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Towards knowledge-based systems in clinical practice: development of an integrated clinical information and knowledge management support system.

Given that clinicians presented with identical clinical information will act in different ways, there is a need to introduce into routine clinical practice methods and tools to support the scientific homogeneity and accountability of healthcare decisions and actions. The benefits expected from such action include an overall reduction in cost, improved quality of care, patient and public opinion satisfaction. Computer-based medical data processing has yielded methods and tools for managing the task away from the hospital management level and closer to the desired disease and patient management level. To this end, advanced applications of information and disease process modelling technologies have already demonstrated an ability to significantly augment clinical decision making as a by-product. The wide-spread acceptance of evidence-based medicine as the basis of cost-conscious and concurrently quality-wise accountable clinical practice suffices as evidence supporting this claim. Electronic libraries are one-step towards an online status of this key health-care delivery quality control environment. Nonetheless, to date, the underlying information and knowledge management technologies have failed to be integrated into any form of pragmatic or marketable online and real-time clinical decision making tool. One of the main obstacles that needs to be overcome is the development of systems that treat both information and knowledge as clinical objects with same modelling requirements. This paper describes the development of such a system in the form of an intelligent clinical information management system: a system which at the most fundamental level of clinical decision support facilitates both the organised acquisition of clinical information and knowledge and provides a test-bed for the development and evaluation of knowledge-based decision support functions.

Artificial Intelligence↗

The Digital Anatomist distributed framework and its applications to knowledge-based medical imaging.

The domain of medical imaging is anatomy. Therefore, anatomic knowledge should be a rational basis for organizing and analyzing images. The goals of the Digital Anatomist Program at the University of Washington include the development of an anatomically based software framework for organizing, analyzing, visualizing and utilizing biomedical information. The framework is based on representations for both spatial and symbolic anatomic knowledge, and is being implemented in a distributed architecture in which multiple client programs on the Internet are used to update and access an expanding set of anatomical information resources. The development of this framework is driven by several practical applications, including symbolic anatomic reasoning, knowledge based image segmentation, anatomy information retrieval, and functional brain mapping. Since each of these areas involves many difficult image processing issues, our research strategy is an evolutionary one, in which applications are developed somewhat independently, and partial solutions are integrated in a piecemeal fashion, using the network as the substrate. This approach assumes that networks of interacting components can synergistically work together to solve problems larger than either could solve on its own. Each of the individual projects is described, along with evaluations that show that the individual components are solving the problems they were designed for, and are beginning to interact with each other in a synergistic manner. We argue that this synergy will increase, not only within our own group, but also among groups as the Internet matures, and that an anatomic knowledge base will be a useful means for fostering these interactions.

Anatomy↗

Development of a knowledge-based electronic patient record.

To help clinicians care for patients with HIV infection, we developed an interactive knowledge-based electronic patient record that integrates rule-based decision support and full-text information retrieval with an online patient record. This highly interactive clinical workstation now allows the clinicians at a large primary care practice (30,000 ambulatory visits per year) to use online information resources and fully electronic patient records during all patient encounters. The resulting practice database is continually updated with outcome data on a cohort of 700 patients with HIV infection. As a byproduct of this integrated system, we have developed improved statistical methods to measure the effects of electronic alerts and reminders.

Acquired Immunodeficiency Syndrome↗

Knowledge-based proteome profiling: considering identified proteins to evaluate separation efficiency by 2-D PAGE.

Proteome profiling techniques rely on the separation of proteins or peptides and their subsequent quantification. The reliability of this technique is still limited because a proteome profiling result does not necessarily represent the true protein composition of the analysed sample, thus seriously hampering proper data interpretation. Many experimentally observed proteome alterations are biologically not significant. It was the aim of this study to use the knowledge of the biological context of proteins in order to establish optimised proteome profiling protocols. While 2-D spot patterns of total cell protein fractions were found to poorly represent the true protein composition, purified subcellular protein fractions were found to better represent the protein composition of the analysed sample. The application of a standardised protocol to different kinds of cells revealed several striking observations. Firstly, the protein composition of cultured cells of various origins is very similar. Secondly, proteome alterations observed with the described protocols do make sense from a biologic point of view and may thus be considered as truly representative for the analysed samples. Thirdly, primary white blood cells isolated from different donors were found to show minor, but reproducible and significant individual differences. We designate the consideration of known properties of identified proteins in proteome profiles as a knowledge-based approach. The present data suggest that this approach may tremendously help to improve the applied techniques and assess the results. We demonstrate that the fulfilment of well-defined criteria of proteome profiles eventually results in reliable and biologically relevant data.

Amino Acid Sequence↗

Knowledge-based model building of the tertiary structures for lectin domains of the selectin family.

A combination of a knowledge-based approach and energy minimization was used to predict the three-dimensional structures of the lectin domains of P-selectin, E-selectin, and L-selectin, respectively. Each of these domains contains 118 amino acids. The starting points for energy minimization were generated based on a framework that consists of a number of separated segments derived from the structure-known carbohydrate-recognition domain of the mannose-binding protein (MBP), which belongs to the same C-type lectin family as the selectin molecules do. The structures thus found for P-, L-, and E-selectin lectin domains share a common feature, i.e., they all contain two alpha-helices, and two antiparallel beta-sheets of which one is formed by two strands (strands 1 and 5) and the other by three (strands 2, 3, and 4). Besides, they all possess two intact disulfide bonds formed by the pair of Cys-19 and Cys-117, and the pair of Cys-90 and Cys-109. The root-mean-square deviations calculated over the set of backbone atoms between P- and L-selectin lectin domains is 3.10 A, that between P- and E-selectin lectin domains 2.48 A, and that between L- and E-selectin lectin domains 3.07 A. A notable feature is the convergence-divergence duality of the 77-107 polypeptide in the three domains; i.e., part of the peptide is folded into a closely similar conformation, and part of it into a highly different one.

Amino Acid Sequence↗

Knowledge-based method for segmentation and analysis of lung boundaries in chest X-ray images.

We present a knowledge-based approach to segmentation and analysis of the lung boundaries in chest X-rays. Image edges are matched to an anatomical model of the lung boundary using parametric features. A modular system architecture was developed which incorporates the model, image processing routines, an inference engine and a blackboard. Edges associated with the lung boundary are automatically identified and abnormal features are reported. In preliminary testing on 14 images for a set of 18 detectable abnormalities, the system showed a sensitivity of 88% and a specificity of 95% when compared with assessment by an experienced radiologist.

Algorithms↗

Non-homology knowledge-based prediction of the papain prosegment folding pattern: a description of plausible folding and activation mechanisms.

BACKGROUND: A detailed knowledge of three-dimensional conformations is necessary in order to understand the close relationship between protein structure and function. Among current methodologies, homology modeling is an important tool for obtaining reliable geometries and it provides a direct alternative to X-ray or NMR techniques. In contrast, predictive methods with no three-dimensional template (non-homology) still require further validation and systematization. RESULTS: Here, we present a non-homology knowledge-based strategy for the structural prediction of the proregion of a cysteine proteinase zymogen. This method analyzes individual sequences and multiple alignments of homologous sequences, making use of different published algorithms and incorporating all available structure-related information to obtain improved predictions. Our strategy yielded acceptable secondary structure and general three-dimensional assignments when compared with crystallographic data from homologous proteins. CONCLUSIONS: We discuss our successes and failures as a contribution to non-homology prediction development. In addition, based on the information analyzed and generated in this work, we propose plausible folding and activation mechanisms for thiol-proteinase precursors that attempt to shed light on the molecular basis of prosegment functions.

Amino Acid Sequence↗

Knowledge-based design and operation of bioprocess systems.

Almost twenty years have passed since the first applications of the knowledge-based approach to bioprocess operations were reported. During this period, approaches such as fuzzy logic, artificial neural network modeling, expert systems and genetic algorithms have been extensively studied and successfully used in the design and control of various bioprocesses. The recent development of these approaches in the design and operation of biological processes is summarized and reviewed, especially focusing on the studies reported in biochemical engineering journals.

Journal Article↗

Docking into knowledge-based potential fields: a comparative evaluation of DrugScore.

A new application of DrugScore is reported in which the knowledge-based pair potentials serve as objective function in docking optimizations. The Lamarckian genetic algorithm of AutoDock is used to search for favorable ligand binding modes guided by DrugScore grids as representations of the protein binding site. The approach is found to be successful in many cases where DrugScore-based re-ranking of already docked ligand conformations does not yield satisfactory results. Compared to the AutoDock scoring function, DrugScore yields slightly superior results in flexible docking.

Algorithms↗

A knowledge-based system paradigm for automatic interpretation of CT scans.

The interpretation of X-ray CT scans is a task which relies on specialized medical expertise, comprising anatomical, modality-dependent, non-visual and radiological knowledge. Most medical imaging techniques generate a single scan or sequence of two-dimensional scans. The radiologist's experience is gained by interpreting two-dimensional scans. The more complex three-dimensional anatomical knowledge becomes significant only when non-standard slice orientations are used. Hence, implicit in the radiologist's knowledge is the appearance of anatomical structures in standard two-dimensional planes, transverse, sagittal and coronal. That is, position with respect to both a coordinate reference system and other structures; intensity ranges for tissue types; contrast between structures; and size within the slices. Further to this, neurological landmarking is used to establish points of reference, i.e. more easily identifiable structures are first found and subsequent hypotheses are formed. With this in mind we have developed a knowledge-based system paradigm that partitions an image by applying the domain-dependent knowledge necessary (1) to set constraints on region-based segmentation and (2) to make explicit the expectation of the appearance of the anatomy under the imaging modality for use in the region grouping phase. This paradigm affords both expectation- and event-driven segmentation by representing grouping knowledge as production rules.

Algorithms↗

Third generation electronic medical record knowledge based perspectives.

There is a need to develop better electronic medical records. One possible solution is to put more and more 'routine' medical knowledge into systems handling medical records. In this paper, we analyze the current state-of-the-art of knowledge-based medical record handling; we mainly consider the work of Rector et al. [1]. We offer a more detailed 'four level' knowledge level model compared to the 'two level' model of Rector. The EMR of the future might be approached with a top-down method, using the above mentioned 'four level' model.

Artificial Intelligence↗

Knowledge-based, interactive, custom anatomical scene creation for medical education: the Biolucida system.

Few biomedical subjects of study are as resource-intensive to teach as gross anatomy. Medical education stands to benefit greatly from applications which deliver virtual representations of human anatomical structures. While many applications have been created to achieve this goal, their utility to the student is limited because of a lack of interactivity or customizability by expert authors. Here we describe the first version of the Biolucida system, which allows an expert anatomist author to create knowledge-based, customized, and fully interactive scenes and lessons for students of human macroscopic anatomy. Implemented in Java and VRML, Biolucida allows the sharing of these instructional 3D environments over the internet. The system simplifies the process of authoring immersive content while preserving its flexibility and expressivity.

Anatomy↗

Does GEM-encoding clinical practice guidelines improve the quality of knowledge bases? A study with the rule-based formalism.

The aim of this work was to determine whether the GEM-encoding step could improve the representation of clinical practice guidelines as formalized knowledge bases. We used the 1999 Canadian recommendations for the management of hypertension, chosen as the knowledge source in the ASTI project. We first clarified semantic ambiguities of therapeutic sequences recommended in the guideline by proposing an interpretative framework of therapeutic strategies. Then, after a formalization step to standardize the terms used to characterize clinical situations, we created the GEM-encoded instance of the guideline. We developed a module for the automatic derivation of a rule base, BR-GEM, from the instance. BR-GEM was then compared to the rule base, BR-ASTI, embedded within the critic mode of ASTI, and manually built by two physicians from the same Canadian guideline. As compared to BR-ASTI, BR-GEM is more specific and covers more clinical situations. When evaluated on 10 patient cases, the GEM-based approach led to promising results.

Artificial Intelligence↗

Personalizing web information for patients: linking patient medical data with the web via a patient personal knowledge base.

This paper describes ongoing study that examines problems with existing patient health information sources and investigates an approach for linking (i.e. integrating) data from a patient's medical record(s) with relevant health information on the web. The aim is to provide patients with simplified, customized and controlled access to web information. Data from patient medical records are extracted and linked with relevant health information on the web through a web search service. These are made available to patients through a web portal that we refer to as the patient knowledge base (PatientKB). Our integration approach utilizes term semantics (i.e. meaning) to enrich the web search and simplify medical terms for patients. In the current implementation, patients have guided, secure and relatively customized access to basic and relevant web information on their diagnoses. Future implementation will attempt to achieve further customization, extensibility and safety features. This paper investigates how ideas presented in an earlier study can be implemented.

Humans↗

Do beez buzz? Rule-based and frequency-based knowledge in learning to spell plural -s.

There has been much discussion about whether certain aspects of human learning depend on the abstraction of rules or on the acquisition of frequency-based knowledge. It has usually been agreed, however, that the spelling of morphological patterns in English (e.g., past tense -ed) and other languages is based on the acquisition of morphological rules, and that these rules take a long time to learn. The regular plural -s ending seems to be an exception: Even young children can spell this correctly, even when it is pronounced /z/ (as in bees). Reported here are 3 studies that show that 5- to 9-year-old children and adults do not usually base their spellings of plural real-word and pseudo-word endings on the morphological rule that all regular plurals are spelled with -s. Instead, participants appeared to use their knowledge of complex but untaught spelling patterns, which is based on the frequency with which certain letters co-occur in written English.

Child↗

A knowledge-based approach to environmental biomonitoring.

This paper presents the design, development and implementation of an integrated GIS-controlled knowledge-based system for environmental monitoring applications, utilizing indigenous flora for assessing quality. The system gathers and combines geographical, ecological, and physicochemical data of organisms' response to pollution within an intelligent computer program that (a) recognises groups of indigenous species suitable for long-term monitoring of a specific pollutant or a combination of pollutants, (b) estimates the ambient concentration of pollutant(s) from the population of the species comprising the bioindicator group and (c) provides biomonitoring capacity indices at national and international/transboundary levels. Significantly, a novel system in the form of a rational framework at the conceptual design level has been developed, that actually contributes towards achieving a cost-effective long-term biomonitoring program, with the flexibility to counter on-course any (anticipated or not) variations/modifications of the surveillance environment: the scheme assumes a robust dynamic cooperation between instrumental and biomonitoring systems, with a view to minimise uncertainty and monitoring costs and increase reliability of pollution control and abatement, aiming eventually at the shifting, partially or totally, from instrumental to natural monitoring. The proposed approach is presently implemented at pilot-scale for establishing a biomonitoring network at a large industrial area in Greece. The results obtained indicate that a cost-effective program can be only attained and maintained under a suitable financial/organizational scheme at the macro level, whereas the micro level viability strongly depends upon careful management of human resources and fixed assets.

Biodiversity↗

Acute effects of knowledge-based work on feeding behavior and energy intake.

The aim of this study was to evaluate the impact of knowledge-based work (KBW) on feeding behavior and spontaneous energy intake with the use of a repeated measures/within-subjects design. We used a two-session protocol including an ad libitum buffet preceded by either rest in a sitting position for 45 min or a cognitive task (reading a document and writing a summary of 350 words using a computer) over the same time period. In this regard, 15 healthy Laval University female students (mean age = 24.1+/-2.2 years, mean BMI = 24.0+/-4.3 kg/m2) were recruited to participate in this study. Anthropometric variables, energy expenditure, heart rate, blood pressure, food intake (dietary record), and appetite sensation markers were measured at each testing session, and two questionnaires [Three-Factor Eating Questionnaire (TFEQ) and State-Trait Anxiety Inventory (STAI)] were administered. In addition, a buffet-type meal was used to measure spontaneous energy intake and macronutrient preferences. We found that the mean energy expenditure of the two conditions was about comparable (difference of 13 kJ between the two tasks) whereas the mean ad libitum energy intake after the KBW task exceeded that measured after rest by 959 kJ (p < 0.01). Although a higher absolute energy intake was observed for the three macronutrients after the KBW task (p < 0.05), no specific preference was detected, as reflected by the comparable percent of energy from each macronutrient in the two conditions. No significant difference in appetite sensation markers was observed between the two conditions, although the subjects ate more in the buffet-type meal after the KBW task. Furthermore, the subjects did not compensate by decreasing food intake for the rest of the day, suggesting a net caloric surplus. We also observed negative correlations between cognitive dietary restraint (TFEQ) and spontaneous energy intake in both conditions. In conclusion, our results demonstrate that mental work solicited by KBW has the potential to induce a higher spontaneous energy intake. This also raises the possibility that KBW adds a new component to sedentariness that might further accentuate the positive energy balance that is more likely to occur when one is inactive.

Adult↗