Market Access Analysis of Biologics and Small-Molecule Inhibitors for Inflammatory Bowel Disease Among US Health Insurance Policies.

BACKGROUND AND AIMS:Treatment pathways for ulcerative colitis (UC) and Crohn's disease (CD) are shifting to a more individualized, risk-stratified approach. The perception is that insurance policies may not have implemented this paradigm shift, particularly regarding access to newer agents. We evaluated patient access to advanced therapies by analyzing policy information from the Managed Markets Insight and Technology database. METHODS:Coverage status as of December 2018 for all US lives was queried for adalimumab, infliximab, infliximab-dyyb, tofacitinib, ustekinumab, and vedolizumab by indication (UC and/or CD) and medical or pharmacy coverage benefit. Coverage status was classified by the number of biologic steps before access to specified drug as "No Biologic," "1 Prior Biologic," "2+ Prior Biologics," "Not Covered." Unknown lives were excluded from the analyses. RESULTS:Coverage analysis was available for approximately 302 million lives under each medical and pharmacy benefit. Our analysis indicates that approximately half of covered lives had access to all agents (except tofacitinib) as first-line therapy; two-thirds had access after one biologic exposure. Among newer agents, vedolizumab had the widest coverage. For indications of UC and CD, 81% of known lives had access to vedolizumab with no prior biologic exposure required ("No Biologic"), 95% after "No Biologic" + "1 prior Biologic." Geographic variations were identified for coverage patterns. CONCLUSIONS:This US-based healthcare policy analysis points to an increased access to advanced therapies for UC and CD. An individualized, risk-stratified treatment approach integrating advanced therapies, including those recently approved, into treatment pathways for UC and CD is feasible

A 12.5 GHz-Spaced Optical Frequency Comb Spanning >400 nm for near-Infrared Astronomical Spectrograph Calibration

A 12.5 GHz-spaced optical frequency comb locked to a Global Positioning disciplined oscillator for near-IR spectrograph calibration is presented. The comb is generated via filtering a 250 MHz-spaced comb. Subsequency nonlinear broadening of the 12.5 GHz comb extends the wavelength range to cover 1380 nm to 1820 nm, providing complete coverage over the H-band transmission widow of Earth's atmosphere. Finite suppression of spurious sidemodes, optical linewidth and instability of the comb have been examined to estmiate potential wavelength biases in spectrograph calibration. Sidemode suppression varies between 20 db and 45 dB, and the optical linewidth is ~350 kHz at 1550 nm. The comb frequency uncertainty is bounded by +/- 30 kHz (corresponding to a radial velocity of +/- 5 cm/s), limited by the Global Positioning System disciplined oscillator reference. These results indicate this comb can readily support radial velocity measurements below 1 m/s in the near-IR.Comment: 16 pages, 12 figures, new file fixes some readability problems on Mac

The Habitable-Zone Planet Finder: A Stabilized Fiber-Fed NIR Spectrograph for the Hobby-Eberly Telescope

We present the scientific motivation and conceptual design for the recently funded Habitable-zone Planet Finder (HPF), a stabilized fiber-fed near-infrared (NIR) spectrograph for the 10 meter class Hobby-Eberly Telescope (HET) that will be capable of discovering low mass planets around M dwarfs. The HPF will cover the NIR Y & J bands to enable precise radial velocities to be obtained on mid M dwarfs, and enable the detection of low mass planets around these stars. The conceptual design is comprised of a cryostat cooled to 200K, a dual fiber-feed with a science and calibration fiber, a gold coated mosaic echelle grating, and a Teledyne Hawaii-2RG (H2RG) NIR detector with a 1.7$\mu$m cutoff. A uranium-neon hollow-cathode lamp is the baseline wavelength calibration source, and we are actively testing laser frequency combs to enable even higher radial velocity precision. We will present the overall instrument system design and integration with the HET, and discuss major system challenges, key choices, and ongoing research and development projects to mitigate risk. We also discuss the ongoing process of target selection for the HPF survey.Comment: 14 pages, 9 figures. To appear in the proceedings of the SPIE 2012 Astronomical Instrumentation and Telescopes conferenc

Concentration of rocuronium in cerebrospinal fluid of patients undergoing cerebral aneurysm clipping†

Background. This study assessed the concentration of rocuronium in the cerebrospinal fluid (CSF) of patients undergoing cerebral aneurysm clipping, and investigated whether the mode of administration (single bolus vs continuous infusion) influenced the CSF concentration. Methods. Twenty patients with subarachnoid haemorrhage were randomly allocated to receive a bolus dose (bolus group), or a bolus followed by a continuous infusion of rocuronium (infusion group) (n=10 for each group). Arterial blood and ventricular CSF were sampled 2 h after the rocuronium bolus. Samples were analysed by liquid chromatography electrospray ionization‐tandem mass spectrometry. Results. Rocuronium could be detected in all the CSF samples. The mean (range) CSF concentration was 2.2 (0.9-4.6) ng ml-1 in the bolus group and 12.4 (2.4-34.6) ng ml-1 in the infusion group; P<0.01. Conclusions. This study demonstrated that rocuronium, normally not considered to cross the blood-brain barrier, is regularly found in the CSF of patients undergoing cerebral clipping; continuous infusion of the drug led to higher plasma and CSF concentrations than after a single bolus dose. Br J Anaesth 2004; 92: 419-2

Astronomical spectrograph calibration with broad-spectrum frequency combs

Broadband femtosecond-laser frequency combs are filtered to spectrographically resolvable frequency-mode spacing, and the limitations of using cavities for spectral filtering are considered. Data and theory are used to show implications to spectrographic calibration of high-resolution, astronomical spectrometers

Observations of Mass Loss from the Transiting Exoplanet HD 209458b

Using the new Cosmic Origins Spectrograph (COS) on the {\it Hubble Space Telescope (HST)}, we obtained moderate-resolution, high signal/noise ultraviolet spectra of HD 209458 and its exoplanet HD 209458b during transit, both orbital quadratures, and secondary eclipse. We compare transit spectra with spectra obtained at non-transit phases to identify spectral features due to the exoplanet's expanding atmosphere. We find that the mean flux decreased by $7.8\pm 1.3$% for the C II 1334.5323\AA\ and 1335.6854\AA\ lines and by $8.2\pm 1.4$% for the Si III 1206.500\AA\ line during transit compared to non-transit times in the velocity interval --50 to +50 km s$^{-1}$. Comparison of the C II and Si III line depths and transit/non-transit line ratios shows deeper absorption features near --10 and +15 km s$^{-1}$ and less certain features near --40 and +30--70 km s$^{-1}$, but future observations are needed to verify this first detection of velocity structure in the expanding atmosphere of an exoplanet. Our results for the C II lines and the non-detection of Si IV 1394.76\AA\ absorption are in agreement with \citet{Vidal-Madjar2004}, but we find absorption during transit in the Si III line contrary to the earlier result. The $8\pm 1$% obscuration of the star during transit is far larger than the 1.5% obscuration by the exoplanet's disk. Absorption during transit at velocities between --50 and +50 km s$^{-1}$ in the C II and Si III lines requires high-velocity ion absorbers, but models that assume that the absorbers are high-temperature thermal ions are inconsistent with the COS spectra. Assuming hydrodynamic model values for the gas temperature and outflow velocity at the limb of the outflow as seen in the C II lines, we find mass-loss rates in the range (8--40)$\times 10^{10}$ g s$^{-1}$.Comment: 25 pages, 4 figures, Astrophysical Journal in pres

Long-term stability of TES satellite radiance measurements

The utilization of Tropospheric Emission Spectrometer (TES) Level 2 (L2) retrieval products for the purpose of assessing long term changes in atmospheric trace gas composition requires knowledge of the overall radiometric stability of the Level 1B (L1B) radiances. The purpose of this study is to evaluate the stability of the radiometric calibration of the TES instrument by analyzing the difference between measured and calculated brightness temperatures in selected window regions of the spectrum. The Global Modeling and Assimilation Office (GMAO) profiles for temperature and water vapor and the Real-Time Global Sea Surface Temperature (RTGSST) are used as input to the Optimal Spectral Sampling (OSS) radiative transfer model to calculate the simulated spectra. The TES reference measurements selected cover a 4-year period of time from mid 2005 through mid 2009 with the selection criteria being; observation latitudes greater than −30° and less than 30°, over ocean, Global Survey mode (nadir view) and retrieved cloud optical depth of less than or equal to 0.01. The TES cloud optical depth retrievals are used only for screening purposes and no effects of clouds on the radiances are included in the forward model. This initial screening results in over 55 000 potential reference spectra spanning the four year period. Presented is a trend analysis of the time series of the residuals (observation minus calculations) in the TES 2B1, 1B2, 2A1, and 1A1 bands, with the standard deviation of the residuals being approximately equal to 0.6 K for bands 2B1, 1B2, 2A1, and 0.9 K for band 1A1. The analysis demonstrates that the trend in the residuals is not significantly different from zero over the 4-year period. This is one method used to demonstrate that the relative radiometric calibration is stable over time, which is very important for any longer term analysis of TES retrieved products (L2), particularly well-mixed species such as carbon dioxide and methane

Using airborne HIAPER Pole-to-Pole Observations (HIPPO) to evaluate model and remote sensing estimates of atmospheric carbon dioxide

In recent years, space-borne observations of atmospheric carbon dioxide (CO_2) have been increasingly used in global carbon-cycle studies. In order to obtain added value from space-borne measurements, they have to suffice stringent accuracy and precision requirements, with the latter being less crucial as it can be reduced by just enhanced sample size. Validation of CO_2 column-averaged dry air mole fractions (XCO_2) heavily relies on measurements of the Total Carbon Column Observing Network (TCCON). Owing to the sparseness of the network and the requirements imposed on space-based measurements, independent additional validation is highly valuable. Here, we use observations from the High-Performance Instrumented Airborne Platform for Environmental Research (HIAPER) Pole-to-Pole Observations (HIPPO) flights from 01/2009 through 09/2011 to validate CO_2 measurements from satellites (Greenhouse Gases Observing Satellite – GOSAT, Thermal Emission Sounder – TES, Atmospheric Infrared Sounder – AIRS) and atmospheric inversion models (CarbonTracker CT2013B, Monitoring Atmospheric Composition and Climate (MACC) v13r1). We find that the atmospheric models capture the XCO_2 variability observed in HIPPO flights very well, with correlation coefficients (r^2) of 0.93 and 0.95 for CT2013B and MACC, respectively. Some larger discrepancies can be observed in profile comparisons at higher latitudes, in particular at 300 hPa during the peaks of either carbon uptake or release. These deviations can be up to 4 ppm and hint at misrepresentation of vertical transport. Comparisons with the GOSAT satellite are of comparable quality, with an r^2 of 0.85, a mean bias μ of −0.06 ppm, and a standard deviation σ of 0.45 ppm. TES exhibits an r^2 of 0.75, μ of 0.34 ppm, and σ of 1.13 ppm. For AIRS, we find an r^2 of 0.37, μ of 1.11 ppm, and σ of 1.46 ppm, with latitude-dependent biases. For these comparisons at least 6, 20, and 50 atmospheric soundings have been averaged for GOSAT, TES, and AIRS, respectively. Overall, we find that GOSAT soundings over the remote Pacific Ocean mostly meet the stringent accuracy requirements of about 0.5 ppm for space-based CO_2 observations

A Suborbital Payload for Soft X-ray Spectroscopy of Extended Sources

We present a suborbital rocket payload capable of performing soft X-ray spectroscopy on extended sources. The payload can reach resolutions of ~100(lambda/dlambda) over sources as large as 3.25 degrees in diameter in the 17-107 angstrom bandpass. This permits analysis of the overall energy balance of nearby supernova remnants and the detailed nature of the diffuse soft X-ray background. The main components of the instrument are: wire grid collimators, off-plane grating arrays and gaseous electron multiplier detectors. This payload is adaptable to longer duration orbital rockets given its comparatively simple pointing and telemetry requirements and an abundance of potential science targets.Comment: Accepted to Experimental Astronomy, 12 pages plus 1 table and 17 figure