A randomized phase 2 study of the 5-HT4 receptor agonist felcisetrag for postoperative gastrointestinal dysfunction after bowel surgery.

BACKGROUND: Felcisetrag (5-hydroxytryptamine-4 receptor [5-HT4] agonist) is under investigation as prophylaxis or active treatment for accelerating resolution of gastrointestinal function post-surgery. METHODS: Phase 2, randomized, placebo-controlled, parallel five-arm, double-blind, multicenter study (NCT03827655) in 209 adults undergoing open or laparoscopic-assisted bowel surgery. Patients received intravenous placebo, felcisetrag 0.1 mg/100 â€‹mL or 0.5 mg/100 â€‹mL pre-surgery only, or pre-surgery and daily post-surgery until return of gastrointestinal function or for up to 10 days. PRIMARY ENDPOINT: time to recovery of gastrointestinal function. RESULTS: Median time to recovery of gastrointestinal function was 2.6 days for both felcisetrag 0.5 â€‹mg daily and 0.5 â€‹mg pre-surgery versus 1.9 days for placebo (p â€‹> â€‹0.05). There were no notable differences in adverse events between treatment arms. CONCLUSIONS: Felcisetrag was well tolerated with no new safety concerns. However, no clinically meaningful difference in time to recovery of gastrointestinal function versus placebo was observed. Further investigation of the utility of 5-HT4 agonists in complicated, open abdominal surgeries may be warranted.

CALIPSO Lidar Calibration at 532 nm: Version 4 Nighttime Algorithm.

Data products from the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) on board Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) were recently updated following the implementation of new (version 4) calibration algorithms for all of the level 1 attenuated backscatter measurements. In this work we present the motivation for and the implementation of the version 4 nighttime 532 nm parallel channel calibration. The nighttime 532 nm calibration is the most fundamental calibration of CALIOP data, since all of CALIOP's other radiometric calibration procedures - i.e., the 532 nm daytime calibration and the 1064 nm calibrations during both nighttime and daytime - depend either directly or indirectly on the 532 nm nighttime calibration. The accuracy of the 532 nm nighttime calibration has been significantly improved by raising the molecular normalization altitude from 30-34 km to 36-39 km to substantially reduce stratospheric aerosol contamination. Due to the greatly reduced molecular number density and consequently reduced signal-to-noise ratio (SNR) at these higher altitudes, the signal is now averaged over a larger number of samples using data from multiple adjacent granules. As well, an enhanced strategy for filtering the radiation-induced noise from high energy particles was adopted. Further, the meteorological model used in the earlier versions has been replaced by the improved MERRA-2 model. An aerosol scattering ratio of 1.01 ± 0.01 is now explicitly used for the calibration altitude. These modifications lead to globally revised calibration coefficients which are, on average, 2-3% lower than in previous data releases. Further, the new calibration procedure is shown to eliminate biases at high altitudes that were present in earlier versions and consequently leads to an improved representation of stratospheric aerosols. Validation results using airborne lidar measurements are also presented. Biases relative to collocated measurements acquired by the Langley Research Center (LaRC) airborne high spectral resolution lidar (HSRL) are reduced from 3.6% ± 2.2% in the version 3 data set to 1.6% ± 2.4 % in the version 4 release.

CALIPSO lidar level 3 aerosol profile product: version 3 algorithm design.

The CALIPSO (Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations) level 3 aerosol profile product reports globally gridded, quality-screened, monthly mean aerosol extinction profiles retrieved by CALIOP (the Cloud-Aerosol Lidar with Orthogonal Polarization). This paper describes the quality screening and averaging methods used to generate the version 3 product. The fundamental input data are CALIOP level 2 aerosol extinction profiles and layer classification information (aerosol, cloud, and clear-air). Prior to aggregation, the extinction profiles are quality-screened by a series of filters to reduce the impact of layer detection errors, layer classification errors, extinction retrieval errors, and biases due to an intermittent signal anomaly at the surface. The relative influence of these filters are compared in terms of sample rejection frequency, mean extinction, and mean aerosol optical depth (AOD). The "extinction QC flag" filter is the most influential in preventing high-biases in level 3 mean extinction, while the "misclassified cirrus fringe" filter is most aggressive at rejecting cirrus misclassified as aerosol. The impact of quality screening on monthly mean aerosol extinction is investigated globally and regionally. After applying quality filters, the level 3 algorithm calculates monthly mean AOD by vertically integrating the monthly mean quality-screened aerosol extinction profile. Calculating monthly mean AOD by integrating the monthly mean extinction profile prevents a low bias that would result from alternately integrating the set of extinction profiles first and then averaging the resultant AOD values together. Ultimately, the quality filters reduce level 3 mean AOD by -24 and -31% for global ocean and global land, respectively, indicating the importance of quality screening.

Minimum aerosol layer detection sensitivities and their subsequent impacts on aerosol optical thickness retrievals in CALIPSO level 2 data products.

Due to instrument sensitivities and algorithm detection limits, level 2 (L2) Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) 532nm aerosol extinction profile retrievals are often populated with retrieval fill values (RFVs), which indicate the absence of detectable levels of aerosol within the profile. In this study, using 4 years (2007-2008 and 2010-2011) of CALIOP version 3 L2 aerosol data, the occurrence frequency of daytime CALIOP profiles containing all RFVs (all-RFV profiles) is studied. In the CALIOP data products, the aerosol optical thickness (AOT) of any all-RFV profile is reported as being zero, which may introduce a bias in CALIOP-based AOT climatologies. For this study, we derive revised estimates of AOT for all-RFV profiles using collocated Moderate Resolution Imaging Spectroradiometer (MODIS) Dark Target (DT) and, where available, AErosol RObotic NEtwork (AERONET) data. Globally, all-RFV profiles comprise roughly 71% of all daytime CALIOP L2 aerosol profiles (i.e., including completely attenuated profiles), accounting for nearly half (45 %) of all daytime cloud-free L2 aerosol profiles. The mean collocated MODIS DT (AERONET) 550 nm AOT is found to be near 0.06 (0.08) for CALIOP all-RFV profiles. We further estimate a global mean aerosol extinction profile, a so-called "noise floor", for CALIOP all-RFV profiles. The global mean CALIOP AOT is then recomputed by replacing RFV values with the derived noise-floor values for both all-RFV and non-all-RFV profiles. This process yields an improvement in the agreement of CALIOP and MODIS over-ocean AOT.

The CALIPSO Version 4 Automated Aerosol Classification and Lidar Ratio Selection Algorithm.

The Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) version 4.10 (V4) level 2 aerosol data products, released in November 2016, include substantial improvements to the aerosol subtyping and lidar ratio selection algorithms. These improvements are described along with resulting changes in aerosol optical depth (AOD). The most fundamental change in V4 level 2 aerosol products is a new algorithm to identify aerosol subtypes in the stratosphere. Four aerosol subtypes are introduced for the stratospheric aerosols: polar stratospheric aerosol (PSA), volcanic ash, sulfate/other, and smoke. The tropospheric aerosol subtyping algorithm was also improved by adding the following enhancements: (1) all aerosol subtypes are now allowed over polar regions, whereas the version 3 (V3) algorithm allowed only clean continental and polluted continental aerosols; (2) a new "dusty marine" aerosol subtype is introduced, representing mixtures of dust and marine aerosols near the ocean surface; and (3) the "polluted continental" and "smoke" subtypes have been renamed "polluted continental/smoke" and "elevated smoke", respectively. V4 also revises the lidar ratios for clean marine, dust, clean continental, and elevated smoke subtypes. As a consequence of the V4 updates, the mean 532 nm AOD retrieved by CALIOP has increased by 0.044 (0.036) or 52 % (40 %) for nighttime (daytime). Lidar ratio revisions are the most influential factor for AOD changes from V3 to V4, especially for cloud-free skies. Preliminary validation studies show that the AOD discrepancies between CALIOP and AERONET/MODIS (ocean) are reduced in V4 compared to V3.

Evaluation of the aerosol vertical distribution in global aerosol models through comparison against CALIOP measurements: AeroCom phase II results.

The ability of 11 models in simulating the aerosol vertical distribution from regional to global scales, as part of the second phase of the AeroCom model intercomparison initiative (AeroCom II), is assessed and compared to results of the first phase. The evaluation is performed using a global monthly gridded data set of aerosol extinction profiles built for this purpose from the CALIOP (Cloud-Aerosol Lidar with Orthogonal Polarization) Layer Product 3.01. Results over 12 subcontinental regions show that five models improved, whereas three degraded in reproducing the interregional variability in Z α0-6 km, the mean extinction height diagnostic, as computed from the CALIOP aerosol profiles over the 0-6 km altitude range for each studied region and season. While the models' performance remains highly variable, the simulation of the timing of the Z α0-6 km peak season has also improved for all but two models from AeroCom Phase I to Phase II. The biases in Z α0-6 km are smaller in all regions except Central Atlantic, East Asia, and North and South Africa. Most of the models now underestimate Z α0-6 km over land, notably in the dust and biomass burning regions in Asia and Africa. At global scale, the AeroCom II models better reproduce the Z α0-6 km latitudinal variability over ocean than over land. Hypotheses for the performance and evolution of the individual models and for the intermodel diversity are discussed. We also provide an analysis of the CALIOP limitations and uncertainties contributing to the differences between the simulations and observations.

Mechanism of phase-energy coupling in f-to-2f interferometry.

White-light generation has been used widely in single-shot f-to-2f interferometers for stabilizing the carrier-envelope (CE) phase of laser amplifiers. The accuracy of the relative phase values measured by such an interferometer is affected by fluctuations in the laser pulse energy. A simple two-step model is proposed to explain the mechanism that couples the laser energy and the CE phase. The model explains the experimentally observed dependence of the group delay between the f and the 2f pulses on the laser energy, as well as the CE phase shift caused by the pulse energy variation.

Determining the phase-energy coupling coefficient in carrier-envelope phase measurements.

For f-to-2f interferometers based on white-light generation in sapphire plates, the accuracy of the carrier-envelope (CE) phase measurement and stabilization is affected by the laser energy fluctuation. The coupling coefficient between the CE phase and the laser energy has been determined by modulating the pulse energy in an in-loop f-to-2f interferometer while measuring the CE phase variation with an out-loop interferometer. When the total spectral phase measured by the in-loop interferometer was locked, a 1% change in laser energy caused a 160 mrad shift in the CE phase of the output pulses.