332 research outputs found

    When assessment defines the content—understanding goals in between teachers and policy

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    © 2020 The Authors. The Curriculum Journal published by John Wiley & Sons Ltd on behalf of British Educational Research Association.Education policy development internationally reflect a widespread expansion of learning outcome orientation in policy, curricula and assessment. In this paper, teachers’ perceptions about their work are explored, as goals and assessment play a more prominent role driven by the introduction of a learning outcomes‐oriented system. This is investigated through interviews of Norwegian teachers and extensive policy analysis of Norwegian policy documents. The findings indicate that the teachers are finding ways to negotiate and adjust to the language in the policies investigated in this study. Furthermore, the findings show that the teachers have developed their professional language according to the policies. The teachers referred to their self‐made criteria and goal sheets as central tools in explicating what is to be learned. In many ways, the tools for assessment, thus determine the content of education as well as what is valued in the educational system.publishedVersio

    Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone

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    It is recognized that some mutated cancer genes contribute to the development of many cancer types, whereas others are cancer type specific. For genes that are mutated in multiple cancer classes, mutations are usually similar in the different affected cancer types. Here, however, we report exquisite tumor type specificity for different histone H3.3 driver alterations. In 73 of 77 cases of chondroblastoma (95%), we found p.Lys36Met alterations predominantly encoded in H3F3B, which is one of two genes for histone H3.3. In contrast, in 92% (49/53) of giant cell tumors of bone, we found histone H3.3 alterations exclusively in H3F3A, leading to p.Gly34Trp or, in one case, p.Gly34Leu alterations. The mutations were restricted to the stromal cell population and were not detected in osteoclasts or their precursors. In the context of previously reported H3F3A mutations encoding p.Lys27Met and p.Gly34Arg or p.Gly34Val alterations in childhood brain tumors, a remarkable picture of tumor type specificity for histone H3.3 driver alterations emerges, indicating that histone H3.3 residues, mutations and genes have distinct functions

    Genomic evolution of breast cancer metastasis and relapse

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    A.G.L. and J.H.R.F. were supported by a Cancer Research UK Program Grant to Simon Tavaré (C14303/A17197).Patterns of genomic evolution between primary and metastatic breast cancer have not been studied in large numbers, despite patients with metastatic breast cancer having dismal survival. We sequenced whole genomes or a panel of 365 genes on 299 samples from 170 patients with locally relapsed or metastatic breast cancer. Several lines of analysis indicate that clones seeding metastasis or relapse disseminate late from primary tumors, but continue to acquire mutations, mostly accessing the same mutational processes active in the primary tumor. Most distant metastases acquired driver mutations not seen in the primary tumor, drawing from a wider repertoire of cancer genes than early drivers. These include a number of clinically actionable alterations and mutations inactivating SWI-SNF and JAK2-STAT3 pathways.Publisher PDFPeer reviewe

    Gitools: Analysis and Visualisation of Genomic Data Using Interactive Heat-Maps

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    Intuitive visualization of data and results is very important in genomics, especially when many conditions are to be analyzed and compared. Heat-maps have proven very useful for the representation of biological data. Here we present Gitools (http://www.gitools.org), an open-source tool to perform analyses and visualize data and results as interactive heat-maps. Gitools contains data import systems from several sources (i.e. IntOGen, Biomart, KEGG, Gene Ontology), which facilitate the integration of novel data with previous knowledge

    Inhibition of Specific NF-ÎșB Activity Contributes to the Tumor Suppressor Function of 14-3-3σ in Breast Cancer

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    14-3-3σ is frequently lost in human breast cancers by genetic deletion or promoter methylation. We have now investigated the involvement of 14-3-3σ in the termination of NF-ÎșB signal in mammary cells and its putative role in cancer relapse and metastasis. Our results show that 14-3-3σ regulates nuclear export of p65-NF-ÎșB following chronic TNFα stimulation. Restoration of 14-3-3σ in breast cancer cells reduces migration capacity and metastatic abilities in vivo. By microarray analysis, we have identified a genetic signature that responds to TNFα in a 14-3-3σ-dependent manner and significantly associates with different breast and other types of cancer. By interrogating public databases, we have found that over-expression of this signature correlates with poor relapse-free survival in breast cancer patients. Finally, screening of 96 human breast tumors showed that NF-ÎșB activation strictly correlates with the absence of 14-3-3σ and it is significantly associated with worse prognosis in the multivariate analysis. Our findings identify a genetic signature that is important for breast cancer prognosis and for future personalized treatments based on NF-ÎșB targeting

    Resource limitation drives spatial organization in microbial groups.

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    Dense microbial groups such as bacterial biofilms commonly contain a diversity of cell types that define their functioning. However, we have a limited understanding of what maintains, or purges, this diversity. Theory suggests that resource levels are key to understanding diversity and the spatial arrangement of genotypes in microbial groups, but we need empirical tests. Here we use theory and experiments to study the effects of nutrient level on spatio-genetic structuring and diversity in bacterial colonies. Well-fed colonies maintain larger well-mixed areas, but they also expand more rapidly compared with poorly-fed ones. Given enough space to expand, therefore, well-fed colonies lose diversity and separate in space over a similar timescale to poorly fed ones. In sum, as long as there is some degree of nutrient limitation, we observe the emergence of structured communities. We conclude that resource-driven structuring is central to understanding both pattern and process in diverse microbial communities

    Differential clonal evolution in oesophageal cancers in response to neo-adjuvant chemotherapy

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    How chemotherapy affects carcinoma genomes is largely unknown. Here we report whole-exome and deep sequencing of 30 paired oesophageal adenocarcinomas sampled before and after neo-adjuvant chemotherapy. Most, but not all, good responders pass through genetic bottlenecks, a feature associated with higher mutation burden pre-treatment. Some poor responders pass through bottlenecks, but re-grow by the time of surgical resection, suggesting a missed therapeutic opportunity. Cancers often show major changes in driver mutation presence or frequency after treatment, owing to outgrowth persistence or loss of sub-clones, copy number changes, polyclonality and/or spatial genetic heterogeneity. Post-therapy mutation spectrum shifts are also common, particularly C>A and TT>CT changes in good responders or bottleneckers. Post-treatment samples may also acquire mutations in known cancer driver genes (for example, SF3B1, TAF1 and CCND2) that are absent from the paired pre-treatment sample. Neo-adjuvant chemotherapy can rapidly and profoundly affect the oesophageal adenocarcinoma genome. Monitoring molecular changes during treatment may be clinically useful

    BioMart Central Portal: an open database network for the biological community

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    BioMart Central Portal is a first of its kind, community-driven effort to provide unified access to dozens of biological databases spanning genomics, proteomics, model organisms, cancer data, ontology information and more. Anybody can contribute an independently maintained resource to the Central Portal, allowing it to be exposed to and shared with the research community, and linking it with the other resources in the portal. Users can take advantage of the common interface to quickly utilize different sources without learning a new system for each. The system also simplifies cross-database searches that might otherwise require several complicated steps. Several integrated tools streamline common tasks, such as converting between ID formats and retrieving sequences. The combination of a wide variety of databases, an easy-to-use interface, robust programmatic access and the array of tools make Central Portal a one-stop shop for biological data querying. Here, we describe the structure of Central Portal and show example queries to demonstrate its capabilities

    Phylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations.

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    Several studies using genome-wide molecular techniques have reported various degrees of genetic heterogeneity between primary tumours and their distant metastases. However, it has been difficult to discern patterns of dissemination owing to the limited number of patients and available metastases. Here, we use phylogenetic techniques on data generated using whole-exome sequencing and copy number profiling of primary and multiple-matched metastatic tumours from ten autopsied patients to infer the evolutionary history of breast cancer progression. We observed two modes of disease progression. In some patients, all distant metastases cluster on a branch separate from their primary lesion. Clonal frequency analyses of somatic mutations show that the metastases have a monoclonal origin and descend from a common 'metastatic precursor'. Alternatively, multiple metastatic lesions are seeded from different clones present within the primary tumour. We further show that a metastasis can be horizontally cross-seeded. These findings provide insights into breast cancer dissemination
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