Clinical trials are an integral component of medical research. Trials require careful design to, for example, maintain the safety of participants, use resources efficiently and allow clinically meaningful conclusions to be drawn. Adaptive clinical trials (i.e. trials that can be altered based on evidence that has accrued) are often more efficient, informative and ethical than standard or non-adaptive trials because they require fewer participants, target more promising treatments, and can stop early with sufficient evidence of effectiveness or harm. The design of adaptive trials requires the pre-specification of adaptions that are permissible throughout the conduct of the trial. Proposed adaptive designs are then usually evaluated through simulation which provides indicative metrics of performance (e.g. statistical power and type-1 error) under different scenarios. Trial simulation requires assumptions about the data generating process to be specified but correctly specifying these in practice can be difficult, particularly for new and emerging diseases. To address this, we propose an approach to design adaptive clinical trials without needing to specify the complete data generating process. To facilitate this, we consider a general Bayesian framework where inference about the treatment effect on a time-to-event outcome can be performed via the partial likelihood. As a consequence, the proposed approach to evaluate trial designs is robust to the specific form of the baseline hazard function. The benefits of this approach are demonstrated through the redesign of a recent clinical trial to evaluate whether a third dose of a vaccine provides improved protection against gastroenteritis in Australian Indigenous infants.
相關內容
With the goal of increasing the speed and efficiency in robotic dual arm manipulation, a novel control approach is presented that utilizes intentional simultaneous impacts to rapidly grasp objects. This approach uses the time-invariant reference spreading framework, in which partly-overlapping ante- and post-impact reference vector fields are used. These vector fields are coupled via the impact dynamics in proximity of the expected impact area, minimizing the otherwise large velocity errors after the impact and the corresponding large control efforts. A purely spatial task is introduced to strongly encourage the synchronization of impact times of the two arms. An interim-impact control phase provides robustness in the execution against the inevitable lack of exact impact simultaneity and the corresponding unreliable velocity error. In this interim phase, a position feedback signal is derived from the ante-impact velocity reference, which is used to enforce sustained contact in all contact points without using velocity error feedback. With an eye towards real-life implementation, the approach is formulated using a QP control framework, and is validated using numerical simulations on a realistic robot model with flexible joints and low-level torque control.
A successful automated program proof is, in software verification, the ultimate triumph. In practice, however, the road to such success is paved with many failed proof attempts. Unlike a failed test, which provides concrete evidence of an actual bug in the program, a failed proof leaves the programmer in the dark. Can we instead learn something useful from it? The work reported here takes advantage of the rich internal information that some automatic provers collect about the program when attempting a proof. If the proof fails, the Proof2Test tool presented in this article uses the counterexample generated by the prover (specifically, the SMT solver underlying the proof environment Boogie, used in the AutoProof system to perform correctness proofs of contract-equipped Eiffel programs) to produce a failed test, which provides the programmer with immediately exploitable information to correct the program. The discussion presents the Proof2Test tool and demonstrates the application of the ideas and tool to a collection of representative examples.
Quantitative notions of bisimulation are well-known tools for the minimization of dynamical models such as Markov chains and ordinary differential equations (ODEs). In \emph{forward bisimulations}, each state in the quotient model represents an equivalence class and the dynamical evolution gives the overall sum of its members in the original model. Here we introduce generalized forward bisimulation (GFB) for dynamical systems over commutative monoids and develop a partition refinement algorithm to compute the coarsest one. When the monoid is $(\mathbb{R}, +)$, we recover %our framework recovers probabilistic bisimulation for Markov chains and more recent forward bisimulations for %systems of nonlinear ODEs. %ordinary differential equations. Using $(\mathbb{R}, \cdot)$ we get %When the monoid is $(\mathbb{R}, \cdot)$ we can obtain nonlinear reductions for discrete-time dynamical systems and ODEs %ordinary differential equations where each variable in the quotient model represents the product of original variables in the equivalence class. When the domain is a finite set such as the Booleans $\mathbb{B}$, we can apply GFB to Boolean networks (BN), a widely used dynamical model in computational biology. Using a prototype implementation of our minimization algorithm for GFB, we find disjunction- and conjunction-preserving reductions on 60 BN from two well-known repositories, and demonstrate the obtained analysis speed-ups. We also provide the biological interpretation of the reduction obtained for two selected BN, and we show how GFB enables the analysis of a large one that could not be analyzed otherwise. Using a randomized version of our algorithm we find product-preserving (therefore non-linear) reductions on 21 dynamical weighted networks from the literature that could not be handled by the exact algorithm.
Electricity load forecasting is a necessary capability for power system operators and electricity market participants. The proliferation of local generation, demand response, and electrification of heat and transport are changing the fundamental drivers of electricity load and increasing the complexity of load modelling and forecasting. We address this challenge in two ways. First, our setting is adaptive; our models take into account the most recent observations available, yielding a forecasting strategy able to automatically respond to changes in the underlying process. Second, we consider probabilistic rather than point forecasting; indeed, uncertainty quantification is required to operate electricity systems efficiently and reliably. Our methodology relies on the Kalman filter, previously used successfully for adaptive point load forecasting. The probabilistic forecasts are obtained by quantile regressions on the residuals of the point forecasting model. We achieve adaptive quantile regressions using the online gradient descent; we avoid the choice of the gradient step size considering multiple learning rates and aggregation of experts. We apply the method to two data sets: the regional net-load in Great Britain and the demand of seven large cities in the United States. Adaptive procedures improve forecast performance substantially in both use cases for both point and probabilistic forecasting.
To meet order fulfillment targets, manufacturers seek to optimize production schedules. Machine learning can support this objective by predicting throughput times on production lines given order specifications. However, this is challenging when manufacturers produce customized products because customization often leads to changes in the probability distribution of operational data -- so-called distributional shifts. Distributional shifts can harm the performance of predictive models when deployed to future customer orders with new specifications. The literature provides limited advice on how such distributional shifts can be addressed in operations management. Here, we propose a data-driven approach based on adversarial learning and job shop scheduling, which allows us to account for distributional shifts in manufacturing settings with high degrees of product customization. We empirically validate our proposed approach using real-world data from a job shop production that supplies large metal components to an oil platform construction yard. Across an extensive series of numerical experiments, we find that our adversarial learning approach outperforms common baselines. Overall, this paper shows how production managers can improve their decision-making under distributional shifts.
We propose a novel technique for analyzing adaptive sampling called the {\em Simulator}. Our approach differs from the existing methods by considering not how much information could be gathered by any fixed sampling strategy, but how difficult it is to distinguish a good sampling strategy from a bad one given the limited amount of data collected up to any given time. This change of perspective allows us to match the strength of both Fano and change-of-measure techniques, without succumbing to the limitations of either method. For concreteness, we apply our techniques to a structured multi-arm bandit problem in the fixed-confidence pure exploration setting, where we show that the constraints on the means imply a substantial gap between the moderate-confidence sample complexity, and the asymptotic sample complexity as $\delta \to 0$ found in the literature. We also prove the first instance-based lower bounds for the top-k problem which incorporate the appropriate log-factors. Moreover, our lower bounds zero-in on the number of times each \emph{individual} arm needs to be pulled, uncovering new phenomena which are drowned out in the aggregate sample complexity. Our new analysis inspires a simple and near-optimal algorithm for the best-arm and top-k identification, the first {\em practical} algorithm of its kind for the latter problem which removes extraneous log factors, and outperforms the state-of-the-art in experiments.
This paper presents a deep learning based model predictive control (MPC) algorithm for systems with unmatched and bounded state-action dependent uncertainties of unknown structure. We utilize a deep neural network (DNN) as an oracle in the underlying optimization problem of learning based MPC (LBMPC) to estimate unmatched uncertainties. Generally, non-parametric oracles such as DNN are considered difficult to employ with LBMPC due to the technical difficulties associated with estimation of their coefficients in real time. We employ a dual-timescale adaptation mechanism, where the weights of the last layer of the neural network are updated in real time while the inner layers are trained on a slower timescale using the training data collected online and selectively stored in a buffer. Our results are validated through a numerical experiment on the compression system model of jet engine. These results indicate that the proposed approach is implementable in real time and carries the theoretical guarantees of LBMPC.
Uncertainty quantification in image restoration is a prominent challenge, mainly due to the high dimensionality of the encountered problems. Recently, a Bayesian uncertainty quantification by optimization (BUQO) has been proposed to formulate hypothesis testing as a minimization problem. The objective is to determine whether a structure appearing in a maximum a posteriori estimate is true or is a reconstruction artifact due to the ill-posedness or ill-conditioness of the problem. In this context, the mathematical definition of having a ``fake structure" is crucial, and highly depends on the type of structure of interest. This definition can be interpreted as an inpainting of a neighborhood of the structure, but only simple techniques have been proposed in the literature so far, due to the complexity of the problem. In this work, we propose a data-driven method using a simple convolutional neural network to perform the inpainting task, leading to a novel plug-and-play BUQO algorithm. Compared to previous works, the proposed approach has the advantage that it can be used for a wide class of structures, without needing to adapt the inpainting operator to the area of interest. In addition, we show through simulations on magnetic resonance imaging, that compared to the original BUQO's hand-crafted inpainting procedure, the proposed approach provides greater qualitative output images. Python code will be made available for reproducibility upon acceptance of the article.
Learning effective high-order feature interactions is very crucial in the CTR prediction task. However, it is very time-consuming to calculate high-order feature interactions with massive features in online e-commerce platforms. Most existing methods manually design a maximal order and further filter out the useless interactions from them. Although they reduce the high computational costs caused by the exponential growth of high-order feature combinations, they still suffer from the degradation of model capability due to the suboptimal learning of the restricted feature orders. The solution to maintain the model capability and meanwhile keep it efficient is a technical challenge, which has not been adequately addressed. To address this issue, we propose an adaptive feature interaction learning model, named as EulerNet, in which the feature interactions are learned in a complex vector space by conducting space mapping according to Euler's formula. EulerNet converts the exponential powers of feature interactions into simple linear combinations of the modulus and phase of the complex features, making it possible to adaptively learn the high-order feature interactions in an efficient way. Furthermore, EulerNet incorporates the implicit and explicit feature interactions into a unified architecture, which achieves the mutual enhancement and largely boosts the model capabilities. Such a network can be fully learned from data, with no need of pre-designed form or order for feature interactions. Extensive experiments conducted on three public datasets have demonstrated the effectiveness and efficiency of our approach. Our code is available at: //github.com/RUCAIBox/EulerNet.
小貼士
登錄享
注冊地址： 北京市海淀區羊坊店路18號2幢3層301-191