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Pemetrexed and immunotherapies (e.g., pembrolizumab) are approved for first-line maintenance (1LM) treatment of nonsquamous advanced/metastatic non-small-cell lung cancer (NSCLC), but real-world data on their use are limited. The objective of this study was to assess 1LM clinical outcomes, safety, and treatment patterns of immunotherapy versus immunotherapy+pemetrexed among patients with advanced/metastatic NSCLC from the EU4 (France, Germany, Italy, Spain)+UK.
Methods
Data from patients in the US, Canada, and EU4+UK with nonsquamous advanced/metastatic NSCLC without targetable mutations were collected via electronic case report form. Physician-identified patients (≥18 y) in the EU4+UK were eligible for this subgroup analysis if they achieved stable disease or complete or partial response with first-line platinum-based chemotherapy+immunotherapy (January 2019 to March 2021) and received 1LM immunotherapy or immunotherapy+pemetrexed. Patients were followed from index (1LM initiation) until last physician contact or death. Outcomes were overall survival (OS), progression-free survival (PFS), treatment patterns and duration, and adverse events.
Results
Among the selected 367 patients (male, 71.9%; mean±StDev age, 63.4±7.2 y; current/former smokers, 85.8%), 203 (55.3%) received immunotherapies, most commonly pembrolizumab (n=173; 85.2%), and 164 (44.7%) received immunotherapy+pemetrexed. Patients receiving immunotherapy had longer median adjusted OS and PFS compared to those receiving immunotherapy+pemetrexed (OS hazard ratio [HR]: 0.63; 95% confidence interval [CI]: 0.36, 0.90; PFS HR: 0.58; 95% CI: 0.38, 0.79). Patients receiving immunotherapy versus patients receiving immunotherapy+pemetrexed had longer median treatment duration (14.0 vs 10.3 mo; p<0.001) and were less likely to experience anemia (19.7% vs 33.5%; p<0.01). Results were similar in the overall study population.
Conclusions
In this real-world study, among the selected patients with nonsquamous advanced/metastatic NSCLC who achieved stable disease or complete or partial response with first-line therapy, the addition of pemetrexed to immunotherapy in 1LM did not appear to confer a clinical benefit. Identifying treatments that can improve clinical outcomes for these patients remains an area of unmet need.
We demonstrate an efficient ultrafast source with 195 fs pulse duration, 54 W average power at 200 kHz repetition rate and near diffraction-limited beam quality. The compact setup incorporates a thin-disk Yb:YAG regenerative amplifier (RA) and a subsequent nonlinear pulse compression stage with periodic-layered Kerr media (PLKM), which is one of the multiple-thin-solid-plate schemes based on nonlinear resonator theory. In virtue of the formation of quasi-stationary spatial soliton in PLKM, the near diffraction-limited beam quality of the RA remained almost undisturbed after post-compression. The nonlinear pulse compression module is simple and efficient with a transmission of 96%. To the best our knowledge, for pulse energy over 200 μJ, this is the highest output power reported for the multiple-thin-solid-plate scheme. This source manifests an economical combination to mitigate the bandwidth limitations of Yb-based high-power chirped pulse amplifiers.
We consider a two-stage submodular maximization problem subject to a cardinality constraint and k matroid constraints, where the objective function is the expected difference of a nonnegative monotone submodular function and a nonnegative monotone modular function. We give two bi-factor approximation algorithms for this problem. The first is a deterministic $\left( {{1 \over {k + 1}}\left( {1 - {1 \over {{e^{k + 1}}}}} \right),1} \right)$-approximation algorithm, and the second is a randomized $\left( {{1 \over {k + 1}}\left( {1 - {1 \over {{e^{k + 1}}}}} \right) - \varepsilon ,1} \right)$-approximation algorithm with improved time efficiency.
A simple, compact, double-pass pumped Nd:YVO4 thin disk laser is demonstrated. Its continuous-wave performance with different Nd doping concentrations and thicknesses is investigated experimentally. The maximum output power of 17.7 W is achieved by employing a 0.5 at.% doped sample, corresponding to an optical-to-optical efficiency of 46% with respect to the absorbed pump power. In addition, a numerical analysis and an experimental study of the temperature distribution, and thermal lens effect of the Nd:YVO4 thin disk, are presented considering the influence of the energy transfer upconversion effect and the temperature dependence of the thermal conductivity tensor. The simulated results are in good agreement with the experimental results.
In order to diminish the occurrence of cavitation bubbles during the liquid-assisted laser machining, ultrasound-assisted underwater femtosecond laser drilling on stainless steel is adopted. This method greatly diminishes the optical disturbance of cavitation bubbles. By investigating and analyzing the effect of laser pulse energy and pulse number on the morphology of the holes, it has been found that ultrasound not only has a remarkable function of forming a hole with clean and flat bottom, but also reduces debris redeposition around the processing area. This method improves the machining quality. Besides, it also improves the depth-to-diameter ratio of the hole about 20%.
This study estimates the willingness-to-pay (WTP) of Beijing residents in order to maintain the improved air quality experienced during the Olympic Games. A double-bounded contingent valuation method is applied to a survey of 566 Beijing residents. The results indicate that the mean annual WTP per household is between CNY 22,000 and 24,000, and the median WTP is around CNY 1,700. The WTP for this actually experienced improvement is significantly higher than the results from previous hypothetical WTP surveys in China.
We propose a deterministic solver for the time-dependent multi-subband Boltzmann transport equation (MSBTE) for the two dimensional (2D) electron gas in double gate metal oxide semiconductor field effect transistors (MOSFETs) with flared out source/drain contacts. A realistic model with six-valleys of the conduction band of silicon and both intra-valley and inter-valley phonon-electron scattering is solved. We propose a second order finite volume method based on the positive and flux conservative (PFC) method to discretize the Boltzmann transport equations (BTEs). The transport part of the BTEs is split into two problems. One is a 1D transport problem in the position space, and the other is a 2D transport problem in the wavevector space. In order to reduce the splitting error, the 2D transport problem in the wavevector space is solved directly by using the PFC method instead of splitting into two 1D problems. The solver is applied to a nanoscale double gate MOSFET and the current-voltage characteristic is investigated. Comparison of the numerical results with ballistic solutions show that the scattering influence is not ignorable even when the size of a nanoscale semiconductor device goes to the scale of the electron mean free path.
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