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Sample records for monotonic dose-response function

  1. Monotone Boolean functions

    Energy Technology Data Exchange (ETDEWEB)

    Korshunov, A D [S.L. Sobolev Institute for Mathematics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk (Russian Federation)

    2003-10-31

    Monotone Boolean functions are an important object in discrete mathematics and mathematical cybernetics. Topics related to these functions have been actively studied for several decades. Many results have been obtained, and many papers published. However, until now there has been no sufficiently complete monograph or survey of results of investigations concerning monotone Boolean functions. The object of this survey is to present the main results on monotone Boolean functions obtained during the last 50 years.

  2. QSAR study on the non-monotonic dose-response curve of PCBs in chicken embryo hepatocyte bioassay

    Institute of Scientific and Technical Information of China (English)

    MU YunSong; ZHANG AiQian; GAO ChangAn; PENG SuFen; WANG LianSheng

    2009-01-01

    Endocrine disrupting chemicals (EDCs) in the natural environment exhibit a unique non-monotonic dose-response curve and it is impossible to select one simple index to characterize the bilogogical activity of these compounds. Quantitative structure-activity relationship (QSAR) study on non-monotonic dose-response curve has become a real challenge presently. In order to explore the possible mechanism for the non-monotonic dose-response curve of polychlorinated biphenyls con-geners (PCBs) in chicken embryo hepatocyte bioassay, AM1 method of ChemOffice was adopted to calculate necessary structure descriptors for PCBs, while the interactions between PCBs and simulated AhR ligand binding domain (LBD) were analyzed by using FlexX in SYBYL7.0. Different binding modes for PCBs have been distinguished not only from aligned conformation but also from free binding energy. Some QSAR models were established separately for both low and high doses ranges, revealing that receptor binding may predominate in the interference of the physiological function of cytochrome P4501A-P4501A in the low doses range. But with the higher doses range, the EROD suppression might he related to acute toxicity owing to molecular polarity or distribution of charges and consequently damage structure and function of chicken embryo hepatocyte.

  3. QSAR study on the non-monotonic dose-response curve of PCBs in chicken embryo hepatocyte bioassay

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Endocrine disrupting chemicals (EDCs) in the natural environment exhibit a unique non-monotonic dose-response curve and it is impossible to select one simple index to characterize the bilogogical activity of these compounds. Quantitative structure-activity relationship (QSAR) study on non-monotonic dose-response curve has become a real challenge presently. In order to explore the possible mechanism for the non-monotonic dose-response curve of polychlorinated biphenyls congeners (PCBs) in chicken embryo hepatocyte bioassay, AM1 method of ChemOffice was adopted to calculate necessary structure descriptors for PCBs, while the interactions between PCBs and simulated AhR ligand binding domain (LBD) were analyzed by using FlexX in SYBYL7.0. Different binding modes for PCBs have been distinguished not only from aligned conformation but also from free binding energy. Some QSAR models were established separately for both low and high doses ranges, revealing that receptor binding may predominate in the interference of the physiological function of cytochrome P4501A-P4501A in the low doses range. But with the higher doses range, the EROD suppression might be related to acute toxicity owing to molecular polarity or distribution of charges and consequently damage structure and function of chicken embryo hepatocyte.

  4. Quantitative structure-activity relationships of selected phenols with non-monotonic dose-response curves

    Institute of Scientific and Technical Information of China (English)

    GAO ChangAn; ZHANG AiQian; LIN Yuan; YIN DaQiang; WANG LianSheng

    2009-01-01

    Particular non-monotonic dose-response curves of many endocrine disrupting chemicals (EDCs) suggest the existence of diverse toxicity mechanisms at different dose levels. As a result, the biologi-cal activities of EDCs cannot be simply exhibited by unique EC/LD<,50. values, and the quantitative structure-activity relationship (QSAR) analysis for non-monotonic dose-response relationship be-comes an unknown field in the environmental science. In this paper, nine phenols with inverted U-shaped dose-response curves in lymphocyte proliferation test of Carassius auratus were selected. The binding interactions between the phenols and several typical EDCs-related receptors were then explored in a molecular simulation study. The estrogen receptor (ER), androgen receptor (AR), thyroid hormone receptor (TR), bacterial O2 sensing FixL protein (FixL), aryl hydrocarbon receptor (AhR), and the peroxisome proliferator-activated receptor (PPAR) were the target receptors in the study. Linear regression QSAR models for the low and high exposure levels of the compounds were developed separately. The results indicated that the lymphocyte proliferation in the low-dose range might involve ER-mediated process, while the proliferation inhibition in the high dose range was dominated by the acute toxicity of phenols due to receptor occupancy and cell damage.

  5. Low dose effects and non-monotonic dose responses for endocrine active chemicals: Science to practice workshop: Workshop summary

    DEFF Research Database (Denmark)

    Beausoleil, Claire; Ormsby, Jean-Nicolas; Gies, Andreas

    2013-01-01

    A workshop was held in Berlin September 12–14th 2012 to assess the state of the science of the data supporting low dose effects and non-monotonic dose responses (“low dose hypothesis”) for chemicals with endocrine activity (endocrine disrupting chemicals or EDCs). This workshop consisted...

  6. Version Spaces and Generalized Monotone Boolean Functions

    NARCIS (Netherlands)

    J.C. Bioch (Cor); T. Ibaraki

    2002-01-01

    textabstractWe consider generalized monotone functions f: X --> {0,1} defined for an arbitrary binary relation <= on X by the property x <= y implies f(x) <= f(y). These include the standard monotone (or positive) Boolean functions, regular Boolean functions and other interesting functions as speci

  7. Version Spaces and Generalized Monotone Boolean Functions

    NARCIS (Netherlands)

    J.C. Bioch (Cor); T. Ibaraki

    2002-01-01

    textabstractWe consider generalized monotone functions f: X --> {0,1} defined for an arbitrary binary relation <= on X by the property x <= y implies f(x) <= f(y). These include the standard monotone (or positive) Boolean functions, regular Boolean functions and other interesting functions as

  8. Monotonicity and bounds on Bessel functions

    Directory of Open Access Journals (Sweden)

    Larry Landau

    2000-07-01

    Full Text Available survey my recent results on monotonicity with respect to order of general Bessel functions, which follow from a new identity and lead to best possible uniform bounds. Application may be made to the "spreading of the wave packet" for a free quantum particle on a lattice and to estimates for perturbative expansions.

  9. Limit properties of monotone matrix functions

    NARCIS (Netherlands)

    Behrndt, Jussi; Hassi, Seppo; de Snoo, Henk; Wietsma, Rudi

    2012-01-01

    The basic objects in this paper are monotonically nondecreasing n x n matrix functions D(center dot) defined on some open interval l = (a, b) of R and their limit values D(a) and D(b) at the endpoints a and b which are, in general, selfadjoint relations in C-n. Certain space decompositions induced b

  10. Nonparametric confidence intervals for monotone functions

    NARCIS (Netherlands)

    Groeneboom, P.; Jongbloed, G.

    2015-01-01

    We study nonparametric isotonic confidence intervals for monotone functions. In [Ann. Statist. 29 (2001) 1699–1731], pointwise confidence intervals, based on likelihood ratio tests using the restricted and unrestricted MLE in the current status model, are introduced. We extend the method to the trea

  11. Competitive learning of monotone Boolean functions

    OpenAIRE

    2014-01-01

    We apply competitive analysis onto the problem of minimizing the number of queries to an oracle to completely reconstruct a given monotone Boolean function. Besides lower and upper bounds on the competitivity we determine optimal deterministic online algorithms for the smallest problem instances.

  12. Nonparametric confidence intervals for monotone functions

    NARCIS (Netherlands)

    Groeneboom, P.; Jongbloed, G.

    2015-01-01

    We study nonparametric isotonic confidence intervals for monotone functions. In [Ann. Statist. 29 (2001) 1699–1731], pointwise confidence intervals, based on likelihood ratio tests using the restricted and unrestricted MLE in the current status model, are introduced. We extend the method to the

  13. Convex functions, monotone operators and differentiability

    CERN Document Server

    Phelps, Robert R

    1993-01-01

    The improved and expanded second edition contains expositions of some major results which have been obtained in the years since the 1st edition. Theaffirmative answer by Preiss of the decades old question of whether a Banachspace with an equivalent Gateaux differentiable norm is a weak Asplund space. The startlingly simple proof by Simons of Rockafellar's fundamental maximal monotonicity theorem for subdifferentials of convex functions. The exciting new version of the useful Borwein-Preiss smooth variational principle due to Godefroy, Deville and Zizler. The material is accessible to students who have had a course in Functional Analysis; indeed, the first edition has been used in numerous graduate seminars. Starting with convex functions on the line, it leads to interconnected topics in convexity, differentiability and subdifferentiability of convex functions in Banach spaces, generic continuity of monotone operators, geometry of Banach spaces and the Radon-Nikodym property, convex analysis, variational princ...

  14. Monotone operators and "bigger conjugate" functions

    CERN Document Server

    Bauschke, Heinz H; Wang, Xianfu; Yao, Liangjin

    2011-01-01

    We study a question posed by Stephen Simons in his 2008 monograph involving "bigger conjugate" (BC) functions and the partial infimal convolution. As Simons demonstrated in his monograph, these function have been crucial to the understanding and advancement of the state-of-the-art of harder problems in monotone operator theory, especially the sum problem. In this paper, we provide some tools for further analysis of BC--functions which allow us to answer Simons' problem in the negative. We are also able to refute a similar but much harder conjecture which would have generalized a classical result of Br\\'ezis, Crandall and Pazy. Our work also reinforces the importance of understanding unbounded skew linear relations to construct monotone operators with unexpected properties.

  15. Completely monotonic functions related to logarithmic derivatives of entire functions

    DEFF Research Database (Denmark)

    Pedersen, Henrik Laurberg

    2011-01-01

    The logarithmic derivative l(x) of an entire function of genus p and having only non-positive zeros is represented in terms of a Stieltjes function. As a consequence, (-1)p(xml(x))(m+p) is a completely monotonic function for all m ≥ 0. This generalizes earlier results on complete monotonicity...... of functions related to Euler's psi-function. Applications to Barnes' multiple gamma functions are given....

  16. Nonlinearity of dose-response functions for carcinogenicity.

    OpenAIRE

    Hoel, D G; Portier, C J

    1994-01-01

    Carcinogenesis data for 315 chemicals were obtained from the National Cancer Institute-National Toxicology Program (NCI-NTP) bioassay programs and were analyzed to examine the shape of carcinogenesis dose-response curves. Tumor site data were more often consistent with a quadratic response than with a linear response, suggesting that the routine use of linear dose-response models will often overestimate risk. Information from in vivo short-term mutagenicity and genotoxicity assays was also ob...

  17. Convex functions, monotone operators and differentiability

    CERN Document Server

    Phelps, Robert R

    1989-01-01

    These notes start with an introduction to the differentiability of convex functions on Banach spaces, leading to the study of Asplund spaces and their intriguing relationship to monotone operators (and more general set-values maps) and Banach spaces with the Radon-Nikodym property. While much of this is classical, some of it is presented using streamlined proofs which were not available until recently. Considerable attention is paid to contemporary results on variational principles and perturbed optimization in Banach spaces, exhibiting their close connections with Asplund spaces. An introductory course in functional analysis is adequate background for reading these notes which can serve as the basis for a seminar of a one-term graduate course. There are numerous excercises, many of which form an integral part of the exposition.

  18. The Number of Monotone and Self-Dual Boolean Functions

    Directory of Open Access Journals (Sweden)

    Haviarova L.

    2014-12-01

    Full Text Available In the present paper we study properties of pre-complete class of Boolean functions - monotone Boolean functions. We discuss interval graph, the abbreviated d.n.f., a minimal d.n.f. and a shortest d.n.f. of this function. Then we present a d.n.f. with the highest number of conjunctionsand we determinate the exact number of them. We count the number of monotone Boolean functions with some special properties. In the end we estimate the number of Boolean functionthat are monotone and self-dual at the same time.

  19. Layered neural networks with non-monotonic transfer functions

    Science.gov (United States)

    Katayama, Katsuki; Sakata, Yasuo; Horiguchi, Tsuyoshi

    2003-01-01

    We investigate storage capacity and generalization ability for two types of fully connected layered neural networks with non-monotonic transfer functions; random patterns are embedded into the networks by a Hebbian learning rule. One of them is a layered network in which a non-monotonic transfer function of even layers is different from that of odd layers. The other is a layered network with intra-layer connections, in which the non-monotonic transfer function of inter-layer is different from that of intra-layer, and inter-layered neurons and intra-layered neurons are updated alternately. We derive recursion relations for order parameters for those layered networks by the signal-to-noise ratio method. We clarify that the storage capacity and the generalization ability for those layered networks are enhanced in comparison with those with a conventional monotonic transfer function when non-monotonicity of the transfer functions is selected optimally. We also point out that some chaotic behavior appears in the order parameters for the layered networks when non-monotonicity of the transfer functions increases.

  20. Stability of dynamical systems on the role of monotonic and non-monotonic Lyapunov functions

    CERN Document Server

    Michel, Anthony N; Liu, Derong

    2015-01-01

    The second edition of this textbook provides a single source for the analysis of system models represented by continuous-time and discrete-time, finite-dimensional and infinite-dimensional, and continuous and discontinuous dynamical systems.  For these system models, it presents results which comprise the classical Lyapunov stability theory involving monotonic Lyapunov functions, as well as corresponding contemporary stability results involving non-monotonicLyapunov functions.Specific examples from several diverse areas are given to demonstrate the applicability of the developed theory to many important classes of systems, including digital control systems, nonlinear regulator systems, pulse-width-modulated feedback control systems, and artificial neural networks.   The authors cover the following four general topics:   -          Representation and modeling of dynamical systems of the types described above -          Presentation of Lyapunov and Lagrange stability theory for dynamical sy...

  1. Monotone viable trajectories for functional differential inclusions

    Science.gov (United States)

    Haddad, Georges

    This paper is a study on functional differential inclusions with memory which represent the multivalued version of retarded functional differential equations. The main result gives a necessary and sufficient equations. The main result gives a necessary and sufficient condition ensuring the existence of viable trajectories; that means trajectories remaining in a given nonempty closed convex set defined by given constraints the system must satisfy to be viable. Some motivations for this paper can be found in control theory where F( t, φ) = { f( t, φ, u)} uɛU is the set of possible velocities of the system at time t, depending on the past history represented by the function φ and on a control u ranging over a set U of controls. Other motivations can be found in planning procedures in microeconomics and in biological evolutions where problems with memory do effectively appear in a multivalued version. All these models require viability constraints represented by a closed convex set.

  2. On Uniqueness of Conjugacy of Continuous and Piecewise Monotone Functions

    Directory of Open Access Journals (Sweden)

    Ciepliński Krzysztof

    2009-01-01

    Full Text Available We investigate the existence and uniqueness of solutions of the functional equation , , where are closed intervals, and , are some continuous piecewise monotone functions. A fixed point principle plays a crucial role in the proof of our main result.

  3. Modeling non-monotone risk aversion using SAHARA utility functions

    NARCIS (Netherlands)

    A. Chen; A. Pelsser; M. Vellekoop

    2011-01-01

    We develop a new class of utility functions, SAHARA utility, with the distinguishing feature that it allows absolute risk aversion to be non-monotone and implements the assumption that agents may become less risk averse for very low values of wealth. The class contains the well-known exponential and

  4. Rational functions with maximal radius of absolute monotonicity

    KAUST Repository

    Loczi, Lajos

    2014-05-19

    We study the radius of absolute monotonicity R of rational functions with numerator and denominator of degree s that approximate the exponential function to order p. Such functions arise in the application of implicit s-stage, order p Runge-Kutta methods for initial value problems and the radius of absolute monotonicity governs the numerical preservation of properties like positivity and maximum-norm contractivity. We construct a function with p=2 and R>2s, disproving a conjecture of van de Griend and Kraaijevanger. We determine the maximum attainable radius for functions in several one-parameter families of rational functions. Moreover, we prove earlier conjectured optimal radii in some families with 2 or 3 parameters via uniqueness arguments for systems of polynomial inequalities. Our results also prove the optimality of some strong stability preserving implicit and singly diagonally implicit Runge-Kutta methods. Whereas previous results in this area were primarily numerical, we give all constants as exact algebraic numbers.

  5. On Uniqueness of Conjugacy of Continuous and Piecewise Monotone Functions

    Directory of Open Access Journals (Sweden)

    Krzysztof Ciepliński

    2009-01-01

    Full Text Available We investigate the existence and uniqueness of solutions φ:I→J of the functional equation φ(f(x=F(φ(x, x∈I, where I,J are closed intervals, and f:I→I, F:J→J are some continuous piecewise monotone functions. A fixed point principle plays a crucial role in the proof of our main result.

  6. Exploring the dose-response relationship between resistance exercise intensity and cognitive function.

    Science.gov (United States)

    Chang, Yu-Kai; Etnier, Jennifer L

    2009-10-01

    The purpose of this study was to explore the dose-response relationship between resistance exercise intensity and cognitive performance. Sixty-eight participants were randomly assigned into control, 40%, 70%, or 100% of 10-repetition maximal resistance exercise groups. Participants were tested on Day 1 (baseline) and on Day 2 (measures were taken relative to performance of the treatment). Heart rate, ratings of perceived exertion, self-reported arousal, and affect were assessed on both days. Cognitive performance was assessed on Day 1 and before and following treatment on Day 2. Results from regression analyses indicated that there is a significant linear effect of exercise intensity on information processing speed, and a significant quadratic trend for exercise intensity on executive function. Thus, there is a dose-response relationship between the intensity of resistance exercise and cognitive performance such that high-intensity exercise benefits speed of processing, but moderate intensity exercise is most beneficial for executive function.

  7. Mixed-effects Gaussian process functional regression models with application to dose-response curve prediction.

    Science.gov (United States)

    Shi, J Q; Wang, B; Will, E J; West, R M

    2012-11-20

    We propose a new semiparametric model for functional regression analysis, combining a parametric mixed-effects model with a nonparametric Gaussian process regression model, namely a mixed-effects Gaussian process functional regression model. The parametric component can provide explanatory information between the response and the covariates, whereas the nonparametric component can add nonlinearity. We can model the mean and covariance structures simultaneously, combining the information borrowed from other subjects with the information collected from each individual subject. We apply the model to dose-response curves that describe changes in the responses of subjects for differing levels of the dose of a drug or agent and have a wide application in many areas. We illustrate the method for the management of renal anaemia. An individual dose-response curve is improved when more information is included by this mechanism from the subject/patient over time, enabling a patient-specific treatment regime.

  8. Absolute Monotonicity of Functions Related To Estimates of First Eigenvalue of Laplace Operator on Riemannian Manifolds

    Directory of Open Access Journals (Sweden)

    Feng Qi

    2014-10-01

    Full Text Available The authors find the absolute monotonicity and complete monotonicity of some functions involving trigonometric functions and related to estimates the lower bounds of the first eigenvalue of Laplace operator on Riemannian manifolds.

  9. Heavy particle irradiation, neurochemistry and behavior: thresholds, dose-response curves and recovery of function

    Science.gov (United States)

    Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.

    2004-01-01

    Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation-induced disruption of dopaminergic function affects a variety of behaviors that are dependent upon the integrity of this system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current report reviews the data relevant to the degree to which these characteristics are common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity.

  10. Heavy particle irradiation, neurochemistry and behavior: thresholds, dose-response curves and recovery of function

    Science.gov (United States)

    Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.

    2004-01-01

    Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation-induced disruption of dopaminergic function affects a variety of behaviors that are dependent upon the integrity of this system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current report reviews the data relevant to the degree to which these characteristics are common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity. c2004 COSPAR. Published by Elsevier Ltd. All rights reserved.

  11. Dynamical zeta functions for piecewise monotone maps of the interval

    CERN Document Server

    Ruelle, David

    2004-01-01

    Consider a space M, a map f:M\\to M, and a function g:M \\to {\\mathbb C}. The formal power series \\zeta (z) = \\exp \\sum ^\\infty _{m=1} \\frac {z^m}{m} \\sum _{x \\in \\mathrm {Fix}\\,f^m} \\prod ^{m-1}_{k=0} g (f^kx) yields an example of a dynamical zeta function. Such functions have unexpected analytic properties and interesting relations to the theory of dynamical systems, statistical mechanics, and the spectral theory of certain operators (transfer operators). The first part of this monograph presents a general introduction to this subject. The second part is a detailed study of the zeta functions associated with piecewise monotone maps of the interval [0,1]. In particular, Ruelle gives a proof of a generalized form of the Baladi-Keller theorem relating the poles of \\zeta (z) and the eigenvalues of the transfer operator. He also proves a theorem expressing the largest eigenvalue of the transfer operator in terms of the ergodic properties of (M,f,g).

  12. On a correspondence between regular and non-regular operator monotone functions

    DEFF Research Database (Denmark)

    Gibilisco, P.; Hansen, Frank; Isola, T.

    2009-01-01

    We prove the existence of a bijection between the regular and the non-regular operator monotone functions satisfying a certain functional equation. As an application we give a new proof of the operator monotonicity of certain functions related to the Wigner-Yanase-Dyson skew information.......We prove the existence of a bijection between the regular and the non-regular operator monotone functions satisfying a certain functional equation. As an application we give a new proof of the operator monotonicity of certain functions related to the Wigner-Yanase-Dyson skew information....

  13. Max-Sum Diversification, Monotone Submodular Functions and Dynamic Updates

    CERN Document Server

    Borodin, Allan; Ye, Yuli

    2012-01-01

    Result diversification has many important applications in databases, operations research, information retrieval, and finance. In this paper, we study and extend a particular version of result diversification, known as max-sum diversification. More specifically, we consider the setting where we are given a set of elements in a metric space and a set valuation function $f$ defined on every subset. For any given subset $S$, the overall objective is a linear combination of $f(S)$ and the sum of the distances induced by $S$. The goal is to find a subset $S$ satisfying some constraints that maximizes the overall objective. This problem is first studied by Gollapudi and Sharma for modular set functions and for sets satisfying a cardinality constraint. We consider an extension of the modular case to the monotone submodular case, for which the previous algorithm no longer applies. Interestingly, we are able to match the 2-approximation using a natural, but different greedy algorithm. We then further extend the problem...

  14. The energy dependence of the lateral dose response functions of detectors with various densities in photon-beam dosimetry

    Science.gov (United States)

    Khee Looe, Hui; Harder, Dietrich; Poppe, Björn

    2017-02-01

    The lateral dose response function is a general characteristic of the volume effect of a detector used for photon dosimetry in a water phantom. It serves as the convolution kernel transforming the true absorbed dose to water profile, which would be produced within the undisturbed water phantom, into the detector-measured signal profile. The shape of the lateral dose response function characterizes (i) the volume averaging attributable to the detector’s size and (ii) the disturbance of the secondary electron field associated with the deviation of the electron density of the detector material from the surrounding water. In previous work, the characteristic dependence of the shape of the lateral dose response function upon the electron density of the detector material was studied for 6 MV photons by Monte Carlo simulation of a wall-less voxel-sized detector (Looe et al 2015 Phys. Med. Biol. 60 6585-07). This study is here continued for 60Co gamma rays and 15 MV photons in comparison with 6 MV photons. It is found (1) that throughout these photon spectra the shapes of the lateral dose response functions are retaining their characteristic dependence on the detector’s electron density, and (2) that their energy-dependent changes are only moderate. This appears as a practical advantage because the lateral dose response function can then be treated as practically invariant across a clinical photon beam in spite of the known changes of the photon spectrum with increasing distance from the beam axis.

  15. Western red cedar dust exposure and lung function: a dose-response relationship.

    Science.gov (United States)

    Noertjojo, H K; Dimich-Ward, H; Peelen, S; Dittrick, M; Kennedy, S M; Chan-Yeung, M

    1996-10-01

    The relationship between levels of cumulative red cedar dust exposure and decline in lung function was explored in an 11-yr follow-up study of 243 sawmill workers who participated in at least two occasions. We also studied 140 office workers in a similar manner as control subjects. Workers with asthma were excluded from the analysis. During the period of the study, 916 personal and 216 area samples of dust were collected from the sawmill. Cumulative wood dust exposure was calculated for each sawmill worker according to the duration and exposure in each job, based on the geometric mean of all dust measurements for that job. Average daily dust exposure was calculated by dividing the total cumulative exposure by the number of days of work. Workers were divided into low-, medium-, and high-exposure groups with mean daily level of exposure of 0.4 mg/m3, respectively. Sawmill workers had significantly greater declines in FEV1 and FVC compared with office workers adjusted for age, smoking, and initial lung function. A dose-response relationship was observed between the level of exposure and the annual decline in FVC. We conclude that exposure to Western red cedar dust is associated with a greater decline in lung function which may lead to development of chronic airflow limitation.

  16. Approximate Representation of a Class of Associative Functions by a Monotone 1-Place Function and Addition

    Institute of Scientific and Technical Information of China (English)

    李中夫; 刘应明

    1994-01-01

    This paper discusses the problem of simple representation of multi-place functions from the viewpoint of "simple approximation". We prove that a class of associative functions, which have a wide range of applications, can be approximately represented by a monotone 1-place function and addition.

  17. MONOTONIZATION IN GLOBAL OPTIMIZATION

    Institute of Scientific and Technical Information of China (English)

    WU ZHIYOU; BAI FUSHENG; ZHANG LIANSHENG

    2005-01-01

    A general monotonization method is proposed for converting a constrained programming problem with non-monotone objective function and monotone constraint functions into a monotone programming problem. An equivalent monotone programming problem with only inequality constraints is obtained via this monotonization method. Then the existingconvexification and concavefication methods can be used to convert the monotone programming problem into an equivalent better-structured optimization problem.

  18. Dose-response characteristics of ketamine effect on locomotion, cognitive function and central neuronal activity

    NARCIS (Netherlands)

    Imre, G; Fokkema, DS; Den Boer, JA; Ter Horst, GJ

    2006-01-01

    The present dose-response study sought to determine the effects of subanesthetic dosages (4-16 mg/kg) of ketamine on locomotion, sensorimotor gating (PP1), working memory, as well as c-fos expression in various limbic regions implicated in the pathogenesis of schizophrenia. In addition, we examined

  19. Bayesian Analysis for Food-Safety Risk Assessment: Evaluation of Dose-Response Functions within WinBUGS

    OpenAIRE

    Williams, Michael S.; Ebel, Eric D.; Jennifer A Hoeting

    2011-01-01

    Bayesian methods are becoming increasingly popular in the field of food-safety risk assessment. Risk assessment models often require the integration of a dose-response function over the distribution of all possible doses of a pathogen ingested with a specific food. This requires the evaluation of an integral for every sample for a Markov chain Monte Carlo analysis of a model. While many statistical software packages have functions that allow for the evaluation of the integral, this functional...

  20. Totally Optimal Decision Trees for Monotone Boolean Functions with at Most Five Variables

    KAUST Repository

    Chikalov, Igor

    2013-01-01

    In this paper, we present the empirical results for relationships between time (depth) and space (number of nodes) complexity of decision trees computing monotone Boolean functions, with at most five variables. We use Dagger (a tool for optimization of decision trees and decision rules) to conduct experiments. We show that, for each monotone Boolean function with at most five variables, there exists a totally optimal decision tree which is optimal with respect to both depth and number of nodes.

  1. Health inequality and non-monotonicity of the health related social welfare function.

    Science.gov (United States)

    Dutta, Indranil

    2007-03-01

    In a recent paper in this journal Abasolo and Tsuchiya [Abasolo, I., Tsuchiya, A., 2004. Exploring social welfare functions and violation of monotonicity: an example from inequalities in health. Journal of Health Economics 23, 313-329] have strongly argued for the use of a non-monotonic health related social welfare function. This note discusses both the limitations of the measure proposed by Abasolo and Tsuchiya [Abasolo, I., Tsuchiya, A., 2004. Exploring social welfare functions and violation of monotonicity: an example from inequalities in health. Journal of Health Economics 23, 313-329] and the problems associated with their empirics. We are able to show how non-monotonicity may lead to paradoxical results and policies. Further we examine the empirics of Abasolo and Tsuchiya [Abasolo, I., Tsuchiya, A., 2004. Exploring social welfare functions and violation of monotonicity: an example from inequalities in health. Journal of Health Economics 23, 313-329] and provide an alternative explanation to the observed patterns in the data that do not violate monotonicity. Finally we briefly mention why the Atkinson-Sen framework may be more appropriate as a way forward.

  2. Horizontal Monotonicity of the Modulus of the Riemann Zeta Function and Related Functions

    CERN Document Server

    Matiyasevich, Yuri; Zvengrowski, Peter

    2012-01-01

    It is shown that the absolute values of Riemann's zeta function and two related functions strictly decrease when the imaginary part of the argument is fixed to any number with absolute value at least 8 and the real part of the argument is negative and increases up to 0; extending this monotonicity to the increase of the real part up to 1/2 is shown to be equivalent to the Riemann Hypothesis. Another result is a double inequality relating the real parts of the logarithmic derivatives of the three functions under consideration.

  3. Enlargements of Monotone Operators Determined by Representing Function

    Directory of Open Access Journals (Sweden)

    M. Rezaei

    2012-03-01

    Full Text Available In this paper, we study a new enlargement of subdifferential for any proper lower semicontinuous function. We know that ε-subdifferential of any proper lower semicontinuous function is an enlargement of its subfifferential and any point from the graph of ε- subdifferential can be approximated by a point from the graph of sub- fifferential. This nice property, apart from its theoretical importance, gives also the possibility to use the enlargement of subdifferentials in finding approximate solutions of inclusions determined by subdifferentials. We define a new enlargement and observe, in the case subdifferentials, the relation between this new enlargement and the ε- subdifferentia

  4. Complete Monotonicity of a Difference Between the Exponential and Trigamma Functions and Properties Related to a Modified Bessel Function

    DEFF Research Database (Denmark)

    Qi, Feng; Berg, Christian

    2013-01-01

    In the paper, the authors find necessary and sufficient conditions for a difference between the exponential function αeβ/t, α, β > 0, and the trigamma function ψ (t) to be completely monotonic on (0,∞). While proving the complete onotonicity, the authors discover some properties related to the fi...... to the first order modified Bessel function of the first kind I1, including inequalities, monotonicity, unimodality, and convexity....

  5. Pancreatic beta cell function increases in a linear dose-response manner following exercise training in adults with prediabetes

    DEFF Research Database (Denmark)

    Malin, Steven K; Solomon, Thomas; Blaszczak, Alecia

    2013-01-01

    composition (dual-energy x-ray absorptiometry and computed tomography) were also measured before and after the intervention. Exercise dose was computed using VO2-heart rate derived linear-regression equations. Subjects expended 474.5±8.8 kcal/session (2372.5±44.1 kcal/week) during the intervention, and lost...... ~8% body weight. Exercise increased first and second phase DI (P2000 kcal/week) are necessary to enhance beta-cell function in adults with poor insulin secretion capacity.......While some studies suggest that a linear dose-response relationship exists between exercise and insulin sensitivity, the exercise dose required to enhance pancreatic beta-cell function is unknown. Thirty-five older, obese adults with prediabetes underwent a progressive 12-week supervised exercise...

  6. Implementation of the New Approach for the Dose-Response Functions Development for the Case of Athens and Greece

    Science.gov (United States)

    Christodoulakis, J.; Tzanis, C. G.; Varotsos, C. A.; Kouremadas, G.

    2016-08-01

    Dose-response functions (DRFs) are functions used for estimating corrosion and/or soiling levels of materials used in constructions and cultural monuments. In order to achieve this, DRFs lean on ground-based measurements of specific air pollution and climatic parameters like nitrogen oxides, ozone, temperature and others. In DRAGON 3 2015 Symposium we presented a new approach which proposed a technique for using satellite-based data for the necessary parameters instead of ground-based expanding in this way: a) the usage of DRFs in cases/areas where there is no availability of in situ measurements, b) the applicability of satellite-based data. In this work we present mapping results of deterioration levels (corrosion and soiling) for the case of Athens, Greece but also for the whole Greece country.

  7. Interior-point algorithm based on general kernel function for monotone linear complementarity problem

    Institute of Scientific and Technical Information of China (English)

    LIU Yong; BAI Yan-qin

    2009-01-01

    A polynomial interior-point algorithm is presented for monotone linear complementarity problem (MLCP) based on:a class of kernel functions with the general barrier term, which are called general kernel functions. Under the mild conditions for the barrier term, the complexity bound of algorithm in terms of such kernel function and its derivatives is obtained. The approach is actually an extension of the existing work which only used the specific kernel functions for the MLCP.

  8. Bifurcations of a predator-prey model with non-monotonic response function

    NARCIS (Netherlands)

    Broer, H.W.; Naudot, Vincent; Roussarie, Robert; Saleh, Khairul

    2005-01-01

    A 2-dimensional predator-prey model with five parameters is investigated, adapted from the Volterra-Lotka system by a non-monotonic response function. A description of the various domains of structural stability and their bifurcations is given. The bifurcation structure is reduced to four organising

  9. Computation of non-monotonic Lyapunov functions for continuous-time systems

    Science.gov (United States)

    Li, Huijuan; Liu, AnPing

    2017-09-01

    In this paper, we propose two methods to compute non-monotonic Lyapunov functions for continuous-time systems which are asymptotically stable. The first method is to solve a linear optimization problem on a compact and bounded set. The proposed linear programming based algorithm delivers a CPA1

  10. An analysis of single-index model with monotonic link function

    Institute of Scientific and Technical Information of China (English)

    ZHU Li-ping; YANG Xiao-yan; YU Zhou; LIU Xiang-rong

    2008-01-01

    The single-index model with monotonic link function is investigated. Firstly,it is showed that the link function h(·) can be viewed by a graphic method. That is,the plot with the fitted response y on the horizontal axis and the observed y on the vertical axis can be used to visualize the link function. It is pointed out that this graphic approach is also applicable even when the link function is not monotonic. Note that many existing nonparametric smoothers can also be used to assess h(·). Therefore,the I-spline approximation of the link function via maximizing the covariance function with a penalty function is investigated in the present work.The consistency of the criterion is constructed. A small simulation is carried out to evidence the efficiency of the approach proposed in the paper.

  11. Marginal Iodide Deficiency and Thyroid Function: Dose-response analysis for quantitative pharmacokinetic modeling

    Science.gov (United States)

    Severe iodine deficiency is known to cause adverse health outcomes and remains a benchmark for understanding the effects of hypothyroidism. However, the implications of marginal iodine deficiency on function of the thyroid axis remain less well known. The current study examined t...

  12. Monotone Boolean approximation

    Energy Technology Data Exchange (ETDEWEB)

    Hulme, B.L.

    1982-12-01

    This report presents a theory of approximation of arbitrary Boolean functions by simpler, monotone functions. Monotone increasing functions can be expressed without the use of complements. Nonconstant monotone increasing functions are important in their own right since they model a special class of systems known as coherent systems. It is shown here that when Boolean expressions for noncoherent systems become too large to treat exactly, then monotone approximations are easily defined. The algorithms proposed here not only provide simpler formulas but also produce best possible upper and lower monotone bounds for any Boolean function. This theory has practical application for the analysis of noncoherent fault trees and event tree sequences.

  13. The dose response relation for rat spinal cord paralysis analyzed in terms of the effective size of the functional subunit

    Science.gov (United States)

    Adamus-Górka, Magdalena; Mavroidis, Panayiotis; Brahme, Anders; Lind, Bengt K.

    2008-11-01

    Radiobiological models for estimating normal tissue complication probability (NTCP) are increasingly used in order to quantify or optimize the clinical outcome of radiation therapy. A good NTCP model should fulfill at least the following two requirements: (a) it should predict the sigmoid shape of the corresponding dose-response curve and (b) it should accurately describe the probability of a specified response for arbitrary non-uniform dose delivery for a given endpoint as accurately as possible, i.e. predict the volume dependence. In recent studies of the volume effect of a rat spinal cord after irradiation with narrow and broad proton beams the authors claim that none of the existing NTCP models is able to describe their results. Published experimental data have been used here to try to quantify the change in the effective dose (D50) causing 50% response for different field sizes. The present study was initiated to describe the induction of white matter necrosis in a rat spinal cord after irradiation with narrow proton beams in terms of the mean dose to the effective volume of the functional subunit (FSU). The physically delivered dose distribution was convolved with a function describing the effective size or, more accurately, the sensitivity distribution of the FSU to obtain the effective mean dose deposited in it. This procedure allows the determination of the mean D50 value of the FSUs of a certain size which is of interest for example if the cell nucleus of the oligodendrocyte is the sensitive target. Using the least-squares method to compare the effective doses for different sizes of the functional subunits with the experimental data the best fit was obtained with a length of about 9 mm. For the non-uniform dose distributions an effective FSU length of 8 mm gave the optimal fit with the probit dose-response model. The method could also be used to interpret the so-called bath and shower experiments where the heterogeneous dose delivery was used in the

  14. Monotonically increasing functions of any quantum correlation can make all multiparty states monogamous

    Energy Technology Data Exchange (ETDEWEB)

    Salini, K. [School of Physics, IISER TVM, CET Campus, Thiruvananthapuram, Kerala 695 016 (India); Prabhu, R.; Sen, Aditi [Harish-Chandra Research Institute, Chhatnag Road, Jhunsi, Allahabad 211 019 (India); Sen, Ujjwal, E-mail: ujjwal@hri.res.in [Harish-Chandra Research Institute, Chhatnag Road, Jhunsi, Allahabad 211 019 (India)

    2014-09-15

    Monogamy of quantum correlation measures puts restrictions on the sharability of quantum correlations in multiparty quantum states. Multiparty quantum states can satisfy or violate monogamy relations with respect to given quantum correlations. We show that all multiparty quantum states can be made monogamous with respect to all measures. More precisely, given any quantum correlation measure that is non-monogamic for a multiparty quantum state, it is always possible to find a monotonically increasing function of the measure that is monogamous for the same state. The statement holds for all quantum states, whether pure or mixed, in all finite dimensions and for an arbitrary number of parties. The monotonically increasing function of the quantum correlation measure satisfies all the properties that are expected for quantum correlations to follow. We illustrate the concepts by considering a thermodynamic measure of quantum correlation, called the quantum work deficit.

  15. Estimation of a monotone percentile residual life function under random censorship.

    Science.gov (United States)

    Franco-Pereira, Alba M; de Uña-Álvarez, Jacobo

    2013-01-01

    In this paper, we introduce a new estimator of a percentile residual life function with censored data under a monotonicity constraint. Specifically, it is assumed that the percentile residual life is a decreasing function. This assumption is useful when estimating the percentile residual life of units, which degenerate with age. We establish a law of the iterated logarithm for the proposed estimator, and its n-equivalence to the unrestricted estimator. The asymptotic normal distribution of the estimator and its strong approximation to a Gaussian process are also established. We investigate the finite sample performance of the monotone estimator in an extensive simulation study. Finally, data from a clinical trial in primary biliary cirrhosis of the liver are analyzed with the proposed methods. One of the conclusions of our work is that the restricted estimator may be much more efficient than the unrestricted one.

  16. On the Boundary Limits of Monotone Sobolev Functions in Variable Exponent Orlicz Spaces

    Institute of Scientific and Technical Information of China (English)

    Toshihide FUTAMURA; Tetsu SHIMOMURA

    2013-01-01

    Our aim in this note is to deal with boundary limits of monotone Sobolev functions with ▽u ∈ Lp(·) logLq(·)(B) for the unit ball B (C) Rn.Here p(·) and q(·) are variable exponents satisfying the log-H(o)lder and the log log-H(o)lder conditions,respectively.

  17. Acute Effects of Classroom Exercise Breaks on Executive Function and Math Performance: A Dose-Response Study.

    Science.gov (United States)

    Howie, Erin K; Schatz, Jeffrey; Pate, Russell R

    2015-01-01

    The purpose of this study was to determine the acute dose-response relationship of classroom exercise breaks with executive function and math performance in 9- to 12-year-old children by comparing 5-min, 10-min, or 20-min classroom exercise breaks to 10 min of sedentary classroom activity. This study used a within-subjects experimental design conducted in the spring of 2012. Ninety-six 4th- and 5th-grade students in 5 classrooms in South Carolina were randomized to receive each of 4 treatments: 5-min, 10-min, or 20-min exercise breaks or 10 min of a sedentary lesson led by research staff. Students completed the Trail-Making Test, an Operational Digit Recall test, and a math fluency test immediately before and after each condition. Planned linear contrasts were used to compare posttest scores between conditions using a repeated-measures mixed model, adjusted for gender, classroom, and the time-varying pretest scores. Potential effect modifiers were added as interaction terms. Math scores were higher after the 10-min and 20-min exercise breaks compared with the sedentary condition (d = 0.24, p = .04, and d = 0.27, p = .02, respectively), and an interaction was observed with gender, IQ, aerobic fitness, and lower engagement in some of the conditions. There were no improvements in executive function tasks. A 10-min and 20-min classroom exercise break moderately improved math performance in students compared with a seated classroom lesson.

  18. Monotone Approximations of Minimum and Maximum Functions and Multi-objective Problems

    Energy Technology Data Exchange (ETDEWEB)

    Stipanovic, Dusan M., E-mail: dusan@illinois.edu [University of Illinois at Urbana-Champaign, Coordinated Science Laboratory, Department of Industrial and Enterprise Systems Engineering (United States); Tomlin, Claire J., E-mail: tomlin@eecs.berkeley.edu [University of California at Berkeley, Department of Electrical Engineering and Computer Science (United States); Leitmann, George, E-mail: gleit@berkeley.edu [University of California at Berkeley, College of Engineering (United States)

    2012-12-15

    In this paper the problem of accomplishing multiple objectives by a number of agents represented as dynamic systems is considered. Each agent is assumed to have a goal which is to accomplish one or more objectives where each objective is mathematically formulated using an appropriate objective function. Sufficient conditions for accomplishing objectives are derived using particular convergent approximations of minimum and maximum functions depending on the formulation of the goals and objectives. These approximations are differentiable functions and they monotonically converge to the corresponding minimum or maximum function. Finally, an illustrative pursuit-evasion game example with two evaders and two pursuers is provided.

  19. Approximating the Influence of a monotone Boolean function in O(\\sqrt{n}) query complexity

    OpenAIRE

    Ron, Dana; Rubinfeld, Ronitt; Safra, Muli; Weinstein, Omri

    2011-01-01

    The {\\em Total Influence} ({\\em Average Sensitivity) of a discrete function is one of its fundamental measures. We study the problem of approximating the total influence of a monotone Boolean function \\ifnum\\plusminus=1 $f: \\{\\pm1\\}^n \\longrightarrow \\{\\pm1\\}$, \\else $f: \\bitset^n \\to \\bitset$, \\fi which we denote by $I[f]$. We present a randomized algorithm that approximates the influence of such functions to within a multiplicative factor of $(1\\pm \\eps)$ by performing $O(\\frac{\\sqrt{n}\\log...

  20. Non-monotonic dynamics and crosstalk in signaling pathways and their implications for pharmacology

    Science.gov (United States)

    van Wijk, Roeland; Tans, Sander J.; Wolde, Pieter Rein Ten; Mashaghi, Alireza

    2015-06-01

    Currently, drug discovery approaches commonly assume a monotonic dose-response relationship. However, the assumption of monotonicity is increasingly being challenged. Here we show that for two simple interacting linear signaling pathways that carry two different signals with different physiological responses, a non-monotonic input-output relation can arise with simple network topologies including coherent and incoherent feed-forward loops. We show that non-monotonicity of the response functions has severe implications for pharmacological treatment. Fundamental constraints are imposed on the effectiveness and toxicity of any drug independent of its chemical nature and selectivity due to the specific network structure.

  1. Sharp Thresholds for Monotone Non Boolean Functions and Social Choice Theory

    CERN Document Server

    Kalai, Gil

    2010-01-01

    A key fact in the theory of Boolean functions $f : \\{0,1\\}^n \\to \\{0,1\\}$ is that they often undergo sharp thresholds. For example: if the function $f : \\{0,1\\}^n \\to \\{0,1\\}$ is monotone and symmetric under a transitive action with $\\E_p[f] = \\eps$ and $\\E_q[f] = 1-\\eps$ then $q-p \\to 0$ as $n \\to \\infty$. Here $\\E_p$ denotes the product probability measure on $\\{0,1\\}^n$ where each coordinate takes the value $1$ independently with probability $p$. The fact that symmetric functions undergo sharp thresholds is important in the study of random graphs and constraint satisfaction problems as well as in social choice.In this paper we prove sharp thresholds for monotone functions taking values in an arbitrary finite sets. We also provide examples of applications of the results to social choice and to random graph problems. Among the applications is an analog for Condorcet's jury theorem and an indeterminacy result for a large class of social choice functions.

  2. On complete monotonicity of the Prabhakar function and non-Debye relaxation in dielectrics

    CERN Document Server

    Mainardi, Francesco

    2016-01-01

    The three parameters Mittag--Leffler function (often referred as the Prabhakar function) has important applications, mainly in physics of dielectrics, in describing anomalous relaxation of non--Debye type. This paper concerns with the investigation of the conditions, on the characteristic parameters, under which the function is locally integrable and completely monotonic; these properties are essential for the physical feasibility of the corresponding models. In particular the classical Havriliak--Negami model is extended to a wider range of the parameters. The problem of the numerical evaluation of the three parameters Mittag--Leffler function is also addressed and three different approaches are discussed and compared. Numerical simulations are hence used to validate the theoretical findings and present some graphs of the function under investigation.

  3. Ergodic averages for monotone functions using upper and lower dominating processes

    DEFF Research Database (Denmark)

    Møller, Jesper; Mengersen, Kerrie

    2007-01-01

    We show how the mean of a monotone function (defined on a state space equipped with a partial ordering) can be estimated, using ergodic averages calculated from upper and lower dominating processes of a stationary irreducible Markov chain. In particular, we do not need to simulate the stationary ...... methods are studied in detail for three models using Markov chain Monte Carlo methods and we also discuss various types of other models for which our methods apply.......We show how the mean of a monotone function (defined on a state space equipped with a partial ordering) can be estimated, using ergodic averages calculated from upper and lower dominating processes of a stationary irreducible Markov chain. In particular, we do not need to simulate the stationary...... Markov chain and we eliminate the problem of whether an appropriate burn-in is determined or not. Moreover, when a central limit theorem applies, we show how confidence intervals for the mean can be estimated by bounding the asymptotic variance of the ergodic average based on the equilibrium chain. Our...

  4. Ergodic averages for monotone functions using upper and lower dominating processes

    DEFF Research Database (Denmark)

    Møller, Jesper; Mengersen, Kerrie

    We show how the mean of a monotone function (defined on a state space equipped with a partial ordering) can be estimated, using ergodic averages calculated from upper and lower dominating processes of a stationary irreducible Markov chain. In particular, we do not need to simulate the stationary ...... methods are studied in detail for three models using Markov chain Monte Carlo methods and we also discuss various types of other models for which our methods apply.......We show how the mean of a monotone function (defined on a state space equipped with a partial ordering) can be estimated, using ergodic averages calculated from upper and lower dominating processes of a stationary irreducible Markov chain. In particular, we do not need to simulate the stationary...... Markov chain and we eliminate the problem of whether an appropriate burn-in is determined or not. Moreover, when a central limit theorem applies, we show how confidence intervals for the mean can be estimated by bounding the asymptotic variance of the ergodic average based on the equilibrium chain. Our...

  5. Necessary and sufficient conditions for a class of functions and their reciprocals to be logarithmically completely monotonic

    OpenAIRE

    Lv Yu-Pei; Sun Tian-Chuan; Chu Yu-Ming

    2011-01-01

    Abstract We prove that the function F α,β (x) = x α Γ β (x)/Γ(βx) is strictly logarithmically completely monotonic on (0, ∞) if and only if (α, β) ∈ {(α, β) : β > 0, β ≥ 2α + 1, β ≥ α + 1}{(α, β) : α = 0, β = 1} and that [F α,β (x)]-1 is strictly logarithmically completely monotonic on (0, ∞) if and only if (α, β) ∈ {(α, β ...

  6. Necessary and sufficient conditions for a class of functions and their reciprocals to be logarithmically completely monotonic

    OpenAIRE

    Lv Yu-Pei; Sun Tian-Chuan; Chu Yu-Ming

    2011-01-01

    Abstract We prove that the function F α,β (x) = x α Γ β (x)/Γ(βx) is strictly logarithmically completely monotonic on (0, ∞) if and only if (α, β) ∈ {(α, β) : β > 0, β ≥ 2α + 1, β ≥ α + 1}{(α, β) : α = 0, β = 1} and that [F α,β (x)]-1 is strictly logarithmically completely monotonic on (0, ∞) if and only if (α, β) ∈ {(α, β ...

  7. Dose-response meta-analysis of differences in means

    Directory of Open Access Journals (Sweden)

    Alessio Crippa

    2016-08-01

    Full Text Available Abstract Background Meta-analytical methods are frequently used to combine dose-response findings expressed in terms of relative risks. However, no methodology has been established when results are summarized in terms of differences in means of quantitative outcomes. Methods We proposed a two-stage approach. A flexible dose-response model is estimated within each study (first stage taking into account the covariance of the data points (mean differences, standardized mean differences. Parameters describing the study-specific curves are then combined using a multivariate random-effects model (second stage to address heterogeneity across studies. Results The method is fairly general and can accommodate a variety of parametric functions. Compared to traditional non-linear models (e.g. E max, logistic, spline models do not assume any pre-specified dose-response curve. Spline models allow inclusion of studies with a small number of dose levels, and almost any shape, even non monotonic ones, can be estimated using only two parameters. We illustrated the method using dose-response data arising from five clinical trials on an antipsychotic drug, aripiprazole, and improvement in symptoms in shizoaffective patients. Using the Positive and Negative Syndrome Scale (PANSS, pooled results indicated a non-linear association with the maximum change in mean PANSS score equal to 10.40 (95 % confidence interval 7.48, 13.30 observed for 19.32 mg/day of aripiprazole. No substantial change in PANSS score was observed above this value. An estimated dose of 10.43 mg/day was found to produce 80 % of the maximum predicted response. Conclusion The described approach should be adopted to combine correlated differences in means of quantitative outcomes arising from multiple studies. Sensitivity analysis can be a useful tool to assess the robustness of the overall dose-response curve to different modelling strategies. A user-friendly R package has been developed to facilitate

  8. Confidence bounds for nonlinear dose-response relationships.

    Science.gov (United States)

    Baayen, C; Hougaard, P

    2015-11-30

    An important aim of drug trials is to characterize the dose-response relationship of a new compound. Such a relationship can often be described by a parametric (nonlinear) function that is monotone in dose. If such a model is fitted, it is useful to know the uncertainty of the fitted curve. It is well known that Wald confidence intervals are based on linear approximations and are often unsatisfactory in nonlinear models. Apart from incorrect coverage rates, they can be unreasonable in the sense that the lower confidence limit of the difference to placebo can be negative, even when an overall test shows a significant positive effect. Bootstrap confidence intervals solve many of the problems of the Wald confidence intervals but are computationally intensive and prone to undercoverage for small sample sizes. In this work, we propose a profile likelihood approach to compute confidence intervals for the dose-response curve. These confidence bounds have better coverage than Wald intervals and are more precise and generally faster than bootstrap methods. Moreover, if monotonicity is assumed, the profile likelihood approach takes this automatically into account. The approach is illustrated using a public dataset and simulations based on the Emax and sigmoid Emax models. Copyright © 2015 John Wiley & Sons, Ltd.

  9. Graphical message transmission using the monotonic vibration function of a smart phone.

    Science.gov (United States)

    Lin, Ray F; Rugama, Allan D

    2016-01-01

    This study aimed at evaluating four vibrotactile capabilities for perceiving graphical information presented on a smart phone. Thirty-two blindfolded college students participated in four experiments to test their capabilities of two-point discrimination, relative and absolute judgments of line thickness, and recognition of basic shapes. All the information was received through the default vibration function of the phone, sensed by their scanning fingers. The results showed a good two-point discrimination accuracy rate, reaching 98.8% when the distance between two points was set at 3.2 mm; the relative judgment of line thickness reached the level of 78.3% accuracy when the two-line width difference ratio was set at 3%; the absolute judgment reached the level of 78.8% when the participants recognised line thickness from one of two. Overall, especially for the shapes judgment, the information transmitted by the various codes may be quite low. These findings should inspire advanced investigations and provide design guidelines. This study tested four vibrotactile capabilities for perception of graphical information when solely using the monotonic vibration function of a smart phone. The results show low information transmission. These findings encourage advanced investigations of new coding systems so that relevant mobile applications could be developed to help the visually impaired.

  10. Sufficient Condition for Monotonicity in Constructing the Distribution Function With Bernoulli Scheme

    Directory of Open Access Journals (Sweden)

    Vedenyapin Aleksandr Dmitrievich

    2015-11-01

    Full Text Available This paper is the construction of the distribution function using the Bernoulli scheme, and is also designed to correct some of the mistakes that were made in the article [2]. Namely, a function built in [2] need not be monotonous, and some formulas need to be adjusted. The idea of building as well as in [2], is based on the model of Cox-Ross-Rubinstein "binary market". The essence of the model was to divide time into N steps, and assuming that the price of an asset at each step can move either up to a certain value with probability p, or down also by some certain value with probability q = 1 - p. Prices in step N can take only a finite number of values. "Success" or "failure" was the changing price for some fixed value in the model of Cox-Ross-Rubinstein. Here as a "success" or "failure" at every step we consider the affiliation of changing the index value to the section [r, S] either to the interval [I, r. Further a function P(r was introduced, which at any step gives us the probability of "success". The maximum index value increase for the all period of time [T, 2T] will be equal nS, and the maximum possible reduction will be equal nI. Then let x ∈ [nI, nS]. This segment will reflect every possible total variation that we can get at the end of a period of time [T, 2T]. The further introduced inequality k ≥ (x - nI/(S - I gives us the minimum number of successes that needed for total changing could be in the section [x, nS] if was n - k reductions with the index value to I. Then was introduced the function r(x, kmin which is defined on the interval (nI, nS] and provided us some assurance that the total index changing could be in the section [x, nS] if successful interval is [r(x, kmin, S] and the amount of success is satisfying to our inequality. The probability of k "successes" and n - k "failures" is calculated according to the formula of Bernoulli, where the probability of "success" is determined by the function P(r, and r is determined

  11. Experimental determination of the lateral dose response functions of detectors to be applied in the measurement of narrow photon-beam dose profiles

    Science.gov (United States)

    Poppinga, D.; Meyners, J.; Delfs, B.; Muru, A.; Harder, D.; Poppe, B.; Looe, HK

    2015-12-01

    This study aims at the experimental determination of the detector-specific 1D lateral dose response function K(x) and of its associated rotational symmetric counterpart K(r) for a set of high-resolution detectors presently used in narrow-beam photon dosimetry. A combination of slit-beam, radiochromic film, and deconvolution techniques served to accomplish this task for four detectors with diameters of their sensitive volumes ranging from 1 to 2.2 mm. The particular aim of the experiment was to examine the existence of significant negative portions of some of these response functions predicted by a recent Monte-Carlo-simulation (Looe et al 2015 Phys. Med. Biol. 60 6585-607). In a 6 MV photon slit beam formed by the Siemens Artiste collimation system and a 0.5 mm wide slit between 10 cm thick lead blocks serving as the tertiary collimator, the true cross-beam dose profile D(x) at 3 cm depth in a large water phantom was measured with radiochromic film EBT3, and the detector-affected cross-beam signal profiles M(x) were recorded with a silicon diode, a synthetic diamond detector, a miniaturized scintillation detector, and a small ionization chamber. For each detector, the deconvolution of the convolution integral M(x)  =  K(x)  ∗  D(x) served to obtain its specific 1D lateral dose response function K(x), and K(r) was calculated from it. Fourier transformations and back transformations were performed using function approximations by weighted sums of Gaussian functions and their analytical transformation. The 1D lateral dose response functions K(x) of the four types of detectors and their associated rotational symmetric counterparts K(r) were obtained. Significant negative curve portions of K(x) and K(r) were observed in the case of the silicon diode and the diamond detector, confirming the Monte-Carlo-based prediction (Looe et al 2015 Phys. Med. Biol. 60 6585-607). They are typical for the perturbation of the secondary electron field by a detector with

  12. Efficient Minimization of Higher Order Submodular Functions using Monotonic Boolean Functions

    CERN Document Server

    Ramalingam, Srikumar; Ladicky, Lubor; Torr, Philip H S

    2011-01-01

    Submodular function minimization is a key problem in a wide variety of applications in machine learning, economics, game theory, computer vision and many others. The general solver has a complexity of $O(n^6+n^5L)$ where $L$ is the time required to evaluate the function and $n$ is the number of variables \\cite{orlin09}. On the other hand, many useful applications in computer vision and machine learning applications are defined over a special subclasses of submodular functions in which that can be written as the sum of many submodular cost functions defined over cliques containing few variables. In such functions, the pseudo-Boolean (or polynomial) representation \\cite{BorosH02} of these subclasses are of degree (or order, or clique size) $k$ where $k<functions. To do this, we define novel mapping that transform submodular functions of order $k$ into quadratic ones, which can be efficiently minim...

  13. Non-monotonicity of Lyapunov functions for functional differential equations with enlightenments for related research methods

    Science.gov (United States)

    Zhao, Xueyan; Deng, Feiqi

    2016-07-01

    In this paper, a particular property of Lyapunov functions for functional differential equations (FDEs) is developed, that is the direct dependence of the signs of the derivatives of the Lyapunov functions on the initial data. This property implies that the derivatives of the Lyapunov functions for FDEs cannot be guaranteed to be negative definite generally, and then makes the FDEs differ from the ordinary differential equations constitutionally. With this property, we give some enlightenments for the research methods for establishing stability theorems or criteria for FDEs, which may help us to form a common view about the choice of the investigation methods on the stability of FDEs. The conclusion is stated in both the deterministic and stochastic versions. Two illustrative examples are given to show and verify our conclusion through the paper.

  14. Dose-response effect of Bifidobacterium lactis HN019 on whole gut transit time and functional gastrointestinal symptoms in adults

    OpenAIRE

    2011-01-01

    Objective. To assess the impact of Bifidobacterium lactis HN019 supplementation on whole gut transit time (WGTT) and frequency of functional gastrointestinal (GI) symptoms in adults. Material and methods. We randomized 100 subjects (mean age: 44 years; 64% female) with functional GI symptoms to consume a proprietary probiotic strain, B. lactis HN019 (Fonterra Research Centre, Palmerston North, New Zealand), at daily doses of 17.2 billion colony forming units (CFU) (high dose; n = 33), 1.8 bil...

  15. Statistical Estimation of Dose-response Functions of Respiratory Diseases and Societal Costs of Haze-related Air Pollution in Brunei Darussalam

    Science.gov (United States)

    Anaman, K. A.; Ibrahim, N.

    - The effects on human health resulting from the January to April 1998 haze-related air pollution episode in Brunei Darussalam were analysed for five groups of diseases of the respiratory system. The analysis concentrated on the statistical estimation of dose-response functions which related the number of cases of respiratory diseases to the level of quality of ambient environment as measured by the pollutants standards index (PSI) and other environmental variables. The total number of cases of the five groups of diseases was shown to be significantly related to PSI and temperature. Societal costs were also estimated. The results showed that societal costs were significantly related to PSI, temperature and relative humidity. Societal costs increased with higher PSI and relative humidity but decreased with increasing temperature.

  16. A Strategy to Model Nonmonotonic Dose-Response Curve and Estimate IC50

    OpenAIRE

    Hui Zhang; Jeanne Holden-Wiltse; Jiong Wang; Hua Liang

    2013-01-01

    The half-maximal inhibitory concentration IC[Formula: see text] is an important pharmacodynamic index of drug effectiveness. To estimate this value, the dose response relationship needs to be established, which is generally achieved by fitting monotonic sigmoidal models. However, recent studies on Human Immunodeficiency Virus (HIV) mutants developing resistance to antiviral drugs show that the dose response curve may not be monotonic. Traditional models can fail for nonmonotonic data and igno...

  17. Fractional calculus, completely monotonic functions, a generalized Mittag-Leffler function and phase-space consistency of separable augmented densities

    CERN Document Server

    An, J

    2012-01-01

    Under the separability assumption on the augmented density, a distribution function can be always constructed for a spherical population with the specified density and anisotropy profile. Then, a question arises, under what conditions the distribution constructed as such is non-negative everywhere in the entire accessible subvolume of the phase-space. We rediscover necessary conditions on the augmented density expressed with fractional calculus. The condition on the radius part R(r^2) -- whose logarithmic derivative is the anisotropy parameter -- is equivalent to R(1/w)/w being a completely monotonic function whereas the condition on the potential part is stated as its derivative up to the order not greater than 3/2-b being non-negative (where b is the central limiting value for the anisotropy parameter). We also derive the set of sufficient conditions on the separable augmented density for the non-negativity of the distribution, which generalizes the condition derived for the generalized Cuddeford system by ...

  18. Classification, Dose-response Modelling and the Evaluation of Biomarkers in a Micro-array Setting

    OpenAIRE

    Lin, Dan

    2008-01-01

    Dose-response microarray experiments consist of monitoring expression levels of thousands of genes with respect to increasing dose of the treatment under investigation. The primary goal of such an experiment is to establish a dose-response relationship, while the secondary goals are to determine the minimum effective dose level and to identify the shape of the dose-response curve. Recently, Lin et al.[1] discussed several testing procedures to test for monotone trend based on isotonic regress...

  19. Multiple periodic solutions of a delayed predator-prey model with non-monotonic functional response and stage structure.

    Science.gov (United States)

    Liu, Yingyuan; Zhang, Xiaolan; Zhou, Tiejun

    2014-01-01

    The paper studies a periodic and delayed predator-prey system with non-monotonic functional responses and stage structure. In the system, both the predator and prey are divided into immature individuals and mature individuals by two fixed ages. It is assumed that the immature predators cannot attack preys, and the case of the mature predators attacking the immature preys is also ignored. Based on Mawhin's coincidence degree, sufficient conditions are obtained for the existence of two positive periodic solutions of the system. An example is presented to illustrate the feasibility of the main results.

  20. Multistability of neural networks with discontinuous non-monotonic piecewise linear activation functions and time-varying delays.

    Science.gov (United States)

    Nie, Xiaobing; Zheng, Wei Xing

    2015-05-01

    This paper is concerned with the problem of coexistence and dynamical behaviors of multiple equilibrium points for neural networks with discontinuous non-monotonic piecewise linear activation functions and time-varying delays. The fixed point theorem and other analytical tools are used to develop certain sufficient conditions that ensure that the n-dimensional discontinuous neural networks with time-varying delays can have at least 5(n) equilibrium points, 3(n) of which are locally stable and the others are unstable. The importance of the derived results is that it reveals that the discontinuous neural networks can have greater storage capacity than the continuous ones. Moreover, different from the existing results on multistability of neural networks with discontinuous activation functions, the 3(n) locally stable equilibrium points obtained in this paper are located in not only saturated regions, but also unsaturated regions, due to the non-monotonic structure of discontinuous activation functions. A numerical simulation study is conducted to illustrate and support the derived theoretical results.

  1. Description of dose response curve

    OpenAIRE

    Al-Samarai, Firas

    2011-01-01

    The book included several methods to estimate LD50, in addition to explain how to use several programs to estimate LD50. Moreover the book illustrate the description of the dose response curves. Firas Al-Samarai

  2. Dose response problems in carcinogenesis.

    Science.gov (United States)

    Crump, K S

    1979-03-01

    The estimation of risks from exposure to carcinogens is an important problem from the viewpoint of protection of human health. It also poses some very difficult dose-response problems. Two dose-response models may fit experimental data about equally well and yet predict responses that differ by many orders of magnitude at low doses. Mechanisms of carcinogenesis are not sufficiently understood so that the shape of the dose-response curve at low doses can be satisfactorily predicted. Mathematical theories of carcinogenesis and statistical procedures can be of use with dose-reponse problems such as this and, in addition, can lead to a better understanding of the mechanisms of carcinogenesis. In this paper, mathematical dose-response models of carcinogenesis are considered as well as various proposed dose-response procedures for estimating carcinogenic risks at low doses. Areas are suggested in which further work may be useful. These areas include experimental design problems, statistical procedures for use with time-to-occurrence data, and mathematical models that incorporate such biological features as pharmacokinetics of carcinogens, synergistic effects, DNA repair, susceptible subpopulations, and immune reactions.

  3. Monotonicity of a Key Function Arised in Studies of Nematic Liquid Crystal Polymers

    Directory of Open Access Journals (Sweden)

    Hongyun Wang

    2007-01-01

    Full Text Available We revisit a key function arised in studies of nematic liquid crystal polymers. Previously, it was conjectured that the function is strictly decreasing and the conjecture was numerically confirmed. Here we prove the conjecture analytically. More specifically, we write the derivative of the function into two parts and prove that each part is strictly negative.

  4. A Characterization of Generalized Monotone Normed Cones

    Institute of Scientific and Technical Information of China (English)

    S.ROMAGUERA; E.A.S(A)NCHEZ-P(E)REZ; O.VALERO

    2007-01-01

    Let C be a cone and consider a quasi-norm p defined on it. We study the structure of the couple (C, p) as a topological space in the case where the function p is also monotone. We characterize when the topology of a quasi-normed cone can be defined by means of a monotone norm. We also define and study the dual cone of a monotone normed cone and the monotone quotient of a general cone.We provide a decomposition theorem which allows us to write a cone as a direct sum of a monotone subcone that is isomorphic to the monotone quotient and other particular subcone.

  5. Multistability of memristive Cohen-Grossberg neural networks with non-monotonic piecewise linear activation functions and time-varying delays.

    Science.gov (United States)

    Nie, Xiaobing; Zheng, Wei Xing; Cao, Jinde

    2015-11-01

    The problem of coexistence and dynamical behaviors of multiple equilibrium points is addressed for a class of memristive Cohen-Grossberg neural networks with non-monotonic piecewise linear activation functions and time-varying delays. By virtue of the fixed point theorem, nonsmooth analysis theory and other analytical tools, some sufficient conditions are established to guarantee that such n-dimensional memristive Cohen-Grossberg neural networks can have 5(n) equilibrium points, among which 3(n) equilibrium points are locally exponentially stable. It is shown that greater storage capacity can be achieved by neural networks with the non-monotonic activation functions introduced herein than the ones with Mexican-hat-type activation function. In addition, unlike most existing multistability results of neural networks with monotonic activation functions, those obtained 3(n) locally stable equilibrium points are located both in saturated regions and unsaturated regions. The theoretical findings are verified by an illustrative example with computer simulations.

  6. Soiling of window glass of building façades: a new Dose-Response Function based on the mass of deposited particles

    Science.gov (United States)

    Ionescu, Anda; Lefèvre, Roger

    2017-04-01

    Materials used in building façades are subject to different types of weathering, an important one being soiling. The material studied here is the silica-soda-lime glass, used for windows and contemporaneous façades. Glass weathering in a polluted environment, sheltered from rain, is dominated by soiling. This phenomenon can be expressed either by an optical parameter, the haze, or by the mass of Deposited and Neoformed Particles by unit of glass surface (DNPs). By contrast to the haze, which is an optical parameter requiring an expensive technology (spectrophotometry), measuring DNPs is much simpler: the glass sample is weighed before and after exposure and the result, divided by the sample surface. After the development of a previous Dose-Response Function (DRF) expressing soiling evolution through haze, this study focuses on the development of a new DRF for soiling expressed in terms of DNPs mass, sheltered from rain. The development of this DRF follows a statistical approach. The general form proposed for the DRF is: DNPs=A(dose1, dose2, …., dosen).g(t) where g(t) represents the temporal trend obtained from standardized data. Data standardization has been employed in order to obtain a general trend independent of the environmental characteristics of the monitoring site. According to previous studies and physical considerations, the analytical form of the temporal trend g(t) was expressed by a function admitting an horizontal asymptote: the saturation level of soling. Ten monitoring campaigns (performed at different European sites) were used; the longest one runs up to 2102 days and the shortest ones, up to 365 days, with 14 to 5 records, respectively. Two different models were fitted by a non-linear regression: the Hill's model and a decreasing exponential model. Both models performed well (R2 ranging from 0.73 to 0.76) and they were further tested in order to get the final form of the DRF. The amplitude function A was considered as a linear combination of

  7. Upper Bound and Lower Bound Estimate of Monotone Increasing Fractal Function%单调递增分形函数上、下界的估计

    Institute of Scientific and Technical Information of China (English)

    马冠忠; 袁瑰霞; 崔振文

    2008-01-01

    Mass distribution principle is one of important tools in studying Hausdorff dimension and Hausdorff measure.In this paper we will give a numerical approximate method of upper bound and lower bound of mass distribution function f(x)(it is a monotone increasing fractal function)and its some applications.

  8. Optimal investment and indifference pricing when risk aversion is not monotone: SAHARA utility functions

    NARCIS (Netherlands)

    A. Chen; A. Pelsser; M. Vellekoop

    2008-01-01

    Abstract. We develop a new class of utility functions, SAHARA utility, with the dis- tinguishing feature that they implement the assumption that agents may become less risk-averse for very low values of wealth. This means that SAHARA utility can be used to characterize risk gambling behavior of an e

  9. The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation

    Science.gov (United States)

    Van Dongen, Hans P A.; Maislin, Greg; Mullington, Janet M.; Dinges, David F.

    2003-01-01

    OBJECTIVES: To inform the debate over whether human sleep can be chronically reduced without consequences, we conducted a dose-response chronic sleep restriction experiment in which waking neurobehavioral and sleep physiological functions were monitored and compared to those for total sleep deprivation. DESIGN: The chronic sleep restriction experiment involved randomization to one of three sleep doses (4 h, 6 h, or 8 h time in bed per night), which were maintained for 14 consecutive days. The total sleep deprivation experiment involved 3 nights without sleep (0 h time in bed). Each study also involved 3 baseline (pre-deprivation) days and 3 recovery days. SETTING: Both experiments were conducted under standardized laboratory conditions with continuous behavioral, physiological and medical monitoring. PARTICIPANTS: A total of n = 48 healthy adults (ages 21-38) participated in the experiments. INTERVENTIONS: Noctumal sleep periods were restricted to 8 h, 6 h or 4 h per day for 14 days, or to 0 h for 3 days. All other sleep was prohibited. RESULTS: Chronic restriction of sleep periods to 4 h or 6 h per night over 14 consecutive days resulted in significant cumulative, dose-dependent deficits in cognitive performance on all tasks. Subjective sleepiness ratings showed an acute response to sleep restriction but only small further increases on subsequent days, and did not significantly differentiate the 6 h and 4 h conditions. Polysomnographic variables and delta power in the non-REM sleep EEG-a putative marker of sleep homeostasis--displayed an acute response to sleep restriction with negligible further changes across the 14 restricted nights. Comparison of chronic sleep restriction to total sleep deprivation showed that the latter resulted in disproportionately large waking neurobehavioral and sleep delta power responses relative to how much sleep was lost. A statistical model revealed that, regardless of the mode of sleep deprivation, lapses in behavioral alertness

  10. A strategy to model nonmonotonic dose-response curve and estimate IC50.

    Science.gov (United States)

    Zhang, Hui; Holden-Wiltse, Jeanne; Wang, Jiong; Liang, Hua

    2013-01-01

    The half-maximal inhibitory concentration IC[Formula: see text] is an important pharmacodynamic index of drug effectiveness. To estimate this value, the dose response relationship needs to be established, which is generally achieved by fitting monotonic sigmoidal models. However, recent studies on Human Immunodeficiency Virus (HIV) mutants developing resistance to antiviral drugs show that the dose response curve may not be monotonic. Traditional models can fail for nonmonotonic data and ignore observations that may be of biologic significance. Therefore, we propose a nonparametric model to describe the dose response relationship and fit the curve using local polynomial regression. The nonparametric approach is shown to be promising especially for estimating the IC[Formula: see text] of some HIV inhibitory drugs, in which there is a dose-dependent stimulation of response for mutant strains. This model strategy may be applicable to general pharmacologic, toxicologic, or other biomedical data that exhibits a nonmonotonic dose response relationship for which traditional parametric models fail.

  11. Free Monotone Transport

    CERN Document Server

    Guionnet, A

    2012-01-01

    By solving a free analog of the Monge-Amp\\`ere equation, we prove a non-commutative analog of Brenier's monotone transport theorem: if an $n$-tuple of self-adjoint non-commutative random variables $Z_{1},...,Z_{n}$ satisfies a regularity condition (its conjugate variables $\\xi_{1},...,\\xi_{n}$ should be analytic in $Z_{1},...,Z_{n}$ and $\\xi_{j}$ should be close to $Z_{j}$ in a certain analytic norm), then there exist invertible non-commutative functions $F_{j}$ of an $n$-tuple of semicircular variables $S_{1},...,S_{n}$, so that $Z_{j}=F_{j}(S_{1},...,S_{n})$. Moreover, $F_{j}$ can be chosen to be monotone, in the sense that $F_{j}=\\mathscr{D}_{j}g$ and $g$ is a non-commutative function with a positive definite Hessian. In particular, we can deduce that $C^{*}(Z_{1},...,Z_{n})\\cong C^{*}(S_{1},...,S_{n})$ and $W^{*}(Z_{1},...,Z_{n})\\cong L(\\mathbb{F}(n))$. Thus our condition is a useful way to recognize when an $n$-tuple of operators generate a free group factor. We obtain as a consequence that the q-deforme...

  12. Two Sequences of Operator Monotone Functions and Strictly Chaotic Order%两组算子单调函数序列与严格Chaotic序

    Institute of Scientific and Technical Information of China (English)

    张蕾; 姜健飞

    2006-01-01

    In this paper we introduce two sequences of operator functions and their dual functions: fk(t) = (tlogt)k-(t-1)k/logk+1 t (k = 1,2,…), gk(t) = (t-1)k-logkt/logk+1 t (k = 1,2,…) and f*k(t)=tklogk+1 t/(t log t)k-(t-1)k(k=1,2,…),g*k(t)= tk logk+1 t/(t-1)k-logkt(k = 1, 2, …) defined on (0,+∞). We find that they are all operator monotone functions with respect to the strictly chaotic order and some ordinary orders among positive invertible operators. Indeed, we extend the results of the operator monotone function tlog t-t+1/log2t, which is widely used in the theory of heat transfer of the heat engineering and fluid mechanics [1].

  13. Loss of local control due to tumor displacement as a function of margin size, dose-response slope, and number of fractions.

    Science.gov (United States)

    Selvaraj, Jothybasu; Uzan, Julien; Baker, Colin; Nahum, Alan

    2013-04-01

    Geometric uncertainties are inevitable in radiotherapy. To account for these uncertainties, a margin is added to the clinical target volume (CTV) to create the planning target volume (PTV), and its size is critical for obtaining an optimal treatment plan. Dose-based (i.e., physical) margin recipes have been published and widely used, but it is important to consider fractionation and the radiobiological characteristics of the tumor when deriving margins. Hence a tumor control probability (TCP)-based margin is arguably more appropriate. Margins required for ≤ 1% loss in mean population TCP (relative to a static tumor) for varying numbers of fractions, varying slope of the dose-response curve (γ50) and varying degrees of dose distribution conformity are investigated for spherical and four-field (4F)-brick dose distributions. To simulate geometric uncertainties, systematic (Σ) and random (σ) tumor displacements were sampled from Gaussian distributions and applied to each fraction for a spherical CTV. Interfraction tumor motion was simulated and the dose accumulated from fraction to fraction on a voxel-by-voxel basis to calculate TCP. PTV margins derived from this work for various fraction numbers and dose-response slopes (γ50) for different degrees of geometric uncertainties are compared with margins calculated using published physical-dose- and TCP-based recipes. Larger margins are required for a decrease in the number of fractions and for an increase in γ50 for both spherical and 4F-brick dose distributions. However, the margins can be close to zero for the 4F-brick distribution for small geometric uncertainties (Σ = 1, σ = 1 mm) irrespective of the number of fractions and the magnitude of γ50 due to the higher "incidental" dose outside the tumor. For Σ = 1 mm and σ = 3 mm, physical-dose-based recipes underestimate the margin only for the combination of hypofractionated treatments and tumors with a high γ50. For all other situations TCP-based margins are

  14. The output factor correction as function of the photon beam field size - direct measurement and calculation from the lateral dose response functions of gas-filled and solid detectors.

    Science.gov (United States)

    Poppinga, Daniela; Delfs, Björn; Meyners, Jutta; Harder, Dietrich; Poppe, Björn; Looe, Hui Khee

    2017-08-28

    lateral response functions of the detectors. To achieve this, the set of previously published 2D lateral dose response functions was complemented by those of the novel detectors PTW PinPoint chamber 31022 (PTW Freiburg, Freiburg, Germany), Razor chamber and Razor Diode (IBA Dosimetry, Schwarzenbruck, Germany). The output correction factors calculated from the lateral dose response functions closely fit with the directly measured output correction factors, thus supporting the latter by an independent method. Copyright © 2017. Published by Elsevier GmbH.

  15. Single toxin dose-response models revisited

    Science.gov (United States)

    Glaholt, SP; Kyker-Snowman, E; Shaw, JR; Chen, CY

    2016-01-01

    The goal of this paper is to offer a rigorous analysis of the sigmoid shape single toxin dose-response relationship. The toxin efficacy function is introduced and four special points, including maximum toxin efficacy and inflection points, on the dose-response curve are defined. The special points define three phases of the toxin effect on mortality: (1) toxin concentrations smaller than the first inflection point or (2) larger then the second inflection point imply low mortality rate, and (3) concentrations between the first and the second inflection points imply high mortality rate. Probabilistic interpretation and mathematical analysis for each of four models, Hill, logit, probit, and Weibull is provided. Two general model extensions are introduced: (1) the multi-target hit model that accounts for the existence of several vital receptors affected by the toxin, and (2) model with a nonzero mortality at zero concentration to account for natural mortality. Special attention is given to statistical estimation in the framework of the generalized linear model with the binomial dependent variable as the mortality count in each experiment, contrary to the widespread nonlinear regression treating the mortality rate as continuous variable. The models are illustrated using standard EPA Daphnia acute (48 hours) toxicity tests with mortality as a function of NiCl or CuSO4 toxin. PMID:27847315

  16. Monotonicity of social welfare optima

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Østerdal, Lars Peter Raahave

    2010-01-01

    This paper considers the problem of maximizing social welfare subject to participation constraints. It is shown that for an income allocation method that maximizes a social welfare function there is a monotonic relationship between the incomes allocated to individual agents in a given coalition...... (with at least three members) and its participation constraint if and only if the aggregate income to that coalition is always maximized. An impossibility result demonstrates that there is no welfare maximizing allocation method in which agents' individual incomes monotonically increase in society......'s income. Thus, for any such allocation method, there are situations where some agents have incentives to prevent society in becoming richer....

  17. Testing Monotonicity of Pricing Kernels

    OpenAIRE

    Timofeev, Roman

    2007-01-01

    In this master thesis a mechanism to test mononicity of empirical pricing kernels (EPK) is presented. By testing monotonicity of pricing kernel we can determine whether utility function is concave or not. Strictly decreasing pricing kernel corresponds to concave utility function while non-decreasing EPK means that utility function contains some non-concave regions. Risk averse behavior is usually described by concave utility function and considered to be a cornerstone of classical behavioral ...

  18. Bayesian Dose-Response Modeling in Sparse Data

    Science.gov (United States)

    Kim, Steven B.

    This book discusses Bayesian dose-response modeling in small samples applied to two different settings. The first setting is early phase clinical trials, and the second setting is toxicology studies in cancer risk assessment. In early phase clinical trials, experimental units are humans who are actual patients. Prior to a clinical trial, opinions from multiple subject area experts are generally more informative than the opinion of a single expert, but we may face a dilemma when they have disagreeing prior opinions. In this regard, we consider compromising the disagreement and compare two different approaches for making a decision. In addition to combining multiple opinions, we also address balancing two levels of ethics in early phase clinical trials. The first level is individual-level ethics which reflects the perspective of trial participants. The second level is population-level ethics which reflects the perspective of future patients. We extensively compare two existing statistical methods which focus on each perspective and propose a new method which balances the two conflicting perspectives. In toxicology studies, experimental units are living animals. Here we focus on a potential non-monotonic dose-response relationship which is known as hormesis. Briefly, hormesis is a phenomenon which can be characterized by a beneficial effect at low doses and a harmful effect at high doses. In cancer risk assessments, the estimation of a parameter, which is known as a benchmark dose, can be highly sensitive to a class of assumptions, monotonicity or hormesis. In this regard, we propose a robust approach which considers both monotonicity and hormesis as a possibility. In addition, We discuss statistical hypothesis testing for hormesis and consider various experimental designs for detecting hormesis based on Bayesian decision theory. Past experiments have not been optimally designed for testing for hormesis, and some Bayesian optimal designs may not be optimal under a

  19. Dose-response effects of omega-3 fatty acids on triglycerides, inflammation, and endothelial function in healthy persons with moderate hypertriglyceridemia123

    Science.gov (United States)

    Skulas-Ray, Ann C; Kris-Etherton, Penny M; Harris, William S; Vanden Heuvel, John P; Wagner, Paul R; West, Sheila G

    2011-01-01

    Background: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to reduce cardiovascular mortality at a dose of ≈1 g/d. Studies using higher doses have shown evidence of reduced inflammation and improved endothelial function. Few studies have compared these doses. Objective: The objective of this study was to compare the effects of a nutritional dose of EPA+DHA (0.85 g/d) with those of a pharmaceutical dose (3.4 g/d) on serum triglycerides, inflammatory markers, and endothelial function in healthy subjects with moderately elevated triglycerides. Design: This was a placebo-controlled, double-blind, randomized, 3-period crossover trial (8 wk of treatment, 6 wk of washout) that compared the effects of 0.85 and 3.4 g EPA+DHA/d in 23 men and 3 postmenopausal women with moderate hypertriglyceridemia (150–500 mg/dL). Results: The higher dose of EPA+DHA lowered triglycerides by 27% compared with placebo (mean ± SEM: 173 ± 17.5 compared with 237 ± 17.5 mg/dL; P = 0.002), whereas no effect of the lower dose was observed on lipids. No effects on cholesterol (total, LDL, and HDL), endothelial function [as assessed by flow-mediated dilation, peripheral arterial tonometry/EndoPAT (Itamar Medical Ltd, Caesarea, Israel), or Doppler measures of hyperemia], inflammatory markers (interleukin-1β, interleukin-6, tumor necrosis factor-α, and high-sensitivity C-reactive protein), or the expression of inflammatory cytokine genes in isolated lymphocytes were observed. Conclusion: The higher dose (3.4 g/d) of EPA+DHA significantly lowered triglycerides, but neither dose improved endothelial function or inflammatory status over 8 wk in healthy adults with moderate hypertriglyceridemia. The trial was registered at clinicaltrials.gov as NCT00504309. PMID:21159789

  20. Monotone Hurwitz numbers in genus zero

    CERN Document Server

    Goulden, I P; Novak, Jonathan

    2012-01-01

    Hurwitz numbers count branched covers of the Riemann sphere with specified ramification data, or equivalently, transitive permutation factorizations in the symmetric group with specified cycle types. Monotone Hurwitz numbers count a restricted subset of the branched covers counted by the Hurwitz numbers, and have arisen in recent work on the the asymptotic expansion of the Harish-Chandra-Itzykson-Zuber integral. In this paper we begin a detailed study of monotone Hurwitz numbers. We prove two results that are reminiscent of those for classical Hurwitz numbers. The first is the monotone join-cut equation, a partial differential equation with initial conditions that characterizes the generating function for monotone Hurwitz numbers in arbitrary genus. The second is our main result, in which we give an explicit formula for monotone Hurwitz numbers in genus zero.

  1. Confidence bounds for nonlinear dose-response relationships

    DEFF Research Database (Denmark)

    Baayen, C; Hougaard, P

    2015-01-01

    . It is well known that Wald confidence intervals are based on linear approximations and are often unsatisfactory in nonlinear models. Apart from incorrect coverage rates, they can be unreasonable in the sense that the lower confidence limit of the difference to placebo can be negative, even when an overall...... test shows a significant positive effect. Bootstrap confidence intervals solve many of the problems of the Wald confidence intervals but are computationally intensive and prone to undercoverage for small sample sizes. In this work, we propose a profile likelihood approach to compute confidence...... intervals for the dose-response curve. These confidence bounds have better coverage than Wald intervals and are more precise and generally faster than bootstrap methods. Moreover, if monotonicity is assumed, the profile likelihood approach takes this automatically into account. The approach is illustrated...

  2. Dose-response aligned circuits in signaling systems.

    Science.gov (United States)

    Yan, Long; Ouyang, Qi; Wang, Hongli

    2012-01-01

    Cells use biological signal transduction pathways to respond to environmental stimuli and the behavior of many cell types depends on precise sensing and transmission of external information. A notable property of signal transduction that was characterized in the Saccharomyces cerevisiae yeast cell and many mammalian cells is the alignment of dose-response curves. It was found that the dose response of the receptor matches closely the dose responses of the downstream. This dose-response alignment (DoRA) renders equal sensitivities and concordant responses in different parts of signaling system and guarantees a faithful information transmission. The experimental observations raise interesting questions about the nature of the information transmission through DoRA signaling networks and design principles of signaling systems with this function. Here, we performed an exhaustive computational analysis on network architectures that underlie the DoRA function in simple regulatory networks composed of two and three enzymes. The minimal circuits capable of DoRA were examined with Michaelis-Menten kinetics. Several motifs that are essential for the dynamical function of DoRA were identified. Systematic analysis of the topology space of robust DoRA circuits revealed that, rather than fine-tuning the network's parameters, the function is primarily realized by enzymatic regulations on the controlled node that are constrained in limiting regions of saturation or linearity.

  3. Simplified Warfarin Dose-response Pharmacodynamic Models

    OpenAIRE

    Kim, Seongho; Gaweda, Adam E.; Wu, Dongfeng; Li, Lang; Shesh N Rai; Brier, Michael E.

    2015-01-01

    Warfarin is a frequently used oral anticoagulant for long-term prevention and treatment of thromboembolic events. Due to its narrow therapeutic range and large inter-individual dose-response variability, it is highly desirable to personalize warfarin dosing. However, the complexity of the conventional kinetic-pharmacodynamic (K-PD) models hampers the development of the personalized dose management. To avert this challenge, we propose simplified PD models for warfarin dose-response relationshi...

  4. Multistability analysis of a general class of recurrent neural networks with non-monotonic activation functions and time-varying delays.

    Science.gov (United States)

    Liu, Peng; Zeng, Zhigang; Wang, Jun

    2016-07-01

    This paper addresses the multistability for a general class of recurrent neural networks with time-varying delays. Without assuming the linearity or monotonicity of the activation functions, several new sufficient conditions are obtained to ensure the existence of (2K+1)(n) equilibrium points and the exponential stability of (K+1)(n) equilibrium points among them for n-neuron neural networks, where K is a positive integer and determined by the type of activation functions and the parameters of neural network jointly. The obtained results generalize and improve the earlier publications. Furthermore, the attraction basins of these exponentially stable equilibrium points are estimated. It is revealed that the attraction basins of these exponentially stable equilibrium points can be larger than their originally partitioned subsets. Finally, three illustrative numerical examples show the effectiveness of theoretical results.

  5. A-monotonicity and applications to nonlinear variational inclusion problems

    Directory of Open Access Journals (Sweden)

    Ram U. Verma

    2004-01-01

    Full Text Available A new notion of the A-monotonicity is introduced, which generalizes the H-monotonicity. Since the A-monotonicity originates from hemivariational inequalities, and hemivariational inequalities are connected with nonconvex energy functions, it turns out to be a useful tool proving the existence of solutions of nonconvex constrained problems as well.

  6. Testing Manifest Monotonicity Using Order-Constrained Statistical Inference

    Science.gov (United States)

    Tijmstra, Jesper; Hessen, David J.; van der Heijden, Peter G. M.; Sijtsma, Klaas

    2013-01-01

    Most dichotomous item response models share the assumption of latent monotonicity, which states that the probability of a positive response to an item is a nondecreasing function of a latent variable intended to be measured. Latent monotonicity cannot be evaluated directly, but it implies manifest monotonicity across a variety of observed scores,…

  7. Inferring mechanisms from dose-response curves

    OpenAIRE

    Chow, Carson C.; Ong, Karen M.; Dougherty, Edward J.; Simons, S. Stoney

    2011-01-01

    The steady state dose-response curve of ligand-mediated gene induction usually appears to precisely follow a first-order Hill equation (Hill coefficient equal to 1). Additionally, various cofactors/reagents can affect both the potency and the maximum activity of gene induction in a gene-specific manner. Recently, we have developed a general theory for which an unspecified sequence of steps or reactions yields a first-order Hill dose-response curve (FHDC) for plots of the final product vs. ini...

  8. Model identification for dose response signal detection

    OpenAIRE

    Bretz, Frank; Dette, Holger; Titoff, Stefanie; Volgushev, Stanislav

    2012-01-01

    We consider the problem of detecting a dose response signal if several competing regression models are available to describe the dose response relationship. In particular, we re-analyze the MCP-Mod approach from Bretz et al. (2005), which has become a very popular tool for this problem in recent years. We propose an improvement based on likelihood ratio tests and prove that in linear models this approach is always at least as powerful as the MCP-Mod method. This result remains ...

  9. Dose-response analysis using R

    DEFF Research Database (Denmark)

    Ritz, Christian; Baty, Florent; Streibig, Jens Carl

    2015-01-01

    Dose-response analysis can be carried out using multi-purpose commercial statistical software, but except for a few special cases the analysis easily becomes cumbersome as relevant, non-standard output requires manual programming. The extension package drc for the statistical environment R provides...

  10. Dose-response-a challenge for allelopathy?

    Science.gov (United States)

    Belz, Regina G; Hurle, Karl; Duke, Stephen O

    2005-04-01

    The response of an organism to a chemical depends, among other things, on the dose. Nonlinear dose-response relationships occur across a broad range of research fields, and are a well established tool to describe the basic mechanisms of phytotoxicity. The responses of plants to allelochemicals as biosynthesized phytotoxins, relate as well to nonlinearity and, thus, allelopathic effects can be adequately quantified by nonlinear mathematical modeling. The current paper applies the concept of nonlinearity to assorted aspects of allelopathy within several bioassays and reveals their analysis by nonlinear regression models. Procedures for a valid comparison of effective doses between different allelopathic interactions are presented for both, inhibitory and stimulatory effects. The dose-response applications measure and compare the responses produced by pure allelochemicals [scopoletin (7-hydroxy-6-methoxy-2H-1-benzopyran-2-one); DIBOA (2,4-dihydroxy-2H-1,4-benzoxaxin-3(4H)-one); BOA (benzoxazolin-2(3H)-one); MBOA (6-methoxy-benzoxazolin-2(3H)-one)], involved in allelopathy of grain crops, to demonstrate how some general principles of dose responses also relate to allelopathy. Hereupon, dose-response applications with living donor plants demonstrate the validity of these principles for density-dependent phytotoxicity of allelochemicals produced and released by living plants (Avena sativa L., Secale cereale L., Triticum L. spp.), and reveal the use of such experiments for initial considerations about basic principles of allelopathy. Results confirm that nonlinearity applies to allelopathy, and the study of allelopathic effects in dose-response experiments allows for new and challenging insights into allelopathic interactions.

  11. Dose response biology: the case of resveratrol.

    Science.gov (United States)

    Calabrese, Edward J; Mattson, Mark P; Calabrese, Vittorio

    2010-12-01

    Resveratrol often displays hormesis-like biphasic dose responses. This occurs in a broad range of biological models and for numerous endpoints of biomedical interest and public health concern. Recognition of the widespread occurrence of the hormetic nature of many of the responses of resveratrol is important on multiple levels. It can help optimize study design protocols by investigators, create a dose-response framework for better addressing dose-related biological complexities and assist in the development of public health and medical guidance with respect to considerations for what is an optimal dose not just for an agent such as resveratrol, but also for the plethora of agents that also act via hormetic mechanisms.

  12. Weighted monotonicity inequalities for unbounded operators

    CERN Document Server

    Hoa, Dinh Trung

    2011-01-01

    Let $\\tau$ be a faithful normal semifinite trace on a von Neumann algebra $\\mathcal{M}$. For a continuous nonnegative convex monotone nondecreasing function $f$ on convex subset $\\Omega$ of $\\mathbb{R}$ and weight nonnegative Borel function $w$ we consider weighted monotonicity inequalities of the form {equation*} \\tau(w(A)^{1/2}f(A)w(A)^{1/2}) \\le \\tau (w(A)^{1/2}f(B)w(A)^{1/2}), {equation*} where $A$ and $B$ are unbounded operators affiliated with respect to algebra $\\mathcal{M}$.

  13. Using machine learning to model dose-response relationships.

    Science.gov (United States)

    Linden, Ariel; Yarnold, Paul R; Nallamothu, Brahmajee K

    2016-12-01

    Establishing the relationship between various doses of an exposure and a response variable is integral to many studies in health care. Linear parametric models, widely used for estimating dose-response relationships, have several limitations. This paper employs the optimal discriminant analysis (ODA) machine-learning algorithm to determine the degree to which exposure dose can be distinguished based on the distribution of the response variable. By framing the dose-response relationship as a classification problem, machine learning can provide the same functionality as conventional models, but can additionally make individual-level predictions, which may be helpful in practical applications like establishing responsiveness to prescribed drug regimens. Using data from a study measuring the responses of blood flow in the forearm to the intra-arterial administration of isoproterenol (separately for 9 black and 13 white men, and pooled), we compare the results estimated from a generalized estimating equations (GEE) model with those estimated using ODA. Generalized estimating equations and ODA both identified many statistically significant dose-response relationships, separately by race and for pooled data. Post hoc comparisons between doses indicated ODA (based on exact P values) was consistently more conservative than GEE (based on estimated P values). Compared with ODA, GEE produced twice as many instances of paradoxical confounding (findings from analysis of pooled data that are inconsistent with findings from analyses stratified by race). Given its unique advantages and greater analytic flexibility, maximum-accuracy machine-learning methods like ODA should be considered as the primary analytic approach in dose-response applications. © 2016 John Wiley & Sons, Ltd.

  14. Monotone Rank and Separations in Computational Complexity

    CERN Document Server

    Li, Yang D

    2011-01-01

    In the paper, we introduce the concept of monotone rank, and using it as a powerful tool, we obtain several important and strong separation results in computational complexity. We show a super-exponential separation between monotone and non-monotone computation in the non-commutative model, and thus give the answer to a longstanding open problem posed by Nisan \\cite{Nis1991} in algebraic complexity. More specifically, we exhibit a homogeneous algebraic function $f$ of degree $d$ ($d$ even) on $n$ variables with the monotone algebraic branching program (ABP) complexity $\\Omega(n^{d/2})$ and the non-monotone ABP complexity $O(d^2)$. We propose a relaxed version of the famous Bell's theorem\\cite{Bel1964}\\cite{CHSH1969}. Bell's theorem basically states that local hidden variable theory cannot predict the correlations produced by quantum mechanics, and therefore is an impossibility result. Bell's theorem heavily relies on the diversity of the measurements. We prove that even if we fix the measurement, infinite amo...

  15. On the sample monotonization problem

    Science.gov (United States)

    Takhanov, R. S.

    2010-07-01

    The problem of finding a maximal subsample in a training sample consisting of the pairs “object-answer” that does not violate monotonicity constraints is considered. It is proved that this problem is NP-hard and that it is equivalent to the problem of finding a maximum independent set in special directed graphs. Practically important cases in which a partial order specified on the set of answers is a complete order or has dimension two are considered in detail. It is shown that the second case is reduced to the maximization of a quadratic convex function on a convex set. For this case, an approximate polynomial algorithm based on linear programming theory is proposed.

  16. Patient factors that influence warfarin dose response.

    Science.gov (United States)

    White, Pamela J

    2010-06-01

    Warfarin has long been the mainstay of oral anticoagulation therapy for the treatment and prevention of venous and arterial thrombosis. The narrow therapeutic index of warfarin, and the complex number of factors that influence international normalized ratio (INR) response, makes optimization of warfarin therapy challenging. Determination of the appropriate warfarin dose during initiation and maintenance therapy requires an understanding of patient factors that influence dose response: age, body weight, nutritional status, acute and chronic disease states, and changes in concomitant drug therapy and diet. This review will examine specific clinical factors that can affect the pharmacokinetics and pharmacodynamics of warfarin, as well as the role of pharmacogenetics in optimizing warfarin therapy.

  17. Robust sampling-sourced numerical retrieval algorithm for optical energy loss function based on log-log mesh optimization and local monotonicity preserving Steffen spline

    Science.gov (United States)

    Maglevanny, I. I.; Smolar, V. A.

    2016-01-01

    We introduce a new technique of interpolation of the energy-loss function (ELF) in solids sampled by empirical optical spectra. Finding appropriate interpolation methods for ELFs poses several challenges. The sampled ELFs are usually very heterogeneous, can originate from various sources thus so called "data gaps" can appear, and significant discontinuities and multiple high outliers can be present. As a result an interpolation based on those data may not perform well at predicting reasonable physical results. Reliable interpolation tools, suitable for ELF applications, should therefore satisfy several important demands: accuracy and predictive power, robustness and computational efficiency, and ease of use. We examined the effect on the fitting quality due to different interpolation schemes with emphasis on ELF mesh optimization procedures and we argue that the optimal fitting should be based on preliminary log-log scaling data transforms by which the non-uniformity of sampled data distribution may be considerably reduced. The transformed data are then interpolated by local monotonicity preserving Steffen spline. The result is a piece-wise smooth fitting curve with continuous first-order derivatives that passes through all data points without spurious oscillations. Local extrema can occur only at grid points where they are given by the data, but not in between two adjacent grid points. It is found that proposed technique gives the most accurate results and also that its computational time is short. Thus, it is feasible using this simple method to address practical problems associated with interaction between a bulk material and a moving electron. A compact C++ implementation of our algorithm is also presented.

  18. Measuring Upper Limb Capacity in Poststroke Patients : Development, Fit of the Monotone Homogeneity Model, Unidimensionality, Fit of the Double Monotonicity Model, Differential Item Functioning, Internal Consistency, and Feasibility of the Stroke Upper Limb Capacity Scale, SULCS

    NARCIS (Netherlands)

    Roorda, Leo D.; Houwink, Annemieke; Smits, Wendy; Molenaar, Ivo W.; Geurts, Alexander C.

    2011-01-01

    Objectives: To develop an easy-to-use scale that measures upper limb capacity, according to the International Classification of Functioning, Disability and Health definition, in patients after stroke, and to investigate certain psychometric properties of this scale. Design: Cohort study. Setting: In

  19. LIMITED MEMORY BFGS METHOD FOR NONLINEAR MONOTONE EQUATIONS

    Institute of Scientific and Technical Information of China (English)

    Weijun Zhou; Donghui Li

    2007-01-01

    In this paper, we propose an algorithm for solving nonlinear monotone equations by combining the limited memory BFGS method (L-BFGS) with a projection method. We show that the method is globally convergent if the equation involves a Lipschitz continuous monotone function. We also present some preliminary numerical results.

  20. Dose response relationship in local radiotherapy for hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hee Chul; Seong, Jin Sil; Han, Kwang Hyub; Chon, Chae Yoon; Moon, Young Myoung; Song, Jae Seok; Suh, Chang Ok [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of)

    2001-06-01

    In this study, it was investigated whether dose response relation existed or not in local radiotherapy for primary hepatocellular carcinoma. From January 1992 to March 2000, 158 patients were included in present study. Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child's class C, tumors occupying more than two thirds of the entire liver, and performance status on the ECOG scale of more than 3. Radiotherapy was given to the field including tumor with generous margin using 6, 10-MV X-ray. Mean tumor dose was 48.2{+-}7.9 Gy in daily 1.8 Gy fractions. Tumor response was based on diagnostic radiologic examinations such as CT scan, MR imaging, hepatic artery angiography at 4-8 weeks following completion of treatment. Statistical analysis was done to investigate the existence of dose response relationship of local radiotherapy when it was applied to the treatment of primary hepatocellular carcinoma. An objective response was observed in 106 of 158 patients, giving a response rate of 67. 1%. Statistical analysis revealed that total dose was the most significant factor in relation to tumor response when local radiotherapy was applied to the treatment of primary hepatocellular carcinoma. Only 29.2% showed objective response in patients treated with dose less than 40 Gy, while 68.6% and 77.1 % showed major response in patients with 40-50 Gy and more than 50 Gy, respectively. Child-Pugh classification was significant factor in the development of ascites, overt radiation induced liver disease and gastroenteritis. Radiation dose was an important factor for development of radiation induced gastroduodenal ulcer. Present study showed the existence of dose response relationship in local radiotherapy for primary hepatocellular carcinoma. Only radiotherapy dose was a significant factor to predict the objective response. Further study is required to predict the maximal tolerance dose in consideration of liver function and non

  1. Monotone partitions and almost partitions

    NARCIS (Netherlands)

    Bonanzinga, M.; Cammaroto, F.; van Mill, J.; Pansera, B.A.

    2014-01-01

    In this paper we are interested in monotone versions of partitionability of topological spaces and weak versions thereof. We identify several classes of spaces with these properties by constructing trees of open sets with various properties.

  2. Maximum likelihood estimation for cytogenetic dose-response curves

    Energy Technology Data Exchange (ETDEWEB)

    Frome, E.L; DuFrain, R.J.

    1983-10-01

    In vitro dose-response curves are used to describe the relation between the yield of dicentric chromosome aberrations and radiation dose for human lymphocytes. The dicentric yields follow the Poisson distribution, and the expected yield depends on both the magnitude and the temporal distribution of the dose for low LET radiation. A general dose-response model that describes this relation has been obtained by Kellerer and Rossi using the theory of dual radiation action. The yield of elementary lesions is kappa(..gamma..d + g(t, tau)d/sup 2/), where t is the time and d is dose. The coefficient of the d/sup 2/ term is determined by the recovery function and the temporal mode of irradiation. Two special cases of practical interest are split-dose and continuous exposure experiments, and the resulting models are intrinsically nonlinear in the parameters. A general purpose maximum likelihood estimation procedure is described and illustrated with numerical examples from both experimental designs. Poisson regression analysis is used for estimation, hypothesis testing, and regression diagnostics. Results are discussed in the context of exposure assessment procedures for both acute and chronic human radiation exposure.

  3. Monotone complete C*-algebras and generic dynamics

    CERN Document Server

    Saitô, Kazuyuki

    2015-01-01

    This monograph is about monotone complete C*-algebras, their properties and the new classification theory. A self-contained introduction to generic dynamics is also included because of its important connections to these algebras. Our knowledge and understanding of monotone complete C*-algebras has been transformed in recent years. This is a very exciting stage in their development, with much discovered but with many mysteries to unravel. This book is intended to encourage graduate students and working mathematicians to attack some of these difficult questions. Each bounded, upward directed net of real numbers has a limit. Monotone complete algebras of operators have a similar property. In particular, every von Neumann algebra is monotone complete but the converse is false. Written by major contributors to this field, Monotone Complete C*-algebras and Generic Dynamics takes readers from the basics to recent advances. The prerequisites are a grounding in functional analysis, some point set topology and an eleme...

  4. Dose-response relationships for carcinogens: a review.

    OpenAIRE

    Zeise, L; Wilson, R.; Crouch, E A

    1987-01-01

    We review the experimental evidence for various shapes of dose-response relationships for carcinogens and summarize those experiments that give the most information on relatively low doses. A brief review of some models is given to illustrate the shapes of dose-response curve expected from them. Our major interest is in the use of dose-response relationships to estimate risks to humans at low doses, and so we pay special attention to experimentally observed and theoretically expected nonlinea...

  5. Why Monotonous Repetition is Unsatisfying

    CERN Document Server

    Salingaros, Nikos A

    2011-01-01

    Human beings prefer ordered complexity and not randomness in their environment, a result of our perceptual system evolving to interpret natural forms. We also recognize monotonously repeating forms as unnatural. Although widespread in today's built environment, such forms generate reactions ranging from boredom to unease. Christopher Alexander has introduced rules for generating forms adapted to natural geometries, which show structured variation with multiple symmetries in a hierarchy of scales. It turns out to be impossible to generate monotonously repeating forms by following those rules. As it is highly probable that traditional artifacts, buildings, and cities were created instinctively using a version of the same rules, this is the reason we never find monotonously repeating forms in traditional cultures.

  6. Review of dose-response curves for acute antimigraine drugs

    DEFF Research Database (Denmark)

    Hougaard, Anders; Tfelt-Hansen, Peer

    2015-01-01

    INTRODUCTION: Dose-response curves for efficacy and tolerability are the important determinants for the choice of doses of acute migraine drugs. Areas covered: Dose-response curves for the efficacy of seven triptans (5-HT1B/1D receptor agonists), a 5-HT1F receptor agonist (lasmiditan) and four oral...... calcitonin-gene related peptide receptor antagonists (telcagepant, MK-3207, BI 44370 TA and BMS-927711) in placebo-controlled trials were reviewed. In addition, dose-response curves for adverse events (AEs) were reviewed. Expert opinion: For most triptans, the dose-response curve for efficacy is flat......, whereas AEs often increase with increasing doses. The two other groups of drugs also have flat dose-response curves for efficacy. Overall, the triptans still have the most favorable efficacy-tolerability profile. Current acute antimigraine drugs do not fulfill the expectations of the patients, and thus...

  7. Insulin dose response analysis of free fatty acid kinetics.

    Science.gov (United States)

    Jensen, Michael D; Nielsen, Søren

    2007-01-01

    Insulin regulation of free fatty acid (FFA) release is an important aspect of metabolic function; however, FFA release is exquisitely sensitive to insulin, which complicates the design and analysis of dose response experiments. We measured FFA ([(3)H]palmitate) and glucose ([(3)H]glucose) kinetics in 7 nonobese men, 7 nonobese women, 7 obese men, and 7 obese women by using a two-step insulin clamp (0.25 and 2.5 mU/kg fat-free mass per minute). Obese men and women were characterized as having a BMI of 28 or greater and body fat of 28% and 40% or greater for men and for women, respectively. Nonobese men and women had 22% and 35% or less body fat, respectively. All volunteers were Caucasian. Glucose disposal increased in a linear fashion with plasma insulin concentrations. The nonlinear suppression of plasma palmitate flux and concentrations could be linearized by logarithmically transforming both the insulin concentration and palmitate axes, except in nonobese men. We repeated the studies in 7 nonobese and 7 obese men, using 1.0 mU/kg fat-free mass per minute as the second insulin dose, which linearized the log-transformed lipolysis measures. The indices of insulin regulation of lipolysis predicted using 2 points (basal and second insulin dose) vs 3 points (basal, low, and high dose) were not different provided the proper second dose was selected. The EC(50) for insulin suppression of lipolysis correlated linearly with plasma triglycerides (r = 0.52, P < .001) and exponentially with insulin sensitivity(glucose) (r = 0.70, P < .001). We conclude that log transformation of insulin dose response data for FFA permits straightforward data analysis and simplifies the estimation of metabolically relevant parameters.

  8. Lack-of-fit tests for assessing mean structures for continuous dose-response data

    DEFF Research Database (Denmark)

    Martinussen, Torben

    2011-01-01

    We review a range of lack-of-fit tests suitable for assessing the appropriateness of the mean function in dose-response models. The review encompasses both well-known tests and new tests based on recent developments in statistics, which we have extended to the dose-response case. We argue...... that the classical methods are inadequate in certain situations, where the new tests may be applied. Power comparisons are carried out by means of extensive simulation studies, covering both designs with and without replicates at small and large sample sizes. Three datasets from dose-response applications illustrate...... differences and similarities between the tests. The results suggest that the new tests perform better and exhibit a wider applicability....

  9. Monotonicity of chi-square test statistics

    OpenAIRE

    Ryu, Keunkwan

    2003-01-01

    This paper establishes monotonicity of the chi-square test statistic. As the more efficient parameter estimator is plugged into the test statistic, the degrees of freedom of the resulting chi-square test statistic monotonically increase.

  10. Dose-response features of neuroprotective agents: an integrative summary.

    Science.gov (United States)

    Calabrese, Edward J

    2008-01-01

    This article provides an integrative summary of the effects of neuroprotective agents on neuronal survival and neurite outgrowth using primary cell cultures, multiple neuronal cell lines, and astroglial cells. These findings are dealt with in considerable detail in the following three articles (Calabrese, 2008a, 2008b, 2008c) of this series of issues of Critical Reviews in Toxicology. The principal finding is that the overwhelming majority of neuroprotective agents display biphasic dose responses, characterized by modest low-dose enhancement/stimulation and high-dose inhibitory responses. The quantitative features of these dose responses are consistent with the hormetic dose-response model. Mechanisms that account for numerous hormetic dose responses of neuroprotective agents are summarized, as well as the clinical implications of specific experimental findings.

  11. Assembled cross-species perchlorate dose-response data

    Data.gov (United States)

    U.S. Environmental Protection Agency — This data set contains dose-response data for perchlorate exposure in multiple species. These data were assembled from peer-reviewed studies. Species included in...

  12. Nonparallel nephrotoxicity dose-response curves of aminoglycosides.

    OpenAIRE

    1981-01-01

    Nephrotoxicity comparisons of aminoglycosides in rats, utilizing large multiples of human doses, have indicated an advantage for netilmicin. However, no nephrotoxicity advantage of netilmicin has been demonstrated at the lower doses used in clinics. Some high-dose studies in rats have also suggested that the slope of the nephrotoxicity dose-response curve of netilmicin was less steep than the slopes of other aminoglycosides. Therefore, the slopes of the nephrotoxicity dose-response curves of ...

  13. A Method to Evaluate Hormesis in Nanoparticle Dose-Responses

    OpenAIRE

    Nascarella, Marc A.; Calabrese, Edward J.

    2012-01-01

    The term hormesis describes a dose-response relationship that is characterized by a response that is opposite above and below the toxicological or pharmacological threshold. Previous reports have shown that this relationship is ubiquitous in the response of pharmaceuticals, metals, organic chemicals, radiation, and physical stressor agents. Recent reports have also indicated that certain nanoparticles (NPs) may also exhibit a hormetic dose-response. We describe the application of three previo...

  14. Dose-response relationship in multistage carcinogenesis: promoters.

    OpenAIRE

    Kitchin, K T; Brown, J. L.; Setzer, R.W.

    1994-01-01

    Published dose-response curves of promoters of multistage carcinogenesis were selected that met the combined criteria of long study times, multiple doses, and low doses. In rat liver, 12 dose-response studies of 7 different promoters (phenobarbital, 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD], clophen A-50 (a polychlorinated biphenyl), alpha-, beta-, and gamma-hexachlorocyclohexane [HCH], and chloroform) were selected. These promoters were studied for 7-86 weeks and either altered hepatic foci...

  15. Cardiac dose-response relationships of oral and intravenous pindolol

    OpenAIRE

    Carruthers, S. George

    1982-01-01

    1 The dose-response curve of pindolol on exercise heart rate has been constructed from observations in healthy male subjects studied 2 h after oral doses of pindolol 0.25 mg, 0.5 mg, 1 mg, 2.5 mg, 5 mg, 10 mg and 20 mg. This dose-response curve has been compared with historical controls who received atenolol, oxprenolol, practolol, propranolol and sotalol.

  16. Generalized convexity, generalized monotonicity recent results

    CERN Document Server

    Martinez-Legaz, Juan-Enrique; Volle, Michel

    1998-01-01

    A function is convex if its epigraph is convex. This geometrical structure has very strong implications in terms of continuity and differentiability. Separation theorems lead to optimality conditions and duality for convex problems. A function is quasiconvex if its lower level sets are convex. Here again, the geo­ metrical structure of the level sets implies some continuity and differentiability properties for quasiconvex functions. Optimality conditions and duality can be derived for optimization problems involving such functions as well. Over a period of about fifty years, quasiconvex and other generalized convex functions have been considered in a variety of fields including economies, man­ agement science, engineering, probability and applied sciences in accordance with the need of particular applications. During the last twenty-five years, an increase of research activities in this field has been witnessed. More recently generalized monotonicity of maps has been studied. It relates to generalized conve...

  17. Some Generalizations of Monotonicity Condition and Applications

    Institute of Scientific and Technical Information of China (English)

    虞旦盛; 周颂平

    2006-01-01

    @@ O Introduction It is well known that there are a great number of interesting results in Fourier analysis established by assuming monotonicity of coefficients, and many of them have been generalized by loosing the condition to quasi-monotonicity, O-regularly varying quasi-monotonicity, etc..

  18. A monotone framework for CCS

    DEFF Research Database (Denmark)

    Nielson, Hanne Riis; Nielson, Flemming

    2009-01-01

    The calculus of communicating systems, CCS, was introduced by Robin Milner as a calculus for modelling concurrent systems. Subsequently several techniques have been developed for analysing such models in order to get further insight into their dynamic behaviour. In this paper we present a static...... analysis for approximating the control structure embedded within the models. We formulate the analysis as an instance of a monotone framework and thus draw on techniques that often are associated with the efficient implementation of classical imperative programming languages. We show how to construct...

  19. Dose-Response Calculator for ArcGIS

    Science.gov (United States)

    Hanser, Steven E.; Aldridge, Cameron L.; Leu, Matthias; Nielsen, Scott E.

    2011-01-01

    The Dose-Response Calculator for ArcGIS is a tool that extends the Environmental Systems Research Institute (ESRI) ArcGIS 10 Desktop application to aid with the visualization of relationships between two raster GIS datasets. A dose-response curve is a line graph commonly used in medical research to examine the effects of different dosage rates of a drug or chemical (for example, carcinogen) on an outcome of interest (for example, cell mutations) (Russell and others, 1982). Dose-response curves have recently been used in ecological studies to examine the influence of an explanatory dose variable (for example, percentage of habitat cover, distance to disturbance) on a predicted response (for example, survival, probability of occurrence, abundance) (Aldridge and others, 2008). These dose curves have been created by calculating the predicted response value from a statistical model at different levels of the explanatory dose variable while holding values of other explanatory variables constant. Curves (plots) developed using the Dose-Response Calculator overcome the need to hold variables constant by using values extracted from the predicted response surface of a spatially explicit statistical model fit in a GIS, which include the variation of all explanatory variables, to visualize the univariate response to the dose variable. Application of the Dose-Response Calculator can be extended beyond the assessment of statistical model predictions and may be used to visualize the relationship between any two raster GIS datasets (see example in tool instructions). This tool generates tabular data for use in further exploration of dose-response relationships and a graph of the dose-response curve.

  20. Curious cases: Altered dose-response relationships in addiction genetics.

    Science.gov (United States)

    Uhl, George R; Drgonova, Jana; Hall, F Scott

    2014-03-01

    Dose-response relationships for most addictive substances are "inverted U"-shaped. Addictive substances produce both positive features that include reward, euphoria, anxiolysis, withdrawal-relief, and negative features that include aversion, dysphoria, anxiety and withdrawal symptoms. A simple model differentially associates ascending and descending limbs of dose-response curves with rewarding and aversive influences, respectively. However, Diagnostic and Statistical Manual (DSM) diagnoses of substance dependence fail to incorporate dose-response criteria and don't directly consider balances between euphoric and dysphoric drug effects. Classical genetic studies document substantial heritable influences on DSM substance dependence. Linkage and genome-wide association studies identify modest-sized effects at any locus. Nevertheless, clusters of SNPs within selected genes display 10(-2)>p>10(-8) associations with dependence in many independent samples. For several of these genes, evidence for cis-regulatory, level-of-expression differences supports the validity of mouse models in which levels of expression are also altered. This review documents surprising, recently defined cases in which convergent evidence from humans and mouse models supports central influences of altered dose-response relationships in mediating the impact of relevant genomic variation on addiction phenotypes. For variation at loci for the α5 nicotinic acetylcholine receptor, cadherin 13, receptor type protein tyrosine phosphatase Δ and neuronal cell adhesion molecule genes, changed dose-response relationships conferred by gene knockouts in mice are accompanied by supporting human data. These observations emphasize desirability of carefully elucidating dose-response relationships for both rewarding and aversive features of abused substances wherever possible. They motivate consideration of individual differences in dose-response relationships in addiction nosology and therapeutics.

  1. CALUX measurements: statistical inferences for the dose-response curve.

    Science.gov (United States)

    Elskens, M; Baston, D S; Stumpf, C; Haedrich, J; Keupers, I; Croes, K; Denison, M S; Baeyens, W; Goeyens, L

    2011-09-30

    Chemical Activated LUciferase gene eXpression [CALUX] is a reporter gene mammalian cell bioassay used for detection and semi-quantitative analyses of dioxin-like compounds. CALUX dose-response curves for 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD] are typically smooth and sigmoidal when the dose is portrayed on a logarithmic scale. Non-linear regression models are used to calibrate the CALUX response versus TCDD standards and to convert the sample response into Bioanalytical EQuivalents (BEQs). Several complications may arise in terms of statistical inference, specifically and most important is the uncertainty assessment of the predicted BEQ. This paper presents the use of linear calibration functions based on Box-Cox transformations to overcome the issue of uncertainty assessment. Main issues being addressed are (i) confidence and prediction intervals for the CALUX response, (ii) confidence and prediction intervals for the predicted BEQ-value, and (iii) detection/estimation capabilities for the sigmoid and linearized models. Statistical comparisons between different calculation methods involving inverse prediction, effective concentration ratios (ECR(20-50-80)) and slope ratio were achieved with example datasets in order to provide guidance for optimizing BEQ determinations and expand assay performance with the recombinant mouse hepatoma CALUX cell line H1L6.1c3.

  2. Guidelines for Use of the Approximate Beta-Poisson Dose-Response Model.

    Science.gov (United States)

    Xie, Gang; Roiko, Anne; Stratton, Helen; Lemckert, Charles; Dunn, Peter K; Mengersen, Kerrie

    2016-10-05

    For dose-response analysis in quantitative microbial risk assessment (QMRA), the exact beta-Poisson model is a two-parameter mechanistic dose-response model with parameters α>0 and β>0, which involves the Kummer confluent hypergeometric function. Evaluation of a hypergeometric function is a computational challenge. Denoting PI(d) as the probability of infection at a given mean dose d, the widely used dose-response model PI(d)=1-(1+dβ)-α is an approximate formula for the exact beta-Poisson model. Notwithstanding the required conditions α1, issues related to the validity and approximation accuracy of this approximate formula have remained largely ignored in practice, partly because these conditions are too general to provide clear guidance. Consequently, this study proposes a probability measure Pr(0 (22α̂)0.50 for 0.020.99) . This validity measure and rule of thumb were validated by application to all the completed beta-Poisson models (related to 85 data sets) from the QMRA community portal (QMRA Wiki). The results showed that the higher the probability Pr(0 dose-response curve.

  3. Monotone data visualization using rational trigonometric spline interpolation.

    Science.gov (United States)

    Ibraheem, Farheen; Hussain, Maria; Hussain, Malik Zawwar

    2014-01-01

    Rational cubic and bicubic trigonometric schemes are developed to conserve monotonicity of curve and surface data, respectively. The rational cubic function has four parameters in each subinterval, while the rational bicubic partially blended function has eight parameters in each rectangular patch. The monotonicity of curve and surface data is retained by developing constraints on some of these parameters in description of rational cubic and bicubic trigonometric functions. The remaining parameters are kept free to modify the shape of curve and surface if required. The developed algorithm is verified mathematically and demonstrated graphically.

  4. Monotone Data Visualization Using Rational Trigonometric Spline Interpolation

    Directory of Open Access Journals (Sweden)

    Farheen Ibraheem

    2014-01-01

    Full Text Available Rational cubic and bicubic trigonometric schemes are developed to conserve monotonicity of curve and surface data, respectively. The rational cubic function has four parameters in each subinterval, while the rational bicubic partially blended function has eight parameters in each rectangular patch. The monotonicity of curve and surface data is retained by developing constraints on some of these parameters in description of rational cubic and bicubic trigonometric functions. The remaining parameters are kept free to modify the shape of curve and surface if required. The developed algorithm is verified mathematically and demonstrated graphically.

  5. Effects of isoflavone-containing soya protein on ex vivo cholesterol efflux, vascular function and blood markers of CVD risk in adults with moderately elevated blood pressure: a dose-response randomised controlled trial.

    Science.gov (United States)

    Richter, Chesney K; Skulas-Ray, Ann C; Fleming, Jennifer A; Link, Christina J; Mukherjea, Ratna; Krul, Elaine S; Kris-Etherton, Penny M

    2017-05-01

    Emerging CVD risk factors (e.g. HDL function and central haemodynamics) may account for residual CVD risk experienced by individuals who meet LDL-cholesterol and blood pressure (BP) targets. Recent evidence suggests that these emerging risk factors can be modified by polyphenol-rich interventions such as soya, but additional research is needed. This study was designed to investigate the effects of an isoflavone-containing soya protein isolate (delivering 25 and 50 g/d soya protein) on HDL function (i.e. ex vivo cholesterol efflux), macrovascular function and blood markers of CVD risk. Middle-aged adults (n 20; mean age=51·6 (sem 6·6) years) with moderately elevated brachial BP (mean systolic BP=129 (sem 9) mmHg; mean diastolic BP=82·5 (sem 8·4) mmHg) consumed 0 (control), 25 and 50 g/d soya protein in a randomised cross-over design. Soya and control powders were consumed for 6 weeks each with a 2-week compliance break between treatment periods. Blood samples and vascular function measures were obtained at baseline and following each supplementation period. Supplementation with 50 g/d soya protein significantly reduced brachial diastolic BP (-2·3 mmHg) compared with 25 g/d soya protein (Tukey-adjusted P=0·03) but not the control. Soya supplementation did not improve ex vivo cholesterol efflux, macrovascular function or other blood markers of CVD risk compared with the carbohydrate-matched control. Additional research is needed to clarify whether effects on these CVD risk factors depend on the relative health of participants and/or equol producing capacity.

  6. Pseudomonas aeruginosa dose response and bathing water infection.

    Science.gov (United States)

    Roser, D J; van den Akker, B; Boase, S; Haas, C N; Ashbolt, N J; Rice, S A

    2014-03-01

    Pseudomonas aeruginosa is the opportunistic pathogen mostly implicated in folliculitis and acute otitis externa in pools and hot tubs. Nevertheless, infection risks remain poorly quantified. This paper reviews disease aetiologies and bacterial skin colonization science to advance dose-response theory development. Three model forms are identified for predicting disease likelihood from pathogen density. Two are based on Furumoto & Mickey's exponential 'single-hit' model and predict infection likelihood and severity (lesions/m2), respectively. 'Third-generation', mechanistic, dose-response algorithm development is additionally scoped. The proposed formulation integrates dispersion, epidermal interaction, and follicle invasion. The review also details uncertainties needing consideration which pertain to water quality, outbreaks, exposure time, infection sites, biofilms, cerumen, environmental factors (e.g. skin saturation, hydrodynamics), and whether P. aeruginosa is endogenous or exogenous. The review's findings are used to propose a conceptual infection model and identify research priorities including pool dose-response modelling, epidermis ecology and infection likelihood-based hygiene management.

  7. Design methods for some dose-response models

    NARCIS (Netherlands)

    Albers, Willem/Wim; Strijbosch, Leo W.G.; Does, Ronald J.M.M.

    1990-01-01

    A recently described design method for one-parameter biomedical models such as limiting or serial dilution assays is generalized to two-parameter models for which the dose-response relationship can be expressed as a linear regression model with parameters α (intercept) and β (slope). Design formulae

  8. Generation of dose-response relationships to assess the effects of acidity in precipitation on growth and productivity of vegetation

    Energy Technology Data Exchange (ETDEWEB)

    Evans, L.S.

    1981-01-01

    Experiments were performed with several plant species in natural environments as well in a greenhouse and/or tissue culture facilities to establish dose-response functions of plant responses to simulated acidic rain in order to determine environmental risk assessments to ambient levels of acidic rain. Response functions of foliar injury, biomass of leaves and seed of soybean and pinto beans, root yields of radishes and garden beets, and reproduction of bracken fern are considered. The dose-response function of soybean seed yields with the hydrogen ion concentration of simulated acidic rainfalls was expressed by the equation y = 21.06-1.01 log x where y = seed yield in grams per plant and x = the hydrogen concentration if ..mu..eq l/sup -1/. The correlation coefficient of this relationship was -0.90. A similar dose-response function was generated for percent fertilization of ferns in a forest understory. When percent fertilization is plotted on logarithmic scale with hydrogen ion concentration of the simulated rain solution, the Y intercept is 51.18, slope -0.041 with a correlation coefficient of -0.98. Other dose-response functions were generated that assist in a general knowledge as to which plant species and which physiological processes are most impacted by acidic precipitation. Some responses did not produce convenient dose-response relationships. In such cases the responses may be altered by other environmental factors or there may be no differences among treatment means.

  9. Radiation Dose-Response Relationships and Risk Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Strom, Daniel J.

    2005-07-05

    The notion of a dose-response relationship was probably invented shortly after the discovery of poisons, the invention of alcoholic beverages, and the bringing of fire into a confined space in the forgotten depths of ancient prehistory. The amount of poison or medicine ingested can easily be observed to affect the behavior, health, or sickness outcome. Threshold effects, such as death, could be easily understood for intoxicants, medicine, and poisons. As Paracelsus (1493-1541), the 'father' of modern toxicology said, 'It is the dose that makes the poison.' Perhaps less obvious is the fact that implicit in such dose-response relationships is also the notion of dose rate. Usually, the dose is administered fairly acutely, in a single injection, pill, or swallow; a few puffs on a pipe; or a meal of eating or drinking. The same amount of intoxicants, medicine, or poisons administered over a week or month might have little or no observable effect. Thus, before the discovery of ionizing radiation in the late 19th century, toxicology ('the science of poisons') and pharmacology had deeply ingrained notions of dose-response relationships. This chapter demonstrates that the notion of a dose-response relationship for ionizing radiation is hopelessly simplistic from a scientific standpoint. While useful from a policy or regulatory standpoint, dose-response relationships cannot possibly convey enough information to describe the problem from a quantitative view of radiation biology, nor can they address societal values. Three sections of this chapter address the concepts, observations, and theories that contribute to the scientific input to the practice of managing risks from exposure to ionizing radiation. The presentation begins with irradiation regimes, followed by responses to high and low doses of ionizing radiation, and a discussion of how all of this can inform radiation risk management. The knowledge that is really needed for prediction of

  10. Vector optimization and monotone operators via convex duality recent advances

    CERN Document Server

    Grad, Sorin-Mihai

    2014-01-01

    This book investigates several duality approaches for vector optimization problems, while also comparing them. Special attention is paid to duality for linear vector optimization problems, for which a vector dual that avoids the shortcomings of the classical ones is proposed. Moreover, the book addresses different efficiency concepts for vector optimization problems. Among the problems that appear when the framework is generalized by considering set-valued functions, an increasing interest is generated by those involving monotone operators, especially now that new methods for approaching them by means of convex analysis have been developed. Following this path, the book provides several results on different properties of sums of monotone operators.

  11. Monotonic Allocation Schemes in Clan Games

    NARCIS (Netherlands)

    Voorneveld, M.; Tijs, S.H.; Grahn, S.

    2000-01-01

    Total clan games are characterized using monotonicity, veto power of the clan members, and a concavity condition reflecting the decreasing marginal contribution of non-clan members to growing coalitions.This decreasing marginal contribution is incorporated in the notion of a bi-monotonic allocation

  12. Monotone models for prediction in data mining

    NARCIS (Netherlands)

    Velikova, M.V.

    2006-01-01

    This dissertation studies the incorporation of monotonicity constraints as a type of domain knowledge into a data mining process. Monotonicity constraints are enforced at two stages¿data preparation and data modeling. The main contributions of the research are a novel procedure to test the degree of

  13. Monotonic Stable Solutions for Minimum Coloring Games

    NARCIS (Netherlands)

    Hamers, H.J.M.; Miquel, S.; Norde, H.W.

    2011-01-01

    For the class of minimum coloring games (introduced by Deng et al. (1999)) we investigate the existence of population monotonic allocation schemes (introduced by Sprumont (1990)). We show that a minimum coloring game on a graph G has a population monotonic allocation scheme if and only if G is (P4,

  14. Monotonicity-preserving linear multistep methods

    NARCIS (Netherlands)

    Hundsdorfer, W.; Ruuth, S.J.; Spiteri, R.J.

    2002-01-01

    In this paper we provide an analysis of monotonicity properties for linear multistep methods. These monotonicity properties include positivity and the diminishing of total variation. We also pay particular attention to related boundedness properties such as the total-variation-bounded (TVB) property

  15. Bayesian multimodel inference for dose-response studies

    Science.gov (United States)

    Link, W.A.; Albers, P.H.

    2007-01-01

    Statistical inference in dose?response studies is model-based: The analyst posits a mathematical model of the relation between exposure and response, estimates parameters of the model, and reports conclusions conditional on the model. Such analyses rarely include any accounting for the uncertainties associated with model selection. The Bayesian inferential system provides a convenient framework for model selection and multimodel inference. In this paper we briefly describe the Bayesian paradigm and Bayesian multimodel inference. We then present a family of models for multinomial dose?response data and apply Bayesian multimodel inferential methods to the analysis of data on the reproductive success of American kestrels (Falco sparveriuss) exposed to various sublethal dietary concentrations of methylmercury.

  16. Model Averaging Software for Dichotomous Dose Response Risk Estimation

    Directory of Open Access Journals (Sweden)

    Matthew W. Wheeler

    2008-02-01

    Full Text Available Model averaging has been shown to be a useful method for incorporating model uncertainty in quantitative risk estimation. In certain circumstances this technique is computationally complex, requiring sophisticated software to carry out the computation. We introduce software that implements model averaging for risk assessment based upon dichotomous dose-response data. This software, which we call Model Averaging for Dichotomous Response Benchmark Dose (MADr-BMD, fits the quantal response models, which are also used in the US Environmental Protection Agency benchmark dose software suite, and generates a model-averaged dose response model to generate benchmark dose and benchmark dose lower bound estimates. The software fulfills a need for risk assessors, allowing them to go beyond one single model in their risk assessments based on quantal data by focusing on a set of models that describes the experimental data.

  17. Optimal designs for dose response curves with common parameters

    OpenAIRE

    Feller, Chrystel; Schorning, Kirsten; Dette, Holger; Bermann, Georgina; Bornkamp, Björn

    2016-01-01

    A common problem in Phase II clinical trials is the comparison of dose response curves corresponding to different treatment groups. If the effect of the dose level is described by parametric regression models and the treatments differ in the administration frequency (but not in the sort of drug) a reasonable assumption is that the regression models for the different treatments share common parameters. This paper develops optimal design theory for the comparison of different regression models ...

  18. Analytical modelling of regional radiotherapy dose response of lung

    Science.gov (United States)

    Lee, Sangkyu; Stroian, Gabriela; Kopek, Neil; AlBahhar, Mahmood; Seuntjens, Jan; El Naqa, Issam

    2012-06-01

    Knowledge of the dose-response of radiation-induced lung disease (RILD) is necessary for optimization of radiotherapy (RT) treatment plans involving thoracic cavity irradiation. This study models the time-dependent relationship between local radiation dose and post-treatment lung tissue damage measured by computed tomography (CT) imaging. Fifty-eight follow-up diagnostic CT scans from 21 non-small-cell lung cancer patients were examined. The extent of RILD was segmented on the follow-up CT images based on the increase of physical density relative to the pre-treatment CT image. The segmented RILD was locally correlated with dose distribution calculated by analytical anisotropic algorithm and the Monte Carlo method to generate the corresponding dose-response curves. The Lyman-Kutcher-Burman (LKB) model was fit to the dose-response curves at six post-RT time periods, and temporal change in the LKB parameters was recorded. In this study, we observed significant correlation between the probability of lung tissue damage and the local dose for 96% of the follow-up studies. Dose-injury correlation at the first three months after RT was significantly different from later follow-up periods in terms of steepness and threshold dose as estimated from the LKB model. Dependence of dose response on superior-inferior tumour position was also observed. The time-dependent analytical modelling of RILD might provide better understanding of the long-term behaviour of the disease and could potentially be applied to improve inverse treatment planning optimization.

  19. Characterization of a developmental toxicity dose-response model.

    OpenAIRE

    Faustman, E M; Wellington, D G; Smith, W P; Kimmel, C A

    1989-01-01

    The Rai and Van Ryzin dose-response model proposed for teratology experiments has been characterized for its appropriateness and applicability in modeling the dichotomous response data from developmental toxicity studies. Modifications were made in the initial probability statements to reflect more accurately biological events underlying developmental toxicity. Data sets used for the evaluation were obtained from the National Toxicology Program and U.S. EPA laboratories. The studies included ...

  20. Linearity of dose-response relationships for human carcinogenic exposures

    Energy Technology Data Exchange (ETDEWEB)

    Smith, A.H. (Univ. of California, Berkeley (USA))

    The shape of dose-response relationships is a critical factor in considering cancer risks for the work place and environmental exposure to carcinogens. Markedly different risk estimates result from assumptions of linearity versus sublinear and threshold assumptions. This paper presents evidence that the relationship between the relative risk of development of cancer and the dose rate to carcinogenic exposures is frequently linear with no evidence for thresholds. Dose-response relationships from four studies of asbestos and lung cancer were examined, all of which were consistent with a linear relationship. Analysis of the relationship between the relative risk of lung cancer and exposure to nickel in a smelter study, selected because of relatively good exposure data, demonstrated a close agreement with a linear relationship. The relationship between the level of arsenic in drinking wter and the prevalence of skin cancer also was linear for males in the highest prevalence age group in Taiwan, although there was some evidence of sublinearity for females and younger persons. Also, the relationships between the number of cigarettes smoked per day and the relative risk of lung cancer was very close to linear in many studies. The analysis of these and other studies involving human exposure to carcinogens provides empirical evidence for linearity when the response variable is a rate ratio measure, rather than a risk difference measure. Linearity in dose-response is biologically plausible, without invoking a one-hit model. Except in special circumstances. the epidemiological evidence supports linear extrapolation of cancer relative risks.

  1. Biphasic dose response in low level light therapy - an update.

    Science.gov (United States)

    Huang, Ying-Ying; Sharma, Sulbha K; Carroll, James; Hamblin, Michael R

    2011-01-01

    Low-level laser (light) therapy (LLLT) has been known since 1967 but still remains controversial due to incomplete understanding of the basic mechanisms and the selection of inappropriate dosimetric parameters that led to negative studies. The biphasic dose-response or Arndt-Schulz curve in LLLT has been shown both in vitro studies and in animal experiments. This review will provide an update to our previous (Huang et al. 2009) coverage of this topic. In vitro mediators of LLLT such as adenosine triphosphate (ATP) and mitochondrial membrane potential show biphasic patterns, while others such as mitochondrial reactive oxygen species show a triphasic dose-response with two distinct peaks. The Janus nature of reactive oxygen species (ROS) that may act as a beneficial signaling molecule at low concentrations and a harmful cytotoxic agent at high concentrations, may partly explain the observed responses in vivo. Transcranial LLLT for traumatic brain injury (TBI) in mice shows a distinct biphasic pattern with peaks in beneficial neurological effects observed when the number of treatments is varied, and when the energy density of an individual treatment is varied. Further understanding of the extent to which biphasic dose responses apply in LLLT will be necessary to optimize clinical treatments.

  2. Monotone Semiflows Generated by Functional Differential Equations,

    Science.gov (United States)

    1986-02-01

    These results have been applied to ordinary differential equations in Rn (see e.g. [10,23]) where the well-known Kamke theorem applies and to nonlinear...sufficient condition (H) Whenever 0 - 0 and ,i(0) = i( 0) it follows that fi(0) ( fi(O). For those familiar with the Kamke (quasimonotone) condition for...ordinary differential equations, (H) will seem quite natural, it reduces to the Kamke condition. The order preserving property of a semiflow is not

  3. Approximations for Monotone and Non-monotone Submodular Maximization with Knapsack Constraints

    CERN Document Server

    Kulik, Ariel; Tamir, Tami

    2011-01-01

    Submodular maximization generalizes many fundamental problems in discrete optimization, including Max-Cut in directed/undirected graphs, maximum coverage, maximum facility location and marketing over social networks. In this paper we consider the problem of maximizing any submodular function subject to $d$ knapsack constraints, where $d$ is a fixed constant. We establish a strong relation between the discrete problem and its continuous relaxation, obtained through {\\em extension by expectation} of the submodular function. Formally, we show that, for any non-negative submodular function, an $\\alpha$-approximation algorithm for the continuous relaxation implies a randomized $(\\alpha - \\eps)$-approximation algorithm for the discrete problem. We use this relation to improve the best known approximation ratio for the problem to $1/4- \\eps$, for any $\\eps > 0$, and to obtain a nearly optimal $(1-e^{-1}-\\eps)-$approximation ratio for the monotone case, for any $\\eps>0$. We further show that the probabilistic domain ...

  4. The global convergence of the non-quasi-Newton methods with non-monotone line search

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The non-quasi-Newton methods for unconstrained optimization was investigated. Non-monotone line search procedure is introduced, which is combined with the non-quasi-Newton family. Under the uniform convexity assumption on objective function, the global convergence of the non-quasi-Newton family was proved.Numerical experiments showed that the non-monotone line search was more effective.

  5. Effects of temperature on monotonic and fatigue properties of carbon fibre epoxy cross ply laminates

    OpenAIRE

    Matsuhisa, Y.; King, J.

    1993-01-01

    The effects of test temperature on damage accumulation behaviour has been studied using "Torayca" T800H / #3631 in conditions of monotonic and fatigue loading. The damage accumulation behaviour was found to vary as a function of the test temperature, with the effect of temperature on the damage behaviour being different between monotonic and fatigue loading.

  6. Effects of temperature on monotonic and fatigue properties of carbon fibre epoxy cross ply laminates

    Energy Technology Data Exchange (ETDEWEB)

    Matsuhisa, Y. (Composite Materials Research Labs., Toray Industries Inc., Ehime (Japan)); King, J.E. (Composite Materials Research Labs., Toray Industries Inc., Ehime (Japan) Dept. of Materials Science and Metallurgy, Univ. of Cambridge (United Kingdom))

    1993-11-01

    The effects of test temperature on damage accumulation behaviour has been studied using ''Torayca'' T800H/[3631] in conditions of monotonic and fatigue loading. The damage accumulation behaviour was found to vary as a function of the test temperature, with the effect of temperature on the damage behaviour being different between monotonic and fatigue loading. (orig.).

  7. Dose-response investigation into glucose facilitation of memory performance and mood in healthy young adults.

    Science.gov (United States)

    Sünram-Lea, Sandra I; Owen, Lauren; Finnegan, Yvonne; Hu, Henglong

    2011-08-01

    It has been suggested that the memory enhancing effect of glucose follows an inverted U-shaped curve, with 25 g resulting in optimal facilitation in healthy young adults. The aim of this study was to further investigate the dose dependency of the glucose facilitation effect in this population across different memory domains and to assess moderation by interindividual differences in glucose regulation and weight. Following a double-blind, repeated measures design, 30 participants were administered drinks containing five different doses of glucose (0 g, 15 g, 25 g, 50 g, and 60 g) and were tested across a range of memory tasks. Glycaemic response and changes in mood state were assessed following drink administration. Analysis of the data showed that glucose administration did not affect mood, but significant glucose facilitation of several memory tasks was observed. However, dose-response curves differed depending on the memory task with only performance on the long-term memory tasks adhering largely to the previously observed inverted U-shaped dose-response curve. Moderation of the response profiles by interindividual differences in glucose regulation and weight was observed. The current data suggest that dose-response function and optimal dose might depend on cognitive domain and are moderated by interindividual differences in glucose regulation and weight.

  8. Viable harvest of monotone bioeconomic models

    CERN Document Server

    De Lara, Michel; Cabrera, Hector Ramirez

    2009-01-01

    Some monospecies age class models, as well as specific multi-species models (with so-called technical interactions), exhibit useful monotonicity properties. This paper deals with discrete time monotone bioeconomics dynamics in the presence of state and control constraints. In practice, these latter ``acceptable configurations'' represent production and preservation requirements to be satisfied for all time, and they also possess monotonicity properties. A state $\\state$ is said to belong to the viability kernel if there exists a trajectory, of states and controls, starting from $\\state$ and satisfying the constraints. Under monotonicity assumptions, we present upper and lower estimates of the viability kernel. This helps delineating domains where a viable management is possible. Numerical examples, in the context of fisheries management, for the Chilean sea bass (\\emph{Dissostichus eleginoides}) and Alfonsino (\\emph{Beryx splendens}) are given.

  9. Hyperbolic monotonicity in the Hilbert ball

    Directory of Open Access Journals (Sweden)

    Reich Simeon

    2006-01-01

    Full Text Available We first characterize -monotone mappings on the Hilbert ball by using their resolvents and then study the asymptotic behavior of compositions and convex combinations of these resolvents.

  10. Development of a dose-response model for SARS coronavirus.

    Science.gov (United States)

    Watanabe, Toru; Bartrand, Timothy A; Weir, Mark H; Omura, Tatsuo; Haas, Charles N

    2010-07-01

    In order to develop a dose-response model for SARS coronavirus (SARS-CoV), the pooled data sets for infection of transgenic mice susceptible to SARS-CoV and infection of mice with murine hepatitis virus strain 1, which may be a clinically relevant model of SARS, were fit to beta-Poisson and exponential models with the maximum likelihood method. The exponential model (k= 4.1 x l0(2)) could describe the dose-response relationship of the pooled data sets. The beta-Poisson model did not provide a statistically significant improvement in fit. With the exponential model, the infectivity of SARS-CoV was calculated and compared with those of other coronaviruses. The does of SARS-CoV corresponding to 10% and 50% responses (illness) were estimated at 43 and 280 PFU, respectively. Its estimated infectivity was comparable to that of HCoV-229E, known as an agent of human common cold, and also similar to those of some animal coronaviruses belonging to the same genetic group. Moreover, the exponential model was applied to the analysis of the epidemiological data of SARS outbreak that occurred at an apartment complex in Hong Kong in 2003. The estimated dose of SARS-CoV for apartment residents during the outbreak, which was back-calculated from the reported number of cases, ranged from 16 to 160 PFU/person, depending on the floor. The exponential model developed here is the sole dose-response model for SARS-CoV at the present and would enable us to understand the possibility for reemergence of SARS.

  11. Quantitative Dose-Response Curves from Subcellular Lipid Multilayer Microarrays

    Science.gov (United States)

    Kusi-Appiah, A. E.; Lowry, T. W.; Darrow, E. M.; Wilson, K.; Chadwick, B. P.; Davidson, M. W.; Lenhert, S.

    2015-01-01

    The dose-dependent bioactivity of small molecules on cells is a crucial factor in drug discovery and personalized medicine. Although small-molecule microarrays are a promising platform for miniaturized screening, it has been a challenge to use them to obtain quantitative dose-response curves in vitro, especially for lipophilic compounds. Here we establish a small-molecule microarray assay capable of controlling the dosage of small lipophilic molecules delivered to cells by varying the sub-cellular volumes of surface supported lipid micro- and nanostructure arrays fabricated with nanointaglio. Features with sub-cellular lateral dimensions were found necessary to obtain normal cell adhesion with HeLa cells. The volumes of the lipophilic drug-containing nanostructures were determined using a fluorescence microscope calibrated by atomic-force microscopy. We used the surface supported lipid volume information to obtain EC-50 values for the response of HeLa cells to three FDA-approved lipophilic anticancer drugs, docetaxel, imiquimod and triethylenemelamine, which were found to be significantly different from neat lipid controls. No significant toxicity was observed on the control cells surrounding the drug/lipid patterns, indicating lack of interference or leakage from the arrays. Comparison of the microarray data to dose-response curves for the same drugs delivered liposomally from solution revealed quantitative differences in the efficacy values, which we explain in terms of cell-adhesion playing a more important role in the surface-based assay. The assay should be scalable to a density of at least 10,000 dose response curves on the area of a standard microtiter plate. PMID:26167949

  12. INFLUENCE OF SUCCINYLCHOLINE ON THE DOSE-RESPONSE RELATIONSHIP OF SUBSEQUENTLY ADMINISTERED ROCURONIUN

    Institute of Scientific and Technical Information of China (English)

    陈锡明; 闻大翔; 杭燕南; 孙大金

    2005-01-01

    Objective To investigate the effect of succinylcholine on the dose-response relationship of subsequently administered rocuronium in healthy patients. Methods Forty-eight ASA physical status Ⅰ-Ⅱ patients,aged 17 -65 years, scheduled for elective general surgery, were randomly assigned to either the rocuronium treatment group (R) or succinylcholine-rocuronium treatment group (SR). General anesthesia was induced with thiopental 4 to 6mg/kg and fentanyl 2 to 5μg/kg intravenously and maintained with 60% nitrous oxide in oxygen. Additional doses of thiopental or fentanyl were administered as required. The dose-response relationship of rocuronium was determined by the single dose-response technique. In R group ( n =24) , rocuronium was given after induction of anesthesia. In SR group (n =24 ) , patients were intubated after 1.5mg/kg of succinylcholine and rocuronium was given after the complete recovery of neuromuscular blockade from succinylcholine. Patients were further randomly divided into 4 subgroups receiving 150, 200, 250 or 300μg/kg of rocuronium respectively in both groups. Neuromuscular function was assessed accelographically with train-of-four (TOF) stimulation at the wrist every 12s (using the TOF Guard(R) accelerometer). The relationship between probit-tranformed percentage depression of first twitch height (Th) of train-of-four stimulation and logarithm dose of rocuronium was analyzed using linear regression.Results The dose-response curve of rocuronium after succinylcholine was shifted to the left in a parallel fashion compared with that of rocuronium given alone. ED50 and ED95 of rocuronium were 193 ±69 and 367 ± 73μg/kg respectively in R group, and 158 ± 35 and 317 ± 80μg/kg respectively in SR group ( P < 0. 05 ). Conclusion Succinylcholine shifts the dose-response curve of rocuronium to the left and potentiates the effects of the neuromuscular blockade by about 15% of subsequently administered rocuronium. Lower doses of rocuronium are

  13. Fundamental investigations of natural and laboratory generated SAR dose response curves for quartz OSL in the high dose range

    DEFF Research Database (Denmark)

    Timar-Gabor, Alida; Constantin, Daniela; Buylaert, Jan-Pieter;

    2015-01-01

    SAR-OSL investigations on quartz from Romanian loess resulted in non concordant fine and coarse-grain ages for equivalent doses higher than ~100 Gy. The laboratory dose response for both grain sizes is well represented by a sum of two saturating exponential functions, fine and coarse grains chara...

  14. Nonparametric estimation for hazard rate monotonously decreasing system

    Institute of Scientific and Technical Information of China (English)

    Han Fengyan; Li Weisong

    2005-01-01

    Estimation of density and hazard rate is very important to the reliability analysis of a system. In order to estimate the density and hazard rate of a hazard rate monotonously decreasing system, a new nonparametric estimator is put forward. The estimator is based on the kernel function method and optimum algorithm. Numerical experiment shows that the method is accurate enough and can be used in many cases.

  15. SU-E-J-51: Dose Response of Common Solid State Detectors in Homogeneous Transverse and Longitudinal Magnetic Fields

    Energy Technology Data Exchange (ETDEWEB)

    Reynolds, M; Fallone, B; Rathee, S [Cross Cancer Institute, Edmonton, AB (Canada)

    2014-06-01

    Purpose: Solid state radiation detectors are often used for dose profiles and percent depth dose measurements. The dose response of selected solid state detectors is evaluated in varying transverse and longitudinal magnetic fields for eventual use in MR-Linac devices. Methods: A PTW 60003 and IBA PFD detector were modeled in the Monte Carlo code PENELOPE, incorporating a magnetic field which was varied in strength and oriented both transversely and longitudinally with respect to the incident photon beam. The detectors' long axis was in turn oriented either parallel or perpendicular to the photon beam. Dose to the active volume of each detector was scored, and its ratio to dose with zero magnetic field strength (dose response) was determined. Accuracy of the simulations was evaluated by measurements using both chambers taken at low field with a small electromagnet. Simulations were also performed in a water phantom to compare to the in air results. Results: Significant dose response was found in transverse field geometries, nearing 20% at 1.5T. The response is highly dependent on relative orientations to the magnetic field and photon beam, and on detector composition. Low field measurements confirm these results. In the presence of longitudinal magnetic fields, the detectors exhibit little dose response, reaching 0.5–1% at 1.5T regardless of detector orientation. Water tank simulations compared well to the in air simulations when not at the beam periphery, where in transverse magnetic fields only, the water tank simulations differed from the in air results. Conclusion: Transverse magnetic fields can cause large deviations in dose response, and are highly position orientation dependent. Comparatively, longitudinal magnetic fields exhibit little to no dose response in each detector as a function of magnetic field strength. Water tank simulations show longitudinal fields are generally easier to work with, but each detector must be evaluated separately.

  16. Modeling and regression analysis of semiochemical dose-response curves of insect antennal reception and behavior.

    Science.gov (United States)

    Byers, John A

    2013-08-01

    Dose-response curves of the effects of semiochemicals on neurophysiology and behavior are reported in many articles in insect chemical ecology. Most curves are shown in figures representing points connected by straight lines, in which the x-axis has order of magnitude increases in dosage vs. responses on the y-axis. The lack of regression curves indicates that the nature of the dose-response relationship is not well understood. Thus, a computer model was developed to simulate a flux of various numbers of pheromone molecules (10(3) to 5 × 10(6)) passing by 10(4) receptors distributed among 10(6) positions along an insect antenna. Each receptor was depolarized by at least one strike by a molecule, and subsequent strikes had no additional effect. The simulations showed that with an increase in pheromone release rate, the antennal response would increase in a convex fashion and not in a logarithmic relation as suggested previously. Non-linear regression showed that a family of kinetic formation functions fit the simulated data nearly perfectly (R(2) >0.999). This is reasonable because olfactory receptors have proteins that bind to the pheromone molecule and are expected to exhibit enzyme kinetics. Over 90 dose-response relationships reported in the literature of electroantennographic and behavioral bioassays in the laboratory and field were analyzed by the logarithmic and kinetic formation functions. This analysis showed that in 95% of the cases, the kinetic functions explained the relationships better than the logarithmic (mean of about 20% better). The kinetic curves become sigmoid when graphed on a log scale on the x-axis. Dose-catch relationships in the field are similar to dose-EAR (effective attraction radius, in which a spherical radius indicates the trapping effect of a lure) and the circular EARc in two dimensions used in mass trapping models. The use of kinetic formation functions for dose-response curves of attractants, and kinetic decay curves for

  17. Environmental standards for ionizing radiation: theoretical basis for dose-response curves.

    Science.gov (United States)

    Upton, A C

    1983-10-01

    The types of injury attributable to ionizing radiation are subdivided, for purposes of risk assessment and radiological protection, into two broad categories: stochastic effects and nonstochastic effects. Stochastic effects are viewed as probablistic phenomena, varying in frequency but not severity as a function of the dose, without any threshold; nonstochastic effects are viewed as deterministic phenomena, varying in both frequency and severity as a function of the dose, with clinical thresholds. Included among stochastic effects are heritable effects (mutations and chromosome aberrations) and carcinogenic effects. Both types of effects are envisioned as unicellular phenomena which can result from nonlethal injury of individual cells, without the necessity of damage to other cells. For the induction of mutations and chromosome aberrations in the low-to-intermediate dose range, the dose-response curve with high-linear energy transfer (LET) radiation generally conforms to a linear nonthreshold relationship and varies relatively little with the dose rate. In contrast, the curve with low-LET radiation generally conforms to a linear-quadratic relationship, rising less steeply than the curve with high-LET radiation and increasing in slope with increasing dose and dose rate. The dose-response curve for carcinogenic effects varies widely from one type of neoplasm to another in the intermediate-to-high dose range, in part because of differences in the way large doses of radiation can affect the promotion and progression of different neoplasms. Information about dose-response relations for low-level irradiation is fragmentary but consistent, in general, with the hypothesis that the neoplastic transformation may result from mutation, chromosome aberration or genetic recombination in a single susceptible cell.

  18. The dose-response relationship for cardiovascular disease is not necessarily linear.

    Science.gov (United States)

    Schneider, Uwe; Ernst, Marina; Hartmann, Matthias

    2017-04-27

    The probability for a complication after radiotherapy is usually a function of dose and volume in the organ or tissue of interest. In most epidemiological studies the risk for a complication is stratified in terms of dose, but not irradiated volume. We show that the obtained risk cannot generally be applied to radiotherapy patients.The epidemiological data of Darby et al. (N Engl J Med 368:2527, 2013) who found a linear relationship between the excess relative risk of major coronary events as function of mean heart dose in patients treated with tangential breast irradiation are analyzed. We have used the relative seriality model for a partly irradiated heart ("a lot to a little") which models radiation therapy using two tangential fields. The relative seriality model was then used to predict NTCP of cardiovascular disease for a homogenously irradiated heart ("a little to a lot"). The relative seriality model was fitted to the data of Darby et al. (N Engl J Med 368:2527, 2013) for tangential breast irradiation. For the situation "a little to a lot" it was found that the dose-response relationship is sigmoidal and contradicts the findings of Darby et al. (N Engl J Med 368:2527, 2013). It was shown in this work that epidemiological studies which predict a linear dose-response relationship for cardiovascular disease can be reproduced by bio-physical models for normal tissue complication. For irradiation situations which were not included in the epidemiological studies, e.g. a homogenous irradiation of the heart ("a little to a lot") the dose-response curve can be different. This could have consequences whether or not IMRT should be used for treating breast cancer. We believe that the results of epidemiological studies should not be generally used to predict normal tissue complications. It is better to use such data to optimize bio-physical models which can then be applied (with caution) to general treatment situations.

  19. The monotonic and fatigue behavior of CFCCs

    Energy Technology Data Exchange (ETDEWEB)

    Miriyala, N.; Liaw, P.K.; McHargue, C.J. [Univ. of Tennessee, Knoxville, TN (United States); Snead, L.L. [Oak Ridge National Laboratory, TN (United States)

    1996-04-01

    Flexure tests were performed to study the fabric orientation effects on the monotonic and fatigue behavior of two commercially available continuous fiber reinforced ceramic composites (CFCCs), namely (i) Nicalon fiber fabric reinforced alumina (Al{sub 2}O{sub 3}) matrix composite fabricated by a direct molten metal oxidation (DIMOX) process and, (ii) Nicalon fiber fabric reinforced silicon carbide (SiC) matrix composite fabricated by an isothermal chemical vapor infiltration (ICVI) process. The fabric orientation effects on the monotonic and fatigue behavior were strong in the Nicalon/Al{sub 2}O{sub 3} composite, while they were relatively weak in the Nicalon/SiC composite.

  20. Monotonicity in the Sample Size of the Length of Classical Confidence Intervals

    CERN Document Server

    Kagan, Abram M

    2012-01-01

    It is proved that the average length of standard confidence intervals for parameters of gamma and normal distributions monotonically decrease with the sample size. The proofs are based on fine properties of the classical gamma function.

  1. Alcohol and cirrhosis: dose--response or threshold effect?

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Grønbaek, Morten; Tolstrup, Janne;

    2004-01-01

    BACKGROUND/AIMS: General population studies have shown a strong association between alcohol intake and death from alcoholic cirrhosis, but whether this is a dose-response or a threshold effect remains unknown, and the relation among alcohol misusers has not been studied. METHODS: A cohort of 6152...... alcohol misusing men and women aged 15-83 were interviewed about drinking pattern and social issues and followed for 84,257 person-years. Outcome was alcoholic cirrhosis mortality. Data was analyzed by means of Cox-regression models. RESULTS: In this large prospective cohort study of alcohol misusers...... there was a 27 fold increased mortality from alcoholic cirrhosis in men and a 35 fold increased mortality from alcoholic cirrhosis in women compared to the Danish population. Number of drinks per day was not significantly associated with death from alcoholic cirrhosis, since there was no additional risk of death...

  2. Dose Response of Alanine Detectors Irradiated with Carbon Ion Beams

    DEFF Research Database (Denmark)

    Herrmann, Rochus; Jäkel, Oliver; Palmans, Hugo

    2011-01-01

    Purpose: The dose response of the alanine detector shows a dependence on particle energy and type, when irradiated with ion beams. The purpose of this study is to investigate the response behaviour of the alanine detector in clinical carbon ion beams and compare the results with model predictions....... Methods: Alanine detectors have been irradiated with carbon ions with an energy range of 89-400 MeV/u. The relative effectiveness of alanine has been measured in this regime. Pristine and spread out Bragg peak depth-dose curves have been measured with alanine dosimeters. The track-structure based alanine......-dose curves deviate from predictions in the peak region, most pronounced at the distal edge of the peak. Conclusions: The used model and its implementation show a good overall agreement for quasi mono energetic measurements. Deviations in depth-dose measurements are mainly attributed to uncertainties...

  3. Dose-response curve estimation: a semiparametric mixture approach.

    Science.gov (United States)

    Yuan, Ying; Yin, Guosheng

    2011-12-01

    In the estimation of a dose-response curve, parametric models are straightforward and efficient but subject to model misspecifications; nonparametric methods are robust but less efficient. As a compromise, we propose a semiparametric approach that combines the advantages of parametric and nonparametric curve estimates. In a mixture form, our estimator takes a weighted average of the parametric and nonparametric curve estimates, in which a higher weight is assigned to the estimate with a better model fit. When the parametric model assumption holds, the semiparametric curve estimate converges to the parametric estimate and thus achieves high efficiency; when the parametric model is misspecified, the semiparametric estimate converges to the nonparametric estimate and remains consistent. We also consider an adaptive weighting scheme to allow the weight to vary according to the local fit of the models. We conduct extensive simulation studies to investigate the performance of the proposed methods and illustrate them with two real examples.

  4. Non-monotonic effect of confinement on the glass transition

    Science.gov (United States)

    Varnik, Fathollah; Franosch, Thomas

    2016-04-01

    The relaxation dynamics of glass forming liquids and their structure are influenced in the vicinity of confining walls. This effect has mostly been observed to be a monotonic function of the slit width. Recently, a qualitatively new behaviour has been uncovered by Mittal and coworkers, who reported that the single particle dynamics in a hard-sphere fluid confined in a planar slit varies in a non-monotonic way as the slit width is decreased from five to roughly two particle diametres (Mittal et al 2008 Phys. Rev. Lett. 100 145901). In view of the great potential of this effect for applications in those fields of science and industry, where liquids occur under strong confinement (e.g. nano-technology), the number of researchers studying various aspects and consequences of this non-monotonic behaviour has been rapidly growing. This review aims at providing an overview of the research activity in this newly emerging field. We first briefly discuss how competing mechanisms such as packing effects and short-range attraction may lead to a non-monotonic glass transition scenario in the bulk. We then analyse confinement effects on the dynamics of fluids using a thermodynamic route which relates the single particle dynamics to the excess entropy. Moreover, relating the diffusive dynamics to the Widom’s insertion probability, the oscillations of the local dynamics with density at moderate densities are fairly well described. At high densities belonging to the supercooled regime, however, this approach breaks down signaling the onset of strongly collective effects. Indeed, confinement introduces a new length scale which in the limit of high densities and small pore sizes competes with the short-range local order of the fluid. This gives rise to a non-monotonic dependence of the packing structure on confinement, with a corresponding effect on the dynamics of structural relaxation. This non-monotonic effect occurs also in the case of a cone-plate type channel, where the degree

  5. Dose-response curve of a microfluidic magnetic bead-based surface coverage sandwich assay.

    Science.gov (United States)

    Cornaglia, Matteo; Trouillon, Raphaël; Tekin, H Cumhur; Lehnert, Thomas; Gijs, Martin A M

    2015-09-25

    Magnetic micro- and nanoparticles ('magnetic beads') have been used to advantage in many microfluidic devices for sensitive antigen (Ag) detection. Today, assays that use as read-out of the signal the number count of immobilized beads on a surface for quantification of a sample's analyte concentration have been among the most sensitive and have allowed protein detection lower than the fgmL(-1) concentration range. Recently, we have proposed in this category a magnetic bead surface coverage assay (Tekin et al., 2013 [1]), in which 'large' (2.8μm) antibody (Ab)-functionalized magnetic beads captured their Ag from a serum and these Ag-carrying beads were subsequently exposed to a surface pattern of fixed 'small' (1.0μm) Ab-coated magnetic beads. When the system was exposed to a magnetic induction field, the magnet dipole attractive interactions between the two bead types were used as a handle to approach both bead surfaces and assist with Ag-Ab immunocomplex formation, while unspecific binding (in absence of an Ag) of a large bead was reduced by exploiting viscous drag flow. The dose-response curve of this type of assay had two remarkable features: (i) its ability to detect an output signal (i.e. bead number count) for very low Ag concentrations, and (ii) an output signal of the assay that was non-linear with respect to Ag concentration. We explain here the observed dose-response curves and show that the type of interactions and the concept of our assay are in favour of detecting the lowest analyte concentrations (where typically either zero or one Ag is carried per large bead), while higher concentrations are less efficiently detected. We propose a random walk process for the Ag-carrying bead over the magnetic landscape of small beads and this model description explains the enhanced overall capture probability of this assay and its particular non-linear dose response curves.

  6. Monotone Comparative Statics for the Industry Composition

    DEFF Research Database (Denmark)

    Laugesen, Anders Rosenstand

    2015-01-01

    We let heterogeneous firms face decisions on a number of complementary activities in a monopolistically-competitive industry. The endogenous level of competition and selection regarding entry and exit of firms introduces a wedge between monotone comparative statics (MCS) at the firm level and MCS...

  7. On a Monotone Ill-posed Problem

    Institute of Scientific and Technical Information of China (English)

    Nguyen BUONG

    2005-01-01

    A class of a posteriori parameter choice strategies for the operator version of Tikhonovregularization (including variants of Morozov's and Arcangeli's methods) is proposed and used in investigating the rate of convergence of the regularized solution for ill-posed nonlinear equation involving a monotone operator in Banach space.

  8. Population Monotonic Path Schemes for Simple Games

    NARCIS (Netherlands)

    Ciftci, B.B.; Borm, P.E.M.; Hamers, H.J.M.

    2006-01-01

    A path scheme for a simple game is composed of a path, i.e., a sequence of coalitions that is formed during the coalition formation process and a scheme, i.e., a payoff vector for each coalition in the path.A path scheme is called population monotonic if a player's payoff does not decrease as the pa

  9. Monotone method for nonlinear nonlocal hyperbolic problems

    Directory of Open Access Journals (Sweden)

    Azmy S. Ackleh

    2003-02-01

    Full Text Available We present recent results concerning the application of the monotone method for studying existence and uniqueness of solutions to general first-order nonlinear nonlocal hyperbolic problems. The limitations of comparison principles for such nonlocal problems are discussed. To overcome these limitations, we introduce new definitions for upper and lower solutions.

  10. Limit points of the monotonic schemes

    CERN Document Server

    Salomon, J

    2005-01-01

    Many numerical simulations in quantum (bilinear) control use the monotonically convergent algorithms of Krotov (introduced by Tannor), Zhu & Rabitz or the general form of Maday & Turinici. This paper presents an analysis of the limit set of controls provided by these algorithms and a proof of convergence in a particular case.

  11. REGULAR RELATIONS AND MONOTONE NORMAL ORDERED SPACES

    Institute of Scientific and Technical Information of China (English)

    XU XIAOQUAN; LIU YINGMING

    2004-01-01

    In this paper the classical theorem of Zareckii about regular relations is generalized and an intrinsic characterization of regularity is obtained. Based on the generalized Zareckii theorem and the intrinsic characterization of regularity, the authors give a characterization of monotone normality of ordered spaces. A new proof of the UrysohnNachbin lemma is presented which is quite different from the classical one.

  12. Strong monotonicity for analytic ordinary differential equations

    Directory of Open Access Journals (Sweden)

    Sebastian Walcher

    2009-09-01

    Full Text Available We present a necessary and sufficient criterion for the flow of an analytic ordinary differential equation to be strongly monotone; equivalently, strongly order-preserving. The criterion is given in terms of the reducibility set of the derivative of the right-hand side. Some applications to systems relevant in biology and ecology, including nonlinear compartmental systems, are discussed.

  13. A monotonic archive for pareto-coevolution.

    Science.gov (United States)

    de Jong, Edwin D

    2007-01-01

    Coevolution has already produced promising results, but its dynamic evaluation can lead to a variety of problems that prevent most algorithms from progressing monotonically. An important open question therefore is how progress towards a chosen solution concept can be achieved. A general solution concept for coevolution is obtained by viewing opponents or tests as objectives. In this setup known as Pareto-coevolution, the desired solution is the Pareto-optimal set. We present an archive that guarantees monotonicity for this solution concept. The algorithm is called the Incremental Pareto-Coevolution Archive (IPCA), and is based on Evolutionary Multi-Objective Optimization (EMOO). By virtue of its monotonicity, IPCA avoids regress even when combined with a highly explorative generator. This capacity is demonstrated on a challenging test problem requiring both exploration and reliability. IPCA maintains a highly specific selection of tests, but the size of the test archive nonetheless grows unboundedly. We therefore furthermore investigate how archive sizes may be limited while still providing approximate reliability. The LAyered Pareto-Coevolution Archive (LAPCA) maintains a limited number of layers of candidate solutions and tests, and thereby permits a trade-off between archive size and reliability. The algorithm is compared in experiments, and found to be more efficient than IPCA. The work demonstrates how the approximation of a monotonic algorithm can lead to algorithms that are sufficiently reliable in practice while offering better efficiency.

  14. Concerns on Monotonic Imbalance Bounding Matching Methods

    OpenAIRE

    Yatracos, Yannis G.

    2013-01-01

    Concerns are expressed for the Monotonic Imbalance Bounding (MIB) property (Iacus et al. 2011) and for MIB matching because i) the definition of the MIB property leads to inconsistencies and the nature of the imbalance measure is not clearly defined, ii) MIB property does not generalize Equal Percent Bias Reducing (EPBR) property, iii) MIB matching does not provide statistical information available with EPBR matching.

  15. Edit Distance to Monotonicity in Sliding Windows

    DEFF Research Database (Denmark)

    Chan, Ho-Leung; Lam, Tak-Wah; Lee, Lap Kei

    2011-01-01

    of a data stream is becoming well-understood over the past few years. Motivated by applications on network quality monitoring, we extend the study to estimating the edit distance to monotonicity of a sliding window covering the w most recent items in the stream for any w ≥ 1. We give a deterministic...

  16. New concurrent iterative methods with monotonic convergence

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Qingchuan [Michigan State Univ., East Lansing, MI (United States)

    1996-12-31

    This paper proposes the new concurrent iterative methods without using any derivatives for finding all zeros of polynomials simultaneously. The new methods are of monotonic convergence for both simple and multiple real-zeros of polynomials and are quadratically convergent. The corresponding accelerated concurrent iterative methods are obtained too. The new methods are good candidates for the application in solving symmetric eigenproblems.

  17. Classification Trees for Problems with Monotonicity Constraints

    NARCIS (Netherlands)

    R. Potharst (Rob); A.J. Feelders

    2002-01-01

    textabstractFor classification problems with ordinal attributes very often the class attribute should increase with each or some of the explaining attributes. These are called classification problems with monotonicity constraints. Classical decision tree algorithms such as CART or C4.5 generally do

  18. Investigating quartz optically stimulated luminescence dose-response curves at high doses

    Energy Technology Data Exchange (ETDEWEB)

    Lowick, Sally E., E-mail: lowick@geo.unibe.c [Institut fuer Geologie, Universitaet Bern, Baltzerstrasse 1-3, 3012 Bern (Switzerland); Preusser, Frank [Institut fuer Geologie, Universitaet Bern, Baltzerstrasse 1-3, 3012 Bern (Switzerland); Wintle, Ann G. [Institute of Geography and Earth Sciences, Aberystwyth University, AberystwythSY23 3DB (United Kingdom)

    2010-10-15

    Despite the general expectation that optically stimulated luminescence (OSL) growth should be described by a simple saturating exponential function, an additional high dose component is often reported in the dose response of quartz. Although often reported as linear, it appears that this response is the early expression of a second saturating exponential. While some studies using equivalent doses that fall in this high dose region have produced ages that correlate well with independent dating, others report that it results in unreliable age determinations. Two fine grain sedimentary quartz samples that display such a response were used to investigate the origin of this additional high dose component: three experiments were conducted to examine their dose-response up to >1000 Gy. The high dose rates provided by laboratory irradiation were found not to induce a sensitivity change in the response to a subsequent test dose, with the latter not being significantly different from those generated following naturally acquired doses. The relative percentage contributions of the fast and medium OSL components remained fixed throughout the dose-response curve, suggesting that the electron traps that give rise to the initial OSL do not change with dose. An attempt was made to investigate a change in luminescence centre recombination probability by monitoring the depletion of the '325 {sup o}C' thermoluminescence (TL) during the optical stimulation that would result in depletion of the OSL signal. The emissions measured through both the conventional ultraviolet (UV), and a longer wavelength violet/blue (VB) window, displayed similar relative growth with dose, although it was not possible to resolve the origin of the VB emissions. No evidence was found to indicate whether the additional component at high doses occurs naturally or is a product of laboratory treatment. However, it appears that these samples display an increased sensitivity of quartz OSL to high doses

  19. Stability of generalized monotonicity with respect to their characterizations

    CERN Document Server

    An, P T

    2002-01-01

    We show that known types of generalized monotone maps are not stable with respect to their characterizations (i.e., the characterizations are not maintained during an arbitrary map of this type is disturbed by an element with sufficiently small norm) then introduce s-quasimonotone maps, which are stable with respect to their characterization. For gradient maps, s-quasimonotonicity is related to s-quasiconvexity of the underlying function. A necessary and sufficient condition for a univariate polynomial to be s-quasimonotone is given. Furthermore, some stability properties of a-quasiconvex functions are presented.

  20. Cancer risk assessment: Optimizing human health through linear dose-response models.

    Science.gov (United States)

    Calabrese, Edward J; Shamoun, Dima Yazji; Hanekamp, Jaap C

    2015-07-01

    This paper proposes that generic cancer risk assessments be based on the integration of the Linear Non-Threshold (LNT) and hormetic dose-responses since optimal hormetic beneficial responses are estimated to occur at the dose associated with a 10(-4) risk level based on the use of a LNT model as applied to animal cancer studies. The adoption of the 10(-4) risk estimate provides a theoretical and practical integration of two competing risk assessment models whose predictions cannot be validated in human population studies or with standard chronic animal bioassay data. This model-integration reveals both substantial protection of the population from cancer effects (i.e. functional utility of the LNT model) while offering the possibility of significant reductions in cancer incidence should the hormetic dose-response model predictions be correct. The dose yielding the 10(-4) cancer risk therefore yields the optimized toxicologically based "regulatory sweet spot". Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. On the rate of convergence of the maximum likelihood estimator of a k-monotone density

    Institute of Scientific and Technical Information of China (English)

    WELLNER; Jon; A

    2009-01-01

    Bounds for the bracketing entropy of the classes of bounded k-monotone functions on [0,A] are obtained under both the Hellinger distance and the Lp(Q) distance,where 1 p < ∞ and Q is a probability measure on [0,A].The result is then applied to obtain the rate of convergence of the maximum likelihood estimator of a k-monotone density.

  2. On the rate of convergence of the maximum likelihood estimator of a K-monotone density

    Institute of Scientific and Technical Information of China (English)

    GAO FuChang; WELLNER Jon A

    2009-01-01

    Bounds for the bracketing entropy of the classes of bounded K-monotone functions on [0, A] are obtained under both the Hellinger distance and the LP(Q) distance, where 1 ≤ p < ∞ and Q is a probability measure on [0, A]. The result is then applied to obtain the rate of convergence of the maximum likelihood estimator of a K-monotone density.

  3. Complexity of Non-Monotonic Logics

    CERN Document Server

    Thomas, Michael

    2010-01-01

    Over the past few decades, non-monotonic reasoning has developed to be one of the most important topics in computational logic and artificial intelligence. Different ways to introduce non-monotonic aspects to classical logic have been considered, e.g., extension with default rules, extension with modal belief operators, or modification of the semantics. In this survey we consider a logical formalism from each of the above possibilities, namely Reiter's default logic, Moore's autoepistemic logic and McCarthy's circumscription. Additionally, we consider abduction, where one is not interested in inferences from a given knowledge base but in computing possible explanations for an observation with respect to a given knowledge base. Complexity results for different reasoning tasks for propositional variants of these logics have been studied already in the nineties. In recent years, however, a renewed interest in complexity issues can be observed. One current focal approach is to consider parameterized problems and ...

  4. Linear Inviscid Damping for Monotone Shear Flows

    CERN Document Server

    Zillinger, Christian

    2014-01-01

    In this article we prove linear stability, inviscid damping and scattering of the 2D Euler equations around regular, strictly monotone shear flows $(U(y),0)$ in a periodic channel under Sobolev perturbations. We treat the settings of an infinite channel, $\\mathbb{T} \\times \\mathbb{R}$, as well as a finite channel, $\\mathbb{T} \\times [0,1]$, with impermeable boundary. We first prove inviscid damping with optimal algebraic rates for strictly monotone shear flows under the assumption of controlling the regularity of the scattered vorticity. Subsequently, we establish linear stability of the scattering equation in Sobolev spaces under perturbations which are of not too large wave-length with respect to $x$, depending on $U''$.

  5. SynergyFinder: a web application for analyzing drug combination dose-response matrix data.

    Science.gov (United States)

    Ianevski, Aleksandr; He, Liye; Aittokallio, Tero; Tang, Jing

    2017-08-01

    Rational design of drug combinations has become a promising strategy to tackle the drug sensitivity and resistance problem in cancer treatment. To systematically evaluate the pre-clinical significance of pairwise drug combinations, functional screening assays that probe combination effects in a dose-response matrix assay are commonly used. To facilitate the analysis of such drug combination experiments, we implemented a web application that uses key functions of R-package SynergyFinder, and provides not only the flexibility of using multiple synergy scoring models, but also a user-friendly interface for visualizing the drug combination landscapes in an interactive manner. The SynergyFinder web application is freely accessible at https://synergyfinder.fimm.fi ; The R-package and its source-code are freely available at http://bioconductor.org/packages/release/bioc/html/synergyfinder.html . jing.tang@helsinki.fi.

  6. Improved selection in totally monotone arrays

    Energy Technology Data Exchange (ETDEWEB)

    Mansour, Y. (Harvard Univ., Cambridge, MA (United States). Aiken Computation Lab.); Park, J.K. (Sandia National Labs., Albuquerque, NM (United States)); Schieber, B. (International Business Machines Corp., Yorktown Heights, NY (United States). Thomas J. Watson Research Center); Sen, S. (AT and T Bell Labs., Murray Hill, NJ (United States))

    1991-01-01

    This paper's main result is an O(({radical}{bar m}lgm)(n lg n) + mlg n)-time algorithm for computing the kth smallest entry in each row of an m {times} n totally monotone array. (A two-dimensional A = a(i,j) is totally monotone if for all i{sub 1} < i{sub 2} and j{sub 1} < j{sup 2}, < a(i{sub 1},j{sub 2}) implies a(i{sub 2},j{sub 1})). For large values of k (in particular, for k=(n/2)), this algorithm is significantly faster than the O(k(m+n))-time algorithm for the same problem due to Kravets and Park. An immediate consequence of this result is an O(n{sup 3/2} lg{sup 2}n)-time algorithm for computing the kth nearest neighbor of each vertex of a convex n-gon. In addition to the main result, we also give an O(n lg m)-time algorithm for computing an approximate median in each row of an m {times} n totally monotone array; this approximate median is an entry whose rank in its row lies between (n/4) and (3n/4) {minus} 1. 20 refs., 3 figs.

  7. Edit Distance to Monotonicity in Sliding Windows

    CERN Document Server

    Chan, Ho-Leung; Lee, Lap-Kei; Pan, Jiangwei; Ting, Hing-Fung; Zhang, Qin

    2011-01-01

    Given a stream of items each associated with a numerical value, its edit distance to monotonicity is the minimum number of items to remove so that the remaining items are non-decreasing with respect to the numerical value. The space complexity of estimating the edit distance to monotonicity of a data stream is becoming well-understood over the past few years. Motivated by applications on network quality monitoring, we extend the study to estimating the edit distance to monotonicity of a sliding window covering the $w$ most recent items in the stream for any $w \\ge 1$. We give a deterministic algorithm which can return an estimate within a factor of $(4+\\eps)$ using $O(\\frac{1}{\\eps^2} \\log^2(\\eps w))$ space. We also extend the study in two directions. First, we consider a stream where each item is associated with a value from a partial ordered set. We give a randomized $(4+\\epsilon)$-approximate algorithm using $O(\\frac{1}{\\epsilon^2} \\log \\epsilon^2 w \\log w)$ space. Second, we consider an out-of-order strea...

  8. A Grid Algorithm for High Throughput Fitting of Dose-Response Curve Data

    OpenAIRE

    Wang, Yuhong; Jadhav, Ajit; Southal, Noel; Huang, Ruili; Nguyen, Dac-Trung

    2010-01-01

    We describe a novel algorithm, Grid algorithm, and the corresponding computer program for high throughput fitting of dose-response curves that are described by the four-parameter symmetric logistic dose-response model. The Grid algorithm searches through all points in a grid of four dimensions (parameters) and finds the optimum one that corresponds to the best fit. Using simulated dose-response curves, we examined the Grid program’s performance in reproducing the actual values that were used ...

  9. Chronic periodontitis and smoking Prevalence and dose-response relationship

    Science.gov (United States)

    Khan, Shahrukh; Khalid, Taimur; Awan, Kamran H.

    2016-01-01

    Objectives: To determine the prevalence and dose-response relationship of chronic periodontitis among smokers in Pakistan. Methods: This is a cross-sectional study among participants seeking dental care in Karachi Medical and Dental College, Karachi, Pakistan. A total of 443 participants with a mean age of 44.3 (±6.5) participated in the study from April 2011 to December 2011. Males comprised 64.7%, and females comprised 35.2%. Participants were interviewed on social demographics and oral habits. Participants with shallow pockets (3.5-5.5 mm) and deep pockets (>5.5 mm) were considered suffering from chronic periodontitis. The characteristics of participants were assessed using frequency distribution for categorical variables and mean (standard deviation) for continuous variables. Results: Among 443 participants, smokers were distributed as 55.1% and non-smokers as 44.9%. Smoking was found to be significantly related to young adults (p<0.007), male gender (p<0.001), and lower education level (p<0.01). Overall prevalence of chronic periodontitis among smokers was estimated at 81.6%. Heavy smoking was found to have significantly high prevalence (p<0.001) and severity (p<0.001) of periodontitis as compared with moderate and light smokers. The multivariate unadjusted model depicted 3.5 times higher risk of chronic periodontitis among smokers (p<0.001). Conclusion: Chronic periodontitis had a high prevalence among smokers. Heavy smoking was found to have a higher risk for having periodontitis. PMID:27464867

  10. Weak monotonicity inequality and partial regularity for harmonic maps

    Institute of Scientific and Technical Information of China (English)

    沈尧天; 严树森

    1999-01-01

    The notion of locally weak monotonicity inequality for weakly harmonic maps is introduced and various results on this class of maps are obtained. For example, the locally weak monotonicity inequality is nearly equivalent to the ε-regularity.

  11. Monotonic Loading of Circular Surface Footings on Clay

    DEFF Research Database (Denmark)

    Ibsen, Lars Bo; Barari, Amin

    2011-01-01

    Appropriate modeling of offshore foundations under monotonic loading is a significant challenge in geotechnical engineering. This paper reports experimental and numerical analyses, specifically investigating the response of circular surface footings during monotonic loading and elastoplastic beha...

  12. Monotonicity Formula and Regularity for General Free Discontinuity Problems

    Science.gov (United States)

    Bucur, Dorin; Luckhaus, Stephan

    2014-02-01

    We give a general monotonicity formula for local minimizers of free discontinuity problems which have a critical deviation from minimality, of order d - 1. This result allows us to prove partial regularity results (that is closure and density estimates for the jump set) for a large class of free discontinuity problems involving general energies associated to the jump set, as for example free boundary problems with Robin conditions. In particular, we give a short proof to the De Giorgi-Carriero-Leaci result for the Mumford-Shah functional.

  13. [Occlusion treatment for amblyopia. Age dependence and dose-response relationship].

    Science.gov (United States)

    Fronius, M

    2016-04-01

    Based on clinical experience and studies on animal models the age of 6-7 years was regarded as the limit for treatment of amblyopia, although functional improvement was also occasionally reported in older patients. New technical developments as well as insights from clinical studies and the neurosciences have attracted considerable attention to this topic. Various aspects of the age dependence of amblyopia treatment are discussed in this article, e. g. prescription, electronic monitoring of occlusion dosage, calculation of indicators for age-dependent plasticity of the visual system, and novel, alternative treatment approaches. Besides a discussion of the recent literature, results of studies by our "Child Vision Research Unit" in Frankfurt are presented: results of a questionnaire about prescription habits concerning age limits of patching, electronic recording of occlusion in patients beyond the conventional treatment age, calculation of dose-response function and efficiency of patching and their age dependence. The results of the questionnaire illustrate the uncertainty about age limits of prescription with significant deviations from the guideline of the German Ophthalmological Society (DOG). Electronic recording of occlusion allowed the quantification of declining dose-response function and treatment efficiency between 5 and 16 years of age. Reports about successful treatment with conventional and novel methods in adults are at variance with the notion of a rigid adult visual system lacking plasticity. Electronic recording of patching allowed new insights into the age-dependent susceptibility of the visual system and contributes to a more evidence-based treatment of amblyopia. Alternative approaches for adults challenge established notions about age limits of amblyopia therapy. Further studies comparing different treatment options are urgently needed.

  14. On the strong monotonicity of the CABARET scheme

    Science.gov (United States)

    Ostapenko, V. V.

    2012-03-01

    The strong monotonicity of the CABARET scheme with single flux correction is analyzed as applied to the linear advection equation. It is shown that the scheme is strongly monotone (has the NED property) at Courant numbers r ∈ (0,0,5), for which it is monotone. Test computations illustrating this property of the CABARET scheme are presented.

  15. New flux based dose-response relationships for ozone for European forest tree species.

    Science.gov (United States)

    Büker, P; Feng, Z; Uddling, J; Briolat, A; Alonso, R; Braun, S; Elvira, S; Gerosa, G; Karlsson, P E; Le Thiec, D; Marzuoli, R; Mills, G; Oksanen, E; Wieser, G; Wilkinson, M; Emberson, L D

    2015-11-01

    To derive O3 dose-response relationships (DRR) for five European forest trees species and broadleaf deciduous and needleleaf tree plant functional types (PFTs), phytotoxic O3 doses (PODy) were related to biomass reductions. PODy was calculated using a stomatal flux model with a range of cut-off thresholds (y) indicative of varying detoxification capacities. Linear regression analysis showed that DRR for PFT and individual tree species differed in their robustness. A simplified parameterisation of the flux model was tested and showed that for most non-Mediterranean tree species, this simplified model led to similarly robust DRR as compared to a species- and climate region-specific parameterisation. Experimentally induced soil water stress was not found to substantially reduce PODy, mainly due to the short duration of soil water stress periods. This study validates the stomatal O3 flux concept and represents a step forward in predicting O3 damage to forests in a spatially and temporally varying climate.

  16. Wehrl entropy, Lieb conjecture and entanglement monotones

    CERN Document Server

    Mintert, F; Mintert, Florian; Zyczkowski, Karol

    2004-01-01

    We propose to quantify the entanglement of pure states of $N \\times N$ bipartite quantum system by defining its Husimi distribution with respect to $SU(N)\\times SU(N)$ coherent states. The Wehrl entropy is minimal if and only if the pure state analyzed is separable. The excess of the Wehrl entropy is shown to be equal to the subentropy of the mixed state obtained by partial trace of the bipartite pure state. This quantity, as well as the generalized (R{\\'e}nyi) subentropies, are proved to be Schur--convex, so they are entanglement monotones and may be used as alternative measures of entanglement.

  17. Dose-response relationships and threshold levels in skin and respiratory allergy

    NARCIS (Netherlands)

    Arts, J.H.E.; Mommers, C.; Heer, C.de

    2006-01-01

    A literature study was performed to evaluate dose-response relationships and no-effect levels for sensitization and elicitation in skin- and respiratory allergy. With respect to the skin, dose-response relationships and no-effect levels were found for both intradermal and topical induction, as well

  18. The key events dose-response framework: its potential for application to foodborne pathogenic microorganisms.

    NARCIS (Netherlands)

    Buchanan, R.L.; Havelaar, A.H.; Smith, M.A.; Whiting, R.C.; Julien, E.

    2009-01-01

    The Key Events Dose-Response Framework (KEDRF) is an analytical approach that facilitates the use of currently available data to gain insight regarding dose-response relationships. The use of the KEDRF also helps identify critical knowledge gaps that once filled, will reduce reliance on assumptions.

  19. Health damage of air pollution : an estimate of a dose-response relationship for The Netherlands

    NARCIS (Netherlands)

    Nentjes, A; Schneider, T

    1998-01-01

    This paper estimates the dose-response relationship between air pollution and the number of work loss days for The Netherlands. The study is based on illness data (work loss days) for the Dutch labor population and average year concentrations of air pollution in 29 districts. The dose-response

  20. Statistical strategies for averaging EC50 from multiple dose-response experiments.

    Science.gov (United States)

    Jiang, Xiaoqi; Kopp-Schneider, Annette

    2015-11-01

    In most dose-response studies, repeated experiments are conducted to determine the EC50 value for a chemical, requiring averaging EC50 estimates from a series of experiments. Two statistical strategies, the mixed-effect modeling and the meta-analysis approach, can be applied to estimate average behavior of EC50 values over all experiments by considering the variabilities within and among experiments. We investigated these two strategies in two common cases of multiple dose-response experiments in (a) complete and explicit dose-response relationships are observed in all experiments and in (b) only in a subset of experiments. In case (a), the meta-analysis strategy is a simple and robust method to average EC50 estimates. In case (b), all experimental data sets can be first screened using the dose-response screening plot, which allows visualization and comparison of multiple dose-response experimental results. As long as more than three experiments provide information about complete dose-response relationships, the experiments that cover incomplete relationships can be excluded from the meta-analysis strategy of averaging EC50 estimates. If there are only two experiments containing complete dose-response information, the mixed-effects model approach is suggested. We subsequently provided a web application for non-statisticians to implement the proposed meta-analysis strategy of averaging EC50 estimates from multiple dose-response experiments.

  1. The analysis of dose-response curve from bioassays with quantal response: Deterministic or statistical approaches?

    Science.gov (United States)

    Mougabure-Cueto, G; Sfara, V

    2016-04-25

    Dose-response relations can be obtained from systems at any structural level of biological matter, from the molecular to the organismic level. There are two types of approaches for analyzing dose-response curves: a deterministic approach, based on the law of mass action, and a statistical approach, based on the assumed probabilities distribution of phenotypic characters. Models based on the law of mass action have been proposed to analyze dose-response relations across the entire range of biological systems. The purpose of this paper is to discuss the principles that determine the dose-response relations. Dose-response curves of simple systems are the result of chemical interactions between reacting molecules, and therefore are supported by the law of mass action. In consequence, the shape of these curves is perfectly sustained by physicochemical features. However, dose-response curves of bioassays with quantal response are not explained by the simple collision of molecules but by phenotypic variations among individuals and can be interpreted as individual tolerances. The expression of tolerance is the result of many genetic and environmental factors and thus can be considered a random variable. In consequence, the shape of its associated dose-response curve has no physicochemical bearings; instead, they are originated from random biological variations. Due to the randomness of tolerance there is no reason to use deterministic equations for its analysis; on the contrary, statistical models are the appropriate tools for analyzing these dose-response relations.

  2. A method to adjust radiation dose-response relationships for clinical risk factors

    DEFF Research Database (Denmark)

    Appelt, Ane Lindegaard; Vogelius, Ivan R

    2012-01-01

    Several clinical risk factors for radiation induced toxicity have been identified in the literature. Here, we present a method to quantify the effect of clinical risk factors on radiation dose-response curves and apply the method to adjust the dose-response for radiation pneumonitis for patients...

  3. Topological recursion and a quantum curve for monotone Hurwitz numbers

    Science.gov (United States)

    Do, Norman; Dyer, Alastair; Mathews, Daniel V.

    2017-10-01

    Classical Hurwitz numbers count branched covers of the Riemann sphere with prescribed ramification data, or equivalently, factorisations in the symmetric group with prescribed cycle structure data. Monotone Hurwitz numbers restrict the enumeration by imposing a further monotonicity condition on such factorisations. In this paper, we prove that monotone Hurwitz numbers arise from the topological recursion of Eynard and Orantin applied to a particular spectral curve. We furthermore derive a quantum curve for monotone Hurwitz numbers. These results extend the collection of enumerative problems known to be governed by the paradigm of topological recursion and quantum curves, as well as the list of analogues between monotone Hurwitz numbers and their classical counterparts.

  4. Kernel-based interior-point methods for monotone linear complementarity problems over symmetric cones

    NARCIS (Netherlands)

    Lesaja, G.; Roos, C.

    2011-01-01

    We present an interior-point method for monotone linear complementarity problems over symmetric cones (SCLCP) that is based on barrier functions which are defined by a large class of univariate functions, called eligible kernel functions. This class is fairly general and includes the classical logar

  5. Testing monotonicity of a hazard: asymptotic distribution theory

    CERN Document Server

    Groeneboom, Piet

    2011-01-01

    Two new test statistics are introduced to test the null hypotheses that the sampling distribution has an increasing hazard rate on a specified interval [0,a]. These statistics are empirical L_1-type distances between the isotonic estimates, which use the monotonicity constraint, and either the empirical distribution function or the empirical cumulative hazard. They measure the excursions of the empirical estimates with respect to the isotonic estimates, due to local non-monotonicity. Asymptotic normality of the test statistics, if the hazard is strictly increasing on [0,a], is established under mild conditions. This is done by first approximating the global empirical distance by an distance with respect to the underlying distribution function. The resulting integral is treated as sum of increasingly many local integrals to which a CLT can be applied. The behavior of the local integrals is determined by a canonical process: the difference between the stochastic process x -> W(x)+x^2 where W is standard two-sid...

  6. Linearization of dose-response curve of the radiochromic film dosimetry system

    Energy Technology Data Exchange (ETDEWEB)

    Devic, Slobodan; Tomic, Nada; Aldelaijan, Saad; DeBlois, Francois; Seuntjens, Jan; Chan, Maria F.; Lewis, Dave [Medical Physics Unit, McGill University, Montreal, Quebec H3G 1A4 (Canada) and Department of Radiation Oncology, SMBD Jewish General Hospital, McGill University, Montreal, Quebec H3T 1E2 (Canada); Executive Administration for Radiation Protection and Safety Medical Devices Sector, Saudi Food and Drug Authority, Riyadh, Kingdom of Saudi Arabia 13312 (Saudi Arabia); Medical Physics Unit, McGill University, Montreal, Quebec H3G 1A4 (Canada) and Department of Radiation Oncology, SMBD Jewish General Hospital, McGill University, Montreal, Quebec H3T 1E2 (Canada); Medical Physics Unit, McGill University, Montreal, Quebec H3G 1A4 (Canada); Department of Medical Physics, Memorial Sloan-Kettering Cancer Center Basking Ridge, New Jersey 07920 (United States); Ashland Inc., Wayne, New Jersey 07470 (United States)

    2012-08-15

    Purpose: Despite numerous advantages of radiochromic film dosimeter (high spatial resolution, near tissue equivalence, low energy dependence) to measure a relative dose distribution with film, one needs to first measure an absolute dose (following previously established reference dosimetry protocol) and then convert measured absolute dose values into relative doses. In this work, we present result of our efforts to obtain a functional form that would linearize the inherently nonlinear dose-response curve of the radiochromic film dosimetry system. Methods: Functional form [{zeta}= (-1){center_dot}netOD{sup (2/3)}/ln(netOD)] was derived from calibration curves of various previously established radiochromic film dosimetry systems. In order to test the invariance of the proposed functional form with respect to the film model used we tested it with three different GAFCHROMIC Trade-Mark-Sign film models (EBT, EBT2, and EBT3) irradiated to various doses and scanned on a same scanner. For one of the film models (EBT2), we tested the invariance of the functional form to the scanner model used by scanning irradiated film pieces with three different flatbed scanner models (Epson V700, 1680, and 10000XL). To test our hypothesis that the proposed functional argument linearizes the response of the radiochromic film dosimetry system, verification tests have been performed in clinical applications: percent depth dose measurements, IMRT quality assurance (QA), and brachytherapy QA. Results: Obtained R{sup 2} values indicate that the choice of the functional form of the new argument appropriately linearizes the dose response of the radiochromic film dosimetry system we used. The linear behavior was insensitive to both film model and flatbed scanner model used. Measured PDD values using the green channel response of the GAFCHROMIC Trade-Mark-Sign EBT3 film model are well within {+-}2% window of the local relative dose value when compared to the tabulated Cobalt-60 data. It was also

  7. The Monotonicity Puzzle: An Experimental Investigation of Incentive Structures

    Directory of Open Access Journals (Sweden)

    Jeannette Brosig

    2010-05-01

    Full Text Available Non-monotone incentive structures, which - according to theory - are able to induce optimal behavior, are often regarded as empirically less relevant for labor relationships. We compare the performance of a theoretically optimal non-monotone contract with a monotone one under controlled laboratory conditions. Implementing some features relevant to real-world employment relationships, our paper demonstrates that, in fact, the frequency of income-maximizing decisions made by agents is higher under the monotone contract. Although this observed behavior does not change the superiority of the non-monotone contract for principals, they do not choose this contract type in a significant way. This is what we call the monotonicity puzzle. Detailed investigations of decisions provide a clue for solving the puzzle and a possible explanation for the popularity of monotone contracts.

  8. Mathematical modeling improves EC50 estimations from classical dose-response curves.

    Science.gov (United States)

    Nyman, Elin; Lindgren, Isa; Lövfors, William; Lundengård, Karin; Cervin, Ida; Sjöström, Theresia Arbring; Altimiras, Jordi; Cedersund, Gunnar

    2015-03-01

    The β-adrenergic response is impaired in failing hearts. When studying β-adrenergic function in vitro, the half-maximal effective concentration (EC50 ) is an important measure of ligand response. We previously measured the in vitro contraction force response of chicken heart tissue to increasing concentrations of adrenaline, and observed a decreasing response at high concentrations. The classical interpretation of such data is to assume a maximal response before the decrease, and to fit a sigmoid curve to the remaining data to determine EC50 . Instead, we have applied a mathematical modeling approach to interpret the full dose-response curve in a new way. The developed model predicts a non-steady-state caused by a short resting time between increased concentrations of agonist, which affect the dose-response characterization. Therefore, an improved estimate of EC50 may be calculated using steady-state simulations of the model. The model-based estimation of EC50 is further refined using additional time-resolved data to decrease the uncertainty of the prediction. The resulting model-based EC50 (180-525 nm) is higher than the classically interpreted EC50 (46-191 nm). Mathematical modeling thus makes it possible to re-interpret previously obtained datasets, and to make accurate estimates of EC50 even when steady-state measurements are not experimentally feasible. The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database, and may be accessed at http://jjj.bio.vu.nl/database/nyman. © 2015 FEBS.

  9. PPA BASED PREDICTION-CORRECTION METHODS FOR MONOTONE VARIATIONAL INEQUALITIES

    Institute of Scientific and Technical Information of China (English)

    He Bingsheng; Jiang Jianlin; Qian Maijian; Xu Ya

    2005-01-01

    In this paper we study the proximal point algorithm (PPA) based predictioncorrection (PC) methods for monotone variational inequalities. Each iteration of these methods consists of a prediction and a correction. The predictors are produced by inexact PPA steps. The new iterates are then updated by a correction using the PPA formula. We present two profit functions which serve two purposes: First we show that the profit functions are tight lower bounds of the improvements obtained in each iteration. Based on this conclusion we obtain the convergence inexactness restrictions for the prediction step. Second we show that the profit functions are quadratically dependent upon the step lengths, thus the optimal step lengths are obtained in the correction step. In the last part of the paper we compare the strengths of different methods based on their inexactness restrictions.

  10. A new non-monotone fitness scaling for genetic algorithm

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The properties of selection operators in the genetic algorithm (GA) are studied in detail. It is indicated that the selection of operations is significant for both improving the general fitness of a population and leading to the schema deceptiveness. The stochastic searching characteristics of GA are compared with those of heuristic methods. The influence of selection operators on the GA' s exploration and exploitation is discussed, and the performance of selection operators is evaluated with the premature convergence of the GA taken as an example based on One-Max function. In order to overcome the schema deceptiveness of the GA, a new type of fitness scaling, non monotone scaling, is advanced to enhance the evolutionary ability of a population. The effectiveness of the new scaling method is tested by a trap function and a needle-in-haystack (NiH) function.

  11. Implementation of a dose-response curve for γ-radiation in the Portuguese population by use of the chromosomal aberration assay.

    Science.gov (United States)

    Martins, V; Antunes, A C; Monteiro Gil, O

    2013-01-20

    An in vitro dose-response curve following exposure to γ-radiation was determined at the IST/ITN, by use of the chromosomal aberration assay. This is the first study of this kind carried out among the Portuguese population. Un-irradiated and γ-irradiated peripheral blood lymphocytes from 16 healthy donors were cultured. A total of 22,395 metaphases were analyzed for frequency and distribution of dicentrics and centric rings, as a function of the radiation dose. The dose-response data for dicentrics and dicentrics plus centric rings were fitted by use of a linear-quadratic model: Y(dic)=(0.0011±0.0006)+(0.0105±0.0035)D+(0.0480±0.0019)D(2) and Y(dic+rings)=(0.0011±0.0006)+(0.0095±0.0036)D+(0.0536±0.0020)D(2). Also, calibration curves related to age and gender were determined, but no significant differences were found. Following the establishment of the dose-response curves, a validation experiment was carried out with three individuals. Real and estimated doses, obtained with the dose-response curves, were in agreement. These results give us confidence to apply both dose-response calibration curves in future biological dosimetry requirements.

  12. Slope of the dose-response curve: usefulness in assessing bronchial responses to inhaled histamine.

    OpenAIRE

    Cockcroft, D. W.; Berscheid, B A

    1983-01-01

    The value of determining the slope of the histamine dose-response curve, in addition to the histamine provocation concentration producing a 20% reduction in FEV1 (PC20-FEV1), was assessed by analysis of histamine dose-response curves in 40 patients selected as having a wide range of increased non-specific bronchial responsiveness to inhaled histamine. The histamine dose-response curves were found to be fit the linear curve (dose v response, mean r2 = 0.97) better than the logarithmic curve (l...

  13. Threshold estimation based on a p-value framework in dose-response and regression settings

    CERN Document Server

    Mallik, Atul; Banerjee, Moulinath; Michailidis, George

    2011-01-01

    We use p-values to identify the threshold level at which a regression function takes off from its baseline value, a problem motivated by applications in toxicological and pharmacological dose-response studies and environmental statistics. We study the problem in two sampling settings: one where multiple responses can be obtained at a number of different covariate-levels and the other the standard regression setting involving limited number of response values at each covariate. Our procedure involves testing the hypothesis that the regression function is at its baseline at each covariate value and then computing the potentially approximate p-value of the test. An estimate of the threshold is obtained by fitting a piecewise constant function with a single jump discontinuity, otherwise known as a stump, to these observed p-values, as they behave in markedly different ways on the two sides of the threshold. The estimate is shown to be consistent and its finite sample properties are studied through simulations. Ou...

  14. Stepsize Restrictions for Boundedness and Monotonicity of Multistep Methods

    KAUST Repository

    Hundsdorfer, W.

    2011-04-29

    In this paper nonlinear monotonicity and boundedness properties are analyzed for linear multistep methods. We focus on methods which satisfy a weaker boundedness condition than strict monotonicity for arbitrary starting values. In this way, many linear multistep methods of practical interest are included in the theory. Moreover, it will be shown that for such methods monotonicity can still be valid with suitable Runge-Kutta starting procedures. Restrictions on the stepsizes are derived that are not only sufficient but also necessary for these boundedness and monotonicity properties. © 2011 Springer Science+Business Media, LLC.

  15. On the monotonicity of multidimensional finite difference schemes

    Science.gov (United States)

    Kovyrkina, O.; Ostapenko, V.

    2016-10-01

    The classical concept of monotonicity, introduced by Godunov for linear one-dimensional difference schemes, is extended to multidimensional case. Necessary and sufficient conditions of monotonicity are obtained for linear multidimensional difference schemes of first order. The constraints on the numerical viscosity are given that ensure the monotonicity of a difference scheme in the multidimensional case. It is proposed a modification of the second order multidimensional CABARET scheme that preserves the monotonicity of one-dimensional discrete solutions and, as a result, ensures higher smoothness in the computation of multidimensional discontinuous solutions. The results of two-dimensional test computations illustrating the advantages of the modified CABARET scheme are presented.

  16. Toward a unified approach to dose-response modeling in ecotoxicology.

    Science.gov (United States)

    Ritz, Christian

    2010-01-01

    This study reviews dose-response models that are used in ecotoxicology. The focus lies on clarification of differences and similarities between models, and as a side effect, their different guises in ecotoxicology are unravelled. A look at frequently used dose-response models reveals major discrepancies, among other things in naming conventions. Therefore, there is a need for a unified view on dose-response modeling in order to improve the understanding of it and to facilitate communication and comparison of findings across studies, thus realizing its full potential. This study attempts to establish a general framework that encompasses most dose-response models that are of interest to ecotoxicologists in practice. The framework includes commonly used models such as the log-logistic and Weibull models, but also features entire suites of models as found in various guidance documents. An outline on how the proposed framework can be implemented in statistical software systems is also provided.

  17. Dose-response regressions for algal growth and similar continuous endpoints: Calculation of effective concentrations

    DEFF Research Database (Denmark)

    Christensen, Erik R.; Kusk, Kresten Ole; Nyholm, Niels

    2009-01-01

    % inhibition). For illustration, data from closed, freshwater algal assays are analyzed using the green alga Pseudokirchneriella subcapitata with growth rate as the response parameter. Dose-response regressions for four test chemicals (tetraethylammonium bromide, musculamine, benzonitrile, and 4...

  18. Scaling Effect of Area-Averaged NDVI: Monotonicity along the Spatial Resolution

    Directory of Open Access Journals (Sweden)

    Hiroki Yoshioka

    2012-01-01

    Full Text Available Changes in the spatial distributions of vegetation across the globe are routinely monitored by satellite remote sensing, in which the reflectance spectra over land surface areas are measured with spatial and temporal resolutions that depend on the satellite instrumentation. The use of multiple synchronized satellite sensors permits long-term monitoring with high spatial and temporal resolutions. However, differences in the spatial resolution of images collected by different sensors can introduce systematic biases, called scaling effects, into the biophysical retrievals. This study investigates the mechanism by which the scaling effects distort normalized difference vegetation index (NDVI. This study focused on the monotonicity of the area-averaged NDVI as a function of the spatial resolution. A monotonic relationship was proved analytically by using the resolution transform model proposed in this study in combination with a two-endmember linear mixture model. The monotonicity allowed the inherent uncertainties introduced by the scaling effects (error bounds to be explicitly determined by averaging the retrievals at the extrema of theresolutions. Error bounds could not be estimated, on the other hand, for non-monotonic relationships. Numerical simulations were conducted to demonstrate the monotonicity of the averaged NDVI along spatial resolution. This study provides a theoretical basis for the scaling effects and develops techniques for rectifying the scaling effects in biophysical retrievals to facilitate cross-sensor calibration for the long-term monitoring of vegetation dynamics.

  19. A grid algorithm for high throughput fitting of dose-response curve data.

    Science.gov (United States)

    Wang, Yuhong; Jadhav, Ajit; Southal, Noel; Huang, Ruili; Nguyen, Dac-Trung

    2010-10-21

    We describe a novel algorithm, Grid algorithm, and the corresponding computer program for high throughput fitting of dose-response curves that are described by the four-parameter symmetric logistic dose-response model. The Grid algorithm searches through all points in a grid of four dimensions (parameters) and finds the optimum one that corresponds to the best fit. Using simulated dose-response curves, we examined the Grid program's performance in reproducing the actual values that were used to generate the simulated data and compared it with the DRC package for the language and environment R and the XLfit add-in for Microsoft Excel. The Grid program was robust and consistently recovered the actual values for both complete and partial curves with or without noise. Both DRC and XLfit performed well on data without noise, but they were sensitive to and their performance degraded rapidly with increasing noise. The Grid program is automated and scalable to millions of dose-response curves, and it is able to process 100,000 dose-response curves from high throughput screening experiment per CPU hour. The Grid program has the potential of greatly increasing the productivity of large-scale dose-response data analysis and early drug discovery processes, and it is also applicable to many other curve fitting problems in chemical, biological, and medical sciences.

  20. MINLIP for the Identification of Monotone Wiener Systems

    CERN Document Server

    Pelckmans, Kristiaan

    2010-01-01

    This paper studies the MINLIP estimator for the identification of Wiener systems consisting of a sequence of a linear FIR dynamical model, and a monotonically increasing (or decreasing) static function. Given $T$ observations, this algorithm boils down to solving a convex quadratic program with $O(T)$ variables and inequality constraints, implementing an inference technique which is based entirely on model complexity control. The resulting estimates of the linear submodel are found to be almost consistent when no noise is present in the data, under a condition of smoothness of the true nonlinearity and local Persistency of Excitation (local PE) of the data. This result is novel as it does not rely on classical tools as a 'linearization' using a Taylor decomposition, nor exploits stochastic properties of the data. It is indicated how to extend the method to cope with noisy data, and empirical evidence contrasts performance of the estimator against other recently proposed techniques.

  1. Dose-response relationships using brain-computer interface technology impact stroke rehabilitation.

    Science.gov (United States)

    Young, Brittany M; Nigogosyan, Zack; Walton, Léo M; Remsik, Alexander; Song, Jie; Nair, Veena A; Tyler, Mitchell E; Edwards, Dorothy F; Caldera, Kristin; Sattin, Justin A; Williams, Justin C; Prabhakaran, Vivek

    2015-01-01

    Brain-computer interfaces (BCIs) are an emerging novel technology for stroke rehabilitation. Little is known about how dose-response relationships for BCI therapies affect brain and behavior changes. We report preliminary results on stroke patients (n = 16, 11 M) with persistent upper extremity motor impairment who received therapy using a BCI system with functional electrical stimulation of the hand and tongue stimulation. We collected MRI scans and behavioral data using the Action Research Arm Test (ARAT), 9-Hole Peg Test (9-HPT), and Stroke Impact Scale (SIS) before, during, and after the therapy period. Using anatomical and functional MRI, we computed Laterality Index (LI) for brain activity in the motor network during impaired hand finger tapping. Changes from baseline LI and behavioral scores were assessed for relationships with dose, intensity, and frequency of BCI therapy. We found that gains in SIS Strength were directly responsive to BCI therapy: therapy dose and intensity correlated positively with increased SIS Strength (p ≤ 0.05), although no direct relationships were identified with ARAT or 9-HPT scores. We found behavioral measures that were not directly sensitive to differences in BCI therapy administration but were associated with concurrent brain changes correlated with BCI therapy administration parameters: therapy dose and intensity showed significant (p ≤ 0.05) or trending (0.05 stroke rehabilitation, therapy frequency may be less important than dose and intensity.

  2. Variable selection in monotone single-index models via the adaptive LASSO.

    Science.gov (United States)

    Foster, Jared C; Taylor, Jeremy M G; Nan, Bin

    2013-09-30

    We consider the problem of variable selection for monotone single-index models. A single-index model assumes that the expectation of the outcome is an unknown function of a linear combination of covariates. Assuming monotonicity of the unknown function is often reasonable and allows for more straightforward inference. We present an adaptive LASSO penalized least squares approach to estimating the index parameter and the unknown function in these models for continuous outcome. Monotone function estimates are achieved using the pooled adjacent violators algorithm, followed by kernel regression. In the iterative estimation process, a linear approximation to the unknown function is used, therefore reducing the situation to that of linear regression and allowing for the use of standard LASSO algorithms, such as coordinate descent. Results of a simulation study indicate that the proposed methods perform well under a variety of circumstances and that an assumption of monotonicity, when appropriate, noticeably improves performance. The proposed methods are applied to data from a randomized clinical trial for the treatment of a critical illness in the intensive care unit.

  3. Stochastic Monotone Markov Integrated Semigroups%随机单调Markov积分半群

    Institute of Scientific and Technical Information of China (English)

    文兴易; 李扬荣

    2009-01-01

    In this paper we discuss the relationship between monotone of Markov integrated semigroups and transition functions,which are closely linked with each other for continuous time Markov chains.By this a necessary and sufficient condition for the minimal q-semigroup to be stochastic monotone is given in terms of their q-matrix only.%讨论了Markov积分半群的单调性和转移函数的单调性的等价性,并得到最小的Q半群是单调的充要条件.

  4. The first and second monotone integral principles for fundamental solutions of uniformly elliptic equations

    CERN Document Server

    Xiao, Jie

    2009-01-01

    Two optimal monotone integral principles (equivalently for the Laplacian, two sharp iso-weighted-volume inequalities) are established through extending the first and second integral bounds of H. Weinberger for the Green functions (i.e., fundamental solutions) of uniformly elliptic equations in terms of the layer-cake formula, a one-dimensional monotone integral principle, and the isoperimetric and Jenson's inequalities with sharp constants. Surprisingly, a special setting of the first principle can be used to not only verify the low-dimensional P\\'olya conjecture for the principal eigenvalue of the Laplacian but also to characterize the geometry of the Nash inequality for a strong uniform elliptic equation.

  5. Comparison of boundedness and monotonicity properties of one-leg and linear multistep methods

    KAUST Repository

    Mozartova, A.

    2015-05-01

    © 2014 Elsevier B.V. All rights reserved. One-leg multistep methods have some advantage over linear multistep methods with respect to storage of the past results. In this paper boundedness and monotonicity properties with arbitrary (semi-)norms or convex functionals are analyzed for such multistep methods. The maximal stepsize coefficient for boundedness and monotonicity of a one-leg method is the same as for the associated linear multistep method when arbitrary starting values are considered. It will be shown, however, that combinations of one-leg methods and Runge-Kutta starting procedures may give very different stepsize coefficients for monotonicity than the linear multistep methods with the same starting procedures. Detailed results are presented for explicit two-step methods.

  6. Monotone measures of ergodicity for Markov chains

    Directory of Open Access Journals (Sweden)

    J. Keilson

    1998-01-01

    Full Text Available The following paper, first written in 1974, was never published other than as part of an internal research series. Its lack of publication is unrelated to the merits of the paper and the paper is of current importance by virtue of its relation to the relaxation time. A systematic discussion is provided of the approach of a finite Markov chain to ergodicity by proving the monotonicity of an important set of norms, each measures of egodicity, whether or not time reversibility is present. The paper is of particular interest because the discussion of the relaxation time of a finite Markov chain [2] has only been clean for time reversible chains, a small subset of the chains of interest. This restriction is not present here. Indeed, a new relaxation time quoted quantifies the relaxation time for all finite ergodic chains (cf. the discussion of Q1(t below Equation (1.7]. This relaxation time was developed by Keilson with A. Roy in his thesis [6], yet to be published.

  7. Remarks on a monotone Markov chain

    Directory of Open Access Journals (Sweden)

    P. Todorovic

    1987-01-01

    Full Text Available In applications, considerations on stochastic models often involve a Markov chain {ζn}0∞ with state space in R+, and a transition probability Q. For each x  R+ the support of Q(x,. is [0,x]. This implies that ζ0≥ζ1≥…. Under certain regularity assumptions on Q we show that Qn(x,Bu→1 as n→∞ for all u>0 and that 1−Qn(x,Bu≤[1−Q(x,Bu]n where Bu=[0,u. Set τ0=max{k;ζk=ζ0}, τn=max{k;ζk=ζτn−1+1} and write Xn=ζτn−1+1, Tn=τn−τn−1. We investigate some properties of the imbedded Markov chain {Xn}0∞ and of {Tn}0∞. We determine all the marginal distributions of {Tn}0∞ and show that it is asymptotically stationary and that it possesses a monotonicity property. We also prove that under some mild regularity assumptions on β(x=1−Q(x,Bx, ∑1n(Ti−a/bn→dZ∼N(0,1.

  8. Robust Monotone Iterates for Nonlinear Singularly Perturbed Boundary Value Problems

    Directory of Open Access Journals (Sweden)

    Boglaev Igor

    2009-01-01

    Full Text Available This paper is concerned with solving nonlinear singularly perturbed boundary value problems. Robust monotone iterates for solving nonlinear difference scheme are constructed. Uniform convergence of the monotone methods is investigated, and convergence rates are estimated. Numerical experiments complement the theoretical results.

  9. Regularization and Iterative Methods for Monotone Variational Inequalities

    Directory of Open Access Journals (Sweden)

    Xiubin Xu

    2010-01-01

    Full Text Available We provide a general regularization method for monotone variational inequalities, where the regularizer is a Lipschitz continuous and strongly monotone operator. We also introduce an iterative method as discretization of the regularization method. We prove that both regularization and iterative methods converge in norm.

  10. Positivity and Monotonicity Preserving Biquartic Rational Interpolation Spline Surface

    Directory of Open Access Journals (Sweden)

    Xinru Liu

    2014-01-01

    Full Text Available A biquartic rational interpolation spline surface over rectangular domain is constructed in this paper, which includes the classical bicubic Coons surface as a special case. Sufficient conditions for generating shape preserving interpolation splines for positive or monotonic surface data are deduced. The given numeric experiments show our method can deal with surface construction from positive or monotonic data effectively.

  11. Mechanisms of Action and Dose-Response Relationships Governing Biological Control of Fusarium Wilt of Tomato by Nonpathogenic Fusarium spp.

    Science.gov (United States)

    Larkin, R P; Fravel, D R

    1999-12-01

    ABSTRACT Three isolates of nonpathogenic Fusarium spp. (CS-1, CS-20, and Fo47), previously shown to reduce the incidence of Fusarium wilt diseases of multiple crops, were evaluated to determine their mechanisms of action and antagonist-pathogen inoculum density relationships. Competition for nutrients, as represented by a reduction in pathogen saprophytic growth in the presence of the biocontrol isolates, was observed to be an important mechanism of action for isolate Fo47, but not for isolates CS-1 and CS-20. All three biocontrol isolates demonstrated some degree of induced systemic resistance in tomato (Lycopersicon esculentum) and watermelon (Citrullus lanatus) plants, as determined by split-root tests, but varied in their relative abilities to reduce disease. Isolate CS-20 provided the most effective control (39 to 53% disease reduction), while Fo47 provided the least effective control (23 to 25% reduction) in split-root tests. Dose-response relationships also differed considerably among the three biocon-trol isolates, with CS-20 significantly reducing disease incidence at antagonist doses as low as 100 chlamydospores per g of soil (cgs) and at pathogen densities up to 10(5) cgs. Isolate CS-1 also was generally effective at antagonist densities of 100 to 5,000 cgs, but only when pathogen densities were below 10(4) cgs. Isolate Fo47 was effective only at antagonist densities of 10(4) to 10(5) cgs, regardless of pathogen density. Epidemiological dose-response models (described by linear, negative exponential, hyperbolic saturation [HS], and logistic [LG] functions) fit to the observed data were used to quantify differences among the biocontrol isolates and establish biocontrol characteristics. Each isolate required a different model to best describe its dose-response characteristics, with the HS/HS, LG/HS, and LG/LG models (pathogen/biocontrol components) providing the best fit for isolates CS-1, CS-20, and Fo47, respectively. Model parameters (defining effective

  12. Permanence of a general discrete-time two-species-interaction model with non-monotonic per capita growth rates

    CERN Document Server

    Kang, Yun

    2011-01-01

    Combined with all density-dependent factors, the per capita growth rate of a species may be non-monotonic. One important consequence is that species may suffer from weak Allee effects or strong Allee effects. In this paper, we study the permanence of a discrete-time two-species-interaction model with non-monotonic per capita growth rates for the first time. By using the average Lyapunov functions and extending the ecological concept of the relative nonlinearity, we find a simple sufficient condition for guaranteeing the permanence of systems that can model complicated two-species interactions. The extended relative nonlinearity allows us to fully characterize the effects of nonlinearities in the per capita growth functions with non-monotonicity. These results are illustrated with specific two species competition and predator-prey models of generic forms with non-monotone per capita growth rates.

  13. Dose response studies and longterm evaluation of auranofin in rheumatoid arthritis.

    Science.gov (United States)

    Champion, G D; Cairns, D R; Bieri, D; Adena, M A; Browne, C D; Cohen, M L; Day, R O; Edmonds, J P; Graham, G G; de Jager, J

    1988-01-01

    Fifty-eight patients with rheumatoid arthritis (RA) entered a double blind trial of auranofin (AF) designed to assess dose response relationships and longterm outcome. Multivariate analysis of repeated measures with trend analysis and discriminant function analysis of standard measures of RA activity were applied to a randomized double blind trial of AF at daily doses of 4, 6 and 8 mg over 6 months. Improvement occurred in each group. There was a highly significant (p less than 0.001) linear trend in the 6 mg group, 73% of whom showed linear improvement. A significant correlation (p less than 0.05) was found between response of individual patients and AF dose (mg/kg/day), but there was no significant correlation between dosage and mean steady state serum gold concentration. No significant correlation was seen between outcome and pretreatment demographic and disease variables. In a subsequent 6 month phase of dosage adjustment, aiming for optimal dosage, no advantage resulted from increasing the dose above 6 mg/day. Patients apparently benefiting from treatment continued an open long-term trial of AF. By 45 months, 33.5% had stopped treatment due to lack of efficacy and 14.5% due to toxicity, mainly rash and diarrhea.

  14. Melatonin entrains free-running blind people according to a physiological dose-response curve.

    Science.gov (United States)

    Lewy, Alfred J; Emens, Jonathan S; Lefler, Bryan J; Yuhas, Krista; Jackman, Angela R

    2005-01-01

    The specific circadian role proposed for endogenous melatonin production was based on a study of sighted people who took low pharmacological doses (500 microg) of this chemical signal for the "biological night": the magnitude and direction of the induced phase shifts were dependent on what time of day exogenous melatonin was administered and were described by a phase-response curve that turned out to be the opposite of that for light. We now report that lower (physiological) doses of up to 300 microg can entrain (synchronize) free-running circadian rhythms of 10 totally blind subjects that would otherwise drift later each day. The resulting log-linear dose-response curve in the physiological range adds support for a circadian function of endogenous melatonin in humans. Efficacy of exogenous doses in the physiological range are of clinical significance for totally blind people who will need to take melatonin daily over their entire lifetimes in order to remain entrained to the 24 h day. Left untreated, their free-running endocrine, metabolic, behavioral, and sleep/wake cycles can be almost as burdensome as not having vision.

  15. Linearization of EBT3 film dose response and virtual film dosimetry for SBRT quality assurance

    Science.gov (United States)

    Cai, M.; Archibald-Heeren, B.; Wang, Y.; Metcalfe, P.

    2017-01-01

    EBT3 film offers high spatial resolution and low energy dependence, making it a suitable choice for quality assurance where high dose gradients are present, such as the case for SBRT. This work presents a simple method to adjust scanner settings so that dose response becomes linear. This linearity eliminates the need to obtain a calibration curve and associated uncertainties in curve fitting. Relative dosimetry can be performed after dose normalization to a reference point. Linearity is also a more robust condition than calibration curve with respect to scanner warm-up conditions, resulting in reduced uncertainty in dose measurement. An in-house developed program reads the film scan and a 2D dose map then constructs both to virtual films using grayscale values. Film intensity value was normalized to dose at reference point. Relative dosimetry was performed by comparing the two resulting images. Patient specific quality assurance was conducted for two SBRT cases. In both plans more than 95% gamma function points passed the gamma criteria of 2%/3mm.

  16. Standard error of inverse prediction for dose-response relationship: approximate and exact statistical inference.

    Science.gov (United States)

    Demidenko, Eugene; Williams, Benjamin B; Flood, Ann Barry; Swartz, Harold M

    2013-05-30

    This paper develops a new metric, the standard error of inverse prediction (SEIP), for a dose-response relationship (calibration curve) when dose is estimated from response via inverse regression. SEIP can be viewed as a generalization of the coefficient of variation to regression problem when x is predicted using y-value. We employ nonstandard statistical methods to treat the inverse prediction, which has an infinite mean and variance due to the presence of a normally distributed variable in the denominator. We develop confidence intervals and hypothesis testing for SEIP on the basis of the normal approximation and using the exact statistical inference based on the noncentral t-distribution. We derive the power functions for both approaches and test them via statistical simulations. The theoretical SEIP, as the ratio of the regression standard error to the slope, is viewed as reciprocal of the signal-to-noise ratio, a popular measure of signal processing. The SEIP, as a figure of merit for inverse prediction, can be used for comparison of calibration curves with different dependent variables and slopes. We illustrate our theory with electron paramagnetic resonance tooth dosimetry for a rapid estimation of the radiation dose received in the event of nuclear terrorism.

  17. Payoff-monotonic game dynamics and the maximum clique problem.

    Science.gov (United States)

    Pelillo, Marcello; Torsello, Andrea

    2006-05-01

    Evolutionary game-theoretic models and, in particular, the so-called replicator equations have recently proven to be remarkably effective at approximately solving the maximum clique and related problems. The approach is centered around a classic result from graph theory that formulates the maximum clique problem as a standard (continuous) quadratic program and exploits the dynamical properties of these models, which, under a certain symmetry assumption, possess a Lyapunov function. In this letter, we generalize previous work along these lines in several respects. We introduce a wide family of game-dynamic equations known as payoff-monotonic dynamics, of which replicator dynamics are a special instance, and show that they enjoy precisely the same dynamical properties as standard replicator equations. These properties make any member of this family a potential heuristic for solving standard quadratic programs and, in particular, the maximum clique problem. Extensive simulations, performed on random as well as DIMACS benchmark graphs, show that this class contains dynamics that are considerably faster than and at least as accurate as replicator equations. One problem associated with these models, however, relates to their inability to escape from poor local solutions. To overcome this drawback, we focus on a particular subclass of payoff-monotonic dynamics used to model the evolution of behavior via imitation processes and study the stability of their equilibria when a regularization parameter is allowed to take on negative values. A detailed analysis of these properties suggests a whole class of annealed imitation heuristics for the maximum clique problem, which are based on the idea of varying the parameter during the imitation optimization process in a principled way, so as to avoid unwanted inefficient solutions. Experiments show that the proposed annealing procedure does help to avoid poor local optima by initially driving the dynamics toward promising regions in

  18. Modeling Dose-response at Low Dose: A Systems Biology Approach for Ionization Radiation.

    Science.gov (United States)

    Zhao, Yuchao; Ricci, Paolo F

    2010-03-18

    For ionization radiation (IR) induced cancer, a linear non-threshold (LNT) model at very low doses is the default used by a number of national and international organizations and in regulatory law. This default denies any positive benefit from any level of exposure. However, experimental observations and theoretical biology have found that both linear and J-shaped IR dose-response curves can exist at those very low doses. We develop low dose J-shaped dose-response, based on systems biology, and thus justify its use regarding exposure to IR. This approach incorporates detailed, molecular and cellular descriptions of biological/toxicological mechanisms to develop a dose-response model through a set of nonlinear, differential equations describing the signaling pathways and biochemical mechanisms of cell cycle checkpoint, apoptosis, and tumor incidence due to IR. This approach yields a J-shaped dose response curve while showing where LNT behaviors are likely to occur. The results confirm the hypothesis of the J-shaped dose response curve: the main reason is that, at low-doses of IR, cells stimulate protective systems through a longer cell arrest time per unit of IR dose. We suggest that the policy implications of this approach are an increasingly correct way to deal with precautionary measures in public health.

  19. Dose-response relationships for the onset of avoidance of sonar by free-ranging killer whales.

    Science.gov (United States)

    Miller, Patrick J O; Antunes, Ricardo N; Wensveen, Paul J; Samarra, Filipa I P; Alves, Ana Catarina; Tyack, Peter L; Kvadsheim, Petter H; Kleivane, Lars; Lam, Frans-Peter A; Ainslie, Michael A; Thomas, Len

    2014-02-01

    Eight experimentally controlled exposures to 1-2 kHz or 6-7 kHz sonar signals were conducted with four killer whale groups. The source level and proximity of the source were increased during each exposure in order to reveal response thresholds. Detailed inspection of movements during each exposure session revealed sustained changes in speed and travel direction judged to be avoidance responses during six of eight sessions. Following methods developed for Phase-I clinical trials in human medicine, response thresholds ranging from 94 to 164 dB re 1 μPa received sound pressure level (SPL) were fitted to Bayesian dose-response functions. Thresholds did not consistently differ by sonar frequency or whether a group had previously been exposed, with a mean SPL response threshold of 142 ± 15 dB (mean ± s.d.). High levels of between- and within-individual variability were identified, indicating that thresholds depended upon other undefined contextual variables. The dose-response functions indicate that some killer whales started to avoid sonar at received SPL below thresholds assumed by the U.S. Navy. The predicted extent of habitat over which avoidance reactions occur depends upon whether whales responded to proximity or received SPL of the sonar or both, but was large enough to raise concerns about biological consequences to the whales.

  20. Benchmarking B-cell epitope prediction with quantitative dose-response data on antipeptide antibodies: towards novel pharmaceutical product development.

    Science.gov (United States)

    Caoili, Salvador Eugenio C

    2014-01-01

    B-cell epitope prediction can enable novel pharmaceutical product development. However, a mechanistically framed consensus has yet to emerge on benchmarking such prediction, thus presenting an opportunity to establish standards of practice that circumvent epistemic inconsistencies of casting the epitope prediction task as a binary-classification problem. As an alternative to conventional dichotomous qualitative benchmark data, quantitative dose-response data on antibody-mediated biological effects are more meaningful from an information-theoretic perspective in the sense that such effects may be expressed as probabilities (e.g., of functional inhibition by antibody) for which the Shannon information entropy (SIE) can be evaluated as a measure of informativeness. Accordingly, half-maximal biological effects (e.g., at median inhibitory concentrations of antibody) correspond to maximally informative data while undetectable and maximal biological effects correspond to minimally informative data. This applies to benchmarking B-cell epitope prediction for the design of peptide-based immunogens that elicit antipeptide antibodies with functionally relevant cross-reactivity. Presently, the Immune Epitope Database (IEDB) contains relatively few quantitative dose-response data on such cross-reactivity. Only a small fraction of these IEDB data is maximally informative, and many more of them are minimally informative (i.e., with zero SIE). Nevertheless, the numerous qualitative data in IEDB suggest how to overcome the paucity of informative benchmark data.

  1. [Dose response curve of paclitaxel measured by histoculture drug response assay].

    Science.gov (United States)

    Yoshimasu, Tatsuya; Oura, Shoji; Hirai, Issei; Kokawa, Yozo; Okamura, Yoshitaka; Furukawa, Tomoko

    2005-04-01

    Dose response curves of paclitaxel were measured by histoculture drug response assay (HDRA) in 11 lung cancer patients. Inhibition rates of paclitaxel at several concentrations were measured and fitted to the sigmoid dose response curve, using non-linear least square analysis, with fitting equation y=A (1-1/(1+exp (b (x-log (ED50)). Parameters A, b, and ED50 were 88.3+/-6.0 (80.0-100.0) %, 9.57+/-4.32 (2.25-15.0), and 26.8+/-8.1 (15.0-41.0) microg/ml, respectively. The parameter b was lower in well-differentiated tumors compared with moderately and poorly-differentiated tumors. Dose response curves of paclitaxel could be measured by HDRA in lung cancer. This method provides us more information for drug sensitivity than the usual HDRA method. This may lead to the improved accuracy of HDRA.

  2. Use of empirical likelihood to calibrate auxiliary information in partly linear monotone regression models.

    Science.gov (United States)

    Chen, Baojiang; Qin, Jing

    2014-05-10

    In statistical analysis, a regression model is needed if one is interested in finding the relationship between a response variable and covariates. When the response depends on the covariate, then it may also depend on the function of this covariate. If one has no knowledge of this functional form but expect for monotonic increasing or decreasing, then the isotonic regression model is preferable. Estimation of parameters for isotonic regression models is based on the pool-adjacent-violators algorithm (PAVA), where the monotonicity constraints are built in. With missing data, people often employ the augmented estimating method to improve estimation efficiency by incorporating auxiliary information through a working regression model. However, under the framework of the isotonic regression model, the PAVA does not work as the monotonicity constraints are violated. In this paper, we develop an empirical likelihood-based method for isotonic regression model to incorporate the auxiliary information. Because the monotonicity constraints still hold, the PAVA can be used for parameter estimation. Simulation studies demonstrate that the proposed method can yield more efficient estimates, and in some situations, the efficiency improvement is substantial. We apply this method to a dementia study.

  3. Historical blunders: how toxicology got the dose-response relationship half right.

    Science.gov (United States)

    Calabrese, E J

    2005-12-14

    Substantial evidence indicates that reliable examples of hormetic dose responses in the toxicological literature are common and generalizable across biological model, endpoint measured and chemical class. Further evaluation revealed that the hormetic dose response model is more common than the threshold dose response model in objective, head-to-head comparisons. Nonetheless, the field of toxicology made a profound error by rejecting the use of the hormetic dose response model in its teaching, research, risk assessment and regulatory activities over nearly the past century. This paper argues that the hormetic dose response model (formerly called the Arndt-Schulz Law) was rejected principally because of its close historical association with the medical practice of homeopathy as a result of the prolonged and bitter feud between traditional medicine and homeopathy. Opponents of the concept of hormesis, making use of strong appeals to authority, were successful in their misrepresentation of the scientific foundations of hormesis and in their unfair association of it with segments of the homeopathic movement with extreme and discreditable views. These misrepresentations became established and integrated within the pharmacology and toxicology communities as a result of their origins in and continuities with traditional medicine and subsequently profoundly impacted a broad range of governmental risk assessment activities further consolidating the rejection of hormesis. This error of judgment was reinforced by toxicological hazard assessment methods using only high and few doses that were unable to assess hormetic responses, statistical modeling processes that were constrained to deny the possibility of hormetic dose response relationships and by the modest nature of the hormetic stimulatory response itself, which required more rigorous study designs to evaluate possible hormetic responses.

  4. Ratio Monotonicity of Polynomials Derived from Nondecreasing Sequences

    CERN Document Server

    Chen, William Y C; Zhou, Elaine L F

    2010-01-01

    The ratio monotonicity of a polynomial is a stronger property than log-concavity. Let P(x) be a polynomial with nonnegative and nondecreasing coefficients. We prove the ratio monotone property of P(x+1), which leads to the log-concavity of P(x+c) for any $c\\geq 1$ due to Llamas and Mart\\'{\\i}nez-Bernal. As a consequence, we obtain the ratio monotonicity of the Boros-Moll polynomials obtained by Chen and Xia without resorting to the recurrence relations of the coefficients.

  5. Dose-response relationship for light intensity and ocular and electroencephalographic correlates of human alertness

    Science.gov (United States)

    Cajochen, C.; Zeitzer, J. M.; Czeisler, C. A.; Dijk, D. J.

    2000-01-01

    Light can elicit both circadian and acute physiological responses in humans. In a dose response protocol men and women were exposed to illuminances ranging from 3 to 9100 lux for 6.5 h during the early biological night after they had been exposed to dose response curve. Half of the maximum alerting response to bright light of 9100 lux was obtained with room light of approximately 100 lux. This sensitivity to light indicates that variations in illuminance within the range of typical, ambient, room light (90-180 lux) can have a significant impact on subjective alertness and its electrophysiologic concomitants in humans during the early biological night.

  6. Dose-response study of N,N-dimethyltryptamine in humans. I. Neuroendocrine, autonomic, and cardiovascular effects.

    Science.gov (United States)

    Strassman, R J; Qualls, C R

    1994-02-01

    To begin applying basic neuropharmacological hypotheses of hallucinogenic drug actions to humans, we generated dose-response data for intravenously administered dimethyltryptamine fumarate's (DMT) neuroendocrine, cardiovascular, autonomic, and subjective effects in a group of experienced hallucinogen users. Dimethyltryptamine, an endogenous mammalian hallucinogen and drug of abuse, was administered intravenously at 0.05, 0.1, 0.2, and 0.4 mg/kg to 11 experienced hallucinogen users, in a double-blind, saline placebo-controlled, randomized design. Treatments were separated by at least 1 week. Peak DMT blood levels and subjective effects were seen within 2 minutes after drug administration, and were negligible at 30 minutes. Dimethyltryptamine dose dependently elevated blood pressure, heart rate, pupil diameter, and rectal temperature, in addition to elevating blood concentrations of beta-endorphin, corticotropin, cortisol, and prolactin. Growth hormone blood levels rose equally in response to all doses of DMT, and melatonin levels were unaffected. Threshold doses for significant effects relative to placebo were also hallucinogenic (0.2 mg/kg and higher). Subjects with five or more exposures to 3,4-methylenedioxymethamphetamine demonstrated less robust pupil diameter effects than those with two or fewer exposures. Dimethyltryptamine can be administered safely to experienced hallucinogen users and dose-response data generated for several measures hypothesized under serotonergic modulatory control. Additional studies characterizing the specific mechanisms mediating DMT's biological effects may prove useful in psychopharmacological investigations of drug-induced and endogenous alterations in brain function.

  7. Fundamental investigations of natural and laboratory generated SAR dose response curves for quartz OSL in the high dose range

    DEFF Research Database (Denmark)

    Timar-Gabor, Alida; Constantin, Daniela; Buylaert, Jan-Pieter

    2015-01-01

    SAR-OSL investigations on quartz from Romanian loess resulted in non concordant fine and coarse-grain ages for equivalent doses higher than ~100 Gy. The laboratory dose response for both grain sizes is well represented by a sum of two saturating exponential functions, fine and coarse grains chara...... equivalent dose of 2000e2500 Gy were found to be below the saturation level of the laboratory dose response curve for both grain sizes; this also applied to the luminescence signals measured after >5000 Gy given on top of natural doses. © 2015 Elsevier Ltd. All rights reserved....... characterised by D01 and D02 values of ~140 and ~1400 Gy and ~65 and ~650 Gy respectively. Pulsed OSL experiments confirmed that this behaviour is almost certainly inherent to quartz and not caused by contamination with another mineral. Natural doseeresponse curves do not follow the same pattern and enter...... saturation much earlier. Analysis of time resolved spectra indicated similar luminescence lifetimes for both fine and coarse quartz grains, and natural and laboratory generated OSL signals seem to use the same non-dosedependent recombination pathways. The natural signals of a sample with an expected...

  8. A sex-specific dose-response curve for testosterone: could excessive testosterone limit sexual interaction in women?

    Science.gov (United States)

    Krapf, Jill M; Simon, James A

    2017-04-01

    Testosterone treatment increases sexual desire and well-being in women with hypoactive sexual desire disorder; however, many studies have shown only modest benefits limited to moderate doses. Unlike men, available data indicate women show a bell-shaped dose-response curve for testosterone, wherein a threshold dosage of testosterone leads to desirable sexual function effects, but exceeding this threshold results in a lack of further positive sexual effects or may have a negative impact. Emotional and physical side-effects of excess testosterone, including aggression and virilization, may counteract the modest benefits on sexual interaction, providing a possible explanation for a threshold dose of testosterone in women. In this commentary, we will review and critically analyze data supporting a curvilinear dose-response relationship between testosterone treatment and sexual activity in women with low libido, and also explore possible explanations for this observed relationship. Understanding optimal dosing of testosterone unique to women may bring us one step closer to overcoming regulatory barriers in treating female sexual dysfunction.

  9. An Extragradient Method and Proximal Point Algorithm for Inverse Strongly Monotone Operators and Maximal Monotone Operators in Banach Spaces

    Directory of Open Access Journals (Sweden)

    Plubtieng Somyot

    2009-01-01

    Full Text Available Abstract We introduce an iterative scheme for finding a common element of the solution set of a maximal monotone operator and the solution set of the variational inequality problem for an inverse strongly-monotone operator in a uniformly smooth and uniformly convex Banach space, and then we prove weak and strong convergence theorems by using the notion of generalized projection. The result presented in this paper extend and improve the corresponding results of Kamimura et al. (2004, and Iiduka and Takahashi (2008. Finally, we apply our convergence theorem to the convex minimization problem, the problem of finding a zero point of a maximal monotone operator and the complementary problem.

  10. An Extragradient Method and Proximal Point Algorithm for Inverse Strongly Monotone Operators and Maximal Monotone Operators in Banach Spaces

    Directory of Open Access Journals (Sweden)

    Somyot Plubtieng

    2009-01-01

    Full Text Available We introduce an iterative scheme for finding a common element of the solution set of a maximal monotone operator and the solution set of the variational inequality problem for an inverse strongly-monotone operator in a uniformly smooth and uniformly convex Banach space, and then we prove weak and strong convergence theorems by using the notion of generalized projection. The result presented in this paper extend and improve the corresponding results of Kamimura et al. (2004, and Iiduka and Takahashi (2008. Finally, we apply our convergence theorem to the convex minimization problem, the problem of finding a zero point of a maximal monotone operator and the complementary problem.

  11. On the Monotone Iterative Method for Set Valued Equation

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    This paper deals with the monotone iterative method for set- valued operator equation in ordered normed space. Some results for the case of single valued operator are generalized here, as an application, a discontinuous nonlinear differential equation problem is discussed.

  12. Monotone method for initial value problem for fractional diffusion equation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Shuqin

    2006-01-01

    Using the method of upper and lower solutions and its associated monotone iterative, consider the existence and uniqueness of solution of an initial value problem for the nonlinear fractional diffusion equation.

  13. Action-Maslov Homomorphism for Monotone Symplectic Manifolds

    CERN Document Server

    Branson, Mark

    2009-01-01

    We explore conditions under which the action-Maslov homomorphism vanishes on monotone symplectic manifolds. Our strategy involves showing that the units in the quantum homology, and thus the Seidel element, have a very specific form. Then we use induction to show that other relevant Gromov-Witten invariants vanish. We prove that these conditions hold for monotone products of projective spaces and for the Grassmannian of 2-planes in $\\C^4$.

  14. Isotonicity of the projection onto the monotone cone

    CERN Document Server

    Németh, A B

    2012-01-01

    A wedge (i.e., a closed nonempty set in the Euclidean space stable under addition and multiplication with non-negative scalars) induces by a standard way a semi-order (a reflexive and transitive binary relation) in the space. The wedges admitting isotone metric projection with respect to the semi-order induced by them are characterized. The obtained result is used to show that the monotone wedge (called monotone cone in regression theory) admits isotone projection.

  15. Monotonic loading of circular surface footings on clay

    Energy Technology Data Exchange (ETDEWEB)

    Ibsen, Lars Bo; Barari, Amin [Aalborg University, Aalborg (Denmark)

    2011-12-15

    Appropriate modeling of offshore foundations under monotonic loading is a significant challenge in geotechnical engineering. This paper reports experimental and numerical analyses, specifically investigating the response of circular surface footings during monotonic loading and elastoplastic behavior during reloading. By using the findings presented in this paper, it is possible to extend the model to simulate the vertical-load displacement response of offshore bucket foundations.

  16. Convergence for pseudo monotone semiflows on product ordered topological spaces

    Science.gov (United States)

    Yi, Taishan; Huang, Lihong

    In this paper, we consider a class of pseudo monotone semiflows, which only enjoy some weak monotonicity properties and are defined on product-ordered topological spaces. Under certain conditions, several convergence principles are established for each precompact orbit of such a class of semiflows to tend to an equilibrium, which improve and extend some corresponding results already known. Some applications to delay differential equations are presented.

  17. Non-monotonic size dependence of diffusion and levitation effect: a mode-coupling theory analysis.

    Science.gov (United States)

    Nandi, Manoj Kumar; Banerjee, Atreyee; Bhattacharyya, Sarika Maitra

    2013-03-28

    We present a study of diffusion of small tagged particles in a solvent, using mode coupling theory (MCT) analysis and computer simulations. The study is carried out for various interaction potentials. For the first time, using MCT, it is shown that only for strongly attractive interaction potential with allowing interpenetration between the solute-solvent pair the diffusion exhibits a non-monotonic solute size dependence which has earlier been reported in simulation studies [P. K. Ghorai and S. Yashonath, J. Phys. Chem. B 109, 5824-5835 (2005)]. For weak attractive and repulsive potential the solute size dependence of diffusion shows monotonic behaviour. It is also found that for systems where the interaction potential does not allow solute-solvent interpenetration, the solute cannot explore the neck of the solvent cage. Thus these systems even with strong attractive interaction will never show any non-monotonic size dependence of diffusion. This non-monotonic size dependence of diffusion has earlier been connected to levitation effect [S. Yashonath and P. Santikary, J. Phys. Chem. 98, 6368 (1994)]. We also show that although levitation is a dynamic phenomena, the effect of levitation can be obtained in the static radial distribution function.

  18. Dose response of subcutaneous GLP-1 infusion in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Torekov, Signe Sørensen; Kipnes, M S; Harley, R E;

    2011-01-01

    To evaluate the dose-response relationship of the recombinant glucagon-like peptide-1 (7-36) amide (rGLP-1) administered by continuous subcutaneous infusion (CSCI) in subjects with type 2 diabetes, with respect to reductions in fasting, postprandial and 11-h serum glucose profiles....

  19. Concord grape juice polyphenols and cardiovascular risk factors: dose-response relationships

    Science.gov (United States)

    Pure fruit juices provide nutritional value with evidence suggesting some of their benefits on biomarkers of cardiovascular disease risk may be derived from their constituent polyphenols, particularly flavonoids. However, few data from clinical trials are available on the dose-response relationship ...

  20. Dose Response Effects of Lisdexamfetamine Dimesylate Treatment in Adults with ADHD: An Exploratory Study

    Science.gov (United States)

    Faraone, Stephen V.; Spencer, Thomas J.; Kollins, Scott H.; Glatt, Stephen J.; Goodman, David

    2012-01-01

    Objective: To explore dose-response effects of lisdexamfetamine dimesylate (LDX) treatment for ADHD. Method: This was a 4-week, randomized, double-blinded, placebo-controlled, parallel-group, forced-dose titration study in adult participants, aged 18 to 55 years, meeting "Diagnostic and Statistical Manual of Mental Disorders" (4th ed., text rev.)…

  1. Empirical Evaluation of Meta-Analytic Approaches for Nutrient and Health Outcome Dose-Response Data

    Science.gov (United States)

    Yu, Winifred W.; Schmid, Christopher H.; Lichtenstein, Alice H.; Lau, Joseph; Trikalinos, Thomas A.

    2013-01-01

    The objective of this study is to empirically compare alternative meta-analytic methods for combining dose-response data from epidemiological studies. We identified meta-analyses of epidemiological studies that analyzed the association between a single nutrient and a dichotomous outcome. For each topic, we performed meta-analyses of odds ratios…

  2. Dose response association of pregnancy cigarette smoke exposure, childhood stature, overweight and obesity

    NARCIS (Netherlands)

    G. Koshy; A. Delpisheh; B.J. Brabin

    2011-01-01

    The combined dose response effects of pregnancy cigarette smoke exposure on childhood overweight, obesity and short stature have not been reported. A community based cross-sectional survey of 3038 children aged 5-11 years from 15 primary schools in Merseyside, UK. Self-completed parental questionnai

  3. Dose-Response Curve of Chromosome Aberrations in Human Lymphocytes Induced by Gamma-Rays

    Directory of Open Access Journals (Sweden)

    Y. Lusiyanti

    2013-12-01

    Full Text Available Chromosome aberration is a biomarker to predict the level of cell damage caused by exposure to ionizing radiation on human body. Dicentric chromosome is a specific chromosome aberration caused by ionizing radiation and is used as a gold standard biodosimetry of individuals over exposed to ionizing radiation. In radiation accident the dicentric assays has been applied as biological dosimetry to estimate radiation absorbed dose and also to confirm the radiation dose received to radiation workers.The purpose of this study was to generate a dose response curve of chromosome aberration (dicentric in human lymphocyte induced by gamma radiation. Peripheral blood samples from three non smoking healthy volunteers aged between 25-48 years old with informed consent were irradiated with dose between 0.1-4.0 Gy and a control using gamma teletherapy source. The culture procedure was conducted following the IAEA standard procedures with slight modifications. Analysis of dose-response curves used was LQ model Y = a + αD + βD2. The result showed that α and β values of the curve obtained were 0.018 ± 0.006 and 0.013 ± 0.002, respectively. Dose response calibration curve for dicentric chromosome aberrations in human lymphocytes induced by gamma-radiation fitted to linear quadratic model. In order to apply the dose response curve of chromosome aberration disentric for biodosimetry, this standar curve still need to be validated.

  4. Pharmacogenetic Predictors of Methylphenidate Dose-Response in Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Froehlich, Tanya E.; Epstein, Jeffery N.; Nick, Todd G.; Melguizo Castro, Maria S.; Stein, Mark A.; Brinkman, William B.; Graham, Amanda J.; Langberg, Joshua M.; Kahn, Robert S.

    2011-01-01

    Objective: Because of significant individual variability in attention-deficit/hyperactivity disorder (ADHD) medication response, there is increasing interest in identifying genetic predictors of treatment effects. This study examined the role of four catecholamine-related candidate genes in moderating methylphenidate (MPH) dose-response. Method:…

  5. Dose response of a new phytse on dry matter, calcium, and phosphorus digestibility in weaned piglets

    NARCIS (Netherlands)

    Bento, M.H.L.; Pedersen, C.; Plumstead, P.W.; Salmon, L.; Nyachoti, C.M.; Bikker, P.

    2012-01-01

    The present study evaluated the dose response of Buttiauxella phytase on apparent total tract digestibility (ATTD) of DM, Ca, and P in weaned pigs at 2 locations. Experimental diets fed to weaned pigs were a positive control (PC), a negative control (NC), and NC supplemented with increasing levels o

  6. Eosinophils in the bronchial mucosa in relation to methacholine dose-response curves in atopic asthma

    NARCIS (Netherlands)

    G.M. Moller (Trude); S.E. Overbeek (Shelley); C.G. van Helden-Meeuwsen; H.C. Hoogsteden (Henk); J.M. Bogaard (Jan)

    1999-01-01

    textabstractAsthma is characterized by both local infiltration of eosinophils in the bronchial mucosa and bronchial hyperreactivity (BHR). A detailed characterization of BHR implies analysis of a histamine or methacholine dose-response curve yielding not only the dose a

  7. Modeling and regression analysis of semiochemical dose-response curves of insect antennal reception and behavior

    Science.gov (United States)

    Dose-response curves with semiochemicals are reported in many articles in insect chemical ecology regarding neurophysiology and behavioral bioassays. Most such curves are shown in figures where the x-axis has order of magnitude increases in dosages versus responses on the y-axis represented by point...

  8. Pharmacogenetic Predictors of Methylphenidate Dose-Response in Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Froehlich, Tanya E.; Epstein, Jeffery N.; Nick, Todd G.; Melguizo Castro, Maria S.; Stein, Mark A.; Brinkman, William B.; Graham, Amanda J.; Langberg, Joshua M.; Kahn, Robert S.

    2011-01-01

    Objective: Because of significant individual variability in attention-deficit/hyperactivity disorder (ADHD) medication response, there is increasing interest in identifying genetic predictors of treatment effects. This study examined the role of four catecholamine-related candidate genes in moderating methylphenidate (MPH) dose-response. Method:…

  9. Estimating the predictive quality of dose-response after model selection.

    Science.gov (United States)

    Hu, Chuanpu; Dong, Yingwen

    2007-07-20

    Prediction of dose-response is important in dose selection in drug development. As the true dose-response shape is generally unknown, model selection is frequently used, and predictions based on the final selected model. Correctly assessing the quality of the predictions requires accounting for the uncertainties caused by the model selection process, which has been difficult. Recently, a new approach called data perturbation has emerged. It allows important predictive characteristics be computed while taking model selection into consideration. We study, through simulation, the performance of data perturbation in estimating standard error of parameter estimates and prediction errors. Data perturbation was found to give excellent prediction error estimates, although at times large Monte Carlo sizes were needed to obtain good standard error estimates. Overall, it is a useful tool to characterize uncertainties in dose-response predictions, with the potential of allowing more accurate dose selection in drug development. We also look at the influence of model selection on estimation bias. This leads to insights into candidate model choices that enable good dose-response prediction.

  10. Physical activity and cancer risk: dose-response and cancer, all sites and site-specific.

    Science.gov (United States)

    Thune, I; Furberg, A S

    2001-06-01

    The association between physical activity and overall and site-specific cancer risk is elaborated in relation to whether any observed dose-response association between physical activity and cancer can be interpreted in terms of how much physical activity (type, intensity, duration, frequency) is needed to influence site- and gender-specific cancer risk. Observational studies were reviewed that have examined the independent effect of the volume of occupational physical activity (OPA) and/or leisure time physical activity (LPA) on overall and site-specific cancer risk. The evidence of cohort and case-control studies suggests that both leisure time and occupational physical activity protect against overall cancer risk, with a graded dose-response association suggested in both sexes. Confounding effects such as diet, body weight, and parity are often included as a covariate in the analyses, with little influence on the observed associations. A crude graded inverse dose-response association was observed between physical activity and colon cancer in 48 studies including 40,674 colon/colorectal cancer cases for both sexes. A dose-response effect of physical activity on colon cancer risk was especially observed, when participation in activities of at least moderate activity (>4.5 MET) and demonstrated by activities expressed as MET-hours per week. An observed inverse association with a dose-response relationship between physical activity and breast cancer was also identified in the majority of the 41 studies including 108,031 breast cancer cases. The dose-response relationship was in particular observed in case-control studies and supported by observations in cohort studies when participation in activities of at least moderate activity (>4.5 MET) and demonstrated by activities expressed by MET-hours per week. This association between physical activity and breast cancer risk is possibly dependent on age at exposure, age at diagnosis, menopausal status and other effect

  11. Effects of measurement strategy and statistical analysis on dose-response relations between physical workload and low back pain

    OpenAIRE

    Jansen, Justin; Burdorf, Alex

    2003-01-01

    textabstractBACKGROUND: In epidemiological studies on physical workloads and back complaints, among the important features in modelling dose-response relations are the measurement strategy of the exposure and the nature of the dose-response relation that is assumed. AIM: To evaluate the effect of these two features on the strength of the dose-response relation between physical load and severe low back pain. METHODS: The study population consisted of 769 workers in nursing homes and homes for ...

  12. Systems Cancer Biology and the Controlling Mechanisms for the J-Shaped Cancer Dose Response: Towards Relaxing the LNT Hypothesis

    OpenAIRE

    Lou, In Chio; Zhao, Yuchao; Wu, YingJie; Ricci, Paolo F

    2012-01-01

    The hormesis phenomena or J-shaped dose response have been accepted as a common phenomenon regardless of the involved biological model, endpoint measured and chemical class/physical stressor. This paper first introduced a mathematical dose response model based on systems biology approach. It links molecular-level cell cycle checkpoint control information to clonal growth cancer model to predict the possible shapes of the dose response curves of Ionizing Radiation (IR) induced tumor transforma...

  13. Dose-response curve to salbutamol during acute and chronic treatment with formoterol in COPD

    Directory of Open Access Journals (Sweden)

    La Piana GE

    2011-07-01

    Full Text Available Giuseppe Emanuele La Piana¹, Luciano Corda², Enrica Bertella¹, Luigi Taranto Montemurro¹, Laura Pini¹, Claudio Tantucci¹¹Cattedra di Malattie dell'Apparato Respiratorio, Università di Brescia, ²Prima Divisione di Medicina Interna, Spedali Civili, Brescia, ItalyBackground: Use of short-acting ß2-agonists in chronic obstructive pulmonary disease (COPD during treatment with long-acting ß2-agonists is recommended as needed, but its effectiveness is unclear. The purpose of this study was to assess the additional bronchodilating effect of increasing doses of salbutamol during acute and chronic treatment with formoterol in patients with COPD.Methods: Ten patients with COPD underwent a dose-response curve to salbutamol (until 800 µg of cumulative dose after a 1-week washout (baseline, 8 hours after the first administration of formoterol 12 µg (day 1, and after a 12-week and 24-week period of treatment with formoterol (12 µg twice daily by dry powder inhaler. Peak expiratory flow, forced expiratory volume in one second (FEV1, forced vital capacity, and inspiratory capacity were measured at the different periods of treatment and at different steps of the dose-response curve.Results: Despite acute or chronic administration of formoterol, maximal values of peak expiratory flow, FEV1, and forced vital capacity after 800 µg of salbutamol were unchanged compared with baseline. The baseline FEV1 dose-response curve was steeper than that at day 1, week 12, or week 24 (P < 0.0001. Within each dose-response curve, FEV1 was different only at baseline and at day 1 (P < 0.001, when FEV1 was still greater at 800 µg than at 0 µg (P < 0.02. In contrast, the forced vital capacity dose-response curves were similar at the different periods, while within each dose-response curve, forced vital capacity was different in all instances (P < 0.001, always being higher at 800 µg than at 0 µg (P < 0.05.Conclusion: In patients with stable COPD, the maximal effect

  14. Driving performance impairments due to hypovigilance on monotonous roads.

    Science.gov (United States)

    Larue, Grégoire S; Rakotonirainy, Andry; Pettitt, Anthony N

    2011-11-01

    Drivers' ability to react to unpredictable events deteriorates when exposed to highly predictable and uneventful driving tasks. Highway design reduces the driving task mainly to a lane-keeping manoeuvre. Such a task is monotonous, providing little stimulation and this contributes to crashes due to inattention. Research has shown that driver's hypovigilance can be assessed with EEG measurements and that driving performance is impaired during prolonged monotonous driving tasks. This paper aims to show that two dimensions of monotony - namely road design and road side variability - decrease vigilance and impair driving performance. This is the first study correlating hypovigilance and driver performance in varied monotonous conditions, particularly on a short time scale (a few seconds). We induced vigilance decrement as assessed with an EEG during a monotonous driving simulator experiment. Road monotony was varied through both road design and road side variability. The driver's decrease in vigilance occurred due to both road design and road scenery monotony and almost independently of the driver's sensation seeking level. Such impairment was also correlated to observable measurements from the driver, the car and the environment. During periods of hypovigilance, the driving performance impairment affected lane positioning, time to lane crossing, blink frequency, heart rate variability and non-specific electrodermal response rates. This work lays the foundation for the development of an in-vehicle device preventing hypovigilance crashes on monotonous roads.

  15. Coloring intersection graphs of x-monotone curves in the plane

    CERN Document Server

    Suk, Andrew

    2012-01-01

    A class of graphs G is \\chi-bounded if the chromatic number of the graphs in G is bounded by some function of their clique number. We show that the class of intersection graphs of simple x-monotone curves in the plane intersecting a vertical line is \\chi-bounded. As a corollary, the class of intersection graphs of rays in the plane is \\chi-bounded.

  16. A projected gradient method with nonmonotonic backtracking technique for solving convex constrained monotone variational inequality problem

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Based on a differentiable merit function proposed by Taji,et al in "Mathematical Programming,1993,58: 369-383",a projected gradient trust region method for the monotone variational inequality problem with convex constraints is presented.Theoretical analysis is given which proves that the proposed algorithm is globally convergent and has a local quadratic convergence rate under some reasonable conditions.The results of numerical experiments are reported to show the effectiveness of the proposed algorithm.

  17. Diagnosis of constant faults in iteration-free circuits over monotone basis

    KAUST Repository

    Alrawaf, Saad Abdullah

    2014-03-01

    We show that for each iteration-free combinatorial circuit S over a basis B containing only monotone Boolean functions with at most five variables, there exists a decision tree for diagnosis of constant faults on inputs of gates with depth at most 7L(S) where L(S) is the number of gates in S. © 2013 Elsevier B.V. All rights reserved.

  18. Dualisation, decision lists and identification of monotone discrete functions

    NARCIS (Netherlands)

    J.C. Bioch (Cor)

    1998-01-01

    textabstractMany data-analysis algorithms in machine learning, datamining and a variety of other disciplines essentially operate on discrete multi-attribute data sets. By means of discretisation or binarisation also numerical data sets can be successfully analysed. Therefore, in this paper we view/i

  19. Dualisation, decision lists and identification of monotone discrete functions

    NARCIS (Netherlands)

    J.C. Bioch (Cor)

    1998-01-01

    textabstractMany data-analysis algorithms in machine learning, datamining and a variety of other disciplines essentially operate on discrete multi-attribute data sets. By means of discretisation or binarisation also numerical data sets can be successfully analysed. Therefore, in this paper we

  20. An update on modeling dose-response relationships: Accounting for correlated data structure and heterogeneous error variance in linear and nonlinear mixed models.

    Science.gov (United States)

    Gonçalves, M A D; Bello, N M; Dritz, S S; Tokach, M D; DeRouchey, J M; Woodworth, J C; Goodband, R D

    2016-05-01

    Advanced methods for dose-response assessments are used to estimate the minimum concentrations of a nutrient that maximizes a given outcome of interest, thereby determining nutritional requirements for optimal performance. Contrary to standard modeling assumptions, experimental data often present a design structure that includes correlations between observations (i.e., blocking, nesting, etc.) as well as heterogeneity of error variances; either can mislead inference if disregarded. Our objective is to demonstrate practical implementation of linear and nonlinear mixed models for dose-response relationships accounting for correlated data structure and heterogeneous error variances. To illustrate, we modeled data from a randomized complete block design study to evaluate the standardized ileal digestible (SID) Trp:Lys ratio dose-response on G:F of nursery pigs. A base linear mixed model was fitted to explore the functional form of G:F relative to Trp:Lys ratios and assess model assumptions. Next, we fitted 3 competing dose-response mixed models to G:F, namely a quadratic polynomial (QP) model, a broken-line linear (BLL) ascending model, and a broken-line quadratic (BLQ) ascending model, all of which included heteroskedastic specifications, as dictated by the base model. The GLIMMIX procedure of SAS (version 9.4) was used to fit the base and QP models and the NLMIXED procedure was used to fit the BLL and BLQ models. We further illustrated the use of a grid search of initial parameter values to facilitate convergence and parameter estimation in nonlinear mixed models. Fit between competing dose-response models was compared using a maximum likelihood-based Bayesian information criterion (BIC). The QP, BLL, and BLQ models fitted on G:F of nursery pigs yielded BIC values of 353.7, 343.4, and 345.2, respectively, thus indicating a better fit of the BLL model. The BLL breakpoint estimate of the SID Trp:Lys ratio was 16.5% (95% confidence interval [16.1, 17.0]). Problems with

  1. TH-E-BRF-03: A Multivariate Interaction Model for Assessment of Hippocampal Vascular Dose-Response and Early Prediction of Radiation-Induced Neurocognitive Dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Farjam, R; Pramanik, P; Srinivasan, A; Chapman, C; Tsien, C; Lawrence, T; Cao, Y [University of Michigan, Ann Arbor, MI (United States)

    2014-06-15

    Purpose: Vascular injury could be a cause of hippocampal dysfunction leading to late neurocognitive decline in patients receiving brain radiotherapy (RT). Hence, our aim was to develop a multivariate interaction model for characterization of hippocampal vascular dose-response and early prediction of radiation-induced late neurocognitive impairments. Methods: 27 patients (17 males and 10 females, age 31–80 years) were enrolled in an IRB-approved prospective longitudinal study. All patients were diagnosed with a low-grade glioma or benign tumor and treated by 3-D conformal or intensity-modulated RT with a median dose of 54 Gy (50.4–59.4 Gy in 1.8− Gy fractions). Six DCE-MRI scans were performed from pre-RT to 18 months post-RT. DCE data were fitted to the modified Toft model to obtain the transfer constant of gadolinium influx from the intravascular space into the extravascular extracellular space, Ktrans, and the fraction of blood plasma volume, Vp. The hippocampus vascular property alterations after starting RT were characterized by changes in the hippocampal mean values of, μh(Ktrans)τ and μh(Vp)τ. The dose-response, Δμh(Ktrans/Vp)pre->τ, was modeled using a multivariate linear regression considering integrations of doses with age, sex, hippocampal laterality and presence of tumor/edema near a hippocampus. Finally, the early vascular dose-response in hippocampus was correlated with neurocognitive decline 6 and 18 months post-RT. Results: The μh(Ktrans) increased significantly from pre-RT to 1 month post-RT (p<0.0004). The multivariate model showed that the dose effect on Δμh(Ktrans)pre->1M post-RT was interacted with sex (p<0.0007) and age (p<0.00004), with the dose-response more pronounced in older females. Also, the vascular dose-response in the left hippocampus of females was significantly correlated with memory function decline at 6 (r = − 0.95, p<0.0006) and 18 (r = −0.88, p<0.02) months post-RT. Conclusion: The hippocampal vascular

  2. Aspartame tablets-gamma dose response and usability for routine radiation processing dosimetry using spectrophotometry

    Energy Technology Data Exchange (ETDEWEB)

    Shinde, S.H. [Radiation Safety Systems Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)]. E-mail: shs_barc@yahoo.com; Mukherjee, T. [Radiation Safety Systems Division, Chemistry Group, Bhabha Atomic Research Centre, Mumbai 400 085 (India)

    2007-02-15

    Aspartame tablets were studied for gamma dose response, using spectrophotometric read-out method. The optimum concentration for ferrous ions was 2x10{sup -4}moldm{sup -3} and xylenol orange with 2.5x10{sup -1}moldm{sup -3} of sulphuric acid for the optimum acidity in FX solution. Wavelength of maximum absorbance is 548nm. Post-irradiation stability is appreciable i.e. for not less than one month. Dose response is non-linear with third order polynomial fit, in the dose range of 1000-10000Gy. This system of aspartame was further used for carrying out relative percentage dose profile measurement in Gamma Cell-220. Results obtained were inter-compared with that of a glutamine dosimeter, which showed that maximum difference between the values of aspartame and glutamine systems is within +/-10%.

  3. A Theoretical Model for the Hormetic Dose-response Curve for Anticancer Agents.

    Science.gov (United States)

    Yoshimasu, Tatsuya; Ohashi, Takuya; Oura, Shoji; Kokawa, Yozo; Kawago, Mitsumasa; Hirai, Yoshimitsu; Miyasaka, Miwako; Nishiguchi, Haruka; Kawashima, Sayoko; Yata, Yumi; Honda, Mariko; Fujimoto, Takahiro; Okamura, Yoshitaka

    2015-11-01

    In the present article, we quantitatively evaluated the dose-response relationship of hormetic reactions of anticancer agents in vitro. Serial dilutions of gemcitabine, cisplatin, 5-fluorouracil, vinorelbine, and paclitaxel were administered to the A549 non-small-cell lung cancer cell line. The bi-phasic sigmoidal curve with hormetic and cytotoxic effects is given by the formula y=(a-b/(1+exp(c(*)log(x)-d)))/(1+exp(e(*)log(x)-f)), that was used to perform a non-linear least square regression. The dose-responses of the five anticancer agents were fitted to this equation. Gemcitabine and 5-fluorouracil, which had the lowest ED50 for their hormetic reaction, had the most pronounced promotive effects out of the five anticancer agents tested. The hormetic reaction progressed exponentially with culturing time. Our theoretical model will be useful in predicting how hormetic reactions affect patients with malignant tumors.

  4. Dose Effects of Ion Beam Exposure on Deinococcus Radiodurans: Survival and Dose Response

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To explore the survival and dose response of organism for different radiation sources is of great importance in the research of radiobiology. In this study, the survival-dose response of Deinococcus radiodurans (E.coli, as the control) for ultra-violet (UV), γ-rays radiation and ion beam exposure was investigated. The shoulder type of survival curves were found for both UV and γ-ray ionizing radiation, but the saddle type of survival curves were shown for H+ 、 N+( 20keV and 30keV) and Ar+ beam exposure. This dose effect of the survival initially decreased withthe increase in dose and then increased in the high dose range and finally decreased again in thehigher dose range. Our experimental results suggest that D. radiodurans, which is considerablyradio-resistant to UV and x-ray and γ-ray ionizing radiation, do not resist ion beam exposure.

  5. Epidemiological methods for assessing dose-response and dose-effect relationships

    DEFF Research Database (Denmark)

    Kjellström, Tord; Grandjean, Philippe

    2007-01-01

    of the Toxic Effects of Metals Aluminum Antimony Arsenic Barium Beryllium Bismuth Cadmium Chromium Cobalt Copper Gallium and Semiconductor Compounds Germanium Indium Iron Lead Manganese Mercury Molybdenum Nickel Palladium Platinum Selenium Silver Tellurium Thallium Tin Titanium Tungsten Uranium Vanadium Zinc...... and their compounds. An entirely new structure and illustrations represent the vast array of advancements made since the last edition. Special emphasis has been placed on the toxic effects in humans with chapters on the diagnosis, treatment and prevention of metal poisoning. This up-to-date reference provides easy...... Selected Molecular Mechanisms of Metal Toxicity and Carcinogenicity General Considerations of Dose-Effect and Dose-Response Relationships Interactions in Metal Toxicology Epidemiological Methods for Assessing Dose-Response and Dose-Effect Relationships Essential Metals: Assessing Risks from Deficiency...

  6. Dose-response relationship between periodontal inflamed surface area and HbA1c in type 2 Diabetics

    NARCIS (Netherlands)

    Nesse, Willem; Linde, Annemiek; Abbas, Frank; Spijkervet, Frederik Karst Lucien; Dijkstra, Pieter Ubele; de Brabander, Eric Carl; Gerstenbluth, Izzy; Vissink, Arjan

    2009-01-01

    Nesse W, Linde A, Abbas F, Spijkervet FKL, Dijkstra PU, de Brabander EC, Gerstenbluth I, Vissink A. Dose-response relationship between periodontal inflamed surface area and HbA1c in type 2 diabetics. J Clin Periodontol 2009; 36: 295-300. doi: 10.1111/j.1600-051X.2009.01377.x. A dose-response relatio

  7. Effects of measurement strategy and statistical analysis on dose-response relations between physical workload and low back pain

    NARCIS (Netherlands)

    J.J.P. Jansen (Justin); A. Burdorf (Alex)

    2003-01-01

    textabstractBACKGROUND: In epidemiological studies on physical workloads and back complaints, among the important features in modelling dose-response relations are the measurement strategy of the exposure and the nature of the dose-response relation that is assumed. AIM: To evaluat

  8. Systems Cancer Biology and the Controlling Mechanisms for the J-Shaped Cancer Dose Response: Towards Relaxing the LNT Hypothesis.

    Science.gov (United States)

    Lou, In Chio; Zhao, Yuchao; Wu, Yingjie; Ricci, Paolo F

    2012-01-01

    The hormesis phenomena or J-shaped dose response have been accepted as a common phenomenon regardless of the involved biological model, endpoint measured and chemical class/physical stressor. This paper first introduced a mathematical dose response model based on systems biology approach. It links molecular-level cell cycle checkpoint control information to clonal growth cancer model to predict the possible shapes of the dose response curves of Ionizing Radiation (IR) induced tumor transformation frequency. J-shaped dose response curves have been captured with consideration of cell cycle checkpoint control mechanisms. The simulation results indicate the shape of the dose response curve relates to the behavior of the saddle-node points of the model in the bifurcation diagram. A simplified version of the model in previous work of the authors was used mathematically to analyze behaviors relating to the saddle-node points for the J-shaped dose response curve. It indicates that low-linear energy transfer (LET) is more likely to have a J-shaped dose response curve. This result emphasizes the significance of systems biology approach, which encourages collaboration of multidiscipline of biologists, toxicologists and mathematicians, to illustrate complex cancer-related events, and confirm the biphasic dose-response at low doses.

  9. Dose-response relationship between periodontal inflamed surface area and HbA1c in type 2 Diabetics

    NARCIS (Netherlands)

    Nesse, Willem; Linde, Annemiek; Abbas, Frank; Spijkervet, Frederik Karst Lucien; Dijkstra, Pieter Ubele; de Brabander, Eric Carl; Gerstenbluth, Izzy; Vissink, Arjan

    Nesse W, Linde A, Abbas F, Spijkervet FKL, Dijkstra PU, de Brabander EC, Gerstenbluth I, Vissink A. Dose-response relationship between periodontal inflamed surface area and HbA1c in type 2 diabetics. J Clin Periodontol 2009; 36: 295-300. doi: 10.1111/j.1600-051X.2009.01377.x. A dose-response

  10. A new method for synthesizing radiation dose-response data from multiple trials applied to prostate cancer

    DEFF Research Database (Denmark)

    Diez, Patricia; Vogelius, Ivan S; Bentzen, Søren M

    2010-01-01

    A new method is presented for synthesizing dose-response data for biochemical control of prostate cancer according to study design (randomized vs. nonrandomized) and risk group (low vs. intermediate-high).......A new method is presented for synthesizing dose-response data for biochemical control of prostate cancer according to study design (randomized vs. nonrandomized) and risk group (low vs. intermediate-high)....

  11. Estimating monotonic rates from biological data using local linear regression.

    Science.gov (United States)

    Olito, Colin; White, Craig R; Marshall, Dustin J; Barneche, Diego R

    2017-03-01

    Accessing many fundamental questions in biology begins with empirical estimation of simple monotonic rates of underlying biological processes. Across a variety of disciplines, ranging from physiology to biogeochemistry, these rates are routinely estimated from non-linear and noisy time series data using linear regression and ad hoc manual truncation of non-linearities. Here, we introduce the R package LoLinR, a flexible toolkit to implement local linear regression techniques to objectively and reproducibly estimate monotonic biological rates from non-linear time series data, and demonstrate possible applications using metabolic rate data. LoLinR provides methods to easily and reliably estimate monotonic rates from time series data in a way that is statistically robust, facilitates reproducible research and is applicable to a wide variety of research disciplines in the biological sciences. © 2017. Published by The Company of Biologists Ltd.

  12. Monotone traveling wavefronts of the KPP-Fisher delayed equation

    CERN Document Server

    Gomez, Adrian

    2010-01-01

    In the early 2000's, Gourley (2000), Wu et al. (2001), Ashwin et al. (2002) initiated the study of the positive wavefronts in the delayed Kolmogorov-Petrovskii-Piskunov-Fisher equation. Since then, this model has become one of the most popular objects in the studies of traveling waves for the monostable delayed reaction-diffusion equations. In this paper, we give a complete solution to the problem of existence and uniqueness of monotone waves in the KPP-Fisher equation. We show that each monotone traveling wave can be found via an iteration procedure. The proposed approach is based on the use of special monotone integral operators (which are different from the usual Wu-Zou operator) and appropriate upper and lower solutions associated to them. The analysis of the asymptotic expansions of the eventual traveling fronts at infinity is another key ingredient of our approach.

  13. DOSE RESPONSE CURVE OF 60Co FOR PREMATURE CONDENSED CHROMOSOME FRAGMENTS OF HUMAN LYMPHOCYTES

    Institute of Scientific and Technical Information of China (English)

    高锦声; 郑斯英; 等

    1995-01-01

    The dose-response curves obtained by premature condensed chromosome(PCC) and conventional cellular genetic methods can be represented by two linear equations.The ratio of the slopes,KPCC/KM1,is about 28,In compartison to the conventional method.The PCC method has many advantages;e.g.it is faster,simopler,more sensitive and accurate.Its significance in the study of radiation damage is also discussed.

  14. Analysis of Dose Response for Circulatory Disease After Radiotherapy for Benign Disease

    Energy Technology Data Exchange (ETDEWEB)

    Little, Mark P., E-mail: mark.little@nih.gov [Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza South, Rockville, Maryland (United States); Kleinerman, Ruth A. [Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza South, Rockville, Maryland (United States); Stovall, Marilyn; Smith, Susan A. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mabuchi, Kiyohiko [Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza South, Rockville, Maryland (United States)

    2012-12-01

    Purpose: To assess the shape of the dose-response for various circulatory disease endpoints, and modifiers by age and time since exposure. Methods and Materials: This was an analysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by circulatory disease endpoint (ischemic heart, cerebrovascular, other circulatory disease). Results: There were significant excess risks for all circulatory disease, with an excess relative risk Gy{sup -1} of 0.082 (95% CI 0.031-0.140), and ischemic heart disease, with an excess relative risk Gy{sup -1} of 0.102 (95% CI 0.039-0.174) (both p = 0.01), and indications of excess risk for stroke. There were no statistically significant (p > 0.2) differences between risks by endpoint, and few indications of curvature in the dose-response. There were significant (p < 0.001) modifications of relative risk by time since exposure, the magnitude of which did not vary between endpoints (p > 0.2). Risk modifications were similar if analysis was restricted to patients receiving radiation, although the relative risks were slightly larger and the risk of stroke failed to be significant. The slopes of the dose-response were generally consistent with those observed in the Japanese atomic bomb survivors and in occupationally and medically exposed groups. Conclusions: There were excess risks for a variety of circulatory diseases in this dataset, with significant modification of risk by time since exposure. The consistency of the dose-response slopes with those observed in radiotherapeutically treated groups at much higher dose, as well as in lower dose-exposed cohorts such as the Japanese atomic bomb survivors and nuclear workers, implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.

  15. Diethylene glycol-induced toxicities show marked threshold dose response in rats

    Energy Technology Data Exchange (ETDEWEB)

    Landry, Greg M., E-mail: Landry.Greg@mayo.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Dunning, Cody L., E-mail: cdunni@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Abreo, Fleurette, E-mail: fabreo@lsuhsc.edu [Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Latimer, Brian, E-mail: blatim@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Orchard, Elysse, E-mail: eorcha@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Division of Animal Resources, Louisiana State University Health Sciences Center, Shreveport, LA (United States); McMartin, Kenneth E., E-mail: kmcmar@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States)

    2015-02-01

    Diethylene glycol (DEG) exposure poses risks to human health because of widespread industrial use and accidental exposures from contaminated products. To enhance the understanding of the mechanistic role of metabolites in DEG toxicity, this study used a dose response paradigm to determine a rat model that would best mimic DEG exposure in humans. Wistar and Fischer-344 (F-344) rats were treated by oral gavage with 0, 2, 5, or 10 g/kg DEG and blood, kidney and liver tissues were collected at 48 h. Both rat strains treated with 10 g/kg DEG had equivalent degrees of metabolic acidosis, renal toxicity (increased BUN and creatinine and cortical necrosis) and liver toxicity (increased serum enzyme levels, centrilobular necrosis and severe glycogen depletion). There was no liver or kidney toxicity at the lower DEG doses (2 and 5 g/kg) regardless of strain, demonstrating a steep threshold dose response. Kidney diglycolic acid (DGA), the presumed nephrotoxic metabolite of DEG, was markedly elevated in both rat strains administered 10 g/kg DEG, but no DGA was present at 2 or 5 g/kg, asserting its necessary role in DEG-induced toxicity. These results indicate that mechanistically in order to produce toxicity, metabolism to and significant target organ accumulation of DGA are required and that both strains would be useful for DEG risk assessments. - Highlights: • DEG produces a steep threshold dose response for kidney injury in rats. • Wistar and F-344 rats do not differ in response to DEG-induced renal injury. • The dose response for renal injury closely mirrors that for renal DGA accumulation. • Results demonstrate the importance of DGA accumulation in producing kidney injury.

  16. Modeling dose-response relationships of the effects of fesoterodine in patients with overactive bladder

    Directory of Open Access Journals (Sweden)

    Cardozo Linda

    2010-08-01

    Full Text Available Abstract Background Fesoterodine is an antimuscarinic for the treatment of overactive bladder, a syndrome of urgency, with or without urgency urinary incontinence (UUI, usually with increased daytime frequency and nocturia. Our objective was to develop predictive models to describe the dose response of fesoterodine. Methods Data from subjects enrolled in double-blind, placebo-controlled phase II and III trials were used for developing longitudinal dose-response models. Results The models predicted that clinically significant and near-maximum treatment effects would be seen within 3 to 4 weeks after treatment initiation. For a typical patient with 11 micturitions per 24 hours at baseline, predicted change was -1.2, -1.7, and -2.2 micturitions for placebo and fesoterodine 4 mg and 8 mg, respectively. For a typical patient with 2 UUI episodes per 24 hours at baseline, predicted change was -1.05, -1.26, and -1.43 UUI episodes for placebo and fesoterodine 4 mg and 8 mg, respectively. Increase in mean voided volume was estimated at 9.7 mL for placebo, with an additional 14.2 mL and 28.4 mL for fesoterodine 4 mg and 8 mg, respectively. Conclusions A consistent dose response for fesoterodine was demonstrated for bladder diary endpoints in subjects with overactive bladder, a result that supports the greater efficacy seen with fesoterodine 8 mg in post hoc analyses of clinical trial data. The dose-response models can be used to predict outcomes for doses not studied or for patient subgroups underrepresented in clinical trials. Trial Registration The phase III trials used in this analysis have been registered at ClinicalTrials.gov (NCT00220363 and NCT00138723.

  17. Modeling dose-response relationships of the effects of fesoterodine in patients with overactive bladder.

    Science.gov (United States)

    Cardozo, Linda; Khullar, Vik; El-Tahtawy, Ahmed; Guan, Zhonghong; Malhotra, Bimal; Staskin, David

    2010-08-19

    Fesoterodine is an antimuscarinic for the treatment of overactive bladder, a syndrome of urgency, with or without urgency urinary incontinence (UUI), usually with increased daytime frequency and nocturia. Our objective was to develop predictive models to describe the dose response of fesoterodine. Data from subjects enrolled in double-blind, placebo-controlled phase II and III trials were used for developing longitudinal dose-response models. The models predicted that clinically significant and near-maximum treatment effects would be seen within 3 to 4 weeks after treatment initiation. For a typical patient with 11 micturitions per 24 hours at baseline, predicted change was -1.2, -1.7, and -2.2 micturitions for placebo and fesoterodine 4 mg and 8 mg, respectively. For a typical patient with 2 UUI episodes per 24 hours at baseline, predicted change was -1.05, -1.26, and -1.43 UUI episodes for placebo and fesoterodine 4 mg and 8 mg, respectively. Increase in mean voided volume was estimated at 9.7 mL for placebo, with an additional 14.2 mL and 28.4 mL for fesoterodine 4 mg and 8 mg, respectively. A consistent dose response for fesoterodine was demonstrated for bladder diary endpoints in subjects with overactive bladder, a result that supports the greater efficacy seen with fesoterodine 8 mg in post hoc analyses of clinical trial data. The dose-response models can be used to predict outcomes for doses not studied or for patient subgroups underrepresented in clinical trials. The phase III trials used in this analysis have been registered at ClinicalTrials.gov (NCT00220363 and NCT00138723).

  18. Dose response of hydrazine - Deproteinated tooth enamel under blue light stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Yuece, Ulkue Rabia, E-mail: ulkuyuce@hotmail.co [Ankara University, Faculty of Engineering, Department of Engineering Physics, 06100, Tandogan - Ankara (Turkey); Meric, Niyazi, E-mail: meric@ankara.edu.t [Ankara University, Faculty of Engineering, Department of Engineering Physics, 06100, Tandogan - Ankara (Turkey); Atakol, Orhan, E-mail: atakol@science.ankara.edu.t [Ankara University, Science Faculty, Department of Chemistry, 06100, Tandogan - Ankara (Turkey); Yasar, Fusun, E-mail: ab121310@adalet.gov.t [Council of Forensic Medicine, Ankara Branch, Ankara (Turkey)

    2010-08-15

    The beta dose response and Optically Stimulated Luminescence (OSL) signal stability characteristics of human tooth enamel deproteinated by hydrazine reagent under blue photon stimulation are reported. Removal of the protein organic component of tooth enamel resulted in a higher OSL sensitivity and slower fading of OSL signals. The effect of chemical sample preparation on the enamel sample sensitivity is discussed and further steps to make this deproteinization treatment suitable for in vitro dose reconstruction studies are suggested.

  19. Testing the Capacity of the National Biological Dose Response Plan (NBDRP) EX40801

    Science.gov (United States)

    2009-11-01

    providing radiation biological dose estimates using the dicentric chromosome assay (DCA). As indicated in the CRTI-06-0146RD charter, the existing...laboratories of the National Biological Dose Response Plan plus two US laboratories. Samples were scored for the dicentric chromosome assay and the CBMN...Wilkins, R.C. QuickScan dicentric chromosome analysis for radiation biodosimetry , Health Physics Journal, In Press (2009). 2. McNamee, J.P., Flegal

  20. Bayesian fitting of a logistic dose-response curve with numerically derived priors.

    Science.gov (United States)

    Huson, L W; Kinnersley, N

    2009-01-01

    In this report we describe the Bayesian analysis of a logistic dose-response curve in a Phase I study, and we present two simple and intuitive numerical approaches to construction of prior probability distributions for the model parameters. We combine these priors with the expert prior opinion and compare the results of the analyses with those obtained from the use of alternative prior formulations.

  1. Childhood adversity specificity and dose-response effect in non-affective first-episode psychosis

    DEFF Research Database (Denmark)

    Trauelsen, Anne Marie; Bendall, Sarah; Jansen, Jens Einar

    2015-01-01

    BACKGROUND: Reviews conclude that childhood and adolescence sexual, physical, emotional abuse and emotional and physical neglect are all risk factors for psychosis. However, studies suggest only some adversities are associated with psychosis. Dose-response effects of several adversities on risk......% of the control group. Childhood and adolescent sexual, physical, emotional abuse, and physical and emotional neglect, separation and institutionalization were about four to 17 times higher for the FEP group (all p

  2. Mathematical Modeling of Allelopathy. III. A Model for Curve-Fitting Allelochemical Dose Responses

    OpenAIRE

    Liu, Li; An, Min; Johnson, Ian R.; Lovett, John V.

    2003-01-01

    Bioassay techniques are often used to study the effects of allelochemicals on plant processes, and it is generally observed that the processes are stimulated at low allelochemical concentrations and inhibited as the concentrations increase. A simple empirical model is presented to analyze this type of response. The stimulation-inhibition properties of allelochemical-dose responses can be described by the parameters in the model. The indices, p% reductions, are calculated to assess the alleloc...

  3. Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Eugene [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Corbett, James R. [Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Moran, Jean M. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Griffith, Kent A. [Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (United States); Marsh, Robin B.; Feng, Mary; Jagsi, Reshma; Kessler, Marc L. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Ficaro, Edward C. [Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Pierce, Lori J., E-mail: ljpierce@umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

    2013-03-15

    Purpose: To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. Methods and Materials: On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses to the heart and coronary arteries were quantified. Results: The mean difference in pre- and post-RT PD was −0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. Conclusions: Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF.

  4. Concord Grape Juice Polyphenols and Cardiovascular Risk Factors: Dose-Response Relationships

    Directory of Open Access Journals (Sweden)

    Jeffrey B. Blumberg

    2015-12-01

    Full Text Available Pure fruit juices provide nutritional value with evidence suggesting some of their benefits on biomarkers of cardiovascular disease risk may be derived from their constituent polyphenols, particularly flavonoids. However, few data from clinical trials are available on the dose-response relationship of fruit juice flavonoids to these outcomes. Utilizing the results of clinical trials testing single doses, we have analyzed data from studies of 100% Concord grape juice by placing its flavonoid content in the context of results from randomized clinical trials of other polyphenol-rich foods and beverages describing the same outcomes but covering a broader range of intake. We selected established biomarkers determined by similar methods for measuring flow-mediated vasodilation (FMD, blood pressure, platelet aggregation, and the resistance of low density lipoprotein cholesterol (LDL to oxidation. Despite differences among the clinical trials in the treatment, subjects, and duration, correlations were observed between the dose and FMD. Inverse dose-response relationships, albeit with lower correlation coefficients, were also noted for the other outcomes. These results suggest a clear relationship between consumption of even modest serving sizes of Concord grape juice, flavonoid intake, and effects on risk factors for cardiovascular disease. This approach to dose-response relationships may prove useful for testing other individual foods and beverages.

  5. Perception and annoyance due to wind turbine noise--a dose-response relationship.

    Science.gov (United States)

    Pedersen, Eja; Waye, Kerstin Persson

    2004-12-01

    Installed global wind power increased by 26% during 2003, with U.S and Europe accounting for 90% of the cumulative capacity. Little is known about wind turbines' impact on people living in their vicinity. The aims of this study were to evaluate the prevalence of annoyance due to wind turbine noise and to study dose-response relationships. Interrelationships between noise annoyance and sound characteristics, as well as the influence of subjective variables such as attitude and noise sensitivity, were also assessed. A cross-sectional study was performed in Sweden in 2000. Responses were obtained through questionnaires (n = 351; response rate 68.4%), and doses were calculated as A-weighted sound pressure levels for each respondent. A statistically significant dose-response relationship was found, showing higher proportion of people reporting perception and annoyance than expected from the present dose-response relationships for transportation noise. The unexpected high proportion of annoyance could be due to visual interference, influencing noise annoyance, as well as the presence of intrusive sound characteristics. The respondents' attitude to the visual impact of wind turbines on the landscape scenery was found to influence noise annoyance.

  6. Arsenite Effects on Mitochondrial Bioenergetics in Human and Mouse Primary Hepatocytes Follow a Nonlinear Dose Response

    Directory of Open Access Journals (Sweden)

    Hemantkumar Chavan

    2017-01-01

    Full Text Available Arsenite is a known carcinogen and its exposure has been implicated in a variety of noncarcinogenic health concerns. Increased oxidative stress is thought to be the primary cause of arsenite toxicity and the toxic effect is thought to be linear with detrimental effects reported at all concentrations of arsenite. But the paradigm of linear dose response in arsenite toxicity is shifting. In the present study we demonstrate that arsenite effects on mitochondrial respiration in primary hepatocytes follow a nonlinear dose response. In vitro exposure of primary hepatocytes to an environmentally relevant, moderate level of arsenite results in increased oxidant production that appears to arise from changes in the expression and activity of respiratory Complex I of the mitochondrial proton circuit. In primary hepatocytes the excess oxidant production appears to elicit adaptive responses that promote resistance to oxidative stress and a propensity to increased proliferation. Taken together, these results suggest a nonlinear dose-response characteristic of arsenite with low-dose arsenite promoting adaptive responses in a process known as mitohormesis, with transient increase in ROS levels acting as transducers of arsenite-induced mitohormesis.

  7. Quality control procedures for dose-response curve generation using nanoliter dispense technologies.

    Science.gov (United States)

    Quintero, Catherine; Rosenstein, Craig; Hughes, Bethany; Middleton, Richard; Kariv, Ilona

    2007-09-01

    With the advancement of high-throughput biomolecular screening techniques to the lead optimization stage, there is a critical need to quality control (QC) dose-response curves generated by robotic liquid handlers to ensure accurate affinity determinations. One challenge in evaluating the performance of liquid handlers is identifying and validating a robust method for testing dispense volumes across different instruments. Although traditional automated liquid handlers are still considered the standard platform in many laboratories, nanoliter dispensers are becoming more common and pose new challenges for routine quality control procedures. For example, standard gravimetric measurements are unreliable for testing the accuracy of nanoliter liquid dispenses. However, nanoliter dispensing technology allows for the conservation of compound, reduces compound carryover from well to well through discrete dispenses, and eliminates the need for intermediate compound dilution steps to achieve a low final DMSO assay concentration. Moreover, an intermediate dilution step in aqueous solution might result in compound precipitation at high concentrations. This study compared representative automation procedures done on a variety of liquid dispensers, including manual, traditional, and nanodispense volumes. The data confirmed the importance of establishing robust QC procedures for dose-response generation in addition to accuracy and precision determinations for each instrument, and they validated the use of nanoliter pipettors for dose-response testing. The results of this study also support the requirement for thorough mixing during serial compound dilutions prepared for high-throughput lead optimization strategies using traditional liquid handlers.

  8. Interpreting 'dose-response' curves using homeodynamic data: with an improved explanation for hormesis.

    Science.gov (United States)

    Stebbing, A R D

    2009-04-15

    A re-interpretation of the 'dose-response' curve is given that accommodates homeostasis. The outcome, or overall effect, of toxicity is the consequence of toxicity that is moderated by homeodynamic responses. Equilibrium is achieved by a balance of opposing forces of toxic inhibition countered by a stimulatory response. A graphical model is given consisting of two linked curves (response vs concentration and effect vs concentration), which provide the basis for a re-interpretation of the 'dose-response' curve. The model indicates that such relationships are non-linear with a threshold, which is due to homeodynamic responses. Subthreshold concentrations in 'dose-response' curves provide the sum of toxic inhibition minus the homeodynamic response; the response itself is unseen in serving its purpose of neutralizing perturbation. This interpretation suggests why the alpha- and beta-curves are non-linear. The beta-curve indicates adaptive overcorrection to toxicity that confers greater resistance to subsequent toxic exposure, with hormesis as an epiphenomenon.

  9. Dose responses for Colletotrichum lindemuthianum elicitor-mediated enzyme induction in French bean cell suspension cultures.

    Science.gov (United States)

    Dixon, R A; Dey, P M; Murphy, D L; Whitehead, I M

    1981-03-01

    The induction of L-phenylalanine ammonialyase (PAL, EC 4.3.1.5) and flavanone synthase in French bean cell suspension cultures in response to heat-released elicitor from cell walls of the phytopathogenic fungus Colletotrichum lindemuthianum is highly dependent upon elicitor concentration. The elicitor dose-response curve for PAL induction shows two maxima at around 17.5 and 50 μg elicitor carbohydrate per ml culture, whereas the flavanone synthase response shows one maximum at around 100 μg ml(-1). The PAL response is independent of the elicitor concentration present during the lag phase of enzyme induction; if the initial elicitor concentration is increased after 2 h by addition of extra elicitor, or decreased by dilution of the cultures, the dose response curves obtained reflect the concentration of elicitor present at the time of harvest. PAL induction is not prevented by addition of methyl sugar derivatives to the cultures; α-methyl-D-glucoside, itself a weak elicitor of PAL activity, elicits a multiphasic PAL response when increasing concentrations are added in the presence of Colletotrichum elicitor. Eight fractions with different monosaccharide compositions, obtained from the crude elicitor by gel-filtration, each elicit different dose-responses for PAL induction; the response to unfractionated elicitor is not the sum of the response to the isolated fractions. There is no correlation between the ability of the fractions to induce PAL in the cultures and their ability to act as elicitors of isoflavonoid phytoalexin accumulation in bean hypocotyls.

  10. Ultimate generalization to monotonicity for uniform convergence of trigonometric series

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Chaundy and Jolliffe proved that if {a n } is a non-increasing (monotonic) real sequence with lim n →∞ a n = 0, then a necessary and sufficient condition for the uniform convergence of the series ∑∞ n=1 a n sin nx is lim n →∞ na n = 0. We generalize (or weaken) the monotonic condition on the coefficient sequence {a n } in this classical result to the so-called mean value bounded variation condition and prove that the generalized condition cannot be weakened further. We also establish an analogue to the generalized Chaundy-Jolliffe theorem in the complex space.

  11. Non-monotonic relationships between emotional arousal and memory for color and location.

    Science.gov (United States)

    Boywitt, C Dennis

    2015-01-01

    Recent research points to the decreased diagnostic value of subjective retrieval experience for memory accuracy for emotional stimuli. While for neutral stimuli rich recollective experiences are associated with better context memory than merely familiar memories this association appears questionable for emotional stimuli. The present research tested the implicit assumption that the effect of emotional arousal on memory is monotonic, that is, steadily increasing (or decreasing) with increasing arousal. In two experiments emotional arousal was manipulated in three steps using emotional pictures and subjective retrieval experience as well as context memory were assessed. The results show an inverted U-shape relationship between arousal and recognition memory but for context memory and retrieval experience the relationship was more complex. For frame colour, context memory decreased linearly while for spatial location it followed the inverted U-shape function. The complex, non-monotonic relationships between arousal and memory are discussed as possible explanations for earlier divergent findings.

  12. Generalized monotone method and numerical approach for coupled reaction diffusion systems

    Science.gov (United States)

    Sowmya, M.; Vatsala, Aghalaya S.

    2017-01-01

    Study of coupled reaction diffusion systems are very useful in various branches of science and engineering. In this paper, we provide a methodology to construct the solution for the coupled reaction diffusion systems, with initial and boundary conditions, where the forcing function is the sum of an increasing and decreasing function. It is known that the generalized monotone method coupled with coupled lower and upper solutions yield monotone sequences which converges uniformly and monotonically to coupled minimal and maximal solutions. In addition, the interval of existence is guaranteed by the lower and upper solutions, which are relatively easy to compute. Using the lower and upper solutions as the initial approximation, we develop a method to compute the sequence of coupled lower and upper solutions on the interval or on the desired interval of existence. Further, if the uniqueness conditions are satisfied, the coupled minimal and maximal solutions converge to the unique solution of the reaction diffusion systems. We will provide some numerical results as an application of our numerical methodology.

  13. Probabilistic Analysis of Pattern Formation in Monotonic Self-Assembly.

    Science.gov (United States)

    Moore, Tyler G; Garzon, Max H; Deaton, Russell J

    2015-01-01

    Inspired by biological systems, self-assembly aims to construct complex structures. It functions through piece-wise, local interactions among component parts and has the potential to produce novel materials and devices at the nanoscale. Algorithmic self-assembly models the product of self-assembly as the output of some computational process, and attempts to control the process of assembly algorithmically. Though providing fundamental insights, these computational models have yet to fully account for the randomness that is inherent in experimental realizations, which tend to be based on trial and error methods. In order to develop a method of analysis that addresses experimental parameters, such as error and yield, this work focuses on the capability of assembly systems to produce a pre-determined set of target patterns, either accurately or perhaps only approximately. Self-assembly systems that assemble patterns that are similar to the targets in a significant percentage are "strong" assemblers. In addition, assemblers should predominantly produce target patterns, with a small percentage of errors or junk. These definitions approximate notions of yield and purity in chemistry and manufacturing. By combining these definitions, a criterion for efficient assembly is developed that can be used to compare the ability of different assembly systems to produce a given target set. Efficiency is a composite measure of the accuracy and purity of an assembler. Typical examples in algorithmic assembly are assessed in the context of these metrics. In addition to validating the method, they also provide some insight that might be used to guide experimentation. Finally, some general results are established that, for efficient assembly, imply that every target pattern is guaranteed to be assembled with a minimum common positive probability, regardless of its size, and that a trichotomy exists to characterize the global behavior of typical efficient, monotonic self-assembly systems

  14. Probabilistic Analysis of Pattern Formation in Monotonic Self-Assembly.

    Directory of Open Access Journals (Sweden)

    Tyler G Moore

    Full Text Available Inspired by biological systems, self-assembly aims to construct complex structures. It functions through piece-wise, local interactions among component parts and has the potential to produce novel materials and devices at the nanoscale. Algorithmic self-assembly models the product of self-assembly as the output of some computational process, and attempts to control the process of assembly algorithmically. Though providing fundamental insights, these computational models have yet to fully account for the randomness that is inherent in experimental realizations, which tend to be based on trial and error methods. In order to develop a method of analysis that addresses experimental parameters, such as error and yield, this work focuses on the capability of assembly systems to produce a pre-determined set of target patterns, either accurately or perhaps only approximately. Self-assembly systems that assemble patterns that are similar to the targets in a significant percentage are "strong" assemblers. In addition, assemblers should predominantly produce target patterns, with a small percentage of errors or junk. These definitions approximate notions of yield and purity in chemistry and manufacturing. By combining these definitions, a criterion for efficient assembly is developed that can be used to compare the ability of different assembly systems to produce a given target set. Efficiency is a composite measure of the accuracy and purity of an assembler. Typical examples in algorithmic assembly are assessed in the context of these metrics. In addition to validating the method, they also provide some insight that might be used to guide experimentation. Finally, some general results are established that, for efficient assembly, imply that every target pattern is guaranteed to be assembled with a minimum common positive probability, regardless of its size, and that a trichotomy exists to characterize the global behavior of typical efficient, monotonic

  15. MONOTONE ITERATION FOR ELLIPTIC PDEs WITH DISCONTINUOUS NONLINEAR TERMS

    Institute of Scientific and Technical Information of China (English)

    Zou Qingsong

    2005-01-01

    In this paper, we use monotone iterative techniques to show the existence of maximal or minimal solutions of some elliptic PDEs with nonlinear discontinuous terms. As the numerical analysis of this PDEs is concerned, we prove the convergence of discrete extremal solutions.

  16. L^p solutions of reflected BSDEs under monotonicity condition

    CERN Document Server

    Rozkosz, Andrzej

    2012-01-01

    We prove existence and uniqueness of L^p solutions of reflected backward stochastic differential equations with p-integrable data and generators satisfying the monotonicity condition. We also show that the solution may be approximated by the penalization method. Our results are new even in the classical case p=2.

  17. A monotonic method for solving nonlinear optimal control problems

    CERN Document Server

    Salomon, Julien

    2009-01-01

    Initially introduced in the framework of quantum control, the so-called monotonic algorithms have shown excellent numerical results when dealing with various bilinear optimal control problems. This paper aims at presenting a unified formulation of such procedures and the intrinsic assumptions they require. In this framework, we prove the feasibility of the general algorithm. Finally, we explain how these assumptions can be relaxed.

  18. On Some Conjectures on the Monotonicity of Some Arithmetical Sequences

    Science.gov (United States)

    2012-01-01

    THE MONOTONICITY OF SOME ARITHMETICAL SEQUENCES ∗ Florian Luca † Centro de Ciencias Matemáticas, Universidad Nacional Autonoma de México, C.P. 58089...visit of P. S. to the Centro de Ciencias Matemáticas de la UNAM in Morelia in August 2012. During the preparation of this paper, F. L. was supported in

  19. Interval Routing and Minor-Monotone Graph Parameters

    NARCIS (Netherlands)

    Bakker, E.M.; Bodlaender, H.L.; Tan, R.B.; Leeuwen, J. van

    2006-01-01

    We survey a number of minor-monotone graph parameters and their relationship to the complexity of routing on graphs. In particular we compare the interval routing parameters κslir(G) and κsir(G) with Colin de Verdi`ere’s graph invariant μ(G) and its variants λ(G) and κ(G). We show that for all the k

  20. Multivariate Regression with Monotone Missing Observation of the Dependent Variables

    NARCIS (Netherlands)

    Raats, V.M.; van der Genugten, B.B.; Moors, J.J.A.

    2002-01-01

    Multivariate regression is discussed, where the observations of the dependent variables are (monotone) missing completely at random; the explanatory variables are assumed to be completely observed.We discuss OLS-, GLS- and a certain form of E(stimated) GLS-estimation.It turns out that

  1. Minimum Cost Spanning Tree Games and Population Monotonic Allocation Schemes

    NARCIS (Netherlands)

    Norde, H.W.; Moretti, S.; Tijs, S.H.

    2001-01-01

    In this paper we present the Subtraction Algorithm that computes for every classical minimum cost spanning tree game a population monotonic allocation scheme.As a basis for this algorithm serves a decomposition theorem that shows that every minimum cost spanning tree game can be written as nonnegati

  2. Size monotonicity and stability of the core in hedonic games

    OpenAIRE

    Dimitrov, Dinko; Sung, Shao Chin

    2011-01-01

    We show that the core of each strongly size monotonic hedonic game is not empty and is externally stable. This is in sharp contrast to other sufficient conditions for core non-emptiness which do not even guarantee the existence of a stable set in such games.

  3. Monotone missing data and repeated controls of fallible authors

    NARCIS (Netherlands)

    Raats, V.M.

    2004-01-01

    Chapters 2 and 3 focus on repeated audit controls with categorical variables. Chapter 4 and 5 introduce and analyse a very general multivariate regression model for (monotone) missing data. In the final Chapter 6 the previous chapters are combined into a more realistic model for repeated audit contr

  4. A POTENTIAL REDUCTION ALGORITHM FOR MONOTONE VARIATIONAL INEQUALITY PROBLEMS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    A potential reduction algorithm is proposed for the solution of monotone variational inequality problems. At each step of the algorithm, a system of linear equations is solved to get the search direction and the Armijo's rule is used to determine the stepsize.It is proved that the algorithm is globally convergent. Computational results are reported.

  5. Relaxing monotonicity in the identification of local average treatment effects

    DEFF Research Database (Denmark)

    Huber, Martin; Mellace, Giovanni

    In heterogeneous treatment effect models with endogeneity, the identification of the local average treatment effect (LATE) typically relies on an instrument that satisfies two conditions: (i) joint independence of the potential post-instrument variables and the instrument and (ii) monotonicity...

  6. Incorporating "Unconscious Reanalysis" into an Incremental, Monotonic Parser

    CERN Document Server

    Sturt, P

    1995-01-01

    This paper describes an implementation based on a recent model in the psycholinguistic literature. We define a parsing operation which allows the reanalysis of dependencies within an incremental and monotonic processing architecture, and discuss search strategies for its application in a head-initial language (English) and a head-final language (Japanese).

  7. Interval Routing and Minor-Monotone Graph Parameters

    NARCIS (Netherlands)

    Bakker, E.M.; Bodlaender, H.L.; Tan, R.B.; Leeuwen, J. van

    2006-01-01

    We survey a number of minor-monotone graph parameters and their relationship to the complexity of routing on graphs. In particular we compare the interval routing parameters κslir(G) and κsir(G) with Colin de Verdi`ere’s graph invariant μ(G) and its variants λ(G) and κ(G). We show that for all the

  8. Reasoning Biases, Non-Monotonic Logics, and Belief Revision

    NARCIS (Netherlands)

    Dutilh Novaes, Catarina; Veluwenkamp, Herman

    2017-01-01

    A range of formal models of human reasoning have been proposed in a number of fields such as philosophy, logic, artificial intelligence, computer science, psychology, cognitive science etc.: various logics (epistemic logics; non-monotonic logics), probabilistic systems (most notably, but not exclusi

  9. Response to Martini and Habeck: Semiochemical dose-response curves fit by kinetic formation functions

    Science.gov (United States)

    Martini and Habeck (2014) correctly describe the conceptual simulation model of Byers (2013) where molecules in an odor filament pass by an antenna causing an electrophysiological antennographic (EAG) response that is proportional to how many of the receptors are hit at least once by a molecule. Inc...

  10. Dose-response effects of zopiclone on night sleep and on nighttime and daytime functioning.

    Science.gov (United States)

    Billiard, M; Besset, A; de Lustrac, C; Brissaud, L

    1987-01-01

    Six normal volunteers, aged 20 to 39 years, underwent 2 adaptation nights and three sessions of 2 consecutive experimental nights and days at 1-week intervals, according to a latin-square design. In the three sessions, subjects received either zopiclone, 3.75 mg or 7.5 mg, or placebo at 2215 h in a double-blind protocol. On nights 1 and 2 of each session, subjects were continuously monitored polygraphically, except for a 45-min provoked wake episode 135 min after sleep onset on night 2. Degree of daytime somnolence was assessed during day 1 by means of a multiple sleep latency test (MSLT) and performance evaluation was carried out during night 2 (0000 h) and day 2 (800 h and 1200 h) by means of a battery of four tests. NREM sleep stages 3 and 4 increased significantly after 3.75 mg and 7.5 mg zopiclone (p less than 0.05). No significant differences between placebo and 3.75 mg and 7.5 mg zopiclone were found at any time in the MSLT. Two performance tests (eye-hand coordination test and choice reaction time test) showed a highly significant impairment (p less than 0.01) at 0000 h with 7.5 mg zopiclone; one test (eye-hand coordination test) showed a significant impairment (p less than 0.05) at 0800 h also with 7.5 mg zopiclone and none at 1200 h. From a subjective point of view, depth and quality of sleep were improved, whereas number of awakenings and feeling on awakening were not modified. Side effects (bitter taste, jitteriness, difficulty to concentrate) were reported only with 7.5 mg zopiclone.

  11. On the Non-Monotonic Variation of the Opposition Surge Morphology with Albedo Exhibited by Satellites' Surface

    Science.gov (United States)

    Deau, E. A.; Spilker, L. J.; Flandes, A.

    2011-01-01

    We used well know phase functions of satellites and rings around the giant planets of our Solar System to study the morphology of the opposition effect (at phase angles alpha morphological model to retrieve the morphological parameters of the surge (A and HWHM). These parameters are found to have a non-monotonic variation with the single scattering albedo, similar to that observed in asteroids, which is unexplained so far. The non-monotonic variation is discussed in the framework of the coherent backscattering and shadow hiding mechanisms.

  12. Almost monotonicity formulas for elliptic and parabolic operators with variable coefficients

    KAUST Repository

    Matevosyan, Norayr

    2010-10-21

    In this paper we extend the results of Caffarelli, Jerison, and Kenig [Ann. of Math. (2)155 (2002)] and Caffarelli and Kenig [Amer. J. Math.120 (1998)] by establishing an almost monotonicity estimate for pairs of continuous functions satisfying u± ≥ 0 Lu± ≥ -1, u+ · u_ = 0 ;in an infinite strip (global version) or a finite parabolic cylinder (localized version), where L is a uniformly parabolic operator Lu = LA,b,cu := div(A(x, s)∇u) + b(x,s) · ∇u + c(x,s)u - δsu with double Dini continuous A and uniformly bounded b and c. We also prove the elliptic counterpart of this estimate.This closes the gap between the known conditions in the literature (both in the elliptic and parabolic case) imposed on u± in order to obtain an almost monotonicity estimate.At the end of the paper, we demonstrate how to use this new almost monotonicity formula to prove the optimal C1,1-regularity in a fairly general class of quasi-linear obstacle-type free boundary problems. © 2010 Wiley Periodicals, Inc.

  13. Effect of Enamel Caries Lesion Baseline Severity on Fluoride Dose-Response

    Directory of Open Access Journals (Sweden)

    Frank Lippert

    2017-01-01

    Full Text Available This study aimed to investigate the effect of enamel caries lesion baseline severity on fluoride dose-response under pH cycling conditions. Early caries lesions were created in human enamel specimens at four different severities (8, 16, 24, and 36 h. Lesions were allocated to treatment groups (0, 83, and 367 ppm fluoride as sodium fluoride based on Vickers surface microhardness (VHN and pH cycled for 5 d. The cycling model comprised 3 × 1 min fluoride treatments sandwiched between 2 × 60 min demineralization challenges with specimens stored in artificial saliva in between. VHN was measured again and changes versus lesion baseline were calculated (ΔVHN. Data were analyzed using two-way ANOVA (p<0.05. Increased demineralization times led to increased surface softening. The lesion severity×fluoride concentration interaction was significant (p<0.001. Fluoride dose-response was observed in all groups. Lesions initially demineralized for 16 and 8 h showed similar overall rehardening (ΔVHN and more than 24 and 36 h lesions, which were similar. The 8 h lesions showed the greatest fluoride response differential (367 versus 0 ppm F which diminished with increasing lesion baseline severity. The extent of rehardening as a result of the 0 ppm F treatment increased with increasing lesion baseline severity, whereas it decreased for the fluoride treatments. In conclusion, lesion baseline severity impacts the extent of the fluoride dose-response.

  14. Alanine aminotransferase and risk of the metabolic syndrome: a linear dose-response relationship.

    Directory of Open Access Journals (Sweden)

    Setor K Kunutsor

    Full Text Available BACKGROUND: Elevated baseline circulating alanine aminotransferase (ALT level has been demonstrated to be associated with an increased risk of the metabolic syndrome (MetS, but the nature of the dose-response relationship is uncertain. METHODS: We performed a systematic review and meta-analysis of published prospective cohort studies to characterize in detail the nature of the dose-response relationship between baseline ALT level and risk of incident MetS in the general population. Relevant studies were identified in a literature search of MEDLINE, EMBASE, and Web of Science up to December 2013. Prospective studies in which investigators reported relative risks (RRs of MetS for 3 or more categories of ALT levels were eligible. A potential nonlinear relationship between ALT levels and MetS was examined using restricted cubic splines. RESULTS: Of the 489 studies reviewed, relevant data were available on 29,815 non-overlapping participants comprising 2,125 incident MetS events from five prospective cohort studies. There was evidence of a linear association (P for nonlinearity=0.38 between ALT level and risk of MetS, characterised by a graded increase in MetS risk at ALT levels 6-40 U/L. The risk of MetS increased by 14% for every 5 U/L increment in circulating ALT level (95% CI: 12-17%. Evidence was lacking of heterogeneity and publication bias among the contributing studies. CONCLUSIONS: Baseline ALT level is associated with risk of the MetS in a linear dose-response manner. Studies are needed to determine whether the association represents a causal relationship.

  15. Dose-response relationship between physical activity and dyslipidemia in youth.

    Science.gov (United States)

    LeBlanc, Allana G; Janssen, Ian

    2010-01-01

    The minimal and optimal amount of physical activity associated with cardiovascular health benefits in young people is unknown. To determine the dose-response relationship between moderate-to-vigorous physical activity (MVPA) with high-risk low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride values in youth. The study sample consisted of 1235 adolescents (12 to 19 years of age) from the 20032004 and 20052006 cycles of the United States National Health and Nutrition Examination Survey. Objective measures of MVPA were obtained over seven days with accelerometers. LDL cholesterol, HDL cholesterol and triglycerides were measured from a fasting blood sample. High-risk values for these lipidslipoproteins were determined using age- and sex-specific thresholds. Logistic regression models were used to determine the dose-response relationships between MVPA and high-risk lipid levels. ORs for high-risk HDL cholesterol and triglyceride values decreased in a curvilinear manner with increasing minutes of MVPA. Compared with no MVPA (0 min), the ORs for high-risk HDL cholesterol values at 15 min, 30 min and 60 min per day of MVPA were 0.29 (95% CI 0.13 to 0.67), 0.24 (95% CI 0.10 to 0.64) and 0.21 (95% CI 0.07 to 0.61), respectively. The corresponding ORs for high-risk triglyceride values were 0.40 (95% CI 0.18 to 0.76), 0.22 (95% CI 0.06 to 0.66) and 0.10 (95% CI 0.01 to 0.51). There was no discernible dose-response relationship between MVPA and LDL cholesterol. Small amounts of MVPA were associated with a large reduction in the likelihood of having high-risk HDL cholesterol and triglyceride values in this representative sample of adolescents.

  16. Breastfeeding Mode and Risk of Breast Cancer: A Dose-Response Meta-Analysis.

    Science.gov (United States)

    Unar-Munguía, Mishel; Torres-Mejía, Gabriela; Colchero, M Arantxa; González de Cosío, Teresita

    2017-05-01

    Breastfeeding reduces women's risk of breast cancer. Since exclusive breastfeeding has a stronger hormonal effect, it could theoretically result in a greater reduction in breast cancer risk than any breastfeeding mode. No meta-analysis has examined breast cancer risk by breastfeeding mode. Research aim: The authors conducted a meta-analysis for breast cancer risk in parous women who breastfed exclusively or in any mode versus parous women who formula fed their infants, and they estimated the summary dose-response association by the accumulated duration of any breastfeeding mode. A systematic review of studies published between 2005 and 2015 analyzing breastfeeding and breast cancer risk in women was conducted in PubMed and EBSCOhost. A meta-analysis ( n = 65 studies) with fixed effects (or random effects, if heterogeneity existed) was carried out stratified by breastfeeding mode and menopausal and parity status. A summary dose-response association was estimated using the generalized least-squares method. The summary relative risk (SRR) for breast cancer in parous women who breastfed exclusively was 0.72, 95% confidence interval (CI) [0.58, 0.90], versus parous women who had never breastfed. For parous women who breastfed in any mode, the SRR was lower in both premenopausal women (0.86, 95% CI [0.80, 0.93]) and postmenopausal women (0.89, 95% CI [0.83, 0.95]). There was no heterogeneity or publication bias. There is weak evidence of a difference between exclusive and any breastfeeding mode ( p = .08). The summary dose-response curve was nonlinear ( p < .001). Exclusive breastfeeding among parous women reduces the risk of breast cancer compared with parous women who do not breastfeed exclusively.

  17. Time course and dose response of alpha tocopherol on oxidative stress in haemodialysis patients

    Directory of Open Access Journals (Sweden)

    Coombes Jeff S

    2009-10-01

    Full Text Available Abstract Background Oxidative stress is associated with increased cardiovascular morbidity and mortality particularly in patients with end stage kidney disease. Although observational data from the general population has shown dietary antioxidant intake is associated with reduced cardiovascular morbidity and mortality, most clinical intervention trials have failed to support this relationship. This may be a consequence of not using an effective antioxidant dose and/or not investigating patients with elevated oxidative stress. The SPACE study, conducted in haemodialysis patients, reported that 800 IU/day of alpha tocopherol significantly reduced cardiovascular disease endpoints. A recent time course and dose response study conducted in hypercholesterolaemic patients that found 1600 IU/day of alpha tocopherol was an optimal dose. There is no such dose response data available for haemodialysis patients. Therefore the aim of this study is to investigate the effect of different doses of oral alpha tocopherol on oxidative stress in haemodialysis patients with elevated oxidative stress and the time taken to achieve this effect. Methods The study will consist of a time-course followed by a dose response study. In the time course study 20 haemodialysis patients with elevated oxidative stress will take either 1600 IU/day natural (RRR alpha tocopherol for 20 weeks or placebo. Blood will be collected every two weeks and analysed for a marker of oxidative stress (plasma F2-isoprostanes and alpha tocopherol. The optimum time period to significantly decrease plasma F2-isoprostanes will be determined from this study. In the dose response study 60 patients will be randomised to receive either placebo, 100, 200, 400, 800 or 1600 IU/day of natural (RRR alpha tocopherol for a time period determined from the time course study. Blood will be collected at baseline and every two weeks and analysed for plasma F2-isoprostanes and alpha tocopherol. It is hypothesised that

  18. IncucyteDRC: An R package for the dose response analysis of live cell imaging data

    OpenAIRE

    Philip J. Chapman; Dominic I. James; Amanda J. Watson; Hopkins, Gemma V.; Waddell, Ian D.; Ogilvie, Donald J.

    2016-01-01

    We present IncucyteDRC, an R package for the analysis of data from live cell imaging cell proliferation experiments carried out on the Essen Biosciences IncuCyte ZOOM instrument. The package provides a simple workflow for summarising data into a form that can be used to calculate dose response curves and EC50 values for small molecule inhibitors. Data from different cell lines, or cell lines grown under different conditions, can be normalised as to their doubling time. A simple graphical web ...

  19. Dose-response of strengthening exercise for treatment of severe neck pain in women

    DEFF Research Database (Denmark)

    Andersen, Christoffer H; Andersen, Lars Louis; Pedersen, Mogens T

    2013-01-01

    Specific strength training is shown relieves neck pain in office workers. The purpose of this study is to evaluate the effectiveness of specific strength training in women with severe neck pain and to analyze the dose-response relationship between training adherence and pain reduction. 118...... untrained women with severe neck pain (>30 mm VAS pain) were included from a larger study, in which the subjects were randomized to 20-weeks specific strength training for the neck/shoulders or to a control group. In the intention-to-treat analysis, the training group experienced greater pain relief than...

  20. Youth suicide attempts and the dose-response relationship to parental risk factors: a population-based study

    DEFF Research Database (Denmark)

    Christiansen, E; Goldney, R D; Beautrai, A L;

    2011-01-01

    illness and low level of income were all significant independent risk factors for offspring's suicide attempts. CONCLUSIONS: Knowledge of the effect of multiple risk factors on the likelihood of suicide attempts in children and adolescents is important for risk assessment. Dose-response effects......BACKGROUND: There is a lack of specific knowledge about the dose-response effect of multiple parental risk factors for suicide attempts among children and adolescents. The aim of this study was to determine the dose-response effect of multiple parental risk factors on an offspring's risk...... to each case and a link to the offspring's biological parents was established. RESULTS: There was a dose-response relationship between the number of exposures and the risk of suicide attempts, with the increased risk seeming to be a multiplicative effect. Parental suicide, suicide attempt, psychiatric...

  1. Influence of lung parenchymal destruction on the different indexes of the methacholine dose-response curve in COPD patients

    NARCIS (Netherlands)

    G.T. Verhoeven; A.F.M. Verbraak (Anton); S. Boere-van der Straat; H.C. Hoogsteden (Henk); J.M. Bogaard (Jan)

    2000-01-01

    textabstractSTUDY OBJECTIVES: The interpretation of nonspecific bronchial provocation dose-response curves in COPD is still a matter of debate. Bronchial hyperresponsiveness (BHR) in patients with COPD could be influenced by the destruction of the parenchyma and the

  2. Patients who do not respond to the "usual" dose: why Terry fell off the dose-response curve.

    Science.gov (United States)

    Preskorn, Sheldon H

    2009-11-01

    Clinical trials are aimed at determining what happens in the "usual" patient; however, clinicians are interested in what happens in their patients even if they are not usual. The usual dose-response relationship is determined as part of the drug development process required for approval of a new drug. However, clinicians are likely to encounter patients who "fall off" the usual dose-response curve because they are either sensitive or resistant to the beneficial (efficacy) or adverse effects of a drug. This column is the first in a series that will examine why specific patients fall off the usual dose-response curve and how clinicians can manage such patients when they encounter them. This column discusses what a dose-response curve is, how it is determined, and why it is clinically important.

  3. Hazard identification and characterisation, and dose response assessment of spore forming pathogens in cooked chilled food containing vegetables

    NARCIS (Netherlands)

    Leusden FM van; MGB

    2001-01-01

    A hazard identification and characterisation, including a preliminary dose response assessment, of sporeforming pathogens in cooked chilled food containing vegetables was performed according to the structure and principles for a quantitative microbiological risk assessment as described by the Codex

  4. Accelerometer-measured dose-response for physical activity, sedentary time, and mortality in US adults

    DEFF Research Database (Denmark)

    Matthews, Charles E; Keadle, S. K.; Troiano, Richard P

    2016-01-01

    Background: Moderate-to-vigorous-intensity physical activity is recommended to maintain and improve health, but the mortality benefits of light activity and risk for sedentary time remain uncertain. Objectives: Using accelerometer-based measures, we 1) described the mortality dose-response for se......Background: Moderate-to-vigorous-intensity physical activity is recommended to maintain and improve health, but the mortality benefits of light activity and risk for sedentary time remain uncertain. Objectives: Using accelerometer-based measures, we 1) described the mortality dose......-response for sedentary time and light-and moderateto-vigorous-intensity activity using restricted cubic splines, and 2) estimated the mortality benefits associated with replacing sedentary time with physical activity, accounting for total activity. Design: US adults (n = 4840) from NHANES (2003-2006) wore...... an accelerometer for #7 d and were followed prospectively for mortality. Proportional hazards models were used to estimate adjusted HRs and 95% CIs for mortality associations with time spent sedentary and in light-and moderate-to-vigorous-intensity physical activity. Splines were used to graphically present...

  5. Mathematical Modeling of Allelopathy. III. A Model for Curve-Fitting Allelochemical Dose Responses

    Science.gov (United States)

    Liu, De Li; An, Min; Johnson, Ian R.; Lovett, John V.

    2003-01-01

    Bioassay techniques are often used to study the effects of allelochemicals on plant processes, and it is generally observed that the processes are stimulated at low allelochemical concentrations and inhibited as the concentrations increase. A simple empirical model is presented to analyze this type of response. The stimulation-inhibition properties of allelochemical-dose responses can be described by the parameters in the model. The indices, p% reductions, are calculated to assess the allelochemical effects. The model is compared with experimental data for the response of lettuce seedling growth to Centaurepensin, the olfactory response of weevil larvae to α-terpineol, and the responses of annual ryegrass (Lolium multiflorum Lam.), creeping red fescue (Festuca rubra L., cv. Ensylva), Kentucky bluegrass (Poa pratensis L., cv. Kenblue), perennial ryegrass (L. perenne L., cv. Manhattan), and Rebel tall fescue (F. arundinacea Schreb) seedling growth to leachates of Rebel and Kentucky 31 tall fescue. The results show that the model gives a good description to observations and can be used to fit a wide range of dose responses. Assessments of the effects of leachates of Rebel and Kentucky 31 tall fescue clearly differentiate the properties of the allelopathic sources and the relative sensitivities of indicators such as the length of root and leaf. PMID:19330111

  6. Bayesian penalized log-likelihood ratio approach for dose response clinical trial studies.

    Science.gov (United States)

    Tang, Yuanyuan; Cai, Chunyan; Sun, Liangrui; He, Jianghua

    2017-02-13

    In literature, there are a few unified approaches to test proof of concept and estimate a target dose, including the multiple comparison procedure using modeling approach, and the permutation approach proposed by Klingenberg. We discuss and compare the operating characteristics of these unified approaches and further develop an alternative approach in a Bayesian framework based on the posterior distribution of a penalized log-likelihood ratio test statistic. Our Bayesian approach is much more flexible to handle linear or nonlinear dose-response relationships and is more efficient than the permutation approach. The operating characteristics of our Bayesian approach are comparable to and sometimes better than both approaches in a wide range of dose-response relationships. It yields credible intervals as well as predictive distribution for the response rate at a specific dose level for the target dose estimation. Our Bayesian approach can be easily extended to continuous, categorical, and time-to-event responses. We illustrate the performance of our proposed method with extensive simulations and Phase II clinical trial data examples.

  7. Hierarchical dose-response modeling for high-throughput toxicity screening of environmental chemicals.

    Science.gov (United States)

    Wilson, Ander; Reif, David M; Reich, Brian J

    2014-03-01

    High-throughput screening (HTS) of environmental chemicals is used to identify chemicals with high potential for adverse human health and environmental effects from among the thousands of untested chemicals. Predicting physiologically relevant activity with HTS data requires estimating the response of a large number of chemicals across a battery of screening assays based on sparse dose-response data for each chemical-assay combination. Many standard dose-response methods are inadequate because they treat each curve separately and under-perform when there are as few as 6-10 observations per curve. We propose a semiparametric Bayesian model that borrows strength across chemicals and assays. Our method directly parametrizes the efficacy and potency of the chemicals as well as the probability of response. We use the ToxCast data from the U.S. Environmental Protection Agency (EPA) as motivation. We demonstrate that our hierarchical method provides more accurate estimates of the probability of response, efficacy, and potency than separate curve estimation in a simulation study. We use our semiparametric method to compare the efficacy of chemicals in the ToxCast data to well-characterized reference chemicals on estrogen receptor α (ERα) and peroxisome proliferator-activated receptor γ (PPARγ) assays, then estimate the probability that other chemicals are active at lower concentrations than the reference chemicals.

  8. Transcriptional profiling of the dose response: a more powerful approach for characterizing drug activities.

    Directory of Open Access Journals (Sweden)

    Rui-Ru Ji

    2009-09-01

    Full Text Available The dose response curve is the gold standard for measuring the effect of a drug treatment, but is rarely used in genomic scale transcriptional profiling due to perceived obstacles of cost and analysis. One barrier to examining transcriptional dose responses is that existing methods for microarray data analysis can identify patterns, but provide no quantitative pharmacological information. We developed analytical methods that identify transcripts responsive to dose, calculate classical pharmacological parameters such as the EC50, and enable an in-depth analysis of coordinated dose-dependent treatment effects. The approach was applied to a transcriptional profiling study that evaluated four kinase inhibitors (imatinib, nilotinib, dasatinib and PD0325901 across a six-logarithm dose range, using 12 arrays per compound. The transcript responses proved a powerful means to characterize and compare the compounds: the distribution of EC50 values for the transcriptome was linked to specific targets, dose-dependent effects on cellular processes were identified using automated pathway analysis, and a connection was seen between EC50s in standard cellular assays and transcriptional EC50s. Our approach greatly enriches the information that can be obtained from standard transcriptional profiling technology. Moreover, these methods are automated, robust to non-optimized assays, and could be applied to other sources of quantitative data.

  9. Dose-response plasma appearance of coffee chlorogenic and phenolic acids in adults.

    Science.gov (United States)

    Renouf, Mathieu; Marmet, Cynthia; Giuffrida, Francesca; Lepage, Mélissa; Barron, Denis; Beaumont, Maurice; Williamson, Gary; Dionisi, Fabiola

    2014-02-01

    Coffee contains phenolic compounds, mainly chlorogenic acids (CGAs). Even though coffee intake has been associated with some health benefits in epidemiological studies, the bioavailability of coffee phenolics is not fully understood. We performed a dose-response study measuring plasma bioavailability of phenolics after drinking three increasing, but still nutritionally relevant doses of instant pure soluble coffee. The study design was a one treatment (coffee) three-dose randomized cross-over design, with a washout period of 2 wks between visits. CGAs, phenolic acids, and late-appearing metabolites all increased with increasing ingested dose. Hence, the sum of area under the curve was significantly higher for the medium to low dose, and high to medium dose, by 2.23- and 2.38-fold, respectively. CGAs were not well absorbed in their intact form, regardless of the dose. CGA and phenolic acids appeared rapidly in plasma, indicating an early absorption in the gastrointestinal tract. Late-appearing metabolites were the most abundant, regardless of the dose. This study confirmed previous findings about coffee bioavailability but also showed that coffee phenolics appear in a positive dose-response manner in plasma when drank at nutritionally relevant doses. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Mathematical Modeling of Allelopathy. III. A Model for Curve-Fitting Allelochemical Dose Responses.

    Science.gov (United States)

    Liu, De Li; An, Min; Johnson, Ian R; Lovett, John V

    2003-01-01

    Bioassay techniques are often used to study the effects of allelochemicals on plant processes, and it is generally observed that the processes are stimulated at low allelochemical concentrations and inhibited as the concentrations increase. A simple empirical model is presented to analyze this type of response. The stimulation-inhibition properties of allelochemical-dose responses can be described by the parameters in the model. The indices, p% reductions, are calculated to assess the allelochemical effects. The model is compared with experimental data for the response of lettuce seedling growth to Centaurepensin, the olfactory response of weevil larvae to alpha-terpineol, and the responses of annual ryegrass (Lolium multiflorum Lam.), creeping red fescue (Festuca rubra L., cv. Ensylva), Kentucky bluegrass (Poa pratensis L., cv. Kenblue), perennial ryegrass (L. perenne L., cv. Manhattan), and Rebel tall fescue (F. arundinacea Schreb) seedling growth to leachates of Rebel and Kentucky 31 tall fescue. The results show that the model gives a good description to observations and can be used to fit a wide range of dose responses. Assessments of the effects of leachates of Rebel and Kentucky 31 tall fescue clearly differentiate the properties of the allelopathic sources and the relative sensitivities of indicators such as the length of root and leaf.

  11. Dose Response Association between Physical Activity and Biological, Demographic, and Perceptions of Health Variables

    Directory of Open Access Journals (Sweden)

    Paul D. Loprinzi

    2013-08-01

    Full Text Available Background: Few population-based studies have examined the association between physical activity (PA and cardiovascular disease risk factors, demographic variables, and perceptions of health status, and we do not have a clear understanding of the dose-response relationship among these variables. Methods: Data from the 2003-2006 National Health and Nutrition Examination Survey was used to examine the dose-response relationship between objectively measured PA and metabolic syndrome (and its individual cardiovascular disease risk factors, demographic variables, and perceptions of health. After exclusions, 5,538 participants 18 years or older were included in the present study, with 2,538 participants providing fasting glucose and 2,527 providing fasting triglyceride data. PA was categorized into deciles. Results: Overall, the health benefits showed a general pattern of increase with each increasing levels of PA. Of the ten PA classifications examined, participants in the highest moderate-to-vigorous physical activity (MVPA category (at least 71 min/day had the lowest odds of developing metabolic syndrome. Conclusion: At a minimum, sedentary adults should strive to meet current PA guidelines (i.e., 150 min/week of MVPA, with additional positive benefits associated with engaging in three times this level of PA.

  12. A Hybrid Approach to Proving Memory Reference Monotonicity

    KAUST Repository

    Oancea, Cosmin E.

    2013-01-01

    Array references indexed by non-linear expressions or subscript arrays represent a major obstacle to compiler analysis and to automatic parallelization. Most previous proposed solutions either enhance the static analysis repertoire to recognize more patterns, to infer array-value properties, and to refine the mathematical support, or apply expensive run time analysis of memory reference traces to disambiguate these accesses. This paper presents an automated solution based on static construction of access summaries, in which the reference non-linearity problem can be solved for a large number of reference patterns by extracting arbitrarily-shaped predicates that can (in)validate the reference monotonicity property and thus (dis)prove loop independence. Experiments on six benchmarks show that our general technique for dynamic validation of the monotonicity property can cover a large class of codes, incurs minimal run-time overhead and obtains good speedups. © 2013 Springer-Verlag.

  13. Measurement of non-monotonic Casimir forces between silicon nanostructures

    Science.gov (United States)

    Tang, L.; Wang, M.; Ng, C. Y.; Nikolic, M.; Chan, C. T.; Rodriguez, A. W.; Chan, H. B.

    2017-01-01

    Casimir forces are of fundamental interest because they originate from quantum fluctuations of the electromagnetic field. Apart from controlling this force via the optical properties of materials, a number of novel geometries have been proposed to generate repulsive and/or non-monotonic Casimir forces between bodies separated by vacuum gaps. Experimental realization of these geometries, however, is hindered by the difficulties in alignment when the bodies are brought into close proximity. Here, using an on-chip platform with integrated force sensors and actuators, we circumvent the alignment problem and measure the Casimir force between two surfaces with nanoscale protrusions. We demonstrate that the force depends non-monotonically on the displacement. At some displacements, the Casimir force leads to an effective stiffening of the nanomechanical spring. Our findings pave the way for exploiting the Casimir force in nanomechanical systems using structures of complex and non-conventional shapes.

  14. A Monotonic Precise Current DAC for Sensor Applications

    Directory of Open Access Journals (Sweden)

    P. Horsky

    2008-12-01

    Full Text Available In this paper a 17 bit monotonic precise current DAC for sensor applications is described. It is working in a harsh automotive environment in a wide temperature range with high output voltage swing and low current consumption. To guarantee monotonicity current division and segmentation techniques are used. To improve the output impedance, the accuracy and the voltage compliance of the DAC, two active cascoding loops and one follower loop are used. The resolution of the DAC is further increased by applying pulse width modulation to one fine LSB current. To achieve low power consumption unused coarse current sources are switched off. Several second order technological effects influencing final performance and circuits dealing with them are discussed.

  15. Computation of Optimal Monotonicity Preserving General Linear Methods

    KAUST Repository

    Ketcheson, David I.

    2009-07-01

    Monotonicity preserving numerical methods for ordinary differential equations prevent the growth of propagated errors and preserve convex boundedness properties of the solution. We formulate the problem of finding optimal monotonicity preserving general linear methods for linear autonomous equations, and propose an efficient algorithm for its solution. This algorithm reliably finds optimal methods even among classes involving very high order accuracy and that use many steps and/or stages. The optimality of some recently proposed methods is verified, and many more efficient methods are found. We use similar algorithms to find optimal strong stability preserving linear multistep methods of both explicit and implicit type, including methods for hyperbolic PDEs that use downwind-biased operators.

  16. Block Monotone Iterative Algorithms for Variational Inequalities with Nonlinear Operators

    Institute of Scientific and Technical Information of China (English)

    Ming-hui Ren; Jin-ping Zeng

    2008-01-01

    Some block iterative methods for solving variational inequalities with nonlinear operators are proposed. Monotone convergence of the algorithms is obtained. Some comparison theorems are also established.Compared with the research work in given by Pao in 1995 for nonlinear equations and research work in given by Zeng and Zhou in 2002 for elliptic variational inequalities, the algorithms proposed in this paper are independent of the boundedness of the derivatives of the nonlinear operator.

  17. Monotonic Property in Field Algebra of G-Spin Model

    Institute of Scientific and Technical Information of China (English)

    蒋立宁

    2003-01-01

    Let F be the field algebra of G-spin model, D(G) the double algebra of a finite group G and D(H) the sub-Hopf algerba of D(G) determined by the subgroup H of G. The paper builds a correspondence between D(H) and the D(H)-invariant sub-C*-algebra AH in F, and proves that the correspondence is strictly monotonic.

  18. Modeling argumentation based semantics using non-monotonic reasoning

    OpenAIRE

    2005-01-01

    Argumentation theory is an alternative style of formalizing non-monotonic reasoning. It seems, argumentation theory is a suitable framework for practical and uncertain reasoning, where arguments support conclusions. Dung's approach is an unifying framework which has played an influential role on argumentation research and Artificial Intelligence. Even though the success of the argumentation theory, it seems that argumentation theory is so far from being efficiently implemented like the logic ...

  19. Stability and monotonicity of Lotka-Volterra type operators

    CERN Document Server

    Mukhamedov, Farrukh

    2009-01-01

    In the present paper, we study Lotka-Volterra (LV) type operators defined in finite dimensional simplex. We prove that any LV type operator is a surjection of the simplex. After, we introduce a new class of LV-type operators, called $M$LV type. We prove convergence of their trajectories and study certain its properties. Moreover, we show that such kind of operators have totaly different behavior than ${\\mathbf{f}}$-monotone LV type operators.

  20. Steepness of the radiation dose-response curve for dose-per-fraction escalation keeping the number of fractions fixed.

    Science.gov (United States)

    Bentzen, Søren M

    2005-01-01

    Clinically, there is growing interest in strategies for intensifying radiation therapy by escalating the dose per fraction. This paper considers the steepness of the dose-response curve in this case. The steepness of a radiation dose-response curve is most conveniently quantified by the normalized dose-response gradient, gamma. Under the assumption of a linear-quadratic dose-effect model, a simple analytical relationship is derived between the gamma-value for a dose-response curve generated by varying the total dose while keeping the number of fractions constant, i.e. escalating the dose per fraction, and the gamma-value for a dose-response curve generated by varying the total dose while keeping the dose per fraction constant. This formulation is compared with clinical dose-response data from the literature and shown to be in good agreement with the observations. Some implications of this formulation for non-uniform dose distributions delivered using 3D conformal radiotherapy or intensity modulated radiotherapy (IMRT) are briefly discussed.

  1. Regional trends in short-duration precipitation extremes: a flexible multivariate monotone quantile regression approach

    Science.gov (United States)

    Cannon, Alex

    2017-04-01

    univariate technique, and cannot incorporate information from additional covariates, for example ENSO state or physiographic controls on extreme rainfall within a region. Here, the univariate MQR model is extended to allow the use of multiple covariates. Multivariate monotone quantile regression (MMQR) is based on a single hidden-layer feedforward network with the quantile regression error function and partial monotonicity constraints. The MMQR model is demonstrated via Monte Carlo simulations and the estimation and visualization of regional trends in moderate rainfall extremes based on homogenized sub-daily precipitation data at stations in Canada.

  2. Monotone traveling wavefronts of the KPP-Fisher delayed equation

    Science.gov (United States)

    Gomez, Adrian; Trofimchuk, Sergei

    In the early 2000's, Gourley (2000), Wu et al. (2001), Ashwin et al. (2002) initiated the study of the positive wavefronts in the delayed Kolmogorov-Petrovskii-Piskunov-Fisher equation u(t,x)=Δu(t,x)+u(t,x)(1-u(t-h,x)), u⩾0, x∈R. Since then, this model has become one of the most popular objects in the studies of traveling waves for the monostable delayed reaction-diffusion equations. In this paper, we give a complete solution to the problem of existence and uniqueness of monotone waves in Eq. (*). We show that each monotone traveling wave can be found via an iteration procedure. The proposed approach is based on the use of special monotone integral operators (which are different from the usual Wu-Zou operator) and appropriate upper and lower solutions associated to them. The analysis of the asymptotic expansions of the eventual traveling fronts at infinity is another key ingredient of our approach.

  3. Solving the power flow equations: a monotone operator approach

    Energy Technology Data Exchange (ETDEWEB)

    Dvijotham, Krishnamurthy [California Inst. of Technology (CalTech), Pasadena, CA (United States); Low, Steven [California Inst. of Technology (CalTech), Pasadena, CA (United States); Chertkov, Michael [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-07-21

    The AC power flow equations underlie all operational aspects of power systems. They are solved routinely in operational practice using the Newton-Raphson method and its variants. These methods work well given a good initial “guess” for the solution, which is always available in normal system operations. However, with the increase in levels of intermittent generation, the assumption of a good initial guess always being available is no longer valid. In this paper, we solve this problem using the theory of monotone operators. We show that it is possible to compute (using an offline optimization) a “monotonicity domain” in the space of voltage phasors. Given this domain, there is a simple efficient algorithm that will either find a solution in the domain, or provably certify that no solutions exist in it. We validate the approach on several IEEE test cases and demonstrate that the offline optimization can be performed tractably and the computed “monotonicity domain” includes all practically relevant power flow solutions.

  4. Inhibitory properties underlying non-monotonic input-output relationship in low-frequency spherical bushy neurons of the gerbil.

    Science.gov (United States)

    Kuenzel, Thomas; Nerlich, Jana; Wagner, Hermann; Rübsamen, Rudolf; Milenkovic, Ivan

    2015-01-01

    Spherical bushy cells (SBCs) of the anteroventral cochlear nucleus (AVCN) receive input from large excitatory auditory nerve (AN) terminals, the endbulbs of Held, and mixed glycinergic/GABAergic inhibitory inputs. The latter have sufficient potency to block action potential firing in vivo and in slice recordings. However, it is not clear how well the data from slice recordings match the inhibition in the intact brain and how it contributes to complex phenomena such as non-monotonic rate-level functions (RLF). Therefore, we determined the input-output relationship of a model SBC with simulated endbulb inputs and a dynamic inhibitory conductance constrained by recordings in brain slice preparations of hearing gerbils. Event arrival times from in vivo single-unit recordings in gerbils, where 70% of SBC showed non-monotonic RLF, were used as input for the model. Model output RLFs systematically changed from monotonic to non-monotonic shape with increasing strength of tonic inhibition. A limited range of inhibitory synaptic properties consistent with the slice data generated a good match between the model and recorded RLF. Moreover, tonic inhibition elevated the action potentials (AP) threshold and improved the temporal precision of output functions in a SBC model with phase-dependent input conductance. We conclude that activity-dependent, summating inhibition contributes to high temporal precision of SBC spiking by filtering out weak and poorly timed EPSP. Moreover, inhibitory parameters determined in slice recordings provide a good estimate of inhibitory mechanisms apparently active in vivo.

  5. Non-monotonic reasoning in conceptual modeling and ontology design: A proposal

    CSIR Research Space (South Africa)

    Casini, G

    2013-06-01

    Full Text Available and modeling of defeasible information and non-monotonic reasoning services. Here we formalize a possible way of introducing non-monotonic reasoning into ORM2 schemas, enriching the language with special set of new constraints....

  6. Dose-response effect of the lercanidipine/enalapril combination: a pooled analysis.

    Science.gov (United States)

    Rizzoni, Damiano

    2016-10-01

    The dose-effect relationship of fixed-dose combinations of anti-hypertensive drugs has been only poorly explored. This pooled analysis investigates the dose-response relationship of fixed-dose lercanidipine + enalapril in patients with mild-to-moderate hypertension. This was an individual patient data analysis of four randomized studies (n = 2340). The primary efficacy variable was the change from baseline in sitting diastolic blood pressure (SDBP). Secondary variables were change from baseline in sitting systolic BP (SSBP), proportion of responder patients, and safety. All fixed-dose combinations were superior to placebo in the reduction of SDBP. The greatest effect was observed with the market-available combination lercanidipine 20 mg/enalapril 20 mg (-15.3 mmHg vs. baseline; p < 0.05). The reduction in SDBP associated with the other two marketed fixed combinations of lercanidipine/enalapril were -10.7 mmHg for the 10 mg/20 mg combination and -9.8 mmHg for the 10 mg/10 mg combination (p < .05 for both comparisons). Similar findings were reported for SSBP reduction: the greatest effect was observed with lercanidipine 20 mg/enalapril 20 mg (-19.2 mmHg). The reduction in SSBP was -12.5 mmHg for the 10 mg/20 mg combination and -11.1 mmHg for the 10 mg/10 mg combination (p < .05 for all comparisons). The highest responder rate was reported with lercanidipine 20 mg/enalapril 20 mg (75.0%); this figure was 56.1% with the 10 mg/20 mg and 53.0% with the 10/10 mg combination. No safety concerns were reported. This pooled analysis of four randomized studies shows evidence of a dose-response effect in BP reduction with different fixed combinations of lercanidipine + enalapril. To our knowledge, this is the first analysis investigating the dose-response effect of a specific fixed-dose combination of anti-hypertensive agents. Further studies on this intriguing topic are however necessary.

  7. Time-optimal monotonic convergent algorithms for the control of quantum systems

    CERN Document Server

    Lapert, M; Sugny, D

    2012-01-01

    We present a new formulation of monotonically convergent algorithms which allows to optimize both the control duration and the field fluence. A standard algorithm designs a control field of fixed duration which both brings the system close to the target state and minimizes its fluence, whereas here we include in addition the optimization of the duration in the cost functional. We apply this new algorithm to the control of spin systems in Nuclear Magnetic Resonance. We show how to implement CNOT gates in systems of two and four coupled spins.

  8. Mixed Monotonicity of Partial First-In-First-Out Traffic Flow Models

    OpenAIRE

    Coogan, Samuel; Arcak, Murat; Kurzhanskiy, Alexander A.

    2015-01-01

    In vehicle traffic networks, congestion on one outgoing link of a diverging junction often impedes flow to other outgoing links, a phenomenon known as the first-in-first-out (FIFO) property. Simplified traffic models that do not account for the FIFO property result in monotone dynamics for which powerful analysis techniques exist. FIFO models are in general not monotone, but have been shown to be mixed monotone - a generalization of monotonicity that enables similarly powerful analysis techni...

  9. Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

    DEFF Research Database (Denmark)

    Appelt, A. L.; Ploen, J.; Vogelius, I. R.

    2013-01-01

    of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect......Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we...... estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination...

  10. SO/sub 2/ dose-response sensitivity classification data for crops and natural vegetation species

    Energy Technology Data Exchange (ETDEWEB)

    Irving, P.M.; Ballou, S.W.

    1980-09-01

    Over the past several years studies have been made on the interaction of sulfur dioxide (SO/sub 2/) and vegetation by performing field research and by developing analytical procedures for applying field observation data to energy impact assessments. As a result of this work, numerous reports have been prepared on crop-pollutant interactions, such as dose-response data; on the applications of such data to screening approaches for identifying crops at risk; and on models that predict crop yield reductions from point source emissions of SO/sub 2/. Data that were used for these studies, such as the crop-at-risk screening procedure, are presented in this report. Maps are also presented that show the national distribution of SO/sub 2/-sensitive crops and natural vegetation.

  11. Dose response of xylitol and sorbitol for EPR retrospective dosimetry with applications to chewing gum.

    Science.gov (United States)

    Israelsson, A; Gustafsson, H; Lund, E

    2013-04-01

    The purpose of this investigation was to study the radiation-induced electron paramagnetic resonance signal in sweeteners xylitol and sorbitol for use in retrospective dosimetry. For both sweeteners and chewing gum, the signal changed at an interval of 1-84 d after irradiation with minimal changes after 4-8 d. A dependence on storage conditions was noticed and the exposure of the samples to light and humidity was therefore minimised. Both the xylitol and sorbitol signals showed linearity with dose in the measured dose interval, 0-20 Gy. The dose-response measurements for the chewing gum resulted in a decision threshold of 0.38 Gy and a detection limit of 0.78 Gy. A blind test illustrated the possibility of using chewing gums as a retrospective dosemeter with an uncertainty in the dose determination of 0.17 Gy (1 SD).

  12. Quantitative aspects of informed consent: considering the dose response curve when estimating quantity of information.

    Science.gov (United States)

    Lynöe, N; Hoeyer, K

    2005-12-01

    Information is usually supposed to be a prerequisite for people making decisions on whether or not to participate in a clinical trial. Previously conducted studies and research ethics scandals indicate that participants have sometimes lacked important pieces of information. Over the past few decades the quantity of information believed to be adequate has increased significantly, and in some instances a new maxim seems to be in place: the more information, the better the ethics in terms of respecting a participant's autonomy. The authors hypothesise that the dose-response curve from pharmacology or toxicology serves as a model to illustrate that a large amount of written information does not equal optimality. Using the curve as a pedagogical analogy when teaching ethics to students in clinical sciences, and also in engaging in dialogue with research institutions, may promote reflection on how to adjust information in relation to the preferences of individual participants, thereby transgressing the maxim that more information means better ethics.

  13. Mass shootings: a meta-analysis of the dose-response relationship.

    Science.gov (United States)

    Wilson, Laura C

    2014-12-01

    A meta-analysis was conducted to examine the dose-response theory as it relates to posttraumatic stress symptoms (PTSSs) following mass shootings. It was hypothesized that greater exposure to a mass shooting would be associated with greater PTSSs. Trauma exposure in the current study was broadly defined as the extent to which a person experienced or learned about a mass shooting. The meta-analysis identified 11 qualifying studies that included 13 independent effect sizes from a total of 8,047 participants. The overall weighted mean effect size, based on a random effects model, was r = .19, p < .001, 95% CI [.13, .25]. Maximum likelihood meta-regressions revealed no significant linear effects of participant gender, participant age, or time elapsed since the shooting on the relationship between exposure and PTSSs. Because so few studies satisfied the inclusion criteria, the present study also documents that this area of the literature is underresearched.

  14. Extended application of dose-response models of infection on injectable insulin products in vials

    Directory of Open Access Journals (Sweden)

    Mostafa Essam Eissa

    2016-09-01

    Full Text Available Microbial contamination from in-use application of multidose pharmaceutical products constitutes health hazard to the consumer especially when considering injectable medicines. In the present study, an attempt has been made to integrate dose-response models of infections with pharmacopeial preservative efficacy test (PET in a single simulation study that supposed accidental reuse of hypodermic syringe. Probability risk ratio of infection from assumed equal doses of two types of microbes by two routes of infection was greater than 1300 at most equivalent administration doses when considering the same reduction factor for both bacteria in the antimicrobial efficacy test (AET. The probability of infection would diminish much more rapidly for Staphylococcus aureus rather than Pseudomonas aeruginosa. The short interval of product administration increased the risk of infection with regular-type of Insulin vials. The current quantitative study provided extension and made the best use of the standard AET but also highlighted its limitations.

  15. Muller's Nobel lecture on dose-response for ionizing radiation: ideology or science?

    Science.gov (United States)

    Calabrese, Edward J

    2011-12-01

    In his Nobel Prize Lecture of December 12, 1946, Hermann J. Muller argued that the dose-response for radiation-induced germ cell mutations was linear and that there was "no escape from the conclusion that there is no threshold". However, assessment of correspondence between Muller and Curt Stern 1 month prior to his Nobel Prize Lecture reveals that Muller knew the results and implications of a recently completed study at the University of Rochester under the direction of Stern, which directly contradicted his Nobel Prize Lecture. This finding is of historical importance since Muller's Nobel Lecture gained considerable international attention and is a turning point in the acceptance of the linearity model in risk assessment for germ cell mutations and carcinogens.

  16. Clinical application of Chamomilla recutita in phlebitis: dose response curve study.

    Science.gov (United States)

    Reis, Paula Elaine Diniz Dos; Carvalho, Emilia Campos de; Bueno, Paula Carolina Pires; Bastos, Jairo Kenupp

    2011-01-01

    This experimental and dose-response curve study aimed to carry out the quality control of the Chamomilla recutita sample, as well as to estimate the ideal dose, for anti-inflammatory effect, of the extract of its capitula, in patients with phlebitis due to peripheral intravenous infusion of antineoplastic chemotherapy and to evaluate the toxicity of this extract in human beings. The therapeutic efficacy, concerning the anti-inflammatory potential, of different doses of Chamomilla recutita extract were analyzed and compared in 25 patients. The time of regression of phlebitis was shorter for groups with 2.5% concentration (mean=29.2h, standard deviation = 8.98) and 5% concentration (mean = 38.8h, standard deviation = 17.47). Local toxicity was almost not observed. This research contributes to the innovation of the nursing clinical practice, since it suggests an alternative for the treatment of phlebitis through the clinical use of phytotherapeutic drugs.

  17. Therapeutic efficacy of endostatin exhibits a biphasic dose-response curve.

    Science.gov (United States)

    Celik, Ilhan; Sürücü, Oguzkan; Dietz, Carsten; Heymach, John V; Force, Jeremy; Höschele, Iris; Becker, Christian M; Folkman, Judah; Kisker, Oliver

    2005-12-01

    We show here that recombinant endostatin protein has a biphasic effect on the inhibition of endothelial cell migration in vitro. In tumor-bearing animals, there is a similar biphasic effect on the inhibition of tumor growth and on circulating endothelial cells after once-daily s.c. injections. This biphasic effect is revealed as a U-shaped curve in which efficacy is optimal between very low and very high doses depending on the tumor type. This result may be applicable to other inhibitors of endothelial growth and to angiogenesis. Furthermore, these results have important implications for clinicians who administer angiogenesis inhibitors for cancer or other angiogenesis-dependent diseases. When these results are taken together with two previous reports of angiogenesis inhibitors with a U-shaped dose-response, they suggest that other regulators of endothelial growth may display a similar pattern.

  18. Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure.

    Directory of Open Access Journals (Sweden)

    Sara C Johnston

    Full Text Available Marburg virus infection in humans causes a hemorrhagic disease with a high case fatality rate. Countermeasure development requires the use of well-characterized animal models that mimic human disease. To further characterize the cynomolgus macaque model of MARV/Angola, two independent dose response studies were performed using the intramuscular or aerosol routes of exposure. All animals succumbed at the lowest target dose; therefore, a dose effect could not be determined. For intramuscular-exposed animals, 100 PFU was the first target dose that was not significantly different than higher target doses in terms of time to disposition, clinical pathology, and histopathology. Although a significant difference was not observed between aerosol-exposed animals in the 10 PFU and 100 PFU target dose groups, 100 PFU was determined to be the lowest target dose that could be consistently obtained and accurately titrated in aerosol studies.

  19. Dose-response modeling for the environmental risk assessment in cases of technogenic soil contamination

    Directory of Open Access Journals (Sweden)

    Shitikov Vladimir Kirilloviсh

    2015-09-01

    Full Text Available The review of regression models for the approximation of dependences "dose- response" was performed based on ecotoxicological results. The advantages and deficiencies of different models as well as the problems arising both in modeling and subsequent interpreting results are discussed for the purpose of ecological rationing and estimation of negative influence risk. Search procedures of best dependences based on statistical criteria and the methods of uncertainty estimation of calculated parameters are shown. Construction of models is illustrated in detail using the analysis of toxicity results of soil samples received from uranium mines tailings in Kadzhi-Say province (Kyrgyzstan. Threshold values of activity for U-238 and Ra-226 radionuclides providing the minimum probability of ecological risk were determined.

  20. On the combination of c- and D-optimal designs: General approaches and applications in dose-response studies.

    Science.gov (United States)

    Holland-Letz, Tim

    2017-03-01

    Dose-response modeling in areas such as toxicology is often conducted using a parametric approach. While estimation of parameters is usually one of the goals, often the main aim of the study is the estimation of quantities derived from the parameters, such as the ED50 dose. From the view of statistical optimal design theory such an objective corresponds to a c-optimal design criterion. Unfortunately, c-optimal designs often create practical problems, and furthermore commonly do not allow actual estimation of the parameters. It is therefore useful to consider alternative designs which show good c-performance, while still being applicable in practice and allowing reasonably good general parameter estimation. In effect, using optimal design terminology this means that a reasonable performance regarding the D-criterion is expected as well. In this article, we propose several approaches to the task of combining c- and D-efficient designs, such as using mixed information functions or setting minimum requirements regarding either c- or D-efficiency, and show how to algorithmically determine optimal designs in each case. We apply all approaches to a standard situation from toxicology, and obtain a much better balance between c- and D-performance. Next, we investigate how to adapt the designs to different parameter values. Finally, we show that the methodology used here is not just limited to the combination of c- and D-designs, but can also be used to handle more general constraint situations such as limits on the cost of an experiment.

  1. Dose Response for Chromosome Aberrations in Human Lymphocytes and Fibroblasts after Exposure to Very Low Doses of High LET Radiation

    Science.gov (United States)

    Hada, M.; George, Kerry; Cucinotta, Francis A.

    2011-01-01

    The relationship between biological effects and low doses of absorbed radiation is still uncertain, especially for high LET radiation exposure. Estimates of risks from low-dose and low-dose-rates are often extrapolated using data from Japanese atomic bomb survivors with either linear or linear quadratic models of fit. In this study, chromosome aberrations were measured in human peripheral blood lymphocytes and normal skin fibroblasts cells after exposure to very low dose (1-20 cGy) of 170 MeV/u Si-28- ions or 600 MeV/u Fe-56-ions. Chromosomes were analyzed using the whole chromosome fluorescence in situ hybridization (FISH) technique during the first cell division after irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving greater than 2 breaks in 2 or more chromosomes). The curves for doses above 10 cGy were fitted with linear or linear-quadratic functions. For Si-28- ions no dose response was observed in the 2-10 cGy dose range, suggesting a non-target effect in this range.

  2. Dose response explorer: an integrated open-source tool for exploring and modelling radiotherapy dose-volume outcome relationships

    Energy Technology Data Exchange (ETDEWEB)

    Naqa, I El [Washington University, Saint Louis, MO (United States); Suneja, G [Brown Medical School, Providence, RI (United States); Lindsay, P E [Washington University, St. Louis, MO (United States); Hope, A J [Washington University, Saint Louis, MO (United States); Alaly, J R [Washington University, Saint Louis, MO (United States); Vicic, M [Washington University, Saint Louis, MO (United States); Bradley, J D [Washington University, Saint Louis, MO (United States); Apte, A [Washington University, Saint Louis, MO (United States); Deasy, J O [Washington University, Saint Louis, MO (United States)

    2006-11-21

    Radiotherapy treatment outcome models are a complicated function of treatment, clinical and biological factors. Our objective is to provide clinicians and scientists with an accurate, flexible and user-friendly software tool to explore radiotherapy outcomes data and build statistical tumour control or normal tissue complications models. The software tool, called the dose response explorer system (DREES), is based on Matlab, and uses a named-field structure array data type. DREES/Matlab in combination with another open-source tool (CERR) provides an environment for analysing treatment outcomes. DREES provides many radiotherapy outcome modelling features, including (1) fitting of analytical normal tissue complication probability (NTCP) and tumour control probability (TCP) models, (2) combined modelling of multiple dose-volume variables (e.g., mean dose, max dose, etc) and clinical factors (age, gender, stage, etc) using multi-term regression modelling, (3) manual or automated selection of logistic or actuarial model variables using bootstrap statistical resampling, (4) estimation of uncertainty in model parameters, (5) performance assessment of univariate and multivariate analyses using Spearman's rank correlation and chi-square statistics, boxplots, nomograms, Kaplan-Meier survival plots, and receiver operating characteristics curves, and (6) graphical capabilities to visualize NTCP or TCP prediction versus selected variable models using various plots. DREES provides clinical researchers with a tool customized for radiotherapy outcome modelling. DREES is freely distributed. We expect to continue developing DREES based on user feedback.

  3. Dose response explorer: an integrated open-source tool for exploring and modelling radiotherapy dose volume outcome relationships

    Science.gov (United States)

    El Naqa, I.; Suneja, G.; Lindsay, P. E.; Hope, A. J.; Alaly, J. R.; Vicic, M.; Bradley, J. D.; Apte, A.; Deasy, J. O.

    2006-11-01

    Radiotherapy treatment outcome models are a complicated function of treatment, clinical and biological factors. Our objective is to provide clinicians and scientists with an accurate, flexible and user-friendly software tool to explore radiotherapy outcomes data and build statistical tumour control or normal tissue complications models. The software tool, called the dose response explorer system (DREES), is based on Matlab, and uses a named-field structure array data type. DREES/Matlab in combination with another open-source tool (CERR) provides an environment for analysing treatment outcomes. DREES provides many radiotherapy outcome modelling features, including (1) fitting of analytical normal tissue complication probability (NTCP) and tumour control probability (TCP) models, (2) combined modelling of multiple dose-volume variables (e.g., mean dose, max dose, etc) and clinical factors (age, gender, stage, etc) using multi-term regression modelling, (3) manual or automated selection of logistic or actuarial model variables using bootstrap statistical resampling, (4) estimation of uncertainty in model parameters, (5) performance assessment of univariate and multivariate analyses using Spearman's rank correlation and chi-square statistics, boxplots, nomograms, Kaplan-Meier survival plots, and receiver operating characteristics curves, and (6) graphical capabilities to visualize NTCP or TCP prediction versus selected variable models using various plots. DREES provides clinical researchers with a tool customized for radiotherapy outcome modelling. DREES is freely distributed. We expect to continue developing DREES based on user feedback.

  4. The dose-response relationship between in-ear occupational noise exposure and hearing loss.

    Science.gov (United States)

    Rabinowitz, Peter M; Galusha, Deron; Dixon-Ernst, Christine; Clougherty, Jane E; Neitzel, Richard L

    2013-10-01

    Current understanding of the dose-response relationship between occupational noise and hearing loss is based on cross-sectional studies prior to the widespread use of hearing protection, and with limited data regarding noise exposures below 85 dBA. We report on the hearing loss experience of a unique cohort of industrial workers, with daily monitoring of noise inside of hearing protection devices. At an industrial facility, workers exhibiting accelerated hearing loss were enrolled in a mandatory programme to monitor daily noise exposures inside of hearing protection. We compared these noise measurements (as time-weighted LAVG) to interval rates of high-frequency hearing loss over a 6-year period using a mixed-effects model, adjusting for potential confounders. Workers' high-frequency hearing levels at study inception averaged more than 40 dB Hearing threshold level (HTL). Most noise exposures were less than 85 dBA (mean LAVG 76 dBA, IQR 74-80 dBA). We found no statistical relationship between LAvg and high-frequency hearing loss (p=0.53). Using a metric for monthly maximum noise exposure did not improve model fit. At-ear noise exposures below 85 dBA did not show an association with risk of high-frequency hearing loss among workers with substantial past noise exposure and hearing loss at baseline. Therefore, effective noise control to below 85 dBA may lead to significant reduction in occupational hearing loss risk in such individuals. Further research is needed on the dose-response relationship of noise and hearing loss in individuals with normal hearing and little prior noise exposure.

  5. Parity and risk of colorectal cancer: a dose-response meta-analysis of prospective studies.

    Directory of Open Access Journals (Sweden)

    Hong-Bo Guan

    Full Text Available BACKGROUND: Association between parity and colorectal cancer (CRC risk has been investigated by several epidemiological studies but results are controversial, yet a comprehensive and quantitative assessment of this association has not been reported so far. METHODS: Relevant published studies of parity and CRC were identified using MEDLINE, EMBASE and Web of Science databases through end of April 2013. Two authors independently assessed eligibility and extracted data. Eleven prospective studies reported relative risk (RR estimates and 95% confidence intervals (CIs of CRC risk associated with parity. We pooled the RR from individual studies using fixed- or random-effects models and carried out heterogeneity and publication bias analyses. RESULTS: The summary RR for the ever parity vs. nulliparous was 0.95 (95% CI: 0.88-1.02, with no heterogeneity (Q = 9.04, P = 0.443, I (2 = 0.5%. Likewise, no significant association was yielded for the highest vs. lowest parity number (RR = 1.02, 95% CI: 0.89-1.17, with moderate heterogeneity (Q = 17.48, P = 0.094, I (2 = 37.1%. Dose-response analysis still indicated no effect of parity on CRC risk and the summary RR of per one livebirth was 0.99 (95% CI: 0.96-1.02, with moderate of heterogeneity (Q = 16.50, P<0.021, I (2 = 57.6%. Similar results were observed among all the subgroup analyses. No evidence of publication bias and significant heterogeneity between subgroups were detected by meta-regression analyses. CONCLUSION: Results of this dose-response meta-analysis of prospective studies found that there was little evidence of an association between parity and CRC risk.

  6. KINETIC SIMULATIONS OF THERMOLUMINESCENCE DOSE RESPONSE: LONG OVERDUE CONFRONTATION WITH THE EFFECTS OF IONISATION DENSITY.

    Science.gov (United States)

    Horowitz, Y S; Eliyahu, I; Oster, L

    2016-12-01

    The reader will time-travel through almost seven decades of kinetic models and mathematical simulations of thermoluminescence (TL) characteristics based on the band-gap theory of the solid state. From post-World-War II, ideas concerning electron trapping mechanisms to the highly idealised one trap-one recombination (OTOR) model first elaborated in 1956 but still in 'high gear' today. The review caresses but purposely avoids in-depth discussion of the endless stream of papers discussing the intricacies of glow peak shapes arising from first-order, second-order, mixed-order and general-order kinetics predominantly based on non-interacting systems, and then on to the more physically realistic scenarios that have attempted to analyse complex systems involving ever greater numbers of interacting trapping centres, luminescent centres and non-luminescent centres. The review emphasises the difficulty the band-gap models have in the simulation of dose response linear/supralinear behaviour and especially the dependence of the supralinearity on ionisation density. The significance of the non-observation of filling-rate supralinearity in the absorption stage is emphasised since it removes from consideration the possibility of TL supralinearity arising from irradiation stage supralinearity. The importance of the simultaneous action of both localised and delocalised transitions has gradually penetrated the mindset of the community of kinetic researchers, but most simulations have concentrated on the shape of glow peaks and the extraction of the glow peak parameters, E (the thermal activation energy) and s (the attempt-to-escape frequency). The simulation of linear/supralinear dose response and its dependence on ionisation density have been largely avoided until recently due to the fundamental schism between the effects of ionisation density and some basic assumptions of the band-gap model. The review finishes with an in-depth presentation and discussion of the most recent

  7. Coffee consumption and risk of fractures: a systematic review and dose-response meta-analysis.

    Science.gov (United States)

    Lee, Dong Ryul; Lee, Jungun; Rota, Matteo; Lee, Juneyoung; Ahn, Hyeong Sik; Park, Sang Min; Shin, Doosup

    2014-06-01

    The data on the association between coffee consumption and the risk of fractures are inconclusive. We performed a comprehensive literature review and meta-analysis to better quantify this association. We identified all potentially relevant articles by searching MEDLINE, EMBASE, Cochrane Library, Web of Science, SCOPUS, and CINAHL (until February 2013). The keywords "coffee," "caffeine," "drink," and "beverage" were used as the exposure factors, and the keyword "fracture" was used as the outcome factor. We determined the overall relative risk (RR) and confidence interval (CI) for the highest and lowest levels of coffee consumption. A dose-response analysis was performed to assess the risk of fractures based on the level of coffee consumption. We included 253,514 participants with 12,939 fracture cases from 9 cohort and 6 case-control studies. The estimated RR of fractures at the highest level of coffee consumption was 1.14 (95% CI: 1.05-1.24; I(2)=0.0%) in women and 0.76 (95% CI: 0.62-0.94; I(2)=7.3%) in men. In the dose-response analysis, the pooled RRs of fractures in women who consumed 2 and 8 cups of coffee per day were 1.02 (95% CI: 1.01-1.04) and 1.54 (95% CI: 1.19-1.99), respectively. Our meta-analysis suggests that daily consumption of coffee is associated with an increased risk of fractures in women and a contrasting decreased risk in men. However, future well-designed studies should be performed to confirm these findings. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. The Shape of the Dose-Response Relationship between Sugars and Caries in Adults.

    Science.gov (United States)

    Bernabé, E; Vehkalahti, M M; Sheiham, A; Lundqvist, A; Suominen, A L

    2016-02-01

    Dental caries is considered a diet-mediated disease, as sugars are essential in the caries process. However, some gaps in knowledge about the sugars-caries relationship still need addressing. This longitudinal study aimed to explore 1) the shape of the dose-response association between sugars intake and caries in adults, 2) the relative contribution of frequency and amount of sugars intake to caries levels, and 3) whether the association between sugars intake and caries varies by exposure to fluoride toothpaste. We used data from 1,702 dentate adults who participated in at least 2 of 3 surveys in Finland (Health 2000, 2004/05 Follow-up Study of Adults' Oral Health, and Health 2011). Frequency and amount of sugars intake were measured with a validated food frequency questionnaire. The DMFT index was the repeated outcome measure. Data were analyzed with fractional polynomials and linear mixed effects models. None of the 43 fractional polynomials tested provided a better fit to the data than the simpler linear model. In a mutually adjusted linear mixed effects model, the amount of, but not the frequency of, sugars intake was significantly associated with DMFT throughout the follow-up period. Furthermore, the longitudinal association between amount of sugars intake and DMFT was weaker in adults who used fluoride toothpaste daily than in those using it less often than daily. The findings of this longitudinal study among Finnish adults suggest a linear dose-response relationship between sugars and caries, with amount of intake being more important than frequency of ingestion. Also, daily use of fluoride toothpaste reduced but did not eliminate the association between amount of sugars intake and dental caries.

  9. An alternate method for estimating the dose-response relationships of neuromuscular blocking drugs.

    Science.gov (United States)

    Kopman, A F; Klewicka, M M; Neuman, G G

    2000-05-01

    Slopes of the dose-response relationships for all available neuromuscular blocking drugs appear to be essentially parallel and to approximate a log-dose/logit value of 4.75. We tested the possibility of estimating both 50% effective dose (ED(50)) and 95% effective dose (ED(95)) values from a single dose-response data point when that slope is postulated. We compared the ED(50) and ED(95) values of rocuronium and succinylcholine calculated by using traditional log-dose/logit regression analysis with the same values obtained by averaging individual estimates of potency as determined by using the Hill equation. After the induction of anesthesia (propofol/alfentanil), tracheal intubation was accomplished without the administration of neuromuscular blocking drugs. Anesthesia was maintained with nitrous oxide and propofol. The evoked electromyographic response to 0.10-Hz single stimuli was continuously recorded. After baseline stabilization, a single IV bolus of succinylcholine (0.08-0.26 mg/kg, n = 50) or rocuronium (0. 13-0.30 mg/kg, n = 40) was administered and the peak effect noted. By using log-dose/logit regression analysis, we calculated ED(50) and ED(95) values for rocuronium of 0.17 and 0.33 mg/kg and 0.14 and 0.27 mg/kg for succinylcholine. When potency was calculated from the Hill equation, the resultant ED(50) and ED(95) values did not differ by more than +/-4% from those obtained by using regression analysis. Averaging of single-dose estimates of neuromuscular potency provides a useful adjunct and reasonable alternative to conventional regression analysis.

  10. Dose-response relationship for breast cancer induction at radiotherapy dose

    Directory of Open Access Journals (Sweden)

    Gruber Günther

    2011-06-01

    Full Text Available Abstract Purpose Cancer induction after radiation therapy is known as a severe side effect. It is therefore of interest to predict the probability of second cancer appearance for the patient to be treated including breast cancer. Materials and methods In this work a dose-response relationship for breast cancer is derived based on (i the analysis of breast cancer induction after Hodgkin's disease, (ii a cancer risk model developed for high doses including fractionation based on the linear quadratic model, and (iii the reconstruction of treatment plans for Hodgkin's patients treated with radiotherapy, (iv the breast cancer induction of the A-bomb survivor data. Results The fitted model parameters for an α/β = 3 Gy were α = 0.067Gy-1 and R = 0.62. The risk for breast cancer is according to this model for small doses consistent with the finding of the A-bomb survivors, has a maximum at doses of around 20 Gy and drops off only slightly at larger doses. The predicted EAR for breast cancer after radiotherapy of Hodgkin's disease is 11.7/10000PY which can be compared to the findings of several epidemiological studies where EAR for breast cancer varies between 10.5 and 29.4/10000PY. The model was used to predict the impact of the reduction of radiation volume on breast cancer risk. It was estimated that mantle field irradiation is associated with a 3.2-fold increased risk compared with mediastinal irradiation alone, which is in agreement with a published value of 2.7. It was also shown that the modelled age dependency of breast cancer risk is in satisfying agreement with published data. Conclusions The dose-response relationship obtained in this report can be used for the prediction of radiation induced secondary breast cancer of radiotherapy patients.

  11. Dose-response study of spinal hyperbaric ropivacaine for cesarean section

    Institute of Scientific and Technical Information of China (English)

    CHEN Xin-zhong; CHEN Hong; LOU Ai-fei; L(U) Chang-cheng

    2006-01-01

    Background: Spinal hyperbaric ropivacaine may produce more predictable and reliable anesthesia than plain ropivacaine for cesarean section. The dose-response relation for spinal hyperbaric ropivacaine is undetermined. This double-blind,randomized, dose-response study determined the ED50 (50% effective dose) and ED95 (95% effective dose) of spinal hyperbaric ropivacaine for cesarean section anesthesia. Methods: Sixty parturients undergoing elective cesarean section delivery with use of combined spinal-epidural anesthesia were enrolled in this study. An epidural catheter was placed at the L1~L2 vertebral interspace,then lumbar puncture was performed at the L3~L4 vertebral interspace, and parturients were randomized to receive spinal hyperbaric ropivacaine in doses of 10.5 mg, 12 mg, 13.5 mg, or 15 mg in equal volumes of 3 ml. Sensory levels (pinprick) were assessed every 2.5 min until a T7 level was achieved and motor changes were assessed by modified Bromage Score. A dose was considered effective ifan upper sensory level to pin prick ofT7 or above was achieved and no intraoperative epidural supplement was required. ED50 and ED95 were determined with use of a logistic regression model. Results: ED50 (95% confidence interval)of spinal hyperbaric ropivacaine was determined to be 10.37 (5.23~11.59) mg and ED95 (95% confidence interval) to be 15.39(13.81~23.59) mg. The maximum sensory block levels and the duration of motor block and the rate ofhypotension, but not onset of anesthesia, were significantly related to the ropivacaine dose. Conclusion: The ED50 and ED95 of spinal hyperbaric ropivacaine for cesarean delivery under the conditions of this study were 10.37 mg and 15.39 mg, respectively. Ropivacaine is suitable for spinal anesthesia in cesarean delivery.

  12. A method for inverse bifurcation of biochemical switches: inferring parameters from dose response curves.

    Science.gov (United States)

    Otero-Muras, Irene; Yordanov, Pencho; Stelling, Joerg

    2014-11-20

    Within cells, stimuli are transduced into cell responses by complex networks of biochemical reactions. In many cell decision processes the underlying networks behave as bistable switches, converting graded stimuli or inputs into all or none cell responses. Observing how systems respond to different perturbations, insight can be gained into the underlying molecular mechanisms by developing mathematical models. Emergent properties of systems, like bistability, can be exploited to this purpose. One of the main challenges in modeling intracellular processes, from signaling pathways to gene regulatory networks, is to deal with high structural and parametric uncertainty, due to the complexity of the systems and the difficulty to obtain experimental measurements. Formal methods that exploit structural properties of networks for parameter estimation can help to overcome these problems. We here propose a novel method to infer the kinetic parameters of bistable biochemical network models. Bistable systems typically show hysteretic dose response curves, in which the so called bifurcation points can be located experimentally. We exploit the fact that, at the bifurcation points, a condition for multistationarity derived in the context of the Chemical Reaction Network Theory must be fulfilled. Chemical Reaction Network Theory has attracted attention from the (systems) biology community since it connects the structure of biochemical reaction networks to qualitative properties of the corresponding model of ordinary differential equations. The inverse bifurcation method developed here allows determining the parameters that produce the expected behavior of the dose response curves and, in particular, the observed location of the bifurcation points given by experimental data. Our inverse bifurcation method exploits inherent structural properties of bistable switches in order to estimate kinetic parameters of bistable biochemical networks, opening a promising route for developments in

  13. Bayesian dose-response analysis for epidemiological studies with complex uncertainty in dose estimation.

    Science.gov (United States)

    Kwon, Deukwoo; Hoffman, F Owen; Moroz, Brian E; Simon, Steven L

    2016-02-10

    Most conventional risk analysis methods rely on a single best estimate of exposure per person, which does not allow for adjustment for exposure-related uncertainty. Here, we propose a Bayesian model averaging method to properly quantify the relationship between radiation dose and disease outcomes by accounting for shared and unshared uncertainty in estimated dose. Our Bayesian risk analysis method utilizes multiple realizations of sets (vectors) of doses generated by a two-dimensional Monte Carlo simulation method that properly separates shared and unshared errors in dose estimation. The exposure model used in this work is taken from a study of the risk of thyroid nodules among a cohort of 2376 subjects who were exposed to fallout from nuclear testing in Kazakhstan. We assessed the performance of our method through an extensive series of simulations and comparisons against conventional regression risk analysis methods. When the estimated doses contain relatively small amounts of uncertainty, the Bayesian method using multiple a priori plausible draws of dose vectors gave similar results to the conventional regression-based methods of dose-response analysis. However, when large and complex mixtures of shared and unshared uncertainties are present, the Bayesian method using multiple dose vectors had significantly lower relative bias than conventional regression-based risk analysis methods and better coverage, that is, a markedly increased capability to include the true risk coefficient within the 95% credible interval of the Bayesian-based risk estimate. An evaluation of the dose-response using our method is presented for an epidemiological study of thyroid disease following radiation exposure.

  14. Dose-response behavior of the bacterium Vibrio fischeri exposed to pharmaceuticals and personal care products.

    Science.gov (United States)

    Ortiz de García, Sheyla; García-Encina, Pedro A; Irusta-Mata, Rubén

    2016-01-01

    The presence of pharmaceuticals and personal care products (PPCPs) in the environment has become a real and widespread concern in recent years. Therefore, the primary goal of this study was to investigate 20 common and widely used PPCPs to assess their individual and combined effect on an important species in one trophic level, i.e., bacteria. The ecotoxicological effects of PPCPs at two different concentration ranges were determined in the bacterium Vibrio fischeri using Microtox(®) and were statistically analyzed using three models in the GraphPad Prism 6 program for Windows, v.6.03. A four-parameter model best fit the majority of the compounds. The half maximal effective concentration (EC50) of each PPCP was estimated using the best-fitting model and was compared with the results from a recent study. Comparative analysis indicated that most compounds showed the same level of toxicity. Moreover, the stimulatory effects of PPCPs at environmental concentrations (low doses) were assessed. These results indicated that certain compounds have traditional inverted U- or J-shaped dose-response curves, and 55% of them presented a stimulatory effect below the zero effect-concentration point. Effective concentrations of 0 (EC0), 5 (EC5) and 50% (EC50) were calculated for each PPCP as the ecotoxicological points. All compounds that presented narcosis as a mode of toxic action at high doses also exhibited stimulation at low concentrations. The maximum stimulatory effect of a mixture was higher than the highest stimulatory effect of each individually tested compound. Moreover, when the exposure time was increased, the hormetic effect decreased. Hormesis is being increasingly included in dose-response studies because this may have a harmful, beneficial or indifferent effect in an environment. Despite the results obtained in this research, further investigations need to be conducted to elucidate the behavior of PPCPs in aquatic environments.

  15. An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats.

    Directory of Open Access Journals (Sweden)

    Jan B W J Cornelissen

    Full Text Available High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment. Previous studies have indicated that bradyzoites are highly infectious for cats. To infect cats, tissue cysts were isolated from the brains of mice infected with oocysts of T. gondii M4 strain, and bradyzoites were released by pepsin digestion. Free bradyzoites were counted and graded doses (1000, 100, 50, 10, and 250 intact tissue cysts were inoculated orally into three cats each. Oocysts shed by these five groups of cats were collected from faeces by flotation techniques, counted microscopically and estimated by real time PCR. Additionally, the number of T. gondii in heart, tongue and brains were estimated, and serology for anti T. gondii antibodies was performed. A Beta-Poisson dose-response model was used to estimate the infectivity of single bradyzoites and linear regression was used to determine the relation between inoculated dose and numbers of oocyst shed. We found that real time PCR was more sensitive than microscopic detection of oocysts, and oocysts were detected by PCR in faeces of cats fed 10 bradyzoites but by microscopic examination. Real time PCR may only detect fragments of T. gondii DNA without the presence of oocysts in low doses. Prevalence of tissue cysts of T. gondii in tongue, heart and brains, and anti T. gondii antibody concentrations were all found to depend on the inoculated bradyzoite dose. The combination of the experimental challenge model and the dose response analysis provides a suitable reference for quantifying the potential reduction in human health risk due to a treatment of domestic cats by vaccination or by therapeutic drug application.

  16. Probiotics reduce symptoms of antibiotic use in a hospital setting: a randomized dose response study.

    Science.gov (United States)

    Ouwehand, Arthur C; DongLian, Cai; Weijian, Xu; Stewart, Morgan; Ni, Jiayi; Stewart, Tad; Miller, Larry E

    2014-01-16

    Probiotics are known to reduce antibiotic associated diarrhea (AAD) and Clostridium difficile associated diarrhea (CDAD) risk in a strain-specific manner. The aim of this study was to determine the dose-response effect of a four strain probiotic combination (HOWARU(®) Restore) on the incidence of AAD and CDAD and severity of gastrointestinal symptoms in adult in-patients requiring antibiotic therapy. Patients (n=503) were randomized among three study groups: HOWARU(®) Restore probiotic 1.70×10(10) CFU (high-dose, n=168), HOWARU(®) Restore probiotic 4.17×10(9) CFU (low-dose, n=168), or placebo (n=167). Subjects were stratified by gender, age, and duration of antibiotic treatment. Study products were administered daily up to 7 days after the final antibiotic dose. The primary endpoint of the study was the incidence of AAD. Secondary endpoints included incidence of CDAD, diarrhea duration, stools per day, bloody stools, fever, abdominal cramping, and bloating. A significant dose-response effect on AAD was observed with incidences of 12.5, 19.6, and 24.6% with high-dose, low-dose, and placebo, respectively (p=0.02). CDAD was the same in both probiotic groups (1.8%) but different from the placebo group (4.8%; p=0.04). Incidences of fever, abdominal pain, and bloating were lower with increasing probiotic dose. The number of daily liquid stools and average duration of diarrhea decreased with higher probiotic dosage. The tested four strain probiotic combination appears to lower the risk of AAD, CDAD, and gastrointestinal symptoms in a dose-dependent manner in adult in-patients.

  17. An Experimental Toxoplasma gondii Dose Response Challenge Model to Study Therapeutic or Vaccine Efficacy in Cats

    Science.gov (United States)

    Cornelissen, Jan B. W. J.; van der Giessen, Joke W. B.; Takumi, Katsuhisa; Teunis, Peter F. M.; Wisselink, Henk J.

    2014-01-01

    High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment. Previous studies have indicated that bradyzoites are highly infectious for cats. To infect cats, tissue cysts were isolated from the brains of mice infected with oocysts of T. gondii M4 strain, and bradyzoites were released by pepsin digestion. Free bradyzoites were counted and graded doses (1000, 100, 50, 10), and 250 intact tissue cysts were inoculated orally into three cats each. Oocysts shed by these five groups of cats were collected from faeces by flotation techniques, counted microscopically and estimated by real time PCR. Additionally, the number of T. gondii in heart, tongue and brains were estimated, and serology for anti T. gondii antibodies was performed. A Beta-Poisson dose-response model was used to estimate the infectivity of single bradyzoites and linear regression was used to determine the relation between inoculated dose and numbers of oocyst shed. We found that real time PCR was more sensitive than microscopic detection of oocysts, and oocysts were detected by PCR in faeces of cats fed 10 bradyzoites but by microscopic examination. Real time PCR may only detect fragments of T. gondii DNA without the presence of oocysts in low doses. Prevalence of tissue cysts of T. gondii in tongue, heart and brains, and anti T. gondii antibody concentrations were all found to depend on the inoculated bradyzoite dose. The combination of the experimental challenge model and the dose response analysis provides a suitable reference for quantifying the potential reduction in human health risk due to a treatment of domestic cats by vaccination or by therapeutic drug application. PMID:25184619

  18. Aged garlic extract reduces blood pressure in hypertensives: a dose-response trial.

    Science.gov (United States)

    Ried, K; Frank, O R; Stocks, N P

    2013-01-01

    Hypertension affects about 30% of adults worldwide. Garlic has blood pressure-lowering properties and the mechanism of action is biologically plausible. Our trial assessed the effect, dose-response, tolerability and acceptability of different doses of aged garlic extract as an adjunct treatment to existing antihypertensive medication in patients with uncontrolled hypertension. A total of 79 general practice patients with uncontrolled systolic hypertension participated in a double-blind randomised placebo-controlled dose-response trial of 12 weeks. Participants were allocated to one of three garlic groups with either of one, two or four capsules daily of aged garlic extract (240/480/960 mg containing 0.6/1.2/2.4 mg of S-allylcysteine) or placebo. Blood pressure was assessed at 4, 8 and 12 weeks and compared with baseline using a mixed-model approach. Tolerability was monitored throughout the trial and acceptability was assessed at 12 weeks by questionnaire. Mean systolic blood pressure was significantly reduced by 11.8±5.4 mm Hg in the garlic-2-capsule group over 12 weeks compared with placebo (P=0.006), and reached borderline significant reduction in the garlic-4-capsule group at 8 weeks (-7.4±4.1 mm Hg, P=0.07). Changes in systolic blood pressure in the garlic-1-capsule group and diastolic blood pressure were not significantly different to placebo. Tolerability, compliance and acceptability were high in all garlic groups (93%) and highest in the groups taking one or two capsules daily. Our trial suggests aged garlic extract to be an effective and tolerable treatment in uncontrolled hypertension, and may be considered as a safe adjunct treatment to conventional antihypertensive therapy.

  19. Universal, non-monotonic structure in the saturation curves of a linear Paul trap

    Science.gov (United States)

    Wells, James; Kwolek, Jonathan; Goodman, Douglas; Blümel, Reinhold; Smith, Winthrop

    2016-05-01

    A common technique to measure ion-atom collision rates in a hybrid trap if the ions have no optical transitions (e.g. alkalis) is to monitor the fluorescence of the neutrals in the presence of a saturated linear Paul trap (LPT). We present numerical simulations, analytical calculations, and experimental results that show that the steady-state ion capacity of an LPT, Ns, exhibits nonlinear, nonmonotonic behavior as a function of ion loading rate, Λ. The steady state as a function of loading rate, Ns(Λ) , shows four distinct regions. In Region I, at the lowest Λ, Ns(Λ) increases monotonically. Then, Ns(Λ) reaches a plateau in Region II, before decreasing to a local minimum in Region III. Finally, in Region IV, Ns(Λ) once again increases monotonically. This behavior appears universal to any Paul trap, regardless of geometry or species trapped. We examine this behavior experimentally as a function of the q stability parameter of the Paul trap and simulate numerically the effect of the particular trap geometry on the onset of each of the four regions. Funding from NSF Grant PHY-1307874.

  20. A gradient Markov chain Monte Carlo algorithm for computing multivariate maximum likelihood estimates and posterior distributions: mixture dose-response assessment.

    Science.gov (United States)

    Li, Ruochen; Englehardt, James D; Li, Xiaoguang

    2012-02-01

    Multivariate probability distributions, such as may be used for mixture dose-response assessment, are typically highly parameterized and difficult to fit to available data. However, such distributions may be useful in analyzing the large electronic data sets becoming available, such as dose-response biomarker and genetic information. In this article, a new two-stage computational approach is introduced for estimating multivariate distributions and addressing parameter uncertainty. The proposed first stage comprises a gradient Markov chain Monte Carlo (GMCMC) technique to find Bayesian posterior mode estimates (PMEs) of parameters, equivalent to maximum likelihood estimates (MLEs) in the absence of subjective information. In the second stage, these estimates are used to initialize a Markov chain Monte Carlo (MCMC) simulation, replacing the conventional burn-in period to allow convergent simulation of the full joint Bayesian posterior distribution and the corresponding unconditional multivariate distribution (not conditional on uncertain parameter values). When the distribution of parameter uncertainty is such a Bayesian posterior, the unconditional distribution is termed predictive. The method is demonstrated by finding conditional and unconditional versions of the recently proposed emergent dose-response function (DRF). Results are shown for the five-parameter common-mode and seven-parameter dissimilar-mode models, based on published data for eight benzene-toluene dose pairs. The common mode conditional DRF is obtained with a 21-fold reduction in data requirement versus MCMC. Example common-mode unconditional DRFs are then found using synthetic data, showing a 71% reduction in required data. The approach is further demonstrated for a PCB 126-PCB 153 mixture. Applicability is analyzed and discussed. Matlab(®) computer programs are provided.

  1. Dose-response effects of systemic anandamide administration in mice sequentially submitted to the open field and elevated plus-maze tests

    Directory of Open Access Journals (Sweden)

    A. Ribeiro

    2009-06-01

    Full Text Available The endocannabinoid system is involved in the control of many physiological functions, including the control of emotional states. In rodents, previous exposure to an open field increases the anxiety-like behavior in the elevated plus-maze. Anxiolytic-like effects of pharmacological compounds that increase endocannabinoid levels have been well documented. However, these effects are more evident in animals with high anxiety levels. Several studies have described characteristic inverted U-shaped dose-response effects of drugs that modulate the endocannabinoid levels. However, there are no studies showing the effects of different doses of exogenous anandamide, an endocannabinoid, in animal models of anxiety. Thus, in the present study, we determined the dose-response effects of exogenous anandamide at doses of 0.01, 0.1, and 1.0 mg/kg in C57BL/6 mice (N = 10/group sequentially submitted to the open field and elevated plus-maze. Anandamide was diluted in 0.9% saline, ethyl alcohol, Emulphor® (18:1:1 and administered ip (0.1 mL/10 g body weight; control animals received the same volume of anandamide vehicle. Anandamide at the dose of 0.1 mg/kg (but not of 0.01 or 1 mg/kg increased (P < 0.05 the time spent and the distance covered in the central zone of the open field, as well as the exploration of the open arms of the elevated plus-maze. Thus, exogenous anandamide, like pharmacological compounds that increase endocannabinoid levels, promoted a characteristic inverted U-shaped dose-response effect in animal models of anxiety. Furthermore, anandamide (0.1 mg/kg induced an anxiolytic-like effect in the elevated plus-maze (P < 0.05 after exposing the animals to the open field test.

  2. SU-D-16A-03: A Radiation Pneumonitis Dose-Response Model Incorporating Non- Local Radiation-Induced Bystander Effect

    Energy Technology Data Exchange (ETDEWEB)

    Gordon, J; Snyder, K; Zhong, H; Chetty, I [Henry Ford Health System, Dept. Radiation Oncology, Detroit, MI (United States)

    2014-06-01

    Purpose: Dose-response models that can reliably predict radiation pneumonitis (RP) to guide radiation therapy (RT) for lung cancer presently do not exist. A model is proposed that incorporates non-local radiationinduced bystander effect (RIBE). Methods: A single sigmoid response function, derived from published data for whole lung irradiation, relates RP probability to cumulative lung damage, regardless of fractionation scheme. Lung damage is assumed to be caused by direct local radiation damage, quantified via the linear-quadratic (LQ) model, and RIBE. Based on published data, RIBE is assumed to be activated when per-fraction dose rises above ∼0.6 Gy, but is constant with dose above that threshold. Integral RIBE damage is assumed proportional to lung volume irradiated above ∼0.6 Gy per fraction. Key model parameters include LQ α and β, and two RIBE parameters: the single-fraction probability δ of damage, and a proportionality parameter κ that relates the potential for RIBE damage to irradiated lung volume. All parameters are tentatively fitted from published data, the RIBE parameters from published RP rates for conventionally fractionated RT (CFRT) and stereotactic body RT (SBRT). Results: The model predicts dose-response curves that are consistent with clinical experience. It provides a tentative explanation for why V20 (33 fractions), V13 (20 fractions) and V5 (<10 fractions) are observed to be correlated with RP. It also provides a plausible explanation for the success of SBRT — RIBE damage increases with the number of fractions, so penalizes CFRT relative to SBRT. Conclusion: The proposed model is relatively simple, extrapolates from published data, plausibly explains several clinical observations, and produces dose-response curves that are consistent with clinical experience. While capable of elaboration, its ability to explain doseresponse experience with different fractionation schemes using a small number of assumptions and parameters is an

  3. Dose-response effects of systemic anandamide administration in mice sequentially submitted to the open field and elevated plus-maze tests.

    Science.gov (United States)

    Ribeiro, A; Ferraz-de-Paula, V; Pinheiro, M L; Palermo-Neto, J

    2009-06-01

    The endocannabinoid system is involved in the control of many physiological functions, including the control of emotional states. In rodents, previous exposure to an open field increases the anxiety-like behavior in the elevated plus-maze. Anxiolytic-like effects of pharmacological compounds that increase endocannabinoid levels have been well documented. However, these effects are more evident in animals with high anxiety levels. Several studies have described characteristic inverted U-shaped dose-response effects of drugs that modulate the endocannabinoid levels. However, there are no studies showing the effects of different doses of exogenous anandamide, an endocannabinoid, in animal models of anxiety. Thus, in the present study, we determined the dose-response effects of exogenous anandamide at doses of 0.01, 0.1, and 1.0 mg/kg in C57BL/6 mice (N = 10/group) sequentially submitted to the open field and elevated plus-maze. Anandamide was diluted in 0.9% saline, ethyl alcohol, Emulphor (18:1:1) and administered ip (0.1 mL/10 g body weight); control animals received the same volume of anandamide vehicle. Anandamide at the dose of 0.1 mg/kg (but not of 0.01 or 1 mg/kg) increased (P open field, as well as the exploration of the open arms of the elevated plus-maze. Thus, exogenous anandamide, like pharmacological compounds that increase endocannabinoid levels, promoted a characteristic inverted U-shaped dose-response effect in animal models of anxiety. Furthermore, anandamide (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze (P open field test.

  4. The Non-Monotonic Effect of Financing Constraints on Investment

    DEFF Research Database (Denmark)

    Hirth, Stefan; Viswanatha, Marc

    We analyze investment timing in a discrete-time framework with two possible investment dates, which is an extension of the model by Lyandres (2007). While Lyandres could only show non-monotonicity of investment in market frictions, we derive an investment threshold that is U-shaped in the firm's ......'s liquid funds, a result similar to the infinite-horizon model by Boyle and Guthrie (2003). However, due to the tractability of our model, we can more clearly explain the relevant trade-offs leading to the U-shape....

  5. Contribution to the ergodic theory of piecewise monotone continuous maps

    OpenAIRE

    Faller, Bastien

    2008-01-01

    This thesis is devoted to the ergodic theory of the piecewise monotone continuous maps of the interval. The coding is a classical approach for these maps. Thanks to the coding, we get a symbolic dynamical system which is almost isomorphic to the initial dynamical system. The principle of the coding is very similar to the one of expansion of real numbers. We first define the coding in a perspective similar to the one of the expansions of real numbers; this perspective was already adopted by Ré...

  6. Deterministic homogenization of parabolic monotone operators with time dependent coefficients

    Directory of Open Access Journals (Sweden)

    Gabriel Nguetseng

    2004-06-01

    Full Text Available We study, beyond the classical periodic setting, the homogenization of linear and nonlinear parabolic differential equations associated with monotone operators. The usual periodicity hypothesis is here substituted by an abstract deterministic assumption characterized by a great relaxation of the time behaviour. Our main tool is the recent theory of homogenization structures by the first author, and our homogenization approach falls under the two-scale convergence method. Various concrete examples are worked out with a view to pointing out the wide scope of our approach and bringing the role of homogenization structures to light.

  7. A Neurodynamic Model to Solve Nonlinear Pseudo-Monotone Projection Equation and Its Applications.

    Science.gov (United States)

    Eshaghnezhad, Mohammad; Effati, Sohrab; Mansoori, Amin

    2016-09-29

    In this paper, a neurodynamic model is given to solve nonlinear pseudo-monotone projection equation. Under pseudo-monotonicity condition and Lipschitz continuous condition, the projection neurodynamic model is proved to be stable in the sense of Lyapunov, globally convergent, globally asymptotically stable, and globally exponentially stable. Also, we show that, our new neurodynamic model is effective to solve the nonconvex optimization problems. Moreover, since monotonicity is a special case of pseudo-monotonicity and also since a co-coercive mapping is Lipschitz continuous and monotone, and a strongly pseudo-monotone mapping is pseudo-monotone, the neurodynamic model can be applied to solve a broader classes of constrained optimization problems related to variational inequalities, pseudo-convex optimization problem, linear and nonlinear complementarity problems, and linear and convex quadratic programming problems. Finally, several illustrative examples are stated to demonstrate the effectiveness and efficiency of our new neurodynamic model.

  8. Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework.

    Science.gov (United States)

    Calabrese, Edward J; Bachmann, Kenneth A; Bailer, A John; Bolger, P Michael; Borak, Jonathan; Cai, Lu; Cedergreen, Nina; Cherian, M George; Chiueh, Chuang C; Clarkson, Thomas W; Cook, Ralph R; Diamond, David M; Doolittle, David J; Dorato, Michael A; Duke, Stephen O; Feinendegen, Ludwig; Gardner, Donald E; Hart, Ronald W; Hastings, Kenneth L; Hayes, A Wallace; Hoffmann, George R; Ives, John A; Jaworowski, Zbigniew; Johnson, Thomas E; Jonas, Wayne B; Kaminski, Norbert E; Keller, John G; Klaunig, James E; Knudsen, Thomas B; Kozumbo, Walter J; Lettieri, Teresa; Liu, Shu-Zheng; Maisseu, Andre; Maynard, Kenneth I; Masoro, Edward J; McClellan, Roger O; Mehendale, Harihara M; Mothersill, Carmel; Newlin, David B; Nigg, Herbert N; Oehme, Frederick W; Phalen, Robert F; Philbert, Martin A; Rattan, Suresh I S; Riviere, Jim E; Rodricks, Joseph; Sapolsky, Robert M; Scott, Bobby R; Seymour, Colin; Sinclair, David A; Smith-Sonneborn, Joan; Snow, Elizabeth T; Spear, Linda; Stevenson, Donald E; Thomas, Yolene; Tubiana, Maurice; Williams, Gary M; Mattson, Mark P

    2007-07-01

    Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose-response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines.

  9. Dose-Response Relation Between Work Hours and Cardiovascular Disease Risk: Findings From the Panel Study of Income Dynamics.

    Science.gov (United States)

    Conway, Sadie H; Pompeii, Lisa A; Roberts, Robert E; Follis, Jack L; Gimeno, David

    2016-03-01

    The aim of this study was to examine the presence of a dose-response relationship between work hours and incident cardiovascular disease (CVD) in a representative sample of U.S. workers. A retrospective cohort study of 1926 individuals from the Panel Study of Income Dynamics (1986 to 2011) employed for at least 10 years. Restricted cubic spline regression was used to estimate the dose-response relationship of work hours with CVD. A dose-response relationship was observed in which an average workweek of 46 hours or more for at least 10 years was associated with an increased risk of CVD. Compared with working 45 hours per week, working an additional 10 hours per week or more for at least 10 years increased CVD risk by at least 16%. Working more than 45 work hours per week for at least 10 years may be an independent risk factor for CVD.

  10. Coffee and tea consumption and risk of lung cancer: a dose-response analysis of observational studies.

    Science.gov (United States)

    Wang, Yaopeng; Yu, Xuyi; Wu, Yili; Zhang, Dongfeng

    2012-11-01

    Results from the recent meta-analysis suggested a favorable effect of green tea consumption and risk of lung cancer, while no significant association was found between black tea consumption and risk of lung cancer. Besides, a significantly positive association was found between coffee consumption and risk of lung cancer. However, the relationship of green tea and coffee consumption is unclear. Thus the dose-response relationship was assessed by restricted cubic spline model and multivariate random-effect meta-regression. Results suggested that a linear dose-response relationship exists between coffee consumption and risk of lung cancer, while the dose-response relationship is nonlinear between green tea consumption and risk of lung cancer.

  11. DATA PREORDERING IN GENERALIZED PAV ALGORITHM FOR MONOTONIC REGRESSION

    Institute of Scientific and Technical Information of China (English)

    Oleg Burdakov; Anders Grimvall; Oleg Sysoev

    2006-01-01

    Monotonic regression (MR) is a least distance problem with monotonicity constraints induced by a partially ordered data set of observations. In our recent publication [In Ser.Nonconvex Optimization and Its Applications, Springer-Verlag, (2006) 83, pp. 25-33],the Pool-Adjacent-Violators algorithm (PAV) was generalized from completely to partially ordered data sets (posets). The new algorithm, called GPAV, is characterized by the very low computational complexity, which is of second order in the number of observations.It treats the observations in a consecutive order, and it can follow any arbitrarily chosen topological order of the poset of observations. The GPAV algorithm produces a sufficiently accurate solution to the MR problem, but the accuracy depends on the chosen topological order. Here we prove that there exists a topological order for which the resulted GPAV solution is optimal. Furthermore, we present results of extensive numerical experiments,from which we draw conclusions about the most and the least preferable topological orders.

  12. Paradigm lost, paradigm found: The re-emergence of hormesis as a fundamental dose response model in the toxicological sciences

    Energy Technology Data Exchange (ETDEWEB)

    Calabrese, Edward J. [Environmental Health Sciences, School of Public Health, Morrill I, N344, University of Massachusetts, Amherst, MA 01003 (United States)]. E-mail: edwardc@schoolph.umass.edu

    2005-12-15

    This paper provides an assessment of the toxicological basis of the hormetic dose-response relationship including issues relating to its reproducibility, frequency, and generalizability across biological models, endpoints measured and chemical class/physical stressors and implications for risk assessment. The quantitative features of the hormetic dose response are described and placed within toxicological context that considers study design, temporal assessment, mechanism, and experimental model/population heterogeneity. Particular emphasis is placed on an historical evaluation of why the field of toxicology rejected hormesis in favor of dose response models such as the threshold model for assessing non-carcinogens and linear no threshold (LNT) models for assessing carcinogens. The paper argues that such decisions were principally based on complex historical factors that emerged from the intense and protracted conflict between what is now called traditional medicine and homeopathy and the overly dominating influence of regulatory agencies on the toxicological intellectual agenda. Such regulatory agency influence emphasized hazard/risk assessment goals such as the derivation of no observed adverse effect levels (NOAELs) and the lowest observed adverse effect levels (LOAELs) which were derived principally from high dose studies using few doses, a feature which restricted perceptions and distorted judgments of several generations of toxicologists concerning the nature of the dose-response continuum. Such historical and technical blind spots lead the field of toxicology to not only reject an established dose-response model (hormesis), but also the model that was more common and fundamental than those that the field accepted. - The quantitative features of the hormetic dose/response are described and placed within the context of toxicology.

  13. Dose-responses from multi-model inference for the non-cancer disease mortality of atomic bomb survivors.

    Science.gov (United States)

    Schöllnberger, H; Kaiser, J C; Jacob, P; Walsh, L

    2012-05-01

    The non-cancer mortality data for cerebrovascular disease (CVD) and cardiovascular diseases from Report 13 on the atomic bomb survivors published by the Radiation Effects Research Foundation were analysed to investigate the dose-response for the influence of radiation on these detrimental health effects. Various parametric and categorical models (such as linear-no-threshold (LNT) and a number of threshold and step models) were analysed with a statistical selection protocol that rated the model description of the data. Instead of applying the usual approach of identifying one preferred model for each data set, a set of plausible models was applied, and a sub-set of non-nested models was identified that all fitted the data about equally well. Subsequently, this sub-set of non-nested models was used to perform multi-model inference (MMI), an innovative method of mathematically combining different models to allow risk estimates to be based on several plausible dose-response models rather than just relying on a single model of choice. This procedure thereby produces more reliable risk estimates based on a more comprehensive appraisal of model uncertainties. For CVD, MMI yielded a weak dose-response (with a risk estimate of about one-third of the LNT model) below a step at 0.6 Gy and a stronger dose-response at higher doses. The calculated risk estimates are consistent with zero risk below this threshold-dose. For mortalities related to cardiovascular diseases, an LNT-type dose-response was found with risk estimates consistent with zero risk below 2.2 Gy based on 90% confidence intervals. The MMI approach described here resolves a dilemma in practical radiation protection when one is forced to select between models with profoundly different dose-responses for risk estimates.

  14. Dose-responses from multi-model inference for the non-cancer disease mortality of atomic bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Schoellnberger, H.; Kaiser, J.C.; Jacob, P. [Institute of Radiation Protection, Helmholtz Zentrum Muenchen, Department of Radiation Sciences, Neuherberg (Germany); Walsh, L. [BfS-Federal Office for Radiation Protection, Neuherberg (Germany)

    2012-05-15

    The non-cancer mortality data for cerebrovascular disease (CVD) and cardiovascular diseases from Report 13 on the atomic bomb survivors published by the Radiation Effects Research Foundation were analysed to investigate the dose-response for the influence of radiation on these detrimental health effects. Various parametric and categorical models (such as linear-no-threshold (LNT) and a number of threshold and step models) were analysed with a statistical selection protocol that rated the model description of the data. Instead of applying the usual approach of identifying one preferred model for each data set, a set of plausible models was applied, and a sub-set of non-nested models was identified that all fitted the data about equally well. Subsequently, this sub-set of non-nested models was used to perform multi-model inference (MMI), an innovative method of mathematically combining different models to allow risk estimates to be based on several plausible dose-response models rather than just relying on a single model of choice. This procedure thereby produces more reliable risk estimates based on a more comprehensive appraisal of model uncertainties. For CVD, MMI yielded a weak dose-response (with a risk estimate of about one-third of the LNT model) below a step at 0.6 Gy and a stronger dose-response at higher doses. The calculated risk estimates are consistent with zero risk below this threshold-dose. For mortalities related to cardiovascular diseases, an LNT-type dose-response was found with risk estimates consistent with zero risk below 2.2 Gy based on 90% confidence intervals. The MMI approach described here resolves a dilemma in practical radiation protection when one is forced to select between models with profoundly different dose-responses for risk estimates. (orig.)

  15. The alanine detector in BNCT dosimetry: Dose response in thermal and epithermal neutron fields

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, T., E-mail: schmito@uni-mainz.de [Institute for nuclear chemistry, Johannes Gutenberg-University, Mainz D-55128 (Germany); Bassler, N. [Department of Physics and Astronomy, Aarhus University, Ny Munkegade 120, Aarhus C, Aarhus 8000 (Denmark); Blaickner, M. [AIT Austrian Institute of Technology GmbH, Vienna A-1220 (Austria); Ziegner, M. [AIT Austrian Institute of Technology GmbH, Vienna A-1220, Austria and TU Wien, Vienna University of Technology, Vienna A-1020 (Austria); Hsiao, M. C. [Insitute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Liu, Y. H. [Nuclear Science and Technology Development Center, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Koivunoro, H. [Department of Physics, University of Helsinki, POB 64, FI-00014, Finland and HUS Medical Imaging Center, Helsinki University Central Hospital, FI-00029 HUS (Finland); Auterinen, I.; Serén, T.; Kotiluoto, P. [VTT Technical Research Centre of Finland, Espoo (Finland); Palmans, H. [National Physical Laboratory, Acoustics and Ionising Radiation Division, Teddington TW11 0LW, United Kingdom and Medical Physics Group, EBG MedAustron GmbH, Wiener Neustadt A-2700 (Austria); Sharpe, P. [National Physical Laboratory, Acoustics and Ionising Radiation Division, Teddington TW11 0LW (United Kingdom); Langguth, P. [Department of Pharmacy and Toxicology, University of Mainz, Mainz D-55128 (Germany); Hampel, G. [Institut für Kernchemie, Johannes Gutenberg-Universität, Mainz D-55128 (Germany)

    2015-01-15

    Purpose: The response of alanine solid state dosimeters to ionizing radiation strongly depends on particle type and energy. Due to nuclear interactions, neutron fields usually also consist of secondary particles such as photons and protons of diverse energies. Various experiments have been carried out in three different neutron beams to explore the alanine dose response behavior and to validate model predictions. Additionally, application in medical neutron fields for boron neutron capture therapy is discussed. Methods: Alanine detectors have been irradiated in the thermal neutron field of the research reactor TRIGA Mainz, Germany, in five experimental conditions, generating different secondary particle spectra. Further irradiations have been made in the epithermal neutron beams at the research reactors FiR 1 in Helsinki, Finland, and Tsing Hua open pool reactor in HsinChu, Taiwan ROC. Readout has been performed with electron spin resonance spectrometry with reference to an absorbed dose standard in a {sup 60}Co gamma ray beam. Absorbed doses and dose components have been calculated using the Monte Carlo codes FLUKA and MCNP. The relative effectiveness (RE), linking absorbed dose and detector response, has been calculated using the Hansen and Olsen alanine response model. Results: The measured dose response of the alanine detector in the different experiments has been evaluated and compared to model predictions. Therefore, a relative effectiveness has been calculated for each dose component, accounting for its dependence on particle type and energy. Agreement within 5% between model and measurement has been achieved for most irradiated detectors. Significant differences have been observed in response behavior between thermal and epithermal neutron fields, especially regarding dose composition and depth dose curves. The calculated dose components could be verified with the experimental results in the different primary and secondary particle fields. Conclusions: The

  16. Habitual Chocolate Consumption May Increase Body Weight in a Dose-Response Manner

    Science.gov (United States)

    Greenberg, James A.; Buijsse, Brian

    2013-01-01

    Objective Habitual chocolate intake was recently found to be associated with lower body weight in three cross-sectional epidemiological studies. Our objective was to assess whether these cross-sectional results hold up in a more rigorous prospective analysis. Methods We used data from the Atherosclerosis Risk in Communities cohort. Usual dietary intake was assessed by questionnaire at baseline (1987–98), and after six years. Participants reported usual chocolate intake as the frequency of eating a 1-oz (∼28 g) serving. Body weight and height were measured at the two visits. Missing data were replaced by multiple imputation. Linear mixed-effects models were used to evaluate cross-sectional and prospective associations between chocolate intake and adiposity. Results Data were from 15,732 and 12,830 participants at the first and second visit, respectively. More frequent chocolate consumption was associated with a significantly greater prospective weight gain over time, in a dose-response manner. For instance, compared to participants who ate a chocolate serving less often than monthly, those who ate it 1–4 times a month and at least weekly experienced an increase in Body Mass Index (kg/m2) of 0.26 (95% CI 0.08, 0.44) and 0.39 (0.23, 0.55), respectively, during the six-year study period. In cross-sectional analyses the frequency of chocolate consumption was inversely associated with body weight. This inverse association was attenuated after excluding participants with preexisting obesity-related illness. Compared to participants without such illness, those with it had higher BMI and reported less frequent chocolate intake, lower caloric intake, and diets richer in fruits and vegetables. They tended to make these dietary changes after becoming ill. Conclusions Our prospective analysis found that a chocolate habit was associated with long-term weight gain, in a dose-response manner. Our cross-sectional finding that chocolate intake was associated with lower body

  17. Quantitative Models of the Dose-Response and Time Course of Inhalational Anthrax in Humans

    Science.gov (United States)

    Schell, Wiley A.; Bulmahn, Kenneth; Walton, Thomas E.; Woods, Christopher W.; Coghill, Catherine; Gallegos, Frank; Samore, Matthew H.; Adler, Frederick R.

    2013-01-01

    Anthrax poses a community health risk due to accidental or intentional aerosol release. Reliable quantitative dose-response analyses are required to estimate the magnitude and timeline of potential consequences and the effect of public health intervention strategies under specific scenarios. Analyses of available data from exposures and infections of humans and non-human primates are often contradictory. We review existing quantitative inhalational anthrax dose-response models in light of criteria we propose for a model to be useful and defensible. To satisfy these criteria, we extend an existing mechanistic competing-risks model to create a novel Exposure–Infection–Symptomatic illness–Death (EISD) model and use experimental non-human primate data and human epidemiological data to optimize parameter values. The best fit to these data leads to estimates of a dose leading to infection in 50% of susceptible humans (ID50) of 11,000 spores (95% confidence interval 7,200–17,000), ID10 of 1,700 (1,100–2,600), and ID1 of 160 (100–250). These estimates suggest that use of a threshold to human infection of 600 spores (as suggested in the literature) underestimates the infectivity of low doses, while an existing estimate of a 1% infection rate for a single spore overestimates low dose infectivity. We estimate the median time from exposure to onset of symptoms (incubation period) among untreated cases to be 9.9 days (7.7–13.1) for exposure to ID50, 11.8 days (9.5–15.0) for ID10, and 12.1 days (9.9–15.3) for ID1. Our model is the first to provide incubation period estimates that are independently consistent with data from the largest known human outbreak. This model refines previous estimates of the distribution of early onset cases after a release and provides support for the recommended 60-day course of prophylactic antibiotic treatment for individuals exposed to low doses. PMID:24058320

  18. Influence of image slice thickness on rectal dose-response relationships following radiotherapy of prostate cancer

    Science.gov (United States)

    Olsson, C.; Thor, M.; Liu, M.; Moissenko, V.; Petersen, S. E.; Høyer, M.; Apte, A.; Deasy, J. O.

    2014-07-01

    When pooling retrospective data from different cohorts, slice thicknesses of acquired computed tomography (CT) images used for treatment planning may vary between cohorts. It is, however, not known if varying slice thickness influences derived dose-response relationships. We investigated this for rectal bleeding using dose-volume histograms (DVHs) of the rectum and rectal wall for dose distributions superimposed on images with varying CT slice thicknesses. We used dose and endpoint data from two prostate cancer cohorts treated with three-dimensional conformal radiotherapy to either 74 Gy (N = 159) or 78 Gy (N = 159) at 2 Gy per fraction. The rectum was defined as the whole organ with content, and the morbidity cut-off was Grade ≥2 late rectal bleeding. Rectal walls were defined as 3 mm inner margins added to the rectum. DVHs for simulated slice thicknesses from 3 to 13 mm were compared to DVHs for the originally acquired slice thicknesses at 3 and 5 mm. Volumes, mean, and maximum doses were assessed from the DVHs, and generalized equivalent uniform dose (gEUD) values were calculated. For each organ and each of the simulated slice thicknesses, we performed predictive modeling of late rectal bleeding using the Lyman-Kutcher-Burman (LKB) model. For the most coarse slice thickness, rectal volumes increased (≤18%), whereas maximum and mean doses decreased (≤0.8 and ≤4.2 Gy, respectively). For all a values, the gEUD for the simulated DVHs were ≤1.9 Gy different than the gEUD for the original DVHs. The best-fitting LKB model parameter values with 95% CIs were consistent between all DVHs. In conclusion, we found that the investigated slice thickness variations had minimal impact on rectal dose-response estimations. From the perspective of predictive modeling, our results suggest that variations within 10 mm in slice thickness between cohorts are unlikely to be a limiting factor when pooling multi-institutional rectal dose data that include slice thickness

  19. Strong asymptotic convergence of evolution equations governed by maximal monotone operators with Tikhonov regularization

    Science.gov (United States)

    Cominetti, R.; Peypouquet, J.; Sorin, S.

    We consider the Tikhonov-like dynamics -u˙(t)∈A(u(t))+ɛ(t)u(t) where A is a maximal monotone operator on a Hilbert space and the parameter function ɛ(t) tends to 0 as t→∞ with ∫0∞ɛ(t) dt=∞. When A is the subdifferential of a closed proper convex function f, we establish strong convergence of u(t) towards the least-norm minimizer of f. In the general case we prove strong convergence towards the least-norm point in A(0) provided that the function ɛ(t) has bounded variation, and provide a counterexample when this property fails.

  20. 单调q矩阵的Feller性质%The Feller Property for the Monotone q-Matrix

    Institute of Scientific and Technical Information of China (English)

    张秀珍; 李扬荣

    2011-01-01

    In this paper, a necessary and sufficient condition for a monotone q-matrix Q to be Feller is given in terms of (Q), where (Q) is the dual of 2. Then, the authors further point out that the minimal (Q)-function (P)(t) is the dual for the minimal Q-function P(t) if Q is monotone and zero-exit.%给出了单调q-矩阵Q是Feller的充分必要条件,进一步指出:若q-矩阵Q是单调零流出的且(Q)是Q的对偶,则最小(Q)-函数(Q)(t)是最小(Q)-函数P(t)的对偶.

  1. Functional Selectivity of Kappa Opioid Receptor Agonists in Peripheral Sensory Neurons

    Science.gov (United States)

    Jamshidi, Raehannah J.; Jacobs, Blaine A.; Sullivan, Laura C.; Chavera, Teresa A.; Saylor, Rachel M.; Prisinzano, Thomas E.; Clarke, William P.

    2015-01-01

    Activation of kappa opioid receptors (KORs) expressed by peripheral sensory neurons that respond to noxious stimuli (nociceptors) can reduce neurotransmission of pain stimuli from the periphery to the central nervous system. We have previously shown that the antinociception dose-response curve for peripherally restricted doses of the KOR agonist (–)-(trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide (U50488) has an inverted U shape. Here, we found that the downward phase of the U50488 dose-response curve was blocked by an inhibitor of extracellular signal-regulated kinase (ERK) activation U0126. Local administration of the selective KOR agonist salvinorin A (Sal-A), also resulted in an inverted U-shaped curve; however, the downward phase was insensitive to U0126. By contrast, inhibition of c-Jun N-terminal kinase (JNK) partially blocked the downward phase of the dose-response curve to Sal-A, suggesting a role for JNK. In cultures of peripheral sensory neurons, U50488 and Sal-A inhibited adenylyl cyclase activity with similar efficacies; however, their ability to activate ERK and JNK differed. Whereas U50488 activated ERK but not JNK, Sal-A activated JNK but not ERK. Moreover, although both U50488 and Sal-A produced homologous desensitization, desensitization to U50488 was blocked by inhibition of ERK activation, whereas desensitization to Sal-A was blocked by inhibition of JNK. Substitution of an ethoxymethyl ether for the C2 position acetyl group of Sal-A reduced stimulation of JNK, prevented desensitization by ethoxymethyl ether for the C2 position acetyl group of Sal-A, and resulted in a monotonic antinociception dose-response curve. Collectively, these data demonstrate the functional selectivity of KOR ligands for signaling in peripheral sensory neurons, which results in differential effects on behavioral responses in vivo. PMID:26297384

  2. Comparison of skin stripping, in vitro release, and skin blanching response methods to measure dose response and similarity of triamcinolone acetonide cream strengths from two manufactured sources.

    Science.gov (United States)

    Pershing, Lynn K; Bakhtian, Shahrzad; Poncelet, Craig E; Corlett, Judy L; Shah, Vinod P

    2002-05-01

    The collective studies compare in vitro drug release, in vivo skin stripping, and skin blanching response methods for dose responsiveness and bioequivalence assessment of triamcinolone acetonide cream products, as a function of application duration, drug concentration, and manufacturer source. Commercially available triamcinolone acetonide creams (0.025%, 0.1%, and 0.5%) from two manufacturers were evaluated in vitro for rate and extent of drug release across synthetic membranes and in vivo for rate, extent, and variability of drug uptake into human stratum corneum and skin blanching response in human forearm skin. Data demonstrate that increasing triamcinolone acetonide cream concentration applied increased the rate and extent of drug released in vitro as well as the extent of drug uptake and skin blanching response in human skin in vivo. No difference (p blanching response methods. Dermatopharmacokinetic analysis of triamcinonide acetonide in vivo is therefore dose responsive to drug concentration applied and application duration and agrees with in vivo skin blanching results. Data support the use of dermatopharmacokinetic methods for bioequivalence and bioavailability assessment of topical drug products.

  3. Nano-silver induces dose-response effects on the nematode Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Ellegaard-Jensen, Lea; Alstrup Jensen, Keld; Johansen, Anders

    2012-01-01

    adverse dose-response effects and mortality on C. elegans. LC50 for AgNP28 was lower than for AgNP1 and, hence, at the present test conditions the PVP-coated AgNP28 was more toxic than AgNP1. Including E. coil in the test medium as a food source increased AgNPs toxicity towards nematodes compared to when......Toxicity of nano-formulated silver to eukaryotes was assessed by exposing nematodes (Caenorhabditis elegans) to two types of silver nanoparticles (AgNPs): with average primary particle diameters of 1 nm (AgNP1) and 28 nm (AgNP28, PVP coated), respectively. Tests were performed with and without...... and AgNP28. Higher toxicity of AgNP28 than AgNP1 may be explained by a combination of effects of coating, Ag-solubility and higher uptake rates due to agglomeration into mu m-size agglomerates in the exposure medium. (C) 2012 Elsevier Inc. All rights reserved....

  4. Dose-Response Effect of Sunlight on Vitamin D2 Production in Agaricus bisporus Mushrooms

    DEFF Research Database (Denmark)

    Urbain, Paul; Jakobsen, Jette

    2015-01-01

    The dose response effect of UV-B irradiation from sunlight on vitamin D2 content of sliced Agaricus bisporus (white button mushroom) during the process of sun-drying was investigated.Real-time UV-B and UV-A data were obtained using a high-performance spectroradiometer. During the first hour...... of sunlight exposure, the vitamin D2 content of the mushrooms increased in a linear manner, with concentrations increasing from 0.1 μg/g up to 3.9 ± 0.8 μg/g dry weight (DW). At the subsequent two measurements one and 3 h later, respectively, a plateau was reached. Two hours of additional exposure triggered...... a significant decline in vitamin D2 content. After just 15 min of sun exposure and an UV-B dose of 0.13 J/cm(2), the vitamin D2 content increased significantly to 2.2 ± 0.5 μg/g DW (P vitamin D2 per 100 g of fresh mushrooms and comparable to levels found...

  5. The notion of hormesis and the dose-response theory: a unified approach.

    Science.gov (United States)

    Murado, M A; Vázquez, J A

    2007-02-07

    According to an opinion which is vigorous and insistently defended for approximately one decade, hormesis (the response of a biological entity to an effector, with stimulatory results at low doses and inhibitory results at high doses) radically puts into question the classic theory of dose-response (DR) relationships and demands a profound revision of environmental protection policies. Herein we show that DR theory, with the modifications which we propose, allows the modelling of various kinds of biphasic responses which are phenomenologically similar to hormetic ones and of well-defined origin, as well as responses which have been treated as genuinely hormetic. Our descriptive approach may also represent a useful resource for experimental design, directed towards identifying some of the potentially heterogeneous mechanisms which underlie the hormetic phenomenon. Finally, it also allows to discuss some factors which prevent the use of the notion of hormesis-perhaps useful in a clinical context, under strictly controlled conditions-to make decisions on environmental protection measures.

  6. Dose - response relationship between noise exposure and the risk of occupational injury

    Directory of Open Access Journals (Sweden)

    Jin-Ha Yoon

    2015-01-01

    Full Text Available Many workers worldwide experience fatality and disability caused by occupational injuries. This study examined the relationship between noise exposure and occupational injuries at factories in Korea. A total of 1790 factories located in northern Gyeonggi Province, Korea was evaluated. The time-weighted average levels of dust and noise exposure were taken from Workplace Exposure Assessment data. Apart occupational injuries, sports events, traffic accidents, and other accidents occurring outside workplaces were excluded. The incidences of occupational injury in each factory were calculated by data from the Korea Workers′ Compensation and Welfare Services. Workplaces were classified according to the incidence of any occupational injuries (incident or nonincident workplaces, respectively. Workplace dust exposure was classified as 90 dB. Workplaces with high noise exposure were significantly associated with being incident workplaces, whereas workplaces with high dust exposure were not. The odds ratios (95% confidence intervals derived from a logistic regression model were 1.68 (1.27-2.24 and 3.42 (2.26-5.17 at 80-89 dB and ≥90 dB versus <80 dB. These associations remained significant when in a separate analysis according to high or low dust exposure level. Noise exposure increases the risk of occupational injury in the workplace. Furthermore, the risk of occupational injury increases with noise exposure level in a dose-response relationship. Therefore, strategies for reducing noise exposure level are required to decrease the risk of occupational injury.

  7. DOSE RESPONSE EFFECT OF Paracoccidioides brasiliensis IN AN EXPERIMENTAL MODEL OF ARTHRITIS

    Directory of Open Access Journals (Sweden)

    Eduardo Alexandre Loth

    2014-06-01

    Full Text Available Paracoccidioidomycosis (PCM is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb and corresponds to prevalent systemic mycosis in Latin America. The aim of the present work was to evaluate the dose response effect of the fungal yeast phase for the standardization of an experimental model of septic arthritis. The experiments were performed with groups of 14 rats that received doses of 103, 104 or 105 P. brasiliensis (Pb18 cells. The fungi were injected in 50 µL of phosphate-buffered saline (PBS directly into the knee joints of the animals. The following parameters were analyzed in this work: the formation of swelling in knees infused with yeast cells and the radiological and anatomopathological alterations, besides antibody titer by ELISA. After 15 days of infection, signs of inflammation were evident. At 45 days, some features of damage and necrosis were observed in the articular cartilage. The systemic dissemination of the fungus was observed in 11% of the inoculated animals, and it was concluded that the experimental model is able to mimic articular PCM in humans and that the dose of 105 yeast cells can be used as standard in this model.

  8. Dose response effect of Paracoccidioides brasiliensis in an experimental model of arthritis.

    Science.gov (United States)

    Loth, Eduardo Alexandre; Biazim, Samia Khalil; Dos Santos, José Henrique Fermino Ferreira; Puccia, Rosana; Brancalhão, Rosimeire Costa; Chasco, Lucinéia de Fátima; Gandra, Rinaldo Ferreira; Simão, Rita de Cássia Garcia; de Franco, Marcello Fabiano

    2014-01-01

    Paracoccidioidomycosis (PCM) is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb) and corresponds to prevalent systemic mycosis in Latin America. The aim of the present work was to evaluate the dose response effect of the fungal yeast phase for the standardization of an experimental model of septic arthritis. The experiments were performed with groups of 14 rats that received doses of 103, 104 or 105 P. brasiliensis (Pb18) cells. The fungi were injected in 50 µL of phosphate-buffered saline (PBS) directly into the knee joints of the animals. The following parameters were analyzed in this work: the formation of swelling in knees infused with yeast cells and the radiological and anatomopathological alterations, besides antibody titer by ELISA. After 15 days of infection, signs of inflammation were evident. At 45 days, some features of damage and necrosis were observed in the articular cartilage. The systemic dissemination of the fungus was observed in 11% of the inoculated animals, and it was concluded that the experimental model is able to mimic articular PCM in humans and that the dose of 105 yeast cells can be used as standard in this model.

  9. Dose - response relationship between noise exposure and the risk of occupational injury.

    Science.gov (United States)

    Yoon, Jin-Ha; Hong, Jeong-Suk; Roh, Jaehoon; Kim, Chi-Nyon; Won, Jong-Uk

    2015-01-01

    Many workers worldwide experience fatality and disability caused by occupational injuries. This study examined the relationship between noise exposure and occupational injuries at factories in Korea. A total of 1790 factories located in northern Gyeonggi Province, Korea was evaluated. The time-weighted average levels of dust and noise exposure were taken from Workplace Exposure Assessment data. Apart occupational injuries, sports events, traffic accidents, and other accidents occurring outside workplaces were excluded. The incidences of occupational injury in each factory were calculated by data from the Korea Workers' Compensation and Welfare Services. Workplaces were classified according to the incidence of any occupational injuries (incident or nonincident workplaces, respectively). Workplace dust exposure was classified as noise exposure as 90 dB. Workplaces with high noise exposure were significantly associated with being incident workplaces, whereas workplaces with high dust exposure were not. The odds ratios (95% confidence intervals) derived from a logistic regression model were 1.68 (1.27-2.24) and 3.42 (2.26-5.17) at 80-89 dB and ≥ 90 dB versus Noise exposure increases the risk of occupational injury in the workplace. Furthermore, the risk of occupational injury increases with noise exposure level in a dose-response relationship. Therefore, strategies for reducing noise exposure level are required to decrease the risk of occupational injury.

  10. Ordered multiple comparisons with the best and their applications to dose-response studies.

    Science.gov (United States)

    Strassburger, K; Bretz, F; Finner, H

    2007-12-01

    This article considers the problem of comparing several treatments (dose levels, interventions, etc.) with the best, where the best treatment is unknown and the treatments are ordered in some sense. Order relations among treatments often occur quite naturally in practice. They may be ordered according to increasing risks, such as tolerability or safety problems with increasing dose levels in a dose-response study, for example. We tackle the problem of constructing a lower confidence bound for the smallest index of all treatments being at most marginally less effective than the (best) treatment having the largest effect. Such a bound ensures at confidence level 1 -alpha that all treatments with lower indices are relevantly less effective than the best competitor. We derive a multiple testing strategy that results in sharp confidence bounds. The proposed lower confidence bound is compared with those derived from other testing strategies. We further derive closed-form expressions for power and sample size calculations. Finally, we investigate several real data sets to illustrate various applications of our methods.

  11. Dose-Response Effect of Sunlight on Vitamin D2 Production in Agaricus bisporus Mushrooms.

    Science.gov (United States)

    Urbain, Paul; Jakobsen, Jette

    2015-09-23

    The dose response effect of UV-B irradiation from sunlight on vitamin D2 content of sliced Agaricus bisporus (white button mushroom) during the process of sun-drying was investigated.Real-time UV-B and UV-A data were obtained using a high-performance spectroradiometer. During the first hour of sunlight exposure, the vitamin D2 content of the mushrooms increased in a linear manner, with concentrations increasing from 0.1 μg/g up to 3.9 ± 0.8 μg/g dry weight (DW). At the subsequent two measurements one and 3 h later, respectively, a plateau was reached. Two hours of additional exposure triggered a significant decline in vitamin D2 content. After just 15 min of sun exposure and an UV-B dose of 0.13 J/cm(2), the vitamin D2 content increased significantly to 2.2 ± 0.5 μg/g DW (P < 0.0001), which is equivalent to 17.6 μg (704 IU) vitamin D2 per 100 g of fresh mushrooms and comparable to levels found in fatty fish like the Atlantic salmon.

  12. Inhibition of food-stimulated acid secretion (intragastric titration) by roxatidine acetate. Dose-response study.

    Science.gov (United States)

    Bonfils, S; Chen, W W; Vatier, J

    1988-01-01

    In 10 healthy male volunteers a dose-response study was carried out with roxatidine acetate, 75, 150, 300, and 600 mg, and placebo on food-stimulated gastric acid secretion (intragastric titration (IGT]. The design of the study, with drug intake 150 min before starting IGT, enabled stable inhibition over the 90-min observation period of the test. Cumulative secretory results showed a dose-related acid secretion inhibition (67% for 75 mg; 87.6% for 150 mg; 98.8% for 300 mg; 99.6% for 600 mg). The results were statistically significantly different from placebo and from each other, except for 300 mg versus 600 mg. With a Lineweaver-Burk plot, the ED50 was 41 mg and r = 0.98. Peak concentrations of roxatidine were observed either at T 150 or T 180. Significant correlation (r = 0.7; p less than 0.001) was obtained for the percentage inhibition with 75 mg and 150 mg together versus peak concentrations. Antisecretory potency with the IGT model applied to normal subjects appears to be of the same order for roxatidine acetate and for ranitidine.

  13. Increasing food deprivation relative to baseline influences D-amphetamine dose-response gradients.

    Science.gov (United States)

    Lotfizadeh, Amin D; Zimmermann, Zachary J; Watkins, Erin E; Edwards, Timothy L; Poling, Alan

    2014-10-01

    Several studies using non-pharmacological discriminative stimuli have found that stimulus control, as evident in generalization gradients, changes when motivation for (i.e., deprivation of) the relevant reinforcer is altered. Drug-discrimination studies, however, have not consistently revealed such an effect. A procedural detail that may account for the lack of a reliable effect in drug-discrimination studies is that motivation was characteristically reduced relative to the training condition in these studies. The present experiment examined how substantially increasing motivation affects D-amphetamine discrimination. Rats initially were trained to discriminate D-amphetamine (1.0 mg/kg) from vehicle (0 mg/kg) injections under 22-h food deprivation conditions. Dose-response gradients were then obtained under 22-h and 46-h deprivation levels. The ED50 was significantly higher with greater deprivation. This finding suggests that increasing motivation relative to the training condition may reduce stimulus control by drugs, while decreasing it may sharpen stimulus control. Copyright © 2014. Published by Elsevier Inc.

  14. Dose-response curve slope helps predict therapeutic potency and breadth of HIV broadly neutralizing antibodies.

    Science.gov (United States)

    Webb, Nicholas E; Montefiori, David C; Lee, Benhur

    2015-09-29

    A new generation of HIV broadly neutralizing antibodies (bnAbs) with remarkable potency, breadth and epitope diversity has rejuvenated interest in immunotherapeutic strategies. Potencies defined by in vitro IC50 and IC80 values (50 and 80% inhibitory concentrations) figure prominently into the selection of clinical candidates; however, much higher therapeutic levels will be required to reduce multiple logs of virus and impede escape. Here we predict bnAb potency at therapeutic levels by analysing dose-response curve slopes, and show that slope is independent of IC50/IC80 and specifically relates to bnAb epitope class. With few exceptions, CD4-binding site and V3-glycan bnAbs exhibit slopes >1, indicative of higher expected therapeutic effectiveness, whereas V2-glycan, gp41 membrane-proximal external region (MPER) and gp120-gp41 bnAbs exhibit less favourable slopes <1. Our results indicate that slope is one major predictor of both potency and breadth for bnAbs at clinically relevant concentrations, and may better coordinate the relationship between bnAb epitope structure and therapeutic expectations.

  15. Dose-response modeling in mental health using stein-like estimators with instrumental variables.

    Science.gov (United States)

    Ginestet, Cedric E; Emsley, Richard; Landau, Sabine

    2017-02-21

    A mental health trial is analyzed using a dose-response model, in which the number of sessions attended by the patients is deemed indicative of the dose of psychotherapeutic treatment. Here, the parameter of interest is the difference in causal treatment effects between the subpopulations that take part in different numbers of therapy sessions. For this data set, interactions between random treatment allocation and prognostic baseline variables provide the requisite instrumental variables. While the corresponding two-stage least squares (TSLS) estimator tends to have smaller bias than the ordinary least squares (OLS) estimator; the TSLS suffers from larger variance. It is therefore appealing to combine the desirable properties of the OLS and TSLS estimators. Such a trade-off is achieved through an affine combination of these two estimators, using mean squared error as a criterion. This produces the semi-parametric Stein-like (SPSL) estimator as introduced by Judge and Mittelhammer (2004). The SPSL estimator is used in conjunction with multiple imputation with chained equations, to provide an estimator that can exploit all available information. Simulated data are also generated to illustrate the superiority of the SPSL estimator over its OLS and TSLS counterparts. A package entitled SteinIV implementing these methods has been made available through the R platform. © 2017 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

  16. Preconditioning is hormesis part I: Documentation, dose-response features and mechanistic foundations.

    Science.gov (United States)

    Calabrese, Edward J

    2016-08-01

    This article provides the first extensive documentation of the dose response features of pre- and postconditioning. Pre- and postconditioning studies with rigorous study designs, using multiple doses/concentrations along with refined dose/concentration spacing strategies, often display hormetic dose/concentration response relationships with considerable generality across biological model, inducing (i.e., conditioning) agent, challenging dose treatment, endpoint, and mechanism. Pre- and postconditioning hormesis dose/concentration-response relationships are reported for 154 diverse conditioning agents, affecting more than 550 dose/concentration responses, across a broad range of biological models and endpoints. The quantitative features of the pre- and postconditioning-induced protective responses are modest, typically being 30-60% greater than control values at maximum, findings that are consistent with a large body (>10,000) of hormetic dose/concentration responses not related to pre- and postconditioning. Regardless of the biological model, inducing agent, endpoint or mechanism, the quantitative features of hormetic dose/concentration responses are similar, suggesting that the magnitude of response is a measure of biological plasticity. This paper also provides the first documentation that hormetic effects account for preconditioning induced early (1-3h) and delayed (12-72h) windows of protection. These findings indicate that pre- and postconditioning are specific types of hormesis.

  17. Pulmonary inflammation and crystalline silica in respirable coal mine dust: dose-response

    Indian Academy of Sciences (India)

    E D Kuempel; M D Attfield; V Vallyathan; N L Lapp; J M Hale; R J Smith; V Castranova

    2003-02-01

    This study describes the quantitative relationships between early pulmonary responses and the estimated lungburden or cumulative exposure of respirable-quartz or coal mine dust. Data from a previous bronchoalveolar lavage (BAL) study in coal miners ( = 20) and nonminers ( = 16) were used including cell counts of alveolar macrophages (AMs) and polymorphonuclear leukocytes (PMNs), and the antioxidant superoxide dismutase (SOD) levels. Miners’ individual working lifetime particulate exposures were estimated from work histories and mine air sampling data, and quartz lung-burdens were estimated using a lung dosimetry model. Results show that quartz, as either cumulative exposure or estimated lung-burden, was a highly statistically significant predictor of PMN response ( < 0.0001); however cumulative coal dust exposure did not significantly add to the prediction of PMNs ( = 0.2) above that predicted by cumulative quartz exposure ( < 0.0001). Despite the small study size, radiographic category was also significantly related to increasing levels of both PMNs and quartz lung burden (-values < 0.04). SOD in BAL fluid rose linearly with quartz lung burden ( < 0.01), but AM count in BAL fluid did not ( > 0.4). This study demonstrates dose-response relationships between respirable crystalline silica in coal mine dust and pulmonary inflammation, antioxidant production, and radiographic small opacities.

  18. Aldrin and dieldrin: a reevaluation of the cancer and noncancer dose-response assessments.

    Science.gov (United States)

    Hooker, Eric P; Fulcher, Keri G; Gibb, Herman J

    2014-05-01

    The dose-response analyses of cancer and noncancer health effects of aldrin and dieldrin were evaluated using current methodology, including benchmark dose analysis and the current U.S. Environmental Protection Agency (U.S. EPA) guidance on body weight scaling and uncertainty factors. A literature review was performed to determine the most appropriate adverse effect endpoints. Using current methodology and information, the estimated reference dose values were 0.0001 and 0.00008 mg/kg-day for aldrin and dieldrin, respectively. The estimated cancer slope factors for aldrin and dieldrin were 3.4 and 7.0 (mg/kg-day)(-1), respectively (i.e., about 5- and 2.3-fold lower risk than the 1987 U.S. EPA assessments). Because aldrin and dieldrin are no longer used as pesticides in the United States, they are presumed to be a low priority for additional review by the U.S. EPA. However, because they are persistent and still detected in environmental samples, quantitative risk assessments based on the best available methods are required. Recent epidemiologic studies do not demonstrate a causal association between aldrin and dieldrin and human cancer risk. The proposed reevaluations suggest that these two compounds pose a lower human health risk than currently reported by the U.S. EPA. © 2013 Society for Risk Analysis.

  19. Towards a Unified Recurrent Neural Network Theory:The Uniformly Pseudo-Projection-Anti-Monotone Net

    Institute of Scientific and Technical Information of China (English)

    Zong Ben XU; Chen QIAO

    2011-01-01

    In the past decades, various neural network models have been developed for modeling the behavior of human brain or performing problem-solving through simulating the behavior of human brain. The recurrent neural networks are the type of neural networks to model or simulate associative memory behavior of human being. A recurrent neural network (RNN) can be generally formalized as a dynamic system associated with two fundamental operators: one is the nonlinear activation operator deduced from the input-output properties of the involved neurons, and the other is the synaptic connections (a matrix) among the neurons. Through carefully examining properties of various activation functions used, we introduce a novel type of monotone operators, the uniformly pseudo-projectionanti-monotone (UPPAM) operators, to unify the various RNN models appeared in the literature. We develop a unified encoding and stability theory for the UPPAM network model when the time is discrete.The established model and theory not only unify but also jointly generalize the most known results of RNNs. The approach has lunched a visible step towards establishment of a unified mathematical theory of recurrent neural networks.

  20. On stability and monotonicity requirements of finite difference approximations of stochastic conservation laws with random viscosity

    KAUST Repository

    Pettersson, Per

    2013-05-01

    The stochastic Galerkin and collocation methods are used to solve an advection-diffusion equation with uncertain and spatially varying viscosity. We investigate well-posedness, monotonicity and stability for the extended system resulting from the Galerkin projection of the advection-diffusion equation onto the stochastic basis functions. High-order summation-by-parts operators and weak imposition of boundary conditions are used to prove stability of the semi-discrete system.It is essential that the eigenvalues of the resulting viscosity matrix of the stochastic Galerkin system are positive and we investigate conditions for this to hold. When the viscosity matrix is diagonalizable, stochastic Galerkin and stochastic collocation are similar in terms of computational cost, and for some cases the accuracy is higher for stochastic Galerkin provided that monotonicity requirements are met. We also investigate the total spatial operator of the semi-discretized system and its impact on the convergence to steady-state. © 2013 Elsevier B.V.

  1. A note on monotone likelihood ratio of the total score variable in unidimensional item response theory.

    Science.gov (United States)

    Unlü, Ali

    2008-05-01

    This note provides a direct, elementary proof of the fundamental result on monotone likelihood ratio of the total score variable in unidimensional item response theory (IRT). This result is very important for practical measurement in IRT, because it justifies the use of the total score variable to order participants on the latent trait. The proof relies on a basic inequality for elementary symmetric functions which is proved by means of few purely algebraic, straightforward transformations. In particular, flaws in a proof of this result by Huynh [(1994). A new proof for monotone likelihood ratio for the sum of independent Bernoulli random variables. Psychometrika, 59, 77-79] are pointed out and corrected, and a natural generalization of the fundamental result to non-linear (quasi-ordered) latent trait spaces is presented. This may be useful for multidimensional IRT or knowledge space theory, in which the latent 'ability' spaces are partially ordered with respect to, for instance, coordinate-wise vector-ordering or set-inclusion, respectively.

  2. Iterative Schemes for Zero Points of Maximal Monotone Operators and Fixed Points of Nonexpansive Mappings and Their Applications

    Directory of Open Access Journals (Sweden)

    Yeol Je Cho

    2008-03-01

    Full Text Available Two iterative schemes for finding a common element of the set of zero points of maximal monotone operators and the set of fixed points of nonexpansive mappings in the sense of Lyapunov functional in a real uniformly smooth and uniformly convex Banach space are obtained. Two strong convergence theorems are obtained which extend some previous work. Moreover, the applications of the iterative schemes are demonstrated.

  3. Iterative Schemes for Zero Points of Maximal Monotone Operators and Fixed Points of Nonexpansive Mappings and Their Applications

    Directory of Open Access Journals (Sweden)

    Cho YeolJe

    2007-01-01

    Full Text Available Two iterative schemes for finding a common element of the set of zero points of maximal monotone operators and the set of fixed points of nonexpansive mappings in the sense of Lyapunov functional in a real uniformly smooth and uniformly convex Banach space are obtained. Two strong convergence theorems are obtained which extend some previous work. Moreover, the applications of the iterative schemes are demonstrated.

  4. The regularized monotonicity method: detecting irregular indefinite inclusions

    DEFF Research Database (Denmark)

    Garde, Henrik; Staboulis, Stratos

    2017-01-01

    In inclusion detection in electrical impedance tomography, the support of perturbations (inclusion) from a known background conductivity is typically reconstructed from idealized continuum data modelled by a Neumann-to-Dirichlet map. Only few reconstruction methods apply when detecting indefinite...... of approximative measurement models, including the Complete Electrode Model, hence making the method robust against modelling error and noise. In particular, we demonstrate that for a convergent family of approximative models there exists a sequence of regularization parameters such that the outer shape...... of the inclusions is asymptotically exactly characterized. Finally, a peeling-type reconstruction algorithm is presented and, for the first time in literature, numerical examples of monotonicity reconstructions for indefinite inclusions are presented....

  5. Convex analysis and monotone operator theory in Hilbert spaces

    CERN Document Server

    Bauschke, Heinz H

    2017-01-01

    This reference text, now in its second edition, offers a modern unifying presentation of three basic areas of nonlinear analysis: convex analysis, monotone operator theory, and the fixed point theory of nonexpansive operators. Taking a unique comprehensive approach, the theory is developed from the ground up, with the rich connections and interactions between the areas as the central focus, and it is illustrated by a large number of examples. The Hilbert space setting of the material offers a wide range of applications while avoiding the technical difficulties of general Banach spaces. The authors have also drawn upon recent advances and modern tools to simplify the proofs of key results making the book more accessible to a broader range of scholars and users. Combining a strong emphasis on applications with exceptionally lucid writing and an abundance of exercises, this text is of great value to a large audience including pure and applied mathematicians as well as researchers in engineering, data science, ma...

  6. Monotonic childhoods: representations of otherness in research writing

    Directory of Open Access Journals (Sweden)

    Denise Marcos Bussoletti

    2011-12-01

    Full Text Available This paper is part of a doctoral thesis entitled “Monotonic childhoods – a rhapsody of hope”. It follows the perspective of a critical psychosocial and cultural study, and aims at discussing the other’s representation in research writing, electing childhood as an allegorical and refl ective place. It takes into consideration, by means of analysis, the drawings and poems of children from the Terezin ghetto during the Second World War. The work is mostly based on Serge Moscovici’s Social Representation Theory, but it is also in constant dialogue with other theories and knowledge fi elds, especially Walter Benjamin’s and Mikhail Bakhtin’s contributions. At the end, the paper supports the thesis that conceives poetics as one of the translation axes of childhood cultures.

  7. Strong convergence theorems for maximal monotone mappings in Banach spaces

    Science.gov (United States)

    Zegeye, Habtu

    2008-07-01

    Let E be a uniformly convex and 2-uniformly smooth real Banach space with dual E*. Let be a Lipschitz continuous monotone mapping with A-1(0)[not equal to][empty set]. For given u,x1[set membership, variant]E, let {xn} be generated by the algorithm xn+1:=[beta]nu+(1-[beta]n)(xn-[alpha]nAJxn), n[greater-or-equal, slanted]1, where J is the normalized duality mapping from E into E* and {[lambda]n} and {[theta]n} are real sequences in (0,1) satisfying certain conditions. Then it is proved that, under some mild conditions, {xn} converges strongly to x*[set membership, variant]E where Jx*[set membership, variant]A-1(0). Finally, we apply our convergence theorems to the convex minimization problems.

  8. Convergence of the natural approximations of piecewise monotone interval maps.

    Science.gov (United States)

    Haydn, Nicolai

    2004-06-01

    We consider piecewise monotone interval mappings which are topologically mixing and satisfy the Markov property. It has previously been shown that the invariant densities of the natural approximations converge exponentially fast in uniform pointwise topology to the invariant density of the given map provided its derivative is piecewise Lipshitz continuous. We provide an example of a map which is Lipshitz continuous and for which the densities converge in the bounded variation norm at a logarithmic rate. This shows that in general one cannot expect exponential convergence in the bounded variation norm. Here we prove that if the derivative of the interval map is Holder continuous and its variation is well approximable (gamma-uniform variation for gamma>0), then the densities converge exponentially fast in the norm.

  9. A COMPARISON OF DIFFERENT CONTRACTION METHODS FOR MONOTONE VARIATIONAL INEQUALITIES

    Institute of Scientific and Technical Information of China (English)

    Bingsheng He; Xiang Wang; Junfeng Yang

    2009-01-01

    It is interesting to compare the efficiency of two methods when their computational loads in each iteration are equal. In this paper, two classes of contraction methods for monotone variational inequalities are studied in a unified framework. The methods of both classes can be viewed as prediction-correction methods, which generate the same test vector in the prediction step and adopt the same step-size rule in the correction step. The only difference is that they use different search directions. The computational loads of each iteration of the different classes are equal. Our analysis explains theoretically why one class of the contraction methods usually outperforms the other class. It is demonstrated that many known methods belong to these two classes of methods. Finally, the presented numerical results demonstrate the validity of our analysis.

  10. A new approximate proximal point algorithm for maximal monotone operator

    Institute of Scientific and Technical Information of China (English)

    HE; Bingsheng(何炳生); LIAO; Lizhi(廖立志); YANG; Zhenhua(杨振华)

    2003-01-01

    The problem concerned in this paper is the set-valued equation 0 ∈ T(z) where T is a maximal monotone operator. For given xk and βk > 0, some existing approximate proximal point algorithms take xk+1 = xk such that xk +ek∈ xk + βkT(xk) and||ek|| ≤ηk||xk - xk||, where {ηk} is a non-negative summable sequence. Instead of xk+1 = xk, the new iterate of the proposing method is given by xk+1 = PΩ[xk - ek], where Ω is the domain of T and PΩ(@) denotes the projection on Ω. The convergence is proved under a significantly relaxed restriction supk>0 ηk < 1.

  11. Dose-Response Relationships of Resistance Training in Healthy Old Adults : A Systematic Review and Meta-Analysis

    NARCIS (Netherlands)

    Borde, Ron; Hortobagyi, Tibor; Granacher, Urs

    2015-01-01

    Background Resistance training (RT) is an intervention frequently used to improve muscle strength and morphology in old age. However, evidence-based, dose-response relationships regarding specific RT variables (e.g., training period, frequency, intensity, volume) are unclear in healthy old adults. O

  12. Dairy Consumption and Incidence of Hypertension : A Dose-Response Meta-Analysis of Prospective Cohort Studies

    NARCIS (Netherlands)

    Soedamah-Muthu, S.S.; Verberne, L.D.M.; Ding, E.L.; Engberink, M.F.; Geleijnse, J.M.

    2012-01-01

    Dairy Consumption and Incidence of Hypertension : A Dose-Response Meta-Analysis Prospective Cohort Studies Sabita S. Soedamah-Muthu, Lisa D.M. Verberne, Eric L. Ding, Mariëlle F. Engberink and Johanna M. Geleijnse Hypertension. published online September 17, 2012; Hypertension is published by the Am

  13. Dose-Response Analysis of RNA-Seq Profiles in Archival Formalin-Fixed Paraffin-Embedded (FFPE) Samples.

    Science.gov (United States)

    Use of archival resources has been limited to date by inconsistent methods for genomic profiling of degraded RNA from formalin-fixed paraffin-embedded (FFPE) samples. RNA-sequencing offers a promising way to address this problem. Here we evaluated transcriptomic dose responses us...

  14. Dose-Response Analysis of RNA-Seq Profiles in Archival Formalin-fixed paraffin-embedded (FFPE) Samples

    Science.gov (United States)

    Formalin-fixed paraffin-embedded (FFPE) samples provide a vast untapped resource for chemical safety and translational science. To date, genomic profiling of FFPE samples has been limited by poor RNA quality and inconsistent results with limited utility in dose-response assessmen...

  15. Nonmonotonic Dose Responses as They Apply to Estrogen, Androgen, and Thyroid Pathways and EPA Testing and Assessment Procedures

    Science.gov (United States)

    A state of the science document providing a judgment on the degree to which nonmonotonic dose-responses are evidenced in the scientific literature and to evaluate the extent to which they may impact U.S. EPA’s chemical testing and risk assessment.

  16. Dose-Response Relationships of Balance Training in Healthy Young Adults : A Systematic Review and Meta-Analysis

    NARCIS (Netherlands)

    Lesinski, Melanie; Hortobagyi, Tibor; Muehlbauer, Thomas; Gollhofer, Albert; Granacher, Urs

    2015-01-01

    Background Balance training (BT) has been used for the promotion of balance and sports-related skills as well as for prevention and rehabilitation of lower extremity sport injuries. However, evidence-based dose-response relationships in BT parameters have not yet been established. Objective The obje

  17. European Academy of Allergy and Clinical Immunology task force report on 'dose-response relationship in allergen-specific immunotherapy'

    DEFF Research Database (Denmark)

    Calderón, M A; Larenas, D; Kleine-Tebbe, J

    2011-01-01

    For a century, allergen-specific immunotherapy (SIT) has proven to be an effective treatment for allergic rhinitis, asthma, and insect sting allergy. However, as allergen doses are frequently adapted to the individual patient, there are few data on dose-response relationship in SIT. Allergen prod...

  18. Dairy consumption is inversely associated with type 2 diabetes: dose-response meta-analysis of prospective cohort studies

    NARCIS (Netherlands)

    Gijsbers, L.; Geleijnse, J.M.; Soedamah-Muthu, S.S.

    2011-01-01

    Observational studies suggest an inverse association between dairy intake and incident type 2 diabetes, but the quantity of dairy is not known. Previous meta-analyses did not take into account the type of dairy product. Therefore, we examined dose-response associations between the intake of total

  19. Methods for meta-analysis of pharmacodynamic dose-response data with application to multi-arm studies of alogliptin

    NARCIS (Netherlands)

    Langford, Oliver; Aronson, Jeffrey K; van Valkenhoef, Gert; Stevens, Richard J

    2016-01-01

    Standard methods for meta-analysis of dose-response data in epidemiology assume a model with a single scalar parameter, such as log-linear relationships between exposure and outcome; such models are implicitly unbounded. In contrast, in pharmacology, multi-parameter models, such as the widely used E

  20. Dose-response relations between occupational exposures to physical and psychosocial factors and the risk of low back pain.

    NARCIS (Netherlands)

    H. Morgenstern; A. Burdorf (Alex); J.P. Jansen (Jeroen)

    2004-01-01

    textabstractAIMS: To assess dose-response relations between occupational exposures to physical and psychosocial factors and the risk of low back pain. METHODS: A cohort of 523 subjects, working in nursing homes and homes for the elderly, was followed prospectively for one year. Phy

  1. Influence of lung parenchymal destruction on the different indexes of the methacholine dose-response curve in COPD patients

    NARCIS (Netherlands)

    G.T. Verhoeven; A.F.M. Verbraak (Anton); S. Boere-van der Straat; H.C. Hoogsteden (Henk); J.M. Bogaard (Jan)

    2000-01-01

    textabstractSTUDY OBJECTIVES: The interpretation of nonspecific bronchial provocation dose-response curves in COPD is still a matter of debate. Bronchial hyperresponsiveness (BHR) in patients with COPD could be influenced by the destruction of the parenchyma and the aug

  2. Dose-Response Analysis of RNA-Seq Profiles in Archival Formalin-Fixed Paraffin-Embedded (FFPE) Samples.

    Science.gov (United States)

    Use of archival resources has been limited to date by inconsistent methods for genomic profiling of degraded RNA from formalin-fixed paraffin-embedded (FFPE) samples. RNA-sequencing offers a promising way to address this problem. Here we evaluated transcriptomic dose responses us...

  3. Continuous Dose-Response Response Relationship of the LDL-Cholesterol-Lowering Effect of Phytosterol Intake 1,2

    NARCIS (Netherlands)

    Demonty, I.; Ras, R.T.; Knaap, van der H.C.M.; Duchateau, G.S.M.J.E.; Meijer, L.; Zock, P.L.; Geleijnse, J.M.; Trautwein, E.A.

    2009-01-01

    Phytosterols (plant sterols and stanols) are well known for their LDL-cholesterol (LDL-C)¿lowering effect. A meta-analysis of randomized controlled trials in adults was performed to establish a continuous dose-response relationship that would allow predicting the LDL-C¿lowering efficacy of different

  4. Construction and validation of a dose-response curve using the comet assay to determine human radiosensitivity to ionizing radiation.

    Science.gov (United States)

    Güerci, A; Zúñiga, L; Marcos, R

    2011-01-01

    Individual radiosensitivity is an individual characteristic associated with an increased reaction to ionizing radiation. The purpose of our work is to establish a dose-response curve useful to classify individuals as radiosensitive or radioresistant. Thus, a dose-response curve was constructed by measuring in vitro responses to increasing doses (0 to 8 Gy) of gamma radiation in the comet assay. The obtained curve fit well with a linear equation in the range of 0 to 8 Gy. The overall dose-response curve was constructed for percent DNA in tail, as a measure of the genetic damage induced by irradiation. To probe the goodness of the constructed curve, a validation study was carried out with whole blood from two donors in a blind study. Results show that, for the two applied doses (2 and 6 Gy), the obtained values fit well inside the interval of confidence of the curve. In conclusion, our results demonstrate the usefulness of the comet assay in determining individual responses to defined doses of gamma radiation. The standard dose-response curve constructed may be used to detect individuals departing from reference values.

  5. Dose response on the 110 °C thermoluminescence peak of un-heated, synthetic Merck quartz

    Energy Technology Data Exchange (ETDEWEB)

    Kaya Keleş, Şule, E-mail: sule.kaya@ankara.edu.tr; Meriç, Niyazi; Polymeris, George S.

    2016-07-15

    Studies on 110 °C TL peak have been carried out using natural quartz from different origins and synthetic quartz produced by different suppliers. The interest in quartz is due to its usage in dating and retrospective dosimetry as a main material; both synthetic and natural types of quartz yield the 110 °C TL peak in their glow curve. In most studies to understand the physical mechanism behind the TL system, synthetic quartz samples are used and there are many investigations about dose response, in both low and high radiation dose region. In these studies generally synthetic quartz samples produced by Sawyer Research Products are used and the studies showed that both heated and un-heated synthetic quartz samples have intense supra-linear responses. Supra-linearity was enhanced by applying a pre-irradiation while several models have been developed towards an explanation to these supra-linearity effects. In this study commercially available synthetic Merck quartz was used. Different combinations of optical filters were used to obtain dose response curves upto 266 Gy and the effect of pre-dose to these dose response curves was studied. Un-pre-dosed Merck quartz samples dose supra-linearity index is below 1 independently on the optical filters; so Merck quartz showed linear or sub-linear dose response.

  6. Intraspecies variability in the dose-response relationship for Salmonella Enteritidis associated with genetic differences in cellular immune response.

    NARCIS (Netherlands)

    Havelaar, A.H.; Garssen, J.; Takumi, K.; Koedam, M.I.; Ritmeester, W.; Fonteyne, L. de la; Bousema, T.; Vos, J.

    2004-01-01

    To evaluate the effects of differences in host cellular immunity, we studied the dose-response relationship for infection with Salmonella enterica serovar Enteritidis (SE) in two different rat strains, skewed towards T helper 1 (Th1, Lewis rats) or T helper 2 (Th2, Brown Norway rats) immunoregulatio

  7. Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose response (BBDR) Model***

    Science.gov (United States)

    A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (HPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the 1-IPT axis. Model calibrations, carried out by adjusting key model...

  8. Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose-response model

    Science.gov (United States)

    A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (BPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the HPT axis. Model calibrations, carried out by adjusting key model p...

  9. Dose-response and concentration-response relation of rocuronium infusion during propofol nitrous oxide and isoflurane nitrous oxide anaesthesia

    NARCIS (Netherlands)

    Kansanaho, M; Olkkola, KT; Wierda, JMKH

    1997-01-01

    The dose-response and concentration-response relation of rocuronium infusion was studied in 20 adult surgical patients during proporfol-nitrous oxide and isoflurane (1 MAC) -nitrous oxide anaesthesia. Neuromuscular block was kept constant, initially at 90% and then at 50% with a closed-loop feedback

  10. Dose-Response Relationships of Balance Training in Healthy Young Adults : A Systematic Review and Meta-Analysis

    NARCIS (Netherlands)

    Lesinski, Melanie; Hortobagyi, Tibor; Muehlbauer, Thomas; Gollhofer, Albert; Granacher, Urs

    Background Balance training (BT) has been used for the promotion of balance and sports-related skills as well as for prevention and rehabilitation of lower extremity sport injuries. However, evidence-based dose-response relationships in BT parameters have not yet been established. Objective The

  11. Dose-response model of murine typhus (Rickettsia typhi: time post inoculation and host age dependency analysis

    Directory of Open Access Journals (Sweden)

    Tamrakar Sushil B

    2012-03-01

    Full Text Available Abstract Background Rickettsia typhi (R. mooseri is the causative agent of murine typhus. It is one of the most widely distributed flea-borne diseases with a relatively mild febrile initial illness with six to 14 days of incubation period. The bacterium is gram negative and an obligate intracellular pathogen. The disease is transmitted to humans and vertebrate host through fleabites or via contact with infected feces. This paper develops dose-response models of different routes of exposure for typhus in rodents. Methods Data from published articles were analyzed using parametric dose-response relationship models. Dose-response relationships were fit to data using the method of maximum likelihood estimation (MLE. Results Dose-response models quantifying the effects of different ages of rats and time post inoculation in BALB/c mice were analyzed in the study. Both the adult rats (inoculated intradermally and newborn rats (inoculated subcutaneously were best fit by exponential models and both distributions could be described by a single dose-response relationship. The BALB/C mice inoculated subcutaneously were best fit by Beta-Poisson models. The time post inoculation analysis showed that there was a definite time and response relationship existed in this case. Conclusions Intradermally or subcutaneously inoculated rats (adult and newborn models suggest that less than 1 plaque-forming unit (PFU (1.33 to 0.38 in 95% confidence limits of the pathogen is enough to seroconvert 50% of the exposed population on average. For the BALB/c mouse time post inoculation model, an average dose of 0.28 plaque-forming units (PFU (0.75 to 0.11 in 95% confidence limits will seroconvert 50% of the exposed mice.

  12. Effects of the pre-irradiation storage procedure on the dose response of a Fricke xylenol orange gel dosimeter

    Directory of Open Access Journals (Sweden)

    Liosi Giulia Maria

    2015-09-01

    Full Text Available The Fricke xylenol orange (FX gel system is a chemical dosimeter characterized by good sensitivity, linear dose response, tissue equivalence, no toxicity, easy preparation, reproducibility and low cost. Thanks to the presence of the gelatinous matrix, the system is particularly suitable to perform reliable 3D mapping of the absorbed dose spatial distribution via magnetic resonance imaging (MRI or optical techniques. The aim of this work is to study in a systematic way the influence of the pre-irradiation storage procedure upon sensitivity, dose response stability and lifetime of use of a FX gel system made with gelatin from porcine skin subjected to homogeneous irradiation. For this purpose, different pre-irradiation storage procedures, in terms of temperature and duration of each storage step, were investigated. In order to evaluate the dose response stability, the optical analyses of the samples were performed up to 6 hours after irradiation. Moreover, the samples were irradiated at time intervals of 24 hours for up to 7 days after preparation in order to evaluate the system lifetime of use. Regardless of their thermal and temporal life, the samples show linear dose responses in the investigated dose range (3-24 Gy and an increase of sensitivity with the time elapsed between preparation and irradiation. Among the three pre-irradiation storage procedures considered here, a procedure that provides the best dose response stability and lifetime of use was identified and recommended for further use. The analyzed dosimetric system possesses good properties that make it promising for medical application, particularly concerning the evaluation of pre-treatment plan quality assurance within the conformational external beam radiotherapy

  13. Parity and pancreatic cancer risk: a dose-response meta-analysis of epidemiologic studies.

    Directory of Open Access Journals (Sweden)

    Hong-Bo Guan

    Full Text Available BACKGROUND: Previous epidemiologic studies have reported inconsistent results between parity and pancreatic cancer (PC risk. To our knowledge, a comprehensive and quantitative assessment of this association has not been conducted. METHODS: Relevant published studies of parity and PC were identified using MEDLINE (PubMed and Web of Science databases until November 2013. Two authors (H-BG and LW independently assessed eligibility and extracted data. Eleven prospective and 11 case-control studies reported relative risk (RR estimates and 95% confidence intervals (CIs of PC associated with parity. Fixed- and random-effects models were used to estimate the summary RR depending on the heterogeneity of effects. RESULTS: The summary RR for PC comparing the highest versus lowest parity was 0.86 (95% CI: 0.73-1.02; Q = 50.49, P<0.001, I2 = 58.4%. Significant inverse associations were also observed in the studies that adjusted for cigarette smoking (RR = 0.81; 95% CI: 0.68-0.98, Type 2 diabetes mellitus (RR = 0.83; 95% CI: 0.75-0.93, and those that included all confounders or important risk factors (RR = 0.85; 95% CI: 0.76-0.96. Additionally, in the dose-response analysis, the summary RR for per one live birth was 0.97 (95% CI: 0.94-1.01; Q = 62.83, P<0.001, I2 = 69.8%, which also indicated a borderline statistically significant inverse effect of parity on PC risk. No evidence of publication bias and significant heterogeneity between subgroups were detected by meta-regression analyses. CONCLUSION: In summary, these findings suggest that higher parity is associated with a decreased risk of PC. Future large consortia or pooled studies are warranted to fully adjust for potential confounders to confirm this association.

  14. Digitoxin medication and cancer; case control and internal dose-response studies

    Directory of Open Access Journals (Sweden)

    Spigset Olav

    2001-08-01

    Full Text Available Abstract Background Digitoxin induces apoptosis in different human malignant cell lines in vitro. In this paper we investigated if patients taking digitoxin for cardiac disease have a different cancer incidence compared to the general population. Methods Computer stored data on digitoxin concentrations in plasma from 9271 patients with cardiac disease were used to define a user population. Age and sex matched controls from the Norwegian Cancer Registry were used to calculate the number of expected cancer cases. Results The population on digitoxin showed a higher incidence of cancer compared to the control population. However, an additional analysis showed that the population on digitoxin had a general increased risk of cancer already, before the start on digitoxin. Leukemia/lymphoma were the cancer types which stood out with the highest risk in the digitoxin population before starting on digitoxin. This indicates that yet unknown risk factors exist for cardiovascular disease and lymphoproliferative cancer. An internal dose-response analysis revealed a relationship between high plasma concentration of digitoxin and a lower risk for leukemia/lymphoma and for cancer of the kidney/urinary tract. Conclusion Morbidity and mortality are high in the population on digitoxin, due to high age and cardiac disease.These factors disturb efforts to isolate an eventual anticancer effect of digitoxin in this setting. Still, the results may indicate an anticancer effect of digitoxin for leukemia/lymphoma and kidney/urinary tract cancers. Prospective clinical cancer trials have to be done to find out if digitoxin and other cardiac glycosides are useful as anticancer agents.

  15. Qualitative and quantitative approaches in the dose-response assessment of genotoxic carcinogens.

    Science.gov (United States)

    Fukushima, Shoji; Gi, Min; Kakehashi, Anna; Wanibuchi, Hideki; Matsumoto, Michiharu

    2016-05-01

    Qualitative and quantitative approaches are important issues in field of carcinogenic risk assessment of the genotoxic carcinogens. Herein, we provide quantitative data on low-dose hepatocarcinogenicity studies for three genotoxic hepatocarcinogens: 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and N-nitrosodiethylamine (DEN). Hepatocarcinogenicity was examined by quantitative analysis of glutathione S-transferase placental form (GST-P) positive foci, which are the preneoplastic lesions in rat hepatocarcinogenesis and the endpoint carcinogenic marker in the rat liver medium-term carcinogenicity bioassay. We also examined DNA damage and gene mutations which occurred through the initiation stage of carcinogenesis. For the establishment of points of departure (PoD) from which the cancer-related risk can be estimated, we analyzed the above events by quantitative no-observed-effect level and benchmark dose approaches. MeIQx at low doses induced formation of DNA-MeIQx adducts; somewhat higher doses caused elevation of 8-hydroxy-2'-deoxyquanosine levels; at still higher doses gene mutations occurred; and the highest dose induced formation of GST-P positive foci. These data indicate that early genotoxic events in the pathway to carcinogenesis showed the expected trend of lower PoDs for earlier events in the carcinogenic process. Similarly, only the highest dose of IQ caused an increase in the number of GST-P positive foci in the liver, while IQ-DNA adduct formation was observed with low doses. Moreover, treatment with DEN at low doses had no effect on development of GST-P positive foci in the liver. These data on PoDs for the markers contribute to understand whether genotoxic carcinogens have a threshold for their carcinogenicity. The most appropriate approach to use in low dose-response assessment must be approved on the basis of scientific judgment.

  16. Energy crop (Sida hermaphrodita) fertilization using digestate under marginal soil conditions: A dose-response experiment

    Science.gov (United States)

    Nabel, Moritz; Bueno Piaz Barbosa, Daniela; Horsch, David; Jablonowski, Nicolai David

    2014-05-01

    The global demand for energy security and the mitigation of climate change are the main drivers pushing energy-plant production in Germany. However, the cultivation of these plants can cause land use conflicts since agricultural soil is mostly used for plant production. A sustainable alternative to the conventional cultivation of food-based energy-crops is the cultivation of special adopted energy-plants on marginal lands. To further increase the sustainability of energy-plant cultivation systems the dependency on synthetic fertilizers needs to be reduced via closed nutrient loops. In the presented study the energy-plant Sida hermaphrodita (Malvaceae) will be used to evaluate the potential to grow this high potential energy-crop on a marginal sandy soil in combination with fertilization via digestate from biogas production. With this dose-response experiment we will further identify an optimum dose, which will be compared to equivalent doses of NPK-fertilizer. Further, lethal doses and deficiency doses will be observed. Two weeks old Sida seedlings were transplanted to 1L pots and fertilized with six doses of digestate (equivalent to a field application of 5, 10, 20, 40, 80, 160t/ha) and three equivalent doses of NPK-fertilizer. Control plants were left untreated. Sida plants will grow for 45 days under greenhouse conditions. We hypothesize that the nutrient status of the marginal soil can be increased and maintained by defined digestate applications, compared to control plants suffering of nutrient deficiency due to the low nutrient status in the marginal substrate. The dose of 40t/ha is expected to give a maximum biomass yield without causing toxicity symptoms. Results shall be used as basis for further experiments on the field scale in a field trial that was set up to investigate sustainable production systems for energy crop production under marginal soil conditions.

  17. Dose response of retinol and isotretinoin in the prevention of nonmelanoma skin cancer recurrence.

    Science.gov (United States)

    Clouser, Mary C; Roe, Denise J; Foote, Janet A; Harris, Robin B; Alberts, David S

    2010-01-01

    Using data from a randomized, double blind, study of the efficacy of retinol or isotretinoin vs. placebo on recurrence of nonmelanoma skin cancer in high-risk subjects, a reanalysis of the original intent to treat analysis was performed in a dose-response format. Cox proportional hazards models describe the relationship between dose quartiles of isotretinoin and retinol use and time to first occurrence of squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) in crude and adjusted models. Neither the isotretinoin nor retinol models showed any significance at any quartile for reduction in first BCC or SCC occurrence. Crude and adjusted retinol models show a statistically significant increase in risk of developing an SCC in the first quartile, whereas only the crude model shows a statistically significant increase in risk in the first quartile of the isotretinoin model. For retinol and SCC, hazard ratios (HRs) for the first quartile were as follows: HR = 2.92, 95% confidence interval (CI) = 1.67-5.10 crude; HR = 1.95, 95% CI = 1.00-3.80 adjusted. For isotretinoin and SCC, HRs for the first quartile were as follows: HR = 2.38, 95% CI = 1.35-4.19 crude; HR = 1.69, 95% CI = 0.87-3.31 adjusted. Test for trend was not significant in any of the models. These analyses confirm the results of the original intent to treat analyses and raise an interesting question related to the potential for increased risk for patients in the first quartile of retinol dose.

  18. Effect of Photon Hormesis on Dose Responses to Alpha Particles in Zebrafish Embryos

    Science.gov (United States)

    Ng, Candy Yuen Ping; Cheng, Shuk Han; Yu, Kwan Ngok

    2017-01-01

    Photon hormesis refers to the phenomenon where the biological effect of ionizing radiation with a high linear energy transfer (LET) value is diminished by photons with a low LET value. The present paper studied the effect of photon hormesis from X-rays on dose responses to alpha particles using embryos of the zebrafish (Danio rerio) as the in vivo vertebrate model. The toxicity of these ionizing radiations in the zebrafish embryos was assessed using the apoptotic counts at 20, 24, or 30 h post fertilization (hpf) revealed through acridine orange (AO) staining. For alpha-particle doses ≥ 4.4 mGy, the additional X-ray dose of 10 mGy significantly reduced the number of apoptotic cells at 24 hpf, which proved the presence of photon hormesis. Smaller alpha-particle doses might not have inflicted sufficient aggregate damages to trigger photon hormesis. The time gap T between the X-ray (10 mGy) and alpha-particle (4.4 mGy) exposures was also studied. Photon hormesis was present when T ≤ 30 min, but was absent when T = 60 min, at which time repair of damage induced by alpha particles would have completed to prevent their interactions with those induced by X-rays. Finally, the drop in the apoptotic counts at 24 hpf due to photon hormesis was explained by bringing the apoptotic events earlier to 20 hpf, which strongly supported the removal of aberrant cells through apoptosis as an underlying mechanism for photon hormesis. PMID:28208665

  19. Isobolographic analysis of interaction between drugs with nonparallel dose-response relationship curves: a practical application.

    Science.gov (United States)

    Luszczki, Jarogniew J

    2007-04-01

    The objective of this study was to characterize the anticonvulsant and acute adverse-effect potentials of topiramate (TPM) and gabapentin (GBP)-two second-generation antiepileptic drugs administered alone and in combination in the maximal electroshock (MES)-induced seizures and chimney test in mice. The anticonvulsant and acute adverse effects of the combination of TPM with GBP at the fixed ratio of 1:1 were determined using the type I isobolographic analysis for nonparallel dose-response relationship curves (DRRCs). To ascertain any pharmacokinetic contribution to the observed interaction between TPM and GBP, total brain concentrations of both drugs were determined. The isobolographic analysis of interaction for TPM and GBP, whose DRRCs were not parallel in both MES and chimney tests, was accompanied with a presentation of all required calculations allowing the determination of lower and upper lines of additivity. The isobolographic analysis revealed that TPM combined with GBP at the fixed-ratio combination of 1:1 interacted supraadditively (synergistically) in terms of suppression of MES-induced seizures, and simultaneously, the combination produced additive interaction with respect to motor coordination impairment (adverse effects) in the chimney test. The evaluation of pharmacokinetic characteristics of interaction for the combination of TPM with GBP revealed that neither TPM nor GBP affected their total brain concentrations in experimental animals, and thus, the observed interaction in the MES test was pharmacodynamic in nature. In conclusion, the combination of TPM with GBP, because of supraadditivity in the MES test and additivity in terms of motor coordination impairment in the chimney test as well as lack of pharmacokinetic interactions between drugs, fulfilled the criterion of a favorable combination, worthy of recommendation in further clinical practice.

  20. Dose-response relationship between sports activity and musculoskeletal pain in adolescents.

    Science.gov (United States)

    Kamada, Masamitsu; Abe, Takafumi; Kitayuguchi, Jun; Imamura, Fumiaki; Lee, I-Min; Kadowaki, Masaru; Sawada, Susumu S; Miyachi, Motohiko; Matsui, Yuzuru; Uchio, Yuji

    2016-06-01

    Physical activity has multiple health benefits but may also increase the risk of developing musculoskeletal pain (MSP). However, the relationship between physical activity and MSP has not been well characterized. This study examined the dose-response relationship between sports activity and MSP among adolescents. Two school-based serial surveys were conducted 1 year apart in adolescents aged 12 to 18 years in Unnan, Japan. Self-administered questionnaires were completed by 2403 students. Associations between time spent in organized sports activity and MSP were analyzed cross-sectionally (n = 2403) and longitudinally (n = 374, students free of pain and in seventh or 10th grade at baseline) with repeated-measures Poisson regression and restricted cubic splines, with adjustment for potential confounders. The prevalence of overall pain, defined as having pain recently at least several times a week in at least one part of the body, was 27.4%. In the cross-sectional analysis, sports activity was significantly associated with pain prevalence. Each additional 1 h/wk of sports activity was associated with a 3% higher probability of having pain (prevalence ratio = 1.03, 95% confidence interval = 1.02-1.04). Similar trends were found across causes (traumatic and nontraumatic pain) and anatomic locations (upper limbs, lower back, and lower limbs). In longitudinal analysis, the risk ratio for developing pain at 1-year follow-up per 1 h/wk increase in baseline sports activity was 1.03 (95% confidence interval = 1.02-1.05). Spline models indicated a linear association (P adolescents played sports, the more likely they were to have and develop pain.