Bayesian data assimilation to support informed decision-making in individualized chemotherapy

An essential component of therapeutic drug/biomarker monitoring (TDM) is to combine patient data with prior knowledge for model-based predictions of therapy outcomes. Current Bayesian forecasting tools typically rely only on the most probable model parameters (maximum a-posteriori (MAP) estimate). This MAP-based approach, however, does neither necessarily predict the most probable outcome nor does it quantify the risks of treatment inefficacy or toxicity. Bayesian data assimilation (DA) methods overcome these limitations by providing a comprehensive uncertainty quantification. We compare DA methods with MAP-based approaches and show how probabilistic statements about key markers related to chemotherapy-induced neutropenia can be leveraged for more informative decision support in individualized chemotherapy. Sequential Bayesian DA proved to be most computational efficient for handling interoccasion variability and integrating TDM data. For new digital monitoring devices enabling more frequent data collection, these features will be of critical importance to improve patient care decisions in various therapeutic areas

Sequential Importance Sampling for Hybrid Model Bayesian Inference to Support Bioprocess Mechanism Learning and Robust Control

Driven by the critical needs of biomanufacturing 4.0, we introduce a probabilistic knowledge graph hybrid model characterizing the risk- and science-based understanding of bioprocess mechanisms. It can faithfully capture the important properties, including nonlinear reactions, partially observed state, and nonstationary dynamics. Given very limited real process observations, we derive a posterior distribution quantifying model estimation uncertainty. To avoid the evaluation of intractable likelihoods, Approximate Bayesian Computation sampling with Sequential Monte Carlo (ABC-SMC) is utilized to approximate the posterior distribution. Under high stochastic and model uncertainties, it is computationally expensive to match output trajectories. Therefore, we create a linear Gaussian dynamic Bayesian network (LG-DBN) auxiliary likelihood-based ABC-SMC approach. Through matching the summary statistics driven through LG-DBN likelihood that can capture critical interactions and variations, the proposed algorithm can accelerate hybrid model inference, support process monitoring, and facilitate mechanism learning and robust control.Comment: 11 pages, 2 figure

How artificial intelligence and machine learning can help healthcare systems respond to COVID-19

The COVID-19 global pandemic is a threat not only to the health of millions of individuals, but also to the stability of infrastructure and economies around the world. The disease will inevitably place an overwhelming burden on healthcare systems that cannot be effectively dealt with by existing facilities or responses based on conventional approaches. We believe that a rigorous clinical and societal response can only be mounted by using intelligence derived from a variety of data sources to better utilize scarce healthcare resources, provide per- sonalized patient management plans, inform policy, and expedite clinical trials. In this paper, we introduce five of the most important challenges in responding to COVID-19 and show how each of them can be addressed by recent develop- ments in machine learning (ML) and artificial intelligence (AI). We argue that the integration of these techniques into local, national, and international healthcare systems will save lives, and propose specific methods by which implementation can happen swiftly and efficiently. We offer to extend these resources and knowledge to assist policymakers seeking to implement these techniques

Recurrent Latent Variable Networks for Session-Based Recommendation

In this work, we attempt to ameliorate the impact of data sparsity in the context of session-based recommendation. Specifically, we seek to devise a machine learning mechanism capable of extracting subtle and complex underlying temporal dynamics in the observed session data, so as to inform the recommendation algorithm. To this end, we improve upon systems that utilize deep learning techniques with recurrently connected units; we do so by adopting concepts from the field of Bayesian statistics, namely variational inference. Our proposed approach consists in treating the network recurrent units as stochastic latent variables with a prior distribution imposed over them. On this basis, we proceed to infer corresponding posteriors; these can be used for prediction and recommendation generation, in a way that accounts for the uncertainty in the available sparse training data. To allow for our approach to easily scale to large real-world datasets, we perform inference under an approximate amortized variational inference (AVI) setup, whereby the learned posteriors are parameterized via (conventional) neural networks. We perform an extensive experimental evaluation of our approach using challenging benchmark datasets, and illustrate its superiority over existing state-of-the-art techniques

Maximizing User Engagement In Short Marketing Campaigns Within An Online Living Lab: A Reinforcement Learning Perspective

ABSTRACT MAXIMIZING USER ENGAGEMENT IN SHORT MARKETING CAMPAIGNS WITHIN AN ONLINE LIVING LAB: A REINFORCEMENT LEARNING PERSPECTIVE by ANIEKAN MICHAEL INI-ABASI August 2021 Advisor: Dr. Ratna Babu Chinnam Major: Industrial & Systems Engineering Degree: Doctor of Philosophy User engagement has emerged as the engine driving online business growth. Many firms have pay incentives tied to engagement and growth metrics. These corporations are turning to recommender systems as the tool of choice in the business of maximizing engagement. LinkedIn reported a 40% higher email response with the introduction of a new recommender system. At Amazon 35% of sales originate from recommendations, while Netflix reports that ‘75% of what people watch is from some sort of recommendation,’ with an estimated business value of $1 billion per year. While the leading companies have been quite successful at harnessing the power of recommenders to boost user engagement across the digital ecosystem, small and medium businesses (SMB) are struggling with declining engagement across many channels as competition for user attention intensifies. The SMBs often lack the technical expertise and big data infrastructure necessary to operationalize recommender systems. The purpose of this study is to explore the methods of building a learning agent that can be used to personalize a persuasive request to maximize user engagement in a data-efficient setting. We frame the task as a sequential decision-making problem, modelled as MDP, and solved using a generalized reinforcement learning (RL) algorithm. We leverage an approach that eliminates or at least greatly reduces the need for massive amounts of training data, thus moving away from a purely data-driven approach. By incorporating domain knowledge from the literature on persuasion into the message composition, we are able to train the RL agent in a sample efficient and operant manner. In our methodology, the RL agent nominates a candidate from a catalog of persuasion principles to drive higher user response and engagement. To enable the effective use of RL in our specific setting, we first build a reduced state space representation by compressing the data using an exponential moving average scheme. A regularized DQN agent is deployed to learn an optimal policy, which is then applied in recommending one (or a combination) of six universal principles most likely to trigger responses from users during the next message cycle. In this study, email messaging is used as the vehicle to deliver persuasion principles to the user. At a time of declining click-through rates with marketing emails, business executives continue to show heightened interest in the email channel owing to higher-than-usual return on investment of$42 for every dollar spent when compared to other marketing channels such as social media. Coupled with the state space transformation, our novel regularized Deep Q-learning (DQN) agent was able to train and perform well based on a few observed users’ responses. First, we explored the average positive effect of using persuasion-based messages in a live email marketing campaign, without deploying a learning algorithm to recommend the influence principles. The selection of persuasion tactics was done heuristically, using only domain knowledge. Our results suggest that embedding certain principles of persuasion in campaign emails can significantly increase user engagement for an online business (and have a positive impact on revenues) without putting pressure on marketing or advertising budgets. During the study, the store had a customer retention rate of 76% and sales grew by a half-million dollars from the three field trials combined. The key assumption was that users are predisposed to respond to certain persuasion principles and learning the right principles to incorporate in the message header or body copy would lead to higher response and engagement. With the hypothesis validated, we set forth to build a DQN agent to recommend candidate actions from a catalog of persuasion principles most likely to drive higher engagement in the next messaging cycle. A simulation and a real live campaign are implemented to verify the proposed methodology. The results demonstrate the agent’s superior performance compared to a human expert and a control baseline by a significant margin (~ up to 300%). As the quest for effective methods and tools to maximize user engagement intensifies, our methodology could help to boost user engagement for struggling SMBs without prohibitive increase in costs, by enabling the targeting of messages (with the right persuasion principle) to the right user

Development and evaluation of uncertainty quantifying machine learning models to predict piperacillin plasma concentrations in critically ill patients

Background: Beta-lactam antimicrobial concentrations are frequently suboptimal in critically ill patients. Population pharmacokinetic (PopPK) modeling is the golden standard to predict drug concentrations. However, currently available PopPK models often lack predictive accuracy, making them less suited to guide dosing regimen adaptations. Furthermore, many currently developed models for clinical applications often lack uncertainty quantification. We, therefore, aimed to develop machine learning (ML) models for the prediction of piperacillin plasma concentrations while also providing uncertainty quantification with the aim of clinical practice. Methods: Blood samples for piperacillin analysis were prospectively collected from critically ill patients receiving continuous infusion of piperacillin/tazobactam. Interpretable ML models for the prediction of piperacillin concentrations were designed using CatBoost and Gaussian processes. Distribution-based Uncertainty Quantification was added to the CatBoost model using a proposed Quantile Ensemble method, useable for any model optimizing a quantile function. These models are subsequently evaluated using the distribution coverage error, a proposed interpretable uncertainty quantification calibration metric. Development and internal evaluation of the ML models were performed on the Ghent University Hospital database (752 piperacillin concentrations from 282 patients). Ensuing, ML models were compared with a published PopPK model on a database from the University Medical Centre of Groningen where a different dosing regimen is used (46 piperacillin concentrations from 15 patients.). Results: The best performing model was the Catboost model with an RMSE and R-2 of 31.94-0.64 and 33.53-0.60 for internal evaluation with and without previous concentration. Furthermore, the results prove the added value of the proposed Quantile Ensemble model in providing clinically useful individualized uncertainty predictions and show the limits of homoscedastic methods like Gaussian Processes in clinical applications. Conclusions: Our results show that ML models can consistently estimate piperacillin concentrations with acceptable and high predictive accuracy when identical dosing regimens as in the training data are used while providing highly relevant uncertainty predictions. However, generalization capabilities to other dosing schemes are limited. Notwithstanding, incorporating ML models in therapeutic drug monitoring programs seems definitely promising and the current work provides a basis for validating the model in clinical practice