Repercussões crónicas nas vias aéreas da hiperóxia neonatal : modelo experimental

RESUMO: O objectivo deste trabalho foi avaliar se a exposição crónica neonatal à hiperóxia mo-derada induz alterações funcionais e estruturais persistentes nas vias aéreas. Desenvolveu-se um modelo animal, no rato, a partir do qual se retiraram implicações para a compreensão das repercussões crónicas da hiperóxia neonatal sobre as vias aéreas de displasia broncopulmonar (DBP), em duas fases distintas: imediatamente após a exposi-ção neonatal a 50%O2 (grupo 50%O2) e após três semanas de recuperação em ar ambiente (grupo 50%O2+Ar).Compararam-se os resultados da resposta do músculo liso de traqueia (MLT) à esti-mulação in vitro com metacolina e salbutamol e avaliaram-se as alterações quantitativas da área de MLT, bem como as alterações qualitativas da estrutura da traqueia. Demonstrou-se que a exposição a 50% de oxigénio não tinha repercussões imediatas sobre a resposta in vitro do MLT à estimulação colinérgica, mas que induzia um aumento do relaxamento em resposta ao salbutamol. A contractilidade do MLT em resposta à estimula-ção com metacolina no grupo 50%O2+Ar foi significativamente superior à do grupo de con-trolo da mesma idade e também superior à observada no grupo 50%O2, enquanto que a resposta ao salbutamol se voltou a aproximar dos valores de controlo após a recuperação em normóxia. Não se observaram diferenças estatisticamente significativas na área de MLT entre os grupos experimental e de controlo, o que se deve provavelmente ao número reduzido de amostras avaliadas e à variabilidade deste parâmetro no grupo de controlo; contudo, verifi-cou-se um aumento médio de 15% imediatamente após a exposição à hiperóxia que persis-tiu após o período de recuperação.As alterações qualitativas sobre a arquitectura da traqueia, avaliadas por microscopia óptica, revelaram no grupo 50%O2 aumentos da espessura da matriz extracelular e da den-sidade de mastócitos desgranulados na submucosa e adventícia vizinhas do MLT, sem outras alterações relativamente ao grupo de controlo com 15 dias. As alterações da matriz extrace-lular foram reversíveis após a recuperação em ar ambiente. A densidade de mastócitos per-maneceu superior à do grupo de controlo de 36 dias de idade, apresentando-se em maior contiguidade com o MLT relativamente ao grupo 50%O2. Em síntese, demonstrou-se que a hiperóxia neonatal crónica em níveis moderados in-duz alterações da resposta contráctil do MLT e da estrutura da traqueia que podem ter ex-pressão funcional após a exposição ter cessado. Assim, o contributo original do presente trabalho foi o desenvolvimento de um modelo animal que permite avaliar os mecanismos pelos quais a hiperóxia é capaz de induzir, isoladamente, alterações crónicas da contracti-lidade, do relaxamento do ML e da estrutura das vias aéreas que podem ser responsáveis pela HRB persistente em doentes sujeitos a oxigenioterapia neonatal.-------------ABSTRACT: The aim of this work was to evaluate whether chronic neonatal exposure to hyperoxia in-duces persistent structural and functional airway changes. An animal model was developed, using neonatal rats, in order to understand the chronic effects of neonatal hyperoxia on the airways, in bronchopulmonary dysplasia, in two distinct phases: immediately after neonatal exposure to 50%O2 (50%O2 group) and after three weeks of recovery at ambient air (50%O2+Ar group).The results from the tracheal smooth muscle (TSM) response to in vitro stimulation with metacholine and salbutamol were compared and quantitative changes in TSM area, as well as qualitative changes in tracheal structure were evaluated. It was demonstrated that while exposure to 50% oxygen had no immediate effects on in vitro TSM response to cholinergic stimulation, it induced an increase in relaxation as a result of salbutamol administration. TSM contractility as a result of methacholine administration in the 50%O2 + Ar group was significantly higher than that of the same-age control group, and also higher than the one observed in the 50%O2 group, whereas the response to salbutamol admini-stration was once again closer to the control values after recovery in normoxia. There were no statistically significant differences in the TSM area between the experi-mental and control groups, which is most likely due to the reduced number of samples evalu-ated and to the variability of this parameter in the control group. However, there was an aver-age increase of 15% immediately after exposure to hyperoxia, which persisted after the recov-ery period. Qualitative changes in tracheal architecture, evaluated by optic microscopy, revealed that the 50%O2 group suffered an increase in the thickness of the extracellular matrix and degranu-lated mast cell density in the submucosa and adventitia adjacent to the TSM, without further changes when compared with the control group at 15 days of age. The changes in extracellular matrix were reversible after recovery in ambient air. Mast cell density remained higher than that of the control group at 36 days of age, and more contiguous to TSM than the 50%O2 group. In conclusion, it has been demonstrated that moderate levels of chronic neonatal hyperoxia in-duce changes in TSM contractile response and tracheal structure, which may be functionally ex-pressed after discontinuation of exposure. Therefore, the original contribution of the present work was the development of an animal model which allows the evaluation of the mechanisms through which hyperoxia alone can induce chronic changes in contractility and relaxation of SM and also in airway structure that can be responsible for the persistent airway hyperrespon-siveness found in patients who were submited to neonatal oxygen therapy.

Flood resilient housing recovery models: a theoretical case study in Maldives

Natural disasters are events that cause general and widespread destruction of the built environment and are becoming increasingly recurrent. They are a product of vulnerability and community exposure to natural hazards, generating a multitude of social, economic and cultural issues of which the loss of housing and the subsequent need for shelter is one of its major consequences. Nowadays, numerous factors contribute to increased vulnerability and exposure to natural disasters such as climate change with its impacts felt across the globe and which is currently seen as a worldwide threat to the built environment. The abandonment of disaster-affected areas can also push populations to regions where natural hazards are felt more severely. Although several actors in the post-disaster scenario provide for shelter needs and recovery programs, housing is often inadequate and unable to resist the effects of future natural hazards. Resilient housing is commonly not addressed due to the urgency in sheltering affected populations. However, by neglecting risks of exposure in construction, houses become vulnerable and are likely to be damaged or destroyed in future natural hazard events. That being said it becomes fundamental to include resilience criteria, when it comes to housing, which in turn will allow new houses to better withstand the passage of time and natural disasters, in the safest way possible. This master thesis is intended to provide guiding principles to take towards housing recovery after natural disasters, particularly in the form of flood resilient construction, considering floods are responsible for the largest number of natural disasters. To this purpose, the main structures that house affected populations were identified and analyzed in depth. After assessing the risks and damages that flood events can cause in housing, a methodology was proposed for flood resilient housing models, in which there were identified key criteria that housing should meet. The same methodology is based in the US Federal Emergency Management Agency requirements and recommendations in accordance to specific flood zones. Finally, a case study in Maldives – one of the most vulnerable countries to sea level rise resulting from climate change – has been analyzed in light of housing recovery in a post-disaster induced scenario. This analysis was carried out by using the proposed methodology with the intent of assessing the resilience of the newly built housing to floods in the aftermath of the 2004 Indian Ocean Tsunami.

Models and tools for value systems analysis in collaborative environments

Dissertation to obtain the degree of Doctor in Electrical and Computer Engineering, specialization of Collaborative Networks

Knowledge Society and Geography: A Theoretical Approach

The transition process between information and knowledge is faster and so the inputs that influence social and political practises. The dissemination of information is now determinant in terms of territorial competitiveness and both public and private sector take large benefits when the data-information- knowledge value chain repeats itself trough space and time. Mankind depends nowadays on the creation and diffusion of good and reliable information. Speed is also important and the greater the speed, the faster the opportunities for global markets. Information must be an input for knowledge and obviously for decision. So, the power of information is unquestionable. This paper focuses on concepts like information, knowledge and other, more geographical and tries to explain how territories change from real to virtual. Knowledge society appears on an evolutional context in which information dissemination is wider and technological potential overwrites traditional notions of Geography. To understand the mutations over the territories, the causes and the consequences emerges the Geography of the Knowledge Society, a new discipline inside Geography with a special concern about modern society and socio-economical developing models.

Participatory Surveillance and Mathematical Models in Epidemiologic Research: Successes and Challenges

Theoretical epidemiology aims to understand the dynamics of diseases in populations and communities. Biological and behavioral processes are abstracted into mathematical formulations which aim to reproduce epidemiological observations. In this thesis a new system for the self-reporting of syndromic data — Influenzanet — is introduced and assessed. The system is currently being extended to address greater challenges of monitoring the health and well-being of tropical communities.(...)

Cognitive models for the concept of angle

Tese de doutoramento em Filosofia

Constraint reasoning for differential models

The basic motivation of this work was the integration of biophysical models within the interval constraints framework for decision support. Comparing the major features of biophysical models with the expressive power of the existing interval constraints framework, it was clear that the most important inadequacy was related with the representation of differential equations. System dynamics is often modelled through differential equations but there was no way of expressing a differential equation as a constraint and integrate it within the constraints framework. Consequently, the goal of this work is focussed on the integration of ordinary differential equations within the interval constraints framework, which for this purpose is extended with the new formalism of Constraint Satisfaction Differential Problems. Such framework allows the specification of ordinary differential equations, together with related information, by means of constraints, and provides efficient propagation techniques for pruning the domains of their variables. This enabled the integration of all such information in a single constraint whose variables may subsequently be used in other constraints of the model. The specific method used for pruning its variable domains can then be combined with the pruning methods associated with the other constraints in an overall propagation algorithm for reducing the bounds of all model variables. The application of the constraint propagation algorithm for pruning the variable domains, that is, the enforcement of local-consistency, turned out to be insufficient to support decision in practical problems that include differential equations. The domain pruning achieved is not, in general, sufficient to allow safe decisions and the main reason derives from the non-linearity of the differential equations. Consequently, a complementary goal of this work proposes a new strong consistency criterion, Global Hull-consistency, particularly suited to decision support with differential models, by presenting an adequate trade-of between domain pruning and computational effort. Several alternative algorithms are proposed for enforcing Global Hull-consistency and, due to their complexity, an effort was made to provide implementations able to supply any-time pruning results. Since the consistency criterion is dependent on the existence of canonical solutions, it is proposed a local search approach that can be integrated with constraint propagation in continuous domains and, in particular, with the enforcing algorithms for anticipating the finding of canonical solutions. The last goal of this work is the validation of the approach as an important contribution for the integration of biophysical models within decision support. Consequently, a prototype application that integrated all the proposed extensions to the interval constraints framework is developed and used for solving problems in different biophysical domains.

Diversity in Teams: Source of Conflict or Source of Creativity? Investigating Hidden Mental Models

The workforce in organizations today is becoming increasingly diverse. Consequently the role of diversity management is heavily discussed with respect to the question how diversity influences the productivity of a group. Empirical studies show that on one hand there is a potential for increasing productivity but on the other hand it might be as well that conflicts arise due to the heterogeneity of the group. Usually according empirical studies are based on interviews, questionnaires and/or observations. These methods imply that answers are highly selective and filtered. In order to make the invisible visible, to have access to mental models of team members the paper will present an empirical study on the self-understanding of groups based on an innovative research method, called “mind-scripting”.

An integrated approach for TQM implementation in SMEs

This paper tackles the broad issue of TQM implementation in SMEs. It includes a review of two models aimed at improving organisational performance, the EFQM Excellence Model and the Balanced Scorecard, which have been widely used in large organisations. Both models are examined as to their suitability and applicability to small and medium sized enterprises. The findings indicate that SMEs can benefit from the adoption of an integrated approach that combines both models if some critical factors are considered in the implementation process. A theoretical framework is proposed, which considers such integration and leads to a gradual implementation of TQM principles and methods in SMEs.

Estimation and hypothesis testing in mixed linear models

Dissertação apresentada para obtenção do Grau de Doutor em Matemática, Estatística, pela Universidade Nova de Lisboa, faculdade de Ciências e Tecnologia

Analysis of glycosylation heterogeneity in antibody production by Pichia pastoris

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau de Mestre em Biotecnologia

A behavioral analysis tool for models of software systems

Trabalho apresentado no âmbito do Mestrado em Engenharia Informática, como requisito parcial para obtenção do grau de Mestre em Engenharia Informática

The computational role of short-term plasticity and the balance of excitation and inhibition in neural microcircuits: experimental and theoretical analysis

The computations performed by the brain ultimately rely on the functional connectivity between neurons embedded in complex networks. It is well known that the neuronal connections, the synapses, are plastic, i.e. the contribution of each presynaptic neuron to the firing of a postsynaptic neuron can be independently adjusted. The modulation of effective synaptic strength can occur on time scales that range from tens or hundreds of milliseconds, to tens of minutes or hours, to days, and may involve pre- and/or post-synaptic modifications. The collection of these mechanisms is generally believed to underlie learning and memory and, hence, it is fundamental to understand their consequences in the behavior of neurons.(...)

Model morphisms (MoMo) to enable language independent information models and interoperable business networks

MSc. Dissertation presented at Faculdade de Ciências e Tecnologia of Universidade Nova de Lisboa to obtain the Master degree in Electrical and Computer Engineering

Simulation of the velocity field in compound channel flow using different closure models

1st European IAHR Congress,6-4 May, Edinburg, Scotland