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In this article we have conducted a reanalysis of the phase III aducanumab (ADU) summary statistics announced by Biogen, in particular the result of the Clinical Dementia Rating-Sum of Boxes (CDR-SB). The results showed that the evidence on the efficacy of the drug is very low and a more clearer view of the results of clinical trials are presented in the Bayesian framework that can be useful for future development and research in the field.

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Surrogate endpoint (SE) for overall survival (OS) in cancer patients is essential to improving the efficiency of oncology drug development. In practice, we may discover a new patient level association with OS in a discovery cohort, and then measure the trial level association across studies in a meta-analysis to validate the SE. In this work, we simulated pairs of metrics to quantify the surrogacy at the patient level and the trial level and evaluated their association, and to understand how well various patient level metrics from the initial discovery would indicate the eventual utility as a SE. Across all the simulation scenarios, we found tight correlation among all the patient level metrics, including C index, integrated brier score and log hazard ratio between SE values and OS; and similar correlation between any of them and the trial level association metric. Despite the continual increase in the true biological link between SE and OS, both patient and trial level metrics often plateaued coincidentally in many scenarios; their association always decreased quickly. Under the SE development framework and data generation models considered here, all patient level metrics are similar in ranking a candidate SE according to its eventual trial level association; incorporating additional biological factors into a SE are likely to have diminished return in improving both patient level and trial level association.

Deep neural networks are vulnerable to adversarial examples that mislead the models with imperceptible perturbations. Though adversarial attacks have achieved incredible success rates in the white-box setting, most existing adversaries often exhibit weak transferability in the black-box setting, especially under the scenario of attacking models with defense mechanisms. In this work, we propose a new method called variance tuning to enhance the class of iterative gradient based attack methods and improve their attack transferability. Specifically, at each iteration for the gradient calculation, instead of directly using the current gradient for the momentum accumulation, we further consider the gradient variance of the previous iteration to tune the current gradient so as to stabilize the update direction and escape from poor local optima. Empirical results on the standard ImageNet dataset demonstrate that our method could significantly improve the transferability of gradient-based adversarial attacks. Besides, our method could be used to attack ensemble models or be integrated with various input transformations. Incorporating variance tuning with input transformations on iterative gradient-based attacks in the multi-model setting, the integrated method could achieve an average success rate of 90.1% against nine advanced defense methods, improving the current best attack performance significantly by 85.1% . Code is available at //github.com/JHL-HUST/VT.

While existing work in robust deep learning has focused on small pixel-level $\ell_p$ norm-based perturbations, this may not account for perturbations encountered in several real world settings. In many such cases although test data might not be available, broad specifications about the types of perturbations (such as an unknown degree of rotation) may be known. We consider a setup where robustness is expected over an unseen test domain that is not i.i.d. but deviates from the training domain. While this deviation may not be exactly known, its broad characterization is specified a priori, in terms of attributes. We propose an adversarial training approach which learns to generate new samples so as to maximize exposure of the classifier to the attributes-space, without having access to the data from the test domain. Our adversarial training solves a min-max optimization problem, with the inner maximization generating adversarial perturbations, and the outer minimization finding model parameters by optimizing the loss on adversarial perturbations generated from the inner maximization. We demonstrate the applicability of our approach on three types of naturally occurring perturbations -- object-related shifts, geometric transformations, and common image corruptions. Our approach enables deep neural networks to be robust against a wide range of naturally occurring perturbations. We demonstrate the usefulness of the proposed approach by showing the robustness gains of deep neural networks trained using our adversarial training on MNIST, CIFAR-10, and a new variant of the CLEVR dataset.

As we seek to deploy machine learning models beyond virtual and controlled domains, it is critical to analyze not only the accuracy or the fact that it works most of the time, but if such a model is truly robust and reliable. This paper studies strategies to implement adversary robustly trained algorithms towards guaranteeing safety in machine learning algorithms. We provide a taxonomy to classify adversarial attacks and defenses, formulate the Robust Optimization problem in a min-max setting and divide it into 3 subcategories, namely: Adversarial (re)Training, Regularization Approach, and Certified Defenses. We survey the most recent and important results in adversarial example generation, defense mechanisms with adversarial (re)Training as their main defense against perturbations. We also survey mothods that add regularization terms that change the behavior of the gradient, making it harder for attackers to achieve their objective. Alternatively, we've surveyed methods which formally derive certificates of robustness by exactly solving the optimization problem or by approximations using upper or lower bounds. In addition, we discuss the challenges faced by most of the recent algorithms presenting future research perspectives.

Generative adversarial networks (GANs) have been extensively studied in the past few years. Arguably the revolutionary techniques are in the area of computer vision such as plausible image generation, image to image translation, facial attribute manipulation and similar domains. Despite the significant success achieved in computer vision field, applying GANs over real-world problems still have three main challenges: (1) High quality image generation; (2) Diverse image generation; and (3) Stable training. Considering numerous GAN-related research in the literature, we provide a study on the architecture-variants and loss-variants, which are proposed to handle these three challenges from two perspectives. We propose loss and architecture-variants for classifying most popular GANs, and discuss the potential improvements with focusing on these two aspects. While several reviews for GANs have been presented, there is no work focusing on the review of GAN-variants based on handling challenges mentioned above. In this paper, we review and critically discuss 7 architecture-variant GANs and 9 loss-variant GANs for remedying those three challenges. The objective of this review is to provide an insight on the footprint that current GANs research focuses on the performance improvement. Code related to GAN-variants studied in this work is summarized on //github.com/sheqi/GAN_Review.

In this paper we study the convergence of generative adversarial networks (GANs) from the perspective of the informativeness of the gradient of the optimal discriminative function. We show that GANs without restriction on the discriminative function space commonly suffer from the problem that the gradient produced by the discriminator is uninformative to guide the generator. By contrast, Wasserstein GAN (WGAN), where the discriminative function is restricted to $1$-Lipschitz, does not suffer from such a gradient uninformativeness problem. We further show in the paper that the model with a compact dual form of Wasserstein distance, where the Lipschitz condition is relaxed, also suffers from this issue. This implies the importance of Lipschitz condition and motivates us to study the general formulation of GANs with Lipschitz constraint, which leads to a new family of GANs that we call Lipschitz GANs (LGANs). We show that LGANs guarantee the existence and uniqueness of the optimal discriminative function as well as the existence of a unique Nash equilibrium. We prove that LGANs are generally capable of eliminating the gradient uninformativeness problem. According to our empirical analysis, LGANs are more stable and generate consistently higher quality samples compared with WGAN.

Person re-identification (re-ID) has attracted much attention recently due to its great importance in video surveillance. In general, distance metrics used to identify two person images are expected to be robust under various appearance changes. However, our work observes the extreme vulnerability of existing distance metrics to adversarial examples, generated by simply adding human-imperceptible perturbations to person images. Hence, the security danger is dramatically increased when deploying commercial re-ID systems in video surveillance, especially considering the highly strict requirement of public safety. Although adversarial examples have been extensively applied for classification analysis, it is rarely studied in metric analysis like person re-identification. The most likely reason is the natural gap between the training and testing of re-ID networks, that is, the predictions of a re-ID network cannot be directly used during testing without an effective metric. In this work, we bridge the gap by proposing Adversarial Metric Attack, a parallel methodology to adversarial classification attacks, which can effectively generate adversarial examples for re-ID. Comprehensive experiments clearly reveal the adversarial effects in re-ID systems. Moreover, by benchmarking various adversarial settings, we expect that our work can facilitate the development of robust feature learning with the experimental conclusions we have drawn.

There is a recent large and growing interest in generative adversarial networks (GANs), which offer powerful features for generative modeling, density estimation, and energy function learning. GANs are difficult to train and evaluate but are capable of creating amazingly realistic, though synthetic, image data. Ideas stemming from GANs such as adversarial losses are creating research opportunities for other challenges such as domain adaptation. In this paper, we look at the field of GANs with emphasis on these areas of emerging research. To provide background for adversarial techniques, we survey the field of GANs, looking at the original formulation, training variants, evaluation methods, and extensions. Then we survey recent work on transfer learning, focusing on comparing different adversarial domain adaptation methods. Finally, we take a look forward to identify open research directions for GANs and domain adaptation, including some promising applications such as sensor-based human behavior modeling.

We evaluate the robustness of Adversarial Logit Pairing, a recently proposed defense against adversarial examples. We find that a network trained with Adversarial Logit Pairing achieves 0.6% accuracy in the threat model in which the defense is considered. We provide a brief overview of the defense and the threat models/claims considered, as well as a discussion of the methodology and results of our attack, which may offer insights into the reasons underlying the vulnerability of ALP to adversarial attack.

Methods that align distributions by minimizing an adversarial distance between them have recently achieved impressive results. However, these approaches are difficult to optimize with gradient descent and they often do not converge well without careful hyperparameter tuning and proper initialization. We investigate whether turning the adversarial min-max problem into an optimization problem by replacing the maximization part with its dual improves the quality of the resulting alignment and explore its connections to Maximum Mean Discrepancy. Our empirical results suggest that using the dual formulation for the restricted family of linear discriminators results in a more stable convergence to a desirable solution when compared with the performance of a primal min-max GAN-like objective and an MMD objective under the same restrictions. We test our hypothesis on the problem of aligning two synthetic point clouds on a plane and on a real-image domain adaptation problem on digits. In both cases, the dual formulation yields an iterative procedure that gives more stable and monotonic improvement over time.

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