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PubMed1998

A Knowledge-Based Systems Approach to Design of Spatial Decision Support Systems for Environmental Management

/ This paper describes a framework for designing spatial decision support systems for environmental management using a knowledge-based systems approach. An architecture for knowledge-based spatial decision supportsystems (KBSDSS) is presented that integrates knowledge-based systems with geographical information systems (GIS) and other problem-solving techniques. A method based on spatial influence diagrams is developed for representation of environmental problems. The spatial influence diagram provides an interface through which knowledge-based systems techniques can be applied to build capabilities for problem formulation, automated design, and execution of a solution process. In addition to the flexibility and developmental advantages of knowledge-based systems, the KBSDSS incorporates expert knowledge to provide assistance for structuring spatial influence diagrams and executing a solution process that automatically integrates the GIS, data base, knowledge base, and different types of models. The framework is illustrated with a system, known as the Islay Land Use Decision Support System (ILUDSS), designed to assist planners in strategic planning of land use for the development of the island of Islay, off the west coast of Scotland.KEY WORDS: Geographical information systems; Spatial decision support systems; Knowledge-based systems; Spatial influence diagrams; Environmental management

Journal Article↗

PubMed1987

Methuselah--an expert system for diagnosis in geriatric psychiatry.

This report is based on the notion that criteria for "successful" diagnosis differ for different medical specialties. Diagnostic judgement in highly unstructured task domains is best characterized as clinical problem formulation with pragmatic implications for interventions. This concept is illustrated by the implementation of a computer-based diagnostic expert system for geriatric psychiatry. The program begins with guiding the patient's interview by the clinician. This is followed by the diagnostic process which is conducted in three steps. In the first step, candidate syndromes of disease states are identified by matching the presenting complaints with symptom lists of clinical syndromes. In the second step, the candidate syndromes serve as the organizers for gathering additional patient data (e.g., information from referral source and past illnesses) to seek constellations of findings which form a coherent clinical context. In this phase, the program can also prompt the clinician to obtain additional information from the patient or other available sources to resolve conflicts or, if necessary, invoke the concurrent presence of two independent syndromes to attain convergence (i.e., minimize the number of unexplained findings). In a final step, the syndromes with highest credence value, reflected by the number of linkages to patient data, are sharpened to specific diagnostic formulations. This is accomplished by frames of diagnoses which are associated with each syndrome. Once again, the patient data can be consulted to achieve optimal matches. A summary statement to the clinician lists the essential supporting evidence for the chosen diagnosis and can communicate alternatives or unresolved issues for clarifying interventions. Although no decisive evidence is available, informal observations of clinicians support the notion that clinical reasoning in highly unstructured domains is largely contextual and seeks apprehension of "gestalts" in successive steps. The diagnostic program of this report aims at simulating this process.

Aged↗

PubMed1992

A general approach for modelling and mathematical investigation of the human upper limb.

This paper is an attempt to systematize and solve the problems connected with biomechanical modelling and mathematical investigation of the upper limb, when all muscles acting on the shoulder, elbow and wrist joint are included. The basic problem is the assumption of a hypothesis for the unit vectors, collinear with muscle forces. The so-called segment-lines modelling of the muscle force direction is proposed for solving this problem. This approach combines the simplicity of the straight line joining the muscle tendon origin to the insertion point, its application for the analytical description of the model and the real description of the muscle anatomical functions. The principle of the anatomically adequate moment is the general criterion for choosing the segments (straight and curvilinear sections) by which the direction of the muscle action is replaced. The different optimization techniques which are used for solving the statically indeterminate problem, formulated for musculoskeletal biomechanical models, are considered. Aiming to obtain strictly positive and continuous solutions for the muscle forces moduli, the application of the Lagrange multipliers method is proposed. The possibility of applying different optimization criteria is explored. A general conclusion may be formulated: if there exists any criterion which is independent of the joint angles, it follows than that it must be dependent on the joint reactions and, in addition, it must be nonlinearly dependent on the muscle forces moduli.

Algorithms↗

PubMed1998

Rapamycin: distribution, pharmacokinetics and therapeutic range investigations: an update.

Based on the findings above, a number of conclusions can be made regarding the distribution, pharmacokinetics, and therapeutic range investigations with RAPA: (a) the majority of the drug is sequestered in erythrocytes, resulting in whole blood concentrations being considerably higher than plasma concentrations; (b) the drug is metabolized by the same cytochrome P450 3A enzyme involved in the metabolism of CsA and FK506. Metabolites are primarily simple demethylations and hydroxylations with 41-O-demethyl RAPA being the major metabolite both in vivo and in vitro; (c) the drug has a relatively long half-life in both humans and animals with 24-h trough concentrations being within the analytical range of HPLC when immunosuppressive doses are administered; (d) the drug exhibits a degree of proportionality between trough concentrations and dose; (e) a strong correlation exists between area under the concentration-time curve and trough blood concentration at steady state; (f) trough concentrations of the drug appear to be related to immunosuppressive efficacy and drug-related side effects; (g) the nephro- and neurotoxic properties of CsA are not augmented by concurrent treatment with RAPA; and (h) phase IIB trial results have shown a decrease of acute rejection episodes from 40% to < 10% among patients treated with full-dose CsA plus RAPA. The studies described here should provide a basis for the establishment of therapeutic monitoring protocols for RAPA. In addition, new derivatives of RAPA, such as SDZ RAD, designed to overcome formulation problems associated with RAPA, while maintaining similar pharmacokinetics and in vivo activity, show promise as alternatives to RAPA.

Animals↗

PubMed1999

About weight factors in the non-linear objective functions used for solving indeterminate problems in biomechanics.

A lot of non-linear objective criteria are applied for solving the indeterminate problems formulated for different biomechanical models--most of them can be covered by the expression [formula in text]. It might be noted, however, that most of the suggested criteria are not applicable if considerable antagonistic co-contractions exist. This could be an effect of treating the agonistic muscles and their respective antagonists in one and the same manner in the objective function. Using a completely inverse approach (the muscle forces are supposed to be known quantities) and a simple 1DOF model (actuated by three agonistic muscles and one corresponding antagonist) it has been shown which values of the weight factors c(i) may predict different levels of muscle forces from the two antagonistic groups. Three hypothetical border variants for magnitudes of the muscle forces are considered (flexor muscles are only active, extensor muscles are only active, considerable co-contraction of flexors and extensors exists). The main conclusions are: the signs of c(i) at agonistic muscles have to be opposite to the c(i) signs at their antagonists; the signs of the weight factors depend on the direction of the net external joint moment; the closer c(i) to zero, the bigger force will be predicted in the ith muscle.

Biomechanical Phenomena↗

PubMed2002

Ecological risk assessment (ERA) and hormesis.

Based on our current state of knowledge, the significance and importance of hormesis is likely to be greater for ecotoxicology, a component of ecological risk assessment (ERA), than for the overall process of ERA. Appropriately determining the role of hormesis in ERA will require extension of hormesis beyond chemical stressors to abiotic (e.g. habitat) and biotic stressors (e.g. species introductions, organism interactions). It will also require determining for all stressors whether at both individual and higher levels of organization, hormesis has positive, neutral or adverse effects. This determination must be made for model organisms, populations and communities. Adverse effects are the least likely, however, neutral effects cannot be ruled out. Presently, consideration of hormetic effects in ERA is most appropriate in a detailed level ecological risk assessment (DLERA), the most complex form of ERA. It is not appropriate in either problem formulation or a screening level ERA (SLERA). Further, for hormetic effects to be recognized and accepted fully into ERA may require a paradigm shift. Three on-going paradigm shifts to which hormesis could be linked are: recognition of the low utility of no-observed effects concentrations (NOECs); recognition of the need for special treatment of essential element dose/concentration-responses, which are similar to hormetic responses; and, the replacement of environmental toxicology with ecological toxicology (ecotoxicology).

Adaptation, Physiological↗

PubMed2000

Nanosuspensions of poorly soluble drugs--reproducibility of small scale production.

The major problem of many newly developed pharmaceutical drugs is their poor solubility in water and simultaneously in organic media. To solve these problems formulation as nanosuspensions is an attractive alternative. During the drug development process screening for an optimal formulation by homogenisation is essential. Time and cost effective production in an initial phase of R&D can be conducted on lab scale by using the Micron Lab 40 in its discontinuous version. In this report reproducibility of small scale production parameters (particle size, size distribution, content of microparticles) was exemplary studied for the drug RMKP22.

Morpholines↗

PubMedDate not supplied

Impairments and disabilities in hand therapy: the necessity of a uniform terminology for communication and research purposes.

Uniformity in the use of professional language is very important in the field of medicine. Impairments and disabilities are terms that are often used interchangeably. To health professionals analyzing a patient's health problem, formulating treatment goals, or writing questionnaires and protocols, the International Classification of Impairments, Disabilities, and Handicaps (ICIDH) offers a conceptual framework that has a great potential to remedy improper use of terms and that can enhance communication. The purpose of this article is twofold: (1) to familiarize the hand therapist with the ICIDH and (2) to present some proposals for a revision of the ICIDH that will make the classification structurally more practical and thereby will facilitate its use.

Hand↗

PubMedDate not supplied

Cell population modeling and parameter estimation for continuous cultures of Saccharomyces cerevisiae.

Saccharomyces cerevisiae is known to exhibit sustained oscillations in chemostats operated under aerobic and glucose-limited growth conditions. The oscillations are reflected both in intracellular and extracellular measurements. Our recent work has shown that unstructured cell population balance models are capable of generating sustained oscillations over an experimentally meaningful range of dilution rates. A disadvantage of such unstructured models is that they lack variables that can be compared directly to easily measured extracellular variables. Thus far, most of our work in model development has been aimed at achieving qualitative agreement with experimental data. In this paper, a segregated model with a simple structured description of the extracellular environment is developed and evaluated. The model accounts for the three most important metabolic pathways involved in cell growth with glucose substrate. As compared to completely unstructured models, the major advantage of the proposed model is that predictions of extracellular variables can be compared directly to experimental data. Consequently, the model structure is well suited for the application of estimation techniques aimed at determining unknown model parameters from available extracellular measurements. A steady-state parameter selection method developed in our group is extended to oscillatory dynamics to determine the parameters that can be estimated most reliably. The chosen parameters are estimated by solving a nonlinear programming problem formulated to minimize the difference between predictions and measurements of the extracellular variables. The efficiency of the parameter estimation scheme is demonstrated using simulated and experimental data.

Cell Count↗

PubMed1997

Characteristics and significance of the amorphous state in pharmaceutical systems.

The amorphous state is critical in determining the solid-state physical and chemical properties of many pharmaceutical dosage forms. This review describes the characteristics of the amorphous state and some of the most common methods that can be used to measure them. Examples of pharmaceutical situations where the presence of the amorphous state plays an important role are presented. The application of our current knowledge to pharmaceutical formulation problems is illustrated, and some strategies for working with amorphous character in pharmaceutical systems are provided.

Chemistry, Pharmaceutical↗

PubMed1997

Validation of a Questionnaire to Screen University Students for Learning Disabilities.

Learning disabilities (LD) may cause academic failures among university students, but minor accommodations may in some instances allow students to progress satisfactorily. The current study validates a questionnaire for detecting students likely to have an LD. University students, 57 with a documented LD and 134 without, completed a Likert-scale questionnaire to assess the degree of self-perceived difficulty for 50 learning or testing situations. Wilcoxon rank sum test, separate logistic regression models, and determination of the best joint set of predictors of LD were carried out. The mean per-item questionnaire score was higher in the LD group (p < 0.0001); 47 individual items were significant predictors (i.e., p < 0.05) of LD status. The best joint set of predictors consisted of items dealing with word pronunciation, comprehending mathematical word problems, formulating summaries, spelling, slow reading rate, finishing tests in the allotted time, note-taking in lectures, and falling asleep while reading. Incorporating responses to these eight items, a formula was derived to determine the probability of LD. Taking 0.26 as the threshold for predicting the presence of an LD, the sensitivity of the questionnaire was 88%, the specificity was 87% for this population. The questionnaire could be an effective screening tool to detect university or professional students who should consider comprehensive testing for LD.

Journal Article↗

PubMed1999

Towards the safer use of non-steroidal anti-inflammatory drugs.

Musculoskeletal conditions afflict most of us at some time in our lives, and we all have relatives and friends who suffer the pain and disability sometimes associated with conditions such as back or neck pain, fibrositis and osteoarthritis. The goal of those of us who try to help individuals with these conditions is to achieve effective, but also safe, management of their musculoskeletal disorders, the commonest symptom of which is pain. This goal can be achieved by better diagnosis and problem formulation (allowing better selection of treatment options); informed selection of non-drug and drug therapeutic options, based on relative cost-benefit considerations; and the judicious, appropriate and safe use of drugs, particularly non-steroidal anti-inflammatory drugs (NSAID). Setting realistic goals and maintaining regular surveillance of patients are also important considerations. Finally, the active involvement of the patient in their own management is associated with better and safer outcomes.

Aged↗

PubMed1987

Diagnosis and intervention in young children: the continuing gap.

Modern diagnostic systems have replaced theory-based, highly inclusive, explanatory terminology with descriptions of symptoms at low levels of inference often empirically determined. This shift has caused, inadvertently, an increased rift between diagnosis and treatment in young children. It is argued that the primary purpose of a diagnostic system is guidance for intervention; this was provided by the omnibus terminology of the early 1900s but is sacrificed when we revert to skin-level descriptors. Treatment of young children, as a result, is largely determined today by intervention philosophies, not by child diagnostic specification. To heal the rift, a proposal is offered for diagnoses in the form of problem formulations--statements of deficiencies in terms of hypothesized interventions--based on what is most central or amenable to change.

Arousal↗

PubMed2000

Prediction of Individual Muscle Forces Using Lagrange Multipliers Method - A Model of the Upper Human Limb in the Sagittal Plane: I. Theoretical Considerations.

Analytical solutions of indeterminate problems formulated for biomechanical models with more than one degree of freedom (DOF) are rarely found. This paper is an extension of the investigations of a 1 DOF model (Raikova, 1996, J. Biomechanics, 763-772) for a more complex 3 DOF model. The proposed model of the human upper limb is in the sagittal plane and includes ten muscle elements, four of them being two-joint ones. The formulated optimization task is solved analytically using the method of Lagrange multipliers. It is supposed that the optimization function is complex but can be approximated by a weighted sum of the squared muscle forces, where the nature of the weight factors of the muscles are unknown. The proposed computational algorithm for determination of the unknown individual muscle forces and joint reactions is easily implemented and may be extended without difficulties for more DOF and muscles. The aim is to establish a means of investigation of the possible weight coefficients for different modelled situations, which will help in searching for their physiological interpretation and analytical description.

Journal Article↗

PubMed2000

Prediction of Individual Muscle Forces Using Lagrange Multipliers Method - A Model of the Upper Human Limb in the Sagittal Plane: II. Numerical Experiments and Sensitivity Analysis.

Using the method of Lagrange multipliers an analytical solution of the optimization problem formulated for a two-dimensional, 3DOF model of the human upper limb has been described in Part I of this investigation. The objective criterion used is the following: [formula: see text], where F(i) -s are the muscle forces modelled and c(i) -s are unknown weight factors. This study is devoted to the numerical experiments performed in order to investigate which sets of the weight factors may predict physiologically reasonable muscle forces and joint reactions. A sensitivity analysis is also presented. The influence of: the gravity forces, different external loads applied to the hand, changes of the weight factors and of joint angle on the optimal solution is studied. A general conclusion may be drawn: using the above mentioned objective criterion, practically all motor tasks performed by the human upper limb may be described if the c(i) -s are properly chosen. These weight factors generally depend on the joint moments and must be different (their magnitudes as well as their signs) for agonistic muscles and for their antagonists.

Journal Article↗

PubMed2002

A comparative analysis based on different strength criteria for evaluation of risk factor for dental implants.

A numerical analysis is developed to study the interaction phenomena between endousseus titanium dental implants and surrounding jawbone tissue. The interest is focused on the most appropriate evaluation of the stress state arising in the tissue because of the implant under physiological loading. The problem is considered with regard to linear elastic response of the one and to short time effect. Different configurations of bone-implant system are described, using axial-symmetrical and three-dimensional models, by means of finite and geometric element method. The investigation attains to the stress states induced in bone that lead to a limit condition near the effective failure surface. The parameter commonly adopted in literature, such as the Von Mises stress, represents an excessive simplification of problem formulation, leading to an incorrect evaluation of the real failure risk for the implant, due to the assumption of the isotropic and deviatoric nature of the adopted stress measure. More suitable criterion can be assumed, such as the Tsai-Wu criterion, to take into account the anisotropy that characterises the response of bone, as well as the influence of a hydrostatic stress state. The analysis developed offers a comparison of results by using different criteria, leading to an evaluation of reliability of the procedure to be followed and addressing also to an evaluation of a risk factor for the implant investigated.

Anisotropy↗

PubMed1995

A risk assessment for lead in birds.

Ecotoxicologists and ecologists have examined the effects of pollutants on individuals and populations largely in terms of one or only a few effects. Yet the recent trend toward a holistic approach to ecological risk assessment suggests that a rigorous paradigm should be applied to toxicants, from hazard identification to risk characterization. Recent discussions have recognized that an up-front problem formulation phase is more critical in ecological risk assessment than it is for human health risk assessment. In this article a modified environmental health risk assessment paradigm is used to examine the risk of lead to birds. This risk analysis is largely conceptual, based on laboratory and field data, and incorporates information currently available. The model expands the hazard identification phase to create a target identification phase that includes the identification of receptors, endpoints, relationships, spatial and temporal scales, and indicators. The target identification phase is unique to the particular hazard, species, population, or community being examined. Lead can cause mortality, or can indirectly affect populations through effects on the food base, avian behavior, reproductive success, and recruitment. Lead can (1) decrease the abundance and availability of prey, (2) bioaccumulate in prey causing increased lead toxicosis in predators, or (3) increase prey availability by interfering with its hiding or escape behavior. Moreover, lower abundance of prey can lead to starvation or nutrient deficiencies, which amplify the absorption and retention of lead. Lead also causes decreases in clutch and egg size, mortality of embryos and nestlings, depression of growth, and deficits in behavior that affect survival. Lead decreases migratory behavior, and increases vulnerability to cold stress, hunters, and other predators. Research needs for evaluating the risk of lead in birds include obtaining data on (1) metal dynamics within various tissues as a function of dose and time since initial exposure, (2) low-level effects on embryos, (3) effects on chicks following fledging and in the period prior to recruitment, (4) effects on adult foraging skills and reproductive behavior, and (5) the relationship between effects from exposure in the laboratory and those from exposure in the wild. This latter point is extremely important, particularly if wild birds have other means of ridding the body of lead not available or less apparent to laboratory birds.

Animals↗

PubMed1997

Robust proofs of NP-hardness for protein folding: general lattices and energy potentials.

This paper addresses the robustness of intractability arguments for simplified models of protein folding that use lattices to discretize the space of conformations that a protein can assume. We present two generalized NP-hardness results. The first concerns the intractability of protein folding independent of the lattice used to define the discrete protein-folding model. We consider a previously studied model and prove that for any reasonable lattice the protein-structure prediction problem is NP-hard. The second hardness result concerns the intractability of protein folding for a class of energy formulas that contains a broad range of mean force potentials whose form is similar to commonly used pair potentials (e.g., the Lennard-Jones potential). We prove that protein-structure prediction is NP-hard for any energy formula in this class. These are the first robust intractability results that identify sources of computational complexity of protein-structure prediction that transcend particular problem formulations.

Models, Chemical↗