X-ray emission from young brown dwarfs in the Orion Nebula Cluster

We use the sensitive X-ray data from the Chandra Orion Ultradeep Project (COUP) to study the X-ray properties of 34 spectroscopically-identified brown dwarfs with near-infrared spectral types between M6 and M9 in the core of the Orion Nebula Cluster. Nine of the 34 objects are clearly detected as X-ray sources. The apparently low detection rate is in many cases related to the substantial extinction of these brown dwarfs; considering only the BDs with $A_V \leq 5$ mag, nearly half of the objects (7 out of 16) are detected in X-rays. Our 10-day long X-ray lightcurves of these objects exhibit strong variability, including numerous flares. While one of the objects was only detected during a short flare, a statistical analysis of the lightcurves provides evidence for continuous (`quiescent') emission in addition to flares for all other objects. Of these, the $\sim$ M9 brown dwarf COUP 1255 = HC 212 is one of the coolest known objects with a clear detection of quiescent X-ray emission. The X-ray properties (spectra, fractional X-ray luminosities, flare rates) of these young brown dwarfs are similar to those of the low-mass stars in the ONC, and thus there is no evidence for changes in the magnetic activity around the stellar/substellar boundary, which lies at $\sim$ M6 for ONC sources. Since the X-ray properties of the young brown dwarfs are also similar to those of M6--M9 field stars, the key to the magnetic activity in very cool objects seems to be the effective temperature, which determines the degree of ionization in the atmosphere.Comment: accepted for ApJS, COUP special issu

The Origin of T Tauri X-ray Emission: New Insights from the Chandra Orion Ultradeep Project

We use the data of the Chandra Orion Ultradeep Project (COUP) to study the nearly 600 X-ray sources that can be reliably identified with optically well characterized T Tauri stars (TTS) in the Orion Nebula Cluster. We detect X-ray emission from more than 97% of the optically visible late-type (spectral types F to M) cluster stars. This proofs that there is no ``X-ray quiet'' population of late-type stars with suppressed magnetic activity. All TTS with known rotation periods lie in the saturated or super-saturated regime of the relation between activity and Rossby numbers seen for main-sequence (MS) stars, but the TTS show a much larger scatter in X-ray activity than seen for the MS stars. Strong near-linear relations between X-ray luminosities, bolometric luminosities and mass are present. We also find that the fractional X-ray luminosity rises slowly with mass over the 0.1 - 2 M_sun range. The plasma temperatures determined from the X-ray spectra of the TTS are much hotter than in MS stars, but seem to follow a general solar-stellar correlation between plasma temperature and activity level. The large scatter about the relations between X-ray activity and stellar parameters seems to be related to the influence of accretion on the X-ray emission. While the X-ray activity of the non-accreting TTS is consistent with that of rapidly rotating MS stars, the accreting stars are less X-ray active (by a factor of ~2-3 on average) and produce much less well defined correlations than the non-accretors. We discuss possible reasons for the suppression of X-ray emission by accretion and the implications of our findings on long-standing questions related to the origin of the X-ray emission from young stars.Comment: accepted for ApJS, COUP Special Issu

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study

Purpose: To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate. Methods: In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. Results: Significantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low ( 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. Conclusions: 177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov : NCT01578239, EudraCT: 2011-005049-11

Position Paper on Young Vascular Surgeons Training of the Mediterranean Federation for the Advancing of Vascular Surgery (MeFAVS):State of the Art and Perspectives

The Mediterranean Federation for the Advancing of Vascular Surgery (MeFAVS) was founded in 2018, with the aim to promote cooperation among vascular professionals within Mediterranean countries. Due to its prominent social and economic impact on national health systems, diabetic peripheral artery was selected as the very first topic to be investigated by the federation. In this second paper, different experiences from delegates of participating countries were shared to define common strategies to harmonize, standardize, and optimize education and training in the Vascular Surgery specialty

First results of the CUORICINO experiment

Preliminary results on double beta decay (DBD) of 130 Te, obtained in the first run of the CUORICINO experiment are presented. The set-up consists of an array of 62 crystals of TeO 2 operating as bolometers in a deep underground dilution unit at a temperature of about 10 mK. Due to a total mass of about 41 kg, CUORICINO represents by far the most massive running cryogenic mass to search for rare events. The achieved lower limit on the neutrinoless DBD is 5.5⋅10 23 years, that corresponds to a limit on the Majorana effective mass between 0.37 and 1.9 eV. Performances of the detectors together with the sensitivity estimation are discussed

Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study

Purpose: To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate. Methods: In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. Results: Significantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low ( 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. Conclusions: 177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov: NCT01578239, EudraCT: 2011-005049-11

Whole mitochondrial genomes unveil the impact of domestication on goat matrilineal variability

Background: The current extensive use of the domestic goat (Capra hircus) is the result of its medium size and high adaptability as multiple breeds. The extent to which its genetic variability was influenced by early domestication practices is largely unknown. A common standard by which to analyze maternally-inherited variability of livestock species is through complete sequencing of the entire mitogenome (mitochondrial DNA, mtDNA). Results: We present the first extensive survey of goat mitogenomic variability based on 84 complete sequences selected from an initial collection of 758 samples that represent 60 different breeds of C. hircus, as well as its wild sister species, bezoar (Capra aegagrus) from Iran. Our phylogenetic analyses dated the most recent common ancestor of C. hircus to ~460,000 years (ka) ago and identified five distinctive domestic haplogroups (A, B1, C1a, D1 and G). More than 90 % of goats examined were in haplogroup A. These domestic lineages are predominantly nested within C. aegagrus branches, diverged concomitantly at the interface between the Epipaleolithic and early Neolithic periods, and underwent a dramatic expansion starting from ~12–10 ka ago. Conclusions: Domestic goat mitogenomes descended from a small number of founding haplotypes that underwent domestication after surviving the last glacial maximum in the Near Eastern refuges. All modern haplotypes A probably descended from a single (or at most a few closely related) female C. aegagrus. Zooarchaelogical data indicate that domestication first occurred in Southeastern Anatolia. Goats accompanying the first Neolithic migration waves into the Mediterranean were already characterized by two ancestral A and C variants. The ancient separation of the C branch (~130 ka ago) suggests a genetically distinct population that could have been involved in a second event of domestication. The novel diagnostic mutational motifs defined here, which distinguish wild and domestic haplogroups, could be used to understand phylogenetic relationships among modern breeds and ancient remains and to evaluate whether selection differentially affected mitochondrial genome variants during the development of economically important breeds