Contribution of EQA to improve Preanalytical practices by systematic verification of Laboratory Services

International literature describes the preanalytical phase as the most susceptible to errors due to the numerous non automated activities it involves Most EQA organizers offer preanalytical schemes to participants. There are basically three types of surveys procedures registration, samples circulation and errors registration The Portuguese EQA Programme ( provides these type of schemes for 13 years, using as a guide the ISO 15189 2012 In order to improve the evaluation of the preanalytical phase, PNAEQ recently launched two other preanalytical EQA schemes, mystery client and presential audits in 2015 and 2016 respectively. The aim of the mystery client survey is to verify whether the information provided to the patient is constant regardless the day and time or if it is dependent on the collaborator. The aim of the presential audit survey is to give the participants a tool to verify if the procedures performed daily are in accordance with laboratorial good practices recommendations. Conclusions: Results from Mystery Client surveys demonstrate the need for written procedures and harmonization of practices for all collaborators, as more than a third of the responses differed in date/time and operator in a global view. In the Presential Audit surveys we highlight as critical points the results regarding questions 3 5 and 6 as they point to specific problems that occurred during the blood collection procedure, such as operator and patient safety, as well as the quality of the sample collected, suggesting the need to review legal and normative issues and to train collaborators. Participants who use systematically these two methodologies are monitoring some of the requirements of ISO 15189:2012, namely 4. 1.2.6, 4.3, 4.4.1, 4.14, 5.4.2 (both), 5.4.4.2 (mystery client) and 5.1.2, 5.2.2, 5.2.5, 5.3.2.5, 5.3.2.7, 5.4.4 (presential audit), contributing to release reliable results for medical decisions. For the future, we will extend the questions and items in evaluation in these two surveys to Microbiology area and continuing to offer training in Preanalytical matters.N/

Asymptotic behaviour for a class of non-monotone delay differential systems with applications

The paper concerns a class of $n$-dimensional non-autonomous delay differential equations obtained by adding a non-monotone delayed perturbation to a linear homogeneous cooperative system of ordinary differential equations. This family covers a wide set of models used in structured population dynamics. By exploiting the stability and the monotone character of the linear ODE, we establish sufficient conditions for both the extinction of all the populations and the permanence of the system. In the case of DDEs with autonomous coefficients (but possible time-varying delays), sharp results are obtained, even in the case of a reducible community matrix. As a sub-product, our results improve some criteria for autonomous systems published in recent literature. As an important illustration, the extinction, persistence and permanence of a non-autonomous Nicholson system with patch structure and multiple time-dependent delays are analysed.Comment: 26 pages, J Dyn Diff Equat (2017

Analyzing customer profitability in hotels using activity based costing

This paper investigates the use of customer profitability analysis (CPA) in four and five star hotels located in Algarve (Portugal). Traditional accounting systems have been criticized for focusing on product, service or department profitability, and not on customer profitability, thus failing to provide effective information to marketing-related decisions. Results are reported by operating departments, whilst marketing activities focus on customer market segments. Recognizing the growing emphasis on customer value creation, and to overcome the mismatch between the provision and use of information in hotels, CPA techniques have been suggested. Notwithstanding their benefits, namely a strategic focus, hotels still apply traditional techniques. A structured questionnaire collected through personal interviews showed that CPA is far from widespread in hotel management; instead, hotels accumulate costs in profit centers and in cost centers. None of the surveyed hotels had adopted activity based costing, despite this technique being viewed as the most appropriate to calculate individual customer profitability.Este artigo investiga a análise de rendibilidade de clientes nos hotéis de quatro e cinco estrelas do Algarve (Portugal). Os sistemas de contabilidade tradicionais focalizam-se na rendibilidade dos produtos, serviços ou departamentos não fornecendo informação eficaz para decisões de marketing. Os resultados são relatados por departamentos, sendo as atividades de marketing direcionadas para segmentos de mercado. Reconhecendo o foco na criação de valor para o cliente e o “desencontro” entre fornecimento e utilização de informação nos hotéis, a literatura tem sugerido técnicas de análise de rendibilidade de clientes. Apesar dos beneficios destas técnicas, nomeadamente o foco estratégico, os hotéis utilizam técnicas tradicionais. Um questionário estruturado recolhido presencialmente revelou que a técnica CPA está pouco difundida no setor; os hotéis acumulam custos por centros de resultados e por centros de custos. Nenhum adopta o custeio baseado nas actividades, embora seja o método mais apropriado para atribuir custos a clientes.info:eu-repo/semantics/publishedVersio

PNAEQ - 13 years of post-analytical EQAS in Portugal

In the last 13 years, PNAEQ provided a specific program on post-analytical phase. In order to raise the offer of schemes in areas like Thrombosis/ Haemostasis, PNAEQ has established a consortium with ECAT Foundation distributing two more schemes: Post- Analytical Platelet Function and Pre- and Post-Analytical in Haemostasis. Furthermore, five of the analytical schemes organized by PNAEQ include a post-analytical interpretation, such as Blood Morphology, Hemoglobinopathies, Hydatidose, Rubella and Toxoplasmosis. The main objective of implementing specific and integrated programs on post-analytical phase is to evaluate the performance of laboratories on these matters in order to improve their quality service. The specific program on post-analytical phase provided by PNAEQ comprises 6 types of surveys: audits (vertical and presential), case simulation, case-study, document evaluation, quality indicators and questionnaires. Each survey represents a different tool to evaluate several items of the post-analytical process (Table 1), as well as the laboratory collaborators involved in each task (Figure 1). The items in evaluation are annually selected in the PNAEQ Working Group on Pre- and Post-Analytical Phase (created in 2015) and in compliance with the Portuguese Legislation and the ISO 15189:2012(E). Since 2007 PNAEQ has distributed 6 types of tools in the Post-Analytical Phase EQA, stabilizing in 3 of them in the last five years: Audits, Case Simulation and Quality Indicators. The participation rate has been increasing since 2015, which can be due to the multiple actions performed by PNAEQ Working Group on Pre- and Post-Analytical Phase. In addition, the Case Simulation surveys are the most participated (74% average) since the participation depends on PNAEQ. For the future, PNAEQ and the Working Group will work on the continuous update of the tools content distributed in each survey according to international references and the experience of other EQA organizers.N/

Evaluation of the Sigma Quality level for Serum Iron determination by two colorimetric methods, Ferrozine and Ferene S

Iron plays important functions in the body such as the formation and functioning of hemoglobin and it’s disorders are among the most common diseases of human1. It is essential to ensure that its levels determination through laboratory tests are accurate and precise. The participation of laboratories in the External Quality Assessment (EQA) allows the increases of the quality level of the laboratory results and improvement of its performance.2This study was developed in the Portuguese Nacional EQA Program (PNAEQ) concerning the laboratories results from the Clinical Chemistry Scheme. The main objective of this study was to evaluate and improve the sigma quality level regarding the Iron parameter and reduce the variability of the laboratories results participating in the EQA program of Clinical Chemistry of the Nacional External Quality Assessment Program (PNAEQ). The mean Sigma quality level indicated that the Ferrozine method had a better performance compared with Ferene S method. Half of the control samples had a sigma quality level higher than 3.0, which is set as the minimum acceptable quality.3 Despite of the improved of the Sigma quality level in the Pilot Test, the results demonstrated a need to improved the analytical process performance and to identified more potential causes and implement new improvement actions. It becomes necessary to raise awareness with the laboratories, improving the Pilot Test participation frequency, resulting in a recurrent and current assessment of the laboratory activity performance. Developing Six Sigma projects on a periodic basis is important for continuously and progressively increasing the level of Sigma quality in laboratory examinations. The main advantage of quality assessment on the sigma scale is providing evidence of overall laboratory performance, taking into account random and systematic errors.N/

Performance of PNAEQ participant’s results for HIV and HCV infection in the First EQA round 2019

The Portuguese National External Quality Assessment Program (PNAEQ) has been collaborating with Labquality since 2002. One of the first schemes distributed to PNAEQ participants was for HIV laboratory tests, followed by HCV laboratory tests scheme in 2003. A suitable scheme for Point of Care Testing (POCT) is available for HIV since 2012 and for HCV since 2018. Given the burden of HIV and HCV diseases, the Portuguese legislation allows, since 2018, that other locations than laboratories, such as pharmacies and Non-Governmental-Organizations (NGOs), perform tests for detect HIV and HCV infection. For this purpose, and in order to assure reliable results that leads to an early correct diagnostic and a timely treatment, leading to a decrease in the person-to-person transmission of HIV and HCV infection, a specific training to perform POCT for HIV and HCV is mandatory for these entities, as well as the participation in such EQA schemes, namely the PNAEQ-Labquality. The performance of PNAEQ participants for HIV and HCV tests in the First EQA round 2019 was considered in general good. For HIV POCT, the user that reported an undetermined result proceeded correctly requesting a second sample for confirmation. Regarding the two incorrect results reported by laboratories, it is necessary to review the internal validation procedure and revalidation of the laboratory test, and implement corrective and preventive actions. The training of participants that used POCT for the first time proved to be effective in acquiring skills to perform the tests properly. PNAEQ will continue to provide education and training in quality control and motivate all the participants to continuously evaluate the results from the internal quality control and the reports from the external quality assessment.N/

Aspectos motivacionais do sucesso na língua materna

[Resumo] o sucesso na Língua Materna nao depende apenas dos aspectos intelectuais da realização dos alunos, mas também de factores de ordem motivacional, sobretudo de cren~as pessoais acerca da capacidade para realizar adequadamente no domínio verbal, que se apresenta estruturante do sucesso escolar global. Neste estudo é analisada a influencia de duas variáveis motivacionais - auto-conceito académico verbal e concep~5es pessoais de inteligencia - no rendimento em Língua Portuguesa, numa amostra de 452 alunos do 9° ano, utilizando como indicadores do rendimento, as notas do 3° período, as informaçoes dos professores e o raciocínio verbal (avaliado através de um teste objectivo), cujas inter-relaçoes serao também estudadas. Os resultados apontam para a existencia de relaçoes positivas entre as variáveis motivacionais e o rendimento na Língua Portuguesa. Por outro lado, as informações dos professores acerca do desempenho dos alunos apresentam relações mais fortes e positivas com a nota do 3° período do que com o raciocínio verbal, demonstrando que a nota no final do período congrega aspectos objectivos e subjectivos da realização dos alunos

New target therapies in hepatocellular carcinoma : a study in cell lines in culture

Trabalho final do 6º Ano Médico com vista à atribuição do grau de Mestre no âmbito do Ciclo de Estudos de Mestrado Integrado em MedicinaO carcinoma hepatocelular é uma doença complexa e devastadora que se mantém resistente à quimioterapia convencional. O desenvolvimento de fármacos dirigidos às vias moleculares envolvidas na sobrevivência e proliferação das células neoplásicas, bem como a sua associação aos agentes convencionais poderá constituir uma nova abordagem no tratamento do carcinoma hepatocelular. O objectivo do presente estudo consiste na avaliação do potencial terapêutico dos novos fármacos dirigidos a alvos moleculares, nomeadamente os inibidores do proteasoma (MG-262), da farnesiltransferase (L-744832) e do mTOR (Everolimus), em monoterapia e em combinação com os agentes da quimioterapia convencional 5-Fluorouracilo e Doxorrubicina, em células de carcinoma hepatocelular em cultura, HUH-7. Para atingir estes objectivos, as células HUH-7 foram incubadas com concentrações crescentes de MG-262, L-744832 e Everolimus em monoterapia e em associação com 5-Fluorouracilo e Doxorrubicina durante diferentes intervalos de tempo. A viabilidade celular foi avaliada pelo teste Alamar Blue e o tipo de morte celular por microscopia óptica e citometria de fluxo, recorrendo à dupla marcação com anexina V e iodeto de propídio. Os mecanismos moleculares envolvidos na acção e citotoxicidade dos fármacos, nomeadamente, a expressão de conjugados de ubiquitina, lamininas A/C, ciclina D1 e de proteínas relacionadas com a morte celular (BAX e BCL2) foram também analisados por citometria de fluxo através de anticorpos monoclonais ligados a fluorocromos. Os resultados obtidos indicam que o MG-262, o L-744832 e o Everolimus têm um efeito antiproliferativo e citotóxico em monoterapia que varia em função da dose utilizada e do tempo de incubação. Induzem morte celular principalmente por apoptose, a qual poderá estar relacionada com o aumento da razão BAX/BCL-2. Às 48h, o IC50 é, respectivamente, 100nM (MG-262), 77μM (L-744832) e 18μM (Everolimus). A combinação destes fármacos com os agentes terapêuticos convencionais demonstra aumento do efeito antiproliferativo para doses inferiores ao IC50 (sinergismo de adição). Além disso, o efeito citotóxico foi observado apenas nas associações do MG-262 com os fármacos da quimioterapia convencional. Este estudo sugere que os inibidores do proteasoma, os inibidores da farnesiltransferase e os inibidores do mTOR poderão constituir uma alternativa terapêutica no tratamento do carcinoma hepatocelular tanto em monoterapia como em associação com os fármacos convencionais. A escolha de um esquema terapêutico adequado será também crucial para o sucesso do tratamento.Hepatocellular carcinoma is a complex and devastating disease which remains highly resistant to commonly used systemic chemotherapy. Alternative treatment strategies focus on specific pathways involved in malignant cell survival and proliferation, as well as combination of different targeted therapies with conventional anticarcinogenic agents may open new horizons in hepatocellular carcinoma therapy. The aim of the present study is to test the therapeutic potential of new targeted drugs in hepatocellular carcinoma, namely the proteasome (MG-262), farnesiltransferase (L-744832) and m-TOR (Everolimus) inhibitors, in monotherapy and in combination with conventional anticarcinogenic agents, 5-Fluorouracil and Doxorrubicin, in the hepatocellular carcinoma cell line, HUH-7. To attaint this purpose, the HCC cell line, HUH-7 cells, were incubated with increasing concentrations of MG-262, L-744832 and Everolimus, both as single agents and in association with 5-Fluorouracil and Doxorrubicin, during different periods of time. Cell viability was evaluated by the Alamar Blue assay and cell death by optic microscopy and flow citometry using annexin V and propidium iodide incorporation. The molecullar mechanisms involved in drug citotoxicity, namely the expression of ubiquitin conjugates, laminin A/C, cyclin D1 and proteins related to cell death (BAX and BCL2), were analysed by flow cytometry using monoclonal antibodies labeled with fluorochromes. The obtained results show that MG-262, L-744832 and Everolimus have an antiproliferative and cytotoxic effect in monotherapy, depending on the applied dose and incubation period, inducing cell death mainly by apoptosis that may be related with the increase in BAX/BCL-2 ratio. The IC50 at 48h for each drug is: MG-262=100nM, L-744832=77μM, Everolimus=18μM. The combination of MG-262, L-744832 and Everolimus with conventional anticarcinogenic drugs reveals an increase in antiproliferative effect for lower doses than the IC50 (addition synergism). However, the cytotoxic effect is only observed with MG-262 in association with the conventional anticarcinogenic drugs. These results suggest that proteasome, farnesiltransferase and mTOR inhibitors may constitute a new potential therapeutic approach in HCC not only in monotherapy, but also in association with conventional therapies. The choice of an optimal drug schedule will also be crucial to the success of the therapy.This work was supported by a grant from GAPI – Office for Support of Investigational Projects, Faculty of Medicine of the University of Coimbra and Callouste Gulbenkian Foundation, Portugal