Theory of didactical situations and instrumental genesis for the design of a cabri elem book

The contributions of two theoretical frameworks (Theory of Didactic Situations and Instrumental Genesis) to the design of a sequence of tasks in the Cabri Elem envi-ronment, where task and technology design are closely linked, are shown. Considering the potential for instrumental genesis as a theory of technology design reveals a fundamental difficulty in dealing with representations. It is hence suggested that the role of the artefact be broadened to include environments, tools, and entities

Satellite passive microwave sea-ice concentration data set inter-comparison for Arctic summer conditions

We report on results of a systematic inter-comparison of 10 global sea-ice concentration (SIC) data products at 12.5 to 50.0 km grid resolution from satellite passive microwave (PMW) observations for the Arctic during summer. The products are compared against SIC and net ice surface fraction (ISF) - SIC minus the per-grid-cell melt pond fraction (MPF) on sea ice - as derived from MODerate resolution Imaging Spectroradiometer (MODIS) satellite observations and observed from ice-going vessels. Like in Kern et al. (2019), we group the 10 products based on the concept of the SIC retrieval used. Group I consists of products of the European Organisation for the Exploitation of Meteorological Satellites (EUMETSAT) Ocean and Sea Ice Satellite Application Facility (OSI SAF) and European Space Agency (ESA) Climate Change Initiative (CCI) algorithms. Group II consists of products derived with the Comiso bootstrap algorithm and the National Oceanographic and Atmospheric Administration (NOAA) National Snow and Ice Data Center (NSIDC) SIC climate data record (CDR). Group III consists of Arctic Radiation and Turbulence Interaction Study (ARTIST) Sea Ice (ASI) and National Aeronautics and Space Administration (NASA) Team (NT) algorithm products, and group IV consists of products of the enhanced NASA Team algorithm (NT2). We find widespread positive and negative differences between PMW and MODIS SIC with magnitudes frequently reaching up to 20 %-25 % for groups I and III and up to 30 %-35 % for groups II and IV. On a pan-Arctic scale these differences may cancel out: Arctic average SIC from group I products agrees with MODIS within 2 %-5 % accuracy during the entire melt period from May through September. Group II and IV products overestimate MODIS Arctic average SIC by 5 %-10 %. Out of group III, ASI is similar to group I products while NT SIC underestimates MODIS Arctic average SIC by 5 %-10 %. These differences, when translated into the impact computing Arctic sea-ice area (SIA), match well with the differences in SIA between the four groups reported for the summer months by Kern et al. (2019). MODIS ISF is systematically overestimated by all products; NT provides the smallest overestimations (up to 25 %) and group II and IV products the largest overestimations (up to 45 %). The spatial distribution of the observed overestimation of MODIS ISF agrees reasonably well with the spatial distribution of the MODIS MPF and we find a robust linear relationship between PMW SIC and MODIS ISF for group I and III products during peak melt, i.e. July and August. We discuss different cases taking into account the expected influence of ice surface properties other than melt ponds, i.e. wet snow and coarse-grained snow/refrozen surface, on brightness temperatures and their ratios used as input to the SIC retrieval algorithms. Based on this discussion we identify the mismatch between the actually observed surface properties and those represented by the ice tie points as the most likely reason for (i) the observed differences between PMW SIC and MODIS ISF and for (ii) the often surprisingly small difference between PMW and MODIS SIC in areas of high melt pond fraction. We conclude that all 10 SIC products are highly inaccurate during summer melt. We hypothesize that the unknown number of melt pond signatures likely included in the ice tie points plays an important role - particularly for groups I and II - and recommend conducting further research in this field

Analysis of hepatitis C virus RNA dimerization and core–RNA interactions

The core protein of hepatitis C virus (HCV) has been shown previously to act as a potent nucleic acid chaperone in vitro, promoting the dimerization of the 3′-untranslated region (3′-UTR) of the HCV genomic RNA, a process probably mediated by a small, highly conserved palindromic RNA motif, named DLS (dimer linkage sequence) [G. Cristofari, R. Ivanyi-Nagy, C. Gabus, S. Boulant, J. P. Lavergne, F. Penin and J. L. Darlix (2004) Nucleic Acids Res., 32, 2623–2631]. To investigate in depth HCV RNA dimerization, we generated a series of point mutations in the DLS region. We find that both the plus-strand 3′-UTR and the complementary minus-strand RNA can dimerize in the presence of core protein, while mutations in the DLS (among them a single point mutation that abolished RNA replication in a HCV subgenomic replicon system) completely abrogate dimerization. Structural probing of plus- and minus-strand RNAs, in their monomeric and dimeric forms, indicate that the DLS is the major if not the sole determinant of UTR RNA dimerization. Furthermore, the N-terminal basic amino acid clusters of core protein were found to be sufficient to induce dimerization, suggesting that they retain full RNA chaperone activity. These findings may have important consequences for understanding the HCV replicative cycle and the genetic variability of the virus

Global patterns of β-diversity along the phylogenetic time-scale : the role of climate and plate tectonics

Aim: We aimed to assess the relative influence of the historical and contemporary processes determining global patterns of current \u3b2-diversity. Specifically, we quantified the relative effects of contemporary climate and historical plate tectonics on \u3b2-diversity at different phylogenetic scales. Location: Global. Time Period: Contemporaneous. Major taxa studied: Mammals and birds. Methods: We analysed the current \u3b2-diversity patterns of birds and mammal assemblages at sequential depths in the phylogeny, that is, from the tips to deeper branches. This was done by slicing bird and mammal phylogenetic trees into 66 time slices of 1 Ma (from 0 to 65 Ma) and recording the branches within each slice. Using global distribution data, we defined the branches\u2019 geographical distribution as the union of the corresponding downstream species distributions. For each time slice, we (a) computed pairwise \u3b2-diversity across all the grid cells for the whole world and (b) estimated the correlation between this \u3b2-diversity matrix and contemporary climatic and geographical distances, and past geological distances, a proxy for plate tectonics. Results: Contemporary climate best explained the \u3b2-diversity of shallow branches (i.e., species). For mammals, the geographical isolation of landmasses generated by plate tectonics best explained the \u3b2-diversity of deeper branches, whereas the effect of past isolation was weaker for birds. Main conclusions: Our study shows that the relative influence of contemporary climate and plate tectonics on the \u3b2-diversity of bird and mammal assemblages varies along the phylogenetic time-scale. Our phylogenetic time-scale approach is general and flexible enough to be applied to a broad spectrum of study systems and spatial scales

Extracorporeal Treatment in Phenytoin Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup

The Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup conducted a systematic literature review using a standardized process to develop evidence-based recommendations on the use of extracorporeal treatment (ECTR) in patients with phenytoin poisoning. The authors reviewed all articles, extracted data, summarized findings, and proposed structured voting statements following a predetermined format. A 2-round modified Delphi method was used to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. 51 articles met the inclusion criteria. Only case reports, case series, and pharmacokinetic studies were identified, yielding a very low quality of evidence. Clinical data from 31 patients and toxicokinetic grading from 46 patients were abstracted. The workgroup concluded that phenytoin is moderately dialyzable (level of evidence = C) despite its high protein binding and made the following recommendations. ECTR would be reasonable in select cases of severe phenytoin poisoning (neutral recommendation, 3D). ECTR is suggested if prolonged coma is present or expected (graded 2D) and it would be reasonable if prolonged incapacitating ataxia is present or expected (graded 3D). If ECTR is used, it should be discontinued when clinical improvement is apparent (graded 1D). The preferred ECTR modality in phenytoin poisoning is intermittent hemodialysis (graded 1D), but hemoperfusion is an acceptable alternative if hemodialysis is not available (graded 1D). In summary, phenytoin appears to be amenable to extracorporeal removal. However, because of the low incidence of irreversible tissue injury or death related to phenytoin poisoning and the relatively limited effect of ECTR on phenytoin removal, the workgroup proposed the use of ECTR only in very select patients with severe phenytoin poisoning

Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire

Idiosyncratic adverse drug reactions are unpredictable, dose independent and potentially life threatening; this makes them a major factor contributing to the cost and uncertainty of drug development. Clinical data suggest that many such reactions involve immune mechanisms, and genetic association studies have identified strong linkage between drug hypersensitivity reactions to several drugs and specific HLA alleles. One of the strongest such genetic associations found has been for the antiviral drug abacavir, which causes severe adverse reactions exclusively in patients expressing the HLA molecular variant B*57:01. Abacavir adverse reactions were recently shown to be driven by drug-specific activation of cytokine-producing, cytotoxic CD8+ T cells that required HLA-B*57:01 molecules for their function. However, the mechanism by which abacavir induces this pathologic T cell response remains unclear. Here we show that abacavir can bind within the F-pocket of the peptide-binding groove of HLA-B*57:01 thereby altering its specificity. This supports a novel explanation for HLA-linked idiosyncratic adverse drug reactions; namely that drugs can alter the repertoire of self-peptides presented to T cells thus causing the equivalent of an alloreactive T cell response. Indeed, we identified specific self-peptides that are presented only in the presence of abacavir, and that were recognized by T cells of hypersensitive patients. The assays we have established can be applied to test additional compounds with suspected HLA linked hypersensitivities in vitro. Where successful, these assays could speed up the discovery and mechanistic understanding of HLA linked hypersensitivities as well as guide the development of safer drugs

‘In the dark’: Voices of parents in marginalised stepfamilies: perceptions and experiences of their parenting support needs

The fastest growing family type in the UK is the stepfamily with social parenting an increasingly normal practice. Parenting policy and practice, which has increased exponentially over the last two decades, has historically been modelled on the biological nuclear family model with marginalised families the main recipients. The possibility that parents in marginalised stepfamilies might have separate and discrete parenting support needs to biological parents seems to be overlooked in policy, practice and research. Rather, the historical legacy of deficit, dysfunction and a ‘whiff’ of poor parenting in marginalised stepfamilies lingers on. The focus of the research was to determine marginalised parents’ perceptions and experiences of parenting in their stepfamily and their parenting support needs. Thematic analysis of the data revealed accounts that were interwoven throughout with strong moral undertones which seemed to categorise their lives. The parenting issues were different and more complex than those they had encountered before. The parents adopted biological family identities, but these didn’t fit with their social roles and often rendered them powerless in their relationships with stepchildren. This appeared to have a cumulative effect which impacted on the already fragile couple relationship. Despite the parents easy articulation of the parenting issues there was a contrasting unease and ambivalence in discussing parenting support needs. Parenting support seemed to be an irrelevance that could be disregarded. Ultimately the moral significance of the parents marginalised class positions appeared to be central to their lives, which has important implications for policy and practice