Evaluation of efficacy and safety of gefitinib as monotherapy in Chinese patients with advanced non-small cell lung cancer and very poor performance status

<p>Abstract</p> <p>Background</p> <p>This paper reports the outcome of gefitinib for Chinese advanced NSCLC patients with poor performance status (PS) at the Peking Union Medical College Hospital.</p> <p>Methods</p> <p>From Oct 2002 to Apr. 2006, 42 advanced NSCLC patients with PS 3/4 received gefitinib 250 mg/day treatment. Median survival (MS) were calculated using the Kaplan-Meier method and a Cox regression model was used to find main factors affecting MS.</p> <p>Results</p> <p>Adverse events (AEs) were generally mild (grade 1 and 2) and reversible. The most frequent AEs were rash 72.2% (26/42) and diarrhea 44.4% (26/42). The objective tumor response rate and stable disease rate were 40.5% and 26.2% respectively, and median survival(MS) of all patients was 10.1 months (95% confidential interval CI, 3.4 ~ 16.8), and progression-free survival(PFS) was 5.7 months (95% CI, 4.5 ~ 6.9). The MS were significantly related with objective response of gefitinib. Objective responses was significantly related with rashes induced with gefitinib.</p> <p>Conclusion</p> <p>Our study suggest that treatment with gefitinib may be well tolerated and beneficial for Chinese patients with poor PS, and the safety and efficacy were similar to patients with good PS.</p

Multisymplectic Geometry and Multisymplectic Preissman Scheme for the KP Equation

The multisymplectic structure of the KP equation is obtained directly from the variational principal. Using the covariant De Donder-Weyl Hamilton function theories, we reformulate the KP equation to the multisymplectic form which proposed by Bridges. From the multisymplectic equation, we can derive a multisymplectic numerical scheme of the KP equation which can be simplified to multisymplectic forty-five points scheme.Comment: 17 papges, 8 figure

Performance of AC-LGAD strip sensor designed for the DarkSHINE experiment

AC-coupled Low Gain Avalanche Detector (AC-LGAD) is a new precise detector technology developed in recent years. Based on the standard Low Gain Avalanche Detector (LGAD) technology, AC-LGAD sensors can provide excellent timing performance and spatial resolution. This paper presents the design and performance of several prototype AC-LGAD strip sensors for the DarkSHINE tracking system, as well as the electrical characteristics and spatial resolution of the prototype sensors from two batches of wafers with different $n^+$ dose.The range of spatial resolutions of 6.5$\mathrm{\mu m}$ $\sim$ 8.2$\mathrm{\mu m}$ and 8.8$\mathrm{\mu m}$ $\sim$ 12.3$\mathrm{\mu m}$ are achieved by the AC-LGAD sensors with 100$\mu m$ pitch size.Comment: 10 pages, 12 figure

Starling: An I/O-Efficient Disk-Resident Graph Index Framework for High-Dimensional Vector Similarity Search on Data Segment

High-dimensional vector similarity search (HVSS) is gaining prominence as a powerful tool for various data science and AI applications. As vector data scales up, in-memory indexes pose a significant challenge due to the substantial increase in main memory requirements. A potential solution involves leveraging disk-based implementation, which stores and searches vector data on high-performance devices like NVMe SSDs. However, implementing HVSS for data segments proves to be intricate in vector databases where a single machine comprises multiple segments for system scalability. In this context, each segment operates with limited memory and disk space, necessitating a delicate balance between accuracy, efficiency, and space cost. Existing disk-based methods fall short as they do not holistically address all these requirements simultaneously. In this paper, we present Starling, an I/O-efficient disk-resident graph index framework that optimizes data layout and search strategy within the segment. It has two primary components: (1) a data layout incorporating an in-memory navigation graph and a reordered disk-based graph with enhanced locality, reducing the search path length and minimizing disk bandwidth wastage; and (2) a block search strategy designed to minimize costly disk I/O operations during vector query execution. Through extensive experiments, we validate the effectiveness, efficiency, and scalability of Starling. On a data segment with 2GB memory and 10GB disk capacity, Starling can accommodate up to 33 million vectors in 128 dimensions, offering HVSS with over 0.9 average precision and top-10 recall rate, and latency under 1 millisecond. The results showcase Starling's superior performance, exhibiting 43.9$\times$ higher throughput with 98% lower query latency compared to state-of-the-art methods while maintaining the same level of accuracy.Comment: This paper has been accepted by SIGMOD 202

Simultaneous evolutionary expansion and constraint of genomic heterogeneity in multifocal lung cancer.

Recent genomic analyses have revealed substantial tumor heterogeneity across various cancers. However, it remains unclear whether and how genomic heterogeneity is constrained during tumor evolution. Here, we sequence a unique cohort of multiple synchronous lung cancers (MSLCs) to determine the relative diversity and uniformity of genetic drivers upon identical germline and environmental background. We find that each multicentric primary tumor harbors distinct oncogenic alterations, including novel mutations that are experimentally demonstrated to be functional and therapeutically targetable. However, functional studies show a strikingly constrained tumorigenic pathway underlying heterogeneous genetic variants. These results suggest that although the mutation-specific routes that cells take during oncogenesis are stochastic, genetic trajectories may be constrained by selection for functional convergence on key signaling pathways. Our findings highlight the robust evolutionary pressures that simultaneously shape the expansion and constraint of genomic diversity, a principle that holds important implications for understanding tumor evolution and optimizing therapeutic strategies.Across cancer types tumor heterogeneity has been observed, but how this relates to tumor evolution is unclear. Here, the authors sequence multiple synchronous lung cancers, highlighting the evolutionary pressures that simultaneously shape the expansion and constraint of genomic heterogeneity

The performance of large-pitch AC-LGAD with different N+ dose

AC-Coupled LGAD (AC-LGAD) is a new 4D detector developed based on the Low Gain Avalanche Diode (LGAD) technology, which can accurately measure the time and spatial information of particles. Institute of High Energy Physics (IHEP) designed a large-size AC-LGAD with a pitch of 2000 {\mu}m and AC pad of 1000 {\mu}m, and explored the effect of N+ layer dose on the spatial resolution and time resolution. The spatial resolution varied from 32.7 {\mu}m to 15.1 {\mu}m depending on N+ dose. The time resolution does not change significantly at different N+ doses, which is about 15-17 ps. AC-LGAD with a low N+ dose has a large attenuation factor and better spatial resolution. Large signal attenuation factor and low noise level are beneficial to improve the spatial resolution of the AC-LGAD sensor