RCAAP Repository

Humanitarian migration relates to the movement of people who feel somehow forced to move. Yet, distinguishing which migration forms fall under the label of humanitarian migration is not straightforward. Migration research has a history of separating between ‘forced’ and ‘voluntary’ migration flows, however, this distinction has been challenged since the 1990s. This chapter includes an overview of research in the broad area of ‘humanitarian migration’, and summarises key research trends concerning refugees, asylum seekers, internally displaced people, victims of trafficking and unaccompanied migrant minors.

Pyrazinamide (PZA) is active against major Mycobacterium tuberculosis species (M. tuberculosis, M. africanum, and M. microti) but not against M. bovis and M. avium. The latter two are mycobacterial species involved in human and cattle tuberculosis and in HIV coinfections, respectively. PZA is a first-line agent for the treatment of human tuberculosis and requires activation by a mycobacterial pyrazinamidase to form the active metabolite pyrazinoic acid (POA). As a result of this mechanism, resistance to PZA, as is often found in tuberculosis patients, is caused by point mutations in pyrazinamidase. In previous work, we have shown that POA esters and amides synthesized in our laboratory were stable in plasma (M. F. Simões, E. Valente, M. J. Gómez, E. Anes, and L. Constantino, Eur J Pharm Sci 37:257-263, 2009, http://dx.doi.org/10.1016/j.ejps.2009.02.012). Although the amides did not present significant activity, the esters were active against sensitive mycobacteria at concentrations 5- to 10-fold lower than those of PZA. Here, we report that these POA derivatives possess antibacterial efficacy in vitro and ex vivo against several species and strains of Mycobacterium with natural or acquired resistance to PZA, including M. bovis and M. avium. Our results indicate that the resistance probably was overcome by cleavage of the prodrugs into POA and a long-chain alcohol. Although it is not possible to rule out that the esters have intrinsic activity per se, we bring evidence here that long-chain fatty alcohols possess a significant antimycobacterial effect against PZA-resistant species and strains and are not mere inactive promoieties. These findings may lead to candidate dual drugs having enhanced activity against both PZA-susceptible and PZA-resistant isolates and being suitable for clinical development.

Rare variants in the phospholipase D3 gene (PLD3) were associated with increased risk for late-onset Alzheimer disease (LOAD). We identified a missense mutation in PLD3 in whole-genome sequence data of a patient with autopsy confirmed Alzheimer disease (AD) and onset age of 50 years. Subsequently, we sequenced PLD3 in a Belgian early-onset Alzheimer disease (EOAD) patient (N = 261) and control (N = 319) cohort, as well as in European EOAD patients (N = 946) and control individuals (N = 1,209) ascertained in different European countries. Overall, we identified 22 rare variants with a minor allele frequency <1%, 20 missense and two splicing mutations. Burden analysis did not provide significant evidence for an enrichment of rare PLD3 variants in EOAD patients in any of the patient/control cohorts. Also, meta-analysis of the PLD3 data, including a published dataset of a German EOAD cohort, was not significant (P = 0.43; OR = 1.53, 95% CI 0.60-3.31). Consequently, our data do not support a role for PLD3 rare variants in the genetic etiology of EOAD in European EOAD patients. Our data corroborate the negative replication data obtained in LOAD studies and therefore a genetic role of PLD3 in AD remains to be demonstrated.

Amyotrophic lateral sclerosis (ALS) is a disease leading to neuromuscular transmission impairment. A2A adenosine receptor (A2AR) function changes with disease stage, but the role of the A(1) receptors (A1Rs) is unknown and may have a functional cross-talk with A2AR. The role of A1R in the SOD1(G93A) mouse model of ALS in presymptomatic (4-6 weeks old) and symptomatic (12-14 weeks old) phases was investigated by recording endplate potentials (EPPs), miniature endplate potentials (MEPPs), and quantal content (q.c.) of EPPs, from Mg(2+) paralyzed hemidiaphragm preparations. In presymptomatic mice, the A1R agonist, N (6)-cyclopentyladenosine (CPA) (50 nM), decreased mean EPP amplitude, MEPP frequency, and q.c. of EPPs, an effect quantitatively similar to that in age-matched wild-type (WT) mice. However, coactivation of A2AR with CGS 21680 (5 nM) prevented the effects of CPA in WT mice but not in presymptomatic SOD1(G93A) mice, suggestive of A1R/A2AR cross-talk disruption in this phase of ALS. DPCPX (50 nM) impaired CGS 21680 facilitatory action on neuromuscular transmission in WT but not in presymptomatic mice. In symptomatic animals, CPA only inhibited transmission if added in the presence of adenosine deaminase (ADA, 1 U/mL). ADA and DPCPX enhanced more transmission in symptomatic mice than in age-matched WT mice, suggestive of increase in extracellular adenosine during the symptomatic phase of ALS. The data documents that at the neuromuscular junction of presymptomatic SOD1(G93A) mice, there is a loss of A1R-A2AR functional cross-talk, while in symptomatic mice there is increased A1R tonic activation, and that with disease progression, changes in A1R-mediated adenosine modulation may act as aggravating factors during the symptomatic phase of ALS.

Rudolph Nureyev’s Romeo and Juliet, first staged in 1977 and filmed in 1995, is a work of intermediality par excellence. Like all ballet productions, its ‘meaning(s)’ emerge(s) from the interaction of multiple semiotic codes (kinesthetic, visual and audio), mediated further by the process of filming that resulted in the Warner Music Video upon which this study centres. Moreoever, it is also an interesting example of intersemiotic translation, based as it is upon both a verbal and a musical text, Shakespeare’s play and Prokofiev’s musical score respectively. This paper examines Nureyev’s version of the tale of the ‘star cross’d lovers’ as a comment upon the era in which he himself lived, the aftermath of the youth revolution when the exuberance and optimism of the sixties was beginning to wear a little thin. In the light of this, his use of gay iconography, images of pestilence and invocations of doom take on a new sinister significance.

Developed in the context of the 60th anniversary of the inauguration of Brasília, this project recaptures this central symbol to the Brazilian cultural imagination. This capture is guided by two main notions: that Brasília was already born as its own ruin and that the permanence of this ruined state, fractured between ideal and reality, is set up as a kind of insomnia. Through these guidelines of ruin and insomnia, this project, developed under the scope of communication design, appropriates Brasília in three aspects: ideological propaganda, affective memory and soundscape. To do so, it uses digital tools with which it reorganises and manipulates images, news pieces and musical productions that make up the imaginary created around the Brazilian capital, using the notion of appropriation as a cultural practice that is typical of the digital culture and of the modern and postmodern experience. This text accompanies, as an historical, theoretical and technical elucidation, an online publication (www.estesconstruirambrasilia.com) that also serves as a critical repository of materials regarding the construction of the city. The project is also composed of a set of postcards and a printed newspaper, both of which result from the appropriation and reinterpretation of historical documents. This set of items aims to constitute a sensitive means of access to the imaginary that composes the Brasília-symbol, keeping in evidence the disturbances that affect its idealization

Backgound: Atrial Fibrillation (AF) is the most prevalent cardiac arrhythmia among older patients, associated with thromboembolic events. Direct Oral Anticoagulants (DOAC) are the treatment of choice for most patients, but its use may have risks on standard dose. However, it is still unclear the effects related with the use of a lower dose off labelled DOAC. Objectives: We conducted a systematic review and meta-analysis to assess the effects of off-label underdose use of DOAC in patients with AF. Methods: MEDLINE, Cochrane Central Register of Controlled Trials, PsycINFO databases and EMBASE were searched for observational longitudinal studies evaluating the outcomes on off label underdosed patients compared with standard dosed patients with AF. We performed a random-effects meta-analysis to estimate the pooled Hazard Ratios (HR) with 95%Cis. Results: Eighteen cohort studies evaluating 237,533 patients with AF were included. Off-label underdose DOAC use is associated with higher risk of all-cause mortality [HR = 1.27 (95%CI 1.09-1.48)] and cardiovascular composite outcomes [HR = 1.32 (95%CI 1.08-1.62)], when compared with standard dose DOAC use. The effects in thromboembolic events [HR = 1.14 (95%CI 1.00-1.31)], major bleeding [HR = 1.02 (95%CI 0.91-1.15)], and composite of ischemic and bleeding events [HR = 1.22 (95%CI 0.79-1.88)] were not statistically significant. The certainty in the evidence was low or very low. Conclusions: Off label underdose DOAC use is associated with higher risk of all-cause mortality and cardiovascular composite outcomes, compared with standard dose.

Background: This study assessed the effectiveness of the NEVERMIND e-health system, consisting of a smart shirt and a mobile application with lifestyle behavioural advice, mindfulness-based therapy, and cognitive behavioural therapy, in reducing depressive symptoms among patients diagnosed with severe somatic conditions. Our hypothesis was that the system would significantly decrease the level of depressive symptoms in the intervention group compared to the control group. Methods: This pragmatic, randomised controlled trial included 425 patients diagnosed with myocardial infarction, breast cancer, prostate cancer, kidney failure, or lower limb amputation. Participants were recruited from hospitals in Turin and Pisa (Italy), and Lisbon (Portugal), and were randomly assigned to either the NEVERMIND intervention or to the control group. Clinical interviews and structured questionnaires were administered at baseline, 12 weeks, and 24 weeks. The primary outcome was depressive symptoms at 12 weeks measured by the Beck Depression Inventory II (BDI-II). Intention-to-treat analyses included 425 participants, while the per-protocol analyses included 333 participants. This trial is registered in the German Clinical Trials Register, DRKS00013391. Findings: Patients were recruited between Dec 4, 2017, and Dec 31, 2019, with 213 assigned to the intervention and 212 to the control group. The sample had a mean age of 59·41 years (SD=10·70), with 44·24% women. Those who used the NEVERMIND system had statistically significant lower depressive symptoms at the 12-week follow-up (mean difference=-3·03, p<0·001; 95% CI -4·45 to -1·62) compared with controls, with a clinically relevant effect size (Cohen's d=0·39). Interpretation: The results of this study show that the NEVERMIND system is superior to standard care in reducing and preventing depressive symptoms among patients with the studied somatic conditions. Funding: The NEVERMIND project received funding from the European Union's Horizon 2020 Research and Innovation Programme under grant agreement No. 689691.

Objective: To assess the cardiovascular safety of fenfluramine when used to treat children and young adults with Dravet syndrome. Methods: Patients with Dravet syndrome who completed one of three phase 3 clinical trials of fenfluramine could enroll in the open-label extension (OLE) study (NCT02823145). All patients started fenfluramine treatment at an oral dose of 0.2 mg/kg/day. The dose was titrated based on efficacy and tolerability to a maximum of 0.7 mg/kg/day (absolute maximum 26 mg/day) or 0.4 mg/kg/day (absolute maximum 17 mg/day) in patients concomitantly receiving stiripentol. Serial transthoracic echocardiography was performed using standardized methods and blinded readings at OLE entry, after 4-6 weeks, and every 3 months thereafter. Valvular heart disease (VHD) was defined as ≥ moderate mitral regurgitation or ≥ mild aortic regurgitation combined with physical signs or symptoms attributable to valve dysfunction. Pulmonary artery hypertension (PAH) was defined as systolic pulmonary artery pressure >35 mmHg. Results: A total of 327 patients (median age, 9.0 years; range, 2-19 years) have enrolled in the OLE and received ≥1 dose of fenfluramine. The median duration of treatment was 23.9 months (range, 0.2-42.6 months) and the median dose of fenfluramine was 0.44 mg/kg/day. No patient demonstrated VHD or PAH at any time during the OLE. Significance/interpretation: This study, which represents the largest, longest, and most rigorous examination of cardiovascular safety of fenfluramine yet reported, found no cases of VHD or PAH. These results, combined with fenfluramine's substantial antiseizure efficacy, support a strong positive benefit-risk profile for fenfluramine in the treatment of Dravet syndrome.

Background: Some patients with chronic coronary syndromes undergo invasive procedures but the efficacy of such interventions remains to be robustly established by randomised sham-controlled trials (RCTs). Purpose: To determine the sham effect in patients with chronic coronary syndromes enrolled in RCTs by performing a systematic review and meta-analysis. Methods: In April 2022, we performed a literature search for published patient-blind RCTs (CENTRAL, MEDLINE®, PsycINFO, and reference lists) with sham procedures, reporting the pre-post effects in the invasive sham arm among patients with Canadian cardiovascular society (CCS) angina or angina equivalents. Results: 16 RCTs were included with 546 patients in the sham arm. Pooled results showed that sham interventions were associated with: improvement of 7% (95% CI 2-11%; I2 = 0%) in exercise time; decrease of 0.78 (95% CI - 1.10 to - 0.47; I2 = 75%) in CCS angina class; decrease of 53% (95% CI 24-71%; I2 = 96%) and 25% (95% CI 20-29%; I2 = 0%) in anginal episodes and nitroglycerine (NTG) use, respectively. Pooled results also showed an improvement in the physical functioning, angina frequency, treatment satisfaction, and disease perception domains of the Seattle Angina Questionnaire (SAQ). Conclusion: Sham interventions in patients with chronic coronary syndromes were associated with a significant decrease in anginal episodes, NTG use, and CCS angina class and increased SAQ quality of life and exercise time. These results highlight the need for previous non sham-controlled trials to be interpreted with caution, and the importance of new invasive interventions to be evaluated versus a sham procedure.

Isolated coronary arteritis without systemic involvement in adults is exceedingly rare. A 60-year-old patient developed recurrent non–ST-segment elevation myocardial infarctions for 1 year. After an initial coronary angiogram that was normal, serial angiograms showed de novo aneurysm formation. The patient responded favorably to corticosteroids, supporting the diagnosis of isolated coronary arteritis.

An Egyptian burial assemblage in the collection of the Museum of Ancient Art and Archaeology of the University of Aarhus, Denmark, comprises an anthropoid coffin, a mummy-cover and a mummy. Several analyses have been carried out on the human remains since their arrival to the Museum in 1950 but these results have never been published nor critically accessed from an Egyptological perspective. Notwithstanding the unique opportunity provided by this burial assemblage to carry out the integrated study of the funerary equipment and the human remains, only recently has the coffin set been thoroughly analysed, described and published. This paper presents the results obtained from former anthropological studies with an Egyptological assessment of the data, comparing them with the information provided by the burial equipment. The critical integration of this data reveals important clues regarding the special social status held by an elderly woman suffering from a severe and chronic disability within the priesthood of Amun during the Twenty-first Dynasty.

No summary/description provided

A produção científica dedicada ao estudo da emigração portuguesa, seja em Portugal, seja no estrangeiro, continua a considerar preponderantemente aqueles e aquelas que deixaram o país como “emigrantes”, e não como “migrantes”. Apesar da mudança que se tem operado desde os finais dos anos 1980 com o sociólogo Abdelmalek Sayad (1999a, 1999b), que viu a necessidade absoluta de restabelecer a integridade do emigrante/imigrante reconciliando estas duas figuras aparentemente diferentes numa só, os/as portugueses/as que partiram continuam a ser referidos/as nos dias de hoje como os/as “emigrantes”. Estes títulos posteriores ao ano 2000 são disso testemunho (não obstante, consideramo-los essenciais à compreensão do fenómeno migratório português!): Desenvolvimento em meio rural: contributos da emigração e do regresso (Gonçalves, 2007); Portugal 2010: The return of the country of emigration? (Malheiros, 2011); L’émigration au Portugal, avatar d’un pays “semipériphérique” (Santos, 2013); Regresso e circulação de emigrantes portugueses no início do século XXI (Oliveira et al., 2016); Regresso ao futuro: A nova emigração e a sociedade portuguesa (Peixoto et al., 2016); L’émigration à l’écran: la rhétorique du succès. La série documentaire Portugueses pelo mundo (Cunha, 2017); A mobilidade académica e a emigração portuguesa qualificada (Gomes, 2019); New and old routes of Portuguese emigration (Pereira & Azevedo, 2019); A emigração portuguesa no século XXI (Pires et al., 2020), etc. Uma série de ideias preconcebidas acompanham a partida destes “emigrantes” e a expectativa do seu regresso, deixando um rasto nos discursos, nas políticas desenhadas para os recuperar, na forma como são representados nos meios de comunicação social ou ainda na forma como são vistos nas comunidades de onde partiram. Assim, o binómio “emigração/regresso” pode representar uma armadilha, no sentido em que inviabiliza uma análise mais ampla e complexa das diversas experiências de movimento(s), espera(s) e imobilidade(s) – entre múltiplas combinações possíveis – que uma mesma pessoa ou família vivencia.

Em 1498, quando Vasco da Gama chegou à Índia, encontrou um mundo estruturado, com rotas marítimas específicas cobrindo todo o espaço do oceano Índico e ligando os principais portos, desde a costa africana até à longínqua China e ao Japão. A progressiva aprendizagem das relações entre os participantes de um comércio próspero permitiu aos portugueses a concepção de um projecto político e militar cujo objectivo claro era o domínio destas vias marítimas. Esse projecto está patente no “Regimento” dado a D. Francisco de Almeida, em 1505, prevendo a construção de um conjunto de fortalezas em pontos estratégicos e a manutenção de uma armada no mar, de forma a impedir os acessos a todos os que recusassem a soberania portuguesa. Afonso de Albuquerque, assumindo o governo do Estado da Índia em 1509, foi o principal obreiro deste projecto de domínio naval, obtido sobretudo com as conquistas de Goa, Malaca e Ormuz.

Pesquisa encomendada pela Comissão Nacional para as Comemorações dos Descobrimentos Portugueses para integrar a Secção Documental da Revista Mare Liberum. Consta de um estudo publicado no nº 13, dividido em três capítulos, seguido de uma colecção de súmulas de documentos ordenada cronologicamente, e de uma bibliografia referindo fontes manuscritas e impressas, guias de documentação e de estudo, para além de outros utensílios, e ainda uma relação de estudos específicos. Segue-se a esta contextualização aprofundada e ao confronto de testemunhos, a publicação, no nº 14, de uma Compilação de Documentos, catorze no total, transcritos do original, cinco dos quais publicados pela primeira vez. Em virtude de razões fundamentadas no terceiro capítulo do Estudo, propõe-se uma fixação com maior rigor da data de dois pareceres anónimos que se publicam. Inquire-se ainda sobre a sua utilização por Diogo do Couto no Diálogo do Soldado Prático que trata dos enganos e desenganos da Índia e sobre a provável troca de documentos e de informações entre aquele autor e Manuel Severim de Faria. Foi publicada pela CNPCDP a Edição conjunta de estudo e compilação de documentos, em 1998 (divulgada no RUL).

In this paper, we examine the accounts in Book 2 so as to access Herodotus effective knowledge of Egyptian temples. Although presenting an accurate portrait of the land and the people, Herodotus’ texts betray an insufficient understanding of the local priestly traditions which probably resulted from an unwelcoming reception by the Egyptian priests. Memphis, stands out as an exception in this panorama, providing Herodotus with a direct contact with the historical sources which later on would be brilliantly used by Manetho to write his History of Egypt.

This contribution focuses on the implications of an enquiry on return migration in a border region. The northeastern region of Trás-osMontes in Portugal is a paradigmatic area of out-migration, from colonial migrations to the ones to western and northern Europe during the Estado Novo, and the more recent migrations post-2008 crisis. The area went through dramatic demographic losses, accounting for a third of its population between the 1960s and 2000s. But it is also one of the areas with the highest rate of new residents - many of them coming (back) from France. The back and forth of inhabitants is only one form of mobilities in the history of the peninsula: as a border region, Trásos-Montes is recently revisiting its transcultural heritage, such as the one of the Sephardic Jewish community, the Mirandese minority and more. Enquiring at the border hence holds many meanings, both in time and space, and both for those who stay and those mobile. Based on Pratt (1991) or Cohen & Sheringham (2017)'s understanding of “contact zones”, I explore the dynamics of place production in such a cultural space of encounters, conflicts, and renewal between several communities, in a region which has historically functioned as a transitional space. The theoretical reflection is accompanied by preliminary results of an ethnographic fieldwork conducted between 2018 and 2020 in the region. The case study of a village embedded in various networks, through out-migration and return migration, shows the extent to which the regional efforts to promote the area as “open to the outside” deny the potential of Portuguese migrants and returnees as active place-makers.

Entre 2010 e 2015, o contexto migratório português alterou-se significativamente em consequência dos impactos sociais da crise financeira e económica, o que resultou num saldo migratório negativo, combinando redução do fluxo de entrada e incremento nas saídas de imigrantes (para novos destinos ou retorno ao país de origem) com o aumento da emigração portuguesa. Neste contexto, alguns casais luso-brasileiros mudaram-se para o Brasil, onde as oportunidades económicas e sociais, naquele período, pareciam mais favoráveis; contudo, entre 2016 e 2019, esse fluxo terá de novo oscilado, favorecendo agora Portugal enquanto espaço de destino. Combinando dados quantitativos sobre casamentos e nascimentos para demonstrar as ligações familiares entre brasileiras/os e portugueses/as e dados qualitativos coletados em entrevistas com famílias luso-brasileiras que vieram para Portugal, este texto procurou escrutinar duas ideias principais: (i) as razões do retorno para Portugal e a relevância dos contextos familiares, neste processo; e (ii) os projetos migratórios futuros e as suas implicações na (im)permanência neste país europeu. Teoricamente este artigo pretende desafiar e discutir categorias migratórias clássicas dos estudos migratórios como emigrantes-imigrantes e, sobretudo, partida e retorno, posicionando-as em contextos binacionais. Pretende-se assim desafiar a noção clássica de retorno a partir de uma perspetiva centrada em sujeitos migrantes mais complexos (os casais mistos) em relação aos espaços originais de referência que, por sua vez, também se vão transformando no quadro da circularidade migratória.

After fourteen decades of medical and technological evolution, infective endocarditis continues to challenge physicians in its daily diagnosis and management. Its increasing incidence, demographic shifts (affecting older patients), microbiology with higher rates of Staphylococcus infection, still frequent serious complications and substantial mortality make endocarditis a very complex disease. Despite this, innovations in the diagnosis, involving microbiology and imaging, and improvements in intensive care and cardiac surgical techniques, materials and timing can impact the prognosis of this disease. Ongoing challenges persist, including rethinking prophylaxis, improving the diagnosis criteria comprising blood culture-negative endocarditis and prosthetic valve endocarditis, timing of surgical intervention, and whether to perform surgery in the presence of ischemic stroke or in intravenous drug users. A combined strategy on infective endocarditis is crucial, involving advanced clinical decisions and protocols, a multidisciplinary approach, national healthcare organization and health policies to achieve better results for our patients.