Severe visceral leishmaniasis in children: the relationship between cytokine patterns and clinical features

Introduction The relationship between severe clinical manifestations of visceral leishmaniasis (VL) and immune response profiles has not yet been clarified, despite numerous studies on the subject. This study aimed to investigate the relationship between cytokine profiles and the presence of immunological markers associated with clinical manifestations and, particularly, signs of severity, as defined in a protocol drafted by the Ministry of Health (Brazil). Methods We conducted a prospective, descriptive study between May 2008 and December 2009. This study was based on an assessment of all pediatric patients with VL who were observed in a reference hospital in Maranhão. Results Among 27 children, 55.5% presented with more than one sign of severity or warning sign. Patients without signs of severity or warning signs and patients with only one warning sign had the highest interferon-gamma (IFN-γ) levels, although their interleukin 10 (IL-10) levels were also elevated. In contrast, patients with the features of severe disease had the lowest IFN-γ levels. Three patients who presented with more than two signs of severe disease died; these patients had undetectable interleukin 2 (IL-2) and IFN-γ levels and low IL-10 levels, which varied between 0 and 36.8pg/mL. Conclusions Our results showed that disease severity was associated with low IFN-γ levels and elevated IL-10 levels. However, further studies with larger samples are needed to better characterize the relationship between disease severity and cytokine levels, with the aim of identifying immunological markers of active-disease severity.

Structural transformation in the product space: Patterns and implications

Product fundamentals are essential in explaining heterogeneity in the product space. The scope for adapting and transferring capabilities into the production of different goods determines the speed and intensity of the structural transformation process and entails dissimilar development opportunities for nations. Future specialization patterns become then partly determined by the current network of products’ relatedness. Building on previous literature, this paper explicitly compares methodological concepts of product connectivity to conclude in favor of the density measure we propose combined with the Revealed Relatedness Index (RRI) approach presented by Freitas and Salvado (2011). Overall, RRI specifications displayed more consistent behavior when different time horizons are equated.

Changes in prescribing patterns of benzodiazepines after training of general practitioners

RESUMO: Introdução: As benzodiazepinas são os fármacos ansiolíticos e hipnóticos mais utilizados. O elevado consumo destes fármacos tem representado uma preocupação devido aos efeitos secundários do seu uso prolongado e dependência. Portugal tem a maior utilização de benzodiazepinas na Europa. Este estudo pretende analisar a alteração do padrão de prescrição de benzodiazepinas após uma intervenção com clínicos gerais. Métodos: A intervenção consistiu numa sessão educacional a um grupo de clínicos gerais. Foi comparado o padrão de prescrição de benzodiazepinas dos médicos intervencionados com o de um grupo de médicos não intervencionado da mesma região e com o de um grupo de médicos não intervencionados de outra região. Analisaram-­‐se as prescrições de 12 meses antes e depois da intervenção. A análise do padrão de prescrição utilizou como metodologia a Dose Diária Definida (DDD) e a Dose Diária Definida por 1000 pacientes por dia (DHD). A análise estatística recorreu a métodos de regressão segmentada. Resultados: Houve uma diminuição no padrão de prescrição de benzodiazepinas no grupo intervencionado após a intervenção (p=0.005). Houve também uma redução no padrão de prescrição no grupo não intervencionada da mesma região (p=0.037) e no grupo não-intervencionado da região diferente (p=0.010). Analisando por género, prescritores do género feminino prescrevem uma quantidade maior de benzodiazepinas. Os clínicos gerais do género feminino intervencionados tiveram a maior redução na prescrição após a intervenção (p=0.008). Discussão: Os dados demonstraram que a intervenção reduziu a prescrição de benzodiazepinas após a intervenção. A diminuição geral do padrão de prescrição poderá ser explicada pelo efeito de Hawthorne ou pela contaminação entre os três grupos de clínicos gerais. Os dados disponíveis não explicam as diferenças nos padrões de prescrição por género. Conclusão: Este estudo demonstra como uma única intervenção tem um impacto positivo na melhoria dos padrões de prescrição. A replicação desta intervenção poderá representar uma oportunidade para alterar a prescrição de benzodiazepinas em Portugal. -----------------------------ABSTRACT: Introduction: Benzodiazepines are the most utilized anxiolytic and hypnotic drugs. The high consumption of benzodiazepines has been a concern due to the reported side effects of long-­‐term use and dependence. Portugal has the highest benzodiazepine utilisation in Europe. This study aims to analyse the change in General Practitioners’ (GPs) benzodiazepine prescription pattern after na intervention period. Methods: An educational session was delivered to a group of intervened GPs. The benzodiazepine prescription pattern of the intervened group was compared to the pattern of a non-­‐intervened matched group from the same region, and to the pattern of another non-­‐intervened matched group from a diferente region. The research time frame was 12 month before and after intervention. The analysis of the prescription trends used the Defined Daily Dose (DDD) and Defined Daily Dose per 1000 patients per day (DHD) methodology. The statistical methods consisted of segmented regression analysis. Results: There was a decrease in benzodiazepine prescription pattern of intervened GPs after intervention (p=0.005). There was also a decrease in benzodiazepine prescription pattern for the non-­‐intervened group from the same region (p=0.037) and for the non-­‐ intervened group from a diferente region (p=0.010). Concerningthe analysis by gender, female gender prescribed a higher amount of benzodiazepines. The intervened female gender prescribers presented the highest decrease in prescription trend after intervention (p=0.008). Discussion: The data demonstrated that the intervention was effective in reducing benzodiazepine prescription after intervention. The general decrease in prescription trend might be explained by a Hawthorne effect or a contamination effect between the three groups of GPs. The available data couldn´t explain the diferences in prescription patterns by gender. Conclusion: This study demonstrates how a single intervention has a positive impact on improving prescription trends. The replication of this intervention might be an opportunity to changing the worrying benzodiazepine utilisation in Portugal.

Evolutionary dynamics of Chlamydia trachomatis genome and identification of molecular patterns of hypothetical protein coding genes

The obligate intracellular bacterium Chlamydia trachomatis is a human pathogen of major public health significance. Strains can be classified into 15 main serovars (A to L3) that preferentially cause ocular infections (A-C), genital infections (D-K) or lymphogranuloma venereum (LGV) (L1-L3), but the molecular basis behind their distinct tropism, ecological success and pathogenicity is not welldefined. Most chlamydial research demands culture in eukaryotic cell lines, but it is not known if stains become laboratory adapted. By essentially using genomics and transcriptomics, we aimed to investigate the evolutionary patterns underlying the adaptation of C. trachomatis to the different human tissues, given emphasis to the identification of molecular patterns of genes encoding hypothetical proteins, and to understand the adaptive process behind the C. trachomatis in vivo to in vitro transition. Our results highlight a positive selection-driven evolution of C. trachomatis towards nichespecific adaptation, essentially targeting host-interacting proteins, namely effectors and inclusion membrane proteins, where some of them also displayed niche-specific expression patterns. We also identified potential "ocular-specific" pseudogenes, and pointed out the major gene targets of adaptive mutations associated with LGV infections. We further observed that the in vivo-derived genetic makeup of C. trachomatis is not significantly compromised by its long-term laboratory propagation. In opposition, its introduction in vitro has the potential to affect the phenotype, likely yielding virulence attenuation. In fact, we observed a "genital-specific" rampant inactivation of the virulence gene CT135, which may impact the interpretation of data derived from studies requiring culture. Globally, the findings presented in this Ph.D. thesis contribute for the understanding of C.trachomatis adaptive evolution and provides new insights into the biological role of C. trachomatishypothetical proteins. They also launch research questions for future functional studies aiming toclarify the determinants of tissue tropism, virulence or pathogenic dissimilarities among C. trachomatisstrains.

Fostering e-participation sustainability through a BPM-driven semantic model

According to a recent Eurobarometer survey (2014), 68% of Europeans tend not to trust national governments. As the increasing alienation of citizens from politics endangers democracy and welfare, governments, practitioners and researchers look for innovative means to engage citizens in policy matters. One of the measures intended to overcome the so-called democratic deficit is the promotion of civic participation. Digital media proliferation offers a set of novel characteristics related to interactivity, ubiquitous connectivity, social networking and inclusiveness that enable new forms of societal-wide collaboration with a potential impact on leveraging participative democracy. Following this trend, e-Participation is an emerging research area that consists in the use of Information and Communication Technologies to mediate and transform the relations among citizens and governments towards increasing citizens’ participation in public decision-making. However, despite the widespread efforts to implement e-Participation through research programs, new technologies and projects, exhaustive studies on the achieved outcomes reveal that it has not yet been successfully incorporated in institutional politics. Given the problems underlying e-Participation implementation, the present research suggested that, rather than project-oriented efforts, the cornerstone for successfully implementing e-Participation in public institutions as a sustainable added-value activity is a systematic organisational planning, embodying the principles of open-governance and open-engagement. It further suggested that BPM, as a management discipline, can act as a catalyst to enable the desired transformations towards value creation throughout the policy-making cycle, including political, organisational and, ultimately, citizen value. Following these findings, the primary objective of this research was to provide an instrumental model to foster e-Participation sustainability across Government and Public Administration towards a participatory, inclusive, collaborative and deliberative democracy. The developed artefact, consisting in an e-Participation Organisational Semantic Model (ePOSM) underpinned by a BPM-steered approach, introduces this vision. This approach to e-Participation was modelled through a semi-formal lightweight ontology stack structured in four sub-ontologies, namely e-Participation Strategy, Organisational Units, Functions and Roles. The ePOSM facilitates e-Participation sustainability by: (1) Promoting a common and cross-functional understanding of the concepts underlying e-Participation implementation and of their articulation that bridges the gap between technical and non-technical users; (2) Providing an organisational model which allows a centralised and consistent roll-out of strategy-driven e-Participation initiatives, supported by operational units dedicated to the execution of transformation projects and participatory processes; (3) Providing a standardised organisational structure, goals, functions and roles related to e-Participation processes that enhances process-level interoperability among government agencies; (4) Providing a representation usable in software development for business processes’ automation, which allows advanced querying using a reasoner or inference engine to retrieve concrete and specific information about the e-Participation processes in place. An evaluation of the achieved outcomes, as well a comparative analysis with existent models, suggested that this innovative approach tackling the organisational planning dimension can constitute a stepping stone to harness e-Participation value.

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.

Anorectal leiomyomas: report of two cases with different anatomical patterns and literature review

Gastrointestinal mesenchymal tumors comprise a rare group of gastrointestinal tract wall tumors that have long been a source of confusion and controversy, especially in terms of pathological classification, preoperative diagnosis, management strategies, and prognosis. This report describes the clinical manifestations and management of 2 rectal leiomyomas and reviews the pertinent literature. Case 1: A 44-year-old woman was admitted reporting a nodule in the right para-anal region for the previous 2 years. At proctological examination, a 4-cm diameter fibrous mass situated in the para-anal region that produced an arch under the smooth muscle on the right rectal wall just above the anorectal ring was noted. Computed tomography and magnetic resonance imaging of the abdomen and pelvis showed the lesion and detected no other abnormalities. Surgical treatment consisted of wide local resection of the tumor through a para-anal incision, with no attempts to perform lymphadenectomy. Case 2: A 40-year-old male patient was admitted reporting constant anal pain for 4 months. He presented a 3-cm submucosal nodule at the anterior rectal wall just above the dentate line. After 2 inconclusive preoperative biopsies, transanal resection of the tumor was performed. Histological analysis of the specimen showed a benign leiomyoma. A review of the literature is presented, emphasizing some clinical and therapeutic aspects of this unusual rectal tumor.

Semantic adaptability for the systems interoperability

In the current global and competitive business context, it is essential that enterprises adapt their knowledge resources in order to smoothly interact and collaborate with others. However, due to the existent multiculturalism of people and enterprises, there are different representation views of business processes or products, even inside a same domain. Consequently, one of the main problems found in the interoperability between enterprise systems and applications is related to semantics. The integration and sharing of enterprises knowledge to build a common lexicon, plays an important role to the semantic adaptability of the information systems. The author proposes a framework to support the development of systems to manage dynamic semantic adaptability resolution. It allows different organisations to participate in a common knowledge base building, letting at the same time maintain their own views of the domain, without compromising the integration between them. Thus, systems are able to be aware of new knowledge, and have the capacity to learn from it and to manage its semantic interoperability in a dynamic and adaptable way. The author endorses the vision that in the near future, the semantic adaptability skills of the enterprise systems will be the booster to enterprises collaboration and the appearance of new business opportunities.

Semantic architecture for sensors

Based on the report for the unit “Sociology of New Information Technologies” of the Master on Computer Sciences at FCT/University Nova Lisbon in 2015-16. The responsible of this curricular unit is Prof. António Moniz

Implementação de um modelo de geometric semantic genetic programming para aplicação naval

Recaí sob a responsabilidade da Marinha Portuguesa a gestão da Zona Económica Exclusiva de Portugal, assegurando a sua segurança da mesma face a atividades criminosas. Para auxiliar a tarefa, é utilizado o sistema Oversee, utilizado para monitorizar a posição de todas as embarcações presentes na área afeta, permitindo a rápida intervenção da Marinha Portuguesa quando e onde necessário. No entanto, o sistema necessita de transmissões periódicas constantes originadas nas embarcações para operar corretamente – casos as transmissões sejam interrompidas, deliberada ou acidentalmente, o sistema deixa de conseguir localizar embarcações, dificultando a intervenção da Marinha. A fim de colmatar esta falha, é proposto adicionar ao sistema Oversee a capacidade de prever as posições futuras de uma embarcação com base no seu trajeto até à cessação das transmissões. Tendo em conta os grandes volumes de dados gerados pelo sistema (históricos de posições), a área de Inteligência Artificial apresenta uma possível solução para este problema. Atendendo às necessidades de resposta rápida do problema abordado, o algoritmo de Geometric Semantic Genetic Programming baseado em referências de Vanneschi et al. apresenta-se como uma possível solução, tendo já produzido bons resultados em problemas semelhantes. O presente trabalho de tese pretende integrar o algoritmo de Geometric Semantic Genetic Programming desenvolvido com o sistema Oversee, a fim de lhe conceder capacidades preditivas. Adicionalmente, será realizado um processo de análise de desempenho a fim de determinar qual a ideal parametrização do algoritmo. Pretende-se com esta tese fornecer à Marinha Portuguesa uma ferramenta capaz de auxiliar o controlo da Zona Económica Exclusiva Portuguesa, permitindo a correta intervenção da Marinha em casos onde o atual sistema não conseguiria determinar a correta posição da embarcação em questão.

Human mobility patterns at the smallest scales

We present a study on human mobility at small spatial scales. Differently from large scale mobility, recently studied through dollar-bill tracking and mobile phone data sets within one big country or continent, we report Brownian features of human mobility at smaller scales. In particular, the scaling exponents found at the smallest scales is typically close to one-half, differently from the larger values for the exponent characterizing mobility at larger scales. We carefully analyze 12-month data of the Eduroam database within the Portuguese university of Minho. A full procedure is introduced with the aim of properly characterizing the human mobility within the network of access points composing the wireless system of the university. In particular, measures of flux are introduced for estimating a distance between access points. This distance is typically non-Euclidean, since the spatial constraints at such small scales distort the continuum space on which human mobility occurs. Since two different ex- ponents are found depending on the scale human motion takes place, we raise the question at which scale the transition from Brownian to non-Brownian motion takes place. In this context, we discuss how the numerical approach can be extended to larger scales, using the full Eduroam in Europe and in Asia, for uncovering the transi- tion between both dynamical regimes.

A domain-specific language for ETL patterns specification in Data Warehousing Systems

During the last few years many research efforts have been done to improve the design of ETL (Extract-Transform-Load) systems. ETL systems are considered very time-consuming, error-prone and complex involving several participants from different knowledge domains. ETL processes are one of the most important components of a data warehousing system that are strongly influenced by the complexity of business requirements, their changing and evolution. These aspects influence not only the structure of a data warehouse but also the structures of the data sources involved with. To minimize the negative impact of such variables, we propose the use of ETL patterns to build specific ETL packages. In this paper, we formalize this approach using BPMN (Business Process Modelling Language) for modelling more conceptual ETL workflows, mapping them to real execution primitives through the use of a domain-specific language that allows for the generation of specific instances that can be executed in an ETL commercial tool.

Description of behavioral patterns of Podocnemis erythrocephala (Spix, 1824) (Testudines: Podocnemididae) (Red-headed river turtle) in captivity, Manaus, Amazonas, Brazil

The biology and ecology of South American turtles is still poorly known, particularly, for the Brazilian species. Laboratory studies are essential to understand the life cycles of aquatic turtles species and to help in formulating management plans for their conservation. As a contribution to the knowledge of Podocnemis erythrocephala species, we give a description of its species-typical behaviors, categorized as: maintenance, locomotion, feeding, agonistic and reproduction, based on captives observations of four pairs of turtles in an aquarium in Manaus, Brazil. Similarities and differences with the repertoires of other turtle species are discussed, concluding that turtles have much more complex adaptative strategies and social life than was believed.

Patterns of Mycobacterium tuberculosis-complex excretion and characterization of super-shedders in naturally-infected wild boar and red deer

Wild boar (Sus scrofa) and red deer (Cervus elaphus) are the main maintenance hosts for bovine tuberculosis (bTB) in continental Europe. Understanding Mycobacterium tuberculosis complex (MTC) excretion routes is crucial to define strategies to control bTB in free-ranging populations, nevertheless available information is scarce. Aiming at filling this gap, four different MTC excretion routes (oronasal, bronchial-alveolar, fecal and urinary) were investigated by molecular methods in naturally infected hunter-harvested wild boar and red deer. In addition MTC concentrations were estimated by the Most Probable Number method. MTC DNA was amplified in all types of excretion routes. MTC DNA was amplified in at least one excretion route from 83.0% (CI95 70.8-90.8) of wild ungulates with bTB-like lesions. Oronasal or bronchial-alveolar shedding were detected with higher frequency than fecal shedding (p < 0.001). The majority of shedders yielded MTC concentrations <10(3) CFU/g or mL. However, from those ungulates from which oronasal, bronchial-alveolar and fecal samples were available, 28.2% of wild boar (CI95 16.6-43.8) and 35.7% of red deer (CI95 16.3-61.2) yielded MTC concentrations >10(3) CFU/g or mL (referred here as super-shedders). Red deer have a significantly higher risk of being super-shedders compared to wild boar (OR = 11.8, CI95 2.3-60.2). The existence of super-shedders among the naturally infected population of wild boar and red deer is thus reported here for the first time and MTC DNA concentrations greater than the minimum infective doses were estimated in excretion samples from both species.

Diversity of sand flies in domiciliary environment of Santarém, state of Pará, Brazil: species composition and abundance patterns in rural and urban areas

This paper aimed to evaluate the richness, abundance and frequency of sand fly occurrence in rural and urban areas American visceral Leishmaniasis -AVL is endemic in the study area of Santarém municipality, Pará state. Sand flies were collected during 1995-2000, using CDC light traps placed in neighborhoods and rural areas of the municipality. A total of 53.454 individuals and 26 species of sand flies were collected. The most abundant species in both urban and rural environments was Lutzomyia longipalpis, vector of AVL in the area. The highest species richness by capture was in rural area. In all years sampled, the largest number of species of sand fly collected was always in rural areas. The species of sand flies in urban and rural area were similar in 11 species. In the rural area other 11 species were found, a total of 22 species. Shannon-Wiener index ranged from 0.12 to 0.84 at rural areas and 0.08 to 0.34 at urban ones. In general, rural localities showed higher diversity (H') of phlebotomines than urban ones. Individual-based rarefaction curves for each area demonstrated that urban localities had the lowest expected number of phlebotomine species and the richest rural ones reach higher expected values with lower amount of individuals than urban sites. The most frequent species were Lutzomyia longipalpis, Evandromyia carmelinoi and Bichromomyia flaviscutellata.