In the last two decades, single-arm trials (SATs) have been effectively used to study anticancer therapies in well-defined patient populations using durable response rates as an objective and interpretable clinical endpoints. With a growing trend of regulatory accelerated approval (AA) requiring randomized controlled trials (RCTs), some confusions have arisen about the roles of SATs in AA. This paper is intended to elucidate conditions under which an SAT may be considered reasonable for AA. Specifically, the paper describes (1) two necessary conditions for designing an SAT, (2) three sufficient conditions that help either optimize the study design or interpret the study results, (3) four conditions that demonstrate substantial evidence of clinical benefits of the drug, and (4) a plan of a confirmatory RCT to verify the clinical benefits. Some further considerations are discussed to help design a scientifically sound SAT and communicate with regulatory agencies. Conditions presented in this paper may serve as a set of references for sponsors using SATs for regulatory decision.
The coexistence of heterogeneous sub-networks in 6G poses new security and trust concerns and thus calls for a perimeterless-security model. Blockchain radio access network (B-RAN) provides a trust-building approach via repeated interactions rather than relying on pre-established trust or central authentication. Such a trust-building process naturally supports dynamic trusted services across various service providers (SP) without the need for perimeter-based authentications; however, it remains vulnerable to environmental and system unreliability such as wireless channel uncertainty. In this study, we investigate channel unreliability in the trust-building framework based on repeated interactions for secure wireless services. We derive specific requirements for achieving cooperation between SP and client via a repeated game model and illustrate the implications of channel unreliability on sustaining trusted access services. We consider the framework optimization to guarantee SP-client cooperation, given a worst-case channel condition. Furthermore, we introduce the concept of cooperation region to represent the robustness of the trust-building process and explore the maximum cooperation area to enhance service resilience. Finally, we present simulations to demonstrate the system performance over fading channels and verify our results.
In the field of lung cancer research, particularly in the analysis of overall survival (OS), artificial intelligence (AI) serves crucial roles with specific aims. Given the prevalent issue of missing data in the medical domain, our primary objective is to develop an AI model capable of dynamically handling this missing data. Additionally, we aim to leverage all accessible data, effectively analyzing both uncensored patients who have experienced the event of interest and censored patients who have not, by embedding a specialized technique within our AI model, not commonly utilized in other AI tasks. Through the realization of these objectives, our model aims to provide precise OS predictions for non-small cell lung cancer (NSCLC) patients, thus overcoming these significant challenges. We present a novel approach to survival analysis with missing values in the context of NSCLC, which exploits the strengths of the transformer architecture to account only for available features without requiring any imputation strategy. More specifically, this model tailors the transformer architecture to tabular data by adapting its feature embedding and masked self-attention to mask missing data and fully exploit the available ones. By making use of ad-hoc designed losses for OS, it is able to account for both censored and uncensored patients, as well as changes in risks over time. We compared our method with state-of-the-art models for survival analysis coupled with different imputation strategies. We evaluated the results obtained over a period of 6 years using different time granularities obtaining a Ct-index, a time-dependent variant of the C-index, of 71.97, 77.58 and 80.72 for time units of 1 month, 1 year and 2 years, respectively, outperforming all state-of-the-art methods regardless of the imputation method used.
Clinical trials are indispensable for medical research and the development of new treatments. However, clinical trials often involve thousands of participants and can span several years to complete, with a high probability of failure during the process. Recently, there has been a burgeoning interest in virtual clinical trials, which simulate real-world scenarios and hold the potential to significantly enhance patient safety, expedite development, reduce costs, and contribute to the broader scientific knowledge in healthcare. Existing research often focuses on leveraging electronic health records (EHRs) to support clinical trial outcome prediction. Yet, trained with limited clinical trial outcome data, existing approaches frequently struggle to perform accurate predictions. Some research has attempted to generate EHRs to augment model development but has fallen short in personalizing the generation for individual patient profiles. Recently, the emergence of large language models has illuminated new possibilities, as their embedded comprehensive clinical knowledge has proven beneficial in addressing medical issues. In this paper, we propose a large language model-based digital twin creation approach, called TWIN-GPT. TWIN-GPT can establish cross-dataset associations of medical information given limited data, generating unique personalized digital twins for different patients, thereby preserving individual patient characteristics. Comprehensive experiments show that using digital twins created by TWIN-GPT can boost the clinical trial outcome prediction, exceeding various previous prediction approaches.
In clinical dictation, utterances after automatic speech recognition (ASR) without explicit punctuation marks may lead to the misunderstanding of dictated reports. To give a precise and understandable clinical report with ASR, automatic punctuation restoration is required. Considering a practical scenario, we propose a fast and light pre-trained model for Chinese medical punctuation restoration based on 'pretraining and fine-tuning' paradigm. In this work, we distill pre-trained models by incorporating supervised contrastive learning and a novel auxiliary pre-training task (Punctuation Mark Prediction) to make it well-suited for punctuation restoration. Our experiments on various distilled models reveal that our model can achieve 95% performance while 10% model size relative to state-of-the-art Chinese RoBERTa.
The advent of wearable and sensor technologies now leads to functional predictors which are intrinsically infinite dimensional. While the existing approaches for functional data and survival outcomes lean on the well-established Cox model, the proportional hazard (PH) assumption might not always be suitable in real-world applications. Motivated by physiological signals encountered in digital medicine, we develop a more general and flexible functional time-transformation model for estimating the conditional survival function with both functional and scalar covariates. A partially functional regression model is used to directly model the survival time on the covariates through an unknown monotone transformation and a known error distribution. We use Bernstein polynomials to model the monotone transformation function and the smooth functional coefficients. A sieve method of maximum likelihood is employed for estimation. Numerical simulations illustrate a satisfactory performance of the proposed method in estimation and inference. We demonstrate the application of the proposed model through two case studies involving wearable data i) Understanding the association between diurnal physical activity pattern and all-cause mortality based on accelerometer data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014 and ii) Modelling Time-to-Hypoglycemia events in a cohort of diabetic patients based on distributional representation of continuous glucose monitoring (CGM) data. The results provide important epidemiological insights into the direct association between survival times and the physiological signals and also exhibit superior predictive performance compared to traditional summary based biomarkers in the CGM study.
One of the most crucial components in the field of biometric security is the automatic speaker verification system, which is based on the speaker's voice. It is possible to utilise ASVs in isolation or in conjunction with other AI models. In the contemporary era, the quality and quantity of neural networks are increasing exponentially. Concurrently, there is a growing number of systems that aim to manipulate data through the use of voice conversion and text-to-speech models. The field of voice biometrics forgery is aided by a number of challenges, including SSTC, ASVSpoof, and SingFake. This paper presents a system for automatic speaker verification. The primary objective of our model is the extraction of embeddings from the target speaker's audio in order to obtain information about important characteristics of his voice, such as pitch, energy, and the duration of phonemes. This information is used in our multivoice TTS pipeline, which is currently under development. However, this model was employed within the SSTC challenge to verify users whose voice had undergone voice conversion, where it demonstrated an EER of 20.669.
The typical training of neural networks using large stepsize gradient descent (GD) under the logistic loss often involves two distinct phases, where the empirical risk oscillates in the first phase but decreases monotonically in the second phase. We investigate this phenomenon in two-layer networks that satisfy a near-homogeneity condition. We show that the second phase begins once the empirical risk falls below a certain threshold, dependent on the stepsize. Additionally, we show that the normalized margin grows nearly monotonically in the second phase, demonstrating an implicit bias of GD in training non-homogeneous predictors. If the dataset is linearly separable and the derivative of the activation function is bounded away from zero, we show that the average empirical risk decreases, implying that the first phase must stop in finite steps. Finally, we demonstrate that by choosing a suitably large stepsize, GD that undergoes this phase transition is more efficient than GD that monotonically decreases the risk. Our analysis applies to networks of any width, beyond the well-known neural tangent kernel and mean-field regimes.
Understanding causality helps to structure interventions to achieve specific goals and enables predictions under interventions. With the growing importance of learning causal relationships, causal discovery tasks have transitioned from using traditional methods to infer potential causal structures from observational data to the field of pattern recognition involved in deep learning. The rapid accumulation of massive data promotes the emergence of causal search methods with brilliant scalability. Existing summaries of causal discovery methods mainly focus on traditional methods based on constraints, scores and FCMs, there is a lack of perfect sorting and elaboration for deep learning-based methods, also lacking some considers and exploration of causal discovery methods from the perspective of variable paradigms. Therefore, we divide the possible causal discovery tasks into three types according to the variable paradigm and give the definitions of the three tasks respectively, define and instantiate the relevant datasets for each task and the final causal model constructed at the same time, then reviews the main existing causal discovery methods for different tasks. Finally, we propose some roadmaps from different perspectives for the current research gaps in the field of causal discovery and point out future research directions.
Ensembles over neural network weights trained from different random initialization, known as deep ensembles, achieve state-of-the-art accuracy and calibration. The recently introduced batch ensembles provide a drop-in replacement that is more parameter efficient. In this paper, we design ensembles not only over weights, but over hyperparameters to improve the state of the art in both settings. For best performance independent of budget, we propose hyper-deep ensembles, a simple procedure that involves a random search over different hyperparameters, themselves stratified across multiple random initializations. Its strong performance highlights the benefit of combining models with both weight and hyperparameter diversity. We further propose a parameter efficient version, hyper-batch ensembles, which builds on the layer structure of batch ensembles and self-tuning networks. The computational and memory costs of our method are notably lower than typical ensembles. On image classification tasks, with MLP, LeNet, and Wide ResNet 28-10 architectures, our methodology improves upon both deep and batch ensembles.
Object detection typically assumes that training and test data are drawn from an identical distribution, which, however, does not always hold in practice. Such a distribution mismatch will lead to a significant performance drop. In this work, we aim to improve the cross-domain robustness of object detection. We tackle the domain shift on two levels: 1) the image-level shift, such as image style, illumination, etc, and 2) the instance-level shift, such as object appearance, size, etc. We build our approach based on the recent state-of-the-art Faster R-CNN model, and design two domain adaptation components, on image level and instance level, to reduce the domain discrepancy. The two domain adaptation components are based on H-divergence theory, and are implemented by learning a domain classifier in adversarial training manner. The domain classifiers on different levels are further reinforced with a consistency regularization to learn a domain-invariant region proposal network (RPN) in the Faster R-CNN model. We evaluate our newly proposed approach using multiple datasets including Cityscapes, KITTI, SIM10K, etc. The results demonstrate the effectiveness of our proposed approach for robust object detection in various domain shift scenarios.