Os temas desenvolvimento sustentável e sustentabilidade vem norteando inúmeras discussões e debates, tanto no meio acadêmico como empresarial, em função da importância reconhecida pela sociedade da abordagem de questões ambientais, sociais e econômicas ou, em muitos casos, avaliações que vão além destas dimensões. O setor agropecuário, incluindo a suinocultura, por fazer uso de recursos naturais, coloca o foco das pesquisas do setor na dimensão ambiental, mas uma análise integrada e interrelacionada de todas as dimensões mostra-se necessária. A necessidade de criação de uma metodologia própria, acessível e composta por indicadores de desempenho específicos, que integrem as três dimensões propostas pelo Triple Bottom Line e baseada na percepção dos produtores para avaliação da suinocultura de terminação, desencadeou a motivação para a presente pesquisa. Construíram-se indicadores de desempenho abrangendo as dimensões social, ambiental e econômica, a fim de adaptar a metodologia M.A.I.S. (Método de Avaliação de Indicadores de sustentabilidade organizacional) para a suinocultura de terminação, em sistemas integrados de produção. Visando validar a ferramenta construída, esta metodologia foi avaliada por meio de uma pesquisa survey junto a 31 propriedades familiares do município de Aratiba (RS), detentor do maior rebanho suíno do Estado do Rio Grande do Sul no ano de 2011. Através deste estudo, foi conferido ao município o status de “em equilíbrio”, apesar da identificação de indicadores classificados como “em desequilíbrio” dentro das três dimensões propostas. O método permitiu, além da classificação, a visualização dos pontos críticos identificados em cada dimensão e em cada sistema produtivo do município amostrado. A aplicação da ferramenta também apontou limitações na construção de alguns indicadores, comprometendo a eficácia e validação do método como um todo. Porém, a análise indissociada e inter-relacionada dos indicadores e das dimensões, permitiu a identificação de pontos crítico que podem nortear o embasamento estratégico de ações públicas e privadas, a fim de contribuir com o desenvolvimento do setor. / The themes sustainable development and sustainability have guided countless discussions and debates in both academic and business circles. This is a direct result of the importance placed on society´s approach to environmental, social and economic issues and, in many cases, evaluations that go beyond these dimensions. The focus of the research has been on the environmental dimension, but an integrated and interrelated analysis of all dimensions is shown to be necessary. The motivation for this research was triggered by the need to create a methodology based on producer´s perception to evaluate finishing pig systems. The methodology needed to be specific to this area, accessible and composed of performance indicators which integrate the three dimensions proposed by Triple Bottom Line. Performance indicators were established encompassing social, environmental and economic dimensions to adapt M.A.I.S. methodology (Method of Evaluation of Organizational Sustainable Indicators) to swine termination in integrated systems of production. The methodology was validated through survey research applied in 2011 to 31 family properties in the rural area of the city of Aratiba, a region with the largest concentration of swine herds in the state of Rio Grande do Sul. As a result of the study, the region was granted the status of “balanced” despite the identification of unbalanced indicators within the three proposed dimensions. In addition to the classification, the method allowed for the visualization of critical points shown inside each dimension and each productive system of the sample properties. The application tool revealed limitations in the construction of some indicators, compromising effectiveness and validation of the method as a whole. However, the undissociated and interrelated analysis of indicators and dimensions allowed for the identification of some critical points that can guide the strategic foundation of public and private actions in order to contribute to the development of the sector.

The interaction of radiation with integrated circuits can provoke transient faults due to the deposit of charge in sensitive nodes of transistors. Because of the decrease the size in the process technology, charge sharing between transistors placed close to each other has been more and more observed. This phenomenon can lead to multiple transient faults. Therefore, it is important to analyze the effect of multiple transient faults in integrated circuits and investigate mitigation techniques able to cope with multiple faults. This work investigates the effect known as single-event-induced charge sharing in integrated circuits. Two main techniques are analyzed to cope with this effect. First, a placement constraint methodology is proposed. This technique uses placement constraints in standard cell based circuits. The objective is to achieve a layout for which the Soft-Error Rate (SER) due charge shared at adjacent cell is reduced. A set of fault injection was performed and the results show that the SER can be minimized due to single-event-induced charge sharing in according to the layout structure. Results show that by using placement constraint, it is possible to reduce the error rate from 12.85% to 10.63% due double faults. Second, Triple Modular Redundancy (TMR) schemes with different levels of granularities limited by majority voters are analyzed under multiple faults. The TMR versions are implemented using a standard design flow based on a traditional commercial standard cell library. An extensive fault injection campaign is then performed in order to verify the softerror rate due to single-event-induced charge sharing in multiple nodes. Results show that the proposed methodology becomes crucial to find the best trade-off in area, performance and soft-error rate when TMR designs are considered under multiple upsets. Results have been evaluated in a case-study circuit Advanced Encryption Standard (AES), synthesized to 90nm Application Specific Integrated Circuit (ASIC) library, and they show that combining the two techniques, the error rate resulted from multiple faults can be minimized or masked. By using TMR with different granularities and placement constraint methodology, it is possible to reduce the error rate from 11.06% to 0.00% for double faults. A detailed study of triple, four and five multiple faults combining both techniques are also described. We also tested the TMR with different granularities in SRAM-based FPGA platform. Results show that the versions with a fine grain scheme (FGTMR) were more effectiveness in masking multiple faults, similarly to results observed in the ASICs. In summary, the main contribution of this master thesis is the investigation of charge sharing effects in ASICs and the use of a combination of techniques based on TMR redundancy and placement to improve the tolerance under multiple faults.

INTRODUÇÃO: Carcinomas de mama triplo-negativos (CMTN) constituem um grupo de tumores heterogêneos caracterizados por sobrevida pobre dos pacientes e falta de terapia-alvo. Receptor andrógeno (AR) tem sido descrito no CMTN, mas o impacto prognóstico da expressão nesse subgrupo não está bem claro. OBJETIVO: Investigar a associação do status de expressão AR analisado por imunohistoquímica em casos de CMTN com parâmetros clínicos (idade, sobrevida) e variáveis patológicas (tamanho do tumor, grau do tumor). MÉTODOS: Foram analisados 62 CMTN por imuno-histoquímica automatizada para receptor andrógeno. A imuno-histoquímica foi avaliada por dois diferentes patologistas e a expressão do biomarcador foi avaliada por H-Score (intensidade mais percentagem de coloração). Kaplan-Meyer foi o método usado para avaliar a sobrevida global, tendo as diferenças nas distribuições sido avaliadas com base na expressão do marcador. RESULTADOS: 26% dos CMTNs foram AR positivos (n = 16) e 74% AR negativos (n = 46). Todos os casos de AR positivos ocorreram em mulheres ≥ 40 anos enquanto 13% dos casos de AR negativos foram vistos em mulheres ≤ 40 anos. 93% (52/56) de todos os CMTNs foram carcinoma ductal invasivo do tipo não especial (ICNST) e 93% (14/15) de AR positivos dos casos de ICNST. O tamanho do tumor variou de 2 a 4,9 cm na maioria dos cânceres AR positivos (n = 8/13; 62%). 60% (n = 9/15) dos casos de AR positivos mostraram grau histológico 3 seguidos de 27% de tumores de grau 2. Não se observou diferença entre pacientes AR positivos e AR negativos quando comparados por idade, tamanho do tumor, grau do tumor e tipo do tumor (p > 0,17). A positividade imuno-histoquímica para ARs também não foi associada com melhor sobrevida (p = 0,737; n = 51) ou sobrevida livre da doença (p = 0,552; n = 45) em CMTNs. CONCLUSÃO: Sob o ponto de vista do prognóstico, a imunorreatividade do AR tem sido associada com melhor sobrevida das pacientes. Esse resultado não foi confirmado na presente série. Isso poderia estar relacionado com o pequeno tamanho amostral ou com uma baixa prevalência de casos de AR positivos especificamente nesse subtipo de câncer de mama. Estudos realizados com maiores amostras são necessários para investigar esse biomarcador em CMTNs. / INTRODUCTION: Triple negative breast carcinomas (TNBC) are a heterogeneous group of tumors characterized by poor patient survival and lack of targeted therapies. Androgen receptor (AR) has been described in TNBC but the prognostic impact of the expression in this subgroup of tumors is not clear. OBJECTIVE: To investigate the association of AR expression status by immunohistochemistry in TNBC cases with clinical (age, survival) and pathological variables (tumor size, tumor grade). METHODS: 62 TNBC were analyzed by automated immunohistochemistry for androgen receptor. Immunohistochemistry was scored by two investigators and biomarker expression was assessed by H-Score (intensity plus the percentage of staining). Kaplan-Meier was used to evaluate overall survival, where differences in distributions were evaluated based on marker expression. RESULTS: 26% of TNBC were AR-positive (n = 16) and 74% AR negative (n = 46). All AR-positive cases occurred in women ≥ 40 years, while 13% of AR-negative cases were seen in women ≤ 40 years. 93% (52/56) of all TNBC were infiltrating ductal carcinomas of no special type (ICNST) and 14/15 (93%) of AR-positive cases were ICNST. Tumor size varied from 2-4.9 cm in the majority of AR-positive cancers (n = 8/13; 62%). 60% (n = 9/15) of AR-positive cases showed histological grade 3 tumors, followed by 27% of grade 2 tumors. No differences were observed between AR-positive and AR-negative patients when compared for age, tumor size, tumor grade and tumor type (all p > 0.17). AR immunohistochemical positivity was also not associated with better overall survival (p = 0.737, n = 51) or disease-free survival (p = 0.552; n = 45) in TNBCs. CONCLUSION: From the prognostic point of view, AR immunoreactivity has been associated with better overall patient survival. Unfortunately, this result could not be confirmed in our series. This could be related to the relatively small series of analyzed samples and to the low prevalence of AR-positive cases in this specific breast cancer subtype. Further studies with bigger samples are needed to investigate this biomarker in TNBC.

INTRODUÇÃO: O câncer de mama é uma importante causa de morbimortalidade, é conhecido por ser uma doença heterogênea. A caracterização clínica e molecular de seus subtipos é fundamental para nortear o prognóstico e o tratamento dessas pacientes. Novos estudos são necessários na melhor caracterização dos tumores triplo-negativos. O estudo da expressão das claudinas pode auxiliar na caracterização desses tumores. OBJETIVO: Investigar a associação da expressão das claudinas 1, 3, 4 e 7 e E-caderina com variáveis clínico-patológicas e fatores prognósticos, em uma série de tumores de mama triplo-negativos (RE-, RP- e HER2-). MÉTODOS: 80 tumores triplo-negativos foram analisados por imunoistoquímica automatizada para as claudinas 1, 3, 4, 7 e E-caderina. A expressão imunoistoquímica foi avaliada pelo escore H (intensidade multiplicada pela porcentagem de marcação). Foram avaliadas as associações entre características clínico-patólogicas e o escore H. Para a avaliação prognóstica das pacientes, curvas de Kaplan-Meier foram construídas a partir dos dados de seguimento das pacientes e do escore H. RESULTADOS: Foi encontrada associação significativa entre o alto escore H da CLDN-1 (HCLDN-1) e pacientes mais idosas e com a presença de necrose, alto escore H da E-caderina (HE-CAD) em pacientes mais jovens e baixo escore H da CLDN-7 (HCLDN-7) e Ki67 positivo. Além disso, pacientes com elevado HCLDN-1 tiveram menor sobrevida geral. Por outro lado, o elevado HCLDN-3 apresentou uma tendência à associação com maior sobrevida geral e sobrevida livre de doença. CONCLUSÕES: A expressão diferencial das claudinas e E-caderina podem auxiliar na caracterização clinico-patológica dos tumores triplo-negativos. Além disso, as claudinas 1 e 3 parecem ser fatores prognósticos para esses tumores. / INTRODUCTION: Breast cancer is a major cause of morbidity and mortality, is known to be a heterogeneous disease. The clinical and molecular characterization of its subtypes is critical to guide the prognosis and treatment of these patients. Further studies are needed for the best characterization of triple-negative tumors. The study of the expression of claudinas can aid in the characterization of these tumors. OBJECTIVE: To investigate the association of expression of claudinas 1, 3, 4 and 7 and E-cadherin with clinicopathological variables and prognosis in a series of triple-negative breast cancers (ER-, PR- and HER2-). METHODS: 80 triple negative tumors were analyzed by automated immunohistochemistry for the claudins 1, 3, 4, 7 and E-cadherin. The immunohistochemical expression was assessed by H-Score (intensity multiplied by the percentage of staining). We evaluated the associations between clinicopathological characteristics and H-Score. For the prognostic assessment of patients, Kaplan-Meier curves were constructed from the follow-up data of patients and H-Score. RESULTS: We found a significant association between high H-Score of CLDN-1 (HCLDN-1) and older patients and the presence of necrosis, high H-Score of E-cadherin (H-CAD) in younger patients and low H-Score CLDN-7-(7-HCLDN) and Ki67 positive. Furthermore, patients with high-HCLDN1 had a lower overall survival. On the other hand, the high HCLDN-3 showed a trend toward association with greater overall survival and disease-free survival. CONCLUSIONS: Differencial expression of claudins and E-cadherin can help in clinic-pathological characterization of triple-negative tumors. Futhermore, claudin 1 and 3 appear to be prognostic factor for these tumors.

abstract: In the United States, 12% of women are typically diagnosed with breast cancer, where 20-30% of these cases are identified as Triple Negative Breast Cancer (TNBC). In the state of Arizona, 810 deaths occur due to breast cancer and more than 4,600 cases are diagnosed every year (American Cancer Society). The lack of estrogen, progesterone, and HER2 receptors in TNBC makes discovery of targeted therapies further challenging. To tackle this issue, a novel multi-component drug vehicle is presented. Previously, we have shown that mitoxantrone, a DNA damaging drug, can sensitize TNBC cells to TRAIL, which is a protein that can selectively kill cancer cells. In this current study, we have formulated aminoglycoside-derived nanoparticles (liposomes) loaded with mitoxantrone, PARP inhibitors, for delivery to cancer cells. PARP inhibitors are helpful in preventing cancer cells from repairing their DNA following damage with other drugs (e.g. mitoxantrone). Various treatment liposome groups, consisting of lipid-containing polymers (lipopolymers) synthesized in our laboratory, were formulated and characterized for their size, surface charge, and stability. PARP inhibitors and treatment of cells for in-vitro and in-vivo experiments with these liposomes resulted in synergistic death of cancer cells. Finally, studies to evaluate the pre-clinical efficacy of these approaches using immuno-deficient mouse models of TNBC disease have been initiated. / Dissertation/Thesis / Masters Thesis Chemical Engineering 2018

Les techniques de réalisation des reconstitutions prothétiques en Odontologie ont été profondément modifiées par l'avènement et le développement de la Conception et Fabrication Assistées par Ordinateur (CFAO). La qualité d'une prothèse fixée est caractérisée par la bonne adaptation de celle-ci sur son pilier dentaire afin d'assurer la longévité de l'assemblage dentoprothétique. L'évaluation de l'adaptation marginale et interne par l'analyse du hiatus est un élément essentiel du contrôle de leur qualité. Cependant, la littérature rapporte de nombreuses méthodes d'évaluation de l'adaptation compromettant d'autant la comparaison pertinente et la validité des valeurs de ces hiatus. Le but de cette thèse est la mise au point d'une méthode de mesure du hiatus dento-prothétique qui bénéficierait de qualités métrologiques suffisantes pour rendre pertinente la comparaison et l'analyse des différentes chaînes de mesure accessibles sur le marché. L'étude des besoins métrologiques de l'évaluation du hiatus et des méthodes de mesure recensés dans la littérature a permis de retenir une chaîne de mesure, dénommée "Triple scan". Grâce aux résultats obtenus au cours de ces travaux, cette méthode semble pertinente pour évaluer tridimensionnellement le hiatus dento-prothétique. Elle a été comparée à d'autres méthodes documentées et validées dans la littérature telles que la méthode des répliques en élastomère et celle utilisant la microtomographie Rx. Les résultats obtenus conduisent à conclure que la méthode "Triple scan" serait plus appropriée dans les expertises approfondies sur les performances des systèmes de CFAO en termes de fidélité aux paramètres fixés et de reproductibilité de leur fabrication. / Techniques for producing prosthetic reconstitutions in odontology have undergone radical change due to the emergence and development of Computer Aided Design and Manufacturing (CAD/CAM). The quality of a fixed prosthesis is characterised by its correct adaptation on its dental abutment to ensure the longevity of the dento-prosthetic assembly. Evaluating the marginal and internal adaptation by analysing the gap is essential for controlling its quality. However, the numerous methods reported in the literature make it difficult to perform a pertinent and valid analysis of the values of these gaps. The purpose of this thesis is the development of a method of measuring the dento-prosthetic gap endowed with sufficient metrological capacities to ensure the pertinence of comparisons and analyses of the different measurement systems available on the market. The study of metrological requirements for evaluating the gap and the measurement methods identified in the literature has led to the selection of measurement system known as II Triple scan". The results obtained during these works demonstrated the pertinence of this method for the 3-dimensional evaluation of the dento­-prosthetic gap. It was compared to other methods documented and validated in the literature such as the elastomer replica method and that using X-ray microtomography. The results obtained lead to the conclusion that the "Triple scan" is the most appropriate for in-depth analysis of the performances of CAD/CAM systems in terms of fidelity to the parameters determined and the reproducibility of fabrication.

INTRODUÇÃO: O câncer de mama é uma importante causa de morbimortalidade, é conhecido por ser uma doença heterogênea. A caracterização clínica e molecular de seus subtipos é fundamental para nortear o prognóstico e o tratamento dessas pacientes. Novos estudos são necessários na melhor caracterização dos tumores triplo-negativos. O estudo da expressão das claudinas pode auxiliar na caracterização desses tumores. OBJETIVO: Investigar a associação da expressão das claudinas 1, 3, 4 e 7 e E-caderina com variáveis clínico-patológicas e fatores prognósticos, em uma série de tumores de mama triplo-negativos (RE-, RP- e HER2-). MÉTODOS: 80 tumores triplo-negativos foram analisados por imunoistoquímica automatizada para as claudinas 1, 3, 4, 7 e E-caderina. A expressão imunoistoquímica foi avaliada pelo escore H (intensidade multiplicada pela porcentagem de marcação). Foram avaliadas as associações entre características clínico-patólogicas e o escore H. Para a avaliação prognóstica das pacientes, curvas de Kaplan-Meier foram construídas a partir dos dados de seguimento das pacientes e do escore H. RESULTADOS: Foi encontrada associação significativa entre o alto escore H da CLDN-1 (HCLDN-1) e pacientes mais idosas e com a presença de necrose, alto escore H da E-caderina (HE-CAD) em pacientes mais jovens e baixo escore H da CLDN-7 (HCLDN-7) e Ki67 positivo. Além disso, pacientes com elevado HCLDN-1 tiveram menor sobrevida geral. Por outro lado, o elevado HCLDN-3 apresentou uma tendência à associação com maior sobrevida geral e sobrevida livre de doença. CONCLUSÕES: A expressão diferencial das claudinas e E-caderina podem auxiliar na caracterização clinico-patológica dos tumores triplo-negativos. Além disso, as claudinas 1 e 3 parecem ser fatores prognósticos para esses tumores. / INTRODUCTION: Breast cancer is a major cause of morbidity and mortality, is known to be a heterogeneous disease. The clinical and molecular characterization of its subtypes is critical to guide the prognosis and treatment of these patients. Further studies are needed for the best characterization of triple-negative tumors. The study of the expression of claudinas can aid in the characterization of these tumors. OBJECTIVE: To investigate the association of expression of claudinas 1, 3, 4 and 7 and E-cadherin with clinicopathological variables and prognosis in a series of triple-negative breast cancers (ER-, PR- and HER2-). METHODS: 80 triple negative tumors were analyzed by automated immunohistochemistry for the claudins 1, 3, 4, 7 and E-cadherin. The immunohistochemical expression was assessed by H-Score (intensity multiplied by the percentage of staining). We evaluated the associations between clinicopathological characteristics and H-Score. For the prognostic assessment of patients, Kaplan-Meier curves were constructed from the follow-up data of patients and H-Score. RESULTS: We found a significant association between high H-Score of CLDN-1 (HCLDN-1) and older patients and the presence of necrosis, high H-Score of E-cadherin (H-CAD) in younger patients and low H-Score CLDN-7-(7-HCLDN) and Ki67 positive. Furthermore, patients with high-HCLDN1 had a lower overall survival. On the other hand, the high HCLDN-3 showed a trend toward association with greater overall survival and disease-free survival. CONCLUSIONS: Differencial expression of claudins and E-cadherin can help in clinic-pathological characterization of triple-negative tumors. Futhermore, claudin 1 and 3 appear to be prognostic factor for these tumors.

INTRODUÇÃO: o câncer de mama é uma doença heterogênea. Há necessidade de critérios diagnósticos e prognósticos mais refinados. O emprego da imunohistoquímica, através do painel prognóstico, fez despontar a figura do carcinoma triplonegativo e, da mesma forma, a histogenética trouxe à evidência o carcinoma basal. Paralelamente, o conhecimento sobre a origem biológica das neoplasias e da sua heterogeneidade vem sendo acentuadamente debatido através do tema das células-tronco tumorais. OBJETIVOS: investigar a prevalência de carcinomas basais e pentanegativos, numa amostra de carcinomas triplonegativos, e estabelecer associações com a expressão de células-tronco tumorais nestes tumores. Verificar diferenças entre estes subtipos com as variáveis clinicopatológicas. MÉTODOS: 94 carcinomas mamários triplonegativos foram testados para CK5/6, HER1, CD44 e CD24. As expressões desses marcadores por imuno-histoquímica automatizada foram avaliadas através de escore simples de positividade (porcentagem de células) e correlacionadas com os dados clínico-patológicos e análise de sobrevivência. RESULTADOS: carcinomas basais apresentam maior grau tumoral que carcinomas pentanegativos (p=0,004). A negatividade para CD44 (p=0,007) e o perfil CD44- CD24+ (p=0,013) foram associados com maior invasão vascular entre carcinomas triplonegativos. A expressão de CD44 foi associada aos carcinomas basais (p=0,007). O perfil CD44-CD24-/low foi associado aos carcinomas pentanegativos (p=0,04). Nenhuma das variáveis em estudo foi associada com os desfechos clínicos. CONCLUSÃO: Carcinomas mamários basais e pentanegativos são subtipos tumorais bastante próximos. Nosso estudo é o primeiro desenhado especificamente para avaliar a presença células tronco-tumorais mamárias entre carcinomas basais e pentanegativos, onde o perfil CD44-CD24-/low foi associado ao subtipo pentanegativo, e o perfil CD44-CD24+ à invasão vascular, resultados que merecem confirmação por histogenética em estudos de maior porte. / INTRODUCTION: Breast cancer is a heterogeneous disease, and there is a need for more refined diagnostic and prognostic criteria. Immunohistochemistry, as a breast prognostic panel, has given rise to triple-negative carcinoma, as well as histogenetics highlighted basal carcinoma. Concomitantly, the understanding of the biological origins of neoplasia and its heterogeneity has been strongly debated through the theme of cancer stem cells. OBJECTIVES: To investigate the prevalence of basal and penta-negative carcinomas in a sample of triple-negative carcinomas and to establish associations with cancer stem cells (CD44/CD24 expression profiles) and the clinicopathological variables within these tumors. METHODS: Ninety-four triplenegative breast carcinomas were tested for CK5/6, HER1, CD44 and CD24. The expression of these markers was evaluated by automated immunohistochemistry using a simple positivity score (percentage of cells) and was correlated with the clinicopathological and survival analysis data. RESULTS: Basal carcinomas had higher tumor grades than penta-negative carcinomas (p=0.004). CD44 negativity (p=0.007) and the CD44-CD24+ phenotype (p=0.013) were associated with increased vascular invasion amongst the triple-negative carcinomas. CD44 expression was associated with basal carcinomas (p=0.007). The CD44-CD24-/low phenotype was associated with penta-negative carcinomas. None of the variables in the study were associated with clinical outcome. CONCLUSION: Basal and penta-negative breast carcinomas are closely related tumor subtypes. Our study is the first to be specifically designed to assess the presence of breast cancer stem cells in basal and pentanegative carcinomas. The CD44-CD24-/low phenotype was associated with the pentanegative subtype, and the CD44-CD24+ phenotype was associated with vascular invasion. These results require histogenetic confirmation in larger studies.

Os temas desenvolvimento sustentável e sustentabilidade vem norteando inúmeras discussões e debates, tanto no meio acadêmico como empresarial, em função da importância reconhecida pela sociedade da abordagem de questões ambientais, sociais e econômicas ou, em muitos casos, avaliações que vão além destas dimensões. O setor agropecuário, incluindo a suinocultura, por fazer uso de recursos naturais, coloca o foco das pesquisas do setor na dimensão ambiental, mas uma análise integrada e interrelacionada de todas as dimensões mostra-se necessária. A necessidade de criação de uma metodologia própria, acessível e composta por indicadores de desempenho específicos, que integrem as três dimensões propostas pelo Triple Bottom Line e baseada na percepção dos produtores para avaliação da suinocultura de terminação, desencadeou a motivação para a presente pesquisa. Construíram-se indicadores de desempenho abrangendo as dimensões social, ambiental e econômica, a fim de adaptar a metodologia M.A.I.S. (Método de Avaliação de Indicadores de sustentabilidade organizacional) para a suinocultura de terminação, em sistemas integrados de produção. Visando validar a ferramenta construída, esta metodologia foi avaliada por meio de uma pesquisa survey junto a 31 propriedades familiares do município de Aratiba (RS), detentor do maior rebanho suíno do Estado do Rio Grande do Sul no ano de 2011. Através deste estudo, foi conferido ao município o status de “em equilíbrio”, apesar da identificação de indicadores classificados como “em desequilíbrio” dentro das três dimensões propostas. O método permitiu, além da classificação, a visualização dos pontos críticos identificados em cada dimensão e em cada sistema produtivo do município amostrado. A aplicação da ferramenta também apontou limitações na construção de alguns indicadores, comprometendo a eficácia e validação do método como um todo. Porém, a análise indissociada e inter-relacionada dos indicadores e das dimensões, permitiu a identificação de pontos crítico que podem nortear o embasamento estratégico de ações públicas e privadas, a fim de contribuir com o desenvolvimento do setor. / The themes sustainable development and sustainability have guided countless discussions and debates in both academic and business circles. This is a direct result of the importance placed on society´s approach to environmental, social and economic issues and, in many cases, evaluations that go beyond these dimensions. The focus of the research has been on the environmental dimension, but an integrated and interrelated analysis of all dimensions is shown to be necessary. The motivation for this research was triggered by the need to create a methodology based on producer´s perception to evaluate finishing pig systems. The methodology needed to be specific to this area, accessible and composed of performance indicators which integrate the three dimensions proposed by Triple Bottom Line. Performance indicators were established encompassing social, environmental and economic dimensions to adapt M.A.I.S. methodology (Method of Evaluation of Organizational Sustainable Indicators) to swine termination in integrated systems of production. The methodology was validated through survey research applied in 2011 to 31 family properties in the rural area of the city of Aratiba, a region with the largest concentration of swine herds in the state of Rio Grande do Sul. As a result of the study, the region was granted the status of “balanced” despite the identification of unbalanced indicators within the three proposed dimensions. In addition to the classification, the method allowed for the visualization of critical points shown inside each dimension and each productive system of the sample properties. The application tool revealed limitations in the construction of some indicators, compromising effectiveness and validation of the method as a whole. However, the undissociated and interrelated analysis of indicators and dimensions allowed for the identification of some critical points that can guide the strategic foundation of public and private actions in order to contribute to the development of the sector.

INTRODUÇÃO: Carcinomas de mama triplo-negativos (CMTN) constituem um grupo de tumores heterogêneos caracterizados por sobrevida pobre dos pacientes e falta de terapia-alvo. Receptor andrógeno (AR) tem sido descrito no CMTN, mas o impacto prognóstico da expressão nesse subgrupo não está bem claro. OBJETIVO: Investigar a associação do status de expressão AR analisado por imunohistoquímica em casos de CMTN com parâmetros clínicos (idade, sobrevida) e variáveis patológicas (tamanho do tumor, grau do tumor). MÉTODOS: Foram analisados 62 CMTN por imuno-histoquímica automatizada para receptor andrógeno. A imuno-histoquímica foi avaliada por dois diferentes patologistas e a expressão do biomarcador foi avaliada por H-Score (intensidade mais percentagem de coloração). Kaplan-Meyer foi o método usado para avaliar a sobrevida global, tendo as diferenças nas distribuições sido avaliadas com base na expressão do marcador. RESULTADOS: 26% dos CMTNs foram AR positivos (n = 16) e 74% AR negativos (n = 46). Todos os casos de AR positivos ocorreram em mulheres ≥ 40 anos enquanto 13% dos casos de AR negativos foram vistos em mulheres ≤ 40 anos. 93% (52/56) de todos os CMTNs foram carcinoma ductal invasivo do tipo não especial (ICNST) e 93% (14/15) de AR positivos dos casos de ICNST. O tamanho do tumor variou de 2 a 4,9 cm na maioria dos cânceres AR positivos (n = 8/13; 62%). 60% (n = 9/15) dos casos de AR positivos mostraram grau histológico 3 seguidos de 27% de tumores de grau 2. Não se observou diferença entre pacientes AR positivos e AR negativos quando comparados por idade, tamanho do tumor, grau do tumor e tipo do tumor (p > 0,17). A positividade imuno-histoquímica para ARs também não foi associada com melhor sobrevida (p = 0,737; n = 51) ou sobrevida livre da doença (p = 0,552; n = 45) em CMTNs. CONCLUSÃO: Sob o ponto de vista do prognóstico, a imunorreatividade do AR tem sido associada com melhor sobrevida das pacientes. Esse resultado não foi confirmado na presente série. Isso poderia estar relacionado com o pequeno tamanho amostral ou com uma baixa prevalência de casos de AR positivos especificamente nesse subtipo de câncer de mama. Estudos realizados com maiores amostras são necessários para investigar esse biomarcador em CMTNs. / INTRODUCTION: Triple negative breast carcinomas (TNBC) are a heterogeneous group of tumors characterized by poor patient survival and lack of targeted therapies. Androgen receptor (AR) has been described in TNBC but the prognostic impact of the expression in this subgroup of tumors is not clear. OBJECTIVE: To investigate the association of AR expression status by immunohistochemistry in TNBC cases with clinical (age, survival) and pathological variables (tumor size, tumor grade). METHODS: 62 TNBC were analyzed by automated immunohistochemistry for androgen receptor. Immunohistochemistry was scored by two investigators and biomarker expression was assessed by H-Score (intensity plus the percentage of staining). Kaplan-Meier was used to evaluate overall survival, where differences in distributions were evaluated based on marker expression. RESULTS: 26% of TNBC were AR-positive (n = 16) and 74% AR negative (n = 46). All AR-positive cases occurred in women ≥ 40 years, while 13% of AR-negative cases were seen in women ≤ 40 years. 93% (52/56) of all TNBC were infiltrating ductal carcinomas of no special type (ICNST) and 14/15 (93%) of AR-positive cases were ICNST. Tumor size varied from 2-4.9 cm in the majority of AR-positive cancers (n = 8/13; 62%). 60% (n = 9/15) of AR-positive cases showed histological grade 3 tumors, followed by 27% of grade 2 tumors. No differences were observed between AR-positive and AR-negative patients when compared for age, tumor size, tumor grade and tumor type (all p > 0.17). AR immunohistochemical positivity was also not associated with better overall survival (p = 0.737, n = 51) or disease-free survival (p = 0.552; n = 45) in TNBCs. CONCLUSION: From the prognostic point of view, AR immunoreactivity has been associated with better overall patient survival. Unfortunately, this result could not be confirmed in our series. This could be related to the relatively small series of analyzed samples and to the low prevalence of AR-positive cases in this specific breast cancer subtype. Further studies with bigger samples are needed to investigate this biomarker in TNBC.