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O fenómeno populista continua a ganhar apoiantes em todo o mundo. Em Portugal, o seu estudo tem-se focado maioritariamente no lado da oferta do populismo. Este facto deveu-se ao país não ter representação populista até 2019, tendo sido considerado uma exceção ao crescimento do movimento na Europa. Atualmente, Portugal carece de análises sobre o apoio ao populismo, ao nível individual. Contribuindo para colmatar esta lacuna, o presente estudo utiliza uma amostra nacional representativa, para analisar a relação entre as atitudes populistas e os traços de personalidade dos cidadãos portugueses. A análise é controlada, ainda, pela eficácia política, identificação partidária, e características sociodemográficas dos inquiridos. Entre os resultados, destaca- se o facto de todos os traços de personalidade surgirem como determinantes das atitudes populistas. Com efeito, os cidadãos portugueses com mais atitudes populistas tendem a ser mais extrovertidos, conscienciosos e neuróticos. Por outro lado, os menos populistas são mais abertos à experiência e mais amáveis. Outras variáveis surgem como importantes preditores de níveis mais elevados de atitudes populistas, como possuir um menor nível de eficácia política, (e em termos de variáveis sociodemográficas) ser do sexo masculino e mais velho. Estes resultados contribuem, não só para aprofundar o conhecimento acerca do populismo ao nível individual, como para enriquecer o debate acerca do caso português, introduzindo uma nova variável explicativa – as características intrínsecas da personalidade dos indivíduos. The populist phenomenon continues to gain supporters all over the world. In Portugal, its study has mostly focused on the supply side of populism. This was due to the country having no populist representation until 2019, and was considered an exception to the growth of the movement in Europe. Currently, Portugal lacks analyses on support for populism at the individual level. Contributing to fill this gap, the present study uses a nationally representative sample, to analyse the relationship between populist attitudes and personality traits of Portuguese citizens. The analysis is also controlled for political efficacy, party identification, and socio-demographic characteristics of the respondents. Among the results, we highlight the fact that all personality traits emerge as determinants of populist attitudes. This means that Portuguese citizens with more populist attitudes tend to be more extroverted, conscientious and neurotic. On the other hand, the less populist ones are more open to experience and more agreeable. Other variables emerge as important predictors of higher levels of populist attitudes, such as having a lower level of political efficacy, (and in terms of socio-demographic variables) being male and older. These results contribute, not only to deepen the knowledge about populism at the individual level, but also to enrich the debate about the Portuguese case, by introducing a new explanatory variable - the intrinsic personality characteristics of individuals. Mestrado em Ciência Política

This paper departs from a reflection of how my time as a doctoral student in the late nineties with the lean construction group at U.C. Berkeley influenced my (ongoing) research journey. I first re...

The manganese(III) porphyrin MnTnHex-2-PyP

Lung cancer (LC) is the leading cause of cancer deaths worldwide, being non-small lung cancer (NSCLC) sub-types the most prevalent. Since most LC cases are only detected during the last stage of the disease the high mortality rate is strongly associated with metastases. For this reason, the migratory and invasive capacity of these cancer cells as well as the mechanisms involved have long been studied to uncover novel strategies to prevent metastases and improve the patients' prognosis. This narrative review provides an overview of the main in vitro migration and invasion assays employed in NSCLC research. While several methods have been developed, experiments using conventional cell culture models prevailed, specifically the wound-healing and the transwell migration and invasion assays. Moreover, it is provided herewith a summary of the available information concerning chemical contaminants that may promote the migratory/invasive properties of NSCLC cells in vitro, shedding some light on possible LC risk factors. Most of the reported agents with pro-migration/invasion effects derive from cigarette smoking [e.g., Benzo(a)pyrene and cadmium] and air pollution. This review further presents several studies in which different dietary/plant-derived compounds demonstrated to impair migration/invasion processes in NSCLC cells in vitro. These chemicals that have been proposed as anti-migratory consisted mainly of natural bioactive substances, including polyphenols non-flavonoids, flavonoids, bibenzyls, terpenes, alkaloids, and steroids. Some of these compounds may eventually represent novel therapeutic strategies to be considered in the future to prevent metastasis formation in LC, which highlights the need for additional in vitro methodologies that more closely resemble the in vivo tumor microenvironment and cancer cell interactions. These studies along with adequate in vivo models should be further explored as proof of concept for the most promising compounds.

Background First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater. Methods This randomised, open-label, phase 3 study was done in 213 medical centres in 32 countries. Eligible patients were adults (≥18 years) with previously untreated locally advanced or metastatic non-small-cell lung cancer without a sensitising EGFR mutation or ALK translocation and with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, life expectancy 3 months or longer, and a PD-L1 TPS of 1% or greater. Randomisation was computer generated, accessed via an interactive voice-response and integrated web-response system, and stratified by region of enrolment (east Asia vs rest of world), ECOG performance status score (0 vs 1), histology (squamous vs non-squamous), and PD-L1 TPS (≥50% vs 1-49%). Enrolled patients were randomly assigned 1:1 in blocks of four per stratum to receive pembrolizumab 200 mg every 3 weeks for up to 35 cycles or the investigator's choice of platinum-based chemotherapy for four to six cycles. Primary endpoints were overall survival in patients with a TPS of 50% or greater, 20% or greater, and 1% or greater (one-sided significance thresholds, p=0·0122, p=0·0120, and p=0·0124, respectively) in the intention-to-treat population, assessed sequentially if the previous findings were significant. This study is registered at ClinicalTrials.gov, number NCT02220894. Findings From Dec 19, 2014, to March 6, 2017, 1274 patients (902 men, 372 women, median age 63 years [IQR 57-69]) with a PD-L1 TPS of 1% or greater were allocated to pembrolizumab (n=637) or chemotherapy (n=637) and included in the intention-to-treat population. 599 (47%) had a TPS of 50% or greater and 818 patients (64%) had a TPS of 20% or greater. As of Feb 26, 2018, median follow-up was 12·8 months. Overall survival was significantly longer in the pembrolizumab group than in the chemotherapy group in all three TPS populations (≥50% hazard ratio 0·69, 95% CI 0·56-0·85, p=0·0003; ≥20% 0·77, 0·64-0·92, p=0·0020, and ≥1% 0·81, 0·71-0·93, p=0·0018). The median surival values by TPS population were 20·0 months (95% CI 15·4-24·9) for pembrolizumab versus 12·2 months (10·4-14·2) for chemotherapy, 17·7 months (15·3-22·1) versus 13·0 months (11·6-15·3), and 16·7 months (13·9-19·7) versus 12·1 months (11·3-13·3), respectively. Treatment-related adverse events of grade 3 or worse occurred in 113 (18%) of 636 treated patients in the pembrolizumab group and in 252 (41%) of 615 in the chemotherapy group and led to death in 13 (2%) and 14 (2%) patients, respectively. Interpretation The benefit-to-risk profile suggests that pembrolizumab monotherapy can be extended as first-line therapy to patients with locally advanced or metastatic non-small-cell lung cancer without sensitising EGFR or ALK alterations and with low PD-L1 TPS. Funding Merck Sharp & Dohme.

Lung cancer (LC) is the leading cause of cancer deaths worldwide, being non-small lung cancer (NSCLC) sub-types the most prevalent. Since most LC cases are only detected during the last stage of the disease the high mortality rate is strongly associated with metastases. For this reason, the migratory and invasive capacity of these cancer cells as well as the mechanisms involved have long been studied to uncover novel strategies to prevent metastases and improve the patients’ prognosis. This narrative review provides an overview of the main in vitro migration and invasion assays employed in NSCLC research. While several methods have been developed, experiments using conventional cell culture models prevailed, specifically the wound-healing and the transwell migration and invasion assays. Moreover, it is provided herewith a summary of the available information concerning chemical contaminants that may promote the migratory/invasive properties of NSCLC cells in vitro, shedding some light on possible LC risk factors. Most of the reported agents with pro-migration/invasion effects derive from cigarette smoking [e.g., Benzo(a)pyrene and cadmium] and air pollution. This review further presents several studies in which different dietary/plant-derived compounds demonstrated to impair migration/invasion processes in NSCLC cells in vitro. These chemicals that have been proposed as anti-migratory consisted mainly of natural bioactive substances, including polyphenols non-flavonoids, flavonoids, bibenzyls, terpenes, alkaloids, and steroids. Some of these compounds may eventually represent novel therapeutic strategies to be considered in the future to prevent metastasis formation in LC, which highlights the need for additional in vitro methodologies that more closely resemble the in vivo tumor microenvironment and cancer cell interactions. These studies along with adequate in vivo models should be further explored as proof of concept for the most promising compounds.

This study addresses a long-standing debate as to why escalation in capital costs is so common over the lifecycle of ‘megaprojects’ – the project-based, multi-party organizational contexts that are set up to develop capital-intensive, long-lived infrastructure. We ground our study on three case studies conducted with theoretical alertness to a range of factors that need to be considered from an organizational governance perspective. Our findings trace cost escalation to fundamental changes of the project governance structure and concomitant renegotiations of the value to be created and the value distribution. Specifically we link substantive cost hikes to, first, early negotiations to agree a value proposition that unifies a core group of autonomous actors under a shared form of governance. And second, to collective action problems that arise as key nonmarket stakeholders are brought into a polycentric governance structure to encourage cooperation in joint local value creation activities. We also associate cost hikes, although less substantive, to market transactions with suppliers and to bilateral agreements with other nonmarket stakeholders that stay excluded from direct participation in governance-related decisions. We discuss implications to our theoretical and empirical understanding of megaproject behavior and performance.

In recent years inhaled systems have shown momentum as patient-personalized therapies emerge. A significant improvement in terms of therapeutic efficacy and/or reduction adverse systemic effects is anticipated from their use owing these systems regional accumulation. Nevertheless, whatever safety and efficacy evidence required for inhaled formulations regulatory approval, it still poses an additional hurdle to gaining market access. In contrast with the formal intravenous medicines approval, the narrower adoption of pulmonary administration might rely on discrepancies in pre-clinical and clinical data provided by the marketing authorization holder to the regulatory authorities. Evidences of a diverse and inconsistent regulatory framework led to concerns over toxicity issues and respiratory safety. However, an overall trend to support general concepts of good practices exists. Current regulatory guidelines1 that supports PK/PD (pharmacokinetics/pharmacodynamic) assessment seeks attention threatening those inhaled formulations set to be approved in the coming years. A more complex scenario arises from the attempt of implementing nanomedicines for pulmonary administration. Cutting-edge image techniques could play a key role in supporting diverse stages of clinical development facilitating this pharmaceutics take off and speed to patients. The ongoing challenge in adapting conventional regulatory frameworks has proven to be tremendously difficult in an environment where market entry relies on multiple collections of evidence. This paper intention is to remind us that an acceptable pre-clinical toxicological program could emerge from, but not only, an accurate and robust data imaging collection. It is our conviction that if implemented, inhaled nanomedicines might have impact in multiple severe conditions, such as lung cancer, by fulfilling the opportunity for developing tailored treatments while solving dose-related toxicity issues; the most limiting threat in conventional lung cancer clinical management.

Immunotherapy [(specifically, antibodies blocking programmed death ligand-1 (PD-L1)] is a valuable option in cancer treatment because it leads to durable tumour regression and improves survival in several cancers. Patients with PD-L1 expressing tumours benefit from this therapy, but currently it can only be determined through biopsy, which may be inconclusive or impossible due to lesion location, associated risks, intratumoral and interlesional heterogeneity. Therefore, radio-immune-imaging with a specific radiopharmaceutical is ideally placed to play an important role when performing real-time, in vivo, whole-body and non-invasive PD-L1 expression mapping. To describe and summarise published scientific data on imaging PD-L1 expression using radiopharmaceuticals and discuss future directions in this research field. A summary review of the literature was done through PubMed to search papers that described and included radiopharmaceuticals to image PD-L1 expression. Only English papers published until April 2018 that detailed laboratorial and animal procedures were selected. Eleven pre-clinical papers published between 2015 and 2018 were included. Four studies used anti-PD-L1 radiopharmaceuticals labelled with Indium-111, 4 with Copper-64, 2 with Fluoride-18 and 1 with both Copper-64 and Gallium-68. All of them had identical protocols and showed similar radiopharmaceutical biodistribution. They reported successful anti-PD-L1 labelling, with high tumour–background ratio (mainly when spleen uptake was saturated with unlabelled/cold antibody). All reported radiopharmaceuticals had high sensitivity and specificity to identify tumours with PD-L1 expression in animal model. Clinical experiments appear to be now justifiable.

We report a case of a 26-year-old female patient treated with nivolumab for peritoneal implants from small-cell ovarian cancer. Pulmonary changes were depicted on follow-up examinations, namely, consolidations and scattered ground glass opacities, without any remarkable pulmonary complaints or laboratory changes. Both infectious and progressive diseases were ruled out. The condition was attributed to nivolumab side effect, and total remission was documented, followed by corticosteroids administration. We present clinical details and imaging findings, followed by a discussion where pulmonary toxicity can often be mistaken with infection or secondary involvement. Keywords: Cancer, Immunotherapy, Pulmonary toxicity

Across the world, computer science programs often present high failure and dropout rates. The difficulties associated with introductory programming courses have long been pointed as one of the most critical factors for this situation. To mitigate students' struggles, the timely assistance provided by the teachers is crucial. To support the teachers in this task, we have developed CodeInsights, which provides them real-time information about the students' performance while solving programming assignments. While CodeInsights has been tested and positively accepted by the teacher in several experiments previously conducted, the students' opinion on the usage of the system has not been carefully addressed. In this paper, we present some of the main features of CodeInsights and present and discuss the main findings of three field experiments in which CodeInsights was used, with a particular focus on the students' reaction to its use.