bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulations of RNA base pairs in a nanodroplet reveal solvation-dependent stability
Authors: Sykes Michael T. , Levitt Michael
Published: July 2007

We show that RNA base pairs have variable stability depending on their degree of solvation. This finding has far-reaching biological implications for nucleic acid structure in a partially solvated cellular environment such as inside RNA–protein complexes. Molecular dynamics simulations of partially solvated Watson–Crick RNA base pairs show that whereas water serves to destabilize a base pair by competing for and disrupting base–base hydrogen bonds, when sufficient water molecules are present, fewer hydrogen bonds are available to disrupt the base pairs and the destabilization effect is reduced. The result is that base pairs exist at a stability minimum when solvated in between 20 and 100 water molecules, the upper limit of which corresponds to the approximate number of water molecules contained in the first hydration shell.
MyD88-mediated signals induce the bactericidal lectin RegIIIγ and protect mice against intestinal Listeria monocytogenes infection
Authors: Brandl Katharina , Plitas George , Schnabl Bernd , DeMatteo Ronald P. , Pamer Eric G.
Published: July 2007

Listeria monocytogenes is a food-borne bacterial pathogen that causes systemic infection by traversing the intestinal mucosa. Although MyD88-mediated signals are essential for defense against systemic L. monocytogenes infection, the role of Toll-like receptor and MyD88 signaling in intestinal immunity against this pathogen has not been defined. We show that clearance of L. monocytogenes from the lumen of the distal small intestine is impaired in MyD88−/− mice. The distal ileum of wild-type (wt) mice expresses high levels of RegIIIγ, which is a bactericidal lectin that is secreted into the bowel lumen, whereas RegIIIγ expression in MyD88−/− mice is nearly undetectable. In vivo depletion of RegIIIγ from the small intestine of wt mice diminishes killing of luminal L. monocytogenes, whereas reconstitution of MyD88-deficient mice with recombinant RegIIIγ enhances intestinal bacterial clearance. Experiments with bone marrow chimeric mice reveal that MyD88-mediated signals in nonhematopoietic cells induce RegIIIγ expression in the small intestine, thereby enhancing bacterial killing. Our findings support a model of MyD88-mediated epithelial conditioning that protects the intestinal mucosa against bacterial invasion by inducing RegIIIγ.
Structural Basis of GLUT1 Inhibition by Cytoplasmic ATP
Authors: Blodgett David M. , De Zutter Julie K. , Levine Kara B. , Karim Pusha , Carruthers Anthony
Published: July 2007

Cytoplasmic ATP inhibits human erythrocyte glucose transport protein (GLUT1)–mediated glucose transport in human red blood cells by reducing net glucose transport but not exchange glucose transport (Cloherty, E.K., D.L. Diamond, K.S. Heard, and A. Carruthers. 1996. Biochemistry. 35:13231–13239). We investigated the mechanism of ATP regulation of GLUT1 by identifying GLUT1 domains that undergo significant conformational change upon GLUT1–ATP interaction. ATP (but not GTP) protects GLUT1 against tryptic digestion. Immunoblot analysis indicates that ATP protection extends across multiple GLUT1 domains. Peptide-directed antibody binding to full-length GLUT1 is reduced by ATP at two specific locations: exofacial loop 7–8 and the cytoplasmic C terminus. C-terminal antibody binding to wild-type GLUT1 expressed in HEK cells is inhibited by ATP but binding of the same antibody to a GLUT1–GLUT4 chimera in which loop 6–7 of GLUT1 is substituted with loop 6–7 of GLUT4 is unaffected. ATP reduces GLUT1 lysine covalent modification by sulfo-NHS-LC-biotin by 40%. AMP is without effect on lysine accessibility but antagonizes ATP inhibition of lysine modification. Tandem electrospray ionization mass spectrometry analysis indicates that ATP reduces covalent modification of lysine residues 245, 255, 256, and 477, whereas labeling at lysine residues 225, 229, and 230 is unchanged. Exogenous, intracellular GLUT1 C-terminal peptide mimics ATP modulation of transport whereas C-terminal peptide-directed IgGs inhibit ATP modulation of glucose transport. These findings suggest that transport regulation involves ATP-dependent conformational changes in (or interactions between) the GLUT1 C terminus and the C-terminal half of GLUT1 cytoplasmic loop 6–7.
Constructing a coherent joint prior while respecting biological realism: application to marine mammal stock assessments
Authors: Brandon John R. , Breiwick Jeffrey M. , Punt André E. , Wade Paul R.
Published: July 2007

Brandon, J. R., Breiwick, J. M., Punt, A. E., and Wade, P. R. 2007. Constructing a coherent joint prior while respecting biological realism: application to marine mammal stock assessments. – ICES Journal of Marine Science, 64: 1085–1100. Bayesian estimation methods, employing the Sampling–Importance–Resampling algorithm, are currently used to perform stock assessments for several stocks of marine mammals, including the Bering–Chukchi–Beaufort Seas stock of bowhead whales (Balaena mysticetus) and walrus (Odobenus rosmarus rosmarus) off Greenland. However, owing to the functional relationships among parameters in deterministic age-structured population dynamics models, placing explicit priors on each life history parameter in addition to the population growth rate parameter results in an incoherent joint prior distribution (i.e. two different priors on the estimated parameters). One solution to constructing a coherent joint prior is to solve for juvenile survival analytically, using values generated from the prior distributions for the remaining parameters. However, certain combinations of model parameter values result in values for juvenile survival that are larger than adult survival, which is biologically implausible. Therefore, to respect biological realism, certain parameter values must be rejected for some or all the remaining parameters. This study investigates several alternative resampling schemes for obtaining a realistic joint prior distribution, given the constraint on survival rates. The sensitivity of assessment results is investigated for data-rich (bowhead) and data-poor (walrus) scenarios. The results based on limited data are especially sensitive to the choice of alternative resampling scheme.
Apparatus for the simultaneous measurement of the X-ray absorption factor developed for a small-angle X-ray scattering beamline
Authors: Morita Takeshi , Tanaka Yoshitada , Ito Kazuki , Takahashi Yoshihiro , Nishikawa Keiko
Published: July 2007

A novel apparatus has been developed that enables the simultaneous determination of the absorption factor during measurement of small-angle X-ray scattering (SAXS) intensities of a sample. It was designed especially for the use of relatively low-energy X-rays at SAXS beamlines of synchrotron facilities. The X-ray intensity of transmittance is measured by a silicon PIN photodiode, which is implanted in a direct beamstop set in a vacuum chamber. Since the assembly transmits an attenuated direct beam to a detector during the scattering measurement, a zero-angle position can be monitored without additional operation. It was confirmed that the linearity between the signal from the photodiode and the intensity of X-rays is good and the photodiode is applicable for the desired purpose. For a performance test, the absorption factors of a supercritical fluid were measured with a wide density range.
Indexation scheme for oriented molecular thin films studied with grazing-incidence reciprocal-space mapping
Authors: Smilgies Detlef-M. , Blasini Daniel R.
Published: July 2007

Thin films of small molecules relevant to organic electronics applications often show a confusing degree of polymorphism. An effective reciprocal-space mapping scheme has been developed in order to find and index thin-film reflections which are related to previously known molecular structures. By method of elimination, thin-film reflections due to novel thin-film phases can thus be identified.
ORNL_SAS: software for calculation of small-angle scattering intensities of proteins and protein complexes
Authors: Tjioe Elina , Heller William T.
Published: July 2007

The programORNL_SAScalculates solution small-angle X-ray and neutron scattering intensity profiles from a wide variety of structures, including atomic-resolution models of proteins and protein complexes, low-resolution models defined in any manner, or combinations of both.ORNL_SASis capable of simultaneously generating multiple intensity profiles, such as a contrast-variation series, and evaluating the quality of the fit of the model profiles to experimental data in a single run of the program. The capabilities of the widely applicable approach make it possible to useORNL_SASas the intensity calculation engine of model-building applications for small-angle scattering data.
Growth units and growth habit of α-BaB2O4crystal
Authors: Wan Songming , Zhang Xia , Zhao Sijie , Zhang Qingli , You Jinglin , Chen Hui , Zhang Guochun , Yin Shaotang
Published: July 2007

The structure of the melt near a crystal–melt interface is a fundamental problem in the dynamics of crystal growth. In this work, high-temperature Raman spectroscopy was applied to investigatein situthe structure of the melt near the α-BaB2O4(α-BBO) crystal–melt interface. A structured melt was found in this region: (B3O6)3−groups form near the interface and vanish towards the bulk melt. The crystal growth habit was then explained by the periodic bond chain (PBC) theory. At the α-BBO crystal–melt interface, the growth units, namely the (B3O6)3−anion groups and Ba2+cations, stack mainly along four types of PBCs. These four PBCs constitute three potential F faces: {10\bar{1} 2}, {01\bar{1} 4} and {10\bar{1} 10}. The predicted results are in good agreement with the observed growth habit of α-BBO crystal.
In situsimultaneous Raman/high-resolution X-ray powder diffraction study of transformations occurring in materials at non-ambient conditions
Authors: Boccaleri Enrico , Carniato Fabio , Croce Gianluca , Viterbo Davide , van Beek Wouter , Emerich Hermann , Milanesio Marco
Published: July 2007

Materials containing disordered moieties and/or amorphous or liquid-like phases or showing surface- or defect-related phenomena constitute a problem with respect to their characterization using X-ray powder diffraction (XRPD), and in many cases Raman spectroscopy can provide useful complementary information. A novel experimental setup has been designed and realized for simultaneousin situRaman/high-resolution XRPD experiments, to take full advantage of the complementarities of the two techniques in investigating solid-state transformations under non-ambient conditions. The added value of the proposed experiment is the perfect synchronization of the two probes with the reaction coordinate and the elimination of possible bias caused by different sample holders and conditioning modes used in `in situbut separate' approaches. The setup was tested on three solid-state transformations: (i) the kinetics of the fluorene–TCNQ solid-state synthesis, (ii) the thermal swelling and degradation of stearate–hydrotalcite, and (iii) the photoinduced (2 + 2)-cyclization of (E)-furylidenoxindole. These experiments demonstrated that, even though the simultaneous Raman/XRPD experiment is more challenging than separate procedures, high-resolution XRPD and Raman data can be collected. A gas blower allows studies from room temperature to 700 K, and 100 K can be reached using a nitrogen cryostream. The flexibility of the experimental setup allows the addition of ancillary devices, such as a UV lamp used to study photoreactivity.
Real-space form factor of spherical particles in kinematic and dynamic scattering
Authors: de Haan Victor-O. , Plomp Jeroen , van Well Ad A.
Published: July 2007

The phase-object approximation for neutron scattering is applied to determine the real-space sample correlation function for a sphere for kinematic and dynamic scattering. The sample correlation function determined in this way corresponds to the kinematic and refraction limits.
A synchrotron X-ray study of structural ordering in the microwave dielectric ceramic system: Ba(Ni1/3Nb2/3)O3–Ba(Zn1/3Nb2/3)O3
Authors: Cernik R. J. , Barwick M. , Azough F. , Freer R.
Published: July 2007

Microwave dielectric ceramics in Ba(Ni1/3Nb2/3)O3–Ba(Zn1/3Nb2/3)O3(BNN–BZN) have been studied using high-resolution synchrotron powder diffraction. Two crystalline phases (cubicPm\bar{3}mand trigonalP\bar{3}m1) have been found to coexist in both the BZN and BNN end members and mixed phases. A direct correlation between cooling rate (513 K h−1to 275 K h−1) after sintering (annealing) and the growth of the trigonal ordered phase has been observed. The effect of annealing time (up to 72 h) at 1573 K has also been investigated for BNN ceramics and has been found to affect the growth of the ordered phase in a similar way to the variation of cooling rate. The degree of order in both BNN and BZN was found to increase with slow cooling and annealing from 28% to 38%, and from 10% to 31%, respectively. The degree of ordering in solid-solution samples prepared from a mixture of BZN and BNN also increased with slow cooling and annealing. In this case, the growth of the ordered phases were less well developed than those of the individual end members. Two surface-specific phases were found in the slowly cooled BZN sample, one of which was confirmed as Ba5Nb4O15by wavelength dispersive spectroscopy (WDS) and Rietveld analysis; the other was found to be Ba8ZnNb6O24by WDS.
Meeting report of the BCA 25th Annual Meeting held at the University of Kent in Canterbury, UK, 16–19 April 2007
Authors: Helliwell John R.
Published: July 2007

A report on the BCA 25th Annual Meeting held at the University of Kent in Canterbury, UK, 16–19 April 2007.
Crystal structures and thermal expansion of α-MgSO4and β-MgSO4from 4.2 to 300 K by neutron powder diffraction
Authors: Fortes A. D. , Wood I. G. , Vočadlo L. , Brand H. E. A. , Knight K. S.
Published: July 2007

Detailed neutron powder diffraction measurements have been carried out on two polymorphs of anhydrous magnesium sulfate, α-MgSO4and β-MgSO4. α-MgSO4is orthorhombic, space groupCmcm(Z= 4); at 4.2 K the unit-cell dimensions area= 5.16863 (3),b= 7.86781 (5),c= 6.46674 (5) Å,V= 262.975 (2) Å3[ρcalc= 3040.16 (2) kg m−3], and at 300 K,a= 5.17471 (3),b= 7.87563 (5),c= 6.49517 (5) Å,V= 264.705 (2) Å3[ρcalc= 3020.29 (2) kg m−3]. The axial and volumetric thermal expansion coefficients are positive at all temperatures and exhibit no unusual behaviour. Structures were refined at 4.2 and 300 K toRP< 3%; less precise structural parameters were determined during warming from 4.2 to 300 K. β-MgSO4has a more complex structure, crystallizing in space groupPbnm(Z= 4); the unit-cell dimensions at 4.2 K area = 4.73431 (8),b= 8.58170 (12),c= 6.67266 (11) Å,V= 271.100 (5) Å3[ρcalc= 2949.04 (5) kg m−3], and at 300 K,a= 4.74598 (7),b= 8.58310 (10),c= 6.70933 (10) Å,V= 273.306 (4) Å3[ρcalc= 2925.42 (4) kg m−3]. The thermal expansivities of theaandcaxes, and the volumetric thermal expansion coefficient, are positive at all temperatures and normally behaved. However, the thermal expansion of thebaxis is both very small and negative below ∼125 K. Structural and thermal motion parameters for β-MgSO4as a function of temperature are also reported.
Structural systematics of 4,4′-disubstituted benzenesulfonamidobenzenes. 1. Overview and dimer-based isostructures
Authors: Gelbrich Thomas , Hursthouse Michael B. , Threlfall Terence L.
Published: July 2007

One hundred 4,4′-disubstituted benzenesulfonamidobenzenes, X–C6H5–SO2–NH–C6H5–Y, where X, Y = NO2, CN, CF3, I, Br, Cl, F, H, Me, OMe, have been synthesized and their crystal structures determined. The resulting set of 133 structures, which includes polymorphic forms, is used to make a comparative study of the molecular packing and the nature of the intermolecular interactions, including the formation of hydrogen-bonding motifs and the influence of the two substituents X and Y on these features. Nine distinct supramolecular connectivity motifs of hydrogen bonding are encountered. There are 74% of all the structures investigated which exhibit one of two motifs based on N—H...O=S interactions, a dimer or a chain. There are three other, infrequent motifs, also employing N—H...O=S links, which exhibit more complexity. Four different chain motifs result from either N—H...O=N, N—H...C[triple-bond]N or N—H...OMe interactions, arising from the presence of a nitro (position Y), nitrile (X or Y) or methoxy (Y) substituent. The program XPac [Gelbrich & Hursthouse (2005). CrystEngComm, 7, 324–336] was used to systematically analyse the packing relationships between crystal structures. Similar discrete (zero-dimensional) and extended (one-dimensional and two-dimensional) structure components, as well as cases of isostructurality were identified. A hierarchy for the classification of the 56 distinct structure types of this set is presented. The most common type, a series of 22 isostructures containing the simple centrosymmetric N—H...O=S-bonded dimer, is discussed in detail.
Using cluster analysis to study transition-metal geometries: four-coordinate complexes with two salicylaldiminato or related ligands
Authors: Parkin Andrew , Barr Gordon , Collins Anna , Dong Wei , Gilmore Christopher J. , Tasker Peter A. , Wilson Chick C.
Published: July 2007

Cluster analysis is shown to be an effective method to analyse and classify metal coordination geometry in a very large number of four-coordinate bis-salicylaldimato (or bis-β-iminoketonate) transition-metal complexes available in the Cambridge Structural Database. The methods described require no prior knowledge of chemistry to be input; retrieved structures are automatically clustered into groups based purely on the geometric similarity of the fragments and these groupings can then be interpreted by the structural chemist.
Structure of unsolvated magnesium borohydride Mg(BH4)2
Authors: Her Jae-Hyuk , Stephens Peter W. , Gao Yan , Soloveichik Grigorii L. , Rijssenbeek Job , Andrus Matthew , Zhao Ji-Cheng
Published: July 2007

We have determined the structures of two phases of unsolvated Mg(BH4)2, a material of interest for hydrogen storage. One or both phases can be obtained depending on the synthesis conditions. The first, a hexagonal phase with space group P61, is stable below 453 K. Upon heating above that temperature it transforms to an orthorhombic phase, with space group Fddd, stable to 613 K at which point it decomposes with hydrogen release. Both phases consist of complex networks of corner-sharing tetrahedra consisting of a central Mg atom and four BH4 units. The high-temperature orthorhombic phase has a strong antisite disorder in the a lattice direction, which can be understood on the basis of atomic structure.
Framework `interstitial' oxygen in La10(GeO4)5(GeO5)O2 apatite electrolyte
Authors: Pramana Stevin S. , Klooster Wim T. , White T. J.
Published: July 2007

Oxygen conduction at low temperatures in apatites make these materials potentially useful as electrolytes in solid-oxide fuel cells, but our understanding of the defect structures enabling ion migration is incomplete. While conduction along [001] channels is dominant, considerable inter-tunnel mobility has been recognized. Using neutron powder diffraction of stoichiometric `La10(GeO4)6O3', it has been shown that this compound is more correctly described as an La10(GeO4)5(GeO5)O2 apatite, in which high concentrations of interstitial oxygen reside within the channel walls. It is suggested that these framework interstitial O atoms provide a reservoir of ions that can migrate into the conducting channels of apatite, via a mechanism of inter-tunnel oxygen diffusion that transiently converts GeO4 tetrahedra to GeO5 distorted trigonal bipyramids. This structural modification is consistent with known crystal chemistry and may occur generally in oxide apatites.
Accurate charge density of the tripeptide Ala-Pro-Ala with the maximum entropy method (MEM): influence of data resolution
Authors: Hofmann Andreas , Kalinowski Roman , Luger Peter , van Smaalen Sander
Published: July 2007

The accurate electron density of Ala-Pro-Ala is determined by the maximum entropy method (MEM), employing the same reflection data measured at 100 K which was used for a multipole refinement by Kalinowski et al. [(2007), Acta Cryst. Accepted for publication]. Properties of the electron density are compared with the corresponding properties of the static electron density from the multipole model and to the dynamic MEM electron density of trialanine at 20 K. It is thus shown that the increased thermal smearing at 100 K leads to lower electron densities in the bond critical points and atomic charges closer to zero for Ala-Pro-Ala than has been obtained for trialanine at 20 K. The influence of the resolution of the data is investigated by a series of MEM calculations. Atomic charges and atomic volumes are found not to depend on the resolution, but the charge density in the BCPs decreases with decreasing resolution of the dataset. The origin of this dependence is found to lie mostly in the more accurate estimate of the atomic displacement parameters (ADPs) for the higher-resolution datasets. If these effects are taken into account, meaningful information on chemical bonding can be obtained with data at a resolution better than d
min = 0.63 Å. Alternatively, low-resolution X-ray diffraction data can be used in accurate electron-density studies by the MEM, if another source of accurate values of the ADPs is available, e.g. from refinements with multipole parameters from a database of transferable multipole parameters.
Clindamycin and taste disorders
Authors: De Groot Mark C. H. , Van Puijenbroek Eugène P.
Published: July 2007

What is already known about this subject.

• The antibiotic clindamycin has a bitter taste when it is used orally.

What this study adds

• A case series on oral as well as i.v. use of clindamycin associated with taste disorders is presented.

• After corrections in a case‐by‐case analysis for several possible confounders such as indication, clindamycin is disproportionally associated with taste disorders.

• Serum and hence saliva and sputum clindamycin levels seem to be responsible for this reversible adverse drug reaction.

Aims

Topical use of clindamycin has been associated with taste disorders in the literature, but little is known about the nature of this adverse drug reaction. The aim of this article was to describe reports of clindamycin‐induced taste disorders and to analyse the factors involved.

Methods

The adverse drug reaction database of the Netherlands Pharmacovigilance Centre was searched for reports concerning taste disorders with antibiotics. Clinical review of the cases and statistical analysis with logistic regression were performed. Characteristics of patients who reported taste disorders were compared for age, gender and formulation in clindamycin vs. other antibiotic users.

Results

Taste disorders were reported in seven (18%) of the clindamycin cases. In five reports an oral formulation was involved, in one report intravenous (i.v.) administration and in one report both formulations were used. Latency was <1 day after start and in one case taste disorders were present repeatedly at 10 min after every i.v. application. The adjusted reporting odds ratio was 7.0 (95% confidence interval 2.8, 17.3) and supports a possible causal relationship.

Conclusions

The association of clindamycin and taste disorders is supported by disproportionality analysis and seems to be independent of possible confounders such as age, gender and infections. The case reports suggest a role for clindamycin concentrations excreted in body fluids like saliva.
Proton pump inhibitor‐induced acute interstitial nephritis
Authors: Härmark Linda , Van Der Wiel Hans E. , De Groot Mark C. H. , Van Grootheest A. C.
Published: July 2007

What is already known about this subject

• In several case reports the use of omeprazole has been associated with interstitial nephritis.

• Recently there have been reports linking other proton pump inhibitors (PPIs) with interstitial nephritis.

What this study adds

• We present supplementary cases received by the Netherlands Pharmacovigilance Centre Lareb, concerning interstitial nephritis in users of PPIs including omeprazole, pantoprazole and rabeprazole.

• In this case series seven patients are presented. In six cases they recovered spontaneously after cessation of the PPI, in one case the patient recovered after treatment with a corticosteroid.

• Further support for this association comes from the worldwide adverse drug reaction database of the World Health Organization.

• This report shows that interstitial nephritis can occur with all PPIs. Health professionals should be aware of this potential serious adverse drug reaction.

Aim

To investigate the association between the use of proton pump inhibitors (PPIs) and acute interstitial nephritis (AIN).

Methods

The Netherlands Pharmacovigilance Centre Lareb received seven case reports of AIN induced by various PPIs. In five of the reports it was mentioned that the diagnosis was confirmed by a renal biopsy.

Results

The time to onset varied between hours to 4 months. In all cases but one the patient spontaneously recovered after withdrawal of the offending agent. In one case the patient received treatment with prednisolone and recovered. In one patient a rechallenge was done 9 days after the initial event. Within 12 h of re‐exposure the patient developed symptoms of AIN.

Conclusions

The mechanism of drug‐induced AIN is unknown, but an immunological mechanism is suspected. Our reports show no relation between dosage, latency, time to recovery, age or gender, supporting the hypothesis that the aetiology of AIN is immunological. Lareb has received reports of AIN with the use of omeprazole, pantoprazole and rabeprazole. This shows that AIN is a complication associated with the whole group of PPIs and not only omeprazole. It is important for health professionals to be aware of this adverse drug reaction, because an accurate and timely diagnosis and withdrawal of the offending drug can prevent potentially life‐threatening renal failure.
The pharmacokinetic profile of sitaxsentan, a selective endothelin receptor antagonist, in varying degrees of renal impairment
Authors: Dhaun Neeraj , Melville Vanessa , Kramer William , Stavros Fiona , Coyne Terrance , Swan Suzanne , Goddard Jane , Webb David J.
Published: July 2007

What is already known about this subject

• The initial indication for endothelin (ET) receptor antagonism as a treatment strategy, primary pulmonary hypertension, is now expanding to include scleroderma, which can cause both pulmonary and renal disease.

• It is important to understand the effects of impaired renal function on the pharmacokinetics of these drugs to allow appropriate dosing in individuals with impaired renal function.

What this study adds

• Sitaxsentan, an oral selective endothelin A receptor antagonist, is licensed for the treatment of pulmonary hypertension, and studies of this drug in CKD are planned.

• The pharmacokinetic profile of sitaxsentan is unchanged in subjects with varying degrees of renal impairment.

• The results of this study will allow confident dosing of sitaxsentan in individuals with renal impairment, and inform future studies.

Aim

To investigate the pharmacokinetic profile of a single 100‐mg oral dose of sitaxsentan, a selective endothelin type A receptor antagonist, in subjects with normal and impaired renal function.

Methods

This was an open label, single oral dose study in subjects with normal [creatinine clearance (CrCL) ≥ 80 ml min−1] and impaired renal function (mild renal impairment CrCL 51–80 ml min−1, moderate impairment CrCL 31–50 ml min−1, severe impairment CrCL ≤ 30 ml min−1). All subjects received a dose of 100 mg sitaxsentan.

Results

Twenty‐four subjects were enrolled, six in each of the normal and three renal impairment groups. The mean plasma sitaxsentan concentrations were comparable across the groups, as were the mean values for Cmax (10.3–13.9 µg ml−1), AUC∞ (18.7–22.5 h µg−1 ml−1), oral clearance (CL/F, 82.3–94.9 ml min−1), volume of distribution (Vz/F, 64.8–69.6 l) and elimination half‐life (t1/2, 8.6–9.6 h). There was substantial overlap among the four groups in the individual subject values for CL/F and Vz/F and no relationship between either of these parameters and CrCL.

Conclusion

After a single 100‐mg oral dose of sitaxsentan there were no differences in its pharmacokinetics among subjects with normal or impaired renal function.
Add‐on therapy with doxazosin in patients with hypertension influences arterial stiffness and albuterol‐mediated arterial vasodilation
Authors: Wykretowicz Andrzej , Guzik Przemyslaw , Krauze Tomasz , Adamska Karolina , Milewska Agata , Wysocki Henryk
Published: July 2007

What is already known about this subject

• Hypertension is associated with increased arterial stiffness and impaired endothelial function.

• Arterial vasodilation depends on endothelial function and can be regulated by β2‐adrenergic stimulation.

• Doxazosin is a known and potent antihypertensive agent. However, its effects on arterial stiffness and vasodilation have not been fully established.

What this study adds

Sixteen‐week add‐on antihypertensive therapy with 4 mg of doxazosin extended release daily:

• Reduces arterial stiffness.

• Improves albuterol‐mediated, i.e. endothelium‐dependent, arterial vasodilation.

• Does not influence nitroglycerin‐mediated, i.e. endothelium‐independent, arterial vasodilation.

Aims

Doxazosin is an antihypertensive agent with largely unknown effects on arterial stiffness and vasodilation. The aim of this study was to determine the effect of the addition of doxazosin extended‐release (ER) to the standard management of hypertension in patients with inadequately controlled blood pressure (BP) on arterial stiffness and arterial vasodilation.

Methods

Twenty patients with inadequately controlled hypertension were treated with 4 mg doxazosin ER daily for 16 weeks as an adjunct to their existing antihypertensive regimen.

Results

Doxazosin ER add‐on therapy was associated with significantly reduced systolic (P < 0.0001) and diastolic (P = 0.0003) BP, improved arterial stiffness (determined by digital volume pulse analysis (P = 0.048) and albuterol‐mediated arterial vasodilation (P = 0.030).

Conclusions

Add‐on therapy with 4 mg of doxazosin ER daily reduces BP and arterial stiffness and improves arterial vasodilation in response to adrenergic stimulation.
No significant effect ofSLCO1B1polymorphism on the pharmacokinetics of rosiglitazone and pioglitazone
Authors: Kalliokoski Annikka , Neuvonen Mikko , Neuvonen Pertti J. , Niemi Mikko
Published: July 2007

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• A common single nucleotide polymorphism (SNP) (c.521T→C) of theSLCO1B1gene, encoding the hepatic uptake transporter organic anion transporting polypeptide (OATP) 1B1, has been associated with marked changes in the pharmacokinetics of the antidiabetic drug repaglinide.

• Rosiglitazone and pioglitazone are competitive inhibitors of OATP1B1 and might thus be its substrates.

• Gemfibrozil, an inhibitor of OATP1B1in vitro, considerably increases the plasma concentrations of rosiglitazone and pioglitazonein vivoin humans.

WHAT THIS STUDY ADDS

• TheSLCO1B1c.521T→C SNP was not associated with changes in rosiglitazone or pioglitazone pharmacokinetics in healthy volunteers.

• OATP1B1 is thus unlikely to play an important role in the disposition of rosiglitazone or pioglitazone.

AIMS

To examine possible effects of polymorphism in theSLCO1B1gene, encoding the hepatic uptake transporter organic anion transporting polypeptide (OATP) 1B1, on the pharmacokinetics of rosiglitazone and pioglitazone in a prospective genotype panel study.

METHODS

Sixteen healthy volunteers with the homozygousSLCO1B1c.521TT genotype (controls), 12 with the heterozygous c.521TC genotype and four with the homozygous c.521CC genotype ingested a single 4‐mg dose of rosiglitazone and a single 15‐mg dose of pioglitazone in a cross‐over study with a wash‐out period of at least 1 week.

RESULTS

SLCO1B1polymorphism had no statistically significant effect on any of the pharmacokinetic variables of rosiglitazone, pioglitazone or their metabolites. The mean ± SD area under the plasma rosiglitazone concentration–time curve from time 0 to infinity (AUC0–∞) was 2024 ± 561 ng ml−1 h in the c.521TT subjects, 1763 ± 288 ng ml−1 h in the c.521TC subjects (geometric mean ratio c.521TC/c.521TT 0.89; 95% confidence interval 0.72, 1.11) and 1729 ± 346 ng ml−1 h in the c.521CC subjects (c.521CC/c.521TT 0.87; 0.63, 1.20). The AUC0–∞of pioglitazone averaged 6244 ± 1909 ng ml−1 h in the c.521TT subjects, 5123 ± 1165 ng ml−1 h in the c.521TC subjects (c.521TC/c.521TT 0.83; 0.65, 1.06) and 4851 ± 1123 ng ml−1 h in the c.521CC subjects (c.521CC/c.521TT 0.79; 0.55, 1.14). There was a significant correlation between the AUC0–∞of rosiglitazone and pioglitazone (r = 0.717,P < 0.001).

CONCLUSIONS

TheSLCO1B1c.521T→C SNP does not affect the pharmacokinetics of rosiglitazone or pioglitazone, indicating that OATP1B1 plays no significant role in the disposition of these drugs.
Numerical comparison of different convergent plate contacts: subduction channel and subduction fault
Authors: De Franco Roberta , Govers Rob , Wortel Rinus
Published: July 2007

At convergent plate boundaries, the properties of the actual plate contact are important for the overall dynamics. Convergent plate boundaries both mechanically decouple and link tectonic plates and accommodate large amounts of strain. We investigate two fundamental physical states of the subduction contact: one based on a fault and the other based on a subduction channel. Using a finite element method, we determine the specific signatures of both states of the subduction contact. We pay particular attention to the overriding plate. In a tectonic setting of converging plates, where the subducting plate is freely moving, the subduction channel reduces compression relative to the fault model. In a land-locked basin setting, where the relative motion between the far field of the plates is zero, the subduction channel model produces tensile stress regime in the overriding plate, even though the amount of slab roll-back is small. The fault model shows a stronger development of slab roll-back and a compressive stress regime in the upper plate. Based on a consistent comparison of fault and channel numerical models, we find that the nature of the plate contact is one of the controlling factors in developing or not of backarc extension. We conclude that, the type of plate contact plays a decisive role in controlling the backarc state of stress. To obtain backarc extension, roll-back is required as an underling geodynamic process, but it is not always a sufficient condition.
Desertification in the Sahel: a reinterpretation of a reinterpretation
Authors: PRINCE STEPHEN D. , WESSELS KONRAD J. , TUCKER COMPTON J. , NICHOLSON SHARON E.
Published: July 2007

In semiarid regions the ratio of annual net primary production to precipitation, rain‐use efficiency (RUE), has been used as an index of desertification. In a recent publication (Hein & de Ridder, 2006) it was proposed that an incorrect understanding of the relationship between RUE and rainfall has led to a misinterpretation of the satellite record of desertification in the African Sahel. Here, we examine this suggestion and show that, contrary to Hein and de Ridder's statement, satellite studies of Sahelian RUE have reported increases, decreases, and constant values since 1981. Furthermore, we find that data do not support their proposal that RUE increases with rainfall, even in nondegraded areas. Hence we reject their corollary, that constant RUE is prima facie evidence of desertification. The fundamental difficulty with the use of RUE for detection of desertification remains, that is the difficulty of estimation of the RUE for nondegraded land at a regional scale.
Large‐scale climatic signatures in lakes across Europe: a meta‐analysis
Authors: BLENCKNER THORSTEN , ADRIAN RITA , LIVINGSTONE DAVID M. , JENNINGS ELEANOR , WEYHENMEYER GESA A. , GEORGE D. GLEN , JANKOWSKI THOMAS , JÄRVINEN MARKO , AONGHUSA CAITRIONA NIC , NÕGES TIINA , STRAILE DIETMAR , TEUBNER KATRIN
Published: July 2007

Recent studies have highlighted the impact of the winter North Atlantic Oscillation (NAO) on water temperature, ice conditions, and spring plankton phenology in specific lakes and regions in Europe. Here, we use meta‐analysis techniques to test whether 18 lakes in northern, western, and central Europe respond coherently to winter climate forcing, and to assess the persistence of the winter climate signal in physical, chemical, and biological variables during the year. A meta‐analysis approach was chosen because we wished to emphasize the overall coherence pattern rather than individual lake responses. A particular strength of our approach is that time‐series from each of the 18 lakes were subjected to the same robust statistical analysis covering the same 23‐year period. Although the strongest overall coherence in response to the winter NAO was exhibited by lake water temperatures, a strong, coherent response was also exhibited by concentrations of soluble reactive phosphorus and soluble reactive silicate, most likely as a result of the coherent response exhibited by the spring phytoplankton bloom. Lake nitrate concentrations showed significant coherence in winter. With the exception of the cyanobacterial biomass in summer, phytoplankton biomass in all seasons was unrelated to the winter NAO. A strong coherence in the abundance of daphnids during spring can most likely be attributed to coherence in daphnid phenology. A strong coherence in the summer abundance of the cyclopoid copepods may have been related to a coherent change in their emergence from resting stages. We discuss the complex nature of the potential mechanisms that drive the observed changes.
Can the plant‐mediated impacts on aphids of elevated CO2 and drought be predicted?
Authors: PRITCHARD J. , GRIFFITHS B. , HUNT E. J.
Published: July 2007

The effects of drought and elevated CO2 on the performance of sap‐feeding aphids is considered. It is assumed that, for these stressors, the major influence will act through altering host plant composition and therefore diet. Changes in the plant may affect the ability to locate phloem tissues, while changes in composition of the sieve element forming the aphid diet may have more direct effects. It is concluded that plant response to conditions where carbon is present in excess (elevated CO2) or its consumption is exceeded by its availability (drought) is heterogeneous at the cellular level. The complexities of the response of the plant to components of climate change are paralleled by the diversity of the responses of aphids to drought and elevated CO2. Potential control points are discussed and it is concluded that current knowledge, both descriptive and mechanistic, supports the view that it is unreasonable to expect that a single plant component can predict the general response of aphids to climate change. Instead, it is more likely that aphids use a variety of cues when interacting with their host plants, and individual species respond to changes in their diet differently. Further work examining the response of both plant and aphid transcriptome and metabolome will support or contradict this hypothesis.
Mental health policy and mental health service user perspectives on involvement: a discourse analysis
Authors: Hui Ada , Stickley Theodore
Published: July 2007

Aim.  This paper is a report of an exploration of the concept of service user involvement in mental health nursing using a discourse analysis approach.

Background.  Service user involvement has come to be expected in mental health nursing policy and practice. This concept, however, is often applied somewhat ambiguously and some writers call for a clearer understanding of what service users actually want.

Method.  A Foucauldian discourse analysis was conducted in 2005, examining literature and health policies published by the United Kingdom government and service users. The discursive perspectives of both were explored and conceptual themes were generated from the data.

Findings.  Concepts occurring within government discourse include language relating to service users, the notion of service user involvement and power. Concepts from the service user discourse include power, change and control, theory, policy and practice, and experiential expertise. Differences in perspectives were found within these themes which distinguished government from service user discourses. Greater flexibility in ideas and perspectives was demonstrated by service users, with a seemingly greater range of theoretical underpinnings.

Conclusion.  Greater awareness is needed of the significance of language, of how subtle inferences may be drawn from the rhetorical language of policies, of how these might affect the involvement of service users, and of the implications for the role of mental health nurses. Nurses need to be aware of these tensions and conflicts in managing their practice and in creating a mental health nursing philosophy of ‘involvement’. If true ‘involvement’ is to ensue, nurses may also need to consider the transfer of power to service users.
Nutritional status and length of stay in patients admitted to an Acute Assessment Unit
Authors: Thomas J. M. , Isenring E. , Kellett E.
Published: July 2007

Background The Redesigning Care initiative at Flinders Medical Centre aimed to improve access to timely, consistent, quality care. This led to the creation of an Acute Assessment Unit (AAU) where all patients are assessed by the Allied Health team on admission. This study aimed to: (i) determine the nutritional status of patients admitted to the AAU using the scored Patient Generated‐Subjective Global Assessment (PG‐SGA); and (ii) determine the association between nutritional status and length of stay (LOS).

Methods A prospective, observational study was conducted in 64 patients (mean age 79.9 ± 11 years, 76% female). Nutritional status was assessed within 48 h of admission and LOS data were collected prospectively.

Results According to PG‐SGA global rating, 53% (n = 34) of patients were malnourished. There was a weak association between PG‐SGA score and LOS (r = 0.250,P = 0.046). The malnourished patients had a longer LOS by 1 day compared to well‐nourished patients, and while this did not reach statistical significance (Z = −0.988,P = 0.323), it has implications for health care costs. LOS overall was short at a median of 4.5 days (range 1–24).

Conclusions A significant proportion of patients admitted to the AAU is malnourished. There was a trend for these patients to have a longer LOS, indicating a critical need for nutritional management; however LOS as a whole was short. While nutrition support in hospital is useful in reinforcing dietary education, the short LOS emphasized the importance of discharge education and follow‐up.
Factors that affect the food choices made by girls and young women, from minority ethnic groups, living in the UK
Authors: Lawrence J. M. , Devlin E. , Macaskill S. , Kelly M. , Chinouya M. , Raats M. M. , Barton K. L. , Wrieden W. L. , Shepherd R.
Published: July 2007

Background  Lower birth weight, often found in infants from minority ethnic groups, may be partly because of the disproportionate representation of ethnic minority groups in low‐income areas. To develop an intervention, to improve the nutritional intake of young women from populations at risk of low‐birth‐weight babies, which would be culturally sensitive and well received by the intended recipients, a community development approach was used to investigate factors that might influence food choice and the nutritional intake of girls and young women from ethnic minority groups.

Methods  Focus group discussions were conducted across the UK, to explore factors that might affect the food choices of girls and young women of African and South Asian decent. The data was analysed using deductive content analysis (Qual. Soc. Res., 1, 2000, 1). Discussions were around the broad themes of buying and preparing food, eating food and dietary changes, and ideas for an intervention to improve diet.

Results  The focus group discussions indicated that all the communities took time, price, health and availability into consideration when making food purchases. The groups were also quite similar in their use of ‘Western’ foods which tended to be of the fast food variety. These foods were used when there was not enough time to prepare a ‘traditional’ meal.

Conclusion  Many issues that affect the food choice of people who move to the UK are common within different ethnic groups. The idea of a practical intervention based on improving cooking skills was popular with all the groups.
The importance of exposure for healthy eating in childhood: a review
Authors: Cooke L.
Published: July 2007

Children's food preferences are strongly associated with their consumption patterns. Identifying the factors that influence preferences is therefore crucial to the development of effective interventions to improve children's diets. Perhaps the most important determinant of a child's liking for a particular food is the extent to which it is familiar. Put simply, children like what they know and they eat what they like. From the very earliest age, children's experiences with food influence both preferences and intake, and research suggests that the earlier and broader that experience, the healthier the child's diet. Laboratory studies of children's food acceptance have indicated that repeated opportunities to taste unfamiliar foods results in increased liking and consumption. In order to investigate whether these results can be replicated in real‐world situations, a series of naturalistic studies testing the efficacy of exposure‐based interventions have been carried out. In a school‐based study large increases in liking and intake of raw red pepper were seen in 5‐ to 7‐year olds and two further studies, in which mothers used exposure techniques to increase children's acceptance of vegetables, achieved similar results. If future large‐scale interventions prove to be successful, training could be offered to health professionals or directly to parents themselves.
Clinical supervision for mental health nurses in Northern Ireland: formulating best practice guidelines
Authors: RICE F. , CULLEN P. , MCKENNA H. , KELLY B. , KEENEY S. , RICHEY R.
Published: July 2007

Nurses work in a constantly challenging and changing environment. Within this context, there is a continuing need for support. Such support will help increase morale, decrease strain and burnout, and encourage self‐awareness and self‐expression. Clinical supervision address all these issues and enhances the quality of care for patients. While clinical supervision is a policy imperative in Northern Ireland, it was clear that there were problems in its implementation in mental health nursing. The aim of this project was to explore ways to make clinical supervision available to all mental health nurses and to improve and evaluate their contribution to patient care. The research team undertook a comprehensive literature review and a baseline survey of relevant stakeholders. Results represent the outcome of the group work. They will assist healthcare providers to develop local policies and procedures on clinical supervision for practising mental health nurses.