Validation of a HPLC/MS method for simultaneous quantification of clonidine,morphine and its metabolites in human plasma

A high‐performance liquid chromatography–tandem mass spectrometry method was developed and validated for the simultaneous quantification of morphine, morphine's major metabolites morphine‐3‐glucuronide and morphine‐6‐glucuronide, and clonidine, to support the pharmacokinetic analysis of an ongoing double‐blinded randomized clinical trial that compares the use of morphine and clonidine in infants diagnosed with neonatal abstinence syndrome. Plasma samples were processed by solid‐phase extraction and separated on an Inertsil ODS‐3 (4 μm) column using an 0.1% formic acid in water–0.1% formic acid in methanol gradient. Detection of the analytes was conducted in the positive multiple reaction monitoring mode. The range of quantitation was 1–1000 ng/mL for morphine, morphine‐3‐glucuronide and morphine‐6‐glucuronide, and 0.25–100 ng/mL for clonidine. Intra‐day and inter‐day accuracy and precision were ≤15% for all analytes across the quantitation range. Extraction recovery rates were ≥94% for morphine, ≥90% for M3G, ≥87% for M6G and ≥ 79% for clonidine. Matrix effect ranged from 85–94% for clonidine to 101–106% for M3G. The method fulfilled all predetermined acceptance criteria and required only 100 μL of starting plasma volume. Furthermore, it was successfully applied to 30 clinical trial plasma samples.     

Symbiotic symmetries of the two-Higgs-doublet model

The new phenomenon of symbiotic symmetries   is described in the context of the Two-Higgs-Doublet Model (THDM). The quartic potential has two or more separate sectors with unequal symmetries, but these unequal symmetries persist even though the different sectors are renormalized by one another. We discuss all such symmetries of the THDM, consistent with the SU(2)×U(1)$\mathit{SU}(2)\times U(1)$ gauge interactions, using the Pauli formalism.     

Borohydride, azide, and chloride anions as terminal ligands on Fe/Mo/S clusters. Synthesis, structure and characterization of [(Cl4-cat)(PPr3) MoFe3S4(X)2]2(Bu4N)4 and [(Cl4-cat)(PPr3)MoFe3S4 (PPr3)(X)]2(Bu4N)2 (X = N3-, BH4-, Cl-) double-fused cubanes. NMR reactivity studies of [(Cl4-cat)(PPr3) MoFe3S4(BH4)2]2(Bu4N)4

Our explorations of the reactivity of Fe/Mo/S clusters of some relevance to the FeMoco nitrogenase have led to new double-fused cubane clusters with the Mo2Fe6S8 core as derivatives of the known (Cl4-cat)2Mo2Fe6S8(PPr3)6 (I) fused double cubane. The new clusters have been obtained by substitution reactions of the PPr3 ligands with Cl-, BH4-, and N3-. By careful control of the conditions of these reactions, the clusters [(Cl4-cat)(PPr3)MoFe3S4(BH4)2]2(Bu4N)4 (II), [(Cl4-cat)(PPr3)MoFe3S4(PPr3)(BH4)]2(Bu4N)2 (III), [(Cl4-cat)(PPr3)MoFe3S4(N3)2]2(Bu4N)4 (IV), [(Cl4-cat)(PPr3)MoFe3S4(PPr3)(N3)]2(Bu4N)2 (V), and [(Cl4-cat)(PPr3)MoFe3S4Cl2]2(Et4N)4 (VI) have been obtained and structurally characterized. A study of their electrochemistry shows that the reduction potentials for the derivatives of I are shifted to more positive values than those of I, suggesting a stabilization of the reduced clusters by the anionic ligands BH4- and N3-. Using 1H NMR spectroscopy, we have explored the lability of the BH4- ligand in II in coordinating solvents and its hydridic character, which is apparent in its reactivity toward proton sources such as MeOH or PhOH.     

Generalized motion by mean curvature as a macroscopic limit of stochastic ising models with long range interactions and Glauber dynamics

We study themacroscopic limit of an appropriately rescaledstochastic Ising model withlong range interactions evolving withGlauber dynamics as well as the correspondingmean field equation, which is nonlinear and nonlocal. In the limit we obtain an interface evolving with normal velocity k, wherek isthe mean curvature and thetransport coefficient is identified by aneffective Green-Kubo type formula. The above assertions are valid for all positive times, the motion of the interface being interpreted in theviscosity sense after the onset of the geometric singularities.Supported by ONRPartially supported by NSF, ARO, ONR and the Alfred P. Sloan Foundation     

Waiting Time for an Almost Perfect Run and Applications in Statistical Process Control

A natural and intuitively appealing generalization of the runs principle arises if instead of looking at fixed-length strings with all their positions occupied by successes, we allow the appearance of a small number of failures. Therefore, the focus is on clusters of consecutive trials which contain large proportion of successes. Such a formation is traditionally called “scan” or alternatively, due to the high concentration of successes within it, almost perfect (success) run. In the present paper, we study in detail the waiting time distribution for random variables related to the first occurrence of an almost perfect run in a sequence of Bernoulli trials. Using an appropriate Markov chain embedding approach we present an efficient recursive scheme that permits the construction of the associated transition probability matrix in an algorithmically efficient way. It is worth mentioning that, the suggested methodology, is applicable not only in the case of almost perfect runs, but can tackle the general discrete scan case as well. Two interesting applications in statistical process control are also discussed.     

Magnetic-Field-Controlled Quantum Critical Points in the Triangular Antiferromagnetic Cs2CuCl4-xBrx Mixed System

The triangular antiferromagnetic Cs₂CuCl_4-xBr_x mixed system is studied by neutron single-crystal diffraction in magnetic field. It shows a rich magnetic phase diagram consisting of four regimes depending on the Br concentration and is characterized by different exchange coupling mechanisms. For the investigated compositions from regime I (0 < x ≤ 1.5), a critical magnetic field B_c is found for a Br concentration x = 0.8 at B_c = 8.10(1) T and for x = 1.1 at B_c = 7.73(1) T and from regime IV (3.2 < x < 4) for x = 3.3 at B_c = 0.99(3) T. For magnetic fields larger than the respective B_c, magnetic superlattice reflections of these compounds are not found. The incommensurate magnetic wave vector q = (0, 0.470, 0) appears below the ordering temperature T_N = 0.51(1) K for Cs₂CuCl_3.2Br_0.8, and q = (0, 0.418, 0) below T_N = 1.00(6) K for Cs₂CuCl_0.3Br_3.7. Neutron diffraction experiments at around 60 mK for x = 3.7 in a magnetic field show the critical magnetic field at B_c = 7.94(16) T and the formation of the second magnetic phase at around 8.5 T depending on the temperature. Inelastic neutron scattering experiments for the compound from regime III (2 < x ≤ 3.2) with x = 2.2 show dynamical correlations at a temperature around 50 mK giving evidence for a spin liquid phase.     

Distributions of the Numbers of Failures and Successes in a Waiting Time Problem

Abstract. In this article we consider infinite sequences of Bernoulli trials and study the exact and asymptotic distribution of the number of failures and the number of successes observed before the r-th appearance of a pair of successes separated by a pre-specified number of failures. Several formulae are provided for the probability mass function, probability generating function and moments of the distribution along with some asymptotic results and a Poisson limit theorem. A number of interesting applications in various areas of applied science are also discussed.     

Generalizations of Runs and Patterns Distributions for Sequences of Binary Trials

Methodology and Computing in Applied Probability - In the present paper we study the distributions of families of patterns which generalize runs and patterns distributions extensively examined in...