Probabilistic Fitting of Glucose Models with Real-Coded Genetic Algorithms

[EN] Type 1 Diabetes patients have to control their blood glucose levels using insulin therapy. Numerous factors (such as carbohydrate intake, physical activity, time of day, etc.) greatly complicate this task. In this article we propose a modeling method that will allow us to make predictions of blood glucose level evolution with a time horizon of 24 hours. This may allow the adjustment of insulin doses in advance and could help to improve the living conditions of diabetes patients. Our approach starts from a system of finite difference equations that characterizes the interaction between insulin and glucose (in the field, this is known as a minimal model). This model has several parameters whose values vary widely depending on patient characteristics and time. Thus, in the first phase of our strategy, We will enrich the patient¿s historical data by adding white Gaussian noise, which will allow us to perform a probabilistic fitting with a 95% confidence interval. Then, the model¿s parameters are adjusted based on the history of each patient using a genetic algorithm and dividing the day into 12 time intervals. In the final stage, we will perform a whole-day forecast from an ensemble of the models fitted in the previous phase. Th e validity of our strategy will be tested using the Parkers¿ error grid analysis. Our experimental results based on data from real diabetic patients show that this technique is capable of robust predictions that take into account all the uncertainty associated with the interaction between insulin and glucose.We acknowledge support from Spanish Ministry of Economy and Competitiveness under project RTI2018-095180- B-I00 and Madrid Regional Goverment - FEDER grants B2017/BMD3773 (GenObIA-CM) and Y2018/NMT-4668 (Micro-Stress- MAP-CM). Devices for adquiring data from patients were adquired with the support of Fundacion Eugenio Rodriguez Pascual 2019 grant - Desarrollo de sistemas adaptativos y bioinspirados para el control glucemico con infusores subcutaneos continuos de insulina y monitores continuos de glucosa (Development of adaptive and bioinspired systems for glycaemic control with continuous subcutaneous insulin infusors and continuous glucose monitors).Cervigón, C.; Velasco, JM.; Burgos-Simon, C.; Villanueva Micó, RJ.; Hidalgo, JI. (2021). Probabilistic Fitting of Glucose Models with Real-Coded Genetic Algorithms. IEEE. 736-743. https://doi.org/10.1109/CEC45853.2021.9504836S73674

Approche comportementale pour la validation et le test système des systèmes embarqués : Application aux dispositifs médicaux embarqués

A Biomedical research seeks good reasoning for solving medical problems, based on intensive work and great debate. It often deals with beliefs or theories that can be proven, disproven or often refined after observations or experiments. The problem is how to make tests without risks for patients, including variability and uncertainty on a number of parameters (patients, evolution of disease, treatments …). Nowadays, medical treatment uses more and more embedded devices such as sensors, actuators, and controllers. Treatment depends on the availability and well-functioning of complex electronic systems, comprising thousands of lines of codes. A mathematical representation of patient or device is presented by a number of variables which are defined to represent the inputs, the outputs and a set of equations describing the interaction of these variables. The objective of this research is to develop tools and methodologies for the development of embedded systems for medical fields. The goal is to be able to model and jointly simulate the medical device as well the human body, at least the part of the body involved in the medical device, to analyze the performance and quality of service (QoS) of the interaction of the device with the human body. To achieve this goal our study focused on several points described below. After starting by defining a prototype of a new global and flexible architecture of mathematical model of human body, which is able to contain required data, we begin by proposing a new global methodology for modeling and simulation human body and medical systems, in order to better understand the best way to model and simulate these systems and for detecting performance and the quality of services of all system components. We use two techniques that help to evaluate the calculated QoS value. The first one calculates an index of severity which indicates the severity of the case studied. The second one using a normalization function that represents the simulation as a point in order to construct a new error grid and use it to evaluate the accuracy of value measured by patients. Using Keil development tools designed for ARM processors, we have declared a new framework in the objective to create a new tester model for the glucose-insulin system, and to define the basic rules for the tester which has the ability to satisfy well-established medical decision criteria. The framework begins by simulating a mathematical model of the human body, and this model was developed to operate in the closed loop of the glucose insulin. Then, the model of artificial pancreas has been implemented to control the mathematical model of human body. Finally a new tester model was created in order to analyze the performance of all the components of the glucose-insulin system.. We have used the suitability of partially observable Markov decision processes to formalize the planning of clinical management.Les progrès des technologies de l'information et de la communication, des MEMS, des capteurs, actionneurs, etc. ont permis l’émergence de différents dispositifs biomédicaux. Ces nouveaux dispositifs, souvent embarqués, contribuent considérablement à l'amélioration du diagnostic et du traitement de certaines maladies, comme le diabète par exemple. Des dispositifs embarqués encore plus complexes sont en cours d’élaboration, leur mise en œuvre nécessite des années de recherche et beaucoup d’expérimentation. Le cœur artificiel, encore en phase de réalisation, est un exemple concret de ces systèmes complexes. La question de la fiabilité, du test de fonctionnement et de sureté de ces dispositifs reste problématique et difficile à résoudre. Plusieurs paramètres (patient, évolution de la maladie, alimentation, activité, traitement, etc.) sont en effet à prendre en compte et la conséquence d’une erreur de fonctionnement peut être catastrophique pour le patient. L'objectif de cette thèse est de développer des outils et des approches méthodologiques permettant la validation et le test au niveau système de ce type de dispositifs. Il s’agit précisément d’étudier la possibilité de modéliser et simuler d’une manière conjointe un dispositif médical ainsi que son interaction avec le corps humain, du moins la partie du corps humain concernée par le dispositif médical, afin de mesurer les performances et la qualité de services (QoS) du dispositif considéré. Pour atteindre cet objectif notre étude a porté sur plusieurs points. Nous avons d’abord mis en évidence une architecture simplifiée d’un modèle de corps humain permettant de représenter et de mieux comprendre les différents mécanismes du corps humain. Nous avons ensuite exploré un ensemble de métriques et une approche méthodologique générique permettant de qualifier la qualité de service d’un dispositif médical donné en interaction avec le corps humain. Afin de valider notre approche, nous l’avons appliquée à un dispositif destiné à la régulation du taux de sucre pour des patients atteints du diabète. La partie du corps humain concernée par cette pathologie à savoir le pancréas a été simulé par un modèle simplifié que nous avons implémenté sur un microcontrôleur. Le dispositif de régulation de l’insuline quant à lui a été simulé par un modèle informatique écrit en C. Afin de rendre les mesures de performances observées indépendantes d’un patient donné, nous avons étudiés différentes stratégies de tests sur différentes catégories de patients. Nous avons pour cette partie mis en œuvre un générateur de modèles capable de reproduire différents états physiologiques de patients diabétiques. L’analyse et l’exploitation des résultats observés peut aider les médecins à considérablement limités les essais cliniques sur des vrai patients et les focaliser uniquement sur les cas les plus pertinent

PATIENT-SPECIFIC CONTROLLER FOR AN IMPLANTABLE ARTIFICIAL PANCREAS

Ph.DDOCTOR OF PHILOSOPH

Desarrollo de una aplicación en Android para la estimación automática de carbohidratos y nutrientes alimenticios mediante captura y análisis de imágenes aplicando algoritmos de Inteligencia artificial

Este trabajo tiene como meta el desarrollo de una App para Android capaz de realizar una foto y reconocer el alimento que está en la misma para luego mostrar: - La información nutricional del alimento (haciendo énfasis en los carbohidratos). - Mostrarle al paciente cual es la ración recomendada de dicho alimento para su dieta. - Grabar toda esta información (siempre proporcional a la cantidad ingerida), en el histórico del paciente. Para este último punto se realizara la integración de esta App con la plataforma glUCModel la cual lleva el histórico de los pacientes junto con sus datos. El objetivo Final es el de ayudar al paciente diabético en su control diario de la enfermedad, proporcionando una herramienta de estimación de carbohidratos y nutrientes fiable

Faculty Publications and Creative Works 1999

One of the ways in which we recognize our faculty at the University of New Mexico is through Faculty Publications & Creative Works. An annual publication, it highlights our faculty\u27s scholarly and creative activities and achievements and serves as a compendium of UNM faculty efforts during the 1999 calendar year. Faculty Publications & Creative Works strives to illustrate the depth and breadth of research activities performed throughout our University\u27s laboratories, studios and classrooms. We believe that the communication of individual research is a significant method of sharing concepts and thoughts and ultimately inspiring the birth of new ideas. In support of this, UNM faculty during 1999 produced over 2,292 works, including 1,837 scholarly papers and articles, 78 books, 82 book chapters, 175 reviews, 113 creative works and 7 patented works. We are proud of the accomplishments of our faculty which are in part reflected in this book, which illustrates the diversity of intellectual pursuits in support of research and education at the University of New Mexico

Faculty Publications and Creative Works 2005

Faculty Publications & Creative Works is an annual compendium of scholarly and creative activities of University of New Mexico faculty during the noted calendar year. Published by the Office of the Vice President for Research and Economic Development, it serves to illustrate the robust and active intellectual pursuits conducted by the faculty in support of teaching and research at UNM. In 2005, UNM faculty produced over 1,887 works, including 1,887 scholarly papers and articles, 57 books, 127 book chapters, 58 reviews, 68 creative works and 4 patented works. We are proud of the accomplishments of our faculty which are in part reflected in this book, which illustrates the diversity of intellectual pursuits in support of research and education at the University of New Mexico

Mathematical approaches for the clinical translation of hyperpolarised 13C imaging in oncology

Dissolution dynamic nuclear polarisation is an emerging clinical technique which enables the metabolism of hyperpolarised 13C-labelled molecules to be dynamically and non- invasively imaged in tissue. The first molecule to gain clinical approval is [1-13C]pyruvate, the conversion of which to [1-13C]lactate has been shown to detect early treatment re- sponse in cancers and correlate with tumour grade. As the technique has recently been translated into humans, accurate and reliable quantitative methods are required in order to detect, analyse and compare regions of altered metabolism in patients. Furthermore, there is a requirement to understand the biological processes which govern lactate pro- duction in tumours in order to draw reliable conclusions from this data. This work begins with a comprehensive analysis of the quantitative methods which have previously been applied to hyperpolarised 13C data and compares these to some novel approaches. The most appropriate kinetic model to apply to hyperpolarised data is determined and some simple, robust quantitative metrics are identified which are suitable for clinical use. A means of automatically segmenting 5D hyperpolarised imaging data using a fuzzy Markov random field approach is presented in order to reliably identify regions of abnormal metabolic activity. The utility of the algorithm is demonstrated on both in silico and animal data. To gain insight into the processes driving lactate metabolism, a mathematical model is developed which is capable of simulating tumour growth and treatment response under a range of metabolic and tissue conditions, focusing on the interaction between tumour and stroma. Finally, hyperpolarised 13C-pyruvate imaging data from the first human subjects to be imaged in Cambridge is analysed. The ability to detect and quantify lactate production in patients is demonstrated through application of the methods derived in earlier chapters. The mathematical approaches presented in this work have the potential to inform both the analysis and interpretation of clinical hyperpolarised 13C imaging data and to aid in the clinical translation of this technique.Joint funded by GlaxoSmithKline and the Cambridge Biomedical Research Centre

Visual Cortex

The neurosciences have experienced tremendous and wonderful progress in many areas, and the spectrum encompassing the neurosciences is expansive. Suffice it to mention a few classical fields: electrophysiology, genetics, physics, computer sciences, and more recently, social and marketing neurosciences. Of course, this large growth resulted in the production of many books. Perhaps the visual system and the visual cortex were in the vanguard because most animals do not produce their own light and offer thus the invaluable advantage of allowing investigators to conduct experiments in full control of the stimulus. In addition, the fascinating evolution of scientific techniques, the immense productivity of recent research, and the ensuing literature make it virtually impossible to publish in a single volume all worthwhile work accomplished throughout the scientific world. The days when a single individual, as Diderot, could undertake the production of an encyclopedia are gone forever. Indeed most approaches to studying the nervous system are valid and neuroscientists produce an almost astronomical number of interesting data accompanied by extremely worthy hypotheses which in turn generate new ventures in search of brain functions. Yet, it is fully justified to make an encore and to publish a book dedicated to visual cortex and beyond. Many reasons validate a book assembling chapters written by active researchers. Each has the opportunity to bind together data and explore original ideas whose fate will not fall into the hands of uncompromising reviewers of traditional journals. This book focuses on the cerebral cortex with a large emphasis on vision. Yet it offers the reader diverse approaches employed to investigate the brain, for instance, computer simulation, cellular responses, or rivalry between various targets and goal directed actions. This volume thus covers a large spectrum of research even though it is impossible to include all topics in the extremely diverse field of neurosciences

Whole-exome capture and next-generation sequencing to discover rare variants predisposing to congenital heart disease

PhD ThesisCongenital heart disease (CHD) is the most common congenital malformation, affecting 8 out of 1000 lives births, yet its aetiology remains largely unresolved. The rapidly growing number of point mutations implicated in isolated CHD suggests that single mutations may contribute significantly to CHD risk. This thesis presents an investigation of the genetic underpinnings of various types of CHD following different study designs. First, I designed a new approach to variant calling which I implemented as the variant caller BAMily. My aim was to develop a method of uncovering putative variants in next-generation sequencing data, shared by a subset of individuals and absent in another subset. I tested the variant caller’s performance against other known variant callers and demonstrated that it provides comparable; and often better, results. This novel variant caller was applied to a study of 8 families in which a disease trait was segregating; along with the variant caller SAMtools, leading to the discovery of likely disease-causing variants in 5 families. Second, I studied de novo mutation in 32 sporadic cases of transposition of the great arteries (TGA) in an attempt to identify genes that, when mutated, lead to TGA. The 32 patients with TGA were sequenced with their parents; as well as one unaffected sibling. To achieve this aim, three variant callers were used: SAMtools, GATK Unified Genotyper and BAMily, the latter acting as a filter. Potential de novo variants were found in GREB1, RBP5, SNX13. Results suggested a complex genetic etiology underlying TGA. Finally, I studied a large series of cases of tetralogy of Fallot (ToF). The study involved 824 patients which ToF and a comparator set of 490 patients with neurodevelopmental disorders lifted from the UK10K project. The aim of the study was to identify genes that, when mutated, play a role in the manifestation of ToF might cluster. For this, I first categorised variants according to their potential to disrupt protein function. I then compared genes in which potentially disease-causing rare variants occurred to lists of genes previously implicated in CHD in the literature. Following this, I identified the clustering of potentially deleterious rare variants across the coding region of genes and exons in ToF patients, hypothesising that variants influencing ToF would cluster in ToF patients. This study led to the discovery of candidate variants in FLT4 and NOTCH1 for non-syndromic ToF. As with TGA, the results I have obtained suggested a complex etiology for ToF