Combined genetic and epigenetic alterations of the TERT promoter affect clinical and biological behaviour of bladder cancer

In urothelial bladder cancer (UBC), risk stratification remains an important unmet need. Limitless self‐renewal, governed by TERT expression and telomerase activation, is crucial for cancer progression. Thus, telomerase activation through the interplay of mutations (TERTp^(Mut)) and epigenetic alterations in the TERT promoter may provide further insight into UBC behavior. Here, we investigated the combined effect of TERTp^(Mut) and the TERTHypermethylated Oncological Region (THOR) status on telomerase activation and patient outcome in a UBC international cohort (n=237). We verified that TERTp^(Mut) were frequent (76.8%) and present in all stages and grades of UBC. Hypermethylation of THOR was associated with higher TERT expression and higher‐risk disease in non‐muscle invasive bladder cancers (NMIBC). TERTp^(Mut) alone predicted disease recurrence (HR: 3.18, 95%CI 1.84 to 5.51, p<0.0001) but not progression in NMIBC. Combined THOR^(high)/TERTp^(Mut) increased the risk of disease recurrence (HR 5.12, p<0.0001) and progression (HR 3.92, p=0.025). Increased THOR hypermethylation doubled the risk of stage progression of both TERTp^(wt) and TERTp^(Mut) NMIBC. These results highlight that both mechanisms are common and coexist in bladder cancer and while TERTp^(Mut) is an early event in bladder carcinogenesis THOR hypermethylation is a dynamic process that contributes to disease progression. While the absence of alterations comprises an extremely indolent phenotype, the combined genetic and epigenetic alterations of TERT bring additional prognostic value in NMIBC and provide a novel insight into telomere biology in cancer

Financialisation and the financial and economic crises: the case of Portugal

Documento elaborado e integrado no Projecto FESSUD, University of Leeds, projecto fundado pela União EuropeiaThe notion of 'financialisation' broadly refers to the growing weight of finance in contemporary economies. Taking this into account, the present study focus on the long-run macroeconomic development and recent financial and economic crisis of the Portuguese economy. Contrary to Greece, Ireland, and Spain, the dismal performance of the Portuguese economy is not solely a post-subprime crisis phenomenon. The sharp discontinuity in GDP growth around the turn of the century is a distinctive feature of Portugal in the EU context and, although several factors account for this discontinuity, the process of financialisation of the Portuguese economy is an essential part of the explanation. This process in Portugal was essentially characterised by a large increase in bank credit to the private sector, resulting from a combination of demand- and supply-side factors that produced a wide availability of credit at historically low interest rates. Thus, we suggest that the Portuguese experience can be labelled a ‘debt-led domestic demand growth’ model. However, after 2000 the Portuguese economy experienced a succession of shocks, and an exhaustion of the domestic debt-led growth at a much earlier stage than other countries, resulting in a sharp economic slowdown, with negative consequences for public finances. The high levels of public and private indebtedness were a decisive factor behind the steep rise in the Portuguese sovereign bonds interest rates between 2010 and 2012. Finally, we assess the impact of financialisation in the current account, investment, consumption, and inequality; articulating these domains with the general growth model. Our conclusion is that the increase in the importance of finance ended having a clear negative impact on the three former domains, while the negative impact on income inequality was less pronounced.info:eu-repo/semantics/publishedVersio

Financialisation in the european periphery and the sovereign debt crisis: the portuguese case

Working papers com arbitragem científicaThe financial sector has acquired great prominence in most developed economies. However, some authors argue that the growth of finance is at the root of the current financial and economic difficulties. This paper aims to analyse this claim by looking at financialisation in the European periphery, focusing on the Portuguese case. The emergence of this phenomenon is contextualised from a historical, economic and international perspective. Based on the analysis of several indicators, the paper concludes that the Portuguese economy exhibits symptoms of financialisation, and that this has not only revealed the structural weaknesses of the Portuguese economy but also played an important role in the emergence of the recent Portuguese sovereign debt crisis.info:eu-repo/semantics/publishedVersio

Report on the financial system in Portugal

Documento elaborado e integrado no Projecto FESSUD, University of Leeds, projecto fundado pela União EuropeiaThis Report assesses the extent, nature, and effects of financialisation in Portugal. It also discusses the contribution of financialisation for the crisis that presently affects the Portuguese economy. The liberalization of the banking sector, the easier access to international financial markets, and the growth of credit fostered the development of the Portuguese financial sector.info:eu-repo/semantics/publishedVersio

Financialisation in the european periphery and the sovereign debt crisis: the portuguese case

Working papers com arbitragem científicaThe financial sector has acquired great prominence in most developed economies. However, some authors argue that the growth of finance is at the root of the current financial and economic difficulties. This paper aims to analyse this claim by looking at financialisation in the European periphery, focusing on the Portuguese case. The emergence of this phenomenon is contextualised from a historical, economic and international perspective. Based on the analysis of several indicators, the paper concludes that the Portuguese economy exhibits symptoms of financialisation, and that this has not only revealed the structural weaknesses of the Portuguese economy but also played an important role in the emergence of the recent Portuguese sovereign debt crisis.info:eu-repo/semantics/publishedVersio

Risk management, the subprime crisis and financialisation: the role of risk management in the generation and transmission of the subprime crisis

Documento elaborado e integrado no Projecto FESSUD, University of Leeds, projecto fundado pela União EuropeiaOver time the financial sector has gained greater relevance in the economy, a phenomenon that some call financialisation. Contrary to the mainstream view, financialisation literature emphasises that risk management by financial corporations will not be socially efficient in a context of deregulated markets and will ultimately lead to an increase of aggregate risk and crises. To assess the validity of such claim, in this paper we review the literature on risk management during the Subprime crisis. These failures fall into three categories: technique and methodology, corporate governance and strategy, and regulation and external factors. These failures can be interpreted in the light of the financialisation perspective, which is therefore a valuable approach when addressing regulatory changes in the financial system.info:eu-repo/semantics/publishedVersio

The non-for-profit banks in Portugal: specificities, social role and evolution

Colecção DINÂMIA'CET-RN - Artigo em revista científica nacional com arbitragem científicaEste artigo procura definir as principais diferenças entre a generalidade dos bancos e os dois bancos com atitude não lucrativa que operam no mercado bancário português (Caixa Agrícola e Caixa Económica-Montepio Geral). Encontramos diferenças em termos da forma de captar fundos; em termos dos critérios de governação; do regime fiscal; da aplicação dos lucros; e da atitude em relação ao lucro. A Caixa Agrícola opera de forma mais próxima dos bancos cooperativos do que a Caixa Económica-Montepio Geral. Ambos os bancos têm vindo a modernizar-se e construir grupos financeiros modernos que oferecem uma enorme variedade de produtos e serviços financeiros, semelhantes à generalidade dos bancos. Contudo, isto não foi suficiente para evitar alguma erosão das suas posições no mercado bancário (quer em termos de crédito concedido quer em termos de depósitos recebidos). O impacto da crise financeira de 2008 na rendibilidade da Caixa Agrícola foi semelhante à média do sector bancário. No caso da Caixa Económica-Montepio Geral, o impacto foi menos grave que na média do sector.This paper establishes the main differences between standard commercial banks and the two non-for-profit banks operating in Portugal (Caixa Agrícola – CA – and Caixa Económica Montepio Geral – CE-MG). In particular, we find differences in the way funds are raised, governance criteria, tax regime, application of profits and attitude towards profit. However, CA is more similar to a typical co-operative/mutual bank than CE-MG. Both banks have modernized and transformed into modern financial groups offering a wide variety of financial products similar to any commercial bank. However, this was not enough to avoid an erosion of their market position in terms of credit and deposits. The 2008 financial crisis’ impact on the profitability of CA was similar to the impact on the industry average, whereas on CE-MG the impact was milder.info:eu-repo/semantics/publishedVersio

A mineração nas unidades de conservação federais a partir da lei nº 9.985/2000

A mineração é uma atividade indispensável para o desenvolvimento, mas, independentemente do método utilizado, provoca danos irreparáveis ao meio ambiente. A situação agrava-se quando é praticada em Unidades de Conservação da natureza. A proteção desses espaços tem amparo na Lei nº 9.985/2000, conhecida como Lei do Sistema Nacional de Unidades de Conservação da Natureza, todavia as divergências de interpretação têm propiciado que a mineração ocorra em unidades nas quais é questionável a sua legalidade. Desse modo, inúmeros projetos de lei estão em andamento, tanto para a reformulação do Código de Mineração quanto para a modificação da legislação ambiental. Com a finalidade de tratar da relação entre a mineração e as Unidades de Conservação Federais a partir da Lei nº 9.985/2000, este trabalho foi concebido em quatro capítulos. O primeiro trata das generalidades sobre as Unidades de Conservação Federais e a mineração no contexto legal brasileiro, ressaltando-se o enquadramento constitucional desses temas. O segundo capítulo discorre sobre a criação dessas unidades em áreas contendo títulos minerários e aborda o dever de indenizar o concessionário do direito de lavra. O terceiro capítulo concentra a discussão sobre a possibilidade de outorga de direitos minerários em Unidades de Conservação, considerando o enquadramento legal e a constatação de mineração em 48 unidades. O último capítulo evidencia que os projetos de lei em tramitação são ineficazes para reger a questão da mineração em Unidades de Conservação. Da análise geral, constata-se que a Lei nº 9.985/2000 admite a mineração “em tese” apenas em Áreas de Proteção Ambiental e Áreas de Relevante Interesse Ecológico, mas a apreciação do caso concreto e a existência do licenciamento ambiental são determinantes para a extração. Entretanto, a mineração tem sido consentida pelo Poder Público, inclusive em Unidades de Conservação de Proteção Integral, o que representa uma ilegalidade