A Design Guide for Open Online Courses

This guide is a comprehensive summary of how we went about creating Citizen Maths, an open online maths course and service. The guide shares our design principles and the techniques we used to put them into practice. Our aim is to provide – with the appropriate ‘translation’ – a resource that will be useful to to other teams who are developing online education initiatives

Motesanib inhibits Kit mutations associated with gastrointestinal stromal tumors

<p>Abstract</p> <p>Background</p> <p>Activating mutations in Kit receptor tyrosine kinase or the related platelet-derived growth factor receptor (PDGFR) play an important role in the pathogenesis of gastrointestinal stromal tumors (GIST).</p> <p>Methods</p> <p>This study investigated the activity of motesanib, an inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3; PDGFR; and Kit, against primary activating Kit mutants and mutants associated with secondary resistance to imatinib. Single- and double-mutant isoforms of Kit were evaluated for their sensitivity to motesanib or imatinib in autophosphorylation assays and in Ba/F3 cell proliferation assays.</p> <p>Results</p> <p>Motesanib inhibited Kit autophosphorylation in CHO cell lines expressing primary activating mutations in exon 9 (AYins503-504, IC₅₀= 18 nM) and exon 11 (V560 D, IC₅₀= 5 nM; Δ552-559, IC₅₀= 1 nM). Motesanib also demonstrated activity against kinase domain mutations conferring imatinib resistance (V560D/V654A, IC₅₀= 77 nM; V560D/T670I, IC₅₀= 277 nM; Y823 D, IC₅₀= 64 nM) but failed to inhibit the imatinib-resistant D816V mutant (IC₅₀> 3000 nM). Motesanib suppressed the proliferation of Ba/F3 cells expressing Kit mutants with IC₅₀values in good agreement with those observed in the autophosphorylation assays.</p> <p>Conclusions</p> <p>In conclusion, our data suggest that motesanib possesses inhibitory activity against primary Kit mutations and some imatinib-resistant secondary mutations.</p

The MafA transcription factor becomes essential to islet β-cells soon after birth

The large Maf transcription factors, MafA and MafB, are expressed with distinct spatial-temporal patterns in rodent islet cells. Analysis of Mafa(-/-) and pancreas-specific Mafa(∆panc) deletion mutant mice demonstrated a primary role for MafA in adult β-cell activity, different from the embryonic importance of MafB. Our interests here were to precisely define when MafA became functionally significant to β-cells, to determine how this was affected by the brief period of postnatal MafB production, and to identify genes regulated by MafA during this period. We found that islet cell organization, β-cell mass, and β-cell function were influenced by 3 weeks of age in Mafa(Δpanc) mice and compromised earlier in Mafa(Δpanc);Mafb(+/-) mice. A combination of genome-wide microarray profiling, electron microscopy, and metabolic assays were used to reveal mechanisms of MafA control. For example, β-cell replication was produced by actions on cyclin D2 regulation, while effects on granule docking affected first-phase insulin secretion. Moreover, notable differences in the genes regulated by embryonic MafB and postnatal MafA gene expression were found. These results not only clearly define why MafA is an essential transcriptional regulator of islet β-cells, but also why cell maturation involves coordinated actions with MafB

Biologics for paediatric severe asthma: Trick or TREAT?

No abstract available

A valoração da pesca em águas continentais

A pesca tem sido, e provavelmente continuará sendo, uma importante fonte de alimento e renda para sociedade. Nesse trabalho os autores mostram que o valor econômico total da pesca nem sempre é reconhecido. O valor econômico total (VET) em rios pode ser dividido em valor de uso direto e valor de não-uso/valor de preservação. VET é a soma de todos os valores de uso e não uso, não importando como são derivados. Os autores mostram que há extrema dificuldade de valorar o valor econômico total o que resultado na baixa valoração da pesca para o setor como um todo. A falta de progresso neste campo é resultado do fraco diálogo entre cientistas e os gestores com os especialistas em economia ambiental e ecológica. A importância integral da pesca pode ser abordada a partir do ponto de vista das populações tradicionais e seu modo de vida que depende de vários recursos naturais. A integração de estudos sobre a pesca precisam ser promovida para incentivar o uso sustentável dos recursos aquáticos em geral e da pesca fluvial, em particular e para trazer à luz a real importância do setor pesqueiro para a sociedade

Accuracy of identifying incident stroke cases from linked healthcare data in UK Biobank

Objective In UK Biobank (UKB), a large population-based prospective study, cases of many diseases are ascertained through linkage to routinely collected, coded national health datasets. We assessed the accuracy of these for identifying incident strokes. Methods In a regional UKB subpopulation (n = 17,249), we identified all participants with ≥1 code signifying a first stroke after recruitment (incident stroke-coded cases) in linked hospital admission, primary care, or death record data. Stroke physicians reviewed their full electronic patient records (EPRs) and generated reference standard diagnoses. We evaluated the number and proportion of cases that were true-positives (i.e., positive predictive value [PPV]) for all codes combined and by code source and type. Results Of 232 incident stroke-coded cases, 97% had EPR information available. Data sources were 30% hospital admission only, 39% primary care only, 28% hospital and primary care, and 3% death records only. While 42% of cases were coded as unspecified stroke type, review of EPRs enabled a pathologic type to be assigned in >99%. PPVs (95% confidence intervals) were 79% (73%–84%) for any stroke (89% for hospital admission codes, 80% for primary care codes) and 83% (74%–90%) for ischemic stroke. PPVs for small numbers of death record and hemorrhagic stroke codes were low but imprecise. Conclusions Stroke and ischemic stroke cases in UKB can be ascertained through linked health datasets with sufficient accuracy for many research studies. Further work is needed to understand the accuracy of death record and hemorrhagic stroke codes and to develop scalable approaches for better identifying stroke types

Critical Review of Theoretical Models for Anomalous Effects (Cold Fusion) in Deuterated Metals

We briefly summarize the reported anomalous effects in deuterated metals at ambient temperature, commonly known as "Cold Fusion" (CF), with an emphasis on important experiments as well as the theoretical basis for the opposition to interpreting them as cold fusion. Then we critically examine more than 25 theoretical models for CF, including unusual nuclear and exotic chemical hypotheses. We conclude that they do not explain the data.Comment: 51 pages, 4 Figure

Contrast-Enhanced MR Imaging of Lymph Nodes in Cancer Patients

The accurate identification and characterization of lymph nodes by modern imaging modalities has important therapeutic and prognostic significance for patients with newly diagnosed cancers. The presence of nodal metastases limits the therapeutic options, and it generally indicates a worse prognosis for the patients with nodal metastases. Yet anatomic imaging (CT and MR imaging) is of limited value for depicting small metastatic deposits in normal-sized nodes, and nodal size is a poor criterion when there is no extracapsular extension or focal nodal necrosis to rely on for diagnosing nodal metastases. Thus, there is a need for functional methods that can be reliably used to identify small metastases. Contrast-enhanced MR imaging of lymph nodes is a non-invasive method for the analysis of the lymphatic system after the interstitial or intravenous administration of contrast media. Moreover, some lymphotrophic contrast media have been developed and used for detecting lymph node metastases, and this detection is independent of the nodal size. This article will review the basic principles, the imaging protocols, the interpretation and the accuracies of contrast-enhanced MR imaging of lymph nodes in patients with malignancies, and we also focus on the recent issues cited in the literature. In addition, we discuss the results of several pre-clinical studies and animal studies that were conducted in our institution