OR07-4E-CIGS (VAPORIZERS): A PUBLIC HEALTH OPPORTUNITY THAT WILL BE MISSED?

The most dangerous and deadly form of tobacco consumption, burning and inhaling tobacco cigarettes, is still free. Total eradication will not be possible for many reasons. Cigarettes have the connotation of the free world and prohibition would not only affect and criminalise marginalised people but also well respected members of our societies. So any attempt to curb the cigarette smoking should be welcomed by all exponents of public health. The dangerousness of cigarettes stems from burning tobacco and thus inhaling numerous toxic ingredients. E-cigs avoid the toxic by-products vaporising the nicotine. The public debate on e-cigs is quite bizarre. Should they fall under tobacco or pharmaceutical laws or others? The arguments against e-cigs follow basically 2 lines. Firstly it is contended that 60mg of nicotine are lethal (e.g. in Tobacco Atlas). Nicotine can be lethal but only in doses of 0.5g-1g or more. Secondly it is said that vapouring paves the way to cigarette smoking, which has not been observed despite enormous growth of the e-cig market. Recently Swiss experts spoke out for allowing nicotine containing fluids in a Delphi study under regulations (e.g. no advertising). So far the sale of nicotine containing fluids is forbidden in Switzerlan

P-52SLOW-RELEASE ORAL MORPHINE (SROM) AS FURTHER MEDICATION IN OPIOID SUBTITUTION TREATMENT (OST): RESULTS FROM A REGISTRATION STUDY

Since 50 years oral methadone is the gold standard in OST. However, some of the heroin dependent patients refrain from this kind of treatment due to different reasons (e.g. no injections, limited well-being, excessive sweating). Additionally the prolongation of the QTc poses a clinical problem in double diagnosed patients as many medications that are necessary in the treatment of these patients, add to the QTc prolongation. Unconfirmed reports from different countries suggested that SROM could be a useful addition to the in Switzerland already registered substitution medications methadone, diamorphine, and buprenorphine. In order to test this assumption we conducted a prospective, multi-dose, open label, non-inferiority, cross-over study in a bi-national, multicentre setting over 11 weeks, in which methadone and SROM were compared (ITT population n = 276). Beyond this time-point, the participants were observed another 25 weeks. Main results were: The proportion of heroin-positive urine samples and retention rates under SROM was equal to the ones under methadone. The mean QTc-interval under methadone was significantly longer than that under SROM. Higher treatment satisfaction, fewer cravings for heroin, and lower mental stress were reported by patients under SROM. More Details will be presented. SROM is now registered in Switzerland as an OST medicatio

Hazard assessment of glacial lake outburst floods from Kyagar glacier, Karakoram mountains, China

Kyagar glacier is located in the Chinese Karakoram mountains. The glacier tongue entirely blocks the riverbed in the upper Shaksgam valley and impounds a glacial lake, which was the source of several violent and disastrous glacial lake outburst floods (GLOFs). A GLOF early warning system was implemented between 2011 and 2013. We present an integrative analysis of the hazard potential of Kyagar lake, taking into account the ice flow dynamics of Kyagar glacier as well as the recent surface mass-balance response to climate change. Comparison of two high-resolution digital elevation models (DEMs) for the ice dam shows surface lowering rates of >5 m a–1 between 2002 and 2011, leading to a significant reduction in the maximum potential lake volume. However, two DEMs covering the entire glacier for the period 2000–10 indicate mass gains in its central part, and flow speed measurements show an acceleration in this region. This pattern of local ice-thickness changes combined with varying ice flow velocities is typical for surge-type glaciers. The velocity of the glacier surface and of the ice dam between 2011 and 2012 are analyzed at high temporal and spatial resolution, based on feature tracking of synthetic aperture radar (SAR) images

LncRNA Meg3 protects endothelial function by regulating the DNA damage response

The role of long non-coding RNAs (lncRNAs) in regulating endothelial function through the DNA damage response (DDR) remains poorly understood. In this study, we demonstrate that lncRNA maternally expressed gene 3 (Meg3) interacts with the RNA binding protein polypyrimidine tract binding protein 3 (PTBP3) to regulate gene expression and endothelial function through p53 signaling a major coordinator of apoptosis and cell proliferation triggered by the DDR. Meg3 expression is induced in endothelial cells (ECs) upon p53 activation. Meg3 silencing induces DNA damage, activates p53 signaling, increases the expression of p53 target genes, promotes EC apoptosis, and inhibits EC proliferation. Mechanistically, Meg3 silencing reduces the interaction of p53 with Mdm2, induces p53 expression, and promotes the association of p53 with the promoters of a subset of p53 target genes. PTBP3 silencing recapitulates the effects of Meg3 deficiency on the expression of p53 target genes, EC apoptosis and proliferation. The Meg3-dependent association of PTBP3 with the promoters of p53 target genes suggests that Meg3 and PTBP3 restrain p53 activation. Our studies reveal a novel role of Meg3 and PTBP3 in regulating p53 signaling and endothelial function, which may serve as novel targets for therapies to restore endothelial homeostasis

Analysis of temporal and spatial variations in hydrometeorological elements in the Yarkant River Basin, China

Yarkant River is a tributary of Tarim River in China, and the basin lacks observational data. To investigate past climatic variations and predict future climate changes, precipitation, air temperature and runoff data from Kaqun hydrological station are analysed at monthly and seasonal scales using detrended fluctuation analysis (DFA). Results show that DFA scaling exponents of monthly precipitation, air temperature and runoff are 0.535, 0.662 and 0.582, respectively. These three factors all show long- range correlations. Their increasing trends will continue in the near future as the climate shifts towards warmer and more humid. Spring and winter precipitation exhibit long-range correlations and will increase in the future. In contrast, summer and autumn precipitation exhibits random fluctuations and does not show stable trends. Air temperature during all seasons exhibits long-range correlations and will continue to increase in the future. Runoff during the spring and summer exhibits weak anti- persistence, but autumn and winter runoff show long-range correlations and increasing trends. The vertical distribution of precipitation was first analysed using observed data and climate reanalysis data. It indicates that precipitation increases with elevations below 2,000 m a.s.l. at a rate of 26 mm per 100 m and decreases with elevations above 2,000 m a.s.l

Endothelial cell-specific deletion of a microRNA accelerates atherosclerosis

Background and aims: Chronic vascular endothelial inflammation predisposes to atherosclerosis; however, the cell-autonomous roles for endothelial-expressing microRNAs (miRNAs) are poorly understood in this process. MiR-181b is expressed in several cellular constituents relevant to lesion formation. The aim of this study is to examine the role of genetic deficiency of the miR-181b locus in endothelial cells during atherogenesis. Methods and Results: Using a proprotein convertase subtilisin/kexin type 9 (PCSK9)-induced atherosclerosis mouse model, we demonstrated that endothelial cell (EC)-specific deletion of miR-181a2b2 significantly promoted atherosclerotic lesion formation, cell adhesion molecule expression, and the influx of lesional macrophages in the vessel wall. Yet, endothelium deletion of miR-181a2b2 did not affect body weight, lipid metabolism, anti-inflammatory Ly6Clow or the pro-inflammatory Ly6Cinterm and Ly6Chigh fractions in circulating peripheral blood mononuclear cells (PBMCs), and pro-inflammatory or anti-inflammatory mediators in both bone marrow (BM) and PBMCs. Mechanistically, bulk RNA-seq and gene set enrichment analysis of ECs enriched from the aortic arch intima, as well as single cell RNA-seq from atherosclerotic lesions, revealed that endothelial miR-181a2b2 serves as a critical regulatory hub in controlling endothelial inflammation, cell adhesion, cell cycle, and immune response during atherosclerosis. Conclusions: Our study establishes that deficiency of a miRNA specifically in the vascular endothelium is sufficient to profoundly impact atherogenesis. Endothelial miR-181a2b2 deficiency regulates multiple key pathways related to endothelial inflammation, cell adhesion, cell cycle, and immune response involved in the development of atherosclerosis

The State of Remote Sensing Capabilities of Cascading Hazards Over High Mountain Asia

Cascading hazard processes refer to a primary trigger such as heavy rainfall, seismic activity, or snow melt, followed by a chain or web of consequences that can cause subsequent hazards influenced by a complex array of preconditions and vulnerabilities. These interact in multiple ways and can have tremendous impacts on populations proximate to or downstream of these initial triggers. High Mountain Asia (HMA) is extremely vulnerable to cascading hazard processes given the tectonic, geomorphologic, and climatic setting of the region, particularly as it relates to glacial lakes. Given the limitations of in situ surveys in steep and often inaccessible terrain, remote sensing data are a valuable resource for better understanding and quantifying these processes. The present work provides a survey of cascading hazard processes impacting HMA and how these can be characterized using remote sensing sources. We discuss how remote sensing products can be used to address these process chains, citing several examples of cascading hazard scenarios across HMA. This work also provides a perspective on the current gaps and challenges, community needs, and view forward toward improved characterization of evolving hazards and risk across HMA