1,005 research outputs found

    Developing a French FrameNet: Methodology and First results

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    International audienceThe Asfalda project aims to develop a French corpus with frame-based semantic annotations and automatic tools for shallow semantic analysis. We present the rst part of the project: focusing on a set of notional domains, we delimited a subset of English frames, adapted them to French data when necessary, and developed the corresponding French lexicon. We believe that working domain by domain helped us to enforce the coherence of the resulting resource, and also has the advantage that, though the number of frames is limited (around a hundred), we obtain full coverage within a given domain

    Teaching Turkish‐Dutch kindergartners Dutch vocabulary with a social robot:Does the robot's use of Turkish translations benefit children's Dutch vocabulary learning?

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    Providing first language (L1) translations in L2 vocabulary interventions may be beneficial for L2 vocabulary learning. However, in linguistically diverse L2 classrooms, teachers cannot provide L1 translations to all children. Social robots do offer such opportunities, as they can be programmed to speak any combination of languages. This study investigates whether providing L1 translations in a robot-assisted L2 vocabulary training facilitates children's learning. Participants were Turkish-Dutch kindergartners (n = 67) who were taught six Dutch (L2) words for which they knew the L1 (Turkish), but not the L2 Dutch form. Half of these words were taught by a Turkish-Dutch bilingual robot, alongside their Turkish translations; the other half by a monolingual Dutch robot. Children also completed Dutch and Turkish receptive vocabulary tests. Results of generalized linear regression models indicated better performance in the Dutch-only condition than in the Turkish-Dutch condition. Children with well-developed Turkish and Dutch vocabulary knowledge outperformed children with less well-developed vocabulary knowledge. The majority of children preferred working with the bilingual robot, but children's preference did not affect word learning. Thus, contrary to our prediction, we found no evidence for a facilitating effect of providing L1 translations through a robot on bilingual children's L2 word learning

    Structural and socio-cultural barriers to accessing mental healthcare among Syrian refugees and asylum seekers in Switzerland.

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    Background: Due to their experiences of major stressful life events, including post-displacement stressors, refugees and asylum seekers are vulnerable to developing mental health problems. Yet, despite the availability of specialized mental health services in Western European host countries, refugees and asylum seekers display low mental healthcare utilization. Objective: The aim of this study was to explore structural and socio-cultural barriers to accessing mental healthcare among Syrian refugees and asylum seekers in Switzerland. Method: In this qualitative study, key-informant (KI) interviews with Syrian refugees and asylum seekers, Swiss healthcare providers and other stakeholders (e.g. refugee coordinators or leaders) were conducted in the German-speaking part of Switzerland. Participants were recruited using snowball sampling. Interviews were audiotaped and transcribed, and then analysed using thematic analysis, combining deductive and inductive coding. Results: Findings show that Syrian refugees and asylum seekers face multiple structural and socio-cultural barriers, with socio-cultural barriers being perceived as more pronounced. Syrian key informants, healthcare providers, and other stakeholders identified language, gatekeeper-associated problems, lack of resources, lack of awareness, fear of stigma and a mismatch between the local health system and perceived needs of Syrian refugees and asylum seekers as key barriers to accessing care. Conclusions: The results show that for Syrian refugees and asylum seekers in Switzerland several barriers exist. This is in line with previous findings. A possible solution for the current situation might be to increase the agility of the service system in general and to improve the willingness to embrace innovative paths, rather than adapting mental healthcare services regarding single barriers and needs of a new target population

    Proposal of early CT morphological criteria for response of liver metastases to systemic treatments in gastroenteropancreatic neuroendocrine tumors:Alternatives to RECIST

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    RECIST 1.1 criteria are commonly used with computed tomography (CT) to evaluate the efficacy of systemic treatments in patients with neuroendocrine tumors (NETs) and liver metastases (LMs), but their relevance is questioned in this setting. We aimed to explore alternative criteria using different numbers of measured LMs and thresholds of size and density variation. We retrospectively studied patients with advanced pancreatic or small intestine NETs with LMs, treated with systemic treatment in the first-and/or second-line, without early progression, in 14 European expert centers. We compared time to treatment failure (TTF) between responders and non-responders according to various criteria defined by 0%, 10%, 20% or 30% decrease in the sum of LM size, and/or by 10%, 15% or 20% decrease in LM density, measured on two, three or five LMs, on baseline (≤1 month before treatment initiation) and first revaluation (≤6 months) contrast-enhanced CT scans. Multivariable Cox proportional hazard models were performed to adjust the association between response criteria and TTF on prognostic factors. We included 129 systemic treatments (long-acting somatostatin analogs 41.9%, chemotherapy 26.4%, targeted therapies 31.8%), administered as first-line (53.5%) or second-line therapies (46.5%) in 91 patients. A decrease ≥10% in the size of three LMs was the response criterion that best predicted prolonged TTF, with significance at multivariable analysis (HR 1.90; 95% CI: 1.06–3.40; p =.03). Conversely, response defined by RECIST 1.1 did not predict prolonged TTF (p =.91), and neither did criteria based on changes in LM density. A ≥10% decrease in size of three LMs could be a more clinically relevant criterion than the current 30% threshold utilized by RECIST 1.1 for the evaluation of treatment efficacy in patients with advanced NETs. Its implementation in clinical trials is mandatory for prospective validation. Criteria based on changes in LM density were not predictive of treatment efficacy. Clinical Trial Registration: Registered at CNIL-CERB, Assistance publique hopitaux de Paris as “E-NETNET-L-E-CT” July 2018. No number was assigned. Approved by the Medical Ethics Review Board of University Medical Center Groningen.</p

    A systematic analysis of host factors reveals a Med23-interferon-Îť regulatory axis against herpes simplex virus type 1 replication

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    Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-Îť) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-Îť induction suggests this is the major transcription factor for IFN-Îť expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-Îť secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-Îť3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-Îť, provides evidence for the crucial role of IFN-Îť in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome

    Development of evidence-based clinical practice guidelines (CPGs): comparing approaches

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    <p>Abstract</p> <p>Background</p> <p>While the potential of clinical practice guidelines (CPGs) to support implementation of evidence has been demonstrated, it is not currently being achieved. CPGs are both poorly developed and ineffectively implemented. To improve clinical practice and health outcomes, both well-developed CPGs and effective methods of CPG implementation are needed. We sought to establish whether there is agreement on the fundamental characteristics of an evidence-based CPG development process and to explore whether the level of guidance provided in CPG development handbooks is sufficient for people using these handbooks to be able to apply it.</p> <p>Methods</p> <p>CPG development handbooks were identified through a broad search of published and grey literature. Documents published in English produced by national or international organisations purporting to support development of evidence-based CPGs were included. A list of 14 key elements of a CPG development process was developed. Two authors read each handbook. For each handbook a judgement was made as to how it addressed each element; assigned as: 'mentioned and clear guidance provided', 'mentioned but limited practical detail provided ', or 'not mentioned'.</p> <p>Results</p> <p>Six CPG development handbooks were included. These were produced by the Council of Europe, the National Health and Medical Research Council of Australia, the National Institute for Health and Clinical Excellence in the UK, the New Zealand Guidelines Group, the Scottish Intercollegiate Guideline Network, and the World Health Organization (WHO).</p> <p>There was strong concordance between the handbooks on the key elements of an evidence-based CPG development process. All six of the handbooks require and provide guidance on establishment of a multidisciplinary guideline development group, involvement of consumers, identification of clinical questions or problems, systematic searches for and appraisal of research evidence, a process for drafting recommendations, consultation with others beyond the guideline development group, and ongoing review and updating of the CPG.</p> <p>Conclusion</p> <p>The key elements of an evidence-based CPG development process are addressed with strong concordance by existing CPG development handbooks. Further research is required to determine why these key elements are often not addressed by CPG developers.</p

    Deciphering mollusc shell production: the roles of genetic mechanisms through to ecology, aquaculture and biomimetics

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    Most molluscs possess shells, constructed from a vast array of microstructures and architectures. The fully formed shell is composed of calcite or aragonite. These CaCO3 crystals form complex biocomposites with proteins, which although typically less than 5% of total shell mass, play significant roles in determining shell microstructure. Despite much research effort, large knowledge gaps remain in how molluscs construct and maintain their shells, and how they produce such a great diversity of forms. Here we synthesize results on how shell shape, microstructure, composition and organic content vary among, and within, species in response to numerous biotic and abiotic factors. At the local level, temperature, food supply and predation cues significantly affect shell morphology, whilst salinity has a much stronger influence across latitudes. Moreover, we emphasize how advances in genomic technologies [e.g. restriction site-associated DNA sequencing (RAD-Seq) and epigenetics] allow detailed examinations of whether morphological changes result from phenotypic plasticity or genetic adaptation, or a combination of these. RAD-Seq has already identified single nucleotide polymorphisms associated with temperature and aquaculture practices, whilst epigenetic processes have been shown significantly to modify shell construction to local conditions in, for example, Antarctica and New Zealand. We also synthesize results on the costs of shell construction and explore how these affect energetic trade-offs in animal metabolism. The cellular costs are still debated, with CaCO3 precipitation estimates ranging from 1-2 J/mg to 17-55 J/mg depending on experimental and environmental conditions. However, organic components are more expensive (~29 J/mg) and recent data indicate transmembrane calcium ion transporters can involve considerable costs. This review emphasizes the role that molecular analyses have played in demonstrating multiple evolutionary origins of biomineralization genes. Although these are characterized by lineage-specific proteins and unique combinations of co-opted genes, a small set of protein domains have been identified as a conserved biomineralization tool box. We further highlight the use of sequence data sets in providing candidate genes for in situ localization and protein function studies. The former has elucidated gene expression modularity in mantle tissue, improving understanding of the diversity of shell morphology synthesis. RNA interference (RNAi) and clustered regularly interspersed short palindromic repeats - CRISPR-associated protein 9 (CRISPR-Cas9) experiments have provided proof of concept for use in the functional investigation of mollusc gene sequences, showing for example that Pif (aragonite-binding) protein plays a significant role in structured nacre crystal growth and that the Lsdia1 gene sets shell chirality in Lymnaea stagnalis. Much research has focused on the impacts of ocean acidification on molluscs. Initial studies were predominantly pessimistic for future molluscan biodiversity. However, more sophisticated experiments incorporating selective breeding and multiple generations are identifying subtle effects and that variability within mollusc genomes has potential for adaption to future conditions. Furthermore, we highlight recent historical studies based on museum collections that demonstrate a greater resilience of molluscs to climate change compared with experimental data. The future of mollusc research lies not solely with ecological investigations into biodiversity, and this review synthesizes knowledge across disciplines to understand biomineralization. It spans research ranging from evolution and development, through predictions of biodiversity prospects and future-proofing of aquaculture to identifying new biomimetic opportunities and societal benefits from recycling shell products.FCT: UID/Multi/04326/2019; European Marine Biological Research Infrastructure Cluster-EMBRIC (EU H2020 research and innovation program) 654008; European Union Seventh Framework Programme [FP7] ITN project 'CACHE: Calcium in a Changing Environment' under REA 60505; NERC Natural Environment Research Council NE/J500173/1info:eu-repo/semantics/publishedVersio
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