This research aims to fill an important gap in focusing on why individuals are able to take part in and/or support activities that have effects on economic, environmental, and social dimensions that are not consistent with their sense of right and wrong. The research focuses on the relationship between supply chain management and moral disengagement, and how this relation affects social responsibility. After observing individuals avoiding responsibility for misconduct an explanatory concept, moral decoupling, was proposed. Moral decoupling considers moral responsibility a flow in the supply chain. Moral decoupling occurs when the flow is restricted. If moral decoupling occurs at an identifiable point it is called a moral decoupling point. The concept was developed by identifying and linking specific supply chain activities and structures with moral disengagement, a theory that explains the deactivation of self regulation. Moral decoupling was able to suggest how to reduce moral disengagement and improve social responsibility. To validate the suggestions a literature review on social responsibility was conducted and identified sixteen elements of social responsibility in supply chain management. The suggestions based on moral disengagement were compared with elements of social responsibility and a large overlap was found. Lastly, suggestions on how to reduce moral disengagement and map moral responsibility in a supply network are proposed, links between elements of social responsibility are presented, and moral coupling is added as a complementary term to moral decoupling. A model explaining the relationship between ethical guidelines, moral responsibility, moral decoupling, and social responsibility is proposed. In relation to current theoretical knowledge the thesis has contributed to the field of socially responsible supply chain management with an application of a new theoretical lens that gives one explanation as to why identifed elements of social responsibility are important. The understanding of social responsibility has reached an increased explanatory depth following the identification of moral disengagement as a generative mechanism, subject to conditions in supply chain management. The research has also applied moral disengagement in a context not identified in earlier research, and shows some of the complexity of applying it to a real-world global context. The elements of social responsibility and moral (de)coupling help practitioners identify what they should focus on to increase social responsibility and also offer an explanation for `why?'. The findings can be used to construct supply chains that are less prone to misconduct and to identify where in the chain it is important to be aware of immoral behavior. The value and originality of this research is centered on the application of a new theoretical lens for socially responsible supply chain management. It is the only identified research in the area which identifies mechanisms on a generative level that explains human behavior and conditions to which those mechanisms are subject. This is also in itself a novel application of moral disengagement in a new research context. / <p>Doctoral thesis for the degree of Doctor of Philosophy in Textile Management at the University of Borås to be publicly defended on Wednesday, December 10, 2014, at 1:00 p.m.,in room M404, University of Bor as, Allégatan 1, Borås</p>

A tese apresenta uma análise sobre registros visuais produzidos no âmbito da Guerra do Paraguai (1864-1870), evento que envolveu Brasil, Argentina e Uruguai em luta contra o Paraguai, em uma conjuntura de consolidação de projetos nacionais na América do Sul. A natureza histórica do conflito é por si propícia à criação de imagens e imaginários. Além disso, a eclosão da guerra ocorreu em um momento em que o estatuto do olhar estava em debate, aliado a uma intensa transformação das tecnologias de reprodução e circulação de imagens. Nesse sentido, buscou-se compreender as imagens analisadas a partir do regime de visualidade em que estavam inseridas. Ou seja, não apenas quanto ao seu conteúdo aparente, mas em suas relações de produção, circulação, consumo e agenciamento. Fundamentado em indícios sobretudo gráficos, este trabalho intenta desvelar práticas visuais em voga a partir do exame do percurso social das imagens, em seus cruzamentos entre tecnologia e estética. Para isso, são analisados quatro conjuntos imagéticos que suscitam questões distintas, sem induzir uma relação de causalidade entre eles. Dos aspectos principais ressalta-se: um deslocamento de usos e sentidos dos desenhos militares a partir da cobertura feita pela imprensa ilustrada do Rio de Janeiro; a sobreposição do conteúdo científico e militar da expedição ao Mato Grosso, analisada a partir do álbum de desenhos de Alfredo Taunay; a natureza iminentemente múltipla das imagens produzidas para o mercado editorial pelo artista suíço Adolf Methfessel; a emergência dos debates raciais na crítica de arte que acompanhou a Exposição Geral de Belas Artes de 1879, associada à falta de prática de ver e representar o negro nas pinturas de história de grande monta. Do exame de fragmentos visuais da guerra, buscou-se historicizar os modos de ver e de fazer ver de um evento que, dessa forma, se demonstra também produtivo e criador, para além dos efeitos nefastos cujas consequências são sentidas até os dias atuais. / This thesis presents an analysis of visual records produced on the scope of the Paraguayan war (1864-1870), an event in which Brazil, Argentina and Uruguay engaged on a fight against Paraguay, while nationalist projects were being stablished in South America. The historical nature of the conflict is for itself worth of the creation of images and imaginaries. Furthermore, the war outbreak occurred on a time that the constitution of the gaze was under debate, alongside to an intense technology transformation on image reproduction and circulation. In this regard, we aimed to ponder the images trough out the visual system in which they were inserted. In other words, not only concerning its apparent content but also its production, circulation, consume and agency relationships. Primarily based on graphic media, this works aims to unveil visual practices in vogue through the analysis of the social path of the images, and its crossings between technology and aesthetics. This required the analysis of four image sets that raise different questions, with no induction of a causality relation between them. Among their main aspects, we emphasize: a displacement of use and sense of the military drawings by Rio de Janeiro\'s illustrated press coverage; the scientific and military conflict overlap of the Mato Grosso expedition, by the analysis of Alfredo Taunya\'s drawing albums; the imminently multiple nature of images by Swiss artist Adolf Methfessel produced to the publishing market; the racial debate rising on art criticism that followed the General Exhibition of Fine Arts of 1879, associated to the lack of practices of seeing and representing the Negro on great mount historical paintings. We have aimed to historicize the ways of seeing and make to see through the examination of visual fragments of the war, thus, showing its productive and creative side, in addition to the nefarious effects and consequences felt to the present day.

Supply chains are increasingly incorporating sustainable elements as mean to meet intensified TBL awareness in the market and to promote competitiveness. Suppliers play a key role in enhancing Triple Bottom Line (TBL) outcomes in supply chain since they are responsible for raw materials that will be incorporated in the final product. Supplier Development (SD) can improve suppliers\' TBL capabilities, improving TBL outcomes throughout the supply chain. This research aims to explore Triple Bottom Line Supplier Development (TBL SD) for an improved TBL performance at supply chain level. To address the research general purpose a systematic literature review was conducted, followed by a basic literature review, in order to identify TBL SD practices, enablers and barriers. The systematic literature analysis was performed with support of QDA Miner software. A survey was performed involving Brazilian buying organizations to investigate the impact of TBL Supplier Development on the organizations\' performance at the operational, environmental and social dimensions. Data were analyzed using Partial Least Square Structural Equation Modeling (PLS SEM) through Smart PLS 3 software. The results obtained point that practices adopted by organizations are in accordance to what literature suggests, highlighting the role of training and resources sharing as important practices adopted. The most impactful enablers to enable TBL SD are supplier evaluation, resources availability, and TBL culture at organizational level. Surprisingly, barriers appeared to be only slightly negatively correlated to TBL SD Adoption. It can be concluded that TBL SD adoption leads to improvements in all TBL legs (Operational, Environmental, and Social) although the impact on environmental performance is stronger. In turn, it was found that enhanced environmental performance can lead to improvements in both social and operational performance. Another interesting finding is that organizations in the Brazilian context are adopting TBL SD for internal reasons, and not due to pressures coming from the local market and community. / As cadeias de suprimentos estão incorporando cada vez mais elementos sustentáveis como meio de atender à crescente conscientização do mercado e promover competitividade. Fornecedores desempenham um papel fundamental no aprimoramento dos resultados sustentáveis na cadeia de fornecimento, uma vez que são responsáveis pelas matérias-primas que serão incorporadas no produto final. Nesse contexto, o desenvolvimento de fornecedores pode melhorar as capabilidades sustentáveis dos fornecedores, entregando melhores resultados a toda a cadeia de suprimentos. Esta pesquisa tem como objetivo explorar o Desenvolvimento de Fornecedores Sustentáveis para um melhor desempenho sustentável no nível da cadeia de suprimentos. Para atingir o objetivo geral da pesquisa, foi realizada uma revisão sistemática de literatura, seguida de uma revisão básica da literatura, a fim de identificar as práticas de desenvolvimento sustentáveis, fatores influenciadores e barreiras. A análise da revisão sistemática da literatura foi realizada com o apoio do software QDA Miner. Uma survey envolvendo organizações brasileiras foi realizada para investigar o impacto da adoção do Desenvolvimento de Fornecedores Sustentáveis no desempenho das organizações pesquisadas, tanto nos aspectos operacionais, ambientais e sociais. Os dados foram analisados usando a Modelagem de Equações Estruturais por Mínimos Quadrados Parciais através do software Smart PLS 3. Os resultados obtidos apontam que as práticas adotadas pelas organizações estão de acordo com o que sugere a literatura, destacando o papel do treinamento e compartilhamento de recursos como práticas importantes adotadas. Os fatores influenciadores mais impactantes para a adoção do Desenvolvimento de Fornecedores Sustentáveis são avaliação de fornecedores, a disponibilidade de recursos e a cultura sustentável no nível organizacional. Surpreendentemente, as barreiras parecem estar ligeiramente correlacionadas de forma negativa com adoção do Desenvolvimento de Fornecedores Sustentáveis. Pode-se concluir que a adoção do Desenvolvimento de Fornecedores Sustentáveis leva a melhorias em todas as dimensões da Sustentabilidade (Operacional, Ambiental e Social), embora o impacto no desempenho ambiental seja mais forte. Por sua vez, o desempenho ambiental pode levar a melhorias no desempenho social e operacional. Outra constatação interessante é que as organizações no contexto brasileiro estão adotando o Desenvolvimento de Fornecedores Sustentáveis por motivos internos, e não devido a pressões vindas do mercado e da comunidade local.

In light of a stronger recognition of the need for sustainable business practices as “business as usual” no longer presents itself as a viable option, this study aims to cast light on the current work of Swedish SMEs with integrative sustainability. Within the academic field of sustainability in business, the latest years have seen the emergence of multiple frameworks that promote a holistic sustainability approach to conducting business. The single firm becomes a connecting member of an extensive stakeholder network and by operating in an economically, environmentally and socially sustainable manner, the business seeks to create value for a variety of stakeholder groups, rather than focusing on monetary objectives set by shareholders. These new integrative frameworks shift the understanding of a firm from a profit-maximiser to that of a value-creator that acts sustainably to cater to the needs of all its stakeholders. However, as the models have only recently featured across academia, their real-life applicability and viability are contested, and in some ways, remains under-researched, particularly in the context of SMEs. With Sweden as a leading example in sustainability implementation, this study attempts to provide insight into how SMEs work with the elements of these frameworks and which opportunities and challenges they encounter during implementation. Through conducting detailed, qualitative and personal semi-structured interviews with the CEOs of six sustainability-minded Swedish SMEs of different industrial backgrounds, this research gauges the current organisational efforts being made in terms of sustainability and relates them to the integrative value-creating frameworks to identify congruences, divergences and room for improvement in line with latest theories. The main conclusions drawn as part of this process include the continued, at least partial, unfamiliarity of businesses with the frameworks, despite a large degree of compatibility of current practical efforts and existing academic theory. Value creation is moving closer to being included in the core of the business model, yet while absolute profit maximisation receives less attention, hesitation towards implementing sustainability more integratively is driven by concerns of losing grounds for profitability. The establishment of clusters and strong relationships leading to mutual synergies is found as a potential way to provide firms with the structural support to shift fully towards value-creation as envisioned by the investigated frameworks.

In this study, sustainability strategy implementation processes are discussed together with internal communication processes in SMEs. Large enterprises are not the only contributor to unsustainable development, but so are SMEs. Additionally, SMEs have a significant negative impact on sustainability as they make up the major part of the world economy. In fact, only in Sweden SMEs make up 99.9% (based on the number of employees) of all businesses. Yet, SMEs have not received much attention in society nor in literature of sustainability and sustainable developmentand are lagging behind in sustainable development. Due to pressure from external stakeholders Sustainability is essential for future business growth as well asto stay competitive in today's marketplace. EU and Swedish legislation together with the next generation of sustainable-conscious consumers, have increased pressure on organisations to take responsibility for their actions. Still, SMEs seem to take a reactive approach. For successful sustainable development, sustainability strategies must be aligned with business strategies. However, SMEs face challenges when implementing sustainability strategies. To ease the implementation process, company-specific tools are needed forSMEs. Internal communication is acknowledgedto be essential for sustainability strategy implementation which is most successful when performed in a contextual specific and conceptual abstract practice. Internal communication further contributes to reducing tension in an organisation when implementing a change which is required during implementation processes.This study has been conducted through a single case study operating in the housing construction industry,based in Sweden. We have usedan exploratory and a qualitative approach where both semi-structured interviews and focus groups were conducted to receive insights from top management and lower-level employees. Our research shows that sustainability strategies, business strategies and communicationstrategies must be balanced to create a shared sustainability vision through short-and long-termgoals to reduce the complexity of sustainable development. Therefore, the role of internal communication in the sustainability strategy implementation processis essential to transformintangible sustainability strategies into tangible features to engage employees and reduce tension within the organisation.

Introdução: O cãncer de mama com fenótipo triplo negativo é definido como um tumor com receptor de estrógno e progesterona negativos e human epidermal growth factor receptor 2 (HER2) negativo. Desde sua primeira descrição, alguns artigos tentaram descrever sua aparência radiológica, sem nenhum consenso. Estas pacientes podem ter características clínicas e imaginológicos distintas. Seria interessante verificar se as características radiológicas desses tumores são as mesmas relatadas no câncer de mama familiar e com mutação do gene BRCA1, muitas vezes associados a esse subtipo tumoral. Estas características que muitas vezes simulariam doenças benignas poderiam atrasar o diagnóstico precoce, refletindo a necessidade de seu conhecimento radiológico na prática. Neste contexto, este estudo poderia auxiliar no reconhecimento precoce de lesões mamárias e alertar o médico para solicitar uma biópsia, consequentemente, resultando num diagnóstico precoce. Objetivo: O principal objetivo desse estudo foi avaliar as características radiológicas dos carcinomas ductais invasivos de mama nos seguintes métodos de diagnóstico por imagem: mamografia, ultrassonografia e ressonância magnética, utilizando a padronização do American College of Radiology Breast Imaging Reporting and Data System (ACR BI-RADS®), comparando os casos de carcinomas com fenótipo triplo negativo dividindo-os em não basal e basal com o uso da citoqueratina 5. Pacientes e Métodos: Revisamos os arquivos de imagens do Instituto de Radiologia (InRad) da Faculdade de Medicina da Universidade de São Paulo (FMUSP) e do Instituto do Câncer do Estado de São Paulo (ICESP), durante o período da coleta de dados, que envolveu 12 anos. Trata-se de estudo descritivo observacional, realizado após a aprovação do comitê de ética. Foram avaliadas 6.952 resultados de biópsias cirúrgicas ou percutâneas por agulha grossa de mama e após a verificação do material radiológico e histológico, chegamos ao resultado de 106 casos. Todas as reações imunohistoquímicas foram lidas por dois patologistas e os exames radiológicos foram avaliados por dois radiologistas, todos especialistas em doenças da mama em suas respectivas áreas. Resultados: A maioria das pacientes incluídas foram mulheres brancas, com idade entre 24-81 anos. Na mamografia, a principal lesão observada foi o nódulo (74,7%), com margem espiculada (36,9%) e forma oval (60,0%), seguido pela assimetria focal (12,6%), lesões ocultas (9,2%) e assimetria global (3,4%). Nenhuma lesão principal se manifestou como microcalcificações. Os tumores avaliados pela ressonância magnética se manifestaram principalmente como lesão nodular (92,0%), com forma irregular (60,0%), margem irregular (44%) e realce heterogêneo (56,0%). A curva tipo 3 (91,7%) foi comumente observada. O isosinal em T2 foi mais freqüentemente observado (52,2%). A ausência de áreas císticas foi observada na maioria das lesões (47,8%). Todos os tumores avaliados pelo ultrassom foram vistos, principalmente como nódulos (98,1%), hipoecoicos (90,3%), com forma irregular (61,2%), margem mal definida (34,7%) e o reforço acústico posterior (32,0%) e halo ecogênico (46,6%) foram comumente observados. Conclusão: Não foram encontradas associações estatisticamente significativas das características tumorais e demográficas com os subtipos de tumores (p > 0,05) na mamografia, ultrassom e ressonância magnética. Houve correlaçãos inversa entre a idade e o tamanho do tumor. Apenas no USG os linfonodos positivos apresentaram em média estatisticamente maior tamanho tumoral associado que os linfonodos negativos (p=0,045). Em nossa série, observamos que embora algumas características tenham sido mais frequentes, não houveram características que mostraram diferença estatisticamente significante entre os subtipos. Assim, não se pode atribuir qualquer característica específica que possa melhorar a acurácia diagnóstica / Introduction: Breast cancer with triple negative phenotype is defined as estrogen receptor negative tumor, progesterone receptor negative and human epidermal growth factor receptor 2 (HER2) negative. Since its first description, some articles have tried to describe its radiological appearance, with no consensus. These patients can have adverse clinical and imaging characteristics. It would be interesting to check if the radiological characteristics of these tumors are the same related in the familiar breast cancer and associated to the mutation of gene BRCA1, many times associated to this tumor subtype. These characteristics, that many times would simulate benign diseases, could delay the early diagnosis, reflecting the need of its radiological knowledge in practice. In this context, this study could help in the early recognition of breast lesions and alert the doctor to require a biopsy, consequently resulting in an early diagnosis. Objectives: The main objective of this study was to evaluate the radiological characteristics of breast invasive ductal breast carcinomas with triple negative invasive phenotype in the following diagnostic image methods: mammography, ultrasound and magnetic resonance, using the American College of Radiology Breast Imaging Reporting and Data System (ACR BIRADS ®) criteria, divided in basal and not basal subtypes with the use of cytokeratin 5. Patients and Methods: We\'ve reviewed the images from the Radiology Institute (InRad) from Faculty of Medicine of the University of São Paulo (FMUSP) and from the Cancer Institute of São Paulo (ICESP), during the period of data collecting, which took 12 years. This aims to be an observational descriptive study, realized after the Ethic Committee\'s approval. 6952 results of breast surgical or percutaneous needle biopsies were evaluated and after checking the radiological and histological material, we came to the result of 106 cases. All the immunohistochemical reactions were read by two pathologists and the radiological exams were evaluated by two radiologists, all specialists in breast illnesses in their respective areas. Results: Most patients included were white women, aging between 24-81 years old. In the mammography, the main lesion observed was the nodule (74,7%), spiculated margin (36,9%) and oval shape (60%), followed by focal asymmetry (12,6%), hidden lesions (9,2%) and global asymmetry (3,4%). No main lesion showed microcalcifications. The tumors evaluated by magnetic resonance imaging showed mainly as nodule (92,0%), irregular shaped (60,0%), irregular margin (44,0%) and heterogeneous enhancement (56,0%). The curve type 3 (91,7%) was generally observed. The isosignal in T2 was most frequently observed (52,2%). The absence of cystic areas was observed in most of the lesions (47,8%). The tumors evaluated by the ultrasound were seen principally as nodules (98,1%), hypoechoic (90,3%), irregular shaped (61,2%), ill-defined margin (34,7%) and with posterior acoustic enhancement (32,0%) and echogenic halo (46,6%). Conclusion: There were no statistically significant associations of tumor and demographic characteristics with tumor subtypes (p > 0.05) in mammography, ultrasound and magnetic resonance imaging. There were inverse correlations between the age and the size of the tumor. Only in USG positive lymph nodes had on average larger tumor size with a statistically significant result that the negative lymph nodes (p = 0,045). In our series, we\'ve observed that, although some characteristics have been more frequent, there were no characteristics which showed difference statistically significant among the subtypes. Therefore, we can not attribute any specific characteristic that can improve the diagnostic accuracy

A integração das espécies de adubos verdes, que imobilizam P, com a aplicação de fontes minerais fosfatadas é uma das medidas agronômicas mais promissoras para melhorar a disponibilidade de P para a cultura principal, com o objetivo de recuperar a fertilidade do solo, aumentar a matéria orgânica do solo e assim, otimizar eficiência de fertilizantes minerais. Os objetivos deste trabalho foram selecionar entre as espécies de adubos verdes mais eficientes em absorver o P na forma menos disponível e pela marcação isotópica destas plantas com ³²P, quantificar o aproveitamento deste nutriente proveniente dos adubos verdes e do fertilizante mineral pela cultura da cana-de-açúcar e do arroz, determinando suas reais contribuições como fonte de P. O estudo foi desenvolvido três fases, em amostras de Latossolo Vermelho Amarelo distrófico típico, com baixo teor de P, em casa-de-vegetação no CENA/USP. O primeiro experimento foi realizado com a finalidade de identificar e selecionar entre as 25 espécies de adubos verdes (AV) mais eficientes em absorver P através de métodos de diluição isotópica. As plantas foram cultivadas em delineamento inteiramente casualizado com três repetições. Com os resultados (13 variáveis) das 25 espécies de adubo verde realizou-se análise estatística de componentes principais (PCA) e de agrupamento hierárquico (AHA) visando grupar os mais similares. A PCA foi explicada pelas duas primeiras componentes, definidas como P acumulado na planta e o valor L, resultando em três grupos, sendo o tremoço a espécies mais eficiente em absorver o P menos disponível, portanto, há diferença entre as espécies quanto à absorção. A partir desses grupos foram selecionadas algumas espécies de adubos verdes para avaliar o aproveitamento do P (AP) do adubo verde e do superfosfato triplo (SFT) pela raiz e parte aérea da cana-de-açúcar (experimento II) e pela parte aérea do arroz (experimento III) através da técnica da diluição isotópica. Para a cana-de-açúcar, foram selecionados braquiária ruziziensis, crotalária juncea, guandu anão, estilosante cv. Campo grande e para o arroz, a crotalária juncea e guandu anão e quatro doses de SFT (0; 30; 60 e 120 mg/vaso de P). Em média, os AVs apresentaram baixo aproveitamento, sendo 0,1 % pela raiz da cana; 0,8% pela parte aérea da cana e 2,0% pelo arroz. Para SFT, o AP pela raiz da cana foi de 1,0%; 9,9% pela parte aérea e 4,0% pelo arroz. Assim, o AP do SFT é superior aos dos adubos verdes para as duas culturas, independente das espécies de adubos verdes. Obtêm-se maior aproveitamento do SFT para ambas as culturas, na dose de 30 mg/vaso de P. O P do adubo verde não é suficiente para suprir a total demanda da cultura principal, mas favorece a absorção do P pela cultura quando associada ao SFT. / Integration of green manures species, which immobilize P, with supplying mineral P sources is one of the most promising agronomic practices for improving the availability of P for the main crop in order to recover soil fertility, increasing soil organic matter and thus optimize the efficiency of mineral fertilizers. The objectives of this work was to select among the green manure species the most efficient in absorbing the less available form of P, and by isotopic labeling of this plants, quantify the use of this nutrient from the green manures and mineral fertilizer by the sugar cane and rice crops, determining their real contributions as a P source. It was developed in three phases, in dystrophic Typical Hapludox, low-P, in the greenhouse in CENA / USP. The first experiment was conducted to identify and select the green manure species the more efficient one in absorbing P by isotopic dilution techniue. The plants were grown in a completely randomized design with three replications. With 25 species of green manures and 13 variables statistical analysis of principal components (PCA) and hierarchical clustering (HCA) were carried out in order to group the most similar ones. The PCA was explained by the first two components, defined as plant accumulated P and the L value, resulting three groups, and the white lupin being the most efficient in absorbing less available P, so there is difference between species on the ability to absorb the less available form of soil P absorption. From these groups some species of green manure were selected to evaluate the P use efficiency (PUE), from green manure and triple superphosphate (TSP), both labeled with ³²P, by sugar cane (experiment II) and rice plant (experiment III) through the isotopic dilution technique. Brachiaria, sunnhemp, dwarf pigeon pea, stylosante cv. campo grande were selected for sugar cane and sunnhemp and dwarf pigeon pea for rice, and four rates of TSP (0, 30, 60 and 120 mg P/ pot). On average, the AVs had low PUE, begin 0.1% by the root of sugar cane, 0.8% by shoot of sugar cane and 2.0% by rice. For TSP, the PUE by sugar cane roots were 1.0%, 9.9% by shoots and 4.0% by rice plants. Thus PUE of TSP is greater than that of green manure for both crops, regardless of green manure species. The highest PUE of TSP for both crops was obtained at rate of 30 mg P/pot. The green manure P is not sufficient to meet total demand for the main crop, but improves the absorption of P by the crop when associated with SFT.

INTRODUÇÃO: Carcinomas mamários triplo-negativos correspondem ao grupo heterogêneo de neoplasias mamárias caracterizadas pela ausência de expressão dos receptores de estrogênio e progesterona e sem amplificação ou superexpressão do HER2. São mais prevalentes em mulheres jovens e em afrodescendentes. Eles se associam frequentemente ao fenótipo basal-símile determinado geneticamente, entretanto, incluem também outros tipos moleculares intrínsecos. Metodologias de análise genética de novas gerações têm permitido sua estratificação em subgrupos distintos, o que justifica a heterogeneidade clínica deste grupo de neoplasias. A identificação desses subgrupos através de marcadores imunoistoquímicos de aplicação prática ainda é pouco explorada, embora seja uma ferramenta promissora na sua estratificação e determinação de alvos terapêuticos. OBJETIVOS: Nosso objetivo é explorar os perfis imunoistoquímicos dos carcinomas mamários triplo-negativos em mulheres com idade até 45 anos e investigar possíveis diferenças entre as cinco regiões geográficas brasileiras. MÉTODOS: Selecionamos 118 amostras de tumores de pacientes com idade até 45 anos, com carcinoma invasivo, blocos de parafina disponíveis e perfil imunoistoquímico triplo-negativo, procedentes das cinco regiões geográficas. Estes casos foram revisados quanto à determinação de tipo e grau histológico e as seguintes características anatomopatológicas: contorno do tumor, presença e fração do componente \"in situ\", embolização vascular peritumoral, tipo e grau da reação estromal, presença de necrose tumoral e formação de túbulos pela neoplasia. Foram selecionadas áreas representativas do tumor para construção de blocos de microarranjos de tecido para estudo imunoistoquímico. Foram pesquisados os seguintes marcadores: citoqueratinas basais 5/6 e 14, citoqueratinas luminais 8 e 18, receptor do fator de crescimento epidérmico (EGFR ou HER1), receptor de androgênio, e-caderina, catenina-beta, claudinas 3, 4 e 7, vimentina, actina de músculo liso, p63, ALDH1 e Ki-67. De acordo com a expressão dos marcadores, os tumores foram classificados nos subgrupos basal-símile (expressão de citoqueratina basal 5/6 e/ou EGFR-positivo), claudina-baixo (claudinas e e-caderina-negativos), mesenquimal (vimentina-positivo), apócrino (receptor de androgênio-positivo), mioepitelial (p63 ou actina de músculo liso positivos), com perfil de células tronco (ALDH1 positivo), ou indefinido (padrões negativo para todos os marcadores). Nestes subtipos, a atividade proliferativa foi analisada através da expressão de Ki-67. As neoplasias provenientes das cinco regiões geográficas foram comparadas quanto às características histológicas e perfis imunoistoquímicos. RESULTADOS: A idade das pacientes variou de 26 anos a 45 anos ( média 38,3 +/-4,9 e mediana de 39 anos ). O tipo histológico mais frequente foi o carcinoma de tipo histológico não especial (107/118 casos; 90,7%). Observamos maior proporção de carcinomas de alto grau nas regiões nordeste, sul e sudeste. Os marcadores imunoistoquímicos não mostraram diferenças nas frequências entre as diferentes regiões geográficas. Observamos baixa atividade proliferativa determinada pela expressão do Ki-67 nos subgrupos com expressão do receptor de androgênio (apócrino) e sem expressão de vimentina (padrão não mesenquimal). Os tumores da região Nordeste, Sul e Sudeste apresentaram maior atividade proliferativa. Tumores ricos em linfócitos intratumorais apresentaram menor expressão de marcadores basais e do perfil basal-símile. CONCLUSÕES: Os subtipos moleculares determinados através da expressão imunoistoquímica não mostraram diferenças nas frequências entre as diferentes regiões geográficas. Os tumores das regiões Nordeste, Sul e Sudeste apresentaram maior atividade proliferativa. Os carcinomas ricos em linfócitos intratumorais apresentaram frequência menor do perfil basal / BACKGROUND: Triple-negative breast carcinomas (TNBC) correspond to a heterogeneous group of neoplasia characterized by the lack of expression of estrogen and progesterone receptors, and by the absence of amplification or overexpression of HER2. They are more prevalent among African descendants and younger women. They are often associated with the basal-like genetic phenotype; however, other intrinsic molecular types are included. Genomic analyses of next-generation methods have allowed stratification of TN breast carcinomas into distinct subgroups, explaining the clinical heterogeneity of this group of neoplasias. The identification of these subgroups by immunohistochemical markers is not well explored, although it represents a potential useful tool for the stratification and determination of therapeutic targets. OBJECTIVES: Our aim is to explore the TNBC immunohistochemical profile in patients of 45 year-old or younger, and to investigate possible differences among the five Brazilian geographic regions. METHODS: We\'ve selected 118 samples of tumors from patients up to 45 years-old from five Brazilian geographic regions, with invasive carcinoma, available paraffin blocks, and triple-negative immunohistochemical profile. All the cases were reviewed as for determination of histologic type and grading, and the following pathological features: tumor contour, presence and percentage of in situ component, peritumoral vascular embolization, type and grade of stromal reaction, presence of tumoral necrosis, and tubule formation by neoplasia. Representative tumor areas were selected for tissue microarray construction for immunohistochemical study. The following markers were studied: Basal cytokeratins 5/6 and 14; luminal cytokeratins 8 and 18; Epidermal growth factor receptor (EGFR or HER1); androgen receptor; e-cadherin; catenin-beta; claudins (3,4 and 7); vimentin; smooth-muscle actin; p63, ALDH1, and Ki-67. According to the expression of the markers, the tumors were grouped in the basal-like subgroups (basal cytokeratins 5/6 and/or EGFR positive), claudin-low (claudins and/or e-cadherin negative), mesenchymal (vimentin-positive), apocrine (androgen receptor positive), myoepithelial (p63 and/or smooth muscle actin positive), stem-cell (ALDH1-positive), or undefined (negative for all markers). In these subtypes the proliferative activity through the Ki-67 expression was analyzed. Neoplasias from the five regions were compared as for histological characteristics and immunohistochemical profiles. RESULTS: The age of patients ranged from 26 years to 45 years (mean 38.3 +/- 4.9 and median of 39 years). The most common histological type was no special histological type (NST) of carcinoma (107/118 cases, 90.7%). We observed a higher proportion of high-grade carcinomas in the regions Northeast, South and Southeast. Compared to the Midwestern and Northern regions there was no statistically significant difference (p = 0.03). The immunohistochemical markers showed no differences in the frequencies between the different geographical regions. We observed low proliferative activity determined by Ki-67 expression in the subgroups with androgen receptor expression (apocrine) and no expression of vimentin (no mesenchymal pattern). Tumors of the Northeast, South and Southeast have higher proliferative activity. There was a lower frequency of immunohistochemical markers associated with basal molecular type between tumors rich in lymphocytes. CONCLUSIONS: The molecular subtypes determined by immunohistochemical expression have shown no differences in the frequencies among the different geographical regions. Tumors in the Northeast, South and Southeast had higher proliferative activity. Carcinomas rich in intratumoral lymphocytes had lower frequency of basal profile

O câncer de mama triplo negativo (TNBC) é um dos tumores mais agressivos, muitas vezes resistentes à terapia sistêmica e com evolução para doença metastática. O entendimento de sua biologia e a concepção de novos tratamentos são essenciais para melhorar o seu prognóstico. Atualmente, as opções de tratamento são reduzidas e a quimioterapia ainda é o tratamento padrão. A expressão de SPARC (secreted protein acidic and rich in cysteine) é supostamente alterada em várias doenças malignas. No entanto, pouco se sabe sobre o valor prognóstico do SPARC em pacientes com TNBC. Usando uma pequena coorte de descoberta de TNBC muito bem caracterizada em relação à expressão do SPARC e comportamento clínico, conseguimos identificar vários genes como diferencialmente expressos na comparação entre amostras de TNBC / SPARC negativo vs. TNBC / SPARC positivo. Cinco desses genes diferencialmente expressos, SOHLH2, DNAJC12, LIM-1, CEACAM-5 e CTAG1A foram escolhidos para serem validados por imuno-histoquímica (IHC) em tissue microarrays (TMAs) contendo uma coorte independente de TNBC. Para acessar o valor prognóstico desses potenciais novos biomarcadores, avaliamos a associação entre a expressão de IHC e os resultados das pacientes pela análise de Kaplan-Meier para a coorte de validação. Foi observado que a coloração negativa da expressão de SOHLH2 e coloração positiva de DNAJC12 e LIM1 mostrou uma tendência a ser correlacionada com um pior prognóstico tanto para a sobrevida livre de doença quanto para sobrevida global. Nossos resultados fornecem novas informações sobre alterações transcriptômicas associadas ao comportamento clínico de TNBC que podem servir como ferramenta potencial para a identificação e caracterização de novos biomarcadores candidatos como fatores prognósticos e preditivos para pacientes com TNBC no futuro / Triple-negative breast cancer (TNBC) is one of the most aggressive, therapy-resistant, and metastatic tumors. Understanding of its biology and designing new treatments are essential to improve its prognosis. Currently, treatment options are reduced, and chemotherapy is still the standard treatment. SPARC (secreted protein acidic and rich in cysteine) expression is reportedly altered in various malignancies. However, little is known regarding the prognostic value of SPARC in TNBC patients. Using a small discovered cohort of TNBC very well characterized regarding SPARC expression status and clinical behavior, we were able to identify several genes as differentially expressed in the comparison between TNBC/SPARC negative vs. TNBC/SPARC positive samples. Five of these differentially expressed genes, SOHLH2, DNAJC12, LIM, CEACAM-5 and CTAG1A were chosen to be validated by immunohistochemistry (IHC) on tissue microarrays (TMAs) containing an independent cohort of TNBC. To access the prognostic value of these potential new biomarkers, we evaluated the association between the IHC expression and patient\'s outcomes by Kaplan-Meier analysis for the validation cohort. We found that negative staining of SOHLH2 expression and positive staining of DNAJC12 and LIM1 showed a trend to be correlated with a poor prognosis for both disease-free survival and overall survival. Our findings provide new information on transcriptome changes associated the clinical behavior of TNBC that may serve as a potential tool for the identification and characterization of new candidate biomarkers as prognostic and predictive factors for patients with TNBC in the future

Dans cette thèse, on étudie la structure de quelques types d'algèbres (binaires et ternaires) munies d'une forme bilinéaire symétrique, non dégénérée et associative (ou invariante). La première partie de cette thèse est consacrée à l'étude des algèbres de Leibniz quadratiques. On montre que ces algèbres sont symétriques. De plus, on utilise la T*-extension et la double extension pour montrer plusieurs résultats sur ce type d'algèbres. Ensuite, on a remarqué que l'anti-commutativité du crochet de Lie donne naissance à de nouveaux types d'invariance pour les algèbres de Leibniz : L'invariance à gauche et l'invariance à droite. Alors, on s'est intéresse à l'étude des algèbres de Leibniz (gauche et droite) munies d'une forme bilinéaire symétrique, non dégénérée et invariante à gauche (et invariante à droite). On prouve que ces algèbres sont Lie admissibles. En second lieu, on s'intéresse aux systèmes triples de Lie et de Jordan. On débute la deuxième partie de cette thèse par la description inductive des systèmes triples de Lie quadratiques au moyen de la double extension. En plus, on introduit la T*extension des systèmes triples de Jordan pseudo-Euclidien. Finalement, on donne deux nouvelles caractérisations des systèmes triples de Jordan semi-simples parmi les systèmes triples de Jordan pseudo-Euclidiens / In this thesis, we study the stucture of several types of algebras endowed with Symmetric, non degenerate and invariant bilinear forms. In the first part, we study quadratic Leibniz algebras. First, we prove that these algebras are symmetric. Then, we use the T*-extension and the double extension to prove some properties of this type of Leibniz algebras. Besides, since we observe that the skew-symmetry of the Leibniz bracket gives rise to other types of invariance for a bilinear form on a Leibniz algebra: The left invariance and the right invariance. We focus on the study of left (resp. right) Leibniz algebras with symmetric, non degenerate and left (resp. right) invariant bilinear form. In particular, we prove that these algebras are Lie admissibles. The second part of this work is dedicated to the study of quadratic Lie triple systems and pseudo-euclidien Jordan triple systems. We start by giving an inductive description of quadratic Lie triple systems using double extension. Next, we introduce the T*-extension of Jordan triple systems. Finally, we give new caracterizations of semi-simple Jordan triple systems among pseudo-euclidian Jordan triple systems