Implementação de um sistema para simulação por Monte Carlo da passagem de fotões através do olho humano mediante a utilização da plataforma GEANT4 - I

Dissertação para obtenção do Grau de Mestre em Engenharia Biomédica

A influência da manutenção industrial no índice global de eficiência (OEE)

Dissertação para obtenção do Grau de Mestre em Engenharia e Gestão Industrial

Imunodeficiência Combinada Grave – O Diagnóstico Precoce é Importante?

Introdução: Os doentes com Imunodeficiência Combinada Grave (SCID) não diagnosticados evoluem inexoravelmente para a morte no primeiro ano de vida. Um elevado índice de suspeição é fundamental para o diagnóstico precoce, o factor mais importante para a sobrevida destas crianças. Objectivo: Apresentam-se três casos clínicos ilustrativos da importância da precocidade diagnóstica no prognóstico final. Casos clínicos: Caso clínico 1: Lactente do sexo masculino, com antecedentes de infecções respiratórias de repetição, internado aos sete meses na UCIP do HDE por pneumonia a Adenovírus com insuficiência respiratória. Necessitou de ventilação mecânica e de duas transfusões de concentrado eritrocitário na primeira semana de internamento. Teve exantema exuberante, interpretado como toxidermia. Evoluiu para doença pulmonar sequelar grave. Aos nove meses foi feito o diagnóstico de SCID hipomorfa com doença do enxerto contra o hospedeiro pós-transfusional, controlada com imunossupressão (ciclosporina e glucocorticoides). Não foi transplantado com células progenitoras hematopoiéticas por não reunir condições clínicas. Na sequência de uma intercorrência respiratória veio a falecer aos 14 meses. Caso clínico 2: Lactente do sexo masculino, internado aos 6 meses no HDE por pneumonia intersticial hipoxemiante. Isolado P. jiroveci no lavado bronco-alveolar e feito o diagnóstico presuntivo de BCGite disseminado em criança com SCID T-B+NK-. Após estabilização clínica e esplenectomia foi transplantado com células progenitoras hematopoiéticas de dador fenoidêntico não aparentado. Dada a BCGite disseminada necessitou de vários ciclos de infusão de células do dador para uma reconstituição imunitária lenta e progressiva. Seis meses pós-transplante está clinicamente bem, com quimerismo linfóide T e NK completo. Caso clínico 3: Lactente do sexo masculino, internado aos 17 dias de vida por infecção respiratória alta e bacteriémia a M. catarrhalis. Reinternado quinze dias depois por sépsis a MRSA e linfopénia. A avaliação efectuada permitiu o diagnóstico de SCID T-B+NK- por defeito na cadeia gamma comum. Transplantado com células progenitoras hematopoiéticas de dador genoidêntico aos 4 meses, sem condicionamento. Clinicamente bem, seis meses pós-transplante, com reconstituição imunitária satisfatória. Conclusão: Esta doença tem uma prevalência não negligenciável e apenas com elevado indice de suspeição se pode estabelecer um plano de tratamento eficaz.

Peritubular Capillaries C4d Deposits in Renal Allograft Biopsies and Anti HLA I/II Alloantibodies Screening. Incidence and Clinical Importance

Aim: To characterise clinically the patients with C4d in peritubular capillaries deposits (C4dPTCD) and/or circulating anti-HLA class I/II alloantibodies. To determine the correlation between positive C4dPTCD and circulating anti-HLA class I/II alloantibodies during episodes of graft dysfunction. Subjects and Methods: C4d staining was performed in biopsies with available frozen tissue obtained between January 2004 and December 2006. The study was prospective from March 2005, when a serum sample was obtained at the time of biopsy to detect circulating anti-HLA class I/II alloantibodies. Results: We studied 109 biopsies in 86 cadaver renal transplant patients. Sixteen of these (14.7%) presented diffuse positive C4dPTCD. There was a 13.5% rate of +C4dPTCD incidence within the first six months of transplantation and 16% after six months (p>0.05). Half of the +C4dPTCD in the first six months was associated with acute humoral rejection. After six months, the majority of +C4dPTCD (n=7/8) was present in biopsies with evidence of interstitial fibrosis/tubular atrophy and/or transplant glomerulopathy. The C4dPTCD was more frequent in patients with positive anti-HCV antibodies(p<0.0001), a previous renal transplant (p=0.007), and with a panel reactivity antibody (PRA) ≥ 50%(p=0.0098). The anti-HCV+ patients had longer time on dialysis (p=0.0019) and higher PRA(p=0.005). Circulating anti-HLA I/II alloantibodies were screened in 46 serum samples. They were positive in 10.9% of samples, all obtained after six months post transplant. Circulating alloantibodies were absent in 92.5% of the C4d negative biopsies. Conclusion: We found an association between the presence of C4dPTCD and 2nd transplant recipients,higher PRA and the presence of anti-HCV antibodies. The presence of HCV antibodies is not a risk factor for C4dPTCD per se, but appears to reflect longer time on dialysis and presensitisation. In renal dysfunction a negative alloantibody screening is associated with a reduced risk of C4dPTCD (<10%).

Biological predictors of survival in limphoma and mechanisms underlying follicular lymphoma transformaion into diffuse large B cell lymphoma (vol I e II)

RESUMO: Os biomarcadores tumorais permitem identificar os doentes com maior risco de recorrência da doença, predizer a resposta tumoral à terapêutica e, finalmente, definir candidatos a novos alvos terapêuticos. Novos biomarcadores são especialmente necessários na abordagem clínica dos linfomas. Actualmente, esses tumores são diagnosticados através de uma combinação de características morfológicas, fenotípicas e moleculares, mas o prognóstico e o planeamento terapêutico estão quase exclusivamente dependentes de características clínicas. Estes factores clínicos são, na maioria dos linfomas, insuficientes numa proporção significativa dos doentes, em particular, aqueles com pior prognóstico. O linfoma folicular (LF) é, globalmente, o segundo subtipo mais comum de linfoma. É tipicamente uma doença indolente com uma sobrevida média entre os 8 e 12 anos, mas é geralmente fatal quando se transforma num linfoma agressivo de alto grau, habitualmente o linfoma difuso de grandes células B (LDGCB). Morfologicamente e funcionalmente, as células do LF recapitulam as células normais do centro germinativo na sua dependência de sobrevivência do microambiente não-tumoral, especialmente das células do sistema imunológico. Biomarcadores preditivos de transformação não existem pelo que um melhor conhecimento da biologia intrínseca de progressão do LF poderá revelar novos candidatos. Nesta tese descrevo duas abordagens distintas para a descoberta de novos biomarcadores. A primeira, o estudo da expressão global de genes ('genomics') obtidos por técnicas de alto rendimento que analisam todo o genoma humano sequenciado, permitindo identificar novas anomalias genéticas que possam representar mecanismos biológicos importantes de transformação. São descritos novos genes e alterações genómicas associados à transformação do LF, sendo especialmente relevantes as relacionadas com os eventos iniciais de transformação em LDGCB. A segunda, baseou-se em várias hipóteses centradas no microambiente do LF, rico em vários tipos de células nãomalignas. Os estudos imunoarquitectural de macrófagos, células T regulatórias e densidade de microvasos efectuado em biopsias de diagnóstico de doentes com LF tratados uniformemente correlacionaram-se significativamente, e independentemente dos critérios clínicos, com a evolução clínica e, mais importante, com o risco de transformação em LDGCB. Nesta tese, foram preferencialmente utilizadas (e optimizadas) técnicas que permitam o uso de amostras fixadas em parafina e formalina (FFPET). Estas são facilmente acessíveis a partir das biopsias de diagnóstico de rotina presentes nos arquivos de todos os departamentos de patologia, facilitando uma transição rápida dos novos marcadores para a prática clínica. Embora o FL fosse o tema principal da tese, os novos achados permitiram estender facilmente hipóteses semelhantes a outros subtipos de linfoma. Assim, são propostos e validados vários biomarcadores promissores e relacionados com o microambiente não tumoral, sobretudo dependentes das células do sistema imunológico, como contribuintes importantes para a biologia dos linfomas. Estes sugerem novas opções para a abordagem clínica destas doenças e, eventualmente, novos alvos terapêuticos.------------- ABSTRACT: Cancer biomarkers provide an opportunity to identify those patients most at risk for disease recurrence, predict which tumours will respond to different therapeutic approaches and ultimately define candidate biomarkers that may serve as targets for personalized therapy. New biomarkers are especially needed in the management of lymphoid cancers. At present, these tumours are diagnosed using a combination of morphologic, phenotypic and molecular features but prognosis and overall survival are mostly dependent on clinical characteristics. In most lymphoma types, these imprecisely assess a significant proportion of patients, in particular, those with very poor outcomes. Follicular lymphoma (FL) is the second most common lymphoma subtype worldwide. It is typically an indolent disease with current median survivals in the range of 8-12 years, but is usually fatal when it transforms into an aggressive high-grade lymphoma, characteristically Diffuse Large B Cell Lymphoma (DLBCL). Morphologically and functionally it recapitulates the normal cells of the germinal center with its survival dependency on non-malignant immune and immunerelated cells. Informative markers of transformation related to the intrinsic biology of FL progression are needed. Within this thesis two separate approaches to biomarker discovery were employed. The first was to study the global expression of genes (‘genomics’) obtained using high-throughput, wholegenome-wide approaches that offered the possibility for discovery of new genetic abnormalities that might represent the important biological mechanisms of transformation. Gene signatures associated with early events of transformation were found. Another approach relied on hypothesis-driven concepts focusing upon the microenvironment, rich in several non-malignant cell types. The immunoarchitectural studies of macrophages, regulatory T cells and microvessel density on diagnostic biopsies of uniformly treated FL patients significantly predicted clinical outcome and, importantly, also informed on the risk of transformation. Techniques that enabled the use of routine formalin fixed paraffin embedded diagnostic specimens from the pathology department archives were preferentially used in this thesis with the goal of fulfilling a rapid bench-to-beside” translation for these new findings. Although FL was the main subject of the thesis the new findings and hypotheses allowed easy transition into other lymphoma types. Several promising biomarkers were proposed and validated including the implication of several non-neoplastic immune cells as important contributors to lymphoma biology, opening new options for better treatment planning and eventually new therapeutic targets and candidate therapeutics.

Induction of phagocytic activity and nitric-oxide production in natural populations of Trypanosoma Cruzi I and II from the state of Paraná, Brazil

Twelve strains of Trypanosoma cruzi isolated from wild reservoirs, triatomines, and chronic chagasic patients in the state of Paraná, southern Brazil, and classified as T. cruzi I and II, were used to test the correlation between genetic and biological diversity. The Phagocytic Index (PI) and nitric-oxide (NO) production in vitro were used as biological parameters. The PI of the T. cruzi I and II strains did not differ significantly, nor did the PI of the T. cruzi strains isolated from humans, triatomines, or wild reservoirs. There was a statistical difference in the inhibition of NO production between T. cruzi I and II and between parasites isolated from humans and the strains isolated from triatomines and wild reservoirs, but there was no correlation between genetics and biology when the strains were analyzed independently of the lineages or hosts from which the strains were isolated. There were significant correlations for Randomly Amplified Polymorphic Deoxyribonucleic acid (RAPD) and biological parameters for T. cruzi I and II, and for humans or wild reservoirs when the lineages or hosts were considered individually.

A Communication Intervention for Training Southern European Oncologists to Recognize Psychosocial Morbidity in Cancer. I - Development of the Model and Preliminary Results on Physicians' Satisfaction

BACKGROUND: The detection of psychosocial distress is a significant communication problem in Southern Europe and other countries. Work in this area is hampered by a lack of data. Because not much is known about training aimed at improving the recognition of psychosocial disorders in cancer patients, we developed a basic course model for medical oncology professionals. METHODS: A specific educational and experiential model (12 hours divided into 2 modules) involving formal teaching (ie, journal articles, large-group presentations), practice in small groups (ie, small-group exercises and role playing), and discussion in large groups was developed with the aim of improving the ability of oncologists to detect emotional disturbances in cancer patients (ie, depression, anxiety, and adjustment disorders). RESULTS: A total of 30 oncologists from 3 Southern European countries (Italy, Portugal, and Spain) participated in the workshop. The training course was well accepted by most participants who expressed general satisfaction and a positive subjective perception of the utility of the course for clinical practice. Of the total participants, 28 physicians (93.3%) thought that had they been exposed to this material sooner, they would have incorporated the techniques received in the workshop into their practices; 2 participants stated they would likely have done so. Half of the doctors (n = 15) believed that their clinical communication techniques were improved by participating in the workshop, and the remaining half thought that their abilities to communicate with cancer patients had improved. CONCLUSIONS: This model is a feasible approach for oncologists and is easily applicable to various oncology settings. Further studies will demonstrate the effectiveness of this method for improving oncologists skills in recognizing emotional disorders in their patients with cancer.

Perinatal Outcome and Change in Body Mass Index in Mothers of Dichorionic Twins: a Longitudinal Cohort Study

We used a prospective cohort to analyze the effect of change in BMI rather than change in weight, in mothers carrying dichorionic twins from a population that did not receive any dietary intervention. A total of 269 mothers (150 nulliparas and 119 multiparas) were evaluated. The average change (%) from the pre-gravid BMI was 7.2+/-6.1, 17.4+/-8.2, and 28.7+/-10.8, at 12-14, 22-25, and 30-34 weeks, respectively, without difference between nulliparas and multiparas. The comparison between maternities below or above the average change from the pregravid BMI failed to demonstrate an advantage (in terms of total twin birthweight and gestational age) of an above average change from the pregravid BMI, even when the lower versus upper quartiles were compared. Our observations reached different conclusions regarding the recommended universal dietary intervention in twin gestations. A cautious approach is advocated towards seemingly harmless excess weight gain, as normal weight women may turn overweight, or even obese, by the end of pregnancy, and be exposed to the untoward effects of obesity on future health and body image.

Hydrogeomechanics for rock engineering: coupling subsurface hydrogeomechanical assessement and hydrogeotechnical mapping on fracturated rock masses

The present work aims to achieve and further develop a hydrogeomechanical approach in Caldas da Cavaca hydromineral system rock mass (Aguiar da Beira, NW Portugal), and contribute to a better understanding of the hydrogeological conceptual site model. A collection of several data, namely geology, hydrogeology, rock and soil geotechnics, borehole hydraulics and hydrogeomechanics, was retrieved from three rock slopes (Lagoa, Amores and Cancela). To accomplish a comprehensive analysis and rock engineering conceptualisation of the site, a multi‐technical approach were used, such as, field and laboratory techniques, hydrogeotechnical mapping, hydrogeomechanical zoning and hydrogeomechanical scheme classifications and indexes. In addition, a hydrogeomechanical data analysis and assessment, such as Hydro‐Potential (HP)‐Value technique, JW Joint Water Reduction index, Hydraulic Classification (HC) System were applied on rock slopes. The hydrogeomechanical zone HGMZ 1 of Lagoa slope achieved higher hydraulic conductivities with poorer rock mass quality results, followed by the hydrogeomechanical zone HGMZ 2 of Lagoa slope, with poor to fair rock mass quality and lower hydraulic parameters. In addition, Amores slope had a fair to good rock mass quality and the lowest hydraulic conductivity. The hydrogeomechanical zone HGMZ 3 of Lagoa slope, and the hydrogeomechanical zones HGMZ 1 and HGMZ 2 of Cancela slope had a fair to poor rock mass quality but were completely dry. Geographical Information Systems (GIS) mapping technologies was used in overall hydrogeological and hydrogeomechanical data integration in order to improve the hydrogeological conceptual site model.

Spatial distribution of dengue in the city of Cruzeiro, São Paulo State, Brazil: use of geoprocessing tools

The aim of this article is to identify patterns in spatial distribution of cases of dengue fever that occurred in the municipality of Cruzeiro, State of São Paulo, in 2006. This is an ecological and exploratory study using the tools of spatial analysis in the preparation of thematic maps with data from Sinan-Net. An analysis was made by area, taking as unit the IBGE census, the analysis included four months in 2006 which show the occurrence of the disease in the city. The thematic maps were constructed by TerraView 3.3.1 software, the same software provided the values of the indicators of Global Moran (I M) every month and the Kernel estimation. In the year 2006, 691 cases of dengue were georeferenced (with a rate of 864.2 cases/100,000 inhabitants); the indicators of Moran and p-values obtained were I M = 0.080 (March) p = 0.11; I M = 0.285 (April) p = 0.01; I M = 0.201 (May) p = 0.01 and I M = 0.002 (June) p = 0.57. The first cases were identified in the Northeast and Central areas of Cruzeiro and the recent cases, in the North, Northeast and Central. It was possible to identify census tracts where the epidemic began and how it occurred temporally and spatially in the city.

Tension-Free Vaginal Tape (T.V.T) - Nova e Revolucionária Técnica para o Tratamento Cirúrgico da Incontinência Urinária de Esforço (I.U.E.) Feminina Introduzida na MAC pelo Núcleo de Ginecologia Urológica

Este artigo pretende fazer uma revisão de uma das últimas e inovadoras alternativas cirúrgicas viáveis para a cura da incontinência urinária de esforço feminina, com um sucesso superior a 86%. É uma cirurgia mini invasiva e que induz um suporte da uretra média livre de tensão, muito eficaz. Tem vantagens, poucas complicações, curto tempo operatório e benefícios para a doente no pós-operatório imediato e tardio.

Índice Proliferativo Ki-67 no Cancro Gástrico

Introdução: O cancro gástrico representa ainda uma das principais causas de mortalidade por doença oncológica a nível mundial, apesar da evolução substancial no seu tratamento. Diversos marcadores biológicos têm sido introduzidos com intuito prognóstico da doença. A proteína Ki-67 através de técnicas imunocitoquímicas tem sido utilizada como um indicador da actividade proliferativa tumoral. No cancro gástrico o seu valor prognóstico ainda não foi estabelecido, sendo os resultados na literatura controversos. Este estudo pretende avaliar o significado biológico do índice proliferativo Ki-67 no cancro gástrico. Métodos: Foram estudados 50 doentes com cancro gástrico submetidos a cirurgia ressectiva. A proteína Ki-67 foi analisada por imunocitoquímica nas peças operatórias. O índice proliferativo Ki-67 foi definido como a percentagem de células tumorais positivas para a proteína. Resultados: Dos 50 casos estudados foi obtido um índice proliferativo Ki-67 de 68.9 ± 24.1%. Foram correlacionadas as variáveis sexo, idade, localização e dimensão tumoral, classificação TNM, estadio e tipo histológico de Lauren. Apenas esta última revelou diferenças estatisticamente significativas entre os respectivos tipos (P = 0.004). Conclusão: Os achados encontrados não permitem definir inequivocamente o valor prognóstico do índice proliferativo Ki-67. Será importante prosseguir o estudo com uma amostra populacional superior, para que conclusões estatisticamente significativas possam ser elaboradas.

Brazilian mosquito (Diptera: Culicidae) fauna: I. Anopheles species from Porto Velho, Rondônia state, western Amazon, Brazil

This study contributes to knowledge of Anopheles species, including vectors of Plasmodium from the western Brazilian Amazon in Porto Velho, Rondônia State. The sampling area has undergone substantial environmental changes as a consequence of agricultural and hydroelectric projects, which have caused intensive deforestation and favored habitats for some mosquito species. The purpose of this study was to diagnose the occurrence of anopheline species from collections in three locations along an electric-power transmission line. Each locality was sampled three times from 2010 to 2011. The principal adult mosquitoes captured in Shannon trap were Anopheles darlingi, An. triannulatus, An. nuneztovari l.s., An.gilesi and An. costai. In addition, larvae were collected in ground breeding sites for Anopheles braziliensis, An. triannulatus, An. darlingi, An. deaneorum, An. marajoara, An. peryassui, An. nuneztovari l.s. and An. oswaldoi-konderi. Anopheles darlingi was the most common mosquito in the region. We discuss Culicidae systematics, fauna distribution, and aspects of malaria in altered habitats of the western Amazon.

"I was a maoist intelectual". Uma leitura crítica em torno dos conceitos "industria cultural" e "popular music" segundo adorno

Reflectir sobre noções como liberdade individual, democracia, o papel dos meios de comunicação e dos produtos culturais, é uma das principais tarefas das ciências sociais e humanas, reflexão particularmente pertinente nestes primeiros anos do séc. XXI marcados pela popularização de dispositivos tecnológicos destinados à circulação de informação em rede e pela virtualização de mecanismos de distribuição de bens de consumo cultural. Adomo constitui hoje uma das fontes mais importantes surgidas nos últimos 50 anos para esta reflexão. Marcado pelo advento do Nacional Socialismo e a perseguição de todos os "degenerados da condição ariana" (judeus, comunistas e homossexuais), Adomo produziu ao longo de quatro décadas, uma reflexão que marcou indelevelmente muitos autores que, escrevendo sobre a contemporaneidade, a adoptaram ou a ela se opuseram. A pergunta que coloco, e que serve de ponto de partida para este artigo, é proposta por Jameson: é hoje possível ler Adomo e Horkheimer junto à piscina? (1990: 248), ou posto de outra forma, que lugar ocupa a obra de Adomo como ferramenta para perspectivar o mundo actual.