Core Health Outcomes In Childhood Epilepsy (CHOICE):Protocol for the selection of a core outcome set

This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: There is increasing recognition that establishing a core set of outcomes to be evaluated and reported in trials of interventions for particular conditions will improve the usefulness of health research. There is no established core outcome set for childhood epilepsy. The aim of this work is to select a core outcome set to be used in evaluative research of interventions for children with rolandic epilepsy, as an exemplar of common childhood epilepsy syndromes. METHODS: First we will identify what outcomes should be measured; then we will decide how to measure those outcomes. We will engage relevant UK charities and health professional societies as partners, and convene advisory panels for young people with epilepsy and parents of children with epilepsy. We will identify candidate outcomes from a search for trials of interventions for childhood epilepsy, statutory guidance and consultation with our advisory panels. Families, charities and health, education and neuropsychology professionals will be invited to participate in a Delphi survey following recommended practices in the development of core outcome sets. Participants will be able to recommend additional outcome domains. Over three rounds of Delphi survey participants will rate the importance of candidate outcome domains and state the rationale for their decisions. Over the three rounds we will seek consensus across and between families and health professionals on the more important outcomes. A face-to-face meeting will be convened to ratify the core outcome set. We will then review and recommend ways to measure the shortlisted outcomes using clinical assessment and/or patient-reported outcome measures. DISCUSSION: Our methodology is a proportionate and pragmatic approach to expediently produce a core outcome set for evaluative research of interventions aiming to improve the health of children with epilepsy. A number of decisions have to be made when designing a study to develop a core outcome set including defining the scope, choosing which stakeholders to engage, most effective ways to elicit their views, especially children and a potential role for qualitative research.This study is part of Changing Agendas on Sleep, Treatment and Learning in Childhood Epilepsy (CASTLE), which is funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research RP-PG-0615-20007

Maternal hypothyroidism in mice influences glucose metabolism in adult offspring

International audienceAims/hypothesis: During pregnancy, maternal metabolic disease and hormonal imbalance may alter fetal beta cell development and/or proliferation, thus leading to an increased risk for developing type 2 diabetes in adulthood. Although thyroid hormones play an important role in fetal endocrine pancreas development, the impact of maternal hypothyroidism on glucose homeostasis in adult offspring remains poorly understood.Methods: We investigated this using a mouse model of hypothyroidism, induced by administration of an iodine-deficient diet supplemented with propylthiouracil during gestation.Results: Here, we show that, when fed normal chow, adult mice born to hypothyroid mothers were more glucose-tolerant due to beta cell hyperproliferation (two- to threefold increase in Ki67-positive beta cells) and increased insulin sensitivity. However, following 8 weeks of high-fat feeding, these offspring gained 20% more body weight, became profoundly hyperinsulinaemic (with a 50% increase in fasting insulin concentration), insulin-resistant and glucose-intolerant compared with controls from euthyroid mothers. Furthermore, altered glucose metabolism was maintained in a second generation of animals.Conclusions/interpretation: Therefore, gestational hypothyroidism induces long-term alterations in endocrine pancreas function, which may have implications for type 2 diabetes prevention in affected individuals

Sobre o que se transporta: (Contra)Transferência(s)

No presente trabalho, as autoras propõem-se pensar as noções de transferência e de contratransferência, pensando em malas (continentes de conteúdos) que imigrantes transportavam para um país estrangeiro, realçando o que cada um, terapeuta e paciente transportam na/para/da relação, tendo por base o modelo psicanalítico, pedra basilar na prática da Psicoterapia de Inspiração Psicanalítica.Inicialmente é apresentada uma perspectiva histórica da leitura destes fenómenos transferenciais. Posteriormente, são expostas algumas teorias e perspectivas que, no entender das autoras, descrevem de forma mais completa e mais próxima da realidade o modo como os fenómenos (contra)-transferenciais surgem no setting psicoterapêutico.A clarificação das noções de transferência e de contratransferência, explicitam a sua pertinência para a prática clínica, numa articulação directa com a psicopatologia tal como a podemos entender em termos clássicos, através das noções de Neurose, Patologia Limite e Psicose. Dada a necessidade de olhar para estes conceitos sob um outro prisma quando se trabalha em instituições, as autoras procuraram um (re)significar do encontro terapêutico, reflectindo-se sobre a pertinência da transferência e de contratransferência, quer para a Psicanálise, como para a Psicoterapia de Inspiração Psicanalítica

Open a GLAM lab

Defining a GLAM Lab: A Galleries, Libraries, Archives and Museums (GLAM) Lab is a place for experimenting with digital collections and data. It is where researchers, artists, entrepreneurs, educators and the interested public can collaborate with an engaged group of partners to create new collections, tools, and services that will help transform the future ways in which knowledge and culture are disseminated. The exchanges and experimentation in a Lab are open, iterative and shared widely. This book describes why and how to open a GLAM Lab and encourages participation in a movement that can transform organisations and the communities they partner with. Building a GLAM Lab: Building a GLAM Lab involves defining its core values to guide future work, fostering a culture that is open, transparent, generous, collaborative, creative, inclusive, bold, ethical, accessible and encourages a mindset of exploration. The Lab should be grounded in user-centred and participatory design processes and its staff should be able to clearly communicate what the Lab is about. It's important to think big but start small and establish quick wins to get up and running. GLAM Lab teams: There are recommendations for the qualities and skills to look for in Labs teams, how to go about finding allies within and outside the institution, and ideas on how to create a nurturing environment for teams to thrive in. Labs teams have no optimal size or composition, and its team members can come from all walks of life. Teams need a healthy culture to ensure a well-functioning Lab which might be augmented intermittently by fellows, interns or researchers-inresidence. For a Lab to have lasting impact it must be integrated into the parent organisation and have the support of staff at all levels. User communities: GLAM Labs will need to engage and connect with potential users and partners. This means rethinking these relationships to help establish clear and targeted messages for specific communities. In turn, this enables Labs to adjust their tools, services and collections to establish deeper partnerships based on co-creation, and open and equal dialogue. Rethinking collections and Data: The book discusses the digital collections which are an integral part of Labs. It provides insights on how to share the collections as data, and how to identify, assess, describe, access, and reuse the collections. In addition, there is information about messy and curated data, digitisation, metadata, rights and preservation. Transformation: Experimentation is the critical core of the Lab's process. Insights about how to transform tools into operational services are demonstrated. It shows that experimentation can prepare the organisational culture and services for transformation. There is an examination of funding and the advantages and disadvantages of various models through discussion of the different mechanisms and options that an organisation can apply to Lab set-ups. Funding and Sustainability: We share insights on how to plan for a Lab's sustainability as well as a step-by-step guide for when an organisation is retiring or decommissioning a Lab. Labs have a pivotal role in the transformation of GLAMs and the book highlights the critical importance of Labs in changing the future of digital cultural heritage.Funded by UCL Qatar (Mmember of Qatar Foundation) and Qatar University Library. There has also been support from the British Library Labs, and the Library of Congress Labs

Sobre o que se transporta: (Contra)transferência(s)

No presente trabalho, as autoras propõem-se pensar as noções de transferência e de contratransferência, pensando em malas (continentes de conteúdos) que imigrantes transportavam para um país estrangeiro, realçando o que cada um, terapeuta e paciente transportam na/para/da relação, tendo por base o modelo psicanalítico, pedra basilar na prática da Psicoterapia de Inspiração Psicanalítica. Inicialmente é apresentada uma perspectiva histórica da leitura destes fenómenos transferenciais. Posteriormente, são expostas algumas teorias e perspectivas que, no entender das autoras, descrevem de forma mais completa e mais próxima da realidade o modo como os fenómenos (contra) - transferenciais surgem no setting psicoterapêutico. A clarificação das noções de transferência e de contratransferência, explicitam a sua pertinência para a prática clínica, numa articulação directa com a psicopatologia tal como a podemos entender em termos clássicos, através das noções de Neurose, Patologia Limite e Psicose. Dada a necessidade de olhar para estes conceitos sob um outro prisma quando se trabalha em instituições, as autoras procuraram um (re)significar do encontro terapêutico, reflectindo-se sobre a pertinência da transferência e de contratransferência, quer para a Psicanálise, como para a Psicoterapia de Inspiração Psicanalítica

Endophytic and epiphytic phyllosphere fungal communities are shaped by different environmental factors in a mediterranean ecosystem

The online version of this article (https://doi.org/10.1007/s00248-018-1161-9) contains supplementary material, which is available to authorized users.The diversity and factors influencing fimgal assemblages in phyllosphere of Mediterranean tree species have been barely studied, especially when endophytic and epiphytic communities are simultaneously considered. In this work, the endophytic and epiphytic fungal communities from olive tree phyllosphere were studied. This tree species is natural from the Mediterranean region and adapted to grow under adverse climatic conditions. The main objectives were to determine whether there are differences between both fungal communities and to examine whether different abiotic (climate-related) and biotic (plant organs) factors play a pivotal role in structuring these communities. Both communities differed in size and composition, with epiphytic community being richer and more abundant, displaying also a dominance of melanized fungi. Season was the major driver of community composition, especially of epiphytes. Other drivers shaping epiphytes were wind speed and temperature, while plant organ, rainfall, and temperature were the major drivers for endophytic composition. In contrast, canopy orientation caused slight variations in community composition of fungi, but with distinct effects in spring and autumn seasons. In conclusion, epiphytic and endophytic communities are not driven by the same factors. Several sources of variation undergo complex interactions to form and maintain phyllosphere fungal community in Mediterranean climates. Climatic parameters have influence on these fungal communities, suggesting that they are likely to be affected by climate changes in a near future.This work is funded by FEDER funds through COMPETE (Programa Operacional Factores de Competitividade) and by national funds by FCT (Fundacao para a Ciencia e a Tecnologia) within the framework of the project EXCL/AGR-PRO/0591/2012. T. Gomes thanks FCT, POPH-QREN, and FSE for PhD SFRH/BD/98127/2013 grant

Composition and Function of Haemolymphatic Tissues in the European Common Shrew

BACKGROUND: Studies of wild animals responding to their native parasites are essential if we are to understand how the immune system functions in the natural environment. While immune defence may bring increased survival, this may come at a resource cost to other physiological traits, including reproduction. Here, we tested the hypothesis that wild common shrews (Sorex araneus), which produce large numbers of offspring during the one breeding season of their short life span, forgo investment in immunity and immune system maintenance, as increased longevity is unlikely to bring further opportunities for mating. In particular, we predicted that adult shrews, with shorter expected lifespans, would not respond as effectively as young animals to infection. METHODOLOGY/PRINCIPAL FINDINGS: We examined haemolymphatic tissues from wild-caught common shrews using light and transmission electron microscopy, applied in conjunction with immunohistology. We compared composition and function of these tissues in shrews of different ages, and the extent and type of inflammatory reactions observed in response to natural parasitic infections. All ages seemed able to mount systemic, specific immune responses, but adult shrews showed some signs of lymphatic tissue exhaustion: lymphatic follicles in adults (n = 21) were both smaller than those in sub-adults (n = 18; Wald = 11.1, p<0.05) and exhibited greater levels of depletion (Wald = 13.3, p<0.05). CONCLUSIONS/SIGNIFICANCE: Contrary to our expectations, shrews respond effectively to their natural parasites, and show little indication of immunosenescence as adults. The pancreas of Aselli, a unique lymphoid organ, may aid in providing efficient immune responses through the storage of large numbers of plasma cells. This may allow older animals to react effectively to previously encountered parasites, but infection by novel agents, and eventual depletion of plasma cell reserves, could both still be factors in the near-synchronous mortality of adult shrews observed shortly after breeding

Overexpression of circulating MiR-30b-5p identifies advanced breast cancer

Breast cancer (BrC) remains the leading cause of cancer-related death in women, mainly due to recurrent and/or metastatic events, entailing the need for biomarkers predictive of progression to advanced disease. MicroRNAs hold promise as noninvasive cancer biomarkers due to their inherent stability and resilience in tissues and bodily fluids. There is increasing evidence that specific microRNAs play a functional role at different steps of the metastatic cascade, behaving as signaling mediators to enable the colonization of a specific organ. Herein, we aimed to evaluate the biomarker performance of microRNAs previously reported as associated with prognosis for predicting BrC progression in liquid biopsies. Background Breast cancer (BrC) remains the leading cause of cancer-related death in women, mainly due to recurrent and/or metastatic events, entailing the need for biomarkers predictive of progression to advanced disease. MicroRNAs hold promise as noninvasive cancer biomarkers due to their inherent stability and resilience in tissues and bodily fluids. There is increasing evidence that specific microRNAs play a functional role at different steps of the metastatic cascade, behaving as signaling mediators to enable the colonization of a specific organ. Herein, we aimed to evaluate the biomarker performance of microRNAs previously reported as associated with prognosis for predicting BrC progression in liquid biopsies. Methods Selected microRNAs were assessed using a quantitative reverse transcription-polymerase chain reaction in a testing cohort of formalin-fixed paraffin-embedded primary (n = 16) and metastatic BrC tissues (n = 22). Then, miR-30b-5p and miR-200b-3p were assessed in a validation cohort #1 of formalin-fixed paraffin-embedded primary (n = 82) and metastatic BrC tissues (n = 93), whereas only miR-30b-5p was validated on a validation cohort #2 of liquid biopsies from BrC patients with localized (n = 20) and advanced (n = 25) disease. ROC curve was constructed to evaluate prognostic performance. Results MiR-30b-5p was differentially expressed in primary tumors and paired metastatic lesions, with bone metastases displaying significantly higher miR-30b-5p expression levels, paralleling the corresponding primary tumors. Interestingly, patients with advanced disease disclosed increased circulating miR-30b-5p expression compared to patients with localized BrC. Conclusions MiR-30b-5p might identify BrC patients at higher risk of disease progression, thus, providing a useful clinical tool for patients’ monitoring, entailing earlier and more effective treatment. Nonetheless, validation in larger multicentric cohorts is mandatory to confirm these findings.Research Center of Portuguese Oncology Institute of Porto (PI 74-CI-IPOP-19-2016). JL and CSG are supported by a PhD fellowship from FCT - Fundação para a Ciência e Tecnologia (SFRH/ BD/132751/2017 and SFRH/BD/92786/2013, respectively). SS is supported by a PhD fellowship IPO/ESTIMA-1 NORTE-01-0145-FEDER-000027. BMC is funded by FCT-Fundação para a Ciência e a Tecnologia (IF/00601/2012