Avaliação do papel dos polimorfismos em enzimas metabolizadoras e enzimas transportadoras de fármacos em neoplasias hematológicas

O cancro é um dos maiores causadores globais de mortalidade e morbilidade, ocorrendo cerca de 14 milhões de novos casos por ano e 8,2 milhões de mortes anuais com esta patologia, números que tendem a aumentar 70% nas próximas duas décadas. A característica tumoral mais nefasta é a sua capacidade de metastização para outros órgãos, um mecanismo que pode ser despoletado pela falha dos mecanismos normais de controlo de crescimento, proliferação e reparação celulares, que facilita o processo de transformação de células normais em células cancerígenas. A oncogénese processa-se em três etapas, a iniciação, a promoção e a progressão e pode ter origem em células estaminais cancerígenas, que regulam as capacidades de propagação e recidiva do tumor. As neoplasias hematológicas resultam de alterações genéticas e /ou epigenéticas que conduzem à desregulação da proliferação, ao bloqueio da diferenciação e/ou à resitência à apoptose. Para além dos fatores de risco exógenos, como agentes carcinogénicos físicos, químicos e biológicos, existem também fatores endógenos, incluindo características genéticas, que podem alterar a predisposição para o aparecimento de neoplasias, bem como influenciar a resposta à terapêutica. Uma das terapêuticas aplicadas no tratamento do cancro é a quimioterapia. Os fármacos administrados a doentes oncológicos seguem normalmente o percurso de absorção, distribuição, metabolização e eliminação. Este curso pode sofrer alterações caso as proteínas transportadoras e metabolizadoras necessárias não atuem corretamente. Para um melhor conhecimento da influência das alterações provocadas por variações nos genes que codificam proteínas transportadoras de efluxo (MDR1, MRP1), proteínas de influxo (OCTN2) e proteínas metabolizadoras (UCK2), o objetivo deste trabalho consistiu na avaliação de polimorfismos nos genes MDR1, MRP1, OCTN2 e UCK2 e da sua relação com a predisposição para o desenvolvimento de neoplasias hematológicas. Para isto, foram utilizadas amostras de 307 doentes com neoplasias hematológicas, 83 de Síndrome Mielodisplásica (SMD), 63 Leucemia Mieloide Aguda (LMA), 16 de Síndrome Mielodisplásica/Neoplasias Mieloproliferativas (SMD/NMP), 77 de Mieloma Múltiplo (MM) e 68 de Gamapatia Monoclonal de Significado Indeterminado (MGUS) e 164 de controlos não neoplásicos e/ou indivíduos saudáveis. As amostras de ADN foram extraídas do sangue periférico com protocolo adequado. De forma a determinar os genótipos correspondentes a cada amostra, realizaram-se técnicas de RFLP-PCR e ARMS-PCR. Posteriormente, calcularam-se estatisticamente as frequências alélicas e genotípicas relativas às variantes polimórficas dos genes MDR1, MRP1, OCTN2 e UCK2 e verificou-se se estavam em Equilíbrio de Hardy-Weinberg. De seguida, avaliou-se a força de associação entre as formas polimórficas e o risco de desenvolvimento de neoplasias hematológicas, através do cálculo do risco relativo por análise de regressão logística. Avaliaram-se ainda os perfis genéticos e a possível relação com o desenvolvimento e progressão da neoplasia com recurso a regressão logística e análise de Kaplan-Meier. De um modo geral as frequências alélicas e genotípicas não se revelaram alteradas comparativamente ao esperado. A análise do odds ratio associado ao polimorfismo rs1045642 do gene MDR1 revelou que o genótipo CT pode constituir um fator de risco aumentado de 1,84x para o desenvolvimento de Gamapatias Monoclonais e 2,27x para o desenvolvimento de Mieloma Múltiplo. Por outro lado, a presença de genótipos portadores do alelo T têm um efeito protetor no desenvolvimento de MM (OR=0,41). O cálculo do risco associado ao polimorfismo rs4148330 do gene MRP1 revela que o genótipo AG é um fator protetor (OR=0,50) para o desenvolvimento de LMA, assim como o alelo G (OR=0,50). Além disso, verificámos que existe uma associação de risco de desenvolver neoplasia com o polimorfismo rs2185268 do gene UCK2. De facto, a presença dos genótipos CC e AC representam um fator de risco 4,59x aumentado para o desenvolvimento de SMD/NMP. O polimorfismo rs274561 do gene OCTN2 não apresenta relação com o risco relativo de desenvolvimento neoplásico. Da avaliação da influência dos polimorfismos em estudo na sobrevivência global dos doentes, podemos assumir que a presença do genótipo GG relativo ao polimorfismo rs2185268 do gene UCK2 representa uma diminuição da sobrevivência em 11 meses. Os resultados obtidos a partir do nosso estudo permitem-nos concluir que os polimorfismos podem ser fatores relevantes na predisposição para o desenvolvimento de neoplasias hematológicas e na progressão destas doenças.

O Contributo dos Sistemas de Informação para a Eficácia da Liderança e para a Mudança do Comportamento Organizacional

O presente trabalho debruça-se sobre os constructos da liderança e do comportamento de auto-eficácia da liderança nas organizações. Reflecte-se sobre a importância dos sistemas de informação no clima organizacional, com efeitos sobre a eficácia na liderança. Trata-se de uma perspetiva pertinente na conjuntura organizacional atual, dado que incide sobre valores patrimoniais intangíveis que, quando dinamizados, dão suporte à performance organizacional. A nossa preocupação central é a auto-eficácia. Através dela pretende-se melhorar a eficiência organizacional, porque minimiza prejuízos e desperdícios. Também se relaciona a eficácia com o desempenho da liderança organizacional e com o capital ‘confiança’. Dessa forma, os novos caminhos passam por auscultar a percepção dos colaboradores sobre a importância da cultura organizacional face ao desempenho e à eficácia de longo prazo na organização. Com a presente reflexão, evidencia-se que a espiritualidade no local de trabalho é um factor de apoio ao desenvolvimento holístico dos colaboradores. Fica sublinhado que é fundamental que os líderes tenham noção e consciência de “si” e dos seus papéis, e como estes se reflectem no seu comportamento quotidiano na organização. O estudo assenta num trabalho de campo, elaborado numa organização intensiva em informação e que presta serviços de consultoria e informática. Os resultados apurados tentam dizer que, globalmente, no estudo longitudinal das hetero-percepções dos gestores directos e indirectos, o gap cultural diminuiu em todas as dimensões relativas às competências dos papéis, sendo vital destacar o quadrante designado por Apoio. As hetero-percepções dos gestores directos demonstram que o menor gap cultural mantem-se no quadrante de Objectivos Racionais e Competir no modelo de CVF, caracterizado por uma cultura de mercado, e relacionado com a fase da Combinação no modelo de SECI (processos que fomentam os relacionamentos e intercâmbios informais – conversão do conhecimento explícito para o explícito). Enquanto que o maior gap cultural reside no quadrante Apoio e Colaborar no modelo CVF, relacionado com a fase da Socialização no modelo de SECI (processos que fomentam os relacionamentos e intercâmbios informais – conhecimento tácito para tácito). Como o gap cultural diminuiu em todas as dimensões, pode realçar uma melhoria das percepções do desempenho organizacional. Contudo, um resultado inesperado está associado ao quadrante Apoio com a cultura de clã, uma vez que são os gestores indirectos na empresa em estudo que fomentam esta cultura, e não os gestores directos, conforme seria desejável. Um resultado favorável para o estudo da auto-eficácia da liderança demonstra que as médias são mais elevadas para atributos de Gestão e Resolução de Problemas. Os resultados que não corresponderam às expectativas iniciais estão associados às médias baixas relativamente aos atributos Sociais/de Comunicação, o que pode ser uma debilidade porque seria desejável que a equipa de gestão tivesse maior sensibilidade perante os capitais sociais, emocionais e espirituais, os quais estão relacionados com estes atributos.

People and their past : is 'community archaeology’ the future?

This thesis looks at how ‘community archaeology’ ideals may influence an inclusive approach to Indigenous heritage management, ensuring Indigenous community power over processes to identify both past and present values of Country. Community archaeology was acclaimed by research archaeologists over a decade ago as a distinctive approach with its own set of practices to incorporate the local community’s perspectives of its past and current associations with place. A core feature of this approach in Australia is the major role the Indigenous community has in decisions about its heritage. Concurrently, considerable concern was being expressed that Indigenous heritage was not sufficiently addressed in environmental impact assessment processes ahead of development. Seen as absent from the process was the inclusion of Indigenous knowledge about both the pre- and post-contact story as well as any scientific advance in understanding an area’s Indigenous history. This research examines these contrasting perspectives seeking to understand the ideals of community archaeology and its potential to value all aspects of Indigenous heritage and so benefit the relevant community. The ideals of community archaeology build on past community collaborations in Australia and also respond to more recent societal recognition of Indigenous rights, reflected in more ethically inclusive planning and heritage statutes. Indigenous communities expressed the view that current systems are still not meeting these policy commitments to give them control over their heritage. This research has examined the on-the-ground reality of heritage work on the outskirts of Canberra and Melbourne. The case studies compare Victorian and ACT heritage management processes across community partnerships with public land managers, and examine how pre-development surveys operate. I conclude that considerable potential for achieving community archaeology ideals exists, and that they are occasionally partially realised, however barriers continue. In essence, the archaeological model persists despite a community archaeology approach requiring a wider set of skills to ensure a comprehensive engagement with an Indigenous community. Other obstacles in the current Indigenous heritage management system include a lack of knowledge and communication about national standards for heritage processes in government agencies and heritage consultants; the administrative framework that can result in inertia or silos between relevant agencies; and funding timeframes that limit possibilities for long-term strategic programs for early identification and management planning for Indigenous heritage. Also, Indigenous communities have varying levels of authority to speak for how their heritage should be managed, yet may not have the resources to do so. This thesis suggests ways to breach these barriers to achieve more inclusive Indigenous heritage management based on community archaeology principles. Policies for a greater acknowledgement of the Indigenous community’s authority to speak for Country; processes that enable and early and comprehensive ‘mapping’ of Country, and long-term resourcing of communities, may have been promised before. In this research I suggest ways to realise such goals.

Indicadores energéticos: instrumentos de apoio ao desenvolvimento sustentável

Energy indicators are tools to support decision-making on energy. The growing debate on sustainable development, contributed to the energy indicators began to incorporate, besides the traditional economic, social and environmental information. Therefore, taking sustainable development into account, it is important to know contributions and limitations of these tools. The overall goal of this study is to analyze the contributions and limitations of the energy indicators as assets to support sustainable development.This study can be classified as descriptive because it relies on bibliographical and documental material. As a result of documental analysis, 55 energy indicators for sustainable development (EISD) were selected. The selection took place by identification of those indicators through the institutions International Atomic Energy Agency (IAEA), Helio International and World Energy Council (WEC), among 19 institutions involved in research on energy identified in the survey. The study stresses that most of the selected indicators focuses on the economic dimension, 19 EISDs (34.54%), followed by 10 EISDs (18.18%) focused on the environmental dimension, 9 EISDs (16.36%) focused on the social issues, 7 EISDs (12.45%) are classified as resilience, 4 EISDs (7.27%) is about governance, 3 EISDs (5.45%) focused on vulnerability and 3 EISDs (5.45%) is about policy. Despite the inclusion of indicators associated with other dimensions than economy, information provided by those indicators emerges as their own limitation. Because, recently, indicators’ information were used to promote sustainable development as well as the opposite. Additionally, the study identified EISDs whose components were not specified. They may enable generation of information far from the real scenario, if components dissociated EISD would be taking into consideration or even the non-consideration of relevant components. Despite limitations, EISDs assisting decision-makers contributes to the pursuit of sustainable development. But they may be improved through information about environmental issues, such as emission of atmospheric pollutants, soil and water, resulting from energy sources, helps identifying which sources are more or less harmful for sustainable development. However, difficulty in collecting data, identifying the components for calculation of each indicator and even interpretation of this, as analyzed, may not only fail to contribute to sustainable development, as can delay taking corrective or preventive decisions.

Impact of a community-based exercise programme on physical fitness in middle-aged and older patients with type 2 diabetes

Objectives: Physical fitness is related to all-cause mortality, quality of life and risk of falls in patients with type 2 diabetes. This study aimed to analyse the impact of a long-term community-based combined exercise program (aerobic + resistance + agility/balance + flexibility) developed with minimum and low-cost material resources on physical fitness in middle-aged and older patients with type 2 diabetes. Methods: This was a non-experimental pre-post evaluation study. Participants (N = 43; 62.92 ± 5.92 years old) were engaged in a community-based supervised exercise programme (consisting of combined aerobic, resistance, agility/balance and flexibility exercises; three sessions per week; 70 min per session) of 9 months' duration. Aerobic fitness (6-Minute Walk Test), muscle strength (30-Second Chair Stand Test), agility/balance (Timed Up and Go Test) and flexibility (Chair Sit and Reach Test) were assessed before (baseline) and after the exercise intervention. Results: Significant improvements in the performance of the 6-Minute Walk Test (Δ = 8.20%, p < 0.001), 30-Second Chair Stand Test (Δ = 28.84%, p < 0.001), Timed Up and Go Test (Δ = 14.31%, p < 0.001), and Chair Sit and Reach Test (Δ = 102.90%, p < 0.001) were identified between baseline and end-exercise intervention time points. Conclusions: A long-term community-based combined exercise programme, developed with low-cost exercise strategies, produced significant benefits in physical fitness in middle-aged and older patients with type 2 diabetes. This supervised group exercise programme significantly improved aerobic fitness, muscle strength, agility/balance and flexibility, assessed with field tests in community settings.

Frame survey (census of boats and fishing gear) Lake Kyoga and Lake Kwania (Uganda), May-June 1990

The census of a fishing industry is called a frame survey. This is a rather comprehensive term, because there are many aspects of a fishery which one might wish to know. This is illustrated by the report on the partial census executed by the ADP/FS on the southern landings of L.Kyoga during December 1988, which deals with many socio-economic aspects of fishermen's households.

SES-RELATED DIFFERENCES IN WORD LEARNING: EFFECTS OF COGNITIVE INHIBITION AND WORD LEARNING

Socioeconomic status (SES) influences language and cognitive development, with discrepancies particularly noticeable in vocabulary development. This study examines how SES-related differences impact the development of syntactic processing, cognitive inhibition, and word learning. 38 4-5-year-olds from higher- and lower-SES backgrounds completed a word-learning task, in which novel words were embedded in active and passive sentences. Critically, unlike the active sentences, all passive sentences required a syntactic revision. Measures of cognitive inhibition were obtained through a modified Stroop task. Results indicate that lower-SES participants had more difficulty using inhibitory functions to resolve conflict compared to their higher-SES counterparts. However, SES did not impact language processing, as the language outcomes were similar across SES background. Additionally, stronger inhibitory processes were related to better language outcomes in the passive sentence condition. These results suggest that cognitive inhibition impact language processing, but this function may vary across children from different SES backgrounds

A more reliable PCR for detection of Mycobacterium tuberculosis in clinical samples

Diagnostic techniques based on PCR have two major problems: false-positive reactions due to contamination with DNA fragments from previous PCRs (amplicons) and false-negative reactions caused by inhibitors that interfere with the PCR. We have improved our previously reported PCR based on the amplification of a fragment of the Mycobacterium tuberculosis complex-specific insertion element IS6110 with respect to both problems. False-positive reactions caused by amplicon contamination were prevented by the use of uracil-N-glycosylase and dUTP instead of dTTP. We selected a new set of primers outside the region spanned by the formerly used primers to avoid false-positive reactions caused by dTTP-containing amplicons still present in the laboratory. With this new primer set, 16 copies of the IS6110 insertion element, the equivalent of two bacteria, could be amplified 10(10) times in 40 cycles, resulting in a mean efficiency of 77% per cycle. To detect the presence of inhibitors of the Taq polymerase, which may cause false-negative reactions, part of each sample was spiked with M. tuberculosis DNA. The DNA purification method using guanidinium thiocyanate and diatoms effectively removed most or all inhibitors of the PCR. However, this was not suitable for blood samples, for which we developed a proteinase K treatment followed by phenol-chloroform extraction. This method permitted detection of 20 M. tuberculosis bacteria per ml of whole blood. Various laboratory procedures were introduced to reduce failure or inhibition of PCR and avoid DNA cross contamination. We have tested 218 different clinical specimens obtained from patients suspected of having tuberculosis. The samples included sputum (n=145), tissue biopsy samples (n=25), cerebrospinal fluid (n=15), blood (n=14), pleural fluid (n=9), feces, (n=7), fluid from fistulae (n=2), and pus from a wound (n=1). The results obtained by PCR were consistent with those obtained with culture, which is the "gold standard." We demonstrate that PCR is a useful technique for the rapid diagnosis of tuberculosis at various sites.

Historic lower Manhattan /

Scale not given.

An Exploration of Auditory Brainstem Encoding of Stop Consonants in Infants and Implications for Language Outcomes

Current trends in speech-language pathology focus on early intervention as the preferred tool for promoting the best possible outcomes in children with language disorders. Neuroimaging techniques are being studied as promising tools for flagging at-risk infants. In this study, the auditory brainstem response (ABR) to the syllables /ba/ and /ga/ was examined in 41 infants between 3 and 12 months of age as a possible tool to predict language development in toddlerhood. The MacArthur-Bates Communicative Development Inventory (MCDI) was used to assess language development at 18 months of age. The current study compared the periodicity of the responses to the stop consonants and phase differences between /ba/ and /ga/ in both at-risk and low-risk groups. The study also examined whether there are correlations among ABR measures (periodicity and phase differentiation) and language development. The study found that these measures predict language development at 18 months.

Using Habitat Equivalency Analysis to Assess the Cost Effectiveness of Restoration Outcomes in Four Institutional Contexts

At the national level, with a fixed amount of resources available for public investment in the restoration of biodiversity, it is difficult to prioritize alternative restoration projects. One way to do this is to assess the level of ecosystem services delivered by these projects and to compare them with their costs. The challenge is to derive a common unit of measurement for ecosystem services in order to compare projects which are carried out in different institutional contexts having different goals (application of environmental laws, management of natural reserves, etc.). This paper assesses the use of habitat equivalency analysis (HEA) as a tool to evaluate ecosystem services provided by restoration projects developed in different institutional contexts. This tool was initially developed to quantify the level of ecosystem services required to compensate for non-market impacts coming from accidental pollution in the US. In this paper, HEA is used to assess the cost effectiveness of several restoration projects in relation to different environmental policies, using case studies based in France. Four case studies were used: the creation of a market for wetlands, public acceptance of a port development project, the rehabilitation of marshes to mitigate nitrate loading to the sea, and the restoration of streams in a protected area. Our main conclusion is that HEA can provide a simple tool to clarify the objectives of restoration projects, to compare the cost and effectiveness of these projects, and to carry out trade-offs, without requiring significant amounts of human or technical resources.

Quando for grande quero ser teu amigo: a brincadeira como mediadora da relação entre as crianças

Relatório de Estágio apresentado à Escola Superior de Educação de Paula Frassinetti para obtenção do grau de Mestre em Educação Pré- escolar e Ensino do 1º Ciclo do Ensino Básico

Uma abordagem dinâmica e atual para o ensino das cônicas na educação básica

Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Exatas, Departamento de Matemática, 2015.

Experiências de (in)justiça com os professores e comportamentos de desvio na adolescência

Tese de Doutoramento em Psicologia na área de especialidade Psicologia Social

Imagem corporal e auto-estima em rapazes pré-adolescentes

Dissertação de Mestrado apresentada ao Instituto Superior de Psicologia Aplicada para obtenção de grau de Mestre na especialidade de Psicologia Clínica.