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Differing contexts have greatly influenced HTA development in various countries, with considerable effort recently made by international HTA networks (e.g., EUnetHTA) and the European Union (EU) to make HTA a more coherent, equal, and efficient process. Medical devices (MDs) present particular challenges for HTA because of frequent, rapid innovation, outcomes influenced by end-user competence, dynamic pricing and often low-quality scientific evidence. Our objective is to describe the development, structure and governance of a National HTA Program for MDs (PNHTADM) in Italy, a highly participatory, stakeholder-engaged, evidence-based process to reform a fragmented system of appraisal and approval. Based largely on EUnetHTA methods, the resulting process delineates a standardized system for proposing MDs by any stakeholders, accrediting HTA producers, setting criteria for prioritization and appraisals, and innovatively linking recommendations with coverage, reimbursement and procurement of MDs. Expected benefits include reduced disparities in pricing and reimbursement policies and improved access to new technologies across 21 regional healthcare systems in Italy's decentralized, universal system, complete with provisions to require additional evidence collection and centrally monitor diffusion. Though devised for Italy, the design, resources and underlying analysis provide a framework for other nations seeking to consolidate HTA initiatives, particularly in light of new EU regulation.

Tuberculosis (TB) is one of the main causes of death from a single pathological agent, Mycobacterium tuberculosis (Mtb). In addition, the emergence of drug-resistant TB strains has exacerbated even further the treatment outcome of TB patients. It is thus needed the search for new therapeutic strategies to improve the current treatment and to circumvent the resistance mechanisms of Mtb. The shikimate kinase (SK) is the fifth enzyme of the shikimate pathway, which is essential for the survival of Mtb. The shikimate pathway is absent in humans, thereby indicating SK as an attractive target for the development of anti-TB drugs. In this work, a combination of in silico and in vitro techniques was used to identify potential inhibitors for SK from Mtb (MtSK). All compounds of our in-house database (Centro de Pesquisas em Biologia Molecular e Funcional, CPBMF) were submitted to in silico toxicity analysis to evaluate the risk of hepatotoxicity. Docking experiments were performed to identify the potential inhibitors of MtSK according to the predicted binding energy. In vitro inhibitory activity of MtSK-catalyzed chemical reaction at a single compound concentration was assessed. Minimum inhibitory concentration values for in vitro growth of pan-sensitive Mtb H37Rv strain were also determined. The mixed approach implemented in this work was able to identify five compounds that inhibit both MtSK and the in vitro growth of Mtb.

Chronic Non-Communicable Diseases (NCDs) have been considered a global health problem, characterized as diseases of multiple factors, which are developed throughout life, and regardless of genetics as a risk factor of important relevance, the increase in mortality attributed to the disease to environmental factors and the lifestyle one leads. Although the reactive species (ROS/RNS) are necessary for several physiological processes, their overproduction is directly related to the pathogenesis and aggravation of NCDs. In contrast, dietary polyphenols have been widely associated with minimizing oxidative stress and inflammation. In addition to their antioxidant power, polyphenols have also drawn attention for being able to modulate both gene expression and modify epigenetic alterations, suggesting an essential involvement in the prevention and/or development of some pathologies. Therefore, this review briefly explained the mechanisms in the development of some NCDs, followed by a summary of some evidence related to the interaction of polyphenols in oxidative stress, as well as the modulation of epigenetic mechanisms involved in the management of NCDs.

The co-integration of spin, superconducting, and topological systems is emerging as an exciting pathway for scalable and high-fidelity quantum information technology. High-mobility planar germanium is a front-runner semiconductor for building quantum processors with spin-qubits, but progress with hybrid superconductor-semiconductor devices is hindered by the difficulty in obtaining a superconducting hard gap, that is, a gap free of subgap states. Here, we address this challenge by developing a low-disorder, oxide-free interface between high-mobility planar germanium and a germanosilicide parent superconductor. This superconducting contact is formed by the thermally-activated solid phase reaction between a metal, platinum, and the Ge/SiGe semiconductor heterostructure. Electrical characterization reveals near-unity transparency in Josephson junctions and, importantly, a hard induced superconducting gap in quantum point contacts. Furthermore, we demonstrate phase control of a Josephson junction and study transport in a gated two-dimensional superconductor-semiconductor array towards scalable architectures. These results expand the quantum technology toolbox in germanium and provide new avenues for exploring monolithic superconductor-semiconductor quantum circuits towards scalable quantum information processing.

Using cycloalkyl and electron-donating groups to decrease the carbonyl electrophilicity, a novel series of 2-(quinoline-4-yloxy)acetamides was synthesized and evaluated as

Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. There is an urgent need for safe, effective, and accessible new treatments since the currently approved drugs have serious limitations. Drug development for Chagas disease has historically been hampered by the complexity of the disease, critical knowledge gaps, and lack of coordinated R&D efforts. This review covers some of the translational challenges associated with the progression of new chemical entities from preclinical to clinical phases of development, and discusses how recent technological advances might allow the research community to answer key questions relevant to the disease and to overcome hurdles in R&D for Chagas disease.

A dissertação tem como corpus de pesquisa o Ensino de História através da música composta no período da Redemocratização Brasileira (1974-1985). O trabalho faz parte do Programa de Pós-graduação em História da Universidade de Caxias do Sul - Mestrado Profissional em História, tendo como linha de pesquisa as Linguagens e Cultura no Ensino de História. A temática desta pesquisa surgiu a partir das reflexões sobre o desenvolvimento de uma aprendizagem mais significativa nas salas de aula, sobretudo no ensino de História. Relacionar o passado com o presente tem sido um desafio para os professores dessa área, já que muitos os consideram "professores do passado". O objetivo é refletir, discutir e apresentar uma proposta metodológica com o uso da música em sala de aula, para ensinar o período da Redemocratização Brasileira. Considerando que, além de culturalmente muito explorada, a música é um recurso facilmente encontrado e de uso cotidiano da maioria dos jovens, a proposta busca auxiliar nesse processo de aprendizagem e tornar cada vez mais reflexivo e eficaz o ensino, utilizando-se das vivências dos educandos. A música como instrumento pedagógico, utilizada de forma simultânea ao livro didático ou texto, facilita a comunicação em um tempo em que a utilização de novas tecnologias está presente no cotidiano do professor e do educando, trazendo informações em tempo real e de forma acessível. O recorte temporal foi escolhido devido a sua importante transição de um período ditatorial para a democracia, no qual a sociedade brasileira manifestava-se culturalmente contra o governo e a realidade vivida. Assim, foram produzidas inúmeras canções que contextualizavam o momento, podendo ser utilizadas hoje como um documento histórico. A Redemocratização Brasileira se estende de 1974 a 1985, período no qual a Abertura Política aconteceu através de atos contínuos, devolvendo aos cidadãos brasileiros a democracia que lhes foi privada durante o período da Ditadura Civil Militar, iniciada em 1964. A pesquisa é qualitativa, pois o texto está baseado na revisão bibliográfica em livros, artigos científicos e dissertações que discorrem sobre o tema tratado, ressaltando alguns autores importantes para este trabalho como Napolitano (2010), Gardner (1995), Ferreira (2018), Seffner (2016), Chauí (2012 Por se tratar do Tempo Presente, as músicas selecionadas para relacionar a História à Redemocratização, ainda fazem parte do cotidiano de muitos brasileiros, e ainda convivemos com pessoas que vivenciaram aquele período. Como produto final desta pesquisa, proponho oficinas para professores, que visam auxiliar em suas práticas profissionais. Os resultados obtidos ao final de pesquisa sinalizam para uma constante atualização nos métodos e estratégias de aprendizagem utilizadas em sala de aula. [resumo fornecido pelo autor] The dissertation has as its research corpus the Teaching of History through music composed in the period of Brazilian Redemocratization (1974-1985). The work is part of the Postgraduate Program in History at the University of Caxias do Sul - Professional Masters in History, having as a research line Languages and Culture in History Teaching. The theme of this research emerged from reflections on the development of more meaningful learning in classrooms, especially in the teaching of History. Relating the past to the present has been a challenge for teachers in this area, as many consider them "teachers of the past". The objective is to reflect, discuss and present a methodological proposal with the use of music in the classroom, to teach the period of Brazilian Redemocratization. Considering that, in addition to being culturally very explored, music is a resource easily found and used daily by most young people, the proposal seeks to assist in this learning process and make teaching increasingly reflective and effective, using the experiences of students. Music as a pedagogical instrument, used simultaneously with the textbook or text, facilitates communication at a time when the use of new technologies is present in the daily life of the teacher and the student, bringing information in real time and in an accessible way. The time frame was chosen due to its important transition from a dictatorial period to democracy, in which Brazilian society culturally manifested itself against the government and the lived reality. Thus, countless songs were produced that contextualized the moment and can be used today as a historical document. The Brazilian Redemocratization extends from 1974 to 1985, a period in which the Political Opening took place through continuous acts, returning to Brazilian citizens the democracy that was deprived of them during the period of the Civil Military Dictatorship, which began in 1964. The research is qualitative, as it the text is based on the bibliographic review in books, scientific articles and dissertations that discuss the subject, highlighting some important authors for this work such as Napolitano (2010), Gardner (1995), Ferreira (2018), Seffner (2016), Chauí (2012). Because it is the present time, the songs selected to relate History to Redemocratization are still part of the daily lives of many Brazilians, and we still live with people who lived through that period. As a final product of this research, I propose workshops for teachers, who aim to assist in their professional practices. The results obtained at the end of the research point to a constant update in the methods and learning strategies used in the classroom. [resumo fornecido pelo autor]

International audience; Coupled tensor approximation has recently emerged as a promising approach for the fusion of hyperspectral and multispectral images, reconciling state of the art performance with strong theoretical guarantees. However, tensor-based approaches previously proposed assume that the different observed images are acquired under exactly the same conditions. A recent work proposed to accommodate inter-image spectral variability in the image fusion problem using a matrix factorization-based formulation, but did not account for spatially-localized variations. Moreover, it lacks theoretical guarantees and has a high associated computational complexity. In this paper, we consider the image fusion problem while accounting for both spatially and spectrally localized changes in an additive model. We first study how the general identifiability of the model is impacted by the presence of such changes. Then, assuming that the high-resolution image and the variation factors admit a Tucker decomposition, two new algorithms are proposed-one purely algebraic, and another based on an optimization procedure. Theoretical guarantees for the exact recovery of the high-resolution image are provided for both algorithms. Experimental results show that the proposed method outperforms state-of-the-art methods in the presence of spectral and spatial variations between the images, at a smaller computational cost.

La cama es un componente esencial en la producción de aves de corral, ya que habitan sobre este material la mayor parte de su ciclo productivo, por consiguiente, en ella se puede encontrar heces, bacterias entéricas, patógenos de importancia zoonótica y/o de transmisión alimentaria, plaguicidas y antimicrobianos, los cuales pueden afectar la sanidad de las aves. Después del ciclo de producción avícola, la cama es comúnmente utilizada como fertilizante orgánico para mejorar la calidad de los suelos y los cultivos. A pesar de su amplio uso en la avicultura y agricultura, se conoce poco acerca de su importancia en la seguridad alimentaria, por lo cual, la presente revisión discute acerca de los patógenos y contaminantes presentes en la cama y sus riesgos para la seguridad alimentaria, además las prácticas de manejo y tratamientos más adecuados. Información que será útil para maximizar los usos de la cama y los desechos avícolas, para que estos no representen un peligro para las personas, animales y el medio ambiente.

There is no doubt that nanotechnology and nanoscience open new doors to new applications and products that can potentially revolutionize the practice field and how we conserve built heritage materials. However, we are living at the beginning of this era and the potential benefits of nanotechnology to specific conservation practice needs are not always fully understood. This opinion/review paper aims to present reflections and answer a question that we are often asked when working directly with stone field conservators: why should we use a nanomaterial instead of a conventional product? Why does size matter? To answer this question, we revise the basic concepts of nanoscience with implications for the built heritage conservation field.

Araticum (Annona crassiflora Mart.) is a native and endemic species to Brazilian Cerrado whose fruits have high sensorial, nutritional, bioactive, and economic potential. Its use in local folk medicine, associated with recent scientific findings, has attracted growing interest from different industrial sectors. Therefore, understanding the scientific advances achieved so far and identifying gaps to be filled is essential to direct future studies and transform accumulated knowledge into innovative technologies and products. In this review, we summarize the phytochemical composition, bioactivities, and food products from araticum fruit that have been reported in the scientific literature over the past 10 years. The compiled data showed that araticum fruit parts contain a wide range of bioactive compounds, particularly phenolic compounds, alkaloids, annonaceous acetogenins, carotenoids, phytosterols, and tocols. These phytochemicals contribute to different biological activities verified in araticum fruit extracts/fractions, including antioxidant, anti-inflammatory, anti-Alzheimer, anticancer, antidiabetic, anti-obesity, antidyslipidemic, antinociceptive, hepatoprotective, healing of the cutaneous wound, antibacterial, and insecticide effects. Despite the promising findings, further studies—particularly toxicological (especially, with byproducts), pre-clinical, and clinical trials—must be conducted to confirm these biological effects in humans and assure the safety and well-being of consumers.

As sementes em geral possuem um período determinado para germinação e após este tempo passam a não serem viáveis para plantio. A giberelina é um hormônio que atua estimulando a germinação em sementes que apresentem algum bloqueio para germinar. Objetivou-se avaliar o efeito da giberelina na emergência e desenvolvimento inicial de plântulas de mamoeiro cultivar golden, com sementes de diferentes idades. Os tratamentos foram sementes com um ano, dois anos e 3 anos, armazenadas em geladeira (10°C). Duzentas sementes de cada idade foram imersas durante 60 minutos em solução de Giberelina ( , na dosagem de 2000 mg.L-1, e 200 de cada idade em água pura como testemunha, e semeadas em bandejas com substrato comercial. Após trinta dias do início da emergência, foi avaliado a porcentagem de emergência, o índice de velocidade de emergência e o tempo médio de emergência. Sessenta dias após o início da emergência foram avaliadas a altura da planta, número de folhas, diâmetro do coleto, comprimento da raiz, massa verde e seca das folhas e das raízes. Sementes de mamão armazenadas por até três anos germinam normalmente e possuem potencial para emergência quando submetidas a tratamento pré germinativo com giberelina.

O estudo do substrato adequado é de grande importância na produção da muda para implantação de um pomar produtivo, pois fornece condições ideais para a germinação e desenvolvimento. Objetivou-se avaliar o efeito de diferentes substratos minerais na emergência e desenvolvimento inicial de plântulas de mamoeiro cultivar aliança. O experimento foi realizado em delineamento em blocos casualizados, com cinco tratamentos e quatro repetições. Foram utilizadas cinquenta sementes por repetição, e para cada avaliação foram consideradas cinco plantas de cada repetição. Os tratamentos utilizados foram compostos de terra pura, areia, perlita, vermiculita, todos na mistura de 3:1 e substrato comercial como testemunha. Após trinta dias do início da emergência foi avaliado a porcentagem de emergência, índice de velocidade de emergência e tempo médio de emergência. Noventa dias após o início da emergência foram avaliadas altura da planta, número de folhas, diâmetro do coleto, comprimento da raiz, massa verde e seca das folhas e das raízes. O substrato vermiculita apresentou os melhores desempenhos para emergência e desenvolvimento inicial de plântulas de mamoeiro CV aliança.

This Special Issue examines the synthesis, characterization, and manufacturing of nanoparticles and their potential advantages and applications for the conservation of built cultural heritage materials [...]

Lignocellulosic materials (some natural fibers) have relevant mechanical properties when incorporated in polymeric matrices, being a renewable source to replace synthetic fibers; however, for good adhesion and durability, it is necessary to modify the fibrous surface structure in order to eliminate unwanted compounds. This work aims to evaluate different conditions of alkaline treatment of tobacco stalk waste using 10 and 15 wt% sodium hydroxide (NaOH) during an exposure time of 3 or 5 h. Thermal, chemical, and morphological characterizations as well as kinetic analysis were performed. Through Fourier transform infrared spectroscopy, it was possible to identify the partial removal of compounds such as lignin, hemicellulose, and extractives, increasing the thermal stability, which was proven by thermogravimetric analysis. Furthermore, X-ray diffraction shows a higher crystallinity index from cellulose after the alkaline treatment. Through the kinetic analysis, it is possible to observe that both methods presented similar activation energy values (Ea). In addition, after the alkaline treatment there was a reduction in Ea, the most evident result being observed in the TSW\10\5 sample, which presented an average value of Ea of 223.95 ± 15.79 kJ/mol by the Flynn–Wall–Ozawa method and 218.74 ± 24.69 kJ/mol by the Friedman method. Scanning electron microscopy showed the exposure of the microfibrils and an enhancement of roughness after alkaline treatment. Tobacco stalk wastes has potential application as reinforcing filler in composite materials since surface alkaline modification provides higher fiber/matrix adhesion through the removal of amorphous compounds.

Sida planicaulis is a weed thought to have originated in Brazil, where it is present in abundant quantities, but also this plant is also found in south-central Florida, Indian Ocean Islands, and th...

Carbon fiber reinforced polymer (CFRP) is widely used in high-tech industries because of its interesting characteristics and properties. This material presents good strength and stiffness, relatively low density, high damping ability, good dimensional stability, and good corrosion resistance. However, the machinability of composite materials is complex because of the matrix/fiber interface, being a challenging machining material. The CFRP milling process is still necessary to meet dimensional tolerances, the manufacture of difficult-to-mold features like pockets or complexes advance surfaces, finish the edges of laminated composites, or drill holes for the assembly of the components. Besides, the demand for low-cost, reconfigurable manufacturing systems of the industry demonstrates that the application of industrial robots (IRs) in the CFRP milling process becomes an alternative for providing automation and flexibility. Therefore, the objective of this work is to evaluate the performance of the low payload IR KUKA KR60 HA in a milling experiment of CFRP, which indicates its potential application as an alternative to milling process. Furthermore, the influence of the cutting tool geometry as well as the cutting parameters in the machining behavior with IRs is evaluated.

Fundamento: A fração de ejeção do ventrículo esquerdo é um dos parâmetros ecocardiográficos mais utilizados na prática clínica. Sua estimativa pelo método bidimensional manual (método de Simpson) tem reprodutibilidade e acurácia limitadas, e métodos semiautomáticos têm sido propostos. Torna-se necessário comparar o método bidimensional semiautomático com métodos mais acurados de avaliação da fração de ejeção do ventrículo esquerdo, como a medida pela ecocardiografia tridimensional automática. Objetivo: Comparar as estimativas da fração de ejeção do ventrículo esquerdo e dos volumes diastólico final e sistólico final do ventrículo esquerdo pelo método bidimensional semiautomático com as obtidas pelo método tridimensional automático. Método: Estudo observacional transversal, com pacientes em ritmo sinusal, fração de ejeção do ventrículo esquerdo >50% e sem cardiopatia estrutural significativa, submetidos ao ecocardiograma transtorácico. Teste t de Student, coeficiente de Pearson e análise de Bland-Altman foram usados na análise estatística. Resultados: Foram incluídos 40 pacientes, sendo: 53% mulheres, 35% hipertensos, 25% dislipidêmicos, 10% diabéticos, 10% tabagistas e 13% com angioplastia prévia. Os valores médios da fração de ejeção do ventrículo esquerdo aos métodos tri e bidimensionais foram 62,1 ± 5,8% e 61,7 ± 5,9% (p = 0,50), respectivamente. Houve forte correlação da fração de ejeção do ventrículo esquerdo determinada melos métodos bi e tridimensional (r = 0,74; p

In this study, phytochemical profiling, and antidiabetic, antitumoral and cytotoxic potential of aqueous extracts of leaves of red variety of

Satellite imaging has a central role in monitoring, detecting and estimating the intensity of key natural phenomena. One important feature of satellite images is the trade-off between spatial/spectral resolution and their revisiting time, a consequence of design and physical constraints imposed by satellite orbit among other technical limitations. In this paper, we focus on fusing multi-temporal, multi-spectral images where data acquired from different instruments with different spatial resolutions is used. We leverage the spatial relationship between images at multiple modalities to generate high-resolution image sequences at higher revisiting rates. To achieve this goal, we formulate the fusion method as a recursive state estimation problem and study its performance in filtering and smoothing contexts. The proposed strategy clearly outperforms competing methodologies, which is shown in the paper for real data acquired by the Landsat and MODIS instruments., Comment: Published in IEEE AeroConf 2022