On Contributing to the Progress of Medical Informatics as Publisher.

May 1st, 2017, will mark Dieter Bergemann's 80th birthday. As Chief Executive Officer and Owner of Schattauer Publishers from 1983 to 2016, the biomedical and health informatics community owes him a great debt of gratitude. The past and present editors of Methods of Information in Medicine, the IMIA Yearbook of Medical Informatics, and Applied Clinical Informatics want to honour and thank Dieter Bergemann by providing a brief biography that emphasizes his contributions, by reviewing his critical role as an exceptionally supportive publisher for Schattauer's three biomedical and health informatics periodicals, and by sharing some personal anecdotes. Over the past 40 years, Dieter Bergemann has been an influential, if behind-the-scenes, driving force in biomedical and health informatics publications, helping to ensure success in the dissemination of our field's research and practice.

The Renewed Promise of Medical Informatics.

The promise of the field of Medical Informatics has been great and its impact has been significant. In 1999, the Yearbook editors of the International Medical Informatics Association (IMIA) - also the authors of the present paper - sought to assess this impact by selecting a number of seminal papers in the field, and asking experts to comment on these articles. In particular, it was requested whether and how the expectations, represented by these papers, had been fulfilled since their publication several decades earlier. Each expert was also invited to comment on what might be expected in the future. In the present paper, these areas are briefly reviewed again. Where did these early papers have an impact and where were they not as successful as originally expected? It should be noted that the extraordinary developments in computer technology observed in the last two decades could not have been foreseen by these early researchers. In closing, some of the possibilities and limitations of research in medical informatics are outlined in the context of a framework that considers six levels of computer applications in medicine and health care. For each level, some predictions are made for the future, concluded with thoughts on fruitful areas for ongoing research in the field.

The birth and evolution of a discipline devoted to information in biomedicine and health care. As reflected in its longest running journal.

BACKGROUND: The journal Methods of Information in Medicine, founded in 1962, has now completed its 50th volume. Its publications during the last five decades reflect the formation of a discipline that deals with information in biomedicine and health care. OBJECTIVES: To report about 1) the journal's origin, 2) the individuals who have significantly contributed to it, 3) trends in the journal's aims and scope, 4) influential papers and 5) major topics published in Methods over the years. METHODS: Methods included analysing the correspondence and journal issues in the archives of the editorial office and of the publisher, citation analysis using the ISI and Scopus databases, and analysing the articles' Medical Subject Headings (MeSH) in MEDLINE. RESULTS: In the journal's first 50 years 208 editorial board members and/or editors contributed to the journal's development, with most individuals coming from Europe and North America. The median time of service was 11 years. At the time of analysis 2,456 articles had been indexed with MeSH. Topics included computerized systems of various types, informatics methodologies, and topics related to a specific medical domain. Some MeSH topic entries were heavily and regularly represented in each of the journal's five decades (e.g. information systems and medical records), while others were important in a particular decade, but not in other decades (e.g. punched-card systems and systems integration). Seven papers were cited more than 100 times and these also covered a broad range of themes such as knowledge representation, analysis of biomedical data and knowledge, clinical decision support and electronic patient records. CONCLUSIONS: Methods of Information in Medicine is the oldest international journal in biomedical informatics. The journal's development over the last 50 years correlates with the formation of this new discipline. It has and continues to stress the basic methodology and scientific fundamentals of organizing, representing and analysing data, information and knowledge in biomedicine and health care. It has and continues to stimulate multidisciplinary communication on research that is devoted to high-quality, efficient health care, to quality of life and to the progress of biomedicine and the health sciences.

Data analysis and data mining: current issues in biomedical informatics.

BACKGROUND: Medicine and biomedical sciences have become data-intensive fields, which, at the same time, enable the application of data-driven approaches and require sophisticated data analysis and data mining methods. Biomedical informatics provides a proper interdisciplinary context to integrate data and knowledge when processing available information, with the aim of giving effective decision-making support in clinics and translational research. OBJECTIVES: To reflect on different perspectives related to the role of data analysis and data mining in biomedical informatics. METHODS: On the occasion of the 50th year of Methods of Information in Medicine a symposium was organized, which reflected on opportunities, challenges and priorities of organizing, representing and analysing data, information and knowledge in biomedicine and health care. The contributions of experts with a variety of backgrounds in the area of biomedical data analysis have been collected as one outcome of this symposium, in order to provide a broad, though coherent, overview of some of the most interesting aspects of the field. RESULTS: The paper presents sections on data accumulation and data-driven approaches in medical informatics, data and knowledge integration, statistical issues for the evaluation of data mining models, translational bioinformatics and bioinformatics aspects of genetic epidemiology. CONCLUSIONS: Biomedical informatics represents a natural framework to properly and effectively apply data analysis and data mining methods in a decision-making context. In the future, it will be necessary to preserve the inclusive nature of the field and to foster an increasing sharing of data and methods between researchers.

Methods in year 50: preserving the past and preparing for the future.

BACKGROUND: Founded in 1962 and, therefore, the oldest international journal in medical informatics, Methods of Information in Medicine will publish its 50th volume in 2011. At the start of the journal's sixth decade, a discussion on the journal's profile seems appropriate. OBJECTIVES: To report on the new opportunities for online access to Methods publications as well as on the recent strategic decisions regarding the journal's aims and editorial policies. METHODS: Describing and analyzing the journal's aims and scope. Reflecting on recent publications and on the journal's development during the last decade. RESULTS: From 2011 forward all articles of Methods from 1962 until the present can be accessed online. Methods of Information in Medicine stresses the basic methodology and scientific fundamentals of processing data, information and knowledge in medicine and health care. Although the journal's major focus is on publications in medical informatics, it has never been restricted to publications only in this discipline. For example, articles in medical biometry, in or close to biomedical engineering, and, later, articles in bioinformatics continue to be a part of this journal. CONCLUSIONS: There is a continuous and, as it seems, ever growing overlap in the research methodology and application areas of the mentioned disciplines. As there is a continuing and even growing need for such a publication forum, Methods of Information in Medicine will keep its broad scope. As an organizational consequence, the journal's number of associate editors has increased accordingly.

The Student Editorial Board of Methods of Information in Medicine--an opportunity to educate tomorrow's peer reviewers.

OBJECTIVE: Peer review is a critical process in the publication of scientific findings; trainees and young investigators, however, have few opportunities to learn systematically how to review manuscripts. Journal editors have an opportunity to engage trainees and young investigators in the peer review process early during their career. METHODS: Methods of Information in Medicine, an official journal of the International Medical Informatics Association, is initiating a Student Editorial Board. The journal invites applications from international graduate and post-doctoral training programs that have a focus on health informatics, biomedical informatics, or a related field. RESULTS: Each year up to six trainees will be invited to join the Student Editorial Board. The trainees will go through a mentored training experience that includes an active involvement in the various aspects of peer review during their one to two-year term of appointment. CONCLUSIONS: The journal expects that the Student Editorial Board will benefit trainees and young investigators in becoming skilled reviewers and engaged peers who can offer professional, constructive, and informative feedback and enhance the process of scientific communication.

Optimization of cutaneous electrically mediated plasmid DNA delivery using novel electrode.

The easy accessibility of skin makes it an excellent target for gene transfer protocols. To take advantage of skin as a target for gene transfer, it is important to establish an efficient and reproducible delivery system. Electroporation is an established technique for enhancing plasmid delivery to many tissues in vivo. A critical component of this technique is the electrode configuration. Electroporation parameters were optimized for transgene expression with minimal tissue damage with a novel electrode. The highest transgene expression and efficiency of individual cell transformation with minimal damage was produced with eight 150 ms pulses at field strength of 100 V/cm. This electrode design offers the potential for easier and more reproducible electrically mediated cutaneous plasmid delivery than the simple electrodes currently commercially available. This electrode can be a valuable tool in determining the applicability of electrically mediated cutaneous gene transfer.

Triangulation applied to Jan H. van Bemmel.

OBJECTIVE: To describe the person of Jan H. van Bemmel from different points of view. METHOD: Triangulation. RESULTS AND CONCLUSIONS: Jan H. van Bemmel successfully contributed to research and education in medical informatics. He inspired a lot of people in The Netherlands and internationally.

On exemplary scientific conduct regarding submission of manuscripts to biomedical informatics journals.

As the Editors of leading international biomedical informatics journals, the authors report on a recent pattern of improper manuscript submissions to journals in our field. As a guide for future authors, we describe ethical and pragmatic issues related to submitting work for peer-reviewed journal publication. We propose a coordinated approach to the problem that our respective journals will follow. This Editorial is being jointly published in the following journals represented by the authors: Computer Methods and Programs in Biomedicine, International Journal of Medical Informatics, Journal of Biomedical Informatics, Journal of the American Medical Informatics Association, and Methods of Information in Medicine.

From phenotype to genotype: issues in navigating the available information resources.

OBJECTIVES: As part of an investigation of connecting health professionals and the lay public to both disease and genomic information, we assessed the availability and nature of the data from the Human Genome Project relating to human genetic diseases. METHODS: We focused on a set of single gene diseases selected from main topics in MEDLINEplus, the NLM's principal resource focused on consumers. We used publicly available websites to investigate specific questions about the genes and gene products associated with the diseases. We also investigated questions of knowledge and data representation for the information resources and navigational issues. RESULTS: Many online resources are available but they are complex and technical. The major challenges encountered when navigating from phenotype to genotype were (1) complexity of the data, (2) dynamic nature of the data, (3) diversity of foci and number of information resources, and (4) lack of use of standard data and knowledge representation methods. CONCLUSIONS: Three major informatics issues arise from the navigational challenges. First, the official gene names are insufficient for navigation of these web resources. Second, navigational inconsistencies arise from difficulties in determining the number and function of alternate forms of the gene or gene product and maintaining currency with this information. Third, synonymy and polysemy cause much confusion. These are severe obstacles to computational navigation from phenotype to genotype, especially for individuals who are novices in the underlying science. Tools and standards to facilitate this navigation are sorely needed.

Aggregating UMLS semantic types for reducing conceptual complexity.

The conceptual complexity of a domain can make it difficult for users of information systems to comprehend and interact with the knowledge embedded in those systems. The Unified Medical Language System (UMLS) currently integrates over 730,000 biomedical concepts from more than fifty biomedical vocabularies. The UMLS semantic network reduces the complexity of this construct by grouping concepts according to the semantic types that have been assigned to them. For certain purposes, however, an even smaller and coarser-grained set of semantic type groupings may be desirable. In this paper, we discuss our approach to creating such a set. We present six basic principles, and then apply those principles in aggregating the existing 134 semantic types into a set of 15 groupings. We present some of the difficulties we encountered and the consequences of the decisions we have made. We discuss some possible uses of the semantic groups, and we conclude with implications for future work.

Evaluating UMLS strings for natural language processing.

The National Library of Medicine's Unified Medical Language System (UMLS) is a rich source of knowledge in the biomedical domain. The UMLS is used for research and development in a range of different applications, including natural language processing (NLP). In this paper we investigate the nature of the strings found in the UMLS Metathesaurus and evaluate them for their usefulness in NLP. We begin by identifying a number of properties that might allow us to predict the likelihood of a given string being found or not found in a corpus. We use a statistical model to test these predictors against our corpus, which is derived from the MEDLINE database. For one set of properties the model correctly predicted 77% of the strings that do not belong to the corpus, and 85% of the strings that do belong to the corpus. For another set of properties the model correctly predicted 96% of the strings that do not belong to the corpus and 29% of the strings that do belong to the corpus.

Usability issues in developing a Web-based consumer health site.

ClinicalTrials.gov is a Web-based system intended for a diverse audience, including patients, family members and other members of the public. Throughout the system design and development process, our decisions have been driven by usability concerns. We first describe the overall design of the site, including the home page, which provides a site overview and rapid access to the information contained within it. Next we discuss the data presentation format which has been standardized in spite of data coming to us from many different sources. We provide a detailed description of the search and browse features that are intended to simplify the complexities of medical terminology and support information discovery. We conclude with a review of our evaluation activities and future plans.

Better access to information about clinical trials.

Access to information about clinical trials is important to researchers, health care professionals, and patients. Many have argued for the establishment of clinical trials registries, citing their substantial benefits. Although some registries do exist, it has been difficult to create comprehensive, easily accessible systems. This paper briefly reviews existing registries, discusses the challenges in building registries, and reviews some of their benefits. The paper concludes with a description of a new, extensive Web-based registry called ClinicalTrials.gov (http://clinicaltrials. gov/), which was developed at the National Institutes of Health (NIH) by the National Library of Medicine as a result of recent legislation calling for a comprehensive, publicly accessible registry of clinical trials. The first version of the system became available in late February 2000 and contains information about approximately 5000 trials. The first release contains primarily NIH-sponsored trials, and new trials are regularly added to the system. Subsequent versions will contain information about trials sponsored by other federal agencies and by the private sector. The system was developed in accordance with basic informatics principles, including adherence to standards, usability considerations, and iterative testing and evaluation.

Digital library research and application.

The last decade has seen an exponential rise in the amount and the nature of information that is available on the Internet. Internet and World Wide Web technology have raised many technical as well as social and economic issues. The paper begins with a description of the recent digital library research initiative funded by the U.S. federal government. Digital library research addresses a host of informatics issues relevant to the current Internet-based environment. The paper continues with a discussion of some problems in information access, including a discussion of the potential of the Unified Medical Language System for navigating among multiple biomedical information systems. Next, some issues in creating Web-accessible resources for health care consumers are addressed, with a focus on recent work at the National Library of Medicine, including a description of the MEDLINEplus system. The paper ends with a brief discussion of some implications of digital library research for the health informatics community.

Design and implementation of a national clinical trials registry.

The authors have developed a Web-based system that provides summary information about clinical trials being conducted throughout the United States. The first version of the system, publicly available in February 2000, contains more than 4,000 records representing primarily trials sponsored by the National Institutes of Health. The impetus for this system has come from the Food and Drug Administration (FDA) Modernization Act of 1997, which mandated a registry of both federally and privately funded clinical trials "of experimental treatments for serious or life-threatening diseases or conditions." The system design and implementation have been guided by several principles. First, all stages of system development were guided by the needs of the primary intended audience, patients and other members of the public. Second, broad agreement on a common set of data elements was obtained. Third, the system was designed in a modular and extensible way, and search methods that take extensive advantage of the National Library of Medicine's Unified Medical Language System (UMLS) were developed. Finally, since this will be a long-term effort involving many individuals and organizations, the project is being implemented in several phases.