Assessing the balance between biodiversity conservation and coastal and estuarine management of the Sado Estuary Natural Reserve, Portugal, using BIO-SAFE

Dissertação apresentada na Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa para obtenção do grau de Mestre em Engenharia do Ambiente, perfil de Engenharia Ecológica

Municipal solid waste management system: decision support through systems analysis

Thesis submitted to the Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia for the degree of Doctor of Philosophy in Environmental Engineering

Biological predictors of survival in limphoma and mechanisms underlying follicular lymphoma transformaion into diffuse large B cell lymphoma (vol I e II)

RESUMO: Os biomarcadores tumorais permitem identificar os doentes com maior risco de recorrência da doença, predizer a resposta tumoral à terapêutica e, finalmente, definir candidatos a novos alvos terapêuticos. Novos biomarcadores são especialmente necessários na abordagem clínica dos linfomas. Actualmente, esses tumores são diagnosticados através de uma combinação de características morfológicas, fenotípicas e moleculares, mas o prognóstico e o planeamento terapêutico estão quase exclusivamente dependentes de características clínicas. Estes factores clínicos são, na maioria dos linfomas, insuficientes numa proporção significativa dos doentes, em particular, aqueles com pior prognóstico. O linfoma folicular (LF) é, globalmente, o segundo subtipo mais comum de linfoma. É tipicamente uma doença indolente com uma sobrevida média entre os 8 e 12 anos, mas é geralmente fatal quando se transforma num linfoma agressivo de alto grau, habitualmente o linfoma difuso de grandes células B (LDGCB). Morfologicamente e funcionalmente, as células do LF recapitulam as células normais do centro germinativo na sua dependência de sobrevivência do microambiente não-tumoral, especialmente das células do sistema imunológico. Biomarcadores preditivos de transformação não existem pelo que um melhor conhecimento da biologia intrínseca de progressão do LF poderá revelar novos candidatos. Nesta tese descrevo duas abordagens distintas para a descoberta de novos biomarcadores. A primeira, o estudo da expressão global de genes ('genomics') obtidos por técnicas de alto rendimento que analisam todo o genoma humano sequenciado, permitindo identificar novas anomalias genéticas que possam representar mecanismos biológicos importantes de transformação. São descritos novos genes e alterações genómicas associados à transformação do LF, sendo especialmente relevantes as relacionadas com os eventos iniciais de transformação em LDGCB. A segunda, baseou-se em várias hipóteses centradas no microambiente do LF, rico em vários tipos de células nãomalignas. Os estudos imunoarquitectural de macrófagos, células T regulatórias e densidade de microvasos efectuado em biopsias de diagnóstico de doentes com LF tratados uniformemente correlacionaram-se significativamente, e independentemente dos critérios clínicos, com a evolução clínica e, mais importante, com o risco de transformação em LDGCB. Nesta tese, foram preferencialmente utilizadas (e optimizadas) técnicas que permitam o uso de amostras fixadas em parafina e formalina (FFPET). Estas são facilmente acessíveis a partir das biopsias de diagnóstico de rotina presentes nos arquivos de todos os departamentos de patologia, facilitando uma transição rápida dos novos marcadores para a prática clínica. Embora o FL fosse o tema principal da tese, os novos achados permitiram estender facilmente hipóteses semelhantes a outros subtipos de linfoma. Assim, são propostos e validados vários biomarcadores promissores e relacionados com o microambiente não tumoral, sobretudo dependentes das células do sistema imunológico, como contribuintes importantes para a biologia dos linfomas. Estes sugerem novas opções para a abordagem clínica destas doenças e, eventualmente, novos alvos terapêuticos.------------- ABSTRACT: Cancer biomarkers provide an opportunity to identify those patients most at risk for disease recurrence, predict which tumours will respond to different therapeutic approaches and ultimately define candidate biomarkers that may serve as targets for personalized therapy. New biomarkers are especially needed in the management of lymphoid cancers. At present, these tumours are diagnosed using a combination of morphologic, phenotypic and molecular features but prognosis and overall survival are mostly dependent on clinical characteristics. In most lymphoma types, these imprecisely assess a significant proportion of patients, in particular, those with very poor outcomes. Follicular lymphoma (FL) is the second most common lymphoma subtype worldwide. It is typically an indolent disease with current median survivals in the range of 8-12 years, but is usually fatal when it transforms into an aggressive high-grade lymphoma, characteristically Diffuse Large B Cell Lymphoma (DLBCL). Morphologically and functionally it recapitulates the normal cells of the germinal center with its survival dependency on non-malignant immune and immunerelated cells. Informative markers of transformation related to the intrinsic biology of FL progression are needed. Within this thesis two separate approaches to biomarker discovery were employed. The first was to study the global expression of genes (‘genomics’) obtained using high-throughput, wholegenome-wide approaches that offered the possibility for discovery of new genetic abnormalities that might represent the important biological mechanisms of transformation. Gene signatures associated with early events of transformation were found. Another approach relied on hypothesis-driven concepts focusing upon the microenvironment, rich in several non-malignant cell types. The immunoarchitectural studies of macrophages, regulatory T cells and microvessel density on diagnostic biopsies of uniformly treated FL patients significantly predicted clinical outcome and, importantly, also informed on the risk of transformation. Techniques that enabled the use of routine formalin fixed paraffin embedded diagnostic specimens from the pathology department archives were preferentially used in this thesis with the goal of fulfilling a rapid bench-to-beside” translation for these new findings. Although FL was the main subject of the thesis the new findings and hypotheses allowed easy transition into other lymphoma types. Several promising biomarkers were proposed and validated including the implication of several non-neoplastic immune cells as important contributors to lymphoma biology, opening new options for better treatment planning and eventually new therapeutic targets and candidate therapeutics.

Integration of sediment contamination with multi–biomarker responses in a novel bioindicator candidate (Sepia officinalis) for risk assessment in impacted estuaries

Dissertação para obtenção do Grau de Mestre em Engenharia do Ambiente

Development of a fuzzy qualitative risk assessment model applied to construction industry

Dissertação para obtenção do Grau de Doutor em Engenharia Industrial

Development of an integrative approach for the characterization of ecological risk on marine transition ecosystems: the Sado Estuary as a case study

Estuaries and other transitional waters are complex ecosystems critically important as nursery and shelter areas for organisms. Also, humans depend on estuaries for multiple socio-economical activities such as urbanism, tourism, heavy industry, (taking advantage of shipping), fisheries and aquaculture, the development of which led to strong historical pressures, with emphasis on pollution. The degradation of estuarine environmental quality implies ecologic, economic and social prejudice, hence the importance of evaluating environmental quality through the identification of stressors and impacts. The Sado Estuary (SW Portugal) holds the characteristics of industrialized estuaries, which results in multiple adverse impacts. Still, it has recently been considered moderately contaminated. In fact, many studies were conducted in the past few years, albeit scattered due to the absence of true biomonitoring programmes. As such, there is a need to integrate the information, in order to obtain a holistic perspective of the area able to assist management and decision-making. As such, a geographical information system (GIS) was created based on sediment contamination and biomarker data collected from a decade-long time-series of publications. Four impacted and a reference areas were identified, characterized by distinct sediment contamination patterns related to different hot spots and diffuse sources of toxicants. The potential risk of sediment-bound toxicants was determined by contrasting the levels of pollutants with available sediment quality guidelines, followed by their integration through the Sediment Quality guideline Quotient (SQG-Q). The SQG-Q estimates per toxicant or class was then subjected to georreferencing and statistical analyses between the five distinct areas and seasons. Biomarker responses were integrated through the Biomarkers Consistency Indice and georreferenced as well through GIS. Overall, in spite of the multiple biological traits surveyed, the biomarker data (from several organisms) are accordant with sediment contamination. The most impacted areas were the shipyard area and adjacent industrial belt, followed by urban and agricultural grounds. It is evident that the estuary, although globally moderately impacted, is very heterogeneous and affected by a cocktail of contaminants, especially metals and polycyclic aromatic hydrocarbon. Although elements (like copper, zinc and even arsenic) may originate from the geology of the hydrographic basin of the Sado River, the majority of the remaining contaminants results from human activities. The present work revealed that the estuary should be divided into distinct biogeographic units, in order to implement effective measures to safeguard environmental quality.

Support in decision-making under uncertainty: a project risk assessment tool development and supplementary advances

A foremost dispute that persists on the contemporary world’s agenda is change. The on-going social/technological/economic changes create a competitive and challenging environment for companies to endure. To benefit from these changes, world economies partially depend on emerging Small and Medium Enterprises (SMEs) and their adaptability skills, and subsequently the development of an integrated capability to innovate has become the prime strategy for most of SMEs to subsist and grow. However, innovation and change are always somewhat bonded to an inherent risk development, which subsequently brings on the necessity of a revision of risk management approaches in innovative processes, whose importance SMEs tend to disregard. Additionally, little efforts have been made to improve and create empirical models, metrics and tools to assist SMEs managing latent risks in their innovative projects. This work seeks to present and discuss a solution to support SMEs in engaging on systematic risk management practices, which consists on an integrated risk assessment and response support web-based tool - Spotrisk® - designed for SMEs. On the other hand, an inherent subjectivity is linked with risk management and identification processes, due to uncertainty trait of its nature, for each individual perceives situations according to his own idiosyncrasy, which brings complications in normalizing risk profiles and procedures. This essay aims to bring insights concerning the support in decision-making processes under uncertainty, by addressing issues related with the risk behavior character among individuals. To address such issues, subjects of neuroscience or psychology are explored and models to identify such character are proposed, as well as models to improve presented tool. This work attempts to go beyond the restrictive aim of endeavoring on technical improvement dissertation, and in embraces an exploratory conceptualization concerning micro, small and medium businesses’ traits regarding risk characters and project risk assessment tools.

Business continuity management at Banif: Defining and selecting recovery strategies

This project aims to delineate recovery strategies for a Portuguese Bank, as a way to increase its preparedness towards unexpected disruptive events, thus avoiding an operational crisis escalation. For this purpose, Business Continuity material was studied, a risk assessment performed, a business impact analysis executed and new strategic framework for selecting strategies adopted. In the end, a set of recovery strategies were chosen that better represented the Bank’s appetite for risk, and recommendations given for future improvements.

A comparative review of risk based portfolio allocations: An empirical study throughout rising yields

Since the financial crisis, risk based portfolio allocations have gained a great deal in popularity. This increase in popularity is primarily due to the fact that they make no assumptions as to the expected return of the assets in the portfolio. These portfolios implicitly put risk management at the heart of asset allocation and thus their recent appeal. This paper will serve as a comparison of four well-known risk based portfolio allocation methods; minimum variance, maximum diversification, inverse volatility and equally weighted risk contribution. Empirical backtests will be performed throughout rising interest rate periods from 1953 to 2015. Additionally, I will compare these portfolios to more simple allocation methods, such as equally weighted and a 60/40 asset-allocation mix. This paper will help to answer the question if these portfolios can survive in a rising interest rate environment.

Assessing fraud risk of selecção, contratação e manutenção de fornecedores process of Sonae Investimentos

The present Work Project (WP) is the result of Sonae’s concern with fraud risk, seeking to implement a method that formally describes and evaluates it in its various forms. In a context of limited human, capital, time and tools’ resources, the Internal Audit (IA) department of the company developed a framework to raise the awareness of top management and identify which processes of its value chain present a higher level of exposure to fraud, with the purpose of redirecting attention to those and prioritizing the creation of new mechanisms to monitor its KPIs’ dynamics.