Le durcissement des normes d’émission, tout autant que l’impératif d’économie,poussent à étudier de nouveaux modes de combustion pour les moteurs. L’autoallumage decharges homogènes à basse température offre de bonnes perspectives quant au rejet de NOx,suies, et CO2. Cependant son control reste délicat, car il est extrêmement sensible à latempérature et la cinétique de l’hydrocarbure. L’assistance par plasma hors-équilibre pourraitfournir une solution. Les expériences sont menées dans une MCR avec des mélanges pauvresd’isooctane/air et un prototype d’allumeur Renault. La combustion obtenue identifiée commeSICI se déroule en deux phases: la propagation d’une flamme comprime les gaz restantjusqu’à leur autoallumage. Le réchauffement du système expérimental est intégré dans leprotocole d’exploitation, afin de quantifier l’effet SICI relativement à l’autoallumage pur.L’effet du plasma semble avant tout dépendre de l’énergie déposée, bien qu’il convergerapidement, quel que soit l’avance du déclenchement. Le comportement asymptotique à hauteénergie s’explique par la thermalisation des filaments, soulignée par comparaison avec l’effetSICI d’un arc classique. A l’inverse, le seuil minimal d’énergie nécessaire semble lié à lacapacité à générer un noyau de flamme viable, rapprochant le phénomène d’un problèmeclassique d’allumage en conditions difficiles. La propagation de la flamme détermine ledéclenchement de l’autoallumage selon une caractéristique linéaire particulièrementremarquable, car indépendante des conditions thermodynamiques du mélange. L’existenced’une flamme froide est mise en avant par des acquisitions de PLIF formaldéhyde. Lapréréaction semble accélérer la propagation du front de flamme. / Emission standards tightening as well as economical needs urge to study newcombustion modes for engines. Low-temperature homogeneous charge auto-ignition offersgood prospects for NOx, soot, and CO2 emissions. However, its control remains sharp for it isextremely influenced by temperature and fuel chemistry. Assisting non-equilibrium plasmascould provide a solution. Experiments are RCM managed with lean isooctane/air mixtures andprototype Renault ignition devise. Combustion occurs in a two steps mode known as SICI:flame propagation compresses the remaining gas to auto-ignition. The experimental settemperature rise is computed in order to measure the SICI effect compared to pure autoignition.The plasma seems to act mainly through the energy dropped, albeit its effect quicklyreaches a maximum, no matter how early it starts. This asymptomatic high energy behaviorrelies on the streamers overheating, as underlined by the look-like SICI effect from a regulararc discharge. On the contrary, minimal required energy appears to be linked to the capabilityof generating a sustainable flame kernel, making it closer to a standard ignition issue in roughconditions. Flame propagation sets auto-ignition start, according to an astonishingly linearcharacteristic not even influenced by charge’s thermodynamic conditions. Cool flame is putforward through formaldehyde PLIF imaging. Prereaction seems to enhance front propagationspeed.

Ce travail consiste en le développement d'une méthodologie pour comprendre les mécanismes de corrosion atmosphérique du fer sur le long terme à l'aide d'outils chimiométriques. Les données structurales et de composition élémentaire sont acquises par microspectrométrie Raman et Microscopie Electronique à Balayage couplée à la Spectroscopie en Dispersion d'Energie (MEB-EDS) sur deux échantillons provenant de barres de fer des cathédrales d'Amiens et de Metz. Ces deux jeux de données sont couplés puis étudiés selon différentes approches multiblocs. La première partie de ce projet étudie les données spectrales couplées pour préserver le maximum d'information des acquisitions et la deuxième étudie les mêmes données réduites en nombre de variables pour en simplifier l'étude. Ces deux approchent convergent vers une même conclusion : des éléments mineurs sont présents au sein de certaines phases cristallines de corrosion, notamment la ferrihydrite qui est associée au silicium, au phosphore et au potassium. Ceci peut à terme influencer les propriétés physicochimiques des phases présentes dans les couches de produits de corrosion et modifier les vitesses de corrosion. / This work aims to develop a methodology in order to understand atmospheric long term corrosion mechanism with chemometric tools on iron materials. Structural and elementary data are acquired with Raman microspectrometry and Scanning Electron Microscopy coupled to Energy Dispersive X-Ray spectroscopy (SEM-EDX) on two samples, one extracted from Amiens’ cathedral and one from Metz’s cathedral. These two datasets are coupled together then studied with several multibloc approaches. The first studies spectral data in order to avoid information loss and the second use the same reduced data in order to simplify the study. These two approaches give same results which leads to: minor elements are colocalized with some crystalline phases. For example, ferrihydrite is colocalized with minor elements (silicon, phosphorus and potassium). This can influence crystalline phase’s physicochimico reactivity properties in corrosion product layer and the corrosion rate.

Colistin is a last-resort antibiotic used to treat serious infections caused by Enterobacteriaceae and other multidrug resistant gram-negative bacteria. Recently discovered plasmid-borne colistin resistance, mediated by the mcr genes, poses a serious risk to colistin therapy. The aim of this diploma thesis was to map the occurrence of Enterobacteriaceae carrying the mcr-1 to 8 genes in hospitalized patients, travellers, prospective colistin-resistant clinical isolates and in a retrospective collection of Enterobacteriaceae using a combination of selective cultivation and qPCR. Isolates with a detected mcr gene were characterized by Whole-Genome Sequencing. The localization of mcr genes was determined and other resistance genes and plasmids were identified. Furthermore, the physiological profile of selected colistin- resistant Escherichia coli isolates was characterized. In the presence of a subinhibitory amount of colistin, a strain carrying the mcr-1 gene may be favored. Later, the mcr-9 gene was described and its occurence was subsequently tested retrospectively. Enterobacter spp. isolates carrying the mcr-9 gene were mostly colistin-sensitive but, in some cases, resistance was induced after exposure to sublethal doses of colistin. The results of the study show that the incidence of plasmid-mediated...

Autophagy is a conserved process that cells use to degrade their own cytoplasmic components by delivery to lysosomes. Autophagy ensures intracellular quality control and is associated with diseases such as cancer and immune disorders. The process of autophagy is controlled by core autophagy (Atg) genes that are conserved from yeast to mammal. Most Atg proteins and their regulators were identified through pioneering studies of the single cell yeast Saccharomyces cerevisiae, and little is known about factors that systematically coordinate autophagy within the tissues of multicellular animals. The goal of this thesis is to identify new autophagy regulators and provide a better understanding of the regulatory mechanisms within multicellular animals. My research determined Macroglobulin complement-related (Mcr), a Drosophila complement orthologue, can activate autophagy during developmental cell death. Unlike most known autophagy regulators, Mcr functions in a cell non-autonomous manner to trigger autophagy in neighboring cells. To my knowledge, this is the first identified autophagy factor that cell non-autonomously activates autophagy. Additionally, I found that Mcr, a secreted protein, instructs the autophagy machinery through the immune receptor Draper, suggesting a relationship between autophagy and the control of inflammation. Lastly, Mcr is dispensable for both nutrient deprivation-induced autophagy in the fat body and developmentally programmed autophagy in the dying midgut of Drosophila. Therefore, this study unveils a mechanism in a multicellular organism by which autophagy is systematically controlled in distinct cell contexts.

Yes / Chemical manufacturing typically requires more than one step, involving multiple batch processes, which makes synthesis at scale laborious and wasteful. Herein, we demonstrate that several reactions can be telescoped into a single continuous process and/or be carried out as a continuous multi-component reaction (MCR), by twin screw extrusion (TSE), in the complete absence of solvent. / EPSRC (EP/L019655/1).

<p>This thesis documents the development and application of a unique database orientated software package, BugsCEP, for environmental and climatic reconstruction from fossil beetle (Coleoptera) assemblages. The software tools are described, and the incorporated statistical methods discussed and evaluated with respect to both published modern and fossil data, as well as the author’s own investigations.</p><p>BugsCEP consists of a reference database of ecology and distribution data for over 5 800 taxa, and includes temperature tolerance data for 436 species. It also contains abundance and summary data for almost 700 sites - the majority of the known Quaternary fossil coleopteran record of Europe. Sample based dating evidence is stored for a large number of these sites, and the data are supported by a bibliography of over 3 300 sources. Through the use of built in statistical methods, employing a specially developed habitat classification system (Bugs EcoCodes), semi-quantitative environmental reconstructions can be undertaken, and output graphically, to aid in the interpretation of sites. A number of built in searching and reporting functions also increase the efficiency with which analyses can be undertaken, including the facility to list the fossil record of species found by searching the ecology and distribution data. The existing Mutual Climatic Range (MCR) climate reconstruction method is implemented and improved upon in BugsCEP, as BugsMCR, which includes predictive modelling and the output of graphs and climate space maps.</p><p>The evaluation of the software demonstrates good performance when compared to existing interpretations. The standardization method employed in habitat reconstructions, designed to enable the inter-comparison of samples and sites without the interference of differing numbers of species and individuals, also appears to be robust and effective. Quantitative climate reconstructions can be easily undertaken from within the software, as well as an amount of predictive modelling. The use of jackknifing variants as an aid to the interpretation of climate reconstructions is discussed, and suggested as a potential indicator of reliability. The combination of the BugStats statistical system with an enhanced MCR facility could be extremely useful in increasing our understanding of not only past environmental and climate change, but also the biogeography and ecology of insect populations in general.</p><p>BugsCEP is the only available software package integrating modern and fossil coleopteran data, and the included reconstruction and analysis tools provide a powerful resource for research and teaching in palaeo-environmental science. The use of modern reference data also makes the package potentially useful in the study of present day insect faunas, and the effects of climate and environmental change on their distributions. The reconstruction methods could thus be inverted, and used as predictive tools in the study of biodiversity and the implications of sustainable development policies on present day habitats.</p><p>BugsCEP can be downloaded from http://www.bugscep.com</p>

Thesis submitted in fulfilment of the requirements for the degree Master of Technology in Information Technology in the Faculty of Informatics & Design at the Cape Peninsula University of Technology / Research on health informatics has seen a steady increase during this decade as the role of information technology in the health sector becomes pertinent. Findings of previous research in this domain have uncovered vast information needs of health workers, particularly in developing countries. However, there is a need to continue with multidisciplinary research in priority areas such as midwifery practice and in the environment of marginalised settings. This study explores the significance of the information needs and information-seeking behaviour or practice of midwives during the antenatal and intrapartum care within the environment of a midwifery unit. Additionally, the researcher obtained permission from Faculty of Informatics and Design – CPUT and Health department authority – Western Cape Government in South Africa, to conduct research in the Elsies River Midwifery Obstetric Unit (ERMOU). The research was carried out as case study in a Midwifery Obstetric Unit in the Western Cape, South Africa. The investigator conducted semi-structured interviews and observations to collect qualitative data of the antenatal and intrapartum care environment. The data was transcribed and analysed using thematic analysis and essomenic modelling. The findings comprehensively point to the importance of this research context. The study found that midwives acquired patients’ information from a handwritten Maternity Case Record (MCR) book and midwives’ colleagues, and often during handovers. In addition, midwives also communicate with each other during care activities in the ERMOU. It was apparent that the use of such communication practices is inadequate, and midwives did not always have sufficient information to make appropriate decisions in the ERMOU. All patient information, referral notes, and reporting is paper-based. In addition, essomenic models were used to depict the midwives’ work activities in the antenatal and intrapartum care environment in the Unit. Furthermore, essomenic models defined all the systematic processes that occur in the ERMOU which is described by midwives’ activities and work environment. To improve communication, future research is recommended to consider the importance of the continuity of the education of midwives. Further research will be on the implementation of nursing informatics and the electronic health record system in the Elsies River Midwifery Obstetric Unit.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2018-02-21T21:24:26Z No. of bitstreams: 1 AlineDeSousaMarques_TESE.pdf: 5792072 bytes, checksum: 2628df662db724e0c0d729e9a2af99c5 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2018-02-22T21:38:32Z (GMT) No. of bitstreams: 1 AlineDeSousaMarques_TESE.pdf: 5792072 bytes, checksum: 2628df662db724e0c0d729e9a2af99c5 (MD5) / Made available in DSpace on 2018-02-22T21:38:32Z (GMT). No. of bitstreams: 1 AlineDeSousaMarques_TESE.pdf: 5792072 bytes, checksum: 2628df662db724e0c0d729e9a2af99c5 (MD5) Previous issue date: 2017-08-18 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Esta tese de doutorado ? um aporte te?rico-pr?tica para o desenvolvimento de estudos que utilizem a bioanal?tica, particulamente materiais biol?gicos provenientes de bact?rias, podendo estes ser isolados, DNA, entre outros, em conjunto com ferramentas quimiom?ticas de an?lise. Para isso, buscou-se identificar diferen?as bacterianas quando submetidas a uma fonte de estresse a partir de diferentes t?cnicas anal?ticas. A primeira abordagem foi realizada partindo da bioespectroscopia, utilizando-se de dados espectrosc?picos obtidos na regi?o do infravermelho. A bioespectroscopia na regi?o do infravermelho ? descrita como uma t?cnica n?o invasiva, de alto rendimento, baixo custo (quando comparado com t?cnica padr?es de an?lise) e objetivas, e que possui um enorme potencial na an?lise de bact?rias, complementando ou mesmo substituindo m?todos de diagn?stico de doen?as convencionalmente conduzidos por especialistas atrav?s de m?todos padr?es de an?lises de alto custo e que necessitam de reagentes espec?ficos. Os dados obtidos a partir da bioespectroscopia em amostras bacterianas s?o complexos e apresentam muitas bandas de sobreposi??o sendo necess?ria a aplica??o de ferramentas matem?ticas para superar estas dificuldades. Para isso, algumas ferramentas matem?ticas, como os m?todos de sele??o de vari?veis, que utilizam a an?lise discriminante linear com Algoritmo de Proje??o Sucessiva (SPA-LDA) e Algoritmo Gen?tico (GA-LDA), geralmente s?o utilizadas com a finalidade de facilitando a extra??o de informa??es relevantes. A espectroscopia na regi?o do infravermelho, em espec?fico infravermelho pr?ximo (NIR) e infravermelho com trasformata de Fourier e reflect?ncia total atenuada (ATR-FTIR), em conjunto com m?todos de sele??o de vari?veis (SPA-LDA e GA-LDA) foram utilizadas na discrimina??o de amostras de bact?rias (Sthaphylococcus aureus, Klebsiella pneumoneae e Pseudomonas aeruginosa). Foram identificados prov?veis biomarcadores como lip?deos e prote?nas em ~1550 cm-1 e 1400 cm-1 e vibra??es de DNA em ~1080 cm-1. Valores de sensibilidade de 75% e 95% para modelos de SPA-LDA e 100% e 93% para modelos GA-LDA foram encontrados. Com base nesses resultados, pode-se concluir que o SPA-LDA e GA-LDA em conjunto com a espectroscopia na regi?o do infravermelho mostraram-se ferramentas eficientes melhorando o tempo e custo de diagn?stico possibilitando o tratamento mais r?pido em rela??o aos m?todos padr?es de diagn?stico e, consequentemente, sendo poss?vel evitar a evolu??o de uma poss?vel infec??o. A segunda abordagem foi avaliar poss?veis mudan?as no perfil lipid?mico de bact?rias resultante de sua exposi??o a uma fonte de estresse externa (Ars?nio (III)), utilizando as cianobact?rias Anabaena sp. e Planktothrix agardhii. Os dados foram obtidos a partir a Cromatografia L?quida- Espectrometria de Massas (LC-MS) que por gerar uma matriz de dados muito extensa foi necess?ria a utiliza??o de uma estrat?gia de sele??o proposta recentemente, definida como ROI (do ingl?s regions of interests) que diminui significativamente o tamanho da matriz de dados obtidas por LC-MS. Resolu??o Multivariada de Curvas com M?nimos Quadrados Alternantes (MCR-ALS) foi utilizado como m?todo de resolu??o das fontes de varia??o, recuperando as informa??es de seus componentes puros que se encontravam misturadas. As massas majorit?rias encontradas, sendo algumas delas 766.54, 565.40 e 871.56 (m/z), determinam que as cianobact?rias estudadas, ao serem submetidas a As(III), sofrem mudan?as relacionadas a estruturas que comp?em os processos fotossint?ticos das mesmas. / This doctoral thesis is a theoretical-practical contribution for the development of studies that use bioanalytical, particularly biological materials from bacteria, which can be isolated, DNA, among others, in conjunction with chemistry analysis tools. For this, it was sought to identify bacterial differences when submitted to a source of stress from different analytical techniques. The first approach was based on biospectroscopy, using spectroscopic data obtained in the infrared region. Biospectroscopy in the infrared region is described as a non-invasive, high-throughput, low-cost (when compared with standard analytical techniques) and objective techniques, and has a huge potential in the analysis of bacteria, complementing or even replacing diagnostic methods of diseases conventionally conducted by skilled persons by standard methods of expensive analyzes and requiring specific reagents. The data obtained from biospectroscopy in bacterial samples are complex and have many overlapping bands and it is necessary to apply mathematical tools to overcome these difficulties. For this, some mathematical tools, such as variable selection methods, using Linear Discriminant Analysis with Successive Projection Algorithm (SPA-LDA) and Genetic Algorithm (GA-LDA), are generally used for the purpose of solving these data, facilitating the extraction of information. Infrared spectroscopy, in specific Near Infrared (NIR) and infrared spectroscopy with Fourier transform and Attenuated Total Reflectance (ATR- FTIR), in conjunction with variable selection methods (SPA-LDA and GA-LDA) was used in the discrimination of bacterial samples (Sthaphylococcus aureus, Klebsiella pneumoneae and Pseudomonas aeruginosa). Possible biomarkers such as lipids and proteins were identified at ~ 1550 cm -1 and 1400 cm -1 and DNA vibrations at ~ 1080 cm -1. Sensitivity values of 75% and 95% for SPA-LDA models and 100% and 93% for GA-LDA models were found. Based on these results, it can be concluded that the SPA-LDA and GA- LDA in conjunction with the infrared spectroscopy showed efficient tools improving the time and cost of diagnosis allowing the treatment faster than the standard methods of diagnosis, and consequently, it is possible to avoid the evolution of a possible infection. The second approach was to evaluate possible changes in the lipid profile of bacteria resulting from its exposure to an external stress source (Arsenic (III)), using the cyanobacteria Anabaena sp. and Planktothrix agardhii. The data were obtained from Liquid Chromatography-Mass Spectrometry (LC-MS), which, in order to generate a very extensive data matrix, required the use of a recent selection strategy, defined as ROI (regions of interest), which significantly decreased the Size of the data matrix obtained by LC-MS. Multivariate Curve Resolution - Alternating Least Squares (MCR-ALS) was used as a method to solve variation sources, retrieving the information of its pure components that were mixed. The majority masses found, such as 766.54, 565.40 and 871.56 (m/z), determine that the studied cyanobacteria, when subjected to As (III), undergo changes related to structures that make up the photosynthetic processes of the same.

[ES] El aumento de la esperanza de vida en la población con edad por encima de 50 años está generando un mayor número de casos detectados de cáncer de próstata (CaP). Por este motivo, los recursos se destinan al diagnóstico en etapas tempranas y al tratamiento efectivo. A pesar de la multitud de estudios basados en biomarcadores y discriminación histológica, es difícil diferenciar con efectividad los casos de CaP con baja agresividad de aquellos que progresarán y acabarán produciendo mortalidad o una disminución en la esperanza de vida del paciente. Con el objetivo de mejorar el diagnostico, localización y gradación de los tumores malignos, las técnicas de imagen por Resonancia Magnética (MRI) son las más adecuadas para el estudio del cáncer, proporcionando métodos de diagnóstico no-invasivos, sensibles y específicos, basados en secuencias morfológicas (T2w) y funcionales (perfusión de la sangre y difusión del agua). Las diferentes características y parámetros extraídos de estas secuencias, conocidos como biomarcadores de imagen, pueden evaluar las diferencias asociadas al desarrollo de los procesos tumorales, como los modelos farmacocinéticos para estudiar angiogénesis (perfusión) y los modelos mono- y bi-exponenciales para estudiar la caída de la señal en difusión con el objetivo de estudiar la celularización. Normalmente, estos biomarcadores de imagen se analizan de forma "univariante", sin aprovechar la información de las estructuras de correlación interna que existen entre ellos. Una manera de mejorar este análisis es mediante la aplicación de las técnicas estadísticas que ofrece el Análisis Multivariante de Imágenes (MIA), obteniendo estructuras (latentes) simplificadas que ayudan a entender la relación entre los parámetros (variables) y sus propios procesos fisiológicos, además de reducir la incertidumbre en la estimación de los biomarcadores. En esta tesis, se han desarrollado nuevos biomarcadores de imagen para perfusión y difusión con la aplicación de alguna de las herramientas de MIA como la Resolución Multivariante de Curvas con Mínimos Cuadrados Alternos (MCR-ALS), obteniendo parámetros que tienen interpretación clínica directa. A continuación, los métodos basados en mínimos cuadrados parciales (PLS) se aplicaron para estudiar la capacidad de clasificación de estos biomarcadores. En primer lugar, los biomarcadores de perfusión se utilizaron para la detección de tumores (control vs lesión). Posteriormente, la combinación de perfusión + difusión + T2 se empleó para estudiar agresividad tumoral con la aplicación de métodos PLS multibloque, en concreto (secuencial) SMB-PLS. Los resultados mostrados indican que los biomarcadores de perfusión obtenidos mediante MCR son mejores que los parámetros farmacocinéticos en la diferenciación de la lesión. Con lo que respecta al estudio de la agresividad tumoral, la combinación de los biomarcadores de difusión (empleando ambos métodos: modelos paramétricos y MCR) y los valores de T2w normalizados proporcionaron los mejores resultados. En conclusión, MIA se puede aplicar a las secuencias morfológicas y funcionales de resonancia magnética para mejorar el diagnóstico y el estudio de la agresividad de los tumores en próstata. Obteniendo nuevos parámetros cuantitativos y combinándolos con los biomarcadores más ampliamente utilizados en el ambiente clínico. / [CAT] El increment de la esperança de vida en la població per damunt dels 50 anys està generant un major nombre de casos detectats de càncer de pròstata (CaP). Per aquest motiu, els recursos es destinen al diagnòstic en etapes primerenques i al tractament efectiu. Tot i la multitud de estudis basats en biomarcadors y discriminació histològica, es difícil diferenciar amb efectivitat els casos de CaP que tenen baixa agressivitat dels que progressaran y acabaran produint mortalitat o una disminució en la esperança de vida del pacient. Amb el objectiu de millorar el diagnòstic, localització y gradació dels tumors malignes, les tècniques de imatge per Ressonància Magnètica (MRI) son els mètodes més adequats per al estudi del càncer, proporcionant metodologies de diagnòstic no-invasius, sensibles y específiques basades en seqüències morfològiques (T2w) y funcionals (perfusió de la sang y difusió del aigua). Les diferents característiques i paràmetres extrets de aquestes seqüències, coneguts com biomarcadors d'imatge, poden avaluar les diferències associades al desenvolupament dels processos tumorals. Primer, amb els models farmacocinétics per a estudiar angiogènesis (perfusió) y segon, amb els models mono- i bi-exponencials per a estudiar la caiguda de la senyal en difusió amb el objectiu de estudiar la cel·lularització. Normalment, aquests biomarcadors d'imatge s'analitzen de forma "univariant", sense aprofitar la informació de las estructures de correlació interna que existeixen entre ells. Una forma de millorar aquest anàlisis es mitjançant la aplicació de las tècniques estadístiques aportades pel Anàlisis Multivariant de Imatges (MIA), obtenint estructures (latents) simplificades què ajuden a entendre la relació entre els paràmetres (variables) i els seus processos fisiològics, a més de reduir la incertesa en la estimació dels biomarcadors. En aquesta tesis, s'han desenvolupat nous biomarcadors d'imatge per a perfusió i difusió amb la aplicació de alguna de las ferramentes de MIA com la Resolució Multivariant de Corbes i Mínims Quadrats Alterns (MCR-ALS), obtenint paràmetres què tenen interpretació clínica directa. A continuació, els mètodes basats en mínims quadrats parcials (PLS) s'han aplicat per a estudiar la capacitat de classificació d'aquests biomarcadors. En primer lloc, els biomarcadors de perfusió s'han utilitzat per a la detecció de tumors (control contra lesió). Posteriorment, la combinació de perfusió + difusió + T2 s'ha utilitzat per a estudiar agressivitat tumoral amb la aplicació de mètodes PLS multi-bloc, en concret (seqüencial) SMB-PLS. Els resultats mostren què els biomarcadors de perfusió obtinguts mitjançant MCR són millors què els paràmetres farmacocinètics en la diferenciació de la lesió. En lo què es refereix al estudi de la agressivitat tumoral, la combinació dels biomarcadors de difusió (utilitzant els dos mètodes: models paramètrics i MCR) i els valors de T2w normalitzats proporcionaren els millors resultats. En conclusió, MIA es pot aplicar a les seqüències morfològiques i funcionals de ressonància magnètica per a millorar el diagnòstic i el estudi de l'agressivitat dels tumors en pròstata. Obtenint nous paràmetres quantitatius y combinant-los amb els biomarcadors més utilitzats en el ambient clínic. / [EN] The increase in life expectancy and population with age higher than 50 years is producing a major number of detected cases of prostate cancer (PCa). For this reason, the resources are focused in the early diagnosis and effective treatment. In spite of multiple studies with histologic discriminant biomarkers, it is hard to clearly differentiate the low aggressiveness PCa cases from those that will progress and produce mortality or rather a decrease in the life expectancy. With the objective of improving the diagnosis, location and gradation of the malignant tumors, Magnetic Resonance Imaging (MRI) has come up as the most appropriate image acquisition technique for cancer studies, which provides a non-invasive, sensitive and specific diagnosis, based on morphological and functional (blood perfusion and water diffusion) sequences. The different characteristics and parameters extracted from these sequences, known as imaging biomarkers, can evaluate the different processes associated to tumor development, like pharmacokinetic modeling for angiogenesis assessment (perfusion) or mono- and bi-exponential signal decay modeling for cellularization (diffusion). Normally, these imaging biomarkers are analyzed in a "univariate" way, without taking advantage of the internal correlation structures among them. One way to improve this analysis is by applying Multivariate Image Analysis (MIA) statistical techniques, obtaining simplified (latent) structures that help to understand the relation between parameters (variables) and the inner physiological processes, moreover reducing the uncertainty in the estimation of the biomarkers. In this thesis, new imaging biomarkers are developed for perfusion and diffusion by applying MIA tools like Multivariate Curve Resolution Alternating Least Squares (MCR-ALS), obtaining parameters with direct clinical interpretation. Partial Least Squares (PLS) based methods are then used for studying the classification capability of these biomarkers. First, perfusion imaging biomarkers have been tested for tumor detection (control vs lesion). Then, diffusion + perfusion have been combined to study tumor aggressiveness by applying PLS-multiblock methods (SMB-PLS). The results showed that MCR-based perfusion biomarkers performed better than state-of-the-art pharmacokinetic parameters for lesion differentiation. Regarding the assessment of tumor aggressiveness, the combination of diffusion-based imaging biomarkers (using both the parametric models and MCR) and normalized T2-weighted measurements provided the best discriminating outcome, while perfusion was not needed as it did not supply additional information. In conclusion, MIA can be applied to morphologic and functional MRI to improve the diagnosis and aggressiveness assessment of prostate tumors by obtaining new quantitative parameters and combining them with state-of-the-art imaging biomarkers. / Aguado Sarrió, E. (2019). Application of multivariate image analysis to prostate cancer for improving the comprehension of the related physiological phenomena and the development and validation of new imaging biomarkers [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/134023 / TESIS

Background: COVID-19 is a dangerous contagious infection which was declared as a global pandemic by World Health Organisation (WHO) in March 2020. It was rapidly spreading worldwide, forcing the world to move into isolation and the software developing companies to change their work settings into remote working. Quality of the software is a significant attribute that determines the success of a project. Code reviews are an essential software development practice and are the first step towards improving the quality of the software. Objectives: The main objective of this research study is to list the challenges that the developers are facing while working from home and investigate the impact of challenges on code review practices. Methods: A multiple case study has been conducted in 5 organizations to understand and analyze the effect of transition on the code review process. We achieved this by conducting semi-structured interviews and participant observation with developers involved in code review practices of each organization considered for the study and qualitatively analyzed the gathered data using thematic analysis. Results: The results indicated challenges concerning team collaboration, infrastructure, productivity and burnout in the early stages of the pandemic. However, later, organizations’ mitigating strategies have helped them cope with the situation, and no significant impact due to working from home were observed on the code review process. Conclusions: Our findings highlight that there is no considerable impact of the challenges factored in due to working from home on the code review process. The major reasons behind that was the modernization of the tools used for code reviews and timely implementation of mitigation strategies by organizations. Based on the mitigation strategies taken by the organisations we formulated guidelines, which can be taken into consideration by the organisations still suffering with the transition to work from home.