Doenças raras na Ilha de S. Miguel : caracterização epidemiológica

RESUMO:O conceito de doenças raras como entidade própria começou a ser divulgado na comunidade médica no início deste século. A perspectiva de congregar múltiplas patologias, com características diferentes, valorizando a baixa frequência com que ocorrem na população interessou a comunidade científica, famílias, indústria e serviços de saúde. Esperava-se encontrar estratégias para melhorar a qualidade dos cuidados de saúde prestados a estes doentes. Uma vez que a informação científica sobre doenças raras está dispersa por diversas fontes o primeiro grande desafio foi sistematizar de forma a obter o “estado da arte”. A investigação que decorreu entre 2001 e 2010 teve como objectivo principal a caracterização dos doentes e das doenças raras numa população com características restritas mas não fechada como é o caso da ilha de S. Miguel nos Açores. Foram identificados 467 doentes a partir de várias fontes e monitorizado o nascimento de recém-nascidos com doença rara durante 10 anos. A prevalência das doenças raras encontrada na ilha de S. Miguel foi de 0,34% e a inerente à definição de doença rara foi de 6 % a 8 % da população na União Europeia. A diferença encontrada poderá decorrer de se ter sobrestimado o verdadeiro valor da prevalência das doenças raras na União Europeia. A incidência de doenças raras determinada na amostra foi de 0,1% e a taxa de mortalidade por causa específica foi de 0,14‰. O diagnóstico foi confirmado por técnicas laboratoriais de citogenética ou genética molecular em 43% dos doentes da amostra. Não foi identificado nenhum agregado populacional com doença rara para além do já conhecido para a DMJ. A criação de uma metodologia de estudo implicou a construção de um registo de doentes. Para tal foi utilizado o conhecimento adquirido anteriormente sobre uma doença rara que serviu de paradigma: a doença de Machado-Joseph. Na sequência dos resultados obtidos foi considerado útil a introdução de variáveis como a figura do cuidador, o cônjuge, o número de filhos do casal, a data da primeira consulta de Genética, o tempo decorrido entre o início dos sintomas e o acesso à consulta de Genética e entre esta actividade e dispor do diagnóstico para melhor compreender o contexto de vida destes doentes na perspectiva de poderem vir a ser incorporadas como indicadores. ----------- ABSTRACT: The concept of rare diseases as a condition began to be disclosed in the medical community at the beginning of this century.The prospect of bringing together multiple pathologies, with different features, enhancing the low frequency with which they occur in the population interested the scientific community, families, industry and health care services. The aim was to find strategies to improve the quality of care provided to these patients. Given that the scientific information on rare diseases is spread out across several sources the first major challenge was to systematize in order to get the "state of the art". The research took place between 2001 and 2010 and had as its main objective the characterization of patients and rare diseases in a population with specific features, but not confined, like in the case of the São Miguel Island in Azores. During 10 years were identified 467 patients from multiple sources and were observed the newborns with rare diseases. Prevalence of rare diseases found in the São Miguel Island was 0,34% compared to the 6% to 8% by definition of rare disease in the population in European Union. This discrepancy may be explained by a likely frequency of overrated rare diseases in European Union. The incidence of rare diseases in the sample was 0,1% and the specific mortality rate was 0,14 ‰. This diagnosis was confirmed by cytogenetic or molecular genetics analysis in 43% of patients in the sample. No population cluster was identified with rare disease besides the already known for Machado-Joseph Disease. The methodology for the study involved the construction of a database of patients. For such purpose it was used previously acquired knowledge on a rare disease paradigm: the Machado-Joseph disease. It was useful to introduce the following variables to properly establish the results: caregiver, spouse, number of children, date of first Genetics appointment, elapsed time between onset of symptoms and access to first appointment as well as this and the final diagnosis to better understand the context of life of these patients in order to incorporate them as rates.

Knowledge management framework based on brain models and human physiology

The life of humans and most living beings depend on sensation and perception for the best assessment of the surrounding world. Sensorial organs acquire a variety of stimuli that are interpreted and integrated in our brain for immediate use or stored in memory for later recall. Among the reasoning aspects, a person has to decide what to do with available information. Emotions are classifiers of collected information, assigning a personal meaning to objects, events and individuals, making part of our own identity. Emotions play a decisive role in cognitive processes as reasoning, decision and memory by assigning relevance to collected information. The access to pervasive computing devices, empowered by the ability to sense and perceive the world, provides new forms of acquiring and integrating information. But prior to data assessment on its usefulness, systems must capture and ensure that data is properly managed for diverse possible goals. Portable and wearable devices are now able to gather and store information, from the environment and from our body, using cloud based services and Internet connections. Systems limitations in handling sensorial data, compared with our sensorial capabilities constitute an identified problem. Another problem is the lack of interoperability between humans and devices, as they do not properly understand human’s emotional states and human needs. Addressing those problems is a motivation for the present research work. The mission hereby assumed is to include sensorial and physiological data into a Framework that will be able to manage collected data towards human cognitive functions, supported by a new data model. By learning from selected human functional and behavioural models and reasoning over collected data, the Framework aims at providing evaluation on a person’s emotional state, for empowering human centric applications, along with the capability of storing episodic information on a person’s life with physiologic indicators on emotional states to be used by new generation applications.

Toxoplasmosis: an examination of knowledge among health professionals and pregnant women in a municipality of the State of Paraná

Introduction The aim of this study was to investigate the knowledge of toxoplasmosis among professionals and pregnant women in the public health services in Paraná, Brazil. Methods A cross-sectional observational and transversal study of 80 health professionals (44 nurses and 36 physicians) and 330 pregnant women [111 immunoglobulin M (IgM)- and IgG-non-reactive and 219 IgG-reactive] was conducted in 2010. An epidemiological data questionnaire was administered to the professionals and to the pregnant women, and a questionnaire about the clinical aspects and laboratory diagnosis of toxoplasmosis was administered to the professionals. Results The participants frequently provided correct responses about prophylactic measures. Regarding the clinical and laboratory aspects, the physicians provided more correct responses and discussed toxoplasmosis with the pregnant women. The professionals had difficulty interpreting the avidity test results, and the physicians stated that they referred pregnant women with high-risk pregnancies to a county reference center. Of the professionals, 53 (91.4%) reported that they instructed women during prenatal care, but only 54 (48.6%) at-risk pregnant women and 99 (45.2%) women who were not at risk reported receiving information about preventive measures. The physicians provided verbal instructions to 120 (78.4%) women, although instructional materials were available in the county. The pregnant women generally lacked knowledge about preventive measures for congenital toxoplasmosis, but the at-risk pregnant women tended to respond correctly. Conclusions This study provides data to direct public health policies regarding the importance of updating the knowledge of primary care professionals. Mechanisms should be developed to increase public knowledge because prophylactic strategies are important for preventing congenital toxoplasmosis.

Illness perception, knowledge and self-care about cervical cancer

Prevention plays a central role in early detection of cervical cancer. Common Sense Model proposes that the nature and organization of illness representations can guide actions related to health and how self-care is exercised. The aim of this study was to describe and compare illness perception, knowledge and self-care in women with and without cancer precursor lesions. Participants were 92 women (aged 18-59) from primary care unity divided into two groups: women with and without premalignant lesion. Measures for illness perception, knowledge and self-care were used. There was no statistically signifi cant difference (t test e chi-square test) between groups in the variables analyzed. Despite the risk for cervical cancer, women with precursor lesions do not adjust their illness perceptions, knowledge and self-care to the situation. These data show the need to warn women against the cervical cancer risks, because their distorted perceptions and lack of knowledge about the disease may hamper the screening and control of cervical cancer.

Species of the subfamily Triatominae Jeannel, 1919 (Hemiptera: Reduviidae) present in the Collection of Chagas Disease Vectors (FIOCRUZ-COLVEC), State of Minas Gerais

Introduction Biological collections are depositories of information on different species and contribute to the knowledge, protection, conservation and maintenance of biodiversity. Methods A list of triatomine species currently included in the Collection of Chagas Disease Vectors (FIOCRUZ-COLVEC) was prepared from the database made available by the Reference Center on Environmental Information. Results COLVEC curatorship houses 4,778 specimens of triatomines, of which 811 come from other American countries (Argentina, Bolivia, Colombia, Costa Rica, the United States of America, Guatemala, Mexico, Peru, Uruguay and Venezuela) and 3,967 are autochthonous from Brazil. Altogether, 56 species of Chagas disease vectors are represented in the COLVEC: two species of the Tribe Cavernicolini Usinger, 1944; fifteen species of the tribe Rhodniini Pinto, 1926, of which 12 are of the genus Rhodnius and 3 are of the genus Psamolestes; and 39 species of the tribe Triatomini Jeannel, 1919, represented by the genus Dipetalogaster, two species of the genus Eratyrus, two of the genus Meccus, seven of the genus Panstrongylus and 27 of the genus Triatoma. Conclusions This list provides important data on the diversity of triatomines currently included in COLVEC, including the expanded area of Panstrongylus lutzi occurrence in the municipalities Pirapora and Januária, State of Minas Gerais. The maintenance and expansion of the collection ensures the preservation of biodiversity and further studies.

Dengue in Brazil and Colombia: a study of knowledge, attitudes, and practices

Introduction This study was conducted in Brazil and Colombia,where dengue is endemic and vector control programs use chemical insecticides. Methods We identified knowledge, attitudes, and practices about dengue and determined the infestation levels of Aedes aegypti in one Brazilian and four Colombian communities. Results The surveys show knowledge of the vector, but little knowledge about diagnosis, prognosis, and treatment. Vector infestation indices show Brazil to have good relative control, while Colombia presents a high transmission risk. Conclusions Given the multidimensionality of dengue control, vertical control strategies are inadequate because they deny contextualized methods, alternative solutions, and local empowerment.

Development of process control strategies exploiting knowledge from systems biology: application to MDCK suspension cells

Madine Darby Canine Kidney (MDCK) cell lines have been extensively evaluated for their potential as host cells for influenza vaccine production. Recent studies allowed the cultivation of these cells in a fully defined medium and in suspension. However, reaching high cell densities in animal cell cultures still remains a challenge. To address this shortcoming, a combined methodology allied with knowledge from systems biology was reported to study the impact of the cell environment on the flux distribution. An optimization of the medium composition was proposed for both a batch and a continuous system in order to reach higher cell densities. To obtain insight into the metabolic activity of these cells, a detailed metabolic model previously developed by Wahl A. et. al was used. The experimental data of four cultivations of MDCK suspension cells, grown under different conditions and used in this work came from the Max Planck Institute, Magdeburg, Germany. Classical metabolic flux analysis (MFA) was used to estimate the intracellular flux distribution of each cultivation and then combined with partial least squares (PLS) method to establish a link between the estimated metabolic state and the cell environment. The validation of the MFA model was made and its consistency checked. The resulted PLS model explained almost 70% of the variance present in the flux distribution. The medium optimization for the continuous system and for the batch system resulted in higher biomass growth rates than the ones obtained experimentally, 0.034 h-1 and 0.030 h-1, respectively, thus reducing in almost 10 hours the duplication time. Additionally, the optimal medium obtained for the continuous system almost did not consider pyruvate. Overall the proposed methodology seems to be effective and both proposed medium optimizations seem to be promising to reach high cell densities.

Primary cilia and the regulation of hedgehog signaling: link to cardiac development

RESUMO: As células eucarióticas evoluíram um sistema de sinalização complexo que lhes permite responder aos sinais extracelulares e intracelulares. Desta forma, as vias de sinalização são essenciais para a sobrevivência da célula e do organismo, uma vez que regulam processos fundamentais, tais como o desenvolvimento, o crescimento, a imunidade, e a homeostase dos tecidos. A via de transdução de sinal Hedgehog (Hh) envolve o receptor Patched1 (Ptch1), que tem um efeito inibidor sobre a proteína Smoothened (Smo) na ausência dos seus ligandos, as proteínas Sonic hedgehog (Shh). Estas proteínas são reguladores fundamentais do desenvolvimento embrionário, como ilustrado pelas malformações drásticas observadas em embriões humanos e de murganho com perturbações da transdução de sinal da via Hh e que incluem polidactilia, defeitos craniofaciais e malformações ósseas. Igualmente importantes são as consequências da ativação inapropriada da via de sinalização Hh na formação de tumores. Curiosamente, os componentes desta via localizam-se nos cílios primários. Além disso, demonstrou-se que esta localização é crucial para a sinalização através da via Hh. Na presença dos ligandos, Ptch1 é internalizado e destinado a degradação ou sequestrado num compartimento da célula de onde não pode desempenhar o seu papel inibitório. A proteína Arl13b é uma pequena GTPase pertencente à família Arf/Arl da superfamília Ras de pequenas GTPases e foi implicada no síndrome de Joubert, uma ciliopatia caracterizada por ataxia congénita cerebelar, hipotonia, atrso mental e cardiopatia congénita. Murganhos deficientes para Arl13b, chamado hennin (hnn) morrem morrem prematuramente ao dia 13,5 de gestação (E13,5) e exibem anomalias morfológicas nos cílios que levam à interrupção da sinalização Hh. Além disso, a Arl13b está diretamente envolvida na regulação da via Hh, controlando a localização de vários componentes desta via nos cílios primários. Neste trabalho, mostramos que a Arl13b se localiza em circular dorsal ruffles (CDRs), que são estruturas de actina envolvidas em macropinocitose e internalização de recetores, e que regula a sua formação. Além disso, aprofundámos o conhecimento do processo de ativação da via de sinalização Hh, mostrando que as CDRs sequestram seletivamente e internalizam o recetor Ptch1. As CDRs formam-se minutos após ativação da via por ligandos Shh ou pelo agonista de Smo SAG e continuam a ser formadas a partir daí, sugerindo uma indução contínua da reorganização do citoesqueleto de actina quando a via está ativada. Observámos ainda que a inibição da formação de CDRs através do silenciamento de WAVE1, uma proteína necessária para a formação destas estruturas, resulta na diminuição da ativação da via de sinalização Hh. Além disso, o bloqueio da macropinocitose, que se segue ao fecho das CDRs, através do silenciamento de uma proteína necessária para a cisão de macropinossomas, nomeadamente a proteína BARS, tem um efeito semelhante. Estes resultados sugerem que as CDRs e a macropinocitose são necessárias para a ativação da via de sinalização Hh e indicam que esta via de internalização controla os níveis de sinal Hh. Durante o desenvolvimento, as células proliferativas dependem do cílio primário para a transdução de várias vias de sinalização. A via Hh induz a diferenciação do músculo cardíaco. Por conseguinte, os murganhos deficientes na via de sinalização Hh exibem uma variedade de defeitos de lateralidade, incluindo alteração do looping do coração, como pode ser visto em murganhos deficientes para Arl13b. Por conseguinte, investigámos o papel da Arl13b no desenvolvimento do coração. Mostramos que a Arl13b é altamente expressa no coração de embriões de murganho e de murganhos adultos ao nível do mRNA e da proteína. Além disso, o perfil de distribuição da Arl13b no coração segue o dos cílios primários, que são essenciais para o desenvolvimento cardíaco. Corações de murganhos hnn no estadio E12,5 mostram um canal átrio-ventricular aberto, espessamento da camada compacta ventricular e aumento do índice mitótico no ventrículo esquerdo. Além disso, um atraso de 1 a 2 dias no desenvolvimento é observado em corações de murganhos hnn, quando comparados com controlos selvagens no estadio E13,5. Assim, estes resultados sugerem que a Arl13b é necessária para o desenvolvimento embrionário do coração e que defeitos cardíacos podem contribuir para a letalidade embrionária de murganhos hnn. Em suma, foi estabelecido um novo mecanismo para a regulação dos níveis de superfície do recetor Ptch1, que envolve a remodelação do citoesqueleto de actina e a formação de CDRs após a ativação da via de sinalização Hh. Este mecanismo permite um feedback negativo que evita a repressão excessiva da via através da remoção de Ptch1 da superfície da célula. Além disso, determinou-se que uma mutação de perda de função na Arl13b causa defeitos cardíacos durante o desenvolvimento, possivelmente relacionados com a associação dos defeitos em cílios primários e na sinalização Hh, existentes em murganhos deficientes para Arl13b. A via de sinalização Hh tem tido um papel central entre as vias de sinalização, uma vez que a sua regulação é crucial para o funcionamento apropriada da célula. Assim, a descoberta de um novo mecanismo de tráfego através de macropinocitose e CDRs que controla a ativação e repressão da via de sinalização Hh traz novas perspetivas de como esta via pode ser regulada e pode ainda conduzir à identificação de novos alvos e estratégias terapêuticas. --------------------ABSTRACT: Eukaryotic cells have evolved a complex signaling system that allows them to respond to extracellular and intracellular cues. Signaling pathways are essential for cell and organism survival, since they regulate fundamental processes such as development, growth, immunity, and tissue homeostasis. The Hedgehog (Hh) pathway of signal transduction involves the receptor Patched1 (Ptch1), which has an inhibitory effect on Smoothened (Smo) in the absence of its ligands, the Sonic hedgehog (Shh) proteins. These proteins are fundamental regulators of embryonic development, as illustrated by the dramatic malformations seen in human and mouse embryos with perturbed Hh signal transduction that include polydactyly, craniofacial defects and skeletal malformations. Equally important are the consequences of inappropriate activation of the Hh signaling response in tumor formation. Interestingly, the components of this pathway localize to primary cilia. Moreover, it has been shown that this localization is crucial for Hh signaling. However, in the presence of the ligands, Ptch1 is internalized and destined for degradation or sequestered in a cell compartment where it no longer can play its inhibitory role. ADP-ribosylation factor-like (Arl) 13b, a small GTPase belonging to Arf/Arl family of the Ras superfamily of small GTPases has been implicated in Joubert syndrome, a ciliopathy characterized by congenital cerebellar ataxia, hypotonia, intellectual disability and congenital heart disease. Arl13b-deficient mice, called hennin (hnn) die at embryonic day 13.5 (E13.5) and display morphological abnormalities in primary cilia that lead to the disruption of Hh signaling. Furthermore, Arl13b is directly involved in the regulation of Hh signaling by controlling the localization of several components of this pathway to primary cilia. Here, we show that Arl13b localizes to and regulates the formation of circular dorsal rufles (CDRs), which are actin-basedstructures known to be involved in macropinocytosis and receptor internalization. Additionally, we extended the knowledge of the Hh signaling activation process by showing that CDRs selectively sequester and internalize Ptch1 receptors. CDRs are formed minutes after Hh activation by Shh ligands or the Smo agonist SAG and keep being formed thereafter, suggesting a continuous induction of actin reorganization when the pathway is switched on. Importantly, we observed that disruption of CDRs by silencing WAVE1, a protein required for CDR formation, results in down-regulation of Hh signaling activation. Moreover, the blockade of macropinocytosis, which follows CDR closure, through silencing of a protein necessary for the fission of macropinosomes, namely BARS has a similar effect. These results suggest that CDRs and macropinocytosis are necessary for activation of Hh signaling and indicate that this pathway of internalization controls Hh signal levels. During development, proliferating cells rely on the primary cilium for the transduction of several signaling pathways. Hh induces the differentiation of cardiac muscle. Accordingly, Hh-deficient mice display a variety of laterality defects, including alteration of heart looping, as seen in Arl13b-deficient mice. Therefore, we investigated the role of Arl13b in heart development. We show that Arl13b is highly expressed in the heart of both embryonic and adult mice at mRNA and protein levels. Also, Arl13b localization profile mimics that of primary cilia, which have been shown to be essential to early heart development. E12.5 hnn hearts show an open atrioventricular channel, increased thickening of the ventricular compact layer and increased mitotic index in the left ventricle. Moreover, a delay of 1 to 2 days in development is observed in hnn hearts, when compared to wild-type controls at E13.5. Hence, these results suggest that Arl13b is necessary for embryonic heart development and that cardiac defects might contribute to the embryonic lethality of hnn mice. Altogether, we established a novel mechanism for the regulation of Ptch1 surface levels, involving cytoskeleton remodeling and CDR formation upon Hh signaling activation. This mechanism allows a negative feedback loop that prevents excessive repression of the pathway by removing Ptch1 from the cell surface. Additionally, we determined that the Arl13b loss-offunction mutation causes cardiac defects during development, possibly related to the associated ciliary and Hh signaling defects found in Arl13b-deficient mice. Hh signaling has taken a center stage among the signaling pathways since its regulation is crucial for the appropriate output and function of the cell. Hence, the finding of a novel trafficking mechanism through CDRs and macropinocytosis that controls Hh signaling activation and repression brings new insights to how this pathway can be regulated and can lead to the discovery of novel therapeutic targets and strategies.

Knowledge and practices related to dengue and its vector: a community-based study from Southeast Brazil

Abstract INTRODUCTION: This study investigated the knowledge of users of primary healthcare services living in Ribeirão Preto, Brazil, about dengue and its vector. METHODS: A cross-sectional survey of 605 people was conducted following a major dengue outbreak in 2013. RESULTS: Participants with higher levels of education were more likely to identify correctly the vector of the disease. CONCLUSIONS: The results emphasize the relevance of health education programs, the continuous promotion of educational campaigns in the media, the role of the television as a source of information, and the importance of motivating the population to control the vector.

The World Health Organization Multi-Professional Patient Safety Curriculum : implementation of key modules and its impact on patient safety knowledge, skills, and attitudes of medical students at the University of Algarve

ABSTRACT - Objectives: We attempted to show how the implementation of the key elements of the World Health Organization Patient Safety Curriculum Guide Multi-professional Edition in an undergraduate curriculum affected the knowledge, skills, and attitudes towards patient safety in a graduate entry Portuguese Medical School. Methods: After receiving formal recognition by the WHO as a Complementary Test Site and approval of the organizational ethics committee , the validated pre-course questionnaires measuring the knowledge, skills, and attitudes to patient safety were administered to the 2nd and3rd year students pursuing a four-year course (N = 46). The key modules of the curriculum were implemented over the academic year by employing a variety of learning strategies including expert lecturers, small group problem-based teaching sessions, and Simulation Laboratory sessions. The identical questionnaires were then administered and the impact was measured. The Curriculum Guide was evaluated as a health education tool in this context. Results: A significant number of the respondents, 47 % (n = 22), reported having received some form of prior patient safety training. The effect on Patient Safety Knowledge was assessed by using the percentage of correct pre- and post-course answers to construct 2 × 2 contingency tables and by applying Fishers’ test (two-tailed). No significant differences were detected (p < 0.05). To assess the effect of the intervention on Patient Safety skills and attitudes, the mean and standard deviation were calculated for the pre and post-course responses, and independent samples were subjected to Mann-Whitney’s test. The attitudinal survey indicated a very high baseline incidence of desirable attitudes and skills toward patient safety. Significant changes were detected (p < 0.05) regarding what should happen if an error is made (p = 0.016), the role of healthcare organizations in error reporting (p = 0.006), and the extent of medical error (p = 0.005). Conclusions: The implementation of selected modules of the WHO Patient Safety Curriculum was associated with a number of positive changes regarding patient safety skills and attitudes, with a baseline incidence of highly desirable patient safety attitudes, but no measureable change on the patient safety knowledge, at the University of Algarve Medical School. The significance of these results is discussed along with implications and suggestions for future research.

Semantic relations extraction from unstructured information for domain ontologies enrichment

Based in internet growth, through semantic web, together with communication speed improvement and fast development of storage device sizes, data and information volume rises considerably every day. Because of this, in the last few years there has been a growing interest in structures for formal representation with suitable characteristics, such as the possibility to organize data and information, as well as the reuse of its contents aimed for the generation of new knowledge. Controlled Vocabulary, specifically Ontologies, present themselves in the lead as one of such structures of representation with high potential. Not only allow for data representation, as well as the reuse of such data for knowledge extraction, coupled with its subsequent storage through not so complex formalisms. However, for the purpose of assuring that ontology knowledge is always up to date, they need maintenance. Ontology Learning is an area which studies the details of update and maintenance of ontologies. It is worth noting that relevant literature already presents first results on automatic maintenance of ontologies, but still in a very early stage. Human-based processes are still the current way to update and maintain an ontology, which turns this into a cumbersome task. The generation of new knowledge aimed for ontology growth can be done based in Data Mining techniques, which is an area that studies techniques for data processing, pattern discovery and knowledge extraction in IT systems. This work aims at proposing a novel semi-automatic method for knowledge extraction from unstructured data sources, using Data Mining techniques, namely through pattern discovery, focused in improving the precision of concept and its semantic relations present in an ontology. In order to verify the applicability of the proposed method, a proof of concept was developed, presenting its results, which were applied in building and construction sector.

Comuns: An Open-Data Provider, Explorer and Analytic Toolbox Based on FOSS

Contém resumo

An agent based architecture to support monitoring in plug and produce manufacturing systems using knowledge extraction

In recent years a set of production paradigms were proposed in order to capacitate manufacturers to meet the new market requirements, such as the shift in demand for highly customized products resulting in a shorter product life cycle, rather than the traditional mass production standardized consumables. These new paradigms advocate solutions capable of facing these requirements, empowering manufacturing systems with a high capacity to adapt along with elevated flexibility and robustness in order to deal with disturbances, like unexpected orders or malfunctions. Evolvable Production Systems propose a solution based on the usage of modularity and self-organization with a fine granularity level, supporting pluggability and in this way allowing companies to add and/or remove components during execution without any extra re-programming effort. However, current monitoring software was not designed to fully support these characteristics, being commonly based on centralized SCADA systems, incapable of re-adapting during execution to the unexpected plugging/unplugging of devices nor changes in the entire system’s topology. Considering these aspects, the work developed for this thesis encompasses a fully distributed agent-based architecture, capable of performing knowledge extraction at different levels of abstraction without sacrificing the capacity to add and/or remove monitoring entities, responsible for data extraction and analysis, during runtime.

Why further investigation of brazilian Strychnos?

During the past fifteen years, African Strychnos species have been pharmacologically and chemically screened by some European Universities, sometimes with the collaboration of some African Institutes. Strychnos usambarensis will be discussed here because of our interest in it, after the discovery of its use in the preparation arrow poison with curarizing activity.The European studies have show thah the African species of Strychnoschemically are very similar to certain South-American species. Indeed, the occurrence in the African species of curarizing quaternary bases, and in the American species of tetanizing tertiary bases, such as akagerine, emphasizes the unity of genus Strychnos in terms of it alkaloids. Many biological activities (antmicrobial, hypotensive, smasmolytic, amoebicial...) have been detected.Finally, the antimitotic properties of some alkaloids will be presented. Besides know antitumor drugs, e.g. alstonine and ellipticine, African species possess new antimitotic products, e.g. strychnopentamine present in Strychnos usambarensis.Because of these findings, the main reasons why further investigate Brazilian Strychnos species are the lack of knowledge about:- the distribution on the species in the southern part of the great Amazon Basin.Accordin to Krukoff, it is possible that new species may be found there.- the distribution of alkaloids in many of know species. Indeed, there is little information on the variation in compposition of the alkaloidal mixtures in the different parts of the plants.- the biological of alkaloids. In the past, interest has been focused too narrowly on possible curarizing properties.Why should Brazilian species not cantain alkaloids with properties similar to those found in the African species?