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At least 649 records · Page 36Linked to original sources
PubMed2006

Support vector classifiers via gradient systems with discontinuous righthand sides.

Gradient dynamical systems with discontinuous righthand sides are designed using Persidskii-type nonsmooth Lyapunov functions to work as support vector machines (SVMs) for the discrimination of nonseparable classes. The gradient systems are obtained from an exact penalty method applied to the constrained quadratic optimization problems, which are formulations of two well known SVMs. Global convergence of the trajectories of the gradient dynamical systems to the solution of the corresponding constrained problems is shown to be independent of the penalty parameters and of the parameters of the SVMs. The proposed gradient systems can be implemented as simple analog circuits as well as using standard software for integration of ODEs, and in order to use efficient integration methods with adaptive stepsize selection, the discontinuous terms are smoothed around a neighborhood of the discontinuity surface by means of the boundary layer technique. The scalability of the proposed gradient systems is also shown by means of an implementation using parallel computers, resulting in smaller processing times when compared with traditional SVM packages.

Algorithms↗
PubMedDate not supplied

Colesevelam hydrochloride: a novel bile acid-binding resin.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and adverse effects of colesevelam hydrochloride, a bile acid-binding resin. METHODS: MEDLINE searches (1966-June 2000) and manufacturer prescribing literature were employed to find articles on colesevelam. Additional studies and abstracts were identified from the bibliographies of reviewed literature. STUDY SELECTION AND DATA EXTRACTION: All articles identified from data sources were evaluated, and all information deemed relevant was included in this review. Priority was given to randomized, double-blind, placebo-controlled studies. FINDINGS: Colesevelam HCl is a nonabsorbed hydrogel with bile acid sequestrant properties. Monotherapy using colesevelam in once-daily or two divided daily doses of 1.5-4.5 g has produced significant reductions in total cholesterol and low-density lipoprotein (LDL) cholesterol. Mean LDL cholesterol decreases to 20% have been noted when the patient is on 3.75-4.5 g/d. Increases in high-density lipoprotein (HDL) cholesterol have been observed (up to 9%), whereas triglycerides (TG) have increased significantly to 25% in some studies. In unpublished studies, combined use of colesevelam plus hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor have produced greater reductions in LDL cholesterol than either the statin or colesevelam administered alone. The efficacy of colesevelam monotherapy is slightly less than or similar to cholestyramine or colestipol in decreasing LDL cholesterol, although colesevelam is more potent on a gram-to-gram basis. Adverse effects have been minimal with colesevelam in published studies; this suggests an advantage over cholestyramine or colestipol therapy. Colesevelam appears to be more cost-effective than the packet dosage form of the brand formulation of the older bile acid resins. Care in selection of an appropriate agent should be exercised when considering the issues of adverse effects and palatability. CONCLUSIONS: Colesevelam alone or combined with an HMG-CoA reductase inhibitor is effective in the reduction of total and LDL cholesterol. Since colesevelam is formulated as a tablet, problems with palatability such as with the powder formulation of the bile acid-binding resins are likely to be eliminated.

Adult↗
PubMed1999

Pharmaceutical properties of fluticasone propionate nasal drops: a new formulation.

A variety of corticosteroid delivery systems have been considered for the treatment of nasal polyposis. Safety considerations favour local delivery of the drug to the nasal cavity. No topical delivery system is entirely without problems, however, and formulations must address issues of microbiological quality, drug stability, reproducible drug delivery and adequate drug distribution at site, while also offering environmental and patient acceptability. Fluticasone propionate has been formulated in a new nasal drop preparation. As a highly water-insoluble compound, the active fluticasone propionate requires micronization to an optimal particle size and subsequent dispersion with a surface-active wetting agent. The product is presented in a unit dose low-density polyethylene container, manufactured by a blow-fill-seal process and stored in an aluminium foil overwrap. Micronized active has been used to promote optimal local drug delivery, and excipients have been selected for low irritancy potential and high formulation stability. There is no microbiological risk with fluticasone propionate unit dose nasal drops 400 microg and therefore no need to include a preservative in the preparation. They provide a convenient and effective treatment option for patients with nasal polyposis.

Administration, Intranasal↗
PubMed1998

Algebraic reconstruction for magnetic resonance imaging under B0 inhomogeneity.

In magnetic resonance imaging, spatial localization is usually achieved using Fourier encoding which is realized by applying a magnetic field gradient along the dimension of interest to create a linear correspondence between the resonance frequency and spatial location following the Larmor equation. In the presence of B0 inhomogeneities along this dimension, the linear mapping does not hold and spatial distortions arise in the acquired images. In this paper, the problem of image reconstruction under an inhomogeneous field is formulated as an inverse problem of a linear Fredholm equation of the first kind. The operators in these problems are estimated using field mapping and the k-space trajectory of the imaging sequence. Since such inverse problems are known to be ill-posed in general, robust solvers, singular value decomposition and conjugate gradient method, are employed to obtain corrected images that are optimal in the Frobenius norm sense. Based on this formulation, the choice of the imaging sequence for well-conditioned matrix operators is discussed, and it is shown that nonlinear k-space trajectories provide better results. The reconstruction technique is applied to sequences where the distortion is more severe along one of the image dimensions and the two-dimensional reconstruction problem becomes equivalent to a set of independent one-dimensional problems. Experimental results demonstrate the performance and stability of the algebraic reconstruction methods.

Humans↗
PubMed2000

Bernstein's theory of movement behavior: historical development and contemporary relevance.

In present-day movement science, N. A. Bernstein's formulation of the problems of motor control is often taken as the starting point. The reliance on Bernstein has not brought agreement among his followers, however. In this article, the authors pose the following question: Does the disagreement arise from the structure of his work itself or from incomplete exploitation of his thinking? By using, inter alia, Bernstein's 24 English and German articles, the authors present an analysis of the development of Bernstein's theory of movement behavior, against the backdrop of the scientific progress in the Soviet Union in Bernstein's time and the clashes between Soviet politics and science. Bernstein addressed in his early articles the measurement and biomechanical analysis of movements. His experimental data soon indicated the need for a new understanding of the organization of movements, which he formulated in terms of coordination. Because of political problems, his work was interrupted; but after being "rehabilitated" and again allowed to work, Bernstein aimed to explain how animals find and optimize the solutions to motor problems. The structure of the theory that ensued was comprehensive exactly by virtue of his repeatedly shifting focus between the different aspects of the organization of movement: More important than the answers he gave were the questions he asked. Moreover, the way he approached those questions may help scientists solve pressing problems in present-day movement science.

Brain↗
PubMed1997

Phasing methods for protein crystallography.

The phase problem has been formulated as one of constrained global minimization and it leads to the minimal principle, which is the theoretical basis of 'Shake-and-Bake'--an algorithm for the automatic solution of the phase problem, ab initio. A related approach (termed 'Half-Baked') that, as in Shake-and-Bake, alternates phase refinement in reciprocal space with density modification in real space, has recently been formulated. The traditional techniques of direct methods have been integrated with isomorphous replacement and anomalous scattering and the first applications have been made. The accurate measurement of a limited number of structure invariants by means of multiple beam X-ray diffraction has become a reality. A feasibility study shows that, in combination with the direct method, the ability to measure the values of the structure invariants experimentally will strengthen existing techniques.

Algorithms↗
PubMed2003

Prediction of beta-sheet topology and disulfide bridges in polypeptides.

An ab initio method has been developed to predict beta architectures in polypeptides. The approach predicts the topology of beta-sheets and disulfide bridges through a novel superstructure-based mathematical framework originally established for chemical process synthesis problems. Two types of superstructure are introduced, both of which emanate from the principle that hydrophobic interactions drive the formation of a beta-structure. The mathematical formulation of the problem results in a set of integer linear programming (ILP) problems that can be solved to global optimality to identify the optimal beta-configuration. These (ILP) models can also predict a ranked ordered list of the best, second-best, third-best, etc., topologies of beta-sheets and disulfide bridges. The approach is shown to perform very well for several benchmark polypeptide systems, as well as polypeptides exhibiting challenging nonsequential beta-sheet topologies folds (56 to 187 amino acids).

Algorithms↗
PubMed2003

Fast rotational matching of rigid bodies by fast Fourier transform acceleration of five degrees of freedom.

The 'fast rotational matching' method (an approach to find the three rotational degrees of freedom in matching problems using just one three-dimensional FFT) is extended to the full six-dimensional (rotation and translation) matching scenario between two three-dimensional objects. By recasting this problem into a formulation involving five angles and just one translational parameter, it was possible to accelerate, by means of fast Fourier transforms, five of the six degrees of freedom of the problem. This method was successfully applied to the docking of atomic structures of components into three-dimensional low-resolution density maps. Timing comparisons performed with our method and with 'fast translational matching' (the standard way to accelerate the translational parameters utilizing fast Fourier transforms) demonstrates that the performance gain can reach several orders of magnitude, especially for large map sizes. This gain can be particularly advantageous for spherical- and toroidal-shaped maps, since the scanning range of the translational parameter would be significantly constrained in these cases. The method can also be harnessed to the complementary surface (or 'exterior docking') problem and to pattern recognition in image processing.

Fourier Analysis↗
PubMedDate not supplied

Setting goals and targets for performance standards within the Swedish health care system.

The development of any health care system towards setting goals and targets and intended outcomes--with national guidelines, a legislative framework, limited resources, consumer influence and competitive forces--makes great demands on the control mechanisms required. The Swedish health care system has no tradition of goal formulation of this type. Hence, the purpose of this article is to clarify the goal-setting process of performance standards, and to examine whether goal setting is a relevant method within the organization of a Swedish county council. Goal setting can be seen partly as a control method and partly as an administrative process. The approach used is a combination of qualitative and quantitative methods. Data have been collected from interviews, observations, notes taken in the field and available performance statistics. The analysis shows that working towards a goal is made easier through a common and simple concept. It 'stands and falls' with the management of the work and its manager. Good communications and information are important prerequisites if goal formulation, through dialogue, is to succeed. This process takes time and can be described as an iterative process, in which a common behaviour pattern develops a 'we-feeling' which spreads among the staff. It is important that the goal is relevant and directly related to the basic objects of the work. It is also crucial that the goal is realistic and reflects a priority. Goal formulation relating to performance standards can be a contributing factor to staff's experience of job satisfaction through increased engagement and motivation, and to the satisfaction of patients/relatives with the care given. It is difficult to formulate performance standards; there are many problems and obstacles. If goal formulation as a control method within the health care system in Sweden is to work, clearer manifestations of political will are necessary and also better measuring methods in order to guage achievement.

Attitude of Health Personnel↗
PubMed1997

The problem of the spreading of a liquid film along a solid surface: a new mathematical formulation.

A new mathematical model is proposed for the spreading of a liquid film on a solid surface. The model is based on the standard lubrication approximation for gently sloping films (with the no-slip condition for the fluid at the solid surface) in the major part of the film where it is not too thin. In the remaining and relatively small regions near the contact lines it is assumed that the so-called autonomy principle holds-i.e., given the material components, the external conditions, and the velocity of the contact lines along the surface, the behavior of the fluid is identical for all films. The resulting mathematical model is formulated as a free boundary problem for the classical fourth-order equation for the film thickness. A class of self-similar solutions to this free boundary problem is considered.

Journal Article↗
PubMed1999

An exact solution for the segment-to-segment multiple sequence alignment problem.

MOTIVATION: In molecular biology, sequence alignment is a crucial tool in studying the structure and function of molecules, as well as the evolution of species. In the segment-to-segment variation of the multiple alignment problem, the input can be seen as a set of non-gapped segment pairs (diagonals). Given a weight function that assigns a weight score to every possible diagonal, the goal is to choose a consistent set of diagonals of maximum weight. We show that the segment-to-segment multiple alignment problem is equivalent to a novel formulation of the Maximum Trace problem: the Generalized Maximum Trace (GMT) problem. Solving this problem to optimality, therefore, may improve upon the previous greedy strategies that are used for solving the segment-to-segment multiple sequence alignment problem. We show that the GMT can be stated in terms of an integer linear program and then solve the integer linear program using methods from polyhedral combinatorics. This leads to a branch-and-cut algorithm for segment-to-segment multiple sequence alignment. RESULTS: We report on our first computational experiences with this novel method and show that the program is able to find optimal solutions for real-world test examples.

Algorithms↗
PubMed2001

A graph layout algorithm for drawing metabolic pathways.

MOTIVATION: A large amount of data on metabolic pathways is available in databases. The ability to visualise the complex data dynamically would be useful for building more powerful research tools to access the databases. Metabolic pathways are typically modelled as graphs in which nodes represent chemical compounds, and edges represent chemical reactions between compounds. Thus, the problem of visualising pathways can be formulated as a graph layout problem. Currently available visual interfaces to biochemical databases either use static images or cannot cope well with more complex, non-standard pathways. RESULTS: This paper presents a new algorithm for drawing pathways which uses a combination of circular, hierarchic and force-directed graph layout algorithms to compute positions of the graph elements representing main compounds and reactions. The algorithm is particularly designed for cyclic or partially cyclic pathways or for combinations of complex pathways. It has been tested on five sample pathways with promising results.

Algorithms↗
PubMed1988

QSAR approaches to predicting toxicity.

Due to the demands of time and the high cost of testing compounds for toxicity in test animals, it would be an advantage to be able to estimate the toxic response of chemical agents using theoretical approaches. Predicting whether a compound will be toxic or nontoxic is a classification problem and the methods of studying quantitative structure activity relationships (QSAR) can be used for this purpose [Hansch, C. (1969) Accounts Chem. Res., 2, 232]. It should be recognized, however, that formulating the QSAR problem as one of active vs. inactive makes it different from classical QSAR problems. This requires that methods be applied that can predict the category of a compound to be used, i.e., so-called methods of pattern recognition (Varmuza, K. (1983) J. Chem. Info. Comp. Sci. 23, 6) being required. There are several methods of pattern recognition that can be used with some being more suitable than others. The nature of this unique QSAR problem, the appropriate methods to apply, and some of the pitfalls of applying QSAR techniques to predicting toxicity are discussed.

Computer Simulation↗
PubMed1999

APOM-project: managing change to the customer in community pharmacy practice.

In 1994, a Ph.D.-study started regarding pharmacy, organization and management (APOM) in the Netherlands. This article describes the final phase of the study in community pharmacy practice: managerial problems in change to the customer and the difference between supported pharmacy managers and independent ones. It appeared that pharmacy managers experienced problems with the formulation and use of aims, norms, and measurements. Although many organizations operating in the pharmaceutical sector are a good source for new ideas, they lack to have the proper support for these problems. The difference between supported and independent pharmacy managers was minimal in the change to the customer. Pharmacy managers are in need of micro-instrumentalization: aims, norms, and monitor instruments for customer activities applicable at their own pharmacy. Moreover, pharmacy managers will have to learn how to deal with the tension between money and care in order to improve the 'grip' on their organization.

Community Pharmacy Services↗
PubMed1969

Note on the stability problem for mammillary matrices.

The importance of the stability problem for matrices of the special form called mammillary matrices has been noted by Hearon (1). The stability problem may be formulated in terms of the Liapounov matrix equation. A constructive procedure, dependent upon the particular structure of mammillary matrices, for the solution of the Liapounov equation and the subsequent solution of the stability problem is described in this note. For an n x n matrix the principal computational steps are the solution of an n x n linear system and the determination of the rank and signature of an n x n symmetric matrix.

Mathematics↗
PubMed2005

Generic model abstraction from examples.

The recognition community has typically avoided bridging the representational gap between traditional, low-level image features and generic models. Instead, the gap has been artificially eliminated by either bringing the image closer to the models using simple scenes containing idealized, textureless objects or by bringing the models closer to the images using 3D CAD model templates or 2D appearance model templates. In this paper, we attempt to bridge the representational gap for the domain of model acquisition. Specifically, we address the problem of automatically acquiring a generic 2D view-based class model from a set of images, each containing an exemplar object belonging to that class. We introduce a novel graph-theoretical formulation of the problem in which we search for the lowest common abstraction among a set of lattices, each representing the space of all possible region groupings in a region adjacency graph representation of an input image. The problem is intractable and we present a shortest path-based approximation algorithm to yield an efficient solution. We demonstrate the approach on real imagery.

Algorithms↗
PubMed2005

A fast algorithm for the construction of universal footprinting templates in DNA.

We introduce and give a complete description of a new graph to be used for DNA sequencing questions. This graph has the advantage over the classical de Bruijn graph that it fully accounts for the double stranded nature of DNA, rather than dealing with single strands. Technically, our graph may be thought of as the quotient of the de Bruijn graph under the natural involution of sending a DNA strand to its complementary strand. However, this involution has fixed points, and this complicates the structure of the quotient graph which we have therefore modified herein. As an application and motivating example, we give an efficient algorithm for constructing universal footprinting templates for n-mers. This problem may be formulated as the task of finding a shortest possible segment of DNA which contains every possible sequence of base pairs of some fixed length n. Previous work by Kwan et al has attacked this problem from a numerical point of view and generated minimal length universal footprinting templates for n = 2, 3, 5, 7, together with unsubstantiated candidates for the case n = 4. We show that their candidates for n = 4 are indeed minimal length universal footprinting templates.

Algorithms↗
PubMedDate not supplied

Acute overdose with sustained release drug formulations. Perspectives in treatment.

Acute overdose with sustained release formulations presents special problems for the health care system. Proper management requires a basic understanding of the pharmacokinetic and pharmacodynamic characteristics of the drugs taken in overdose because different techniques employed by the manufacturers to produce sustained release formulations lead to differences in these characteristics in comparison with conventional formulations. In general, with sustained-release formulations, there is a prolongation of the time for the patient to manifest toxicity ('preclinical phase'), as well as the period of high drug concentrations and clinical toxicity ('toxic phase') and the resolution phase (clinical improvement with declining drug concentrations). Continued drug absorption over a prolonged period alters the normal drug concentration-time profile. The prolonged absorption half-life may appear as an increase in elimination half-life, even though the clearance of the drug stays the same. Gastrointestinal decontamination is extremely important in the management of overdose with sustained release formulations. We advocate an aggressive decontamination approach to management, especially in the preclinical phase. With a history of potentially toxic ingestion of an adsorbable drug, a charcoal stool following administration of oral activated charcoal should be a minimum requirement for discharge of the patient. Gastrointestinal decontamination is critical in the preclinical and the toxic phases and may be of value during the resolution phase until the drug concentrations decline to the therapeutic range.

Delayed-Action Preparations↗