IMPORTANCE: Opioid-related mortality and national prescribing guidelines have led to tapering of doses among patients prescribed long-term opioid therapy for chronic pain. There is limited ...information about risks related to tapering, including overdose and mental health crisis. OBJECTIVE: To assess whether there are associations between opioid dose tapering and rates of overdose and mental health crisis among patients prescribed stable, long-term, higher-dose opioids. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study using deidentified medical and pharmacy claims and enrollment data from the OptumLabs Data Warehouse from 2008 to 2019. Adults in the US prescribed stable higher doses (mean ≥50 morphine milligram equivalents/d) of opioids for a 12-month baseline period with at least 2 months of follow-up were eligible for inclusion. EXPOSURES: Opioid tapering, defined as at least 15% relative reduction in mean daily dose during any of 6 overlapping 60-day windows within a 7-month follow-up period. Maximum monthly dose reduction velocity was computed during the same period. MAIN OUTCOMES AND MEASURES: Emergency or hospital encounters for (1) drug overdose or withdrawal and (2) mental health crisis (depression, anxiety, suicide attempt) during up to 12 months of follow-up. Discrete time negative binomial regression models estimated adjusted incidence rate ratios (aIRRs) of outcomes as a function of tapering (vs no tapering) and dose reduction velocity. RESULTS: The final cohort included 113 618 patients after 203 920 stable baseline periods. Among the patients who underwent dose tapering, 54.3% were women (vs 53.2% among those who did not undergo dose tapering), the mean age was 57.7 years (vs 58.3 years), and 38.8% were commercially insured (vs 41.9%). Posttapering patient periods were associated with an adjusted incidence rate of 6.3 overdose events per 100 person-years compared with 4.9 events per 100 person-years in non-tapered periods (adjusted incidence rate difference, 1.4 per 100 person-years 95% CI, 0.7-2.1; aIRR, 1.28 95% CI, 1.15-1.43). Tapering was associated with an adjusted incidence rate of 7.4 mental health crisis events per 100 person-years compared with 4.3 events per 100 person-years among nontapered periods (adjusted incidence rate difference, 3.1 per 100 person-years 95% CI, 2.1-4.1; aIRR, 1.74 95% CI, 1.50-2.01). Increasing maximum monthly dose reduction velocity by 10% was associated with an aIRR of 1.05 for overdose (95% CI, 1.03-1.08) and of 1.14 for mental health crisis (95% CI, 1.11-1.17). CONCLUSIONS AND RELEVANCE: Among patients prescribed stable, long-term, higher-dose opioid therapy, tapering events were significantly associated with increased risk of overdose and mental health crisis. Although these findings raise questions about potential harms of tapering, interpretation is limited by the observational study design.
Thermal fiber drawing is an efficient technique for producing optical fiber tapers whose operation regime gradually varies between multi-mode and single-mode. Here we present a comprehensive ...theoretical analysis of tapering optical fibers through changing their drawing speed on a standard fiber draw tower. We analytically calculate the drawing speed, drawing acceleration, and time needed to produce different kinds of fiber tapers and analyze the derived expressions to find the optimal fabrication parameters for the tapers. The obtained results inform how to most efficiently draw optical fiber tapers of different adiabatic shapes using the minimal pulling force for a given tapering ratio.
High-gain millimeter-wave antennas based on spoof surface plasmon polaritons (SPPs) are proposed in this article. Since the dispersion of spoof SPP modes supported by metallic grooves is insensitive ...to their lateral width, we propose two millimeter-wave antennas with wide SPP grooves, namely an SPP tapering rod antenna and an SPP leaky-wave antenna. The widened grooves enlarge the aperture size of the antennas, enhancing the antenna gains. Both antennas are fed by a standard waveguide and are fabricated by 3-D printing with surface metallization. Based on the similar principle of conventional dielectric rod antennas, the proposed SPP rod antenna achieves broadband and high gain. The measured |S 11 | is below −16.5 dB from 50 to 75 GHz, and the antenna gain varies from 16.06 to 19.3 dBi. By employing periodic modulation, the SPP leaky-wave antenna operates from 50 to 70 GHz for |S 11 | below −10 dB. This leaky-wave antenna with 24 modulated periods achieves 20.1-23.9 dBi gain in the operating band with a beam-scanning range from −39° to −3°.
The conversion efficiency of a conventional free-electron laser (FEL) is on the level of Pierce parameter, which means that only a small portion of electron beam energy is converted into the electric ...field. Undulator tapering is a common way to enhance the FEL efficiency, however, it has limited effect when applying in the FEL oscillator. Inspired by the fast kicker developed in the high-repetition-rate FELs and storage rings, in this paper we propose to kick the electron beam orbit transversely in a transverse gradient undulator (TGU) after the FEL is saturated in oscillator. The electron beam will experience a different undulator strength after the beam orbit is deflected to the off-axis position. It can be regarded as a dynamic tapering method within the macrobunch while the dynamic detuning on the undulator strength with the normal tapering method is almost impossible in oscillator. Though the TGU will reduce the initial small-signal gain, the FEL efficiency still can be greatly enhanced. Numerical simulations demonstrated that the maximum FEL power can be enhanced to more than 3 times of the normal FEL oscillator.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
The FEL performance strongly correlates with the undulator field quality. The definition of mechanical tolerances for the undulator magnets allows us to achieve the wished field quality. ...These mechanical tolerances should be defined both on short and long-range errors. With long-range errors, we address problems like deformations of the yoke caused by the support structures or unwanted tapering, which can arise in the positioning procedure of the ideally parallel undulator coils. In this contribution, we quantify the effect and set tolerances of a few types of long-range errors on the FEL radiation generated specifically from superconducting undulator coils.
This letter presents the research progress of a pulsed G-band 50 W traveling wave tube (TWT) with pencil beam focused by periodic permanent magnet (PPM). Three approaches have been combined to ...improve the tube's operation performances including setting the operating point near the cutoff frequency, using the folded waveguide (FWG) slow wave structure (SWS) with modified circular bends (MCBs), and adopting phase velocity tapering (PVT) technique. The measured output power can be over 50 W at 5% duty cycle with a bandwidth of 3.6 GHz when the beam voltage is 24.25 kV and the beam current is 59 mA. Corresponding electronic efficiency and gain are higher than 3.5% and 35 dB, respectively. The results provide a demonstration of a compact terahertz amplifier with high power, high electronic efficiency and significant bandwidth.
IMPORTANCE: Few treatments are available for patients with glucocorticoid-dependent polymyalgia rheumatica. IL-6 antagonists may reduce disease activity in patients with active ...glucocorticoid-dependent polymyalgia rheumatica. OBJECTIVE: To compare the efficacy of tocilizumab vs placebo in patients with glucocorticoid-dependent polymyalgia rheumatica. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, parallel-group, placebo-controlled randomized clinical trial enrolled 101 patients with polymyalgia rheumatica at 17 hospitals in France from February 2017 to October 2019. Final follow-up occurred in November 2020. Inclusion criteria were persistent disease activity (polymyalgia rheumatica activity score computed using the C-reactive protein level CRP PMR-AS >10) and prednisone dose greater than or equal to 10 mg per day. INTERVENTIONS: Patients were randomly assigned to receive intravenous tocilizumab (8 mg/kg; n = 51) or placebo (n = 50) every 4 weeks for 24 weeks, combined with predefined standardized tapering of oral prednisone. MAIN OUTCOMES AND MEASURES: The primary efficacy end point was CRP PMR-AS less than 10 (range, 0-100; higher values indicate greater activity; no minimal clinically important difference defined) combined with either prednisone dose less than or equal to 5 mg per day or a decrease in prednisone dose greater than or equal to 10 mg from baseline at week 24. There were 11 secondary outcomes assessed at week 24 included in this report, including disease activity (measured by CRP PMR-AS) and the proportion of patients no longer taking prednisone. RESULTS: Of the 101 randomized patients (mean age, 67.2 years; 68 67.3% women), 100 (99%) received at least 1 infusion and 100 completed the trial. The primary end point was achieved in 67.3% of patients in the tocilizumab group and 31.4% of patients in the placebo group (adjusted difference, 36.0% 95% CI, 19.4%-52.6%; adjusted relative risk, 2.3 95% CI, 1.5-3.6; P < .001). Of 11 reported secondary end points at 24 weeks, 7 showed significant differences favoring tocilizumab, including mean CRP PMR-AS score (7.5 95% CI, 5.4-9.6 vs 14.9 95% CI, 11.4-18.4; adjusted difference, −7.5 95% CI, −11.2 to −3.8; P < .001) and the percentage of patients no longer receiving prednisone (49.0% vs 19.6%; adjusted difference, 29.3% 95% CI, 18.9%-39.7%; adjusted relative risk, 2.5 95% CI, 1.8-3.5; P < .001). The most frequent adverse events were infections, experienced by 23 patients (46.9%) in the tocilizumab group and 20 (39.2%) in the placebo group. CONCLUSIONS AND RELEVANCE: Among patients with active polymyalgia rheumatica despite prednisone therapy, tocilizumab, compared with placebo, resulted in a significantly greater percentage of patients with a CRP PMR-AS less than 10 with reduced prednisone requirements at week 24. Further research is needed to confirm efficacy and to determine the balance of potential benefits and harms. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02908217
This paper reports a 60-GHz four-element beam-tapering phased-array transmitter with a lower sidelobe level (SLL). The array factor and the error vector magnitude (EVM) were calculated to explain the ...low sidelobe characteristic of a nonuniform amplitude array and to emphasize the importance of phase compensation, respectively. The phase-compensated radio frequency (RF) variable gain amplifiers (VGAs) were proposed to compensate the gain variance of phase shifters and, simultaneously, excite the nonuniform amplitude to each array element. The proposed VGA improves the relative phase error by 2° and the OP1dB by 2.4 dB within a gain control range of 5 dB, compared to the current steering without any compensation. Implemented in a commercial 65-nm CMOS process, the integrated array chip displays an root-mean-square (rms) gain error of <0.53 dB and an rms phase error of <8.8° in the frequency range of 57-66 GHz, while consuming a dc power of 403.2 mW and occupying a chip area of 2.88 mm 2 . The fabricated array was integrated with a <inline-formula> <tex-math notation="LaTeX">1 \times 4 </tex-math></inline-formula> Teflon array antenna to verify the beamforming and beam-tapering operations. With proper gain and phase control, the integrated array decreases the SLL by up to 5.2 dB, and the minimum SLL is −15.2 dB. To the best of the authors' knowledge, this is the first report on the implementation of CMOS beam-tapering arrays in the 60-GHz band.
We investigate taper tapping in three types of single-mode fibers using simulations and experiments: Standard single-mode fiber (SMF), bend-resistant single-mode fiber (BR-SMF) with a shallow index ...trench, and bend-insensitive single-mode fiber (BI-SMF) with a deep index trench. Both trench-assisted fibers demonstrate a larger mode field expansion than the standard single-mode fiber, making them more susceptible to taper-tapping than standard single-mode fibers. Tapering both SSMF and BR-SMF fibers to as little as 25μm diameter results in a high information extraction efficiency for an eavesdropper (≥−20 dB) while maintaining low loss for the legitimate channel (≤1 dB), underlining the vulnerability of all fiber types to taper tapping. We also use optical time-domain reflectometry (OTDR) to identify changes in the fiber before and after tapering. Changes in the back reflected power of ≤0.5 dB and ≤0.25 dB are observed in 25μm tapers in SMF and BR-SMF respectively.
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•Entropy generation analysis on a tapered multi-stenosed artery is studied.•Effects of viscous dissipation, radiation, and magnetic field are also discussed.•The Crank-Nicolson scheme ...is applied to solve the mathematical modeling.•For the realistic behavior of blood, Reynold's viscosity model is considered.•The current findings may be helpful for biomedical scientists.
This paper deals with the heat transfer and entropy generation analysis of unsteady blood flow through a tapered multi-stenosed artery incorporating hybrid nanoparticles (gold and alumina) with Joule heating, viscous dissipation, radiation, and inclined magnetic field. For the realistic behavior of blood, Reynold’s viscosity model is considered in this study. The Crank-Nicolson scheme is applied to solve the continuity, momentum, and energy equations with appropriate initial and boundary conditions. The important findings are represented graphically and have been analyzed for different values of the dimensionless parameters. The velocity contours for several emerging parameters are presented to study the overall behavior of blood flow patterns. It is observed that the axial flow accelerates with increasing wall slip velocity (ws) due to the presence of the hydrodynamic wall slip effect. The velocity profile increases as the concentration of Au nanoparticles increases, while the reverse effect is noted for the concentration of Al2O3 nanoparticles. The current findings may be helpful for biomedical scientists who are interested in investigating the treatment of various cardiovascular diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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