Population Physiology: Leveraging Electronic Health Record Data to Understand Human Endocrine Dynamics

Studying physiology and pathophysiology over a broad population for long periods of time is difficult primarily because collecting human physiologic data can be intrusive, dangerous, and expensive. One solution is to use data that have been collected for a different purpose. Electronic health record (EHR) data promise to support the development and testing of mechanistic physiologic models on diverse populations and allow correlation with clinical outcomes, but limitations in the data have thus far thwarted such use. For example, using uncontrolled population-scale EHR data to verify the outcome of time dependent behavior of mechanistic, constructive models can be difficult because: (i) aggregation of the population can obscure or generate a signal, (ii) there is often no control population with a well understood health state, and (iii) diversity in how the population is measured can make the data difficult to fit into conventional analysis techniques. This paper shows that it is possible to use EHR data to test a physiological model for a population and over long time scales. Specifically, a methodology is developed and demonstrated for testing a mechanistic, time-dependent, physiological model of serum glucose dynamics with uncontrolled, population-scale, physiological patient data extracted from an EHR repository. It is shown that there is no observable daily variation the normalized mean glucose for any EHR subpopulations. In contrast, a derived value, daily variation in nonlinear correlation quantified by the time-delayed mutual information (TDMI), did reveal the intuitively expected diurnal variation in glucose levels amongst a random population of humans. Moreover, in a population of continuously (tube) fed patients, there was no observable TDMI-based diurnal signal. These TDMI-based signals, via a glucose insulin model, were then connected with human feeding patterns. In particular, a constructive physiological model was shown to correctly predict the difference between the general uncontrolled population and a subpopulation whose feeding was controlled

Predictability Bounds of Electronic Health Records

The ability to intervene in disease progression given a person’s disease history has the potential to solve one of society’s most pressing issues: advancing health care delivery and reducing its cost. Controlling disease progression is inherently associated with the ability to predict possible future diseases given a patient’s medical history. We invoke an information-theoretic methodology to quantify the level of predictability inherent in disease histories of a large electronic health records dataset with over half a million patients. In our analysis, we progress from zeroth order through temporal informed statistics, both from an individual patient’s standpoint and also considering the collective effects. Our findings confirm our intuition that knowledge of common disease progressions results in higher predictability bounds than treating disease histories independently. We complement this result by showing the point at which the temporal dependence structure vanishes with increasing orders of the time-correlated statistic. Surprisingly, we also show that shuffling individual disease histories only marginally degrades the predictability bounds. This apparent contradiction with respect to the importance of time-ordered information is indicative of the complexities involved in capturing the health-care process and the difficulties associated with utilising this information in universal prediction algorithms.General Electric CompanyAT&T FoundationNational Science Foundation (U.S.)American Society for Engineering Education. National Defense Science and Engineering Graduate FellowshipAudi Volkswage

Identifying and mitigating biases in EHR laboratory tests

AbstractElectronic health record (EHR) data show promise for deriving new ways of modeling human disease states. Although EHR researchers often use numerical values of laboratory tests as features in disease models, a great deal of information is contained in the context within which a laboratory test is taken. For example, the same numerical value of a creatinine test has different interpretation for a chronic kidney disease patient and a patient with acute kidney injury. We study whether EHR research studies are subject to biased results and interpretations if laboratory measurements taken in different contexts are not explicitly separated. We show that the context of a laboratory test measurement can often be captured by the way the test is measured through time.We perform three tasks to study the properties of these temporal measurement patterns. In the first task, we confirm that laboratory test measurement patterns provide additional information to the stand-alone numerical value. The second task identifies three measurement pattern motifs across a set of 70 laboratory tests performed for over 14,000 patients. Of these, one motif exhibits properties that can lead to biased research results. In the third task, we demonstrate the potential for biased results on a specific example. We conduct an association study of lipase test values to acute pancreatitis. We observe a diluted signal when using only a lipase value threshold, whereas the full association is recovered when properly accounting for lipase measurements in different contexts (leveraging the lipase measurement patterns to separate the contexts).Aggregating EHR data without separating distinct laboratory test measurement patterns can intermix patients with different diseases, leading to the confounding of signals in large-scale EHR analyses. This paper presents a methodology for leveraging measurement frequency to identify and reduce laboratory test biases

Activity understanding and unusual event detection in surveillance videos

PhDComputer scientists have made ceaseless efforts to replicate cognitive video understanding abilities of human brains onto autonomous vision systems. As video surveillance cameras become ubiquitous, there is a surge in studies on automated activity understanding and unusual event detection in surveillance videos. Nevertheless, video content analysis in public scenes remained a formidable challenge due to intrinsic difficulties such as severe inter-object occlusion in crowded scene and poor quality of recorded surveillance footage. Moreover, it is nontrivial to achieve robust detection of unusual events, which are rare, ambiguous, and easily confused with noise. This thesis proposes solutions for resolving ambiguous visual observations and overcoming unreliability of conventional activity analysis methods by exploiting multi-camera visual context and human feedback. The thesis first demonstrates the importance of learning visual context for establishing reliable reasoning on observed activity in a camera network. In the proposed approach, a new Cross Canonical Correlation Analysis (xCCA) is formulated to discover and quantify time delayed pairwise correlations of regional activities observed within and across multiple camera views. This thesis shows that learning time delayed pairwise activity correlations offers valuable contextual information for (1) spatial and temporal topology inference of a camera network, (2) robust person re-identification, and (3) accurate activity-based video temporal segmentation. Crucially, in contrast to conventional methods, the proposed approach does not rely on either intra-camera or inter-camera object tracking; it can thus be applied to low-quality surveillance videos featuring severe inter-object occlusions. Second, to detect global unusual event across multiple disjoint cameras, this thesis extends visual context learning from pairwise relationship to global time delayed dependency between regional activities. Specifically, a Time Delayed Probabilistic Graphical Model (TD-PGM) is proposed to model the multi-camera activities and their dependencies. Subtle global unusual events are detected and localised using the model as context-incoherent patterns across multiple camera views. In the model, different nodes represent activities in different decomposed re3 gions from different camera views, and the directed links between nodes encoding time delayed dependencies between activities observed within and across camera views. In order to learn optimised time delayed dependencies in a TD-PGM, a novel two-stage structure learning approach is formulated by combining both constraint-based and scored-searching based structure learning methods. Third, to cope with visual context changes over time, this two-stage structure learning approach is extended to permit tractable incremental update of both TD-PGM parameters and its structure. As opposed to most existing studies that assume static model once learned, the proposed incremental learning allows a model to adapt itself to reflect the changes in the current visual context, such as subtle behaviour drift over time or removal/addition of cameras. Importantly, the incremental structure learning is achieved without either exhaustive search in a large graph structure space or storing all past observations in memory, making the proposed solution memory and time efficient. Forth, an active learning approach is presented to incorporate human feedback for on-line unusual event detection. Contrary to most existing unsupervised methods that perform passive mining for unusual events, the proposed approach automatically requests supervision for critical points to resolve ambiguities of interest, leading to more robust detection of subtle unusual events. The active learning strategy is formulated as a stream-based solution, i.e. it makes decision on-the-fly on whether to request label for each unlabelled sample observed in sequence. It selects adaptively two active learning criteria, namely likelihood criterion and uncertainty criterion to achieve (1) discovery of unknown event classes and (2) refinement of classification boundary. The effectiveness of the proposed approaches is validated using videos captured from busy public scenes such as underground stations and traffic intersections

Context, spacetime loops, and the interpretation of quantum mechanics

Three postulates are discussed: first that well-defined properties cannot be assigned to an isolated system, secondly that quantum unitary evolution is atemporal, and thirdly that some physical processes are never reversed. It is argued that these give useful insight into quantum behaviour. The first postulate emphasizes the fundamental role in physics of interactions and correlations, as opposed to internal properties of systems. Statements about physical interactions can only be framed in a context of further interactions. This undermines the possibility of objectivity in physics. However, quantum mechanics retains objectivity through the combination of the second and third postulates. A rule is given for determining the circumstances in which physical evolution is non-unitary. This rule appeals to the absence of spacetime loops in the future evolution of a set of interacting systems. A single universe undergoing non-unitary evolution is a viable interpretation.Comment: 19 pages. For special issue of J.Phys.A, "The Quantum Universe", on the occasion of 70th birthday of Professor Giancarlo Ghirard

A planetary nervous system for social mining and collective awareness

We present a research roadmap of a Planetary Nervous System (PNS), capable of sensing and mining the digital breadcrumbs of human activities and unveiling the knowledge hidden in the big data for addressing the big questions about social complexity. We envision the PNS as a globally distributed, self-organizing, techno-social system for answering analytical questions about the status of world-wide society, based on three pillars: social sensing, social mining and the idea of trust networks and privacy-aware social mining. We discuss the ingredients of a science and a technology necessary to build the PNS upon the three mentioned pillars, beyond the limitations of their respective state-of-art. Social sensing is aimed at developing better methods for harvesting the big data from the techno-social ecosystem and make them available for mining, learning and analysis at a properly high abstraction level. Social mining is the problem of discovering patterns and models of human behaviour from the sensed data across the various social dimensions by data mining, machine learning and social network analysis. Trusted networks and privacy-aware social mining is aimed at creating a new deal around the questions of privacy and data ownership empowering individual persons with full awareness and control on own personal data, so that users may allow access and use of their data for their own good and the common good. The PNS will provide a goal-oriented knowledge discovery framework, made of technology and people, able to configure itself to the aim of answering questions about the pulse of global society. Given an analytical request, the PNS activates a process composed by a variety of interconnected tasks exploiting the social sensing and mining methods within the transparent ecosystem provided by the trusted network. The PNS we foresee is the key tool for individual and collective awareness for the knowledge society. We need such a tool for everyone to become fully aware of how powerful is the knowledge of our society we can achieve by leveraging our wisdom as a crowd, and how important is that everybody participates both as a consumer and as a producer of the social knowledge, for it to become a trustable, accessible, safe and useful public good. Graphical abstrac