificial Pancreas (AP) in Latin America have been defined in 2 stages. The first stage was carried out in November 2016 with the UVA controller (developed by the Center for Diabetes Technology and already clinically tested), and the second will be performed during the first semester of 2017 with the ARG (Automat...

Many biotechnological processes have optimal substrate concentrations where a maximum growth rate is achieved. In this work an extremum seeking controller and a gradient estimator are proposed to maximize the growth rate in fed-batch bioprocesses even when the substrate to growth rate map is unknown. Both the controller and estimator are obtained w...

This work presents a dynamic model for an autonomous underwater vehicle (AUV), a validation of this model together with the simulator obtained from its application and an implementation of sliding mode reference conditioning (SMRC). This last technique is proposed in order to follow a path at maximum speed with bounded errors in a dynamical framewo...

This work presents a dynamic model for an autonomous underwater vehicle (AUV), a validation of this model together with the simulator obtained from its application and an implementation of sliding mode reference conditioning (SMRC). This last technique is proposed in order to follow a path at maximum speed with bounded errors in a dynamical framewo...

This paper deals with the design of feeding rates for dual-substrate fed-batch processes where the main control objective is the regulation of the microbial growth rate. To this end, feedback of the growth rate error is incorporated to a biomass proportional dual feeding law. A second-order sliding mode observer is used to estimate the growth rate,...

Many biotechnological processes have optimal substrate concentrations where a maximum growth rate is achieved. In this work an extremum seeking controller and a gradient estimator are proposed to maximize the growth rate in fed-batch bioprocesses even when the substrate to growth rate map is unknown. Both the controller and estimator are obtained w...

In this work, a closed loop algorithm which combines two different control strategies is presented. First, a Switched Linear Parameter-Varying (SLPV) controller with different switching regions related to hyper- and euglycemia situations is designed, providing stability and performance guarantees. In [1], its closed loop performance has been succes...

The on-line estimation of non-measurable substances and key process variables is relevant for the real-time monitoring of the bioprocesses. This paper deals with the on-line estimation of microbial growth rate and biomass concentration based on measures of the product concentration. The algorithm does not require a model of the growth rate and it c...

This work focuses in the estimation of the specific production rate of intracellular products in fed-batch processes, for the case where high cell densities are present. Particularly, a new volume model is proposed for the high cell density case where a large amount of intracellular product is stored. Based on the model ant the on-line volume measu...

This paper addresses the estimation of the specific production rate of intracellular products and the modeling of the bioreactor volume dynamics in high cell density fed-batch reactors. In particular, a new model for the bioreactor volume is proposed, suitable to be used in high cell density cultures where large amounts of intracellular products ar...

This work presents a general model-based methodology to scale-up fed-batch bioprocesses. The idea behind this approach is to establish a dynamics hierarchy, based on a model of the process, that allows the designer to determine the proper scale factors as well as at which point of the fed-batch the process should be scaled up. Here, concepts and to...

This work presents a reactive geometric invariance method for the coordination of multi-robot systems. Some of the constraints representing the coordination of the multi-robot system are defined in terms of robot sensors that are not affected by the robot kinematics error, e.g., due to miscalibrations or lack of repeatability, in order to obtain ac...

This paper focuses on the specific growth rate estimation problem in a Polyhydroxybutyrate bioplastic production process by industrial fermentation. The kinetics of the process are unknown and there are uncertainties in the model parameters and inputs. During the first hours of the growth phase of the process, biomass concentration can be measured...

The distinguishability of the non-measured states is relevant for the design and implementation of state observers. The aim of this study is to examine the observability of a fed-batch multi-substrate process with additive growth rate. Based on the model equations, sufficient conditions to fulfill the observability rank condition were determined. R...

In this work the problem of estimating some variables of interest for monitoring and control of photo-fermentation processes is addressed. The focus is on a batch cultivation of Rhodobacter capsulatus where biohydrogen production rate is represented by a Luedeking-Piret expression. The use of second-order sliding mode algorithms to estimate biomass...

The regulation of the biomass specific growth rate is an important goal in many biotechnological applications. To achieve this goal in fed-batch processes, several control strategies have been developed employing a closed loop version of the exponential feeding law, an estimation of the controlled variable and some error feedback term. Moreover, in...

In this work, a control strategy to guarantee a minimum dissolved oxygen concentration in aerobic fed-batch bioprocesses is proposed. The strategy is equally applicable to avoid low oxygen concentrations that might be detrimental for metabolites production, to prevent metabolic changes and to maintain an oxygen level in the culture compatible with...

This brief presents a reactive reference conditioning algorithm for robot collision avoidance based on geometric invariance and sliding-mode (SM) ideas. First, constraints are defined in terms of the measurements given by the robot's sensors in order to guarantee that collisions will not occur. Then, a supervisory loop ensures the fulfillment of th...

Among the possible meanings of the word, this paper will discuss coordinated action to refer to the act on references of systems to achieve some collective behavior desired but considering the constraints and capabilities of each system. To this end, we develop a new methodology based on conditioning techniques reference using geometric invariance...

Specific kinetic rates are key variables regarding metabolic activity in bioprocesses. They are non-linear functions of concentrations and operating conditions and therefore of difficult access for process control. In this paper, a multiple kinetic rates observer based on second-order sliding mode ideas is proposed. The main difference with other p...

The artificial pancreas aims at the automatic delivery of insulin for glycemic control in patients with type 1 diabetes, i.e., closed-loop glucose control. One of the challenges of the artificial pancreas is to avoid controller over-reaction leading to hypoglycemia, especially in the late post prandial period. In this work, an original proposal bas...

This paper addresses the problem of coordinating dynamical systems with possibly different dynamics (e.g., linear and nonlinear, different orders, constraints, etc.) to achieve some desired collective behavior under the constraints and capabilities of each system. To this end, we develop a new methodology based on reference conditioning techniques...