Optimal sequential enrichment designs for phase II clinical trials

In the early phase development of molecularly targeted agents (MTAs), a commonly encountered situation is that the MTA is expected to be more effective for a certain biomarker subgroup, say marker-positive patients, but there is no adequate evidence to show that the MTA does not work for the other subgroup, that is, marker-negative patients. After establishing that marker-positive patients benefit from the treatment, it is often of great clinical interest to determine whether the treatment benefit extends to marker-negative patients. The authors propose optimal sequential enrichment (OSE) designs to address this practical issue in the context of phase II clinical trials. The OSE designs evaluate the treatment effect first in marker-positive patients and then in marker-negative patients if needed. The designs are optimal in the sense that they minimize the expected sample size or the maximum sample size under the null hypothesis that the MTA is futile. An efficient, accurate optimization algorithm is proposed to find the optimal design parameters. One important advantage of the OSE design is that the go/no-go interim decision rules are specified prior to the trial conduct, which makes the design particularly easy to use in practice. A simulation study shows that the OSE designs perform well and are ethically more desirable than the commonly used marker-stratified design. The OSE design is applied to an endometrial carcinoma trial

A Real-Time Video-based Eye Tracking Approach for Driver Attention Study

nowing the driver's point of gaze has significant potential to enhance driving safety, eye movements can be used as an indicator of the attention state of a driver; but the primary obstacle of integrating eye gaze into today's large scale real world driving attention study is the availability of a reliable, low-cost eye-tracking system. In this paper, we make an attempt to investigate such a real-time system to collect driver's eye gaze in real world driving environment. A novel eye-tracking approach is proposed based on low cost head mounted eye tracker. Our approach detects corneal reflection and pupil edge points firstly, and then fits the points with ellipse. The proposed approach is available in different illumination and driving environment from simple inexpensive head mounted eye tracker, which can be widely used in large scale experiments. The experimental results illustrate our approach can reliably estimate eye position with an accuracy of average 0.34 degree of visual angle in door experiment and 2--5 degrees in real driving environments

Decentralized H

For large-scale systems which are modeled as interconnection of N networked control systems with uncertain missing measurements probabilities, a decentralized state feedback H∞ controller design is considered in this paper. The occurrence of missing measurements is assumed to be a Bernoulli random binary switching sequence with an unknown conditional probability distribution in an interval. A state feedback H∞ controller is designed in terms of linear matrix inequalities to make closed-loop system exponentially mean square stable and a prescribed H∞ performance is guaranteed. Sufficient conditions are derived for the existence of such controller. A numerical example is also provided to demonstrate the validity of the proposed design approach

Study on transient voltage distribution characteristics of transformer windings

Very fast transient overvoltage (VFTO) with large waveform steepness and high amplitude can cause great harm to winding insulation of transformers and other equipment connected to it. Therefore, a transformer winding model is designed and described in this paper. Transient overvoltage test is carried out by pinning method and non-contact measuring sensor respectively. Then the simulation results are compared with those of VFTO distribution calculation program for transformer equipment. The results show that the simulation results are close to the actual test results. Finally, combining with the experimental measurement and simulation data, the potential distribution in transformer windings under the effect of fast transient overvoltage is analysed to guide the overvoltage protection of transformer winding insulation

Deep3DSketch+\+: High-Fidelity 3D Modeling from Single Free-hand Sketches

The rise of AR/VR has led to an increased demand for 3D content. However, the traditional method of creating 3D content using Computer-Aided Design (CAD) is a labor-intensive and skill-demanding process, making it difficult to use for novice users. Sketch-based 3D modeling provides a promising solution by leveraging the intuitive nature of human-computer interaction. However, generating high-quality content that accurately reflects the creator's ideas can be challenging due to the sparsity and ambiguity of sketches. Furthermore, novice users often find it challenging to create accurate drawings from multiple perspectives or follow step-by-step instructions in existing methods. To address this, we introduce a groundbreaking end-to-end approach in our work, enabling 3D modeling from a single free-hand sketch, Deep3DSketch+$\backslash$+. The issue of sparsity and ambiguity using single sketch is resolved in our approach by leveraging the symmetry prior and structural-aware shape discriminator. We conducted comprehensive experiments on diverse datasets, including both synthetic and real data, to validate the efficacy of our approach and demonstrate its state-of-the-art (SOTA) performance. Users are also more satisfied with results generated by our approach according to our user study. We believe our approach has the potential to revolutionize the process of 3D modeling by offering an intuitive and easy-to-use solution for novice users.Comment: Accepted at IEEE SMC 202

In vitro and in vivo effects of rat kidney vascular endothelial cells on osteogenesis of rat bone marrow mesenchymal stem cells growing on polylactide-glycoli acid (PLGA) scaffolds

It is well established that vascularization is critical for osteogenesis. However, adequate vascularization also remains one of the major challenges in tissue engineering of bone. This problem is further accentuated in regeneration of large volume of tissue. Although a complex process, vascularization involves reciprocal regulation and functional interaction between endothelial and osteoblast-like cells during osteogenesis. This prompted us to investigate the possibility of producing bone tissue both in vitro and ectopically in vivo using vascular endothelial cells because we hypothesized that the direct contact or interaction between vascular endothelial cells and bone marrow mesenchymal stem cells are of benefit to osteogenesis in vitro and in vivo. For that purpose we co-cultured rat bone marrow mesenchymal stem cells (MSC) and kidney vascular endothelial cells (VEC) with polylactide-glycolic acid scaffolds. In vitro experiments using alkaline phosphatase and osteocalcin assays demonstrated the proliferation and differentiation of MSC into osteoblast-like cells, especially the direct contact between VEC and MSC. In addition, histochemical analysis with CD31 and von-Willebrand factor staining showed that VEC retained their endothelial characteristics. In vivo implantation of MSC and VEC co-cultures into rat's muscle resulted in pre-vascular network-like structure established by the VEC in the PLGA. These structures developed into vascularized tissue, and increased the amount and size of the new bone compared to the control group (p < 0.05). These results suggest that the vascular endothelial cells could efficiently stimulate the in vitro proliferation and differentiation of osteoblast-like cells and promote osteogenesis in vivo by the direct contact or interaction with the MSC. This technique for optimal regeneration of bone should be further investigated