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PubMed2005

Improving the TMDL process using watershed risk assessment principles.

Ecological risk assessment (ERA) evaluates potential causal relationships between multiple sources and stressors and impacts on valued ecosystem components. ERAs applied at the watershed scale have many similarities to the place-based analyses that are undertaken to develop Total Maximum Daily Loads (TMDLs), in which linkages are established between stressors, sources, and water quality standards, including support of designated uses. TMDLs focus on achieving water quality standards associated with attainment of designated uses. In attempting to attain the water quality standard, many TMDLs focus on the stressor of concern rather than the ecological endpoint or indicators of the designated use that the standard is meant to protect. A watershed ecological risk assessment (WERA), at least in theory, examines effects of most likely stressors, as well as their probable sources in the watershed, to prioritize management options that will most likely result in meeting environmental goals or uses. Useful WERA principles that can be applied to TMDL development include: development and use of comprehensive conceptual models in the Problem Identification step of TMDLs; use of a transparent process for selecting Numeric Targets for TMDLs based on assessment endpoints derived from the management goal or designated use under consideration; analysis of co-occurring stressors likely to cause beneficial use impairment based on the conceptual model; use of explicit uncertainty analyses in the Linkage Analysis step of TMDL development; and frequent stakeholder interactions throughout the process. WERA principles are currently most applicable to those TMDLs in which there is no numeric standard and, therefore, indicators and targets need to be developed, such as many nutrient or sediment TMDLs. WERA methods can also be useful in determining TMDL targets in situations where simply targeting the water quality standard may re-attain the numeric criterion but not the broader designated use. Better incorporation of problem formulation principles from WERA into the TMDL development process would be helpful in improving the scientific rigor of TMDLs.

Ecology↗

PubMed2000

Integrating environmental restoration and ecological restoration: long-term stewardship at the department of energy.

With the ending of the Cold War, several federal agencies are reclaiming land through remediation and restoration and are considering potential future land uses that are compatible with current uses and local needs. Some sites are sufficiently contaminated that it is likely that the responsible federal agency will retain control over the land for the foreseeable future, providing them with a stewardship mission. This is particularly true of some of the larger Department of Energy (DOE) facilities contaminated during the production of nuclear weapons. The use of the term "restoration" is explored in this paper because the word means different things to the public, ecologists, and environmental managers responsible for contaminated sites, such as Superfund sites and the DOE facilities. While environmental restoration usually refers to remediation and removal of hazardous wastes, ecological restoration refers to the broader process of repairing damaged ecosystems and enhancing their productivity and/or biodiversity. The goals of the two types of restoration can be melded by considering environmental restoration as a special case of ecological restoration, one that involves risk reduction from hazardous wastes, and by broadening environmental restoration to include a more extensive problem-formulation phase (both temporal and spatial), which includes the goal of reestablishing a functioning ecosystem after remediation. Further, evaluating options for the desired post remediation result will inform managers and policy-makers concerning the feasibility and efficacy of environmental restoration itself.

Journal Article↗

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↗

PubMed2005

Estimating the exposure of birds and mammals to pesticides in long-term risk assessments.

This paper reviews current EU pesticide risk assessment guidance [European Commission (2002) Guidance document on risk assessment for birds and mammals under council directive 91/414/EEC, SANCO/4145/2000EC 2002], and examines some of its assumptions and problems arising from them. Issues associated with obtaining data that adequately describes exposure over the appropriate time-scale are common to both acute and long-term risk assessments but are probably less problematic for long-term exposure. Improvements in problem formulation and ways in which temporal and spatial factors might be incorporated into long-term risk assessments are suggested. The most important temporal issue for long-term risk is how best to model the degree to which wildlife habits are predictable from day to day. In relation to spatial factors, it is suggested that long-term risk assessments could make better use of pesticide usage data that sample usage patterns throughout the UK. The usefulness of detailed simulated farming landscapes populated by wildlife represented as agent-based models, should be explored.

Animals↗

PubMed2006

First step for an ecological risk assessment to evaluate the impact of diffuse pollution in lake Vela (Portugal).

Lake Vela, located in the Portuguese littoral-centre, is a temperate shallow lake exhibiting a high trophic status. This aquatic ecosystem has been potentially exposed to contamination generated by agricultural and livestock activities held in their drainage basin, which seriously compromise their health. This work summarizes some background information and presents the problem formulation step of the ERA. Therefore, it evaluates the characteristics of the stressor(s), describes the ecological system and receptors and suggests a conceptual model, which predicts the potential exposure pathways, relating suspected sources to the defined endpoints. This introductory step also described an analysis plan on the entire study, which includes a delineation of the assessment design, data needs, measures, and methods for conducting the analysis phase of the risk assessment process.

Ecology↗

PubMed2006

Empowerment: a goal or a means for health promotion?

Empowerment is a concept that has been much used and discussed for a number of years. However, it is not always explicitly clarified what its central meaning is. The present paper intends to clarify what empowerment means, and relate it to the goals of health promotion. The paper starts with the claim that health-related quality of life is the ultimate general goal for health promotion, and continues by briefly presenting definitions of some central concepts: "welfare", "health" and "quality of life". Several suggestions as to what empowerment is are then discussed: autonomy, freedom, knowledge, self-esteem, self-confidence, and control over health or life. One conclusion of this discussion is that empowerment can be seen as a complex goal which includes aspects of the three central concepts welfare, health and quality of life. To the extent that the empowerment goals aimed at are health-related, it is concluded that empowerment is a legitimate goal for health promotion. But empowerment is not only a goal, it can also be described as a process or as an approach. This process, or approach, in a fundamental way involves the participants in problem formulation, decision making and action, which means that the experts have to relinquish some of their control and power.

Attitude to Health↗

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↗

PubMed2005

A technical feasibility study of surfactant-free drug suspensions using octenyl succinate-modified starches.

Many new drugs exhibit poor wetting behaviour and low aqueous solubility. This is particularly an issue for preclinical studies like toxicological trials, in which considerably higher doses and volumes are being administered compared to clinical studies. Preclinical vehicles typically contain high levels of surfactants that can exert biological effects. However, the biological inertness of vehicles is pivotal for the application in preclinical studies stressing the need in finding new excipients to solve formulation problems of today's drug discovery. The present study investigated the technical feasibility of surfactant-free suspensions using a new poorly soluble drug as model. It was shown that octenyl succinate-modified starches adequately wetted the drug and homogenous tasteless suspensions were obtained. The polymer xanthan gum was identified as macroscopically compatible gelling agent. Concentration effects of xanthan, drug and different modified starches were studied in a D-optimal design with respect to rheological properties. The suspensions were also tested in an analytical centrifuge using NIR transmission profiles to obtain a measure of sedimentation stability under accelerated conditions. The modified starches exhibited only little influence on the viscosity as well as on the yield point in contrast to the rheological effects of xanthan gum. This gelling agent was the main stabilising excipient as the modified starches hindered to a lesser extent sedimentation. The most stable suspensions displayed convenient flow properties. The viscosity at 100 s(-1) and 25 degrees C was in technically acceptable range of 120-140 mPa s in view of a application via gavage or a syringe in animal studies. The results demonstrated that surfactant-free drug suspensions with excellent technical performance can be obtained using octenyl succinate-modified starches. The vehicles were tasteless and based on the experience of modified starches in the food industry, the vehicles should exhibit good tolerability. The future use of such surfactant-free drug suspensions in toxicological, pharmacokinetic and pharmacodynamic studies will have to determine their advantage in terms of biological inertness.

Chemistry, Pharmaceutical↗

PubMed2006

Framework for use of toxicity screening tools in context-based decision-making.

One of the principal applications of toxicology data is to inform risk assessments and support risk management decisions that are protective of human health. Ideally, a risk assessor would have available all of the relevant information on (a) the toxicity profile of the agent of interest; (b) its interactions with living systems; and (c) the known or projected exposure scenarios: to whom, how much, by which route(s), and how often. In practice, however, complete information is seldom available. Nonetheless, decisions still must be made. Screening-level assays and tools can provide support for many aspects of the risk assessment process, as long as the limitations of the tools are understood and to the extent that the added uncertainty the tools introduce into the process can be characterized and managed. Use of these tools for decision-making may be an end in itself for risk assessment and decision-making or a preliminary step to more extensive data collection and evaluation before assessments are undertaken or completed and risk management decisions made. This paper describes a framework for the application of screening tools for human health decision-making, although with some modest modification, it could be made applicable to environmental settings as well. The framework consists of problem formulation, development of a screening strategy based on an assessment of critical data needs, and a data analysis phase that employs weight-of-evidence criteria and uncertainty analyses, and leads to context-based decisions. Criteria for determining the appropriate screening tool(s) have been identified. The choice and use of the tool(s) will depend on the question and the level of uncertainty that may be appropriate for the context in which the decision is being made. The framework is iterative, in that users may refine the question(s) as they proceed. Several case studies illustrate how the framework may be used effectively to address specific questions for any endpoint of toxicity.

Animals↗

PubMed2005

A finite element based algorithm for determining interfacial tension (gamma) from pendant drop profiles.

This paper introduces a robust algorithm to determine the interfacial tension (gamma) from pendant drop profiles using the Galerkin finite element method (gamma-PD-FEM) to solve the axisymmetric form of the Young-Laplace (YL) equation. In this algorithm, the theoretical profiles are generated by solving the spherical coordinate form of the YL equation. gamma-PD-FEM also solves for the parameter estimates by minimizing the difference between the theoretical and experimental surface functions, f(theta). This technique is compared to the widely used method of converting the YL equation to the three arc length-based (ALB) first-order ODEs developed by Bashforth and Adams (BA) in 1883, or as denoted in this paper, the gamma-PD-BA method. The drop apex is the initial condition for the gamma-PD-BA algorithm and the integration is terminated at a specified location along the drop profile. In contrast to techniques based on the BA approach, computation of the theoretical drop profile in gamma-PD-FEM is obtained from a second-order ordinary differential equation and requires boundary conditions at the drop apex and at the contact line of the drop to the nozzle. By incorporating both boundary conditions into the problem formulation, the algorithm can also determine if the drop shape is at static equilibrium. Results to be presented include an outline of the computer algorithm, and comparison of gamma values obtained from the gamma-PD-FEM and the traditional gamma-PD-BA method using simulated and experimental drop profile data sets.

Journal Article↗

PubMed2005

Radionuclides in fruit systems: model-model intercomparison study.

Modeling is widely used to predict radionuclide distribution following accidental radionuclide releases. Modeling is crucial in emergency response planning and risk communication, and understanding model uncertainty is important not only in conducting analysis consistent with current regulatory guidance, but also in gaining stakeholder and decision-maker trust in the process and confidence in the results. However, while methods for dealing with parameter uncertainty are fairly well developed, an adequate representation of uncertainties associated with models remains rare. This paper addresses uncertainty about a model's structure (i.e., the relevance of simplifying assumptions and mathematical equations) that is seldom addressed in practical applications of environmental modeling. The use of several alternative models to derive a range of model outputs or risks is probably the only available technique to assess consistency in model prediction. Since each independent model requires significant resources for development and calibration, multiple models are not generally applied to the same problem. This study uses results from one such model intercomparison conducted by the Fruits Working Group, which was created under the International Atomic Energy Agency (IAEA) BIOMASS (BIOsphere Modelling and ASSessment) Program. Model-model intercomparisons presented in this study were conducted by the working group for two different scenarios (acute or continuous deposition), one radionuclide ((137)Cs), and three fruit-bearing crops (strawberries, apples, and blackcurrants). The differences between models were as great as five orders of magnitude for short-term predictions following acute radionuclide deposition. For long-term predictions and for the continuous deposition scenario, the differences between models were about two orders of magnitude. The difference between strawberry, apple, and blackcurrant contamination predicted by one model is far less than the difference in prediction of contamination for a single plant species given by different models. This study illustrates the importance of problem formulation and implementation of an analytic-deliberative process in risk characterization.

Cesium Radioisotopes↗

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↗