Diffuse γ\gamma-ray emission from misaligned active galactic nuclei

Active galactic nuclei (AGN) with jets seen at small viewing angles are the most luminous and abundant objects in the $\gamma$-ray sky. AGN with jets misaligned along the line-of-sight appear fainter in the sky, but are more numerous than the brighter blazars. We calculate the diffuse $\gamma$-ray emission due to the population of misaligned AGN (MAGN) unresolved by the Large Area Telescope (LAT) on the {\it Fermi} Gamma-ray Space Telescope ({\it Fermi}). A correlation between the $\gamma$-ray luminosity and the radio-core luminosity is established and demonstrated to be physical by statistical tests, as well as compatible with upper limits based on {\it Fermi}-LAT data for a large sample of radio-loud MAGN. We constrain the derived $\gamma$-ray luminosity function by means of the source count distribution of the radio galaxies (RGs) detected by the {\it Fermi}-LAT. We finally calculate the diffuse $\gamma$-ray flux due to the whole MAGN population. Our results demonstrate that the MAGN can contribute from 10% up to nearly the entire measured Isotropic Gamma-Ray Background (IGRB). We evaluate a theoretical uncertainty on the flux of almost an order of magnitude.Comment: Accepted for publication in Ap

The New Paradigms in Clinical Research: From Early Access Programs to the Novel Therapeutic Approaches for Unmet Medical Needs.

Despite several innovative medicines gaining worldwide approval in recent years, there are still therapeutic areas for which unsatisfied therapeutic needs persist. For example, high unmet clinical need was observed in patients diagnosed with type 2 diabetes mellitus and hemophilia, as well as in specific age groups, such as the pediatric population. Given the urgent need to improve the therapy of clinical conditions for which unmet clinical need is established, clinical testing, and approval of new medicines are increasingly being carried out through accelerated authorization procedures. Starting from 1992, the Food and Drug Administration and the European Medicines Agency have supported the so-called Early Access Programs (EAPs). Such procedures, which can be based on incomplete clinical data, allow an accelerated marketing authorization for innovative medicines. The growth in pharmaceutical research has also resulted in the development of novel therapeutic approaches, such as biotech drugs and advanced therapy medicinal products, including new monoclonal antibodies for the treatment of asthma, antisense oligonucleotides for the treatment of Duchenne muscular dystrophy and spinal muscular atrophy, and new anticancer drugs that act on genetic biomarkers rather than any specific type of cancer. Even though EAPs and novel therapeutic approaches have brought huge benefits for public health, their implementation is limited by several challenges, including the high risk of safety-related label changes for medicines authorized through the accelerated procedure, the high costs, and the reimbursement and access concerns. In this context, regulatory agencies should provide the best conditions for the implementation of the described new tools

Gamma-ray anisotropies from dark matter in the Milky Way: the role of the radial distribution

The annihilation of dark matter particles in the halo of galaxies may end up into gamma rays, which travel almost unperturbed till to their detection at Earth. This annihilation signal can exhibit an anisotropic behavior quantified by the angular power spectrum, whose properties strongly depend on the dark matter distribution and its clumpiness. We use high resolution pure dark matter N-body simulations to quantify the contribution of different components (main halo and satellites) to the global signal as a function of the analytical profile adopted to describe the numerical results. We find that the smooth main halo dominates the angular power spectrum of the gamma-ray signal up to quite large multipoles, where the sub-haloes anisotropy signal starts to emerge, but the transition multipole strongly depends on the assumed radial profile. The extrapolation down to radii not resolved by current numerical simulations can affect both the normalization and the shape of the gamma-ray angular power spectrum. For the sub-haloes described by an asymptotically cored dark matter distribution, the angular power spectrum shows an overall smaller normalization and a flattening at high multipoles. Our results show the criticality of the dark matter density profile shape in gamma-ray anisotropy searches, and evaluate quantitatively the intrinsic errors occurring when extrapolating the dark matter radial profiles down to spatial scales not yet explored by numerical simulations.Comment: 7 pages, 8 figures. It matches the version published in MNRA

Nodular Thyroid Disease in the Era of Precision Medicine

Management of thyroid nodules in the era of precision medicine is continuously changing. Neck ultrasound plays a pivotal role in the diagnosis and several ultrasound stratification systems have been proposed in order to predict malignancy and help clinicians in therapeutic and follow-up decision. Ultrasound elastosonography is another powerful diagnostic technique and can be an added value to stratify the risk of malignancy of thyroid nodules. Moreover, the development of new techniques in the era of "Deep Learning," has led to a creation of machine-learning algorithms based on ultrasound examinations that showed similar accuracy to that obtained by expert radiologists. Despite new technologies in thyroid imaging, diagnostic surgery in 50-70% of patients with indeterminate cytology is still performed. Molecular tests can increase accuracy in diagnosis when performed on "indeterminate" nodules. However, the more updated tools that can be used to this purpose in order to "rule out" (Afirma GSC) or "rule in" (Thyroseq v3) malignancy, have a main limitation: the high costs. In the last years various image-guided procedures have been proposed as alternative and less invasive approaches to surgery for symptomatic thyroid nodules. These minimally invasive techniques (laser and radio-frequency ablation, high intensity focused ultrasound and percutaneous microwave ablation) results in nodule shrinkage and improvement of local symptoms, with a lower risk of complications and minor costs compared to surgery. Finally, ultrasound-guided ablation therapy was introduced with promising results as a feasible treatment for low-risk papillary thyroid microcarcinoma or cervical lymph node metastases

Two-photon excitation and relaxation of the 3d-4d resonance in atomic Kr

Two-photon excitation of a single-photon forbidden Auger resonance has been observed and investigated using the intense extreme ultraviolet radiation from the free electron laser in Hamburg. At the wavelength 26.9 nm (46 eV) two photons promoted a 3d core electron to the outer 4d shell. The subsequent Auger decay, as well as several nonlinear above threshold ionization processes, were studied by electron spectroscopy. The experimental data are in excellent agreement with theoretical predictions and analysis of the underlying multiphoton processes

A New GEM-like Imaging Detector with Electrodes Coated with Resistive Layers

We have developed and tested several prototypes of GEM-like detectors with electrodes coated with resistive layers: CuO or CrO. These detectors can operate stably at gains close to 10E5 and they are very robust. We discovered that the cathodes of these detectors could be coated by CsI layers and in such a way the detectors gain high efficiency for the UV photons. We also demonstrated that such detectors can operate stably in the cascade mode and high overall gains (~10E6) are reachable. This opens applications in several areas, for example in RICH or in noble liquid TPCs. Results from the first applications of these devices for UV photon detection at room and cryogenic temperatures are given.Comment: Presented at the IEEE Nuclear Science Symposium, San Diego, California, October 200

Analysis of HDL-microRNA panel in heterozygous familial hypercholesterolemia subjects with LDL receptor null or defective mutation

In the last years increasing attention has been given to the connection between genotype/phenotype and cardiovascular events in subjects with familial hypercholesterolemia (FH). MicroRNAs (miRs) bound to high-density lipoprotein (HDL) may contribute to better discriminate the cardiovascular risk of FH subjects. Our aim was to evaluate the HDL-miR panel in heterozygous FH (HeFH) patients with an LDLR null or defective mutation and its association with pulse wave velocity (PWV). We evaluated lipid panel, HDL-miR panel and PWV in 32 LDLR null mutation (LDLR-null group) and 35 LDLR defective variant (LDLR-defective group) HeFH patients. HDL-miR-486 and HDL-miR-92a levels were more expressed in the LDLR-null group than the LDLR-defective group. When we further stratified the study population into three groups according to both the LDLR genotype and history of ASCVD (LDLR-null/not-ASCVD, LDLR-defective/not-ASCVD and LDLR/ASCVD groups), both the LDLR/ASCVD and the LDLR-null/not-ASCVD groups had a higher expression of HDL-miR-486 and HDL-miR-92a than the LDLR-defective/not-ASCVD group. Finally, HDL-miR-486 and HDL-miR-92a were independently associated with PWV. In conclusion, the LDLR-null group exhibited HDL-miR-486 and HDL-miR-92a levels more expressed than the LDLR-defective group. Further studies are needed to evaluate these HDL-miRs as predictive biomarkers of cardiovascular events in FH