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The project EcoPLis - Human Occupations in the Pleistocene Ecotones of the River Lis - started in central Portugal in 2015. It aims to understand the behavioural ecology of hominins during the Pleistocene in a region where sub-rectilinear rivers link the coast to the inland mountains through open riverine and canyon environments. This project is rooted in Leiria’s mapping project - CARQLEI - managed by the City Council that has been mapping archaeological sites and off-sites since 2004, including some identified by Cultural Resource Management projects. One of the most important aims of EcoPLis is the systematic recording and spatial analysis of raw material sources. The Lis basin has a large diversity of rocks suitable for knapping and multiple sources of these materials can be found both in primary and secondary sources. Although rocks are readily available, some materials were selectively sourced and used in the production of stone tools, e.g. chert, quartzite and quartz. The last two are allochthonous, showing great diversity and are highly abundant in river and marine gravels. On the other hand, chert is autochthonous, and it can thus be obtained from secondary and subprimary positions, and extracted from primary outcrops that are considerably limited in space, such as those of the Ribeira das Chitas valley. In this paper we present a tentative map of raw material types and availability in the Lis basin and a preliminary geochemical analysis of chert specimens collected in primary, sub-primary and secondary positions. Our goal is to set a framework for the future investigation of raw material provenance relative to the excavated sites, including a provisional geochemical characterization of the main sources.

Background: Valvular heart disease (VHD) is an important cause of mortality and morbidity and has been subject to important changes in management. The VHD II survey was designed by the EURObservational Research Programme of the European Society of Cardiology to analyze actual management of VHD and to compare practice with guidelines. Methods: Patients with severe native VHD or previous valvular intervention were enrolled prospectively across 28 countries over a 3-month period in 2017. Indications for intervention were considered concordant if the intervention was performed or scheduled in symptomatic patients, corresponding to Class I recommendations specified in the 2012 European Society of Cardiology and in the 2014 American Heart Association/American College of Cardiology VHD guidelines. Results: A total of 7247 patients (4483 hospitalized, 2764 outpatients) were included in 222 centers. Median age was 71 years (interquartile range, 62–80 years); 1917 patients (26.5%) were ≥80 years; and 3416 were female (47.1%). Severe native VHD was present in 5219 patients (72.0%): aortic stenosis in 2152 (41.2% of native VHD), aortic regurgitation in 279 (5.3%), mitral stenosis in 234 (4.5%), mitral regurgitation in 1114 (21.3%; primary in 746 and secondary in 368), multiple left-sided VHD in 1297 (24.9%), and right-sided VHD in 143 (2.7%). Two thousand twenty-eight patients (28.0%) had undergone previous valvular intervention. Intervention was performed in 37.0% and scheduled in 26.8% of patients with native VHD. The decision for intervention was concordant with Class I recommendations in symptomatic patients with severe single left-sided native VHD in 79.4% (95% CI, 77.1–81.6) for aortic stenosis, 77.6% (95% CI, 69.9–84.0) for aortic regurgitation, 68.5% (95% CI, 60.8–75.4) for mitral stenosis, and 71.0% (95% CI, 66.4–75.3) for primary mitral regurgitation. Valvular interventions were performed in 2150 patients during the survey; of them, 47.8% of patients with single left-sided native VHD were in New York Heart Association class III or IV. Transcatheter procedures were performed in 38.7% of patients with aortic stenosis and 16.7% of those with mitral regurgitation. Conclusions: Despite good concordance between Class I recommendations and practice in patients with aortic VHD, the suboptimal number in mitral VHD and late referral for valvular interventions suggest the need to improve further guideline implementation.

The scientific advances in the research on artificial neural networks have raised the computer's generative potential, with interesting developments in the computational art. Projects in this direction include the development of an artificial neural network that learns an artist's painting style and applies it to other images, as well as the Google Brain project, which investigates the use of neural networks for the automatic production of songs and texts. In the present work, we describe an experiment carried out with the aim of creating poems in an autonomous way. The approach consisted in adopting a recurrent neural network of the LSTM type and training it on a body of poems in the Portuguese language from the 16th to the 20th centuries, involving 604 thousand characters. The trained network is able to generate new poems in the learned style and is undergoing an evaluation process. Os avan��os cient��ficos na pesquisa sobre redes neurais artificiais t��m elevado o potencial gerativo do computador, com interessantes desdobramentos na ��rea de arte computacional. Projetos nesse sentido incluem o desenvolvimento de uma rede neural artificial que aprende o estilo de pintura de um artista e o aplica a outras imagens, bem como o projeto Google Brain, o qual investiga a utiliza����o de redes neurais para a produ����o autom��tica de m��sicas e de textos. No presente trabalho, descrevemos um experimento realizado com o objetivo de criar poemas de maneira aut��noma. A abordagem consistiu em adotar uma rede neural recorrente do tipo LSTM e trein��-la sobre um corpo de poemas na l��ngua portuguesa dos s��culos XVI ao XX, envolvendo mais de um milh��o de caracteres. A rede treinada consegue gerar novos poemas no estilo aprendido e est�� passando por um processo de avalia����o.

The current paradigm of medical therapy for heart failure with reduced ejection fraction (HFrEF) is triple neurohormonal blockade with an angiotensin-converting enzyme inhibitor (ACEI), a beta-blocker (BB) and a mineralocorticoid receptor antagonist (MRA). However, three-year mortality remains over 30%. Stimulation of counter-regulatory systems in addition to neurohormonal blockade constitutes a new paradigm, termed neurohormonal modulation. Sacubitril/valsartan is the first element of this new strategy. PARADIGM-HF was the largest randomized clinical trial conducted in HFrEF. It included 8442 patients and compared the efficacy and safety of sacubitril/valsartan versus enalapril. The primary endpoint was the composite of cardiovascular mortality and hospitalization due to HF, which occurred in 914 (21.8%) patients receiving sacubitril/valsartan and in 1117 (26.5%) patients receiving enalapril (HR 0.8, 95% CI 0.73-0.87, p=0.0000002; NNT 21). Sacubitril/valsartan reduced both primary endpoint components, as well as sudden cardiac death, death due to worsening HF, and death from all causes. Patients on sacubitril/valsartan reported less frequent deterioration of HF and of quality of life, and discontinued study medication less frequently because of an adverse event. PARADIGM-HF demonstrated the superiority of sacubitril/valsartan over enalapril, with a 20% greater impact on cardiovascular mortality compared to ACEIs. Accordingly, in 2016, the European (ESC) and American (ACC/AHA/HFSA) cardiology societies simultaneously issued a class I recommendation for the replacement of ACEIs by sacubitril/valsartan in patients resembling PARADIGM-HF trial participants. publishersversion published

Made available in DSpace on 2019-03-11T12:47:07Z (GMT). No. of bitstreams: 1 tese_12292_SUZANA GONÇALVES CARVALHO20190308-111655.pdf: 2328807 bytes, checksum: 12046af4b7f90073c7e295cdc878d9ab (MD5) Previous issue date: 2019-02-18 A leishmaniose cutânea é uma doença zoonose, sendo causada por protozoários do gênero Leishmania. A leishmaniose cutânea canina (LCC) é considerada uma antropozoonose e, atualmente não existe farmacoterapia disponível, no Brasil, para o seu tratamento. Assim, a busca por alternativas farmacêuticas para uso nos animais tem sido objeto de inúmeras pesquisas. Neste cenário, a atividade leishmanicida da furazolidona vem sendo estudada por diversos pesquisadores e, uma vez que o fármaco não é utilizado no tratamento das leishmanioses no homem, seu uso para o tratamento da LCC pode ser considerado. Relatos ciêntíficos apontam a furazolidona como um quimioterápico com boa atividade leishmanicida. Contudo, problemas de toxicidade animal também são relatados, o que pode estar relacionado a sua baixa solubilidade e altas doses requeridas para que o efeito terapêutico seja alcançado. Entre as inúmeras alternativas farmacotécnicas disponíveis para contornar problemas de solubilidade, a formação de complexos de inclusão com ciclodextrinas merece destaque. Além de melhorar a solubilidade e a biodisponibilidade das moléculas hóspedes, a formação de complexos de inclusão (CIs) pode aumentar a estabilidade e favorecer o mascaramento do sabor dos fármacos. Neste contexto, o objetivo do presente estudo foi preparar CIs entre a furazolidona (FZD) e duas ciclodextrinas de interesse farmacêutico: a β-ciclodextrina (βCD) e a hidroxi-propil-β-ciclodextrina (HPβCD). Os CIs foram preparados nas razões molares 1:1 e 1:2 (FZD:CD) pelos métodos de malaxagem e liofilização. A presença de amorfização das partículas e o sucesso da complexação foram confirmadas empregando técnicas de caracterização física e química, a saber: calorimetria exploratória diferencial (DSC), termogravimetria (TG/DTG), microscopia eletrônica de varredura (MEV), difração de raios X (DRX), espectroscopia Raman e ressonância magnética nuclear (RMN) de 13C no estado sólido. Após a caracterização físico-química, avaliou-se a atividade leishmanicida 7 utilizando o método calorimétrico de redução da resazurina em formas promastigotas. A citotoxicidade foi avaliada sobre macrófagos provenientes de monócitos THP-1, empregando-se o ensaio calorimétrico com MTT. Os processos de malaxagem e liofilização escolhidos para a obtenção dos complexos, se mostraram simples e de fácil execução, passíveis de serem escalonadas. A presença de amorfização e a indicação de complexação para os produtos obtidos a partir da β-CD e da HP-β-CD, na razão molar 1:2, preparadas por liofilização, foi confirmada por todas as técnicas utilizadas. Em todos os demais produtos, foi constatada a ocorrência de interações entre o fármaco e as ciclodextrinas em estudo, indicando a formação de agregados do tipo não-complexo. Todas as amostras apresentaram atividade leishmanicida e se mostraram não tóxicas para macrófagos THP-1. Os valores do IC50 para os produtos de complexação MHFZD1:2 e LHFZD1:2 foram 2,7 e 3,02 µg/mL, respectivamente, sendo ambos considerados promissores para o desenvolvimento de medicamentos de uso veterinário com vistas ao uso no tratamento de leismanioses em cães.

Background: The perioperative management of antiplatelet therapy in noncardiac surgery patients who have undergone previous percutaneous coronary intervention (PCI) remains a dilemma. Continuing dual antiplatelet therapy (DAPT) may carry a risk of bleeding, while stopping antiplatelet therapy may increase the risk of perioperative major adverse cardiovascular events (MACE). Methods: Occurrence of Bleeding and Thrombosis during Antiplatelet Therapy In Non-Cardiac Surgery (OBTAIN) was an international prospective multicentre cohort study of perioperative antiplatelet treatment, MACE, and serious bleeding in noncardiac surgery. The incidences of MACE and bleeding were compared in patients receiving DAPT, monotherapy, and no antiplatelet therapy before surgery. Unadjusted risk ratios were calculated taking monotherapy as the baseline. The adjusted risks of bleeding and MACE were compared in patients receiving monotherapy and DAPT using propensity score matching. Results: A total of 917 patients were recruited and 847 were eligible for inclusion. Ninety-six patients received no antiplatelet therapy, 526 received monotherapy with aspirin, and 225 received DAPT. Thirty-two patients suffered MACE and 22 had bleeding. The unadjusted risk ratio for MACE in patients receiving DAPT compared with monotherapy was 1.9 (0.93–3.88), P=0.08. There was no difference in MACE between no antiplatelet treatment and monotherapy 1.03 (0.31–3.46), P=0.96. Bleeding was more frequent with DAPT 6.55 (2.3–17.96) P=0.0002. In a propensity matched analysis of 177 patients who received DAPT and 177 monotherapy patients, the risk ratio for MACE with DAPT was 1.83 (0.69–4.85), P=0.32. The risk of bleeding was significantly greater in the DAPT group 4.00 (1.15–13.93), P=0.031. Conclusions: OBTAIN showed an increased risk of bleeding with DAPT and found no evidence for protective effects of DAPT from perioperative MACE in patients who have undergone previous PCI.

Made available in DSpace on 2020-01-14T18:13:19Z (GMT). No. of bitstreams: 1 gmr18022geneticdiversitynativepopulation.pdf: 694093 bytes, checksum: 73dd25b4adfd325840e37aa0db62c48b (MD5) Previous issue date: 2019

Os recursos genéticos vegetais são definidos como parte essencial da biodiversidade, constituídos pela variabilidade genética presente em espécies de plantas de uso atual ou potencial em programas de melhoramento genético, biotecnologia e áreas afins.

Author(s): Chahine, Lana M; Siderowf, Andrew; Barnes, Janel; Seedorff, Nicholas; Caspell-Garcia, Chelsea; Simuni, Tanya; Coffey, Christopher S; Galasko, Douglas; Mollenhauer, Brit; Arnedo, Vanessa; Daegele, Nichole; Frasier, Mark; Tanner, Caroline; Kieburtz, Karl; Marek, Kenneth; The Parkinson’s Progression Markers Initiative | Abstract: BackgroundImproved prediction of Parkinson's disease (PD) progression is needed to support clinical decision-making and to accelerate research trials.ObjectivesTo examine whether baseline measures and their 1-year change predict longer-term progression in early PD.MethodsParkinson's Progression Markers Initiative study data were used. Participants had disease duration ≤2 years, abnormal dopamine transporter (DAT) imaging, and were untreated with PD medications. Baseline and 1-year change in clinical, cerebrospinal fluid (CSF), and imaging measures were evaluated as candidate predictors of longer-term (up to 5 years) change in Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score and DAT specific binding ratios (SBR) using linear mixed-effects models.ResultsAmong 413 PD participants, median follow-up was 5 years. Change in MDS-UPDRS from year-2 to last follow-up was associated with disease duration (β= 0.351; 95% CI = 0.146, 0.555), male gender (β= 3.090; 95% CI = 0.310, 5.869), and baseline (β= -0.199; 95% CI = -0.315, -0.082) and 1-year change (β= 0.540; 95% CI = 0.423, 0.658) in MDS-UPDRS; predictors in the model accounted for 17.6% of the variance in outcome. Predictors of percent change in mean SBR from year-2 to last follow-up included baseline rapid eye movement sleep behavior disorder score (β= -0.6229; 95% CI = -1.2910, 0.0452), baseline (β= 7.232; 95% CI = 2.268, 12.195) and 1-year change (β= 45.918; 95% CI = 35.994,55.843) in mean striatum SBR, and 1-year change in autonomic symptom score (β= -0.325;95% CI = -0.695, 0.045); predictors in the model accounted for 44.1% of the variance.ConclusionsBaseline clinical, CSF, and imaging measures in early PD predicted change in MDS-UPDRS and dopamine-transporter binding, but the predictive value of the models was low. Adding the short-term change of possible predictors improved the predictive value, especially for modeling change in dopamine-transporter binding.

Phage Display combined with Supramolecular Ligand Display enables selection for phosphate-binding motifs

Made available in DSpace on 2019-12-07T00:38:19Z (GMT). No. of bitstreams: 1 Advances.pdf: 1634397 bytes, checksum: f0f838c56647d56690d89bb526cbf629 (MD5) Previous issue date: 2019

Basil is an aromatic herb that stands out fo its economic importance. It is consumed in natura and sed to obtain essential oil. The cultivation of this species in several regions of the world has allowed variations by natural crosses and euploidy, leading to the wide genetic variability found nowadays. Considering the importance of this species, we aimed to analyze the genetic diversity of 27 basil genotypes using ISSR molecular markers. Fourteen primers were employed for DNA amplification, resulting in 86% polymorphism. Based on the Jaccard?s dissimilarity index, the highest index (0.80) was observed between the individuals BAS001 and BAS012, while the lowest index (0.18) was detected between the genotypes BAS014 and BAS015. The genetic similarity among individuals was calculated, forming four distinct clusters. Most individuals (40.7%) were allocated in cluster I. The polymorphic information content (PIC) (0.89) indicated considerable levels of genetic diversity among genotypes. In this sense, the ISSR markers were efficient in the detection of polymorphisms between the accessions, suggesting the genetic variability of the collection. This result demonstrates the importance of the use of molecular markers and the advantages that this information provides to the breeding of the species. O manjericão é uma erva aromática que se destaca por possuir importância econômica. É consumido in natura e também utilizado na obtenção de óleo essencial. O cultivo desta espécie em diversas regiões do mundo permitiu que surgissem variações mediante cru-zamentos naturais e euploidia, ocasionando a ampla variabilidade genética existente. Considerando a importância desta espécie, este trabalho teve como objetivo analisar a diversidade genética de 27 genótipos de manjericão usando marcadores moleculares ISSR. Qua-torze primers foram utilizados para amplificação do DNA, resultando em 86% de polimorfismo. Com base no índice de dissimilaridade de Jaccard, observou-se o maior índice (0,80) entre os indivíduos BAS001 e BAS012, enquanto que o menor índice de dissimilari-dade (0,18) foi detectado entre os genótipos BAS014 e BAS015. A semelhança genética entre indivíduos foi calculada, formando quatro grupos distintos. A maioria dos indivíduos (40,7%) foi agrupada no grupo I. O conteúdo de informação polimórfica (PIC) (0,89) indicou níveis consideráveis de diversidade genética entre os genótipos. Neste sentido, os marcadores ISSR foram eficientes na detecção de polimorfismos entre os acessos e confirmaram que é possível inferir a variabilidade genética na coleção. Isso demonstra a importância do uso de marcadores moleculares e as vantagens que esta informação pode oferecer ao melhoramento genético das espécies. Made available in DSpace on 2020-01-14T18:11:51Z (GMT). No. of bitstreams: 1 18069991hb3702180.pdf: 930033 bytes, checksum: 67f007a25226e9386cfea7bf3789e54d (MD5) Previous issue date: 2019

The aim of this study was to evaluate the reaction of Habanero-type advanced inbred lines, developed by Embrapa Hortaliças breeding program, to RP and PC. Made available in DSpace on 2019-12-06T00:36:27Z (GMT). No. of bitstreams: 1 20193746.pdf: 1691906 bytes, checksum: 3905f1893691395212eb1a077c8617f2 (MD5) Previous issue date: 2019