Function Fx Research Articles

Sensitivity and specificity of strategies to identify patients with hemostasis abnormalities leading to an increased risk of bleeding before scheduled intervention: the Hemorisk study

BackgroundPreoperative identification of patients with hemostasis abnormalities leading to an increased bleeding risk is based on routine hemostasis tests: prothrombin time (PT), activated partial thromboplastin time (APTT), and platelet count. Because of their low predictive performance, guidelines recommend replacing them with structured bleeding risk questionnaires, but none is validated in this population. ObjectivesTo assess the diagnostic accuracy of 3 strategies, performed at the preanesthesia visit before scheduled interventions, and to identify patients with hemostasis abnormalities leading to an increased bleeding risk MethodsA multicenter study was performed in 7 French academic hospitals, involving patients scheduled for surgical intervention, without antiplatelet/anticoagulant treatment. The 3 strategies consisted of 1-a structured screening questionnaire; 2-PT, APTT, and platelet count ordered in selected patients; and 3-systematic PT, APTT, and platelet count. The reference standard comprised von Willebrand factor activity/antigen, factor (F)VIII, FIX, FXI, platelet function analyzer, and, when required, FII, FV, FX, and FVII and hemostasis consultation. ResultsEighteen (1.2%) of 1484 patients had a hemostasis abnormality leading to an increased bleeding risk according to reference standard. In the overall cohort, sensitivity of the questionnaire-based strategy was 50% (95% CI, 26%-74%; specificity, 87% [95% CI, 85%-88%]); sensitivity was 0% (95% CI, 0%-41%) in men vs 82% (95% CI, 48%-98%) in women. For selective routine tests, sensitivity was 33% (95% CI, 13%-59%) and specificity 97% (95% CI, 96%-98%). Corresponding values for systematic routine tests were 44% (95% CI, 22%-69%) and 93% (95% CI, 91%-94%). ConclusionSensitivity was low for all 3 strategies investigated. The structured screening questionnaire had clinically acceptable diagnostic accuracy only in women.

Abstract 3352: A CRISPR-enabled function genomics profiling platform in acute leukemia: Updates from a pilot study of Function (Fx) Heme utilizing fresh patient samples

Abstract Introduction: In this study we utilized a novel primary cell CRISPR/Cas9 profiling approach to identify gene dependencies in fresh acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) patient samples. The primary aim of this prospective study was to demonstrate the feasibility of the CRISPR-based personalized functional genomic testing with fresh patient samples in the clinical setting. Methods: AML and ALL patient peripheral blood samples (10-16 mL) were obtained at time of initial diagnosis and/or at relapse, and if feasible post-treatment. Primary cells were transduced with lentivirus harboring Cas9 enzyme and a ‘drug targets’ sgRNA panel. Transduced cells were harvested at early (input) and Day 8 timepoints, and sgRNA distribution was assessed by amplicon sequencing of DNA barcodes. Changes in barcode abundance were quantitated and aggregated to calculate gene-level phenotype scores, enabling identification of gene dependencies. Results: 37 patients were included in the study, 23 with AML, 9 with Philadelphia (Ph) (+) ALL, 5 with Ph (-) ALL. The majority of patients had adverse or poor risk disease. The average age of patients was 52.6, range 18-84. 23 were male, 14 female; 20 identified as white, 17 as other. 20 patients were sampled at initial diagnosis, 12 were sampled at time of relapse and 5 at time of refractory disease. Serial samples were collected from 9 patients. 34 patients received treatment following sample collection. The majority of patients received intensive chemotherapy or a hypomethylating agent with venetoclax, however 15 patients received some form of targeted therapy. At the time of the abstract submission, Fx Heme results were available for 23 patients and among these, we identified potential treatment targets in 10 samples (43%). Importantly, 60% of the positive samples have a dependency on a gene clinically targetable by an approved leukemia drug. In addition, our profiling platform enabled the discovery of novel druggable dependencies in 100% of the positive samples. Conclusions: With this pilot study we demonstrated that utilizing small volume fresh patient samples to assess CRISPR-defined gene dependencies on targeted therapies in AML and ALL is feasible, timely, and results in clear Fx Heme dependency gene output. Our data indicates that CRISPR-based comprehensive functional profiling has the potential to add valuable information beyond traditional NGS methods to determine the optimal therapy for patients with AML and ALL. Future directions include translating further into the clinical setting and correlating Fx Heme dependence with response to targeted treatment in acute leukemia patients. Citation Format: Kaitlyn C. Dykes, Tuyet R. Tan, Karl Hodel, Kathleen Tran, Maci Meyers, Leonardo Hagmann, Michele Baltay, Peter Kilfeather, Yali Li, Christian Schmedt, Srinath Sampath, Srihari Sampath, Tiffany N. Tanaka, Stephane Corbel. A CRISPR-enabled function genomics profiling platform in acute leukemia: Updates from a pilot study of Function (Fx) Heme utilizing fresh patient samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3352.

Application Of Multipoint Secant-Type Method ForFinding Roots 0f Nonlinear Equations

In this paper, we introduce a family of pk-order iterative schemes for finding the simple root of a nonlinear algebraic equation of the function fx=0 by using the divided difference approximation. The proposed method uses one evaluation of the function per iteration and can achieve convergence order pk. The error equation and asymptotic convergence constant are proved theoretically and numerically. Numerical examples are included to demonstrate the exceptional convergence speed of the proposed method and thus verify the theoretical results

The weighted characteristic function of the multivariate PIT: Independence and goodness-of-fit tests

Many authors have exploited the fact that the distribution of the multivariate probability integral transformation (PIT) of a continuous random vector X∈Rd with cumulative distribution function FX is free of the marginal distributions. While most of these methods are based on the cdf of W=FX(X), this paper introduces the weighted characteristic function (WCf) of W. A sample version of the WCf of W based on pseudo-observations is proposed and its weak limit in a space of complex functions is formally established. This result can be used to define test statistics for multivariate independence and goodness-of-fit in copula models, whose asymptotic behaviour comes from the weak convergence of the empirical WCf process. Simulations show the good sampling properties of these new tests, and an illustration is given on the multivariate Cook and Johnson dataset.

Asynchronous finite differences in most probable distribution with finite numbers of particles

For a discrete function fx on a discrete set, the finite difference can be either forward and backward. If fx is a sum of two such functions fx=f1x+f2x, the first order difference of Δfx can be grouped into four possible combinations, in which two are the usual synchronous ones Δff1x+Δff2x and Δbf1x+Δbf2x, and other two are asynchronous ones Δff1x+Δbf2x and Δbf1x+Δff2x, where Δf and Δb denote the forward and backward difference respectively. Thus, the first order variation equation δfx=0 for this function fx gives at most four different solutions which contain both true and false one. A formalism of the discrete calculus of variations is developed to single out the true one by means of comparison of the second order variations, in which the largest value in magnitude indicates the true solution, yielding the exact form of the distributions for Boltzmann, Bose and Fermi system without requiring the numbers of particle to be infinitely large. When there is only one particle in the system, all distributions reduce to be the Boltzmann one.

Inference on distribution functions under measurement error

This paper is concerned with inference on the cumulative distribution function (cdf) FX∗ in the classical measurement error model X=X∗+ϵ. We consider the case where the density of the measurement error ϵ is unknown and estimated by repeated measurements, and show validity of a bootstrap approximation for the distribution of the deviation in the sup-norm between the deconvolution cdf estimator and FX∗. We allow the density of ϵ to be ordinary or super smooth. We also provide several theoretical results on the bootstrap and asymptotic Gumbel approximations of the sup-norm deviation for the case where the density of ϵ is known. Our approximation results are applicable to various contexts, such as confidence bands for FX∗ and its quantiles, and for performing various cdf-based tests such as goodness-of-fit tests for parametric models of X∗, two sample homogeneity tests, and tests for stochastic dominance. Simulation and real data examples illustrate satisfactory performance of the proposed methods.

Stochastic global optimization using tangent minorants for Lipschitz functions

This paper deals with global stochastic optimization where the decision variable belongs to a compact subset X of R. The objective function is the mathematical expectation of a partial bivariate Lipschitz function fx,Θ depending on a decision variable x and a random variableΘ, whose probability distribution depends on x. In the first part of the present paper, we propose a branch and bound algorithm based on tangent minorants that provides a global minimum. In the second part, we consider the case where the function f is discontinuous. We show the manner we correct that discontinuity without modifying the global minimum of Efx,Θ. We also illustrate how to extend this framework to multidimensional stochastic optimization problems by using the Alienor method. Then we validate the proposed method by applying it to some test functions and compare it to known algorithms.

Radial distributions of power and fuel temperature in annular U3Si2 fuel with FeCrAl cladding

The present work performs systematic study on neutronic properties of annular fuel due to its high efficiency in heat transfer and low peak fuel temperature. Recent physical experiment on annular fuel indicates the present neutronic study is urgent and necessary. The present work concentrates on the investigations on the reactivity and radial distributions of power and fuel temperature for various annular fuels with different moderator to fuel ratios and different inner to outer coolant ratios. An analytical formula fx,s including fuel exposure (s) and relative radial (x) is proposed to describe the radial power distributions. fx,s has a second order polynomial dependence on s with coefficients following a double exponential form versus x. Monte Carlo simulations show that the suggested function fx,s gives a nice description on simulation data with rather small deviations and can immediately provide radial distribution of power and burnup at any fuel exposure and relative radius. The present analytical formula can be directly used for determining radial fuel temperature distribution. Numerical results based on radial power distributions show that about 150 K peak fuel temperature is reduced by dual-coolant annular design. In addition, the radial fuel temperature distributions in annular fuels are quite flatter than that in cylindric fuel rod.

The damped pendulum random differential equation: A comprehensive stochastic analysis via the computation of the probability density function

This paper deals with the damped pendulum random differential equation: Ẍ(t)+2ω0ξẊ(t)+ω02X(t)=Y(t), t∈[0,T], with initial conditions X(0)=X0 and Ẋ(0)=X1. The forcing term Y(t) is a stochastic process and X0 and X1 are random variables in a common underlying complete probability space (Ω,F,P). The term X(t) is a stochastic process that solves the random differential equation in both the sample path and in the Lp senses. To understand the probabilistic behavior of X(t), we need its joint finite-dimensional distributions. We establish mild conditions under which X(t) is an absolutely continuous random variable, for each t, and we find its probability density function fX(t)(x). Thus, we obtain the first finite-dimensional distributions. In practice, we deal with two types of forcing term: Y(t) is a Gaussian process, which occurs with the damped pendulum stochastic differential equation of Itô type; and Y(t) can be approximated by a sequence {YN(t)}N=1∞ in L2([0,T]×Ω), which occurs with Karhunen–Loève expansions and some random power series. Finally, we provide numerical examples in which we choose specific random variables X0 and X1 and a specific stochastic process Y(t), and then, we find the probability density function of X(t).

Non-Parametric Estimation of Conditional Densities: A New Method

Let X = (X1,...,Xp) be a stochastic vector having joint density function fX(x) with partitions X1 = (X1,...,Xk) and X2 = (Xk 1,...,Xp). A new method for estimating the conditional density function of X1 given X2 is presented. It is based on locally Gaussian approximations, but simplified in order to tackle the curse of dimensionality in multivariate applications, where both response and explanatory variables can be vectors. We compare our method to some available competitors, and the error of approximation is shown to be small in a series of examples using real and simulated data, and the estimator is shown to be particularly robust against noise caused by independent variables. We also present examples of practical applications of our conditional density estimator in the analysis of time series. Typical values for k in our examples are 1 and 2, and we include simulation experiments with values of p up to 6. Large sample theory is established under a strong mixing condition.

Discrete uniform limit law for additive functions on shifted primes

The sufficient and necessary conditions for a weak convergence of distributions of a set of strongly additive functions fx , x ⩾ 2, the arguments of which run through shifted primes, to the discrete uniform law are obtained. The case when fx (p) ∈ {0, 1} for every prime pis considered.

New estimators of distribution functions

ABSTRACTThis article considers the estimation of a distribution function FX(x) based on a random sample X1, X2, …, Xn when the sample is suspected to come from a close-by distribution F0(x). The new estimators, namely the preliminary test (PTE) and Stein-type estimator (SE) are defined and compared with the “empirical distribution function” (edf) under local departure. In this case, we show that Stein-type estimators are superior to edf and PTE is superior to edf when it is close to F0(x). As a by-product similar estimators are proposed for population quantiles.

The mean wasted life time of a component of system

A reliability inspection model in which a component of a technical system has lifetime X and inspection time S is considered. It is assumed that X and S are random variables with absolutely continuous joint distribution function FX,S, and the joint probability density function fX,S. Firstly, we consider mean residual life function of the component under two different setups of inspection. Secondly, we consider an inspection model where at the inspection time the component is replaced with its spare regardless of whether the component is alive or failed at this time. Under condition that 0<t<S<X we are interested in expected value of X−S, which is the mean wasted time of intact at time t component in the case if it will not be failed at inspection time, but will be replaced with the new one. We derive formula for mean wasted life time expressed in terms of fX,S and partial derivatives of FX,S. Some examples with graphical representations are also provided.

Euler-Poincaré pairing, Dirac index and elliptic pairing for Harish-Chandra modules

Let G be a connected real reductive group with maximal compact subgroup K of equal rank, and let M be the category of Harish-Chandra modules for G. We relate three differentely defined pairings between two finite length modules X and Y in M : the Euler-Poincare pairing, the natural pairing between the Dirac indices of X and Y , and the elliptic pairing of [2]. (The Dirac index IDir(X) is a virtual finite dimensional representation of K, the spin double cover of K.) Analogy with the case of Hecke algebras studied in [7] and [6] and a formal (but not rigorous) computation lead us to conjecture that the first two pairings coincide. In the second part of the paper, we show that they are both computed as the indices of Fredholm pairs (defined here in an algebraic sense) of operators acting on the same spaces. We construct Euler-Poincare functions fX for any finite length Harish-Chandra module X. These functions are very cuspidal in the sense of Labesse, and their orbital integrals on elliptic elements coincide with the character of X. From this we deduce that the Dirac index pairing coincide with the elliptic pairing. These results are the archimedean analog of results of Schneider-Stuhler [21] for p-adic groups.

On Banach–Mazur limits

A positive functional x∗ on the space ℓ∞ of all bounded sequences is called a Banach–Mazur limit if ‖x∗‖=1 and x∗x=x∗Tx for all x=(x1,x2,…)∈ℓ∞, where T is the forward shift operator on ℓ∞, i.e., Tx=(0,x1,x2,…). The set of all Banach–Mazur limits is denoted by BM and a collection of extreme points of BM is denoted by extBM. Let ac0={x∈ℓ∞:x∗x=0for allx∗∈BM}. The following sequence spaces D(ac0)={x∈ℓ∞:x⋅ac0⊆ac0}andI(ac0)=ac0+−ac0+ are studied. In particular, if z∈ℓ∞ then z∈D(ac0) iff z−Tz∈I(ac0); moreover, z∈D(ac0) iff x∗{n:|zn−x∗z|≥ϵ}=0 for all ϵ>0 and x∗∈extBM. Order properties of Banach–Mazur limits are considered. Some properties of extBM are derived. We used the representation of functionals x∗∈BM as Borel measures on βN∖N. The cardinalities of some subset of BM are given. We also consider some questions of the probability theory for finite additive measures. E.g., for every x∗∈BM there exists an element x∈ℓ∞ such that the distribution function Fx∗,x(t)=x∗{n:xn≤t} is continuous on R. Two definitions of a variance are suggested. It is shown that Radon–Nikodym theorem is not valid for finite additive measures: the relations 0≤x∗≤y∗∈ℓ∞∗ do not imply the existence of w∈ℓ∞ satisfying x∗x=y∗(wx) for all x∈ℓ∞.

Optimal searching for a randomly located target in a bounded known region

This paper addresses the problem of searching for a randomly located target in a bounded known region by a single searcher. The searcher wishes to find the target's position, that is given by the value of the two independent double truncated random variables X; Y and they have joint symmetric probability density function fx; y. It is desired to search in an optimal manner to minimise the expected value of the time for detecting the target, assuming double truncated circular normal distributed estimates of its position.

On Censored Bivariate Random Variables: Copula, Characterization, and Estimation

Let (X, Y) be a bivariate random vector with joint distribution function FX, Y(x, y) = C(F(x), G(y)), where C is a copula and F and G are marginal distributions of X and Y, respectively. Suppose that (Xi, Yi), i = 1, 2, …, n is a random sample from (X, Y) but we are able to observe only the data consisting of those pairs (Xi, Yi) for which Xi ⩽ Yi. We denote such pairs as (X*i, Yi*), i = 1, 2, …, ν, where ν is a random variable. The main problem of interest is to express the distribution function FX, Y(x, y) and marginal distributions F and G with the distribution function of observed random variables X* and Y*. It is shown that if X and Y are exchangeable with marginal distribution function F, then F can be uniquely determined by the distributions of X* and Y*. It is also shown that if X and Y are independent and absolutely continuous, then F and G can be expressed through the distribution functions of X* and Y* and the stress–strength reliability P{X ⩽ Y}. This allows also to estimate P{X ⩽ Y} with the truncated observations (X*i, Yi*). The copula of bivariate random vector (X*, Y*) is also derived.

Barbour path functions and related operator means

We consider Barbour path function Fx(a,b)=a⋅bax+ba(1−x)x+ba(1−x) (0⩽x⩽1, a,b>0) as an approximation of the exponential function (or the geometric mean path) Gx(a,b)=a1−xbx (0⩽x⩽1, a,b>0) by a linear fractional function, which interpolates Gx(a,b) at x=0,12 and 1. If a=1 and b=t, then both the functions Fx(1,t) and Gx(1,t) are operator monotone in t, parameterized with x.We also consider the order relation between the integral mean for the Barbour path function and another mean.

On Complementary Edge Magic Labeling of Certain Graphs

By G(p, q) we denote a graph having p vertices and q edges, by V(G) and E(G) the vertex set and the edge - set of G respectively. But the vertices and edges are called the elements of the graph. A (p, q) - graph G is called the edge - magic if there exists a bijective function f: V(G) U E(G)  {1,2, ,p+q} such that f(u)+f(v)+f(uv)=k is a constant called the valence of f for any edge uv of G. Given an edge magic f of a graph G(p, q) the function () fx such that () fx =p+q+1-f(x) for all elements of G is said to be complementary to f(x) or complementary edge magic labeling () fx . The purpose of this article is to search for certain graphs Km, n (m, n ≥ 1), Cn (n ≥ 3), np2, f n (fan) Bn (bwk) and nG (n ≥ 2) where G is bipar- tite or tripartite which have complementary edge magic strength.

RXTE observation of recent flaring activity from the transient X-ray pulsar 2S 1553−542

We summarize the analysis of observations made by the Rossi X-ray Timing Explorer and the Swift/Burst Alert Telescope at the time of the recent flaring activity of the transient X-ray pulsar 2S 1553−542. The binary system is characterized by the projected semimajor axis ax sin i of 168 ± 18 light-seconds, the binary orbital period Porb of 29.56 ± 0.53 d and the X-ray mass function fx(M) of 5.3 ± 1.2 M⊙. We also found Pspin= 9.2829 ± 0.0003 s with s s−1, i.e. a spin-up rate of yr−1. The spin period is found to decrease more slowly than that of most other X-ray pulsars. As the flare decays with time, the structure and X-ray counts in the pulse profile showed considerable variability. However, no significant structural variability is seen in single-peaked pulse profiles in different energy bands. Pulsed fraction decreases with the decay of the flare but its value at different energy bands showed a discontinuity. Using X-ray spectroscopy at different orbital cycles, we have detected the presence of the Fe Kα emission line in the spectra with a minimum significance of 3σ. Apart from a consistent increase in blackbody temperature, other spectral parameters are found to be stable throughout orbital cycles. From detailed spectral and timing analysis, we concluded that the X-ray flare is spectrally hard and we confirmed the nature of the compact object as a transient, accretion-powered, spin-up X-ray pulsar with a Be-type companion.