Overview of the shuttle imaging radar-B preliminary scientific results.

The Shuttle Imaging Radar-B experiment consisted of a large number of scientific investigations in the earth sciences. Nine oceanographic experiments were conducted to study the generation and propagation of surface waves, the dynamics of internal waves, oil slick detection, and the properties of southern polar ice. Stereo imaging from space allowed three-dimensional viewing of surface features. Geologic experiments were conducted to study subsurface penetration, structural mapping, and lithologic classification. Imaging radar angular scatterometry was used in the vegetation cover, forest type, and urban areas classification experiments. This article provides an overview of the scientific results, some of which are also presented in this issue.

Shuttle imaging radar experiment.

The shuttle imaging radar (SIR-A) acquired images of a variety of the earth's geologic areas covering about 10 million square kilometers. Structural and geomorphic features such as faults, folds, outcrops, and dunes are clearly visible in both tropical and arid regions. The combination of SIR-A and Seasat images provides additional information about the surface physical properties: topography and roughness. Ocean features were also observed, including large internal waves in the Andaman Sea.

Metabolic inhibitors accentuate the anti-tumoral effect of HDAC5 inhibition.

The US FDA approval of broad-spectrum histone deacetylase (HDAC) inhibitors has firmly laid the cancer community to explore HDAC inhibition as a therapeutic approach for cancer treatment. Hitting one HDAC member could yield clinical benefit but this required a complete understanding of the functions of the different HDAC members. Here we explored the consequences of specific HDAC5 inhibition in cancer cells. We demonstrated that HDAC5 inhibition induces an iron-dependent reactive oxygen species (ROS) production, ultimately leading to apoptotic cell death as well as mechanisms of mitochondria quality control (mitophagy and mitobiogenesis). Interestingly, adaptation of HDAC5-depleted cells to oxidative stress passes through reprogramming of metabolic pathways towards glucose and glutamine. Therefore, interference with both glucose and glutamine supply in HDAC5-inhibited cancer cells significantly increases apoptotic cell death and reduces tumour growth in vivo; providing insight into a valuable clinical strategy combining the selective inhibition of HDAC5 with various inhibitors of metabolism as a new therapy to kill cancer cells.

Ultraviolet light-induced transformation of human cells to anchorage-independent growth.

We have developed a system for ultraviolet light (UV) transformation of human embryonic cells to anchorage-independent growth. The procedure involves multiple UV irradiations, post irradiation growth, and plating in soft agar. Transformants are obtained at frequencies from 1 to 80 per 10(5) cells at UV exposures to 25 J/sq m. The resulting transformants can be subcultured on solid surfaces. The cells show crisscrossing and piling up; they reach 2- to 5-fold higher saturation densities than the parental cells. Some subcultures show increased plating efficiency in soft agar and increased life span. The susceptibility of the UV transformation process to apparent photoenzymatic reversal implies that purimidine dimers play a role in its induction.

Point-of-Care Knowledge-Based Resource Needs of Clinicians: A Survey from a Large Academic Medical Center.

OBJECTIVE: To better understand the literature searching preferences of clinical providers we conducted an institution-wide survey assessing the most preferred knowledge searching techniques. MATERIALS AND METHODS: A survey regarding literature searching preferences was sent to 1862 unique clinical providers throughout Mayo Clinic. The survey consisted of 25 items asking respondents to select which clinical scenarios most often prompt literature searches as well as identify their most preferred knowledge resources. RESULTS: A total of 450 completed surveys were returned and analyzed (24% response rate). 48% of respondents perform literature searches for more than half of their patient interactions with 91% of all searches occurring either before or within 3 hours of the patient interaction. When a search is performed 57% of respondents prefer synthesized information sources as compared to only 13% who prefer original research. 82% of knowledge searches are performed on a workstation or office computer while just 10% occur on a mobile device or at home. CONCLUSION: Providers in our survey demonstrate a need to answer clinical questions on a regular basis, especially in the diagnosis and therapy domains. Responses suggest that most of these searches occur using synthesized knowledge sources in the patient care setting within a very short time from the patient interaction.

Riboflavin metabolism in the hypothyroid newborn.

In the hypothyroid rat the flavin adenine dinucleotide (FAD) content of the liver is similar to that observed in rats maintained on a riboflavin-deficient diet. Thyroxine regulates the enzyme flavin kinase. Human adults with hypothyroidism have levels of erythrocyte glutathione reductase (EGR), an FAD-containing enzyme, in the range indicative of riboflavin deficiency, which can be corrected with thyroxine therapy. In the present study six newborns with severe congenital hypothyroidism because of athyrosis, ectopic thyroidism, or congenital hypothyroidism with Down's syndrome had normal levels of EGR, and treatment with thyroxine had no effect on these levels.

Follow-up of children overexposed to lead.

The purpose of this study is to assess the nature and magnitude of the deleterious health effects of subclinical over-exposure to lead in children. The study stems from concerns about the impact on the health of children in city slums who ingest leaded paint without overt evidence of poisoning and the health implication of rising levels of lead in the environment from automotive emissions. The study sample was derived mainly from a registry of children on whom blood lead determinations had been made by the New York City Department of Health and was supplemented by siblings of the registry cases and children from a lead belt area who had extractions of deciduous teeth in dental clinics. Information was obtained through parental interview, medical records, and psychometric evaluation. The data show that deleterious health effects occur in children who were treated for severe lead poisoning and in children without diagnosed lead poisoning who had elevated blood leads (>/=0.06 mg-%). In the absence of diagnosed lead poisoning or elevated blood leads, excess lead exposure, measured in terms of high levels of lead in teeth, was not associated with deleterious health effects.

From data to knowledge through concept-oriented terminologies: experience with the Medical Entities Dictionary.

Knowledge representation involves enumeration of conceptual symbols and arrangement of these symbols into some meaningful structure. Medical knowledge representation has traditionally focused more on the structure than the symbols. Several significant efforts are under way, at local, national, and international levels, to address the representation of the symbols though the creation of high-quality terminologies that are themselves knowledge based. This paper reviews these efforts, including the Medical Entities Dictionary (MED) in use at Columbia University and the New York Presbyterian Hospital. A decade's experience with the MED is summarized to serve as a proof-of-concept that knowledge-based terminologies can support the use of coded patient data for a variety of knowledge-based activities, including the improved understanding of patient data, the access of information sources relevant to specific patient care problems, the application of expert systems directly to the care of patients, and the discovery of new medical knowledge. The terminological knowledge in the MED has also been used successfully to support clinical application development and maintenance, including that of the MED itself. On the basis of this experience, current efforts to create standard knowledge-based terminologies appear to be justified.

Beyond the superhighway: exploiting the Internet with medical informatics.

As in other areas of society, the Internet and the World Wide Web are becoming important topics in medical informatics. This is evident from the recent American Medical Informatics Association's 1996 Annual Fall Symposium, where the theme was "Beyond the Superhighway: Exploiting the Internet with Medical Informatics." Of the over 330 papers and abstracts published in the Proceedings, one third dealt with the Internet and/or the Web. In some cases, system developers demonstrated how this technology can do old tasks in new ways. In other cases, researchers described new tasks that are now possible with this technology. Still others examined this technology to show how it can be evaluated and improved. This paper summarizes their accomplishments.

Auditing the Unified Medical Language System with semantic methods.

OBJECTIVE: The National Library of Medicine's (NLM) Unified Medical Language System (UMLS) includes a Metathesaurus (Meta), which is a compilation of medical terms drawn from over 30 controlled vocabularies, and a Semantic Net, which contains the semantic types used to categorize Meta concepts and the semantic relations to connect them. Meta has been constructed through lexical matching techniques and human review. The purpose of this study was to audit the Meta using semantic techniques to identify possible inconsistencies. METHODS: Five different techniques were applied: (1) detection of ambiguity in Meta concepts with two or more semantic types, (2) detection of interchangeable keyword synonyms, (3) detection of redundant pairs of Meta concepts (using lexical matching combined with keyword synonyms), (4) detection of inconsistent parent-child relationships in Meta (based on the semantic type information), and (5) discovery of pairs of semantic types for which relations could be added to the Semantic Net, based on "other" relationships between Meta concepts. RESULTS: Of 57,592 concepts with multiple semantic types, 1817 (3.2%) were judged to be ambiguous. Keyword analysis showed 7121 pairs of interchangeable words. Using the keyword pairs, 5031 pairs of potentially redundant concepts were suggested, of which 3274 (65.1%) were judged to actually be redundant. Review of the 100,586 parent-child relationships revealed 544 (0.54%) that were incorrect. Review of the 219,664 "Other" relationships suggested 1299 places in the Semantic Net where relations between pairs of semantic types could be added. CONCLUSION: Semantic techniques, alone or in combination, can be used to audit the UMLS to detect inconsistencies that are not detectable through lexical techniques alone. Use of these methods to augment the UMLS maintenance process will lead to improvement in the UMLS.

A schema for representing medical language applied to clinical radiology.

OBJECTIVE: Develop a representational schema for clinical concepts and apply it to the task of encoding radiology reports of the chest. DESIGN: The schema was developed following a manual analysis of sample reports from the domain. The schema has two main components: the Medical Entities Dictionary (MED), which specifies the formal representation of the concepts in the domain and of their structures, and the natural-language processor, which specifies the linguistic expressions of the concepts. The schema was evaluated by applying it to a test set of 7,500 reports. Two-hundred reports from the test set were manually analyzed by a medical expert to determine the accuracy and success rate of the system. RESULTS: 82% of the 7,500 reports that contained relevant clinical information were successfully structured automatically. For the smaller set of 200 reports, 80% were structured successfully with an accuracy rate of 97%. CONCLUSIONS: The schema is a formal representation for clinical concepts in radiology reports, and provides domain coverage that is particularly well-suited for natural-language processing of radiology for use in a decision support system.

Knowledge-based approaches to the maintenance of a large controlled medical terminology.

OBJECTIVE: Develop a knowledge-based representation for a controlled terminology of clinical information to facilitate creation, maintenance, and use of the terminology. DESIGN: The Medical Entities Dictionary (MED) is a semantic network, based on the Unified Medical Language System (UMLS), with a directed acyclic graph to represent multiple hierarchies. Terms from four hospital systems (laboratory, electrocardiography, medical records coding, and pharmacy) were added as nodes in the network. Additional knowledge about terms, added as semantic links, was used to assist in integration, harmonization, and automated classification of disparate terminologies. RESULTS: The MED contains 32,767 terms and is in active clinical use. Automated classification was successfully applied to terms for laboratory specimens, laboratory tests, and medications. One benefit of the approach has been the automated inclusion of medications into multiple pharmacologic and allergenic classes that were not present in the pharmacy system. Another benefit has been the reduction of maintenance efforts by 90%. CONCLUSION: The MED is a hybrid of terminology and knowledge. It provides domain coverage, synonymy, consistency of views, explicit relationships, and multiple classification while preventing redundancy, ambiguity (homonymy) and misclassification.

Access to data: comparing AccessMed with Query by Review.

OBJECTIVE: To evaluate the performance of tools for authoring patient database queries. DESIGN: Query by Review, a tool that exploits the training that users have undergone to master a result review system, was compared with AccessMed, a vocabulary browser that supports lexical matching and the traversal of hierarchical and semantic links. Seven subjects (Medical Logic Module authors) were asked to use both tools to gather the vocabulary terms necessary to perform each of eight laboratory queries. MEASUREMENTS: The proportion of queries that were correct; intersubject agreement. RESULTS: Query by Review had better performance than AccessMed (38% correct queries versus 18%, p = 0.002), but both figures were low. Poor intersubject agreement (28% for Query by Review and 21% for AccessMed) corroborated the relatively low performance. Subjects appeared to have trouble distinguishing laboratory tests from laboratory batteries, picking terms relevant to the particular data type required, and using classes in the vocabulary's hierarchy. CONCLUSION: Query by Review, with its more constrained user interface, performed somewhat better than AccessMed, a more general tool. Neither tool achieved adequate performance, however, which points to the difficulty of formulating a query for a clinical database and the need for further work.

Internet as clinical information system: application development using the World Wide Web.

Clinical computing application development at Columbia-Presbyterian Medical Center has been limited by the lack of a flexible programming environment that supports multiple client user platforms. The World Wide Web offers a potential solution, with its multifunction servers, multiplatform clients, and use of standard protocols for displaying information. The authors are now using the Web, coupled with their own local clinical data server and vocabulary server, to carry out rapid prototype development of clinical information systems. They have developed one such prototype system that can be run on most popular computing platforms from anywhere on the Internet. The Web paradigm allows easy integration of clinical information with other local and Internet-based information sources. The Web also simplifies many aspects of application design; for example, it includes facilities for the use of encryption to meet the authors' security and confidentiality requirements. The prototype currently runs on only the Web server in the Department of Medical Informatics at Columbia University, but it could be run on other Web servers that access the authors' clinical data and vocabulary servers. It could also be adapted to access clinical information from other systems with similar server capabilities. This approach may be adaptable for use in developing institution-independent standards for data and application sharing.

Studying the human-computer-terminology interface.

OBJECTIVE: To explore the use of an observational, cognitive-based approach for differentiating between successful, suboptimal, and failed entry of coded data by clinicians in actual practice, and to detect whether causes for unsuccessful attempts to capture true intended meaning were due to terminology content, terminology representation, or user interface problems. DESIGN: Observational study with videotaping and subsequent coding of data entry events in an outpatient clinic at New York Presbyterian Hospital. PARTICIPANTS: Eight attending physicians, 18 resident physicians, and 1 nurse practitioner, using the Medical Entities Dictionary (MED) to record patient problems, medications, and adverse reactions in an outpatient medical record system. MEASUREMENTS: Classification of data entry events as successful, suboptimal, or failed, and estimation of cause; recording of system response time and total event time. RESULTS: Two hundred thirty-eight data entry events were analyzed; 71.0 percent were successful, 6.3 percent suboptimal, and 22.7 percent failed; unsuccessful entries were due to problems with content in 13.0 percent of events, representation problems in 10.1 percent of events, and usability problems in 5.9 percent of events. Response time averaged 0.74 sec, and total event time averaged 40.4 sec. Of an additional 209 tasks related to drug dose and frequency terms, 94 percent were successful, 0.5 percent were suboptimal, and 6 percent failed, for an overall success rate of 82 percent. CONCLUSIONS: Data entry by clinicians using the outpatient system and the MED was generally successful and efficient. The cognitive-based observational approach permitted detection of false-positive (suboptimal) and false-negative (failed due to user interface) data entry.

A general natural-language text processor for clinical radiology.

OBJECTIVE: Development of a general natural-language processor that identifies clinical information in narrative reports and maps that information into a structured representation containing clinical terms. DESIGN: The natural-language processor provides three phases of processing, all of which are driven by different knowledge sources. The first phase performs the parsing. It identifies the structure of the text through use of a grammar that defines semantic patterns and a target form. The second phase, regularization, standardizes the terms in the initial target structure via a compositional mapping of multi-word phrases. The third phase, encoding, maps the terms to a controlled vocabulary. Radiology is the test domain for the processor and the target structure is a formal model for representing clinical information in that domain. MEASUREMENTS: The impression sections of 230 radiology reports were encoded by the processor. Results of an automated query of the resultant database for the occurrences of four diseases were compared with the analysis of a panel of three physicians to determine recall and precision. RESULTS: Without training specific to the four diseases, recall and precision of the system (combined effect of the processor and query generator) were 70% and 87%. Training of the query component increased recall to 85% without changing precision.

Toward a medical-concept representation language. The Canon Group.

The Canon Group is an informal organization of medical informatics researchers who are working on the problem of developing a "deeper" representation formalism for use in exchanging data and developing applications. Individuals in the group represent experts in such areas as knowledge representation and computational linguistics, as well as in a variety of medical subdisciplines. All share the view that current mechanisms for the characterization of medical phenomena are either inadequate (limited or rigid) or idiosyncratic (useful for a specific application but incapable of being generalized or extended). The Group proposes to focus on the design of a general schema for medical-language representation including the specification of the resources and associated procedures required to map language (including standard terminologies) into representations that make all implicit relations "visible," reveal "hidden attributes," and generally resolve ambiguous or vague references. The Group is proceeding by examining large numbers of texts (records) in medical sub-domains to identify candidate "concepts" and by attempting to develop general rules and representations for elements such as attributes and values so that all concepts may be expressed uniformly.

The Canon Group's effort: working toward a merged model.

OBJECTIVE: To develop a representational schema for clinical data for use in exchanging data and applications, using a collaborative approach. DESIGN: Representational models for clinical radiology were independently developed manually by several Canon Group members who had diverse application interests, using sample reports. These models were merged into one common model through an iterative process by means of workshops, meetings, and electronic mail. RESULTS: A core merged model for radiologic findings present in a set of reports that subsumed the models that were developed independently. CONCLUSIONS: The Canon Group's modeling effort focused on a collaborative approach to developing a representational schema for clinical concepts, using chest radiography reports as the initial experiment. This effort resulted in a core model that represents a consensus. Further efforts in modeling will extend the representational coverage and will also address issues such as scalability, automation, evaluation, and support of the collaborative effort.

Representing the UMLS as an object-oriented database: modeling issues and advantages.

OBJECTIVE: The Unified Medical Language System (UMLS) combines many well-established authoritative medical informatics terminologies in one knowledge representation system. Such a resource is very valuable to the health care community and industry. However, the UMLS is very large and complex and poses serious comprehension problems for users and maintenance personnel. The authors present a representation to support the user's comprehension and navigation of the UMLS. DESIGN: An object-oriented database (OODB) representation is used to represent the two major components of the UMLS-the Metathesaurus and the Semantic Network-as a unified system. The semantic types of the Semantic Network are modeled as semantic type classes. Intersection classes are defined to model concepts of multiple semantic types, which are removed from the semantic type classes. RESULTS: The authors provide examples of how the intersection classes help expose omissions of concepts, highlight errors of semantic type classification, and uncover ambiguities of concepts in the UMLS. The resulting UMLS OODB schema is deeper and more refined than the Semantic Network, since intersection classes are introduced. The Metathesaurus is classified into more mutually exclusive, uniform sets of concepts. The schema improves the user's comprehension and navigation of the Metathesaurus. CONCLUSIONS: The UMLS OODB schema supports the user's comprehension and navigation of the Metathesaurus. It also helps expose and resolve modeling problems in the UMLS.

Toward vocabulary domain specifications for health level 7-coded data elements.

The "vocabulary problem" has long plagued the developers, implementers, and users of computer-based systems. The authors review selected activities of the Health Level 7 (HL7) Vocabulary Technical Committee that are related to vocabulary domain specification for HL7 coded data elements. These activities include: 1) the development of two sets of principles to provide guidance to terminology stakeholders, including organizations seeking to deploy HL7-compliant systems, terminology developers, and terminology integrators; 2) the completion of a survey of terminology developers; 3) the development of a process for HL7 registration of terminologies; and 4) the maintenance of vocabulary domain specification tables. As background, vocabulary domain specification is defined and the relationship between the HL7 Reference Information Model and vocabulary domain specification is described. The activities of the Vocabulary Technical Committee complement the efforts of terminology developers and other stakeholders. These activities are aimed at realizing semantic interoperability in the context of the HL7 Message Development Framework, so that information exchange and use among disparate systems can occur for the delivery and management of direct clinical care as well as for purposes such as clinical research, outcome research, and population health management.