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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.

Background: Oral activated factor XI (FXIa) inhibitors may modulate coagulation to prevent thromboembolic events without substantially increasing bleeding. We explored the pharmacodynamics, safety, and efficacy of the oral FXIa inhibitor asundexian for secondary prevention after acute myocardial infarction (MI). Methods: We randomized 1601 patients with recent acute MI to oral asundexian 10, 20, or 50 mg or placebo once daily for 6 to 12 months in a double-blind, placebo-controlled, phase 2, dose-ranging trial. Patients were randomized within 5 days of their qualifying MI and received dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor. The effect of asundexian on FXIa inhibition was assessed at 4 weeks. The prespecified main safety outcome was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding comparing all pooled asundexian doses with placebo. The prespecified efficacy outcome was a composite of cardiovascular death, MI, stroke, or stent thrombosis comparing pooled asundexian 20 and 50 mg doses with placebo. Results: The median age was 68 years, 23% of participants were women, 51% had ST-segment–elevation MI, 80% were treated with aspirin plus ticagrelor or prasugrel, and 99% underwent percutaneous coronary intervention before randomization. Asundexian caused dose-related inhibition of FXIa activity, with 50 mg resulting in >90% inhibition. Over a median follow-up of 368 days, the main safety outcome occurred in 30 (7.6%), 32 (8.1%), 42 (10.5%), and 36 (9.0%) patients receiving asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian versus placebo: hazard ratio, 0.98 [90% CI, 0.71–1.35]). The efficacy outcome occurred in 27 (6.8%), 24 (6.0%), 22 (5.5%), and 22 (5.5%) patients assigned asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian 20 and 50 mg versus placebo: hazard ratio, 1.05 [90% CI, 0.69–1.61]). Conclusions: In patients with recent acute MI, 3 doses of asundexian, when added to aspirin plus a P2Y12 inhibitor, resulted in dose-dependent, near-complete inhibition of FXIa activity without a significant increase in bleeding and a low rate of ischemic events. These data support the investigation of asundexian at a dose of 50 mg daily in an adequately powered clinical trial of patients who experienced acute MI. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04304534; URL: https://www.clinicaltrialsregister.eu/ctr-search/search ; Unique identifier: 2019-003244-79.

Aim: Determine the clinical utility and economic differences over a 90-day period between robotic arm-assisted total hip arthroplasty (RATHA) and manual total hip arthroplasty (MTHA). Methods: Leveraging a nationwide commercial payer database, pre-covid THA procedures were identified. Following a 1:5 propensity score match, 1732 RATHA and 8660 MTHA patients were analyzed. Index costs, index lengths of-stay, and 90-day episode-of-care utilization and costs were evaluated. Results: Episode of care costs for RATHA was found to be $1573 lower compared with MTHA (p Conclusion: Index and post-index EOC hospital utilization and costs were lower for RATHA compared with MTHA.

We describe the readout electronics for Kinetic Inductance Detectors (KIDs) that we are developing based on a 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 y-distortions. The COSMO readout electronics requires a sampling rate in the range of tens of kHz, due to both a fast modulation of the signal with a spinning optical element and the short time constant of the Kinetic Inductance Detectors (KIDs) used in COSMO. 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 at about 12 kHz.

As evidence signifies that short-stay total knee arthroplasties (TKA) can be safe options, it is important to identify factors that contribute to early discharge. There is evidence that robotic-assisted TKAs may lead to shorter lengths of postoperative stays. However, this has not been evaluated as the primary outcome of interest in a large-scale population. The purpose of this study was to compare manual and robotic-assisted TKAs with regard to: (1) length of stay (LOS) and (2) discharge dispositions. TKAs performed between January 1, 2018, to March 31, 2019, were identified. After applying inclusion and exclusion criteria, a total of 10,296 patients were included: 5,993 in the manual and 4,303 in the robotic-assisted group. Length of stay, discharge dispositions, and Charlson comorbidity indices (CCIs) were recorded for all patients. The mean LOS was significantly lower in robotic-assisted (1.68 ± 0.86 days) compared with manual (1.86 ± 0.94 days) TKA procedures (p

In this observational, retrospective study, we performed economic analyses between robotic arm-assisted total knee arthroplasty (RATKA) and manual total knee arthroplasty (MTKA). Specifically, we compared: (1) index costs including computed tomography (CT) scans; (2) 90-day postoperative health care utilization, (3) 90-day episode-of-care (EOC) costs, and (4) lengths of stay between CT scan-based robotically-assisted versus MTKAs. A large national database, Blue Health Intelligence (BHI), was used for RATKAs and MTKAs performed between April 1, 2017 and September 30, 2019. Based on strict inclusion–exclusion criteria, with propensity score matching, 4,135 RATKAs and 4,135 MTKAs were identified and analyzed. Index costs to the payer for RATKA patients were found to be less than those for MTKA patients ($29,984 vs. $31,280, p

The Large Scale Polarization Explorer (LSPE) is a cosmology program for the measurement of large scale curl-like features (B-modes) in the polarization of the Cosmic Microwave Background. Its goal is to constrain the background of inflationary gravity waves traveling through the universe at the time of matter-radiation decoupling. The two instruments of LSPE are meant to synergically operate by covering a large portion of the northern microwave sky. LSPE/STRIP is a coherent array of receivers planned to be operated from the Teide Observatory in Tenerife, for the control and characterization of the low-frequency polarized signals of galactic origin; LSPE/SWIPE is a balloon-borne bolometric polarimeter based on 330 large throughput multi-moded detectors, designed to measure the CMB polarization at 150 GHz and to monitor the polarized emission by galactic dust above 200 GHz. The combined performance and the expected level of systematics mitigation will allow LSPE to constrain primordial B-modes down to a tensor/scalar ratio of $10^{-2}$. We here report the status of the STRIP pre-commissioning phase and the progress in the characterization of the key subsystems of the SWIPE payload (namely the cryogenic polarization modulation unit and the multi-moded TES pixels) prior to receiver integration., 8 pages, 5 figures, Accepted for publication in Journal of Low Temperature Physics

Robotic-assisted total knee arthroplasty (RA-TKA) has been shown to improve the accuracy of bone resection, reduce radiographic outliers, and decrease iatrogenic injury. However, it has also been shown that RA-TKA surgical times can be longer than manual surgery during adoption. The purpose of this article was to investigate (1) the characteristics of the operative time curves and trends, noting the amount of surgeons who improved, for those who performed at least 12 cases (based on initial modeling); (2) the proportion of RA surgeons who achieved the same operative times for RA-TKA as compared with manual TKAs; and (3) the number of RA-TKA cases until a steady-state operative time was achieved. TKA operative times were collected from 30 hospitals for 146 surgeons between January 1, 2016, and December 31, 2019. A hierarchical Bayesian model was used to estimate the difference between the mean RA-TKA times by case interval and the weighted baseline for manual times. The learning curve was observed at the 12th case. Therefore, operative times were analyzed for each surgeon who performed at least 12 RA-TKA cases to determine the percentage of these surgeons who trended toward a decrease or increase in their times. These surgeons were further analyzed to determine the proportion who achieved the same operating times as manual TKAs. A further hierarchical Bayesian model was used to determine when these surgeons achieved steady-state operative times. There were 60 surgeons (82%) who had decreasing surgical times over the first 12 RA-TKA cases. The remaining 13 (18%) had increasing surgical times (mean increase of 0.59 minutes/case). Approximately two-thirds of the surgeons (64%) achieved the same operating times as manual cases. The steady-state time neutrality occurred between 15 and 20 cases and beyond. This study demonstrated the learning curve for a large cohort of RA-TKAs. This model demonstrated a learning curve between 15 and 20 cases and beyond. These are important findings for this innovative technology.

The MIllimeter Sardinia radio Telescope Receiver based on Array of Lumped elements kids, MISTRAL, is a millimetric ($\simeq 90GHz$) multipixel camera being built for the Sardinia Radio Telescope. It is going to be a facility instrument and will sample the sky with 12 arcsec angular resolution, 4 arcmin field of view, through 408 Kinetic Inductance Detectors (KIDs). The construction and the beginning of commissioning is planned to be in 2022. MISTRAL will allow the scientific community to propose a wide variety of scientific cases including protoplanetary discs study, star forming regions, galaxies radial profiles, and high angular resolution measurements of the Sunyaev Zel'dovich (SZ) effect with the investigation of the morphology of galaxy cluster and the search for the Cosmic Web., Comment: 18 pages, 6 figure, accepted for pubblication in the International Journal of Modern Physics D

The Q&U Bolometric Interferometer for Cosmology (QUBIC) is a novel kind of polarimeter optimized for the measurement of the B-mode polarization of the Cosmic Microwave Back-ground (CMB), which is one of the major challenges of observational cosmology. The signal is expected to be of the order of a few tens of nK, prone to instrumental systematic effects and polluted by various astrophysical foregrounds which can only be controlled through multichroic observations. QUBIC is designed to address these observational issues with a novel approach that combines the advantages of interferometry in terms of control of instrumental systematics with those of bolometric detectors in terms of wide-band, background-limited sensitivity., Contribution to the 2022 Cosmology session of the 33rd Rencontres de Blois. arXiv admin note: substantial text overlap with arXiv:2203.08947

The LiteBIRD collaboration: et al, A methodology to provide the polarization angle requirements for different sets of detectors, at a given frequency of a CMB polarization experiment, is presented. The uncertainties in the polarization angle of each detector set are related to a given bias on the tensor-to-scalar ratio r parameter. The approach is grounded in using a linear combination of the detector sets to obtain the CMB polarization signal. In addition, assuming that the uncertainties on the polarization angle are in the small angle limit (lower than a few degrees), it is possible to derive analytic expressions to establish the requirements. The methodology also accounts for possible correlations among detectors, that may originate from the optics, wafers, etc. The approach is applied to the LiteBIRD space mission. We show that, for the most restrictive case (i.e., full correlation of the polarization angle systematics among detector sets), the requirements on the polarization angle uncertainties are of around 1 arcmin at the most sensitive frequency bands (i.e., ≈ 150 GHz) and of few tens of arcmin at the lowest (i.e., ≈ 40 GHz) and highest (i.e., ≈ 400 GHz) observational bands. Conversely, for the least restrictive case (i.e., no correlation of the polarization angle systematics among detector sets), the requirements are ≈ 5 times less restrictive than for the previous scenario. At the global and the telescope levels, polarization angle knowledge of a few arcmins is sufficient for correlated global systematic errors and can be relaxed by a factor of two for fully uncorrelated errors in detector polarization angle. The reported uncertainty levels are needed in order to have the bias on r due to systematics below the limit established by the LiteBIRD collaboration., This work is supported in Japan by ISAS/JAXA for Pre-Phase A2 studies, by the acceleration program of JAXA research and development directorate, by the World Premier InJCAP04(2022)029– 19ternational Research Center Initiative (WPI) of MEXT, by the JSPS Core-to-Core Program of A. Advanced Research Networks, and by JSPS KAKENHI Grant Numbers JP15H05891, JP17H01115, and JP17H01125. The Italian LiteBIRD phase A contribution is supported by the Italian Space Agency (ASI Grants No. 2020-9-HH.0 and 2016-24-H.1-2018), the National Institute for Nuclear Physics (INFN) and the National Institute for Astrophysics (INAF). The French LiteBIRD phase A contribution is supported by the Centre National d’Etudes Spatiale (CNES), by the Centre National de la Recherche Scientifique (CNRS), and by the Commissariat à l’Energie Atomique (CEA). The Canadian contribution is supported by the Canadian Space Agency. The US contribution is supported by NASA grant no. 80NSSC18K0132. Norwegian participation in LiteBIRD is supported by the Research Council of Norway (Grant No. 263011). The Spanish LiteBIRD phase A contribution is supported by the Spanish Agencia Estatal de Investigación (AEI), project refs. ESP2017-83921C2-1-R, PID2019-110610RB-C21, PID2020-120514GB-I00, ProID2020010108,and funding from Unidad de Excelencia María de Maeztu (MDM-2017-0765) co-funded with EU FEDER funds. Funds that support the Swedish contributions come from the Swedish National Space Agency (SNSA/Rymdstyrelsen) and the Swedish Research Council (Reg. no. 201903959). The German participation in LiteBIRD is supported in part by the Excellence Cluster ORIGINS, which is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy (Grant No. EXC-2094 — 390783311). We m

A prototype version of the Q & U Bolometric Interferometer for Cosmology (QUBIC) underwent a campaign of testing in the laboratory at Astroparticle Physics and Cosmology in Paris. We report the results of this Technological Demonstrator which successfully shows the feasibility of the principle of Bolometric Interferometry. Characterization of QUBIC includes the measurement of the synthesized beam, the measurement of interference fringes, and the measurement of polarization performance. A modulated and frequency tunable millimetre-wave source in the telescope far-field is used to simulate a point source. The QUBIC pointing is scanned across the point source to produce beam maps. Polarization modulation is measured using a rotating Half Wave Plate. The measured beam matches well to the theoretical simulations and gives QUBIC the ability to do spectro imaging. The polarization performance is excellent with less than 0.5\% cross-polarization rejection. QUBIC is ready for deployment on the high altitude site at Alto Chorillo, Argentina to begin scientific operations., Part of a series of 8 papers on QUBIC accepted by JCAP for a special issue: https://iopscience.iop.org/journal/1475-7516/page/QUBIC_status_and_forecast

OBJECTIVES Previous studies on Medicare populations have shown improved outcomes and decreased 90-day episode-of-care costs with robotic arm-assisted total knee arthroplasty (RATKA). The purpose of this study was to evaluate expenditures and utilization following RATKA in the population younger than 65 years. STUDY DESIGN This is a retrospective longitudinal analysis of a commercial claims data set. METHODS TKA procedures were identified using the OptumInsight Inc database. The procedures were stratified in 2 groups: the RATKA and manual TKA (MTKA) cohorts. Propensity score matching was performed at 1:5. Utilization and associated costs were analyzed for 90 days following the index procedure. A total of 357 RATKA and 1785 MTKA procedures were included in this analysis. RESULTS Within 90 days post surgery, patients who had RATKA were less likely to utilize inpatient services (2.24% vs 4.37%; P = .0444) and skilled nursing facilities (1.68% vs 6.05%; P

Dual-mobility constructs have been shown to significantly and substantially decrease dislocations after revision total hip arthroplasty (THA). The authors have previously shown that dual-mobility (DM) constructs are cost-effective given their ability to decrease dislocations and re-revision for dislocation. The goal was to report the costs of DM and large femoral head (LFH) constructs in revision THAs from a European health care payer perspective. A Markov model was constructed to analyze the costs incurred by payers in the United Kingdom, Germany, Italy, and Spain over 3 years in revision THAs with DM or LFH constructs. Model states and probabilities were derived from prospectively collected registry data in 302 patients who underwent revision THA with a DM or 40-mm LFH construct and were then mapped to corresponding procedural reimbursement codes and tariffs for each country. Costs were weighted average national payments for reintervention procedures performed in the 3 years following revision THA. Probabilistic sensitivity analysis examined the effect of combined uncertainty across all model parameters. During a 3-year period following revision THA, reintervention rates were 9% for DM constructs and 19% for LFH constructs ( P =.01). Comparing DM and LFH constructs, cumulative incremental costs over 3-years' follow-up were £428 vs £1447 in the United Kingdom, euro 451 vs euro 1272 in Germany, euro 540 vs euro 1425 in Italy, and euro 523 vs euro 1562 in Spain, respectively. At mid-term follow-up, DM constructs used in revision THAs were associated with a significantly lower risk of reintervention, which translated to lower health care payer costs compared with LFH constructs among European health care payers. [ Orthopedics . 2020;43(4):250–255.]

International audience; The Q and U Bolometric Interferometer for Cosmology (QUBIC) Technical Demonstrator (TD) aiming to shows the feasibility of the combination of interferometry and bolometric detection. The electronic readout system is based on an array of 128 NbSi Transition Edge Sensors cooled at 350mK readout with 128 SQUIDs at 1K controlled and amplified by an Application Specific Integrated Circuit at 40K. This readout design allows a 128:1 Time Domain Multiplexing. We report the design and the performance of the detection chain in this paper. The technological demonstrator unwent a campaign of test in the lab. Evaluation of the QUBIC bolometers and readout electronics includes the measurement of I-V curves, time constant and the Noise Equivalent Power. Currently the mean Noise Equivalent Power is ~ 2 x 10-16W= p √Hz

Aim: To evaluate 90-day episode-of-care (EOC) resource consumption in robotic-assisted total hip arthroplasty (RATHA) versus manual total hip arthroplasty (mTHA). Methods: THA procedures were identified in Medicare 100% data. After propensity score matching 1:5, 938 RATHA and 4,670 mTHA cases were included. 90-day EOC cost, index costs, length of stay and post-index rehabilitation utilization were assessed. Results: RATHA patients were significantly less likely to have post-index inpatient rehabilitation or skilled nursing facility admissions and used fewer home health agency visits, compared with mTHA patients. Total 90-day EOC costs for RATHA patients were found to be US$785 less than those of mTHA patients (p = 0.0095). Conclusion: RATHA was associated with an overall lower 90-day EOC cost when compared with mTHA. The savings associated with RATHA were driven by reduced utilization and cost of post-index rehabilitation services.

We present the design, manufacturing, and testing of a 37-element array of corrugated feedhorns for Cosmic Microwave Background CMB) measurements between 140 and 170 GHz. The array was designed to be coupled to Kinetic Inductance Detector arrays, either directly (for total power measurements) or through an orthomode transducer (for polarization measurements). We manufactured the array in platelets by chemically etching aluminum plates of 0.3 mm and 0.4 mm thickness. The process is fast, low-cost, scalable, and yields high-performance antennas compared to other techniques in the same frequency range. Room temperature electromagnetic measurements show excellent repeatability with an average cross polarization level about − 20 dB, return loss about − 25 dB, first sidelobes below − 25 dB and far sidelobes below − 35 dB. Our results qualify this process as a valid candidate for state-of-the-art CMB experiments, where large detector arrays with high sensitivity and polarization purity are of paramount importance in the quest for the discovery of CMB polarizationB-modes.

This study performed a health care utilization analysis between robotic arm assisted total knee arthroplasty (rTKA) and manual total knee arthroplasty (mTKA) techniques. Specifically, we compared (1) index costs and (2) discharge dispositions, as well as (3) 30-day (4) 60-day, and (5) 90-day (a) episode-of-care costs, (b) postoperative health care utilization, and (c) readmissions. The 100% Medicare Standard Analytical Files were used for rTKAs and mTKAs performed between January 1, 2016, and March 31, 2017. Based on strict inclusion–exclusion criteria and 1:5 propensity score matching, 519 rTKA and 2,595 mTKA patients were analyzed. Total episode payments, health care utilization, and readmissions, at 30-, 60-, and 90-day time points were compared using generalized linear model, binomial regression, log link, Mann–Whitney, and Pearson's chi-square tests. The rTKA versus mTKA cohort average total episode payment was US$17,768 versus US$19,899 (p

Cardiovascular disease remains the leading cause of death in adults in the United States and constitutes a substantial portion of overall national health expenditures. Aspirin is generally recommended for primary cardiovascular event prevention based on a given patient's underlying cardiovascular event risk profile, particularly for those aged 50-69 years with a 10-year risk of coronary heart disease of ≥ 10%. Evidence-based clinical guidelines are in agreement for secondary prevention consisting of lifelong, low-dose aspirin therapy following a cardiovascular event. Despite these recommendations, research suggests suboptimal concordance between guidelines and clinical practice.To evaluate the budget impact of appropriate low-dose aspirin use for primary and secondary cardiovascular event prevention compared with current rates of low-dose aspirin use.An economic model measuring budget spend for cardiovascular events, aspirin, and aspirin-related adverse events was developed from the perspective of a U.S. payer. The model compared current rates of aspirin use to appropriate rates of aspirin use according to guideline recommendations for both primary and secondary cardiovascular event prevention.For a hypothetical plan with 1 million members, an estimated 18,026 patients were on aspirin therapy for primary cardiovascular event prevention, while guidelines recommend that 55,788 patients should have been on aspirin therapy for this indication. Optimal aspirin use in the primary cardiovascular event prevention population reduced the number of nonfatal myocardial infarctions (MIs; -367), ischemic strokes (-232), and deaths (-60), with an increase in the number of gastrointestinal bleeds (169) and hemorrhagic strokes (98). Evidence-based guideline-compliant use of aspirin for primary cardiovascular event prevention resulted in total cost savings of approximately $4.2 million over a 5-year time horizon. For secondary cardiovascular event prevention, an estimated 48,663 patients were on aspirin, while clinical guidelines recommend that 71,316 patients should have been on aspirin therapy for this indication. Optimal aspirin use in secondary cardiovascular event prevention reduced the number of nonfatal MIs (-515), ischemic strokes (-375), and deaths (-217), with an increase in the number of gastrointestinal bleeds (98) and hemorrhagic strokes (58). Evidence-based guideline-compliant use of aspirin for secondary cardiovascular event prevention resulted in total cost savings of approximately $11 million over a 5-year time horizon.Appropriate low-dose aspirin use for primary and secondary cardiovascular event prevention can result in improved patient outcomes with significant cost savings for U.S. payers. As a simple and inexpensive prophylactic measure for cardiovascular event prevention, aspirin use should be carefully considered in all appropriate at-risk adult patients.Development of this manuscript and the corresponding budget impact analysis was funded by Bayer. Coppolecchia, Williamson, and Cameron are employees of Bayer. Carlton, Lennert, and Moradi are employees of Xcenda, a consulting firm that received funding from Bayer to assist in the completion of this study. Khalaf-Gillard was an employee of Xcenda at the time of the study. The corresponding poster was presented at the Academy of Managed Care Pharmacy Nexus 2017; October 16-19, 2017; Dallas, TX.

Additional file 1. Baseline characteristics of all 375 patients with septic shock included in our analysis.

Additional file 2: Syndecan1, Sphingosine-1-phosphate, VE-cadherin and circulating biomarkers. Table 1. Circulating biomarkers, albumin and lactate levels by tertiles of Syndecan-1 on day 1; Table 2. Circulating biomarkers, albumin and lactate levels by tertiles of S1P on day 1; Table 3. Circulating biomarkers, albumin and lactate levels by tertiles of VE-Cadherin on day 1. Figure 1. Spearman rank correlation coefficient for SYN-1, S1P and VE-cadherin on days 1, 2 and 7.

QUBIC (Q \& U Bolometric Interferometer for Cosmology) is an international ground-based experiment dedicated in the measurement of the polarized fluctuations of the Cosmic Microwave Background (CMB). It is based on bolometric interferometry, an original detection technique which combine the immunity to systematic effects of an interferometer with the sensitivity of low temperature incoherent detectors. QUBIC will be deployed in Argentina, at the Alto Chorrillos mountain site near San Antonio de los Cobres, in the Salta province. The QUBIC detection chain consists in 2048 NbSi Transition Edge Sensors (TESs) cooled to 350mK.The voltage-biased TESs are read out with Time Domain Multiplexing based on Superconducting QUantum Interference Devices (SQUIDs) at 1 K and a novel SiGe Application-Specific Integrated Circuit (ASIC) at 60 K allowing to reach an unprecedented multiplexing (MUX) factor equal to 128. The QUBIC experiment is currently being characterized in the lab with a reduced number of detectors before upgrading to the full instrument. I will present the last results of this characterization phase with a focus on the detectors and readout system., Conference proceedings submitted to the Journal of Low Temperature Physics for LTD18

International audience; We describe the in-flight performance of the horn-coupled lumped element kinetic inductance detector arrays of the balloon-borne OLIMPO experiment. These arrays have been designed to match the spectral bands of OLIMPO: 150, 250, 350, and $460\,\hbox {GHz}$, and they have been operated at $0.3\,\hbox {K}$ and at an altitude of ${37.8}\,\hbox {km}$ during the stratospheric flight of the OLIMPO payload, in Summer 2018. During the first hours of flight, we tuned the detectors and verified their large dynamics under the radiative background variations due to elevation increase of the telescope and to the insertion of the plug-in room-temperature differential Fourier transform spectrometer into the optical chain. We have found that the detector noise equivalent powers are close to be photon noise limited and lower than those measured on the ground. Moreover, the data contamination due to primary cosmic rays hitting the arrays is less than 3% for all the pixels of all the arrays and less than 1% for most of the pixels. These results can be considered the first step of KID technology validation in a representative space environment.

IntroductionThis study performed a healthcare utilization analysis between robotic-arm assisted and manual TKA techniques at three intervals to better understand intra-episode trends that can lead to optimized care pathways. Specifically, we compared: (1) index costs; and (2) discharge dispositions; as well as (3) 30-; (4) 60-; and (5) 90- day: a) total episode-of-care costs, b) post-operative healthcare utilization, and c) readmissions.MethodsThe Medicare 100% Standard Analytical Files was queried for robotic and manual TKAs (rTKA and mTKA) performed between January 1, 2016 and March 31, 2017. Based on strict inclusion and exclusion criteria, and 1:5 propensity score matching, 519 robotic and 2,595 manual TKA patients were analyzed. Total episode payments, healthcare utilization, and readmissions, at 30-, 60-, and 90-day time points were compared between cohorts with a generalized Linear Model, Binomial Regression, log link, Mann-Whitney, and Pearson's Chi Squared tests with pResultsThe robotic vs. manual cohort average total episode payment was $17,768 vs. $19,899 (pDiscussionRobotic TKA is associated with significantly lower 30-, 60-, and 90-day post- operative costs and healthcare utilization. These results are of marked importance given the emphasis to contain and reduce healthcare costs for total joints arthroplasties. This analysis provides initial economic insight into robotic-arm assisted TKA with promising results.

Background:The purpose of this study was to evaluate hospital admissions for revision surgeries associated with robotic-arm assisted unicompartmental knee arthroplasty (rUKA) vs. manual UKA (mUKA) procedures.Methods:Patients ≥18 years of age who received either a mUKA or a rUKA procedure were candidates for inclusion and were identified by the presence of appropriate billing codes. Procedures performed between March 1st, 2013 and July 31st, 2015 were used to calculate the rate of surgical revisions occurring within 24-months of the index procedure. Following propensity matching, 246 rUKA and 492 mUKA patients were included. Revision rates and the associated costs were compared between the two cohorts. The Mann-Whitney U test, was used to compare continuous variables, and fisher’s exact tests was used to analyze discrete categorical variables.Results:At 24-months following the primary UKA procedure, patients who underwent rUKA had fewer revision procedures (0.81% [2/246] vs. 5.28% [26/492]; p=0.002), shorter mean LOS (2.00 vs. 2.33 days; p>0.05), and incurred lower mean costs for the index stay plus revisions ($26,001 vs. $27,915; p>0.05) than mUKA patients. Length of stay at index, and index costs were also lower for rUKA patients (1.77 vs. 2.02 days; p=.0047) and ($25,786 vs. $26,307; p>0.05).Conclusions:Study results demonstrate that patients who underwent rUKA had fewer revision procedures, shorter LOS, and incurred lower mean costs (although not statistically different) during the index admission and at 24-months post-operative. These results could be important for payers as the prevalence of end-stage knee OA increases alongside the demand for cost-efficient treatments.

IntroductionOne way to potentially help contain the rising healthcare costs is the utilization of technological advances, such as robotic-assistive technology, for total knee arthroplasty (TKA). Therefore, the purpose of this study was to perform a cost analysis between robotic-arm assisted TKA and manual TKA (mTKA) techniques. Specifically, we compared: 1) 90-day EOC costs, as well as several variables within the episode, including 2) index costs; 3) index lengths-of-stay (LOS); 4) discharge disposition; and 5) readmission rates.MethodsA retrospective claims analysis was performed on Medicare FFS beneficiaries who underwent rTKA and mTKA procedures between January 1, 2016 and March 31, 2017. Patients were matched rTKA to mTKA in a 1-to-5 ratio, yielding 519 rTKAs and 2,595 mTKAs. The overall 90-day EOC costs, including the index procedures, LOS, discharge dispositions, and readmissions were compared between cohorts.ResultsOverall 90-day EOC costs ($18,568 vs. $20,960) as well as index facility costs ($12,384 vs. $13,024; p=0.0001) were found to be less than that for rTKA vs. mTKA. rTKA also accrued $1,744 fewer costs than mTKA (5,234 vs. $6,978; p=DiscussionThe results from this study show rTKA to be associated with significantly lower 90-day EOC costs. These lower rTKA patient costs are likely attributable to the significantly lower index costs, increased likelihood of being discharged to home, shorter LOS, and decreased readmission rates, when compared to mTKA patient costs.

We analyze the effect of polarized diffuse emission in the calibration of wide-beam mm-wave polarimeters, when using the Crab Nebula as a reference source for both polarized brightness and polarization angle. We show that, for CMB polarization experiments aiming at detecting B-mode in a scenario with a tensor to scalar ratio $r \sim 0.001$, wide (a few degrees in diameter), precise ($\sigma_Q$ , $\sigma_U$ $\sim$ 20 $\mu$$K_{CMB}$ arcmin), high angular resolution ($< \mathrm{FWHM}$) reference maps are needed to properly take into account the effects of diffuse polarized emission and avoid significant bias in the calibration.

E rilevante la mancanza di studi in letteratura sulla reale utilita dei sistemi PoCT in eventi complessi, quali i disastri e le grandi emergenze, nonostante l’analisi dei processi sanitari nelle grandi catastrofi degli ultimi anni abbia confermato la necessita di un uso proattivo del PoCT in queste circostanze. All’interno degli standard di cura in condizioni di crisi delineati dall’Institute of Medicine, non vi e ancora sufficiente attenzione sulle modalita di impiego dei sistemi PoCT e non vengono previste procedure specifiche di intervento diagnostico nell’ambito del percorso terapeutico. Non appaiono infatti adeguati i modelli di intervento elaborati in tempo di pace o in condizioni ordinarie, data la diversita del contesto; per questo sta emergendo il piu largo concetto di punto di necessita, in luogo del punto di cura. Tuttavia la Medicina di Laboratorio non e stata ancora chiamata a chiarire il campo e il contesto d’azione dell’attivita diagnostica in vitro in queste particolari condizioni. Il principale scopo dell’articolo e definire per la prima volta alcune raccomandazioni relative ai criteri, ai modelli flessibili e alle strategie da attuare in condizioni di crisi: in particolare si fa riferimento ad alcune caratteristiche dei dispositivi (robustezza e tipologia di prestazioni), alle necessita dell’innovazione tecnologica e all’emergente esigenza di test diversi e mirati. Viene inoltre rivisto il concetto di leadership del coordinatore PoCT (con riferimento al set di abilita, all’analisi dell’esposizione al rischio e al piano di emergenza), sostenuta la necessita di nuove procedure per la formazione e l’addestramento (telemedicina, risorse web e impiego di smartphone) e infine riservata particolare attenzione alle strategie per la garanzia di qualita dei risultati dei test di laboratorio, dato il prevedibile incremento di potenziali rischi di errore nelle situazioni di crisi.

We describe the design and in–flight performance of the cryostat and the self–contained\ud\udHe refrigerator for the OLIMPO balloon–borne experiment, a spectrophotometer to measure the Sunyaev–Zel’dovich effect in clusters of galaxies.\ud\udThe\udHe refrigerator provides the 0.3 K operation temperature for the four arrays of kinetic inductance detectors working in 4 bands centered at 150, 250, 350 and 460 GHz. The cryostat provides the 1.65 K base temperature for the\ud\udHe refrigerator, and cools down the reimaging optics and the filters chain at about 2 K.\ud\udThe integrated system was designed for a hold time of about 15 days, to achieve the sensitivity required by the planned OLIMPO observations, and successfully operated during the first long–duration stratospheric flight of OLIMPO in July 2018.\ud\udThe cryostat features two tanks, one for liquid nitrogen and the other one for liquid helium. The long hold time has been achieved by means of custom stiff G10 fiberglass tubes support, which ensures low thermal conductivity and remarkable structural stiffness; multi–layer superinsulation, and a vapour cooled shield, all reducing the heat load on the liquid helium tank.\ud\udThe system was tested in the lab, with more than 15 days of unmanned operations, and then in the long duration balloon flight in the stratosphere. In both cases, the detector temperature was below 300 mK, with thermal stability better than\ud\ud0.5 mK.\ud\udThe system also operated successfully in the long duration stratospheric balloon flight.

We are developing a Lumped Element Kinetic Inductance Detector (LEKID) array able to operate in the W-band (75-110 GHz) in order to perform ground-based Cosmic Microwave Background (CMB) and mm-wave astronomical observations. The W-band is close to optimal in terms of contamination of the CMB from Galactic synchrotron, free-free, and thermal interstellar dust. In this band, the atmosphere has very good transparency, allowing interesting ground-based observations with large (>30 m) telescopes, achieving high angular resolution (, 16th International Workshop on Low Temperature Detectors, Grenoble 20-24 July 2015, Journal of Low Temperature Physics, Accepted

The goal of the Cryogenic wide-Area Light Detectors with Excellent Resolution project is the development of light detectors with large active area and noise energy resolution smaller than 20 eV RMS using phonon-mediated kinetic inductance detectors. The detectors are developed to improve the background suppression in large-mass bolometric experiments such as CUORE, via the double read-out of the light and the heat released by particles interacting in the bolometers. In this work, we present the design and the fabrication process, starting from the silicon wafer arriving to the single chip. The Al thin films (40 nm) are evaporated on high-quality, high-resistivity (> $$10\,\mathrm{k \Omega }\,$$ cm) Si(100) substrates using an electron beam evaporator in a high-vacuum chamber. Detectors are patterned in direct-write mode, using electron beam lithography , positive tone resist poly-methyl methacrylate and lift-off process. Finally the wafer is diced into 20 $$\times $$ 20 mm $$^2$$ chips and assembled in a holder OFHC copper (oxygen-free high conductivity) using PTFE supports.

In vitro evolution of enzymes represents a powerful device to evolve new or to improve weak enzymatic functions. In the present work a semi-rational engineering approach has been used to design an efficient and thermostable organophosphate hydrolase, starting from a lactonase scaffold (SsoPox from Sulfolobus solfataricus). In particular, by in vitro evolution of the SsoPox ancillary promiscuous activity, the triple mutant C258L/I261F/W263A has been obtained which, retaining its inherent stability, showed an enhancement of its hydrolytic activity on paraoxon up to 300-fold, achieving absolute values of catalytic efficiency up to 10(5) M(-1) s(-1). The kinetics and structural determinants of this enhanced activity were thoroughly investigated and, in order to evaluate its potential biotechnological applications, the mutant was tested in formulations of different solvents (methanol or ethanol) or detergents (SDS or a commercial soap) for the cleaning of pesticide-contaminated surfaces.

As normal inhabitants of diverse ecosystems, including the human gastrointestinal tract, the enterococci, and especially the two species Enterococcus faecalis and Enterococcus faecium, can be considered ubiquitous with regard to our natural environment. E. faecium has gained special importance thanks to beneficial strains marketed as probiotics, and because of its beneficial role in traditional fermented foods such as artisanal cheeses in some Southern European countries. Yet, following reports on the increasing association of some enterococcal strains with nosocomial infections such as endocarditis and bacteraemia, it became evident that strains from clinical origin are frequently highly resistant to ‘last-defence-line’ antibiotics such as the glycopeptide derivatives. For this reason enterococci have been classified in risk group 2 in the European Directive 93/88. With this paper it is intended to clarify the uncertain situation around the safety of the species E. faecium, also with referring to intra-species heterogeneity. In fact, well established scientific and surveillance data support the safety of some probiotic E. faecium strains for both human and animal applications. As a model, summarising yet extensive information is provided on the efficacy and safety of E. faecium SF68®, a pharmaceutical probiotic with a long history of safe use. We propose the approach presented in this review as a model for the evaluation of safety of probiotic strains of this species.

We present an analysis of the main systematic effects that could impact the measurement of CMB polarization with the proposed CORE space mission. We employ timeline-to-map simulations to verify that the CORE instrumental set-up and scanning strategy allow us to measure sky polarization to a level of accuracy adequate to the mission science goals. We also show how the CORE observations can be processed to mitigate the level of contamination by potentially worrying systematics, including intensity-to-polarization leakage due to bandpass mismatch, asymmetric main beams, pointing errors and correlated noise. We use analysis techniques that are well validated on data from current missions such as Planck to demonstrate how the residual contamination of the measurements by these effects can be brought to a level low enough not to hamper the scientific capability of the mission, nor significantly increase the overall error budget. We also present a prototype of the CORE photometric calibration pipeline, based on that used for Planck, and discuss its robustness to systematics, showing how CORE can achieve its calibration requirements. While a fine-grained assessment of the impact of systematics requires a level of knowledge of the system that can only be achieved in a future study phase, the analysis presented here strongly suggests that the main areas of concern for the CORE mission can be addressed using existing knowledge, techniques and algorithms.

Future observations of cosmic microwave background (CMB) polarisation have the potential to answer some of the most fundamental questions of modern physics and cosmology, including: what physical process gave birth to the Universe we see today? What are the dark matter and dark energy that seem to constitute 95% of the energy density of the Universe? Do we need extensions to the standard model of particle physics and fundamental interactions? Is the ΛCDM cosmological scenario correct, or are we missing an essential piece of the puzzle? In this paper, we list the requirements for a future CMB polarisation survey addressing these scientific objectives, and discuss the design drivers of the COREmfive space mission proposed to ESA in answer to the "M5" call for a medium-sized mission. The rationale and options, and the methodologies used to assess the mission's performance, are of interest to other future CMB mission design studies. COREmfive has 19 frequency channels, distributed over a broad frequency range, spanning the 60-600 GHz interval, to control astrophysical foreground emission. The angular resolution ranges from 2′ to 18′, and the aggregate CMB sensitivity is about 2 μKċarcmin. The observations are made with a single integrated focal-plane instrument, consisting of an array of 2100 cryogenically-cooled, linearly-polarised detectors at the focus of a 1.2-m aperture cross-Dragone telescope. The mission is designed to minimise all sources of systematic effects, which must be controlled so that no more than 10-4 of the intensity leaks into polarisation maps, and no more than about 1% of E-type polarisation leaks into B-type modes. COREmfive observes the sky from a large Lissajous orbit around the Sun-Earth L2 point on an orbit that offers stable observing conditions and avoids contamination from sidelobe pick-up of stray radiation originating from the Sun, Earth, and Moon. The entire sky is observed repeatedly during four years of continuous scanning, with a combination of three rotations of the spacecraft over different timescales. With about 50% of the sky covered every few days, this scan strategy provides the mitigation of systematic effects and the internal redundancy that are needed to convincingly extract the primordial B-mode signal on large angular scales, and check with adequate sensitivity the consistency of the observations in several independent data subsets. COREmfive is designed as a "near-ultimate" CMB polarisation mission which, for optimal complementarity with ground-based observations, will perform the observations that are known to be essential to CMB polarisation science and cannot be obtained by any other means than a dedicated space mission. It will provide well-characterised, highly-redundant multi-frequency observations of polarisation at all the scales where foreground emission and cosmic variance dominate the final uncertainty for obtaining precision CMB science, as well as 2′ angular resolution maps of high-frequency foreground emission in the 300-600 GHz frequency range, essential for complementarity with future ground-based observations with large telescopes that can observe the CMB with the same beamsize.

We discuss the potential of a next generation space-borne Cosmic Microwave Background (CMB) experiment for studies of extragalactic sources. Our analysis has particular bearing on the definition of the future space project, CORE, that has been submitted in response to ESA's call for a Medium-size mission opportunity as the successor of the Planck satellite. Even though the effective telescope size will be somewhat smaller than that of Planck, CORE will have a considerably better angular resolution at its highest frequencies, since, in contrast with Planck, it will be diffraction limited at all frequencies. The improved resolution implies a considerable decrease of the source confusion, i.e. substantially fainter detection limits. In particular, CORE will detect thousands of strongly lensed high-z galaxies distributed over the full sky. The extreme brightness of these galaxies will make it possible to study them, via follow-up observations, in extraordinary detail. Also, the CORE resolution matches the typical sizes of high-z galaxy proto-clusters much better than the Planck resolution, resulting in a much higher detection efficiency; these objects will be caught in an evolutionary phase beyond the reach of surveys in other wavebands. Furthermore, CORE will provide unique information on the evolution of the star formation in virialized groups and clusters of galaxies up to the highest possible redshifts. Finally, thanks to its very high sensitivity, CORE will detect the polarized emission of thousands of radio sources and, for the first time, of dusty galaxies, at mm and sub-mm wavelengths, respectively.

Lensing of the cosmic microwave background (CMB) is now a well-developed probe of the clustering of the large-scale mass distribution over a broad range of redshifts. By exploiting the non-Gaussian imprints of lensing in the polarization of the CMB, the CORE mission will allow production of a clean map of the lensing deflections over nearly the full-sky. The number of high-S/N modes in this map will exceed current CMB lensing maps by a factor of 40, and the measurement will be sample-variance limited on all scales where linear theory is valid. Here, we summarise this mission product and discuss the science that will follow from its power spectrum and the cross-correlation with other clustering data. For example, the summed mass of neutrinos will be determined to an accuracy of 17 meV combining CORE lensing and CMB two-point information with contemporaneous measurements of the baryon acoustic oscillation feature in the clustering of galaxies, three times smaller than the minimum total mass allowed by neutrino oscillation measurements. Lensing has applications across many other science goals of CORE, including the search for B-mode polarization from primordial gravitational waves. Here, lens-induced B-modes will dominate over instrument noise, limiting constraints on the power spectrum amplitude of primordial gravitational waves. With lensing reconstructed by CORE, one can "delens" the observed polarization internally, reducing the lensing B-mode power by 60 %. This can be improved to 70 % by combining lensing and measurements of the cosmic infrared background from CORE, leading to an improvement of a factor of 2.5 in the error on the amplitude of primordial gravitational waves compared to no delensing (in the null hypothesis of no primordial B-modes). Lensing measurements from CORE will allow calibration of the halo masses of the tens of thousands of galaxy clusters that it will find, with constraints dominated by the clean polarization-based estimators. The 19 frequency channels proposed for CORE will allow accurate removal of Galactic emission from CMB maps. We present initial findings that show that residual Galactic foreground contamination will not be a significant source of bias for lensing power spectrum measurements with CORE.

We describe a space-borne, multi-band, multi-beam polarimeter aiming at a precise and accurate measurement of the polarization of the Cosmic Microwave Background. The instrument is optimized to be compatible with the strict budget requirements of a medium-size space mission within the Cosmic Vision Programme of the European Space Agency. The instrument has no moving parts, and uses arrays of diffraction-limited Kinetic Inductance Detectors to cover the frequency range from 60 GHz to 600 GHz in 19 wide bands, in the focal plane of a 1.2 m aperture telescope cooled at 40 K, allowing for an accurate extraction of the CMB signal from polarized foreground emission. The projected CMB polarization survey sensitivity of this instrument, after foregrounds removal, is 1.7 μKċarcmin. The design is robust enough to allow, if needed, a downscoped version of the instrument covering the 100 GHz to 600 GHz range with a 0.8 m aperture telescope cooled at 85 K, with a projected CMB polarization survey sensitivity of 3.2 μKċarcmin.

Background: The use of aspirin in the primary prevention of cardiovascular events remains controversial. We aimed to assess the efficacy and safety of aspirin versus placebo in patients with a moderate estimated risk of a first cardiovascular event. Methods: ARRIVE is a randomised, double-blind, placebo-controlled, multicentre study done in seven countries. Eligible patients were aged 55 years (men) or 60 years (women) and older and had an average cardiovascular risk, deemed to be moderate on the basis of the number of specific risk factors. We excluded patients at high risk of gastrointestinal bleeding or other bleeding, or diabetes. Patients were randomly assigned (1:1) with a computer-generated randomisation code to receive enteric-coated aspirin tablets (100 mg) or placebo tablets, once daily. Patients, investigators, and others involved in treatment or data analysis were masked to treatment allocation. The primary efficacy endpoint was a composite outcome of time to first occurrence of cardiovascular death, myocardial infarction, unstable angina, stroke, or transient ischaemic attack. Safety endpoints were haemorrhagic events and incidence of other adverse events, and were analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00501059. Findings: Between July 5, 2007, and Nov 15, 2016, 12 546 patients were enrolled and randomly assigned to receive aspirin (n=6270) or placebo (n=6276) at 501 study sites. Median follow-up was 60 months. In the intention-to-treat analysis, the primary endpoint occurred in 269 (4·29%) patients in the aspirin group versus 281 (4·48%) patients in the placebo group (hazard ratio [HR] 0·96; 95% CI 0·81–1·13; p=0·6038). Gastrointestinal bleeding events (mostly mild) occurred in 61 (0·97%) patients in the aspirin group versus 29 (0·46%) in the placebo group (HR 2·11; 95% CI 1·36–3·28; p=0·0007). The overall incidence rate of serious adverse events was similar in both treatment groups (n=1266 [20·19%] in the aspirin group vs n=1311 [20·89%] in the placebo group. The overall incidence of adverse events was similar in both treatment groups (n=5142 [82·01%] vs n=5129 [81·72%] in the placebo group). The overall incidence of treatment-related adverse events was low (n=1050 [16·75%] vs n=850 [13·54%] in the placebo group; p

Our comprehension of the dawn of universe grew incredibly during last years, pointing to the existence of the cosmic inflation. The primordial B-mode polarization of the Cosmic Microwave Background (CMB) represents a unique probe to confirm this hypothesis. The detection of such small perturbations of the CMB is a challenge that will be faced in the near future by a new dedicated satellite mission.

A new opportunity for astronomy, cosmology, physics, and atmospheric observations is the possibility to fly stratospheric payloads at 30 - 40 km of altitude during the polar night. The absence of solar irradiation for long periods, and the extremely low temperature and stable environment of the winter stratosphere represent ideal environmental conditions while performing astrophysical observations. Here we present a small and efficient platform, able to communicate, supply power and navigate in the harsh environment of the polar stratosphere. After a balloon failure in January 2017, the payload was successfully flown in December 2017 from 78$^\circ$N, in Longyearbyen, Svalbard, Norway. Duration was limited to 21 hr, due to a southern trajectory that caused solar illumination and loss of lift. The instrument acquired and transmitted environmental data, and the thermal performance of the power system are outstanding. The payload also included a set of attitude sensors, to monitor payload movements. The information collected on this flight is essential to qualify the attitude control system sensors, and for the design if the thermal and power system of the next generation LSPE-SWIPE telescope, devoted to the measurement of the polarization of the Cosmic Microwave Background radiation from a stratospheric balloon during the Arctic polar night., Comment: Workshop Science with stratospheric balloons, Italian Space Agency, December 18-19, 2017. In press

BACKGROUND Critically ill patients with severe sepsis or septic shock may need relatively high colistin daily doses for efficacy against multidrug-resistant and extensively drug-resistant gram-negative rods. However, acute kidney injury (AKI) may represent a major dose-limiting adverse effect of colistin. We sought to determine AKI occurrence and to identify factors influencing AKI risk in severely ill patients receiving colistin according to a recently proposed dosing strategy. METHODS A prospective, observational, cohort study involving patients with severe sepsis or septic shock who received colistin was performed. AKI was defined according to Acute Kidney Injury Network criteria. Colistin administration was driven by a modified pharmacokinetics-pharmacodynamics (PK/PD)-based dosing approach. RESULTS Of 70 patients who received colistin at a median daily dose of 9 million IU (MIU; interquartile range, 5.87-11.1 MIU), 31 (44%) developed AKI. In univariate analysis, age, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA), score and baseline renal impairment were significantly associated with AKI. Moreover, patients with AKI were less frequently treated with adjuvant ascorbic acid (P = .003). In multivariate analysis, independent predictors of AKI were baseline renal impairment (adjusted hazard ratio, 4.15; 95% confidence interval, 1.9-9.2; P < .001) and age (1.03; 1.0-1.05; P = .028), whereas a strong independent renal-protective role emerged for ascorbic acid (0.27; .12-.57; P < .001). CONCLUSIONS In severely ill patients receiving colistin according to a PK/PD-driven dosing approach, baseline renal impairment and older age strongly predict AKI occurrence, but concomitant administration of ascorbic acid markedly reduces AKI risk, allowing safer use of colistin.