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    STOCHASTIC SEASONAL MODELS FOR GLUCOSE PREDICTION IN TYPE 1 DIABETES

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    [ES] La diabetes es un importante problema de salud mundial, siendo una de las enfermedades no transmisibles más graves después de las enfermedades cardiovasculares, el cáncer y las enfermedades respiratorias crónicas. La prevalencia de la diabetes ha aumentado constantemente en las últimas décadas, especialmente en países de ingresos bajos y medios. Se estima que 425 millones de personas en todo el mundo tenían diabetes en 2017, y para 2045 este número puede aumentar a 629 millones. Alrededor del 10% de las personas con diabetes padecen diabetes tipo 1, caracterizada por una destrucción autoinmune de las células beta en el páncreas, responsables de la secreción de la hormona insulina. Sin insulina, la glucosa plasmática aumenta a niveles nocivos, provocando complicaciones vasculares a largo plazo. Hasta que se encuentre una cura, el manejo de la diabetes depende de los avances tecnológicos para terapias de reemplazo de insulina. Con la llegada de los monitores continuos de glucosa, la tecnología ha evolucionado hacia sistemas automatizados. Acuñados como "páncreas artificial", los dispositivos de control de glucosa en lazo cerrado suponen hoy en día un cambio de juego en el manejo de la diabetes. La investigación en las últimas décadas ha sido intensa, dando lugar al primer sistema comercial a fines de 2017, y muchos más están siendo desarrollados por las principales industrias de dispositivos médicos. Sin embargo, como dispositivo de primera generación, muchos problemas aún permanecen abiertos y nuevos avances tecnológicos conducirán a mejoras del sistema para obtener mejores resultados de control glucémico y reducir la carga del paciente, mejorando significativamente la calidad de vida de las personas con diabetes tipo 1. En el centro de cualquier sistema de páncreas artificial se encuentra la predicción de glucosa, tema abordado en esta tesis. La capacidad de predecir la glucosa a lo largo de un horizonte de predicción dado, y la estimación de las tendencias futuras de glucosa, es la característica más importante de cualquier sistema de páncreas artificial, para poder tomar medidas preventivas que eviten por completo el riesgo para el paciente. La predicción de glucosa puede aparecer como parte del algoritmo de control en sí, como en sistemas basados en técnicas de control predictivo basado en modelo (MPC), o como parte de un sistema de supervisión para evitar episodios de hipoglucemia. Sin embargo, predecir la glucosa es un problema muy desafiante debido a la gran variabilidad inter e intra-sujeto que sufren los pacientes, cuyas fuentes solo se entienden parcialmente. Esto limita las prestaciones predictivas de los modelos, imponiendo horizontes de predicción relativamente cortos, independientemente de la técnica de modelado utilizada (modelos fisiológicos, basados en datos o híbridos). La hipótesis de partida de esta tesis es que la complejidad de la dinámica de la glucosa requiere la capacidad de caracterizar grupos de comportamientos en los datos históricos del paciente que llevan naturalmente al concepto de modelado local. Además, la similitud de las respuestas en un grupo puede aprovecharse aún más para introducir el concepto clásico de estacionalidad en la predicción de glucosa. Como resultado, los modelos locales estacionales están en el centro de esta tesis. Se utilizan varias bases de datos clínicas que incluyen comidas mixtas y ejercicio para demostrar la viabilidad y superioridad de las prestaciones de este enfoque.[CA] La diabetisés un important problema de salut mundial, sent una de les malalties no transmissibles més greus després de les malalties cardiovasculars, el càncer i les malalties respiratòries cròniques. La prevalença de la diabetis ha augmentat constantment en les últimes dècades, especialment en països d'ingressos baixos i mitjans. S'estima que 425 milions de persones a tot el món tenien diabetis en 2017, i per 2045 aquest nombre pot augmentar a 629 milions. Al voltant del 10% de les persones amb diabetis pateixen diabetis tipus 1, caracteritzada per una destrucció autoimmune de les cèl·lules beta en el pàncrees, responsables de la secreció de l'hormona insulina. Sense insulina, la glucosa plasmàtica augmenta a nivells nocius, provocant complicacions vasculars a llarg termini. Fins que es trobi una cura, el maneig de la diabetis depén dels avenços tecnològics per a teràpies de reemplaçament d'insulina. Amb l'arribada dels monitors continus de glucosa, la tecnologia ha evolucionat cap a sistemes automatitzats. Encunyats com "pàncrees artificial", els dispositius de control de glucosa en llaç tancat suposen avui dia un canvi de joc en el maneig de la diabetis. La investigació en les últimes dècades ha estat intensa, donant lloc al primer sistema comercial a finals de 2017, i molts més estan sent desenvolupats per les principals indústries de dispositius mèdics. No obstant això, com a dispositiu de primera generació, molts problemes encara romanen oberts i nous avenços tecnològics conduiran a millores del sistema per obtenir millors resultats de control glucèmic i reduir la càrrega del pacient, millorant significativament la qualitat de vida de les persones amb diabetis tipus 1. Al centre de qualsevol sistema de pàncrees artificial es troba la predicció de glucosa, tema abordat en aquesta tesi. La capacitat de predir la glucosa al llarg d'un horitzó de predicció donat, i l'estimació de les tendències futures de glucosa, és la característica més important de qualsevol sistema de pàncrees artificial, per poder prendre mesures preventives que evitin completament el risc per el pacient. La predicció de glucosa pot aparèixer com a part de l'algoritme de control en si, com en sistemes basats en técniques de control predictiu basat en model (MPC), o com a part d'un sistema de supervisió per evitar episodis d'hipoglucèmia. No obstant això, predir la glucosa és un problema molt desafiant degut a la gran variabilitat inter i intra-subjecte que pateixen els pacients, les fonts només s'entenen parcialment. Això limita les prestacions predictives dels models, imposant horitzons de predicció relativament curts, independentment de la tècnica de modelatge utilitzada (models fisiològics, basats en dades o híbrids). La hipòtesi de partida d'aquesta tesi és que la complexitat de la dinàmica de la glucosa requereix la capacitat de caracteritzar grups de comportaments en les dades històriques del pacient que porten naturalment al concepte de modelatge local. A més, la similitud de les respostes en un grup pot aprofitar-se encara més per introduir el concepte clàssic d'estacionalitat en la predicció de glucosa. Com a resultat, els models locals estacionals estan al centre d'aquesta tesi. S'utilitzen diverses bases de dades clíniques que inclouen menjars mixtes i exercici per demostrar la viabilitat i superioritat de les prestacions d'aquest enfocament.[EN] Diabetes is a significant global health problem, one of the most serious noncommunicable diseases after cardiovascular diseases, cancer and chronic respiratory diseases. Diabetes prevalence has been steadily increasing over the past decades, especially in low- and middle-income countries. It is estimated that 425 million people worldwide had diabetes in 2017, and by 2045 this number may rise to 629 million. About 10% of people with diabetes suffer from type 1 diabetes, characterized by autoimmune destruction of the beta-cells in the pancreas, responsible for the secretion of the hormone insulin. Without insulin, plasma glucose rises to deleterious levels, provoking long-term vascular complications. Until a cure is found, the management of diabetes relies on technological developments for insulin replacement therapies. With the advent of continuous glucose monitors, technology has been evolving towards automated systems. Coined as "artificial pancreas", closed-loop glucose control devices are nowadays a game-changer in diabetes management. Research in the last decades has been intense, yielding a first commercial system in late 2017 and many more are in the pipeline of the main medical devices industry. However, as a first-generation device, many issues still remain open and new technological advancements will lead to system improvements for better glycemic control outputs and reduced patient's burden, improving significantly the quality of life of people with type 1 diabetes. At the core of any artificial pancreas system is glucose prediction, the topic addressed in this thesis. The ability to predict glucose along a given prediction horizon, and estimation of future glucose trends, is the most important feature of any artificial pancreas system, in order to be able to take preventive actions to entirely avoid risk to the patient. Glucose prediction can appear as part of the control algorithm itself, such as in systems based on model predictive control (MPC) techniques, or as part of a monitoring system to avoid hypoglycemic episodes. However, predicting glucose is a very challenging problem due to the large inter- and intra-subject variability that patients suffer, whose sources are only partially understood. These limits models forecasting performance, imposing relatively short prediction horizons, despite the modeling technique used (physiological, data-driven or hybrid approaches). The starting hypothesis of this thesis is that the complexity of glucose dynamics requires the ability to characterize clusters of behaviors in the patient's historical data naturally yielding to the concept of local modeling. Besides, the similarity of responses in a cluster can be further exploited to introduce the classical concept of seasonality into glucose prediction. As a result, seasonal local models are at the core of this thesis. Several clinical databases including mixed meals and exercise are used to demonstrate the feasibility and superiority of the performance of this approach.This work has been supported by the Spanish Ministry of Economy and Competitiveness (MINECO) under the FPI grant BES-2014-069253 and projects DPI2013-46982-C2-1-R and DPI2016-78831-C2-1-R. Moreover, with relation to this grant, a short stay was done at the end of 2017 at the Illinois Institute of Technology, Chicago, United States of America, under the supervision of Prof. Ali Cinar, for four months from 01/09/2017 to 29/12/2017.Montaser Roushdi Ali, E. (2020). STOCHASTIC SEASONAL MODELS FOR GLUCOSE PREDICTION IN TYPE 1 DIABETES [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/136574TESI

    The k-means algorithm: A comprehensive survey and performance evaluation

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    © 2020 by the authors. Licensee MDPI, Basel, Switzerland. The k-means clustering algorithm is considered one of the most powerful and popular data mining algorithms in the research community. However, despite its popularity, the algorithm has certain limitations, including problems associated with random initialization of the centroids which leads to unexpected convergence. Additionally, such a clustering algorithm requires the number of clusters to be defined beforehand, which is responsible for different cluster shapes and outlier effects. A fundamental problem of the k-means algorithm is its inability to handle various data types. This paper provides a structured and synoptic overview of research conducted on the k-means algorithm to overcome such shortcomings. Variants of the k-means algorithms including their recent developments are discussed, where their effectiveness is investigated based on the experimental analysis of a variety of datasets. The detailed experimental analysis along with a thorough comparison among different k-means clustering algorithms differentiates our work compared to other existing survey papers. Furthermore, it outlines a clear and thorough understanding of the k-means algorithm along with its different research directions

    Machine Learning and Integrative Analysis of Biomedical Big Data.

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    Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues

    Workshop on Fuzzy Control Systems and Space Station Applications

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    The Workshop on Fuzzy Control Systems and Space Station Applications was held on 14-15 Nov. 1990. The workshop was co-sponsored by McDonnell Douglas Space Systems Company and NASA Ames Research Center. Proceedings of the workshop are presented

    A study of distributed clustering of vector time series on the grid by task farming

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    Traditional data mining methods were limited by availability of computing resources like network bandwidth, storage space and processing power. These algorithms were developed to work around this problem by looking at a small cross-section of the whole data available. However since a major chunk of the data is kept out, the predictions were generally inaccurate and missed out on significant features that was part of the data. Today with resources growing at almost the same pace as data, it is possible to rethink mining algorithms to work on distributed resources and essentially distributed data. Distributed data mining thus holds great promise. Using grid technologies, data mining can be extended to areas which were not previously looked at because of the volume of data being generated, like climate modeling, web usage, etc. An important characteristic of data today is that it is highly decentralized and mostly redundant. Data mining algorithms which can make efficient use of distributed data has to be thought of. Though it is possible to bring all the data together and run traditional algorithms, this has a high overhead, in terms of bandwidth usage for transmission, preprocessing steps which have to be to handle every format the received data. By processing the data locally, the preprocessing stage can be made less bulky and also the traditional data mining techniques would be able to work on the data efficiently. The focus of this project is to use an existing data mining technique, fuzzy c-means clustering to work on distributed data in a simulated grid environment and to review the performance of this approach viz., the traditional approach

    ESTIMATION OF GREENHOUSE GAS AND ODOUR EMISSIONS FROM COLD REGION MUNICIPAL BIOLOGICAL NUTRIENT REMOVAL WASTEWATER TREATMENT PROCESSES

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    Rising human populations and ever-increasing demand for potable water result in increased municipal wastewater production. The collection, treatment, and management of municipal wastewaters include energy-intensive processes leading to the generation and emission of greenhouse, potentially toxic, and odorous gases. The main goal of this thesis was to advance knowledge of greenhouse gas (including carbon dioxide, CO2; methane, CH4; and nitrous oxide, N2O) and smelly compound (including ammonia, NH3; and hydrogen sulphide, H2S) emissions from typical municipal wastewater treatment plants (MWTPs) to accurately describe their emission rate estimates (EREs) using operating parameters. This research included laboratory and field assessments of greenhouse gas (GHG) and odour emissions in conjunction with monitored operating parameters. Laboratory-scale reactors simulating open-to-air treatment processes including primary and secondary clarifiers and anaerobic, anoxic, and aerobic reactors, were used to monitor gas EREs using wastewater samples taken from the analogous MWTP processes in winter and summer seasons. The Saskatoon Wastewater Treatment plan (SWTP) is a state-of-the-art biological nutrient removal (BNR) type MWTP and a Class IV treatment facility in Canada which was selected as a case study given its highly variable seasonal temperatures from −40 °C to 30 °C and its geographic location near the University of Saskatchewan. The experimental results were then used to develop a variety of novel machine learning models describing gas EREs with further optimization of operating parameters using genetic algorithm (GA). Studied machine learning models were artificial data generation algorithms (including generative adversarial network, GAN) and data-driven models (including artificial neural network, ANN; adaptive network-based fuzzy inference systems, ANFIS; and linear/non-linear regression models). To my knowledge, this is the first application of GAN used for MWTP modelling purposes. Results indicated that anaerobic digestion EREs averagely reached 4,443 kg CH4/d, 9,145 kg CO2/d, and 59.7 kg H2S/d. In contrast, GHG and odour ERE variabilities given ambient temperature changes were more noticeable for open-to-air treatment processes such that the winter EREs were 45,129 kg CO2/d, 21.9 kg CH4/d, 3.20 kg N2O/d, and insignificant for H2S and NH3. The higher temperature for the summer samples resulted in increased EREs for CH4, N2O, and H2S EREs of 33.0 kg CH4/d, 3.87 kg N2O/d, and 2.29 kg H2S/d, respectively, and still insignificant NH3 emissions. However, the CO2 EREs were reduced to 37,794 kg CO2/d, and interestingly, NH3 emissions were still negligible. Overall, the aerobic reactor was the dominant source of GHG emissions for both seasons, and changes in the aerobic reactor aeration rates (in reactor) and BNR treatment configurations (from site) further impacted the EREs. The integration of field monitoring data with data-driven models showed that the ANN, ANFIS, and regression models provided reasonable EREs using: (1) volatile fatty acids, total/fixed/volatile solids, pH, and inflow rate for anaerobic digestion biogas generations; and (2) hydraulic retention time, temperature, total organic carbon, dissolved oxygen, phosphate, and nitrogen concentrations for aerobic GHG emissions. However, when both model accuracy and uncertainty were considered there appears to be a compromise between these parameters with no model having simultaneously both high accuracy and low uncertainty. Additionally, and interestingly, virtual data augmentation using GAN was found to be a valuable resource in supplementation of limited data for improved modelling outcomes. GA was also coupled with the data-driven models to determine optimal operating parameters resulting in either GHG emission maximization given biogas could be beneficial for energy generation or GHG emission minimization given the aerobic reactor is an open-to-air process that can impact nearby residential neighbourhood air quality. The current study provides a hybrid methodology of mathematical modelling and experiments that can be used to accurately estimate and optimize the GHG and odour EREs from other MWTPs in Canada and worldwide
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