Prognostic role of the LCS6 KRAS variant in locally advanced rectal cancer: results of the EXPERT-C trial.

Background: Lethal-7 (let-7) is a tumour suppressor miRNA which acts by down-regulating several oncogenes including KRAS. A single-nucleotide polymorphism (rs61764370, T > G base substitution) in the let-7 complementary site 6 (LCS-6) of KRAS mRNA has been shown to predict prognosis in early-stage colorectal cancer (CRC) and benefit from anti-epidermal growth factor receptor monoclonal antibodies in metastatic CRC. Patients and methods: We analysed rs61764370 in EXPERT-C, a randomised phase II trial of neoadjuvant CAPOX followed by chemoradiotherapy, surgery and adjuvant CAPOX plus or minus cetuximab in locally advanced rectal cancer. DNA was isolated from formalin-fixed paraffin-embedded tumour tissue and genotyped using a PCR-based commercially available assay. Kaplan–Meier method and Cox regression analysis were used to calculate survival estimates and compare treatment arms. Results: A total of 155/164 (94.5%) patients were successfully analysed, of whom 123 (79.4%) and 32 (20.6%) had the LCS-6 TT and LCS-6 TG genotype, respectively. Carriers of the G allele were found to have a statistically significantly higher rate of complete response (CR) after neoadjuvant therapy (28.1% versus 10.6%; P = 0.020) and a trend for better 5-year progression-free survival (PFS) [77.4% versus 64.5%: hazard ratio (HR) 0.56; P = 0.152] and overall survival (OS) rates (80.3% versus 71.9%: HR 0.59; P = 0.234). Both CR and survival outcomes were independent of the use of cetuximab. The negative prognostic effect associated with KRAS mutation appeared to be stronger in patients with the LCS-6 TT genotype (HR PFS 1.70, P = 0.078; HR OS 1.79, P = 0.082) compared with those with the LCS-6 TG genotype (HR PFS 1.33, P = 0.713; HR OS 1.01, P = 0.995). Conclusion: This analysis suggests that rs61764370 may be a biomarker of response to neoadjuvant treatment and an indicator of favourable outcome in locally advanced rectal cancer possibly by mitigating the poor prognosis of KRAS mutation. In this setting, however, this polymorphism does not appear to predict cetuximab benefit.

FcγRIIa and FcγRIIIa polymorphisms and cetuximab benefit in the microscopic disease

Purpose: FcγR polymorphisms have been reported to enhance the immune-mediated effects of cetuximab in metastatic colorectal cancer. There are no data on the relationship between these polymorphisms and cetuximab in the early-stage setting. We performed a pharmacogenomic analysis of EXPERT-C, a randomized phase II trial of neoadjuvant CAPOX followed by chemoradiotherapy, surgery, and adjuvant CAPOX ± cetuximab in high-risk, locally advanced rectal cancer.

Experimental Design: FcγRIIa-H131R and FcγRIIIa-V158F polymorphisms were analyzed on DNA from peripheral blood samples. Kaplan–Meier method and Cox regression analysis were used to calculate survival estimates and compare treatment arms.

Results: Genotyping was successfully performed in 105 of 164 (64%) patients (CAPOX = 54, CAPOX-C = 51). No deviation from the Hardy–Weinberg equilibrium or association of these polymorphisms with tumor RAS status was observed. FcγRIIa-131R (HR, 0.38; P = 0.058) and FcγRIIIa-158F alleles (HR, 0.21; P = 0.007) predicted improved progression-free survival (PFS) in patients treated with cetuximab. In the CAPOX-C arm, carriers of both 131R and 158F alleles had a statistically significant improvement in PFS (5 years: 78.4%; HR, 0.22; P = 0.002) and overall survival (OS; 5 years: 86.4%; HR, 0.24; P = 0.018) when compared with patients homozygous for 131H and/or 158V (5-year PFS: 35.7%; 5-year OS: 57.1%). An interaction between cetuximab benefit and 131R and 158F alleles was found for PFS (P = 0.017) and remained significant after adjusting for prognostic variables (P = 0.003).

Conclusion: This is the first study investigating FcγRIIa and FcγRIIIa polymorphisms in patients with early-stage colorectal cancer treated with cetuximab. We showed an increased clinical benefit from cetuximab in the presence of 131R and 158F alleles.

A Microbial Link to Weathering of Postglacial Rocks and Sediments, Mount Viso Area, Western Alps, Demonstrated through Analysis of a Soil/Paleosol Bio/Chronosequence

Understanding the mechanism associated with rates of weathering and evolution of rocks→sediment→soil→paleosol in alpine environments raises questions related to the impact of microbial mediation versus various diverse abiotic chemical/physical processes, even including the overall effect of cosmic impact/airburst during the early stage of weathering in Late Glacial (LG) deposits. This study is of a chronosequence of soils/paleosols, with an age range that spans the post–Little Ice Age (post-LIA; <150 yr), the Little Ice Age (LIA; AD 1500–1850), the middle Neoglacial (∼3 ka)–Younger Dryas (YD; <12.8 ka), and the LG (<15 ka). The goal is to elicit trends in weathering, soil morphogenesis, and related eubacterial population changes over the past 13–15 k.yr. The older LG/YD paleosols in the sequence represent soil morphogenesis that started during the closing stage of Pleistocene glaciation. These are compared with undated soils of midto late Neoglacial age, the youngest of LIA and post-LIA age. All profiles formed in a uniform parentmaterial ofmetabasalt composition and in moraine, rockfall, protalus, and alluvial fan deposits. Elsewhere in Europe,North America, and Asia, the cosmic impact/airburst event at 12.8 ka often produced a distinctive, carbon-rich “black mat” layer that shows evidence of high-temperature melting. At this alpine site, older profiles of similar LG age contain scorched and melted surface sediments that are otherwise similar in composition to the youngest/thinnest profiles developing in the catchment today. Moreover, microbial analysis of the sediments offers new insight into the genesis of these sediments: the C and Cu (u = unweathered) horizons in LG profiles present at 12.8 ka (now Ah/Bw) show bacterial population structures that differ markedly from recent alluvial/protalus sample bacterial populations. We propose here that these differences are, in part, a direct consequence of the age/cosmic impact/weathering processes that have occurred in the chronosequence. Of the several questions that emerge from these sequences, perhaps the most important involve the interaction of biotic-mineral factors, which need to be understood if we are to generally fully appreciate the role played by microbes in rock weathering.

Det är alltid bäst innan förändring : En studie om motivation vid förändring, individens upplevelse & ledares påverkan

Förändringar är vanligt förekommande i organisationer och forskning visar att många förändringsinitiativ tyvärr misslyckas. Genomförandet av förändringar som fokuserar på individens motivation är lyckosamma i bemärkelsen att personalen trivs och att arbetet inte blir lidande. Studien syftar till att ta reda på hur ledare kan arbeta för att främja medarbetares motivation vid organisationsförändringar. Genom ett kvalitativt perspektiv och en deduktiv ansats har vi undersökt vad som påverkar och främjar medarbetares motivation vid organisationsförändringar. Undersökningen har genomförts på två avdelningar i ett stort företag i Gästrikland som vid tiden för insamling av data, genomgick en förändring. Studien är en fallstudie med avsikt att undersöka den specifika skiftformsförändringen som företaget genomgick. Tillvägagångssättet för insamlingen av material är en process som ämnar att, genom delaktighet och diskussion ta reda på vad som motiverar medarbetare under förändringar. Analysen av resultatet visar att individernas grundläggande behov i arbetet, till viss del inte varit uppfyllda vilket har lett till att en del personal givit uttryck för att de är omotiverade och att de känner ett motstånd mot förändringen. Det upplevda motståndet består i en rad olika känslor, bland annat; chock, oro och förvirring som uppkommer på grund av osäkerhet och brist på kontroll rörande individens arbetssituation. Känslorna hämmar motivationen och kan ge en upplevelse av att de grundläggande behoven i arbetet inte är uppfyllda, även fast de kan vara det. Studien visar att ledare kan påverka motståndet och främja medarbetares motivation under förändringar dels genom att bjuda in till delaktighet i ett så tidigt stadie som möjligt i förändringsprocesssen och dels genom att på ett tydligt sätt kommunicera och informera kring förändringens innebörd. Det gör att individen upplever kontroll över sin framtid i arbetet vilket påverkar upplevelsen av att de grundläggande behoven inte skulle vara uppfyllda och gynnar motivationen. Ledare behöver även vara lyhörda för att alla upplever förändringar olika och läsa av behov och önskemål och anpassa eventuellt stöd efter det.

Études in vivo et in vitro sur le potentiel néphroprotecteur de plantes médicinales anti-diabétiques de la pharmacopée traditionnelle des Cris de la Baie-James

Notre équipe a identifié le thé Labrador [Rhododendron groenlandicum L. (Ericaceae)] comme une plante potentiellement antidiabétique de la pharmacopée traditionnelle des Cris de la Baie James orientale. Dans la présente étude, nous avons évalué les effets néphroprotecteurs potentiels de la plante. De la microalbuminurie et de la fibrose rénale ont été développées chez des souris alimentées avec une diète grasse (DG). Le R. groenlandicum améliore d’une façon non-significative la microalbuminurie, avec des valeurs de l’aire sous la courbe (ACR) diminuant de 0.69 à 0.53. La valeur de la fibrose rénale qui était, à l’origine, de 4.85 unités arbitraires (UA) dans des souris alimentées à la DG, a chuté à 3.27 UA après avoir reçu un traitement de R. groenlandicum. Le R. groenlandicum a réduit la stéatose rénale de presque la moitié alors que l’expression du facteur de modification Bcl-2 (Bmf) a chuté de 13.96 UA à 9.43 UA. Dans leur ensemble les résultats suggèrent que le traitement avec R. groenlandicum peut améliorer la fonction rénale altérée par DG. Dans l’étude subséquente, notre équipe a identifié 17 espèces de la forêt boréale, de la pharmacopée traditionnelle des Cris de la Baie James orientale, qui ont présenté des activités biologiques prometteuses in vitro et in vivo dans le contexte du DT2. Nous avons maintenant examiné ces 17 extraits afin d’identifier lesquels possèdent un potentiel cytoprotecteur rénale en utilisant des cellules Madin Darby Canine Kidney (MDCK) mises à l’épreuve dans un médium hypertonique. Nous concluons que plusieurs plantes antidiabétiques Cris exercent une activité de protection rénale qui pourrait être pertinente dans le contexte de la néphropathie diabétique (ND) qui affecte une proportion importante des Cris. La G. hispidula et la A. balsamea sont parmi les plantes les plus puissantes dans ce contexte et elles semblent protectrices principalement en inhibant la caspase 9 dans la voie de signalisation apoptotique mitochondriale. Finalement, nous avons utilisé une approche de fractionnement guidée par un test biologique pour identifier les fractions actives et les composés de A. balsamea avec un potentiel de protection rénale in vitro dans des cellules MDCK mises au défi avec un médium hypertonique. La fraction d’hexane (Hex) possède le potentiel le plus élevé parmi toutes les fractions de solvant contre les dommages cellulaires induits par le stress hypertonique. Dans des études précédentes, trois composés purs ont été identifiés à partir de la fraction Hex, à savoir, l’acide abiétique, l’acide déhydroabiétique et le squalène. L’acide abiétique se distinguait par son effet puissant dans le maintien de la viabilité des cellules MDCK (AnnV-/PI-) à un niveau relativement élevé (augmentation de 25.48% relative au stress hypertonique, P<0.0001), ainsi qu’une réduction significative (diminution de 20.20% par rapport au stress hypertonique, P<0.0001) de l’apoptose de stade précoce (AnnV+/PI-). L’acide abiétique peut donc servir à normaliser les préparations traditionnelles d’A. balsamea et à trouver des applications potentielles dans le traitement de la néphropathie diabétique. Les trois études ont été intrinsèquement liées les unes aux autres, par conséquent, nous avons réussi à identifier R. groenlandicum ainsi que A. balsamea comme nouvelles plantes prometteuses contre la néphropathie diabétique. Nous croyons que ces résultats profiteront à la communauté crie pour la gestion des complications diabétiques, en particulier la néphropathie diabétique. En parallèle, nos données pourraient faire avancer l'essai clinique de certaines plantes médicinales de la pharmacopée traditionnelle des Cris de la Baie James orientale du Canada.

Infrared image enhancement based on hybrid-domain consideration and data fusion methods

Au cours des dernières décennies, l’effort sur les applications de capteurs infrarouges a largement progressé dans le monde. Mais, une certaine difficulté demeure, en ce qui concerne le fait que les objets ne sont pas assez clairs ou ne peuvent pas toujours être distingués facilement dans l’image obtenue pour la scène observée. L’amélioration de l’image infrarouge a joué un rôle important dans le développement de technologies de la vision infrarouge de l’ordinateur, le traitement de l’image et les essais non destructifs, etc. Cette thèse traite de la question des techniques d’amélioration de l’image infrarouge en deux aspects, y compris le traitement d’une seule image infrarouge dans le domaine hybride espacefréquence, et la fusion d’images infrarouges et visibles employant la technique du nonsubsampled Contourlet transformer (NSCT). La fusion d’images peut être considérée comme étant la poursuite de l’exploration du modèle d’amélioration de l’image unique infrarouge, alors qu’il combine les images infrarouges et visibles en une seule image pour représenter et améliorer toutes les informations utiles et les caractéristiques des images sources, car une seule image ne pouvait contenir tous les renseignements pertinents ou disponibles en raison de restrictions découlant de tout capteur unique de l’imagerie. Nous examinons et faisons une enquête concernant le développement de techniques d’amélioration d’images infrarouges, et ensuite nous nous consacrons à l’amélioration de l’image unique infrarouge, et nous proposons un schéma d’amélioration de domaine hybride avec une méthode d’évaluation floue de seuil amélioré, qui permet d’obtenir une qualité d’image supérieure et améliore la perception visuelle humaine. Les techniques de fusion d’images infrarouges et visibles sont établies à l’aide de la mise en oeuvre d’une mise en registre précise des images sources acquises par différents capteurs. L’algorithme SURF-RANSAC est appliqué pour la mise en registre tout au long des travaux de recherche, ce qui conduit à des images mises en registre de façon très précise et des bénéfices accrus pour le traitement de fusion. Pour les questions de fusion d’images infrarouges et visibles, une série d’approches avancées et efficaces sont proposés. Une méthode standard de fusion à base de NSCT multi-canal est présente comme référence pour les approches de fusion proposées suivantes. Une approche conjointe de fusion, impliquant l’Adaptive-Gaussian NSCT et la transformée en ondelettes (Wavelet Transform, WT) est propose, ce qui conduit à des résultats de fusion qui sont meilleurs que ceux obtenus avec les méthodes non-adaptatives générales. Une approche de fusion basée sur le NSCT employant la détection comprime (CS, compressed sensing) et de la variation totale (TV) à des coefficients d’échantillons clairsemés et effectuant la reconstruction de coefficients fusionnés de façon précise est proposée, qui obtient de bien meilleurs résultats de fusion par le biais d’une pré-amélioration de l’image infrarouge et en diminuant les informations redondantes des coefficients de fusion. Une procédure de fusion basée sur le NSCT utilisant une technique de détection rapide de rétrécissement itératif comprimé (fast iterative-shrinking compressed sensing, FISCS) est proposée pour compresser les coefficients décomposés et reconstruire les coefficients fusionnés dans le processus de fusion, qui conduit à de meilleurs résultats plus rapidement et d’une manière efficace.

Innovating at the margins: the System of Rice Intensification in India and transformative social innovation

I explore transformative social innovation in agriculture through a particular case of agroecological innovation, the System of Rice Intensification (SRI) in India. Insights from social innovation theory that emphasize the roles of social movements and the reengagement of vulnerable populations in societal transformation can help reinstate the missing “social” dimension in current discourses on innovation in India. India has a rich and vibrant tradition of social innovation wherein vulnerable communities have engaged in collective experimentation. This is often missed in official or formal accounts. Social innovations such as SRI can help recreate these possibilities for change from outside the mainstream due to newer opportunities that networks present in the twenty-first century. I show how local and international networks led by Civil Society Organizations have reinterpreted and reconstructed game-changing macrotrends in agriculture. This has enabled the articulation and translation of an alternative paradigm for sustainable transitions within agriculture from outside formal research channels. These social innovations, however, encounter stiff opposition from established actors in agricultural research systems. Newer heterogeneous networks, as witnessed in SRI, provide opportunities for researchers within hierarchical research systems to explore, experiment, and create newer norms of engagement with Civil Society Organizations and farmers. I emphasize valuing and embedding diversity of practices and institutions at an early stage to enable systems to be more resilient and adaptable in sustainable transitions.

Sono e esquemas mal-adaptativos precoces em estudantes do ensino superior

Contextualização: Recentemente tem-se verificado um aumento do número de estudos que relacionam conceitos da personalidade, tais como os Esquemas Mal-adaptativos Precoces (EMP), com a psicopatologia e com outras condições, tais como a obesidade, a dor crónica e o comportamento sexual agressivo. No entanto, a investigação acerca da relação entre os problemas de sono e os EMP encontra-se ainda numa fase inicial. Objetivos: Os objetivos do presente estudo foram investigar uma potencial relação entre os EMP e a má qualidade de sono em estudantes do ensino superior e observar que EMP apresentavam associações de maior magnitude com a qualidade de sono nesta população específica. Métodos: Estudantes de diversas universidades e institutos de ensino superior de Portugal foram convidados a responder a uma versão online dos questionários Escala Básica de Sintomas de Insónia e Qualidade de Sono (BaSIQS) e Questionário de Esquemas de Young (YSQ-S3). A partir da amostra total obtida de estudantes do ensino superior de nacionalidade portuguesa (N = 1253) foi selecionada uma primeira subamostra (n1 = 409), usando como critérios de inclusão a idade (entre os 18 e os 25 anos) e as pontuações extremas de qualidade de sono da BaSIQS (má versus boa qualidade de sono). A partir da n1 extraiu-se uma segunda subamostra de participantes (n2 = 249), com características de um estudante “típico” do ensino superior (estatuto de aluno ordinário, solteiro, sem filhos, sem problemas de saúde, não medicado). Para estudar a relação entre os EMP, medidos pelo YSQ-S3, e a qualidade de sono foi aplicada uma MANOVA (Análise de Variância Multivariada) para cada um dos cinco domínios esquemáticos (“Distanciamento e Rejeição”, “Autonomia e Desempenho Deteriorados”, “Limites Deteriorados”, “Influência dos Outros” e “Vigilância Excessiva e Inibição”), para ambas as subamostras (n1 e n2). Resultados: No que diz respeito à n2, os estudantes com má qualidade de sono apresentaram níveis significativamente mais elevados dos EMP “Abandono/ Instabilidade”, “Desconfiança/ Abuso”, “Isolamento Social/ Alienação” (Domínio “Distanciamento e Rejeição”), “Vulnerabilidade ao Mal e à Doença” (Domínio “Autonomia e Desempenho Deteriorados”), “Grandiosidade/ Limites Indefinidos” (Domínio “Limites Deteriorados”), “Autossacrifício” (Domínio “Influência dos Outros”) e “Negativismo/ Pessimismo” (Domínio “Vigilância Excessiva e Inibição”). Conclusões: Estes dados mostram que os EMP estão associados à má qualidade de sono. No entanto, são necessários estudos adicionais para melhor compreender esta relação e a sua implicação na prática clínica.

The strategic role of design in supporting knowledge exchange

Within the last decade design has had a strategic role in tackling escalating environmental, social and economic problems. Through design thinking, creative methods have been applied to problem solving in a process of collaboration and designers working in new territories and knowledge domains. As the designer has moved further afield the method of Knowledge Exchange (KE) has become more recognised as a democratic approach to collaboration with the ethos that everyone has something creative and productive to offer. This paper provides reflections on early stage findings from a strategic design innovation process in which collaborative partnerships between academics, SMEs and designers emerged through KE and suggests that there is value to be had from using design strategically for not only those from a business or academic background but also for those from the design community and points to a need for more training for designers from all disciplines in how to use design strategically

Evolution of protein bound Maillard reaction end-products and free Amadori compounds in low lactose milk in presence of fructosamine oxidase I

Thermal treatments and storage influence milk quality, particularly in low lactose milk as the higher concentration of reducing sugars can lead to the increased formation of the Maillard reaction products (MRPs). The control of the Amadori products (APs) formation is the key step to mitigate the Maillard reaction (MR) in milk. The use of fructosamine oxidases, (Faox) provided promising results. In this paper, the effects of Faox I were evaluated by monitoring the concentration of free and bound MRPs in low lactose milk during shelf life. Results showed that the enzyme reduced the formation of protein-bound MRPs down to 79% after six days at 37 °C. Faox I lowered the glycation of almost all the free amino acids resulting effective on basic and polar amino acids. Data here reported corroborate previous findings on the potentiality of Faox enzymes in controlling the early stage of the MR in foods.

Caractérisation des effets de l’hyperglycémie chronique dans la choroïde d’yeux diabétiques

But: Le diabète est un problème important de santé publique et la complication oculaire la plus commune est la rétinopathie diabétique (RD). Certaines études indiquent que la choroïde des patients diabétiques est affectée sans signe apparent de RD. Notre hypothèse est que l’élévation du stress oxydant liée à l’hyperglycémie chronique affecte la fonction choroïdienne à un stade précoce de la RD. Nous proposons d’étudier la glycolyse, le métabolisme mitochondrial, le stress nitrosatif et la méthylation de l’ADN ainsi que de caractériser les modifications histologiques dans la choroïde diabétique. Méthodes: L’expression des gènes/protéines associés à la glycolyse, au métabolisme mitochondrial et à la production de l’oxyde nitrique a été comparée par profilage génique et immunobuvardage Western entre les choroïdes saines et diabétiques. Les niveaux globaux de méthylation et d’hydroxyméthylation de l’ADN ont été quantifiés par immunoslot blot et HPLC-MS/MS dans ces tissus. Enfin, des coupes tissulaires d’yeux de donneurs sains ou diabétiques avec RD non proliférante (RDNP) ou proliférante (RDP) ont été colorées au trichrome de Masson et au Weigert. L’épaisseur de la choroïde et de la membrane de Bruch, ainsi que la densité et le diamètre des vaisseaux sanguins choroïdiens ont été analysés. Résultats: Nos résultats montrent une dérégulation de l’expression de certains transcrits de la choroïde diabétique, mais peu de différences au niveau de l’expression protéique des cibles validées. Le niveau global de méthylation de l’ADN est similaire entre les donneurs sains et diabétiques. Nos analyses histologiques démontrent une diminution de l’épaisseur de la choroïde et une dégénérescence des choriocapillaires et des veines/veinules chez les donneurs diabétiques atteints de RDP. Conclusions: L’étude de la choroïde est importante, car l’atteinte de ce tissu a de graves répercussions sur la fonction rétinienne. L’identification de cibles dans la choroïde ouvre de nouvelles perspectives pour un traitement préventif de la RD.

A poesia na revista alegretense "Ibirapuitã" (1938/1939)

A revista Ibirapuitã foi criada pelo poeta e jornalista Felisberto Soares Coelho, em Alegrete, interior do Rio Grande do Sul, ao final dos anos trinta. O periódico promoveu a divulgação de autores locais e considerável efervescência cultural no município. No presente trabalho, busca-se o resgate da poesia veiculada pela revista em sua fase inicial, compreendida entre os anos de 1938 e 1939, por se tratar de gênero que se destaca ao longo de seu percurso editorial. Ademais, pretende-se analisar tal produção abarcada em uma organização temática, estabelecendo relações com a história da literatura. Por meio da localização, catalogação e leitura do mensário foram selecionados trinta e nove poemas, obedecendo ao critério de freqüência/ocorrência de publicação de cada colaborador. Como resultado, além da análise da produção poética, pretende-se organizar uma antologia acompanhada de notas biobibliográficas e material iconográfico. Desta forma, pretende-se facilitar o acesso pela comunidade a uma das publicações que possivelmente contribuiu para a formação do sistema literário sul-rio-grandense, proporcionando abertura a novos estudos referentes à história da literatura alegretense.

Functional alkali tantalate 2D structures for microelectronics and related applications

Alkali tantalates and niobates, including K(Ta / Nb)O3, Li(Ta / Nb)O3 and Na(Ta / Nb)O3, are a very promising ferroic family of lead-free compounds with perovskite-like structures. Their versatile properties make them potentially interesting for current and future application in microelectronics, photocatalysis, energy and biomedics. Among them potassium tantalate, KTaO3 (KTO), has been raising interest as an alternative for the well-known strontium titanate, SrTiO3 (STO). KTO is a perovskite oxide with a quantum paraelectric behaviour when electrically stimulated and a highly polarizable lattice, giving opportunity to tailor its properties via external or internal stimuli. However problems related with the fabrication of either bulk or 2D nanostructures makes KTO not yet a viable alternative to STO. Within this context and to contribute scientifically to the leverage tantalate based compounds applications, the main goals of this thesis are: i) to produce and characterise thin films of alkali tantalates by chemical solution deposition on rigid Si based substrates, at reduced temperatures to be compatible with Si technology, ii) to fulfil scientific knowledge gaps in these relevant functional materials related to their energetics and ii) to exploit alternative applications for alkali tantalates, as photocatalysis. In what concerns the synthesis attention was given to the understanding of the phase formation in potassium tantalate synthesized via distinct routes, to control the crystallization of desired perovskite structure and to avoid low temperature pyrochlore or K-deficient phases. The phase formation process in alkali tantalates is far from being deeply analysed, as in the case of Pb-containing perovskites, therefore the work was initially focused on the process-phase relationship to identify the driving forces responsible to regulate the synthesis. Comparison of phase formation paths in conventional solid-state reaction and sol-gel method was conducted. The structural analyses revealed that intermediate pyrochlore K2Ta2O6 structure is not formed at any stage of the reaction using conventional solid-state reaction. On the other hand in the solution based processes, as alkoxide-based route, the crystallization of the perovskite occurs through the intermediate pyrochlore phase; at low temperatures pyrochlore is dominant and it is transformed to perovskite at >800 °C. The kinetic analysis carried out by using Johnson-MehlAvrami-Kolmogorow model and quantitative X-ray diffraction (XRD) demonstrated that in sol-gel derived powders the crystallization occurs in two stages: i) at early stage of the reaction dominated by primary nucleation, the mechanism is phase-boundary controlled, and ii) at the second stage the low value of Avrami exponent, n ~ 0.3, does not follow any reported category, thus not permitting an easy identification of the mechanism. Then, in collaboration with Prof. Alexandra Navrotsky group from the University of California at Davis (USA), thermodynamic studies were conducted, using high temperature oxide melt solution calorimetry. The enthalpies of formation of three structures: pyrochlore, perovskite and tetragonal tungsten bronze K6Ta10.8O30 (TTB) were calculated. The enthalpies of formation from corresponding oxides, ∆Hfox, for KTaO3, KTa2.2O6 and K6Ta10.8O30 are -203.63 ± 2.84 kJ/mol, - 358.02 ± 3.74 kJ/mol, and -1252.34 ± 10.10 kJ/mol, respectively, whereas from elements, ∆Hfel, for KTaO3, KTa2.2O6 and K6Ta10.8O30 are -1408.96 ± 3.73 kJ/mol, -2790.82 ± 6.06 kJ/mol, and -13393.04 ± 31.15 kJ/mol, respectively. The possible decomposition reactions of K-deficient KTa2.2O6 pyrochlore to KTaO3 perovskite and Ta2O5 (reaction 1) or to TTB K6Ta10.8O30 and Ta2O5 (reaction 2) were proposed, and the enthalpies were calculated to be 308.79 ± 4.41 kJ/mol and 895.79 ± 8.64 kJ/mol for reaction 1 and reaction 2, respectively. The reactions are strongly endothermic, indicating that these decompositions are energetically unfavourable, since it is unlikely that any entropy term could override such a large positive enthalpy. The energetic studies prove that pyrochlore is energetically more stable phase than perovskite at low temperature. Thus, the local order of the amorphous precipitates drives the crystallization into the most favourable structure that is the pyrochlore one with similar local organization; the distance between nearest neighbours in the amorphous or short-range ordered phase is very close to that in pyrochlore. Taking into account the stoichiometric deviation in KTO system, the selection of the most appropriate fabrication / deposition technique in thin films technology is a key issue, especially concerning complex ferroelectric oxides. Chemical solution deposition has been widely reported as a processing method to growth KTO thin films, but classical alkoxide route allows to crystallize perovskite phase at temperatures >800 °C, while the temperature endurance of platinized Si wafers is ~700 °C. Therefore, alternative diol-based routes, with distinct potassium carboxylate precursors, was developed aiming to stabilize the precursor solution, to avoid using toxic solvents and to decrease the crystallization temperature of the perovskite phase. Studies on powders revealed that in the case of KTOac (solution based on potassium acetate), a mixture of perovskite and pyrochlore phases is detected at temperature as low as 450 °C, and gradual transformation into monophasic perovskite structure occurs as temperature increases up to 750 °C, however the desired monophasic KTaO3 perovskite phase is not achieved. In the case of KTOacac (solution with potassium acetylacetonate), a broad peak is detected at temperatures <650 °C, characteristic of amorphous structures, while at higher temperatures diffraction lines from pyrochlore and perovskite phases are visible and a monophasic perovskite KTaO3 is formed at >700 °C. Infrared analysis indicated that the differences are due to a strong deformation of the carbonate-based structures upon heating. A series of thin films of alkali tantalates were spin-coated onto Si-based substrates using diol-based routes. Interestingly, monophasic perovskite KTaO3 films deposited using KTOacac solution were obtained at temperature as low as 650 °C; films were annealed in rapid thermal furnace in oxygen atmosphere for 5 min with heating rate 30 °C/sec. Other compositions of the tantalum based system as LiTaO3 (LTO) and NaTaO3 (NTO), were successfully derived as well, onto Si substrates at 650 °C as well. The ferroelectric character of LTO at room temperature was proved. Some of dielectric properties of KTO could not be measured in parallel capacitor configuration due to either substrate-film or filmelectrode interfaces. Thus, further studies have to be conducted to overcome this issue. Application-oriented studies have also been conducted; two case studies: i) photocatalytic activity of alkali tantalates and niobates for decomposition of pollutant, and ii) bioactivity of alkali tantalate ferroelectric films as functional coatings for bone regeneration. Much attention has been recently paid to develop new type of photocatalytic materials, and tantalum and niobium oxide based compositions have demonstrated to be active photocatalysts for water splitting due to high potential of the conduction bands. Thus, various powders of alkali tantalates and niobates families were tested as catalysts for methylene blue degradation. Results showed promising activities for some of the tested compounds, and KNbO3 is the most active among them, reaching over 50 % degradation of the dye after 7 h under UVA exposure. However further modifications of powders can improve the performance. In the context of bone regeneration, it is important to have platforms that with appropriate stimuli can support the attachment and direct the growth, proliferation and differentiation of the cells. In lieu of this here we exploited an alternative strategy for bone implants or repairs, based on charged mediating signals for bone regeneration. This strategy includes coating metallic 316L-type stainless steel (316L-SST) substrates with charged, functionalized via electrical charging or UV-light irradiation, ferroelectric LiTaO3 layers. It was demonstrated that the formation of surface calcium phosphates and protein adsorption is considerably enhanced for 316L-SST functionalized ferroelectric coatings. Our approach can be viewed as a set of guidelines for the development of platforms electrically functionalized that can stimulate tissue regeneration promoting direct integration of the implant in the host tissue by bone ingrowth and, hence contributing ultimately to reduce implant failure.

Remoção de instrumentos fraturados em Endodontia

A área da Endodontia está em constante progresso. Os materiais utilizados nos instrumentos Endodônticos, primordialmente, eram construídos com base em cordas de piano. Seguiu-se uma fase em que estes eram de aço de carbono, mas sofriam corrosão significativa devido ao cloro presente no hipoclorito de sódio, bem como aos processos de esterilização a vapor. Foi necessário evoluir novamente e foram introduzidos os instrumentos de aço inoxidável. Estes apresentavam alta resistência e dureza, mas algumas desvantagens devido à falta de flexibilidade. Atualmente, os instrumentos de NiTi proporcionam uma melhor flexibilidade e efeito de memória de forma. A fratura de instrumentos em Endodontia pode ocorrer por dois grandes fatores: a torção e a flexão por fadiga cíclica, podendo também ser a conjugação de ambos. Fatores anatômicos, como a curvatura e a largura do canal ou outros fatores como ciclos de esterilização, número de usos, etc., podem influenciar uma fratura mais precoce dos instrumentos. A incidência da fratura de instrumentos, embora seja pouco frequente, pode ser reduzida a um mínimo absoluto se os clínicos usarem as características de torque e de stress adequadas. Um bom conhecimento dos procedimentos clínicos, da anatomia, dos materiais e a utilização de instrumentos como o microscópio podem ajudar a prevenir ou a resolver a fratura dos instrumentos. No entanto, a melhor forma de prevenir a fratura é a sua prevenção. A desinfeção é o procedimento mais importante para o sucesso de um tratamento Endodôntico, portanto para que isto seja possível, é necessária uma boa conformação canalar. A presença de um instrumento no interior do canal pode comprometer a desinfecção, especialmente caso tenha ocorrido numa fase precoce da preparação canalar. Aquando da fratura de um instrumento, deve-se refletir sobre os procedimentos a seguir, podendo-se optar por várias abordagens, nomeadamente pela manutenção do instrumento no canal e obturação incorporando o fragmento, pela remoção do segmento através de diversas técnicas (ultrassons ou técnicas de microtubos, etc.), e ainda pela realização do bypass ou pela cirurgia Endodôntica. Em última instância pode ser realizada a extração do elemento dentário.

Síndrome de Sjögren Primário

A Síndrome de Sjögren (SS) é uma das três patologias autoimunes mais frequentes na população mundial, ainda assim frequentemente infradiagnosticada. Esta síndrome é uma doença autoimune crónica que afeta as glândulas exócrinas, particularmente as glândulas salivares e lacrimais. A SS primária (SSp) afeta especificamente as glândulas exócrinas, enquanto que a SS secundária (SSs) aparece associada a outras patologias autoimunes sistémicas. A SS é caracterizada, histopatologicamente, por um infiltrado inflamatório linfocitário que interfere com a função glandular normal. Afeta 0,5% da população mundial, sendo claramente mais predominante em mulheres (9:1 versus homens), principalmente por volta dos 50 anos (após a menopausa), ainda que também possa aparecer depois da menarca (entre os 20 e os 30 anos). Considera se que a etiologia da SS é multifatorial. Fatores genéticos, ambientais, hormonais e virais estão implicados na sua etiopatogénese. É muito importante o papel dos Médicos Dentistas no diagnóstico da SSp, uma vez que na maior parte dos casos são eles quem detetam os primeiros sintomas, mais propriamente a boca seca. Diversos testes auxiliares são utilizados para o diagnóstico desta doença, tais como: o teste de Schimer, o teste de Rosa Bengala, a Sialometria, a Sialografia, a Biópsia das glândulas salivares, entre outros. A SSp, regra geral, tem um curso não doloroso, sendo a boca seca e a secura ocular as suas duas características clínicas mais salientes. A maior parte das manifestações orais que se apresentam nestes pacientes são resultado de hipofunção das glândulas salivares (da boca seca), tais como: a cárie dentária, a doença periodontal, as infeções fúngicas, entre outras. Esta doença também se pode associar a problemas a nível sistémico, que podem ser subdivididos em não viscerais (pele, artralgia, mialgia) e viscerais (pulmão, coração, rim, sistema gastrointestinal, sistema endócrino e sistema nervoso central e periférico). O tratamento é empírico, sintomático e direcionado a tratar as complicações da doença mais inicial, que consiste em limitar os danos da xerostomia e da queratoconjuntivite. A prevenção dos sintomas a nível oral e ocular é fundamental em pacientes com SSp, para assim terem maior qualidade de vida.