Rebecca S. Crowley

CONCENTRATIONS OF LEPTIN IN THE SERUM OF PREGNANT, LACTATING, AND CYCLING RATS AND OF LEPTIN MESSENGER RIBONUCLEIC ACID IN RAT PLACENTAL TISSUE

Leptin concentrations were measured in the serum of cycling, pregnant, and lactating Sprague-Dawley rats. Serum leptin concentrations did not vary significantly during the estrous cycle. In contrast, as gestation advanced, serum leptin concentrations increased significantly, p < 0.0001. Following delivery, leptin concentrations declined and remained stable during lactation. Leptin messenger ribonucleic acid (mRNA) was identified in the visceral adipose tissue and placenta of rats sacrificed on days 14 and 21 of pregnancy. The relative abundance of placental leptin mRNA increased approximately 4 to 5 fold from day 14 to 21 of gestation. The pattern of elevated leptin concentrations in the serum of late pregnant rats is similar to that reported in pregnant women, therefore the rat may be a useful model for the study of leptin during pregnancy. The increase in leptin in the serum of late pregnant rats, as well as an increase in placental mRNA, raises the possibility that leptin may serve a physiological role for the late parturient rat and/or its young.

Towards a Data Sharing Culture: Recommendations for Leadership from Academic Health Centers

Rebecca Crowley and colleagues propose that academic health centers can and should lead the transition towards a culture of biomedical data sharing.

Methodological Review: Natural Language Processing methods and systems for biomedical ontology learning

While the biomedical informatics community widely acknowledges the utility of domain ontologies, there remain many barriers to their effective use. One important requirement of domain ontologies is that they must achieve a high degree of coverage of the domain concepts and concept relationships. However, the development of these ontologies is typically a manual, time-consuming, and often error-prone process. Limited resources result in missing concepts and relationships as well as difficulty in updating the ontology as knowledge changes. Methodologies developed in the fields of Natural Language Processing, information extraction, information retrieval and machine learning provide techniques for automating the enrichment of an ontology from free-text documents. In this article, we review existing methodologies and developed systems, and discuss how existing methods can benefit the development of biomedical ontologies.

An intelligent tutoring system for visual classification problem solving

OBJECTIVE This manuscript describes the development of a general intelligent tutoring system for teaching visual classification problem solving. MATERIALS AND METHODS The approach is informed by cognitive theory, previous empirical work on expertise in diagnostic problem-solving, and our own prior work describing the development of expertise in pathology. The architecture incorporates aspects of cognitive tutoring system and knowledge-based system design within the framework of the unified problem-solving method description language component model. Based on the domain ontology, domain task ontology and case data, the abstract problem-solving methods of the expert model create a dynamic solution graph. Student interaction with the solution graph is filtered through an instructional layer, which is created by a second set of abstract problem-solving methods and pedagogic ontologies, in response to the current state of the student model. RESULTS In this paper, we outline the empirically derived requirements and design principles, describe the knowledge representation and dynamic solution graph, detail the functioning of the instructional layer, and demonstrate two implemented interfaces to the system. CONCLUSION Using the general visual classification tutor, we have created SlideTutor, a tutoring system for microscopic diagnosis of inflammatory diseases of skin.

caTIES: a grid based system for coding and retrieval of surgical pathology reports and tissue specimens in support of translational research.

The authors report on the development of the Cancer Tissue Information Extraction System (caTIES)--an application that supports collaborative tissue banking and text mining by leveraging existing natural language processing methods and algorithms, grid communication and security frameworks, and query visualization methods. The system fills an important need for text-derived clinical data in translational research such as tissue-banking and clinical trials. The design of caTIES addresses three critical issues for informatics support of translational research: (1) federation of research data sources derived from clinical systems; (2) expressive graphical interfaces for concept-based text mining; and (3) regulatory and security model for supporting multi-center collaborative research. Implementation of the system at several Cancer Centers across the country is creating a potential network of caTIES repositories that could provide millions of de-identified clinical reports to users. The system provides an end-to-end application of medical natural language processing to support multi-institutional translational research programs.

Anaphoric relations in the clinical narrative: corpus creation

OBJECTIVE The long-term goal of this work is the automated discovery of anaphoric relations from the clinical narrative. The creation of a gold standard set from a cross-institutional corpus of clinical notes and high-level characteristics of that gold standard are described. METHODS A standard methodology for annotation guideline development, gold standard annotations, and inter-annotator agreement (IAA) was used. RESULTS The gold standard annotations resulted in 7214 markables, 5992 pairs, and 1304 chains. Each report averaged 40 anaphoric markables, 33 pairs, and seven chains. The overall IAA is high on the Mayo dataset (0.6607), and moderate on the University of Pittsburgh Medical Center (UPMC) dataset (0.4072). The IAA between each annotator and the gold standard is high (Mayo: 0.7669, 0.7697, and 0.9021; UPMC: 0.6753 and 0.7138). These results imply a quality corpus feasible for system development. They also suggest the complementary nature of the annotations performed by the experts and the importance of an annotator team with diverse knowledge backgrounds. LIMITATIONS Only one of the annotators had the linguistic background necessary for annotation of the linguistic attributes. The overall generalizability of the guidelines will be further strengthened by annotations of data from additional sites. This will increase the overall corpus size and the representation of each relation type. CONCLUSION The first step toward the development of an anaphoric relation resolver as part of a comprehensive natural language processing system geared specifically for the clinical narrative in the electronic medical record is described. The deidentified annotated corpus will be available to researchers.

Methodological Review: Coreference resolution: A review of general methodologies and applications in the clinical domain

Coreference resolution is the task of determining linguistic expressions that refer to the same real-world entity in natural language. Research on coreference resolution in the general English domain dates back to 1960s and 1970s. However, research on coreference resolution in the clinical free text has not seen major development. The recent US government initiatives that promote the use of electronic health records (EHRs) provide opportunities to mine patient notes as more and more health care institutions adopt EHR. Our goal was to review recent advances in general purpose coreference resolution to lay the foundation for methodologies in the clinical domain, facilitated by the availability of a shared lexical resource of gold standard coreference annotations, the Ontology Development and Information Extraction (ODIE) corpus.

The CAP cancer protocols – a case study of caCORE based data standards implementation to integrate with the Cancer Biomedical Informatics Grid

BackgroundThe Cancer Biomedical Informatics Grid (caBIG™) is a network of individuals and institutions, creating a world wide web of cancer research. An important aspect of this informatics effort is the development of consistent practices for data standards development, using a multi-tier approach that facilitates semantic interoperability of systems. The semantic tiers include (1) information models, (2) common data elements, and (3) controlled terminologies and ontologies. The College of American Pathologists (CAP) cancer protocols and checklists are an important reporting standard in pathology, for which no complete electronic data standard is currently available.MethodsIn this manuscript, we provide a case study of Cancer Common Ontologic Representation Environment (caCORE) data standard implementation of the CAP cancer protocols and checklists model – an existing and complex paper based standard. We illustrate the basic principles, goals and methodology for developing caBIG™ models.ResultsUsing this example, we describe the process required to develop the model, the technologies and data standards on which the process and models are based, and the results of the modeling effort. We address difficulties we encountered and modifications to caCORE that will address these problems. In addition, we describe four ongoing development projects that will use the emerging CAP data standards to achieve integration of tissue banking and laboratory information systems.ConclusionThe CAP cancer checklists can be used as the basis for an electronic data standard in pathology using the caBIG™ semantic modeling methodology.

A system for coreference resolution for the clinical narrative

OBJECTIVE To research computational methods for coreference resolution in the clinical narrative and build a system implementing the best methods. METHODS The Ontology Development and Information Extraction corpus annotated for coreference relations consists of 7214 coreferential markables, forming 5992 pairs and 1304 chains. We trained classifiers with semantic, syntactic, and surface features pruned by feature selection. For the three system components--for the resolution of relative pronouns, personal pronouns, and noun phrases--we experimented with support vector machines with linear and radial basis function (RBF) kernels, decision trees, and perceptrons. Evaluation of algorithms and varied feature sets was performed using standard metrics. RESULTS The best performing combination is support vector machines with an RBF kernel and all features (MUC score=0.352, B(3)=0.690, CEAF=0.486, BLANC=0.596) outperforming a traditional decision tree baseline. DISCUSSION The application showed good performance similar to performance on general English text. The main error source was sentence distances exceeding a window of 10 sentences between markables. A possible solution to this problem is hinted at by the fact that coreferent markables sometimes occurred in predictable (although distant) note sections. Another system limitation is failure to fully utilize synonymy and ontological knowledge. Future work will investigate additional ways to incorporate syntactic features into the coreference problem. CONCLUSION We investigated computational methods for coreference resolution in the clinical narrative. The best methods are released as modules of the open source Clinical Text Analysis and Knowledge Extraction System and Ontology Development and Information Extraction platforms.

Factors Affecting Feeling-of-knowing in a Medical Intelligent Tutoring System – the role of Immediate Feedback as a Metacognitive Scaffold

Previous studies in our laboratory have shown the benefits of immediate feedback on cognitive performance for pathology residents using an intelligent tutoring system (ITS) in pathology. In this study, we examined the effect of immediate feedback on metacognitive performance, and investigated whether other metacognitive scaffolds will support metacognitive gains when immediate feedback is faded. Twenty-three participants were randomized into intervention and control groups. For both groups, periods working with the ITS under varying conditions were alternated with independent computer-based assessments. On day 1, a within-subjects design was used to evaluate the effect of immediate feedback on cognitive and metacognitive performance. On day 2, a between-subjects design was used to compare the use of other metacognitive scaffolds (intervention group) against no metacognitive scaffolds (control group) on cognitive and metacognitive performance, as immediate feedback was faded. Measurements included learning gains (a measure of cognitive performance), as well as several measures of metacognitive performance, including Goodman–Kruskal gamma correlation (G), bias, and discrimination. For the intervention group, we also computed metacognitive measures during tutoring sessions. Results showed that immediate feedback in an intelligent tutoring system had a statistically significant positive effect on learning gains, G and discrimination. Removal of immediate feedback was associated with decreasing metacognitive performance, and this decline was not prevented when students used a version of the tutoring system that provided other metacognitive scaffolds. Results obtained directly from the ITS suggest that other metacognitive scaffolds do have a positive effect on G and discrimination, as immediate feedback is faded. We conclude that immediate feedback had a positive effect on both metacognitive and cognitive gains in a medical tutoring system. Other metacognitive scaffolds were not sufficient to replace immediate feedback in this study. However, results obtained directly from the tutoring system are not consistent with results obtained from assessments. In order to facilitate transfer to real-world tasks, further research will be needed to determine the optimum methods for supporting metacognition as immediate feedback is faded.