Variational calculations of rovibrational states: a precise high-energy potential surface for HCN [and discussion]

We report the results of variational calculations of the rovibrational energy levels of HCN for J = 0, 1 and 2, where we reproduce all the ca. 100 observed vibrational states for all observed isotopic species, with energies up to 18000 cm$^{-1}$, to about $\pm $1 cm$^{-1}$, and the corresponding rotational constants to about $\pm $0.001 cm$^{-1}$. We use a hamiltonian expressed in internal coordinates r$_{1}$, r$_{2}$ and $\theta $, using the exact expression for the kinetic energy operator T obtained by direct transformation from the cartesian representation. The potential energy V is expressed as a polynomial expansion in the Morse coordinates y$_{i}$ for the bond stretches and the interbond angle $\theta $. The basis functions are built as products of appropriately scaled Morse functions in the bond-stretches and Legendre or associated Legendre polynomials of cos $\theta $ in the angle bend, and we evaluate matrix elements by Gauss quadrature. The hamiltonian matripx is factorized using the full rovibrational symmetry, and the basis is contracted to an optimized form; the dimensions of the final hamiltonian matrix vary from 240 $\times $ 240 to 1000 $\times $ 1000.We believe that our calculation is converged to better than 1 cm$^{-1}$ at 18 000 cm$^{-1}$. Our potential surface is expressed in terms of 31 parameters, about half of which have been refined by least squares to optimize the fit to the experimental data. The advantages and disadvantages and the future potential of calculations of this type are discussed.

Paraben esters: review of recent studies of endocrine toxicity, absorption, esterase and human exposure, and discussion of potential human health risks

This toxicology update reviews research over the past four years since publication in 2004 of the first measurement of intact esters of p-hydroxybenzoic acid (parabens) in human breast cancer tissues, and the suggestion that their presence in the human body might originate from topical application of bodycare cosmetics. The presence of intact paraben esters in human body tissues has now been confirmed by independent measurements in human urine, and the ability of parabens to penetrate human skin intact without breakdown by esterases and to be absorbed systemically has been demonstrated through studies not only in vitro but also in vivo using healthy human subjects. Using a wide variety of assay systems in vitro and in vivo, the oestrogen agonist properties of parabens together with their common metabolite (p-hydroxybenzoic acid) have been extensively documented, and, in addition, the parabens have now also been shown to possess androgen antagonist activity, to act as inhibitors of sulfotransferase enzymes and to possess genotoxic activity. With the continued use of parabens in the majority of bodycare cosmetics, there is a need to carry out detailed evaluation of the potential for parabens, together with other oestrogenic and genotoxic co-formulants of bodycare cosmetics, to increase female breast cancer incidence, to interfere with male reproductive functions and to influence development of malignant melanoma which has also recently been shown to be influenced by oestrogenic stimulation. Copyright (C) 2008 John Wiley & Sons, Ltd.

The significance of "nonsignificance" in randomized controlled studies: a discussion inspired by a double-blinded study on St. John's Wort (Hypericum perforatum L.) for premenstrual symptoms

Objectives: This study aimed to investigate the efficacy of St. John's wort extract (SJW) as a treatment for premenstrual symptoms. Design: The study was a randomized, double-blinded, placebo-controlled trial, with two parallel treatment groups. After a no-treatment baseline cycle, volunteers were randomized to either SJW or placebo for a further two menstrual cycles. Settings/location: A postal trial conducted from The University of Reading, Berkshire, England. Subjects: One hundred and sixty-nine (169) normally menstruating women who experienced recurrent premenstrual symptoms were recruited onto the study. One hundred and twenty-five (125) completed the protocol and were included in the analysis. Interventions: Six hundred milligrams (600) mg of SJW (standardized to contain 1800 mug of hypericin) or placebo (containing lactose and cellulose). Outcome measure: A menstrual diary was used to assess changes in premenstrual symptoms. The anxiety-related subgroup of symptoms of this instrument was used as the primary outcome measure. Results: After averaging the effects of treatment over both treatment cycles it was found that there was a trend for SJW to be superior to placebo. However, this finding was not statistically significant. Conclusion: The possibility that this nonsignificant finding resulted from insufficient statistical power in the study, rather than a lack of efficacy of SJW, is discussed. Following this discussion the recommendation is made that, in future, similar studies should be powered to detect a minimum clinically relevant difference between treatments.

Metal complexes of cyclen and cyclam derivatives useful for medical applications: a discussion based on thermodynamic stability constants and structural data

A series of the most common chelators used in magnetic resonance imaging ( MRI) and in radiopharmaceuticals for medical diagnosis and tumour therapy, H(4)dota, H(4)teta, H(8)dotp and H(8)tetp, is examined from a chemical point of view. Differences between 12- and 14-membered tetraazamacrocyclic derivatives with methylcarboxylate and methylphosphonate pendant arms and their chelates with divalent first-series transition metal and trivalent lanthanide ions are discussed on the basis of their thermodynamic stability constants, X- ray structures and theoretical studies.

Mononuclear and binuclear ruthenium(II) complexes with 4-(phenyl) thiosemicarbazone of benzaldehyde: a discussion on the relative stabilities of the four-membered and five-membered chelate rings formed by the ligand

Three new ruthenium complexes of the formulae cis-[Ru(PPh3)(2)(BzTscbz)(2)] (1a), [Ru-2(PPh3)(2)(BzTscbz)(4)] (1b) and [Ru(PPh3)(2)(BzTscHbz)(2)](ClO4)(2) (2) [BzTscHbz = 4-(phenyl) thiosemicarbazone of benzaldehyde] have been synthesized and characterized by various physicochemical methods including X-ray structure determinations for 1a and 1b. The relative stabilities of the four-membered versus five-membered chelate rings formed by the deprotonated ligand BzTscbz are discussed on the basis of the experimental results and some semi-empirical as well as DFT calculations. (c) 2005 Elsevier Ltd. All rights reserved.

The significance of "nonsignificance" in randomized controlled studies: a discussion inspired by a double-blinded study on St. John's Wort (Hypericum perforatum L.) for premenstrual symptoms

Objectives: This study aimed to investigate the efficacy of St. John's wort extract (SJW) as a treatment for premenstrual symptoms. Design: The study was a randomized, double-blinded, placebo-controlled trial, with two parallel treatment groups. After a no-treatment baseline cycle, volunteers were randomized to either SJW or placebo for a further two menstrual cycles. Settings/location: A postal trial conducted from The University of Reading, Berkshire, England. Subjects: One hundred and sixty-nine (169) normally menstruating women who experienced recurrent premenstrual symptoms were recruited onto the study. One hundred and twenty-five (125) completed the protocol and were included in the analysis. Interventions: Six hundred milligrams (600) mg of SJW (standardized to contain 1800 mug of hypericin) or placebo (containing lactose and cellulose). Outcome measure: A menstrual diary was used to assess changes in premenstrual symptoms. The anxiety-related subgroup of symptoms of this instrument was used as the primary outcome measure. Results: After averaging the effects of treatment over both treatment cycles it was found that there was a trend for SJW to be superior to placebo. However, this finding was not statistically significant. Conclusion: The possibility that this nonsignificant finding resulted from insufficient statistical power in the study, rather than a lack of efficacy of SJW, is discussed. Following this discussion the recommendation is made that, in future, similar studies should be powered to detect a minimum clinically relevant difference between treatments.