AIM To determine whether ribavirin(RBV) concentrations differ according to cirrhosis stage among cirrhotic patients treated with interferon-free regimens. METHODS We included patients with hepatitis C virus and cirrho...AIM To determine whether ribavirin(RBV) concentrations differ according to cirrhosis stage among cirrhotic patients treated with interferon-free regimens. METHODS We included patients with hepatitis C virus and cirrhosis [Child-Pugh(CP) A or B], Glomerular Filtration Rate ≥ 60 mL/min, who started therapy with DAAs and weightbased RBV between October 2014 and February 2016. RBV plasma levels were assessed during the treatment. We focused our analysis on the first 8 wk of therapy. RESULTS We studied 68 patients: 54 with compensated(CP-B) and 14 with decompensated(CP-A) cirrhosis. Patients withdecompensated cirrhosis displayed significantly higher RBV concentrations than those with compensated cirrhosis at week 1, 2, 4 and 8(P < 0.035). RBV levels were positively correlated with Hb loss over the treatment(P < 0.04). Majority(71%) of CP-B patients required a RBV dosage reduction during the treatment. After adjustment for confounders, Child-Pugh class remained significantly associated(95%CI: 35, 348, P = 0.017) to RBV levels, independently from baseline per-Kg RBV dosage. CONCLUSION Liver decompensation might affect RBV clearance leading to an overexposure and increased related toxicities in decompensated cirrhosis. Our findings underscore the importance of an early ribavirin therapeutic drug monitoring and suggest that an initial lower RBV dose, rather than weight-based, might be considered in those with advanced liver disease(CP-B) treated with directacting antivirals.展开更多
The atomic cluster expansion is a general polynomial expansion of the atomic energy in multi-atom basis functions.Here we implement the atomic cluster expansion in the performant C++code PACE that is suitable for use ...The atomic cluster expansion is a general polynomial expansion of the atomic energy in multi-atom basis functions.Here we implement the atomic cluster expansion in the performant C++code PACE that is suitable for use in large-scale atomistic simulations.We briefly review the atomic cluster expansion and give detailed expressions for energies and forces as well as efficient algorithms for their evaluation.We demonstrate that the atomic cluster expansion as implemented in PACE shifts a previously established Pareto front for machine learning interatomic potentials toward faster and more accurate calculations.Moreover,general purpose parameterizations are presented for copper and silicon and evaluated in detail.We show that the Cu and Si potentials significantly improve on the best available potentials for highly accurate large-scale atomistic simulations.展开更多
The use of micro-/nanoelectromechanical resonators for the room temperature detection of electromagnetic radiation at infrared frequencies has recently been investigated,showing thermal detection capabilities that cou...The use of micro-/nanoelectromechanical resonators for the room temperature detection of electromagnetic radiation at infrared frequencies has recently been investigated,showing thermal detection capabilities that could potentially outperform conventional microbolometers.The scaling of the device thickness in the nanometer range and the achievement of high infrared absorption in such a subwavelength thickness,without sacrificing the electromechanical performance,are the two key challenges for the implementation of fast,high-resolution micro-/nanoelectromechanical resonant infrared detectors.In this paper,we show that by using a virtually massless,high-electrical-conductivity,and transparent graphene electrode,floating at the van der Waals separation of a few angstroms from a piezoelectric aluminum nitride nanoplate,it is possible to implement ultrathin(460 nm)piezoelectric nanomechanical resonant structures with improved electromechanical performance(450% improved frequency×quality factor)and infrared detection capabilities(4100×improved infrared absorptance)compared with metal-electrode counterparts,despite their reduced volumes.The intrinsic infrared absorption capabilities of a submicron thin graphene–aluminum nitride plate backed with a metal electrode are investigated for the first time and exploited for the first experimental demonstration of a piezoelectric nanoelectromechanical resonant thermal detector with enhanced infrared absorptance in a reduced volume.Moreover,the combination of electromagnetic and piezoelectric resonances provided by the same graphene–aluminum nitride-metal stack allows the proposed device to selectively detect short-wavelength infrared radiation(by tailoring the thickness of aluminum nitride)with unprecedented electromechanical performance and thermal capabilities.These attributes potentially lead to the development of uncooled infrared detectors suitable for the implementation of high performance,miniaturized and power-efficient multispectral infrared imaging systems.展开更多
文摘AIM To determine whether ribavirin(RBV) concentrations differ according to cirrhosis stage among cirrhotic patients treated with interferon-free regimens. METHODS We included patients with hepatitis C virus and cirrhosis [Child-Pugh(CP) A or B], Glomerular Filtration Rate ≥ 60 mL/min, who started therapy with DAAs and weightbased RBV between October 2014 and February 2016. RBV plasma levels were assessed during the treatment. We focused our analysis on the first 8 wk of therapy. RESULTS We studied 68 patients: 54 with compensated(CP-B) and 14 with decompensated(CP-A) cirrhosis. Patients withdecompensated cirrhosis displayed significantly higher RBV concentrations than those with compensated cirrhosis at week 1, 2, 4 and 8(P < 0.035). RBV levels were positively correlated with Hb loss over the treatment(P < 0.04). Majority(71%) of CP-B patients required a RBV dosage reduction during the treatment. After adjustment for confounders, Child-Pugh class remained significantly associated(95%CI: 35, 348, P = 0.017) to RBV levels, independently from baseline per-Kg RBV dosage. CONCLUSION Liver decompensation might affect RBV clearance leading to an overexposure and increased related toxicities in decompensated cirrhosis. Our findings underscore the importance of an early ribavirin therapeutic drug monitoring and suggest that an initial lower RBV dose, rather than weight-based, might be considered in those with advanced liver disease(CP-B) treated with directacting antivirals.
基金The authors acknowledge helpful discussions with Marc Cawkwell.R.D.acknowledges funding through the German Science Foundation(DFG),project number 405621217Sandia National Laboratories is a multimission laboratory managed and operated by National Technology&Engineering Solutions of Sandia,LLC,a wholly owned subsidiary of Honeywell International Inc.,for the U.S.Department of Energy’s National Nuclear Security Administration under contract DE-NA0003525.
文摘The atomic cluster expansion is a general polynomial expansion of the atomic energy in multi-atom basis functions.Here we implement the atomic cluster expansion in the performant C++code PACE that is suitable for use in large-scale atomistic simulations.We briefly review the atomic cluster expansion and give detailed expressions for energies and forces as well as efficient algorithms for their evaluation.We demonstrate that the atomic cluster expansion as implemented in PACE shifts a previously established Pareto front for machine learning interatomic potentials toward faster and more accurate calculations.Moreover,general purpose parameterizations are presented for copper and silicon and evaluated in detail.We show that the Cu and Si potentials significantly improve on the best available potentials for highly accurate large-scale atomistic simulations.
基金This work was partially supported by the DARPA Young Faculty Award(N66001-12-1-4221)the NSF CAREER Award(ECCS-1350114)+2 种基金DARPA MTO(N66001-14-1-4011)under the RF-FPGA Program,the NSF CAREER Award(ECCS-1351424)the U.S.Department of Homeland Security,Science and Technology Directorate,Office of University Programs,under Grant Award 2013-ST-061-ED0001a Northeastern University Tier-1 seed grant.
文摘The use of micro-/nanoelectromechanical resonators for the room temperature detection of electromagnetic radiation at infrared frequencies has recently been investigated,showing thermal detection capabilities that could potentially outperform conventional microbolometers.The scaling of the device thickness in the nanometer range and the achievement of high infrared absorption in such a subwavelength thickness,without sacrificing the electromechanical performance,are the two key challenges for the implementation of fast,high-resolution micro-/nanoelectromechanical resonant infrared detectors.In this paper,we show that by using a virtually massless,high-electrical-conductivity,and transparent graphene electrode,floating at the van der Waals separation of a few angstroms from a piezoelectric aluminum nitride nanoplate,it is possible to implement ultrathin(460 nm)piezoelectric nanomechanical resonant structures with improved electromechanical performance(450% improved frequency×quality factor)and infrared detection capabilities(4100×improved infrared absorptance)compared with metal-electrode counterparts,despite their reduced volumes.The intrinsic infrared absorption capabilities of a submicron thin graphene–aluminum nitride plate backed with a metal electrode are investigated for the first time and exploited for the first experimental demonstration of a piezoelectric nanoelectromechanical resonant thermal detector with enhanced infrared absorptance in a reduced volume.Moreover,the combination of electromagnetic and piezoelectric resonances provided by the same graphene–aluminum nitride-metal stack allows the proposed device to selectively detect short-wavelength infrared radiation(by tailoring the thickness of aluminum nitride)with unprecedented electromechanical performance and thermal capabilities.These attributes potentially lead to the development of uncooled infrared detectors suitable for the implementation of high performance,miniaturized and power-efficient multispectral infrared imaging systems.
