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Prostate cancer (PrCa) is one of the most hereditable human cancers, however, only a small fraction of patients has been shown to carry deleterious variants in known cancer predisposition genes.Whole-exome sequencing was performed in multiple affected members of 45 PrCa families to select the best candidate genes behind part of the PrCa missing hereditability. Recurrently mutated genes were prioritised, and further investigated by targeted next-generation sequencing in the whole early-onset and/or familial PrCa series of 462 patients.PRUNE2 stood out from our analysis when also considering the available data on its association with PrCa development. Ten germline pathogenic/likely pathogenic variants in the PRUNE2 gene were identified in 13 patients. The most frequent variant was found in three unrelated patients and identical-by-descent analysis revealed that the haplotype associated with the variant is shared by all the variant carriers, supporting the existence of a common ancestor.This is the first report of pathogenic/likely pathogenic germline variants in PRUNE2 in PrCa patients, namely in those with early-onset/familial disease. Importantly, PRUNE2 was the most frequently mutated gene in the whole series, with a deleterious germline variant identified in 2.8% of the patients, representing a novel prostate cancer predisposition gene.

O presente Caso de Ensino apresenta a Análise de Portfólio apoiada na Matriz BCG, e sua possível utilização na gestão de destinos turísticos. O trabalho utiliza uma abordagem aplicada, visando facilitar a compreensão da técnica e a sua difusão entre os acadêmicos de turismo e os gestores em geral. O documento é apresentado em forma de problema, no qual os estudantes vivem o dilema de priorizar a alocação de recursos promocionais entre diferentes Unidades Estratégicas de Negócios, visando resgatar os fluxos turísticos perdidos durante a Pandemia de Covid-19. Para solucionar o problema, os estudantes deverão familiarizar-se e analisar criticamente a Matriz de Crescimento e Atratividade de um destino, e a partir dela sugerir uma política de alocação de recursos que possibilite promover eficientemente aquele destino no período pós-pandemia. O trabalho está dividido em duas partes, a problematização, envolvendo o caso propriamente dito e a Matriz BCG, e as notas de ensino, com orientações para aplicação do material em sala de aula. Para melhor aprendizado recomenda-se separar as notas de ensino e retê-las, até que os estudantes assimilem adequadamente a Matriz BCG e discutam profundamente o caso e seus possíveis encaminhamentos. Para melhor solução do caso, recomenda-se trabalhar em grupos de dois a quatro elementos.

Postural instability is considered one of the most incapacitating motor symptoms and a primary cause of falls in Parkinson’s disease (PD), compromising the autonomy and well-being of people suffering from this condition. Usually, the clinical examination used to evaluate this symptom is the pull test since it does not require any instruments and is easy to perform. However, this test is difficult to standardize and is not sensitive to subtle but significant changes. Recent studies have shown that inertial measurement units constitute a portable and cost-effective solution to measure postural sway, which provides metrics sensitive to balance disorders as postural instability. Further studies are required to monitor patients’ postural conditions and implement an adequate treatment to improve postural stability, it is crucial to quantify balance under dynamic conditions. Hence, the proposed research focused on investigating the hypothesis of whether it is possible to differentiate between all the scores of the pull test through postural and gait metrics extracted from raw acceleration and angular velocity signals from the center of mass of patients with PD acquired while performing basic day-to-day tasks. A cross-sectional study was followed, including 23 patients, and the achieved results showed that most of the estimated metrics can differentiate the pull test scores (ρ-value≤0.048, R2≥0.513). Overall, satisfactory results were achieved as the statistical analysis revealed gait and postural metrics estimated under dynamic conditions were considered relevant to distinguish between the scores of the pull test.

Baseando-nos nas análises genealógica e epistemológica propostas por Foucault e Lantéri-Laura, nosso objetivo principal é discernir quais são as principais linhas discursivas que constituíram o saber em torno da perversão, produzindo um sujeito dito perverso. Emerge de maneira fundamental dessa leitura como a ideia de transgressão de limites acompanha a história dos perversos: seja o limite moral imposto pela autoridade divina, seja o limite jurídico determinado pela lei penal, seja o limite do normal definido pela medicina, a perversão sempre aponta para o excesso transgressor. Tais leituras constituem o solo epistemológico sobre o qual Freud se apoia na concepção de uma metapsicologia cujo eixo central é a sexualidade. O discurso freudiano subverte o estatuto da perversão ao afirmá-la como dimensão inescapável da sexualidade e da constituição da subjetividade humana.

Prostate cancer (PrCa) is among the three top most frequent and deadlier cancers worldwide. The discovery of PARP inhibitors for the treatment of tumors having deleterious variants in homologous recombination repair (HRR) genes has placed PrCa in the roadmap of precision medicine. Still, the overall contribution of HRR genes for the 10-20% of the carcinomas arising in men with early-onset/familial PrCa has not been fully clarified. We used Targeted Next Generation Sequencing (T-NGS) covering eight HRR genes (ATM, BRCA1, BRCA2, BRIP1, CHEK2, NBN, PALB2 and RAD51C) and an analysis pipeline querying both small and large genomic variations, to clarify both their global and relative contribution for hereditary PrCa predisposition in a series of 462 early-onset/familial PrCa cases. Deleterious variants were found in 3.9% of the patients, with CHEK2 and ATM being the most frequently mutated genes (38.9% and 22.2% of the carriers, respectively), followed by PALB2 and NBN (11.1% of the carriers, each), and then by BRCA2, RAD51C, and BRIP1 (5.6% of the carriers each). Using the same NGS data, exonic rearrangements were found in two patients, one pathogenic in BRCA2 and one of unknown significance in BRCA1. Additionally, 5.4% of the patients were carriers of variants of unknown significance (VUS). These results support the utility of T-NGS to clarify the genetic heterogeneity that underlies PrCa predisposition, allowing to detect both small and large genomic variations, and unveil CHEK2 and ATM as the major HRR genes associated with early-onset and familial PrCa, respectively.

Este artigo visa apresentar uma reflexão sobre a pesquisa interdisciplinar para a compreensão da construção da imagem corporativa. Inicialmente, pondera-se por que este tipo de pesquisa seria o mais indicado para a realização de uma investigação científica; depois, fundamenta-se sobre os principais conceitos que lastreiam as disciplinas envolvidas na investigação proposta; logo em seguida, propõe-se um possível exemplo de modelo de feitura desse tipo de estudo e análise para o tema em questão; por fim, foram empreendidas breves considerações acerca das reflexões levantadas neste documento.

Analisar o discurso organizacional em quatro peças oriundas da Propaganda Institucional (PI) de um Instituto, cujo negócio versa sobre à promoção do desenvolvimento sustentável e do bem-estar social, é o objetivo deste trabalho. Assim, este estudo focou na Responsabilidade Ambiental (RA), um dos pilares da Sustentabilidade Empresarial (SE), e em investigar como este discurso é construído para persuadir e sensibilizar o leitor/co-enunciador a adquirir um posicionamento pró-ambiente. Para tanto, estudou-se a construção do ethos organizacional (via léxico e argumentos) e a embreagem textual presentes nessas peças publicitários. Foi utilizado como aporte teórico os pressupostos da: SE (focando-se na RA), da PI e da Análise do Discurso (AD) de linha francesa, esta última também constitui a metodologia seguida para o exame do material selecionado. Na AD, teoria e metodologia são indissociáveis, isto é, só é possível se falar em metodologia envolvendo os elementos teóricos. Igualmente, para se empreender esta pesquisa, foram realizados dois tipos de análises: a dos dados linguísticos e a dos argumentos usados nas produções textuais examinadas.

This work project aims at examining the cultural differences in time-use between linguist icregions in Switzerland using a Spatial Regression Discontinuity Design. It identifies and analyzes within-country time allocation disparities between Latin-speaking and German-speaking parts of Switzerland, using data from the Swiss Labor Force Survey. The proposed RDD methodology selects a few observations close to the language border, the "Röstigraben", where local randomization is a reasonable assumption. The findings point to a language effect on the labour market outcomes of mothers and fathers. In 2020, the analysis shows that mothers exposed to Germanic culture work 19 hours per week less overall than French- and Italian-speaking mothers. By the decomposition of the time allocation between market and domestic work, Iidentify that this effect is mainly driven by market work. German-speaking fathers dedicate 7.5hours more to paid labour. Comparing with the conventional inference approach that relies on the continuity assumption, I find that the randomization-based RD treatment effect reported is quite stable and robust to the estimation method used.

Funder: Victorian Cancer Agency, Funder: NIHR Manchester Biomedical Research Centre, Funder: Cancer Research UK, Funder: Cancer Council Tasmania, Funder: Instituto de Salud Carlos III, Funder: Cancer Australia, Funder: NIHR Oxford Biomedical Research Centre, Funder: Fundación Científica de la Asociación Española Contra el Cáncer, Funder: Cancer Council South Australia, Funder: Swedish Cancer Society, Funder: NIHR Cambridge Biomedical Research Centre, Funder: Institut Català de la Salut, Funder: Cancer Council Victoria, Funder: Prostate Cancer Foundation of Australia, Funder: National Institutes of Health, BACKGROUND: Lynch syndrome is a rare familial cancer syndrome caused by pathogenic variants in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2, that cause predisposition to various cancers, predominantly colorectal and endometrial cancer. Data are emerging that pathogenic variants in mismatch repair genes increase the risk of early-onset aggressive prostate cancer. The IMPACT study is prospectively assessing prostate-specific antigen (PSA) screening in men with germline mismatch repair pathogenic variants. Here, we report the usefulness of PSA screening, prostate cancer incidence, and tumour characteristics after the first screening round in men with and without these germline pathogenic variants. METHODS: The IMPACT study is an international, prospective study. Men aged 40-69 years without a previous prostate cancer diagnosis and with a known germline pathogenic variant in the MLH1, MSH2, or MSH6 gene, and age-matched male controls who tested negative for a familial pathogenic variant in these genes were recruited from 34 genetic and urology clinics in eight countries, and underwent a baseline PSA screening. Men who had a PSA level higher than 3·0 ng/mL were offered a transrectal, ultrasound-guided, prostate biopsy and a histopathological analysis was done. All participants are undergoing a minimum of 5 years' annual screening. The primary endpoint was to determine the incidence, stage, and pathology of screening-detected prostate cancer in carriers of pathogenic variants compared with non-carrier controls. We used Fisher's exact test to compare the number of cases, cancer incidence, and positive predictive values of the PSA cutoff and biopsy between carriers and non-carriers and the differences between disease types (ie, cancer vs no cancer, clinically significant cancer vs no cancer). We assessed screening outcomes and tumour characteristics by pathogenic variant status. Here we present results from the first round of PSA screening in the IMPACT study. This study is registered with ClinicalTrials.gov, NCT00261456, and is now closed to accrual. FINDINGS: Between Sept 28, 2012, and March 1, 2020, 828 men were recruited (644 carriers of mismatch repair pathogenic variants [204 carriers of MLH1, 305 carriers of MSH2, and 135 carriers of MSH6] and 184 non-carrier controls [65 non-carriers of MLH1, 76 non-carriers of MSH2, and 43 non-carriers of MSH6]), and in order to boost the sample size for the non-carrier control groups, we randomly selected 134 non-carriers from the BRCA1 and BRCA2 cohort of the IMPACT study, who were included in all three non-carrier cohorts. Men were predominantly of European ancestry (899 [93%] of 953 with available data), with a mean age of 52·8 years (SD 8·3). Within the first screening round, 56 (6%) men had a PSA concentration of more than 3·0 ng/mL and 35 (4%) biopsies were done. The overall incidence of prostate cancer was 1·9% (18 of 962; 95% CI 1·1-2·9). The incidence among MSH2 carriers was 4·3% (13 of 305; 95% CI 2·3-7·2), MSH2 non-carrier controls was 0·5% (one of 210; 0·0-2·6), MSH6 carriers was 3·0% (four of 135; 0·8-7·4), and none were detected among the MLH1 carriers, MLH1 non-carrier controls, and MSH6 non-carrier controls. Prostate cancer incidence, using a PSA threshold of higher than 3·0 ng/mL, was higher in MSH2 carriers than in MSH2 non-carrier controls (4·3% vs 0·5%; p=0·011) and MSH6 carriers than MSH6 non-carrier controls (3·0% vs 0%; p=0·034). The overall positive predictive value of biopsy using a PSA threshold of 3·0 ng/mL was 51·4% (95% CI 34·0-68·6), and the overall positive predictive value of a PSA threshold of 3·0 ng/mL was 32·1% (20·3-46·0). INTERPRETATION: After the first screening round, carriers of MSH2 and MSH6 pathogenic variants had a higher incidence of prostate cancer compared with age-matched non-carrier controls. These findings support the use of targeted PSA screening in these men to identify those with clinically significant prostate cancer. Further annual screening rounds will need to confirm these findings. FUNDING: Cancer Research UK, The Ronald and Rita McAulay Foundation, the National Institute for Health Research support to Biomedical Research Centres (The Institute of Cancer Research and Royal Marsden NHS Foundation Trust; Oxford; Manchester and the Cambridge Clinical Research Centre), Mr and Mrs Jack Baker, the Cancer Council of Tasmania, Cancer Australia, Prostate Cancer Foundation of Australia, Cancer Council of Victoria, Cancer Council of South Australia, the Victorian Cancer Agency, Cancer Australia, Prostate Cancer Foundation of Australia, Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III, Fondo Europeo de Desarrollo Regional (FEDER), the Institut Català de la Salut, Autonomous Government of Catalonia, Fundação para a Ciência e a Tecnologia, National Institutes of Health National Cancer Institute, Swedish Cancer Society, General Hospital in Malmö Foundation for Combating Cancer.

The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families. We thank the funding support from IPO-Porto Research Center (CI-IPOP-16-2012) and from Fundação para a Ciência e a Tecnologia (FCT; PEst-OE/SAU/ UI0776/2014 and PTDC/DTP-PIC/1308/2014). The following authors were awarded with grants from FCT: PPa (UID/DTP/00776/2013/POCI-01-0145-FEDER-006868), SM (SFRH/BD/71397/2010) and PPi (SFRH/BD/73719/2010). The PRACTICAL consortium (http://practical.icr.ac.uk/) was supported by the Canadian Institutes of Health Research, European Commission’s Seventh Framework Programme grant agreement n° 223175 (HEALTH-F2-2009-223175), Cancer Research UK Grants C5047/A7357, C1287/A10118, C1287/A16563, C5047/A3354, C5047/A10692, C16913/A6135, and The National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative grant: No. 1 U19 CA 148537-01 (the GAME-ON initiative). Genotyping of the OncoArray was funded by the US National Institutes of Health (NIH) [U19 CA 148537 for ELucidating Loci Involved in Prostate cancer SuscEptibility (ELLIPSE) project and X01HG007492 to the Center for Inherited Disease Research (CIDR) under contract number HHSN268201200008I] and by Cancer Research UK grant A8197/A16565. Additional analytic support was provided by NIH NCI U01 CA188392 (PI: Schumacher). We would also like to thank the following for funding support: The Institute of Cancer Research and The Everyman Campaign, The Prostate Cancer Research Foundation, Prostate Research Campaign UK (now PCUK), The Orchid Cancer Appeal, Rosetrees Trust, The National Cancer Research Network UK, The National Cancer Research Institute (NCRI) UK. We are grateful for support of NIHR funding to the NIHR Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, NIHR funding to the Manchester Biomedical Research Centre and the Manchester Academic Health Sciences Centre.

Atendendo à sua génese e evolução, o turismo criativo é considerado uma evolução do turismo cultural, mais apto a dar resposta, não só às necessidades dos atuais visitantes, que procuram experiências mais ativas e com maior grau de envolvimento, como também à necessidade dos destinos de se diferenciarem e assegurarem a competitividade da sua oferta. Embora o turismo criativo tenha vindo a receber uma atenção crescente por parte do meio académico, em muito devido ao seu posicionamento privilegiado enquanto estratégia de desenvolvimento turístico, os estudos focam, fundamentalmente, a perspetiva da oferta Importa, neste sentido, desenvolver estudos que explorem as perceções dos consumidores relativamente à disponibilidade, relevância e qualidade de experiências criativas dos destinos, uma vez que estas são frequentemente identificadas enquanto importantes indutores de valor nos produtos turísticos. Face ao exposto, o objetivo do presente estudo exploratório é compreender simultaneamente as perceções dos visitantes e dos principais agentes turísticos. O enquadramento geográfico do presente estudo é Guimarães, destino de turismo cultural situado no Norte de Portugal, classificado pela UNESCO como Património Mundial. As preceções dos visitantes foram analisadas tendo como base um questionário autoadministrado e, no caso das empresas turísticas, nomeadamente hotéis, restaurantes e empresas de animação turística, uma entrevista semiestruturada. Os resultados do presente estudo visam retirar conclusões relativamente ao desenvolvimento e promoção de experiências criativas e duradouras. Atendendo à bibliografia existente relativa à perspetiva da procura, especificamente em destinos com as características de Guimarães, este estudo visa ser um contributo para a bibliografia sobre turismo criativo.

Este trabalho visa estudar como a Sustentabilidade Empresarial (ou seu discurso) se desfaz diante de uma crise mal gerida. Para tanto, analisou-se a crise vivenciada pela Vale desencadeada a partir do rompimento da barragem dessa companhia em Córrego do Feijão, Brumadinho (MG). Para tanto, faz-se uma revisão teórica de conceitos de Sustentabilidade e de Discurso, bem como os de crise e gestão dessa, visando analisar o caso em questão, o qual foi acompanhado em cobertura jornalística, entre 25/01 e 24/02/19, via Jornal Hoje da Rede Globo de Televisão. Como resultado, obteve-se o posicionamento da Vale frente ao ocorrido terminou por desencadear uma crise de imagem.

This paper aims to study how Corporate Sustainability (or its discourse) falls apart in the face of a poorly managed crisis. To this end, we analyzed the crisis experienced by Vale triggered by the rupture of the dam of this company in Córrego do Feijão, Brumadinho (MG). Therefore, a theoretical review of the concepts of Sustainability and Discourse, as well as those of crisis and management, is carried out, aiming to analyze the case in question, which was followed in news coverage, between 01/25 to 02/24/19, via Jornal Hoje of Rede Globo de Televisão. As a result, Vale's position in the face of what happened ended up triggering an image crisis. Este documento tiene como objetivo estudiar cómo la sostenibilidad corporativa (o su discurso) se desmorona ante una crisis mal gestionada. Con este fin, analizamos la crisis experimentada por Vale provocada por la ruptura de la presa de esta empresa en Córrego do Feijão, Brumadinho (MG). Por lo tanto, se realiza una revisión teórica de los conceptos de Sostenibilidad y Discurso, así como los de crisis y gestión, con el objetivo de analizar el caso en cuestión, que se siguió en la cobertura de noticias, entre el 25/01 hasta 24/24/19, vía Jornal Hoje (JH) de Rede Globo de Televisão. Como resultado, se logró la posición de Vale frente al evento, desencadenando una crisis de imagen. Este trabalho visa estudar como a Sustentabilidade Empresarial (ou seu discurso) se desfaz diante de uma crise mal gerida. Para tanto, analisou-se a crise vivenciada pela Vale desencadeada a partir do rompimento da barragem dessa companhia em Córrego do Feijão, Brumadinho (MG). Para tanto, faz-se uma revisão teórica de conceitos de Sustentabilidade e de Discurso, bem como os de crise e gestão dessa, visando analisar o caso em questão, o qual foi acompanhado em cobertura jornalística, entre 25/01 e 24/02/19, via Jornal Hoje da Rede Globo de Televisão. Como resultado, obteve-se o posicionamento da Vale frente ao ocorrido terminou por desencadear uma crise de imagem.

A forma de se comunicar sofreu várias transformações significativas no final do século XX e no XXI. As redes sociais, tão presentes hoje, são formas de interação social usadas há mais de dois mil anos, mas, atualmente, são mediadas pela tecnologia e têm uma gama de ferramentas para realizá-las. O mesmo acontece com as mídias sociais que seriam as tecnologias virtuais utilizadas para o compartilhamento de dados, usando-se da interação para a disseminação de informações variadas. Assim, objetivou estudar, neste artigo, o WhatsApp e a sua versão Business, como também o uso desses nas Comunicações que compõem a Organizacional, bem como se visou distinguir as redes sociais das mídias sociais para situar a ferramenta comunicacional estudada em ambos os fenômenos. Para tanto, utilizou-se as teorias que versam sobre a Comunicação Organizacional e sobre as ferramentas de comunicação digitais.

[Excerto] O crescimento dos salários tem sido alvo de atenção, tanto por parte de decisores de políticas públicas, como por parte de investigadores académicos. A principal razão relaciona-se com o fraco crescimento dos salários, situação que se agravou desde a crise financeira de 2008 (OCDE, 2018a). Em Portugal, por exemplo, após a Grande Recessão de 2008-2012, o salário médio nominal só registou crescimentos anuais superiores a 1% a partir de 2016, sendo esta taxa de crescimento inferior à média observada entre países da OCDE (INE, 2020). Em 2018, o salário-base médio (mensal, bruto) de trabalhadores por conta de outrem em Portugal situava-se nos 970€ (PORDATA, 2020). No entanto, se considerarmos a evolução dos preços, o salário médio real de 2018 era semelhante ao de 20091 . Os baixos salários observados em Portugal, associados a taxas de crescimento salariais baixas, fazem com que o nosso país tenha vindo a cair no ranking/ordenação do salário anual médio da OCDE desde 20152 . Em 2019, Portugal ocupava a 3.ª pior posição de entre os países da União Europeia constantes desse ranking (OECD, 2020). Esta evolução é preocupante, dado que o salário médio é um dos principais indicadores do bem-estar económico de uma sociedade (Abraham et al., 1998; Myck et al., 2006). [...], Fundação Calouste Gulbenkian

[Excerto] O estudo “O Salário Médio em Portugal – Retrato atual e evolução recente”, da autoria de Priscila Ferreira (U. Minho), Marta C. Lopes (European University Institute) e Lara P. Tavares (Centro de Administração e Políticas Públicas da Universidade de Lisboa), descreve a evolução dos salários desde a introdução do euro até 2017, cobrindo assim vários ciclos da economia portuguesa. Tem como objetivo apresentar tendências dos salários para diversos tipos de trabalhadores e contribuir para aumentar a consciência e sensibilidade em relação a este tema. O tema é discutido com rigor, indo além da análise descritiva. [...], Fundação Calouste Gulbenkian

Este estudo analisa a evolução do salário (base bruto real) médio, desde a introdução do Euro até 2017, e foca-se no grupo dos trabalhadores por conta de outrem, a tempo completo, com remuneração mensal base completa, com idades compreendidas entre os 18 e os 65 anos. Como a média esconde realidades e padrões de flutuação diversos, estudam-se também medidas de dispersão dos salários (e.g., rácios entre percentis da distribuição salarial). A análise para Portugal é feita usando os Quadros de Pessoal, que permitem estudar praticamente o universo dos trabalhadores portugueses por conta de outrem do sector privado. No entanto, para situar em perspetiva a evolução do salário médio em Portugal, faz-se também uma comparação com três países da União Europeia: a Alemanha, como referência de um salário médio elevado; a Espanha, como referência de uma estrutura institucional e de uma força de trabalho idênticas às portuguesas; e a Polónia, em representação de um país com um salário médio mais baixo do que o português. Ao cobrir vários ciclos económicos da economia portuguesa, este estudo analisa ainda as consequências da Grande Recessão (2008-2012), ao contrastar esse período com as fases de expansão económica que o antecederam e lhe sucederam. Este estudo procura responder às seguintes questões: Que grupos de trabalhadores tiveram taxas de crescimento salarial acima da média entre 2002 e 2017? Que grupos viram o seu salário médio diminuir? Os salários dos portugueses estão cada vez mais iguais ou mais díspares? Qual o impacto da Grande Recessão na evolução dos salários? Como se compara Portugal com outros países europeus, em matéria de evolução do salário médio, da carga fiscal e da produtividade?, Fundação Calouste Gulbenkian

Bladder cancer constitutes one of the deadliest genitourinary diseases, especially when diagnosed at late stages. These tumours harbour microenvironmental niches characterized by low levels of oxygen (hypoxia) and limited glucose supply due to poor vascularization. However, the synergic contribution of these features to disease development is poorly understood. Here, we demonstrated that cells with distinct histopathological and molecular backgrounds responded similarly to such stimuli. Cancer cells arrested proliferation, significantly increased invasive capacity in vitro and enhanced tolerance to cisplatin-based chemotherapy. Reoxygenation and access to glucose restored basal proliferation and invasion levels without triggering stress-induced apoptosis, denoting significant cellular plasticity in adapting to microenvironmental cues. Whole transcriptomics showed major molecular reprogramming, supporting main functional alterations. Metabolomics evidenced fatty acids β-oxidation as main bioenergetic pathway rather than anaerobic glycolysis generally adopted by hypoxic cells. Joint pathway analysis also suggested relevant alterations in mucin-type O-glycan biosynthesis. Glycomics confirmed a major antagonization of O-glycosylation pathways, leading to simple cell glycophenotypes characterized by the accumulation of immature short-chain O-glycans such as Tn and STn antigens at the cell surface. Glycoengineered models reflecting simple cell glycophenotypes were developed and functional studies in vitro and in vivo showed that Tn and STn overexpression decreased proliferation and promoted chemoresistance, reinforcing their close link with tumour aggressiveness. Collectively, we have demonstrated that hypoxia and glucose deprivation trigger more aggressive cell behaviours, in what appears to be an escape mechanism from microenvironmental stress. We propose that, altered glycosylation may be used to target these subpopulations, paving the way for precision oncology.

"LucAs Architecture books is a series of bilingual (nl/en) publications celebrating the architecture project, and more precisely the architecture project of the student. The books consist of a selection of student architecture work extracted from last year’s architecture studios at KU Leuven Faculty of Architecture—Sint Lucas Ghent and Brussels. As in the two first editions, this book is also the opportunity to invite Eugeen Liebaut to confer a specific coloration to the selection. Next to the participation in the selection process, Eugeen highlights the work of one student an one particularly inspiring and fertile studio. More than the projects themselves, the publication positions the image, the plan, the section, the sketch, the scale model or the work document at the center of the attention. An image often reveals more than a long discourse."

Simple Summary It is well-recognised the strong contribution of genetic factors to prostate cancer (PrCa) susceptibility, thus genetic screening is critical for presymptomatic diagnosis and identification of individuals at high-risk. In this context, recurrent founder variants in cancer predisposing genes, by providing specific targets for early identification of carriers at risk of developing the disease, may be leveraged to implement cost-efficient targeted genetic screening strategies. The goal of this study was to investigate whether CHEK2 c.349A>G, the only recurrent “likely pathogenic” variant in CHEK2 gene reported in the Portuguese population, plays an important role in PrCa development, and the possibility of a founder effect behind its origin. Our results clearly demonstrate that c.349A>G in the CHEK2 tumour-suppressor gene is a founder variant significantly associated with an increased risk of PrCa, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families. Abstract The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case–control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1–3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.

The original version of this Article contained an error in the spelling of the author Manuela Gago-Dominguez, which was incorrectly given as Manuela G. Dominguez. This has now been corrected in both the PDF and HTML versions of the Article.

The objective of this work is to analyze the organizational discourse in four pieces from the Institutional Advertising (IA) of an Institute, whose business deals with the promotion of sustainable development and social well-being. Thus, this study focused on Environmental Responsibility (ER), one of the pillars of Corporate Sustainability (CS), and on investigating how this discourse is built to persuade and sensitize the reader/co-enunciator to acquire a pro-environment position. To this end, we studied the construction of the organizational ethos (via lexicon and arguments) and the textual clutch present in these advertising pieces. The assumptions of: CS (focusing on ER), PI and Discourse Analysis (DA) of the French line were used as theoretical input, the latter also constituting the methodology followed for the examination of the selected material. In DA, theory and methodology are inseparable, that is, it is only possible to speak of methodology involving theoretical elements. Also, to undertake this research, two types of analysis were carried out: that of linguistic data and that of the arguments used in the textual productions examined. Analisar o discurso organizacional em quatro peças oriundas da Propaganda Institucional (PI) de um Instituto, cujo negócio versa sobre à promoção do desenvolvimento sustentável e do bem-estar social, é o objetivo deste trabalho. Assim, este estudo focou na Responsabilidade Ambiental (RA), um dos pilares da Sustentabilidade Empresarial (SE), e em investigar como este discurso é construído para persuadir e sensibilizar o leitor/co-enunciador a adquirir um posicionamento pró-ambiente. Para tanto, estudou-se a construção do ethos organizacional (via léxico e argumentos) e a embreagem textual presentes nessas peças publicitários. Foi utilizado como aporte teórico os pressupostos da: SE (focando-se na RA), da PI e da Análise do Discurso (AD) de linha francesa, esta última também constitui a metodologia seguida para o exame do material selecionado. Na AD, teoria e metodologia são indissociáveis, isto é, só é possível se falar em metodologia envolvendo os elementos teóricos. Igualmente, para se empreender esta pesquisa, foram realizados dois tipos de análises: a dos dados linguísticos e a dos argumentos usados nas produções textuais examinadas.

In this work we demonstrate the fabrication and characterization of a temperature insensitive, two-dimensional curvature sensor using a resin based Fabry-Pérot interferometer, constructed using a multicore fiber (MCF). The fabrication simplicity makes this fiber device very attractive compared to the already reported technologies. Furthermore, the sensitivity reached (>400 pm/m-1), 7 times higher than the one reported for fiber Bragg gratings written on a similar MCF. The reconstruction of the amplitude and curvature has been performed for, showing errors lower than 4%. A numerical study has also been developed, allowing us to understand the sensor response at different fiber sensor geometries.

Publisher's version (útgefin grein)., Background: Mutations in BRCA2 cause a higher risk of early-onset aggressive prostate cancer (PrCa). The IMPACT study is evaluating targeted PrCa screening using prostate-specific-antigen (PSA) in men with germline BRCA1/2 mutations. Objective: To report the utility of PSA screening, PrCa incidence, positive predictive value of PSA, biopsy, and tumour characteristics after 3 yr of screening, by BRCA status. Design, setting, and participants: Men aged 40–69 yr with a germline pathogenic BRCA1/2 mutation and male controls testing negative for a familial BRCA1/2 mutation were recruited. Participants underwent PSA screening for 3 yr, and if PSA > 3.0 ng/ml, men were offered prostate biopsy. Outcome measurements and statistical analysis: PSA levels, PrCa incidence, and tumour characteristics were evaluated. Statistical analyses included Poisson regression offset by person-year follow-up, chi-square tests for proportion t tests for means, and Kruskal-Wallis for medians. Results and limitations: A total of 3027 patients (2932 unique individuals) were recruited (919 BRCA1 carriers, 709 BRCA1 noncarriers, 902 BRCA2 carriers, and 497 BRCA2 noncarriers). After 3 yr of screening, 527 men had PSA > 3.0 ng/ml, 357 biopsies were performed, and 112 PrCa cases were diagnosed (31 BRCA1 carriers, 19 BRCA1 noncarriers, 47 BRCA2 carriers, and 15 BRCA2 noncarriers). Higher compliance with biopsy was observed in BRCA2 carriers compared with noncarriers (73% vs 60%). Cancer incidence rate per 1000 person years was higher in BRCA2 carriers than in noncarriers (19.4 vs 12.0; p = 0.03); BRCA2 carriers were diagnosed at a younger age (61 vs 64 yr; p = 0.04) and were more likely to have clinically significant disease than BRCA2 noncarriers (77% vs 40%; p = 0.01). No differences in age or tumour characteristics were detected between BRCA1 carriers and BRCA1 noncarriers. The 4 kallikrein marker model discriminated better (area under the curve [AUC] = 0.73) for clinically significant cancer at biopsy than PSA alone (AUC = 0.65). Conclusions: After 3 yr of screening, compared with noncarriers, BRCA2 mutation carriers were associated with a higher incidence of PrCa, younger age of diagnosis, and clinically significant tumours. Therefore, systematic PSA screening is indicated for men with a BRCA2 mutation. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers. Patient summary: We demonstrate that after 3 yr of prostate-specific antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than in those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening. © 2019 The Authors We demonstrate that after 3 yr of prostate-specific-antigen (PSA) testing, we detect more serious prostate cancers in men with BRCA2 mutations than those without these mutations. We recommend that male BRCA2 carriers are offered systematic PSA screening., We demonstrate that, after four annual PSA screening rounds, BRCA2 mutation carriers have a higher incidence of PrCa, are diagnosed at a younger age, and present with more clinically significant tumours than BRCA2 noncarriers. Further follow-up is required to assess the role of screening in BRCA1 mutation carriers. Therefore, these data support the use of systematic PSA screening in male BRCA2 carriers. Author contributions : Rosalind A. Eeles had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design : Aaronson, Ardern-Jones, Bancroft, Bangma, Castro, Dearnaley, Eccles, Evans, Eyfjord, Falconer, Foster, Gronberg, Hamdy, Johannsson, Khoo, Kote-Jarai, Lilja, Lindeman, Lubinski, Mahle, Mikropoulos, Mitra, Moynihan, Page, Rennert, Suri. Acquisition of data: All authors. Analysis and interpretation of data: All authors. Drafting of the manuscript: All authors. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis : Page, Bancroft, Brook, Assel, Vickers, Lilja. Obtaining funding : Eeles and all IMPACT collaborating sites obtained their own funding for running the study at their site. Administrative, technical, or material support: All authors. Supervision: Eeles. Other : None. Financial disclosures: Rosalind A. Eeles certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Hans Lilja holds patents for intact PSA assays, and is named, along with Andrew J. Vickers, on a patent application for a statistical method to detect prostate cancer. The patents have been licensed and commercialised as the 4 Kscore by OPKO Health. Drs. Vickers and Lilja receive royalties from sales of this test. Additionally, Dr. Lilja owns stock and Dr. Vickers owns stock options in OPKO. Professor Rosalind Eeles: Royal Marsden Hospital—Nov 2017; support from Janssen; honorarium as speaker £1100; University of Chicago invited talk May 2018; honorarium as speaker Rosalind A. Eeles certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Hans Lilja holds patents for intact PSA assays, and is named, along with Andrew J. Vickers, on a patent application for a statistical method to detect prostate cancer. The patents have been licensed and commercialised as the 4 Kscore by OPKO Health. Drs. Vickers and Lilja receive royalties from sales of this test. Additionally, Dr. Lilja owns stock and Dr. Vickers owns stock options in OPKO. Professor Rosalind Eeles: Royal Marsden Hospital—Nov 2017; support from Janssen; honorarium as speaker £1100; University of Chicago invited talk May 2018; honorarium as speaker $1000. The remaining authors have no other conflict of interest to declare.000. The remaining authors have no other conflict of interest to declare. Funding/Support and role of the sponsor : This research is coordinated by the Institute of Cancer Research, London, UK, and is supported by grants from Cancer Research UK (grant references C5047/A21332, C5047/A13232, and C5047/A17528) and the Ronald and Rita McAulay Foundation. Judith Offman is supported by Cancer Research UK Programme Grant reference C8161/A16892. Mr. and Mrs. Jack Baker are acknowledged for supporting the study in NorthShore University HealthSystem, Evanston, IL, USA and Myriad Genetics Laboratory, Salt Lake City, UT, USA, for providing research BRCA testing rates for NorthShore University HealthSystem patients. We acknowledge funding from the National Institute for Health Research (NIHR) to the Biomedical Research Center at the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, at Manchester University Foundation Trust (IS-BRC-1215-20007), the Oxford Biomedical Research Centre Program, and the Cambridge Clinical Research Centre, NIHR Cambridge Biomedical Research Centre. We acknowledge that in Australia, this project was cofunded by Cancer Council Tasmania and Cancer Australia (grant number 1006349 [2011–2013]), Prostate Cancer Foundation of Australia (grant number PCFA PRO4 [2008]), Cancer Councils of Victoria and South Australia (grant number 400048 [2006–2008]), the Victorian Cancer Agency Clinical Trial Capacity CTCB08_14, Cancer Australia and Prostate Cancer Foundation of Australia (2014–2016; grant number 1059423), and Translational grants EOI09_50. The Association of International Cancer Research funded data collection in The Netherlands (AICR 10-0596). We acknowledge funding from the Basser Center for BRCA (to Susan Domchek). This work was supported in part by the National Institutes of Health/National Cancer Institute (NIH/NCI) with a Cancer Center Support Grant to Memorial Sloan Kettering Cancer Center (P30 CA008748), a SPORE grant in Prostate Cancer to Dr. H. Scher (P50-CA92629), the Sidney Kimmel Center for Prostate and Urologic Cancers, David H. Koch through the Prostate Cancer Foundation. This work was also supported in part by the NIHR Oxford Biomedical Research Centre Program in UK, the Swedish Cancer Society (CAN 2017/559), the Swedish Research Council (VR-MH project no. 2016-02974), and General Hospital in Malmö Foundation for Combating Cancer. We acknowledge funding from the Slovenian Research Agency, Research programme P3-0352. We thank CERCA Program/Generalitat de Catalunya for their institutional support. Elena Castro acknowledges funding from Prostate Cancer Foundation. We acknowledge the support of the Asociación Española Contra el Cáncer (AECC), the Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economía y Competitividad), “Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa” (PI10/01422, PI13/00285, PIE13/00022, PI16/00563, JR18/00011 and CIBERONC), and the Institut Català de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338 and PERIS Project MedPerCan). We acknowledge funding support from Fundação para a Ciência e a Tecnologia to the IPO Porto study (project grant PTDC/DTP-PIC/1308/2014 to Manuel R. Teixeira and fellowship grant SFRH/BD/116557/2016 to Marta Cardoso).

This thesis analyses the impact of job and unemployment protection on unemployment duration, wages, and fertility. The first chapter provides an extensive literature review on the impact of potential duration of unemployment benefi ts on unemployment duration, which is compared to a survival analysis that accounts for unobserved heterogeneity. The second chapter makes use of control function approach, with selection on treatment and outcome variables, to evaluate the impact of unemployment duration on re-employment wages. The third chapter uses both reduced-form and structural modelling approaches to evaluate the impact of job security on labour supply and fertility decisions.

The recurrent germline mutation HOXB13 p.(Gly84Glu) (G84E) has recently been identified as a risk factor for prostate cancer. In a recent study, we have performed full sequencing of the HOXB13 gene in 462 Portuguese prostate cancer patients with early-onset and/or familial/hereditary disease, and identified two novel missense mutations, p.(Ala128Asp) (A128D) and p.(Phe240Leu) (F240L), that were predicted to be damaging to protein function. In the present work we aimed to investigate the potential oncogenic role of these mutations, comparing to that of the recurrent G84E mutation and wild-type HOXB13. We induced site-directed mutagenesis in a HOXB13 expression vector and established in vitro cell models of prostate carcinogenesis with stable overexpression of either the wild-type or the mutated HOXB13 variants. By performing in vitro assays we observed that, while the wild-type promotes proliferation, also observed with the F240L variant along with a decrease in apoptosis, the A128D mutation decreases apoptosis and promotes anchorage independent growth. No phenotypic impact was observed for the G84E mutation in the cell line model used. Our data show that specific HOXB13 mutations are involved in the acquisition of different cancer-associated capabilities and further support an oncogenic role for HOXB13 in prostate carcinogenesis.

Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (PC, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10(−9); T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55–2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04–6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa(1).

Este artigo visa estudar a imagem empresarial construída discursivamente a partir da apresentação das ações de Responsabilidade Corporativa (RC) de um dos maiores grupos portugueses, a empresa multinacional, o Jerónimo Martins. A RC se constitui componente importante para a perpetuação dos negócios implementados nas organizações atualmente, como igualmente na valorização do capital reputacional. Para tanto, estudou-se o ethos organizacional (formado a partir das escolhas lexicais, como também via escolha dos argumentos disposto nas produções textuais selecionadas), uma vez que esse elemento retórico termina por representar a estruturação da imagem corporativa num discurso. Desta forma, buscou-se a explicitação desse elemento nos textos publicados no primeiro capítulo de um documento da Comunicação Dirigida (CD) existente no referido Grupo, a saber: o Relatório de Responsabilidade Corporativa 2016. Visando a realização deste trabalho, foi utilizado como aporte teórico os pressupostos da citada Responsabilidade, da Comunicação Organizacional (com foco na CD) e da Análise do Discurso de linha francesa, sendo que esta última também se constitui a metodologia seguida para a feitura da pesquisa. Para se empreender este estudo, foram realizados dois tipos de análises: a dos dados linguísticos e a dos argumentos usados nas produções textuais examinadas. Como resultado, obteve-se a mencionada imagem, bem como se observou que essa se edificou de forma positiva através da construção do ethos oriundo do discurso da RC. This article aims to study the corporate image constructed discursively from the presentation of the Corporate Responsibility (CR) actions of one of the largest Portuguese groups, the multinational company, Jerónimo Martins. The CR is an important component for the perpetuation of the businesses implemented in the organizations today, as well as for the valorization of reputational capital. For this, the organizational ethos (formed from the lexical choices, as well as the choice of the arguments in the selected textual productions) was studied, since this rhetorical element ends up representing the structuring of the corporate image in a discourse. In this way, this element was explicated in the texts published in the first chapter of a document of the Directed Communication (DC) existing in said Group, namely: Relatório de Responsabilidade Corporativa 2016. In order to carry out this work, it was used as contribution theoretical aspects of the aforementioned Responsibility, the Organizational Communication (with focus on the DC) and the Discourse Analysis of the French line, the latter also constituting the methodology used to carry out the research. In order to undertake this study, two types of analysis were carried out: the linguistic data and the arguments used in the textual productions examined. As a result, the aforementioned image was obtained, and it was observed that it was positively built through the construction of the ethos that came from the CR discourse.

Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P < 5.0 × 10-8) with PrCa and one locus significantly associated with early-onset PrCa (≤55 years). Our findings include missense variants rs1800057 (odds ratio (OR) = 1.16; P = 8.2 × 10-9; G>C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10-9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa 1 .