Comparative analysis of multicriteria decision making methods

Dissertação para obtenção do Grau de Mestre em Engenharia Electrotécnica e de Computadores

Using epidemiological survey data to infer geographic distributions of leishmaniasis vector species

An important aspect of tropical medicine is analysis of geographic aspects of risk of disease transmission, which for lack of detailed public health data must often be reduced to an understanding of the distributions of critical species such as vectors and reservoirs. We examine the applicability of a new technique, ecological niche modeling, to the challenge of understanding distributions of such species based on municipalities in the state of São Paulo in which a group of 5 Lutzomyia sandfly species have been recorded. The technique, when tested based on independent occurrence data, yielded highly significant predictions of species' distributions; minimum sample sizes for effective predictions were around 40 municipalities.

Sand fly captures with Disney traps in area of occurrence of Leishmania (Leishmania) amazonensis in the state of Mato Grosso do Sul, mid-western Brazil

INTRODUCTION: The work was conducted to study phlebotomine fauna (Diptera: Psychodidae) and aspects of American cutaneous leishmaniasis transmission in a forested area where Leishmania (Leishmania) amazonensis occurs, situated in the municipality of Bela Vista, State of Mato Grosso do Sul, Brazil. METHODS: The captures were conducted with modified Disney traps, using hamster (Mesocricetus auratus) as bait, from May 2004 to January 2006. RESULTS: Ten species of phlebotomine sandflies were captured: Brumptomyia avellari, Brumptomyia brumpti, Bichromomyia flaviscutellata, Evandromyia bourrouli, Evandromyia lenti, Lutzomyia longipalpis, Psathyromyia campograndensis, Psathyromyia punctigeniculata, Psathyromyia shannoni and Sciopemyia sordellii. The two predominant species were Ev bourrouli (57.3%) and Bi flaviscutellata (41.4%), present at all sampling sites. Two of the 36 hamsters used as bait presented natural infection with Leishmania. The parasite was identified as Leishmania (Leishmania) amazonensis. CONCLUSIONS: Analysis of the results revealed the efficiency of Disney traps for capturing Bichromomyia flaviscutellata and the simultaneous presence of both vector and the Leishmania species transmitted by the same can be considered a predictive factor of the occurrence of leishmaniasis outbreaks for the human population that occupies the location.

Caracterização do papel dos genes TYMS e MTR no desenvolvimento de Cancro Colo-Rectal

RESUMO: O cancro colo-rectal (CCR) é um dos cancros que possui maior taxa de mortalidade a nível mundial. Em Portugal esta patologia é responsável pela morte de cerca de 3700 pessoas por ano, sendo que estes números aumentam de ano para ano. Ao longo das últimas décadas o papel das alterações genéticas na etiologia das patologias oncológicas tem vindo a ter cada vez mais um maior destaque. O número de estudos que avaliam a importância de polimorfismos, mutações, alterações na regulação génica e interacções entre genes no desenvolvimento destas patologias tem aumentado exponencialmente. Com o aumento do conhecimento da forma como estas alterações influenciam o desenvolvimento do cancro surgiram os primeiros meios de diagnóstico genético, levando assim a uma alteração da forma como são encarados o diagnóstico e a prevenção destas doenças. No CCR as formas hereditárias com alterações genéticas inequivocamente identificadas representam apenas 5% dos casos. Existem cerca de 25% que representam formas hereditárias para as quais ainda não foram estabelecidos os padrões de alterações genéticas subjacentes. Desta forma, estudos que venham contribuir para um maior conhecimento dos mecanismos moleculares responsáveis pelo aumento da susceptibilidade dos indivíduos para o desenvolvimento de CCR são extremamente importantes. O CCR é uma patologia multifactorial, onde factores genéticos interagem com factores ambientais no surgimento e desenvolvimento da doença. Assim, torna-se essencial integrar o estudo das alterações genéticas no contexto ambiental onde os indivíduos em estudo se encontram. No caso desta patologia um dos principais factores ambientais estudado é a nutrição. Vários estudos têm sido realizados ao longo dos últimos anos de forma a compreender como pode a ingestão dos nutrientes influenciar o desenvolvimento de CCR e de que forma interage com as alterações genéticas individuais. O ciclo do folato é um dos processos metabólicos onde o papel da nutrição em interacção com alterações genéticas mais tem sido estudado nos últimos anos. Deste cruzamento entre o estudo das alterações genéticas e ambientais surge a Nutrigenética. O conjunto de estudos da presente tese tem como objectivo aumentar o conhecimento do papel das alterações em genes do ciclo do folato, em interacção com factores nutricionais e de estilo de vida, não só no desenvolvimento de CCR, mas também de outra patologia do tracto gastrointestinal, a Doença de Crohn (DC), uma doença inflamatória muitas vezes associada como factor de risco para o desenvolvimento de CCR. Este estudo debruçou-se essencialmente no estudo dos genes timidilato sintetase (TYMS) e metionina sintetase (MTR) em populações com CCR e DC, bem como no padrão nutricional destas populações com particular incidência nos nutrientes envolvidos no ciclo do folato (folato, metionina, vitamina B6, vitamina B12). Analisando o conjunto de resultados obtidos para os estudos do CCR podemos concluir que quer a TYMS quer a MTR possuem um papel relevante na susceptibilidade para desenvolver esta patologia, assim como têm destaque no funcionamento do ciclo celular durante o processo oncogénico. Os resultados demonstram que os factores que levam a uma menor disponibilidade de grupos metil no ciclo de folato (baixos níveis de folato, alteração da actividade de MTR, elevada expressão de TYMS) constituem factores de risco, muito provavelmente por contribuírem para uma desregulação dos níveis de metionina disponível para a metilação do DNA da célula. Demonstram ainda que em células tumorais ocorrem alterações na regulação do ciclo do folato de forma a favorecer a síntese de DNA em detrimento da metilação do mesmo, alterando para isso a expressão dos genes de forma a que o fluxo de grupos metil provenientes do folato sejam encaminhados para a enzima TYMS. O polimorfismo de deleção 6pb da TYMS surge como um factor de diagnóstico e de prognóstico de CCR para a população portuguesa. Dos factores nutricionais analisados apenas o folato aparenta ter um papel relevante na modelação do risco de desenvolver CCR. Na doença de Crohn (DC) podemos verificar que a homocisteína e o seu metabolismo poderão contribuir para o aparecimento e desenvolvimento da patologia. O aumento da homocisteína poderá ser o responsável por um aumento da resposta auto-imune do organismo, promovendo o aparecimento da DC. O polimorfismo A2756G MTR desempenha um papel preponderante como factor de diagnóstico da DC, tendo sido associado pela primeira vez a esta patologia. Tem também um papel importante no desenvolvimento da doença, uma vez que está associado a uma idade de diagnóstico mais baixa, sugerindo assim que o desenvolvimento da doença ocorre de forma mais precoce. Concluindo, com este estudo pensamos ter contribuído para um melhor entendimento do papel do ciclo do folato no desenvolvimento de CCR e DC, sendo um ponto de partida para futuras investigações que possam revelar cada vez melhor as complexas interacções metabólicas desta via e a sua influência nas patologias estudadas. Do nosso estudo destacamos a importância de uma análise global das várias etapas do ciclo do folato para que se possa compreender a dinâmica que se estabelece no desenvolvimento destas patologias, podendo diversas alterações, quer a nível genético quer a nível nutricional, exercerem efeitos diferentes consoante o estado dos restantes intervenientes do ciclo do folato. Acreditamos que no futuro este estudo permitirá que o conhecimento do ciclo do folato tenha cada vez mais uma relevância fundamental a nível de diagnóstico e terapêutica destas patologias.------------ ABSTRACT: Colorectal Cancer (CRC) is one of the cancers that have a higher rate of mortality worldwide. In Portugal this pathology is responsible for the deaths of about 3700 people per year, and these numbers increase each year. Over the past few decades the role of genetic changes in the etiology of oncological pathologies has had an increasingly greater emphasis. The number of studies that evaluate the importance of polymorphisms, mutations, changes in gene regulation and gene interactions in the development of these diseases has increased exponentially. With the increased knowledge of how these changes influence the development of cancer, appeared the first means for genetic diagnostic, leading to a change in the way diagnosis is seen and in the prevention of these diseases. In CRC the hereditary forms with clearly identified genetic changes represent only 5% of cases. There are about 25% representing hereditary forms for which the patterns of genetic changes haven’t been established. In this way, studies that will contribute to a greater understanding of the molecular mechanisms responsible for increased susceptibility of individuals to the CRC development are extremely important. CRC is a multifactorial pathology, where genetic factors interact with environmental factors in the emergence and development of the disease.Thus, it is essential to integrate the study of genetic changes in the environmental context of the individuals under study. In the case of this pathology one of the main environmental factors studied is nutrition. Several studies have been conducted over the past few years in order to understand how the intake of nutrients can influence the development of CRC and how nutrients interact with the individual genetic changes. The folate cycle is one of the metabolic processes where the role of nutrition in interaction with genetic alterations has been studied in recent years. This cross between the study of genetic and environmental changes developed Nutrigenetics. The set of studies of this thesis aims to increase awareness of the role of changes in genes of the folate cycle, in interaction with nutritional factors and lifestyle, not only in the development of CRC, but also of another pathology of the gastrointestinal tract, Crohn's disease (CD), an inflammatory disease often associated as a risk factor for the development of CRC. This study dealt mainly in the study of genes thymidylate synthase (TYMS) and methionine synthase (MTR) in populations with CRC and CD, as well as in the nutritional pattern of these populations with particular focus on nutrients involved in the folate cycle (folate, methionine, vitamin B6, vitamin B12). Analyzing the results obtained for the CRC studies we conclude that either the MTR TYMS have a relevant role in susceptibility to develop this pathology, and have an important role in the functioning of the cell cycle during oncogenesis. The results show that the factors that lead to a lower availability of methyl groups in folate cycle (low levels of folate, change the activity of MTR, high expression of TYMS) constitute risk factors, most likely by contribute to a dysregulation of methionine levels available for DNA methylation of the cell. Our results also demonstrate that in tumor cells occur changes in the regulation of the folate cycle in order to promote the synthesis of DNA, to the detriment of methylation of the same by changing the expression of genes so that the methyl groups from folate are forwarded to the TYMS enzyme reaction. The deletion polymorphism 6bp of TYMS emerges as a diagnostic and prognostic factor of CCR for the Portuguese population. Nutritional factors analyzed only folate appears to have a major role in modulating the risk of developing CCR.In Crohn’s disease (CD) we can check that homocysteine and its metabolism may contribute to the emergence and development of this pathology. Increased homocysteine may be responsible for an increase in the body's autoimmune response, promoting the emergence of CD. The polymorphism A2756G MTR plays a leading role as a factor of diagnosis of DC, having been associated with this pathology for the first time. It also has an important role in the development of the disease, since it is associated with a lower diagnostic age, suggesting that the development of the disease occurs earlier. In conclusion, our study has contributed to a better understanding of the role of folate cycle in the development of CRC and CD, being a starting point for future research that may prove increasingly complex metabolic interactions in this via and its influence on the pathologies studied. In our study we highlight the importance of a comprehensive analysis of the various steps of the folate cycle in order to understand the dynamics that settles in the development of these pathologies, and a number of amendments, whether at the genetic level or at the nutritional level, exercise different effects depending on the stage of the remaining participants in the folate cycle. We believe that in the future this study will allow the knowledge of folate cycle to have increasingly a fundamental relevance at the level of diagnosis and treatment of these diseases.

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.

Adverse reactions following mass drug administration with diethylcarbamazine in lymphatic filariasis endemic areas in the Northeast of Brazil

INTRODUCTION: The Global Programme to Eliminate Lymphatic Filariasis was launched with the goal of eliminating this disease via the annual mass drug administration (MDA) of a single dose of antifilarial drugs. Adverse drug reactions following MDA are a major factor of poor treatment adherence in several countries. This study assessed the occurrence of adverse drug reactions (ADRs) following the first round of mass treatment in two communities treated with different dosages of diethylcarbamazine (DEC) in the City of Recife, Brazil. METHODS: Population-based cross-sectional surveys were conducted in a random sample of the population living in both communities (Areas I and II). The dose of DEC recommended by the WHO (6mg/kg) was calculated based on the individual's weight-for-age. In Area II, weight differences between the genders were also considered when determining dosage. Data were obtained through interviews conducted in the first 12 to 48h and on the 5th day after MDA during household visits. RESULTS: A total of 487 and 365 individuals were interviewed in Areas I and II, respectively. The prevalence of ADRs in Area I (23.6; 95%CI: 19.1-29.5) was higher than in Area II (16.2; 95%CI:11.9-21.5)(p=0.0078). The prevalence of ADRs among females was higher than in males in Area I (p=0.0021). In Area II, no significant difference between the genders was observed (p=0.1840). Age was not associated with ADRs in either area. CONCLUSIONS: Adjusting MDA dosage schedules according to weight-for-age and sex may be may contribute to reduce the occurrence of adverse drug reactions in the population.

Search-for-yield in Portuguese fixed-income mutual funds and monetary policy

This paper studies the effects of monetary policy on mutual fund risk taking using a sample of Portuguese fixed-income mutual funds in the 2000-2012 period. Firstly I estimate time-varying measures of risk exposure (betas) for the individual funds, for the benchmark portfolio, as well as for a representative equally-weighted portfolio, through 24-month rolling regressions of a two-factor model with two systematic risk factors: interest rate risk (TERM) and default risk (DEF). Next, in the second phase, using the estimated betas, I try to understand what portion of the risk exposure is in excess of the benchmark (active risk) and how it relates to monetary policy proxies (one-month rate, Taylor residual, real rate and first principal component of a cross-section of government yields and rates). Using this methodology, I provide empirical evidence that Portuguese fixed-income mutual funds respond to accommodative monetary policy by significantly increasing exposure, in excess of their benchmarks, to default risk rate and slightly to interest risk rate as well. I also find that the increase in funds’ risk exposure to gain a boost in return (search-for-yield) is more pronounced following the 2007-2009 global financial crisis, indicating that the current historic low interest rates may incentivize excessive risk taking. My results suggest that monetary policy affects the risk appetite of non-bank financial intermediaries.

Momentum risk: An approach following the correlations between active stocks

The momentum anomaly has been widely documented in the literature. However, there are still many issues where there is no consensus and puzzles left unexplained. One is that strategies based on momentum present a level of risk that is inconsistent with the diversification that it offers. Moreover, recent studies indicate that this risk is variable over time and mostly strategy-specific. This work project hypothesises and proves that this evidence is explained by the portfolio constitution of the momentum strategy over time, namely the covariance and correlation between companies in the top and down deciles and across them.

Factors associated with neural alterations and physical disabilities in patients with leprosy in São Luis, State of Maranhão, Brazil

Introduction Leprosy is a chronic infectious disease that is caused by Mycobacterium leprae. The objective of this study was to evaluate the risk factors that are associated with neural alterations and physical disabilities in leprosy patients at the time of diagnosis. Methods A prospective cross-sectional study was conducted on 155 leprosy patients who participated in a program that aimed to eliminate leprosy from São Luis, State of Maranhão. Results Patients who were 31-45 years of age, were older than 60 years of age or had a partner were more likely to have a disability. Patients with partners were 1.14 times more likely (p = 0.025) to have disabilities of the hands. The frequency of disabilities in the feet among the patients with different clinical forms of leprosy was statistically significant. Conclusions The identification of risk factors that are associated with neural alterations and physical disabilities in leprosy patients is important for diagnosing the disease because this approach enables physicians to plan and prioritize actions for the treatment and monitoring of patients.

Dimensions of source credibility in the case of user-generated advertisements

User-generated advertising changed the world of advertising and changed the strategies used by marketers. Many researchers explored the dimensions of source credibility in traditional media and online advertising. However, little previous research explored the dimensions of source credibility in the context of user-generated advertising. This exploratory study aims to investigate the different dimensions of source credibility in the case of user-generated advertising. More precisely, this study will explore the following factors: (1) objectivity, (2) trustworthiness, (3) expertise, (4) familiarity, (5) attractiveness and (6) frequency. The results suggest that some of the dimensions of source credibility (objectivity, trustworthiness, expertise, familiarity and attractiveness) remain the same in the case of user-generated advertising. Additionally, a new dimension is added to the factors that explain source credibility (reputation). Furthermore, the analysis suggests that the dimension “frequency” is not an explanatory factor of credibility in the case of user-generated advertisement. The study also suggests that companies using user-generated advertisement as part of their overall marketing strategy should focus on objectivity, trustworthiness, expertise, attractiveness and reputation when selecting users that will communicate sponsored user-generated advertisements.

Cerebral vasculopathy in children with sickle cell disease A study of genetic modulators of the disease

Sickle cell disease (SCD) is a genetic disorder with recessive transmission, caused by the mutation HBB:c.20A>T. It originates hemoglobin S that forms polymers inside the erythrocyte, upon deoxygenation, deforming it and ultimately leading to premature hemolysis. The disease presents with high heterogeneity of clinical manifestations, the most devastating of which, ischemic stroke, occurs in 11% of patients until 20 years of age. In this study, we tried to identify genetic modifiers of risk and episodes of stroke by studying 66 children with SCD, grouped according to the degree of cerebral vasculopathy (Stroke, Risk and Control). Association studies were performed between the three phenotypic groups and hematological and biochemical parameters of patients, as well as with 23 polymorphic regions in genes related to vascular cell adhesion (VCAM-1, THBS-1 and CD36), vascular tonus (NOS3 and ET-1) and inflammation (TNF-α and HMOX-1). Relevant data was collected from patient’s medical records. Known genetic modulators of SCD (beta-globin cluster haplotype and HBA and BCL11A genotypes) and putative genetic modifiers of cerebral vasculopathy were characterized. Differences in their distribution among groups were assessed. VCAM-1 rs1409419 allele C and NOS3 rs207044 allele C were associated to stroke events, while VCAM-1 rs1409419 allele T was found to be protective. Alleles 4a and 4b of NOS3 27 bp VNTR appeared to be respectively associated to stroke risk and protection. HMOX-1 longer STRs seemed to predispose to stroke. Higher hemoglobin F levels were found in Control group, as a result of Senegal haplotype or of BCL11A rs11886868 allele T, and higher lactate dehydrogenase levels, marker of hemolysis, were found in Risk group. Molecular mechanisms underlying the modifier functions of the relevant genetic variants are discussed.

Optimization of wastewater quality in the Sines refinery

In order to address and resolve the wastewater contamination problem of the Sines refinery with the main objective of optimizing the quality of this stream and reducing the costs charged to the refinery, a dynamic mass balance was developed nd implemented for ammonia and polar oil and grease (O&G) contamination in the wastewater circuit. The inadequate routing of sour gas from the sour water stripping unit and the kerosene caustic washing unit, were identified respectively as the major source of ammonia and polar substances present in the industrial wastewater effluent. For the O&G content, a predictive model was developed for the kerosene caustic washing unit, following the Projection to Latent Structures (PLS) approach. Comparison between analytical data for ammonia and polar O&G concentrations in refinery wastewater originating from the Dissolved Air Flotation (DAF) effluent and the model predictions of the dynamic mass balance calculations are in a very good agreement and highlights the dominant impact of the identified streams for the wastewater contamination levels. The ammonia contamination problem was solved by rerouting the sour gas through an existing clogged line with ammonia salts due to a non-insulated line section, while for the O&G a dynamic mass balance was implemented as an online tool, which allows for prevision of possible contamination situations and taking the required preventive actions, and can also serve as a basis for establishing relationships between the O&G contamination in the refinery wastewater with the properties of the refined crude oils and the process operating conditions. The PLS model developed could be of great asset in both optimizing the existing and designing new refinery wastewater treatment units or reuse schemes. In order to find a possible treatment solution for the spent caustic problem, an on-site pilot plant experiments for NaOH recovery from the refinery kerosene caustic washing unit effluent using an alkaline-resistant nanofiltration (NF) polymeric membrane were performed in order to evaluate its applicability for treating these highly alkaline and contaminated streams. For a constant operating pressure and temperature and adequate operating conditions, 99.9% of oil and grease rejection and 97.7% of chemical oxygen demand (COD) rejection were observed. No noticeable membrane fouling or flux decrease were registered until a volume concentration factor of 3. These results allow for NF permeate reuse instead of fresh caustic and for significant reduction of the wastewater contamination, which can result in savings of 1.5 M€ per year at the current prices for the largest Portuguese oil refinery. The capital investments needed for implementation of the required NF membrane system are less than 10% of those associated with the traditional wet air oxidation solution of the spent caustic problem. The operating costs are very similar, but can be less than half if reusing the NF concentrate in refinery pH control applications. The payback period was estimated to be 1.1 years. Overall, the pilot plant experimental results obtained and the process economic evaluation data indicate a very competitive solution through the proposed NF treatment process, which represents a highly promising alternative to conventional and existing spent caustic treatment units.

Introducing risk parity on momentum and carry portfolios

The momentum and carry anomalies have been extensively documented in the literature. However, there are still many issues relating to the risks associated to them that are left unexplained. One is the fact that an investor holds for too long the most volatile assets, both under momentum and carry strategies. Therefore, they present a level of risk and a probability of extreme events to happen inconsistent. This work project hypothesizes and proves the introduction of risk parity rules on the weights of the portfolios do increase risk rewarding of carry strategies. However, it fails under momentum strategies.

Vaccines in pregnancy: a review of their importance in Brazil

Neonates and young children remain susceptible to many serious infectious diseases preventable through vaccination. In general, current vaccines strategies to prevent infectious diseases are unable to induce protective levels of antibodies in the first 6 months of life. Women vaccinated during pregnancy are capable of producing immunoglobulin antibodies that are transported actively to the fetus, and maternal immunization can benefit both the mother and the child. With few exceptions, maternal immunization is not a routine, because of the concerns related to the safety of this intervention. Ethical and cultural issues make the studies on maternal immunization difficult; however, in the last decade, the development of new vaccines, which are very immunogenic and safe has reactivated the discussions on maternal immunization. In this paper we present a review of the literature about maternal immunization based on MEDLINE data (1990 to 2002). The most important conclusions are: 1) there is no evidence of risk to the fetus by immunizing pregnant women with toxoids, polysaccharide, polysaccharide conjugated and inactive viral vaccines; 2) most viral attenuated vaccines are probably safe too, but data is still insufficient to demonstrate their safety; therefore these vaccines should be avoided in pregnant women; 3) in Brazil, there is a need for a maternal immunization program against tetanus. Many new candidate vaccines for maternal immunization are available, but studies should be conducted to evaluate their safety and efficacy, as well as regional priorities based on epidemiological data.