Multi-resolution anisotropy studies of ultrahigh-energy cosmic rays detected at the Pierre Auger Observatory

We report a multi-resolution search for anisotropies in the arrival directions of cosmic rays detected at the Pierre Auger Observatory with local zenith angles up to $80^\circ$ and energies in excess of 4 EeV ($4 \times 10^{18}$ eV). This search is conducted by measuring the angular power spectrum and performing a needlet wavelet analysis in two independent energy ranges. Both analyses are complementary since the angular power spectrum achieves a better performance in identifying large-scale patterns while the needlet wavelet analysis, considering the parameters used in this work, presents a higher efficiency in detecting smaller-scale anisotropies, potentially providing directional information on any observed anisotropies. No deviation from isotropy is observed on any angular scale in the energy range between 4 and 8 EeV. Above 8 EeV, an indication for a dipole moment is captured; while no other deviation from isotropy is observed for moments beyond the dipole one. The corresponding $p$-values obtained after accounting for searches blindly performed at several angular scales, are $1.3 \times 10^{-5}$ in the case of the angular power spectrum, and $2.5 \times 10^{-3}$ in the case of the needlet analysis. While these results are consistent with previous reports making use of the same data set, they provide extensions of the previous works through the thorough scans of the angular scales.Comment: Published version. Added journal reference and DOI. Added Report Numbe

Calibration of the Logarithmic-Periodic Dipole Antenna (LPDA) Radio Stations at the Pierre Auger Observatory using an Octocopter

An in-situ calibration of a logarithmic periodic dipole antenna with a frequency coverage of 30 MHz to 80 MHz is performed. Such antennas are part of a radio station system used for detection of cosmic ray induced air showers at the Engineering Radio Array of the Pierre Auger Observatory, the so-called Auger Engineering Radio Array (AERA). The directional and frequency characteristics of the broadband antenna are investigated using a remotely piloted aircraft (RPA) carrying a small transmitting antenna. The antenna sensitivity is described by the vector effective length relating the measured voltage with the electric-field components perpendicular to the incoming signal direction. The horizontal and meridional components are determined with an overall uncertainty of 7.4^{+0.9}_{-0.3} % and 10.3^{+2.8}_{-1.7} % respectively. The measurement is used to correct a simulated response of the frequency and directional response of the antenna. In addition, the influence of the ground conductivity and permittivity on the antenna response is simulated. Both have a negligible influence given the ground conditions measured at the detector site. The overall uncertainties of the vector effective length components result in an uncertainty of 8.8^{+2.1}_{-1.3} % in the square root of the energy fluence for incoming signal directions with zenith angles smaller than 60{\deg}.Comment: Published version. Updated online abstract only. Manuscript is unchanged with respect to v2. 39 pages, 15 figures, 2 table

The mortality of colorectal cancer in relation to the initial symptom at presentation to primary care and to the duration of symptoms: a cohort study using medical records

The association between the staging of colorectal cancer and mortality is well known. Much less researched is the relationship between the duration of symptoms and outcome, and whether particular initial symptoms carry a different prognosis. We performed a cohort study of 349 patients with primary colorectal cancer in whom all their prediagnostic symptoms and investigation results were known. Survival data for 3–8 years after diagnosis were taken from the cancer registry. Six features were studied: rectal bleeding, abdominal pain, diarrhoea, constipation, weight loss, and anaemia. Two of these were significantly associated with different staging and mortality. Rectal bleeding as an initial symptom was associated with less advanced staging (odds ratio from one Duke's stage to the next 0.50, 95% confidence interval 0.31, 0.79; P=0.003) and with reduced mortality (Cox's proportional hazard ratio (HR) 0.56 (0.41, 0.79); P=0.001. Mild anaemia, with a haemoglobin of 10.0–12.9 g dl−1, was associated with more advanced staging (odds ratio 2.2 (1.2, 4.3); P=0.021) and worse mortality (HR 1.5 (0.98, 2.3): P=0.064). When corrected for emergency admission, sex, and the site of the tumour, the HR for mild anaemia was 1.7 (1.1, 2.6); P=0.015. No relationship was found between the duration of symptoms and staging or mortality

A prospective study of peri-diagnostic and surgical wait times for patients with presumptive colorectal, lung, or prostate cancer

The objective of this study was to prospectively measure peri-diagnostic and surgical time intervals for patients with suspected colorectal, lung, or prostate cancer. Prospective eligible patients were referred to a regional hospital in Ottawa, Canada between February 2004 and February 2005 for diagnostic assessment of presumptive colorectal, lung, or prostate cancer. Chart abstractions were used to measure nine time intervals; the primary interval was the date of referral for diagnostic assessment to the date the patient was informed of the diagnosis. Health-related quality-of-life (HRQL) was assessed 5 days following the patient being informed of their diagnosis. The median (IQR) time for the primary interval was 71 (30–110), 37 (29–49), and 81 (56–100) days for colorectal, lung, and prostate patients, respectively (Kruskal–Wallis P=0.0001). This interval was significantly less for colorectal patients diagnosed with cancer than for those without cancer (median difference=59.0 days; Wilcoxon P=0.003). No differences in HRQL existed for patients with cancer and those without. Colorectal and prostate patients wait longer between referral for suspected cancer and being informed of their diagnosis than current recommendations. The shorter diagnostic intervals for colorectal patients with cancer suggest clinicians have an effective process for triaging patients referred for diagnostic assessment

A hepatitis B virus causes chronic infections in equids worldwide

Preclinical testing of novel therapeutics for chronic hepatitis B (CHB) requires suitable animal models. Equids host homologs of hepatitis C virus (HCV). Because coinfections of hepatitis B virus (HBV) and HCV occur in humans, we screened 2,917 specimens from equids from five continents for HBV. We discovered a distinct HBV species (Equid HBV, EqHBV) in 3.2% of donkeys and zebras by PCR and antibodies against EqHBV in 5.4% of donkeys and zebras. Molecular, histopathological, and biochemical analyses revealed that infection patterns of EqHBV resembled those of HBV in humans, including hepatotropism, moderate liver damage, evolutionary stasis, and potential horizontal virus transmission. Naturally infected donkeys showed chronic infections resembling CHB with high viral loads of up to 2.6 × 109 mean copies per milliliter serum for >6 mo and weak antibody responses. Antibodies against Equid HCV were codetected in 26.5% of donkeys seropositive for EqHBV, corroborating susceptibility to both hepatitis viruses. Deltavirus pseudotypes carrying EqHBV surface proteins were unable to infect human cells via the HBV receptor NTCP (Na+/taurocholate cotransporting polypeptide), suggesting alternative viral entry mechanisms. Both HBV and EqHBV deltavirus pseudotypes infected primary horse hepatocytes in vitro, supporting a broad host range for EqHBV among equids and suggesting that horses might be suitable for EqHBV and HBV infections in vivo. Evolutionary analyses suggested that EqHBV originated in Africa several thousand years ago, commensurate with the domestication of donkeys. In sum, EqHBV naturally infects diverse equids and mimics HBV infection patterns. Equids provide a unique opportunity for preclinical testing of novel therapeutics for CHB and to investigate HBV/ HCV interplay upon coinfection

Design, upgrade and characterization of the silicon photomultiplier front-end for the AMIGA detector at the Pierre Auger Observatory

AMIGA (Auger Muons and Infill for the Ground Array) is an upgrade of the Pierre Auger Observatory to complement the study of ultra-high-energy cosmic rays (UHECR) by measuring the muon content of extensive air showers (EAS). It consists of an array of 61 water Cherenkov detectors on a denser spacing in combination with underground scintillation detectors used for muon density measurement. Each detector is composed of three scintillation modules, with 10 m$^2$ detection area per module, buried at 2.3 m depth, resulting in a total detection area of 30 m$^2$. Silicon photomultiplier sensors (SiPM) measure the amount of scintillation light generated by charged particles traversing the modules. In this paper, the design of the front-end electronics to process the signals of those SiPMs and test results from the laboratory and from the Pierre Auger Observatory are described. Compared to our previous prototype, the new electronics shows a higher performance, higher efficiency and lower power consumption, and it has a new acquisition system with increased dynamic range that allows measurements closer to the shower core. The new acquisition system is based on the measurement of the total charge signal that the muonic component of the cosmic ray shower generates in the detector.Comment: 40 pages, 33 figure

Influences on pre-hospital delay in the diagnosis of colorectal cancer: a systematic review

Colorectal cancer is a major global health problem, with survival varying according to stage at diagnosis. Delayed diagnosis can result from patient, practitioner or hospital delay. This paper reports the results of a review of the factors influencing pre-hospital delay – the time between a patient first noticing a cancer symptom and presenting to primary care or between first presentation and referral to secondary care. A systematic methodology was applied, including extensive searches of the literature published from 1970 to 2003, systematic data extraction, quality assessment and narrative data synthesis. Fifty-four studies were included. Patients' non-recognition of symptom seriousness increased delay, as did symptom denial. Patient delay was greater for rectal than colon cancers and the presence of more serious symptoms, such as pain, reduced delay. There appears to be no relationship between delay and patients' age, sex or socioeconomic status. Initial misdiagnosis, inadequate examination and inaccurate investigations increased practitioner delay. Use of referral guidelines may reduce delay, although evidence is currently limited. No intervention studies were identified. If delayed diagnosis is to be reduced, there must be increased recognition of the significance of symptoms among patients, and development and evaluation of interventions that are designed to ensure appropriate diagnosis and examination by practitioners

Deep-learning based reconstruction of the shower maximum Xmax using the water-Cherenkov detectors of the Pierre Auger Observatory

The atmospheric depth of the air shower maximum Xmax is an observable commonly used for the determination of the nuclear mass composition of ultra-high energy cosmic rays. Direct measurements of Xmax are performed using observations of the longitudinal shower development with fluorescence telescopes. At the same time, several methods have been proposed for an indirect estimation of Xmax from the characteristics of the shower particles registered with surface detector arrays. In this paper, we present a deep neural network (DNN) for the estimation of Xmax. The reconstruction relies on the signals induced by shower particles in the ground based water-Cherenkov detectors of the Pierre Auger Observatory. The network architecture features recurrent long short-term memory layers to process the temporal structure of signals and hexagonal convolutions to exploit the symmetry of the surface detector array. We evaluate the performance of the network using air showers simulated with three different hadronic interaction models. Thereafter, we account for long-term detector effects and calibrate the reconstructed Xmax using fluorescence measurements. Finally, we show that the event-by-event resolution in the reconstruction of the shower maximum improves with increasing shower energy and reaches less than 25 g/cm2 at energies above 2×1019 eV