Enhancing phase I dose-finding trials design through dynamic borrowing information and handling late-onset toxicity

Introduction: In recent years, there has been a growing trend among regulatory agencies to consider the use of historical controls in clinical trials as a means of improving the efficiency of trial design. In this paper, to enhance the statistical operating characteristic of Phase I dose-finding trials, we propose a novel model-assisted design method named “MEM-Keyboard”.Methods: The proposed design is based on the multisource exchangeability models (MEMs) that allows for dynamic borrowing of information from multiple supplemental data sources, including historical trial data, to inform the dose-escalation process. Furthermore, with the frequent occurrence of delayed toxicity in novel anti-cancer drugs, we extended our proposed method to handle late-onset toxicity by incorporating historical data. This extended method is referred to as “MEM-TITE-Keyboard” and aims to improve the efficiency of early clinical trials.Results: Simulation studies have indicated that the proposed methods can improve the probability of correctly selecting the maximum tolerated dose (MTD) with an acceptable level of risk, compared to designs that do not account for information borrowing and late-onset toxicity.Discussion: The MEM-Keyboard and MEM-TITE-Keyboard, easy to implement in practice, provide a useful tool for identifying MTD and accelerating drug development

JujubeNet: A high-precision lightweight jujube surface defect classification network with an attention mechanism

Surface Defect Detection (SDD) is a significant research content in Industry 4.0 field. In the real complex industrial environment, SDD is often faced with many challenges, such as small difference between defect imaging and background, low contrast, large variation of defect scale and diverse types, and large amount of noise in defect images. Jujubes are naturally growing plants, and the appearance of the same type of surface defect can vary greatly, so it is more difficult than industrial products produced according to the prescribed process. In this paper, a ConvNeXt-based high-precision lightweight classification network JujubeNet is presented to address the practical needs of Jujube Surface Defect (JSD) classification. In the proposed method, a Multi-branching module using Depthwise separable Convolution (MDC) is designed to extract more feature information through multi-branching and substantially reduces the number of parameters in the model by using depthwise separable convolutions. What’s more, in our proposed method, the Convolutional Block Attention Module (CBAM) is introduced to make the model concentrate on different classes of JSD features. The proposed JujubeNet is compared with other mainstream networks in the actual production environment. The experimental results show that the proposed JujubeNet can achieve 99.1% classification accuracy, which is significantly better than the current mainstream classification models. The FLOPS and parameters are only 30.7% and 30.6% of ConvNeXt-Tiny respectively, indicating that the model can quickly and effectively classify JSD and is of great practical value

Observation of the orbital Rashba-Edelstein magnetoresistance

We report the observation of magnetoresistance (MR) that could originate from the orbital angular momentum (OAM) transport in a permalloy (Py)/oxidized Cu (Cu*) heterostructure: the orbital RashbaEdelstein magnetoresistance. The angular dependence of the MR depends on the relative angle between the induced OAM and the magnetization in a similar fashion as the spin Hall magnetoresistance. Despite the absence of elements with large spin-orbit coupling, we find a sizable MR ratio, which is in contrast to the conventional spin Hall magnetoresistance which requires heavy elements. Through Py thicknessdependence studies, we conclude another mechanism beyond the conventional spin-based scenario is responsible for the MR observed in Py/Cu* structures-originated in a sizable transport of OAM. Our findings not only suggest the current-induced torques without using any heavy elements via the OAM channel but also provide an important clue towards the microscopic understanding of the role that OAM transport can play for magnetization dynamics

Progress of the special-subjects study on the construction of comprehensive geological disaster prevention and control system in Yunnan Province

The establishment of the comprehensive geological disaster prevention and control system in Yunnan province stands as China’s most extensive and grand-scale endeavor in safeguarding the prevention and control of geological disasters in China. Its implementation has led to a significant reduction in the occurrence of geological disasters, resulting in a substantial decrease in both casualties and missing persons affected by such disasters. This accomplishment has yielded remarkable outcomes in disaster prevention and mitigation. Based on the results of 12 series monographic studies, this paper provides an overview of the implementation of the system and its disaster prevention and mitigation effects. It summarizes the main scientific and technological achievements, with a particular focus on the causes and patterns of plateau geological disasters, understanding of special rock and soil disaster control mechanisms, susceptibility zoning evaluation, comprehensive remote sensing identification of geological hazards, progress in automated monitoring and early warning, and the development of geological environment information standard system. These achievements can provide valuable insights for the comprehensive geological disaster prevention and control in Yunnan Province

Real-Time Area Angle Monitoring Using Synchrophasors: A Practical Framework and Utility Deployment

This article develops a practical framework of Area Angle Monitoring (AAM) to monitor in real time the stress of bulk power transfer across an area of a power transmission system. Area angle is calculated from synchrophasor measurements in real time to provide alert to system operators if the area angle exceeds pre-defined thresholds. This article proposes a general method to identify the warning threshold of area angle and a simplified method to quickly update area angle thresholds under significant topology change. A mitigation strategy to relieve the area stress is also proposed. In order to handle the limited coverage of synchrophasor measurements, this article proposes a method to estimate phase angles for boundary buses without synchrophasor measurements, which extends the application scenario of AAM. AAM is verified for a power transmission area in the Western Electricity Coordinating Council system with both simulated data and synchrophasor measurements recorded from real events. A utility deployment for real-time application of AAM with livestream and recorded synchrophasor data is described

Real-Time Monitoring of Area Angles with Synchrophasor Measurements

This paper develops a comprehensive framework of Area Angle Monitoring (AAM) to monitor the stress of bulk power transfer across an area of a power transmission system in real-time. Area angle is calculated from synchrophasor measurements to provide alert to system operators if the area angle exceeds pre-defined thresholds. This paper proposes general methods to identify these warning and emergency thresholds, and tests a mitigation strategy to relieve the area stress when the area angle exceeds the threshold. In order to handle the limited coverage of synchrophasor measurements, this paper proposes methods to estimate phase angles for boundary buses without synchrophasor measurements, which extends the application of AAM. AAM is verified for a power transmission area in the Western Electricity Coordinating Council system with both simulated data and synchrophasor measurements recorded from real events. A utility deployment to test the framework for monitoring area angle with live-stream and recorded synchrophasor data is described

Dominance of HIV-1 Subtype CRF01_AE in Sexually Acquired Cases Leads to a New Epidemic in Yunnan Province of China

BACKGROUND: Dating back to the first epidemic among injection drug users in 1989, the Yunnan province has had the highest number of human immunodeficiency virus type 1 (HIV-1) infections in China. However, the molecular epidemiology of HIV-1 in Yunnan has not been fully characterized. METHODS AND FINDINGS: Using immunoassays, we identified 103,015 accumulated cases of HIV-1 infections in Yunnan between 1989 and 2004. We studied 321 patients representing Yunnan's 16 prefectures from four risk groups, 11 ethnic populations, and ten occupations. We identified three major circulating subtypes: C/CRF07_BC/CRF08_BC (53%), CRF01_AE (40.5%), and B (6.5%) by analyzing the sequence of p17, which is part of the gag gene. For patients with known risk factors, 90.9% of injection drug users had C/CRF07_BC/CRF08_BC viruses, whereas 85.4% of CRF01_AE infections were acquired through sexual transmission. No distinct segregation of CRF01_AE viruses was found among the Dai ethnic group. Geographically, C/CRF07_BC/CRF08_BC was found throughout the province, while CRF01_AE was largely confined to the prefectures bordering Myanmar. Furthermore, C/CRF07_BC/CRF08_BC viruses were found to consist of a group of viruses, including C, CRF08_BC, CRF07_BC, and new BC recombinants, based on the characterization of their reverse transcriptase genes. CONCLUSIONS: This is the first report of a province-wide HIV-1 molecular epidemiological study in Yunnan. While C/CRF07_BC/CRF08_BC and CRF01_AE are codominant, the discovery of many sexually transmitted CRF01_AE cases is new and suggests that this subtype may lead to a new epidemic in the general Chinese population. We discuss implications of our results for understanding the evolution of the HIV-1 pandemic and for vaccine development