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In the quest for the faint primordial B-mode polarization of the Cosmic Microwave Background, three are the key requirements for any present or future experiment: an utmost sensitivity, excellent control over instrumental systematic effects and over Galactic foreground contamination. Bolometric Interferometry (BI) is a novel technique that matches them all by combining the sensitivity of bolometric detectors, the control of instrumental systematics from interferometry and a software-based, tunable, in-band spectral resolution due to its ability to perform band-splitting during data analysis (spectral imaging). In this paper, we investigate how the spectral imaging capability of BI can help in detecting residual contamination in case an over-simplified model of foreground emission is assumed in the analysis. To mimic this situation, we focus on the next generation of ground-based CMB experiment, CMB-S4, and compare its anticipated sensitivities, frequency and sky coverage with a hypothetical version of the same experiment based on BI, CMB-S4/BI, assuming that lineof-sight (LOS) frequency decorrelation is present in dust emission but is not accounted for during component separation. We show results from a Monte-Carlo analysis based on a parametric component separation method (FGBuster), highlighting how BI has the potential to diagnose the presence of foreground residuals in estimates of the tensor-to-scalar ratio r in the case of unaccounted Galactic dust LOS frequency decorrelation.

COSMO is a ground-based instrument to measure the spectral distortions (SD) of the Cosmic Microwave Background (CMB). In this paper, we present preliminary results of electromagnetic simulations of its reference blackbody calibrator. HFSS simulations provide a calibrator reflection coefficient of R ∼ 10 - 6 , corresponding to an emissivity ϵ = 1 - R = 0.999999 . We also provide a forecast for the instrument performance by using an ILC-based simulation. We show that COSMO can extract the isotropic Comptonization parameter (modeled as | y | = 1.77 · 10 - 6 ) as | y | = ( 1.79 ± 0.19 ) · 10 - 6 , in the presence of the main Galactic foreground (thermal dust) and of CMB anisotropies, and assuming perfect atmospheric emission removal.

With this contribution we show the readout electronics for kinetic inductance detectors (KIDs) that we are developing based on commercial IQ transceivers from National Instruments and using a Virtex 5 class FPGA. It will be the readout electronics of the COSmic Monopole Observer (COSMO) experiment, a ground based cryogenic Martin–Puplett Interferometer searching for the cosmic microwave background spectral distortions. The readout electronics require a sampling rate in the range of tens of kHz, which is both due to a fast rotating mirror modulating the signal and the time constant of the COSMO KIDs. In this contribution we show the capabilities of our readout electronics using Niobium KIDs developed by Paris Observatory for our 5 K cryogenic system. In particular, we demonstrate the capability to detect 23 resonators from frequency sweeps and to readout the state of each resonator with a sampling rate of about 8 kHz. The readout is based on a finite-state machine where the first two states look for the resonances and generate the comb of tones, while the third one performs the acquisition of phase and amplitude of each detector in free running. Our electronics are based on commercial modules, which brings two key advantages: they can be acquired easily and it is relative simple to write and modify the firmware within the LabView environment in order to meet the needs of the experiment.

The benefit of adjuvant immunotherapy after nephrectomy in renal cell carcinoma (RCC) is controversial. The present study aimed to examine the possible benefit of adjuvant immunotherapy in various clinical settings. We retrospectively reviewed 436 patients with pT1-3N0-2M0 RCC who underwent radical or partial nephrectomy with curative intent at our institution between 1981 and 2009. Of them, 98 (22.5%) patients received adjuvant interferon-α (IFN-α) after surgery (adjuvant IFN-α group), while 338 (77.5%) did not (control group). The primary endpoint was cancer-specific survival (CSS). Univariate and multivariate analyses were conducted using log-rank tests and Cox proportional hazards models, respectively. Fifty-two (11.9%) patients died from RCC with a median follow-up period of 96 months. Preliminary univariate analyses comparing CSS among treatment groups in each TNM setting revealed that CSS in the control group was equal or superior to that in the adjuvant IFN-α group in earlier stages, while the opposite trend was observed in more advanced stages. We evaluated the TNM cutoffs and demonstrated maximized benefit of adjuvant IFN-α in patients with pT2b-3cN0 (P = 0.0240). In multivariate analysis, ≥pT3 and pN1-2 were independent predictors for poor CSS in all patients. In the subgroups with ≥pT2 disease (n = 123), pN1-2 and no adjuvant treatment were significant poor prognostic factors. Adjuvant immunotherapy after nephrectomy may be beneficial in pT2b-3cN0 RCC. Careful consideration is, however, required for interpretation of this observational study because of its selection bias and adverse effects of IFN-α.

In this paper we present the European Low Frequency Survey (ELFS), a project that will enable the detection of primordial B-mode polarization by measuring the Galactic and extra-Galactic foregrounds in the 5– 120 GHz frequency window. Indeed, the main difficulty in measuring the Bmode polarization comes not just from its sheer faintness, but from the fact that many other objects in the Universe also emit polarized microwaves, which mask the faint CMB signal. The first stage of this project will be carried out in synergy with the Simons Array (SA) collaboration, installing a 5.5–11 GHz coherent receiver at the focus of one of the three 3.5m SA telescopes in Atacama, Chile (“ELFS on SA”). The receiver will be equipped with a fully digital backend based on the latest Xilinx RF System-on-Chip devices that will provide frequency resolution of 1MHz across the whole observing band, allowing us to clean the scientific signal from unwanted radio frequency interference, particularly from low-Earth orbit satellite mega-constellations. This paper reviews the scientific motivation for ELFS and its instrumental characteristics, and provides an update on the development of ELFS on SA.

Renal cell carcinoma (RCC) represents 2%-3% of all cancers in adults, and its pathogenesis is mainly related to altered cellular response to hypoxia. Lenvatinib, a novel multitarget tyrosine kinase inhibitor (TKI), represents a therapeutic option, in combination with mammalian target of rapamycin (mTOR) inhibitor everolimus, for the treatment of metastatic RCC (mRCC). The objective of this article is to review the evidence about the treatment of mRCC with combination of lenvatinib plus everolimus. Phase I studies supported clinical activity of lenvatinib in mRCC. A randomized, Phase II, open-label, multicenter trial demonstrated the clinical efficacy of combination treatment with lenvatinib plus everolimus in patients with progressive mRCC after prior therapy with TKI. Median progression-free survival was improved by 9 months with the combination therapy compared to the single-agent everolimus, with an overall response rate of 43% for the experimental regimen. Lenvatinib plus everolimus appeared to be slightly less toxic than single-agent lenvatinib and more toxic than single-agent everolimus; grade 3-4 adverse events occurred in 71% of patients. Currently, lenvatinib plus everolimus has US Food and Drug Administration approval for its use in mRCC after failure of previous treatment with TKI. The combination therapy with lenvatinib plus everolimus might be a promising choice for second-line treatment of mRCC patients. Based on the results of the Phase II trial, it is possible to speculate that the combination therapy could be appropriate for patients with high disease burden or strongly symptomatic patients.

In the past few years, new drugs made their appearance in the first-line setting of treatment for metastatic renal cell carcinoma (mRCC), and cabozantinib is one among them. The present systematic review aims to point out any evidence published to date about first-line treatment with cabozantinib for mRCC patients, describing their outcome in all end points explored by the literature. PRISMA guidelines were followed. A systematic assessment of literature and peer- reviewed presentations was performed by searching PubMed and major oncology meeting resources, from the database inception until June 25, 2018. The following keywords were used: \"cabozantinib or cabozantinib-s-malate or XL184\" and \"renal cell carcinoma or kidney cancer or clear cell renal carcinoma or renal cancer\" and \"first-line or untreated or treatment-naïve or primary treatment\". All types of original clinical studies were included, evaluating either cabozantinib monotherapy or any systemic drug combination containing cabozantinib for previously untreated patients with mRCC. From potential 75 titles and abstracts, seven publications were selected. One was the main report of a randomized clinical trial (the CABOSUN study); four papers reported updated results, secondary or subgroup analyses from the same study population; and further two reports consisted of network meta-analyses. From the additional search for ongoing clinical trials, six studies currently in progress were reported. According to the reported evidence, cabozantinib may be a viable first-line option in mRCC patients with intermediate or poor risk according to International Metastatic Renal Cell Carcinoma Database Consortium model. It offers an undoubtful advantage in terms of progression-free survival, despite quite high rates of G3-4 toxicity, modest objective response rate, and no survival advantage. Nevertheless, given the availability of an immunotherapy combination that significantly improved overall survival for the same population in a Phase III trial and the indisputable efficacy of cabozantinib as second-line treatment, this drug may be devoted as a rescue option in patients progressive to primary therapy.

In this paper we present the European Low Frequency Survey (ELFS), a project that will enable the detection of primordial B-mode polarization by measuring the Galactic and extra-Galactic foregrounds in the 5– 120 GHz frequency window. Indeed, the main difficulty in measuring the Bmode polarization comes not just from its sheer faintness, but from the fact that many other objects in the Universe also emit polarized microwaves, which mask the faint CMB signal. The first stage of this project will be carried out in synergy with the Simons Array (SA) collaboration, installing a 5.5–11 GHz coherent receiver at the focus of one of the three 3.5m SA telescopes in Atacama, Chile (“ELFS on SA”). The receiver will be equipped with a fully digital backend based on the latest Xilinx RF System-on-Chip devices that will provide frequency resolution of 1MHz across the whole observing band, allowing us to clean the scientific signal from unwanted radio frequency interference, particularly from low-Earth orbit satellite mega-constellations. This paper reviews the scientific motivation for ELFS and its instrumental characteristics, and provides an update on the development of ELFS on SA.

The Q&U Bolometric Interferometer for Cosmology (QL’BIC) is the first bolometric interferometer designed to measure the primordial B -mode polarization of the Cosmic Microwave Background (CMB). Bolometric interferometry is a novel technique that combines the sensitivity of bolometric detectors with the control of systematic effects that is typical of interferometry, both key features in the quest for the faint signal of the primordial B -modes. A unique feature is the so-called “spectral imaging”, i.e., the ability to recover the sky signal in several sub-bands within the physical band during data analysis. This feature provides an in-band spectral resolution of ∆ v / v ~ 0.04 that is unattainable by a traditional imager. This is a key tool for controlling the Galactic foregrounds contamination. In this paper, we describe the principles of bolometric interferometry, the current status of the QU BIC experiment and future prospects.

Q and U Bolometric Interferometer for Cosmology (QUBIC) is a Fizeau interferometer sensitive to linear polarisation, to be deployed at the Antarctic station of Dome C. This experiment in its final configuration will be operated at 97, 150 and 220 GHz and is intended to target CMB primordial B-modes in a multipole window 20 < ℓ < 150 . A sensitivity of r = 0.05 (95 % CL) can be reached by the first module alone, after 2 years of operation. Here we review in particular its working principles, and we show how the QUBIC interferometric configuration can be considered equivalent to a pupil-plane filtered imaging system. In this context, we show how our instrument can be self-calibrated. Finally, we conclude by showing an overview of the first dual-band module (150/220 GHz), which will serve also as a demonstrator for the subsequent units, and review the technological choices we made for each subsystem, with particular emphasis on the detection system.