Fibrosis of Peritoneal Membrane, Molecular Indicators of Aging and Frailty Unveil Vulnerable Patients in Long-Term Peritoneal Dialysis

Funding: Sociedade Portuguesa de Nefrologia (SPN) SPN funded a project and Ana Rita Martins, MD, Nephrology fellow, for a residence at Jiménez Díaz Foundation University Hospital, Madrid under the scope of novel serum biomarkers of CKD. iNOVA4Health research program (UIDP/04462/2020) is also acknowledged to support J.M.Peritoneal membrane status, clinical data and aging-related molecules were investigated as predictors of long-term peritoneal dialysis (PD) outcomes. A 5-year prospective study was conducted with the following endpoints: (a) PD failure and time until PD failure, (b) major cardiovascular event (MACE) and time until MACE. A total of 58 incident patients with peritoneal biopsy at study baseline were included. Peritoneal membrane histomorphology and aging-related indicators were assessed before the start of PD and investigated as predictors of study endpoints. Fibrosis of the peritoneal membrane was associated with MACE occurrence and earlier MACE, but not with the patient or membrane survival. Serum α-Klotho bellow 742 pg/mL was related to the submesothelial thickness of the peritoneal membrane. This cutoff stratified the patients according to the risk of MACE and time until MACE. Uremic levels of galectin-3 were associated with PD failure and time until PD failure. This work unveils peritoneal membrane fibrosis as a window to the vulnerability of the cardiovascular system, whose mechanisms and links to biological aging need to be better investigated. Galectin-3 and α-Klotho are putative tools to tailor patient management in this home-based renal replacement therapy.publishersversionpublishe

The incidence of smoking and risk factors for smoking initiation in medical faculty students: cohort study

BACKGROUND: Medical education requires detailed investigation because it is a period during which the attitudes and behaviors of physicians develop. The purpose of this study was to calculate the yearly smoking prevalence and incidence rates of medical faculty students and to identify the risk factors for adopting smoking behaviour. METHODS: This is a cohort study in which every student was asked about their smoking habits at the time of first registration to the medical faculty, and was monitored every year. Smoking prevalence, yearly incidence of initiation of smoking and average years of smoking were calculated in analysis. RESULTS: At the time of registration, 21.8% of the students smoked. At the end of six years, males had smoked for an average of 2.6 ± 3.0 years and females for 1.0 ± 1.8 years (p < 0.05). Of the 93 medical students who were not smokers at the time of registration, 30 (32.3%) were smokers at the end of the 6 years of the course. CONCLUSION: The first 3 years of medical education are the most risky period for initiation of smoking. We found that factors such as being male, having a smoking friend in the same environment and having a high trait anxiety score were related to the initiation of smoking. Targeted smoking training should be mandatory for students in the Medical Faculty

Techniques for measuring aerosol attenuation using the Central Laser Facility at the Pierre Auger Observatory

The Pierre Auger Observatory in Malargüe, Argentina, is designed to study the properties of ultra-high energy cosmic rays with energies above 10(18) eV. It is a hybrid facility that employs a Fluorescence Detector to perform nearly calorimetric measurements of Extensive Air Shower energies. To obtain reliable calorimetric information from the FD, the atmospheric conditions at the observatory need to be continuously monitored during data acquisition. In particular, light attenuation due to aerosols is an important atmospheric correction. The aerosol concentration is highly variable, so that the aerosol attenuation needs to be evaluated hourly. We use light from the Central Laser Facility, located near the center of the observatory site, having an optical signature comparable to that of the highest energy showers detected by the FD. This paper presents two procedures developed to retrieve the aerosol attenuation of fluorescence light from CLF laser shots. Cross checks between the two methods demonstrate that results from both analyses are compatible, and that the uncertainties are well understood. The measurements of the aerosol attenuation provided by the two procedures are currently used at the Pierre Auger Observatory to reconstruct air shower data

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

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

Evidence for a mixed mass composition at the &#8216;ankle&#8217; in the cosmic-ray spectrum

We report a first measurement for ultrahigh 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 \u2018ankle\u2019 at lg\u2061(E/eV)=18.5\u201319.0 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 disfavored as the sole explanation of the ultrahigh-energy cosmic-ray flux at Earth

The Pierre Auger Observatory status and latest results

The Pierre Auger Observatory, in Argentina, is the present flagship experiment studying ultrahigh-energy cosmic rays (UHECRs). Facing the challenge due to low cosmic-ray flux at the highest energies, the Observatory has been taking data for more than a decade, reaching an exposure of over 50 000 km2sr yr. The combination of a large surface detector array and fluorescence telescopes provides a substantial improvement in energy calibration and extensive air shower measurements, resulting in data of unprecedented quality. Moreover, the installation of a denser subarray has allowed extending the sensitivity to lower energies. Altogether, this contributes to provide important information on key questions in the UHECR field in the energy range from 0.1 EeV up to 100 EeV. A review of main results from the Pierre Auger Observatory is presented with a particular focus on the energy spectrum measurements, the mass composition studies, the arrival directions analyses, the search for neutral cosmic messengers, and the investigation of high-energy hadronic interactions. Despite this large amount of valuable results, the understanding of the nature of UHECRs and of their origin remains an open science case that the Auger collaboration is planning to address with the AugerPrime project to upgrade the Observatory

The Pierre Auger Observatory Upgrade

It is planned to operate the Pierre Auger Observatory until at least the end of 2024. An upgrade of the experiment has been proposed in order to provide additional measurements to allow one to elucidate the mass composition and the origin of the flux suppression at the highest energies, to search for a flux contribution of protons up to the highest energies and to reach a sensitivity to a contribution as small as 10% in the flux suppression region, to study extensive air showers and hadronic multi-particle production. With operation planned until 2024, event statistics will more than double compared with the existing Auger data set, with the critical added advantage that every event will now have mass information. Obtaining additional composition-sensitive information will not only help to better reconstruct the properties of the primary particles at the highest energies, but also improve the measurements in the energy range just above the ankle. Furthermore, measurements with the new detectors will help to reduce systematic uncertainties related to the modelling hadronic showers and to limitations in the reconstruction algorithms. A description of the principal proposed Auger upgrade will be presented. The Auger upgrade promises high-quality future data, and real scope for new physics