Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

Connexin-43 hemichannels orchestrate NOD-like receptor protein-3 (NLRP3) inflammasome activation and sterile inflammation in tubular injury.

Background: Without aviable cure, chronic kidney disease is a global health concern. Inflammatory damage in and around the renal tubules dictates disease severity and is contributed to by multiple cell types. Activated in response to danger associated molecular patterns (DAMPs) including ATP, the NOD-like receptor protein-3 (NLRP3) inflammasome is integral to this inflammation. In vivo, we have previously observed that increased expression of Connexin 43 (Cx43) is linked to inflammation in chronic kidney disease (CKD) whilst in vitro studies in human proximal tubule cells highlight a role for aberrant Cx43 hemichannel mediated ATP release in tubule injury. A role for Cx43 hemichannels in priming and activation of the NLRP3 inflammasome in tubule epithelial cells remains to be determined. Methods Using the Nephroseq database, analysis of unpublished transcriptomic data, examined gene expression and correlation in human CKD. The unilateral ureteral obstruction (UUO) mouse model was combined with genetic (tubule-specific Cx43 knockout) and specific pharmacological blockade of Cx43 (Peptide5), to explore a role for Cx43- hemichannels in tubule damage. Human primary tubule epithelial cells were used as an in vitro model of CKD. Results Increased Cx43 and NLRP3 expression correlates with declining glomerular filtration rate and increased proteinuria in biopsies isolated from patients with CKD. Connexin 43-tubule deletion prior to UUO protected against tubular injury, increased expression of proinflammatory molecules, and significantly reduced NLRP3 expression and downstream signalling mediators. Accompanied by a reduction in F4/80 macrophages and fibroblast specific protein (FSP1+) fibroblasts, Cx43 specific hemichannel blocker Peptide5 conferred similar protection in UUO mice. In vitro, Peptide5 determined that increased Cx43-hemichannel activity primes and activates the NLRP3 inflammasome via ATP-P2X7 receptor signalling culminating in increased secretion of chemokines and cytokines, each of which are elevated in individuals with CKD. Inhibition of NLRP3 and caspase 1 similarly decreased markers of tubular injury, whilst preventing the perpetual increase in Cx43-hemichannel activity. Conclusion Aberrant Cx43-hemichannel activity in kidney tubule cells contributes to tubule inflammation via activation of the NLRP3 inflammasome and downstream paracrine mediated cell signalling. Use of hemichannel blocker

Facing internet fake-medicine and web para-pharmacy in the total absence of official recommendations from medical societies

Purpose: Internet fake information, parapharmacy and counterfeit drugs are a market of hundreds of billion dollars. Misleading internet data decrease patients' compliance to medical care, promote use of questionable and detrimental practices, and jeopardize patient outcome. This is particularly harmful among cancer patients, especially when pain and nutritional aspects are considered. Provision of Web recommendations for the general audience (patients, relatives, general population) from official medical-providers might be useful to outweigh the detrimental internet information produced by non-medical providers. Methods: 370 oncology and anesthesiology related societies were analyzed. Our objective was to evaluate the magnitude of web-recommendation for cancer cachexia and cancer pain for the general audience provided by official medical organizations' web sites at global level. Results: Magnitude of web-recommendations at global level was surprisingly scant both for coverage and consistency. Seven official medical societies provided updated web-recommendation for cancer cachexia to their patients/family members, and 15 for cancer pain. Scantiness was unrelated by continent, developmental index, oncology tradition, economic-geographic area and society type scrutinized. Conclusions: Patients need expert advice when exposed to fake internet information largely dominated by paramedical market profits. In this era of "new media" the patients' net-education represents a new major educational challenge for medical societies

Facing internet fake-medicine and web para-pharmacy in the total absence of official recommendations from medical societies

Purpose: Internet fake information, parapharmacy and counterfeit drugs are a market of hundreds of billion dollars. Misleading internet data decrease patients' compliance to medical care, promote use of questionable and detrimental practices, and jeopardize patient outcome. This is particularly harmful among cancer patients, especially when pain and nutritional aspects are considered. Provision of Web recommendations for the general audience (patients, relatives, general population) from official medical-providers might be useful to outweigh the detrimental internet information produced by non-medical providers. Methods: 370 oncology and anesthesiology related societies were analyzed. Our objective was to evaluate the magnitude of web-recommendation for cancer cachexia and cancer pain for the general audience provided by official medical organizations' web sites at global level. Results: Magnitude of web-recommendations at global level was surprisingly scant both for coverage and consistency. Seven official medical societies provided updated web-recommendation for cancer cachexia to their patients/family members, and 15 for cancer pain. Scantiness was unrelated by continent, developmental index, oncology tradition, economic-geographic area and society type scrutinized. Conclusions: Patients need expert advice when exposed to fake internet information largely dominated by paramedical market profits. In this era of "new media" the patients' net-education represents a new major educational challenge for medical societies

Time Series Retrieval using DTW-Preserving Shapelets

International audienceDynamic Time Warping (DTW) is a very popular similarity measure used for time series classification, retrieval or clustering. DTW is, however, a costly measure, and its application on numerous and/or very long time series is difficult in practice. This paper proposes a new approach for time series retrieval: time series are embedded into another space where the search procedure is less computationally demanding, while still accurate. This approach is based on transforming time series into high-dimensional vectors using DTW-preserving shapelets. That transform is such that the relative distance between the vectors in the Euclidean transformed space well reflects the corresponding DTW measurements in the original space. We also propose strategies for selecting a subset of shapelets in the transformed space, resulting in a trade-off between the complexity of the transformation and the accuracy of the retrieval. Experimental results using the well known UCR time series demonstrate the importance of this trade-off

Additional file 1 of Connexin-43 hemichannels orchestrate NOD-like receptor protein-3 (NLRP3) inflammasome activation and sterile inflammation in tubular injury

Additional file 1: Figure 1. Generation of a transgenic (Pax8-rtTA-cre:cx43 flox Cx43-/-) mouse model. (Panel a) Scheme of the transgenic construct used to delete Cx43 in renal tubular cells. The reverse tetracycline-dependent transactivator (rtTA) drives the expression of Cre recombinase specifically in the renal tubular compartment (controlled by Pax8 promoter) after doxycycline administration. (Panel b) An illustration of the experimental design using WT controls and mice with and without Cx43 tubule-specific deletion, subjected to UUO. Kidneys were collected after 10 days of UUO for RNA extraction, renal morphometry and immunostainings. (Panel c) Connexin 43 immunostainings (in green) were performed on cryosections from injured kidneys of mice with and without Cx43 tubule-specific deletion after 10 days of UUO. Connexin 43 is undetectable in UUO-Cx43-/- mice. Sections were counterstained with Evans Blue (red). (Panel d) Connexin 43 mRNA increased expression was blunted in injured kidneys of mice with Cx43 tubule-specific deletion after 10 days of UUO

Does BCR/ABL1 positive acute myeloid leukaemia exist?

The BCR/ABL1 fusion gene, usually carried by the Philadelphia chromosome (Ph) resulting from t(9;22)(q34;q11) or variants, is pathognomonic for chronic myeloid leukaemia (CML). It is also occasionally found in acute lymphoblastic leukaemia (ALL) mostly in adults and rarely in de novo acute myeloid leukaemia (AML). Array Comparative Genomic Hybridization (aCGH) was used to study six Ph(+)AML, three bi-lineage and four Ph(+)ALL searching for specific genomic profiles. Surprisingly, loss of the IKZF1 and/or CDKN2A genes, the hallmark of Ph(+)ALL, were recurrent findings in Ph(+)AML and accompanied cryptic deletions within the immunoglobulin and T cell receptor genes. The latter two losses have been shown to be part of ‘hot spot’ genome imbalances associated with BCR/ ABL1 positive pre-B lymphoid phenotype in CML and Ph(+)ALL. We applied Significance Analysis of Microarrays (SAM) to data from the ‘hot spot’ regions to the Ph(+)AML and a further 40 BCR/ABL1(+) samples looking for differentiating features. After exclusion of the most dominant markers, SAM identified aberrations unique to de novo Ph(+)AML that involved relevant genes. While the biological and clinical significance of this specific genome signature remains to be uncovered, the unique loss within the immunoglobulin genes provides a simple test to enable the differentiation of clinically similar de novo Ph(+) AML and myeloid blast crisis of CML