Thyroid eye disease is a debilitating, disfiguring, and potentially blinding periocular condition for which no Food and Drug Administration-approved medical therapy is available. Strong evidence has ...implicated the insulin-like growth factor I receptor (IGF-IR) in the pathogenesis of this disease.
In a randomized, double-masked, placebo-controlled, phase 3 multicenter trial, we assigned patients with active thyroid eye disease in a 1:1 ratio to receive intravenous infusions of the IGF-IR inhibitor teprotumumab (10 mg per kilogram of body weight for the first infusion and 20 mg per kilogram for subsequent infusions) or placebo once every 3 weeks for 21 weeks; the last trial visit for this analysis was at week 24. The primary outcome was a proptosis response (a reduction in proptosis of ≥2 mm) at week 24. Prespecified secondary outcomes at week 24 were an overall response (a reduction of ≥2 points in the Clinical Activity Score plus a reduction in proptosis of ≥2 mm), a Clinical Activity Score of 0 or 1 (indicating no or minimal inflammation), the mean change in proptosis across trial visits (from baseline through week 24), a diplopia response (a reduction in diplopia of ≥1 grade), and the mean change in overall score on the Graves' ophthalmopathy-specific quality-of-life (GO-QOL) questionnaire across trial visits (from baseline through week 24; a mean change of ≥6 points is considered clinically meaningful).
A total of 41 patients were assigned to the teprotumumab group and 42 to the placebo group. At week 24, the percentage of patients with a proptosis response was higher with teprotumumab than with placebo (83% 34 patients vs. 10% 4 patients, P<0.001), with a number needed to treat of 1.36. All secondary outcomes were significantly better with teprotumumab than with placebo, including overall response (78% of patients 32 vs. 7% 3), Clinical Activity Score of 0 or 1 (59% 24 vs. 21% 9), the mean change in proptosis (-2.82 mm vs. -0.54 mm), diplopia response (68% 19 of 28 vs. 29% 8 of 28), and the mean change in GO-QOL overall score (13.79 points vs. 4.43 points) (P≤0.001 for all). Reductions in extraocular muscle, orbital fat volume, or both were observed in 6 patients in the teprotumumab group who underwent orbital imaging. Most adverse events were mild or moderate in severity; two serious events occurred in the teprotumumab group, of which one (an infusion reaction) led to treatment discontinuation.
Among patients with active thyroid eye disease, teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life than placebo; serious adverse events were uncommon. (Funded by Horizon Therapeutics; OPTIC ClinicalTrials.gov number, NCT03298867, and EudraCT number, 2017-002763-18.).
The Practice of Pulse Processing Fowler, J. W.; Alpert, B. K.; Doriese, W. B. ...
Journal of low temperature physics,
07/2016, Letnik:
184, Številka:
1-2
Journal Article
Recenzirano
Odprti dostop
The analysis of data from X-ray microcalorimeters requires great care; their excellent intrinsic energy resolution cannot usually be achieved in practice without a statistically near-optimal pulse ...analysis and corrections for important systematic errors. We describe the essential parts of a pulse-analysis pipeline for data from X-ray microcalorimeters, including steps taken to reduce systematic gain variation and the unwelcome dependence of filtered pulse heights on the exact pulse-arrival time. We find these steps collectively to be essential tools for getting the best results from a microcalorimeter-based X-ray spectrometer.
The Sudbury Neutrino Observatory (SNO) used an array of 3He proportional counters to measure the rate of neutral-current interactions in heavy water and precisely determined the total active (nu_x) ...8B solar neutrino flux. This technique is independent of previous methods employed by SNO. The total flux is found to be 5.54_-0.31;+0.33(stat)-0.34+0.36(syst)x10(6) cm(-2) s(-1), in agreement with previous measurements and standard solar models. A global analysis of solar and reactor neutrino results yields Deltam2=7.59_-0.21;+0.19x10(-5) eV2 and theta=34.4_-1.2;+1.3 degrees. The uncertainty on the mixing angle has been reduced from SNO's previous results.
The readout requirements for instruments based on transition-edge sensors (TESs) have dramatically increased over the last decade as demand for systems with larger arrays and faster sensors has ...grown. Emerging systems are expected to contain many thousands of sensors and/or sensors with time constants as short as 100 ms. These requirements must be satisfied while maintaining low noise, high dynamic range, and low crosstalk. A promising readout candidate for future TES arrays is the microwave SQUID multiplexer, which offers several gigahertz of readout bandwidth per pair of coaxial cables. In microwave SQUID multiplexing, sensor signals are coupled to RF-SQUIDs embedded in superconducting microwave resonators, which are probed via a common microwave feedline and read out using gigahertz signals. This form of SQUID multiplexing moves complexity from the cryogenic stages to room temperature hardware and digital signal processing firmware which must synthesize the microwave tones and process the information contained within them. To demultiplex signals from the microwave SQUID multiplexer, we have implemented an FPGA-based firmware architecture that is flexible enough to read out a variety of differently optimized TESs. A gamma-ray spectrometer targeted at nuclear materials accounting applications, known as SLEDGEHAMMER, is an early adopter of microwave SQUID multiplexing and is driving our current firmware development effort. This instrument utilizes 300 kHz full-width half-maximum resonators with 256 channels in a one gigahertz wide band. We have recently demonstrated undegraded readout of 128 channels using two ROACH2s on a single pair of coaxial cables. This manuscript describes the firmware implementation for the readout electronics of these early array-scale demonstrations.
To test bound-state quantum electrodynamics (BSQED) in the strong-field regime, we have performed high precision x-ray spectroscopy of the 5g-4f and 5f- 4d transitions (BSQED contribution of 2.4 and ...5.2 eV, respectively) of muonic neon atoms in the low-pressure gas phase without bound electrons. Muonic atoms have been recently proposed as an alternative to few-electron high-Z ions for BSQED tests by focusing on circular Rydberg states where nuclear contributions are negligibly small. We determined the 5g_{9/2}- 4f_{7/2} transition energy to be 6297.08±0.04(stat)±0.13(syst) eV using superconducting transition-edge sensor microcalorimeters (5.2-5.5 eV FWHM resolution), which agrees well with the most advanced BSQED theoretical prediction of 6297.26 eV.
Reactive nitrogen (Nr) compounds have different fates in the atmosphere due to differences in the governing processes of physical transport, deposition and chemical transformation. Nr compounds ...addressed here include reduced nitrogen (NHx: ammonia (NH3) and its reaction product ammonium (NH4+)), oxidized nitrogen (NOy: nitrogen monoxide (NO) + nitrogen dioxide (NO2) and their reaction products) as well as organic nitrogen compounds (organic N). Pollution abatement strategies need to take into account the differences in the governing processes of these compounds when assessing their impact on ecosystem services, biodiversity, human health and climate. NOx (NO + NO2) emitted from traffic affects human health in urban areas where the presence of buildings increases the residence time in streets. In urban areas this leads to enhanced exposure of the population to NOx concentrations. NOx emissions generally have little impact on nearby ecosystems because of the small dry deposition rates of NOx. These compounds need to be converted into nitric acid (HNO3) before removal through deposition is efficient. HNO3 sticks quickly to any surface and is thereby either dry deposited or incorporated into aerosols as nitrate (NO3−). In contrast to NOx compounds, NH3 has potentially high impacts on ecosystems near the main agricultural sources of NH3 because of its large ground-level concentrations along with large dry deposition rates. Aerosol phase NH4+ and NO3− contribute significantly to background PM2.5 and PM10 (mass of aerosols with an aerodynamic diameter of less than 2.5 and 10 μm, respectively) with an impact on radiation balance as well as potentially on human health. Little is known quantitatively and qualitatively about organic N in the atmosphere, other than that it contributes a significant fraction of wet-deposited N, and is present in both gaseous and particulate forms. Further studies are needed to characterise the sources, air chemistry and removal rates of organic N emissions.
Plasma instabilities have been studied for many decades in the terrestrial ionosphere via remote and in‐situ measurement techniques. The study of these kilometer‐scale instabilities has provided ...crucial insight into coupling between the neutral atmosphere and ionosphere. A special high‐time cadence observation mode developed for the Mars Atmosphere and Volatile EvolutioN (MAVEN) mission has demonstrated for the first time that kilometer‐scale density fluctuations exist at Mars. Density and associated magnetic fluctuations are observed to occur both in and out of phase with each other, suggesting that multiple instability mechanisms are active, similar to Earth. The unique solar wind interaction with Mars and its localized crustal magnetic fields appears to play an important role in the formation of these irregularity events, which form preferentially during meridionally pointing magnetic field within the ionosphere. This is in contrast to Earth where the strong dipole magnetic field dominates in the terrestrial ionosphere.
Key Points
Kilometer‐scale ionospheric density irregularities are fully resolved for the first time at Mars
A range of irregularity characteristics suggests that multiple formation mechanisms are active at Mars, as at Earth
The unique interaction between Mars and the solar wind appears to play an important role in irregularity formation
We consider how to analyze microcalorimeter pulses for quantities that are nonlinear in the data, while preserving the signal-to-noise advantages of linear optimal filtering. We successfully apply ...our chosen approach to compute the electrothermal feedback energy deficit (the “Joule energy”) of a pulse, which has been proposed as a linear estimator of the deposited photon energy.
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