MOEA/D with Uniformly Randomly Adaptive Weights

When working with decomposition-based algorithms, an appropriate set of weights might improve quality of the final solution. A set of uniformly distributed weights usually leads to well-distributed solutions on a Pareto front. However, there are two main difficulties with this approach. Firstly, it may fail depending on the problem geometry. Secondly, the population size becomes not flexible as the number of objectives increases. In this paper, we propose the MOEA/D with Uniformly Randomly Adaptive Weights (MOEA/DURAW) which uses the Uniformly Randomly method as an approach to subproblems generation, allowing a flexible population size even when working with many objective problems. During the evolutionary process, MOEA/D-URAW adds and removes subproblems as a function of the sparsity level of the population. Moreover, instead of requiring assumptions about the Pareto front shape, our method adapts its weights to the shape of the problem during the evolutionary process. Experimental results using WFG41-48 problem classes, with different Pareto front shapes, shows that the present method presents better or equal results in 77.5% of the problems evaluated from 2 to 6 objectives when compared with state-of-the-art methods in the literature

Coronary computed tomography angiography-adapted Leaman score as a tool to noninvasively quantify total coronary atherosclerotic burden

To describe a coronary computed tomography angiography (CCTA)-adapted Leaman score (CT-LeSc) as a tool to quantify total coronary atherosclerotic burden with information regarding localization, type of plaque and degree of stenosis and to identify clinical predictors of a high coronary atherosclerotic burden as assessed by the CT-LeSc. Single center prospective registry including a total of 772 consecutive patients undergoing CCTA (Dual-source CT) from April 2011 to March 2012. For the purpose of this study, 581 stable patients referred for suspected coronary artery disease (CAD) without previous myocardial infarction or revascularization procedures were included. Pre-test CAD probability was determined using both the Diamond-Forrester extended CAD consortium method (DF-CAD consortium model) and the Morise score. Cardiovascular risk was assessed with the HeartScore. The cut-off for the 3rd tercile (CT-LeSc ≥8.3) was used to define a population with a high coronary atherosclerotic burden. The median CT-LeSc in this population (n = 581, 8,136 coronary segments evaluated; mean age 57.6 ± 11.1; 55.8 % males; 14.6 % with diabetes) was 2.2 (IQR 0-6.8). In patients with CAD (n = 341), the median CT-LeSc was 5.8 (IQR 3.2-9.6). Among patients with nonobstructive CAD, most were classified in the lowest terciles (T1, 43.0 %; T2, 36.1 %), but 20.9 % were in the highest tercile (T3). The majority of the patients with obstructive CAD were classified in T3 (78.2 %), but 21.8 % had a CT-LeSc in lower terciles (T1 or T2). The independent predictors of a high CT-LeSc were: Male sex (OR 1.73; 95 % CI 1.04-2.90) diabetes (OR 2.91; 95 % CI 1.61-5.23), hypertension (OR 2.54; 95 % CI 1.40-4.63), Morise score ≥16 (OR 1.97; 95 % CI 1.06-3.67) and HeartScore ≥5 (OR 2.42; 95 % CI 1.41-4.14). We described a cardiac CT adapted Leaman score as a tool to quantify total (obstructive and nonobstructive) coronary atherosclerotic burden, reflecting the comprehensive information about localization, degree of stenosis and type of plaque provided by CCTA. Male sex, hypertension, diabetes, a HeartScore ≥5 % and a Morise score ≥16 were associated with a high coronary atherosclerotic burden, as assessed by the CT-LeSc. About one fifth of the patients with nonobstructive CAD had a CT-LeSc in the highest tercile, and this could potentially lead to a reclass

The respiratory research agenda in primary care in Portugal: a Delphi study

Background: A research agenda can help to stimulate and guide research. The International Primary Care Respiratory Group (IPCRG) published a Research Needs Statement (RNS) in 2010 in which 145 research questions were identified. In 2012, priorities for respiratory research were established, based on these questions. To date, there has been no statement on primary care respiratory research needs in Portugal. The aim of the study was to develop a national consensus on research priorities in respiratory diseases in primary care in Portugal and to assess the applicability of the priorities for respiratory research set by the IPCRG. Method: We conducted a Delphi study by electronic mail with a panel of experts on respiratory disease from primary and secondary care in Portugal. In the first round, the research needs in respiratory disease in Portugal were identified. In the second round, 196 research questions in six disease areas, derived from the first round and from the IPCRG Respiratory needs statement, were prioritised on a five-point Likert-type scale. In the third round, the questions were prioritized again with feed-back provided on the median scores for each item in the second round. Consensus was considered to have been reached when 80 % of the participants gave a score of 4 or 5 out of five on a given item. Results: The 40 experts identified 121 respiratory research questions in Round 1 and expressed their views on 196 questions in Rounds 2 and 3. Twelve research questions (6 %) reached consensus. There were five questions in the asthma domain on early diagnosis, pulmonary function tests, the use of inhalers, and adherence to treatment. There were four questions in the chronic obstructive pulmonary disease domain on vaccinations, on routine monitoring and evaluation of treatment, on diagnosis, and on adherence to treatments. There was one question in the smoking domain on the effects of brief counselling. There were two questions on respiratory tract infections on the treatment of children and on the prescription of antibiotics. An additional 23 research questions (12 %) achieved consensus between 75 and 79 %. Conclusion: The results reflect the Portuguese reality in response the international agenda for research on respiratory diseases published by the IPCRG. They can support the development of future respiratory disease research in Portugal.Financial support for this work was provided by FEDER funds through the Operational Programme Competitiveness Factors - COMPETE and National Funds through FCT - Foundation for Science and Technology under the project POCI-01-0145-FEDER-007038; and by the project NORTE-01-0145-FEDER-000013, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). PMT is partially supported by a grant from the International Primary Care Respiratory Group

Preliminary in vitro evaluation of the anti-proliferative activity of guanylhydrazone derivatives

Guanylhydrazones have shown promising antitumor activity in preclinical tumor models in several studies. In this study, we aimed at evaluating the cytotoxic effect of a series of synthetic guanylhydrazones. Different human tumor cell lines, including HCT-8 (colon carcinoma), MDA-MB-435 (melanoma) and SF-295 (glioblastoma) were continuous exposed to guanylhydrazone derivatives for 72 hours and growth inhibition of tumor cell lines and macrophages J774 was measured using tetrazolium salt (MTT) assay. Compounds 7, 11, 16 and 17 showed strong cytotoxic activity with IC50 values lower than 10 μmol L–1 against four tumor cell lines. Among them, 7 was less toxic to non-tumor cells. Finally, the obtained data suggest that guanylhydrazones may be regarded as potential lead compounds for the design of novel anticancer agents

MDL28170, a Calpain Inhibitor, Affects Trypanosoma cruzi Metacyclogenesis, Ultrastructure and Attachment to Rhodnius prolixus Midgut

BACKGROUND: Trypanosoma cruzi is the etiological agent of Chagas' disease. During the parasite life cycle, many molecules are involved in the differentiation process and infectivity. Peptidases are relevant for crucial steps of T. cruzi life cycle; as such, it is conceivable that they may participate in the metacyclogenesis and interaction with the invertebrate host. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we have investigated the effect of the calpain inhibitor MDL28170 on the attachment of T. cruzi epimastigotes to the luminal midgut surface of Rhodnius prolixus, as well as on the metacyclogenesis process and ultrastructure. MDL28170 treatment was capable of significantly reducing the number of bound epimastigotes to the luminal surface midgut of the insect. Once the cross-reactivity of the anti-Dm-calpain was assessed, it was possible to block calpain molecules by the antibody, leading to a significant reduction in the capacity of adhesion to the insect guts by T. cruzi. However, the antibodies were unable to interfere in metacyclogenesis, which was impaired by the calpain inhibitor presenting a significant reduction in the number of metacyclic trypomastigotes. The calpain inhibitor also promoted a direct effect against bloodstream trypomastigotes. Ultrastructural analysis of epimastigotes treated with the calpain inhibitor revealed disorganization in the reservosomes, Golgi and plasma membrane disruption. CONCLUSIONS/SIGNIFICANCE: The presence of calpain and calpain-like molecules in a wide range of organisms suggests that these proteins could be necessary for basic cellular functions. Herein, we demonstrated the effects of MDL28170 in crucial steps of the T. cruzi life cycle, such as attachment to the insect midgut and metacyclogenesis, as well as in parasite viability and morphology. Together with our previous findings, these results help to shed some light on the functions of T. cruzi calpains. Considering the potential roles of these molecules on the interaction with both invertebrate and vertebrate hosts, it is interesting to improve knowledge on these molecules in T. cruzi

The national inventory of geological heritage: methodological approach and results

A existência de um inventário nacional de património geológico é fundamental para se poderem implementar estratégias de geoconservação. Este trabalho apresenta a metodologia usada no desenvolvimento do mais completo inventário de geossítios, realizado até ao momento em Portugal, assim como os principais resultados obtidos. O inventário vai integrar o Sistema de Informação do Património Natural e o Cadastro Nacional dos Valores Naturais Classificados, ambos geridos pelo Instituto de Conservação da Natureza e da Biodiversidade.The existence of a national inventory of the geological heritage is of paramount importance for the implementation of a geoconservation strategy. This paper presents the methodological approach used to produce the most complete geosites inventory in Portugal, so far, and the obtained results. This inventory will be uploaded into the National Database of Natural Heritage managed by the Portuguese authority for nature conservation.Este trabalho é apoiado pela Fundação para a Ciência e a Tecnologia, através do financiamento plurianual do CGUP e do projecto de investigação “Identificação, caracterização e conservação do património geológico: uma estratégia de geoconservação para Portugal” (PTDC/CTE-GEX/64966/2006).info:eu-repo/semantics/publishedVersio

Dilatação dos confins: caminhos, vilas e cidades na formação da Capitania de São Paulo (1532-1822)

Este ensaio analisa a formação da rede urbana das capitanias de São Vicente e Santo Amaro, depois unidas na Capitania de São Paulo. Discute o processo de apropriação do sertão, a pulsação e dilatação dos confins ao sabor dos deslocamentos humanos e de interesses políticos. Interpreta o papel de capelas, freguesias, vilas e cidades no controle e produção de territórios metropolitanos em solos ultramarinos.This essay analyzes the development of urban networks in the Captaincies of São Vicente and Santo Amaro, later merged into the Captaincy of São Paulo. It discusses the process of appropriation of the sertão (backcountry), the commotion and expansion beyond the confines to the tune of population movements and political interests. The paper also interprets the role of chapels, parishes, villages and towns in initiatives to create and control metropolitan areas on overseas soil