Diagnóstico no invasivo de patologías humanas combinando análisis de aliento y modelización con redes neuronales

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Químicas, leída el 09-09-2016It is currently known that there is a direct relation between the moment a disease is detected or diagnosed and the consequences it will have on the patient, as an early detection is generally linked to a more favorable outcome. This concept is the basis of the present research, due to the fact that its main goal is the development of mathematical tools based on computational artificial intelligence to safely and non-invasively attain the detection of multiple diseases. To reach these devices, this research has focused on the breath analysis of patients with diverse diseases, using several analytical methodologies to extract the information contained in these samples, and multiple feature selection algorithms and neural networks for data analysis. In the past, it has been shown that there is a correlation between the molecular composition of breath and the clinical status of a human being, proving the existence of volatile biomarkers that can aid in disease detection depending on their presence or amount. During this research, two main types of analytical approaches have been employed to study the gaseous samples, and these were cross-reactive sensor arrays (based on organically functionalized silicon nanowire field-effect transistors (SiNW FETs) or gold nanoparticles (GNPs)) and proton transfer reaction-mass spectrometry (PTR-MS). The cross-reactive sensors analyze the bulk of the breath samples, offering global, fingerprint-like information, whereas PTR-MS quantifies the volatile molecules present in the samples. All of the analytical equipment employed leads to the generation of large amounts of data per sample, forcing the need of a meticulous mathematical analysis to adequately interpret the results. In this work, two fundamental types of mathematical tools were utilized. In first place, a set of five filter-based feature selection algorithms (χ2 (chi2) score, Fisher’s discriminant ratio, Kruskal-Wallis test, Relief-F algorithm, and information gain test) were employed to reduce the amount of independent in the large databases to the ones which contain the greatest discriminative power for a further modeling task. On the other hand, and in relation to mathematical modeling, artificial neural networks (ANNs), algorithms that are categorized as computational artificial intelligence, have been employed. These non-linear tools have been used to locate the relations between the independent variables of a system and the dependent ones to fulfill estimations or classifications. The type of ANN that has been used in this thesis coincides with the one that is more commonly employed in research, which is the supervised multilayer perceptron (MLP), due to its proven ability to create reliable models for many different applications...Actualmente es sabido que existe una relación directa entre el momento en el cual se detecta o diagnostica una enfermedad y las consecuencias que tendrá sobre el paciente, ya que una detección temprana va generalmente ligada a un desarrollo más favorable. Este concepto es el cimiento de la presente investigación, cuyo objetivo fundamental es el desarrollo de herramientas basadas en inteligencia artificial computacional que consigan, mediante medios seguros y no invasivos, la detección de diversas enfermedades. Para alcanzar dichos sistemas, los estudios han sido enfocados en el análisis de muestras de aliento de pacientes de diversas enfermedades, empleando varias técnicas para extraer información, y diversos algoritmos de selección de variables y redes neuronales para el procesamiento matemático. En el pasado, se ha comprobado que hay una correlación entre la composición molecular del aliento y el estado clínico de una persona, evidenciando la existencia de biomarcadores volátiles que pueden ayudar a detectar enfermedades, ya sea por su presencia o por su cantidad. Durante el transcurso de esta investigación, se han empleado esencialmente dos tipos de técnicas analíticas para estudiar las muestras gaseosas, y estas son conjuntos de sensores de reactividad cruzada (basados en transistores de efecto de campo con nanocables de silicio (SiNW FETs) o en nanopartículas de oro (GNPs), ambos funcionalizados con cadenas orgánicas) y equipos de reacción de transferencia de protones con espectrometría de masas (PTR-MS). Los sensores de reactividad cruzada analizan el aliento en su conjunto, extrayéndose información de la muestra global, mientras que usando PTR-MS, se cuantifican las moléculas volátiles presentes en las muestras analizadas. Todas las técnicas empleadas desembocan en la generación de grandes cantidades de datos por muestra, por lo que un análisis matemático exhaustivo es necesario para poder sacar el máximo rendimiento de los estudios. En este trabajo, se emplearon principalmente dos tipos de herramientas matemáticas. Las primeras son un grupo de cinco algoritmos de selección de variables, concretamente, filtros de variables (cálculos basados en estadística de χ2 (chi2), ratio discriminante de Fisher, análisis de Kruskal-Wallis, algoritmo relief-F y test de ganancia de información), que se han empleado en las bases de datos con grandes cantidades de variables independientes para localizar aquellas con mayor importancia o poder discriminativo para una tarea de modelización matemática posterior. Por otro lado, en cuando a dicha modelización, se ha empleado un tipo de algoritmo que se cataloga dentro del área de la inteligencia artificial computacional: las redes neuronales artificiales (ANNs). Estas herramientas matemáticas de naturaleza no lineal se han utilizado para localizar las relaciones existentes entre las variables independientes de un sistema y las variables dependientes o parámetros a estimar o clasificar. Se ha empleado el tipo de ANN supervisada más extensamente usado en investigación, que son los perceptrones multicapa (MLPs), debido a su habilidad contrastada para originar modelos fiables para numerosas aplicaciones...Fac. de Ciencias QuímicasTRUEunpu

Earth as Interface: Exploring chemical senses with Multisensory HCI Design for Environmental Health Communication

As environmental problems intensify, the chemical senses -that is smell and taste, are the most relevantsenses to evidence them.As such, environmental exposure vectors that can reach human beings comprise air,food, soil and water[1].Within this context, understanding the link between environmental exposures andhealth[2]is crucial to make informed choices, protect the environment and adapt to new environmentalconditions[3].Smell and taste lead therefore to multi-sensorial experiences which convey multi-layered information aboutlocal and global events[4]. However, these senses are usually absent when those problems are represented indigital systems. The multisensory HCIdesign framework investigateschemical sense inclusion withdigital systems[5]. Ongoing efforts tackledigitalization of smell and taste for digital delivery, transmission or substitution [6]. Despite experimentsproved technological feasibility, its dissemination depends on relevant applicationdevelopment[7].This thesis aims to fillthose gaps by demonstratinghow chemical senses provide the means to link environment and health based on scientific andgeolocation narratives [8], [9],[10]. We present a Multisensory HCI design process which accomplished symbolicdisplaying smell and taste and led us to a new multi-sensorial interaction system presented herein. We describe the conceptualization, design and evaluation of Earthsensum, an exploratory case study project.Earthsensumoffered to 16 participants in the study, environmental smell and taste experiences about real geolocations to participants of the study. These experiences were represented digitally using mobilevirtual reality (MVR) and mobile augmented reality (MAR). Its technologies bridge the real and digital Worlds through digital representations where we can reproduce the multi-sensorial experiences. Our study findings showed that the purposed interaction system is intuitive and can lead not only to a betterunderstanding of smell and taste perception as also of environmental problems. Participants comprehensionabout the link between environmental exposures and health was successful and they would recommend thissystem as education tools. Our conceptual design approach was validated and further developments wereencouraged.In this thesis,we demonstratehow to applyMultisensory HCI methodology to design with chemical senses. Weconclude that the presented symbolic representation model of smell and taste allows communicatingtheseexperiences on digital platforms. Due to its context-dependency, MVR and MAR platforms are adequatetechnologies to be applied for this purpose.Future developments intend to explore further the conceptual approach. These developments are centredon the use of the system to induce hopefully behaviourchange. Thisthesisopens up new application possibilities of digital chemical sense communication,Multisensory HCI Design and environmental health communication.À medida que os problemas ambientais se intensificam, os sentidos químicos -isto é, o cheiroe sabor, são os sentidos mais relevantes para evidenciá-los. Como tais, os vetores de exposição ambiental que podem atingir os seres humanos compreendem o ar, alimentos, solo e água [1]. Neste contexto, compreender a ligação entre as exposições ambientais e a saúde [2] é crucial para exercerescolhas informadas, proteger o meio ambiente e adaptar a novas condições ambientais [3]. O cheiroe o saborconduzemassima experiências multissensoriais que transmitem informações de múltiplas camadas sobre eventos locais e globais [4]. No entanto, esses sentidos geralmente estão ausentes quando esses problemas são representados em sistemas digitais. A disciplina do design de Interação Humano-Computador(HCI)multissensorial investiga a inclusão dossentidos químicos em sistemas digitais [9]. O seu foco atual residena digitalização de cheirose sabores para o envio, transmissão ou substituiçãode sentidos[10]. Apesar dasexperimentaçõescomprovarem a viabilidade tecnológica, a sua disseminação está dependentedo desenvolvimento de aplicações relevantes [11]. Estatese pretendepreencher estas lacunas ao demonstrar como os sentidos químicos explicitama interconexãoentre o meio ambiente e a saúde, recorrendo a narrativas científicas econtextualizadasgeograficamente[12], [13], [14]. Apresentamos uma metodologiade design HCImultissensorial que concretizouum sistema de representação simbólica de cheiro e sabor e nos conduziu a um novo sistema de interação multissensorial, que aqui apresentamos. Descrevemos o nosso estudo exploratório Earthsensum, que integra aconceptualização, design e avaliação. Earthsensumofereceu a 16participantes do estudo experiências ambientais de cheiro e sabor relacionadas com localizações geográficasreais. Essas experiências foram representadas digitalmente através derealidade virtual(VR)e realidade aumentada(AR).Estas tecnologias conectamo mundo real e digital através de representações digitais onde podemos reproduzir as experiências multissensoriais. Os resultados do nosso estudo provaramque o sistema interativo proposto é intuitivo e pode levar não apenas a uma melhor compreensão da perceção do cheiroe sabor, como também dos problemas ambientais. O entendimentosobre a interdependência entre exposições ambientais e saúde teve êxitoe os participantes recomendariam este sistema como ferramenta para aeducação. A nossa abordagem conceptual foi positivamentevalidadae novos desenvolvimentos foram incentivados. Nesta tese, demonstramos como aplicar metodologiasde design HCImultissensorialpara projetar com ossentidos químicos. Comprovamosque o modelo apresentado de representação simbólica do cheiroe do saborpermite comunicar essas experiênciasem plataformas digitais. Por serem dependentesdocontexto, as plataformas de aplicações emVR e AR são tecnologias adequadaspara este fim.Desenvolvimentos futuros pretendem aprofundar a nossa abordagemconceptual. Em particular, aspiramos desenvolvera aplicaçãodo sistema para promover mudanças de comportamento. Esta tese propõenovas possibilidades de aplicação da comunicação dos sentidos químicos em plataformas digitais, dedesign multissensorial HCI e de comunicação de saúde ambiental

Artificial Olfaction in the 21st Century

The human olfactory system remains one of the most challenging biological systems to replicate. Humans use it without thinking, where it can measure offer protection from harm and bring enjoyment in equal measure. It is the system's real-time ability to detect and analyze complex odors that makes it difficult to replicate. The field of artificial olfaction has recruited and stimulated interdisciplinary research and commercial development for several applications that include malodor measurement, medical diagnostics, food and beverage quality, environment and security. Over the last century, innovative engineers and scientists have been focused on solving a range of problems associated with measurement and control of odor. The IEEE Sensors Journal has published Special Issues on olfaction in 2002 and 2012. Here we continue that coverage. In this article, we summarize early work in the 20th Century that served as the foundation upon which we have been building our odor-monitoring instrumental and measurement systems. We then examine the current state of the art that has been achieved over the last two decades as we have transitioned into the 21st Century. Much has been accomplished, but great progress is needed in sensor technology, system design, product manufacture and performance standards. In the final section, we predict levels of performance and ubiquitous applications that will be realized during in the mid to late 21st Century

Computational Optimization of Metal-Organic Framework (MOF) Arrays for Chemical Sensing

Although commercial gas sensors exist for applications such as product quality control, industrial food monitoring, and smoke detection, there are many potential applications for which adequate gas sensing technology is lacking. There is an unmet need for gas sensors to detect natural gas leaks, for disease detection via breath analysis, and for environmental monitoring, to name just a few examples. Current gas sensors do not exhibit the sensitivity and/or selectivity required to detect trace amounts of the required gases in complex gas mixture environments (e.g., ambient air or a patient’s breath). It is known that arrays of sensors, or electronic noses, improve chemical detection when compared to single sensor elements. Although some work has been done to optimize sensor device performance, there are many potential sensing materials that have not yet been extensively explored. Herein, we explore the use of metal-organic framework (MOF) materials in sensor arrays, exploiting their high adsorption capabilities to yield more selective and sensitive electronic noses. As a relatively new class of materials, MOFs have not been thoroughly investigated for gas sensing applications. In particular, prior to our work, there had only been a few investigations of MOF sensor arrays and those were limited to purely experimental work that relied heavily on trial-and-error. We demonstrate that leveraging computational modeling and optimization to rationally design MOF sensor arrays can yield significantly improved sensing performance. Our novel computational method was carried out first by predicting individual MOF sensor responses via molecular simulations. Then, we developed a method to analyze those individual responses and provide output signals for entire sensor arrays to predict unknown gas mixtures. Following this, the prediction ability of each array was evaluated according to the Kullback-Liebler divergence (KLD), where we determined the best arrays for detecting methane-in-air mixtures. Finally, we developed and validated a genetic algorithm that enables the optimization of large MOF arrays

Environmental engineering applications of electronic nose systems based on MOX gas sensors

Nowadays, the electronic nose (e-nose) has gained a huge amount of attention due to its ability to detect and differentiate mixtures of various gases and odors using a limited number of sensors. Its applications in the environmental fields include analysis of the parameters for environmental control, process control, and confirming the efficiency of the odor-control systems. The e-nose has been developed by mimicking the olfactory system of mammals. This paper investigates e-noses and their sensors for the detection of environmental contaminants. Among different types of gas chemical sensors, metal oxide semiconductor sensors (MOXs) can be used for the detection of volatile compounds in air at ppm and sub-ppm levels. In this regard, the advantages and disadvantages of MOX sensors and the solutions to solve the problems arising upon these sensors’ applications are addressed, and the research works in the field of environmental contamination monitoring are overviewed. These studies have revealed the suitability of e-noses for most of the reported applications, especially when the tools were specifically developed for that application, e.g., in the facilities of water and wastewater management systems. As a general rule, the literature review discusses the aspects related to various applications as well as the development of effective solutions. However, the main limitation in the expansion of the use of e-noses as an environmental monitoring tool is their complexity and lack of specific standards, which can be corrected through appropriate data processing methods applications

Smell, smells and smelling in Victorian supernatural fiction of the fin de siècle

PhD ThesisMy PhD examines how writers at the fin de siècle responded to new understandings of smell, smells and smelling in their representations of the supernatural, demonstrating how those understandings were harnessed to nascent disciplines and technologies concerned with the limits and potential of the human subject. It recovers a lost history of smell and explains how shifts in the meaning of ‘smell’ (verb and noun) were witnessed and interrogated by writers in the period. Drawing attention to significant omissions from foundational accounts of olfaction in the nineteenth century, the thesis performs five key reclamatory readings to illuminate a number of supernatural stories. Firstly, it considers cross-channel influences on the articulation and reception of smell- description, drawing out a specifically British experience of scent that relates to the defaecalisation of the River Thames between 1858 and 1875. It then uncovers the origin, and demonstrates the literary manifestation, of analogies between music and scent. The thesis analyses how smells and noses in fin-de-siècle supernatural tales responded to new discursive possibilities afforded by late nineteenth-century developments in rhinoplasty, anaesthesia, nursing and Tractarian theology. The possible over-estimation of H. G. Wells’s reputation for early alignment with Darwinian theory is also considered through a recuperation of George William Piesse’s The Art of Perfumery (1855). Finally, it considers smellers and noses in Henry Rider Haggard’s She (1887), Richard Marsh’s The Beetle (1897), Bram Stoker’s Dracula (1897), Oscar Wilde’s The Picture of Dorian Gray (1891) and a range of prose fiction by Vernon Lee and Arthur Machen. Overall, it argues that in fin-de-siècle supernatural fiction the epistemology of smell, smells and smelling provided writers with new ways of testing, expanding and representing the boundaries of human identity

Nanochips and medical applications

Ο όρος «νανοτσιπ» αναφέρεται σε ένα ολοκληρωμένο κύκλωμα (τσιπ) με νανοϋλικά και δομές στη νανοκλίμακα (1-100nm). Ένα ολοκληρωμένο κύκλωμα είναι μια συλλογή ηλεκτρονικών εξαρτημάτων, όπως τρανζίστορ, δίοδοι, πυκνωτές και αντιστάσεις. Τα σημερινά τρανζίστορ είναι στη νανοκλίμακα, αλλά μπορούν να τροποποιηθούν με νανοδομές για την κατασκευή βιοαισθητήρων που μπορούν να πραγματοποιούν ανίχνευση βιομορίων, όπως ιόντα, μόρια DNA, αντισώματα και αντιγόνα με μεγάλη ευαισθησία. Υλικά και Μέθοδοι: Πραγματοποιήθηκε συστηματική αναζήτηση βιβλιογραφίας με χρήση των ηλεκτρονικών βάσεων δεδομένων PubMed, Google Scholar και Scopus για την ανάπτυξη και χρήση νανοτσίπ σε ιατρικές εφαρμογές. Για τον προσδιορισμό των σχετικών εργασιών, τα κριτήρια συμπερίληψης αναφέρονται σε άρθρα στην αγγλική γλώσσα, άρθρα βιβλιογραφικού περιεχομένου ή/και έρευνών. Τα κριτήρια αποκλεισμού ήταν άρθρα εφημερίδων, περιλήψεις συνεδρίων και επιστολές. Αποτελέσματα: Τεχνικές in-vivo και in-vitro έχουν χρησιμοποιηθεί για την ανίχνευση μορίων DNA, ιόντων, αντισωμάτων, σημαντικών πρωτεϊνών και καρκινικών δεικτών, όχι μόνο από δείγματα αίματος αλλά και από ιδρώτα, σάλιο και άλλα βιολογικά υγρά. Διαγνωστική εφαρμογή των νανοτσίπ αποτελεί και η ανίχνευση πτητικών οργανικών ενώσεων μέσω τεστ εκπνεόμενης αναπνοής. Υπάρχουν και αρκετές θεραπευτικές εφαρμογές αυτών των συσκευών ημιαγωγών όπως τσιπ διασύνδεσης εγκεφάλου-υπολογιστή για παραλυτικές ή επιληπτικές καταστάσεις, κατασκευή «βιονικών» οργάνων όπως τεχνητός αμφιβληστροειδής, τεχνητό δέρμα και ρομποτικά προθετικά άκρα για ακρωτηριασμένους ή ρομποτική χειρουργική. Συμπέρασμα: Η χρήση των νανοτσίπ στην ιατρική είναι ένας αναδυόμενος τομέας με αρκετές θεραπευτικές εφαρμογές όπως η διάγνωση, η παρακολούθηση της υγείας και της φυσικής κατάστασης και η κατασκευή «βιονικών» οργάνων.Background: The term “nanochip” pertains to an integrated circuit (chip) with nanomaterials and components in the nano-dimension (1-100nm). An integrated circuit is essentially a collection of electronic components, like transistors, diodes, capacitors, and resistors. Current transistors are in the nanoscale but can also be modified with nanostructures like nanoribbons and nanowires to manufacture biosensors that can perform label-free, ultrasensitive detection of biomolecules like ions, DNA molecules, antibodies and antigens. Materials and Methods: A systematic literature search was conducted using the electronic databases PubMed, Google Scholar and Scopus for the development and use of nanochips in medical applications. For the identification of relevant papers, the inclusion criteria referred to articles in the English language, review and/or research articles. The exclusion criteria were newspaper articles, conference abstracts and letters. Results: In-vivo and In-vitro techniques have been used for detection of DNA molecules, ions, antibodies, important proteins, and tumor markers, not only from blood samples but also from sweat, saliva and other biological fluids. Another diagnostic application of nanochips is detection of volatile organic compounds via a breath test. There are also several therapeutic applications of these semiconductor devices like brain-computer interface chips for paralytic or epileptic conditions, manufacture of “bionic” organs like artificial retinas, artificial skin and robotic prostheses for amputees or robotic surgery. Conclusion: The use of nanochips in medicine is an emerging field with several therapeutic applications like diagnostics, health and fitness monitoring, and manufacture of “bionic” organs

Mapping Dynamic Relations in Sound and Space Perception

The research investigates the dynamic relations between sound, space and the audience perception as related to an artist’s intention. What is the relation between sound and space in the sonic arts, and to what kind of merger does it lead? What relationship exists between the intention of the composer and the perception of the audience regarding architectural and environmental spaces? Is there a common thread of perception of architectural and environmental spaces among participants? Is embodiment a key for the perception of the dynamic relations of sound and space? The framework for the investigation is based on a map of three defined spaces (Real, Virtual, and Hyperbiological) included in a portfolio of six works (three electroacoustic compositions, two sound installations, and one performance), which lead to the analysis of the perception of space, namely, the perception of architectural and environmental spaces as required by the portfolio. The original knowledge resides in the exploration of a potential common representation (space and sound perception being, of course, a personal representation) of internal perceptual spaces and mental imageries generated by the works. The act of listening plays a major role in the development of the portfolio presented and includes Pauline Oliveros’ concept of deep listening (Oliveros 2005). Sound and space are intimately related in the portfolio. One particular element emerging from this relationship is the plastic quality of sound, meaning that sound is considered and observed as a material that is shaped by space. From this perspective the research investigates the ‘sculptural’ and morphological quality of the relationship between sound and space. The results include the specific language and signature of the artworks that delineate the intersection of music and fine arts. The portfolio pays a large tribute to several iconic artists present in the outposts of sound blurred by space. Composers and artists are therefore presented in the theoretical section in order to highlight how their pioneering works have influenced and informed the present research portfolio. The analysis of the perception of the artworks relates to a methodology based on an empirical survey inspired by phenomenology

Soundscapes for Social Change: Community and Consciousness through Sound Design Rhetorics

By applying a “sound-mapping” methodology that incorporates qualitative interviews and field research, I argue that theater sound design provides new means to connect sonic rhetorics with social change. I examine theater sound design as an ecological composing practice that lends itself to empathy, community, action, and pedagogy; and further argue that there is rhetorical potential in what I call “soundscapes for social change,” a concept that encourages sonic agency and sound as contemporary resistance. The theater setting introduces sound and vibration experiences carefully calculated and developed to impact a variety of audiences and stir their imaginations through sensory experiences, accessed not just through the ear but also through the body