Prescription patterns of pharmaceuticals

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Economics from the NOVA – School of Business and Economics

Constituição e transcendência: os casos dos regimes comunitários do entre-guerras

Tede de Doutoramento, na especialidade de Ciências Políticas apresentada à FDUNL

Ruling the Empire: The Portuguese Colonial Office (1820s-1926)

Portugal was one of the first and most enduring European colonial powers of modern times: 1415 and 1975 mark the beginning and the end of a long empire cycle that left impressive imprints in many places. Since it started, the overseas expansion and the exploration of the colonial resources were closely articulated with state-building and the preservation of national independence. A forerunner at the Great Age of Discoveries, but a latecomer in the era of industrialization, in the 19th and early-20th centuries Portugal was a peripheral country, and the economic gap with the rich and industrialized core of Europe was wide. During this period, however, the country faced the critical challenge of ruling vast and geographically scattered overseas territories, and of preserving them from the greed of strong imperialist powers. This article starts by outlining the major developments in the Portuguese colonial policy over a century, since the 1820s until 1926. The independence of Brazil (1822) was a crucial turning point, which brought about a shift towards Africa. The First Republic (1910-1926), pervaded by a nationalist ideology, gave a new impetus to the efforts towards a more effective colonisation. Symptomatically, a Ministry of Colonies was then established for the first time. Second, it describes and analyses the transformation of the central office for colonial affairs – from a small ministerial department to an autonomous ministry -, stressing the increasing bureaucratic specialisation, the growth of the apparatus and its staff, and the introduction of new criteria for the selection and promotion of permanent officials (namely a higher profile given to careers in local colonial administration). Finally, it presents a collective biography of both the politicians (Cabinet ministers) and the administrators (directors-general) who ran the Colonial Office for a large period of the Constitutional Monarchy (from 1851 to 1910) and during the First Republic, thus enabling to assess the impact of regime change on elite circulation and career patterns.

Durability to marine environment of innovative products for consolidation and chromatic reintegration of historical renders

9th International Masonry Conference 2014, 7-9 July, Universidade do Minho, Guimarães

Análise comparativa do direito de acesso a cuidados de saúde no serviço nacional de saúde português e sistema de saúde norte-americano (EUA)

RESUMO - O presente estudo situa-se nas áreas gerais da Saúde Pública, dos Sistemas de Saúde e do Acesso à Prestação de Cuidados de Saúde e procura analisar o conteúdo e concretização do Direito de Acesso a Cuidados de Saúde na perspectiva de dois sistemas de saúde paradigmaticamente distintos, um sistema de acesso universal, representado pelo Serviço Nacional de Saúde português e um sistema de saúde de “não universal”, cujo paradigma é o modelo existente nos Estados Unidos da América, onde entidades gestoras de cuidados, Managed Care Organizations, são chamadas a desempenhar um papel central no acesso e prestação de cuidados de saúde. O vasto campo de investigação representado pela problemática do acesso a cuidados de saúde e a necessidade de limitar o trabalho de investigação subjazem à definição de quatro vertentes a analisar: (a) a existência ou não de uma base legal que preveja e regule o exercício do direito de acesso a cuidados de saúde; (b) o conteúdo deste direito no âmbito de cada um dos sistemas em estudo; (c) as condições de concretização do acesso a cuidados de saúde em ambos os sistemas, e, por último (d) a existência de garantias de efectivação do mesmo. Analisados os sistemas em estudo à luz das vertentes apresentadas, concluímos que a existência de um quadro normativo próprio, que explicite o conteúdo e condições de efectivação do direito, apresenta maiores garantias de concretização do exercício do Direito de Acesso a Cuidados de Saúde, entendendo-se que um sistema de acesso dependente da actuação de entidades gestoras de cuidados não beneficia o acesso a cuidados de saúde, nomeadamente por não garantir equidade no momento de procura e necessidade de cuidados. Os dados apresentados foram recolhidos através do recurso a uma metodologia qualitativa. A análise documental foi aplicada na recolha dos dados relativos à evolução e caracterização dos sistemas, bem como às condições de acesso. No âmbito do sistema de saúde de acesso universal, ou seja, o caso português, procedeu-se essencialmente à análise dos normativos aplicáveis. No que se refere ao sistema de saúde norte-americano, na ausência de base legal aplicável, recorreu-se sobretudo à análise de literatura e documentos. A participação no vi Second Biennal Seminar in Law and Bioethics1 e na 30th Annual Health Law Professors Conference2, realizados em Bóston, EUA, em Julho de 2007, permitiram uma melhor percepção da actual situação da prestação de cuidados naquele País, nomeadamente de algumas das reformas em curso, bem como um melhor entendimento das características do sistema prestador norte-americano em si mesmo. 1 Seminário organizado nos dias 30 e 31 de Maio, numa colaboração entre a Escola Nacional de Saúde Pública e o Departamento de Direito da saúde, Bioética e Direitos Humanos da Escola de Saúde Pública da Universidade de Bóston, sob o tema: “Law and ethics in rationing Access to care in a high-cost global economy”. A nossa participação deveu-se a um convite da Prof.ª Paula Lobato de Faria para colaborar na sessão sobre o sistema de saúde português. 2 Reunião realizada em Bóston nos dias 31 de Maio a 2 de Junho, sobretudo a sessão dedicada ao tema “New Models for Reform”, sobre os novos modelos de sistema de saúde em desenvolvimento nos EUA.

Res Publica: Citizenship and Political Representation in Portugal, 1820-1926

The term res publica (literally “thing of the people”) was coined by the Romans to translate the Greek word politeia, which, as we know, referred to a political community organised in accordance with certain principles, amongst which the notion of the “good life” (as against exclusively private interests) was paramount. This ideal also came to be known as political virtue. To achieve it, it was necessary to combine the best of each “constitutional” type and avoid their worst aspects (tyranny, oligarchy and ochlocracy). Hence, the term acquired from the Greeks a sense of being a “mixed” and “balanced” system. Anyone that was entitled to citizenship could participate in the governance of the “public thing”. This implied the institutionalization of open debate and confrontation between interested parties as a way of achieving the consensus necessary to ensure that man the political animal, who fought with words and reason, prevailed over his “natural” counterpart. These premises lie at the heart of the project which is now being presented under the title of Res Publica: Citizenship and Political Representation in Portugal, 1820-1926. The fact that it is integrated into the centenary commemorations of the establishment of the Republic in Portugal is significant, as it was the idea of revolution – with its promise of rupture and change – that inspired it. However, it has also sought to explore events that could be considered the precursor of democratization in the history of Portugal, namely the vintista, setembrista and patuleia revolutions. It is true that the republican regime was opposed to the monarchic. However, although the thesis that monarchy would inevitably lead to tyranny had held sway for centuries, it had also been long believed that the monarchic system could be as “politically virtuous” as a republic (in the strict sense of the word) provided that power was not concentrated in the hands of a single individual. Moreover, various historical experiments had shown that republics could also degenerate into Caesarism and different kinds of despotism. Thus, when absolutism began to be overturned in continental Europe in the name of the natural rights of man and the new social pact theories, initiating the difficult process of (written) constitutionalization, the monarchic principle began to be qualified as a “monarchy hedged by republican institutions”, a situation in which not even the king was exempt from isonomy. This context justifies the time frame chosen here, as it captures the various changes and continuities that run through it. Having rejected the imperative mandate and the reinstatement of the model of corporative representation (which did not mean that, in new contexts, this might not be revived, or that the second chamber established by the Constitutional Charter of 1826 might not be given another lease of life), a new power base was convened: national sovereignty, a precept that would be shared by the monarchic constitutions of 1822 and 1838, and by the republican one of 1911. This followed the French example (manifested in the monarchic constitution of 1791 and in the Spanish constitution of 1812), as not even republicans entertained a tradition of republicanism based upon popular sovereignty. This enables us to better understand the rejection of direct democracy and universal suffrage, and also the long incapacitation (concerning voting and standing for office) of the vast body of “passive” citizens, justified by “enlightened”, property- and gender-based criteria. Although the republicans had promised in the propaganda phase to alter this situation, they ultimately failed to do so. Indeed, throughout the whole period under analysis, the realisation of the potential of national sovereignty was mediated above all by the individual citizen through his choice of representatives. However, this representation was indirect and took place at national level, in the hope that action would be motivated not by particular local interests but by the common good, as dictated by reason. This was considered the only way for the law to be virtuous, a requirement that was also manifested in the separation and balance of powers. As sovereignty was postulated as single and indivisible, so would be the nation that gave it soul and the State that embodied it. Although these characteristics were common to foreign paradigms of reference, in Portugal, the constitutionalization process also sought to nationalise the idea of Empire. Indeed, this had been the overriding purpose of the 1822 Constitution, and it persisted, even after the loss of Brazil, until decolonization. Then, the dream of a single nation stretching from the Minho to Timor finally came to an end.

Transcriptional regulation of the mannosyltransferase-encoding gene pigm in inherited glycosylphosphatidylinositol (GPI) deficiency

RESUMO:O glicosilfosfatidilinositol (GPI) é um complexo glicolipídico utlizado por dezenas de proteínas, o qual medeia a sua ancoragem à superfície da célula. Proteínas de superfície celular ancoradas a GPI apresentam várias funções essenciais para a manutenção celular. A deficiência na síntese de GPI é o que caracteriza principalmente a deficiência hereditária em GPI, um grupo de doenças autossómicas raras que resultam de mutações nos genes PIGA, PIGL, PIGM, PIGV, PIGN, PIGO e PIGT, os quais sao indispensáveis para a biossíntese do GPI. Uma mutação pontual no motivo rico em GC -270 no promotor de PIGM impede a ligação do factor de transcrição (FT) Sp1 à sua sequência de reconhecimento, impondo a compactação da cromatina, associada à hipoacetilação de histonas, e consequentemente, impedindo a transcrição de PIGM. Desta forma, a adição da primeira manose ao GPI é comprometida, a síntese de GPI diminui assim como as proteínas ligadas a GPI à superficie das células. Pacientes com Deficiência Hereditária em GPI-associada a PIGM apresentam trombose e epilesia, e ausência de hemólise intravascular e anemia, sendo que estas duas últimas características definem a Hemoglobinúria Paroxística Nocturna (HPN), uma doença rara causada por mutações no gene PIGA. Embora a mutação que causa IGD seja constitutiva e esteja presente em todos os tecidos, o grau de deficiência em GPI varia entre células do mesmo tecido e entre células de tecidos diferentes. Por exemplo nos granulócitos e linfócitos B a deficiência em GPI é muito acentuada mas nos linfócitos T, fibroblastos, plaquetas e eritrócitos é aproximadamente normal, daí a ausência de hemólise intravascular. Os eventos transcricionais que estão na base da expressão diferencial da âncora GPI nas células hematopoiéticas são desconhecidos e constituem o objectivo geral desta tese. Em primeiro lugar, os resultados demonstraram que os níveis de PIGM mRNA variam entre células primárias hematopoiéticas normais. Adicionalmente, a configuração dos nucleossomas no promotor de PIGM é mais compacta em células B do que em células eritróides e tal está correlacionado com os níveis de expressão de PIGM, isto é, inferior nas células B. A presença de vários motivos de ligação para o FT específico da linhagem megacariocítica-eritróide GATA-1 no promotor de PIGM sugeriu que GATA-1 desempenha um papel regulador na sua transcrição. Os resultados mostraram que muito possivelmente GATA-1 desempenha um papel repressor em vez de activador da expressão de PIGM. Resultados preliminares sugerem que KLF1, um factor de transcrição restritamente eritróide, regula a transcrição de PIGM independentemente do motivo -270GC. Em segundo lugar, a investigação do papel dos FTs Sp demonstrou que Sp1 medeia directamente a transcrição de PIGM em ambas as células B e eritróide. Curiosamente, ao contrário do que acontece nas células B, em que a transcrição de PIGM requer a ligação do FT geral Sp1 ao motivo -270GC, nas células eritróides Sp1 regula a transcrição de PIGM ao ligar-se a montante e não ao motivo -270GC. Para além disso, demonstrou-se que Sp2 não é um regulador directo da transcrição de PIGM quer nas células B quer nas células eritróides. Estes resultados explicam a ausência de hemólise intravascular nos doentes com IGD associada a PIGM, uma das principais características que define a HPN. Por último, resultados preliminares mostraram que a repressão da transcrição de PIGM devida à mutação patogénica -270C>G está associada com a diminuição da frequência de interacções genómicas em cis entre PIGM e os seus genes “vizinhos”, sugerindo adicionalmente que a regulação de PIGM e desses genes é partilhada. No seu conjunto, os resultados apresentados nesta tese contribuem para o conhecimento do controlo transcricional de um gene housekeeping, específico-detecido, por meio de FTs genéricos e específicos de linhagem.-------------ABSTRACTC: Glycosylphosphatidylinositol (GPI) is a complex glycolipid used by dozens of proteins for cell surface anchoring. GPI-anchored proteins have various functions that are essential for the cellular maintenance. Defective GPI biosynthesis is the hallmark of inherited GPI deficiency (IGD), a group of rare autosomal diseases caused by mutations in PIGA, PIGL, PIGM, PIGV, PIGN, PIGO and PIGT, all genes indispensable for GPI biosynthesis. A point mutation in the -270GC-rich box in the core promoter of PIGM disrupts binding of the transcription factor (TF) Sp1 to it, imposing nucleosome compaction associated with histone hypoacetylation, thus abrogating transcription of PIGM. As a consequence of PIGM transcriptional repression, addition of the first mannose residue onto the GPI core and thus GPI production are impaired; and expression of GPI-anchored proteins on the surface of cells is severely impaired. Patients with PIGM-associated IGD suffer from life-threatening thrombosis and epilepsy but not intravascular haemolysis and anaemia, two defining features of paroxysmal nocturnal haemoglobinuria (PNH), a rare disease caused by somatic mutations in PIGA. Although the disease-causing mutation in IGD is constitutional and present in all tissues, the degree of GPI deficiency is variable and differs between cells of the same and of different tissues. Accordingly, GPI deficiency is severe in granulocytes and B cells but mild in T cells, fibroblasts, platelets and erythrocytes, hence the lack of intravascular haemolysis.The transcriptional events underlying differential expression of GPI in the haematopoietic cells of PIG-M-associated IGD are not known and constitute the general aim of this thesis. Firstly, I found that PIGM mRNA levels are variable amongst normal primary haematopoietic cells. In addition, the nucleosome configuration in the promoter of PIGM is more compacted in B cells than in erythroid cells and this correlated with the levels of PIGM mRNA expression, i.e., lower in B cells. The presence of several binding sites for GATA-1, a mega-erythroid lineage-specific transcription factor (TF), at the PIGM promoter suggested that GATA-1 has a role on PIGM transcription. My results showed that GATA-1 in erythroid cells is most likely a repressor rather than an activator of PIGM expression. Preliminary data suggested that KLF1, an erythroid-specific TF, regulates PIGM transcription but independently of the -270GC motif. Secondly, investigation of the role of the Sp TFs showed that Sp1 directly mediates PIGM transcriptional regulation in both B and erythroid cells. However, unlike in B cells in which active PIGM transcription requires binding of the generic TF Sp1 to the -270GC-rich box, in erythroid cells, Sp1 regulates PIGM transcription by binding upstream of but not to the -270GC-rich motif. Additionally, I showed that Sp2 is not a direct regulator of PIGM transcription in B and erythroid cells. These findings explain lack of intravascular haemolysis in PIGM-associated IGD, a defining feature of PNH. Lastly, preliminary work shows that transcriptional repression of PIG-M by the pathogenic -270C>G mutation is associated with reduced frequency of in cis genomic interactions between PIGM and its neighbouring genes, suggesting a shared regulatory link between these genes and PIGM. Altogether, the results presented in this thesis provide novel insights into tissuespecific transcriptional control of a housekeeping gene by lineage-specific and generic TFs.

O Conselho de Estado na monarquia constitucional: uma reflexão preliminar

This article summarises the transformations in the State Council’s functions and membership throughout the Portuguese Constitutional Monarchy, and makes a preliminary attempt to scrutinise the political role played by an institution designed since its inception to advise the monarch. In spite of the parsimony of contemporary sources, and even contradictory empirical evidence, it seems indisputable that in several critical occasions the monarch’s political decisions were influenced by the dominant view in the State Council. Finally, the article presents the collective biography of the 73 individuals appointed to the State Council between 1833 and 1910 – who may be defined as the inner circle of the ruling elite - focusing on basic background features (birthplace, age, education, occupation, noble titles and political experience).

Real-time collaborative editing of OutSystems DSL models

Real-time collaborative editing systems are common nowadays, and their advantages are widely recognized. Examples of such systems include Google Docs, ShareLaTeX, among others. This thesis aims to adopt this paradigm in a software development environment. The OutSystems visual language lends itself very appropriate to this kind of collaboration, since the visual code enables a natural flow of knowledge between developers regarding the developed code. Furthermore, communication and coordination are simplified. This proposal explores the field of collaboration on a very structured and rigid model, where collaboration is made through the copy-modify-merge paradigm, in which a developer gets its own private copy from the shared repository, modifies it in isolation and later uploads his changes to be merged with modifications concurrently produced by other developers. To this end, we designed and implemented an extension to the OutSystems Platform, in order to enable real-time collaborative editing. The solution guarantees consistency among the artefacts distributed across several developers working on the same project. We believe that it is possible to achieve a much more intense collaboration over the same models with a low negative impact on the individual productivity of each developer.

Liberdade e tolerância religiosa: "portugueses não católicos" no ultramar do século XIX

The personal legal status of native non catholic people of Portuguese colonial Empire during the nineteenth century, their position in what concerns Portuguese citizenship, is the main subject of this article. While discussing constitutional articles on religion, Portuguese deputies of the nineteenth century were confronted with a set of problems about that status which they find difficult to solve: should non catholic peoples who were born in Portuguese colonial territory be treated as plain Portuguese citizens or where they just “savage people”, “colonial subjects” or, in a more optimistic approach, “civilizing subjects”. The results were not conclusive, giving rise to an “uncertainty principle” which enabled central and local government to decide in an almost casuistic way about native people status and rights.

A Constituição e o Direito Justo

Também publicado em DELGADO, José Pina (org.) e SILVA, Mário Ramos Pereira (org.) "Estudos em Comemoração do XXº Aniversário da Constituição da República de Cabo Verde", Praia: Edições do ISCJS, 2013, [9]-29 pp

A restrição ao sigilo bancário decorrente do regime de branqueamento de capitais

Technologic and socio-economic mutations have always determined challenges not only to lawyers, but to law itself. These phenomena have occurred specially when trying to deal with the hard task of finding solutions for the current increasing mismatch of social interests, for example, bank secrecy and money laundering. Usually occurring simultaneously, they are typical examples of outcomes generated by technological and socio-economic innovations that have become fashionable and captured international attention. At the same time, bank secrecy and money laundering support interests belonging to different dimensions, deserving to be balanced in the light of the heterogeneous mechanisms provided by the law to its practitioners and society as a hole. In order to achieve an outcome in accordance with the Rule of Law´s principles, lawyers´ tools are consequently subordinated to constitutional and social justice. Guided by this purpose, we performed the present study, aiming to analyse bank secrecy and money laundering in the light of the current stablished juridical procedures. We intended to develop a prudent point of view that is also in accordance with social reality. In sum, we demonstrate that bank secrecy should adopt a flexible character, embedding new settings and following the socio-economic path in a globalized world with constant innovations.

O dever de obediência a ordens ilegais na Guarda Nacional Republicana

The Republican National Guard (GNR) is a military structure and hierarchical force where discipline and obedience is a serious matter, but at the same time, the scope of its activity relates to the protection of the rights, freedoms and guarantees of citizens and the primacy of public interest. While security force, GNR ensures democratic law, guarantee the internal security and the rights of citizens. The controversial issue that lies at the heart of this work its related with the balance between the hierarchy and the written law. The hierarchy, also established by law, with given powers, exist to apply the law. However, the rule of law has exceptions. Which institute to prioritize, hierarchy or the law. And within the law, its rules or the exceptions. Who decides? The GNR's officers have to obey the laws and regulations and comply with the accuracy and timeliness determinations, orders and instructions issued by a superior, given in terms of service, as long as does not involve the practice of crime. The GNR´s officer with command tasks exercises power of authority inherent in these functions, and the corresponding disciplinary authority, being responsible for acts by himself or by his order are practiced. Identify situations of exception to law enforcement, the situations in which one must obey illegal orders, is difficult and thankless, it requires conferred authority and raises the weight of responsibility for decisions and orders issued.

Produção de electricidade em Portugal

In the present work we intend to do an analysis of the production of electricity in special regime in Portugal. We will focus in particular in the remuneration system through the feed-in tariffs. First, we will excurse throughout different legal diplomas that regulated the special regime in Portugal, exploring which guarantees were conferred to electricity generators throughout the years. We intend to also evaluate how the producers remunerative rights were (or not) protected in the various legislative changes. In the second part of the dissertation we will examine whether the feed-in tariffs may be considered as State aid. Due to the inclusion of the subject in EU Law, we will analyze EU regulation and case law to support our position about the Portuguese regime. Finally, and to the extent that the production of electricity in special regime has undergone several changes to its remunerative regime in the last few years, we propose to analyze more carefully the amendments in question. We will scrutinize the reasons that based the amendments in question, which are mainly based on the economic crisis suffered by the country. We will also examine how those changes may jeopardize the remunerative rights of the producers.