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We have developed a publicly accessible database (ALFRED, the ALlele FREquency Database) that catalogues allele frequency data for a wide range of population samples and DNA polymorphisms. This database is web-accessible through our laboratory (Kidd Lab) Web site: http://info.med.yale.edu/genetics/kkidd. ALFRED currently contains data on 60 populations and 156 genetic systems including single nucleotide polymorphisms (SNPs), short tandem repeat polymorphisms (STRPs), variable number of tandem repeats (VNTRs) and insertion-deletion polymorphisms. While data are not available for all population-DNA polymorphism combinations, over 2000 allele frequency tables have been entered. Our database is designed (i) to address our specific research requirements as well as broader scientific objectives; (ii) to allow researchers and interested educators to easily navigate and retrieve data of interest to them; and (iii) to integrate links to other related public databases such as dbSNP, GenBank and PubMed.

IMM/Serve is a computer-based guideline that provides patient-specific recommendations regarding childhood immunization. IMM/Serve is currently installed at an estimated 75 sites within the US Indian Health Service (IHS), with plans to extend its use to roughly 150 additional sites nationwide by the end of the year 2000. The dissemination of IMM/Serve within the IHS provides a case study with concrete examples that illustrate the diverse informatics issues that arise in the widespread dissemination of a computer-based clinical guideline.

The Olfactory Receptor Database (ORDB) is a WWW-accessible database that has been expanded from an olfactory receptor resource to a chemoreceptor resource. It stores data on six classes of G-protein-coupled sensory chemoreceptors: (i) olfactory receptor-like proteins, (ii) vomeronasal receptors, (iii) insect olfactory receptors, (iv) worm chemo-receptors, (v) taste papilla receptors and (vi) fungal pheromone receptors. A complementary database of the ligands of these receptors (OdorDB) has been constructed and is publicly available in a pilot mode. The database schema of ORDB has been changed from traditional relational to EAV/CR (Entity-Attribute-Value with Classes and Relationships), which allows the interoperability of ORDB with other related databases as well as the creation of intra-database associations among objects. This inter-operability facilitates users to follow information from odor molecule binding to its putative receptor, to the properties of the neuron expressing the receptor, to a computational model of activity of olfactory bulb neurons. In addition, tools and resources have been added allowing users to access interactive phylogenetic trees and alignments of sensory chemoreceptors. ORDB is available via the WWW at http://ycmi.med. yale.edu/senselab/ordb/

We present a Web-accessible database (ALFRED) that allows public access to gene frequency data for a diverse set of population samples and genetic systems. The data in ALFRED are modeled based on the experience and needs of a single laboratory, but with the expectation that the database will meet the needs of a much broader scientific community that needs population-specific gene frequency estimates. Our database currently contains data on more than 40 populations representing most major regions of the world and data on more than 150 genetic systems including SNPs, STRPs, and insertion-deletion polymorphisms. While data are not available for all population-genetic system combinations, over 2000 allele frequency tables already exist. In this paper, we enumerate the broad needs in the scientific domain, describe their significance, and describe how we have designed the database to meet those needs. We compare our database with dbSNP, the NCBI database that has a broader but overlapping purpose.

Objective: To query a clinical data repository (CDR) for answers to clinical questions to determine whether different types of fields (coded and free text) would yield confirmatory, complementary, or conflicting information and to discuss the issues involved in producing the discrepancies between the fields., Methods: The appropriate data fields in a subset of a CDR (5,135 patient records) were searched for the answers to three questions related to surgical procedures. Each search included at least one coded data field and at least one free-text field. The identified free-text records were then searched manually to ensure correct interpretation. The fields were then compared to determine whether they agreed with each other, were supportive of each other, contained no entry (absence of data), or were contradictory., Results: The degree of concordance varied greatly according to the field and the question asked. Some fields were not granular enough to answer the question. The free-text fields often gave an answer that was not definitive. Absence of data was most logically interpreted in some cases as lack of completion of data and in others as a negative answer. Even with a question as specific as which side a hernia was on, contradictory data were found in 5 to 8 percent of the records., Conclusions: Using the data in the CDR to answer clinical questions can yield significantly disparate results depending on the question and which data fields are searched. A database cannot just be queried in automated fashion and the results reported. Both coded and textual fields must be searched to obtain the fullest assessment. This can be expected to result in information that may be confirmatory, complementary, or conflicting. To yield the most accurate information possible, final answers to questions require human judgment and may require the gathering of additional information.

The paper describes Commander, a prototype computer program designed to help verify the completeness of a computer-based clinical practice guideline built using if then rules. It also describes the application of Commander to a guideline for childhood immunization. Commander is designed to help identify incomplete rule sets, where there are clinically meaningful conditions to which the guideline does not respond. To allow this, the user defines semantic constraints, in the form of if-then statements, which indicate combinations of conditions which are not meaningful. In an iterative process, Commander takes the guideline rules, together with an increasingly refined set of constraints and helps focus in on any combinations of conditions to which the guideline does not respond. When applied to the clinical guideline for childhood immunization, Commander was able to dramatically reduce the number of potential combinations of conditions for consideration and also identified several areas of incompleteness in the rules.

The authors used a relatively new advertising medium to increase public awareness of their children's hospital. They found that street pole banners, a form of outdoor advertising, made a measurable, positive impression on consumer consciousness. Banners effectively supplemented a product awareness campaign that included more traditional media. This study is the first documentation of the use of banners to market health care services. Using a two-phase approach, respondents were surveyed via telephone before and after exposure. Results of the follow-up survey show significant increases in levels of awareness and preference. The authors hope their report on the successful use of street pole banners will spur further research on the use of this innovative media.

A significant problem faced by immunization registries is that the dates of a patient's previous vaccinations may not be known. These incomplete histories can pose a problem when attempting to use a computer-based guideline to produce patient-specific immunization recommendations automatically. This paper describes an overall approach, together with 3 specific strategies, developed to help deal with this problem. The paper then describes our experience applying the approach to a database containing over 400,000 immunization histories. The paper also discusses a number of the issues raised in adapting a computer-based guideline to accommodate incomplete patient data of this sort.

The Olfactory Receptor Database (ORDB) is a WWW-accessible database that stores data on Olfactory Receptor-like molecules (ORs) and has been open to the public since June 1996. It contains a public and a private area. The public area includes published DNA and protein sequence data for ORs, links to OR models and data on their expression, chromosomal localization and source organism, as well as (i) links to bibliography through PubMed and (ii) interactive WWW-based tools, such as BLAST homology searching. The private area functions as a service to laboratories that are actively cloning receptors. Source laboratories enter the sequences of the receptor clones they have characterized to the private database and can search for identical or near identical OR sequences in both public and private databases. If another laboratory has cloned and deposited an identical or closely matching sequence there are means for communication between the laboratories to help avoid duplication of work. ORDB is available via the WWW at http://crepe.med.yale.edu/ORDB/HTML

What is neuroinformatics? What is the Human Brain Project? Why should you care? Supported by a consortium of US funding agencies, the Human Brain Project aims to bring to the analysis of brain function the same advantages of Internet-accessible databases and database tools that have been crucial to the development of molecular biology and the Human Genome Project. The much greater complexity of neural data, however, makes this a far more challenging task. As a pilot project in this new initiative, we review some of the progress that has been made and indicate some of the problems, challenges and opportunities that lie ahead.

A critical problem in neuroscience is the lack of database tools for integrating neuronal property data. We report here the development of a combined object oriented-relational database (NeuronDB, http://senselab.med.yale.edu/neurondb) that meets these needs by providing tools for integrating data within neurons and comparing data across neurons. It focuses on three types of neuronal properties voltage-gated channels, neurotransmitter receptors, and neurotransmitters. The data are organized in relation to different regions of neurons as represented in canonical forms; using simple canonical models of complex cells as a vehicle for indexing information permits the database to be searchable across different neurons. Using these multidimensional search tools, users can locate specific properties in specific regions of a neuron; obtain integrated summaries of all properties within a region; and carry out searches to compare properties across equivalent compartments in different neurons. These tools thus permit searches of the multidimensional neuron property space equivalent to homology searches of sequence databases. NeuronDB is accessible over the Internet; it provides immediate links to citation indexes and abstracts supporting the deposited data, and annotations that indicate the state of acceptance of the data. Users are encouraged to contribute data. The ability to input the data from NeuronDB directly to NEURON and GENESIS is being developed. As a shared Web resource, NeuronDB should enhance the efforts of neuroscientists and neuronal modellers to analyze and compare the functional operations of different types of neurons.

IMM/Test is a prototype software tool built to generate test cases that can be used to help test and verify the internal logic of an immunization forecasting program. A forecasting program takes as input a child's immunization history and produces recommendations as to which vaccinations are due and which should be scheduled next. IMM/Test was developed to test a specific immunization forecasting program, IMM/Serve. In addition, IMM/Test has been incorporated into a broader Web-based tool, IMM/Web, which allows the user (e.g., a member of an immunization registry staff) to customize the parameters used for immunization forecasting (e.g., the minimum ages for each dose and the minimum wait intervals between doses) to reflect local practice. IMM/Web then generates a customized set of test cases that may be used to test the user's immunization forecasting program. The user may also request that the test cases be automatically passed to IMM/Serve to analyze using the newly defined parameters. The paper describes the internal design of IMM/Test and IMM/Web and discusses certain lessons learned in the implementation of the two programs., (Copyright 1998 Academic Press.)

IMM/Def is a prototype computer program designed to facilitate the building and maintenance of a rule-based program which performs childhood immunization forecasting. An immunization forecasting program takes as input a child's immunization history and produces recommendations as to which vaccinations are due and which should be scheduled next. A significant amount of the knowledge required for immunization forecasting can be expressed in tabular form, including the parameters that indicate the minimum age when each dose may be given and the minimum intervals between doses. The choice of which of these sets of parameters apply to a particular case depends upon additional clinical logic. To perform forecasting, this logic must be applied in three temporal contexts: (1) a dose is due now, (2) a dose is not yet due, and (3) a dose must be scheduled to follow a dose which is due now. Building and maintaining this logic by hand is a formidable challenge. IMM/Def demonstrates how this task can be simplified by first defining immunization "definition logic" which can be automatically translated into if-then rules for each of the three contexts. The approach has been applied successfully to the six childhood vaccination series which are routinely administered. A key advantage is that IMM/Def allows one to have two specifications of the logic that can be examined independently and that can be cross-checked to help assure completeness, consistency, and accuracy of the logic. The paper describes how IMM/Def performs its translation and discusses several design issues and lessons learned., (Copyright 1998 Academic Press.)

ACT/DB is a client-server database application for storing clinical trials and outcomes data, which is currently undergoing initial pilot use. It stores most of its data in entity-attribute-value form. Such data are segregated according to data type to allow indexing by value when possible, and binary large object data are managed in the same way as other data. ACT/DB lets an investigator design a study rapidly by defining the parameters (or attributes) that are to be gathered, as well as their logical grouping for purposes of display and data entry. ACT/DB generates customizable data entry. The data can be viewed through several standard reports as well as exported as text to external analysis programs. ACT/DB is designed to encourage reuse of parameters across multiple studies and has facilities for dictionary search and maintenance. It uses a Microsoft Access client running on Windows 95 machines, which communicates with an Oracle server running on a UNIX platform. ACT/DB is being used to manage the data for seven studies in its initial deployment.

As clinical practice guidelines are increasingly implemented in computer-based form, a major challenge will be to maintain their domain knowledge as new national recommendations are developed and as local customization is required. This maintenance may also need to be performed for any computer-based tools developed to help in the guideline knowledge maintenance process itself. This paper uses the domain of childhood immunization to explore certain issues involved. It describes 1) two recent changes to the national recommendations dealing with the DTP and Polio vaccine series, and 2) several customizations requested by the immunization registries of the State of Oregon and the US Indian Health Service. It then describes how these guideline practice variations are currently handled in three computer-based tools, IMM/Serve, IMM/Def, and IMM/Test. Finally, it discusses how the use of these tools can provide one approach to characterizing the complexity of guideline variations.

IMM/Graph is a visual model designed to help knowledge-base developers understand and refine the guideline logic for childhood immunization. The IMM/Graph model is domain-specific and was developed to help build a knowledge-based system that makes patient-specific immunization recommendations. A "visual vocabulary" models issues specific to the immunization domain, such as (1) the age a child is first eligible for each vaccination dose, (2) recommended, "past due" and maximum ages, (3) minimum waiting periods between doses, (4) the vaccine brand or preparation to be given, and (5) the various factors affecting the time course of vaccination. Several lessons learned in the course of developing IMM/Graph include the following: (1) The intended use of the model may influence the choice of visual presentation; (2) There is a potentially interesting interplay between the use of visual and textual information in creating the visual model; (3) Visualization may help a development team better understand a complex clinical guideline and may also help highlight areas of incompleteness.

IMM/Serve is a computer program which implements the clinical guidelines for childhood immunization. IMM/Serve accepts as input a child's immunization history. It then indicates which vaccinations are due and which vaccinations should be scheduled next. The clinical guidelines for immunization are quite complex and are modified quite frequently. As a result, it is important that IMM/Serve's knowledge be represented in a format that facilitates the maintenance of that knowledge as the field evolves over time. To achieve this goal, IMM/Serve uses four representations for different parts of its knowledge base: (1) Immunization forecasting parameters that specify the minimum ages and wait-intervals for each dose are stored in tabular form. (2) The clinical logic that determines which set of forecasting parameters applies for a particular patient in each vaccine series is represented using if-then rules. (3) The temporal logic that combines dates, ages, and intervals to calculate recommended dates, is expressed procedurally. (4) The screening logic that checks each previous dose for validity is performed using a decision table that combines minimum ages and wait intervals with a small amount of clinical logic. A knowledge maintenance tool, IMM/Def, has been developed to help maintain the rule-based logic. The paper describes the design of IMM/Serve and the rationale and role of the different forms of knowledge used.

Motivation: The increasing availability of biological databases on the World-Wide Web and hypertext links between them has made a wealth of information easily accessible to biologists. Additional retrieval capabilities can be achieved by storing explicitly specified biological relationships between different entities as discrete database entries., Results: We have built CySPID, a prototype database about the cytoskeleton that explores the approach of explicitly representing biological relationships. The stored relationships are displayed along with other retrieved information, can be used to make hyperlinks to related entities, and can be used to search for entities with specified properties. CySPID is extensible in that new types of relationships may be created without altering the database schema., Availability: CySPID is available for public use (http://ycmi.med.yale.edu/cyspid/). The CGI scripts used by CySPID are available upon request.

An olfactory receptor database (ORDB) is being developed to facilitate analysis of this large gene family. ORDB currently contains over 400 olfactory receptor sequences and related information, and is available via the World Wide Web. We plan to incorporate functional data, structural models, spatial localization and other categories of information, toward an integrated model of olfactory receptor function.

The Integrated Advanced Information Management System (IAIMS) program promotes an integrated approach to information management within a medical center. Since the IAIMS program was conceived, many of the initial IAIMS technologic needs have been quite widely achieved or are planned for implementation in many medical centers. At the same time, the IAIMS frontier is being steadily pushed to new issues that need to be addressed to achieve the full power of the IAIMS vision. The paper discusses 1) levels of integration where IAIMS has been successfully pursued to date and 2) challenging areas in which research is required to approach the full potential of the IAIMS in the future.

Objective: To evaluate use of information resources during the first year of IAIMS implementation at the Yale-New Haven Medical Center. The evaluation asked: (1) Which information resources are being used? (2) Who uses information resources? (3) Where are information resources used? (4) Are multiple sources of information being integrated?, Design: Measures included monthly usage data for resources delivered network-wide, in the Medical Library, and in the Hospital; online surveys of library workstation users; an annual survey of a random, stratified sample of Medical Center faculty, postdoctoral trainees, students, nurses, residents, and managerial and professional staff; and user comments., Results: Eighty-three percent of the Medical Center community use networked information resources, and use of resources is increasing. Both status (faculty, student, nurse, etc.) and mission (teaching, research, patient care) affect use of individual resources. Eighty-eight percent of people use computers in more than one location, and increases in usage of traditional library resources such as MEDLINE are due to increased access from outside the Library. Both survey and usage data suggest that people are using multiple resources during the same information seeking session., Conclusions: Almost all of the Medical Center community is using networked information resources in more settings. It is necessary to support increased demand for information access from remote locations and to specific populations, such as nurses. People are integrating information from multiple sources, but true integration within information systems is just beginning. Other institutions are advised to incorporate pragmatic evaluation into their IAIMS activities and to share evaluation results with decision-makers.

Kidney biopsies from Pima Indians with type II diabetes were analyzed. Subjects were classified clinically as having early diabetes (n = 10), microalbuminuria (n = 17), normoalbuminuria, despite a duration of diabetes equal to that of the subjects with microalbuminuria (n = 12), or clinical nephropathy (n = 12). Subjects with microalbuminuria exhibited moderate increases in glomerular and mesangial volume when compared with those with early diabetes, but could not be distinguished from subjects who remained normoalbuminuric after an equal duration of diabetes. Subjects with clinical nephropathy exhibited global glomerular sclerosis and more prominent structural abnormalities in nonsclerosed glomeruli. Marked mesangial expansion was accompanied by a further increase in total glomerular volume. Glomerular capillary surface area remained stable, but the glomerular basement membrane thickness was increased and podocyte foot processes were broadened. Broadening of podocyte foot processes was associated with a reduction in the number of podocytes per glomerulus and an increase in the surface area covered by remaining podocytes. These findings suggest that podocyte loss contributes to the progression of diabetic nephropathy.

IMM/Web is a prototype Web site designed to assist in the maintenance of the knowledge required to perform computer-based forecasting for childhood immunization. IMM/Web operates in conjunction with IMM/Serve, a immunization forecasting program that takes a child's immunization history and produces recommendations as to which vaccinations are due, and which should be scheduled next. IMM/Serve's domain knowledge is expressed in both tabular and rule-based form. Using IMM/Web, the various tabular forecasting parameters can be modified via the Web. Test cases can then be generated automatically which can be used to help verify the new version of logic. Finally, the test cases can be automatically passed for IMM/Serve to analyze using the newly defined parameters. The IMM/Web project is exploring how the process of updating, customizing, and testing new versions of a computer-based clinical guideline might be performed and guided in an organized fashion via the World-Wide Web.

Research groups within the Human Brain Project are developing technologies to help organize and make accessible the vast quantities of information being accumulated in the neurosciences. The goal of this work is to provide systems that enable this complex information from many diverse sources to be synthesized into a coherent theory of nervous system function. Our initial approach to this problem has been to create several small databases. While addressing the issues of each individual database, we are also considering how each might be incorporated into an integrated cluster of databases. In this paper, we describe a pilot project in which we construct a database of computational models of neuronal function. This database allows models to be created and run and their results reviewed through a World Wide Web interface. Because models encapsulate knowledge in a formal manner about how neuronal systems function, we also discuss how this database forms a natural center for our initial attempts at creating a cluster of related databases. General issues of database development in the context of the Web are also discussed.

Sperm competition can be a powerful selective force in the evolution of mating systems. Several odonate species have attracted study to assess the extent and mechanism of last-male sperm precedence. Members of the genus Ischnura (Zygoptera) display a particularly interesting range of mating systems, and Ischnura elegans was selected for study. Polymorphic microsatellites were cloned, sequenced and used to determine paternity of I. elegans larvae, to reveal patterns of sperm precedence. More than 3000 larvae, collected from both wild and captively bred I. elegans females, were typed for one or two microsatellite loci and paternity was determined by comparison with parental genotypes. Microsatellite typing showed that most wild-caught females had mated with several males. Analysis of offspring from females which mated in captivity showed that multiple-matings result in a large proportion of last-male sperm precedence (mean value for immediate last male precedence is 0.79 +/- 0.2 (+/- s.d.; n = 11, range = 0.44-1)). There is appreciable variation in the extent and patterns of immediate and longer-term precedence, which could reflect differences in male sperm removal ability or selective use of sperm by females.

A rule-based program, IMM/Serve, is being developed to help guide childhood immunization for initial use, within Oregon. The program is designed primarily for automated use with an online immunization registry, but can also be used interactively by a single user. The paper describes IMM/Serve and discusses 1) the sources of complexity in immunization logic, 2) the potential advantages of a rule-based approach for representing that logic, and 3) the potential advantage of such a program evolving to become the standard of care. Related projects include 1) a computer-based tool to help verify the completeness of the logic, 2) a tool that allows a central part of the logic to be generated automatically, and 3) an approach that allows visualization of the logic graphically.

Objective: To examine the issues involved in mapping an existing structured controlled vocabulary, the Medical Entities Dictionary (MED) developed at Columbia University, to an institutional vocabulary, the laboratory and pharmacy vocabularies of the Yale New Haven Medical Center., Design: 200 Yale pharmacy terms and 200 Yale laboratory terms were randomly selected from database files containing all of the Yale laboratory and pharmacy terms. These 400 terms were then mapped to the MED in three phases: mapping terms, mapping relationships between terms, and mapping attributes that modify terms., Results: 73% of the Yale pharmacy terms mapped to MED terms. 49% of the Yale laboratory terms mapped to MED terms. After certain obsolete and otherwise inappropriate laboratory terms were eliminated, the latter rate improved to 59%. 23% of the unmatched Yale laboratory terms failed to match because of differences in granularity with MED terms. The Yale and MED pharmacy terms share 12 of 30 distinct attributes. The Yale and MED laboratory terms share 14 of 23 distinct attributes., Conclusion: The mapping of an institutional vocabulary to a structured controlled vocabulary requires that the mapping be performed at the level of terms, relationships, and attributes. The mapping process revealed the importance of standardization of local vocabulary subsets, standardization of attribute representation, and term granularity.

The Yale Center for Medical Informatics has offered Medical Informatics training since 1986. The paper describes the overall structure of the training program, focusing primarily on the postdoctoral fellowship, a major component of which involves an independent project which the fellow carries out under faculty supervision. The paper outlines a number of areas in which such projects have been performed, describes the previous backgrounds and post-training career directions of the trainees, and discusses certain observations based on our experience with the program.

This paper describes an approach that provides Internet-based support for a genome center to map human chromosome 12, as a collaboration between laboratories at the Albert Einstein College of Medicine in Bronx, New York, and the Yale University School of Medicine in New Haven, Connecticut. Informatics is well established as an important enabling technology within the genome mapping community. The goal of this paper is to use the chromosome 12 project as a case study to introduce a medical informatics audience to certain issues involved in genome informatics and in the Internet-based support of collaborative bioscience research. Central to the approach described is a shared database (DB/12) with Macintosh clients in the participating laboratories running the 4th Dimension database program as a user-friendly front end, and a Sun SPARCstation-2 server running Sybase. The central component of the database stores information about yeast artificial chromosomes (YACs), each containing a segment of human DNA from chromosome 12 to which genome markers have been mapped, such that an overlapping set of YACs (called a "contig") can be identified, along with an ordering of the markers. The approach also includes 1) a map assembly tool developed to help biologists interpret their data, proposing a ranked set of candidate maps, 2) the integration of DB/12 with external databases and tools, and 3) the dissemination of the results. This paper discusses several of the lessons learned that apply to many other areas of bioscience, and the potential role for the field of medical informatics in helping to provide such support.

Study Design: The biomechanical stability of three different methods of cervical spine stabilization was evaluated in a porcine model. Specimens were tested in flexion, extension, and axial rotation., Objectives: Our goal was to determine if posterior lateral mass plating after anterior reconstruction provided more stability compared with unicortical or bicortical anterior plate fixation after a simulated corpectomy., Summary of Background Data: Previous implant biomechanical evaluations use ligamentous and intervertebral disc disruption models under constrained and nonrepetitive loading. This study examines implant performance using a corpectomy model loaded for multiple cycles, allowing for unconstrained motion., Methods: Twenty-one porcine cervical spines were destabilized with a one-level cervical corpectomy and reconstructed with an anterior methacrylate graft. Each construct was stabilized with either an AO Morscher plate system with unicortical, self-locking screws; a Caspar plate with biocortical screws; or two posterior lateral mass plates. Testing with cyclic loads was performed on an MTS machine in flexion, extension, and axial rotation., Results: There was no statistical difference between the two anterior forms of fixation in flexion, extension, or axial rotation. Posterior lateral mass plating was significantly more stable than either anterior construct. Screw loosening was seen more frequently with bicortical Caspar plating., Conclusions: After a single-level cervical corpectomy and idealized grafting, all three surgical constructs provided stability equal to or greater than the intact condition in flexion, extension, and axial rotation. In unstable cervical spine injury patterns involving anterior disruption, this study supports the use of anterior grafting combined with posterior lateral mass plating to achieve maximum stability.

Objective: To explore the software design issues involved in implementing an operational information sources map (ISM) knowledge base (KB) and system of navigational tools that can help medical users access network-based information sources relevant to a biomedical question., Design: A pilot biomedical ISM KB and associated client-server software (ISM/Explorer) have been developed to help students, clinicians, researchers, and staff access network-based information sources, as part of the National Library of Medicine's (NLM) multi-institutional Unified Medical Language System (UMLS) project. The system allows the user to specify and constrain a search for a biomedical question of interest. The system then returns a list of sources matching the search. At this point the user may request 1) further information about a source, 2) that the list of sources be regrouped by different criteria to allow the user to get a better overall appreciation of the set of retrieved sources as a whole, or 3) automatic connection to a source., Results: The pilot system operates in client-server mode and currently contains coded information for 121 sources. It is in routine use from approximately 40 workstations at the Yale School of Medicine. The lessons that have been learned are that: 1) it is important to make access to different versions of a source as seamless as possible, 2) achieving seamless, cross-platform access to heterogeneous sources is difficult, 3) significant differences exist between coding the subject content of an electronic information resource versus that of an article or a book, 4) customizing the ISM to multiple institutions entails significant complexities, and 5) there are many design trade-offs between specifying searches and viewing sets of retrieved sources that must be taken into consideration., Conclusion: An ISM KB and navigational tools have been constructed. In the process, much has been learned about the complexities of development and evaluation in this new environment, which are different from those for Gopher, wide area information servers (WAIS), World-Wide-Web (WWW), and MOSAIC resources.

Sophisticated network-based informatics support will increasingly be required for collaborating biomedical laboratories located in different geographic locations, both to accommodate the massive amount of data being generated in certain fields, and to allow different types of data produced at different laboratories to be analyzed in an integrated fashion. The paper describes the experience of the Yale Center for Medical Informatics in providing informatics support for collaborative projects in gene mapping (as part of the national Human Genome Project) and neuroscience (as part of the national Human Brain Project). The paper describes the informatics needs of the two projects and the solutions being developed, describes certain lessons learned, and discusses certain broader issues that arise.

Building a map of restriction sites from double-digest gel data can be a complex and frustrating task, especially when many DNA fragments are detected or when the gel results are ambiguous. 'Double Digester' is an interactive, graphical computer program which helps researchers understand and resolve such data. It explicitly represents the experimental data, the associated uncertainties, the researcher's hypotheses and possible map interpretations. Alternative solutions are frequently possible, and the differences between them may help determine which additional experiments might resolve ambiguities. Initial use has confirmed the benefits of this approach, and has suggested ways in which it can be refined and extended. Double Digester meets the need for a practical tool to help build restriction maps, and also illustrates how a computer-based tool can confront experimental uncertainty in an integrated fashion.

Expert system applications in the biomedical domain have long been hampered by the difficulty inherent in maintaining and extending large knowledge bases. We have developed a knowledge-based method for automatically augmenting such knowledge bases. The method consists of automatically integrating data contained in commercially available, external, online databases with data contained in an expert system's knowledge base. We have built a prototype system, named DBX, using this technique to augment an expert system's knowledge base as a decision support aid and as a bibliographic retrieval tool. In this paper, we describe this prototype system in detail, illustrate its use, and discuss the lessons we have learned in its implementation.

This study examined the consequences of nephrectomy in United States Army personnel who lost a kidney due to trauma during World War II (WWII). Records of 62 servicemen who underwent nephrectomy at an average age of 25 years were obtained. Mortality was compared with that of WWII servicemen of the same age. Medical records of 28 deceased subjects were reviewed for evidence of kidney disease. Medical histories were obtained and blood pressure and kidney function were assessed in 28 living subjects. Two subjects could not be located, and four subjects declined to participate. Mortality at 45 years was not increased in nephrectomized subjects. Kidney disease present in six of 28 deceased subjects was attributable to causes other than prior nephrectomy. Glomerular sclerosis was not increased in 10 subjects who had autopsy examinations. The prevalence of hypertension was not increased in living subjects. Five of 28 living subjects had abnormal renal function manifested by proteinuria greater than 250 mg/day in four cases (range: 377 to 535 mg/day) and serum creatinine levels greater than 1.5 mg/dl in three cases (range: 1.7 to 1.9 mg/dl). Conditions other than nephrectomy could have contributed to impairment of renal function in each of these subjects. These findings suggest that uninephrectomy in young adults has few major adverse consequences over 45 years.

As computer technology advances, clinicians and biomedical researchers are becoming more dependent upon information from online databases and information systems. By using specially configured computer workstations and high-speed computer networks, it is now possible to access this information in a rapid and straightforward manner. To empower users by providing these capabilities, the authors are assembling a variety of network workstations to be located throughout Yale-New Haven Medical Center. At the heart of the workstation is NetMenu, a program designed to help users connect to a number of important online information systems, including a hospital order entry and results reporting system, a drug reference, bibliographic retrieval systems, and educational programs. In addition, as part of the National Library of Medicine's Unified Medical Language System (UMLS) project, the authors have developed a local prototype of the UMLS Information Sources Map (ISM) and a companion query assistant program to complement the NetMenu in helping users select and connect automatically to information services relevant to a particular question. The ISM query assistant draws from a listing of many online information sources accessible via local and international networks.

Clinicians in patient care settings must be able to locate relevant recent medical literature quickly. Computer literacy is increasing, but many clinicians remain ill at ease with search strategies for online bibliographic databases. As part of an ongoing project to simplify the translation of clinical questions into effective searches, a Unified Medical Language System (UMLS) Metathesaurus tool was designed. The authors compared bibliographic searches by relatively inexperienced users employing only GRATEFUL MED to searches done using GRATEFUL MED augmented with this tool. The users were clinicians examining questions related to a test set of clinical cases. Their problems and successes were monitored; the results suggest that the addition of a thesaurus helps resolve some problems in citation retrieval that trouble the novice user. By helping the user understand indexing terms in context and by reducing typing errors, a thesaurus can help provide an intelligent solution to lexical mismatches in bibliographic retrieval.

This paper describes a prototype information sources map (ISM), an on-line information source finder, for Occupational and Environmental Medicine (OEM). The OEM ISM was built as part of the Unified Medical Language System (UMLS) project of the National Library of Medicine. It allows a user to identify sources of on-line information appropriate to a specific OEM question, and connect to the sources. In the OEM ISM we explore a domain-specific method of indexing information source contents, and also a domain-specific user interface. The indexing represents a domain expert's opinion of the specificity of an information source in helping to answer specific types of domain questions. For each information source, an index field represents whether a source might provide useful information in an occupational, industrial, or environmental category. Additional fields represent the degree of specificity of a source in individual question types in each category. The paper discusses the development, design, and implementation of the prototype OEM ISM.

NetMenu is a program, developed at Yale, which enables straightforward access to online information systems. NetMenu has been deployed in several diverse settings within our medical center. In the hospital, NetMenu is functioning as a front-end for our clinical workstation providing access to the hospital information system, the clinical laboratory computer, a drug database and several bibliographic databases. The medical libraries are utilizing NetMenu for both medical education workstations and for scholarly information workstations. This paper describes our initial experience in the implementation, support, and maintenance of NetMenu as an institutional menu of information sources.

Psych Topix is a knowledge-based program which guides the clinician from an on-line clinical report to a search of the psychiatric literature or of other relevant databases. It provides this guidance by using an outline of key topics in a clinical field to provide "concept-based" links. Each topic is augmented with an activation expression to signal when that topic is potentially relevant to a case, and with database search expressions to allow focused retrieval of information. The bibliographic retrieval component of Psych Topix is currently operational as part of the daily, routine operation of a psychiatric consultation service. The system is also implemented in a demonstration mode to provide retrieval from three additional textual databases. The current Psych Topix system provides a working demonstration of the clinical feasibility of using concept-based links to facilitate the focused, automated transition between on-line medical databases.