This research focuses on addressing two pertinent problems in machine learning (ML) which are (a) the supervised classification of time series and (b) the need for large amounts of labeled images for training supervised classifiers. The novel contributions are two-fold. The first problem of time series classification is addressed by proposing to transform time series into domain-specific 2D features such as scalograms and recurrence plot (RP) images. The second problem which is the need for large amounts of labeled image data, is tackled by proposing a new way of using a reinforcement learning (RL) technique as a supervised classifier by using multimodal (joint representation) scalograms and RP images. The motivation for using such domain-specific features is that they provide additional information to the ML models by capturing domain-specific features (patterns) and also help in taking advantage of state-of-the-art image classifiers for learning the patterns from these textured images. Thus, this research proposes a multimodal fusion (MMF) - deep reinforcement learning (DRL) approach as an alternative technique to traditional supervised image classifiers for the classification of time series. The proposed MMF-DRL approach produces improved accuracy over state-of-the-art supervised learning models while needing fewer training data. Results show the merit of using multiple modalities and RL in achieving improved performance than training on a single modality. Moreover, the proposed approach yields the highest accuracy of 90.20% and 89.63% respectively for two physiological time series datasets with fewer training data in contrast to the state-of-the-art supervised learning model ChronoNet which gave 87.62% and 88.02% accuracy respectively for the two datasets with more training data.

ε-Differential Privacy (DP) has been popularly used for anonymizing data to protect sensitive information and for machine learning (ML) tasks. However, there is a trade-off in balancing privacy and achieving ML accuracy since ε-DP reduces the model’s accuracy for classification tasks. Moreover, not many studies have applied DP to time series from sensors and Internet-of-Things (IoT) devices. In this work, we try to achieve the accuracy of ML models trained with ε-DP data to be as close to the ML models trained with non-anonymized data for two different physiological time series. We propose to transform time series into domain-specific 2D (image) representations such as scalograms, recurrence plots (RP), and their joint representation as inputs for training classifiers. The advantages of using these image representations render our proposed approach secure by preventing data leaks since these image transformations are irreversible. These images allow us to apply state-of-the-art image classifiers to obtain accuracy comparable to classifiers trained on non-anonymized data by ex- ploiting the additional information such as textured patterns from these images. In order to achieve classifier performance with anonymized data close to non-anonymized data, it is important to identify the value of ε and the input feature. Experimental results demonstrate that the performance of the ML models with scalograms and RP was comparable to ML models trained on their non-anonymized versions. Motivated by the promising results, an end-to-end IoT ML edge-cloud architecture capable of detecting input drifts is designed that employs our technique to train ML models on ε-DP physiological data. Our classification approach ensures the privacy of individuals while processing and analyzing the data at the edge securely and efficiently.

Investigating novel treatment approaches to combat Clostridioides difficile Rusha Pal ABSTRACT Clostridioides difficile is the leading cause of antibiotic-induced diarrhea and colitis in hospitals and communities worldwide. The enteric pathogen, classified to be an "urgent threat" by the United States Center for Disease Control and Prevention (CDC), capitalizes on disrupted intestinal microbiome to establish infection with disease symptoms ranging from mild diarrhea to potentially fatal conditions. Disruption of the intestinal microbiome, caused mostly by antibiotic use, enables C. difficile to colonize and proliferate within the host. Paradoxically, antibiotics are used to treat C. difficile infection. These antibiotics decimate the gut microbial community further, thus priming the gastrointestinal tract to become more prone to recurrence of infection. To tackle this clinical setback, we utilized a combination of traditional and non-traditional drug discovery approaches and identified chemical entities and targeted treatment options effective against this toxin-producing intestinal pathogen. Herein, we exploited the strategy of high-throughput screening to identify leads that harbor anticlostridial activity. Our primary phenotypic screen of FDA-approved drugs and natural product libraries led to the identification of novel molecules that were further characterized for their anticlostridial efficacy both in vitro and in vivo. The most potent scaffolds identified were those of mitomycin C, mithramycin A, aureomycin, NP-003875, NAT13-338148, NAT18-355531, and NAT18-355768. Of these, mithramycin A, aureomycin, and NP-003875 were also found to harbor anti-virulence properties as they inhibited toxin production by the pathogen. Furthermore, natural product NP-003875 could confer protection to 100% of the infected mice from clinical manifestations of the disease in a primary infection model of C. difficile. Our final approach has been to develop targeted therapeutics called peptide nucleic acids (PNAs). PNAs are antisense agents capable of inhibiting gene expression in bacteria. In this study, antisense inhibition of the RNA polymerase  subunit gene (rpoA) of C. difficile was found to be bactericidal for the pathogen and could also inhibit the expression of its virulence factors. Additionally, antisense inhibition of the C. difficile rpoA gene was found to be non-deleterious for the tested commensal microflora strains. Given their intriguing anticlostridial properties, it can be concluded that our research opened exciting possibilities that can be further evaluated to uncover new treatments for CDI. / Doctor of Philosophy / Investigating novel treatment approaches to combat Clostridioides difficile Rusha Pal LAYMAN LANGUAGE ABSTRACT Clostridioides difficile is a prominent human pathogen that can colonize the gut and cause fatal infections. C. difficile is the most common cause of microbial healthcare-associated infection and results in substantial morbidity and mortality. The "most urgent worldwide public health threat" label has been assigned to C. difficile by the United States Centers for Disease Control and Prevention (CDC). There is a pressing need to develop new classes of antibiotics with improved efficacy to treat C. difficile infections (CDI). To address the need for novel strategies to combat the growing problem of CDI, we screened FDA-approved drugs and natural products library in search of novel drugs that possess potent and specific anticlostridial activity. Several promising hits were identified and evaluated successfully both in vitro and in vivo. The most potent and novel hits that displayed exceptional activity were mitomycin C, mithramycin A, aureomycin, NP-003875, NAT13-338148, NAT18-355531, and NAT18-355768. Furthermore, a murine model of C. difficile infection revealed that compound NP-003875 conferred 100% protection to the infected mice from clinical manifestations of the disease. Interestingly, these compounds were non-toxic to the gut microflora and human cells. Our final approach has been to develop non-traditional therapeutics to target specific genes in C. difficile. These novel therapeutics are called peptide nucleic acids (PNA). Herein, we designed a PNA targeting RNA polymerase  subunit gene (rpoA) of C. difficile. The designed PNA could successfully inhibit the growth of the pathogen and expression of its virulence factors. In conclusion, our research opened exciting possibilities that can be further evaluated to uncover new treatments for CDI.

The perioperative use of regional anesthesia and local anesthetics is part of almost every anesthesiologist’s daily clinical practice. Retrospective analyses and results from experimental studies pointed towards a potential beneficial effect of the local anesthetics regarding outcome—i.e., overall and/or recurrence-free survival—in patients undergoing cancer surgery. The perioperative period, where the anesthesiologist is responsible for the patients, might be crucial for the further course of the disease, as circulating tumor cells (shed from the primary tumor into the patient’s bloodstream) might form new micro-metastases independent of complete tumor removal. Due to their strong anti-inflammatory properties, local anesthetics might have a certain impact on these circulating tumor cells, either via direct or indirect measures, for example via blunting the inflammatory stress response as induced by the surgical stimulus. This narrative review highlights the foundation of these principles, features recent experimental and clinical data and provides an outlook regarding current and potential future research activities.

The relationship of statin therapy with recurrence of atrial fibrillation (AF) after cardioversion (CV) has been evaluated by several investigations, which provided conflicting results and particularly long-term data is scarce. We sought to examine whether upstream statin therapy is associated with long-term recurrence of AF after CV. This was a single-center registry study including consecutive AF patients (n = 454) undergoing CV. Cox regression models were performed to estimate AF recurrence comparing patients with and without statins. In addition, we performed a propensity score matched analysis with a 1:1 ratio. Statins were prescribed to 183 (40.3%) patients. After a median follow-up period of 373 (207–805) days, recurrence of AF was present in 150 (33.0%) patients. Patients receiving statins had a significantly lower rate of AF recurrence (log-rank p < 0.001). In univariate analysis, statin therapy was associated with a significantly reduced rate of AF recurrence (HR 0.333 (95% CI 0.225–0.493), p = 0.001), which remained significant after adjustment (HR 0.238 (95% CI 0.151–0.375), p < 0.001). After propensity score matching treatment with statins resulted in an absolute risk reduction of 27.5% for recurrent AF (21 (18.1%) vs. 53 (45.7%); p < 0.001). Statin therapy was associated with a reduced risk of long-term AF recurrence after successful cardioversion.

Tesis por compendio / [ES] La tesis "Teoría Combinatoria de Números, Recurrencia de Operadores y Dinámica Lineal" se sitúa dentro del estudio de la dinámica de operadores lineales, o Dinámica Lineal. El objetivo de este trabajo es estudiar múltiples nociones de recurrencia, que pueden presentar los sistemas dinámicos lineales, y que clasificaremos mediante la Teoría Combinatoria de Números. La Dinámica Lineal estudia las órbitas generadas por las iteraciones de una transformación lineal. Las propiedades más estudiadas en esta rama durante los últimos 30 años han sido la hiperciclicidad (existencia de órbitas densas) y el caos (con sus múltiples definiciones), siendo esta un área de investigación muy activa y obteniéndose un considerable número de resultados profundos e interesantes. Nosotros nos centraremos en la recurrencia, propiedad muy estudiada para sistemas dinámicos clásicos no lineales, pero prácticamente nueva en Dinámica Lineal pues no es hasta 2014, con el artículo de Costakis, Manoussos y Parissis titulado "Recurrent linear operators", cuando se empieza a estudiar esta noción de manera sistemática en el contexto de operadores actuando en espacios de Banach. La situación básica de la que parte nuestro estudio es la siguiente: "T : X ---> X" será un operador lineal y continuo actuando sobre un F-espacio "X" , aunque a veces necesitaremos que el espacio subyacente "X" sea un espacio de Fréchet, de Banach o de Hilbert. Dado un vector "x" y un entorno "U" de "x" estudiaremos el conjunto de retorno "N_T(x,U) = { n : T^n(x) está en U }" y dependiendo de su tamaño, observado mediante la Teoría Combinatoria de Números, diremos que el vector "x" presenta una propiedad de recurrencia u otra. La memoria de la tesis se ha realizado por compendio de artículos y consta de cuatro capítulos y un apéndice: 1. Adaptación de la "versión de autor" del artículo "Frequently recurrent operators. Journal of Functional Analysis, 283 (12) (2022), artículo núm. 109713, 36 páginas". En este se definen por primera vez las fuertes nociones de recurrencia reiterada, U-frecuente y frecuente, y sus propiedades básicas son estudiadas. Finalmente se generaliza el estudio mediante el concepto de F-recurrencia, que se conecta con la noción de F-hiperciclicidad. 2. Adaptación al formato de la tesis de la "versión de autor" revisada del artículo "Recurrence properties: An approach via invariant measures. Journal de Mathématiques Pures et Appliquées, 169 (2023), 155-188". En este se relaciona la recurrencia de operadores con la Teoría Ergódica y los sistemas dinámicos que conservan la medida. 3. Adaptación de la "versión de autor" del preprint "Questions in linear recurrence: From the T+T-problem to lineability". Se resuelve negativamente un problema abierto de 2014: Sea "T : X ---> X" un operador recurrente. ¿Es cierto que el operador "T+T" es recurrente en "X+X"? Para resolverlo introducimos la casi-rigidez, que será, para la recurrencia, la noción análoga a la propiedad débil-mezclante (topológica) para la transitividad/hiperciclicidad; y luego construimos operadores recurrentes pero no casi-rígidos en todo espacio de Banach infinito-dimensional y separable. 4. Adaptación de la "versión de autor" revisada del preprint " Recurrent subspaces in Banach spaces". En este se estudia la propiedad de espaciabilidad (existencia de un subespacio vectorial cerrado y de dimensión infinita) para el conjunto de vectores recurrentes. - Apéndice. Para conseguir un carácter auto-contenido hemos añadido un apéndice con los resultados básicos de Teoría Combinatoria de Números que se han utilizado en los trabajos que componen la memoria. Siguiendo la normativa establecida por la Escuela de Doctorado también se incluye: - Introducción; - Discusión general de los resultados; - Conclusiones. / [CAT] La tesi "Teoria Combinatòria de Nombres, Recurrència d'Operadors i Dinàmica Lineal" se situa dins de l'estudi de la dinàmica d'operadors lineals, o simplement Dinàmica Lineal. L'objectiu d'aquest treball és estudiar múltiples nocions de recurrència, que poden presentar els sistemes dinàmics lineals, i que classificarem mitjançant la Teoria Combinatòria de Nombres. La Dinàmica Lineal estudia les òrbites generades per les iteracions d'una transformació lineal. Les propietats més estudiades en aquesta branca de les matemàtiques als darrers 30 anys han estat la hiperciclicitat (existència d'òrbites denses) i el caos (amb les seves múltiples definicions), sent aquesta una àrea de recerca molt activa i obtenint-se un considerable nombre de resultats profunds i interessants. Nosaltres ens centrarem en la recurrència, propietat molt estudiada per a sistemes dinàmics clàssics no lineals, però, pràcticament nova en Dinàmica Lineal doncs no és fins al 2014, amb l'article de Costakis, Manoussos i Parissis titulat "Recurrent linear operators", quan es comença a estudiar aquesta noció de manera sistemàtica en el context d'operadors actuant en espais de Banach. La situació bàsica de la qual parteix el nostre estudi és la següent: "T : X ---> X" serà un operador lineal i continu actuant sobre un F-espai "X", encara que de vegades necessitarem que l'espai subjacent X siga un espai de Fréchet, de Banach o de Hilbert. Llavors, donat un vector "x" i un entorn "U" de "x" estudiarem el conjunt de retorn "N_T(x,U) = { n : T^n(x) està en U }" i depenent de la seva mida, observada des del punt de vista de la Teoria Combinatòria de Nombres, direm que el vector "x" presenta una o altra propietat de recurrència. La memòria de la tesi s'ha realitzat per compendi d'articles i consta de quatre capítols i un apèndix: 1. Adaptació de la "versió d'autor" revisada de l'article "Frequently recurrent operators. Journal of Functional Analysis, 283 (12) (2022), article núm. 109713, 36 pàgines". En aquest es defineixen per primera vegada les nocions de recurrència reiterada, U-freqüent i freqüent, i les seves propietats bàsiques són estudiades. Finalment es generalitza l'estudi mitjançant el concepte de F-recurrència, que es connecta amb la noció de F-hiperciclicitat. 2. Adaptació al format de la tesi de la "versió d'autor" revisada de l'article "Recurrence properties: An approach via invariant measures. Journal de Mathématiques Pures et Appliquées, 169 (2023), 155-188". Es relaciona la recurrència d'operadors amb la Teoria Ergòdica i els sistemes dinàmics que conserven la mesura. 3. Adaptació de la "versió d'autor" del preprint "Questions in linear recurrence: From the T+T-problem to lineability". En aquest es resol un problema obert de l'any 2014: Siga "T : X ---> X" un operador recurrent. És cert que l'operador "T+T" és recurrent en "X+X"? Per resoldre'l introduïm la quasi-rigidesa, que serà, per a la recurrència, la noció anàloga a la propietat feble-barrejant (topològica) per a la transitivitat/hiperciclicitat; i després construïm operadors recurrents però no quasi-rígids en tot espai de Banach infinit-dimensional i separable. 4. Adaptació de la "versió d'autor" del preprint "Recurrent subspaces in Banach spaces". S'inclou l'estudi de la propietat d'espaiabilitat (existència d'un subespai vectorial tancat i de dimensió infinita) per al conjunt de vectors recurrents. - Apèndix:Per aconseguir un caràcter auto-contingut hem afegit un apèndix amb resultats bàsics de Teoria Combinatòria de Nombres que es donen per suposats en els treballs que componen la memòria. Seguint la normativa establerta per l'Escola de Doctorat també s'inclou: - Introducció; - Discussió general dels resultats; - Conclusions. / [EN] The thesis "Combinatorial Number Theory, Recurrence of Operators and Linear Dynamics" is part of the study of the dynamics of linear operators, simply called Linear Dynamics. The objective of this work is to study multiple notions of recurrence, that linear dynamical systems can present, and which will be classified through Combinatorial Number Theory. Linear Dynamics studies the orbits generated by the iterations of a linear transformation. The two most studied properties in this branch of mathematics during the last 30 years have been hypercyclicity (existence of dense orbits) and chaos (with its multiple definitions), being this a very active research area with a considerable number of exceptionally deep but also interesting results. We will focus on recurrence, a property widely studied in the classical setting of non-linear dynamical systems, but practically new with respect to Linear Dynamics since it was not until 2014, with the article by Costakis, Manoussos and Parissis entitled "Recurrent linear operators", when this notion started to be systematically studied in the context of operators acting on Banach spaces. The basic situation from which our study starts is the following: "T : X ---> X" will be a continuous linear operator acting on an F-space "X", although sometimes we will need the underlying space X to be a Fréchet, Banach or Hilbert space. Given a vector "x" and a neighbourhood "U" of "x" we will study the return set "N_T(x,U) = { n : T^n(x) is in U }" and depending on its size, observed from the Combinatorial Number Theory point of view, we will say that the vector "x" presents one property of recurrence or another. The thesis memoir is a compendium of articles and it has four chapters and one appendix: 1. Adaptation of the revised "author version" of article "Frequently recurrent operators. Journal of Functional Analysis, 283 (12) (2022), paper no. 109713, 36 pages". Here, the strong notions of reiterative, U-frequent and frequent recurrence are defined for the first time, and their basic properties are studied. The theory is finally generalized through the concept of F-recurrence, which is connected to the notion of F-hypercyclicity. 2. Adaptation of the revised "author version" of article "Recurrence properties: An approach via invariant measures. Journal de Mathématiques Pures et Appliquées, 169 (2023), 155-188". In this chapter the recurrence properties for linear operators are related to Ergodic Theory and measure preserving systems. 3. Adaptation of the revised "author version" of the preprint "Questions in linear recurrence: From the T+T-problem to lineability". We solve in the negative an open problem posed in 2014: Let "T : X ---> X" be a recurrent operator. Is it true that the operator "T+T" is recurrent on "X+X"? In order to do that we establish the analogous notion, for recurrence, to that of (topological) weak-mixing for transitivity/hypercyclicity, namely quasi-rigidity; and then we construct recurrent but not quasi-rigid operators on every separable infinite-dimensional Banach space. 4. Adaptation of the revised "author version" of the preprint "Recurrent subspaces in Banach spaces". In this chapter we study the spaceability (existence of an infinite-dimensional closed subspace) for the set of recurrent vectors. - Appendix. Looking for a self-contained text we have added an appendix with some of the basic Combinatorial Number Theory results that are taken for granted along the different chapters/articles forming this memoir. Following the regulations established by the Doctoral School the next sections are also included: - Introduction; - General discussion of the results; - Conclusions. / This thesis has been written at the “Institut Universitari de Matemàtica Pura i Aplicada” (IUMPA) of the “Universitat Politècnica de València” (UPV), during the period of enjoyment of a scholarship of the “Programa de Formación de Profesorado Universitario” granted by the “Ministerio de Ciencia, Innovación y Universidades”, reference number: FPU2019/04094. The research exposed has also been partially funded by the project “Dinámica de operadores” (MCIN/AEI/10.13039/501100011033, Project PID2019-105011GB-I00), thanks to which the author carried out a 3-month research stay in Lille, France (September-December 2021), that was supervised by Professor Sophie Grivaux; and also by the travel grant awarded by the “Fundació Ferran Sunyer i Balaguer” which allowed the author to carry out a 3-month research stay in Mons, Belgium (April-June 2023), supervised by Professor Karl Grosse-Erdmann. / López Martínez, A. (2023). Combinatorial Number Theory, Recurrence of Operators and Linear Dynamics [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/196101 / Compendio

The aim of this thesis is to determine the relationship between natural resources and peace, by examining whether a correlation exists between conflicts related to natural resources and conflict recurrence. The hypothesis is that conflicts with distribution mechanisms increase the likelihood of conflict recurrence. This is tested through the application of Mill’s Method of Difference and a SFC, cross-case comparison of two conflicts in Angola between 1991 and 2002. The first conflict between UNITA and the government of Angola was characterized by the usage of diamonds for rebel group financing, whereas the second conflict between various separatist groups and the Angolan government in the enclave of Cabinda concerned the inequitable distribution of oil revenues. The findings show that both conflicts resumed, showing little support for the paper’s hypothesis. This thesis’ empirical data derives from different sources of secondary nature. The findings suggest that the paper’s hypothesis lacks sufficient support and therefore, alternative explanations are put forward in order to explain the inconsistency with the hypothesis — thus encouraging other avenues for research that take aim at disaggregating the relationship between natural resources and the prospects for post-conflict peace.

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