Obstacles and levers related to implementing and sustaining innovative pedagogical teachings to meet the needs of primary care and support workers and patients. Descriptive qualitative research

editorial reviewe

cDNA cloning and expression of a hamster α-thrombin receptor coupled to Ca2+ mobilization

AbstractThe serine protease α-thrombin (thrombin) potently stimulates G-protein-coupled signaling pathways and DNA synthesis in CCL39 hamster lung fibroblasts. To clone a thrombin receptor cDNA, selective amplification of mRNA sequences displaying homology to the transmembrane domains of G-protein-coupled receptor genes was performed by polymerase chain reaction. Using reverse transcribed poly(A)+ RNA from CCL39 cells and degenerate primers corresponding to conserved regions of several phospholipase C-coupled receptors, three novel putative receptor sequences were identified. One corresponds to an mRNA transcript of 3.4 kb in CCL39 cells and a relatively abundant cDNA. Microinjection of RNA transcribed in vitro from this cDNA in Xenopus oocytes leads to the expression of a functional thrombin receptor. The hamster thrombin receptor consists of 427 amino acid residues with 8 hydrophobic domains, including one at the extreme N-terminus that is likely to represent a signal peptide. A thrombin consensus cleavage site is present in the N-terminal extracellular region of the receptor sequence followed by a negatively charged cluster of residues present in a number of proteins that interact with the anion-binding exosite of thrombin

Climatic Risk and Distribution Atlas of European Bumblebees

Bumble bees represent one of the most important groups of pollinators. In addition to their ecological and economic relevance, they are also a highly charismatic group which can help to increase the interest of people in realizing, enjoying and conserving natural systems. However, like most animals, bum- ble bees are sensitive to climate. In this atlas, maps depicting potential risks of climate change for bumble bees are shown together with informative summary statistics, ecological back- ground information and a picture of each European species. Thanks to the EU FP7 project STEP, the authors gathered over one million bumblebee records from all over Europe. Based on these data, they modelled the current climatic niche for almost all European species (56 species) and projected future climatically suitable conditions using three climate change scenarios for the years 2050 and 2100. While under a moderate change scenario only 3 species are projected to be at the verge of extinction by 2100, 14 species are at high risk under an intermediate change scenario. Under a most severe change scenario as many as 25 species are projected to lose almost all of their climatically suitable area, while a total of 53 species (77% of the 69 European species) would lose the main part of their suitable area. Climatic risks for bumblebees can be extremely high, depending on the future development of human society, and the corresponding effects on the climate. Strong mitigation strategies are needed to preserve this important species group and to ensure the sustainable provision of pollination services, to which they considerably contribute

HIV-1 drug-resistance patterns among patients on failing treatment in a large number of European countries

Background: Information about patterns of HIV-1 drug resistance among treatment-exposed patients is crucial for the development of novel effective drugs. Currently no system exists that monitors patterns of resistance in patients failing therapy. Methods: The study included 1,988 HIV-1 sequences from patients experiencing therapy failure collected between 2000 and 2004 in 15 European countries. Genotypic resistance was interpreted using the ANRS algorithm. Phenotypic resistance was predicted using the Virco geno- to phenotype system. Results: 80.7% of the sequences included at least one drug-resistance mutation. Mutations were found for NRTIs (73.5%), NNRTIs (48.5%), and protease inhibitors (35.8%). Ninety percent of sequences with genotypic resistance harbored M184V, M41L, K103N, D67N, and/or T215Y. Among NRTIs, resistance was most frequently predicted for lamivudine. About half of all sequences had reduced susceptibility for NNRTIs. Resistance to most boosted protease inhibitors was found in &lt; 25%. No sequence had resistance to all currently available drugs. Conclusion: Levels of resistance among patients with therapy failure were high. The patterns of resistance reflect resistance to drugs available for a longer time. Fully suppressive regimens can be designed even for the most mutated HIV because boosted protease inhibitors have remained active against most circulating viruses and new drug classes have become available.</p

Miser sur Liège Airport, c’est développer notre capacité de nuire

L’ambition actuelle autour de Liège Airport doit être radicalement revue.8. Decent work and economic growth13. Climate action12. Responsible consumption and productio

Cross-validated stepwise regression for identification of novel non-nucleoside reverse transcriptase inhibitor resistance associated mutations

<p>Abstract</p> <p>Background</p> <p>Linear regression models are used to quantitatively predict drug resistance, the phenotype, from the HIV-1 viral genotype. As new antiretroviral drugs become available, new resistance pathways emerge and the number of resistance associated mutations continues to increase. To accurately identify which drug options are left, the main goal of the modeling has been to maximize predictivity and not interpretability. However, we originally selected linear regression as the preferred method for its transparency as opposed to other techniques such as neural networks. Here, we apply a method to lower the complexity of these phenotype prediction models using a 3-fold cross-validated selection of mutations.</p> <p>Results</p> <p>Compared to standard stepwise regression we were able to reduce the number of mutations in the reverse transcriptase (RT) inhibitor models as well as the number of interaction terms accounting for synergistic and antagonistic effects. This reduction in complexity was most significant for the non-nucleoside reverse transcriptase inhibitor (NNRTI) models, while maintaining prediction accuracy and retaining virtually all known resistance associated mutations as first order terms in the models. Furthermore, for etravirine (ETR) a better performance was seen on two years of unseen data. By analyzing the phenotype prediction models we identified a list of forty novel NNRTI mutations, putatively associated with resistance. The resistance association of novel variants at known NNRTI resistance positions: 100, 101, 181, 190, 221 and of mutations at positions not previously linked with NNRTI resistance: 102, 139, 219, 241, 376 and 382 was confirmed by phenotyping site-directed mutants.</p> <p>Conclusions</p> <p>We successfully identified and validated novel NNRTI resistance associated mutations by developing parsimonious resistance prediction models in which repeated cross-validation within the stepwise regression was applied. Our model selection technique is computationally feasible for large data sets and provides an approach to the continued identification of resistance-causing mutations.</p

Oncological patients' reactions to COVID-19 pandemic: A single institution prospective study.

peer reviewedBACKGROUND: The spread of the COVID-19 pandemic has led to a rapid reorganization in all human and hospital activities, with impact on cancer patients. AIM: An analysis of cancer patients fears, and awareness of COVID-19 has been done in this study. METHODS AND RESULTS: We analyzed cancer patients' reactions to the pandemic and their perception of oncological care reorganization, through a 12-item survey, proposed at the peak of pandemic and 3 months later. Overall, 237 patients were included in the study. During the peak of pandemic 34.6% of patients were more worried about COVID-19 than cancer versus 26.4% in the post-acute phase (p = .013). Although 49.8% of patients in the acute phase and 42.3% in the post-acute phase considered their risk of death if infected ≥50%, and more than 70% of patients thought to be at higher risk of complications, the majority of them did not consider the possibility to stop or delay their treatment. Patients were more interested in following news about COVID-19 than cancer and they complied with all preventive measures in more than 90% of the cases. CONCLUSIONS: Although cancer patients worried about COVID-19 and evaluated the risk of complication or death due to COVID-19 as extremely high, they were still asking for the best oncological treatment

CITY AUTOMATED TRANSPORT SYSTEM (CATS): THE LEGACY OF AN INNOVATIVE EUROPEAN PROJECT

CATS is a collaborative European project promoting driverless vehicles that ended in December 2014. This contribution explains how the project evolved, including the handling of unexpected events and concentrating on lessons learned. The constructor and vehicle had to be changed for economic reasons in the middle of the project timeline. A second constructor went bankrupt, although access to his vehicles could be secured. For security and legal reasons, part of the final demonstration was relocated at short notice to the EPFL campus in Lausanne, Switzerland, where around 1600 people were transported during 16 days of vehicle operation. Reactions to the driverless vehicle concept were overwhelmingly positive. Implications for the acceptability of driverless vehicles in Europe and elsewhere are discussed