The determinants of location choice: Single plants versus multi-plants

This paper adopts a count data model to explore the distinction between single plant and multi-plant location choices. It is hypothesized that start-up location decisions would be determined by supply variables (land, labour and capital costs, workforce and technological characteristics); demand variables (market size and market accessibility) and agglomeration economies. We use plant data and focus on location choices within Portuguese municipalities. Our research shows that new multi-plants are particularly sensitive to urbanization economies, land costs and the size of the local market, while new single plants are more responsive to labour costs, both localization and urbanization economies and accessibility to main markets

Proximity and R&D Cooperation between firms: Location, R&D and Output in an Oligopoly with Spillovers

This paper aims at explaining how proximity between firms affects cooperation in R&D. For that purpose, it is proposed a three-stage game amongst three firms where each firm decides about location, R&D and output. Firms’ decision about location determines a R&D spillover, which is inversely related to the distance between firms. R&D output is assumed to be cost reducing and exhibit diminishing returns. Cooperation is only allowed in the R&D stage. Our results allow us to conclude that there is a positive relationship between R&D output equilibrium and the distance between firms when firms act independently. When firms cooperate in R&D, R&D output for a cooperating firm increases with the degree of information sharing between them, as well as with a reduction of the distance between cooperating firms. Firms’ decision about location is also affected by R&D activities: if R&D activities run independently, the clustering of firms only occurs for a convex spillover function; if R&D activities run cooperatively, clustering is always observed if there is an increased information sharing between firms. Keywords: Location, R&D cooperation, R&D spillover

Evolution and adaptation of Streptococcus pneumoniae population in the era of expanded conjugate vaccines

Tese de mestrado, Ciências Biofarmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2018Streptococcus pneumoniae (or pneumococcus) is one of the most important causes of bacterial infections mainly in young children, immunocompromised individuals of all ages and the elderly. It is responsible for meningitis, bacteremia and pneumonia, as well as sinusitis and otitis media. Besides this, the natural way of living of this bacterium is through asymptomatic nasopharyngeal colonization. Colonization rates are generally high among young children, the major reservoir and source of transmission of pneumococci. Once colonization is the first step for pneumococcal disease and is essential for bacteria spreading between individuals, this has been an important focus of research. Most pneumococcus have a polysaccharide capsule that is responsible for the existence of close to 100 variants (or serotypes) and that is considered its main virulence factor. For this reason, the capsule has been the main target for pneumococcal vaccine design. In Portugal, pneumococcal conjugate vaccines (PCVs) were only introduced in the Nacional Immunization Program in 2015. In the era of multivalent pneumococcal conjugated vaccines, epidemiological and surveillance studies are of major importance to obtain information that will help our understanding of serotype and clonal replacement changes occurring in carriage and disease as a consequence of vaccination. To obtain this information, microbial typing tools are fundamental to provide data about the evolution of bacterial population. Serotyping tools are widely used to address the effectiveness of pneumococcal vaccination. However, it is known that capsular type alone may not give the full picture regarding vaccine impact. The aim of this study was to address the clonal evolution and adaptation of the pneumococcus after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) in Portugal. For that, we used multilocus sequence typing (MLST), the ‘gold standard’ of molecular typing for the pneumococcus. We analyzed close to 700 nasopharyngeal isolates from children attending day-care centers, collected before introduction of PCV13 (2009 – 2010) and in the years afterwards (2011 – 2016) in two regions of Portugal. Our focus turned into answering main questions regarding the clonal evolution leading to persistence of some vaccine-types and emergence of non-vaccine types, overtime. The results showed that, regarding the few vaccine-types that are still in circulation, for most cases it is one major clone, that was already in circulation before vaccine introduction, that is responsible for the persistence of that serotype, as it is the case of the clonal complex (CC) 179 associated with serotype 19F. Besides that, whenever there is high clonal diversity and the presence of antimicrobial resistant clones before vaccine introduction, in most cases it is the resistant clone that is maintained overtime. Regarding non-vaccine types we detected clonal expansion associated with clones that were already in circulation and the emergence of novel, previously undetected clones. In this group of serotypes, antimicrobial resistance did not have such an important role as the one detected for the vaccine-type clones. We found few capsular switch events, but we could not correlate this phenomenon with vaccine impact. With this study we could conclude that PCV13 impacts on the pneumococcal population beyond capsular type and that this population is able to genetically adapt and evolve to this pressure.Streptococcus pneumoniae (ou pneumococos) é uma das principais causas de infeções bacterianas, principalmente em crianças, indivíduos imunocomprometidos de todas as idades e idosos. É um agente causativo de meningite, bacteriemia e pneumonia, assim como sinusite e otite. Apesar disto, o estilo de vida natural desta bactéria é através da colonização assintomática da nasofaringe. As taxas de colonização são geralmente elevadas em crianças, os principais reservatórios e fontes de transmissão de pneumococos. Uma vez que a colonização precede sempre a infeção e é essencial para a transmissão entre indivíduos, esta tem sido um foco importante de investigação. A maior parte das estirpes de pneumococos contêm uma cápsula polissacarídea que é responsável pela existência de cerca de 100 variantes (ou serotipos) e que é considerada o seu principal fator de virulência. Por esta razão, a cápsula tem sido utilizada no desenvolvimento de vacinas pneumocócicas. Em Portugal, a vacina pneumocócica polissacarídea conjugada apenas foi introduzida no Plano Nacional de Vacinação em 2015. Na presente época, em que estão disponíveis vacinas multivalentes, os estudos epidemiológicos e de vigilância são de enorme importância de forma a alcançar toda a informação que ajudará a perceber particularidades como a substituição de serotipos e clones que ocorre em colonização e em infeção como consequência da vacinação. De forma a obter esta informação, ferramentas de tipagem microbiana são fundamentais para fornecer dados acerca da evolução populacional bacteriana. Métodos de tipagem capsular são frequentemente utilizados para testar a eficácia da vacina pneumocócica. No entanto, a cápsula pode não fornecer toda a informação relativamente ao impacto da vacina. O principal objetivo deste estudo foi verificar a evolução e adaptação clonal do pneumococo após a introdução da vacina pneumocócica conjugada 13-valente (PCV13) em Portugal. Para isso, utilizámos a técnica ‘multilocus sequence typing’ (MLST), que é atualmente o padrão para tipagem molecular de pneumococos. Analisámos cerca de 700 isolados da nasofaringe recolhidas de crianças que frequentam infantários antes da introdução da PCV13 (2009 – 2010) e nos anos seguintes (2011 – 2016) em duas regiões de Portugal. Após análise dos dados, o nosso objetivo foi responder a algumas questões relacionadas com a evolução clonal que permitiu a persistência de alguns serotipos vacinais e a emergência dos serotipos não vacinais, ao longo do tempo. Os nossos resultados mostram que, relativamente aos poucos serotipos vacinais que ainda estão em circulação, na maioria dos casos é um clone principal, que já estava em circulação antes da introdução da vacina, que é responsável pela persistência dos serotipos, como é o caso do complexo clonal (CC) 179 associado ao serotipo 19F. Para além disto, quando há grande diversidade clonal e a presença de clones resistentes a agentes antimicrobianos antes da introdução da vacina, na maioria dos casos é o clone resistente que é mantido ao longo do tempo. Relativamente aos serotipos não vacinais detetámos expansão clonal associada a clones que já estavam em circulação e emergência de novos clones que não tinham ainda sido detetados. Neste grupo de serotipos, a resistências a agentes antimicrobianos não mostrou ser tão importante como nos clones associados a serotipos vacinais. Também detetámos alguns eventos de alteração da cápsula, no entanto, não conseguimos correlacioná-los com o impacto da vacina. Com este estudo podemos concluir que a vacina tem um impacto na população de pneumococos que vai para além do serotipo, e que esta população é capaz de se adaptar e evoluir geneticamente em resposta a esta pressão

O Consumo Alcoólico Estará Aumentado em Adolescentes com Fat Bingeing?

Evidence has been suggesting that neurochemical and behavioral adaptations emerging during one addictive behavior may enable a subsequent, different, addiction, even when the first one has ended. Such association seems remarkably accurate to fat bingeing and ethanol consumption, which constitute a relevant example of addictive patterns sequential association, particularly in adolescence. Therefore, the main purpose of the following review is to comprehend if adolescents who have engaged on fat bingeing escalated their ethanol consumption, after fat bingeing terminus, and secondly, in a positive scenario, to highlight why such association may happen. After searching databases such as MEDLINE (PubMed) and Clarivate Analytics Web of Science, all articles focused on adolescent humans or adolescent rats or adolescent mice, that included topics on fat bingeing and consequent ethanol consumption, were considered. Gathered results strengthened the referred hypothesis. Reports stating that adolescent fat bingers engage on escalated ethanol consumption were fundamentally supported by a prevalent fast food and ethanol cultures, bingers ‘shared personality traits, adolescence ‘susceptibilities for addictive behaviors and neurochemical and behavioral craving installment after fat bingeing cessation. Given that adolescence is a key structural and functional phase of human development, and that fat and ethanol consumption are linked to harmful physiological and social effects, priority must be given to multidisciplinary interventions aiming to challenge addictions, both pharmacologically and psychotherapeutically.A evidência tem sugerido que existem alterações, de índole neuroquímica e comportamental, que ocorrem durante uma perturbação aditiva e que propiciam uma perturbação aditiva subsequente, inclusive após a primeira ter terminado. Esta associação, entre dependências de substâncias, parece ser bastante representativa para fat bingeing e consumo alcoólico, que constituem, então, um exemplo representativo de associação sequencial entre perturbações aditivas, particularmente na adolescência. Assim, o objetivo principal da seguinte revisão é verificar se adolescentes com fat bingeing, tiveram aumento do consumo alcoólico, após término do fat bingeing, e num cenário positivo, compreender porque é que tal associação acontece. Depois de uma pesquisa em bases de dados, como a MEDLINE (PubMed) e a Clarivate Analytics Web of Science, foram considerados os artigos que incluíram fat bingeing e consumo alcoólico em adolescentes, quer humanos quer ratos. Os resultados reunidos defendem fortemente a hipótese questionada. Os diferentes estudos, que afirmaram que adolescentes com fat bingeing têm consumo alcoólico aumentado, baseiam‑se, fundamentalmente: na vigente cultura de fat food e consumo alcoólico, nos traços de personalidade transversais a doentes com dependência de substâncias, nas suscetibilidades inerentes à própria adolescência para dependência, e na instalação neuroquímica e comportamental de craving, após a cessação de fat bingeing. Tendo em conta que a adolescência é uma fase chave no desenvolvimento estrutural e funcional do ser humano, e conhecendo os efeitos pejorativos, fisiológicos e sociais, do fat bingeing e do consumo alcoólico, é recomendado que seja dada prioridade a intervenções multidisciplinares, de nível psicoterapêutico e farmacológico, que possam combater as perturbações consideradas

Modelling Location Decisions - The role of R&D activities

In this essay, we intend to evaluate the importance of R&D (Research and Development) activities for firms' decision about location. For that purpose, we use micro-level data for the Portuguese industrial sector and focus on the location choices made by new starting firms during 1992-2000 within 275 municipalities. We consider two samples: the first one includes the entire manufacturer sector, while the second one restricts for those industrial branches that were R&D intensive. The set of explanatory variables includes a group of technological variables, such as R&D expenditures and human capital stock, as well as other explanatory variables that account for location specific characteristics and that are traditionally stressed by urban and regional theory, such as production costs (labor costs, land costs and taxes), demand indicators and agglomeration economies (urbanization and localization economies). The model is based on the random utility maximization framework but proceeds through a Poisson regression model for panel data, due to its equivalence with the conditional logit model. Through the estimation of the model, we were able to conclude that for the entire manufacturer sector, the main determinants for location decisions were the labor and land costs and the localization and urbanization economies. However, when considering the R&D intensive sample, those traditional location determinants lose importance, whilst the technological variables, such as the R&D expenditures, become relevant

Developing gene-edited models to study mis-splicing in Hypertrophic Cardiomyopathy

Exonic variants that cause abnormal mRNA splicing have been reported in human disease. However, this phenomenon is relatively unstudied in Hypertrophic Cardiomyopathy, a complex genetic cardiac disease with more than 1500 pathogenic mutations identified in over 14 genes. The lack of suitable models to study the causal mechanism of HCM-associated variants poses a drawback to the understanding of the molecular basis underlying this disease. The recent emergence of CRISPR/Cas9 and hiPSCs technologies are an exciting approach to generate disease models that better recapitulate the characteristics of the human heart. Three gene-edited clones harbouring the MYBPC3 c.1090G>A variant were generated using the CRISPR/Cas9 system. This variant is predicted to disrupt the recognition of the donor splice-site and lead to the skipping of exon 12. However, throughout the gene-editing process and due to long time in culture, these cells lost expression of pluripotency markers and could not be differentiated into cardiomyocytes to perform further experiments. In parallel, a patient-derived HCM cell line (Xutl, p.I1250fs) and Gibco and TCLab control lines were differentiated into cardiomyocytes using a 2D protocol. The hiPSCs-CMs obtained expressed high levels of fetal sarcomeric-genes TNNT2 and TTN isoforms, when compared to the adult human heart. Morphologically, they also displayed characteristics that are compatible to those of embryonic cardiomyocytes. Therefore, these hiPSCs-CMs have an immature phenotype and could not fully recapitulate the characteristics of adult cardiomyocytes. For disease-modelling purposes, mature hiPSCs-CMs that are comparable to those found in the adult heart are required and 3D differentiation protocols are some of the approaches being implemented. Even though optimization of the gene-editing and cardiac differentiation protocols is essential for the success of subsequent experiments, the work performed in this thesis provided important advances in the development of improved cellular models to study complex genetic diseases, such as HCM

Modelling Location Decisions - The role of R&D activities

In this essay, we intend to evaluate the importance of R&D (Research and Development) activities for firms' decision about location. For that purpose, we use micro-level data for the Portuguese industrial sector and focus on the location choices made by new starting firms during 1992-2000 within 275 municipalities. We consider two samples: the first one includes the entire manufacturer sector, while the second one restricts for those industrial branches that were R&D intensive. The set of explanatory variables includes a group of technological variables, such as R&D expenditures and human capital stock, as well as other explanatory variables that account for location specific characteristics and that are traditionally stressed by urban and regional theory, such as production costs (labor costs, land costs and taxes), demand indicators and agglomeration economies (urbanization and localization economies). The model is based on the random utility maximization framework but proceeds through a Poisson regression model for panel data, due to its equivalence with the conditional logit model. Through the estimation of the model, we were able to conclude that for the entire manufacturer sector, the main determinants for location decisions were the labor and land costs and the localization and urbanization economies. However, when considering the R&D intensive sample, those traditional location determinants lose importance, whilst the technological variables, such as the R&D expenditures, become relevant.

Firms' Location and R&D Cooperation in an Oligopoly with Spillovers

This paper aims at explaining if firms's decision about location revises when firms cooperate or compete in R&D. For that purpose, it is proposed a three-stage game amongst three firms where each firm decides about location, R&D and output. Firms' decision about location determines a R&D spillover, which is inversely related to the distance between firms. R&D output is assumed to be cost-reducing and exhibit diminishing returns. Cooperation is only allowed in the R&D stage. Our results allow us to conclude that there is a positive relationship between R&D output equilibrium and the distance between firms when firms acts independently. When firms cooperate in R&D, the R&D output for a cooperating firm increases with the degree of information sharing between them, as well as with a reduction of the distance between cooperating firms. Firms' decision about location is also affected by R&D activities: if R&D activities run independently, the clustering of firms only occurs for a convex spillover function; if R&D activities run cooperatively, clustering is always observed if there is an increased information sharing between firms.Location, R&D cooperation, R&D spillovers

Proximity and R&D Cooperation between firms: Location, R&D and Output in an Oligopoly with Spillovers

This paper aims at explaining how proximity between firms affects cooperation in R&D. For that purpose, it is proposed a three-stage game amongst three firms where each firm decides about location, R&D and output. Firms’ decision about location determines a R&D spillover, which is inversely related to the distance between firms. R&D output is assumed to be cost reducing and exhibit diminishing returns. Cooperation is only allowed in the R&D stage. Our results allow us to conclude that there is a positive relationship between R&D output equilibrium and the distance between firms when firms act independently. When firms cooperate in R&D, R&D output for a cooperating firm increases with the degree of information sharing between them, as well as with a reduction of the distance between cooperating firms. Firms’ decision about location is also affected by R&D activities: if R&D activities run independently, the clustering of firms only occurs for a convex spillover function; if R&D activities run cooperatively, clustering is always observed if there is an increased information sharing between firms. Keywords: Location, R&D cooperation, R&D spillovers

The effects of narcissism on the CEO’s propensity to take risk

Mestrado em FinançasOs Chief Executive Officers (CEOs) são indivíduos com poder na tomada de decisão e com impacto significativo na sociedade. Se os CEOs demonstrarem tendências grandiosas, e.g., se tiverem tendência para o narcisismo, estes irão, provavelmente, incorrer em acções com mais risco. Dada a influência dos CEOs e os perigos que podem advir do narcisismo, é de extrema importância, tanto para fins académicos, como para questões de bem-estar, estudar os impactos que este aspecto pode ter nos CEOs e a sua conexão com comportamentos consistentes com a tomada de risco. Assim sendo, uma amostra dos CEOs das Sociedades Anónimas Portuguesas foi utilizada. Os resultados mostram que o narcisismo tem uma relação positiva com a propensão ao risco dos CEOs. Estas evidências sugerem que contratar CEOs com características narcisistas pode levar a empresa a incorrer em mais riscos, este aspecto não deve ser ignorado, sobretudo se este tiver um efeito negativo no bem-estar dos stakeholders.Chief Executive Officers (CEOs) are individuals with power on decisions and that will impact on society. If the CEOs display grandiose tendencies, i.e., if they display narcissism tendencies, they may be more likely to incur in riskier actions. Given the influence of CEOs, and the dangers that may arise from narcissism, it is of major importance, for both academic and well-being purposes to study the impacts that this trait may have on CEOs and its connection to risk taking behaviors. To that end, a sample of the Portuguese CEOs of joint stock companies was used. The results show that narcissism is positively related to the CEO's propensity to risk. These findings suggest that hiring CEOs with narcissistic traits may lead the company to incur in more risk and that shall not be ignored, in particular if it has a detrimental effect on the stakeholder's wealth.info:eu-repo/semantics/publishedVersio