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At least 883 records · Page 49Linked to original sources

PubMed2001

Su-6668. SUGEN.

SUGEN is developing SU-6668, a tyrosine kinase inhibitor that inhibits three distinct growth factor receptor targets, for the potential treatment of cancer [304530]. The compound is in phase I trials in the UK and US [321260], [374505]. A report in January 2001 stated that phase I/II trials for hematological and solid tumors were expected to commence shortly thereafter [395657]. In May 2001, phase I data from a dose-escalation study conducted at UCLA were presented at the 37th ASCO meeting in San Francisco, CA. By that time, 74 patients had been enrolled in this study which aimed to determine the toxicities of SU-6668 when delivered to fed and fasting patients. SU-6668 was administered orally either once or twice-daily at doses of 100 to 2400 mg/m2 to patients diagnosed as having advanced malignancies. Accrual in phase I is continuing to define the toxicities of doses > 200 mg/m2 twice-daily [409984], [411418]. In December 1998, SUGEN filed an IND with the FDA for the clinical testing of this compound with oral and iv formulations [310237]. In November 1998, SUGEN entered into a collaboration with the Cancer Research Campaign (CRC) to conduct a phase I trial of SU-6668 at the Royal Marsden Hospital, UK using an iv formulation [304530]. After the first six patients had been treated, the trial was halted owing to problems with the iv formulation. Some toxicities, including nausea, vomiting, fatigue and tumor pain were observed [413538]. No licensing agreement as involved between the CRC and SUGEN for this trial [408572].

Animals↗

PubMed2001

[Vision-impaired patients. Nursing diagnoses].

The author analyzes the most habitual problems one encounters in patients suffering a visual deficit, using the NANDA diagnostic taxonomy. The author formulates and classifies these problems as well as the specific nursing treatments which should be carried out when dealing with each one of these problems.

Humans↗

PubMed2002

Bayesian framework for least-squares support vector machine classifiers, gaussian processes, and kernel Fisher discriminant analysis.

The Bayesian evidence framework has been successfully applied to the design of multilayer perceptrons (MLPs) in the work of MacKay. Nevertheless, the training of MLPs suffers from drawbacks like the nonconvex optimization problem and the choice of the number of hidden units. In support vector machines (SVMs) for classification, as introduced by Vapnik, a nonlinear decision boundary is obtained by mapping the input vector first in a nonlinear way to a high-dimensional kernel-induced feature space in which a linear large margin classifier is constructed. Practical expressions are formulated in the dual space in terms of the related kernel function, and the solution follows from a (convex) quadratic programming (QP) problem. In least-squares SVMs (LS-SVMs), the SVM problem formulation is modified by introducing a least-squares cost function and equality instead of inequality constraints, and the solution follows from a linear system in the dual space. Implicitly, the least-squares formulation corresponds to a regression formulation and is also related to kernel Fisher discriminant analysis. The least-squares regression formulation has advantages for deriving analytic expressions in a Bayesian evidence framework, in contrast to the classification formulations used, for example, in gaussian processes (GPs). The LS-SVM formulation has clear primal-dual interpretations, and without the bias term, one explicitly constructs a model that yields the same expressions as have been obtained with GPs for regression. In this article, the Bayesian evidence framework is combined with the LS-SVM classifier formulation. Starting from the feature space formulation, analytic expressions are obtained in the dual space on the different levels of Bayesian inference, while posterior class probabilities are obtained by marginalizing over the model parameters. Empirical results obtained on 10 public domain data sets show that the LS-SVM classifier designed within the Bayesian evidence framework consistently yields good generalization performances.

Artificial Intelligence↗

PubMedDate not supplied

Fuzzy least squares support vector machines for multiclass problems.

In least squares support vector machines (LS-SVMs), the optimal separating hyperplane is obtained by solving a set of linear equations instead of solving a quadratic programming problem. But since SVMs and LS-SVMs are formulated for two-class problems, unclassifiable regions exist when they are extended to multiclass problems. In this paper, we discuss fuzzy LS-SVMs that resolve unclassifiable regions for multiclass problems. We define a membership function in the direction perpendicular to the optimal separating hyperplane that separates a pair of classes. Using the minimum or average operation for these membership functions, we define a membership function for each class. Using some benchmark data sets, we show that recognition performance of fuzzy LS-SVMs with the minimum operator is comparable to that of fuzzy SVMs, but fuzzy LS-SVMs with the average operator showed inferior performance.

Fuzzy Logic↗

PubMed2004

Multiple causes of difficulty in insight: the case of the nine-dot problem.

Theories of insight problems are often tested by formulating hypotheses about the particular difficulties of individual insight problems. Such evaluations often implicitly assume that there is a single difficulty. We argue that the quantitatively small effects of many studies arise because the difficulty of many insight problems is determined by multiple factors, so the removal of 1 factor has limited effect on the solution rate. Difficulties can reside either in problem perception, in prior knowledge, or in the processing of the problem information. We support this multiple factors perspective through 3 experiments on the 9-dot problem (N.R.F. Maier, 1930). Our results lead to a significant reformulation of the classical hypothesis as to why this problem is difficult. The results have general implications for our understanding of insight problem solving and for the interpretation of data from studies that aim to evaluate hypotheses about the sources of difficulty of particular insight problems.

Cognition↗

PubMed2004

A graph-theoretic approach for the separation of b and y ions in tandem mass spectra.

MOTIVATION: Ion-type identification is a fundamental problem in computational proteomics. Methods for accurate identification of ion types provide the basis for many mass spectrometry data interpretation problems, including (a) de novo sequencing, (b) identification of post-translational modifications and mutations and (c) validation of database search results. RESULTS: Here, we present a novel graph-theoretic approach for solving the problem of separating b ions from y ions in a set of tandem mass spectra. We represent each spectral peak as a node and consider two types of edges: type-1 edge connecting two peaks probably of the same ion types and type-2 edge connecting two peaks probably of different ion types. The problem of ion-separation is formulated and solved as a graph partition problem, which is to partition the graph into three subgraphs, representing b, y and others ions, respectively, through maximizing the total weight of type-1 edges while minimizing the total weight of type-2 edges within each partitioned subgraph. We have developed a dynamic programming algorithm for rigorously solving this graph partition problem and implemented it as a computer program PRIME (PaRtition of Ion types in tandem Mass spEctra). The tests on a large amount of simulated mass spectra and 19 sets of high-quality experimental Fourier transform ion cyclotron resonance tandem mass spectra indicate that an accuracy level of approximately 90% for the separation of b and y ions was achieved. AVAILABILITY: The executable code of PRIME is available upon request. CONTACT: xyn@bmb.uga.edu.

Algorithms↗

PubMed2001

Entropy-based analysis of the number partitioning problem.

In this paper we apply the multicanonical method of statistical physics on the number partitioning problem (NPP). This problem is a basic NP-hard problem from computer science, and can be formulated as a spin-glass problem. We compute the spectral degeneracy, which gives us information about the number of solutions for a given cost E and cardinality difference m. We also study an extension of this problem for Q partitions. We show that a fundamental difference on the spectral degeneracy of the generalized (Q>2) NPP exists, which could explain why it is so difficult to find good solutions for this case.

Journal Article↗

PubMed1990

Diurnal variation of carbamazepine and carbamazepine-10,11-epoxide in plasma and saliva in children with epilepsy: a comparison between conventional and slow-release formulations.

In order to overcome the problems of interdosage fluctuations of body fluid concentrations of carbamazepine, a slow-release formulation has been developed. In an open, controlled, within-patient study, the diurnal plasma concentrations of carbamazepine and its 10,11-epoxide were measured in 25 epileptic children first treated with conventional carbamazepine tablets (Tegretol) and then with the Tegretol slow-release preparation. The diurnal plasma concentration curves during treatment with the slow-release formulation showed significantly less variation over 24 hours than during treatment with the ordinary preparation, as measured by the fluctuation index. Mean concentration values also differed significantly, which is explained by a somewhat reduced bioavailability (22% less) of the slow-release formulation. There were no differences in efficacy and tolerability between the two formulations, but there was a clear-cut reduction of reported side effects, especially tiredness, on treatment with the slow-release formulation. For that reason, the slow-release formulation should be a major advantage in treating children with epilepsy, in order to avoid interference with cognitive functions. In 12 children, simultaneous measurements of the concentration of carbamazepine and its epoxide in saliva were made and compared with the plasma values. As expected, the concentration curves corresponded, indicating that saliva sampling is an appropriate alternative for monitoring the concentration of carbamazepine. All children remained on the slow-release preparation after the trial and were followed up for 12 months or more.

Adolescent↗

PubMed2002

Sulfometuron incorporation in cationic micelles adsorbed on montmorillonite.

The aim of this study was to understand the interactions between alkylammonium cations present as monomers and micelles and a clay mineral, montmorillonite, to develop slow release formulations of anionic herbicides, such as sulfometuron (SFM) whose leaching in soils is an environmental and economic problem. In the proposed formulation the herbicide is incorporated in positively charged micelles of quaternary amine cations, which in turn adsorb on the negatively charged clay. The adsorption of hexadecyltrimethylammonium (HDTMA) and octadecyltrimethylammonium (ODTMA) on montmorillonite was studied above and below their critical micelle concentrations (CMC). At concentrations above the CMC, the loading exceeded the clay's cation exchange capacity (CEC) and indicated higher affinity of the cation with the longer alkyl chain. An adsorption model could adequately simulate adsorption at concentrations below the CMC, and yield fair predictions for the effect of ionic strength. The model indicated that above the CMC adsorbed micelles contributed significantly to the amount of ODTMA adsorbed. Evidence for adsorption of ODTMA micelles on montmorillonite was provided by X-ray diffraction, freeze-fracture electron microscopy, and dialysis bag measurements. SFM was not adsorbed directly on the clay mineral, and adsorbed at low levels, when the organic cation was adsorbed as monomers. In contrast, a large fraction of SFM adsorbed on the clay mineral when incorporated in micelles that adsorbed on the clay.

Adsorption↗

PubMed1975

Statistics and medical experimentation.

Starting from a review of four major experimental areas in medicine (Polio, Coronary Surgery, Diabetes, Breast Cancer), some of the special statistical problems arising in the design and analysis of clinical experiments are reviewed, and the limitations of current formulations are emphasized. Particular attention is given to the ethical dilemma and an alternative formulation of the inference/decision problem is proposed.

Aged↗

PubMed2005

The use of unlicensed and off-label medicines in the neonate.

The use of unlicensed and off-label medicines in neonates in intensive care is common and widespread. Up to 93% of babies receive at least one unlicensed or off-label medicine during their stay in intensive care. Such practice is an essential part of their care and should be done based on the best evidence available. However, problems arise - on an every-day basis - because of the lack of appropriate information and licensed medicine formulations for neonates. These problems include the selection of appropriate medicine and dose, administration and the increased risk of medication errors. Initiatives to improve the situation are underway in the US and are proposed in Europe. However, more urgent action is required to stop these babies continuing to be deprived of their basic human rights to safe, effective and high-quality therapy.

Contraindications↗

PubMed1989

[Operations research in group feeding programs: techniques for the identification and analysis of management problems].

The operations of the group feeding programs (PAG--"Programas de Alimentación a Grupos"--) can be viewed as a sequence of decisions and activities that according to their direction, order, relationship and dependency, will influence the quality and quantity of the service's delivery. While searching for the essential characteristics of a PAG: components, relationship, variables, pertinent parameters, restrictions, underlying criteria and objective functions, operations research can be useful for its analysis, the identification of its management problems, and to develop, evaluate and finally, implement solutions. Various operation research techniques are presented in this article, which are geared towards responding to those knowledge needs of the national technicians and program managers, in order to give a solid foundation to solutions for the management problems identified in a PAG. Failures of different quantitative models had been due, mainly, to the tendency to formulate models or investigate problems without users being prepared to implement the solutions. The techniques presented herein take into consideration the interaction between specialists and users.

Food Services↗

PubMed2006

Antagonistic activity of one-joint muscles in three-dimensions using non-linear optimisation.

Non-linear optimisation, such as the type presented by R.D. Crowninshield and R.A. Brand [The prediction of forces in joint structures: Distribution of intersegmental resultants, Exercise Sports Sci. Rev. 9 (1981) 159], has been frequently used to obtain a unique set of muscle forces during human or animal movements. In the past, analytical solutions of this optimisation problem have been presented for single degree-of-freedom models, and planar models with a specific number of muscles and a defined musculoskeletal geometry. Results of these studies have been generalised to three-dimensional problems and for general formulations of the musculoskeletal geometry without corresponding proofs. Here, we extend the general solution of the above non-linear, constrained, planar optimisation problem to three-dimensional systems of arbitrary geometry. We show that there always exists a set of intersegmental moments for which the given static optimisation formulation will predict co-contraction of a pair of antagonistic muscles unless they are exact antagonists. Furthermore, we provide, for a given three-dimensional system consisting of single joint muscles, a method that describes all the possible joint moments that give co-contraction for a given pair of antagonistic muscles.

Animals↗

PubMed1996

Reversal of cyclosporine malabsorption in diabetic recipients of simultaneous pancreas and kidney transplant using a microemulsion formulation.

In view of the known problems that diabetic recipients have with drug absorption and of the potential advantages of the microemulsion formulation of cyclosporine (Neoral), 17 previously diabetic recipients of simultaneous pancreas and kidney allografts were studied before and after conversion from Sandimmune (SIM) to Neoral (NEO) formulations of cyclosporine a mean of 4.75 +/- 2.0 years after transplantation. The aims of this study were to determine whether there were changes in the absorption profiles using the 2 formulations and to analyze the safety of conversion from SIM to NEO on a 1:1 ratio. Pharmacokinetic, clinical, and renal function parameters were measured 2 weeks before, and 2 and 4 weeks after conversion. Pharmacokinetics demonstrated that, when taking SIM, only 5 patients had "good absorption" (maximal concentration >500 ng/ml and time to maximal concentration < / = 2 hr), but after conversion to NEO, 14 at week +2, and 13 at week +4 were good absorbers (P<0.02 and <0.01, respectively). There was a 50% reduction in the time to maximal blood concentration (from 3.2 +/- 1.9 hr with SIM, to 1.8 +/- 1.3 hr on NEO [P<0.007]) and a 36% increase in trough and a 143% increase (P<0.01) in maximal blood concentrations, although the 9-hr cyclosporine AUC showed an 89% increase (P<0.01). There was an 18% mean reduction in dose per kilogram prescribed 4 weeks after conversion. Renal function, measured by serum creatinine and technecium-99m diethylenetriamine pentaacetic acid glomerular filtration rate, was not altered and no adverse events were attributed to NEO. This study confirmed that previously diabetic recipients of simultaneous renal pancreas allografts had variable and poor absorption of cyclosporine using conventional Sandimmune and that this absorption was improved by conversion to Neoral.

Absorption↗

PubMed2003

Laboratory procedures for the diagnosis of gastrointestinal tract diseases of dogs and cats.

An increasing number of laboratory tests are available for diagnosis of gastrointestinal tract diseases in dogs and cats. Use of these tests can lead to more accurate and rapid diagnoses. This review discusses laboratory tests, both new and old, and the role they currently play in the evaluation of animals presented with gastrointestinal problems. A minimum database helps assess the severity of the disorder, detect extra-gastrointestinal causes of problems and assists in formulating diagnostic and therapeutic plans. Faecal examination remains one of the most important diagnostic procedures in the investigation of gastrointestinal problems. Zinc sulphate faecal flotation is an excellent routine screening technique for helminth and protozoal infections, including giardiasis. Rectal cytology can assist in the diagnosis of large bowel disorders. Interpretation of faecal immunodiagnostic tests is hampered by insufficient knowledge of test sensitivities and specificities. Routine faecal cultures are not warranted and faecal occult blood tests are rarely indicated. Serum tests for gastric inflammation are now under development. The serum trypsin-like immunoreactivity test remains the gold standard technique for the diagnosis of exocrine pancreatic insufficiency. Breath hydrogen tests can be helpful in assessing the functional relevance of mild abnormalities in small-bowel biopsy specimens. Subnormal concentrations of serum cobalamin appear to be more specific indicators of gastrointestinal disease in cats than in dogs. Tests for small intestinal bacterial overgrowth remain controversial and assessment of gastrointestinal permeability has yet to prove its value in the diagnostic assessment of companion animals with gastrointestinal problems. Faecal alpha1-protease inhibitor shows promise for the diagnosis of protein-losing enteropathy.

Journal Article↗

PubMed2006

Structured one-class classification.

The one-class classification problem aims to distinguish a target class from outliers. The spherical one-class classifier (SOCC) solves this problem by finding a hypersphere with minimum volume that contains the target data while keeping outlier samples outside. SOCC achieves satisfactory performance only when the target samples have the same distribution tendency in all orientations. Therefore, the performance of the SOCC is limited in the way that many superfluous outliers might be mistakenly enclosed. The authors propose to exploit target data structures obtained via unsupervised methods such as agglomerative hierarchical clustering and use them in calculating a set of hyperellipsoidal separating boundaries. This method is named the structured one-class classifier (TOCC). The optimization problem in TOCC can be formulated as a series of second-order cone programming problems that can be solved with acceptable efficiency by primal-dual interior-point methods. The experimental results on artificially generated data sets and benchmark data sets demonstrate the advantages of TOCC.

Journal Article↗

PubMed1997

The inverse problem of electrocardiography: a solution in terms of single- and double-layer sources of the epicardial surface.

An approach to the inverse problem of electrocardiography that involves an estimation of the electric potentials (double-layer equivalent sources) on the heart's epicardial surface from the electrocardiographic potentials that are measurable on the body surface has received considerable attention. This report deals with a heretofore unexplored extension of this approach, one that yields, in addition to the electric potentials on the epicardial surface, the normal components of their gradients (single-layer equivalent sources). We show that this formulation has at least three advantages over the formulation in term of epicardial potentials alone: (1) single-layer equivalent sources, which reflect the flow of current across the epicardial surface, are well suited for the imaging of regional ischemia and infarction; (2) the transfer matrix linking the epicardial and body-surface potentials for this formulation is less ill conditioned than that for the formulation in terms of potentials alone; (3) the input vector for inverse calculations consists of spatially filtered (rather that directly measured and therefore noise) body-surface potentials. To establish the feasibility of this new formulation of the inverse problem and to compare it with the formulation in terms of potentials alone, we used a realistically shaped boundary-element model of human torso. By calculating singular values less ill conditioned. We then directly calculated epicardial and body-surface potentials for a single dipole located centrally and for three simultaneously active dipoles located eccentrically in the torso's heart region and used these results to test three methods that are prerequisites of a successful inverse solution: Tikhonov regularization, linearly constrained least squares, and an L-curve method. The feasibility of the new formulation was demonstrated by the fact that the method based on the linearly constrained least squares improved on overregularized Tikhonov solutions over a wide range of regularization parameters, and it yielded solutions that were more accurate than the best-possible Tikhonov solutions. Moreover, the L-curve solution procedure, which requires no a priori information about the solution, yielded slightly underregularized, but accurate, estimates for the optimal regularization parameter and the corresponding best-possible Tikhonov solution. Our results also showed that replacing--in the interest computational economy--quadrature formulas for the planar triangles with various approximate formulas for the nodes of the model reduces the accuracy of the inverse solution.

Electrocardiography↗

PubMed1999

Parental use of alcohol and children's behavioural health: a household production analysis.

This study uses the 1988 National Health Interview Survey (NHIS) data to examine the effects of both heavy and problem drinking as well as moderate or light parental alcohol use on children's behaviour problems. The analysis is formulated within Becker's household production function framework. The production of child behavioural health is estimated using items from the Behavior Problems Index, a battery of 32 questions about behaviour problems which is derived from the Child Behavior Checklist (CBCL), a widely-used parent report instrument. Measures of parents' alcohol consumption are constructed from the NHIS Alcohol Supplement that was administered to one randomly selected adult in each household in 1988. Ordinary least squares (OLS) and two-stage least squares (TSLS) results are presented. The results provide consistent evidence that parental alcohol use is an input with negative marginal product in the production of child behavioural health, regardless of which parent drinks. The magnitude of the effect is generally larger in the TSLS specification. There is also strong evidence of relationships between some family structure variables and child behavioural health and between parental physical health and child behavioural health.

Adolescent↗