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An open medical imaging workstation architecture for platform-independent 3-D medical image processing and visualization.

A need for an entirely new medical workstation design was identified to increase the deployment of 3-D medical imaging and multimedia communication. Recent wide acceptance of the Word Wide Web (WWW) as a general communication service within the global network has shown how big the impact of standards and open systems can be. Information is shared among heterogeneous systems and diverse applications on various hardware platforms only by agreeing on a common format for information distribution. For medical image communications, the Digital Imaging and Communication in Medicine (DICOM) standard is possibly anticipating such a role. Logically, the next step is open software: platform-independent tools, which can as easily be transferred and used on multiple platforms. Application of the platform-independent programming language Java enables creation of plug-in tools, which can easily extend the basic system. Performance problems inherent to all interpreter systems can be circumvented by using a hybrid approach. Computationally intensive functions like image processing functions can be integrated into a natively implemented optimized image processing kernel. Plug-in tools implemented in Java can utilize the kernel functions via a Java-wrapper library. This approach is comparable to the implementation of computationally intensive operations in hardware.

Computer Communication Networks↗

Automatic particle detection through efficient Hough transforms.

Manual selection of single particles in images acquired using cryo-electron microscopy (cryoEM) will become a significant bottleneck when a very large number of images are required to achieve three-dimensional reconstructions at near atomic resolution. Investigation of fast, accurate approaches for automatic particle detection has become one of the current challenges in the cryoEM community. At the same time, the investigation is hampered by the fact that few benchmark particles or image datasets exist in the community. The unavailability of such data makes it difficult to evaluate newly developed algorithms and to leverage expertise from other disciplines. The paper presents our recent contribution to this effort. It also describes our newly developed computational framework for particle detection, through the application of edge detection and a sequence of ordered Hough transforms. Experimental results using keyhole limpet hemocyanin (KLH) as a model particle are very promising. In addition, it introduces a newly established web site, designed to support the investigation of automatic particle detection by providing an annotated image dataset of KLH available to the general scientific community.

Algorithms↗

Public health education and practice using geographic information system technology.

The use of geographic information system (GIS) technology allows public health practitioners to explore disparities in health, analyze disease outbreaks, and prioritize the use of limited resources for improving population health. Nursing students benefit from use of World Wide Web GIS resources as they develop knowledge and skill in assessing population health and planning interventions. This article identifies the benefits of GIS for public health practitioners, presents a communicable disease control application of GIS, and discusses a GIS module used in an undergraduate nursing education course. Uniform standards for making health data available for public use with GIS are discussed.

Diffusion of Innovation↗

Decision support for diagnosis of lyme disease.

This paper describes the development of a Bayesian model for diagnosis of patients suspected of Lyme disease, and the integration of such a model into a medical information system. A Bayesian network incorporating the clinical history and laboratory results has been constructed. Because many of the symptoms are not exclusive to Lyme disease and they develop over time, the clinical history is important for making the correct diagnosis. The model is based on time slices, where each time slice contains the observed pathological picture from one consultation with for example, the general practitioner. Since the time intervals between consultations typically are not equivalent, we have developed a novel method that can handle non-equivalent time intervals between the time slices in the network. The method is based on a description of the general development pattern of Lyme disease, which is implemented in a model that states the conditional probabilities of experiencing a certain pathological picture given time since infection. The model has been integrated into a web-based medical information system, called Borrelia Systems, which has enabled us to evaluate the model during a progressive diagnostic process. The integration has been accomplished through the development of a Bayesian Application Framework. This framework specifies a communication data structure in XML providing a graphical user interface and database components, which can be used when developing systems that are based on Bayesian networks. The framework generalizes the integration of Bayesian networks so that it is possible to switch network without manually having to update or change the system.

Bayes Theorem↗

The electric pencil: CD-ROM and DVD.

This article is an introduction to and comparison of CD-ROM and DVD optical disc technologies, applications and standards with an overview of CD-ROM recording and production. Also discussed is the impact of optical disc technology on biomedical media and the relationship to the World Wide Web.

CD-ROM↗

Searching for information on the Internet using the UMLS and Medical World Search.

Medical World Search is a search engine for medical information on the Internet that distinguishes itself from other search engines by its built-in knowledge of medical terminology through its use of the National Library of Medicine's UMLS and its carefully selected but large database of medical sites. After discussing some of the previous uses of the UMLS for medical information retrieval, we describe the Medical World Search system. In October 1996, Medical World Search became operational on the World Wide Web at http:@www.mwsearch.poly.edu. It has been operating uninterrupted since then. We review our experiences with creating a search engine for medical information on the Internet and using the UMLS in this application. The UMLS has some clear advantages in this application. Some aspects of the UMLS also decrease its usefulness in information retrieval. Medical World Search's usage by medical information seekers is summarized. future directions for research are outlined.

Computer Communication Networks↗

Significance of predation by protists in aquatic microbial food webs.

Predation in aquatic microbial food webs is dominated by phagotrophic protists, yet these microorganisms are still understudied compared to bacteria and phytoplankton. In pelagic ecosystems, predaceous protists are ubiquitous, range in size from 2 gm flagellates to > 100 microm ciliates and dinoflagellates, and exhibit a wide array of feeding strategies. Their trophic states run the gamut from strictly phagotrophic, to mixotrophic: partly autotrophic and partly phagotrophic, to primarily autotrophic but capable of phagotrophy. Protists are a major source of mortality for both heterotrophic and autotrophic bacteria. They compete with herbivorous meso- and macro-zooplankton for all size classes of phytoplankton. Protist grazing may affect the rate of organic sinking flux from the euphotic zone. Protist excretions are an important source of remineralized nutrients, and of colloidal and dissolved trace metals such as iron, in aquatic systems. Work on predation by protists is being facilitated by methodological advances, e.g., molecular genetic analysis of protistan diversity and application of flow cytometry to study population growth and feeding rates. Examples of new research areas are studies of impact of protistan predation on the community structure of prey assemblages and of chemical communication between predator and prey in microbial food webs.

Animals↗

Can clinical trials requiring frequent participant contact be conducted over the Internet? Results from an online randomized controlled trial evaluating a topical ointment for herpes labialis.

BACKGROUND: The Internet has tremendous appeal for conducting randomized clinical trials and may be especially applicable to trials requiring frequent participant contact. Trials of cold sore remedies, for example, often require daily clinic visits during outbreaks, imposing substantial burden on participants. An Internet-based randomized clinical trial design may reduce this burden, permitting frequent symptom reports with considerably less effort. OBJECTIVE: To evaluate the feasibility of a Web-based randomized clinical trial requiring frequent participant interaction, using a 6-month, double-blind, randomized, placebo-controlled pilot trial of a topical ointment containing dioctyl sodium sulfosuccinate (DSS) (Zilex; Meditech Pharmaceuticals, Inc, Scottsdale, Arizona, USA) intended for treatment of recurrent herpes labialis. A secondary objective was to obtain preliminary data on effectiveness outcomes, to assist in planning a fully-powered trial of DSS. METHODS: Adults with physician-confirmed herpes labialis were recruited to apply to the trial. Eligible applicants were randomized to DSS or placebo, mailed to them upon enrolment with instructions to apply topically every 2 hours for the duration of every cold sore outbreak. Participants were instructed to complete online questionnaires at 2-week intervals and, at the initiation of a cold sore, daily "outbreak questionnaires" until outbreak termination. Feasibility outcome measures included trial participant characteristics, frequency of cold sores, participant retention and adherence (to study medication), and data completeness. Treatment effectiveness outcome measures included outbreak duration, days to crust formation, and pain. RESULTS: Of the 292 individuals applying, 182 screened eligible; 32 participants with confirmed herpes labialis enrolled in the trial. 16 were randomized into the verum group and 16 into the placebo group. 29 (91%) participants completed the trial. During the trial, 34 outbreaks were reported among 23 (72%) participants, resulting in a cold sore incidence rate of 19.8 per 100 person-months of observation. Online data were available for 32 outbreaks; the absence of a resolution date made it impossible to accurately calculate the duration of 12 (38%) outbreaks. Although the DSS treatment group had a shorter mean outbreak duration (6.6 vs 7.7 days, P =.2) and fewer mean days to crust formation (3.5 vs 4.9, P =.1), these differences did not reach statistical significance. The DSS group has statistically significant lower mean pain scores (3.1 vs 7.6, P =.04), but participants in this group also consumed more acetaminophen tablets than the placebo group (1.1 versus 0.5, P=.55). Adherence to medication was similar in both groups: 7 (50%) of the verum group reported using the cream as directed compared to 6 (46.2%) in the placebo group; (P =.8). CONCLUSIONS: We efficiently recruited participants and achieved high overall retention rates. However, participant adherence to the daily outbreak visit schedules was low and only 7 (50%) participants used the cream as directed. These limitations could be addressed in future Internet-based studies by using Personal Digital Assistants (PDAs), using reminder devices, and providing incentives. By enhancing participant adherence, clinical trials requiring frequent participant contact may be feasible over the Internet.

Administration, Topical↗

Faculty and student experiences with Web-based discussion groups in a large lecture setting.

The exchange of ideas in a discussion format is a more effective way of developing critical thinking in students than a traditional lecture format. Although research has shown that discussion groups are more effective for developing skills in application, analysis, and synthesis of content, it is difficult to implement in a large lecture setting. The author discusses how computer discussion groups were incorporated into a class of 117 nursing students.

Attitude of Health Personnel↗

Diabetes and the World Wide Web.

The World Wide Web has become remarkably quickly an alternative source of information for patients and their relatives, as well as students and health-care professionals. A whole plethora of websites and Internet-based applications related to diabetes have appeared in recent years. In this column, selected issues surrounding the use of such websites are considered and the need for more evaluation of such diabetes sites, as well as the Internet medium itself, is highlighted.

Diabetes Mellitus↗

Improving false discovery rate estimation.

MOTIVATION: Recent attempts to account for multiple testing in the analysis of microarray data have focused on controlling the false discovery rate (FDR). However, rigorous control of the FDR at a preselected level is often impractical. Consequently, it has been suggested to use the q-value as an estimate of the proportion of false discoveries among a set of significant findings. However, such an interpretation of the q-value may be unwarranted considering that the q-value is based on an unstable estimator of the positive FDR (pFDR). Another method proposes estimating the FDR by modeling p-values as arising from a beta-uniform mixture (BUM) distribution. Unfortunately, the BUM approach is reliable only in settings where the assumed model accurately represents the actual distribution of p-values. METHODS: A method called the spacings LOESS histogram (SPLOSH) is proposed for estimating the conditional FDR (cFDR), the expected proportion of false positives conditioned on having k 'significant' findings. SPLOSH is designed to be more stable than the q-value and applicable in a wider variety of settings than BUM. RESULTS: In a simulation study and data analysis example, SPLOSH exhibits the desired characteristics relative to the q-value and BUM. AVAILABILITY: The Web site www.stjuderesearch.org/statistics/splosh.html has links to freely available S-plus code to implement the proposed procedure.

Algorithms↗

A heuristic approach for detecting RNA H-type pseudoknots.

MOTIVATION: RNA H-type pseudoknots are ubiquitous pseudoknots that are found in almost all classes of RNA and thought to play very important roles in a variety of biological processes. Detection of these RNA H-type pseudoknots can improve our understanding of RNA structures and their associated functions. However, the currently existing programs for detecting such RNA H-type pseudoknots are still time consuming and sometimes even ineffective. Therefore, efficient and effective tools for detecting the RNA H-type pseudoknots are needed. RESULTS: In this paper, we have adopted a heuristic approach to develop a novel tool, called HPknotter, for efficiently and accurately detecting H-type pseudoknots in an RNA sequence. In addition, we have demonstrated the applicability and effectiveness of HPknotter by testing on some sequences with known H-type pseudoknots. Our approach can be easily extended and applied to other classes of more general pseudoknots. AVAILABILITY: The web server of our HPknotter is available for online analysis at http://bioalgorithm.life.nctu.edu.tw/HPKNOTTER/ CONTACT: cllu@mail.nctu.edu.tw, chiu@cc.nctu.edu.tw

Algorithms↗

Virioplankton: viruses in aquatic ecosystems.

The discovery that viruses may be the most abundant organisms in natural waters, surpassing the number of bacteria by an order of magnitude, has inspired a resurgence of interest in viruses in the aquatic environment. Surprisingly little was known of the interaction of viruses and their hosts in nature. In the decade since the reports of extraordinarily large virus populations were published, enumeration of viruses in aquatic environments has demonstrated that the virioplankton are dynamic components of the plankton, changing dramatically in number with geographical location and season. The evidence to date suggests that virioplankton communities are composed principally of bacteriophages and, to a lesser extent, eukaryotic algal viruses. The influence of viral infection and lysis on bacterial and phytoplankton host communities was measurable after new methods were developed and prior knowledge of bacteriophage biology was incorporated into concepts of parasite and host community interactions. The new methods have yielded data showing that viral infection can have a significant impact on bacteria and unicellular algae populations and supporting the hypothesis that viruses play a significant role in microbial food webs. Besides predation limiting bacteria and phytoplankton populations, the specific nature of virus-host interaction raises the intriguing possibility that viral infection influences the structure and diversity of aquatic microbial communities. Novel applications of molecular genetic techniques have provided good evidence that viral infection can significantly influence the composition and diversity of aquatic microbial communities.

Animals↗

Techniques for optimization of queries on integrated biological resources.

Today, scientific data are inevitably digitized, stored in a wide variety of formats, and are accessible over the Internet. Scientific discovery increasingly involves accessing multiple heterogeneous data sources, integrating the results of complex queries, and applying further analysis and visualization applications in order to collect datasets of interest. Building a scientific integration platform to support these critical tasks requires accessing and manipulating data extracted from flat files or databases, documents retrieved from the Web, as well as data that are locally materialized in warehouses or generated by software. The lack of efficiency of existing approaches can significantly affect the process with lengthy delays while accessing critical resources or with the failure of the system to report any results. Some queries take so much time to be answered that their results are returned via email, making their integration with other results a tedious task. This paper presents several issues that need to be addressed to provide seamless and efficient integration of biomolecular data. Identified challenges include: capturing and representing various domain specific computational capabilities supported by a source including sequence or text search engines and traditional query processing; developing a methodology to acquire and represent semantic knowledge and metadata about source contents, overlap in source contents, and access costs; developing cost and semantics based decision support tools to select sources and capabilities, and to generate efficient query evaluation plans.

Algorithms↗

PMN/platelets coinfused in guinea pig hearts Exposed to low-flow ischemia have no additive cardiodepressive effect.

Recent studies revealed an additive cardiodepressive effect of polymorphonuclear granulocytes (PMN) and thrombocytes in hearts exposed to a no-flow ischemia. To find out whether or not this is also true for isolated guinea pig hearts exposed to a low-flow ischemia, the current study was performed. PMN or thrombocytes, together or separately, were applied as a 1-min bolus (1,000/microl or 20,000/microl, respectively) during ischemia or in reperfusion in the presence of thrombin (0.3 U/ml perfusate). Recovery of external heart work and intracoronary cell retention were quantified in percent. Sole application of PMN or platelets during ischemia and reperfusion significantly compromised myocardial function, whereas coapplication of PMN and platelets did not exhibit any further cardiodepressive effect. Coapplication of cells almost prevented intracoronary platelet retention during ischemia and in reperfusion, as opposed to sole platelet application. Known blockers of endogenously released anti-platelet substances like nitric oxide, PGI(2) or adenosine did not mediate a further aggravation of myocardial dysfunction. The platelet-activating factor (PAF) antagonist WEB 2170 BS, however, significantly improved recovery of external heart work during ischemia and in reperfusion. This indicates that an additive cardiodepressive effect of PMN and platelets in working guinea pig hearts exposed to a low-flow ischemia, cannot be demonstrated, whereas PAF antagonists seem to be cardioprotective, under these conditions. Even addition of fibrinogen to the perfusate, did not show an additive cardiodepressive effect of coapplication of PMN and platelets.

Animals↗

Rapid method for preparation of nuclei from a mucin-producing solid tumor.

Nuclei were prepared from the human colon mucin-producing tumor GW-39. The method described involves incubation in beta-mercaptoethanol under mild conditions and results in the preparation of nuclei free of the mucin web that initially enmeshes them. A sensitive colorimetric immunoassay was used to confirm that nuclei prepared in this fashion were generally free of contaminating mucin. This method is mild, rapid, and should be applicable to other mucin-producing tumors.

Cell Fractionation↗

See one, do one, teach one: advanced technology in medical education.

UNLABELLED: The concept of "learning by doing" has become less acceptable, particularly when invasive procedures and high-risk care are required. Restrictions on medical educators have prompted them to seek alternative methods to teach medical knowledge and gain procedural experience. Fortunately, the last decade has seen an explosion of the number of tools available to enhance medical education: web-based education, virtual reality, and high fidelity patient simulation. This paper presents some of the consensus statements in regard to these tools agreed upon by members of the Educational Technology Section of the 2004 AEM Consensus Conference for Informatics and Technology in Emergency Department Health Care, held in Orlando, Florida. FINDINGS: Web-based teaching: 1) Every ED should have access to medical educational materials via the Internet, computer-based training, and other effective education methods for point-of-service information, continuing medical education, and training. 2) Real-time automated tools should be integrated into Emergency Department Information Systems [EDIS] for contemporaneous education. Virtual reality [VR]: 1) Emergency physicians and emergency medicine societies should become more involved in VR development and assessment. 2) Nationally accepted protocols for the proper assessment of VR applications should be adopted and large multi-center groups should be formed to perform these studies. High-fidelity simulation: Emergency medicine residency programs should consider the use of high-fidelity patient simulators to enhance the teaching and evaluation of core competencies among trainees. CONCLUSIONS: Across specialties, patient simulation, virtual reality, and the Web will soon enable medical students and residents to... see one, simulate many, do one competently, and teach everyone.

Career Choice↗