The IMPACT framework and implementation for accessible in silico clinical phenotyping in the digital era.

Clinical phenotyping is often a foundational requirement for obtaining datasets necessary for the development of digital health applications. Traditionally done via manual abstraction, this task is often a bottleneck in development due to time and cost requirements, therefore raising significant interest in accomplishing this task via in-silico means. Nevertheless, current in-silico phenotyping development tends to be focused on a single phenotyping task resulting in a dearth of reusable tools supporting cross-task generalizable in-silico phenotyping. In addition, in-silico phenotyping remains largely inaccessible for a substantial portion of potentially interested users. Here, we highlight the barriers to the usage of in-silico phenotyping and potential solutions in the form of a framework of several desiderata as observed during our implementation of such tasks. In addition, we introduce an example implementation of said framework as a software application, with a focus on ease of adoption, cross-task reusability, and facilitating the clinical phenotyping algorithm development process.

A Pseudo-Value Approach to Analyze the Semantic Similarity of the Speech of Children With and Without Autism Spectrum Disorder.

Conversational impairments are well known among people with autism spectrum disorder (ASD), but their measurement requires time-consuming manual annotation of language samples. Natural language processing (NLP) has shown promise in identifying semantic difficulties when compared to clinician-annotated reference transcripts. Our goal was to develop a novel measure of lexico-semantic similarity - based on recent work in natural language processing (NLP) and recent applications of pseudo-value analysis - which could be applied to transcripts of children's conversational language, without recourse to some ground-truth reference document. We hypothesized that: (a) semantic coherence, as measured by this method, would discriminate between children with and without ASD and (b) more variability would be found in the group with ASD. We used data from 70 4- to 8-year-old males with ASD (N = 38) or typically developing (TD; N = 32) enrolled in a language study. Participants were administered a battery of standardized diagnostic tests, including the Autism Diagnostic Observation Schedule (ADOS). ADOS was recorded and transcribed, and we analyzed children's language output during the conversation/interview ADOS tasks. Transcripts were converted to vectors via a word2vec model trained on the Google News Corpus. Pairwise similarity across all subjects and a sample grand mean were calculated. Using a leave-one-out algorithm, a pseudo-value, detailed below, representing each subject's contribution to the grand mean was generated. Means of pseudo-values were compared between the two groups. Analyses were co-varied for nonverbal IQ, mean length of utterance, and number of distinct word roots (NDR). Statistically significant differences were observed in means of pseudo-values between TD and ASD groups (p = 0.007). TD subjects had higher pseudo-value scores suggesting that similarity scores of TD subjects were more similar to the overall group mean. Variance of pseudo-values was greater in the ASD group. Nonverbal IQ, mean length of utterance, or NDR did not account for between group differences. The findings suggest that our pseudo-value-based method can be effectively used to identify specific semantic difficulties that characterize children with ASD without requiring a reference transcript.

Evaluation of patient-level retrieval from electronic health record data for a cohort discovery task.

OBJECTIVE: Growing numbers of academic medical centers offer patient cohort discovery tools to their researchers, yet the performance of systems for this use case is not well understood. The objective of this research was to assess patient-level information retrieval methods using electronic health records for different types of cohort definition retrieval. MATERIALS AND METHODS: We developed a test collection consisting of about 100 000 patient records and 56 test topics that characterized patient cohort requests for various clinical studies. Automated information retrieval tasks using word-based approaches were performed, varying 4 different parameters for a total of 48 permutations, with performance measured using B-Pref. We subsequently created structured Boolean queries for the 56 topics for performance comparisons. In addition, we performed a more detailed analysis of 10 topics. RESULTS: The best-performing word-based automated query parameter settings achieved a mean B-Pref of 0.167 across all 56 topics. The way a topic was structured (topic representation) had the largest impact on performance. Performance not only varied widely across topics, but there was also a large variance in sensitivity to parameter settings across the topics. Structured queries generally performed better than automated queries on measures of recall and precision but were still not able to recall all relevant patients found by the automated queries. CONCLUSION: While word-based automated methods of cohort retrieval offer an attractive solution to the labor-intensive nature of this task currently used at many medical centers, we generally found suboptimal performance in those approaches, with better performance obtained from structured Boolean queries. Future work will focus on using the test collection to develop and evaluate new approaches to query structure, weighting algorithms, and application of semantic methods.

A pilot prospective feasibility study of organ-at-risk definition using Target Contour Testing/Instructional Computer Software (TaCTICS), a training and evaluation platform for radiotherapy target delineation.

Target volume delineation is a critical, but time-consuming step in the creation of radiation therapy plans used in the treatment of many types of cancer. However, variability in target volume definitions can introduce substantial differences in resulting doses to tumors and critical structures. We developed TaCTICS, a web-based educational training software application targeted towards non-expert users. We report on a small, prospective study to evaluate the utility of this online tool in improving conformance of regions-of-interest (ROIs) with a reference set. Eight residents contoured a set of structures for a head-and-neck cancer case. Subsequently, they were provided access to TaCTICS as well as contouring atlases to allow evaluation of their contours in reference to other users as well as reference ROIs. The residents then contoured a second case using these resources. Volume overlap metrics between the users showed a substantial improvement following the intervention. Additionally, 66% of users reported that they found TaCTICS to be a useful educational tool and all participants reported they would like to use TaCTICS to track their contouring skills over the course of their residency.

A multi-lingual web service for drug side-effect data.

In this paper, we describe a system that provides drug side-effect data for use as a component in service-oriented architectures. Our system uses "Web 2.0" techniques to collect data from a variety of public sources, and can provide its output in a variety of human languages (e.g. Spanish and Arabic). To demonstrate our tool's versatility and the ease with which it may be integrated into larger systems, we present several front-ends that use our system, including SMS ("text message"), "instant messenger", and iPhone interfaces. We enlisted a panel of Argentinean clinicians to review and rate the quality of our system's Spanish-language output in order to investigate whether freely-available general-purpose machine translation technology (Google's translation API) is adequate for consumer medical applications. Our raters found that Google's translation quality varied greatly among drugs, and we conclude that it is better used as a starting point than as a complete translation solution.

A scientific collaboration tool built on the facebook platform.

We describe an application ("Medline Publications")written for the Facebook platform that allows users to maintain and publish a list of their own Medline-indexed publications, as well as easily access their contacts lists. The system is semi-automatic in that it interfaces directly with the National Library of Medicine's PubMed database to find and retrieve citation data. Furthermore, the system has the capability to present the user with sets of other users with similar publication profiles. As of July 2008,Medline Publications has attracted approximately 759 users, 624 of which have listed a total of 5,193 unique publications.

Furrow microtubules and localized exocytosis in cleaving Xenopus laevis embryos.

In dividing Xenopus eggs, furrowing is accompanied by expansion of a new domain of plasma membrane in the cleavage plane. The source of the new membrane is known to include a store of oogenetically produced exocytotic vesicles, but the site where their exocytosis occurs has not been described. Previous work revealed a V-shaped array of microtubule bundles at the base of advancing furrows. Cold shock or exposure to nocodazole halted expansion of the new membrane domain, which suggests that these microtubules are involved in the localized exocytosis. In the present report, scanning electron microscopy revealed collections of pits or craters, up to approximately 1.5 micro m in diameter. These pits are evidently fusion pores at sites of recent exocytosis, clustered in the immediate vicinity of the deepening furrow base and therefore near the furrow microtubules. Confocal microscopy near the furrow base of live embryos labeled with the membrane dye FM1-43 captured time-lapse sequences of individual exocytotic events in which irregular patches of approximately 20 micro m(2) of unlabeled membrane abruptly displaced pre-existing FM1-43-labeled surface. In some cases, stable fusion pores, approximately 2 micro m in diameter, were seen at the surface for up to several minutes before suddenly delivering patches of unlabeled membrane. To test whether the presence of furrow microtubule bundles near the surface plays a role in directing or concentrating this localized exocytosis, membrane expansion was examined in embryos exposed to D(2)O to induce formation of microtubule monasters randomly under the surface. D(2)O treatment resulted in a rapid, uniform expansion of the egg surface via random, ectopic exocytosis of vesicles. This D(2)O-induced membrane expansion was completely blocked with nocodazole, indicating that the ectopic exocytosis was microtubule-dependent. Results indicate that exocytotic vesicles are present throughout the egg subcortex, and that the presence of microtubules near the surface is sufficient to mobilize them for exocytosis at the end of the cell cycle.