Objetivo do estudo: Estimar a prevalência de lesões malignas e prémalignas nos pólipos endometriais e correlacionar com fatores associados com risco de neoplasia de endométrio. Métodos: Revisados dados sobre características clínicas e resultado anatomopatológico dos pólipos ressecados em histeroscopias cirúrgicas com polipectomia realizados entre janeiro de 2005 e julho de 2013 no Hospital de Clínicas de Porto Alegre (HCPA). Resultados: Incluídas 359 pacientes submetidas a polipectomias histeroscópicas. 87,2% das pacientes apresentaram pólipos benignos e 9,9% apresentaram hiperplasia sem atipias. Pólipos com hiperplasia atýpica corresponderam a 2,6% da amostra, enquanto que adenocarcinoma de endométrio foi encontrado de 0,3% dos casos. Verificou-se correlação de resultado maligno/pré-maligno dos pólipos com idade da paciente, seu status menopausal e a presença de sangramento uterino anormal. Todas as mulheres com resultados malignos/pré-malignos apresentaram sangramento uterino anormal. Observou-se maior frequência de malignidade dos pólipos entre usuárias de tamoxifeno, porém sem significância estatística (p 0,059%). Não houve correlação com hipertensão arterial, diabetes mellitus, obesidade, uso de terapia hormonal, espessura endometrial ou diâmetro do pólipo. Conclusão: A prevalência de lesões malignas/pré-malignas nos pólipos endometriais é baixa, tendo sido nula nas pacientes sem sangramento. Não se recomenda a exérese rotineira dos pólipos em pacientes assintomáticas. / Objective: To estimate the prevalence of malignant and premalignant lesions among endometrial polyps and correlate this prevalence with risk factors for endometrial neoplasms. Methods: Review of clinical and histopathological data on polyps resected during hysteroscopic polypectomies performed from January 2005 through July 2013 at Hospital de Clínicas de Porto Alegre (HCPA), Brazil. Results: The sample comprised 359 patients who underwent hysteroscopic polypectomy. Overall, 87.2% of patients had benign polyps and 9.9% had hyperplasia without atypia. Polyps with atypical hyperplasia were found in 2.6% of patients, and endometrial adenocarcinoma, in 0.3%. Polyp malignancy/premalignancy correlated with patient age, menopausal status, and presence of abnormal uterine bleeding. All women with malignant/premalignant lesions had abnormal uterine bleeding.The rate of polyp malignancy was higher among tamoxifen users, although the difference did not reach statistical significance (p=0.059). There was no correlation with hypertension, diabetes mellitus, obesity, hormone replacement therapy, endometrial thickness, or polyp diameter. Conclusion: The prevalence of malignancy/premalignancy among endometrial polyps is low; no cases were identified in patients without uterine bleeding. Routine excision of asymptomatic polyps cannot be recommended.

Objetivo do estudo: Estimar a prevalência de lesões malignas e prémalignas nos pólipos endometriais e correlacionar com fatores associados com risco de neoplasia de endométrio. Métodos: Revisados dados sobre características clínicas e resultado anatomopatológico dos pólipos ressecados em histeroscopias cirúrgicas com polipectomia realizados entre janeiro de 2005 e julho de 2013 no Hospital de Clínicas de Porto Alegre (HCPA). Resultados: Incluídas 359 pacientes submetidas a polipectomias histeroscópicas. 87,2% das pacientes apresentaram pólipos benignos e 9,9% apresentaram hiperplasia sem atipias. Pólipos com hiperplasia atýpica corresponderam a 2,6% da amostra, enquanto que adenocarcinoma de endométrio foi encontrado de 0,3% dos casos. Verificou-se correlação de resultado maligno/pré-maligno dos pólipos com idade da paciente, seu status menopausal e a presença de sangramento uterino anormal. Todas as mulheres com resultados malignos/pré-malignos apresentaram sangramento uterino anormal. Observou-se maior frequência de malignidade dos pólipos entre usuárias de tamoxifeno, porém sem significância estatística (p 0,059%). Não houve correlação com hipertensão arterial, diabetes mellitus, obesidade, uso de terapia hormonal, espessura endometrial ou diâmetro do pólipo. Conclusão: A prevalência de lesões malignas/pré-malignas nos pólipos endometriais é baixa, tendo sido nula nas pacientes sem sangramento. Não se recomenda a exérese rotineira dos pólipos em pacientes assintomáticas. / Objective: To estimate the prevalence of malignant and premalignant lesions among endometrial polyps and correlate this prevalence with risk factors for endometrial neoplasms. Methods: Review of clinical and histopathological data on polyps resected during hysteroscopic polypectomies performed from January 2005 through July 2013 at Hospital de Clínicas de Porto Alegre (HCPA), Brazil. Results: The sample comprised 359 patients who underwent hysteroscopic polypectomy. Overall, 87.2% of patients had benign polyps and 9.9% had hyperplasia without atypia. Polyps with atypical hyperplasia were found in 2.6% of patients, and endometrial adenocarcinoma, in 0.3%. Polyp malignancy/premalignancy correlated with patient age, menopausal status, and presence of abnormal uterine bleeding. All women with malignant/premalignant lesions had abnormal uterine bleeding.The rate of polyp malignancy was higher among tamoxifen users, although the difference did not reach statistical significance (p=0.059). There was no correlation with hypertension, diabetes mellitus, obesity, hormone replacement therapy, endometrial thickness, or polyp diameter. Conclusion: The prevalence of malignancy/premalignancy among endometrial polyps is low; no cases were identified in patients without uterine bleeding. Routine excision of asymptomatic polyps cannot be recommended.

Yes / Aspirin and eicosapentaenoic acid (EPA) have colorectal polyp prevention activity, alone and in combination. This study measured levels of plasma and rectal mucosal oxylipins in participants of the seAFOod 2 × 2 factorial, randomised, placebo-controlled trial, who received aspirin 300 mg daily and EPA 2000 mg free fatty acid, alone and in combination, for 12 months. Resolvin (Rv) E1, 15-epi-lipoxin (LX) A4 and respective precursors 18-HEPE and 15-HETE (with chiral separation) were measured by ultra-high performance liquid chromatography-tandem mass spectrometry in plasma taken at baseline, 6 months and 12 months, as well as rectal mucosa obtained at trial exit colonoscopy at 12 months, in 401 trial participants. Despite detection of S- and R- enantiomers of 18-HEPE and 15-HETE in ng/ml concentrations, RvE1 or 15‑epi-LXA4 were not detected above a limit of detection of 20 pg/ml in plasma or rectal mucosa, even in individuals randomised to both aspirin and EPA. We have confirmed in a large clinical trial cohort that prolonged (12 months) treatment with EPA is associated with increased plasma 18-HEPE concentrations (median [inter-quartile range] total 18-HEPE 0.51 [0.21-1.95] ng/ml at baseline versus 0.95 [0.46-4.06] ng/ml at 6 months [P

Coral reefs are among the most biodiverse ecosystems in the world, being essential for marine life. The engineers of these ecosystems, reef-building corals, live in association with a great diversity of microorganisms, which can affect their host’s health in beneficial or detrimental manners. Corals are currently threatened by climate change and other environmental stressors, that lead to the phenomenon of coral bleaching, in which these animals lose their endosymbiotic algae. Even though the stressors that cause coral bleaching are known, the exact cellular and molecular mechanisms that provoke this process are still undiscovered. The lack of information regarding micro-scale processes that happen in unhealthy corals could be resolved with more efforts in developing micro-scale studying models. The use of individual polyps that bail-out of the coral skeleton induced by acute stress has been suggested as a model to study these processes. However, little is known about how these polyps change after bailing-out of a colony, which could become a problem once reliable models should be consistent and well understood. Thus, investigating these changes and optimizing a methodology to minimize them is crucial to establish these polyps as models to study corals. Herein, we investigated microbiological changes of isolated polyps by performing an experiment to study shifts in their microbiome after the separation from the colony. Before the experiment, different methods to isolate polyps were tested to find the one that granted the highest survival. After finding that salinity-induced separation was the most efficient, this method was used to study the microbiome of coral polyps. We found that while no significant changes in the microbiome could be observed immediately after the separation of polyps from their colony compared to coral fragments, this pattern changed after two weeks. We propose that the maintenance of polyps without fixation to a substrate might be the cause for such changes, and that polyps able to attach to a substrate and regrow as a colony might still recover a microbiome composition closer to coral fragments. Finally, a new microfluidic device for fixation and maintenance of coral polyps was developed and tested for use in future experiments.

No description available.

Nesta tese, organizada em capítulos, são apresentados diferentes estudos sobre processos que afetam a história de vida, o potencial de dispersão, as preferências do assentamento larval e o recrutamento efetivo do coral invasor Tubastraea coccinea. No primeiro capítulo, demonstra-se que plânulas produzidas por T. coccinea são capazes de sofrer metamorfose e agregar-se em grupos de até oito pólipos ainda na coluna d´água, sem que ocorra previamente assentamento larval. Nesta seção, foi avaliada também a sobrevivência de propágulos para testar se diferentes níveis de agregação possibilitam uma extensão do período planctônico e, portanto, um aumento do potencial de dispersão. Os resultados obtidos mostram que pólipos natantes sobrevivem mais que plânulas, provavelmente por serem capazes de se alimentar e, assim, suprir a alta demanda energética associada à natação e à procura de um substrato favorável para o assentamento. Grupos de dois ou mais pólipos sobrevivem mais que pólipos solitários. Porém, a mortalidade não diferiu entre agrupamentos pequenos (2-3 pólipos) e grandes (4-8 pólipos), o que sugere que existe um limite para o tamanho ótimo dessas colônias pelágicas. A maioria dos grupos de pólipos que se mantém nadando na coluna d´água (80%) permanece viva após seis meses, o que sugere que a capacidade de sofrer metamorfose no ambiente pelágico e formar colônias de pólipos planctônicos é uma característica chave na história de vida da espécie, incrementando o potencial de dispersão, a conectividade entre populações e a capacidade de colonização de novos ambientes. No segundo capítulo, é caracterizada primeiramente a distribuição espacial de colônias adultas e pólipos fundadores do coral T. coccinea sobre substratos rochosos com diferentes orientações. Para isso, foi avaliada a consistência desses padrões para duas escalas espaciais, uma pequena (de dezenas de metros) e outra intermediária (de unidades de quilômetros). Posteriormente, estudaram-se as preferências durante o assentamento larval e os padrões de recrutamento sobre superfícies com diferentes orientações através de experimentos de campo e laboratório. O objetivo principal desta secção foi determinar se os padrões de distribuição de recrutas e colônias adultas podem ser explicados por processos que ocorrem durante etapas larvais ou pós-larvais iniciais. Os resultados indicam que tanto a flutuabilidade das larvas quanto o comportamento ativo de natação, não relacionado com condições de luminosidade, são fatores que determinam claramente o padrão de distribuição do coral. Como parte desse padrão, observou-se que a densidade de recrutas juvenis é maior em substratos orientados para baixo, sendo quase nula nas superfícies orientadas para cima. Com exceção da quase ausência de indivíduos sobre áreas orientadas para cima, existem diferenças substanciais entre a distribuição de recrutas e adultos para as demais orientações, principalmente para superfícies verticais. Essas diferenças podem estar relacionadas com o escoamento costeiro, o qual é intenso na região de estudo e pode causar depósito excessivo de sedimentos sobre superfícies positivas, inibindo o desenvolvimento de colônias deste coral. Por outro lado, interações competitivas com outras espécies de corais azooxantelados poderiam ser a causa da diminuição da abundância de T. coccinea em substratos negativos. No terceiro e último capítulo desta tese avaliou-se o potencial de interação de Tubastraea coccinea com espécies representativas de uma comunidade bentônica do litoral norte do Estado de São Paulo, recentemente invadida. Amostragens no campo, visando estimar a densidade de recrutas juvenis de T. coccinea sobre diferentes tipos de manchas formadas por organismos incrustantes, foram usadas para obter uma primeira inferência sobre o potencial de facilitação, ou inibição, do recrutamento. Os cnidários Carijoa riisei, Parazoanthus sp e Obelia dichotoma afetaram negativamente o recrutamento do coral sol, enquanto que algas incrustantes coralináceas facilitaram o recrutamento e podem facilitar a colonização do coral. O papel da mediação alelopática foi avaliado a partir de experimentos de laboratório, nos quais foram medidas diferentes componentes do assentamento larval em função da exposição das larvas a extratos brutos de várias espécies acompanhantes. Os testes mostraram a ocorrência geral de alelopatias negativas, as quais em alguns casos levaram apenas à inibição do assentamento, mas em outros à rápida mortalidade das larvas, sugerindo a ação de metabólitos tóxicos. Adicionalmente, foram realizados estudos comparativos de comunidades com a presença, ou ausência, do coral invasor, considerando fatores relevantes para a sua ocorrência, como a orientação do substrato. As comunidades invadidas por T. coccinea tendem a apresentar maior riqueza e equitatividade. A invasão no local de estudo é relativamente recente, pelo que os resultados encontrados devem estar mais relacionados a diferenças na susceptibilidade dessas comunidades à invasão, do que a eventuais efeitos das colônias do coral sol desenvolvidas nas mesmas. Se for assim, o estabelecimento do coral sol no litoral do Estado de São Paulo poderá implicar em uma perda significativa da diversidade biológica de substratos consolidados rasos. Os dados obtidos nesse estudo, abordando aspectos relevantes da vida pelágica e bentônica de T. coccinea, constituem um acervo de informação que poderá subsidiar planos de controle e monitoramento da espécie invasora, contribuindo ao estabelecimento de critérios de gestão de áreas de conservação. / In this thesis, organized in chapters, we present studies on the processes affecting the life history, dispersal potential, larval settlement preferences, and effective recruitment of the invasive coral Tubastraea coccinea. In the first chapter we report, for the first time, that larvae produced by the sun coral may metamorphose and aggregate in the water column without previous settling on any substrate. We then compared the survival of different types of propagules to test whether alternative development pathways allow longer pelagic life, and thus higher dispersal potential. Our results show that single-polyps live longer than planulae, probably because they can feed and sustain minimal metabolic activity. Clustered polyps live longer than solitary polyps, as expected if per capita polyp mortality rates are similar between these categories. However, mortality rate did not differ between small (2-3 polyps) and large (4-8 polyps) clusters, indicating that, in overall conditions, polyp performance attain a maximum at intermediate aggregations, setting an eventual adaptive upper limit to cluster size. In our experiment, over 80% of swimming colonies remained alive for a period exceeding six months. We conclude that pelagic metamorphosis and cluster formation may be an important mechanism allowing connectivity among populations and the colonization of new habitats. Moreover, founder individuals resulting from pelagic polyp aggregation can generate greater genetic variability in benthic developing colonies. In the second chapter, we first characterized spatial distributions of adult colonies and single-polyp recruits of the invasive azooxanthellate coral Tubastraea coccinea over substrates of different orientation, and evaluated their consistency at both small (several tens of meters) and intermediate (a few km) spatial scales. We then assessed, through field and laboratory experiments, larval preferences and relative settlement and recruitment rates on surfaces with different orientations to determine whether processes taking place during the larval and early post-larval stages could help explain the distribution patterns of recruits and adult colonies. Results suggest that larval passive buoyancy and active larval behavior, unrelated to light conditions, determine a clear settlement distribution pattern, in which the density of settlers is highest at undersurfaces and almost nil at upward facing horizontal substrates. Except for an almost absence of settlers, recruits and adult individuals on upward facing horizontal habitat, there is substantial mismatch between the distribution of settlers and that of recruits and adult colonies. The latter were also common in vertical substrates in the field. We speculate that coastal runoff at the study area and subsequent sedimentation may inhibit coral development on flat upward facing habitat, and that competitive interference and pre-emptive interactions with native azooxanthellate corals could constrain abundance of T. coccinea in underface horizontal habitat. In the third and final chapter of this thesis, the interactions of representative species of the benthic community of the north shore of São Paulo state with the exotic coral, recently introduced at the study site, were evaluated. Field surveys of the density of juvenile recruits of T. coccinea on different types of patches formed by fouling organisms allowed us to detect the effect of competitor species that inhibit coral recruitment. The Cnidarians Carijoa riisei, Parazoanthus sp and Obelia dichotoma negatively affected the juvenile recruitment of the sun coral. Conversely, it was observed that the recruitment of this scleractinian is considerably greater on several other species (chiefly fouling coralline algae), which act as facilitators and promote coral colonization. The role of allelopathic interactions mediating larval settlement was investigated through a settlement experiment using extracts of different companion species. Results indicated a general negative allelopathic response, either limited to settlement inhibition or leading acute mortality, the latter suggesting toxic effects. We also conducted comparative studies of communities with and without the invasive coral, considering other factors that could influence coral occurrence, such as substratum orientation. Species richness and evenness were general higher in invaded communities. The sun coral invasion is relatively recent in the study area and, therefore, these results are probably related to differences in the susceptibility of these assemblages to be invaded, rather than eventual effects of established colonies on them. If this is so, the establishment of T. coccinea in São Paulo state may lead to a significant loss of biological diversity in shallow rocky habitat. Our data give a full account of relevant aspects of the pelagic and benthic life of this invasive coral, and constitute a collection with no precedence that may subsidize plans of control and monitoring of this invasive species, contributing to the establishment of criteria used in the management of conservation areas.

This thesis examines the benefits and costs of screening for colorectal cancer in the context of an organised population screening programme. It uses microsimulation modelling to derive an optimally cost-effective screening protocol for various combinations of the available screening tests. ¶ First a mathematical model for the natural history of colorectal cancer is derived, based on analyses of Australian population and hospital-based cancer registries combined with data from published studies. Then a model for population based screening is derived based mainly on data from published screening studies, including the four major published randomised controlled trials of faecal occult blood test (FOBT) screening. These two models are used to simulate the application of a screening programme to the Australian population. The simulations are applied to a period of 40 years following 1990 (the study’s base year), with both costs and benefits discounted back to the base year at an annual rate of 3%.¶ The models are applied to simulating a population screening programme based on FOBT with a colonoscopy follow up of positive tests. This simulation suggests that the optimal application of such a programme would be to offer annual screening to people aged 50 to 84 years. Such a programme would lead to a cumulative fall in years of life lost to colorectal cancer (YLL) of 28.5% at a cost per year of life saved (YLS) of $8,987. These costs and benefits are consistent with those arising from other currently funded health interventions. They are also consistent with the cost per YLS which Australian governments appear willing to pay for health interventions when justified on the basis of cost-effectiveness. The fall in colorectal cancer deaths from this screening programme should be first detectable by a national monitoring system after around three years of screening. However the full benefits from screening would not be realised before around 30 years of screening.¶ These simulations are based on the standard guaiac FOBT, but the results suggest that significant cost-effective gains could be made by using the newer immunochemical FOBT. Further cost-effect gains could be made by offering sigmoidoscopy every five years in addition to annual FOBT.¶ The models are then applied to simulating population screening programmes using colonoscopy and sigmoidoscopy as primary screening tools. Offering colonoscopy every ten years to all people aged from 45 to 85 leads to an overall fall in cumulative YLL of 37.6%, at a cost of $15,585 per YLS. Offering sigmoidoscopy every three years to all people aged 40 to 85 leads to an overall fall in cumulative YLL of 29.1%, at a cost of $4,862 per YLS. Both of these cost and benefit results are also consistent with the cost per YLS which Australian governments appear willing to pay. The fall in deaths with colonoscopy screening would also be detectable after three years of screening but the fall with sigmoidoscopy screening would not be detectable until after six years of screening. Sigmoidoscopy would need around 35 years of screening to reach its potential gains while colonoscopy screening would not reach its full potential during the 40 year screening period.¶ Finally the models are applied to targeting people at higher risk of cancer. The results show that offering colonoscopy every five years to people at higher risk because of a family history of colorectal cancer is a cost-effective addition to the annual FOBT screening programme.¶ An earlier version of chapter two of this thesis has been published as Stevenson CE 1995. Statistical models for cancer screening. Statistical Methods in Medical Research; 4: 19–23.¶ An expanded version of chapter two, along with parts of chapter one, has been published as Stevenson CE 1998. Models of screening. In: Encyclopedia of Biostatistics. Armitage P, Colton T, eds. John Wiley and Sons Ltd, pp 3999–4022.

München, Techn. Univ., Diss., 2004.

Techn. Universiẗat, Diss., 2003--Darmstadt. / Dateien im PDF-Format.

Nous avons l’habitude de penser que l’organisme pluricellulaire, comme un certain homme et un certain cheval, est un modèle de l’individu. Toutefois, la philosophie contemporaine des sciences de la vie propose un certain nombre de définitions de l’individualité biologique qui provoquent des débats sans fin. Nous proposons une analyse historique des modifications de la notion d’individu qui ne vise pas à régler les débats, mais à comprendre la diversité des pensées portant sur cette notion. Nous commençons par analyser la découverte de la régénération du polype d’eau douce, faite au milieu du XVIIIe siècle par Abraham Trembley. Nous arrivons à mettre en lumière la rénovation philosophique effectuée au début de XXe siècle par Henri Bergson. L’histoire de la notion d’individu biologique présente des pensées qui transforment l’évidence en problématique. L’invention et la réinterprétation des concepts biologiques comme l’organisme, la cellule, la division du travail, le milieu, la sélection naturelle et la vie, permettent à la pensée biologique de remettre en cause la définition étymologique du terme d’individu, l’identification de l’individu et de l’organisme et la possibilité même de déterminer le niveau d’organisation correspondant à l’individu. La pluralité des concepts d’individu ne signifie pas qu’il faille renoncer à l’usage du terme en biologie. Au contraire, elle permet de mettre au jour l’ontologie impliquée dans les théories biologiques pour poser en termes précis les problèmes biologiques et philosophiques. La pensée de l’individualité biologique ouvre un vaste champ de recherche où les philosophes et les biologistes ont à travailler ensemble. / From a commonsense perspective, the multicellular organisms such as men and horses are thought of as typical examples of biological individuals. But contemporary philosophers of biology present a number of definitions of biological individuality which stimulate an intense debate over deciding the level of organization to which the biological individuality corresponds. This research proposes a historical analysis, which doesn’t aim to solve the conceptual issues, but to understand the diversity of biological thinking about individuality. From the regeneration of the polyp discovered by Abraham Trembley in the middle of the 18th century to the philosophical renovation achieved by Henri Bergson at the beginning of the 20th century, the biological thinking called into question the basis on which the notion of biological individuality was built. The invention and the reinterpretation of the concepts such as the organism, the cell, the division of labor, the milieu, the natural selection and the life, allowed to ask if the biological individuality can be defined as indivisibility, secondly if it can be identified with the organism, and finally if one can determine the level of organization to which the biological individuality corresponds. The diversity of concepts of biological individuality doesn’t mean that this term is dispensable for the biological research. It allows to present the biological and philosophical problems in more precise terms, so that the biologists and philosophers can cooperate to tackle them.