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PubMed2005

Drug discovery in the kinase inhibitory field using the Nested Chemical Library technology.

Kinase inhibitors are at the forefront of modern drug research, where mostly three technologies are used for hit-and-lead finding: high throughput screening of random libraries, three-dimensional structure-based drug design based on X-ray data, and focused libraries around limited number of new cores. Our novel Nested Chemical Library (NCL) (Vichem Chemie Research Ltd., Budapest, Hungary) technology is based on a knowledge base approach, where focused libraries around selected cores are used to generate pharmacophore models. NCL was designed on the platform of a diverse kinase inhibitory library organized around 97 core structures. We have established a unique, proprietary kinase inhibitory chemistry around these core structures with small focused sublibraries around each core. All the compounds in our NCL library are stored in a big unified Structured Query Language database along with their measured and calculated physicochemical and ADME/toxicity (ADMET) properties, together with thousands of molecular descriptors calculated for each compound. Biochemical kinase inhibitory assays on selected, cloned kinase enzymes for a few hundred NCL compound sets can provide sufficient biological data for rational computerized design of new analogues, based on our pharmacophore model-generating 3DNET4W QSPAR (quantitative structure-property/activity relationships) approach. Using this pharmacophore modeling approach and the ADMET filters, we can preselect synthesizable compounds for hit-and-lead optimization. Starting from this point and integrating the information from QSPAR, high-quality leads can be generated within a small number of optimization cycles. Applying NCL technology we have developed lead compounds for several validated kinase targets.

Algorithms↗

PubMed2006

NQ-Flipper: validation and correction of asparagine/glutamine amide rotamers in protein crystal structures.

The error rate of asparagine (Asn) and glutamine (Gln) amide rotamers in protein crystal structures is in the order of 20% and as a consequence the current Protein Database (PDB) contains approximately half a million incorrect Asn and Gln side-chain rotamers. Here we present NQ-Flipper, a web service based on knowledge-based potentials of mean force to automatically detect and correct erroneous rotamers. We achieve excellent agreement with expert curated data.

Asparagine↗

PubMed2005

The Critical Care Safety Study: The incidence and nature of adverse events and serious medical errors in intensive care.

OBJECTIVE: Critically ill patients require high-intensity care and may be at especially high risk of iatrogenic injury because they are severely ill. We sought to study the incidence and nature of adverse events and serious errors in the critical care setting. DESIGN: We conducted a prospective 1-year observational study. Incidents were collected with use of a multifaceted approach including direct continuous observation. Two physicians independently assessed incident type, severity, and preventability as well as systems-related and individual performance failures. SETTING: Academic, tertiary-care urban hospital. PATIENTS: Medical intensive care unit and coronary care unit patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcomes of interest were the incidence and rates of adverse events and serious errors per 1000 patient-days. A total of 391 patients with 420 unit admissions were studied during 1490 patient-days. We found 120 adverse events in 79 patients (20.2%), including 66 (55%) nonpreventable and 54 (45%) preventable adverse events as well as 223 serious errors. The rates per 1000 patient-days for all adverse events, preventable adverse events, and serious errors were 80.5, 36.2, and 149.7, respectively. Among adverse events, 13% (16/120) were life-threatening or fatal; and among serious errors, 11% (24/223) were potentially life-threatening. Most serious medical errors occurred during the ordering or execution of treatments, especially medications (61%; 170/277). Performance level failures were most commonly slips and lapses (53%; 148/277), rather than rule-based or knowledge-based mistakes. CONCLUSIONS: Adverse events and serious errors involving critically ill patients were common and often potentially life-threatening. Although many types of errors were identified, failure to carry out intended treatment correctly was the leading category.

Aged↗

PubMed1997

Vision without knowledge.

A brain-damaged patient (D.F.) with visual form agnosia is described and discussed. D.F. has a profound inability to recognize objects, places and people, in large part because of her inability to make perceptual discriminations of size, shape or orientation, despite having good visual acuity. Yet she is able to perform skilled actions that depend on that very same size, shape and orientation information that is missing from her perceptual awareness. It is suggested that her intact vision can best be understood within the framework of a dual processing model, according to which there are two cortical processing streams operating on different coding principles, for perception and for action, respectively. These may be expected to have different degrees of dependence on top-down information. One possibility is that D.F.'s lack of explicit awareness of the visual cues that guide her behaviour may result from her having to rely on a processing system which is not knowledge-based in a broad sense. Conversely, it may be that the perceptual system can provide conscious awareness of its products in normal individuals by virtue of the fact that it does interact with a stored base of visual knowledge.

Adult↗

PubMed1990

Evaluating rural nurses for preparation in implementing nutrition interventions.

With the increase in wellness programs, earlier hospital discharges, higher health care costs, and more home health care, rural nurses are required to generalize their practices and draw from a more extensive knowledge base. The purpose of this study was to examine nursing interventions, specifically nutrition education practices, based on nutrition knowledge that is used in health promotion. A stratified random sample of rural nurses from hospitals, nursing homes, and community health agencies in North Dakota was invited to participate in this study. Data were obtained via questionnaires. The questionnaire consisted of two parts: the first analyzing demographic data and the second analyzing nutrition knowledge. Nutrition information requests were received by 90.9 percent of the practicing registered nurses. The community/public health nurses had the highest nutrition knowledge scores while medical-surgical hospital nurses had the lowest nutrition knowledge scores. With nutrition information and education being a frequently sought intervention by the rural health client, it would seem that registered nurses should be highly prepared and knowledgeable to meet these clients' needs.

Evaluation Studies as Topic↗

PubMed1995

Understanding adverse events: human factors.

(1) Human rather than technical failures now represent the greatest threat to complex and potentially hazardous systems. This includes healthcare systems. (2) Managing the human risks will never be 100% effective. Human fallibility can be moderated, but it cannot be eliminated. (3) Different error types have different underlying mechanisms, occur in different parts of the organisation, and require different methods of risk management. The basic distinctions are between: Slips, lapses, trips, and fumbles (execution failures) and mistakes (planning or problem solving failures). Mistakes are divided into rule based mistakes and knowledge based mistakes. Errors (information-handling problems) and violations (motivational problems) Active versus latent failures. Active failures are committed by those in direct contact with the patient, latent failures arise in organisational and managerial spheres and their adverse effects may take a long time to become evident. (4) Safety significant errors occur at all levels of the system, not just at the sharp end. Decisions made in the upper echelons of the organisation create the conditions in the workplace that subsequently promote individual errors and violations. Latent failures are present long before an accident and are hence prime candidates for principled risk management. (5) Measures that involve sanctions and exhortations (that is, moralistic measures directed to those at the sharp end) have only very limited effectiveness, especially so in the case of highly trained professionals. (6) Human factors problems are a product of a chain of causes in which the individual psychological factors (that is, momentary inattention, forgetting, etc) are the last and least manageable links. Attentional "capture" (preoccupation or distraction) is a necessary condition for the commission of slips and lapses. Yet, its occurrence is almost impossible to predict or control effectively. The same is true of the factors associated with forgetting. States of mind contributing to error are thus extremely difficult to manage; they can happen to the best of people at any time. (7) People do not act in isolation. Their behaviour is shaped by circumstances. The same is true for errors and violations. The likelihood of an unsafe act being committed is heavily influenced by the nature of the task and by the local workplace conditions. These, in turn, are the product of "upstream" organisational factors. Great gains in safety can ve achieved through relatively small modifications of equipment and workplaces. (8) Automation and increasing advanced equipment do not cure human factors problems, they merely relocate them. In contrast, training people to work effectively in teams costs little, but has achieved significant enhancements of human performance in aviation. (9) Effective risk management depends critically on a confidential and preferable anonymous incident monitoring system that records the individual, task, situational, and organisational factors associated with incidents and near misses. (10) Effective risk management means the simultaneous and targeted deployment of limited remedial resources at different levels of the system: the individual or team, the task, the situation, and the organisation as a whole.

Accidents, Occupational↗

PubMedDate not supplied

An outline of the forensic nursing role.

Nurses working within secure institutions are agents for both therapy and custody. With its distinctive client group, predominantly institution-based care, exceptional knowledge base and clinical focus on mental disorder and deviance, forensic nursing can justifiably claim the status of a specialty.

Dangerous Behavior↗

PubMed2006

The Yapunyah project: embedding Aboriginal and Torres Strait Islander perspectives in the nursing curriculum.

The Yapunyah Project is an initiative of the Faculty of Health at Queensland University of Technology. It was instigated to further improve the development of cultural competence in health graduates with respect to Aboriginal and Torres Strait Islander perspectives. The project was informed by the cultural competence in healthcare delivery models of Campinha-Bacote (1998a) and Cross, Bazron, Dennis and Isaacs (1989) and by the cultural safety reforms to nursing curricula in New Zealand. The Yapunyah Project involved extensive consultation and collaboration with Indigenous staff and health experts in the local Aboriginal and Torres Strait Islander community. A core curriculum, and associated graduate transcultural competencies, were informed by these discussions and earlier reforms in health curricula by the Committee of Deans of Australian Medical Schools and the Royal Australian College of General Practitioners. Although the overall project involved four separate schools within the faculty, this paper details the experience of embedding Indigenous perspectives within the undergraduate nursing curriculum. The experience has been a challenging and positive one, and the reforms have been supported by a sustainable framework. This paper outlines how one university faculty is endeavouring to educationally prepare nursing students to practice with evidence-based transcultural nursing knowledge based on culture care values, beliefs, and traditional lifeways of Indigenous people of Australia. As such, the project aims to contribute to the improvement and promotion of the health and well-being of Indigenous Australians in culturally and ethnohistorically meaningful ways.

Australia↗

PubMed1997

European Citizens Advisory Systems based on telematics for communication and health.

The objective of Citizens Advisory Systems for Health in Europe is to provide background information in preventive health care, to offer data-based and knowledge-based facilities and to reduce costs within the national and European wide health systems. In order to do so, easily accessible human-computer-dialogues and systems have to or have been already developed, allowing every citizen to obtain the right information at the right place at any time with any intensity which is wished. The paper will describe the already existing standards, will explain the ideal type and the technical and social implications which have to be taken into consideration for these systems.

Computer Communication Networks↗

PubMedDate not supplied

Category-specific naming and modality-specific imagery.

Some attempts to explain category-specific disorders have stressed how different modality knowledge bases (i.e., visual knowledge vs motoric/functional knowledge) may underlie the distinction between living and nonliving things. This study examined 60 normal subjects for the relationship between picture naming in four subcategories (animals, fruit/vegetables, praxic and nonpraxic objects) and imagery vividness in seven modalities. Participants made more nonliving than living errors; and females made more nonliving errors than males. There was a significant correlation between naming of animals and fruits/vegetables and visual imagery vividness; however, this association was also significant for praxic and nonpraxic object naming. There was no evidence of associations between kinesthetic imagery and praxic object naming or gustatory/olfactory imagery and fruit/vegetable naming. These findings accord with the notion of a general association between visual imagery and picture naming, but provide no support for more specific links between modality-specific imagery vividness and naming in different categories.

Adolescent↗

PubMed1989

Urinary tract infection in spinal cord injury.

Loss of normal bladder function results in increased risk of developing urinary tract infection. Recurrent bacteriuria continues to be a problem in most spinal cord injured persons regardless of the bladder emptying method used. Lower urinary tract complications have decreased with intermittent catheterization, but the effect of increased intravesical pressure and presence of bacteriuria on renal function are still undetermined. Current methods of neurogenic bladder management are often based on professional or institutional presuppositions rather than scientific data. Although there are many unanswered questions about the role of urinary tract infection in spinal cord injury patients, treatment should be based on scientific knowledge, even though the knowledge base is still limited. Preservation of renal function is the ultimate goal of any method of neurogenic bladder management. Although a person with spinal cord injury is described, the material covered is applicable to other neurogenic bladder disturbances.

Humans↗

PubMed1993

Structuration and acquisition of medical knowledge. Using UMLS in the conceptual graph formalism.

The use of a taxonomy, such as the concept type lattice (CTL) of Conceptual Graphs, is a central structuring piece in a knowledge-based system. The knowledge it contains is constantly used by the system, and its structure provides a guide for the acquisition of other pieces of knowledge. We show how UMLS can be used as a knowledge resource to build a CTL and how the CTL can help the process of acquisition for other kinds of knowledge. We illustrate this method in the context of the MENELAS natural language understanding project.

Artificial Intelligence↗

PubMed1993

Radiographic evaluation of pedal osseous tumors.

Osseous tumors of the foot are uncommon lesions. The approach to making the correct diagnosis should be based upon a knowledge of the types of tumor that may be encountered and a systematic analysis of the characteristics of the lesion. Proper use of imaging techniques will help to narrow the differential diagnosis. Consultation among colleagues is very important for diagnosing a specific lesion, for broadening one's knowledge base, and for improving patient care. Topics discussed in this article include fluoroscopy, magnification views, and characteristics of lesions and patterns of destruction.

Adolescent↗

PubMed2003

Adapting the contents of computer-based instruction based on knowledge tests maintains effectiveness of nutrition education.

BACKGROUND: Nutrition education of many medical students continues to be inadequate. Computer-based instruction in nutrition is a resource that introduces a new level of flexibility for instructors and students while maintaining a high level of educational quality. Previous evaluations have demonstrated the efficacy of our programs on nutrient physiology and the role of nutrition in the disease process, but some students complained about the time spent on content that they had covered in other courses. OBJECTIVE: We wanted to explore the effectiveness of an abbreviated program version that bypassed topics that the students had mastered already. DESIGN: Multiple-choice questions were used to determine knowledge of 117 second-year medical students in each of the main knowledge areas covered by our Nutrition and Cancer instructional module. The students were then randomly assigned to complete either the full version or a shortened version adapted to their demonstrated knowledge. Four days later the same as well as new questions were used to compare knowledge gain between the 2 groups. RESULTS: The shorter time spent with the tailored version than with the full version (2.5 h versus <1.5 h) decreased learning efficacy to only a small extent. More tailored-version users than full-version users were interested in further computer-based instruction (59% versus 41%, P < 0.05), suggesting better acceptance. CONCLUSIONS: Our experience underscores the power of computer-based instruction to bring nutrition education to medical students. The newly developed adaptive features of the nutrition programs may also be helpful for practicing physicians to efficiently bridge knowledge gaps.

Computer-Assisted Instruction↗

PubMed1989

Context-based automated detection of epileptogenic sharp transients in the EEG: elimination of false positives.

This paper describes a knowledge-based system for the elimination of false positives in the automated detection of epileptogenic sharp transients in the EEG. The system makes comprehensive use of spatial and temporal context information available on 16 channels of EEG, EKG, EMG, and EOG. A knowledge-based implementation is used because of the ease with which it allows the contextual rules to be expressed and refined. The resulting system is shown to be capable of rejecting a wide variety of artifacts commonly found in EEG recordings, artifacts that cause numerous false positive detections in systems making less comprehensive use of context.

Artificial Intelligence↗

PubMed2002

Knowledge fields and inner patterns in clinical laboratory science.

OBJECTIVE: The purpose of the study was to clarify the knowledge base of clinical laboratory science (CLS). This research was motivated by questions concerning the knowledge base itself and its abilities to meet the demands of reality. The following questions were therefore asked to achieve the purposes of the study: What are the knowledge fields and inner patterns in CLS? Which research objects could CLS focus on in order to promote development in practice, education, and research? DESIGN: The findings of the study were arrived at by means of hypothetical-deductive approach and inductive, content analytical strategy. The journal Clinical Laboratory Science of the American Society for Clinical Laboratory Science (ASCLS) provides the source material for the analysis. SETTING: Abo Akademi University, Faculty of Social and Caring Sciences. RESULTS: The findings of the study are discussed in the light of starting points of the theory of science and lead to nine hypotheses concerning CLS. CONCLUSION: The purpose of the present study was to create clarity in CLS as a science of its own. This has been achieved by capturing and describing facts and qualities, and thereafter presenting fundamental hypotheses in CLS. The results of this study give a thought structure for continued development and deepening within the theory and practice of CLS.

Clinical Laboratory Techniques↗

PubMed1995

A computer system for analysis and integrated description of regulation of the molecular-genetic system of interferon induction and action.

A new theoretical approach to elaboration of an information-analytical integrated knowledge base containing data on regulation and function of biological systems is presented. The knowledge base incorporates: (i) a reference database containing experimental data on the structural-functional organization of a biological system; (ii) a dynamic mathematical model for analysis of the evolution of the system over time; and (iii) an interpretation module of simulation results. Application of this approach to theoretical investigation of the interferon system in the case of viral infection is discussed. The approach is specific in that it uses mathematical modeling technology, which allows one to generate mathematical models of different degrees of complexity in the analysis of the diverse aspects of biological system behavior. This approach allows one not only to store and to treat available experimental data, but also to acquire new knowledge about the behavior of a biological system. The proposed approach is implemented as a computer system for the IBM PC and compatibles.

Algorithms↗

PubMed2001

Symbolic representation of anatomical knowledge: concept classification and development strategies.

In this paper a novel approach to anatomy knowledge representation is described. The focus of the present research has been on the development of a representational framework where the conceptual level has been implemented by using hierarchical and nonhierarchical conceptual networks. This has allowed handling the demand for multiple views of anatomy (systemic and topographical views). The terminological level of the knowledge representation has been implemented by using a compositional strategy which has avoided the explicit storage of the terms used to express composite concepts. Hierarchical relations and composite concept representations have required supervision of both the inheritance and concept reconstruction. For this purpose heuristic knowledge has been stored in terms of consistency rules in the knowledge base. As proof of the capability of this system, we show how the knowledge base has been used to provide symbolic access to spatial information consisting of a reduced set of images from the Visible Human Dataset.

Anatomy, Cross-Sectional↗