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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 $$R\sim 10^{-6}$$ R ∼ 10 - 6 , corresponding to an emissivity $$\epsilon =1-R=0.999999$$ 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 $$|y|=1.77 \cdot 10^{-6}$$ | y | = 1.77 · 10 - 6 ) as $$|y|=(1.79\pm 0.19)\cdot 10^{-6}$$ | 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.

Funding Acknowledgements Type of funding sources: None. Background Conflicting data exist regarding the prognostic significance of hypertensive response to exercise (HRE), commonly defined according to absolute peak systolic blood pressure (SBP) values. Limited evidence is available regarding the impact of workload-indexed HRE in patients at different stages of the heart failure (HF) spectrum as defined by the American College of Cardiology/American Heart Association HF staging system. Purpose We evaluated the SBP/Workload slope during exercise across the HF spectrum and investigated the haemodynamic, functional and prognostic correlates of HRE. Methods We prospectively enrolled 58 healthy controls, 201 subjects at risk of developing HF (HF Stages A-B), and 369 patients with a definite diagnosis of HF (Stage C); among the latter, 143 had preserved (HFpEF) and 226 reduced (HFrEF) left ventricular ejection fraction. All patients underwent a combined cardiopulmonary-exercise stress echocardiography test. For each patient, we recorded the first (i.e., within the first minute of exercise) and last (i.e., at peak effort) BP measurement during the ramp protocol. The SBP/Workload slope (Figure 1) was calculated as the ratio of the difference in SBP over the corresponding increment in watts (W): (SBPpeak – SBPfirst)/(Wpeak – Wfirst). In each subgroup, we divided patients according to SBP/Workload slope tertiles; HRE was defined as the highest sex-specific SBP/Workload slope tertile in each HF stage. The primary outcome was a composite of all-cause mortality and hospitalization for cardiovascular reasons. Results Median SBP/Workload slope was 0.53 mmHg/W, interquartile range 0.36-0.72 mmHg/W; the slope was 39% steeper in women than in men (p Conclusion HRE, as evaluated by the SBP/Workload slope, is associated with distinct pathophysiological features and impaired functional capacity across the HF spectrum, especially in Stages A-B and in patients with HFpEF. Patients with HRE in these subgroups may be at increased risk of adverse cardiovascular outcomes.

Funding Acknowledgements Type of funding sources: None. Background Congestion is a key driver of symptoms, disease progression and prognosis for patients with heart failure (HF), irrespective of left ventricular ejection fraction (LVEF). However, clinically overt congestion is often undiagnosed unless severe. Recent research has shown that ultrasonographic quantification of systemic venous (i.e. inferior vena cava), renal venous and lung (B-lines) congestion is feasible and identifies HF patients with a worse prognosis. Purpose Whether a simultaneous multi-organ evaluation of congestion by ultrasound may improve risk stratification in HF is unknown. In the present study, we assessed signs of ultrasonographic congestion in the inferior vena cava, lungs and kidneys in HF patients across the LVEF spectrum and investigated their association with pathophysiology, clinical characteristics and prognosis. Methods We prospectively enrolled 326 patients with a prior clinical diagnosis of HF attending a routine follow-up visit. We also enrolled 102 consecutive patients with cardiovascular risk factors (including hypertension, type II diabetes mellitus or chronic ischaemic heart disease) and no history of HF; these latter patients had NT-proBNP levels 50%, and were not taking loop diuretics. All patients underwent a complete clinical assessment, blood and urine tests, and an ultrasound evaluation. Ultrasound congestion was defined as inferior vena cava ≥21 mm, highest tertile of lung B-lines or discontinuous renal venous flow. Results The final population consisted of 310 HF patients (median age 77 years, median NT-proBNP 1037 ng/L, 51% with LVEF Conclusion Simultaneous assessment of pulmonary, systemic venous and kidney congestion by ultrasound identifies a high prevalence of sub-clinical congestion associated with poor outcomes in HF, irrespective of LVEF. The speed of investigation, along with the widespread availability and relatively low cost of ultrasound, makes this protocol easy to implement for real-time assessment of congestion.

Polarization modulator units (PMUs) represent a critical and powerful component in CMB polarization experiments to suppress the 1/f noise component and mitigate systematic uncertainties induced by detector gain drifts and beam asymmetries. The LiteBIRD mission (expected launch in the late 2020 s) will be equipped with 3 PMUs, one for each of the 3 telescopes, and aims at detecting the primordial gravitational waves with a sensitivity of $$\delta r δ r < 0.001 . Each PMU is based on a continuously rotating transmissive half-wave plate held by a superconducting magnetic bearing in the 5 K environment. To achieve and monitor the rotation a number of subsystems is needed: clamp and release system and motor coils for the rotation; optical encoder, capacitive, Hall and temperature sensors to monitor its dynamic stability. In this contribution, we present a preliminary thermal design of the harness configuration for the PMUs of the mid- and high- frequency telescopes. The design is based on both the stringent system constraint for the total thermal budget available for the PMUs ($$\lesssim$$ ≲ 4 mW at 5 K) and on the requirements for different subsystem: coils currents (up to 10 mA), optical fibers for encoder readout, 25 MHz bias signal for temperature and levitation monitors.

Background Ventricular-arterial coupling (VAC) can be evaluated as the ratio between arterial stiffness (pulse wave velocity, PWV) and myocardial deformation (global longitudinal strain, GLS). Objectives To evaluate VAC across the spectrum of heart failure (HF). Methods We introduced a Doppler-derived, single-beat technique to estimate aortic arch PWV (aa-PWV) in addition to tonometry-derived carotid-femoral PWV (cf-PWV). We measured PWVs and 3D-GLS in 155 healthy controls, 75 subjects at risk of developing HF (American College of Cardiology/American Heart Association Stage A-B) and 236 patients in HF Stage C with preserved (HFpEF, n=104) or reduced ejection fraction (HFrEF, n=132). We evaluated peak oxygen consumption (VO2) and peripheral extraction (AVO2diff) using combined cardiopulmonary-echocardiography exercise stress. Results aa-PWV was obtainable in all subjects and significantly lower than cf-PWV in all subgroups (p Conclusion Abnormal VAC is directly correlated with greater severity of HF and worse functional capacity. HFpEF shows a worse VAC than HFrEF when expressed by aa-PWV/3D-GLS. Funding Acknowledgement Type of funding sources: None.

Introduction The mechanisms underlying endothelial dysfunction (ED) in obesity are poorly understood. Neurofibromin 2 (NF2) is a scaffold-like protein involved in cell growth and survival. However, its role in the vascular endothelium is unknown. Purpose To investigate NF2 function in obesity-related ED. Methods Human aortic endothelial cells (HAECs) were exposed to palmitic acid (PA, 200 uM) or vehicle for 48 hours. Gene silencing of NF2 was performed by small interfering RNA (siRNA). Gene and protein expression were assessed by real time PCR and Western blot, respectively. The interaction of NF2 with endothelial proteins was investigated by co-immunoprecipitation. A constitutive active mutant form of NF2 (Ala518) was employed to study the effects of NF2 gain-of-function. To specifically investigate NF2 role in the vascular endothelium, we generated mice with endothelium-specific deletion of NF2 (NF2 ECKO) by crossing NF2flox/flox mice with tamoxifen-inducible endothelial-specific Cre mice [Cdh5(PAC)-CreERT2]. Endothelium-dependent relaxations to acetylcholine (Ach) were assessed in aortas from NF2 ECKO and wild type (WT) littermates, fed a control and a high fat diet (60 kcal% fat) for 20 weeks. NF2 signalling and endothelial function were also assessed in small visceral fat arteries (VFA) isolated from 18 obese and 18 age-matched healthy subjects undergoing bariatric surgery and cholecystectomy, respectively. Gene in silencing of NF2 by siRNA was performed in VFA from obese patients. Results In HAECs, PA promoted NF2 activation by decreasing its phosphorylation at Ser518. Akt and MYPT-1 were responsible for NF2 dephosphorylation. In PA-treated HAECs, NF2 was mainly found in the plasma membrane as compared to other cell fractions. Among different membrane proteins implicated in endothelial homeostasis, NF2 binds and activates Caveolin 1 (Cav-1), a pivotal repressor of endothelial NO synthase (eNOS). NF2 knockdown in PA-treated HAECs prevented eNOS–Cav-1 interaction, thus preserving eNOS activity and NO levels. By contrast, HAECs expressing the constitutive active mutant form of NF2 displayed reduced eNOS activity. In aortas from obese mice, we found that NF2-Cav-1 interaction was responsible for impaired eNOS activity and ED. Cav-1 gene silencing in NF2-overexpressing aortas prevented ED, thus confirming the direct involvement of Cav-1 in NF2-induced ED. Interestingly, Ach-dependent vasorelaxation was preserved in obese NF2 ECKO mice as compared to WT littermates. Moreover, NO bioavailability was preserved in aortas from NF2 ECKO mice. In VFA from obese patients, NF2 was upregulated, and its activity negatively correlated with Ach-dependent vasorelaxation. Of note, NF2 gene silencing in VFA from obese patients rescued ED. Conclusions In human endothelial cells, mice with endothelium-specific deletion of NF2 and VFA from obese patients, we show that NF2 drives ED by repressing Cav-1. Targeting NF2 may prevent ED in obese patients. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Holcim Stiftung

Background Angiotensin receptor-neprilysin inhibitor (ARNI) is a cornerstone of treatment in heart failure (HF) with reduced ejection fraction (HFrEF), but its effectiveness shows interindividual differences. Objectives To evaluate the predictive value of echo-derived hemodynamic forces (HDF), together with other echocardiographic, biohumoral and cardiopulmonary parameters on a) response to ARNI after 6 months; b) adverse cardiovascular events at follow-up. Methods Eighty-nine consecutive HFrEF patients from two HF centers performed clinical evaluation, laboratory analyses, rest echocardiography and cardiopulmonary exercise testing. Response to ARNI at 6 months was considered in patients without HF admissions, death, or urgent heart transplant and with a ≥50% reduction in NT-proBNP levels and/or ≥10% increase in left ventricle ejection fraction. After 6 months, patients were followed up for a composite endpoint of cardiovascular death, HF-related hospitalization and new-onset atrial fibrillation. Results Response to ARNI was documented in 45/89 (51%) of patients. At baseline, responders and non-responders were paired in clinical assessment, conventional echocardiography, functional status and therapy. At multivariate logistic regression analysis, HDF-derived whole cardiac cycle left ventricle strength (wLVS) was the only independent predictor of ARNI response at 6 months (odds ratio 1.36, 95% confidence interval 1.10–1.67; p=0.004). A wLVS ≥3.7% showed a good accuracy in predicting ARNI response (AUC = 0.736, 0.607–0.840; p Conclusions HDF analysis may help predict ARNI response and optimize follow-up and medical/device strategies in patients with HfrEF. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Fondazione Toscana Gabriele Monasterio, Pisa, Italy

Reduced muscle mass represents one of the top ranked phenotypic criteria for malnutrition proposed by the Global Leadership Initiative on Malnutrition. Although height-indexed fat-free mass (FFMI) thresholds have been proposed as useful surrogate measures of reduced muscle mass, the independent prognostic value of BIA-derived FFMI by bioelectric impedance analysis (BIA) in patients with cancer still needs to be fully explored.Data on body mass index (BMI), 6-month percentage of weight loss (%WL), FFMI by BIA and quality of life (QoL by EORTC Quality of Life Questionnaire [EORTC QLQ-C30]) of Italian and German patients observed prospectively until death or censoring were used (N = 1217). Patients were stratified in 5 risk categories according to a robustly validated scoring system based on BMI and %WL. Low FFMI was defined as follows: men,17 kg/mReduced FFMI was found in 234 patients (19.2%). After a median follow-up of 57 months [25th-75th, 31-60], 620 patients (50.9%) had died. The study detected differences in survival between patients presenting with and without reduced FFMI (14.0 months vs. 45.1 months; P 0.001). The fully-adjusted hazard ratio of mortality for low FFMI was 1.46 [95%CI, 1.18-1.81] (P 0.001). Low FFMI was also independently associated with reduced QoL: fully-adjusted odds ratio, 1.50 [95%CI, 1.00-2.25] (P = 0.050).Reduced FFMI by BIA independently predicted survival and was associated with impaired QoL. Altered body composition should always be considered in all patients with cancer as additional phenotypic criterion of poor prognosis and BIA offers the possibility of multiple, noninvasive bedside assessments.

Risk Management (RM) is awell recognised approach to addressprojects uncertainties, to provideaccurate CAPEX estimates and tohave proactive responses tounplanned events.However, RM is often presented asa standard and repetitive process,disregard to projects diversechallenges. This acceptance is amain obstacle to its successfulimplementation, because this canlead to over complex risk studies forsimple matter or, on the contrary,scarce results for intricate issues.Drilling & Completion projectspresent a high versatility ofsituations (from a standard onshoreworkover to a very challenging deepoffshore exploratory campaign).Project challenges can be verydifferent: technical (HP/HT, newtechnologies, etc), environmental(sensitive areas, deep offshoreconditions, etc), economic (marketconditions, etc), or strategic(partnership, etc).The natural consequence is thateach project requires an adequateresponse in terms of RM. Actually,RM toolbox encompasses a numberof different studies, such as riskregisters, risk mapping, probabilisticCAPEX/schedule, fault trees, etc.Not all studies should besystematically performed. Thus, theRM approach must be tailored toeach project challenges, in order tobring the highest added value to thedecision makers. eni Drilling, Completion &Production optimization departmenthas built an integrated RM systemthat provides a properly designedworkflow for treating each projectwith a suitable approach accordingto its maturity and other technical,environmental, economic or strategiccriteria.This paper takes advantage of aneni experience on a well campaignand describes how RM approachsupported strategic decisions on theimplementation of technologies(RSS, continuous circulating system,aluminium drill pipe, ceramicprotectors and centralisers) to reducewell operations uncertainties. Thiscase study encompasses thecomplete decision loop, from thecost/benefit analysis of eachtechnology to the measured benefitsfrom the rig operations in terms ofperformance enhancement.Finally, it substantiates the values ofRM in investment decision byaddressing RM in a practical way.This case study will definitely helpto spread a RM culture withinproject management organizations.

Funding Acknowledgements Type of funding sources: None. Background Ventricular-arterial coupling (VAC) can be evaluated as the ratio between arterial stiffness (pulse wave velocity, PWV) and myocardial deformation (global longitudinal strain, GLS). Objectives To evaluate VAC across the spectrum of heart failure (HF). Methods We introduced a Doppler-derived, single-beat technique to estimate aortic arch PWV (aa-PWV) in addition to tonometry-derived carotid-femoral PWV (cf-PWV). We measured PWVs and GLS in 155 healthy controls, 75 subjects at risk of developing HF (American College of Cardiology/American Heart Association Stage A-B) and 236 patients in HF Stage C with preserved (HFpEF, n=104) or reduced ejection fraction (HFrEF, n=132). We evaluated peak oxygen consumption (VO2) and peripheral extraction (AVO2diff) using combined cardiopulmonary-echocardiography exercise stress. Results aa-PWV was obtainable in all subjects and significantly lower than cf-PWV in all subgroups (p Conclusion Abnormal VAC is directly correlated with greater severity of HF and worse functional capacity. HFpEF shows a worse VAC than HFrEF when expressed by aa-PWV/GLS.

We present the design, manufacturing and performance of the horn-switch system developed for the technological demonstrator of QUBIC (the $Q$\&$U$ Bolometric Interferometer for Cosmology). This system is constituted of 64 back-to-back dual-band (150\,GHz and 220\,GHz) corrugated feed-horns interspersed with mechanical switches used to select desired baselines during the instrument self-calibration. We manufactured the horns in aluminum platelets milled by photo-chemical etching and mechanically tightened with screws. The switches are based on steel blades that open and close the wave-guide between the back-to-back horns and are operated by miniaturized electromagnets. We also show the current development status of the feedhorn-switch system for the QUBIC full instrument, based on an array of 400 horn-switch assemblies., 30 pages, 28 figures. Accepted for submission to JCAP

Funding Acknowledgements Type of funding sources: None. Background. Recent evidence shows that increased epicardial adipose tissue (EAT) thickness is associated with metabolic syndrome, microvascular dysfunction and enhanced pericardial restraint. Purpose. We measured echocardiography-derived EAT thickness in a population of heart failure (HF) patients with reduced (HFrEF) and preserved (HFpEF) ejection fraction to examine the relationship between EAT and prognosis at clinical follow-up. Methods. We prospectively enrolled 393 consecutive HF outpatients (205 HFrEF, 188 HFpEF) who had been referred to our hospital due to dyspnoea and/or effort intolerance. We performed a resting clinical and biohumoral evaluation, followed by combined cardiopulmonary-echocardiography exercise stress. We considered a composite endpoint of cardiovascular death and HF-related hospitalization during follow-up. Results. Patients with HFpEF displayed greater EAT thickness (median 8 mm, interquartile range [IQR] 4–12 mm) than HFrEF (median 3 mm, IQR 2–6 mm; p Conclusion. EAT accumulation is increased in HFpEF compared to HFrEF and carries different prognostic meanings in the two subsets. In HFpEF, EAT thickening portends adverse outcomes, which may be due to the secretion of pro-inflammatory and pro-atherogenic adipokines and increased mechanical restraint. In HFrEF, EAT thinning is associated with a worse prognosis, probably reflecting a more advanced catabolic state (e.g., cardiac cachexia). Larger studies are needed to determine whether or not EAT has a causal role in influencing progression and survival in the different HF phenotypes. Abstract Figure 1

Funding Acknowledgements Type of funding sources: None. Background. Valvular heart disease (VHD) determines non-physiological, inefficient blood flow within the left ventricle, resulting in abnormal vortex formation and energy loss (EL). EL evaluation could provide valuable insights in addition to more common parameters of left ventricle systolic and diastolic dysfunction. Vector flow mapping (VFM) is a novel, non-invasive echocardiographic technique that measures EL through the study of intraventricular flow. Purpose. To assess EL throughout the whole cardiac cycle in patients with severe primary left-sided VHD before cardiac valve intervention. Methods. VFM is based on the continuity equation applied to colour Doppler and speckle tracking echocardiography, acquired from the apical long-axis view. VFM estimates blood flow velocity and vortex characteristics to quantify energy dissipation (i.e., EL) due to blood viscosity in a turbulent flow. EL was calculated frame by frame and averaged over three beats. Results. We enrolled 20 healthy controls (55 ± 19 years old, 65% male) and 73 patients (70 ± 17 years old, 59% male) with severe VHD before cardiac surgery: 30 with primary mitral regurgitation (MR), 8 with mitral stenosis (MS), 15 with aortic regurgitation (AR), 20 with aortic stenosis (AS). All patients had a left ventricle (LV) ejection fraction ≥50% and no wall motion abnormalities. We observed an increased number of vortexes in patients with VHD when compared to controls, especially in mid-diastole (p = 0.003). This is reflected in a significantly higher EL during the whole cardiac cycle in VHD patients than controls (p Conclusions. In addition to standard baseline echocardiography, VFM can quantitatively evaluate the energy dissipation in different subsets of VHD. EL is not uniform during the cardiac cycle, as diastole seems significantly more affected than systole. The assessment of EL after valve intervention is ongoing. VFM could provide further insights into the pathophysiology of heart valve disease and help to evaluate the efficacy of the procedure (repair/replacement) performed. Abstract Figure 1 Abstract Figure 2

Funding Acknowledgements Type of funding sources: None. Background. Recent evidence shows epicardial adipose tissue (EAT) acts as a paracrine organ and may directly alter myocardial function by exerting mechanical compression. Purpose. We evaluated EAT thickness through transthoracic echocardiography and investigated its relationship with cardiopulmonary fitness and cardiovascular haemodynamics at rest and during exercise in a population of heart failure (HF) patients with reduced (HFrEF) and preserved (HFpEF) ejection fraction. Methods. We prospectively enrolled 393 consecutive HF outpatients (205 HFrEF, 188 HFpEF) who had been referred to our hospital due to dyspnoea and/or effort intolerance, together with 44 healthy controls. We performed a resting state-of-the-art echocardiographic evaluation, followed by combined cardiopulmonary-echocardiography exercise stress. Results. EAT thickness was higher in HFpEF (median 8 mm, interquartile range [IQR] 4–12 mm) and progressively reduced in controls (median 5 mm, IQR 3–7 mm; p As there are no definite cut-off values to define increased EAT, patients were divided based on the median EAT value (5 mm) of the overall population. Thinner EAT (≤5 mm) was associated with worse LV systolic dysfunction (peak average S’) and remodeling (3D LV mass index) in HFrEF. In HFpEF, on the other hand, increased EAT (>5 mm) was related to worse right ventricular systolic dysfunction (3D right ventricular ejection fraction) and more severe left atrio-ventricular (left atrium reservoir strain/left ventricle global longitudinal strain) and right ventriculo-arterial (tricuspid annular plane systolic excursion/systolic pulmonary artery pressure) coupling (Figure 2). Conclusion. In HFpEF, increased EAT thickness is associated with a worse hemodynamic profile and functional capacity. Conversely, in HFrEF, EAT thinning portends more advanced LV dysfunction and impaired cardiopulmonary fitness. Abstract Figure 1 Abstract Figure 2

et al., Feedhorn- and orthomode transducer- (OMT) coupled transition edge sensor (TES) bolometers have been designed and micro-fabricated to meet the optical specifications of the LiteBIRD high frequency telescope (HFT) focal plane. We discuss the design and optical characterization of two LiteBIRD HFT detector types: dual-polarization, dual-frequency-band pixels with 195/280 GHz and 235/337 GHz band centers. Results show well-matched passbands between orthogonal polarization channels and frequency centers within 3% of the design values. The optical efficiency of each frequency channel is conservatively reported to be within the range 0.64−0.72, determined from the response to a cryogenic, temperature-controlled thermal source. These values are in good agreement with expectations and either exceed or are within 10% of the values used in the LiteBIRD sensitivity forecast. Lastly, we report a measurement of loss in Nb/SiNx/Nb microstrip at 100 mK and over the frequency range 200–350 GHz, which is comparable to values previously reported in the literature., This work is supported by NASA under grant no. 80NSSC18K0132.

We describe the setup for the broadband millimeter/submillimeter characterization of the quasi-optical elements and the dielectric materials commonly used in microwave receivers operated in microwave astronomy. The setup is made of a large aperture (100 mm) Fourier transform spectrometer coupled to a transition edge superconducting detector. The system has been assembled and characterized in different configurations and operation modes for the acquisition of interferograms from various kinds of samples. After the initial test runs, the configuration is now being updated to ensure a broader range of measurements, including reflectance and scattering. We plan to first use this testbed for the characterization of the dielectric materials used in the LSPE/SWIPE experiment, devoted to the study the polarization of the Cosmic Microwave Background.

International audience; The Q & U Bolometric Interferometer for Cosmology (QUBIC) is a cosmology experiment that aims to measure the B-mode polarization of the cosmic microwave background (CMB). Measurements of the primordial B-mode pattern of the CMB polarization are in fact among the most exciting goals in cosmology as it would allow testing of the inflationary paradigm. Many experiments are attempting to measure the B-modes, from the ground and the stratosphere, using imaging Stokes polarimeters. The QUBIC collaboration developed an innovative concept to measure CMB polarization using bolometric interferometry. This approach mixes the high sensitivity of bolometric detectors with the accurate control of systematics due to the interferometric layout of the instrument. We present the calibration results for the Technological Demonstrator, before its commissioning in the Argentinian observing site and preparation for first light.

The MIllimetric Sardinia radio Telescope Receiver based on Array of Lumped elements KIDs, MISTRAL, is a cryogenic W-band (77–103 GH) LEKID camera which will be integrated at the Gregorian focus of the 64 m aperture Sardinia Radio Telescope, in Italy, in Autumn 2022. This instrument, thanks to its high angular resolution ($$\sim 13~{\mathrm{arcsec}}$$ ∼ 13 arcsec ) and the wide instantaneous field of view ($$\sim 4~{\mathrm{arcmin}}$$ ∼ 4 arcmin ), will allow continuum surveys of the mm-wave sky with a variety of scientific targets, spanning from extragalactic astrophysics to solar system science. In this contribution, we will describe the design of the MISTRAL camera, with a particular focus on the optimisation and test of a prototype of the focal plane.

The COSmic Monopole Observer (COSMO) is an experiment to measure low-level spectral distortions in the isotropic component of the Cosmic Microwave Background (CMB). Deviations from a pure blackbody spectrum are expected at low level ($, Comment: To be published on the proceedings of the 16th Marcel Grossmann Meeting on Recent Developments in Theoretical and Experimental General Relativity, Astrophysics and Relativistic Field Theories (MG16) - 5-9 July 2021. Online Conference, Italy - http://www.icra.it/mg/mg16/

BACKGROUND & AIMS: The aim of this study was to evaluate the nutritional support management in mechanically ventilated coronavirus disease 2019 (COVID-19) patients and explore the association between early caloric deficit and mortality, taking possible confounders (i.e. obesity) into consideration. METHODS: This was a prospective study carried out during the first pandemic wave in the intensive care units (ICUs) of two referral University Hospitals in Lombardy, Italy. Two hundred twenty-two consecutive mechanically ventilated COVID-19 patients were evaluated during the ICU stay. In addition to major demographic and clinical data, we recorded information on the route and amount of nutritional support provided on a daily basis. RESULTS: Among patients still in the ICUs and alive on day 4 (N = 198), 129 (65.2%) and 72 (36.4%) reached a satisfactory caloric and protein intake, respectively, mainly by enteral route. In multivariable analysis, a satisfactory caloric intake on day 4 was associated with lower mortality (HR = 0.46 [95%CI, 0.42-0.50], P

Purpose: This cross-sectional study aimed at comparing the quality of life (Qol), the prevalence of psychiatric diagnosis and pharmacological treatment in 104 candidates to bariatric surgery according to the degree of obesity (class 2 vs. class ≥ 3 obesity). Methods: All surgical candidates underwent a detailed psychiatric interview based on DSM-5 criteria, including sociodemographic, clinical, psychological and psychiatric data. Participants completed the Binge Eating Scale (BES) and the 12-Item Short Form Health Survey (SF-12). Results: Overall, bariatric candidates reported a significant impairment in the physical (PCS 38.8 [95% CI 36.2–41.5]) and mental (MCS 42.2 [95% CI 40.4–43.9]) components of Qol compared to population norms (p < 0.001 for both). Subjects with class 2 obesity scored significantly lower in the MCS compared to those with class 3 (38.7 (8.1) vs. 43.6 (8.4), p = 0.008). No other statistically significant differences were found between the two groups in terms of sociodemographic and clinical variables. Conclusion: These data support the usefulness of Qol assessment in bariatric candidates as a sensible screening parameter, especially in patients with lower BMI, in whom MCS could identify the need for early psychosocial intervention. Level of evidence: Level III,case-control analyticstudy.

Background & Aims Great interest has been raised by the possible protective role of vitamin D in coronavirus disease 2019 (COVID-19), but objective data on 25(OH)vitamin D deficiency in hospitalized COVID-19 patients are not conclusive. The aim of this study was to determine the prevalence of 25(OH)vitamin D deficiency in COVID-19 patients admitted to an Italian referral hospital and explore its association with clinical outcomes and the markers of disease severity. Methods In this single-center cohort study, 129 consecutive adult COVID-19 patients hospitalized in an Italian referral center were enrolled from March to April 2020. 25(OH)Vitamin D serum levels were assessed 48 hours since hospital admission and categorized into: normal (≥30 ng/mL), insufficient (

The COVID-19 outbreak has drastically changed practices inside hospitals, which include oncology routines. In oncology, malnutrition was and certainly still is a frequent problem associated with an increase in treatment-related toxicity, a reduced response to cancer treatment, an impaired quality of life, and a worse overall prognosis. Even in this situation of healthcare crisis, nutritional support in cancer care is an essential element. During the current COVID-19 pandemic, there is a concrete high risk to see a dramatic worsening of cancer patients' nutritional status, who are left without adequate clinical and nutritional support. The consequences are already reasonably foreseeable and will have a severe negative impact after the emergency. Therefore, we believe that it is essential to try to continue, as far as possible, the activity of clinical nutrition in oncology, by revolutionizing the setting and the approach to patients. For this purpose, the Clinical Nutrition and Dietetics Unit and the Medical Oncology Unit of our hospital, one of the largest community hospital in Lombardy that has been involved in the COVID-19 outbreak management since its inception, have reorganized the clinical routine activity in strict collaboration since the very beginning of the emergency, to better face up to the challenge, while preserving cancer patients' needs.

Background: The aim of the present prospective study (ClinicalTrials.gov Identifier: NCT02111538) was to assess the prognostic value of phase angle (PhA), derived from bioimpedance vectorial analys...

H. Sugai, et al., Recent developments of transition-edge sensors (TESs), based on extensive experience in ground-based experiments, have been making the sensor techniques mature enough for their application on future satellite cosmic microwave background (CMB) polarization experiments. LiteBIRD is in the most advanced phase among such future satellites, targeting its launch in Japanese Fiscal Year 2027 (2027FY) with JAXA’s H3 rocket. It will accommodate more than 4000 TESs in focal planes of reflective low-frequency and refractive medium-and-high-frequency telescopes in order to detect a signature imprinted on the CMB by the primordial gravitational waves predicted in cosmic inflation. The total wide frequency coverage between 34 and 448 GHz enables us to extract such weak spiral polarization patterns through the precise subtraction of our Galaxy’s foreground emission by using spectral differences among CMB and foreground signals. Telescopes are cooled down to 5 K for suppressing thermal noise and contain polarization modulators with transmissive half-wave plates at individual apertures for separating sky polarization signals from artificial polarization and for mitigating from instrumental 1/f noise. Passive cooling by using V-grooves supports active cooling with mechanical coolers as well as adiabatic demagnetization refrigerators. Sky observations from the second Sun–Earth Lagrangian point, L2, are planned for 3 years. An international collaboration between Japan, the USA, Canada, and Europe is sharing various roles. In May 2019, the Institute of Space and Astronautical Science, JAXA, selected LiteBIRD as the strategic large mission No. 2., This work was supported by World Premier International Research Center Initiative (WPI), MEXT, Japan, by JSPS Core-to-Core Program, A. Advanced Research Networks, and by JSPS KAKENHI Grant Numbers JP15H05891, JP17H01115, and JP17H01125. The Italian contribution to the LiteBIRD phase A is supported by the Italian Space Agency (ASI Grant No. 2016-24- H.1-2018) and the National Institute for Nuclear Physics (INFN). The French contribution to the LiteBIRD phase A is supported by the Centre National d’Etudes Spatiale (CNES), by the Centre National de la Recherche Scientifque (CNRS), and by the Commissariat à l’Energie Atomique (CEA). A Concurrent Design Facility study focused on the MHFT and Sub-Kelvin coolers has been led by the European Space Agency (ESA). The Canadian contribution to LiteBIRD is supported by the Canadian Space Agency. The US contribution is supported by NASA Grant no. 80NSSC18K0132

The design of new natural gas liquefaction facilities is closely aligned with the quality of the immediately available feed gas and the SPA’s agreed with customers. However, the lifetime of the facilities often extends beyond the lifetime of both the gas source and the duration of the SPA’s. Recent statistics indicate up to 60 MTPA of global liquefaction capacity is not utilized. Qualitative based approaches are often adopted to assess how an LNG plant responds to a change in feed gas specification. However a more valuable approach uses a quantitative analysis which can achieve an optimal outcome via individual tuning of a potentially large number of plant variables. Such an approach starts by performing actual plant capacity tests for different operating modes and process variables to capture baseline operation performance data. The plant test results are to validate a detailed plant simulation model which includes all the plant variables of interest. The validated model can then help identify the optimum operating condition and the benefits of a range of potential modifications. The methodology was used to identify solutions to a typical problem in a multi-train facility where a change from rich feed stock was accompanied by the presence of aromatics in a significantly leaner feed gas. Detailed modelling of the plant enabled an understanding of the solubility of the aromatics in the lean gas. The previously validated model of the real plant behaviour was then used to evaluate the benefits of changes to the key operating parameters and minor modifications to the plant itself. This resulted in a significantly more efficient and cost-effective solution than simply importing LPG which would have been the solution normally taken by a traditional "qualitative" approach. A similar approach was used to address an associated commercial challenge of satisfying a SPA demanding a high HHV with a leaner feed gas. In this case the solution relied not only on the technical insight afforded by the quantitative analysis but also a recognition that accurate tuning of the operational process allows a reduction in the conservatism of the product specification. Furthermore, with minor modifications, a multi-train process with segregated storage can be operated in multiple HHV mode provided careful procedures are employed to mitigate operational risks. This paper demonstrates how a holistic, detailed, quantitative analysis of gas liquefaction process can provide a good insight into the capability of existing plant to respond to changes in feedstock quality. The outlined methodology combined with a good understanding of the commercial features of the LNG business offers the possibility to better exploit the significant and growing amount of unused gas liquefaction capacity around the world.

Background Serum uric acid (SUA) is increasingly recognised as an important predictor of cardiovascular disease (CVD) and total mortality. However, the levels of SUA that discriminate across the different strata of risk for CVD and total mortality remain unknown, complicating the identification of subjects at high or low mortality risk for SUA in clinical practice. Purpose In this study we used a large Italian population comprising >3ehz748.0326 subjects to assess the threshold of SUA that increases the risk of total and CVD mortality. Methods The URic Acid Right for heArt Health (URRAH) study is a regional-basis multicentre cohort study which collected data from prospective studies and databases from different hypertension centres, including subjects with at least one measure of SUA and a follow-up of about 20 years. Total mortality was defined as mortality for any causes, cardiovascular mortality as death due to fatal myocardial infraction, stroke or heart failure. Multivariate dichotomic logistic and Cox regression models were used to confirm the relationship between SUA and mortality status both from cardiovascular and any causes, while ROC curves were used to identify the threshold of SUA that better discriminated people at higher or lower mortality risk. Results A total of 22.275 subjects had SUA and mortality information. Logistic regression identified a direct and strong association between SUA and an increased risk of total (OR 1.176, 95% CI 1.127–1.227) and CVD (OR 1.147, 95% CI 1.093–1.203) mortality, independently of other CVD risk factors (age, BMI, LDL cholesterol, diagnosis of diabetes, hypertension, chronic kidney disease, alcohol consumption and smoking). Cox models confirmed the presence of an independent association between SUA and any causes (HR 1.123, 95% CI 1.090–1.567) and CVD (HR 1.124, 95% CI 1.081–1.169) mortality. ROC curve analysis identified a cut-off value od SUA [(4.79 mg/dL (95% CI 4.7–5.4 mg/dl)] able to discriminate total mortality status, and a different one [(5.60 mg/dL (95% CI 5.09–5.89 mg/dl)] able to identify CVD mortality status. Multivariate Cox analysis adjusted for confounders confirmed that subjects with SUA >4.79 mg/dl had a significantly higher total mortality (HR 1.293, 95% CI 1.181–1.416) compared to those with SUA 5.60 mg/dl had a significantly higher CVD mortality (HR 1.428, 95% CI 1.273–1.600) than those with SUA Conclusion Levels of SUA that increase the risk of total and CVD mortality are significantly lower than those commonly used for the definition of hyperuricemia in clinical practice. Our data provide the first large evidence of a level of “cardiovascular” SUA that might be used in clinical practice to identify subjects at greater risk of total and CVD mortality.

The Q & U Bolometric Interferometer for Cosmology, QUBIC, is an innovative experiment designed to measure the polarization of the Cosmic Microwave Background and in particular the signature left therein by the inflationary expansion of the Universe. The expected signal is extremely faint, thus extreme sensitivity and systematic control are necessary in order to attempt this measurement. QUBIC addresses these requirements using an innovative approach combining the sensitivity of Transition Edge Sensor cryogenic bolometers, with the deep control of systematics characteristic of interferometers. This makes QUBIC unique with respect to others classical imagers experiments devoted to the CMB polarization. In this contribution we report a description of the QUBIC instrument including recent achievements and the demonstration of the bolometric interferometry performed in lab. QUBIC will be deployed at the observation site in Alto Chorrillos, in Argentina at the end of 2019., Accepted for publication in the Journal of Low Temperature Physics

Background and aims: Recently, the albuminocentric view of diabetic kidney disease (DKD) in type 2 diabetes (T2DM) has been changing. Therefore, the relationship between diabetic retinopathy (DR) and chronic kidney disease (CKD) has to be addressed according to this new clinical presentation of DKD. The aim of this study was to evaluate, in a real-world setting, the correlation DR–DKD in T2DM. Methods and results: A total of 2068 type 2 diabetic patients enrolled in a multicenter cross-sectional study were investigated. Albuminuric subjects were largely prevalent among subjects with DR (p = 0.019). In the whole study population, no difference in albumin excretion rate (AER) was observed between presence/absence of DR; instead, AER was significantly higher among patients with glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 (CKD) (p = 0.009), above all in those with CKD and AER ≥0.03 g/24 h (p = 0.005). Multivariate analysis confirmed that eGFR (O.R. 0.976; 95% C.I.: 0.960–1.028; p < 0.001) and AER (O.R. 1.249; 95% C.I. 1.001–1.619; p = 0.004) were independently associated with DR and HDL–cholesterol (O.R.: 1.042; 95% C.I.: 1.011–1.120; p = 0.014). Additionally, among patients with eGFR

Aim: To investigate the associations of blood pressure variability (BPV), expressed as long-term (visit-to-visit) and short-term (ambulatory blood pressure monitoring [ABPM] and home blood pressure monitoring [HBPM]) and all-cause mortality, major adverse cardiovascular events (MACEs), extended MACEs, microvascular complications (MiCs) and hypertension-mediated organ damage (HMOD) in adult patients with type 2 diabetes. Materials and methods: PubMed, Medline, Embase, Cinahl, Web of Science, ClinicalTrials.gov and grey literature databases were searched for studies including patients with type 2 diabetes, at least one variable of BPV (visit-to-visit, HBPM, ABPM) and evaluation of the incidence of at least one of the following outcomes: all-cause mortality, MACEs, extended MACEs and/or MiCs and/or HMOD. The extracted information was analyzed using random effects meta-analysis and meta-regression. Results: Data from a total of 377 305 patients were analyzed. Systolic blood pressure (SBP) variability was associated with a significantly increased risk of all-cause mortality (HR 1.12, 95% CI 1.04–1.21), MACEs (HR 1.01, 95% CI 1.04–1.17), extended MACEs (HR 1.07, 95% CI 1.03–1.11) and MiCs (HR 1. 12, 95% CI 1.01–1.24), while diastolic blood pressure was not. Associations were mainly driven from studies on long-term SBP variability. Qualitative analysis showed that BPV was associated with the presence of HMOD expressed as carotid intima-media thickness, pulse wave velocity and left ventricular hypertrophy. Results were independent of mean blood pressure, glycaemic control and serum creatinine levels. Conclusions: Our results suggest that BPV might provide additional information rather than mean blood pressure on the risk of cardiovascular disease in patients with type 2 diabetes. © 2019 John Wiley & Sons Ltd

Background: Nutritional support, including nutritional counseling and oral nutritional supplements (ONSs), has been recommended at the earliest opportunity in head and neck (H&N) cancer patients. The limited available evidence on the efficacy of immunonutrition during chemoradiotherapy (CT-RT) in H&N cancer patients is positive with regard to some secondary endpoints, but is still scanty, particularly with regard to toxicity and treatment tolerance. We hypothesize that early systematic provision of ONSs with a high-protein–high-calorie mixture containing immunonutrients (Impact) compared to standard high-calorie–high-protein nutritional blends, in addition to nutritional counseling, may be beneficial to patients with H&N cancer during CT-RT. Hence, we designed the present study to evaluate the efficacy, in terms of treatment tolerance, toxicity and response, body weight, body composition, protein-calorie intake, quality of life (QoL), fatigue, muscle strength and immunological profile of the early systematic provision of ONSs enriched in immunonutrients compared to isonitrogenous standard blends, in H&N cancer patients undergoing CT-RT. Methods: This is a pragmatic, bicentric, randomized (1:1), parallel-group, open label, controlled, pilot clinical trial. Discussion: Many efforts are still to be taken to improve the efficacy of nutritional support in oncology. Immunonutrition represents a promising approach also in H&N cancer patients, but the evidence on its efficacy in improving clinical outcomes during CT-RT is still inconclusive. The present pilot study, which guarantees the early provision of nutritional assessment and support to all the enrolled patients in accordance with the recent guidelines and recommendations, could represent one of the first proofs of the clinical effectiveness of early oral immunonutrition in cancer patients undergoing CT-RT and could stimulate further large randomized trials, potentially resulting in the improvement of supportive care quality. Trial registration: This study is registered on ClinicalTrials.gov Identifier: NCT04611113.