Certain of the problems in arriving at a psychodynamic formulation of specific psychological factors producing psychosomatic illness.
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Humans↗
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Direct comparison of muscle force predictions using linear and nonlinear programming.
Estimating forces in muscles and joints during locomotion requires formulations consistent with available methods of solving the indeterminate problem. Direct comparisons of results between differing optimization methods proposed in the literature have been difficult owing to widely varying model formulations, algorithms, input data, and other factors. We present an application of a new optimization program which includes linear and nonlinear techniques allowing a variety of cost functions and greater flexibility in problem formulation. Unified solution methods such as the one demonstrated here, offer direct evaluations of such factors as optimization criteria and constraints. This unified method demonstrates that nonlinear formulations (of the sort reported) allow more synergistic activity and in contrast to linear formulations, allow antagonistic activity. Concurrence of EMG activity and predicted forces is better with nonlinear predictions than linear predictions. The prediction of synergistic and antagonistic activity expectedly leads to higher joint force predictions. Relaxation of the requirement that muscles resolve the entire intersegmental moment maintains muscle synergism in the nonlinear formulation while relieving muscle antagonism and reducing the predicted joint contact force. Such unified methods allow more possibilities for exploring new optimization formulations, and in comparing the solutions to previously reported formulations.
Algorithms↗
Rate-distortion optimal video summary generation.
The need for video summarization originates primarily from a viewing time constraint. A shorter version of the original video sequence is desirable in a number of applications. Clearly, a shorter version is also necessary in applications where storage, communication bandwidth, and/or power are limited. The summarization process inevitably introduces distortion. The amount of summarization distortion is related to its "conciseness," or the number of frames available in the summary. If there are m frames in the original sequence and n frames in the summary, we define the summarization rate as m/n, to characterize this "conciseness". We also develop a new summarization distortion metric and formulate the summarization problem as a rate-distortion optimization problem. Optimal algorithms based on dynamic programming are presented and compared experimentally with heuristic algorithms. Practical constraints, like the maximum number of frames that can be skipped, are also considered in the formulation and solution of the problem.
Algorithms↗
The SAS maximal principle: a new approach to the phase problem.
The phase problem, when single-wavelength anomalous scattering (SAS) diffraction data are available, is formulated as a problem in global optimization. Although the objective function has a myriad of local maxima, its global maxima, never more than two, are readily accessible and easily identified by virtue of their isolation. The ability to determine the global maxima of the objective function represents the latest and most successful attempt to go directly from the known probabilistic estimates of the three-phase structure invariants to the values of the individual phases. The relationship between the maxima of the objective function and the solutions of the newly formulated system of SAS tangent equations plays a key role in this development.
Linear Models↗
A hybrid hopfield network-simulated annealing approach for frequency assignment in satellite communications systems.
A hybrid Hopfield network-simulated annealing algorithm (HopSA) is presented for the frequency assignment problem (FAP) in satellite communications. The goal of this NP-complete problem is minimizing the cochannel interference between satellite communication systems by rearranging the frequency assignment, for the systems can accommodate the increasing demands. The HopSA algorithm consists of a fast digital Hopfield neural network which manages the problem constraints hybridized with a simulated annealing which improves the quality of the solutions obtained. We analyze the problem and its formulation, describing and discussing the HopSA algorithm and solving a set of benchmark problems. The results obtained are compared with other existing approaches in order to show the performance of the HopSA approach.
Journal Article↗
Aspects of consumer search for health information: a framework for structuring information problems.
Consumer search for health information is the focus of increasing scholarly activity and administrative thinking. It has drawn attention in many circles of inquiry including marketing, health-care, and public policy. Because of this widespread attention, the literature is rather fragmented and therefore research problems are not easily defined. This paper presents an integrative framework to help formulate health information problems more precisely and to distinguish important areas for continued research efforts. Three major aspects of consumer search for health information are identified: sources, effort, and topics. These aspects- and the interrelationships among them--comprise the framework. Related research can be categorized and synthesized, and then critical gaps in the research streams become more evident. Furthermore, the framework can be applied to particular information problems to both clarify the issues and to communicate those issues to health care managers and relevant constituencies. Applied examples discussed in this paper are: (1) direct-to-consumer advertising, (2) telephone information services, and (3) hospital mortality data.
Advertising↗
Application of the boundary-element method to the interaction of light with single and coupled metallic nanoparticles.
The boundary-element method is applied to the interaction of light with resonant metallic nanoparticles. At a certain wavelength, excitation of a surface plasmon takes place, which leads to a resonantly enhanced near-field amplitude and a large scattering cross section. The resonance wavelength for different scatterer geometries is determined. Alteration of the scattering properties in the presence of other metallic nanoparticles is discussed. To treat this problem, a novel formulation of the boundary-element method is presented that solves the interaction problem for all the coupled particles.
Journal Article↗
Segmentation given partial grouping constraints.
We consider data clustering problems where partial grouping is known a priori. We formulate such biased grouping problems as a constrained optimization problem, where structural properties of the data define the goodness of a grouping and partial grouping cues define the feasibility of a grouping. We enforce grouping smoothness and fairness on labeled data points so that sparse partial grouping information can be effectively propagated to the unlabeled data. Considering the normalized cuts criterion in particular, our formulation leads to a constrained eigenvalue problem. By generalizing the Rayleigh-Ritz theorem to projected matrices, we find the global optimum in the relaxed continuous domain by eigendecomposition, from which a near-global optimum to the discrete labeling problem can be obtained effectively. We apply our method to real image segmentation problems, where partial grouping priors can often be derived based on a crude spatial attentional map that binds places with common salient features or focuses on expected object locations. We demonstrate not only that it is possible to integrate both image structures and priors in a single grouping process, but also that objects can be segregated from the background without specific object knowledge.
Algorithms↗
An uncertainty analysis of the flood-stage upstream from a bridge.
The paper begins with the formulation of the problem in the form of a general performance function. Next the Latin hypercube sampling (LHS) technique--a modified version of the Monte Carlo method is briefly described. The essential uncertainty analysis of the flood-stage upstream from a bridge starts with a description of the hydraulic model. This model concept is based on the HEC-RAS model developed for subcritical flow under a bridge without piers in which the energy equation is applied. The next section contains the characteristic of the basic variables including a specification of their statistics (means and variances). Next the problem of correlated variables is discussed and assumptions concerning correlation among basic variables are formulated. The analysis of results is based on LHS ranking lists obtained from the computer package UNCSAM. Results fot two examples are given: one for independent and the other for correlated variables.
Disasters↗
The vaccine formulation and its role in inflammatory processes in fish--effects and adverse effects.
Adjuvants are helper substances that assist in the development of vaccine efficacy by enhancing the magnitude, extending the duration and/or directing the nature of the immune response. Most fish vaccines for injection are formulated with oil adjuvants and provide a strong and long-lasting immunity. Inherent problems of such formulations are the injection-site reactions, the challenge being to balance adjuvanticity against reactogenicity to produce a sufficient level of protection with as few side-effects as possible. Current findings on cellular inflammatory responses to oil adjuvanted vaccines in fish and on prediction factors for the effect versus side-effect balance are being discussed. The focus of future vaccine formulation studies will probably comprise the effect of formulation parameters on antigen retention, and the effect of antigen purity and concentration on recipient fish responses at the cellular and cytokine level.
Adjuvants, Immunologic↗
An analysis of standardized disease classification system for health care planning.
This paper deals with the development of the standardized disease classification system, which generates usable statistics for comprehensive health care planning. It is used by ARCH (a regional health planning agency) to obtain a measure of acute hospital utilization and regional health status. A sample of 35,000 patients discharged from 39 acute-care facilities in the St. Louis bistate region was examined and tested. The existing disease classification systems (three versions of ICD and SNDO) were converted into the standardized system. Its application results in a better conceptualization of current health problems. It aids in the formulation and monitoring of health problems.
Disease↗
Motion analysis in the hemicochlea.
Optical flow techniques are often used to estimate velocity fields to represent motion in successive video images. Usually the method is mathematically ill-posed, because the single scalar equation representing the conservation of local intensity contains more than one unknown velocity component. Instead of regularizing the problem using optimization techniques, we formulate a well-posed problem for the gerbil hemicochlea preparation by introducing an in-plane incompressibility constraint, and then show that local brightness is also conserved. We solve the resulting system using a Lagrangian description of the conservation equations. With this approach, the displacement of isointensity contours on sequential images determines the normal component of velocity of an area element, while the tangential component is computed from the local constant area constraint. We have validated our method using pairs of images generated from our calculations of the vibrational deformation in a cross section of the organ of Corti and tectorial membrane in the mammalian cochlea, and quantified the superior performance of our method when complex artificial motion is applied to a noisy image obtained from the hemicochlea preparation. The micromechanics of the organ of Corti and the tectorial membrane is then analyzed by our new method.
Algorithms↗
Approaches to reducing subvisible particle counts in lyophilized parenteral formulations.
Reduction in subvisible particle counts in parenteral formulations is an important requirement. Despite selection of best container/closure and use of processing conditions where the drug is most soluble and stable, lyophilized formulations often demonstrate problems of subvisible particle counts greater than the permitted compendial limits. We have studied some formulation and processing approaches with different compounds with the intention of developing lyophilized products, which after reconstitution, pass compendial subvisible particle limits for large volume parenterals (LVP). The approaches studied were targeted to reduce "intrinsic" subvisible particle counts and included the addition of a solubilizing agent, pH adjustment, charcoal treatment of the process solution, and use of a filter with finer pore size for filtering the solution prior to lyophilization. Although the relative efficiency of each of these parameters in reducing subvisible particle counts was found to be slightly different for each compound, the inclusion of a solubilizing agent and charcoal treatment of the processing solution were found to have the most pronounced effect. The combination of two or more parameters was often found to be even more effective. It is suggested that these approaches may be useful in developing other lyophilized products that yield low subvisible particle counts on reconstitution.
Charcoal↗
Preventing the gastrointestinal consequences of stress-related mucosal disease.
Stress-related mucosal disease (SRMD) and subsequent upper gastrointestinal (GI) bleeding remain significant concerns in critically ill patients and place them at a high risk of death. Even under circumstances in which GI bleeding is detected, it is difficult to control. Thus, appropriate preventative therapy is the key to reducing mortality in patients at risk for stress-related ulceration and bleeding. Although several factors (e.g., hypoperfusion of the GI tract, reflux of bile salts) contribute to the development of stress-related ulceration, acid is presumed to be a major contributor to this disease state. Current preventative treatment strategies use histamine2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs), which suppress acid secretion, and sucralfate, which provides a protective barrier against acid in the GI tract. For the past several years, H2RAs have been preferentially used over PPIs in the hospital setting because H2RAs are available in liquid and intravenous formulations, easing administration problems in the critically ill. However, extemporaneously compounded oral PPI suspensions and the recently approved intravenous formulations of pantoprazole and lansoprazole have eliminated some of the administration issues previously associated with PPIs. Additionally, study data with PPI formulations suggest efficacy in stress ulcer prophylaxis compared with H2RAs. This article provides an overview of SRMD and compares and contrasts the 3 drug classes (i.e., H2RAs, PPIs, and sucralfate) currently used for prevention of this serious complication observed in critically ill patients.
Anti-Ulcer Agents↗
The nonsteady state modeling of freeze drying: in-process product temperature and moisture content mapping and pharmaceutical product quality applications.
INTRODUCTION: Theoretical models of the freeze-drying process are potentially useful to guide the design of a freeze-drying process as well as to obtain information not readily accessible by direct experimentation, such as moisture distribution and glass transition temperature, Tg, within a vial during processing. Previous models were either restricted to the steady state and/or to one-dimensional problems. While such models are useful, the restrictions seriously limit applications of the theory. An earlier work from these laboratories presented a nonsteady state, two-dimensional model (which becomes a three-dimensional model with an axis of symmetry) of sublimation and desorption that is quite versatile and allows the user to investigate a wide variety of heat and mass transfer problems in both primary and secondary drying. The earlier treatment focused on the mathematical details of the finite element formulation of the problem and on validation of the calculations. The objective of the current study is to provide the physical rational for the choice of boundary conditions, to validate the model by comparison of calculated results with experimental data, and to discuss several representative pharmaceutical applications. To validate the model and evaluate its utility in studying distribution of moisture and glass transition temperature in a representative product, calculations for a sucrose-based formulation were performed, and selected results were compared with experimental data. THEORETICAL MODEL: The model is based on a set of coupled differential equations resulting from constraints imposed by conservation of energy and mass, where numerical results are obtained using finite element analysis. Use of the model proceeds via a "modular software package" supported by Technalysis Inc. (Passage/ Freeze Drying). This package allows the user to define the problem by inputing shelf temperature, chamber pressure, container properties, product properties, and numerical analysis parameters required for the finite element analysis. Most input data are either available in the literature or may be easily estimated. Product resistance to water vapor flow, mass transfer coefficients describing secondary drying, and container heat transfer coefficients must normally be measured. Each element (i.e., each small subsystem of the product) may be assigned different values of product resistance to accurately describe the nonlinear resistance behavior often shown by real products. During primary drying, the chamber pressure and shelf temperature may be varied in steps. During secondary drying, the change in gas composition from pure water to mostly inert gas is calculated by the model from the instantaneous water vapor flux and the input pumping capacity of the freeze dryer. RESULTS: Comparison of the theoretical results with the experiment data for a 3% sucrose formulation is generally satisfactory. Primary drying times agree within two hours, and the product temperature vs. time curves in primary drying agree within about +/-1 degrees C. The residual moisture vs. time curve is predicted by the theory within the likely experimental error, and the lack of large variation in moisture within the vial (i.e., top vs. side vs. bottom) is also correctly predicted by theory. The theoretical calculations also provide the time variation of "Tg-T" during both primary and secondary drying, where T is product temperature and Tg is the glass transition temperature of the product phase. The calculations demonstrate that with a secondary drying protocol using a rapid ramp of shelf temperature, the product temperature does rise above Tg during early secondary drying, perhaps being a factor in the phenomenon known as "cake shrinkage." CONCLUSION: The theoretical results of in-process product temperature, primary drying time, and moisture content mapping and history are consistent with the experimental results, suggesting the theoretical model should be useful in process development and "trouble-shooting" applications.
Chemistry, Pharmaceutical↗
Psychiatric diagnosis as an ethical problem.
Psychiatrists diagnose mental illness in patients against a climate of opinion in which the value of diagnosis is questioned and non-medical formulations of the problems of psychiatric patients are put forward. Nevertheless the classic diagnostic terminology shows no sign of disappearing. The patients may find that a psychiatric diagnostic label is a stigma and has bad consequences. They may also object to standard methods of treatment. Given this situation the right of the patient to a full explanation of the diagnosis and the rationale of the treatment offered seems to be incontrovertible. If this information were given to patients it would, in addition, help them to make sense out of their often puzzling experiences and indicate that fellow sufferers existed.
Ethics, Medical↗
On the inverse problem in flow cytometry recovering DNA distribution from FMF data.
The problem of recovering DNA distribution from cytofluorometric experimental data was investigated. Theoretical analysis led to a convenient formulation of the problem and to uniqueness results for its solution. A minimization algorithm has been implemented to get the optimal estimate of G1, S, G2, and M phase percentages. This algorithm was tested in some experimental cases.
Animals↗
Multielectrode venous catheter mapping as a high quality constraint for electrocardiographic inverse solution.
A persistent challenge in solving inverse problems in electrocardiography is the application of suitable constraints to the calculation of cardiac sources. Whether one formulates the inverse problem in terms of epicardial potentials or activation wavefronts, the problem is physically ill-posed and hence results in numerically unstable computations. Suitable physiological constraints applied with appropriate weighting can recover useful inverse solutions. However, it is often difficult to determine the best possible constraints and their optimal weighting. We have recently begun to use multielectrode catheters as a means of mapping epicardial signals in animal models. To accommodate the sparse sampling of this venous catheter based approach, we have applied statistical signal processing methods to estimate complete epicardial maps of activation time and epicardial potentials. Such measurements--and the estimated maps from them--also have the potential to provide high quality constraints for electrocardiographic inverse problems because they provide direct--albeit sparse--access to the desired solution. In this presentation we describe several approaches we have applied to extract useful constraints from sparsely sampled epicardial signals as well as a training set of epicardial maps, and use them to improve the quality of computed inverse solutions. Results suggest that combining various information sources provides valuable constraint information. Such a multimodal approach to cardiac mapping is clinically and technically viable and offers a possible means to overcome a major remaining limitation of inverse electrocardiography.
Animals↗