Impacts of tourism on coastal areas

The socioeconomics of the Anthropocene are exposing coastal regions to multiple pressures, including climate change hazards, resource degradation, urban development, and inequality. Tourism is often raised as either a panacea to, or exacerbator of, such threats to ecosystems and sustainable livelihoods. To better understand the impacts of tourism on coastal areas, Scopus and Web of Science databases were searched for the top-100 cited papers on coastal tourism. Web of Science suggested ‘highly cited’ papers were also included to allow for more recent high impact papers. Of the papers retrieved, forty-four focused on the impacts of tourism. Social/cultural and environmental impacts were viewed as mostly negative, while economic impacts were viewed as mostly positive but only of actual benefit to a few. In addition, when compared with recent whole-of-sector reviews and reports it was evident that coastal tourism is increasingly a global enterprise dominated by large corporations that leverage various interests across local to transnational scales. Through this global enterprise, even the positive economic benefits identified were overshadowed by a broader system of land and property development fuelling local wealth inequity and furthering the interests of offshore beneficiaries. Only two highly cited papers discussed tourism within a broader context of integrated coastal zone management, suggesting that tourism is mostly assessed as a discrete sector within the coastal zone and peripheral to other coastal management considerations or the global tourism sector as a whole. The findings have relevance to the holistic management of coasts, coastal tourism, and the achievement of sustainable development goals in a way that considers the increasing threats from coastal hazards, resource extraction and urbanisation, as well as the pervasive impacts of international business systems from local to global scales

Impact of EMA regulatory label changes on systemic diclofenac initiation, discontinuation, and switching to other pain medicines in Scotland, England, Denmark, and The Netherlands

Purpose: In June 2013 a European Medicines Agency referral procedure concluded that diclofenac was associated with an elevated risk of acute cardiovascular events and contraindications, warnings, and changes to the product information were implemented across the European Union. This study measured the impact of the regulatory action on the prescribing of systemic diclofenac in Denmark, The Netherlands, England, and Scotland. Methods: Quarterly time series analyses measuring diclofenac prescription initiation, discontinuation and switching to other systemic nonsteroidal anti-inflammatory (NSAIDs), topical NSAIDs, paracetamol, opioids, and other chronic pain medication in those who discontinued diclofenac. Absolute effects were estimated using interrupted time series regression. Results: Overall, diclofenac prescription initiations fell during the observation periods of all countries. Compared with Denmark where there appeared to be amore limited effect, the regulatory action was associated with significant immediate reductions in diclofenac initiation in The Netherlands (−0.42%, 95% CI, −0.66% to −0.18%), England (−0.09%, 95% CI, −0.11% to −0.08%), and Scotland (−0.67%, 95% CI, −0.79% to −0.55%); and falling trends in diclofenac initiation in the Netherlands (−0.03%, 95% CI, −0.06% to −0.01% per quarter) and Scotland (−0.04%, 95% CI, −0.05% to −0.02% per quarter). There was no significant impact on diclofenac discontinuation in any country. The regulatory action was associated with modest differences in switching to other pain medicines following diclofenac discontinuation. Conclusions: The regulatory action was associated with significant reductions in overall diclofenac initiation which varied by country and type of exposure. There was no impact on discontinuation and variable impact on switching

Liver carcinogenesis by FOS-dependent inflammation and cholesterol dysregulation

233294Human hepatocellular carcinomas (HCCs), which arise on a background of chronic liver damage and inflammation, express c-Fos, a component of the AP-1 transcription factor. Using mouse models, we show that hepatocyte-specific deletion of c-Fos protects against diethylnitrosamine (DEN)-induced HCCs, whereas liver-specific c-Fos expression leads to reversible premalignant hepatocyte transformation and enhanced DEN-carcinogenesis. c-Fos-expressing livers display necrotic foci, immune cell infiltration, and altered hepatocyte morphology. Furthermore, increased proliferation, dedifferentiation, activation of the DNA damage response, and gene signatures of aggressive HCCs are observed. Mechanistically, c-Fos decreases expression and activity of the nuclear receptor LXRα, leading to increased hepatic cholesterol and accumulation of toxic oxysterols and bile acids. The phenotypic consequences of c-Fos expression are partially ameliorated by the anti-inflammatory drug sulindac and largely prevented by statin treatment. An inverse correlation between c-FOS and the LXRα pathway was also observed in human HCC cell lines and datasets. These findings provide a novel link between chronic inflammation and metabolic pathways important in liver cancer.We thank Drs. N. Djouder, M. Petruzzelli, R. Ricci, F.X Real, K.D. Bissig, and members of the Wagner laboratory for critical reading of the manuscript and valuable sugges- tions; Dr. H. Schönthaler for help with the bioinformatics analysis; V. Bermeo for technical help; and G. Luque, S. Leceta, and G. Medrano for assisting with mouse experiments. The E.F. Wagner laboratory is supported by grants from the Spanish Ministry of Economy, Industry, and Competitiveness (BFU2012-40230 and SAF2015-70857, co- funded by the European Regional Development Fund), a European Research Council– advanced grant (ERC-FCK/2008/37), and Worldwide Cancer Research (13-0216). R. Hamacher was supported by the Deutsche Forschungsgemeinschaft (HA 6068/1-1), M.K. Thomsen by AUFF Nova, and S.C. Hasenfuss by a Boehringer Ingelheim Fonds PhD fellowship. The authors declare no competing financial interests. Author contributions: L. Bakiri and R. Hamacher designed and performed exper- iments, analyzed data, prepared figures, and wrote the manuscript. O. Graña analyzed RNA-seq and public microarray data, A. Guío-Carrión provided expert technical assis- tance, R. Campos-Olivas acquired and analyzed NMR data, L. Martinez analyzed flow cytometry data, M.K. Thomsen performed experiments with human cell lines, S.C. Hasenfuss performed experiments with primary hepatocytes and data mining, and H.P. Dienes performed pathological analysis on tissue sections. E.F. Wagner directed the study, approved the data, and wrote and edited the paper. All authors read and commented on the manuscript.S

Atom laser coherence and its control via feedback

We present a quantum-mechanical treatment of the coherence properties of a single-mode atom laser. Specifically, we focus on the quantum phase noise of the atomic field as expressed by the first-order coherence function, for which we derive analytical expressions in various regimes. The decay of this function is characterized by the coherence time, or its reciprocal, the linewidth. A crucial contributor to the linewidth is the collisional interaction of the atoms. We find four distinct regimes for the linewidth with increasing interaction strength. These range from the standard laser linewidth, through quadratic and linear regimes, to another constant regime due to quantum revivals of the coherence function. The laser output is only coherent (Bose degenerate) up to the linear regime. However, we show that application of a quantum nondemolition measurement and feedback scheme will increase, by many orders of magnitude, the range of interaction strengths for which it remains coherent.Comment: 15 pages, 6 figures, revtex

Impact of EMA regulatory label changes on hydroxyzine initiation, discontinuation and switching to other medicines in Denmark, Scotland, England and the Netherlands:an interrupted time series regression analysis

Background: Hydroxyzine is indicated for the management of anxiety, skin and sleep disorders. In 2015, the European Medicines Agency (EMA) concluded that hydroxyzine was pro-arrhythmogenic and changes to the product information were implemented in Europe. This study aimed to evaluate their impact in Denmark, Scotland, England and the Netherlands. Method: Quarterly time series analyses measuring hydroxyzine initiation, discontinuation, and switching to other antihistamines, benzodiazepines and antidepressants in Denmark, England, Scotland and the Netherlands from 2009 to 2018. Data were analysed using interrupted time series regression. Results: Hydroxyzine initiation in quarter one 2010 in Denmark, Scotland, England and the Netherlands per 100 000 was: 23.5, 91.5, 35.9 and 34.4 respectively. Regulatory action was associated with a significant: immediate fall in hydroxyzine initiation per 100 000 in England (−12.05, 95%CI −18.47 to −5.63) and Scotland (−19.01, 95%CI −26.99 to −11.02); change to a negative trend in hydroxyzine initiation per 100 000/quarter in England (−1.72, 95%CI −2.69 to −0.75) and Scotland (−2.38, 95%CI −3.32 to −1.44). Regulatory action was associated with a significant: immediate rise in hydroxyzine discontinuation per 100 000 in England (3850, 95%CI 440-7240). No consistent changes were observed in the Netherlands or Denmark. Regulatory action was associated with no switching to other antihistamines, benzodiazepines or antidepressants following hydroxyzine discontinuation in any country. Conclusion: The 2015 EMA regulatory action was associated with heterogeneous impact with reductions in hydroxyzine initiation varying by country. There was limited impact on discontinuation with no strong evidence suggesting unintended consequences of major switching to other antihistamines, benzodiazepines or antidepressants

Responses of marine benthic microalgae to elevated CO<inf>2</inf>

Increasing anthropogenic CO2 emissions to the atmosphere are causing a rise in pCO2 concentrations in the ocean surface and lowering pH. To predict the effects of these changes, we need to improve our understanding of the responses of marine primary producers since these drive biogeochemical cycles and profoundly affect the structure and function of benthic habitats. The effects of increasing CO2 levels on the colonisation of artificial substrata by microalgal assemblages (periphyton) were examined across a CO2 gradient off the volcanic island of Vulcano (NE Sicily). We show that periphyton communities altered significantly as CO2 concentrations increased. CO2 enrichment caused significant increases in chlorophyll a concentrations and in diatom abundance although we did not detect any changes in cyanobacteria. SEM analysis revealed major shifts in diatom assemblage composition as CO2 levels increased. The responses of benthic microalgae to rising anthropogenic CO2 emissions are likely to have significant ecological ramifications for coastal systems. © 2011 Springer-Verlag

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Time Trends of Acrylamide Exposure in Europe: Combined Analysis of Published Reports and Current HBM4EU Studies

More than 20 years ago, acrylamide was added to the list of potential carcinogens found in many common dietary products and tobacco smoke. Consequently, human biomonitoring studies investigating exposure to acrylamide in the form of adducts in blood and metabolites in urine have been performed to obtain data on the actual burden in different populations of the world and in Europe. Recognizing the related health risk, the European Commission responded with measures to curb the acrylamide content in food products. In 2017, a trans-European human biomonitoring project (HBM4EU) was started with the aim to investigate exposure to several chemicals, including acrylamide. Here we set out to provide a combined analysis of previous and current European acrylamide biomonitoring study results by harmonizing and integrating different data sources, including HBM4EU aligned studies, with the aim to resolve overall and current time trends of acrylamide exposure in Europe. Data from 10 European countries were included in the analysis, comprising more than 5500 individual samples (3214 children and teenagers, 2293 adults). We utilized linear models as well as a non-linear fit and breakpoint analysis to investigate trends in temporal acrylamide exposure as well as descriptive statistics and statistical tests to validate findings. Our results indicate an overall increase in acrylamide exposure between the years 2001 and 2017. Studies with samples collected after 2018 focusing on adults do not indicate increasing exposure but show declining values. Regional differences appear to affect absolute values, but not the overall time-trend of exposure. As benchmark levels for acrylamide content in food have been adopted in Europe in 2018, our results may imply the effects of these measures, but only indicated for adults, as corresponding data are still missing for children