Measurement of internal diameters of capillaries and glass syringes using gravimetric and optical methods for microflow applications

This work performed under 18HLT08 MeDDII project has received funding from the EMPIR programme co-financed by the Participating States and from the European Union’s Horizon 2020 research and innovation programme. The Authors would like to acknowledge Abir Wissam Boudaoud for her help in CETIAT inner diameter measurements and Václav Duchoň and Petr Grolich from CMI for their work on the glass syringe diameter calibration. © 2022 the author(s), published by De Gruyter, Berlin/Boston.OBJECTIVES: Microflow measurement devices are used in several science and health applications, mainly drug delivery. In the last decade, several new methods based on optical technology were developed, namely the front tracking and interferometric method, in which the knowledge of the inner diameter of the syringe or the capillary used is critical. Only a few National Metrology Institutes (NMIs) can perform inner diameter measurements below 1 mm, which requires expensive technology. Therefore, IPQ, in cooperation with CETIAT, CMI and UNIDEMI, under the EMPIR project 18HLT08 MeDDII - Metrology for Drug Delivery, developed new measurement methods for small inner diameter tubes based on the gravimetric principle and optical methods in order to simplify the apparatus used for this type of measurements without increasing uncertainty. METHODS: The gravimetric experimental setup consists of measuring the liquid volume on a specific length of the glass tube. The optical method used is based on the front track principle that uses a high-resolution camera and ImageJ software, to determine the diameter at both ends of each capillary. RESULTS: To validate the developed methods, a comparison was performed between CETIAT, CMI and IPQ and the results obtained were all consistent. CONCLUSIONS: This work allowed the determination of inner diameter of syringes or capillaries using two different methods with relative expanded uncertainties from 0.1 to 0.5% ( k=2), that can be applied for flow measurements using optical technology.publishersversionepub_ahead_of_prin

Processos de transformação urbana: Uma tipificação baseada na urbanidade, na centralidade e na evolução da população dos territórios

Os processos de transformação urbanos são dos fenómenos que mais atenção têm recebido nas ciências regionais ou urbanas. Mas a complexidade e diversidade destes processos, as suas múltiplas manifestações a diferentes escalas, têm desafiado a sua categorização e identificação. Este artigo contribui para esta problemática ao propor uma tipologia de transformações urbanas para Portugal Continental baseada em três dimensões – a urbanidade, a centralidade e a evolução da população. A urbanidade traduz o grau de urbanização de uma determinada área, considerando as suas características demográficas ou de uso do solo. A centralidade refere-se ao posicionamento no sistema urbano mais amplo, sendo aferida através de variáveis que expressam a sua hierarquia funcional. A evolução da população permite traduzir parte da dinâmica de transformação, obtendo-se pela diferença entre a população residente em diferentes períodos. O trabalho adota as freguesias como unidades territoriais de base, recorrendo a técnicas clássicas (de redução de variáveis e de identificação de clusters) por forma a identificar a associação das diferentes unidades territoriais a processos de transformação urbana reconhecidos na literatura

Assessment of drug delivery devices working at microflow rates

Funding Information: Research funding: This work performed under the 18HLT08 MeDD II project has received funding from the EMPIR program co-financed by the Participating States and from the European Union’s Horizon 2020 research and innovation program. For more information on the project refer to the website www.drugmetrology.com . Publisher Copyright: © 2022 the author(s), published by De Gruyter, Berlin/Boston.Almost every medical department in hospitals around the world uses infusion devices to administer fluids, nutrition, and medications to patients to treat many different diseases and ailments. There have been several reports on adverse incidents caused by medication errors associated with infusion equipment. Such errors can result from malfunction or improper use, or even inaccuracy of the equipment, and can cause harm to patients' health. Depending on the intended use of the equipment, e.g. if it is used for anaesthesia of adults or for medical treatment of premature infants, the accuracy of the equipment may be more or less important. A well-defined metrological infrastructure can help to ensure that infusion devices function properly and are as accurate as needed for their use. However, establishing a metrological infrastructure requires adequate knowledge of the performance of infusion devices in use. This paper presents the results of various tests conducted with two types of devices.publishersversionpublishe

The knowledge transfer from science to practice – a survey with EU researchers

Group members came from 12 European countries, six from new (Bulgaria, Czech Republic, Estonia, Hungary, Poland and Slovenia) and six from old EU member states (Germany, Spain, Finland, Italy, The Netherlands, Portugal). The aim of the work was to analyze the role of the scientists in a dialogue between them and the practitioners within the organic production sector. Another important aim was to find the best practice models of such dialogue as the examples to be followed by others. In order to reach this aim the survey with the scientists has been conducted by all project partners; every partner has conducted the survey with 10 selected scientists from own country. Only the scientists possessing PhD level and actively working in the organic sector could be selected. Key areas of the questionnaire were directed to the (A) person (gender, age, years of activity in teaching and/or researching), (B) number of projects, papers, trainings and interviews, (C) Examples of best practice models, (D) Estimations of potential collaboration and dialog between scientists and stakeholders, (E) Estimations about the success of personal activities with regard to the improvement of the four fields (farming, processing, trading & marketing), (F) Estimates of the improvement of communication and knowledge transfer from science to practice, (G) Estimates of potential threats for good communication and knowledge transfer among scientists and practitioners. Interviewees were finally asked for general remarks and comments. The results indicate that there is not a big difference between the scientists from the old EU member states and new EU member states in most of the analyzed areas. The main difference is that the scientists from the new EU member states provide more training sessions for practitioners outside their institutions compared to the researchers from the old EU member states. The results reveal also a relatively low level of the researchers’ activity in conducting the implementation projects and writing the popular papers, both in the old and new EU member states

A Planetary Microlensing Event with an Unusually Red Source Star: MOA-2011-BLG-291

We present the analysis of planetary microlensing event MOA-2011-BLG-291, which has a mass ratio of $q=(3.8\pm0.7)\times10^{-4}$ and a source star that is redder (or brighter) than the bulge main sequence. This event is located at a low Galactic latitude in the survey area that is currently planned for NASA's WFIRST exoplanet microlensing survey. This unusual color for a microlensed source star implies that we cannot assume that the source star is in the Galactic bulge. The favored interpretation is that the source star is a lower main sequence star at a distance of $D_S=4.9\pm1.3\,$kpc in the Galactic disk. However, the source could also be a turn-off star on the far side of the bulge or a sub-giant in the far side of the Galactic disk if it experiences significantly more reddening than the bulge red clump stars. However, these possibilities have only a small effect on our mass estimates for the host star and planet. We find host star and planet masses of $M_{\rm host} =0.15^{+0.27}_{-0.10}M_\odot$ and $m_p=18^{+34}_{-12}M_\oplus$ from a Bayesian analysis with a standard Galactic model under the assumption that the planet hosting probability does not depend on the host mass or distance. However, if we attempt to measure the host and planet masses with host star brightness measurements from high angular resolution follow-up imaging, the implied masses will be sensitive to the host star distance. The WFIRST exoplanet microlensing survey is expected to use this method to determine the masses for many of the planetary systems that it discovers, so this issue has important design implications for the WFIRST exoplanet microlensing survey

Avaliação de impacto territorial para operações de revitalização urbana: guia metodológico em contexto de aplicação real

Os processos de monitorização e avaliação das políticas públicas têm vindo a assumir um papel cada vez mais importante na execução dos instrumentos de cofinanciamento da Política de Coesão. Mais do que um conjunto de princípios vertidos na legislação da avaliação dos fundos estruturais, reconhece-se o esforço contínuo para fortalecer estes processos, dotando a avaliação operacional e estratégica das intervenções de uma base empírica mais robusta. Porém, não é possível identificar um roteiro metodológico único, que seja aplicável a todas as áreas e domínios de atuação. A complexidade e especificidade de cada programa e ação requerem uma avaliação mais especializada, mobilizando bases concetuais, teorias e modelos analíticos melhor ajustados aos múltiplos objetivos das intervenções e ao tipo de informação existente e possível de recolher em cada contexto. Para avaliar e gerir o impacto das intervenções no terreno colocam-se desafios acrescidos, que resultam da dificuldade de encontrar métricas ou variáveis que operacionalizem adequadamente indicadores de desempenho dos projetos ou, muitas vezes, da ausência de indicadores de desempenho diretamente relacionados com cada projeto e a sua temática. Este estudo propõe e testa metodologias de avaliação de impacto de intervenções de requalificação urbana, cofinanciadas por programas do Portugal2020 – essencialmente os programas operacionais regionais. Para o efeito, são desenvolvidas e aplicadas duas metodologias complementares, que permitem avaliar os efeitos destas intervenções nas preferências de localização habitacional, tendo por base os mecanismos de mercado de habitação e a análise de preferências reveladas (valor de mercado) e de preferências declaradas (ranking / score de preferências por diferentes atributos urbanísticos). No primeiro caso, a metodologia assenta num modelo de avaliação de impacto contrafactual (AIC), centrado na abordagem da diferença nas diferenças, com o fim de perceber o impacto de intervenções localizadas de revitalização nos preços da habitação das áreas intervencionadas, face a áreas, similares, não intervencionadas. Esta abordagem, aplicada com fins demonstradores ao aglomerado urbano Aveiro-ílhavo,recorre a técnicas de econometria e adota um conjunto de procedimentos que permitam lidar com a natureza geográfica do fenómeno. Uma das inovações metodológicas a apontar centra-se na definição de comparáveis territoriais (unidades de controlo e de tratamento), fundamentais para uma análise contrafactual, onde se aplicaram algoritmos de propagação de rótulos, para identificação e delimitação de unidades territoriais de base, e análise de clusters, para determinação dos comparáveis territoriais. Os resultados demonstram que a evolução dos preços é influenciada pelo fato de um imóvel habitacional pertencer a uma zona de intervenção, tendo o valor destas habitações registado um aumento médio de 1,51€/m2 acima da trajetória expectável. Uma vez que o mercado de habitação pode ser entendido como um elemento redutor na avaliação de preferências da população (só uma ínfima parte da população participa no mercado em cada período de tempo), propõe-se uma proposta metodológica complementar, que procura avaliar a forma como as intervenções de revitalização urbana influenciam as estruturas de preferências dos cidadãos por diferentes ambientes urbanos. Esta proposta aplica os princípios da AIC mas operacionaliza os seus conceitos com o recurso a técnicas de inquirição combinadas com um modelo de análise multicritério. Além de incentivar uma abordagem mais participada no processo de avaliação, este racional promove a integração de uma dimensão mais subjetiva inerente às opiniões e perceções de impacto. Os resultados obtidos, ainda que assentes numa base exploratória, demonstram que os indivíduos apresentam estruturas de preferência rígidas, tendencialmente inalteráveis quando confrontadas com diferentes ambientes urbanos. Uma análise exploratória adicional aos fatores explicativos das preferências declaradas sugere que os territórios intervencionados são os menos atrativos para a localização residencial global da população inquirida e, não obstante observar-se uma clara maioria de inquiridos que consideram que intervenção melhorou o ambiente urbano, a contribuição da intervenção para a explicação da estrutura de preferências é negativa, sugerindo que o tipo concreto de intervenção realizada possa acentuar a menor atratividade destes ambientes urbanos para a localização residencial. Estes últimos resultados apontam para a necessidade de identificar e contemplar outros atributos ou dimensões na modelação e avaliação de impacto de intervenções desta natureza. Por fim, este estudo aponta para a necessidade de definir objetivos concretos dos projetos associando-lhes indicadores de resultado – aspetos que no caso de estudo adotado tiveram de ser inferidos pela equipa de investigação (assunções). As duas abordagens exploratórias, ancoradas em dados reais, permitem uma estratégia flexível de mensuração dos indicadores de resultado, identificando estratégias para responder aos desafios da avaliação contrafactual de intervenções de revitalização urbana, apresentando recomendações metodológicas e técnicas para informar futuros processos de avaliação.The monitoring and evaluation of public policies have been assuming an increasingly important role in the implementation of the co-financing instruments of the Cohesion Policy. More than a mere collection of principles outlined in the legislation for the evaluation of structural funds, there is an ongoing effort to implement better evaluation processes. This involves facilitating operational and strategic assessments of interventions, based on more robust empirical methods. However, it is impossible to identify a single methodological roadmap applicable to all areas and domains of action. The complexity and specificity of each program and action require a more specialized evaluation, mobilizing conceptual bases, theories, and analytical models better suited to the multiple objectives of the interventions and the type of information that is available and possible to collect in each context. Assessing and managing the impact of interventions in practice presents additional challenges, resulting from the difficulty of finding metrics or variables that adequately operationalize performance indicators of the projects or, frequently, from the absence of performance indicators directly related to each project and its subejcts. This study proposes and tests methodologies for evaluating the impact of urban regeneration interventions co-financed by programs under Portugal2020 - essentially the regional operational programs. For this purpose, two complementary methods are developed and applied, allowing the evaluation of the effects of these interventions on housing location preferences based on housing market mechanisms and the analysis of revealed preferences (market value) and stated preferences (ranking/score of preferences for different urban attributes). In the first case, the methodology is based on a counterfactual impact evaluation model (AIC), focused on the difference-in-differences approach, to understand the impact of localized revitalization interventions on housing prices in the surrounding areas, compared to similar nonintervened areas. This approach, applied demonstratively to the Aveiro-ílhavo urban cluster, uses econometric techniques and adopts a set of procedures that deal with the geographical nature of the phenomenon. One of the methodological innovations is the definition of territorial comparables (control and treatment units), which are essential for a counterfactual analysis. And which involved label propagation algorithms, for identifying and delimitating territorial base units, and cluster analysis, for determining territorial comparables. The results demonstrate that the price evolution is influenced by the fact that a residential property belongs to an intervention zone, with the value of these properties experiencing an average increase of €1.51/m2 above the expected trajectory. Since the housing market can be understood as a limiting factor in the evaluation of population preferences (only a tiny portion of the population participates in the market in each period), a complementary methodological proposal is put forward, which seeks to evaluate how urban regeneration interventions influence citizens' preference structures for different urban environments. This proposal applies the principles of AIC but operationalizes its concepts using inquiry techniques combined with multicriteria analysis. In addition to promoting a more participatory approach in the evaluation process, this rationale integrates a more subjective dimension inherent to opinions and perceptions of impact. The results, albeit on an experimental basis, demonstrate that individuals have rigid preference structures, which tend to remain unchanged when confronted with different urban environments. An additional exploratory analysis of the explanatory factors of stated preferences suggests that the intervened territories are less attractive for the general residential location of the surveyed population. Despite a clear majority of respondents classifying the intervention as introducing an improvement in the urban environment, the contribution of the intervention to explaining the preference structure is negative, suggesting that the specific type of intervention carried out may accentuate the lower attractiveness of these urban environments for residential locations. These latest results point to the need to identify and consider other attributes or dimensions in the modeling and impact evaluation of interventions of this nature. Finally, this study emphasizes the need to define specific project objectives and associate them with outcome indicators - aspects that, in the adopted case study, had to be inferred by the research team (assumptions). The two exploratory approaches, grounded in real data, allow for a flexible strategy of measuring outcome indicators, identifying strategies to address the challenges of counterfactual evaluation exercises of urban regeneration interventions, and providing methodological and technical recommendations to guide future evaluation processes.publishe

Evaluation of phthalazinone phosphodiesterase inhibitors with improved activity and selectivity against Trypanosoma cruzi

BACKGROUND: Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, needs urgent alternative therapeutic options as the treatments currently available display severe limitations, mainly related to efficacy and toxicity. OBJECTIVES: As phosphodiesterases (PDEs) have been claimed as novel targets against T. cruzi, our aim was to evaluate the biological aspects of 12 new phthalazinone PDE inhibitors against different T. cruzi strains and parasite forms relevant for human infection. METHODS: In vitro trypanocidal activity of the inhibitors was assessed alone and in combination with benznidazole. Their effects on parasite ultrastructural and cAMP levels were determined. PDE mRNA levels from the different T. cruzi forms were measured by quantitative reverse transcription PCR. RESULTS: Five TcrPDEs were found to be expressed in all parasite stages. Four compounds displayed strong effects against intracellular amastigotes. Against bloodstream trypomastigotes (BTs), three were at least as potent as benznidazole. In vitro combination therapy with one of the most active inhibitors on both parasite forms (NPD-040) plus benznidazole demonstrated a quite synergistic profile (xΣ FICI = 0.58) against intracellular amastigotes but no interaction (xΣ FICI = 1.27) when BTs were assayed. BTs treated with NPD-040 presented disrupted Golgi apparatus, a swollen flagellar pocket and signs of autophagy. cAMP measurements of untreated parasites showed that amastigotes have higher ability to efflux this second messenger than BTs. NPD-001 and NPD-040 increase the intracellular cAMP content in both BTs and amastigotes, which is also released into the extracellular milieu. CONCLUSIONS: The findings demonstrate the potential of PDE inhibitors as anti-T. cruzi drug candidates