2,392 research outputs found

    Unraveling the genetic background of individuals with a clinical familial hypercholesterolemia phenotype

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    Familial hypercholesterolemia (FH) is a common genetic disorder of lipid metabolism caused by pathogenic/likely pathogenic variants in LDLR, APOB, and PCSK9 genes. Variants in FH-phenocopy genes (LDLRAP1, APOE, LIPA, ABCG5, and ABCG8), polygenic hypercholesterolemia, and hyperlipoprotein (a) [Lp(a)] can also mimic a clinical FH phenotype. We aim to present a new diagnostic tool to unravel the genetic background of clinical FH phenotype. Biochemical and genetic study was performed in 1,005 individuals with clinical diagnosis of FH, referred to the Portuguese FH Study. A next-generation sequencing panel, covering eight genes and eight SNPs to determine LDL-C polygenic risk score and LPA genetic score, was validated, and used in this study. FH was genetically confirmed in 417 index cases: 408 heterozygotes and 9 homozygotes. Cascade screening increased the identification to 1,000 FH individuals, including 11 homozygotes. FH-negative individuals (phenotype positive and genotype negative) have Lp(a) >50 mg/dl (30%), high polygenic risk score (16%), other monogenic lipid metabolism disorders (1%), and heterozygous pathogenic variants in FH-phenocopy genes (2%). Heterozygous variants of uncertain significance were identified in primary genes (12%) and phenocopy genes (7%). Overall, 42% of our cohort was genetically confirmed with FH. In the remaining individuals, other causes for high LDL-C were identified in 68%. Hyper-Lp(a) or polygenic hypercholesterolemia may be the cause of the clinical FH phenotype in almost half of FH-negative individuals. A small part has pathogenic variants in ABCG5/ABCG8 in heterozygosity that can cause hypercholesterolemia and should be further investigated. This extended next-generation sequencing panel identifies individuals with FH and FH-phenocopies, allowing to personalize each person’s treatment according to the affected pathway

    Implementa√ß√£o de indicadores de OEE e sustentabilidade para avalia√ß√£o e melhoria dos setores de lava√ß√£o e revestimentos de uma ind√ļstria corticeira

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    Atualmente a ind√ļstria enfrenta momentos de alta competitividade no mercado e de grande exig√™ncia por parte dos clientes. Para que as empresas consigam prosperar neste ambiente competitivo, devem melhorar continuamente os seus processos e consequentemente aumentar a efici√™ncia dos seus equipamentos. Os clientes procuram, cada vez mais, produtos sustent√°veis e amigos do ambiente, pelo que a sustentabilidade √© tamb√©m uma nova grande preocupa√ß√£o da ind√ļstria. O presente projeto de disserta√ß√£o foi realizado na unidade industrial Vasconcelos & Lyncke pertencente √† Amorim Cork, S.A. Esta unidade industrial foca-se na transforma√ß√£o de rolhas de corti√ßa natural e tem vindo a deparar-se com uma baixa efici√™ncia nos setores da lava√ß√£o e dos revestimentos. O presente projeto visa o aumento da efici√™ncia global dos setores da lava√ß√£o e dos revestimentos, bem como a realiza√ß√£o de uma an√°lise √† sustentabilidade global dos processos nos setores mencionados. Inicialmente, realizou-se um estudo aprofundado dos setores da lava√ß√£o e dos revestimentos recorrendo ao c√°lculo dos √≠ndices de Disponibilidade, Performance, Qualidade e consequentemente do Overall Equipment Effectiveness (OEE), bem como dos √≠ndices escolhidos para a Sustentabilidade Ambiental, Financeira e Social. Deste diagnostico, foram identificadas v√°rias oportunidades de melhoria para os setores em estudo. De seguida, foi elaborada uma adapta√ß√£o de um Value Stream Mapping (VSM) onde foram identificadas outras oportunidades de melhoria que n√£o seriam poss√≠veis de verificar atrav√©s dos indicadores acima mencionados. Com as oportunidades de melhoria identificadas, foi criado um plano de a√ß√Ķes onde se interligaram os objetivos a alcan√ßar com a sua prioridade e as solu√ß√Ķes poss√≠veis. As solu√ß√Ķes incidiram maioritariamente na aplica√ß√£o de ferramentas Lean, tais como, SMED, quadro de nivelamento de produ√ß√£o (Heijunka), Gest√£o Visual, normaliza√ß√£o de procedimentos de trabalho, mas tamb√©m na forma√ß√£o e sensibiliza√ß√£o dos operadores e na cria√ß√£o de amostras padr√£o. Ap√≥s a implementa√ß√£o das melhorias propostas, verificou-se um aumento do OEE do setor da lava√ß√£o em 19%, atingindo o valor de 77% em maio. Quanto ao setor dos revestimentos, verificou-se um aumento de 19%, alcan√ßando um valor de 66% no mesmo m√™s. As melhorias implementadas apresentaram um impacto maioritariamente positivo nos indicadores da sustentabilidade. Os resultados obtidos cumprem com os objetivos iniciais da empresa bem como os objetivos a que o presente projeto se prop√īs, sem comprometer gravemente a sua sustentabilidade.Currently, the industry is facing moments of high competitiveness in the market and high customer demands. For companies to thrive in this competitive environment, they must continuously improve their processes and consequently increase the efficiency of their equipment. Customers are gradually looking for sustainable and environmentally friendly products, so sustainability is also a new major concern for the industry. This dissertation project was carried out at the Vasconcelos & Lyncke industrial unit belonging to Amorim Cork, S.A. This industrial unit transforms natural cork stoppers and has been facing low efficiency in the washing and coating sectors. This project aims to increase the global efficiency of the washing and coating sectors, as well as to conduct an analysis of the overall sustainability of the processes carried out in the aforementioned sectors. Initially, an in-depth study of the washing and coating sectors was carried out by calculating the indices of Availability, Performance, Quality and consequently the Overall Equipment Effectiveness (OEE), as well as the indices chosen for Environmental, Financial and Social Sustainability. From this diagnosis, several improvement opportunities were identified for the sectors under study. Next, an adaptation of a Value Stream Mapping (VSM) was elaborated where other improvement opportunities were identified that would not be possible to verify through the indicators mentioned above. With the improvement opportunities identified, an action plan was developed where the objectives were linked to their priority and the possible solutions. These solutions focused mainly on the application of Lean tools, such as SMED, the production levelling table (Heijunka), Visual Management, Standard Work, but also on the training and awareness of operators and the creation of samples. After the implementation of the proposed improvements, the OEE of the washing sector increased by 19%, reaching 77% in May. As for the coatings sector, there was a 20% increase, reaching a value of 66% in the same month. The improvements implemented had a mostly positive impact on the sustainability indicators. The results obtained meet the company's initial goals as well as the goals that this project set for itself, without compromising its sustainability

    Environmental accounting and reporting in Italian local governments: a longitudinal analysis of changes in context, content and process

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    This research aims at contributing to a better understanding of changes in local governments‚Äô accounting and reporting practices. Particularly, ‚Äėwhy‚Äô, ‚Äėwhat‚Äô and ‚Äėhow‚Äô environmental aspects are included and the significance of changes across time. It adopts an interpretative approach to conduct a longitudinal analysis of case studies. Pettigrew and Whipp‚Äôs framework on context, content and process is used as a lens to distinguish changes under each dimension and analyse their interconnections. Data is collected from official documents and triangulated with semi-structured interviews. The legal framework defines as boundaries of the accounting information the territory under local governments‚Äô jurisdiction and their immediate surrounding area. Organisational environmental performance and externalities are excluded from the requirements. An interplay between the local outer context, political commitment and organisational culture justifies the implementation of changes beyond what is regulated and the implementation of transformational changes. Local governments engage in international networks to gain access to funding and implement changes, leading to adopting the dominant environmental agenda. Key stakeholders, like citizens, are not engaged in the accounting and reporting process. Thus, there is no evidence that the environmental aspects addressed and related changes align with stakeholders‚Äô needs and expectations, which jeopardises its significance. Findings from the current research have implications in other EU member states due to the harmonisation of accounting and reporting practices and the common practice across the EU in using external funding to conceptualise and implement changes. This implies that other local governments could also be representing a limited account related to environmental aspects

    Beginnings of the phenomenon of metallic hoards in the current Portuguese territory. The case studies of Espite (Ourém) and Caldelas (Leiria)

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    Disserta√ß√£o de Mestrado em Arqueologia e Territ√≥rio apresentada √† Faculdade de LetrasA presente disserta√ß√£o pretende estudar o fen√≥meno da deposi√ß√£o de artefactos met√°licos (cobre e bronze) nos seus per√≠odos mais recuados ‚Äď Calcol√≠tico e Bronze Inicial/M√©dio ‚Äď no atual territ√≥rio portugu√™s. Constatada a aus√™ncia de estudos de conjunto em torno desta problem√°tica, realizou-se, numa primeira inst√Ęncia, o levantamento e a sistematiza√ß√£o dos dados existentes dispersos pela bibliografia, visando a produ√ß√£o de um cat√°logo o mais representativo poss√≠vel do fen√≥meno em estudo. Tendo por base esse cat√°logo, desenvolveram-se duas abordagens a distintas escalas. Por um lado, efetuou-se a an√°lise do fen√≥meno em todo o territ√≥rio portugu√™s sustentada nas evid√™ncias arqueol√≥gicas reunidas. Por outro, procedeu-se ao estudo monogr√°fico dos dep√≥sitos de Espite (Our√©m) e de Caldelas (Leiria), ambos representativos dos primeiros momentos deste fen√≥meno no territ√≥rio hoje portugu√™s. No estudo desses casos valorizou-se um conjunto de diferentes vertentes como a interpreta√ß√£o da hist√≥ria dos achados e respetiva historiografia, a desloca√ß√£o aos locais de achado e sua caracteriza√ß√£o aproximada, a an√°lise morfo-tipol√≥gica e funcional dos artefactos, e, ainda, a an√°lise arqueometal√ļrgica, concretamente a identifica√ß√£o da composi√ß√£o qu√≠mica dos objetos. Atrav√©s da conjuga√ß√£o dessas duas abordagens procurou-se construir uma primeira s√≠ntese sobre a problem√°tica, atendendo √†s principais particularidades identificadas nos mais antigos dep√≥sitos met√°licos, bem como aos poss√≠veis modelos deposicionais e regionalismos observados a n√≠vel dos conte√ļdos e contextos por todo o territ√≥rio portugu√™s.This dissertation aims to study the phenomenon of the deposition of metallic artefacts (copper and bronze) in its earliest periods - Chalcolithic and Early/Middle Bronze Age - in the current Portuguese territory. Given the lack of studies on this issue, the first step was to survey and systematize the existing data dispersed in the bibliography, in order to produce a catalog as representative as possible of the phenomenon under study. Based on this catalog, two approaches were carried out at different scales. On the one hand, an analysis of the phenomenon in the entire Portuguese territory, supported by the archaeological evidence gathered. On the other hand, a monographic study of the Espite (Our√©m) and Caldelas (Leiria) hoards, both representative of the first moments of this phenomenon in what is now the Portuguese territory. Several different aspects were valued in the study of these cases, such as the interpretation of the history of the finds and the respective historiography, the visit to the sites and their approximate characterization, the analysis of the artefacts in terms of morphology and functionality, and also the archaeometallurgical analysis, namely the identification of the chemical composition of the objects. By combining these two approaches we have tried to build a first synthesis on the issue, taking into account the main particularities identified in the oldest metallic hoards, as well as the possible models and regionalisms observed in terms of hoard contents and contexts throughout the Portuguese territory

    Redu√ß√£o do Consumo Espec√≠fico de Vapor na Unidade de Produ√ß√£o de √ďleos Vegetais e Biodiesel

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    O aumento do consumo de energia e o impacto que este tem causado no ambiente, ao longo do tempo, t√™m pressionado a ind√ļstria a procurar solu√ß√Ķes energ√©ticas eficientes, particularmente, na implementa√ß√£o de medidas de redu√ß√£o dos consumos energ√©ticos. Na maioria das ind√ļstrias, o vapor √© a utilidade mais utilizada como transporte de energia t√©rmica, contudo, este tem um custo relativamente elevado que dever√° ser reduzido. Em 2018, e segundo o Relat√≥rio de Sustentabilidade, a Sovena Oilseeds Portugal, SA, pertencente ao Grupo Sovena, foi respons√°vel por cerca de 54% do consumo energ√©tico do grupo dos quais 50% deveram-se √† produ√ß√£o e consumo desta utilidade. Assim, com o objetivo de reduzir o consumo espec√≠fico de vapor, foram sugeridas a√ß√Ķes de melhoria focadas na identifica√ß√£o e monitoriza√ß√£o do consumo desta utilidade. Por forma a consolidar o conhecimento dos equipamentos consumidores de vapor assim como dos seus caudais, para cada f√°brica (F√°brica 1, F√°brica 2, Refinaria, Pr√©-tratamento e Biodiesel) foram elaboradas folhas de c√°lculo com base no balan√ßo m√°ssico e energ√©tico. Estas estimam o consumo de vapor para cen√°rios de produ√ß√£o distintos e servir√£o como complemento na identifica√ß√£o de eventuais problemas ou inefici√™ncias que possam surgir. No setor da extra√ß√£o de √≥leo vegetais, a f√°brica 1 √© respons√°vel por 29% do consumo total de vapor e a f√°brica 2 por 52%, tendo como principais consumidores os dessolventizadores, os cozedores, os pr√©-cozedores, o expander, o permutador 21E e a coluna 22A. J√° na atividade de produ√ß√£o de biodiesel, respons√°vel por 8% do consumo total, os grandes consumidores s√£o os permutadores de calor 166 E4 e 160 E3 da f√°brica de Biodiesel. A monitoriza√ß√£o dos consumos totais de energia √© uma ferramenta insuficiente para uma correta an√°lise do desempenho do processo, tendo em conta a especificidade da atividade produtiva. Desta forma, o consumo espec√≠fico de energia √© o indicador mais utilizado quando se pretende comparar a efici√™ncia entre diferentes processos ou cen√°rios no fabrico de um determinado produto. De modo a reduzir o consumo de vapor foram sugeridas algumas propostas de melhoria, tais como, instala√ß√£o de um novo permutador de calor e do efluente 0 na extra√ß√£o de √≥leos vegetais, repara√ß√£o ou substitui√ß√£o dos purgadores de vapor com fuga, redu√ß√£o das perdas de calor nas v√°lvulas e amplia√ß√£o da rede de caudal√≠metros, nomeadamente, nos principais consumidores, de forma a eliminar a monitoriza√ß√£o dos consumos energ√©ticos baseada na estimativa. A aplica√ß√£o destas novas medidas traduz-se numa redu√ß√£o do consumo espec√≠fico de vapor de 3%, correspondendo a uma poupan√ßa anual de 8 Mton de vapor e 220 mil ‚ā¨/ano

    Cadomian/Pan-African consolidation of the Iberian Massif assessed by its detrital and inherited zircon populations: is the ~610Ma age peak a persistent Cadomian magmatic inheritance or the key to unravel its Pan-African basement?

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    This work assessed the age distribution of Cadomian/Pan-African orogenic events (550-590 and 605-790Ma, respectively) in several zones of Iberian Massif by means of detrital and inherited zircon analysis compilation. Detrital zircon age spectra show that throughout the late Neoproterozoic-to-Early Ordovician era (~120Ma sedimentary record), the main systematic peak occurs at ~610Ma, followed by peaks at typical Cadomian ages (~590-550Ma). Inherited zircons incorporated in Cambrian-to-Lower Ordovician igneous rocks show typical Cadomian ages (~590-550Ma) but, once again, a remarkably consistent Pan-African ~610Ma peak occurs. In accordance with compiled zircon data and taking into account the evidence of North African peri-cratonic inliers, Ediacaran (~610Ma) zircons incorporated in Paleozoic magmas provide indirect evidence of Pan-African magmatism, suggesting that these magmas and synorogenic sediments are likely to constitute the cryptic stratigraphic infrastructure of most of the Iberian Massif. The main source of ~610Ma inherited zircons may be the lateral chrono-equivalents of the Saghro and Bou Salda-M`Gouna Groups (Anti-Atlas, Morocco) and/or coeval igneous rocks from West African Craton or Trans-Sahara Belt, emplaced at a stratigraphic level below the late-Ediacaran sediments of the Ossa Morena Zone and the Central Iberian Zone. Assuming that the Iberian crust is a fragment of the Pan-African orogen, a relative paleoposition situated between the West African Craton and the Trans-Saharan Belt during the Late Neoproterozoic is proposed. The closed-system behaviour of Stenian-Tonian detrital zircon ages in the Trans-Sahara Belt suggests that this mega-cordillera acted as a barrier, in paleogeographic terms, separating the Sahara Metacraton from Iberia. In Iberia, the opening of the system to Stenian-Tonian detrital zircons during the Ordovician indicates that, at that time, the Trans-Saharan Belt had already become a vast peneplain, which favoured a large drainage system with a long-distance transport mechanism that fed the passive continental margins

    Equine-Assisted Therapeutic Intervention in Institutionalized Children: Case Studies

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    A significant number of institutionalized children have behavior problems. Socio-emotional skills are fundamental for their adaptation and success throughout life and are usually weakened in this population. Equine-assisted services (EAS) are a form of therapeutic mediation that facilitates and requires the practitioner’s participation, contributing to the promotion of various psychomotor and socio-emotional dimensions. This study was developed during 17 sessions of EAS with a psychomotor intervention, which took place individually and weekly and lasted approximately 45 min, with three institutionalized children. A quantitative and qualitative assessment was carried out before and after the intervention to study the effects of an EAS intervention on socio-emotional competencies in the three institutionalized children. There was an improvement in skills, with an impact on intrapersonal skills and marked improvement in self-regulation and self-control, in addition to an improvement in the intentionality of movement and adequacy of gesture to the context. This type of intervention underlies a renewed educational and therapeutic approach, contributing to mental health promotion in this populatio

    Spatiotemporal dynamics of cytokines expression dictate fetal liver hematopoiesis

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    During embryogenesis, yolk-sac and intra-embryonic-derived hematopoietic progenitors, comprising the precursors of adult hematopoietic stem cells, converge into the fetal liver. With a new staining strategy, we defined all non-hematopoietic components of the fetal liver and found that hepatoblasts are the major producers of hematopoietic growth factors. We identified mesothelial cells, a novel component of the stromal compartment, producing Kit ligand, a major hematopoietic cytokine. A high-definition imaging dataset analyzed using a deep-learning based pipeline allowed the unambiguous identification of hematopoietic and stromal populations, and enabled determining a neighboring network composition, at the single cell resolution. Throughout active hematopoiesis, progenitors preferentially associate with hepatoblasts, but not with stellate or endothelial cells. We found that, unlike yolk sac-derived progenitors, intra-embryonic progenitors respond to a chemokine gradient created by CXCL12-producing stellate cells. These results revealed that FL hematopoiesis is a spatiotemporal dynamic process, defined by an environment characterized by low cytokine concentrations

    New Tool for Signal Patients at Risk

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    Introduction: Pancreas transplantation is currently the only treatment that can re-establish normal endocrine pancreatic function. Despite all efforts, pancreas allograft survival and rejection remain major clinical problems. The purpose of this study was to identify features that could signal patients at risk of pancreas allograft rejection. Methods: We collected 74 features from 79 patients who underwent simultaneous pancreas‚Äďkidney transplantation (SPK) and used two widely-applicable classification methods, the Naive Bayesian Classifier and Support Vector Machine, to build predictive models. We used the area under the receiver operating characteristic curve and classification accuracy to evaluate the predictive performance via leave-one-out cross-validation. Results: Rejection events were identified in 13 SPK patients (17.8%). In feature selection approach, it was possible to identify 10 features, namely: previous treatment for diabetes mellitus with long-term Insulin (U/I/day), type of dialysis (peritoneal dialysis, hemodialysis, or pre-emptive), de novo DSA, vPRA_Pre-Transplant (%), donor blood glucose, pancreas donor risk index (pDRI), recipient height, dialysis time (days), warm ischemia (minutes), recipient of intensive care (days). The results showed that the Naive Bayes and Support Vector Machine classifiers prediction performed very well, with an AUROC and classification accuracy of 0.97 and 0.87, respectively, in the first model and 0.96 and 0.94 in the second model. Conclusion: Our results indicated that it is feasible to develop successful classifiers for the prediction of graft rejection. The Naive Bayesian generated nomogram can be used for rejection probability prediction, thus supporting clinical decision making.publishersversionpublishe
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