El paisaje urbano de Mérida en torno al 711

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Relationship marketing in the pharmaceutical industry

Background: Patients trust the treatment choices that can make a difference to their health to physicians, giving room for an agency relationship to be established between both stakeholders. Additionally, pharmaceutical companies, which belong to one the most profitable sectors, invest a lot of money to get recognition of their brands by physicians, which may include, many times, a transfer of value from the manufacturers to medical doctors. These ways of working can be viewed with caution by the general 4 public, as it can give room for a potential conflict of interest towards the ultimate endpoint, that is improving patients’ health. Despite this potential misperception, pharmaceutical companies keep their ways of working. The objective of this work is to study the relationship between pharmaceutical industry and physicians on prescription behaviour, and the exact role it may play. Methods: To study this problem statement, in an attempt to answer it, a combination of methods will be used. Literary review will be conducted to assess updated information on the problem being studied. This also includes checking information in Plataforma da Transparência of INFARMED, I.P. Nonetheless, the subject of this dissertation work will be mainly assessed through primary data collected via a market research study targeted to HIV physicians. Results: Fourty two HIV specialists participated in this market research. Efficacy was by far the most important attribute they value when selecting a treatment regimen. The combined three attributes that matter the most when choosing a treatment were efficacy, safety and convenience. The effectiveness on how companies communicated these attributes was found to have a positive impact on their prescription choices. Additionally, it was found that promotional sessions positively impact the prescription behaviour of physicians. Conclusion: No major effects on prescription behaviour were found for most of the marketing activities performed by pharmaceutical companies, with exception for promotional sessions, that were found to have a positive impact on the prescription behaviour for naïve patients

Development of new Catechol-Omethyltransferase inhibitors

The Catechol-O-methyltransferase (COMT, EC 2.2.1.6) is an enzyme responsible for the Omethylation of catechol substrates, such as catecholamines and catechol estrogens. Considering its physiological functions and the existence of polymorphisms, several studies associate COMT with the pathogenesis of several neurological disorders, especially with Parkinson’s Disease (PD) as well as with cardiovascular and hormone-dependent cancers, like breast cancers. Given the important role that COMT has in the catecholamines and catechol estrogens metabolism, COMT has become a relevant therapeutic target. Currently, the most effective and clinically approved by the Federal Drug Administration and the European Medicines Agency for the PD therapy consists of the use of Levodopa, combined with COMT inhibitors. Since the commercially available inhibitors for this enzyme still display a lot of disadvantages, like hepatoxicity, difficulty to reach the brain, among others, the main goal of this work was to develop new COMT inhibitors with potential clinical interest for the PD therapy. For this, triazolopyrimidinics were prepared through the Biginelli reaction, that can be considered catechol bioisosteres, therefore have a higher potential to interact with COMT. This hypothesis was confirmed through molecular docking, being predicted similar interactions as the ones that the catecholic substrates forms with the COMT active site. Their inhibitory properties were evaluated in human recombinant COMT lysates, after the compounds’ incubation at 10 and 100 µM. Contrary to what was expected, the compounds increased the enzyme specific activity, being considered COMT stabilizers. The compounds cytotoxicity was also evaluated in neural dopaminergic rat cells (N27), in the same concentrations. The vast majority of compounds at 10 µM did not exhibited cytotoxicity, being observed similar values to those of the commercial COMT inhibitors, Entacapone and Tolcapone, in the studied cell line. As expected, with the increase in compounds’ concentration (100 µM) a decrease in the relative cell proliferation was observed, reaching values considered to be cytotoxic. Altogether, the synthesized compounds at the concentration of 10 µM stabilized COMT and did not induce cytotoxicity in the N27 cells. In sum, these compounds may be useful for thermal stability assays, crystallography, structure-activity relationship studies and display potential to be studied in specific breast cancers cell lines.A Catecol-O-metiltransferase (COMT, EC 2.2.1.6)) é a enzima responsável pela O-metilação de substratos catecólicos, como as catecolaminas e os estrogénios com estrutura catecólica. Considerando as suas funções fisiológicas e a existência de polimorfismos, vários estudos associam a COMT com a patogénese de várias desordens neurológicas, especialmente com a Doença de Parkinson (DP) e também com doenças cardiovasculares e cancros hormonodependentes, como cancros da mama. Devido à importância que a COMT tem no metabolismo das catecolaminas e dos estrogénios catecólicos, a COMT tornou-se nas últimas décadas num importante alvo terapêutico. Atualmente, a terapia mais eficaz e clinicamente aprovadas pela Federal Drug Administration e European Medicines Agency para a doença de Parkinson consiste no uso de Levodopa, combinada com inibidores da COMT. Uma vez que os inibidores desta enzima comercialmente disponíveis ainda apresentam diversas desvantagens, como hepatotoxicidade, dificuldade em alcançar o cérebro, entre outras, o objetivo principal deste trabalho foi desenvolver novos inibidores da COMT com potencial clínico para a terapia da DP. Para isto, foram preparados triazolopirimidínicos através da reação de Biginelli, os quais podem ser considerados bioisósteros de catecóis, podendo por isso ter potencial para interagir com a COMT. Esta hipótese foi confirmada através de docking molecular, prevendo-se interações moleculares semelhantes às dos substratos catecóis com o centro ativo da COMT. As suas propriedades inibitórias foram avaliadas em lisados recombinantes da enzima, após incubação dos compostos nas concentrações de 10 e 100 µM. Contrariamente ao expectável, os compostos aumentaram a atividade específica da enzima, podendo ser considerados estabilizadores da COMT. Foi ainda avaliada a citoxicidade dos mesmos em células dopaminérgicas neuronais de rato (N27) nas mesmas concentrações. A grande maioria dos compostos a 10 µM não mostrou citotoxicidade, observando-se valores semelhantes aos dos inibidores comerciais da COMT, Entacapone e Tolcapone, na linha celular N27. Como esperado com o aumento da concentração (100 µM) ocorreu um decréscimo na proliferação celular, atingindo valores já considerados citotóxicos. No geral, os compostos sintetizados, na concentração de 10 µM estabilizaram a COMT e não induziram citoxicidade nas células N27. Em suma, as moléculas sintetizadas podem ser úteis para estudos de estabilidade térmica, de cristalografia, de relação estrutura-atividade e apresentam potencialidade para ser estudados em linhas celulares especificas do cancro da mama

Nuclear power : a risky endeavor or an opportunity for the future?

In an age where a worldwide climate strategy is needed to mitigate the effects of climate change and global warming, the use of nuclear power as a source of electricity generation is currently a topic of discussion, amidst debates over energy decarbonization and security. This dissertation examines, theoretically and empirically, the effects of the closures of nuclear power plants on electricity prices and mortality. Using state-level monthly data on temperature, mortality, demographics, and the electricity market, I perform an event study that quantifies the impact of the closure of five nuclear power plants that were nearby and stopped operating at roughly the same time. Following the shutdown of nuclear power plants, it is anticipated that energy prices will rise, making access to temperature-regulating devices less affordable and exposing more people to extreme temperatures, which is anticipated to increase mortality rates. Results show that in almost all regions, residential electricity expenditure and prices decreased and exogenously increased after the nuclear plants’ closure. As predicted, electricity demand is inelastic, particularly in the summer months, and increased following the nuclear plant shutdowns. Importantly, extreme temperatures positively affect mortality, and I estimate that the coinciding exposure to them and the lower level of electricity expenditure have caused up to additional 2776 deaths per year. This evidence has important implications for the assessment of the effects of the USA’s decision to partially move away from nuclear power and the design of accompanying measures.Numa época em que uma política climática mundial é necessária para mitigar os efeitos das alterações climáticas e do aquecimento global, a utilização da energia nuclear como mecanismo para a produção de eletricidade é, atualmente, um tema em discussão, inserido nos debates sobre a descarbonização da produção de eletricidade e a independência energética. A presente dissertação examina, em termos teóricos e empíricos, o efeito do encerramento de centrais nucleares na mortalidade e no preço e consumo de energia elétrica. Usando dados mensais, ao nível estadual, relativos a temperatura, mortalidade, demografia e ao mercado da eletricidade, desenvolvo um event study que quantifica o impacto do encerramento de cinco centrais nucleares geograficamente próximas, cujas operações cessaram aproximadamente na mesma altura. Na sequência deste evento, espera-se que a energia se torne mais dispendiosa, expondo mais pessoas a temperaturas extremas, com potenciais consequências para a mortalidade. Os resultados indicam que, em quase todas as regiões, o preço e consumo de eletricidade no mercado residencial respetivamente aumentaram de forma exógena e diminuíram, após o encerramento das centrais nucleares. A elasticidade da procura de eletricidade é inelástica, particularmente nos meses de verão, tendo aumentado aquando do encerramento das centrais nucleares. Finalmente, mostro que temperaturas extremas fazem a mortalidade subir, e estimo que a exposição às mesmas, coincidindo com um menor consumo de eletricidade, tenham causado 2776 óbitos adicionais anualmente. Esta evidência tem implicações importantes para a avaliação dos efeitos da decisão dos EUA sobre a continuidade da energia nuclear e para o desenho de políticas públicas

The Role of Best Practices to Appraise Open Source Software

Thousands of open source software (OOS) projects are available for collaboration in platforms like Github or Sourceforge.  However, like traditional software, OOS projects have different quality levels.  The developer, or the end-user, need to know the quality of a given project before starting the collaboration  or its usage---they might of course to trust in the package before taking a decision.  In the context of OSS, trustability is a much more sensible concern; mainly end-users usually prefer to pay for  proprietary software, to feel more confident in the package quality.  OSS projects can be assessed like traditional software packages using the well known software metrics.  In this paper we want to go further and propose a finer grain process to do such quality analysis,  precisely tuned for this unique development environment.  As it is known, along the last years, open source communities have created their own standards and \emph{best practices}.  Nevertheless, the classic software metrics do not take into account the \emph{best practices}  established by the community.  We feel that it could be worthwhile to consider this peculiarity as a complementary source of assessment data.  Taking Ruby OSS community and projects as framework, this paper discusses the role of  \emph{best practices} in measuring software quality

Towards circular economy in the textiles and clothing value chain through blockchain technology and IoT : a review

The textile and clothing industry sector has today a big environmental impact, not only due to the consumption of water and the use of toxic chemicals but also due to the increasing levels of textile waste. One way to reduce the problem is to circularise the, currently linear, textile and clothing value chain, by using discarded clothes as raw material for the production of new clothes, transforming it into a model of circular economy. This way, while reducing the need to produce new raw materials (e.g. cotton), the problem of textile waste produced is also reduced, thus contributing to a more sustainable industry. In this article, we review the current approaches for traceability in the textile and clothing value chain, and study a set of technologies we deem essential for promoting the circular economy in this value chain – namely, the blockchain technology – for registering activities on traceable items through the value chain, and the Internet of Things (IoT) technology, for easily identifying the traceable items’ digital twins.EC18-399D-CF16 | ANTÓNIO MIGUEL RIBEIRO DOS SANTOS ROSADO DA CRUZN/

Eco-gamification platform to promote consumers engagement in the textile and clothing circular value chain

The textile and clothing (T&C) value chain is one of the most polluting in the world and one that produces the most waste. It is, therefore, important to encourage the circular economy (CE) model in this sector to reduce pollution, mitigate the effects of waste production, and, consequently, increase environmental sustainability. Leveraging end-consumer engagement in a CE mindset in the T&C sector is crucial, as they are the last player in a typical linear value chain. Therefore, a platform that supports and promotes sustainable tasks to manage one’s fashion products, through the use of gamification techniques, can be of utmost importance. In this article, we identify impactful carbon footprint consumer actions and solutions for the T&C consumer phase. After that, we survey gamification frameworks for analyzing techniques, at the system design level, which enable the engagement of the final consumer in the CE process. Then, we select and use one of such frameworks, Gameful Design Heuristics (GDH), for defining the gamification structure needed to implement on a business-to-consumer-to-consumer (B2C2C) context of a circular economy process, linking it to the aforementioned actions and solutions. As result, we present a B2C2C circular business process model for the T&C value chain and propose the design model of a gamified platform for the final consumers, which allows them to register the consumer-to-business (C2B) and consumer-to-consumer (C2C) activities, from the circular value chain’s business process, and benefit from a game-like experience. All the model features have been mapped to the GDH framework heuristics, validating that it is possible to support a set of defined heuristics of applied gamification for promoting CE in the T&C value chain.1B13-0D51-D4CD | Pedro Miguel FariaN/

Ansiedade dos estudantes perante o ensino clínico um estudo com estudantes de enfermagem

Con respecto a los estudiantes de enfermería, los factores de ansiedad durante su período de formación y las especificidades de las enseñanzas clínicas, muestran en algunas investigaciones, que los aspectos relacionados con el contexto clínico o la relación con los pacientes a menudo traen ansiedad al estudiante. Además de las situaciones complejas y problemáticas, los propios estudiantes sienten que están continuamente siendo evaluados, y de allí surge el problema de la ansiedad referido por muchos estudiantes en el contexto de la práctica clínica. El presente estudio, de carácter exploratorio, transversal y naturaleza cuantitativa, pretende conocer cuáles son los factores de estrés que son mencionados por un conjunto de estudiantes (N = 327), de la Licenciatura en Enfermería, que respondió a un protocolo de investigación constituido por una encuesta de caracterización socio-demográfica y por el Estado-Índice de Ansiedad Rasgo (Y Form). El análisis realizado permitió poner a prueba las cualidades psicométricas del instrumento, así como confirmar el análisis factorial de la versión portuguesa. En cuanto a los resultados obtenidos se concluye que, si bien no hay diferencias significativas en términos de ansiedad relacionada con los factores de caracterización socio-demográfica, los altos índices de ansiedad pueden ser explicados por la propia enseñanza clínica y por el impacto de la primera toma de contacto de los estudiantes con la práctica de enfermería.Regarding nursing students, the anxiety factors during their formation period and the specificities of clinical teachings, some research show that the aspects related with the clinical context or the relationship with the patients often bring anxiety to the student. Besides the situations being complex and problematic, the students themselves feel that they are continuously being evaluated, and from there arises the problem of anxiety referred by many students in the context of clinical practice. The present study, of exploratory, transversal and quantitative nature aims to know what stress factors are mentioned by a set of students (N=327), from the degree in Nursing, that answered an investigation protocol constituted by a socio-demographic characterization survey and by the State- Trait Anxiety Index (Y Form). The analysis made allowed to test the psychometric qualities of the instrument as well as confirm the factorial analysis of its portuguese version. In terms of obtained results we conclude that although there are no significant differences in terms of anxiety related to the factors of socio-demographic characterization, the high anxiety indices can be explained by the clinical teaching itself and by the impact of the students’ first contact with the nursing practice.Relativamente aos estudantes de enfermagem, fatores de ansiedade durante o seu processo de formação e aos aspetos específicos do ensino clínico, algumas investigações mostram que aspetos relacionados com o contexto clínico ou a relação com os docentes acarretam níveis de ansiedade nos estudantes. Para além de serem situações complexas e problemáticas para os estudantes, eles próprios sentem que estão em momentos contínuos de avaliação daí o problema da ansiedade referido por muitos estudantes nos contextos das práticas. O presente estudo de natureza exploratória, transversal e quantitativa tem como objetivo conhecer quais os fatores de ansiedade referidos por um conjunto de estudantes (N=327) do Curso de Licenciatura em Enfermagem, que responderam a um protocolo de investigação constituído por um questionário de caracterização sociodemográfica e pela Escala State-Trait Anxiety Inventory (Forma Y). As análises efetuadas permitiram testar as qualidades psicométricas do instrumento bem como confirmar as análises fatoriais da versão portuguesa do mesmo. Em termos dos resultados obtidos conclui-se que apesar de não existirem diferenças significativas em termos da ansiedade relacionada com os fatores de caracterização sociodemográfica os elevados índices de ansiedade poderão ser explicados pelo próprio ensino clínico e pelo impacto do primeiro confronto dos estudantes com a prática clínica.peerReviewe