Phosphodiesterase Type 5 Inhibitors, Sport and Doping

Phosphodiesterase type 5 inhibitors (PDE5i) (e.g., sildenafil, tadalafil, vardenafil, and avanafil) are drugs commonly used to treat erectile dysfunction, pulmonary arterial hypertension, and benign prostatic hyperplasia. PDE5i are not prohibited by the World Anti-Doping Agency (WADA) but are alleged to be frequently misused by healthy athletes to improve sporting performance. In vitro and in vivo studies have reported various effects of PDE5i on cardiovascular, muscular, metabolic, and neuroendocrine systems and the potential, therefore, to enhance performance of healthy athletes during training and competition. This suggests well-controlled research studies to examine the ergogenic effects of PDE5i on performance during activities that simulate real sporting situations are warranted to determine if PDE5i should be included on the prohibited WADA list. In the meantime, there is concern that some otherwise healthy athletes will continue to misuse PDE5i to gain an unfair competitive advantage over their competitors

Thyroid autoimmunity, thyroglobulin autoantibodies and thyroid cancer prognosis

Relevance of thyroid autoimmunity to prognosis of papillary thyroid carcinoma is still unsettled. We decided to investigate the impact of thyroid autoimmunity on prognosis of papillary thyroid carcinoma and the handling of TgAbs. We evaluated the clinical course of a large group of patients according to the presence (PTC-LT) or absence (PTC) of lymphocytic thyroiditis at histology. We studied 194 consecutive patients with a diagnosis of PTC and treated with total thyroidectomy plus ¹³¹I ablation between 2007 and 2009. Median follow-up (with 25th-75th percentiles) was 84·0 (56·4-118·0) months. The remission criteria were: basal Tg <0·2 ng/mL (or stimulated Tg <1), TgAbs <8 IU/mL (otherwise "decreasing TgAb trend", a decline of ≥20% in sequential TgAb measurements) and unremarkable imaging. PTC-LT and PTC patients had comparable treatment.TgAbs were detectable in 72·5% of PTC-LT and 16·5% of PTC patients. Time to remission was longer in the detectable than in the undetectable TgAb cohort (28·5 vs· 7·5 months [median]; HR 0·54, CI 0·35-0·83, p=0·005). When comparing PTC-LT to PTC patients the difference was maintained in the detectable TgAb (29·3 vs 13·0 months; HR 0·38, CI 0·18-0·80; p=0·01), but not in the undetectable TgAb cohort (7·7 vs 7·3 months; HR 0·90, CI 0·55-1·47; p=0·68). Using the decreasing TgAb trend, the influence of detectable TgAbs on time to remission was abolished. Thyroid autoimmunity does not influence the prognosis of papillary thyroid carcinoma. A decreasing TgAb trend seems an appropriate criterion to establish the remission of papillary thyroid carcinoma

Il gozzo multinodulare

SommarioSi definisce gozzo l'incremento diffuso o nodulare della ghiandola tiroidea. Il suo sviluppo è legato a fattori genetici e ambientali, di cui il più importante è rappresentato dalla carenza iodica. L'inquadramento clinico prevede un'attenta valutazione dei sintomi, dei segni, dei risultati degli esami ormonali, delle caratteristiche ecografiche e citologiche. Il trattamento deve essere poi individualizzato tenendo conto della disponibilità di molteplici opzioni terapeutiche

PolarLight: a CubeSat X-ray Polarimeter based on the Gas Pixel Detector

The gas pixel detector (GPD) is designed and developed for high-sensitivity astronomical X-ray polarimetry, which is a new window about to open in a few years. Due to the small mass, low power, and compact geometry of the GPD, we propose a CubeSat mission Polarimeter Light (PolarLight) to demonstrate and test the technology directly in space. There is no optics but a collimator to constrain the field of view to 2.3 degrees. Filled with pure dimethyl ether (DME) at 0.8 atm and sealed by a beryllium window of 100 micron thick, with a sensitive area of about 1.4 mm by 1.4 mm, PolarLight allows us to observe the brightest X-ray sources on the sky, with a count rate of, e.g., ~0.2 counts/s from the Crab nebula. The PolarLight is 1U in size and mounted in a 6U CubeSat, which was launched into a low Earth Sun-synchronous orbit on October 29, 2018, and is currently under test. More launches with improved designs are planned in 2019. These tests will help increase the technology readiness for future missions such as the enhanced X-ray Timing and Polarimetry (eXTP), better understand the orbital background, and may help constrain the physics with observations of the brightest objects.Comment: Accepted for publication in Experimental Astronom

Gas pixel detectors for high-sensitivity x-ray polarimetry

We discuss a new class of Micro Pattern Gas Detectors, the Gas Pixel Detector (GPD), in which a complete integration between the gas amplification structure and the read-out electronics has been reached. An Application-Specific Integrated Circuit (ASIC) built in deep sub-micron technology has been developed to realize a monolithic device that is, at the same time, the pixelized charge collecting electrode and the amplifying, shaping and charge measuring front-end electronics. The CMOS chip has the top metal layer patterned in a matrix of 80 μm pitch hexagonal pixels, each of them directly connected to the underneath electronics chain which has been realized in the remaining five layers of the 0.35 μm VLSI technology. Results from tests of a first prototype of such detector with 2k pixels and a full scale version with 22k pixels are presented. The application of this device for Astronomical X-Ray Polarimetry is discussed. The experimental detector response to polarized and unpolarized X-ray radiation is shown. Results from a full MonteCarlo simulation for two astronomical sources, the Crab Nebula and the Hercules X1, are also reported

Equalizing the Pixel Response of the Imaging Photoelectric Polarimeter On-Board the IXPE Mission

The Gas Pixel Detector is a gas detector, sensitive to the polarization of X-rays, currently flying on-board IXPE - the first observatory dedicated to X-ray polarimetry. It detects X-rays and their polarization by imaging the ionization tracks generated by photoelectrons absorbed in the sensitive volume, and then reconstructing the initial direction of the photoelectrons. The primary ionization charge is multiplied and ultimately collected on a finely-pixellated ASIC specifically developed for X-ray polarimetry. The signal of individual pixels is processed independently and gain variations can be substantial, of the order of 20%. Such variations need to be equalized to correctly reconstruct the track shape, and therefore its polarization direction. The method to do such equalization is presented here and is based on the comparison between the mean charge of a pixel with respect to the other pixels for equivalent events. The method is shown to finely equalize the response of the detectors on board IXPE, allowing a better track reconstruction and energy resolution, and can in principle be applied to any imaging detector based on tracks.Comment: Accepted for publication in The Astronomical Journal. 10 pages, 19 figure

X-ray Polarimetry of the accreting pulsar 1A~0535+262 in the supercritical state with PolarLight

The X-ray pulsar 1A 0535+262 exhibited a giant outburst in 2020, offering us a unique opportunity for X-ray polarimetry of an accreting pulsar in the supercritical state. Measurement with PolarLight yielded a non-detection in 3-8 keV; the 99% upper limit of the polarization fraction (PF) is found to be 0.34 averaged over spin phases, or 0.51 based on the rotating vector model. No useful constraint can be placed with phase resolved polarimetry. These upper limits are lower than a previous theoretical prediction of 0.6-0.8, but consistent with those found in other accreting pulsars, like Her X-1, Cen X-3, 4U 1626-67, and GRO J1008-57, which were in the subcritical state, or at least not confidently in the supercritical state, during the polarization measurements. Our results suggest that the relatively low PF seen in accreting pulsars cannot be attributed to the source not being in the supercritical state, but could be a general feature.Comment: accepted for publication in Ap

First light from a very large area pixel array for high-throughput x-ray polarimetry

We report on a large active area (15x15mm2), high channel density (470 pixels/mm2), self-triggering CMOS analog chip that we have developed as pixelized charge collecting electrode of a Micropattern Gas Detector. This device, which represents a big step forward both in terms of size and performance, is the last version of three generations of custom ASICs of increasing complexity. The CMOS pixel array has the top metal layer patterned in a matrix of 105600 hexagonal pixels at 50μm pitch. Each pixel is directly connected to the underneath full electronics chain which has been realized in the remaining five metal and single poly-silicon layers of a standard 0.18μm CMOS VLSI technology. The chip has customizable self-triggering capability and includes a signal pre-processing function for the automatic localization of the event coordinates. In this way it is possible to reduce significantly the readout time and the data volume by limiting the signal output only to those pixels belonging to the region of interest. The very small pixel area and the use of a deep sub-micron CMOS technology has brought the noise down to 50 electrons ENC. Results from in depth tests of this device when coupled to a fine pitch (50μm on a triangular pattern) Gas Electron Multiplier are presented. The matching of readout and gas amplification pitch allows getting optimal results. The application of this detector for Astronomical X-Ray Polarimetry is discussed. The experimental detector response to polarized and unpolarized X-ray radiation when working with two gas mixtures and two different photon energies is shown. Results from a full MonteCarlo simulation for several galactic and extragalactic astronomical sources are also reported

A population of gamma-ray emitting globular clusters seen with the Fermi Large Area Telescope

Globular clusters with their large populations of millisecond pulsars (MSPs) are believed to be potential emitters of high-energy gamma-ray emission. Our goal is to constrain the millisecond pulsar populations in globular clusters from analysis of gamma-ray observations. We use 546 days of continuous sky-survey observations obtained with the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope to study the gamma-ray emission towards 13 globular clusters. Steady point-like high-energy gamma-ray emission has been significantly detected towards 8 globular clusters. Five of them (47 Tucanae, Omega Cen, NGC 6388, Terzan 5, and M 28) show hard spectral power indices $(0.7 < \Gamma <1.4)$ and clear evidence for an exponential cut-off in the range 1.0-2.6 GeV, which is the characteristic signature of magnetospheric emission from MSPs. Three of them (M 62, NGC 6440 and NGC 6652) also show hard spectral indices $(1.0 < \Gamma < 1.7)$, however the presence of an exponential cut-off can not be unambiguously established. Three of them (Omega Cen, NGC 6388, NGC 6652) have no known radio or X-ray MSPs yet still exhibit MSP spectral properties. From the observed gamma-ray luminosities, we estimate the total number of MSPs that is expected to be present in these globular clusters. We show that our estimates of the MSP population correlate with the stellar encounter rate and we estimate 2600-4700 MSPs in Galactic globular clusters, commensurate with previous estimates. The observation of high-energy gamma-ray emission from a globular cluster thus provides a reliable independent method to assess their millisecond pulsar populations that can be used to make constraints on the original neutron star X-ray binary population, essential for understanding the importance of binary systems in slowing the inevitable core collapse of globular clusters.Comment: Accepted for publication in A&A. Corresponding authors: J. Kn\"odlseder, N. Webb, B. Pancraz