Evidence for a mixed mass composition at the `ankle' in the cosmic-ray spectrum

We report a first measurement for ultra-high energy cosmic rays of the correlation between the depth of shower maximum and the signal in the water Cherenkov stations of air-showers registered simultaneously by the fluorescence and the surface detectors of the Pierre Auger Observatory. Such a correlation measurement is a unique feature of a hybrid air-shower observatory with sensitivity to both the electromagnetic and muonic components. It allows an accurate determination of the spread of primary masses in the cosmic-ray flux. Up till now, constraints on the spread of primary masses have been dominated by systematic uncertainties. The present correlation measurement is not affected by systematics in the measurement of the depth of shower maximum or the signal in the water Cherenkov stations. The analysis relies on general characteristics of air showers and is thus robust also with respect to uncertainties in hadronic event generators. The observed correlation in the energy range around the `ankle' at $\lg(E/{\rm eV})=18.5-19.0$ differs significantly from expectations for pure primary cosmic-ray compositions. A light composition made up of proton and helium only is equally inconsistent with observations. The data are explained well by a mixed composition including nuclei with mass $A > 4$. Scenarios such as the proton dip model, with almost pure compositions, are thus disfavoured as the sole explanation of the ultrahigh-energy cosmic-ray flux at Earth.Comment: Published version. Added journal reference and DOI. Added Report Numbe

Epstein-Barr virus: clinical and epidemiological revisits and genetic basis of oncogenesis

Epstein-Barr virus (EBV) is classified as a member in the order herpesvirales, family herpesviridae, subfamily gammaherpesvirinae and the genus lymphocytovirus. The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4). It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature. It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus. Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis. Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors. EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitt's lymphoma (BL), Hodgkin's disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g. Peripheral T-cell lymphomas; PTCL and Anaplastic large cell lymphomas; ALCL). It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL). In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs). Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBV- associated tumors. We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancie

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings: The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p<0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding: Novo Nordisk, Denmark

The Pierre Auger Observatory Status And Latest Results

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Astrophysical Interpretation Of Pierre Auger Observatory Measurements Of The Uhecr Energy Spectrum And Mass Composition

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Evidence For A Mixed Mass Composition At The ‘ankle’ In The Cosmic-ray Spectrum

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An Indication of Anisotropy in Arrival Directions of Ultra-high-energy Cosmic Rays through Comparison to the Flux Pattern of Extragalactic Gamma-Ray Sources

A new analysis of the data set from the Pierre Auger Observatory provides evidence for anisotropy in the arrival directions of ultra-high-energy cosmic rays on an intermediate angular scale, which is indicative of excess arrivals from strong, nearby sources. The data consist of 5514 events above 20 EeV with zenith angles up to 80 degrees. recorded before 2017 April 30. Sky models have been created for two distinct populations of extragalactic gamma-ray emitters: active galactic nuclei from the second catalog of hard Fermi-LAT sources (2FHL) and starburst galaxies from a sample that was examined with Fermi-LAT. Flux-limited samples, which include all types of galaxies from the Swift-BAT and 2MASS surveys, have been investigated for comparison. The sky model of cosmic-ray density constructed using each catalog has two free parameters, the fraction of events correlating with astrophysical objects, and an angular scale characterizing the clustering of cosmic rays around extragalactic sources. A maximum-likelihood ratio test is used to evaluate the best values of these parameters and to quantify the strength of each model by contrast with isotropy. It is found that the starburst model fits the data better than the hypothesis of isotropy with a statistical significance of 4.0 sigma, the highest value of the test statistic being for energies above 39 EeV. The three alternative models are favored against isotropy with 2.7 sigma-3.2 sigma significance. The origin of the indicated deviation from isotropy is examined and prospects for more sensitive future studies are discussed

A Targeted Search for Point Sources of EeV Photons with the Pierre Auger Observatory

Simultaneous measurements of air showers with the fluorescence and surface detectors of the Pierre Auger Observatory allow a sensitive search for EeV photon point sources. Several Galactic and extragalactic candidate objects are grouped in classes to reduce the statistical penalty of many trials from that of a blind search and are analyzed for a significant excess above the background expectation. The presented search does not find any evidence for photon emission at candidate sources, and combined p-values for every class are reported. Particle and energy flux upper limits are given for selected candidate sources. These limits significantly constrain predictions of EeV proton emission models from non-transient Galactic and nearby extragalactic sources, as illustrated for the particular case of the Galactic center region

Inferences on mass composition and tests of hadronic interactions from 0.3 to 100 EeV using the water-Cherenkov detectors of the Pierre Auger Observatory

We present a new method for probing the hadronic interaction models at ultrahigh energy and extracting details about mass composition. This is done using the time profiles of the signals recorded with the water-Cherenkov detectors of the Pierre Auger Observatory. The profiles arise from a mix of the muon and electromagnetic components of air showers. Using the risetimes of the recorded signals, we define a new parameter, which we use to compare our observations with predictions from simulations. We find, first, inconsistencies between our data and predictions over a greater energy range and with substantially more events than in previous studies. Second, by calibrating the new parameter with fluorescence measurements from observations made at the Auger Observatory, we can infer the depth of shower maximum Xmax for a sample of over 81,000 events extending from 0.3 to over 100 EeV. Above 30 EeV, the sample is nearly 14 times larger than what is currently available from fluorescence measurements and extending the covered energy range by half a decade. The energy dependence of ?Xmaxcopyright is compared to simulations and interpreted in terms of the mean of the logarithmic mass. We find good agreement with previous work and extend the measurement of the mean depth of shower maximum to greater energies than before, reducing significantly the statistical uncertainty associated with the inferences about mass composition