High tumor budding stratifies breast cancer with metastatic properties.

Tumor budding refers to single or small cluster of tumor cells detached from the main tumor mass. In colon cancer high tumor budding is associated with positive lymph nodes and worse prognosis. Therefore, we investigated the value of tumor budding as a predictive feature of lymph node status in breast cancer (BC). Whole tissue sections from 148 surgical resection specimens (SRS) and 99 matched preoperative core biopsies (CB) with invasive BC of no special type were analyzed on one slide stained with pan-cytokeratin. In SRS, the total number of intratumoral (ITB) and peripheral tumor buds (PTB) in ten high-power fields (HPF) were counted. A bud was defined as a single tumor cell or a cluster of up to five tumor cells. High tumor budding equated to scores averaging >4 tumor buds across 10HPFs. In CB high tumor budding was defined as ≥10 buds/HPF. The results were correlated with pathological parameters. In SRS high PTB stratified BC with lymph node metastases (p ≤ 0.03) and lymphatic invasion (p ≤ 0.015). In CB high tumor budding was significantly (p = 0.0063) associated with venous invasion. Pathologists are able, based on morphology, to categorize BC into a high and low risk groups based in part on lymph node status. This risk assessment can be easily performed during routine diagnostics and it is time and cost effective. These results suggest that high PTB is associated with loco-regional metastasis, highlighting the possibility that this tumor feature may help in therapeutic decision-making.

Expression of the hyaluronan-mediated motility receptor RHAMM in tumor budding cells identifies aggressive colorectal cancers.

Expression of the hyaluronan-mediated motility receptor (RHAMM, CD168) predicts adverse clinicopathological features and decreased survival for colorectal cancer (CRC) patients. Using full tissue sections, we investigated the expression of RHAMM in tumor budding cells of 103 primary CRCs to characterize the biological processes driving single-cell invasion and early metastatic dissemination. RHAMM expression in tumor buds was analyzed with clinicopathological data, molecular features and survival. Tumor budding cells at the invasive front of CRC expressed RHAMM in 68% of cases. Detection of RHAMM-positive tumor budding cells was significantly associated with poor survival outcome (P = .0312), independent of TNM stage and adjuvant therapy in multivariate analysis (P = .0201). RHAMM-positive tumor buds were associated with frequent lymphatic invasion (P = .0007), higher tumor grade (P = .0296), and nodal metastasis (P = .0364). Importantly, the prognostic impact of RHAMM expression in tumor buds was maintained independently of the number of tumor buds found in an individual case (P = .0246). No impact of KRAS/BRAF mutation, mismatch repair deficiency and CpG island methylation was observed. RHAMM expression identifies an aggressive subpopulation of tumor budding cells and is an independent adverse prognostic factor for CRC patients. These data support ongoing efforts to develop RHAMM as a target for precision therapy.

Androgen receptor status is highly conserved during tumor progression of breast cancer

BACKGROUND With the advent of new and more efficient anti-androgen drugs targeting androgen receptor (AR) in breast cancer (BC) is becoming an increasingly important area of investigation. This would potentially be most useful in triple negative BC (TNBC), where better therapies are still needed. The assessment of AR status is generally performed on the primary tumor even if the tumor has already metastasized. Very little is known regarding discrepancies of AR status during tumor progression. To determine the prevalence of AR positivity, with emphasis on TNBCs, and to investigate AR status during tumor progression, we evaluated a large series of primary BCs and matching metastases and recurrences. METHODS AR status was performed on 356 primary BCs, 135 matching metastases, and 12 recurrences using a next-generation Tissue Microarray (ngTMA). A commercially available AR antibody was used to determine AR-status by immunohistochemistry. AR positivity was defined as any nuclear staining in tumor cells ≥1 %. AR expression was correlated with pathological tumor features of the primary tumor. Additionally, the concordance rate of AR expression between the different tumor sites was determined. RESULTS AR status was positive in: 87 % (307/353) of primary tumors, 86.1 % (105/122) of metastases, and in 66.7 % (8/12) of recurrences. TNBC tested positive in 11.4 %, (4/35) of BCs. A discrepant result was seen in 4.3 % (5/117) of primary BC and matching lymph node (LN) metastases. Three AR negative primary BCs were positive in the matching LN metastasis, representing 17.6 % of all negative BCs with lymph node metastases (3/17). Two AR positive primary BCs were negative in the matching LN metastasis, representing 2.0 % of all AR positive BCs with LN metastases (2/100). No discrepancies were seen between primary BC and distant metastases or recurrence (n = 17). CONCLUSIONS Most primary (87 %) and metastasized (86.1 %) BCs are AR positive including a significant fraction of TNBCs (11.4 %). Further, AR status is highly conserved during tumor progression and a change only occurs in a small fraction (4.1 %). Our study supports the notion that targeting AR could be effective for many BC patients and that re-testing of AR status in formerly negative or mixed type BC's is recommended.

Solving the minimum vertex floodlight problem with hybrid metaheuristics

In this paper we propose four approximation algorithms (metaheuristic based), for the Minimum Vertex Floodlight Set problem. Urrutia et al. [9] solved the combinatorial problem, although it is strongly believed that the algorithmic problem is NP-hard. We conclude that, on average, the minimum number of vertex floodlights needed to illuminate a orthogonal polygon with n vertices is n/4,29.

Estudio de la calidad del agua en cisternas de captación de agua de lluvia en escuelas rurales de Alagoas (Brasil)

El presente trabajo se centra en el estudio de la calidad del agua de Sistemas de Recogida de agua de lluvia en escuelas del Semiárido Alagoano de Brasil. Aspectos de la obra civil también son incluidos. Los Sistemas principalmente están formados por un área de captación de agua de lluvia, cisternas de placas de cemento, canalizaciones que las unen y una bomba manual para la retirada del agua de la cisterna. Se analizaron 206 muestras de parámetros básicos de la calidad del agua – conductividad eléctrica, turbidez, pH, cloro residual y colifomes fecales- en 15 cisternas escolares, 3 comunitarias y 2 domiciliarias durante 5 meses. Las propiedades físico-químicas mostraron casi siempre valores acordes con la legislación brasileña (PORTARIA Nº 518/2004), aunque en algunos casos se encontraron pH alcalinos causados por el cemento de la cisterna que disminuyen la eficacia de la cloración, único tratamiento empleado en la zona. Por otra parte, los análisis en mini laboratorio de coliformes fecales resultaron positivos en un 27% de las veces, siendo inadecuado para el consumo humano según la normativa del país. Sin embargo, cuando se desviaban las primeras lluvias contenientes de contaminantes del tejado, las bacterias disminuían casi por completo. Se ha recomendado por lo tanto, además de otros aspectos, la utilización de dispositivos automáticos y de bajo coste para la retirada de las primeras aguas. Otras influencias en la calidad del agua también fueron halladas.

La casa en imágenes : pulsos, ecos y huellas del habitar contemporáneo

La imagen fotográfica es un bloque espacio tiempo congelado, un fragmento referido al antes y el después de algo. Al contemplar una fotografía de un interior doméstico, descubrimos un entretejido sutil entre el habitante y su hábitat. Somos capaces de recaer en más detalles de los que el ojo humano puede apreciar en su visión cotidiana, siempre ligada al devenir espacio temporal. El acto de fotografiar el hogar, de congelar unidades habitadas infinitesimales, se revela como una manifestación radical del modo unipersonal de habitar de cada fotógrafo, profesional o aficionado, y por extensión, dado que hoy todos somos fotógrafos; de cada habitante. Por un lado, la fotografía se piensa aquí como herramienta, capaz de desvelar, de poner en el mundo, los elementos, percepciones y acontecimientos, que subyacen imbricados en la construcción del hogar. Por otro, la imagen se entiende como medio de expresión y de comunicación, como el lenguaje universal de nuestro tiempo, por todos conocido y utilizado. En este momento de interconexión máxima, entre redes, datos y capas de cognición, de velocidad y aceleración, esta tesis doctoral se plantea como una vuelta a la reflexión, a la contemplación del objeto imagen, desde la certeza de que para que ésta hable hay que darle tiempo. Así, la investigación hay que entenderla desde una base ontológica y fenomenológica; desde la experiencia del ser que habita un entorno concreto y determinado. Se enmarca en el actual entorno socio cultural de occidente, se busca desvelar el significado y modo de habitar del habitante común, poniendo de manifiesto aquello que acontece para que una casa cualquiera, de un habitante cualquiera, devenga hogar. Los primeros indicios sobre el tema surgirán del análisis y la reinterpretación hermenéutica de un atlas de imágenes del habitar: cuerpo de imágenes reunido a partir de series fotográficas de hogares, de habitantes anónimos, puestos a luz por la mirada de un grupo de artistas. Posteriormente, ponemos a prueba el conocimiento adquirido en el análisis anterior, mientras que expandimos la investigación hacia el sentir del habitante común, mediante la realización de tres experimentos participativos, o estudios de campo cualitativos. Los resultados, de ambos grupos de casos de estudio, se compilan, organizan y estructuran en una taxonomía del habitar. Esta taxonomía está compuesta por cuarenta y siete parámetros, que explicitan la naturaleza compleja del hogar del siglo XXI. Este hogar es entendido como un constructo personal de cada habitante, un proceso que acontece en el tiempo y en el espacio, y que entraña la propia construcción del habitante. Esta extensa taxonomía se organiza según tres ámbitos del ser humano, en el primero se expresan los factores relacionados con el modo de "estar físicamente" en el hogar, incluyendo: al propio habitante, la casa como espacio arquitectónico y como materialidad: objetos, muebles, iconos y símbolos que pueblan el hogar. En segundo lugar, se manifiestan los parámetros relacionados con el modo de “percibir”: por un lado, aquello que se deriva de lo que se ve, y por otro, lo que se deriva de aquello que no se ve, pero se siente. En tercer lugar, se explicitan los factores relativos al habitante que "crea/juega" su hogar, quién por un lado, es en el mundo actuando, y que por otro, siente el mundo construyéndolo mediante una serie de relaciones que establece con él. Finalmente, la investigación intenta revelar las sinergias, conexiones y relaciones, entre todos estos elementos extraídos del sentir del habitante común, y que fueron inducidos mediante el análisis y reinterpretación de los casos de estudio, poniendo de manifiesto un orden de cosas en el habitar occidental contemporáneo. ABSTRACT The photographic image is a frozen space time block, a fragment referred to a something before and after. When we stare at the photography of domestic interiors we discover a subtle interweaving between the inhabitant and her habitat. We are able to acknowledge infinite more details than the human eye, in its continuous quotidian vision always linked to the space time progression, appreciates. The act of photographing the home, of freezing infinitesimal inhabited units, reveals as a radical statement of the concept of inhabiting for each photographer, professional or amateur, and by extension, as we today all are photographers, for each inhabitant. On the one hand, photography is here conceived as a tool that is capable of revealing, "of placing in the world" the elements, perceptions and happenings that underlie imbricated in the construction of a home. On the other hand, image is thought as an expression and communication media, as the universal language of our time (as far as it is known and used by all of us). In this precise moment of maximum interconnection between networks, data and cognitive layers; of speed and acceleration, this PhD Dissertation is conceived as a return to reflection; to the contemplation of object image, from the certainty of its need of time for talking. Therefore, this research from an ontological and phenomenological base; from the experience of the self who inhabits a determined and concrete environment, that of the western countries at the present, pursues to unveil the meaning and way of inhabiting of a common dweller and manifest what conforms the transformation of any house, of any inhabitant into a home. The first clues will arise from the analysis and hermeneutical reinterpretation of the Atlas of inhabiting; an assembled body of images of anonymous inhabitants houses, brought into life through a group of artist´s glance. Afterwards, we will test the analysis´s acquired knowledge, while extending the investigation to the feel of the common inhabitant (and no longer the expert^ artist) through the execution of three participative experiments conceived as qualitative field works. The results of both case study groups, will be compiled, organized and structured in a taxonomy of the inhabiting. This taxonomy is composed by forty seven parameters that explicitly state the complex nature of the XXI century home, regarded as a personal construct of every single inhabitant, as a process that happens through time and space and that entails the construction of the inhabitant. This wide taxonomy is organized regarding three spheres of the human being, In first place, those elements related to the way of “physically being” at home are expressed, including: the inhabitant its self, the house as architectural space and as materiality: objects, furniture, icons and symbols that fill the home. In second place, parameters related to the way of “perceiving“ are manifested; on the one hand, those that derive from what we see; on the other hand, those that derive from what we do not see, but feel. In third place, those factors deriving from the inhabitant as a home "creator/player" who is acting in the world and feeling the world while constructing it through a myriad of relationships he establishes with it. Finally, the investigation tries to reveal the synergies, connections and relations between all these elements extracted from the feelings of the common inhabitant, induced through the analysis and reinterpretation of the case studies, and therefore exposing a state of things belonging to western world at present.

Placenta acreta

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Estudo de caso : Um quadro típico de FHL numa doente atípica

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Risco cardiovascular em doentes com lúpus eritematoso sistémico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Inspeção-Geral da Educação e Ciência e Avaliação das Escolas : o caso da autoavaliação de um agrupamento de escolas : um olhar a partir de quem avalia e de quem é avaliado

Relatório de estágio de mestrado, Educação (Área de especialidade em Administração Educacional), Universidade de Lisboa, Instituto de Educação, 2016

Hipertensão arterial mascarada no idoso

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

The mechanisms and qualifications of the selective permeability in transport across biological barriers : the example of kyotorphin

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

As deusas Inanna e Ištar: semânticas de poder com traços de amor e guerra

A presente dissertação de mestrado centra-se na divindade suméria Inanna e na sua homóloga semita Ištar. Recolhemos e analisamos conjuntos de mitos, narrativas, hinos, oráculos, canções e orações, de proveniências e cronologias distintas, para compor um retrato cuja complexidade ultrapassa as questões do género e apela a sentimentos transversais ao ser humano. Num panteão com uma miríade de divindades altamente especializadas, Inanna/Ištar destaca-se pelo facto de acumular funções. Deusa trifuncional, regente do Amor e da Guerra, era igualmente a representação divina do planeta Vénus. Numa primeira abordagem, essa singularidade é um factor desconcertante para a sua compreensão. Pelo seu carácter problemático, foi o principal incentivo para o nosso estudo. Examinando as suas diferentes manifestações, propomos um eixo comum para a sua aparente ambivalência, interpretando o amor e a guerra como metáforas com um mesmo significado: poder. Vemos assim como a guerreira e a noiva se complementam em vez de se contradizerem. Ao lado do rei, no leito sagrado ou no campo de batalha, exprimem sempre a bênção divina assegurando a legitimidade dos seus actos enquanto representante dos deuses na Terra e, por conseguinte, garante da ordem. A permanência no tempo do sistema de crenças originalmente fixado por mão suméria, resistindo a conquistas e mudanças dinásticas, e a sua difusão no espaço, transpondo fronteiras naturais e artificiais, demonstram que os povos do Crescente Fértil o partilharam, não obstante algumas alterações semânticas. Na perspectiva da história das religiões, este olhar projetado sobre o passado permite ainda entender melhor a mente do homem mesopotâmico e acompanhar as consequências das alterações culturais no tecido sociopolítico da época. Afloramos também alguns aspectos de continuidade, manifestados através da presença de influências mesopotâmicas na literatura e religião gregas, mais especificamente em Afrodite e Deméter, deusas do amor e da fertilidade, respectivamente. Por fim, sugerimos a permanência de categorias mentais que transportam o passado até aos dias de hoje, ligando a Antiguidade à Actualidade.