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Identification of optimal dose combinations in early phase dose-finding trials is challenging, due to the trade-off between precisely estimating the many parameters required to flexibly model the possibly non-monotonic dose-response surface, and the small sample sizes in early phase trials. This difficulty is even more pertinent in the context of personalized dose-finding, where patient characteristics are used to identify tailored optimal dose combinations. To overcome these challenges, we propose the use of Bayesian optimization for finding optimal dose combinations in standard ("one size fits all") and personalized multi-agent dose-finding trials. Bayesian optimization is a method for estimating the global optima of expensive-to-evaluate objective functions. The objective function is approximated by a surrogate model, commonly a Gaussian process, paired with a sequential design strategy to select the next point via an acquisition function. This work is motivated by an industry-sponsored problem, where focus is on optimizing a dual-agent therapy in a setting featuring minimal toxicity. To compare the performance of the standard and personalized methods under this setting, simulation studies are performed for a variety of scenarios. Our study concludes that taking a personalized approach is highly beneficial in the presence of heterogeneity.

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Two algorithms for computing the rational univariate representation of zero-dimensional ideals with parameters are presented in the paper. Different from the rational univariate representation of zero-dimensional ideals without parameters, the number of zeros of zero-dimensional ideals with parameters under various specializations is different, which leads to choosing and checking the separating element, the key to computing the rational univariate representation, is difficult. In order to pick out the separating element, by partitioning the parameter space we can ensure that under each branch the ideal has the same number of zeros. Subsequently with the help of the extended subresultant theorem for parametric cases, two ideas are given to conduct the further partition of parameter space for choosing and checking the separating element. Based on these, we give two algorithms for computing rational univariate representations of zero-dimensional ideals with parameters. Furthermore, the two algorithms have been implemented on the computer algebra system Singular. Experimental data show that the second algorithm has the better performance in contrast to the first one.

Long-tailed data is prevalent in real-world classification tasks and heavily relies on supervised information, which makes the annotation process exceptionally labor-intensive and time-consuming. Unfortunately, despite being a common approach to mitigate labeling costs, existing weakly supervised learning methods struggle to adequately preserve supervised information for tail samples, resulting in a decline in accuracy for the tail classes. To alleviate this problem, we introduce a novel weakly supervised labeling setting called Reduced Label. The proposed labeling setting not only avoids the decline of supervised information for the tail samples, but also decreases the labeling costs associated with long-tailed data. Additionally, we propose an straightforward and highly efficient unbiased framework with strong theoretical guarantees to learn from these Reduced Labels. Extensive experiments conducted on benchmark datasets including ImageNet validate the effectiveness of our approach, surpassing the performance of state-of-the-art weakly supervised methods.

We initiate the study of nonsmooth optimization problems under bounded local subgradient variation, which postulates bounded difference between (sub)gradients in small local regions around points, in either average or maximum sense. The resulting class of objective functions encapsulates the classes of objective functions traditionally studied in optimization, which are defined based on either Lipschitz continuity of the objective or H\"{o}lder/Lipschitz continuity of its gradient. Further, the defined class contains functions that are neither Lipschitz continuous nor have a H\"{o}lder continuous gradient. When restricted to the traditional classes of optimization problems, the parameters defining the studied classes lead to more fine-grained complexity bounds, recovering traditional oracle complexity bounds in the worst case but generally leading to lower oracle complexity for functions that are not ``worst case.'' Some highlights of our results are that: (i) it is possible to obtain complexity results for both convex and nonconvex problems with the (local or global) Lipschitz constant being replaced by a constant of local subgradient variation and (ii) mean width of the subdifferential set around the optima plays a role in the complexity of nonsmooth optimization, particularly in parallel settings. A consequence of (ii) is that for any error parameter $\epsilon > 0$, parallel oracle complexity of nonsmooth Lipschitz convex optimization is lower than its sequential oracle complexity by a factor $\tilde{\Omega}\big(\frac{1}{\epsilon}\big)$ whenever the objective function is piecewise linear with polynomially many pieces in the input size. This is particularly surprising as existing parallel complexity lower bounds are based on such classes of functions. The seeming contradiction is resolved by considering the region in which the algorithm is allowed to query the objective.

Integrating multiple observational studies to make unconfounded causal or descriptive comparisons of group potential outcomes in a large natural population is challenging. Moreover, retrospective cohorts, being convenience samples, are usually unrepresentative of the natural population of interest and have groups with unbalanced covariates. We propose a general covariate-balancing framework based on pseudo-populations that extends established weighting methods to the meta-analysis of multiple retrospective cohorts with multiple groups. Additionally, by maximizing the effective sample sizes of the cohorts, we propose a FLEXible, Optimized, and Realistic (FLEXOR) weighting method appropriate for integrative analyses. We develop new weighted estimators for unconfounded inferences on wide-ranging population-level features and estimands relevant to group comparisons of quantitative, categorical, or multivariate outcomes. The asymptotic properties of these estimators are examined. Through simulation studies and meta-analyses of TCGA datasets, we demonstrate the versatility and reliability of the proposed weighting strategy, especially for the FLEXOR pseudo-population.

Untargeted metabolomics based on liquid chromatography-mass spectrometry technology is quickly gaining widespread application given its ability to depict the global metabolic pattern in biological samples. However, the data is noisy and plagued by the lack of clear identity of data features measured from samples. Multiple potential matchings exist between data features and known metabolites, while the truth can only be one-to-one matches. Some existing methods attempt to reduce the matching uncertainty, but are far from being able to remove the uncertainty for most features. The existence of the uncertainty causes major difficulty in downstream functional analysis. To address these issues, we develop a novel approach for Bayesian Analysis of Untargeted Metabolomics data (BAUM) to integrate previously separate tasks into a single framework, including matching uncertainty inference, metabolite selection, and functional analysis. By incorporating the knowledge graph between variables and using relatively simple assumptions, BAUM can analyze datasets with small sample sizes. By allowing different confidence levels of feature-metabolite matching, the method is applicable to datasets in which feature identities are partially known. Simulation studies demonstrate that, compared with other existing methods, BAUM achieves better accuracy in selecting important metabolites that tend to be functionally consistent and assigning confidence scores to feature-metabolite matches. We analyze a COVID-19 metabolomics dataset and a mouse brain metabolomics dataset using BAUM. Even with a very small sample size of 16 mice per group, BAUM is robust and stable. It finds pathways that conform to existing knowledge, as well as novel pathways that are biologically plausible.

Data-driven optimization models have the potential to significantly improve hospital capacity management, particularly during demand surges, when effective allocation of capacity is most critical and challenging. However, integrating models into existing processes in a way that provides value requires recognizing that hospital administrators are ultimately responsible for making capacity management decisions, and carefully building trustworthy and accessible tools for them. In this study, we develop an interactive, user-friendly, electronic dashboard for informing hospital capacity management decisions during surge periods. The dashboard integrates real-time hospital data, predictive analytics, and optimization models. It allows hospital administrators to interactively customize parameters, enabling them to explore a range of scenarios, and provides real-time updates on recommended optimal decisions. The dashboard was created through a participatory design process, involving hospital administrators in the development team to ensure practical utility, trustworthiness, transparency, explainability, and usability. We successfully deployed our dashboard within the Johns Hopkins Health System during the height of the COVID-19 pandemic, addressing the increased need for tools to inform hospital capacity management. It was used on a daily basis, with results regularly communicated to hospital leadership. This study demonstrates the practical application of a prospective, data-driven, interactive decision-support tool for hospital system capacity management.

We explore a spectral initialization method that plays a central role in contemporary research on signal estimation in nonconvex scenarios. In a noiseless phase retrieval framework, we precisely analyze the method's performance in the high-dimensional limit when sensing vectors follow a multivariate Gaussian distribution for two rotationally invariant models of the covariance matrix C. In the first model C is a projector on a lower dimensional space while in the second it is a Wishart matrix. Our analytical results extend the well-established case when C is the identity matrix. Our examination shows that the introduction of biased spatial directions leads to a substantial improvement in the spectral method's effectiveness, particularly when the number of measurements is less than the signal's dimension. This extension also consistently reveals a phase transition phenomenon dependent on the ratio between sample size and signal dimension. Surprisingly, both of these models share the same threshold value.

Previous stance detection studies typically concentrate on evaluating stances within individual instances, thereby exhibiting limitations in effectively modeling multi-party discussions concerning the same specific topic, as naturally transpire in authentic social media interactions. This constraint arises primarily due to the scarcity of datasets that authentically replicate real social media contexts, hindering the research progress of conversational stance detection. In this paper, we introduce a new multi-turn conversation stance detection dataset (called \textbf{MT-CSD}), which encompasses multiple targets for conversational stance detection. To derive stances from this challenging dataset, we propose a global-local attention network (\textbf{GLAN}) to address both long and short-range dependencies inherent in conversational data. Notably, even state-of-the-art stance detection methods, exemplified by GLAN, exhibit an accuracy of only 50.47\%, highlighting the persistent challenges in conversational stance detection. Furthermore, our MT-CSD dataset serves as a valuable resource to catalyze advancements in cross-domain stance detection, where a classifier is adapted from a different yet related target. We believe that MT-CSD will contribute to advancing real-world applications of stance detection research. Our source code, data, and models are available at \url{//github.com/nfq729/MT-CSD}.

Incompleteness is a common problem for existing knowledge graphs (KGs), and the completion of KG which aims to predict links between entities is challenging. Most existing KG completion methods only consider the direct relation between nodes and ignore the relation paths which contain useful information for link prediction. Recently, a few methods take relation paths into consideration but pay less attention to the order of relations in paths which is important for reasoning. In addition, these path-based models always ignore nonlinear contributions of path features for link prediction. To solve these problems, we propose a novel KG completion method named OPTransE. Instead of embedding both entities of a relation into the same latent space as in previous methods, we project the head entity and the tail entity of each relation into different spaces to guarantee the order of relations in the path. Meanwhile, we adopt a pooling strategy to extract nonlinear and complex features of different paths to further improve the performance of link prediction. Experimental results on two benchmark datasets show that the proposed model OPTransE performs better than state-of-the-art methods.

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.

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