Drug Interaction in Psycho-Oncology: Antidepressants and Antineoplastics

Background and Objectives: Although there is a growing impact of psychiatric and depressive disorders in cancer patients, literature on the idiosyncrasies of antidepressants (ADs) used in those conditions and their interactions with antineoplastic agents (ANs) is scarce. Sharing the same biotransformation pathways enhances the risk of drug interaction between ADs and ANs, specifically when compounds are inducers, inhibitors or substrates of cytochrome P450 (CYP 450). In cancer patients, such drug interactions may result in less efficacy of the drug and/or increase of their side effects. Therefore, the choice of AD should be cautious (safe and effective) and well supported. The main purpose of this review was to analyze the individual pharmacokinetic properties of the most used ADs and ANs in order to summarize the risk of possible drug interactions between them, anticipating the consequences of their coadministration. Methods: The authors reviewed books and PubMed online articles published in the last 6 years. Results: Most of the ANs are subject to transformation by CYP 450 3A4 and their coadministration with ADs, that have inhibitory properties of this CYP isoform, such as fluoxetine, sertraline, paroxetine and fluvoxamine, may result in the loss of the AN's efficacy or higher toxicity. Conclusion: Among the ADs, escitalopram, citalopram, venlafaxine, mirtazapine and milnacipran stand out for their weak CYP 450 inhibitory potential and their safety profile in those patients

Operationalizing psychic distance International Market Selection based on a knowledge perspective : the case of Miitik, a Portuguese beachwear company

Back in the days, Internationalization was a process exclusive to companies of great dimension. It requires a rather high amount of resources, reason why it was difficult and expensive for smaller companies to achieve. However, as the years went by, communication channels have improved and the world has become closer as information costs decreased. Given this, nowadays not only big multinationals but also Micro, Small and Medium Enterprises (SME’s) have increased its operations abroad. If in the past internationalizing was considered an option, but some support that it has become a necessity given the high market concentration across many industries. Nevertheless, although it is advantageous to expand operations, it doesn’t mean it has become an easy process. In fact, SME’s still face several obstacles that must be considered and tackled. As an example of the previous lines, I found Miitik. Miitik is a retailing beachwear start-up based in Portugal. The company started its operations 4 years ago and currently operates only in Portugal. Although it has sold some products abroad, it is not representative at all in the total sales. At the moment, the beachwear industry in Portugal is rather saturated both by big multinationals and also by other small actors, as Miitik. Due to this, Miitik has been struggling to achieve its financial goals. One of the options would be to internationalize, however the company is lacking resources and some insights about with countries to chase. This thesis has the aim to support Miitik with its International Market Selection.No passado, Internacionalização era um processo adoptado essencialmente por grandes multinacionais. Tal acontecia, pois consiste num processo que involve diversos recursos, o que tornava bastante dificil e dispendioso para pequenas empresas de obter. No entanto, com o decorrer dos anos, os canais de comunicação evoluiram bastante, o que levou a que a obtenção de informação se tenha tornado mais fácil e o mundo tenha ficado mais próximo. Posto isto, hoje em dia não apenas as grandes multinacionais, mas também as pequenas e médias empresas têm expandido as suas operações no estrangeiro. Se no passado internacionalização era considerado uma opção, hoje em dia é uma necessidade. Ainda que internacionalizar seja de facto vantajoso, não significa que seja um processo fácil, viste que continuam a existir diversas barreiras no processo. Como exemplo do previamente exposto, temos a Miitik, uma start-up de comércio de fatos de banho sediada em Portugal. A empresa iniciou as suas operarações há 4 anos e atua principalmente no mercado português. Apesar de ter efectuado algumas vendas no estrangeiro, estas não são representativas no total de vendas. Actualmente, a indústria de fatos de banho em Portugal, encontra-se especialmente saturada tanto por grandes multinacionais como por PME’s. Por consequente, a empresa não tem conseguido alcançar os resultados desejados. Uma das soluções passaria por expandir as suas operações no estrangeiro, no entanto a empresa escasseia em recursos e tem pouco conhecimento acerca de mercados estrangeiros. Esta tese tem o objectivo de ajudar a Miitik quanto à sua selecção de mercados

Detection and identifitication of registration and fishing gear in vessels

Illegal, unreported and unregulated (IUU) fishing is a global menace to both marine ecosystems and sustainable fisheries. IUU products often come from fisheries lacking conservation and management measures, which allows the violation of bycatch limits or unreported catching. To counteract such issue, some countries adopted vessel monitoring systems (VMS) in order to track and monitor the activities of fishing vessels. The VMS approach is not flawless and as such, there are still known cases of IUU fishing. The present work is integrated in a project PT2020 SeeItAll of the company Xsealence and was included in INOV tasks in which a monitoring system using video cameras in the Ports (Non-boarded System) was developed, in order to detect registrations of vessels. This system registers the time of entry or exit of the vessel in the port. A second system (Boarded System) works with a camera placed in each vessel and an automatic learning algorithm detects and records fishing activities, for a comparison with the vessel’s fishing report.A pesca ilegal, não declarada e não regulamentada (INDNR) é uma ameaça global tanto para os ecossistemas marinhos quanto para a pesca sustentável. Os produtos INDNR são frequentemente provenientes de pescas que não possuem medidas de conservação e de gestão, o que permite a violação dos limites das capturas ou a captura não declarada. Para contrariar esse problema, alguns países adotaram sistemas de monitoramento de embarcações (VMS) para acompanhar e monitorar as atividades dos navios de pesca. A abordagem VMS não é perfeita e, como tal, ainda há casos conhecidos de pesca INDNR. O presente trabalho encontra-se integrado num projeto PT2020 SeeItAll da empresa Xsealence. Este trabalho integrado nas tarefas do INOV no qual foi desenvolvido um sistema de monitorização das entradas dos navios nos Portos (Sistema não embarcado) no qual pretende-se desenvolver um sistema que detete as matriculas dos navios registando a hora de entrada e saída do porto com recurso da camaras de vídeo. A outra componente (sistema embarcado) é colocada em cada embarcação uma camara de video e, recorrendo a aprendizagem automática e um sistema de CCTV, são detetadas as atividades de pesca e gravadas, para posterior comparação com o relatório de pesca do navio

Development of traceless strategies for the selective release of BET inhibitors in cancer cells

Epigenome-targeting drugs are an emerging class of therapeutic agents against a variety of human cancers. This results from the increasingly clear understanding of histone post-translational modifications and their role in tumorigenesis and tumor progression. Proteins of the bromodomain and extraterminal (BET) family, in particular, are epigenetic regulators of great interest as biological targets. These family of proteins is comprised of BRD2, BRD3, BRD4 and BRDT, which bind to chromatin through recognition of acetylated lysine residues (KAc) on histone tails, leading to the recruitment and co-activation of master regulatory transcription factors including the oncogene MYC. Preclinical modulation of BET protein function in malignant models through small molecule inhibition has therefore resulted in marked phenotypic changes and promising therapeutic benefits, driving multiple effectors into clinical evaluation. However, early clinical trials have had modest results with only a few, short-lived, responses in both hematologic and solid tumors. Relevant toxicities were observed in many patients, including severe thrombocytopenia, fatigue, gastrointestinal (GI)-side effects, nausea, vomiting, and which significantly limited compliance to treatment. The targeted delivery of BET inhibitors to cancer cells can, on the other hand, markedly improve their therapeutic index and overall efficacy. Through the conjugation of the therapeutic agent to a tumor-cellspecific ligand via a cleavable linker, it is possible to enhance the accumulation of drug at the tumor site while sparing healthy cells and the associated collateral toxicity. This project describes the engineering of a conditionally stable construct for the efficient, targeted and traceless release of a BETbromodomain protein effector in cancer cells. Based on published evidence and organic chemistry methodologies, a BET inhibitor was designed to retain high binding efficacy to target proteins and potent antitumor activity, while enabling targeted delivery approaches. The derivatised compound, featuring a tertiary amine suitable to accommodate a self-immolative release mechanism, engaged BET protein targets with great affinity as determined by different biophysical assays. Crystallography studies and molecular modeling of compounds in complex with target proteins provided further mechanistic insights into their mode of binding, revealing unprecedented bond formation and establishing a rationale for the exquisite binding observed. At the cellular level the tertiary-amine containing BET inhibitor exhibited potent antitumor activity against several human cancer cell lines from different tissues. Particularly in the context of prostate cancer, cellular target engagement strategies have shown successful binding of compounds to BET bromodomain proteins, while flow cytometry analysis displayed potent perturbations of cell cycle progression. Concomitantly, a substantial suppression of Myc protein levels was observed following compound treatment in a dose- and time-dependent manner, further corroborated by transcriptome analysis data showing a significant down-regulation of MYC and MYC-related gene signatures. Additional transcriptional perturbations were found in several growth-promoting gene signatures and known downstream effectors of BET bromodomain protein activity, further supporting the antitumoral efficacy and therapeutic potential of the tertiary-amine containing BET inhibitor. Finally, the derivatised BET bromodomain effector was assembled in a unique ligand-targeted conjugate for its selective delivery in prostate cancer cells. The tertiary-amine functionality of the drug was used to tether a self-immolating motif, which allows for intracellular release upon an enzymatic trigger, further conjugated to a ligand that specifically targets prostate cancer cells. The data observed confirmed the labile nature of the release mechanism and selective liberation of the tertiary-amine derivative in the presence of a triggering event. Furthermore, in a mice model of prostate cancer it is shown that the unique ligand-linker-BET inhibitor conjugate has a remarkably superior therapeutic activity than that of the BET inhibitor alone, thus suggesting a therapeutic advantage over the nontargeted counterparts.Hovione Farmaciência S

Delimitação de perímetros de protecção em sistemas aquíferos fissurados: caso de estudo na Serra da Gardunha, Centro de Portugal

A crescente necessidade e importância das águas subterrâneas exige uma protecção adequada deste recurso através da delimitação de perímetros de protecção em torno das captações. Para tal, torna-se necessária uma abordagem específica e ajustada às caraterísticas locais para obter soluções mais adequadas. Os métodos analíticos permitem a delimitação das zonas de protecção utilizando parâmetros hidrogeológicos. Neste trabalho são comparados dois métodos analíticos - método do raio fixo e de Wyssling - na definição dos peímetros de proteção de duas captações localizadas na Serra da Gardunha. As captações de Eirinhas nº 1 e Eirinhas Nº2 estão incluídas no subsistema de Casal da Serra (Serra da Gardunha), correspondendo a galerias subterrâneas, semihorizontais e alongadas, com uma secção com cerca de 1,80m de altura e 0,60m de largura. As rochas graníticas mostram fracturas intensas em que nalguns locais estão bastante degradadas. A água subterrânea escorre aproximadamente paralela à topografia, indicando uma curta permanência, como sugerido pela baixa mineralização que apresentam. O círculo dos perímetros de proteção com o método de raio fixo mostra círculos centrados nas captações, ultrapassando os limites da zona de recarga presumida, tanto a montante como a jusante. O método de Wyssling, por sua vez, ao considerar o gradiente hidráulico na delimitação dos perímetros mostra áreas de protecção mais ajustadas à realidade, tanto a montante como a jusante.info:eu-repo/semantics/publishedVersio

A systematic literature review

Albuquerque, V., Dias, M. S., & Bacao, F. (2021). Machine learning approaches to bike-sharing systems: A systematic literature review. ISPRS International Journal of Geo-Information, 10(2), 1-25. [62]. https://doi.org/10.3390/ijgi10020062Cities are moving towards new mobility strategies to tackle smart cities’ challenges such as carbon emission reduction, urban transport multimodality and mitigation of pandemic hazards, emphasising on the implementation of shared modes, such as bike-sharing systems. This paper poses a research question and introduces a corresponding systematic literature review, focusing on machine learning techniques’ contributions applied to bike-sharing systems to improve cities’ mobility. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) method was adopted to identify specific factors that influence bike-sharing systems, resulting in an analysis of 35 papers published between 2015 and 2019, creating an outline for future research. By means of systematic literature review and bibliometric analysis, machine learning algorithms were identified in two groups: classification and prediction.publishersversionpublishe

Design epidérmico: do uso à experiência uma perspectiva de design experiencial

A necessidade do culto da imagem e o exponencial aumento do consumo, bem como a urgente intensificação da dimensão da moda, revelam-se em algo que se expressa à flor da pele. Se em tempos a pele foi sendo entendida como estanque e imutável, como produto de um acaso da natureza, como algo perene e eterno, esta parece ter vindo, aos poucos, a perder essa dimensão axiomática. Assim, e ao invés de uma obrigatoriedade, a pele encerra-se cada vez mais como uma possibilidade, como uma alternativa, como fruto de uma opção individual e contextual. As crescentes possibilidades de alterar a forma e feitio, bem como a sua dimensão eminentemente reactiva e interactiva, fazem com que o conceito de pele se aproxime cada vez mais do design: na sua forma potencialmente mutável (morfologia), na íntima relação que o sujeito desenvolve com o tempo e o espaço em que se insere (“espumas”), na construção de um acontecimento e acção constantes (performance), na possível experiência que dela se pode retirar (experiência e uso). Neste sentido pele e design remetem, ambos, para algo que determina e é determinado, que julga e é julgado, que molda e é moldado proporcionando, a todo o instante, uma possível realidade e experiência centradas no design e no utilizador

Multistage morphology-based license-plate location algorithm

This paper describes a new license-plate location algorithm using a sequential multistage approach, where each stage consists of a different sub-algorithm. All the proposed subalgorithms make use of morphological operations performed over both gray-scale and binary images. In order to ascertain the performance of the proposed algorithm, and to fairly compare it with license-plate location algorithms developed by other authors, a well-defined evaluation method is used. Results have shown that the proposed algorithm produces at least one accurate license-plate location hypothesis for 97.18% of 673 images acquired at a highway toll fence.ISCTE, Living Data, Brisa, S.A

Evaluation of license-plate location algorithms

We propose a new evaluation method for license-plate location algorithms. As a first step towards a comparison of the algorithms described in the literature over the years, we have implemented some relevant algorithms with different approaches and compared them using the proposed evaluation method. The software used for evaluation and a set of annotated evaluation images are both readily available, making the reproduction of the presented results possible. The availability of both software and an evaluation set allows the results presented in this paper to be used as benchmarks when developing plate location algorithms.ISCTE, Living Data, Brisa, S.A

La entrevista cognitiva mejorada: cómo interrogar a un testigo de manera eficaz

La entrevista cognitiva está considerada como una de las técnicas más eficaces para mejorar la calidad de la declaración de un testigo. Inicialmente incluía cuatro técnicas: reinstauración del contexto, contarlo todo, cambio de perspectiva y cambio de orden, pero se han introducido otras nuevas, dando lugar a la entrevista cognitiva mejorada. Esta nueva entrevista, además de mejorar la calidad de la declaración de los testigos, también parece ser útil para otros propósitos, como detectar mentiras, o para mejorar el bienestar mental de las víctimas. Repasamos brevemente la investigación existente y las técnicas más relevantes para ambos tipos de entrevista