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Objectives: Bayesian anomaly detection computes posterior probabilities of anomalous events by combining prior beliefs and evidence from data. However, the specification of prior probabilities can be challenging. This paper describes a Bayesian prior in the context of disease outbreak detection. The goal is to provide a meaningful, easy-to-use prior that yields a posterior probability of an outbreak that performs at least as well as a standard frequentist approach. If this goal is achieved, the resulting posterior could be usefully incorporated into a decision analysis about how to act in light of a possible disease outbreak.Methods: This paper describes a Bayesian method for anomaly detection that combines learning from data with a semi-informative prior probability over patterns of anomalous events. A univariate version of the algorithm is presented here for ease of illustration of the essential ideas. The paper describes the algorithm in the context of disease-outbreak detection, but it is general and can be used in other anomaly detection applications. For this application, the semi-informative prior specifies that an increased count over baseline is expected for the variable being monitored, such as the number of respiratory chief complaints per day at a given emergency department. The semi-informative prior is derived based on the baseline prior, which is estimated from using historical data.Results: The evaluation reported here used semi-synthetic data to evaluate the detection performance of the proposed Bayesian method and a control chart method, which is a standard frequentist algorithm that is closest to the Bayesian method in terms of the type of data it uses. The disease-outbreak detection performance of the Bayesian method was statistically significantly better than that of the control chart method when proper baseline periods were used to estimate the baseline behavior to avoid seasonal effects. When using longer baseline periods, the Bayesian method performed as well as the control chart method. The time complexity of the Bayesian algorithm is linear in the number of the observed events being monitored, due to a novel, closed-form derivation that is introduced in the paper.Conclusions: This paper introduces a novel prior probability for Bayesian outbreak detection that is expressive, easy-to-apply, computationally efficient, and performs as well or better than a standard frequentist method. [ABSTRACT FROM AUTHOR]

Despite growing support for the adoption of electronic health records (EHR) to improve U.S. healthcare delivery, EHR adoption in the United States is slow to date due to a fundamental failure of the healthcare information technology marketplace. Reasons for the slow adoption of healthcare information technology include a misalignment of incentives, limited purchasing power among providers, variability in the viability of EHR products and companies, and limited demonstrated value of EHRs in practice. At the 2004 American College of Medical Informatics (ACMI) Retreat, attendees discussed the current state of EHR adoption in this country and identified steps that could be taken to stimulate adoption. In this paper, based upon the ACMI retreat, and building upon the experiences of the authors developing EHR in academic and commercial settings we identify a set of recommendations to stimulate adoption of EHR, including financial incentives, promotion of EHR standards, enabling policy, and educational, marketing, and supporting activities for both the provider community and healthcare consumers. [ABSTRACT FROM AUTHOR]

Background:  The early identification of outbreaks of both known and novel influenza-like illnesses (ILIs) is an important public health problem., Objective:  This study aimed to describe the design and testing of a tool that detects and tracks outbreaks of both known and novel ILIs, such as the SARS-CoV-2 worldwide pandemic, accurately and early., Methods:  This paper describes the ILI Tracker algorithm that first models the daily occurrence of a set of known ILIs in hospital emergency departments in a monitored region using findings extracted from patient care reports using natural language processing. We then show how the algorithm can be extended to detect and track the presence of an unmodeled disease that may represent a novel disease outbreak., Results:  We include results based on modeling diseases like influenza, respiratory syncytial virus, human metapneumovirus, and parainfluenza for 5 emergency departments in Allegheny County, Pennsylvania, from June 1, 2014, to May 31, 2015. We also include the results of detecting the outbreak of an unmodeled disease, which in retrospect was very likely an outbreak of the enterovirus D68 (EV-D68)., Conclusions:  The results reported in this paper provide support that ILI Tracker was able to track well the incidence of 4 modeled influenza-like diseases over a 1-year period, relative to laboratory-confirmed cases, and it was computationally efficient in doing so. The system was also able to detect a likely novel outbreak of EV-D68 early in an outbreak that occurred in Allegheny County in 2014 as well as clinically characterize that outbreak disease accurately., (©John M Aronis, Ye Ye, Jessi Espino, Harry Hochheiser, Marian G Michaels, Gregory F Cooper. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 13.08.2024.)

Background: Genomic variants of the disease are often discovered nowadays through population-based genome-wide association studies (GWAS). Identifying genomic variations potentially underlying a phenotype, such as hypertension, in an individual is important for designing personalized treatment; however, population-level models, such as GWAS, may not capture all the important, individualized factors well. In addition, GWAS typically requires a large sample size to detect the association of low-frequency genomic variants with sufficient power. Here, we report an individualized Bayesian inference (IBI) algorithm for estimating the genomic variants that influence complex traits, such as hypertension, at the level of an individual (e.g., a patient). By modeling at the level of the individual, IBI seeks to find genomic variants observed in the individual's genome that provide a strong explanation of the phenotype observed in this individual., Results: We applied the IBI algorithm to the data from the Framingham Heart Study to explore the genomic influences of hypertension. Among the top-ranking variants identified by IBI and GWAS, there is a significant number of shared variants (intersection); the unique variants identified only by IBI tend to have relatively lower minor allele frequency than those identified by GWAS. In addition, IBI discovered more individualized and diverse variants that explain hypertension patients better than GWAS. Furthermore, IBI found several well-known low-frequency variants as well as genes related to blood pressure that GWAS missed in the same cohort. Finally, IBI identified top-ranked variants that predicted hypertension better than GWAS, according to the area under the ROC curve., Conclusions: The results support IBI as a promising approach for complementing GWAS, especially in detecting low-frequency genomic variants as well as learning personalized genomic variants of clinical traits and disease, such as the complex trait of hypertension, to help advance precision medicine., (© 2023. The Author(s).)

Objective: To evaluate the technical feasibility and potential value of a digital assistant that prompts intensive care unit (ICU) rounding teams to use evidence-based practices based on analysis of their real-time discussions., Methods: We evaluated a novel voice-based digital assistant which audio records and processes the ICU care team's rounding discussions to determine which evidence-based practices are applicable to the patient but have yet to be addressed by the team. The system would then prompt the team to consider indicated but not yet delivered practices, thereby reducing cognitive burden compared to traditional rigid rounding checklists. In a retrospective analysis, we applied automatic transcription, natural language processing, and a rule-based expert system to generate personalized prompts for each patient in 106 audio-recorded ICU rounding discussions. To assess technical feasibility, we compared the system's prompts to those created by experienced critical care nurses who directly observed rounds. To assess potential value, we also compared the system's prompts to a hypothetical paper checklist containing all evidence-based practices., Results: The positive predictive value, negative predictive value, true positive rate, and true negative rate of the system's prompts were 0.45 ± 0.06, 0.83 ± 0.04, 0.68 ± 0.07, and 0.66 ± 0.04, respectively. If implemented in lieu of a paper checklist, the system would generate 56% fewer prompts per patient, with 50%±17% greater precision., Conclusion: A voice-based digital assistant can reduce prompts per patient compared to traditional approaches for improving evidence uptake on ICU rounds. Additional work is needed to evaluate field performance and team acceptance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In this paper we investigate which airborne pollutants have a short-term causal effect on cardiovascular and respiratory disease using the Ancestral Probabilities (AP) procedure, a novel Bayesian approach for deriving the probabilities of causal relationships from observational data. The results are largely consistent with EPA assessments of causality, however, in a few cases AP suggests that some pollutants thought to cause cardiovascular or respiratory disease are associated due purely to confounding. The AP procedure utilizes maximal ancestral graph (MAG) models to represent and assign probabilities to causal relationships while accounting for latent confounding. The algorithm does so locally by marginalizing over models with and without causal features of interest. Before applying AP to real data, we evaluate it in a simulation study and investigate the benefits of providing background knowledge. Overall, the results suggest that AP is an effective tool for causal discovery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Nurse-led rounding checklists are a common strategy for facilitating evidence-based practice in the intensive care unit (ICU). To streamline checklist workflow, some ICUs have the nurse or another individual listen to the conversation and customize the checklist for each patient. Such customizations assume that individuals can reliably assess whether checklist items have been addressed., Objective: To evaluate whether 1 critical care nurse can reliably assess checklist items on rounds., Methods: Two nurses performed in-person observation of multidisciplinary ICU rounds. Using a standardized paper-based assessment tool, each nurse indicated whether 17 items related to the ABCDEF bundle were discussed during rounds. For each item, generalizability coefficients were used as a measure of reliability, with a single-rater value of 0.70 or greater considered sufficient to support its assessment by 1 nurse., Results: The nurse observers assessed 118 patient discussions across 15 observation days. For 11 of 17 items (65%), the generalizability coefficient for a single rater met or exceeded the 0.70 threshold. The generalizability coefficients (95% CIs) of a single rater for key items were as follows: pain, 0.86 (0.74-0.97); delirium score, 0.74 (0.64-0.83); agitation score, 0.72 (0.33-1.00); spontaneous awakening trial, 0.67 (0.49-0.83); spontaneous breathing trial, 0.80 (0.70-0.89); mobility, 0.79 (0.69-0.87); and family (future/past) engagement, 0.82 (0.73-0.90)., Conclusion: Using a paper-based assessment tool, a single trained critical care nurse can reliably assess the discussion of elements of the ABCDEF bundle during multidisciplinary rounds., (©2023 American Association of Critical-Care Nurses.)

Volatiles expelled from subducted plates promote melting of the overlying warm mantle, feeding arc volcanism. However, debates continue over the factors controlling melt generation and transport, and how these determine the placement of volcanoes. To broaden our synoptic view of these fundamental mantle wedge processes, we image seismic attenuation beneath the Lesser Antilles arc, an end-member system that slowly subducts old, tectonized lithosphere. Punctuated anomalies with high ratios of bulk-to-shear attenuation ( Q κ -1 / Q μ -1  > 0.6) and V P / V S (>1.83) lie 40 km above the slab, representing expelled fluids that are retained in a cold boundary layer, transporting fluids toward the back-arc. The strongest attenuation (1000/ Q S  ~ 20), characterizing melt in warm mantle, lies beneath the back-arc, revealing how back-arc mantle feeds arc volcanoes. Melt ponds under the upper plate and percolates toward the arc along structures from earlier back-arc spreading, demonstrating how slab dehydration, upper-plate properties, past tectonics, and resulting melt pathways collectively condition volcanism.

Cells within a tumor microenvironment (TME) dynamically communicate and influence each other's cellular states through an intercellular communication network (ICN). In cancers, intercellular communications underlie immune evasion mechanisms of individual tumors. We developed an individualized causal analysis framework for discovering tumor specific ICNs. Using head and neck squamous cell carcinoma (HNSCC) tumors as a testbed, we first mined single-cell RNA-sequencing data to discover gene expression modules (GEMs) that reflect the states of transcriptomic processes within tumor and stromal single cells. By deconvoluting bulk transcriptomes of HNSCC tumors profiled by The Cancer Genome Atlas (TCGA), we estimated the activation states of these transcriptomic processes in individual tumors. Finally, we applied individualized causal network learning to discover an ICN within each tumor. Our results show that cellular states of cells in TMEs are coordinated through ICNs that enable multi-way communications among epithelial, fibroblast, endothelial, and immune cells. Further analyses of individual ICNs revealed structural patterns that were shared across subsets of tumors, leading to the discovery of 4 different subtypes of networks that underlie disparate TMEs of HNSCC. Patients with distinct TMEs exhibited significantly different clinical outcomes. Our results show that the capability of estimating individual ICNs reveals heterogeneity of ICNs and sheds light on the importance of intercellular communication in impacting disease development and progression., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: XL is a founder and director of Deep Rx Inc., (Copyright: © 2022 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Head and neck squamous cell cancer (HNSCC) is an aggressive cancer resulting from heterogeneous causes. To reveal the underlying drivers and signaling mechanisms of different HNSCC tumors, we developed a novel Bayesian framework to identify drivers of individual tumors and infer the states of driver proteins in cellular signaling system in HNSCC tumors. First, we systematically identify causal relationships between somatic genome alterations (SGAs) and differentially expressed genes (DEGs) for each TCGA HNSCC tumor using the tumor-specific causal inference (TCI) model. Then, we generalize the most statistically significant driver SGAs and their regulated DEGs in TCGA HNSCC cohort. Finally, we develop machine learning models that combine genomic and transcriptomic data to infer the protein functional activation states of driver SGAs in tumors, which enable us to represent a tumor in the space of cellular signaling systems. We discovered four mechanism-oriented subtypes of HNSCC, which show distinguished patterns of activation state of HNSCC driver proteins, and importantly, this subtyping is orthogonal to previously reported transcriptomic-based molecular subtyping of HNSCC. Further, our analysis revealed driver proteins that are likely involved in oncogenic processes induced by HPV infection, even though they are not perturbed by genomic alterations in HPV+ tumors.

Background: Oral case presentation is a crucial skill of physicians and a key component of team-based care. However, consistent and objective assessment and feedback on presentations during training are infrequent., Objective: To determine the potential value of applying natural language processing, computer software that extracts meaning from text, to transcripts of oral case presentations as a strategy to assess their quality automatically and objectively., Methods: We transcribed a collection of simulated oral case presentations. The presentations were from eight critical care fellows and one critical care attending. They were instructed to review the medical charts of 11 real intensive care unit patient cases and to audio record themselves, presenting each case as if they were doing so on morning rounds. We then used natural language processing to convert the transcripts from human-readable text into machine-readable numbers. These numbers represent details of the presentation style and content. The distance between the numeric representation of two different transcripts negatively correlates with the similarity of those two transcripts. We ranked fellows on the basis of how similar their presentations were to the attending's presentations., Results: The 99 presentations included 260 minutes of audio (mean length: 2.6 ± 1.24 min per case). On average, 23.88 ± 2.65 sentences were spoken, and each sentence had 14.10 ± 0.67 words, 3.62 ± 0.15 medical concepts, and 0.75 ± 0.09 medical adjectives. When ranking fellows on the basis of how similar their presentations were to the attending's presentation, we found a gap between the five fellows with the most similar presentations and the three fellows with the least similar presentations (average group similarity scores of 0.62 ± 0.01 and 0.53 ± 0.01, respectively). Rankings were sensitive to whether presentation style or content information were weighted more heavily when calculating transcript similarity., Conclusion: Natural language processing enabled the ranking of case presentations on the basis of how similar they were to a reference presentation. Although additional work is needed to convert these rankings, and underlying similarity scores, into actionable feedback for trainees, these methods may support new tools for improving medical education., (Copyright © 2022 by the American Thoracic Society.)

Machine learning algorithms that derive predictive models are useful in predicting patient outcomes under uncertainty. These are often "population" algorithms which optimize a static model to predict well on average for individuals in the population; however, population models may predict poorly for individuals that differ from the average. Personalized machine learning algorithms seek to optimize predictive performance for every patient by tailoring a patient-specific model to each individual. Ensembles of decision trees often outperform single decision tree models, but ensembles of personalized models like decision paths have received little investigation. We present a novel personalized ensemble, called Lazy Random Forest (LazyRF), which consists of bagged randomized decision paths optimized for the individual for whom a prediction will be made. LazyRF outperformed single and bagged decision paths and demonstrated comparable predictive performance to a population random forest method in terms of discrimination on clinical and genomic data while also producing simpler models than the population random forest.

Eye tracking is used widely to investigate attention and cognitive processes while performing tasks in electronic medical record (EMR) systems. We explored a novel application of eye tracking to collect training data for a machine learning-based clinical decision support tool that predicts which patient data are likely to be relevant for a clinical task. Specifically, we investigated in a laboratory setting the accuracy of eye tracking compared to manual annotation for inferring which patient data in the EMR are judged to be relevant by physicians. We evaluated several methods for processing gaze points that were recorded using a low-cost eye-tracking device. Our results show that eye tracking achieves accuracy and precision of 69% and 53%, respectively compared to manual annotation and are promising for machine learning. The methods for processing gaze points and scripts that we developed offer a first step in developing novel uses for eye tracking for clinical decision support., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

With the extensive deployment of electronic medical record (EMR) systems, EMR usability remains a significant source of frustration to clinicians. There is a significant research need for software that emulates EMR systems and enables investigators to conduct laboratory-based human-computer interaction studies. We developed an open-source software package that implements the display functions of an EMR system. The user interface emphasizes the temporal display of vital signs, medication administrations, and laboratory test results. It is well suited to support research about clinician information-seeking behaviors and adaptive user interfaces in terms of measures that include task accuracy, time to completion, and cognitive load. The Simple EMR System is freely available to the research community and is on GitHub., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Background: Malaria is a major cause of death in children under five years old in low- and middle-income countries such as Malawi. Accurate diagnosis and management of malaria can help reduce the global burden of childhood morbidity and mortality. Trained healthcare workers in rural health centers manage malaria with limited supplies of malarial diagnostic tests and drugs for treatment. A clinical decision support system that integrates predictive models to provide an accurate prediction of malaria based on clinical features could aid healthcare workers in the judicious use of testing and treatment. We developed Bayesian network (BN) models to predict the probability of malaria from clinical features and an illustrative decision tree to model the decision to use or not use a malaria rapid diagnostic test (mRDT)., Methods: We developed two BN models to predict malaria from a dataset of outpatient encounters of children in Malawi. The first BN model was created manually with expert knowledge, and the second model was derived using an automated method. The performance of the BN models was compared to other statistical models on a range of performance metrics at multiple thresholds. We developed a decision tree that integrates predictions with the costs of mRDT and a course of recommended treatment., Results: The manually created BN model achieved an area under the ROC curve (AUC) equal to 0.60 which was statistically significantly higher than the other models. At the optimal threshold for classification, the manual BN model had sensitivity and specificity of 0.74 and 0.42 respectively, and the automated BN model had sensitivity and specificity of 0.45 and 0.68 respectively. The balanced accuracy values were similar across all the models. Sensitivity analysis of the decision tree showed that for values of probability of malaria below 0.04 and above 0.40, the preferred decision that minimizes expected costs is not to perform mRDT., Conclusion: In resource-constrained settings, judicious use of mRDT is important. Predictive models in combination with decision analysis can provide personalized guidance on when to use mRDT in the management of childhood malaria. BN models can be efficiently derived from data to support clinical decision making.

Predictive models can be useful in predicting patient outcomes under uncertainty. Many algorithms employ "population" methods, which optimize a single model to perform well on average over an entire population, but the model may perform poorly on some patients. Personalized methods optimize predictive performance for each patient by tailoring the model to the individual. We present a new personalized method based on decision trees: the Personalized Decision Path using a Bayesian score (PDP-Bay). Performance on eight synthetic, genomic, and clinical datasets was compared to that of decision trees and a previously described personalized decision path method in terms of area under the ROC curve (AUC) and expected calibration error (ECE). Model complexity was measured by average path length. The PDP-Bay model outperformed the decision tree in terms of both AUC and ECE. The results support the conclusion that personalization may achieve better predictive performance and produce simpler models than population approaches., (©2020 AMIA - All rights reserved.)

Objective: Patient information can be retrieved more efficiently in electronic medical record (EMR) systems by using machine learning models that predict which information a physician will seek in a clinical context. However, information-seeking behavior varies across EMR users. To explicitly account for this variability, we derived hierarchical models and compared their performance to nonhierarchical models in identifying relevant patient information in intensive care unit (ICU) cases., Materials and Methods: Critical care physicians reviewed ICU patient cases and selected data items relevant for presenting at morning rounds. Using patient EMR data as predictors, we derived hierarchical logistic regression (HLR) and standard logistic regression (LR) models to predict their relevance., Results: In 73 pairs of HLR and LR models, the HLR models achieved an area under the receiver operating characteristic curve of 0.81, 95% confidence interval (CI) [0.80-0.82], which was statistically significantly higher than that of LR models (0.75, 95% CI [0.74-0.76]). Further, the HLR models achieved statistically significantly lower expected calibration error (0.07, 95% CI [0.06-0.08]) than LR models (0.16, 95% CI [0.14-0.17])., Discussion: The physician reviewers demonstrated variability in selecting relevant data. Our results show that HLR models perform significantly better than LR models with respect to both discrimination and calibration. This is likely due to explicitly modeling physician-related variability., Conclusion: Hierarchical models can yield better performance when there is physician-related variability as in the case of identifying relevant information in the EMR., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Background: Protein phosphorylation networks play an important role in cell signaling. In these networks, phosphorylation of a protein kinase usually leads to its activation, which in turn will phosphorylate its downstream target proteins. A phosphorylation network is essentially a causal network, which can be learned by causal inference algorithms. Prior efforts have applied such algorithms to data measuring protein phosphorylation levels, assuming that the phosphorylation levels represent protein activity states. However, the phosphorylation status of a kinase does not always reflect its activity state, because interventions such as inhibitors or mutations can directly affect its activity state without changing its phosphorylation status. Thus, when cellular systems are subjected to extensive perturbations, the statistical relationships between phosphorylation states of proteins may be disrupted, making it difficult to reconstruct the true protein phosphorylation network. Here, we describe a novel framework to address this challenge., Results: We have developed a causal discovery framework that explicitly represents the activity state of each protein kinase as an unmeasured variable and developed a novel algorithm called "InferA" to infer the protein activity states, which allows us to incorporate the protein phosphorylation level, pharmacological interventions and prior knowledge. We applied our framework to simulated datasets and to a real-world dataset. The simulation experiments demonstrated that explicit representation of activity states of protein kinases allows one to effectively represent the impact of interventions and thus enabled our framework to accurately recover the ground-truth causal network. Results from the real-world dataset showed that the explicit representation of protein activity states allowed an effective and data-driven integration of the prior knowledge by InferA, which further leads to the recovery of a phosphorylation network that is more consistent with experiment results., Conclusions: Explicit representation of the protein activity states by our novel framework significantly enhances causal discovery of protein phosphorylation networks.

Background: Complex electronic medical records (EMRs) presenting large amounts of data create risks of cognitive overload. We are designing a Learning EMR (LEMR) system that utilizes models of intensive care unit (ICU) physicians' data access patterns to identify and then highlight the most relevant data for each patient., Objectives: We used insights from literature and feedback from potential users to inform the design of an EMR display capable of highlighting relevant information., Methods: We used a review of relevant literature to guide the design of preliminary paper prototypes of the LEMR user interface. We observed five ICU physicians using their current EMR systems in preparation for morning rounds. Participants were interviewed and asked to explain their interactions and challenges with the EMR systems. Findings informed the revision of our prototypes. Finally, we conducted a focus group with five ICU physicians to elicit feedback on our designs and to generate ideas for our final prototypes using participatory design methods., Results: Participating physicians expressed support for the LEMR system. Identified design requirements included the display of data essential for every patient together with diagnosis-specific data and new or significantly changed information. Respondents expressed preferences for fishbones to organize labs, mouseovers to access additional details, and unobtrusive alerts minimizing color-coding. To address the concern about possible physician overreliance on highlighting, participants suggested that non-highlighted data should remain accessible. Study findings led to revised prototypes, which will inform the development of a functional user interface., Conclusion: In the feedback we received, physicians supported pursuing the concept of a LEMR system. By introducing novel ways to support physicians' cognitive abilities, such a system has the potential to enhance physician EMR use and lead to better patient outcomes. Future plans include laboratory studies of both the utility of the proposed designs on decision-making, and the possible impact of any automation bias., Competing Interests: None declared., (Thieme. All rights reserved.)

Oceanic lithosphere carries volatiles, notably water, into the mantle through subduction at convergent plate boundaries. This subducted water exercises control on the production of magma, earthquakes, formation of continental crust and mineral resources. Identifying different potential fluid sources (sediments, crust and mantle lithosphere) and tracing fluids from their release to the surface has proved challenging 1 . Atlantic subduction zones are a valuable endmember when studying this deep water cycle because hydration in Atlantic lithosphere, produced by slow spreading, is expected to be highly non-uniform 2 . Here, as part of a multi-disciplinary project in the Lesser Antilles volcanic arc 3 , we studied boron trace element and isotopic fingerprints of melt inclusions. These reveal that serpentine-that is, hydrated mantle rather than crust or sediments-is a dominant supplier of subducted water to the central arc. This serpentine is most likely to reside in a set of major fracture zones subducted beneath the central arc over approximately the past ten million years. The current dehydration of these fracture zones coincides with the current locations of the highest rates of earthquakes and prominent low shear velocities, whereas the preceding history of dehydration is consistent with the locations of higher volcanic productivity and thicker arc crust. These combined geochemical and geophysical data indicate that the structure and hydration of the subducted plate are directly connected to the evolution of the arc and its associated seismic and volcanic hazards.

Background: Electronic medical record (EMR) systems capture large amounts of data per patient and present that data to physicians with little prioritization. Without prioritization, physicians must mentally identify and collate relevant data, an activity that can lead to cognitive overload. To mitigate cognitive overload, a Learning EMR (LEMR) system prioritizes the display of relevant medical record data. Relevant data are those that are pertinent to a context-defined as the combination of the user, clinical task, and patient case. To determine which data are relevant in a specific context, a LEMR system uses supervised machine learning models of physician information-seeking behavior. Since obtaining information-seeking behavior data via manual annotation is slow and expensive, automatic methods for capturing such data are needed., Objective: The goal of the research was to propose and evaluate eye tracking as a high-throughput method to automatically acquire physician information-seeking behavior useful for training models for a LEMR system., Methods: Critical care medicine physicians reviewed intensive care unit patient cases in an EMR interface developed for the study. Participants manually identified patient data that were relevant in the context of a clinical task: preparing a patient summary to present at morning rounds. We used eye tracking to capture each physician's gaze dwell time on each data item (eg, blood glucose measurements). Manual annotations and gaze dwell times were used to define target variables for developing supervised machine learning models of physician information-seeking behavior. We compared the performance of manual selection and gaze-derived models on an independent set of patient cases., Results: A total of 68 pairs of manual selection and gaze-derived machine learning models were developed from training data and evaluated on an independent evaluation data set. A paired Wilcoxon signed-rank test showed similar performance of manual selection and gaze-derived models on area under the receiver operating characteristic curve (P=.40)., Conclusions: We used eye tracking to automatically capture physician information-seeking behavior and used it to train models for a LEMR system. The models that were trained using eye tracking performed like models that were trained using manual annotations. These results support further development of eye tracking as a high-throughput method for training clinical decision support systems that prioritize the display of relevant medical record data., (©Andrew J King, Gregory F Cooper, Gilles Clermont, Harry Hochheiser, Milos Hauskrecht, Dean F Sittig, Shyam Visweswaran. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 02.04.2020.)

Over the past decade, outbreaks of new or reemergent viruses such as severe acute respiratory syndrome (SARS) virus, Middle East respiratory syndrome (MERS) virus, and Zika have claimed thousands of lives and cost governments and healthcare systems billions of dollars. Because the appearance of new or transformed diseases is likely to continue, the detection and characterization of emergent diseases is an important problem. We describe a Bayesian statistical model that can detect and characterize previously unknown and unmodeled diseases from patient-care reports and evaluate its performance on historical data., Competing Interests: The authors have declared that no competing interests exist.

Background: Electronic medical record (EMR) systems need functionality that decreases cognitive overload by drawing the clinician's attention to the right data, at the right time. We developed a Learning EMR (LEMR) system that learns statistical models of clinician information-seeking behavior and applies those models to direct the display of data in future patients. We evaluated the performance of the system in identifying relevant patient data in intensive care unit (ICU) patient cases., Methods: To capture information-seeking behavior, we enlisted critical care medicine physicians who reviewed a set of patient cases and selected data items relevant to the task of presenting at morning rounds. Using patient EMR data as predictors, we built machine learning models to predict their relevancy. We prospectively evaluated the predictions of a set of high performing models., Results: On an independent evaluation data set, 25 models achieved precision of 0.52, 95% CI [0.49, 0.54] and recall of 0.77, 95% CI [0.75, 0.80] in identifying relevant patient data items. For data items missed by the system, the reviewers rated the effect of not seeing those data from no impact to minor impact on patient care in about 82% of the cases., Conclusion: Data-driven approaches for adaptively displaying data in EMR systems, like the LEMR system, show promise in using information-seeking behavior of clinicians to identify and highlight relevant patient data., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The prediction and characterization of outbreaks of infectious diseases such as influenza remains an open and important problem. This paper describes a framework for detecting and characterizing outbreaks of influenza and the results of testing it on data from ten outbreaks collected from two locations over five years. We model outbreaks with compartment models and explicitly model non-influenza influenza-like illnesses., (This is an Open Access article. Authors own copyright of their articles appearing in the Journal of Public Health Informatics. Readers may copy articles without permission of the copyright owner(s), as long as the author and OJPHI are acknowledged in the copy and the copy is used for educational, not-for-profit purposes.)

In recent years, great strides have been made for causal structure learning in the high-dimensional setting and in the mixed data-type setting when there are both discrete and continuous variables. However, due to the complications involved with modeling continuous-discrete variable interactions, the intersection of these two settings has been relatively understudied. The current paper explores the problem of efficiently extending causal structure learning algorithms to high-dimensional data with mixed data-types. First, we characterize a model over continuous and discrete variables. Second, we derive a degenerate Gaussian (DG) score for mixed data-types and discuss its asymptotic properties. Lastly, we demonstrate the practicality of the DG score on learning causal structures from simulated data sets.

Cancer is mainly caused by somatic genome alterations (SGAs). Precision oncology involves identifying and targeting tumor-specific aberrations resulting from causative SGAs. We developed a novel tumor-specific computational framework that finds the likely causative SGAs in an individual tumor and estimates their impact on oncogenic processes, which suggests the disease mechanisms that are acting in that tumor. This information can be used to guide precision oncology. We report a tumor-specific causal inference (TCI) framework, which estimates causative SGAs by modeling causal relationships between SGAs and molecular phenotypes (e.g., transcriptomic, proteomic, or metabolomic changes) within an individual tumor. We applied the TCI algorithm to tumors from The Cancer Genome Atlas (TCGA) and estimated for each tumor the SGAs that causally regulate the differentially expressed genes (DEGs) in that tumor. Overall, TCI identified 634 SGAs that are predicted to cause cancer-related DEGs in a significant number of tumors, including most of the previously known drivers and many novel candidate cancer drivers. The inferred causal relationships are statistically robust and biologically sensible, and multiple lines of experimental evidence support the predicted functional impact of both the well-known and the novel candidate drivers that are predicted by TCI. TCI provides a unified framework that integrates multiple types of SGAs and molecular phenotypes to estimate which genome perturbations are causally influencing one or more molecular/cellular phenotypes in an individual tumor. By identifying major candidate drivers and revealing their functional impact in an individual tumor, TCI sheds light on the disease mechanisms of that tumor, which can serve to advance our basic knowledge of cancer biology and to support precision oncology that provides tailored treatment of individual tumors., Competing Interests: The authors have declared that no competing interests exist.

Volcanism is the surface expression of magma intrusion, crystallization, assimilation and hybridization processes operating throughout the crust over a range of time periods. Many magmas, including those erupted at subduction zones, have complex textures that reflect these processes. Here, we use textural and geochemical characteristics of calcic amphiboles to help identify multiple ingredients of subduction zone magmatism at Mt Lamington volcano, Papua New Guinea. Our approach uses existing trace element partitioning schemes to calculate the compositions of amphibole equilibrium melts (AEMs). The AEM compositions show that Mt Lamington andesites and plutonic enclaves are dominated by fractionation of amphibole + plagioclase + biotite, with assimilation of plagioclase and zircon. Magnesiohastingsite crystals in the andesite and diktytaxitic mafic enclaves reflect multiple episodes of recharge by more primitive, geochemically variable melts. The andesite also contains clots with rounded grains and melt on grain boundaries. These features indicate slow crystallization, and the retention of melt films could significantly enhance the potential for remobilization of crystals by infiltrating melts or during magma mixing. Variations in crystallization conditions could thus significantly affect the mush microstructure. We suggest that this could result in a significant bias of the volcanic record towards the preferential incorporation of more slowly cooled plutonic material from the lower crust or from more thermally mature plumbing systems. This article is part of the Theo Murphy meeting issue 'Magma reservoir architecture and dynamics'.

Quantifying the storage conditions and evolution of different magmatic components within sub-volcanic plumbing systems is key to our understanding of igneous processes and products. Whereas erupted magmas represent a portion of the eruptible volcanic system, plutonic xenoliths provide a complementary record of the mushy roots of the plumbing system that cannot be mobilised easily to form lavas and consequently offer a unique record of magma diversity within the sub-volcanic plumbing system. Here, we present a detailed petrological and geochemical study of erupted plutonic xenoliths from the island of Sint Eustatius (Statia), in the northern Lesser Antilles volcanic arc. The plutonic xenoliths are predominantly gabbroic, but vary in texture, mineral assemblage and crystallisation sequence. We report major, trace and volatile (H 2 O and CO 2 ) concentrations of xenolith-hosted melt inclusions (MIs) and interstitial glass. The MIs have a very large range in major element (49-78 wt% SiO 2 and 0.1-6.1 wt% MgO) and trace element concentration (72-377 ppm Sr, 32-686 ppm Ba, 39-211 ppm Zr). Their chemistry varies systematically with host phase and sample type. Significantly, it shows that (1) plutonic xenoliths record a complete differentiation sequence from basalt to rhyolite (2) apatite, but not zircon, saturation was reached during crystallisation, (3) amphibole breakdown reactions play a role in the genesis of shallow gabbronorite assemblages, and (4) mixing between crystal cargos and multiple discrete bodies occurred. Residual melt volatile contents are high (≤ 9.1 wt% H 2 O and ≤ 1350 ppm CO 2 ), returning volatile saturation pressures of 0-426 MPa. Multiple reaction geobarometry and experimental comparisons indicate that equilibration took place in the upper-middle crust (0-15 km). We infer that the Statia plutonic xenoliths represent portions of a large heterogeneous crystal mush within which a great diversity of melts was stored and mixed prior to eruption. Our data show that compositional variations in magmatic plumbing systems exceed those observed in volcanic products, a likely consequence of the blending that occurs prior to and during eruption.

Poor electronic medical record (EMR) usability is detrimental to both clinicians and patients. A better EMR would provide concise, context sensitive patient data, but doing so entails the difficult task of knowing which data are relevant. To determine the relevance of patient data in different contexts, we collect and model the information seeking behavior of clinicians using a learning EMR (LEMR) system. Sufficient data were collected to train predictive models for 80 different targets (e.g., glucose level, heparin administration) and 27 of them had AUROC values of greater than 0.7. These results are encouraging considering the high variation in information seeking behavior (intraclass correlation 0.40). We plan to apply these models to a new set of patient cases and adapt the LEMR interface to highlight relevant patient data, and thus provide concise, context sensitive data.

Objectives: To assess the performance of a Bayesian case detector (BCD) for influenza surveillance and clinical diagnosis., Methods: BCD uses a Bayesian network classifier to compute the posterior probability of a patient having influenza based on 31 findings from narrative clinical notes. To assess the potential for disease surveillance, we calculated area under the receiver operating characteristic curve (AUC) to indicate BCD's ability to differentiate between influenza and non-influenza encounters in emergency department settings. To assess the potential for clinical diagnosis, we measured AUC for diagnosing influenza cases among encounters having influenza-like illnesses. We also evaluated the performance of BCD using dynamically estimated influenza prevalence, and measured sensitivity, specificity and positive predictive value., Results: For influenza surveillance, BCD differentiated between influenza and non-influenza encounters well with an AUC of 0.90 and 0.97 with dynamic influenza prevalence (P < 0.0001). For clinical diagnosis, the addition of dynamic influenza prevalence to BCD significantly improved AUC from 0.63 to 0.85 to distinguish influenza from other causes of influenza-like illness., Conclusions and Policy Implications: BCD can serve as an influenza surveillance and a differential diagnosis tool via our dynamic prevalence approach. It enhances the communication between public health and clinical practice.

Bayesian network (BN) structure learning algorithms are almost always designed to recover the structure that models the relationships that are shared by the instances in a population . While accurately learning such population-wide Bayesian networks is useful, learning Bayesian networks that are specific to each instance is often important as well. For example, to understand and treat a patient (instance), it is critical to understand the specific causal mechanisms that are operating in that particular patient. We introduce an instance-specific BN structure learning method that searches the space of Bayesian networks to build a model that is specific to an instance by guiding the search based on attributes of the given instance (e.g., patient symptoms, signs, lab results, and genotype). The structure discovery performance of the proposed method is compared to an existing state-of-the-art BN structure learning method, namely an implementation of the Greedy Equivalence Search algorithm called FGES, using both simulated and real data. The results show that the proposed method improves the precision of the model structure that is output, when compared to GES, especially for those variables that exhibit context-specific independence.

In this paper we outline two novel scoring methods for learning Bayesian networks in the presence of both continuous and discrete variables, that is, mixed variables. While much work has been done in the domain of automated Bayesian network learning, few studies have investigated this task in the presence of both continuous and discrete variables while focusing on scalability. Our goal is to provide two novel and scalable scoring functions capable of handling mixed variables. The first method, the Conditional Gaussian (CG) score, provides a highly efficient option. The second method, the Mixed Variable Polynomial (MVP) score, allows for a wider range of modeled relationships, including non-linearity, but it is slower than CG. Both methods calculate log likelihood and degrees of freedom terms, which are incorporated into a Bayesian Information Criterion (BIC) score. Additionally, we introduce a structure prior for efficient learning of large networks and a simplification in scoring the discrete case which performs well empirically. While the core of this work focuses on applications in the search and score paradigm, we also show how the introduced scoring functions may be readily adapted as conditional independence tests for constraint-based Bayesian network learning algorithms. Lastly, we describe ways to simulate networks of mixed variable types and evaluate our proposed methods on such simulations., Competing Interests: This work has been completed without any conflicts of interest.

Precision oncology involves identifying drugs that will effectively treat a tumor and then prescribing an optimal clinical treatment regimen. However, most first-line chemotherapy drugs do not have biomarkers to guide their application. For molecularly targeted drugs, using the genomic status of a drug target as a therapeutic indicator has limitations. In this study, machine learning methods (e.g., deep learning) were used to identify informative features from genome-scale omics data and to train classifiers for predicting the effectiveness of drugs in cancer cell lines. The methodology introduced here can accurately predict the efficacy of drugs, regardless of whether they are molecularly targeted or nonspecific chemotherapy drugs. This approach, on a per-drug basis, can identify sensitive cancer cells with an average sensitivity of 0.82 and specificity of 0.82; on a per-cell line basis, it can identify effective drugs with an average sensitivity of 0.80 and specificity of 0.82. This report describes a data-driven precision medicine approach that is not only generalizable but also optimizes therapeutic efficacy. The framework detailed herein, when successfully translated to clinical environments, could significantly broaden the scope of precision oncology beyond targeted therapies, benefiting an expanded proportion of cancer patients. Mol Cancer Res; 16(2); 269-78. ©2017 AACR ., (©2017 American Association for Cancer Research.)

In this paper we present a new non-parametric calibration method called ensemble of near isotonic regression (ENIR). The method can be considered as an extension of BBQ (Pakdaman Naeini, Cooper and Hauskrecht, 2015b), a recently proposed calibration method, as well as the commonly used calibration method based on isotonic regression (IsoRegC) (Zadrozny and Elkan, 2002). ENIR is designed to address the key limitation of IsoRegC which is the monotonicity assumption of the predictions. Similar to BBQ, the method post-processes the output of a binary classifier to obtain calibrated probabilities. Thus it can be used with many existing classification models to generate accurate probabilistic predictions. We demonstrate the performance of ENIR on synthetic and real datasets for commonly applied binary classification models. Experimental results show that the method outperforms several common binary classifier calibration methods. In particular, on the real data we evaluated, ENIR commonly performs statistically significantly better than the other methods, and never worse. It is able to improve the calibration power of classifiers, while retaining their discrimination power. The method is also computationally tractable for large scale datasets, as it is O ( N log N ) time, where N is the number of samples.

Outbreaks of infectious diseases such as influenza are a significant threat to human health. Because there are different strains of influenza which can cause independent outbreaks, and influenza can affect demographic groups at different rates and times, there is a need to recognize and characterize multiple outbreaks of influenza. This paper describes a Bayesian system that uses data from emergency department patient care reports to create epidemiological models of overlapping outbreaks of influenza. Clinical findings are extracted from patient care reports using natural language processing. These findings are analyzed by a case detection system to create disease likelihoods that are passed to a multiple outbreak detection system. We evaluated the system using real and simulated outbreaks. The results show that this approach can recognize and characterize overlapping outbreaks of influenza. We describe several extensions that appear promising., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Eye-tracking is a valuable research tool that is used in laboratory and limited field environments. We take steps toward developing methods that enable widespread adoption of eye-tracking and its real-time application in clinical decision support. Eye-tracking will enhance awareness and enable intelligent views, more precise alerts, and other forms of decision support in the Electronic Medical Record (EMR). We evaluated a low-cost eye-tracking device and found the device's accuracy to be non-inferior to a more expensive device. We also developed and evaluated an automatic method for mapping eye-tracking data to interface elements in the EMR (e.g., a displayed laboratory test value). Mapping was 88% accurate across the six participants in our experiment. Finally, we piloted the use of the low-cost device and the automatic mapping method to label training data for a Learning EMR (LEMR) which is a system that highlights the EMR elements a physician is predicted to use.

Objectives: This study evaluates the accuracy and portability of a natural language processing (NLP) tool for extracting clinical findings of influenza from clinical notes across two large healthcare systems. Effectiveness is evaluated on how well NLP supports downstream influenza case-detection for disease surveillance., Methods: We independently developed two NLP parsers, one at Intermountain Healthcare (IH) in Utah and the other at University of Pittsburgh Medical Center (UPMC) using local clinical notes from emergency department (ED) encounters of influenza. We measured NLP parser performance for the presence and absence of 70 clinical findings indicative of influenza. We then developed Bayesian network models from NLP processed reports and tested their ability to discriminate among cases of (1) influenza, (2) non-influenza influenza-like illness (NI-ILI), and (3) 'other' diagnosis., Results: On Intermountain Healthcare reports, recall and precision of the IH NLP parser were 0.71 and 0.75, respectively, and UPMC NLP parser, 0.67 and 0.79. On University of Pittsburgh Medical Center reports, recall and precision of the UPMC NLP parser were 0.73 and 0.80, respectively, and IH NLP parser, 0.53 and 0.80. Bayesian case-detection performance measured by AUROC for influenza versus non-influenza on Intermountain Healthcare cases was 0.93 (using IH NLP parser) and 0.93 (using UPMC NLP parser). Case-detection on University of Pittsburgh Medical Center cases was 0.95 (using UPMC NLP parser) and 0.83 (using IH NLP parser). For influenza versus NI-ILI on Intermountain Healthcare cases performance was 0.70 (using IH NLP parser) and 0.76 (using UPMC NLP parser). On University of Pisstburgh Medical Center cases, 0.76 (using UPMC NLP parser) and 0.65 (using IH NLP parser)., Conclusion: In all but one instance (influenza versus NI-ILI using IH cases), local parsers were more effective at supporting case-detection although performances of non-local parsers were reasonable.

Objectives: This study evaluates the accuracy and transferability of Bayesian case detection systems (BCD) that use clinical notes from emergency department (ED) to detect influenza cases., Methods: A BCD uses natural language processing (NLP) to infer the presence or absence of clinical findings from ED notes, which are fed into a Bayesain network classifier (BN) to infer patients' diagnoses. We developed BCDs at the University of Pittsburgh Medical Center (BCDUPMC) and Intermountain Healthcare in Utah (BCDIH). At each site, we manually built a rule-based NLP and trained a Bayesain network classifier from over 40,000 ED encounters between Jan. 2008 and May. 2010 using feature selection, machine learning, and expert debiasing approach. Transferability of a BCD in this study may be impacted by seven factors: development (source) institution, development parser, application (target) institution, application parser, NLP transfer, BN transfer, and classification task. We employed an ANOVA analysis to study their impacts on BCD performance., Results: Both BCDs discriminated well between influenza and non-influenza on local test cases (AUCs > 0.92). When tested for transferability using the other institution's cases, BCDUPMC discriminations declined minimally (AUC decreased from 0.95 to 0.94, p<0.01), and BCDIH discriminations declined more (from 0.93 to 0.87, p<0.0001). We attributed the BCDIH decline to the lower recall of the IH parser on UPMC notes. The ANOVA analysis showed five significant factors: development parser, application institution, application parser, BN transfer, and classification task., Conclusion: We demonstrated high influenza case detection performance in two large healthcare systems in two geographically separated regions, providing evidentiary support for the use of automated case detection from routinely collected electronic clinical notes in national influenza surveillance. The transferability could be improved by training Bayesian network classifier locally and increasing the accuracy of the NLP parser.

Defining processes that are synthetic lethal with p53 mutations in cancer cells may reveal possible therapeutic strategies. In this study, we report the development of a signal-oriented computational framework for cancer pathway discovery in this context. We applied our bipartite graph-based functional module discovery algorithm to identify transcriptomic modules abnormally expressed in multiple tumors, such that the genes in a module were likely regulated by a common, perturbed signal. For each transcriptomic module, we applied our weighted k-path merge algorithm to search for a set of somatic genome alterations (SGA) that likely perturbed the signal, that is, the candidate members of the pathway that regulate the transcriptomic module. Computational evaluations indicated that our methods-identified pathways were perturbed by SGA. In particular, our analyses revealed that SGA affecting TP53, PTK2, YWHAZ, and MED1 perturbed a set of signals that promote cell proliferation, anchor-free colony formation, and epithelial-mesenchymal transition (EMT). These proteins formed a signaling complex that mediates these oncogenic processes in a coordinated fashion. Disruption of this signaling complex by knocking down PTK2, YWHAZ, or MED1 attenuated and reversed oncogenic phenotypes caused by mutant p53 in a synthetic lethal manner. This signal-oriented framework for searching pathways and therapeutic targets is applicable to all cancer types, thus potentially impacting precision medicine in cancer. Cancer Res; 76(23); 6785-94. ©2016 AACR., Competing Interests: The authors declare no conflict of interest pertaining to this manuscript., (©2016 American Association for Cancer Research.)

Learning accurate probabilistic models from data is crucial in many practical tasks in data mining. In this paper we present a new non-parametric calibration method called ensemble of near isotonic regression (ENIR). The method can be considered as an extension of BBQ [20], a recently proposed calibration method, as well as the commonly used calibration method based on isotonic regression (IsoRegC) [27]. ENIR is designed to address the key limitation of IsoRegC which is the monotonicity assumption of the predictions. Similar to BBQ, the method post-processes the output of a binary classifier to obtain calibrated probabilities. Thus it can be used with many existing classification models to generate accurate probabilistic predictions. We demonstrate the performance of ENIR on synthetic and real datasets for commonly applied binary classification models. Experimental results show that the method outperforms several common binary classifier calibration methods. In particular on the real data, ENIR commonly performs statistically significantly better than the other methods, and never worse. It is able to improve the calibration power of classifiers, while retaining their discrimination power. The method is also computationally tractable for large scale datasets, as it is O ( N log N ) time, where N is the number of samples.

Medical errors remain a significant problem in healthcare. This paper investigates a data-driven outlier-based monitoring and alerting framework that uses data in the Electronic Medical Records (EMRs) repositories of past patient cases to identify any unusual clinical actions in the EMR of a current patient. Our conjecture is that these unusual clinical actions correspond to medical errors often enough to justify their detection and alerting. Our approach works by using EMR repositories to learn statistical models that relate patient states to patient-management actions. We evaluated this approach on the EMR data for 24,658 intensive care unit (ICU) patient cases. A total of 16,500 cases were used to train statistical models for ordering medications and laboratory tests given the patient state summarizing the patient's clinical history. The models were applied to a separate test set of 8158 ICU patient cases and used to generate alerts. A subset of 240 alerts generated by the models were evaluated and assessed by eighteen ICU clinicians. The overall true positive rates for the alerts (TPARs) ranged from 0.44 to 0.71. The TPAR for medication order alerts specifically ranged from 0.31 to 0.61 and for laboratory order alerts from 0.44 to 0.75. These results support outlier-based alerting as a promising new approach to data-driven clinical alerting that is generated automatically based on past EMR data., (Copyright © 2016 Elsevier Inc. All rights reserved.)