RCAAP Repository

The idea of textual variation was notably rejected in the early days of critique génétique, but versions have been playing a prominent role in most editorial schools of genetic orientation. This article presents a systematic review of the literature to distinguish the main working definitions and editorial approaches to the notion of version, both in genetic analogue editions and digital archives based on text encoding and computer-assisted collation.

O excesso de peso e a obesidade são fatores de risco estabelecidos para várias neoplasias e estão associados a piores outcomes. Embora seja reconhecido o estado de ‘metainflamação’ associado, pouco se conhece sobre o seu impacto na resposta à imunoterapia (IT). Estudos em doentes com melanoma metastático e carcinoma de células renais tratados com IT demonstraram que estes fatores estão associados a maior sobrevivência livre de progressão (SLP) e sobrevivência global (SG). Estudos recentes mostraram uma associação semelhante no cancro do pulmão de não-pequenas células (CPNPC). Este é um estudo de coorte retrospetivo de doentes com CPNPC avançado tratados com pembrolizumab (1ª linha) ou nivolumab (2ª linha), em monoterapia. Os doentes foram categorizados em IMC<25 Kg/m2 e IMC25 Kg/m2, de acordo com as definições da OMS. Foram incluídos 114 doentes, 70,2% do sexo masculino e 37,7% com IMC25 Kg/m2. Os grupos encontravam-se bem balanceados em todas as características, com exceção da existência de menos fumadores ativos (p=0,034), mais tumores com expressão de PD-L150% (p=0,025) e mais doentes dislipidémicos (p=0,047) no grupo com IMC25 Kg/m2. Embora em análise univariada não se tenha verificado nenhuma associação entre o IMC e a SLP (HR=1,029; CI 95% 0,660-1,605; p=0,898) ou SG (HR=1,012; IC 95% 0,638-1,607; p=0,959), em modelo multivariado os doentes com IMC25 Kg/m2 tiveram uma menor SLP (HR=2,180; IC 95% 1,049-4,532; p=0,037) e SG (HR=2,364; IC 95% 1,062-5,263; p=0,035). Curiosamente, verificou-se que a dislipidemia estava associada a maior SLP tanto em análise univariada (HR=0,572; IC 95% 0,355-0,920; p=0,021) como multivariada (HR=0,421; IC 95% 0,206-0,859; p=0,017). Estes resultados diferem dos obtidos noutros estudos, enfatizando a relação complexa entre o excesso de peso, inflamação e imunoterapia. A associação encontrada entre a dislipidemia e a SLP, não descrita noutros estudos, sugere que outros fatores podem ter um papel nesta relação, carecendo de estudos adicionais.

A leptospirose é uma infeção multissistémica causada pela bactéria Leptospira. É neste momento considerada uma zoonose reemergente, com elevada distribuição mundial, sendo endémica em países de clima tropical e subtropical. No nosso país, o arquipélago dos Açores é considerado uma região endémica. Esta doença é transmitida pelo contacto direto com fluidos de animais infetados com a bactéria, ou pelo contacto indireto com o solo e a água (locais onde a bactéria sobrevive por vários meses). Os reservatórios naturais mais comuns são os roedores, mas canídeos, bovinos e suínos também podem ser afetados. Deste modo, fatores de risco incluem: trabalhadores agrícolas, pastores, trabalhadores de matadouros ou atividades recreativas de lazer perto de fontes de água parada (como seja a pesca, a canoagem ou a natação). Clinicamente, manifesta-se, na maioria das vezes, por uma síndrome gripal like com sinais e sintomas inespecíficos que podem incluir febre, mialgias, cefaleias e náuseas. Contudo, numa minoria dos casos, evolui para insuficiência renal, insuficiência hepática, meningite, insuficiência respiratória, diátese hemorrágica ou choque séptico. Estas alterações poderão ser fatais. O diagnóstico baseia-se em testes diretos que detetam a bactéria ou os seus componentes, como por exemplo, culturas, microscopia ou técnicas de amplificação de DNA. E em testes indiretos serológicos como por exemplo o MAT e o ELISA. O tratamento inclui medidas sintomáticas, nomeadamente na presença de insuficiência renal ou insuficiência respiratória; e antibioterapia com penicilina, ceftriaxona ou doxiciclina. Medidas de prevenção são essenciais no combate a esta zoonose. Estas medidas incluem: isolamento, diagnóstico e tratamento de animais infetados, melhorias habitacionais que diminuam o contacto entre humanos e ratos e deteção e tratamento de águas contaminadas. Esta revisão procura documentar a transmissão, a clínica e as descobertas a nível da patogénese desta doença.

The scope of this thesis is to study the evolution of the EU's Africa policy in a timeframe of seven years between 2000 and 2007 - from the first to the second EUAfrica Summit. The study aims to identify dominant EU motives and forces in shaping a Joint Strategic Partnership between the two continents and its importance for the EU's positioning in the world. On the one hand, the study will investigate documents relating to the EU-Africa dialogue, and considered key to determine which interests, actors, and discourse have been dominant; on the other hand, it will investigate documents linked to parallel EU strategies over the same period likewise considered key to the evolution of the EU's Africa policy. The thesis is that EU Africa policies must be seen in a wider political context in which the EU aims to project itself in the world as a significant international actor with the power to actively influence world politics through a more integrated approach by integrating, mainstreaming and coordinating external policies and instruments including strategies leading to a greater visibility in the world. The study concludes that Africa represents an important field of interest for the EU. Motives and interests are mixed and include political, economic, military, security, social, environmental and moral aspects. Africa's geographical proximity, its historical relations with EU Member States and low political sensitivity as a region compared to for example the Middle East are important factors that have allowed for a high degree of Member State consensus on coordinating different policy instruments as a means to establish a coherent and effective foreign policy through initiatives ranging from development aid, over humanitarian assistance to military action with initiatives covering conflict prevention, conflict management and peacekeeping missions.

Background: In keeping with the fundamental practice of transparency in the discussion and resolution of ethics conflicts raised by research, a summary of ethics issues raised during Portuguese biomonitoring in health surveillance and research is presented and, where applicable, their resolution is described. Methods: Projects underway aim to promote the surveillance of public health related to the presence of solid waste incinerators or to study associations between human exposure to environmental factors and adverse health effects. The methodological approach involves biomonitoring of heavy metals, dioxins and/or other persistent organic pollutants in tissues including blood, human milk and both scalp and pubic hair in groups such as the general population, children, pregnant women or women attempting pregnancy. As such, the projects entail the recruitment of individuals representing different demographic and health conditions, the collection of body tissues and personal data, and the processing of the data and results. Results: The issue of autonomy is raised during the recruitment of participants and during the collection of samples and data. This right is protected by the requirement for prior written, informed consent from the participant or, in the case of children, from their guardian. Recruitment has been successful, among eligible participants, in spite of incentives rarely being offered. The exception has been in obtaining guardians' consent for children's participation, particularly for blood sampling. In an attempt to mitigate the harm-benefit ratio, current research efforts include alternative less invasive biomarkers. Surveys are currently being conducted under contract as independent biomonitoring actions and as such, must be explicitly disclosed as a potential conflict of interests. Communication of results to participants is in general only practised when a health issue is present and corrective action possible. Concerning human milk a careful approach is taken, considering breast-feeding's proven benefits. Conclusion: No national legislation currently accounts for the surveillance component of biomonitoring as distinct from research. Ethics issues arising within the domain of research are resolved according to available regulations. For issues encountered during surveillance, the same principles are used as guidance, completed by the authors' best judgement and relevant ethics committees' findings.

A resistência a antibióticos é cada vez mais um problema global associado a elevadas taxas de mortalidade e aumentos de gastos em saúde. CR-KP trata-se de um dos principais microorganismos que apresenta resistências a antibióticos. Os mecanismos de resistências a antibióticos passam pela expressão de bombas de efluxo, mutação dos canais de porina ou através da produção de enzimas que têm a capacidade de hidrolisar o antibiótico. Relativamente à resistência aos carbapenemos, a produção de carbapenemases (enzimas que hidrolisam carbapenemos), são o mecanismo mais identificado. KPC é a carbapenemase com mais interesse clínico, pois é também a mais prevalente. Encontra-se codificada em plasmídeos e por isso tem a capacidade de ser transferível entre diferentes espécies de bactérias, contribuindo assim para a disseminação da resistência a carbapenemos. Atualmente, apesar de existirem algumas alternativas terapêuticas para o tratamento de infeções causadas por CR-KP, é fundamental identificar a quais os fatores de risco para colonização/infeção, de forma a selecionar a antibioterapia o mais dirigida possível. A utilização prévia de antibioterapia, internamento em Unidade de Cuidados Intensivos, recurso a procedimentos invasivos, transplante de órgão ou células, bem como a existência de doenças crónicas prévias foram identificados como os principais fatores de risco.

As propriedades fisiológicas de filtração e elevada pressão glomerular do rim tornam-no um alvo da lesão imunomediada, sendo por isso frequente o envolvimento renal no percurso clínicos de várias doenças autoimunes (DAIs). A doença indiferenciada do tecido conjuntivo (DITC) é uma doença autoimune sistémica caracterizada por um percurso clínico estável, não evolutivo, ligeiro, onde o envolvimento renal não é esperado. A podocitopatia lúpica (PL) é uma entidade clínica recente caracterizada por apagamento difuso dos pedicelos e que se manifesta por síndrome nefrótico. Inicialmente descrita no lúpus eritematoso sistémico (LES), conta agora com uma crescente lista de entidades clínicas associadas. Apresento um caso de uma mulher de 40 anos com DITC com cerca de 20 anos de evolução que desenvolve síndrome nefrótico no contexto de uma podocitopatia com características semelhantes às descritas no LES. Neste trabalho, proponho-me a rever os conceitos fundamentais do envolvimento renal no contexto das doenças autoimunes focando-me na lesão podocitária e nos desafios que este caso clínico constituiu. Revejo ainda os possíveis mecanismos fisiopatológicos envolvidos na lesão podocitária nas doenças autoimunes nas quais tem sido descrita. Apresento, por fim, uma tabela resumo dos casos clínicos de podocitopatias em doenças autoimunes encontrados na literatura.

Staphylococcus aureus é o agente oportunista mais frequentemente isolado nas secreções respiratórias dos doentes com Fibrose Quística. Esta bactéria persiste durante períodos extensos nas vias aéreas apesar de esquemas antimicrobianos agressivos e repetitivos. Durante a colonização pulmonar crónica, S. aureus é exposto a numerosas pressões seletivas impostas pelo ambiente dinâmico e hostil do pulmão de FQ, levando ao estabelecimento de uma população bacteriana heterogénea fenotípica. Small Colony Variants (SCV) é uma subpopulação bacteriana auxotrófica de crescimento lento que exibe características morfológicas, fisiológicas e metabólicas distintas, que facilitam o desenvolvimento de infeções persistentes, recorrentes e refratárias a terapêutica standard. O diagnóstico laboratorial de SCV de S. aureus representa um desafio para o microbiologista clínico, dado que requere a aplicação de métodos de diagnóstico especiais, não empregados rotineiramente pela maioria dos laboratórios clínicos de FQ. Até a data, poucos laboratórios clínicos reportam a presença de isolados de SCV de S. aureus. Estudos epidemiológicos demonstraram que doentes pediátricos tal como adultos estão frequentemente colonizados por SCV de S. aureus. A idade avançada, exposição prévia a Sulfametoxazol-trimetoprim, coinfecção com Pseudomonas aeruginosa e declínio da função pulmonar constituem fatores de risco independentes para emergência de SCV de S. aureus. São necessários mais estudos para determinar se a presença de SCV de S. aureus representa um marcador de doença pulmonar avançada ou se desempenha um papel patogénico na progressão da doença pulmonar. As implicações diagnósticas e clínicas de SCV de S. aureus enfatizam a importância na monitorização e vigilância deste fenótipo, de forma a aumentar o conhecimento do seu significado clínico na doença pulmonar na FQ.

As lesões traumáticas do diafragma, onde se englobam a rotura, as lacerações e as contusões diafragmáticas podem ocorrer em casos de trauma toracoabdominal e, numa elevada percentagem associam-se a lesões de outros órgãos. A maioria das roturas diafragmáticas com herniação associada, ocorrem na hemícupula esquerda dado esta ser uma zona de maior suscetibilidade, não só pela ausência de proteção que é conferida pelo fígado à hemicúpula direita, mas, também, por fisiologicamente ser considerada uma zona de maior fraqueza. As hérnias diafragmáticas traumáticas, apesar de pouco frequentes, podem causar complicações potencialmente fatais. Porém, em geral a evolução depende do mecanismo de trauma, da severidade das lesões de órgão, do estado hemodinâmico do doente e do tempo decorrido até ao diagnóstico. Dado estas lesões serem, muitas vezes, de difícil deteção nos seus estádios iniciais e por não existirem, até ao momento, exames complementares de diagnóstico “gold-standard”, é necessário um alto nível de suspeição e um exame minucioso para que o seu diagnóstico seja feito. Uma vez que o diafragma se encontra em continuo movimento, a sua taxa de reparação espontânea é praticamente nula, levando a que o tamanho da lesão vá aumentando progressivamente, até ter tamanho suficiente para permitir a herniação do conteúdo abdominal para a cavidade torácica. Assim, na grande maioria dos casos, uma atitude expectante não é possível ou aconselhada, sendo necessária intervenção cirúrgica.

Introdução: Métodos prévios de estimativa de idade requerem estádios pré-definidos de desenvolvimento e apesar da sua utilidade, estes podem incorporar erros devido ao subjetivismo na designação de estádios. Um método proposto por Cameriere apresenta a vantagem de não classificar estádios dentários, mas identificar medidas normalizadas dos ápices abertos que tenham uma forte correlação com a idade do indivíduo. Objetivo: O objetivo desta investigação consistiu em avaliar a sensibilidade e a especificidade do ponto de corte de 0,08 pelo índice de maturidade do terceiro molar de Cameriere para os 18 anos de idade aplicado a uma população portuguesa. Foram igualmente determinados os pontos de corte para as idades de 14, 15, 16, 17, 18, 19, 20 e 21 anos. Materiais e Métodos: Foram selecionadas 350 ortopantomografias. As medições foram realizadas no programa informático ImageJ. Foram calculados os pontos de corte para as respetivas idades na população portuguesa. Posteriormente, os resultados foram analisados estatisticamente. Resultados e Discussão: Para o ponto de corte de 0,08 para a idade de 18 anos obteve- se uma sensibilidade de 78,99%, especificidade de 93,48%, uma precisão de 88,54%, um valor preditivo positivo de 86,24% e uma probabilidade a posteriori de Bayes de 92,82%. Os pontos de corte determinados para as idades de 14, 15, 16, 17, 18, 19, 20 e 21 anos de idade para a população portuguesa obtiveram uma precisão de 83,67%, 86,25%, 85,67%, 87,68%, 88,54%, 88,54%, 89,40% e 87,11%, respetivamente. Conclusão: Este estudo conclui que o ponte de corte de 0,08 determinado por Cameriere para a idade legal dos 18 anos tem aplicação na população portuguesa, sendo útil para aplicação no âmbito médico-legal. Contudo, outros pontos de corte podem ser aplicados, caso se pretenda privilegiar a sensibilidade em detrimento da especificidade (ou vice-versa). Todos os pontos de corte determinados para a população portuguesa têm aplicação no âmbito médico-legal.

Objectives: This study aims to evaluate the cytocompatibility of three provisional restoration materials and predict neurotoxic potential of their monomers. These materials are Tab 2000® (methyl methacrylate based), ProTemp 4™ (bis-acrylic based) and Structur 3® (urethane dimethacrylate based). Materials and methods: Resin samples were incubated in a cell culture medium and the cytotoxic effects of these extracts were studied in 3T3 fibroblast cells through MTT and crystal violet assays as well as ROS assessment. The presence of relevant leached monomers was determined by HPLC. Additionally, the blood-brain barrier (BBB) permeability to these resin-based monomers was predicted using ACD/Labs algorithms model. Results: Cell survival rates were compared with the resin extracts, and Structur 3® was statistically significant different from the others (p < 0.001) at all-time incubation periods. All materials induced a dose-dependent loss of cell viability; however, only Structur 3 extracts were cytotoxic against 3T3 fibroblasts. The highest cytotoxic effect (77%, p < 0.001) was observed at 24 h incubation period, which may be associated with the presence of urethane dimethacrylate (UDMA) leached monomers. Furthermore, the computational model showed that most monomers under study are expectedly capable of crossing the BBB. Conclusions: Our results showed that Structur 3® is not cytocompatible with our cell model and UDMA is a potential neurotoxic compound. Clinical relevance: These results indicate that only ProTemp 4™ and Tab 2000® are safe for provisional restorations.

The interaction between bacteriophages, bacteria and the human host as a tripartite system has recently captured attention. The taxonomic diversity of bacteriophages, as a natural parasite of bacteria, still remains obscure in human body biomes, representing a so-called "viral dark matter." Here, we isolated and characterized coliphages from blood, urine and tracheal aspirates samples collected at a tertiary care hospital in Austria. Phages were more often isolated from blood, followed by urine and tracheal aspirates. Phylogenetic analysis and genome comparisons allowed the identification of phages belonging to the Tunavirinae subfamily, and to the Peduovirus and Tequintavirus genera. Tunavirinae phages cluster together and are found in samples from 14 patients, suggesting their prevalence across a variety of human samples. When compared with other phage genomes, the highest similarity level was at 87.69% average nucleotide identity (ANI), which suggests that these are in fact a newly isolated phage species. Tequintavirus phages share a 95.90% with phage 3_29, challenging the ANI threshold currently accepted to differentiate phage species. The isolated phages appear to be virulent, with the exception of the Peduovirus members, which are integrative and seem to reside as prophages in bacterial genomes.

In cancer, recurrent somatic single-nucleotide variants-which are rare in most paediatric cancers-are confined largely to protein-coding genes1-3. Here we report highly recurrent hotspot mutations (r.3A>G) of U1 spliceosomal small nuclear RNAs (snRNAs) in about 50% of Sonic hedgehog (SHH) medulloblastomas. These mutations were not present across other subgroups of medulloblastoma, and we identified these hotspot mutations in U1 snRNA in only <0.1% of 2,442 cancers, across 36 other tumour types. The mutations occur in 97% of adults (subtype SHHδ) and 25% of adolescents (subtype SHHα) with SHH medulloblastoma, but are largely absent from SHH medulloblastoma in infants. The U1 snRNA mutations occur in the 5' splice-site binding region, and snRNA-mutant tumours have significantly disrupted RNA splicing and an excess of 5' cryptic splicing events. Alternative splicing mediated by mutant U1 snRNA inactivates tumour-suppressor genes (PTCH1) and activates oncogenes (GLI2 and CCND2), and represents a target for therapy. These U1 snRNA mutations provide an example of highly recurrent and tissue-specific mutations of a non-protein-coding gene in cancer.

Infant gliomas have paradoxical clinical behavior compared to those in children and adults: low-grade tumors have a higher mortality rate, while high-grade tumors have a better outcome. However, we have little understanding of their biology and therefore cannot explain this behavior nor what constitutes optimal clinical management. Here we report a comprehensive genetic analysis of an international cohort of clinically annotated infant gliomas, revealing 3 clinical subgroups. Group 1 tumors arise in the cerebral hemispheres and harbor alterations in the receptor tyrosine kinases ALK, ROS1, NTRK and MET. These are typically single-events and confer an intermediate outcome. Groups 2 and 3 gliomas harbor RAS/MAPK pathway mutations and arise in the hemispheres and midline, respectively. Group 2 tumors have excellent long-term survival, while group 3 tumors progress rapidly and do not respond well to chemoradiation. We conclude that infant gliomas comprise 3 subgroups, justifying the need for specialized therapeutic strategies.

Background: Migraine attacks are unpredictable, precluding preemptive interventions and leading to lack of control over individuals' lives. Although there are neurophysiological changes 24-48 hours before migraine attacks, so far, they have not been used in patients' management. This study evaluates the applicability and the ability to identify pre-attack changes of daily "at home" electroencephalography obtained with a portable system for migraine patients. Methods: Patients with episodic migraine fulfilling ICHD-3 beta criteria used a mobile system composed of a wireless EEG device (BrainStation®, Neuroverse®, Inc., USA) and mobile application (BrainVitalsM®, Neuroverse®, Inc., USA) to self-record their neural activity daily at home while resting and while performing an attention task, over the course of 2 weeks. Standard EEG spectral analysis and event-related brain potentials (ERP) methods were used and recordings were grouped by time from migraine attacks (i.e. "Interictal day", "24 h Before Migraine", "Migraine day" and "Post Migraine"). Results: Twenty-four patients (22 women) recorded an average of 13.3 ± 1.9 days and had 2 ± 0.9 attacks. Twenty-four hours before attack onset, there was a statistically significant modulation of relative power in the delta (decrease) and beta (increase) frequency bands, at rest, and a significant reduction of the amplitude and inter-trial coherence measures of an attention event-related brain potential (P300). Conclusions: This proof-of-concept study shows that brain state monitoring, utilising an easy-to-use wearable EEG system to track neural modulations at home, can identify physiological changes preceding a migraine attack enabling valuable pre-symptom prediction and subsequent early intervention.

O consumo de tabaco fumado, é a causa de mais de meio milhão de mortes/ano na União Europeia (UE). Para se poder avaliar a eficácia das medidas preventivas, é importante fazer a monitorização da prevalência do consumo de tabaco. A comparação entre países, pode ajudar a identificar boas práticas nesse controlo. Objectivos: Descrever o estado actual e a evolução da epidemia tabágica em vários países da EU e caracterizar a situação Portuguesa. Métodos: A descrição dos hábitos tabágicos e a sua evolução, na população com mais de 15 anos, em vários Países da UE, foi feita com base nos inquéritos realizados pelo Eurobarómetro entre 1995 e 2007. A caracterização dos hábitos tabágicos dos adolescentes escolarizados foi feita com base nos dados do Health Behaviour in School-Aged Children referentes a 1993-4 e 2002. Na análise da situação portuguesa foi utilizada, adicionalmente, a informação disponível nos Inquéritos Nacionais de Saúde realizados entre 1987 e 2005/06. Resultados: A prevalência de fumadores na população adulta na maioria dos países Europeus considerados é superior a 25%. A prevalência média de fumadores e de fumadoras na população de jovens escolarizados é da ordem dos 18%, em ambos os sexos. Na maioria dos países estudados a prevalência do consumo de tabaco nas raparigas é superior à dos rapazes. Apesar de Portugal ter das mais baixas prevalências na população com mais de 15 anos (30,6% nos homens e 11,6% nas mulheres), constata-se, no entanto, elevadas prevalências nas faixas etárias de 25-34 e dos 35-44 em homens (39,9% e 44,6% respectivamente) e em mulheres (17,6 e 21,2% respectivamente). A percentagem de raparigas fumadoras com 15 anos de idade, era em 2002 de 19,5%, valor próximo do grupo de países europeus com mais elevada prevalência de adolescentes fumadoras. Na EU registou- se, na última década (1996-2006), uma diminuição do consumo de tabaco na maioria dos países, tanto na população adulta como nos jovens escolarizados. Em Portugal, o consumo estabilizou nos homens e nos jovens de 15 anos, mas regista um aumento apreciável na população feminina adulta e escolarizada. Conclusões: Apesar de Portugal apresentar valores globais relativamente baixos de prevalência no contexto Europeu, os substanciais aumentos verificados na população feminina são particularmente preocupantes não só pelo impacto na saúde das mulheres mas também pelas consequências pré e pós natais que o fumo na mulher acarreta. Esta situação ilustra, entre nós, a falência das estratégias preventivas, nomeadamente ao nível da escola. Tobacco smoking is the cause of more than half million deaths/year in the European Union (EU). Monitoring smoking prevalence is an important tool to evaluate the epidemic and its evolution and to assess the effectiveness of preventive measures. The comparison between countries may help us identify good control practices. Objective: To describe the current state and evolution of the smoking epidemic in several EU countries, and to characterize the Portuguese situation in comparison with those countries. Methods: To characterize smoking habits and their evolution in the population over 15 years old, several Eurobarometer reports from 1995 to 2007 were used. The characterization of School Aged Children’s smoking habits was based on the Health Behaviour in School-Aged Children data of 1993-4 and 2002. The Portuguese situation also used the information available from the National Health Surveys of 1987 up to 2005/06. Results: The global prevalence of smoking in adult population in most of the European countries is over 25%. The average prevalence of male and female smokers in School- Aged Children over 15 years of age is approximately 18% if we consider both genders together. In most countries the prevalence of tobacco consumption is higher in girls when compared to boys. In Portugal, the prevalence in the population over 15 years of age has one of the lowest values among European countries (30,6 % for men and 11,6% for women). Despite these crude prevalence rates, high age-sex-specific prevalence rates were found in age groups 25-34 and 35-44 in men (39,9% e 44,6% respectively) and in women (17,6 e 21,2% respectively). In 2002, at the age of 15, the percentage of daily smoking girls in Portugal was 19.5%. This value reveals that Portugal is among the countries with higher prevalence rates of smoking among adolescent girls. Over the last decade (1996-2006), a decrease in tobacco consumption has been observed in most EU countries, both in adult population and in School-Aged Children. In Portugal, this consumption has levelled off in adult men and in youngsters aged 15, but shows a significant increase in female adults and school-aged girls. Conclusions: Although Portugal presents low global prevalence rates in the European context, the substantial increases observed in the young adult female population are of particular concern because of its impact on women’s health and the risk of pre and post-natal associated childhood exposure. These results reveal that current preventive strategies in Portugal are ineffective in reducing smoking prevalence among children and young adults.

Background: Biomarker-based risk predictions of dementia in people with mild cognitive impairment are highly relevant for care planning and to select patients for treatment when disease-modifying drugs become available. We aimed to establish robust prediction models of disease progression in people at risk of dementia. Methods: In this modelling study, we included people with mild cognitive impairment (MCI) from single-centre and multicentre cohorts in Europe and North America: the European Medical Information Framework for Alzheimer's Disease (EMIF-AD; n=883), Alzheimer's Disease Neuroimaging Initiative (ADNI; n=829), Amsterdam Dementia Cohort (ADC; n=666), and the Swedish BioFINDER study (n=233). Inclusion criteria were a baseline diagnosis of MCI, at least 6 months of follow-up, and availability of a baseline Mini-Mental State Examination (MMSE) and MRI or CSF biomarker assessment. The primary endpoint was clinical progression to any type of dementia. We evaluated performance of previously developed risk prediction models-a demographics model, a hippocampal volume model, and a CSF biomarkers model-by evaluating them across cohorts, incorporating different biomarker measurement methods, and determining prognostic performance with Harrell's C statistic. We then updated the models by re-estimating parameters with and without centre-specific effects and evaluated model calibration by comparing observed and expected survival. Finally, we constructed a model combining markers for amyloid deposition, tauopathy, and neurodegeneration (ATN), in accordance with the National Institute on Aging and Alzheimer's Association research framework. Findings: We included all 2611 individuals with MCI in the four cohorts, 1007 (39%) of whom progressed to dementia. The validated demographics model (Harrell's C 0·62, 95% CI 0·59-0·65), validated hippocampal volume model (0·67, 0·62-0·72), and updated CSF biomarkers model (0·72, 0·68-0·74) had adequate prognostic performance across cohorts and were well calibrated. The newly constructed ATN model had the highest performance (0·74, 0·71-0·76). Interpretation: We generated risk models that are robust across cohorts, which adds to their potential clinical applicability. The models could aid clinicians in the interpretation of CSF biomarker and hippocampal volume results in individuals with MCI, and help research and clinical settings to prepare for a future of precision medicine in Alzheimer's disease. Future research should focus on the clinical utility of the models, particularly if their use affects participants' understanding, emotional wellbeing, and behaviour.

Secondary forests and human-made forest gaps are conspicuous features of tropical landscapes. Yet, behavioral responses to these aspects of anthropogenically modified forests remain poorly investigated. Here, we analyze the effects of small human-made clearings and secondary forests on tropical bats by examining the guild- and species-level activity patterns of phyllostomids sampled in the Central Amazon, Brazil. Specifically, we contrast the temporal activity patterns and degree of temporal overlap of 6 frugivorous and 4 gleaning animalivorous species in old-growth forest and second-growth forest and of 4 frugivores in old-growth forest and forest clearings. The activity patterns of frugivores and gleaning animalivores did not change between old-growth forest and second-growth, nor did the activity patterns of frugivores between old-growth forest and clearings. However, at the species level, we detected significant differences for Artibeus obscurus (old-growth forest vs. second-growth) and A. concolor (old-growth forest vs. clearings). The degree of temporal overlap was greater than random in all sampled habitats. However, for frugivorous species, the degree of temporal overlap was similar between old-growth forest and second-growth; whereas for gleaning animalivores, it was lower in second-growth than in old-growth forest. On the contrary, forest clearings were characterized by increased temporal overlap between frugivores. Changes in activity patterns and temporal overlap may result from differential foraging opportunities and dissimilar predation risks. Yet, our analyses suggest that activity patterns of bats in second-growth and small forest clearings, 2 of the most prominent habitats in humanized tropical landscapes, varies little from the activity patterns in old-growth forest.

Wind energy production has expanded to meet climate change mitigation goals, but negative impacts of wind turbines have been reported on wildlife. Soaring birds are among the most affected groups with alarming fatality rates by collision with wind turbines and an escalating occupation of their migratory corridors. These birds have been described as changing their flight trajectories to avoid wind turbines, but this behaviour may lead to functional habitat loss, as suitable soaring areas in the proximity of wind turbines will likely be underused. We modelled the displacement effect of wind turbines on black kites (Milvus migrans) tracked by GPS. We also evaluated the impact of this effect at the scale of the landscape by estimating how much suitable soaring area was lost to wind turbines. We used state-of-the-art tracking devices to monitor the movements of 130 black kites in an area populated by wind turbines, at the migratory bottleneck of the Strait of Gibraltar. Landscape use by birds was mapped from GPS data using dynamic Brownian bridge movement models, and generalized additive mixed modelling was used to estimate the effect of wind turbine proximity on bird use while accounting for orographic and thermal uplift availability. We found that areas up to approximately 674 m away from the turbines were less used than expected given their uplift potential. Within that distance threshold, bird use decreased with the proximity to wind turbines. We estimated that the footprint of wind turbines affected 3%-14% of the areas suitable for soaring in our study area. We present evidence that the impacts of wind energy industry on soaring birds are greater than previously acknowledged. In addition to the commonly reported fatalities, the avoidance of turbines by soaring birds causes habitat losses in their movement corridors. Authorities should recognize this further impact of wind energy production and establish new regulations that protect soaring habitat. We also showed that soaring habitat for birds can be modelled at a fine scale using publicly available data. Such an approach can be used to plan low-impact placement of turbines in new wind energy developments.

Migratory decisions, such as the selection of stopover sites, are critical for the success of post‐breeding migratory movements and subsequent survival. Recent advances in bio‐logging have revealed the stopover strategies of many long‐distance migrants, but far less attention has been given to short‐distance migrants. We investigated the stopover ecology of an endangered grassland bird, the Little Bustard Tetrax tetrax, a short‐distance migrant in Iberia. Using high‐resolution spatial GPS/GSM data, 27 male Little Bustards breeding in southern Portugal were tracked between 2009 and 2011. We studied post‐breeding movements using Dynamic Brownian Bridge models to identify the main stopover sites, and generalized linear mixed models to examine habitat selection in stopovers. During their post‐breeding movements, males were essentially nocturnal migrants, making frequent stopovers while maintaining a relatively fast pace to reach more productive agricultural post‐breeding areas. Stopovers occurred in most post‐breeding movements (83%) regardless of the total distance covered (average 64.3 km), and most stopovers (84%) lasted less than 24 h. Birds used mostly agricultural non‐irrigated and irrigated croplands as stopover sites and avoided other land uses and rugged terrain. There was a negative relationship between stopovers and the proximity to roads, but not to power lines. The high frequency of stopovers during post‐breeding movements, despite the short distances travelled, together with the nocturnal migratory behaviour of bustards, may impose additional risks to a bird mainly threatened by collision with power lines in non‐breeding areas. We also conclude that even for short‐distance migrants, habitat connectivity between breeding and post‐breeding areas is likely to be a key conservation concern.