Comparative evaluation of adverse effects in the use of powder trivalent antivenom and liquid antivenoms in Bothrops snake bites

INTRODUCTION: Snake bite, a problem in public health, generally occurs where there is no electric power. METHODS: A comparative clinical study was conducted with 102 victims of Bothrops snake bite, from the state of Amazonas, Brazil; 58 victims were treated with liofilizated trivalent antivenom serum (SATL) and 44 victims treated with liquid bivalent and monovalent antivenom serum (SAMBL). RESULTS: 17% (10/58) of patients presented adverse effects with the SATL and 25% (11/44) with the SAMBL. CONCLUSIONS: There was no statistic difference in number of adverse effects between the two types of snake bite antivenom.

Essays on bounded rationality: Individual decision and strategic interaction

Economics is a social science which, therefore, focuses on people and on the decisions they make, be it in an individual context, or in group situations. It studies human choices, in face of needs to be fulfilled, and a limited amount of resources to fulfill them. For a long time, there was a convergence between the normative and positive views of human behavior, in that the ideal and predicted decisions of agents in economic models were entangled in one single concept. That is, it was assumed that the best that could be done in each situation was exactly the choice that would prevail. Or, at least, that the facts that economics needed to explain could be understood in the light of models in which individual agents act as if they are able to make ideal decisions. However, in the last decades, the complexity of the environment in which economic decisions are made and the limits on the ability of agents to deal with it have been recognized, and incorporated into models of decision making in what came to be known as the bounded rationality paradigm. This was triggered by the incapacity of the unboundedly rationality paradigm to explain observed phenomena and behavior. This thesis contributes to the literature in three different ways. Chapter 1 is a survey on bounded rationality, which gathers and organizes the contributions to the field since Simon (1955) first recognized the necessity to account for the limits on human rationality. The focus of the survey is on theoretical work rather than the experimental literature which presents evidence of actual behavior that differs from what classic rationality predicts. The general framework is as follows. Given a set of exogenous variables, the economic agent needs to choose an element from the choice set that is avail- able to him, in order to optimize the expected value of an objective function (assuming his preferences are representable by such a function). If this problem is too complex for the agent to deal with, one or more of its elements is simplified. Each bounded rationality theory is categorized according to the most relevant element it simplifes. Chapter 2 proposes a novel theory of bounded rationality. Much in the same fashion as Conlisk (1980) and Gabaix (2014), we assume that thinking is costly in the sense that agents have to pay a cost for performing mental operations. In our model, if they choose not to think, such cost is avoided, but they are left with a single alternative, labeled the default choice. We exemplify the idea with a very simple model of consumer choice and identify the concept of isofin curves, i.e., sets of default choices which generate the same utility net of thinking cost. Then, we apply the idea to a linear symmetric Cournot duopoly, in which the default choice can be interpreted as the most natural quantity to be produced in the market. We find that, as the thinking cost increases, the number of firms thinking in equilibrium decreases. More interestingly, for intermediate levels of thinking cost, an equilibrium in which one of the firms chooses the default quantity and the other best responds to it exists, generating asymmetric choices in a symmetric model. Our model is able to explain well-known regularities identified in the Cournot experimental literature, such as the adoption of different strategies by players (Huck et al. , 1999), the inter temporal rigidity of choices (Bosch-Dom enech & Vriend, 2003) and the dispersion of quantities in the context of di cult decision making (Bosch-Dom enech & Vriend, 2003). Chapter 3 applies a model of bounded rationality in a game-theoretic set- ting to the well-known turnout paradox in large elections, pivotal probabilities vanish very quickly and no one should vote, in sharp contrast with the ob- served high levels of turnout. Inspired by the concept of rhizomatic thinking, introduced by Bravo-Furtado & Côrte-Real (2009a), we assume that each per- son is self-delusional in the sense that, when making a decision, she believes that a fraction of the people who support the same party decides alike, even if no communication is established between them. This kind of belief simplifies the decision of the agent, as it reduces the number of players he believes to be playing against { it is thus a bounded rationality approach. Studying a two-party first-past-the-post election with a continuum of self-delusional agents, we show that the turnout rate is positive in all the possible equilibria, and that it can be as high as 100%. The game displays multiple equilibria, at least one of which entails a victory of the bigger party. The smaller one may also win, provided its relative size is not too small; more self-delusional voters in the minority party decreases this threshold size. Our model is able to explain some empirical facts, such as the possibility that a close election leads to low turnout (Geys, 2006), a lower margin of victory when turnout is higher (Geys, 2006) and high turnout rates favoring the minority (Bernhagen & Marsh, 1997).

Princípios de terapêutica antibiótica na doença crítica

RESUMO: A infeção é frequente durante a doença crítica, quer como causa da doença crítica quer como complicação da sua evolução. Paradoxalmente, os avanços da medicina moderna aumentaram eles próprios o risco de infeção, ao permitir a sobrevida até idades avançadas, ao criar um novo grupo de doentes imunodeprimidos, nomeadamente doentes tratados com fármacos que interferem com as suas defesas naturais (corticóides, citostáticos), ao aumentar o tempo de vida de hospedeiros com comorbilidades debilitantes. Os antibióticos são um dos elos essenciais no tratamento da infeção. Contudo o seu uso também promove a seleção e crescimento de bactérias resistentes. Para além disso as doses convencionais de antibióticos foram selecionadas numa altura em que a resistência era um fenómeno raro e podem não ser atualmente as mais adequadas. Existe hoje muita evidência acumulada que os doentes críticos sofrem alterações da sua farmacocinética (PK) que podem facilitar a ocorrência de falência terapêutica ou de toxicidade tanto por sub como por sobredosagem de antibióticos. Essas alterações são complexas e difíceis de estudar. Finalmente, também a farmacodinâmica (PD) dos antibióticos pode estar alterada nesta população, podendo haver necessidade de ajustar os alvos terapêuticos de forma individual. O objetivo deste trabalho foi investigar a relação entre a terapêutica antibiótica, as suas características PK e PD, a carga bacteriana e o prognóstico dos doentes críticos. O plano de investigação incluiu: 1. Dados da epidemiologia portuguesa de doentes críticos com infeção; 2. Avaliação da relação entre a carga bacteriana, o tempo até ao início do tratamento antibiótico e o prognóstico dos doentes críticos; 3. Avaliação da evolução da PK durante o tratamento da infeção; 4. Um estudo multicêntrico para avaliação da eficácia da terapêutica com um β- lactâmico doseado de acordo com a relação PK/PD. Na introdução é descrita a importância dos antibióticos, a sua origem e o problema crescente das resistências bacterianas relacionadas com o seu emprego e abuso. É salientada a importância de racionalizar a posologia, de acordo com os conceitos de PK e de PD. No Capítulo 1 são apresentados dados de epidemiologia portuguesa de infeção em doentes críticos, sobretudo retirados de dois estudos prospetivos, observacionais, os quais incluíram mais de 50% da capacidade de internamento em cuidados intensivos existente em Portugal. No Capítulo 2 são descritos os conceitos de PK e as suas alterações nos doentes críticos. De seguida são revistos os conceitos de PD de antibióticos e a sua aplicação a esta população, em particular durante as infeções graves (Capítulo 3). Nos capítulos seguintes são aprofundadas estas alterações da PK nos doentes críticos e as suas causas, de forma a destacar a importância da monitorização da concentração dos antibióticos. São apresentados os dados duma revisão sistemática de PK de antibóticos nesta população (Capítulo 4), pormenorizadas as alterações da PD que comprometem a eficácia da terapêutica antibiótica, facilitam o desenvolvimento de resistências e podem levar a falência terapêutica (Capítulo 5). Consequentemente a compreensão global destas alterações, da sua relevância clínica e a revisão da evidência disponível facilitou o desenvolvimento do próprio plano global de investigação (Capítulos 6 e 7). No Capítulo 6.1 são descritos os antibióticos tempo-dependente e a importância de aumentar o seu tempo de perfusão. Foi desenhado um estudo multicêntrico para comparar a eficácia e segurança da perfusão contínua da piperacilina tazobactam (um antibiótico β-lactâmico associado a um inibidor de β-lactamases) com a mesma dose do antibiótico, administrado em dose convencional, intermitente. A importância de dosear corretamente os antibióticos concentração-dependente foi também avaliada num estudo a primeira dose dos aminoglicosídeos (Capítulo 6.2). Outras estratégias para melhorar os resultados assistenciais dos doentes infetados são abordadas no Capítulo 7, em particular a importância da terapêutica antibiótica precoce, a avaliação da carga bacteriana e a compreensão da variação da PK ao longo do tratamento da infeção. Foi desenvolvido um algoritmo de abordagem terapêutica que incluiu estas alterações da PK e da PD nos doentes críticos. Finalmente no Capítulo 8 são descritos mecanismos de desenvolvimento das resistências bacterianas bem como estratégias para a sua abordagem. O Capítulo final (Capítulo 9) aponta um plano para futuras áreas de trabalho. O elemento chave identificado neste trabalho de investigação é o reconhecimento da variabilidade significativa da PK dos antibióticos durante a doença crítica, a qual condiciona a sua posologia. Estas alterações estão relacionadas com a própria gravidade da doença e tendem a diminuir ao longo do seu tratamento. No entanto nem a gravidade da doença nem as características individuais as permitem prever de forma aceitável pelo que a utilização duma posologia universal, independente da situação clínica concreta, pode ser inadequada. As estratégias para melhorar os resultados assistenciais dos doentes críticos infetados devem ser baseadas na individualização da posologia antibiótica de acordo com os princípios da PK e da PD, preferencialmente apoiadas em doseamentos da sua concentração. ------------------------------------ ABSTRACT: Infection commonly occurred during critical illness, either as a cause or complicating the course of the disease. Advances in medicine had paradoxically increase the risk of infection, both by improving survival to older ages and by introducing a new group of immunosuppressed patients, those who are treated with drugs that interfere with their natural defenses (corticosteroids, cytostatics) and those who survived longer with aggressive diseases. Antibiotics are of paramount importance for treating infection. However the use of these drugs also promote the selection and growth of resistant bacteria. Furthermore conventional antibiotic doses were calculated for less severe patients during a time when resistance was rare. Nowadays there is increasing evidence that critically ill patients experiment altered pharmacokinetics (PK) that may lead to therapeutic failure and/or drug toxicity. Equally, such PK alterations are complex and challenging to investigate. Finally pharmacodynamics (PD) may also be different in this population and antibiotic targets may need to be tailored to the individual patient. The aim of this research was to investigate the relationship between antibiotic therapy, its PK and PD, bacterial burden and critically ill patients outcomes. The research plan comprised of: 1. Epidemiological portuguese data of critically ill infected patients; 2. Relationship between burden of bacteria, time until the start of antibiotics and patient outcomes; 3. Evaluation of PK during treatment of infection; 4. A multicentre study evaluating PK guided β-lactam therapy. The introductory chapter outlines the importance of antibiotics, its origins, the problem of increasing bacteria resistance, related to its use and overuse and the importance of rational drug dosing using PK and PD concepts. In Chapter 1 portuguese epidemiological data of infections in critically ill patients is presented, mostly coming from two prospective observational studies, encompassing more than 50% of critically ill beds available in Portugal. Chapter 2 describes the concepts of PK and the changes occurring in critically ill patients. This is followed by a review of the concepts of PD of antibiotics and its application to this population, especially during severe infections (Chapter 3). In the following chapter these changes in antibiotics PK in critical illness are and its causes are detailed, to outline the importance of therapeutic drug monitoring. Data on a systematic review of antibiotics PK in those patients is provided (Chapter 4). The following chapter (Chapter 5) elucidates important changes in PD, that compromises antibiotic therapy, facilitate the occurrence of resistance and may lead to therapeutic failure. Thus, an understanding of the clinical problem and available evidence facilitated the development of a comprehensive research plan (Chapter 6 and Chapter 7). Chapter 6.1 describes time-dependent antibiotics and the importance of extending its perfusion time. A multicenter study was designed to compare the continuous infusion of piperacillin tazobactam (a β-lactam antibiotic) with the same daily dose, prescribed in a conventional, intermittent dose. The importance of correct dosing of antibiotics was also assessed through a study addressing aminoglycoside (a concentration-dependent antibiotic) therapy (Chapter 6.2), focusing on its first dose. Strategies to improve severe infected patients outcomes were addressed in Chapter 7, namely the importance of early antibiotic therapy, assessing the burden of bacteria and understanding changes in antibiotic concentration during the course of infection. An algorithm to include all the described changes in both PK and PD of critically ill patients was developed. Finally in Chapter 8 mechanisms of the increasing resistance of bacteria are described and strategies to address that problem are proposed. The closing chapter (Chapter 9) lays a roadmap for future work. The key finding of this research is the significant variability of the antibiotics PK during critical illness, which makes dosing a challenging issue. These changes are related to the severity of the infection itself and improve through the course of the disease. However neither disease severity nor individual characteristics are useful to predict PK changes. Therefore, the use of a universal dose approach, regardless of the individual patient, may not be the best approach. Strategies to improve patients’ outcomes should be based on tailoring antibiotics to the individual patient, according to PK and PD principles, preferentially supported by therapeutic drug monitoring.

A intervenção da seguradora nas acções propostas contra o segurado

The problem to be discussed results from the relationship established between the insurer and insured by the conclusion of an insurance contract, namely an optional liability insurance contract, to cover the risks taken by the insured resulting from the occurrence of a claim, such as those arising from the emergence of the liability and consequent obligation to compensate damages caused to a third party. This thesis concerns thus the debate between those who consider that, in the optional insurance, the third party may require compliance with the provision to both the insured and the insurer (in the case of voluntary joinder, pursuant to Art. 27 CCP, which corresponds Art. 32 of the New Code of Civil Procedure, Law n. 41/2013 of 26 June, which entered into force on 1 September, hereinafter New Code) - insurance contract on behalf of a third party conception - in the same way that the insured defendant can bring the insurer to intervene as co-defendant in the main process, pursuant al. a) of art. 325 of the CCP (corresponding to art. 316 of the New Code - main intervention caused), and those who argue that the insurer may only intervene in the action as an ancillary party, to assist the defendant, lacking interest, therefore, in necessary or volunteer joinder, with the consequence that the insurer cannot be sued as a main party - only ancillary intervention is justifiable (cf. art. 330 CPC, which corresponds to art. 321 of the New Code).

Measurement of exclusive γγ→ℓ+ℓ− production in proton--proton collisions at s√=7 TeV with the ATLAS detector

This Letter reports a measurement of the exclusive γγ→ℓ+ℓ−(ℓ=e,μ) cross-section in proton--proton collisions at a centre-of-mass energy of 7 TeV by the ATLAS experiment at the LHC, based on an integrated luminosity of 4.6 fb−1. For the electron or muon pairs satisfying exclusive selection criteria, a fit to the dilepton acoplanarity distribution is used to extract the fiducial cross-sections. The cross-section in the electron channel is determined to be σexcl.γγ→e+e−=0.428±0.035(stat.)±0.018(syst.) pb for a phase-space region with invariant mass of the electron pairs greater than 24 GeV, in which both electrons have transverse momentum pT>12 GeV and pseudorapidity |η|<2.4. For muon pairs with invariant mass greater than 20 GeV, muon transverse momentum pT>10 GeV and pseudorapidity |η|<2.4, the cross-section is determined to be σexcl.γγ→μ+μ−=0.628±0.032(stat.)±0.021(syst.) pb. When proton absorptive effects due to the finite size of the proton are taken into account in the theory calculation, the measured cross-sections are found to be consistent with the theory prediction.

Electrically tunable resonant scattering in fluorinated bilayer graphene

Adatom-decorated graphene offers a promising new path towards spintronics in the ultrathin limit. We combine experiment and theory to investigate the electronic properties of dilutely fluorinated bilayer graphene, where the fluorine adatoms covalently bond to the top graphene layer. We show that fluorine adatoms give rise to resonant impurity states near the charge neutrality point of the bilayer, leading to strong scattering of charge carriers and hopping conduction inside a field-induced band gap. Remarkably, the application of an electric field across the layers is shown to tune the resonant scattering amplitude from fluorine adatoms by nearly twofold. The experimental observations are well explained by a theoretical analysis combining Boltzmann transport equations and fully quantum-mechanical methods. This paradigm can be generalized to many bilayer graphene-adatom materials, and we envision that the realization of electrically tunable resonance may be a key advantage in graphene-based spintronic devices.

Determination of the top-quark pole mass using t(t)over-bar+1-jet events collected with the ATLAS experiment in 7 TeV pp collisions

The normalized differential cross section for top-quark pair production in association with at least one jet is studied as a function of the inverse of the invariant mass of the tt¯+1-jet system. This distribution can be used for a precise determination of the top-quark mass since gluon radiation depends on the mass of the quarks. The experimental analysis is based on proton--proton collision data collected by the ATLAS detector at the LHC with a centre-of-mass energy of 7 TeV corresponding to an integrated luminosity of 4.6 fb−1. The selected events were identified using the lepton+jets top-quark-pair decay channel, where lepton refers to either an electron or a muon. The observed distribution is compared to a theoretical prediction at next-to-leading-order accuracy in quantum chromodynamics using the pole-mass scheme. With this method, the measured value of the top-quark pole mass, mpolet, is: mpolet =173.7 ± 1.5 (stat.) ± 1.4 (syst.) +1.0−0.5 (theory) GeV. This result represents the most precise measurement of the top-quark pole mass to date.

Benchmarking sobre técnicas de otimização para modelos de apoio à decisão na medicina intensiva

Dissertação de mestrado integrado em Engenharia e Gestão de Sistemas de Informação

Fine time scaling of purifying selection on human nonsynonymous mtDNA mutations based on the worldwide population tree and mother-child pairs

A high-resolution mtDNA phylogenetic tree allowed us to look backward in time to investigate purifying selection. Purifying selection was very strong in the last 2,500 years, continuously eliminating pathogenic mutations back until the end of the Younger Dryas (∼11,000 years ago), when a large population expansion likely relaxed selection pressure. This was preceded by a phase of stable selection until another relaxation occurred in the out-of-Africa migration. Demography and selection are closely related: expansions led to relaxation of selection and higher pathogenicity mutations significantly decreased the growth of descendants. The only detectible positive selection was the recurrence of highly pathogenic nonsynonymous mutations (m.3394T>C-m.3397A>G-m.3398T>C) at interior branches of the tree, preventing the formation of a dinucleotide STR (TATATA) in the MT-ND1 gene. At the most recent time scale in 124 mother-children transmissions, purifying selection was detectable through the loss of mtDNA variants with high predicted pathogenicity. A few haplogroup-defining sites were also heteroplasmic, agreeing with a significant propensity in 349 positions in the phylogenetic tree to revert back to the ancestral variant. This nonrandom mutation property explains the observation of heteroplasmic mutations at some haplogroup-defining sites in sequencing datasets, which may not indicate poor quality as has been claimed.

The relevance of bacterial interactions on oral health

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Engenharia Clínica)

Hume e o problema moral

Tese de Doutoramento em Filosofia (área de especialização em Filosofia Moderna e Contemporânea).

A bio-inspired computational model for motion detection

Tese de Doutoramento (Programa Doutoral em Engenharia Biomédica)

Relatório de atividade profissional

Relatório de atividade profissional de mestrado em Ciências – Formação Contínua de Professores (área de especialização em Biologia e Geologia)

Ingestão de plásticos por aves marinhas na Costa Norte de Portugal

Dissertação de mestrado em Ecologia

Enfoques sobre la ciudadanía. Philosophical Perspectives on Citizenship.

La necesidad que da origen al presente proyecto se relaciona con la ausencia de un tratamiento de la cuestión de la ciudadanía que haga interactuar distintos enfoques filosóficos -el principal indicador de esta carencia es la ausencia de producciones académicas que den cuenta de la complejidad que adquiere la temática si se la aborda desde los problemas que nos proporcionan otras perspectivas filosóficas y políticas-. En este sentido, el problema general del proyecto apunta a hacer discutir diferentes abordajes conceptuales para pensar la ciudadanía. Específicamente, trabajamos a partir de dos enfoques: 1) la discusión entre liberales y comunitaristas y sus actuales derivas y 2) la cuestión de la biopolítica y su relación con la temática de la ciudadanía. Se procura revisar la discusión liberales-comunitaristas propia de las ciencias políticas, interpelándola a partir de conceptos como los de dominación, relaciones de poder, control sobre la vida, disciplina, entre otros provenientes de la filosofía práctica, la teoría social, las ciencias de la educación, etc. Nuestra investigación parte de la hipótesis de que hacer discutir las problemáticas que se disputan liberales-comunitaristas, con la Teoría Crítica de la Escuela de Frankfurt y con los recientes fenómenos biopolíticos, permite un abordaje que atiende a la efectiva complejidad de las prácticas de ciudadanía en nuestra vida en común en las sociedades democráticas contemporáneas. Esto permitirá complejizar los presupuestos con los que tradicionalmente se ha pensado la ciudadanía, a partir sobre todo de los fenómenos socio-políticos más recientes, como los nuevos movimientos sociales, las discusiones acerca de la legislación del aborto y la eutanasia, los esfuerzos de los estados nacionales por incrementar medidas de seguridad que van desde la imposición de fuertes barreras a la inmigración hasta la realización de guerras preventivas. Entendemos que estos, entre otros fenómenos, desafían la hermenéutica tradicional sobre la ciudadanía. Es de esta manera que se buscará comprender los límites y alcances de las ideas de ciudadanía, entendiéndola como un concepto histórico formador de subjetividades. La metodología se basa en una perspectiva interdisciplinaria que proporciona las herramientas para un análisis conceptual de la temática de la ciudadanía. Esta metodología está orientada al desarrollo de un marco teórico que resulte productivo para investigaciones de campo en las ciencias sociales, así como también para la elaboración de un material bibliográfico destinado a docentes abocados a la ciudadanía. Otro de los propósitos fundamentales es el de formar una red entre diferentes equipos de investigación a nivel nacional a partir de las “I Jornadas Nacionales sobre Ciudadanía” y de la organización de un seminario especializado con un profesor visitante. As far as the general topic of citizenship concerns philosophy, the theoretical problem of how to reconcile the different perspectives, assuming that this is an enterprise that can be done, remains an open question. Furthermore, the absence of academic material dealing with the problem seems to be a good indicator of this tendency. The main focus of the present Project aims at coping with some of the most notorious theoretical approaches to citizenship. More specifically, we will analyze the next two approaches: 1) the debate libertarians-communitarians and 2) the relationship between biopolitics and citizenship. Our purpose is to revise the discussion libertarians-communitarians incorporating concepts such as domination, power-relationships, life-control, among others that find their roots in practical philosophy, social theory, education and so on. To the extent that theories of citizenship are only provided with the usual conceptual machinery, some of the most remarkable phenomena of our democratic societies will stand for them out of reach: the existence of new social movements, abortion and euthanasia, inmigration, etc. Our hypothesis is that by making the debate libertarians-communitarians interact with the Critical Theory as well as with biopolitical concepts, we will be in a better position to try to understand these diverse phenomena. With the development of some sort of a new hermeneutics, we expect to criticize the old ideas related to citizenship and to re-elaborate them in a way that allows us to understand this concept in a less-fundamental, historical sense. Methodologically, we will adopt a multi-dimensional approach which expects to be fruitful to many other investigations in the area of social sciences. The Project pretends to be useful as a consultation resource for educators in a bibliographical index to design their curricula. At the same time,a seminar with a visiting profesor, the organization of a Congres will be our main objectives.