Der Amazonas befindet sich im Wandel. Seine Regenwälder sind zunehmend durch die expandierende Landwirtschaft bedroht. Brandrodungen und die meist extensive Weidewirtschaft verantworten großflächige Ökosystemschäden und hohe Treibhausgasemissionen. Erdbeobachtungssysteme wie die Landsat und Sentinel-2 Satelliten ermöglichen eine großflächige Analyse dieser Entwicklungen und sind unerlässlich zur Evaluierung von Maßnahmen zum Schutze des Amazonas. Allerdings sind in den Kerntropen Fernerkundungsanalysen aufgrund des Bewölkungsgrades sehr herausfordernd. Diese Arbeit zielt daher auf eine verbesserte Erkennung landwirtschaftlicher Prozesse, wie sie an Entwaldungsfronten und speziell in der Region Novo Progresso, Pará, Brasilien, typisch sind. Dazu wurde zunächst der EO Time Series Explorer entwickelt, um verschiedene Dimensionen dichter Multisensorzeitserien interaktiv zur Erstellung von Referenzdaten in Wert zu setzen. Mit den Clear Observation Sequences (COS) wurde darauf basierend ein neuer Ansatz zur Erfassung hoch-dynamischer landwirtschaftlicher Prozesse entwickelt, etwa Feuer mit geringer Brandlast oder Bodenbearbeitungsmaßnahmen. Darauf aufbauend wurde schließlich der Landnutzungswandel in der Region Novo Progresso zwischen 2014 und 2020 untersucht. Die Ergebnisse zeigen einen alarmierenden Anstieg der Entwaldung und eine Zunahme landwirtschaftlicher Feuer seit der Präsidentschaft von Jair Bolsonaro. Differenziert nach Landnutzungszonen und Betriebsgrößen wird deutlich, dass Schutzgebiete weniger wirksam sind und insbesondere größere Landwirtschaftsbetriebe die Entwaldung vorantreiben. Diese Arbeit zeigt den hohen Wert einer synergetischen Nutzung unterschiedlicher Satellitenzeitserien für die fernerkundliche Analyse landwirtschaftlicher Prozesse. Eine weitere Verdichtung der Zeitserien mit räumlich und spektral höherauflösenden Sensoren bietet weiteres Verbesserungspotential bei der Beschreibung landwirtschaftlicher Dynamiken. / The Amazon is in transition, and its rainforests are increasingly threatened by agricultural expansion. A slash-and-burn agriculture and mostly extensive cattle grazing are responsible for large-scale ecosystem damage and high levels of greenhouse gas emission. Earth observation systems such as the Landsat and Sentinel-2 satellites enable large-scale analysis of these developments and are essential for evaluating measures to protect the Amazon. However, cloud cover makes remote sensing analysis challenging in the core tropics. The present work aims to improve the detection of agricultural processes typical of deforestation frontiers, focusing specifically on the Novo Progresso region, Pará, Brazil. To that end, the EO Time Series Explorer was developed to interactively visualize the different dimensions of dense multi-sensor time series and to create reference data. Based on this software tool, the Clear Observation Sequences (COS) approach was developed to capture highly dynamic agricultural processes such as low-load fires or tillage operations. Finally, the investigation of land-use changes in the Novo Progresso region between 2014 and 2020 shows an alarming increase in deforestation and agricultural fires since Jair Bolsonaro’s accession to the presidency. Analysis by land-use zone and property size shows that protected areas have become less effective and that larger properties are driving deforestation. This work demonstrates the value of synergistic use of satellite time series for remote sensing analysis of agricultural processes. Further densification of time series using higher spatial and spectral resolution sensors promises to further improve the description of agricultural dynamics.

La biopsie du ganglion sentinelle (GS) est actuellement la technique de référence pour le diagnostic des métastases ganglionnaires du cancer du sein. Cependant, les traceurs utilisés pour la cartographie du GS (colorant bleu et radiocolloïde) ne sont pas idéaux et peuvent occasionner des réactions allergiques et engendrer des coûts importants. Une alternative à l'utilisation de ces traceurs repose sur le repérage du GS par imagerie de fluorescence proche infrarouge à l'aide de nanoparticules. Deux types de nanoparticules ont été étudiés : les Quantum Dots (QDs) à base d'indium et les nanoparticules de silice (NPSi) renfermant de la cyanine 7. Dans un modèle murin de carcinome mammaire, tous les GS envahis par les métastases ont pu être visualisés grâce à la fluorescence des QDs-indium. L'étude de biodistribution a mis en évidence une capture majeure des QDs au point d'injection et dans les ganglions associée à une faible concentration dans le foie et la rate. La toxicité des QDs a été évaluée in vitro et a démontré une toxicité fortement réduite des QDs-indium par rapport aux QDs-cadmium. Les NPSi présentent les avantages suivants : biocompatibilité, amélioration de la rétention dans le ganglion et des propriétés photophysiques par rapport au fluorophore libre. Le GS est rapidement visualisable par fluorescence suite à l'injection de NPSi. Le suivi des souris, pendant 3 mois post-injection, n'a révélé aucun signe de toxicité générale ou hépatique. Ces deux types de nanoparticules fluorescentes sont particulièrement bien adaptés à la cartographie du GS et pourraient avantageusement remplacer les traceurs employés actuellement / Sentinel lymph node (SLN) biopsy is a reliable technique for the diagnosis of metastases in breast cancer. However, the tracers used (blue dye and radiocolloid) are not optimal because they can cause allergic reactions and major costs in waste processing. Our strategy was to use near-infrared emitting nanoparticles for the mapping of SLN: indium-based Quantum Dots (QDs) and cyanine 7 embedded in silica nanoparticles (SiNP). In a murine model of mammary carcinoma, all SLN containing lymphatic metastases could be visualized with fluorescent indium-based QDs. The biodistribution study concluded that the major organs of retention were the injection point and lymph nodes whereas liver and spleen accumulated fewer QDs. The cytotoxicity tests demonstrated a weak in vitro toxicity of indium- compared to cadmium-based QDs. SiNP show several advantages over free fluorophore such as biocompatibility, better retention in the SLN and greatest photophysical properties. SLN could be mapped as soon as 5 minutes after SiNP injection. The in vivo toxicity in mice was followed during 3 months after injection and did not reveal any signs of general or hepatic toxicity. Both fluorescent nanoparticles are thus well adapted for the mapping of the SLN and could be a favourable substitute to the actually tracers

The eco-epidemiology of bovine tuberculosis (Tb) in wild deer (mainly red deer Cervus elaphus) in New Zealand was investigated. Bovine Tb is caused by Mycobacterium bovis. Specific aims were to clarify the likely routes of infection in deer, and to determine the status of deer as hosts of Tb, the likely rates and routes of inter- and intra-species transmission between deer and other wildlife hosts, the role of deer in spreading Tb, and the likely utility of deer as sentinels of Tb presence in wildlife. As the possum (Trichosurus vulpecula) is the main wildlife host of Tb, the research also included some investigation of transmission routes in possums. Patterns of infection were measured in 994 deer killed between 1993 and 2003. Tb prevalence varied between areas (range 8–36%). Few deer had generalised infection, with 21–68% of infected deer having no visible lesions, depending on the area. The retropharyngeal lymph nodes and oropharyngeal tonsils were commonly infected. No dependent fawns less than 0.75 years old were infected, indicating intra-species transmission is rare in wild deer. Where possums were not controlled, the net (cumulative) force of infection in young (1–4 y) deer was 0.10–0.24 per year in males and 0.09–0.12 per year in females, but much lower in older deer (less than 0.05 per year). Possum control reduced the net force of infection quickly, and eventually to zero. However, Tb persisted in possum-controlled areas through immigration of infected deer and, for almost a decade, through the survival of resident deer infected before possum control. Tb was lost from infected deer at an exponential rate of 0.13 per year, mostly as a result of deer recovering from infection rather than dying from it. Wild deer do die of Tb, but there was no discernible effect on age structure. The occurrence of infection in deer was not linked to the local deer or possum density at their kill sites (i.e. in their home range), but the area-wide prevalence of Tb in deer was closely correlated with Tb levels in possums, which were in turn correlated with area-wide measures of possum density. For wild deer in New Zealand, Tb is a persistent but usually inconsequential disease of the lymphatic system. It is acquired mainly by young independent deer, usually orally via the tonsils, and probably as a result of licking infected possums. Many species fed on deer carrion, including possums. Most possums encountering carrion did not feed on it, but a few fed for long periods. Other scavengers such ferrets (Mustela furo), hawks (Circus approximans), and weka (a hen-sized flightless native bird; Gallirallus australis) fed in a way that probably increased the infectivity of carrion to possums. Commercial deer hunting may have facilitated the historical establishment of Tb in possums. Scavenging (including cannibalism) and interactions with dead and dying possums are identified for the first time as potentially important routes for transmission of Tb to possums, and I develop new hypotheses involving peri- and post-mortem transmission in possums that explain many of the epidemiological patterns that are characteristic of the disease in possum. In continuous native forest, deer home range size averaged 250 hectares for six young females, and over twice that for two males. Over 90% of infected deer are likely to die within 2 km (females) or 6 km (males) of where they acquired Tb, but deer could occasionally carry Tb up to 30 km. Deer will be useful as sentinels, but only where other sentinels are rare, because the force of infection for a deer with a single infected possum in its home range is only 0.004 per year, compared to greater than 0.2 per year for deliberately released pigs. Deer are occasionally capable of initiating new cycles of infection in wildlife, but deer control is not essential to eradicate Tb from wildlife.

This study investigated commensal feeding interactions between the European harvestman (P. opilio L.) and the predatory mites Balaustium spp. and Anystis baccarum L. It also investigated the feeding behaviour of P. opilio. Experiments were conducted in the laboratory using standardised temperature, humidity, photoperiod and experimental arenas, with eggs of the brown blowfly (Calliphora stygia F.) as prey facsimiles. Due to initial difficulties in obtaining enough predatory mites, mite feeding was manually simulated piercing blowfly eggs with a minuten pin. P. opilio consumed significantly more freeze-killed than live blowfly eggs, indicating that freezing induced chemical and/or physical changes to blowfly eggs that are detected by P. opilio. Significantly more manually pierced eggs were consumed by P. opilio compared with unpierced ones, demonstrating that piercing caused a chemical and/or physical to the egg and increased the feeding rates of P. opilio. Different densities of eggs had no effect on the numbers eaten by P. opilio and placing single pierced eggs next to groups of unpierced eggs also had no effect on the numbers of unpierced eggs eaten. These results suggest that P. opilio does not exhibit klinokinesis or orthokinesis to intensify its search for prey around the area where previous prey were located. P. opilio ate significantly more brown blowfly eggs that had previously been fed on by mites, demonstrating that a short term commensal interaction existed. However, further work is required to demonstrate if the relationship is commensal in the longer term. A comparison between hand-pierced and mite-pierced eggs showed that P. opilio ate significantly more of the former indicating that mite and hand piercing were quantitatively different. The potential for, and importance of, other commensal or mutual relationships between predators in agroecosystems is discussed. The lack of klinokinesis and orthokinesis in P. opilio is compared with other predators and parasitoids that do exhibit these behaviours. The means by which prey are detected by P. opilio are discussed in relation to interpreting behaviours such as prey inspection. Concerns about the effect of pre-treatment and handling of sentinel prey and the problems of using prey facsimiles are raised.

Το λεμφαγγειακό σύστημα διαδραματίζει σημαντικό ρόλο στη διατήρηση της ομοιόστασης των ιστών, στην ανοσολογική απόκριση του οργανισμού, στην απορρόφηση των λιπών από τον πεπτικό σωλήνα, και στη διασπορά των καρκινικών κυττάρων. Η πρόσφατη ανακάλυψη ειδικών για τα λεμφαγγειακά ενδοθηλιακά κύτταρα δεικτών και αναπτυξιακών παραγόντων, όπως επίσης και η δημιουργία γενετικών μοντέλων ποντικιών με διαταραγμένη τη λειτουργία του λεμφαγγειακού συστήματος, παρείχαν σημαντικότατες πληροφορίες για τη μοριακή ρύθμιση της εμβρυικής ανάπτυξης του λεμφαγγειακού συστήματος και της φυσιολογίας του. Τα σχετικά πρόσφατα αναγνωρισμένα μοριακά σηματοδοτικά μονοπάτια από τα οποία ρυθμίζεται η λεμφαγγειογένεση επέτρεψαν τη μελέτη της σχετιζόμενης με όγκους λεμφαγγειογένεσης. Οι μελέτες αυτές κατέδειξαν ότι η σχετιζόμενη με τους όγκους λεμφαγγειογένεση αποτελεί σημαντικό στοιχείο της μεταστατικής διαδικασίας, ενώ παράλληλα αναδεικνύουν συνεχώς καινούρια μόρια/σηματοδοτικά μονοπάτια-ρυθμιστές της εν λόγω διαδικασίας. / The lymphatic vascular system plays an important role in the maintenance of fluid homeostasis, in the afferent immune response, in the intestinal lipid uptake and in the metastatic spread of malignant cells. The recent discovery of specific markers and growth factors for lymphatic endothelium and the establishment of genetic mouse models with impairment of lymphatic function have provided novel insights into the molecular control of the lymphatic system in physiology and in embryonic development. Recently, molecular pathways that signal for lymphangiogenesis have been described allowing analyses of tumor lymphangiogenesis to be performed. These studies demonstrate that tumor lymphangiogenesis is a major component of the metastatic process, while at the same time new molecules and transduction pathways are discovered to regulate tumor lymphatics growth.

Supraglacial lakes in the ablation zone of the Greenland Ice Sheet (GrIS) often drain rapidly (in hours to days) by hydraulically-driven fracture (“hydrofracture”) in the summer. Hydrofracture can deliver large meltwater volumes to the ice-bed interface and open-up surface-to-bed connections, thereby routing surface meltwater to the subglacial system, altering basal water pressures and, consequently, the velocity profile of the GrIS. The study of rapidly draining lakes is thus important for developing coupled hydrology and ice-dynamics models, which can help predict the GrIS’s future mass balance. Remote sensing is commonly used to identify the location, timing and magnitude of rapid lake-drainage events for different regions of the GrIS and, with the increased availability of high-quality satellite data, may be able to offer additional insights into the GrIS’s surface hydrology. This study uses new remote-sensing datasets and develops novel analytical techniques to produce improved knowledge of rapidly draining lake behaviour in west Greenland over recent years. While many studies use 250 m MODerate-resolution Imaging Spectroradiometer (MODIS) imagery to monitor intra- and inter-annual changes to lakes on the GrIS, no existing research with MODIS calculates changes to individual and total lake volume using a physically-based method. The first aim of this research is to overcome this shortfall by developing a fully-automated lake area and volume tracking method (“the FAST algorithm”). For this, various methods for automatically calculating lake areas and volumes with MODIS are tested, and the best techniques are incorporated into the FAST algorithm. The FAST algorithm is applied to the land-terminating Paakitsoq and marine-terminating Store Glacier regions of west Greenland to investigate the incidence of rapid lake drainage in summer 2014. The validation and application of the FAST algorithm show that lake areas and volumes (using a physically-based method) can be calculated accurately using MODIS, that the new algorithm can identify rapidly draining lakes reliably, and that it therefore has the potential to be used widely across the GrIS to generate novel insights into rapidly draining lakes. The controls on rapid lake drainage remain unclear, making it difficult to incorporate lake drainage into models of GrIS hydrology. The second aspect of this study therefore investigates whether various hydrological, morphological, glaciological and surface-mass-balance controls can explain the incidence of rapid lake drainage on the GrIS. These potential controlling factors are examined within an Exploratory Data Analysis statistical technique to elicit statistical similarities and differences between the rapidly and non-rapidly draining lake types. The results show that the lake types are statistically indistinguishable for almost all factors, except lake area. It is impossible, therefore, to elicit an empirically-supported, deterministic method for predicting hydrofracture in models of GrIS hydrology. A frequent problem in remote sensing is the need to trade-off high spatial resolution for low temporal resolution, or vice versa. The final element of this thesis overcomes this problem in the context of monitoring lakes on the GrIS by adapting the FAST algorithm (to become “the FASTER algorithm”) to use with a combined Landsat 8 and Sentinel-2 satellite dataset. The FASTER algorithm is applied to a large, predominantly land-terminating region of west Greenland in summers 2016 and 2017 to track changes to lakes, identify rapidly draining lakes, and ascertain the extra quantity of information that can be generated by using the two satellites simultaneously rather than individually. The FASTER algorithm can monitor changes to lakes at both high spatial (10 to 30 m) and temporal (~3 days) resolution, overcoming the limitation of low spatial or temporal resolution associated with previous remote sensing of lakes on the GrIS. The combined dataset identifies many additional rapid lake-drainage events than would be possible with Landsat 8 or Sentinel-2 alone, due to their low temporal resolutions, or with MODIS, due to its inferior spatial resolution.

Orientador: Luiz Carlos Zeferino / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-12T08:55:33Z (GMT). No. of bitstreams: 1 Vieira_SabasCarlos_D.pdf: 1418388 bytes, checksum: 1d70cc451697cfbd93e48319a0284d4e (MD5) Previous issue date: 2008 / Resumo: Objetivos: Avaliar a detecção do linfonodo sentinela em pacientes com câncer do colo do útero utilizando a combinação de azul patente com tecnécio99m e complicações associadas ao uso do azul patente. Sujeitos e métodos: Este foi um estudo de uma série de casos, para o qual foram selecionadas 56 mulheres com diagnóstico de câncer do colo do útero estádios Ia2,Ib1,Ib2 e IIa da FIGO, que se submeteram ao procedimento de identificação do linfonodo sentinela. O período de realização do estudo foi de maio de 2006 a dezembro de 2007. O estudo é apresentado em dois artigos: o primeiro consiste na detecção do linfonodo sentinela no câncer do colo do útero pela combinação do azul patente com tecnécio 99m e avalia a concordância entre a linfocintigrafia pré-operatória e o mapeamento linfático intra-operatório com o gama probe; o segundo consiste na avaliação das alterações da oximetria de pulso das pacientes submetidas à cirurgia após a injeção do azul patente. Resultados: No primeiro artigo identificou-se pelo menos um linfonodo sentinela em 83,13% das pacientes e a localização mais freqüente destes linfonodos foi na cadeia ilíaca externa. A sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo foram, respectivamente, 80%, 100%, 100% e 97,67% no histopatológico de congelação. Além disso, observou-se que linfocintigrafia pré operatória detecta um número consideravelmente menor de linfonodos sentinelas quando comparado ao mapeamento linfático intra-operatório com o gama probe. No segundo estudo observou-se que somente uma paciente apresentou reação anafilática. Treze pacientes apresentaram queda de oximetria de pulso (menor que 96% de saturação) após a injeção do azul patente no colo do útero, que durou em média cinco minutos e sem repercussões clínicas; essa queda se associou de forma limítrofe com tumores maiores e localizados ao redor do orifício externo do canal cervical. Conclusões: Concluiu-se que a combinação do azul patente com o tecnécio99m demonstrou excelentes resultados na detecção do linfonodo sentinela; a linfocintigrafia pré-operatória não oferece qualquer vantagem em relação ao mapeamento linfático intra-operatório com azul patente e tecnécio99m. Não houve repercussões clínicas devido à queda da oximetria de pulso e essas alterações se correlacionaram, embora com significância limítrofe, com tumores maiores e localizados ao redor do orifício cervical externo. / Abstract: Objectives: To evaluate sentinel lymph node detection in cervical cancer patients using a combination of patent blue dye and technetium99m and assess complications associated with the use of patent blue dye. Subjects and methods: This study investigated a case series that selected 56 women diagnosed with FIGO stage Ia2, Ib1, Ib2 and IIa cervical cancer who underwent a procedure for sentinel lymph node identification. The study was conducted from May 2006 to December 2007 and was described in two articles. The first article was about a study of sentinel lymph node detection in cervical cancer using a combination of patent blue dye and technetium99m. It assessed the agreement between preoperative lymphoscintigraphy and intraoperative lymphatic mapping with a gamma probe. The second article focused on the evaluation of changes in pulse oximetry readings in patients undergoing surgery after patent blue injection. Results: In the first article, at least one sentinel lymph node was identified in 83.13% of the patients and the most frequent site for finding sentinel lymph nodes was the external iliac chain. The sensitivity, specificity, positive predictive value and negative predictive value were 80%, 100%, 100% and 97.67% respectively on histopathology examination of frozen biopsy. In addition, it was observed that preoperative lymphoscintigraphy detected a substantially lower number of sentinel lymph nodes when compared to intraoperative lymphatic mapping with a gamma probe. In the second study, only one patient presented with an anaphylactic reaction. Thirteen patients showed a decrease in pulse oximetry readings (less than 96% saturation) after patent blue injection into the cervix, which lasted an average of five minutes and had no clinical repercussions. There was a borderline association between this decline in oxygen saturation values and tumors that were larger and located around the external cervical os. Conclusions: It was concluded that a combination of patent blue dye and technetium99m demonstrated excellent results in the detection of sentinel lymph nodes. Preoperative lymphoscintigraphy offers no advantage in relation to intraoperative lymphatic mapping with patent blue dye and technetium99m. There were no clinical repercussions due to lower oxygen saturation values. These changes correlated with tumors that were larger and located around the external cervical os, although the significance of this correlation was borderline. / Doutorado / Ciencias Biomedicas / Doutor em Tocoginecologia

Résumé:IntroductionLa chirurgie reste le seul traitement à visée curative pour les patients porteurs d’un cancer colorectal (CCR) primitif ou métastatique. L’établissement précis de l’extension de la maladie, au niveau de la tumeur primitive, des ganglions loco-régionaux et des métastases à distance représente un élément essentiel pour la prise en charge thérapeutique. Les ganglions locorégionaux et la technique du ganglion sentinellePour les patients présentant un CCR non métastatique, l’analyse pathologique des ganglions (pN) conditionne la décision d’administrer ou non une chimiothérapie adjuvante. Les patients présentant un envahissement ganglionnaire (pN+) recevront un traitement adjuvant, celui-ci n’étant le plus souvent pas indiqué chez les patients sans envahissement ganglionnaire (pN0). Près de 20 à 30% des patients classés pN0 vont cependant développer des récidives tumorales. Parmi ces patients, il est probable qu’une partie ait été sous-classée au moment du diagnostic. La technique du ganglion sentinelle (GS) permet d’identifier les ganglions les plus susceptibles d’être envahis et de réaliser des analyses anatomopathologiques plus approfondies sur un nombre plus limité d’échantillon. Cette technique est recommandée dans le cancer du sein et dans le mélanome, mais son rôle reste discuté dans le CCR. Le premier volet de cette thèse concerne les résultats d’études cliniques que nous avons menées pour évaluer le rôle de la technique du GS au bleu patenté (BP) et de l’imagerie en fluorescence (IF) au vert d’indocyanine ou indocyanine green (ICG) dans le staging ganglionnaire des patients présentant un CCR. Les principaux objectifs de ces travaux étaient d’évaluer la faisabilité de ces techniques et leur apport dans le staging des patients présentant un CCR.Notre première étude sur la technique du GS au BP, représentant la plus grande cohorte monocentrique européenne, a permis de démontrer la faisabilité de la technique. En outre, cette approche a modifié le geste chirurgical dans 12% des cas (technique in vivo) et a permis de reclasser 10% des patients initialement classés pN0 en pN+ par la réalisation de coupes sériées spécifiquement réalisées sur les ganglions démontrés comme GS. Dans une seconde étude sur la technique du GS comparant l’IF-ICG à la technique au BP, nous avons montré que ces 2 techniques étaient complémentaires, permettant d’augmenter la sensibilité globale pour la détection des métastases ganglionnaires. De plus, l’IF-ICG apparaît comme plus sensible chez les patients présentant une surcharge pondérale. En termes de sensibilité, la recherche du GS par IF est supérieure à la technique BP, ces résultats restant cependant limités, notamment en raison d’un taux élevé de faux négatifs (FN) pour les tumeurs localement avancées (pT3-4). Les métastases ganglionnaires et la carcinose péritonéaleDans le CCR, les patients métastatiques, présentant une carcinose péritonéale (CP) et/ou un envahissement ganglionnaire, ont un pronostic sombre. La chirurgie d’exérèse de la CP associée à une chimiothérapie hyperthermique intrapéritonéale (CHIP) et la réalisation de curages ganglionnaires chez les patients porteurs d’une maladie oligométastatique permettent toutefois d’obtenir des survies prolongées et parfois des guérisons, avec des résultats similaires à ceux observés chez les patients opérés pour métastases hépatiques isolées. Pour la CP, l’étendue de la maladie et la radicalité de la résection sont les principaux facteurs pronostiques de survie. La sensibilité des examens d’imagerie conventionnelle et métabolique reste cependant faible pour déterminer l’extension de la maladie péritonéale. L’évaluation de l’étendue de la CP et son exérèse sont donc essentiellement fondées sur la palpation et l’exploration visuelle réalisée durant l’intervention chirurgicale, représentant un facteur limitant pour la radicalité de la chirurgie. De façon similaire, chez les patients présentant une maladie métastatique ganglionnaire limitée, la détection peropératoire est souvent difficile, nécessitant la réalisation de curages étendus de principe, afin de s’assurer de l’exérèse des ganglions pathologiques.L’utilisation de l’IF après injection iv intra-opératoire d’ICG a été rapportée comme une technique permettant la détection de tissu tumoral tant visible que non visible (infraclinique), pouvant potentiellement aider le chirurgien et guider les gestes de résection. Aucune étude n’avait particulièrement analysé le rôle de l’IF-ICG dans la détection de CP et de métastases ganglionnaires de CCR. Le second volet de cette thèse concerne l’évaluation de l’apport de l’IF après injection iv d’ICG pour la détection de la CP et des métastases ganglionnaires dans le CCR. L’objectif primaire était de vérifier si les métastases péritonéales (MP) et ganglionnaires visibles par le chirurgien étaient effectivement détectées par l’IF-ICG peropératoire. En parallèle, nous avons évalué si l’IF-ICG permettait de détecter une maladie infraclinique, non détectée par le chirurgien dans les conditions habituelles. La première étude de cette seconde partie a permis de montrer que les MP étaient visualisées comme hyperfluorescentes à l’IF-ICG pour autant qu’elles ne soient pas d’origine mucineuse. De plus, l’IF-ICG a permis de détecter des MP non visualisées en lumière visible, permettant d’adapter le geste chirurgical et d’augmenter la radicalité de la résection dans près de 38% des cas. Dans une seconde étude, nous avons rapporté que la technique d’IF utilisée in vivo et ex vivo après injection iv d’ICG permettait d’identifier des ganglions métastatiques, détectés ou non par les imageries conventionnelles et métaboliques préopératoires. Les résultats de cette étude constituant une preuve de concept ont été ensuite confirmés dans une étude rétrospective réalisée sur l’analyse ex vivo des ganglions de patients ayant reçu une injection iv d’ICG. Dans ce travail, nous avons montré que les ganglions envahis étaient plus fluorescents que les ganglions non envahis. Toutefois, cette preuve de concept doit encore être confirmée et évaluée plus largement dans une étude prospective. Ces 2 travaux montrent donc le bénéfice potentiel de l’utilisation de l’IF après injection iv d’ICG à 2 niveaux, pour guider la chirurgie en améliorant la détection peropératoire des sites métastatiques infracliniques et pour guider l’analyse histologique, en identifiant des ganglions fluorescents sur la pièce de résection, permettant une étude anatomopathologique plus ciblée et plus approfondie. Conclusions et perspectivesNos travaux sur la recherche du GS dans le CCR par la technique au BP et à l’IF-ICG ont montré que ces techniques étaient faisables mais que leurs sensibilités restaient limitées, en particulier chez les patients porteurs de tumeurs localement avancées. Dans la CP d’origine colorectale, nous avons montré que l’IF-ICG permettait d’améliorer la stadification de la CP des patients opérés de métastases péritonéales non mucineuses, de révéler des lésions non visibles dans les conditions standards et d’améliorer la radicalité de la chirurgie. Pour la détection de ganglions métastatiques, nous avons montré que l’IF-ICG permettait, in vivo, de détecter des ganglions infracliniques durant l’intervention et ex vivo, de guider l’analyse anatomopathologique de la pièce de résection. Enfin, nous pensons que ces observations pourraient nous permettre d’élaborer un nouveau concept de GS systémique par opposition au GS classique correspondant aux ganglions de drainage anatomique de la tumeur. Nous proposons que les capacités particulières de rétention de l’ICG dans les tissus cancéreux après injection par voie systémique pourraient permettre d’identifier des sites ganglionnaires métastatiques en dehors des sites de drainage révélés par les injections de marqueurs au sein ou en périphérie de la tumeur elle-même. Pour vérifier cette hypothèse, nous avons élaboré un nouveau protocole d’une étude clinique prospective dans laquelle la détection du GS systémique après injection iv d’ICG sera comparée aux résultats obtenus suite à l’injection péritumorale de BP. Les ganglions révélés par ces 2 techniques seront recherchés ex vivo sur la pièce de résection et analysés en anatomopathologie. Outre la démonstration de métastases ganglionnaires extra-anatomiques, nous pensons que cette approche systémique pourrait permettre de réduire le taux de FN observé suite à une injection péritumorale, notamment pour les tumeurs localement avancées, celles-ci pouvant perturber le drainage lymphatique selon les voies anatomiques. Summary:This thesis reports several clinical research works on the role of indocyanine green (ICG) fluorescence imaging (FI) for the detection of colorectal tumoral tissue. We first evaluate and compare the role of ICG-FI in the detection of sentinel lymph node (SLN) in colorectal cancer (CRC) in view to upstage patients. We have reported that both techniques (blue dye and ICG-FI) are similar in term of sensitivity with a high rate of false negative results. Therefore, we think that new approaches for SLN detection should be developped in CRC. Secondarily, we evaluate the role of ICG-FI after IV ICG injection for the detection of peritoneal carcinomatosis (PC) from CRC origin. We have reported that ICG-FI is able to detect non-mucinous PM with a sensitivity of 86%. Moreover, ICG-FI was able to guide surgery modifying the surgical procedure in 38% of patients. Thirdly, we investigate the role of ICG-FI for the detection lymph node (LN) metastases. We have reported that ICG-FI performed after IV ICG injection is able to detect LN metastases both in vivo and ex vivo. These findings have been confirmed in a retrospective study. Fiinally, we propose a new protocol to evaluate a new approach for SLN detection. In comparison with the standard technique using peritumoral injection, we propose a new approach using systemic (intravenous) ICG injection. We have called this approach the 'systemic' SLN detetion. This approach will be compared with the standard one using peritumoral blue dye injection. Sensitivity, specificity of both technique will be compared. In conclusion, the results of these preliminary clinical studies using ICG-FI for tumoral staging and treatment are encouraging and further larger studies should be performed. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished

Background: A landmark study suggested that wide excision of intermediate-thickness melanoma with sentinel lymph node biopsy (SLNB) and subsequent completion lymph node dissection (CLND) for regional disease may improve prognostication and disease-free survival (DFS) compared with those undergoing wide excision alone. However, these benefits were relatively small and not associated with an improvement in disease-specific survival (DSS). It remains unknown if SLNB and subsequent treatments are beneficial in elderly patients who have a decreased overall (OS) due to other causes. Methods: Adults ≥ 70 years of age, who underwent surgical intervention for intermediate-thickness cutaneous melanoma from 2000-2013 were identified from a prospectively-maintained database. Clinicopathologic variables measured included age, gender, anatomic site, histologic type, tumor thickness, ulceration, receipt and result of SLNB, completion of CLND, OS, and DFS. Results: Ninety-one patients underwent excision of an intermediate-thickness melanoma. Forty-nine patients (54%) received a SLNB. Seven of these biopsies (14%) were positive, and five patients went on to receive CLND. Five-year OS was 41% in patients who did not receive SLNB and 52% in patients who did receive SLNB (p=0.11). DFS was similar between groups independent of receipt of SLNB. Conclusion: Among elderly patients with intermediate-thickness melanoma, patients who received SLNB had similar 5-year OS and DFS compared with those who did not receive SLNB. Routine SLNB for intermediate-thickness melanoma patients may not significantly change outcomes for this age group, and clinical decision-making should consider individual patient comorbidities and goals of care.

Throughout the world, there is a great demand to map out the increasing environmental changes and life habitats on Earth. The vast majority of Earth Observations today, are collected using satellites. The Global Watch Center (GWC) initiative was started with the purpose of producing a global situational awareness of the premises for all life on Earth. By collecting, studying and analyzing vast amounts of data in an automatic, scalable and transparent way, the GWC aims are to work towards reaching the United Nations (UN) Sustainable Development Goals (SDG). The GWC vision is to make use of qualified accessible data together with leading organizations in order to lay the foundation of the important decisions that have the biggest potential to make an actual difference for the common awaited future. As a show-case for the initiative, the UN strategic department has recommended a specific use-case, involving mapping large accumulation of waste in areas greatly affected, which they believe will profit the initiative very much. This Master Thesis aim is, in an automatic and scalable way, to detect and classify dumpsites in Kampala, the capital of Uganda, by using available satellite imagery. The hopes are that showing technical feasibility and presenting interesting remarks will aid in spurring further interest in coming closer to a realization of the initiative. The technical approach is to use a lightweight version of Automatic Target Recognition. This is conventionally used in military applications but is here used, to detect and classify features of large accumulations of solid-waste by using techniques from the field of Image Analysis and Data Mining. Choice of data source, this study's area of interest as well as choice of methodology for Feature Extraction and choice of the Machine Learning algorithm Support Vector Machine will all be described and implemented. With a classification precision of 95 percent will technical results be presented, with the ambition to promote further work and contribute to the GWC initiative with valuable information for later realization.