bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Calcination Temperature on Surface Oxygen Vacancies and Catalytic Performance Towards CO Oxidation of Co3O4 Nanoparticles Supported on SiO2
Authors: Li Jin-bing , Jiang Zhi-quan , Qian Kun , Huang Wei-xin
Published: March 2012

Co3O4/SiO2 catalysts for CO oxidation were prepared by conventional incipient wetness impregnation followed by calcination at various temperatures. Their structures were characterized with X-ray diffraction (XRD), laser Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), temperature-programmed reduction (TPR) and X-ray absorption fine structure (XAFS) spectroscopy. Both XRD and Raman spectroscopy only detect the existence of Co3O4 crystallites in all catalysts. However, XPS results indicate that excess Co2+ ions are present on the surface of Co3O4 in Co3O4(200)/SiO2 as compared with bulk Co3O4. Meanwhile, TPR results suggest the presence of surface oxygen vacancies on Co3O4 in Co3O4(200)/SiO2, and XAFS results demonstrate that Co3O4 in Co3O4(200)/SiO2 contains excess Co2+. Increasing calcination temperature results in oxidation of excess Co2+ and the decrease of the concentration of surface oxygen vacancies, consequently the formation of stoichiometric Co3O4 on supported catalysts. Among all Co3O4/SiO2 catalysts, Co3O4(200)/SiO2 exhibits the best catalytic performance towards CO oxidation, demonstrating that excess Co2+ and surface oxygen vacancies can enhance the catalytic activity of Co3O4 towards CO oxidation. These results nicely demonstrate the effect of calcination temperature on the structure and catalytic performance towards CO oxidation of silica-supported Co3O4 catalysts and highlight the important role of surface oxygen vacancies on Co3O4.
Diffusion Monte Carlo Study of Bond Dissociation Energies for BH2, B(OH)2, BCl2, and BCl
Authors: Li Hui-ran , Cheng Xin-lu , Zhang Hong
Published: March 2012

On basis of bond dissociation energies (BDEs) for BH2, B(OH)2, BCl2, and BCl, the diffusion Monte Carlo (DMC) method is applied to explore the BDEs of HB-H, HOB-OH, ClB-Cl, and B-Cl. The effect of the choice of orbitals, as well as the backflow transformation, is studied. The Slater-Jastrow DMC algorithm gives BDEs of 359.1±0.12 kJ/mol for HB-H, 410.5±0.50 kJ/mol for HOB-OH, 357.8±1.46 kJ/mol for ClB-Cl, and 504.5±0.96 kJ/mol for B-Cl using B3PW91 orbitals and similar BDEs when B3LYP orbitals are used. DMC with backflow corrections (BF-DMC) gives a HB-H BDE of 369.9±0.12 kJ/mol which is close to one of the available experimental value (375.8 kJ/mol). In the case of HOB-OH BDE, the BF-DMC calculation is 446.0±1.84 kJ/mol that is closer to the experimental BDE. The BF-DMC BDE for ClB-Cl is 343.2±2.34 kJ/mol and the BF-DMC B-Cl BDE is 523.3±0.33 kJ/mol, which are close to the experimental BDEs, 341.9 and 530.0 kJ/mol, respectively.
Array-enhanced Logical Stochastic Resonance in Coupled Bistable Systems
Authors: Wu Hao , Jiang Hui-jun , Hou Zhong-huai
Published: March 2012

We investigate the impact of coupling on the reliability of the logic system as well as the logical stochastic resonance (LSR) phenomenon in the coupled logic gates system. It is found that compared with single logic gate, the coupled system could yield reliable logic outputs in a much wider noise region, which means coupling can obviously improve the reliability of the logic system and thus enhance the LSR effect. Moreover, we find that the enhancement is larger for larger system size, whereas for large enough size the enhancement seems to be saturated. Finally, we also examine the effect of coupling strength, it can be observed that the noise region where reliable logic outputs can be obtained evolves non-monotonically as the coupling strength increases, displaying a resonance-like effect.
Hydrogenation and Ammoniation of SrTiO3 for an Enhanced Visible-light Photocatalysis
Authors: Sun Tao , Zhao You-yuan , Lu Ming
Published: March 2012

Hydrogenation and ammoniation of SrTiO3 (STO), a normal ultraviolet photocatalyst, were performed by annealing STO〈100〉 in H2:N2=5%:95% and NH3, respectively, at various temperatures T. It was found that hydrogenation at T≥900 °C remarkably enhanced the UV photocatalytic ability of STO, but the visible-light photocatalysis was still unavailable, while ammoniation at T≥800 °C introduced the N doping, resulting in visible-light photocatalytic activity. Furthermore, when a hydrogenated STO was subjected to ammoniation, the visible-light photocatalytic ability was nearly the same as that of the ammoniated one; but the hydrogenation of an ammoniated one significantly enhanced visible-light photocatalysis, indicating a synergetic effect of hydrogenation and ammoniation. Discussions and identifications have been made to analyze these results.
Formation Mechanistism Study of TiO2 Film Comprising Nanotubes and Nanoparticles
Authors: Yang Di , Wang Yi-quan , Ren Guo-bin , Feng Shuai , Chen Yuan-yuan , Wang Wen-zhong
Published: March 2012

A novel titanium dioxide (TiO2) film comprising both nanotubes and nanopaticles was fabricated by an anodization process of the modified titanium. The local electric field at the anodized surface was simulated and its influence on the morphology of the TiO2 film was discussed. The results show that the electric field strength is enhanced by the covering. The growth rate of TiO2 increases with the assist of the local electric field. However, TiO2 dissolution is hindered since the local electric field prevents [TiF6]6− from diffusing. It means that the balance condition for the formation of nanotubes is broken, and TiO2 nanoparticles are formed. Moreover, the crystal structure of the TiO2 film was confirmed using X-ray diffraction and Raman analysis. The anatase is a main phase for the proposed film.
Why Do People Let Their Long‐term Care Insurance Lapse? Evidence from the Health and Retirement Study
Authors: Li Yong , Jensen Gail A.
Published: March 2012

This paper empirically analyzes how often and why individuals drop their long‐term care insurance (LTCI) coverage, using data from the 2002‐2008 Health and Retirement Study. It finds that over a two‐year period 13% of LTCI policies lapse. It also finds that the probability of an LTCI lapse increases with a lack of consumer knowledge about their policy's benefit provisions, with prior encounters with the long‐term care system, with less expensive policies, and with less generous policies. These findings raise the possibility that some policyholders may not understand their coverage limitations, and learn about them only after actually using long‐term care services. Greater consumer awareness of LTCI policy features and limitations may help reduce lapse rates and increase the stability of the LTCI market.
First Report of Rust Caused by Pucciniastrum circaeae on Fuchsia × hybrida in Italy
Authors: Garibaldi A. , Gilardi G. , Ortu G. , Gullino M. L.
Published: March 2012

Fuchsia is a genus of flowering plants that is native to South America and New Zealand and belongs to the family Onagraceae. In September 2011, 2-year-old potted plants of Fuchsia × hybrida, cv. Citation, in a garden located near Biella (northern Italy) showed signs and symptoms of a previously unknown disease. Typically, infected plants showed leaf chlorosis followed by the appearance of necrosis on the adaxial leaf surfaces, while the abaxial surfaces showed orange uredinia irregularly distributed. As the disease progressed, infected leaves turned yellow and wilted. Affected plants showed a progressive phylloptosis and also flowering was negatively affected. Urediniospores were globose, yellow to orange, and measured 14.6 to 25.9 (average 19.6) μm. Teliospores were not observed. Morphological characteristics of the fungus corresponded to those of the genus Pucciniastrum. DNA extraction and PCR amplification were carried out with Terra PCR Direct Polymerase Mix (Clontech, Saint Germain-en-Laye, France) and primers ITS1/ITS4 (4). A 700-bp PCR product was sequenced and a BLASTn search (1) confirmed that the sequence corresponded with a 96% identity to Pucciniastrum circaeae. The nucleotide sequence has been assigned the GenBank Accession No. JQ029688. Pathogenicity tests were performed by spraying leaves of healthy 1-year-old potted Fuchsia × hybrida plants with an aqueous suspension of 1 × 103 urediniospores ml–1. The inoculum was obtained from infected leaves. Plants sprayed only with water served as controls. Three plants were used for each treatment. Plants were covered with plastic bags for 4 days after inoculation and maintained outdoors at temperatures ranging between 18 and 25°C. Lesions developed on leaves 20 days after inoculation with the urediniospore suspension, showing the same symptoms as the original plants, whereas control plants remained healthy. The organism that was recovered from the lesions after inoculation was the same as the one obtained from the diseased plants. The pathogenicity test was carried out twice with similar results. The presence of P. fuchsiae, later identified as P. epilobii, was repeatedly reported in the United States (3). P. epilobii and P. circaeae have closely related hosts and morphologically similar urediniospores. These species were reported to form a single group in molecular phylogenetic trees (2). This is, to our knowledge, the first report of P. circaeae on Fuchsia × hybrida in Italy.

References: (1) S. F. Altschul et al. Nucleic Acids Res. 25:3389, 1997 (2) Y. M. Liang et al. Mycoscience 47:137, 2006. (3) L. B. Loring and L. F. Roth. Plant Dis. Rep. 48:99, 1964. (4) T. J. White et al. PCR Protocols: A Guide to Methods and Applications. M. A. Innis et al., eds. Academic Press, San Diego, 1990.
Acute Kidney Injury and Extrarenal Organ Dysfunction
Authors: Yap Steven C. , Lee H. Thomas , Warner David S.
Published: March 2012

Acute kidney injury (AKI) is a frequent complication in the intensive care unit with limited therapeutic modalities. Although survival from isolated AKI has improved with recent advancements in renal replacement therapy, mortality from AKI complicated by multiorgan dysfunction has remained unchanged and is estimated to be approximately 50%. Hence, defining and better understanding the pathophysiology of distant organ dysfunction associated with AKI is clinically important because it may lead to new treatment strategies. In animal models, it has become increasingly clear that AKI is not an isolated event but results in remote organ dysfunction involving the heart, lungs, liver, intestines, and brain through an inflammatory mechanism that involves neutrophil migration, cytokine expression, and increased oxidative stress. The purpose of this brief review is to summarize the human and basic science evidence for AKI and its detrimental effects on distant organs.
Two newXP(O)[NHC(CH3)3]2phosphoramidates, withX= (CH3)2N and [(CH3)3CNH]2P(O)(O)
Authors: Pourayoubi Mehrdad , Tarahhomi Atekeh , Karimi Ahmadabad Fatemeh , Fejfarová Karla , Lee Arie van der , Dušek Michal
Published: March 2012

InN,N′-di-tert-butyl-N′′,N′′-dimethylphosphoric triamide, C10H26N3OP, (I), andN,N′,N′′,N′′′-tetra-tert-butoxybis(phosphonic diamide), C16H40N4O3P2, (II), the extended structures are mediated by P(O)...(H—N)2interactions. The asymmetric unit of (I) consists of six independent molecules which aggregate through P(O)...(H—N)2hydrogen bonds, givingR21(6) loops and forming two independent chains parallel to theaaxis. Of the 12 independenttert-butyl groups, five are disordered over two different positions with occupancies ranging from 1 \over 6 to 5 \over 6. In the structure of (II), the asymmetric unit contains one molecule. P(O)...(H—N)2hydrogen bonds giveS(6) andR22(8) rings, and the molecules form extended chains parallel to thecaxis. The structures of (I) and (II), along with similar structures having (N)P(O)(NH)2and (NH)2P(O)(O)P(O)(NH)2skeletons extracted from the Cambridge Structural Database, are used to compare hydrogen-bond patterns in these families of phosphoramidates. The strengths of P(O)[...H—N]x(x= 1, 2 or 3) hydrogen bonds are also analysed, using these compounds and previously reported structures with (N)2P(O)(NH) and P(O)(NH)3fragments.
Absolute configuration of strictosidinic acid
Authors: Castro Rosane de P. , Matos Carolina da S. , Nascimento Cláudia A. do , Oliveira Cecília M. A. , Kato Lucília , Lião Luciano M. , Sabino José R.
Published: March 2012

The absolute configuration of strictosidinic acid, (2S,3R,4S)-3-ethenyl-2-(β-D-glucopyranosyloxy)-4-{[(1S)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl]methyl}-3,4-dihydro-2H-pyran-5-carboxylate, was determined from its sodium chloride trihydrate, poly[[diaqua((2S,3R,4S)-3-ethenyl-2-(β-D-glucopyranosyloxy)-4-{[(1S)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-2-ium-1-yl]methyl}-3,4-dihydro-2H-pyran-5-carboxylate)sodium] chloride monohydrate], {[Na(C26H32N2O9)(H2O)2]Cl·H2O}n. The strictosidinic acid molecule participates in intermolecular hydrogen bonds of the O—H...O and O—H...Cl types. The solid-state conformation was observed as a zwitterion, based on a charged pyridine N atom and a carboxylate group, the latter mediating the packing through coordination with the sodium cation.
1-(4-tert-Butylbenzyl)pyrimidine-2,4(1H,3H)-dione
Authors: Wang Hong-Sheng , Li Gong-Chun
Published: March 2012

The asymmetric unit of the title compound, C15H18N2O2, contains two independent molecules with essentially identical geometries and conformations. The dihedral angles between the benzene and pyrimidine rings in the two molecules are 89.96 (11) and 73.91 (11)°. The six methyl groups are disordered over two sets of sites, with site occupancies of 0.545 (4):0.455 (4) and 0.542 (7):0.458 (7) in the two molecules. The crystal structure is stabilized by N—H...O hydrogen bonds.
(R)-Doxylaminium (R,R)-tartrate
Authors: Dayananda A.S. , Dutkiewicz Grzegorz , Yathirajan H. S. , Kubicki Maciej
Published: March 2012

In the title compound (systematic name: (R)-dimethyl{2-[1-phenyl-1-(pyridin-2-yl)ethoxy]ethyl}azanium (R,R)-3-carboxy-2,3-dihydroxypropanoate), C17H23N2O+·C4H5O6−, the doxylaminium cation is protonated at the N atom. The tartrate monoanions are linked by short, almost linear O—H...O hydrogen bonds into chains extended along [100]. These chains are interlinked by anion–pyridine O—H...N hydrogen bonds into a two-dimensional grid structure. WeakC—H...O interactions also play a role in the crystal packing. An intramolecular hydroxy–carboxylate O—H...O hydrogen bond influences the conformation of the anion: the hydrogen-bonded fragment is almost planar, the maximum deviation from the mean plane being 0.059 (14) Å. In the cation, the aromatic rings are almost perpendicular [dihedral angle = 84.94 (8)°] and the conformation of the O—C—C—N chain isgauche(−), the dihedral angle is −76.6 (2)°. The absolute configuration was assigned on the basis of known chirality of the parent compound.
2-Methylpyridinium 5-(2,4-dinitrophenyl)-1,3-dimethylbarbiturate
Authors: Sridevi Gunaseelan , Kalaivani Doraisamyraja
Published: March 2012

In the title molecular salt [systematic name: 2-methylpyridinium 5-(2,4-dinitrophenyl)-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olate], C6H8N+·C12H9N4O7−, the cation and anion are linked a through strong N—H...O hydrogen bond. In the crystal, C—H...O interactions link the ions, generating a chain along [010].
1-(4-Chloro-2-fluorophenyl)-4-difluoromethyl-3-methyl-1H-1,2,4-triazol-5(4H)-one
Authors: Ren Dong-mei , Wang Yong-yi
Published: March 2012

In the crystal structure of the title compound, C10H7ClF3N3O, pairs of molecules are connected into dimersviapairs of C—H...O hydrogen bonds. The dihedral angle between the benzene ring and attached triazolone ring is 53.2 (1)°.
catena-Poly[[(dichloridozinc)-μ-4,4′-bis(1H-imidazol-1-yl)biphenyl-κ2N3:N3′] 0.25-hydrate]
Authors: Ning Yong-Xia , Fan Wen , Xie Gang
Published: March 2012

In the title one-dimensional coordination polymer, {[ZnCl2(C18H14N4)]·0.25H2O}n, the ZnIIatom is coordinated by two chloride ions and two 4,4′-bis(1H-imidazol-1-yl)biphenyl ligands, generating a distorted tetrahedral ZnCl2N2geometry. The dihedral angle between the benzene rings of the ligand is 51.0 (1)° and the dihedral angles between the benzene rings and their attached imidazole rings are 18.7 (2) and 45.9 (1)°. The bridging ligand leads to [10-1] polymeric chains in the crystal and the disordered water molecule (occupancy 0.25) forms O—H...Cl hydrogen bonds.
5-(4-Methylphenylsulfonyl)-1,3-dithiolo[4,5-c]pyrrole-2-thione
Authors: Zheng Ning-Juan , Yin Bing-Zhu
Published: March 2012

The asymmetric unit of the title compound, C12H9NO2S4, contains one half-molecule with the N, two S amd four C atoms lying on a mirror plane. The molecule exhibits a V-shaped conformation, with a dihedral angle of 87.00 (7)° between the benzene and dithiolopyrrole rings. The methyl group was treated as rotationally disordered between two orientations in a 1:1 ratio. In the crystal, weak C—H...O hydrogen bonds link the molecules into chains in [010].
3,3′-Dihydroxy-6,6′-bis(hydroxymethyl)-2,2′-(pentane-1,1-diyl)di-4H-pyran-4-one
Authors: Liu Mu-Song , Hu Pan-Pan , Zhou Tao
Published: March 2012

In the title molecule, C17H20O8, the two pyran rings form a dihedral angle of 61.2 (2)°. The two hydroxymethyl groups are each disordered over two sets of sites in a 0.764 (3):0.236 (3) ratio. In the crystal, O—H...O hydrogen bonds link the molecules into layers parallel to theacplane.
Poly[diaquadi-μ-hydroxido-κ4O:O-dinitrato-κ4O:O′-bis[3-(pyridin-4-yl-κN)-5-(pyridin-3-yl)-1,2,4-oxadiazole]dicopper(II)]
Authors: Wu Longfei , Huang Linxia , Shu Mouhai
Published: March 2012

The title compound, [Cu2(NO3)2(OH)2(C12H8N4O)2(H2O)2]n, consists of a neutral polymeric CuIIcomplex in which each CuIIatom has a distorted octahedral geometry defined by a pyridyl N atom from a 3-(pyridin-3-yl)-5-(pyridin-4-yl)-1,2,4-oxadiazole ligand and five O atoms from a water molecule, two nitrates and two hydroxides. Two CuIIions are bridged by two hydroxide anions resulting in a Cu2O2loop, located across an inversion center and connected by the nitrate anions into a broad two-dimensional polymeric structure parallel to (100). In the crystal, there are O—H...O hydrogen bonds between the coodinated water molecule and the nitrate and hydroxide, and between the hydroxide and the nitrate. Intermolecular π–π interactions are present between pyridine rings in adjacent two-dimensional structures, with a centroid–centroid distance of 3.582 (2) Å.
Tetrakis(μ-2-iodobenzoato-κ2O:O′)bis[aquacopper(II)]
Authors: Aydın Ömür , Çaylak Delibaş Nagihan , Necefoğlu Hacali , Hökelek Tuncer
Published: March 2012

In the centrosymmetric binuclear title complex, [Cu2(C7H4IO2)4(H2O)2], the two CuIIions [Cu...Cu = 2.6009 (5) Å] are bridged by four 2-iodobenzoate (IB) ligands. The four nearest O atoms around each CuIIion form a distorted square-planar arrangement, the distorted square-pyramidal coordination being completed by the O atom of the water molecule at a distance of 2.1525 (16) Å. The dihedral angle between the benzene ring and the carboxylate group is 25.67 (13)° in one of the independent IB ligands and 6.44 (11)° in the other. The benzene rings of the two independent IB ligands are oriented at a dihedral angle of 86.61 (7)°. In the crystal, O—H...O interactions link the molecules into a two-dimensional network. π–π contacts between the benzene rings [centroid–centroid distances = 3.810 (2) and 3.838 (2) Å] may further stabilize the structure.
5-Cyclohexyl-2-methyl-3-(4-methylphenylsulfonyl)-1-benzofuran
Authors: Choi Hong Dae , Seo Pil Ja , Lee Uk
Published: March 2012

In the title compound, C22H24O3S, the cyclohexyl ring adopts a chair conformation. The 4-methylphenyl ring makes a dihedral angle of 80.95 (4)° with the mean plane [mean deviation = 0.011 (1) Å] of the benzofuran fragment. In the crystal, molecules are linked by weak C—H...O and C—H...π interactions.
(E)-3-[(2-Hydroxy-3-methoxybenzylidene)amino]benzoic acid
Authors: Kargar Hadi , Sharafi Zahra , Kia Reza , Ghelenji Safoora , Tahir Muhammad Nawaz
Published: March 2012

In the title compound, C15H13NO4, the dihedral angle between the substituted benzene rings is 9.9 (8)°. Part of the molecule (the salicylaldimine segment) is disordered over two sets of sites, with a refined site-occupancy ratio of 0.550 (14):0.450 (14). Intramolecular O—H...N hydrogen bonds formS(6) ring motifs. In the crystal, pairs of O—H...O hydrogen bonds link molecules into centrosymmetric dimers withR22(8) ring motifs. The crystal packing also features C—H...π interactions.
On the relation between seismic interferometry and the simultaneous‐source method
Authors: Wapenaar Kees , van der Neut Joost , Thorbecke Jan
Published: March 2012

In seismic interferometry the response to a virtual source is created from responses to sequential transient or simultaneous noise sources. Most methods use crosscorrelation, but recently seismic interferometry by multidimensional deconvolution (MDD) has been proposed as well. In the simultaneous‐source method (also known as blended acquisition), overlapping responses to sources with small time delays are recorded. The crosstalk that occurs in imaging of simultaneous‐source data can be reduced by using phase‐encoded sources or simultaneous noise sources, by randomizing the time interval between the shots, or by inverting the blending operator. Seismic interferometry and the simultaneous‐source method are related. In this paper we make this relation explicit by deriving deblending as a form of seismic interferometry by MDD. Moreover, we discuss a deblending algorithm for blended data acquired at the surface.
Addition of time‐dependent covariates to a survival model significantly improved predictions for daily risk of hospital death
Authors: Wong Jenna , Taljaard Monica , Forster Alan J. , Escobar Gabriel J. , van Walraven Carl
Published: March 2012

Rational, aims and objectives  The study aims to determine the extent to which the addition of post‐admission information via time‐dependent covariates improved the ability of a survival model to predict the daily risk of hospital death.

Method  Using administrative and laboratory data from adult inpatient hospitalizations at our institution between 1 April 2004 and 31 March 2009, we fit both a time‐dependent and a time‐fixed Cox model for hospital mortality on a randomly chosen 66% of hospitalizations. We compared the predictive performance of these models on the remaining hospitalizations.

Results  All comparative measures clearly indicated that the addition of time‐dependent covariates improved model discrimination and prominently improved model calibration. The time‐dependent model had a significantly higher concordance probability (0.879 versus 0.811) and predicted significantly closer to the number of observed deaths within all risk deciles. Over the first 32 admission days, the integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were consistently above zero (average IDI of +0.0200 and average NRI of 62.7% over the first 32 days).

Conclusions  The addition of time‐dependent covariates significantly improved the ability of a survival model to predict a patient's daily risk of hospital death. Researchers should consider adding time‐dependent covariates when seeking to improve the performance of survival models.
Clinical risk management in hospitals: strategy, central coordination and dialogue as key enablers
Authors: Briner Matthias , Manser Tanja , Kessler Oliver
Published: March 2012

Objective  The study aims to identify key enablers fostering clinical risk management (CRM) in hospitals to guide health care in this vital area of patient safety.

Method  A cross‐sectional survey was conducted at the national level in 324 Swiss hospitals in 2007–2008 to assess the relationship between key elements and systematic CRM. Therefore, a comprehensive monitoring instrument for CRM was used for the first time. Organizational factors (e.g. strategy, coordination, resources) and structural conditions (e.g. hospital size) were tested as key elements. CRM was assessed by evaluating its maturity (i.e. the level of CRM development) by 12 theoretically derived indices joining together essential aspects of CRM at the hospital level and the service level. Chi‐square measures were used to analyse the relationships between organizational factors or structural conditions and maturity of CRM.

Results  Participation in this voluntary survey was good, with CRM experts of 138 out of 324 hospitals responding (response rate 43%). Three key enablers for CRM were identified: implementing a function for central CRM coordination, assuring dialogue with and between the different hospital services, and developing strategic CRM objectives.

Conclusions  This study offers, for the first time, an assessment of the maturity of hospitals' CRM and identifies key enablers related to CRM. This is a feasible first step in guiding hospitals to shape their CRM and presents a basis for future studies, for example, linking CRM to outcome data.
Considerations for extrapolating in vivo bioequivalence data across species and routes
Authors: MODRIC S. , BERMINGHAM E. , HEIT M. , LAINESSE C. , THOMPSON C.
Published: March 2012

Modric, S., Bermingham, E., Heit, M., Lainesse, C., Thompson, C. Considerations for extrapolating in vivo bioequivalence data across species and routes. J. vet. Pharmacol. Therap.35 (Suppl. 1), 45–52.

The purpose of this article is to discuss the numerous species‐specific and route‐specific factors that can influence the peak and extent of exposure of an active pharmaceutical ingredient as they relate to the demonstration of bioequivalence between veterinary drug products (test and reference formulations). Evaluation of potential circumstances when species‐to‐species or route‐to‐route extrapolations of bioequivalence data could be considered is provided, together with suggestions for alternative statistical analysis. It is concluded that further research is much needed in this area to establish an appropriate scientific basis for across‐species and across‐route comparisons.
Demonstrating bioequivalence using clinical endpoint studies
Authors: BERMINGHAM E. , Del CASTILLO J. R. E. , LAINESSE C. , PASLOSKE K. , RADECKI S.
Published: March 2012

Bermingham, E., del Castillo, J. R. E., Lainesse, C., Pasloske, K., Radecki, S. Demonstrating bioequivalence using clinical endpoint studies. J. vet. Pharmacol. Therap.35 (Suppl. 1), 31–37.

For drug products not amenable to blood level studies, clinical endpoint studies have been used as an indirect measure of formulation difference in bioavailability between test and reference products. However, clinical endpoint studies are not as sensitive in detecting formulation differences as blood level studies and offer numerous challenges to both regulatory authorities and sponsors. The objective of this article is not to suggest new regulatory policies, but to explore new methodologies and alternative solutions to clinical endpoint bioequivalence (BE) studies, which are used when a blood level study is not considered to be appropriate. To achieve this objective, this article identifies situations where a clinical endpoint study might be appropriate, lists the advantages and disadvantages of this type of study design, and discusses possible alternative solutions. It is concluded that future evidence‐based research is needed to explore new methodologies such as clinical trial simulations of various study designs, new statistical methods, and new in vitro methods to demonstrate BE.
Pharmacokinetics and pharmacodynamics of stereoisomeric drugs with particular reference to bioequivalence determination
Authors: LEES P. , HUNTER R. P. , REEVES P. T. , TOUTAIN P. L.
Published: March 2012

Lees, P., Hunter, R. P., Reeves, P. T., Toutain, P. L. Pharmacokinetics and pharmacodynamics of stereoisomeric drugs with particular reference to bioequivalence determination.J. vet. Pharmacol. Therap.35(Suppl. 1), 17–29.

Drugs containing one or more chiral centres exist in stereoisomeric molecular forms. Most commonly, drugs containing a single asymmetric carbon atom exist in two enantiomeric forms, designated as eutomer (the more potent) and distomer (the less potent). As well as differences in potency and other pharmacodynamic properties, most members of enantiomeric pairs commonly differ also in their pharmacokinetic profiles. This article reviews factors underlying differences in pharmacological properties of enantiomers. The relevance of such differences for studies designed to evaluate the bioequivalence of products containing chiral drugs is also reviewed.
Introduction to the bioequivalence theme issue
Authors: MARTINEZ M. N. , HUNTER R. P.
Published: March 2012

Martinez, M. N., Hunter, R. P. Introduction to the bioequivalence theme issue. J. vet. Pharmacol. Therap. 35 (Suppl. 1), 1–2.

This introduction provides an overview of the veterinary bioequivalence initiative and of the foundational goals and objectives of this theme issue.
Assessing product bioequivalence for extended‐release formulations and drugs with long half‐lives
Authors: GEHRING R. , MARTINEZ M.
Published: March 2012

Gehring, R., Martinez, M. Assessing product bioequivalence for extended‐release formulations and drugs with long half‐lives. J. vet. Pharmacol. Therap.35 (Suppl. 1), 3–9.

When a drug product remains in the body for a duration of hours or days, estimating the extent of drug exposure is relatively straightforward. For immediate release (IR) dosage forms, the peak drug concentration (Cmax) and time to peak concentrations (Tmax) are typically adequate for comparing product rates of drug absorption. However, unique complexities need to be addressed when a drug remains in the system for a duration of months or years. Specifically, if the long duration of exposure is attributable to formulation effects, Cmax and Tmax may not be adequate to compare the rate of drug absorption, especially when there are multiphasic absorption processes. In this case, it may be appropriate to use partial (segmented areas) for comparing product profiles. However, the decision of how the curves are segmented is not straightforward. Points to consider are discussed in this manuscript. Alternatively, if the long half‐life is due to the pharmacokinetics (PK) of the active pharmaceutical ingredient and not to formulation effects, Cmax and Tmax may be appropriate metrics for the rate of absorption but decisions regarding the duration of blood sampling needed to capture the AUC should be based upon an assessment of the inherent variability in drug absorption and elimination. Furthermore, it is important to be confident that the absorption phase is complete. In this manuscript, we explore some of the difficulties associated with determining optimal metrics for comparing the rate and extent of product release for long half life drugs when the long duration of exposure is attributable to either the inherent drug PK or to formulation effects.
Challenges associated with the demonstration of bioequivalence of intramammary products in ruminants
Authors: LAINESSE C. , GEHRING R. , PASLOSKE K. , SMITH G. , SOBACK S. , WAGNER S. , WHITTEM T.
Published: March 2012

Lainesse, C., Gehring, R., Pasloske, K., Smith, G., Soback, S., Wagner, S., Whittem, T. Challenges associated with the demonstration of bioequivalence of intramammary products in ruminants. J. vet. Pharmacol. Therap. 35 (Suppl. 1), 65–79.

This article explores the numerous challenges encountered when the goal is to demonstrate bioequivalence (BE) between test and reference intramammary (IMM) products in ruminants. Numerous pathophysiological factors of mastitis and physicochemical properties of IMM formulations are implicated in the difficulties in confirming BE for this dosage form. Advantages and disadvantages of current BE study designs are discussed, and alternative perspectives are outlined. Ongoing and future research increasing our knowledge of the pharmacokinetics and pharmacodynamics of antimicrobial drugs delivered through this route is crucial to better understanding the implications of clinically significant formulation differences in the demonstration of BE and may also help in developing more effective IMM formulations for ruminants.
Estimating product bioequivalence for highly variable veterinary drugs
Authors: CLAXTON R. , COOK J. , ENDRENYI L. , LUCAS A. , MARTINEZ M. N. , SUTTON S. C.
Published: March 2012

Claxton, R., Cook, J., Endrenyi, L., Lucas, A., Martinez, M. N., Sutton, S. C. Estimating product bioequivalence for highly variable veterinary drugs. J. vet. Pharmacol. Therap.35 (Suppl. 1), 11–16.

The occurrence of drugs and drug formulations associated with large intrasubject pharmacokinetic (PK) variability has been well described in humans and is likewise encountered in veterinary medicine. The scaled average bioequivalence (SABE) approach adopted by CDER of the FDA for the determination of bioequivalence (BE) of highly variable drugs (HVD) needs to be considered when applied to veterinary dosage forms. However, because of some of the unique challenges that are encountered within the framework of veterinary medicine, variations of CDER’s approach are presented. The present manuscript discusses HVD and highly variable veterinary drugs (HVVD) from the perspective of possible alternative approaches to support the assessment of product BE in veterinary medicine. Limitations in the use of 3‐ and 4‐way crossover study designs are enumerated. In addition to a need for a statistical analysis of HVVD when using a parallel study design, the use of the secondary criteria (test‐to‐reference ratio), definition of σ0, and average BE with expanding limits are raised. A number of the details need to be finalized, from the selection of a regulatory constant to the determination of ‘highly variable’ in a veterinary drug product. Academicians, industrial scientists, and regulators should continue this discussion and resolve these details.
Cardiolipin synthase is required for Streptomyces coelicolor morphogenesis
Authors: Jyothikumar Vinod , Klanbut Khanungkan , Tiong John , Roxburgh James S. , Hunter Iain S. , Smith Terry K. , Herron Paul R.
Published: March 2012

The fluid mosaic model has recently been amended to account for the existence of membrane domains enriched in certain phospholipids. In rod‐shaped bacteria, the anionic phospholipid cardiolipin is enriched at the cell poles but its role in the morphogenesis of the filamentous bacterium Streptomyces coelicolor is unknown. It was impossible to delete clsA (cardiolipin synthase; SCO1389) unless complemented by a second copy of clsA elsewhere in the chromosome. When placed under the control of an inducible promoter, clsA expression, phospholipid profile and morphogenesis became inducer dependent. TLC analysis of phospholipid showed altered profiles upon depletion of clsA expression. Analysis of cardiolipin by mass spectrometry showed two distinct cardiolipin envelopes that reflected differences in acyl chain length; the level of the larger cardiolipin envelope was reduced in concert with clsA expression. ClsA‐EGFP did not localize to specific locations, but cardiolipin itself showed enrichment at hyphal tips, branch points and anucleate regions. Quantitative analysis of hyphal dimensions showed that the mycelial architecture and the erection of aerial hyphae were affected by the expression of clsA. Overexpression of clsA resulted in weakened hyphal tips, misshaped aerial hyphae and anucleate spores and demonstrates that cardiolipin synthesis is a requirement for morphogenesis in Streptomyces.
Portal hypertension after combined liver and intestinal transplantation, a diagnostic and therapeutic challenge?
Authors: Monbaliu Diethard , Vandersmissen Jo , De Hertogh Gert , Van Assche Gert , Hoffman Ilse , Knops Noël , Debbaut Charlotte , Heye Sam , Pirenne Jacques , Maleux Geert
Published: March 2012

Monbaliu D, Vandersmissen J, De Hertogh G, Van Assche G, Hoffman I, Knops N, Debbaut C, Heye S, Pirenne J, Maleux G. Portal hypertension after combined liver and intestinal transplantation, a diagnostic and therapeutic challenge?  Pediatr Transplantation 2012: 00: 000–000. © 2012 John Wiley & Sons A/S.

Abstract:  A widely accepted technique to transplant the liver‐bowel bloc is first to perform a piggyback anastomosis of the donor suprahepatic vena cava to the recipient vena cava; second to restore the arterial blood supply through an aortic interposition graft; and third to ensure venous drainage of the native foregut. The venous drainage of the native foregut can be restored through an end‐to‐end portocaval anastomosis between the donor infrahepatic vena cava and the recipient portal vein. Stenosis of this anastomosis can lead to portal hypertension presenting with upper GI congestion, bleeding, and hypersplenism. We report the successful treatment of this complication using an e‐PTFE‐covered stent inserted following balloon angioplasty.
Effects of dietary supplementation of fermented garlic powder on growth performance, apparent total tract digestibility, blood characteristics and faecal microbial concentration in weanling pigs
Authors: Yan L. , Kim I. H.
Published: March 2012

A total of 144 weanling pigs (5.5 ± 0.42 kg) were used in a 5‐week trial to evaluate the effect of fermented garlic powder (FGP) supplementation in weaning pigs. Pigs were randomly allocated to the following four dietary treatments: (i) control (CON; basal diet), (ii) FGP0.5 (CON + 0.5 g/kg FGP), (iii) FGP1 (CON + 1 g/kg FGP), (iv) FGP2 (CON + 2 g/kg FGP). There were six replications with six pigs (three barrows and three gilts) per pen. Pigs fed FGP0.5 treatments increased (p < 0.05) average daily gain (ADG) and average daily feed intake (ADFI) during 3–5 and 0–5 week. No difference was observed on gain/ feed (G/F) ratio in this study. The inclusion of FGP1 and FGP2 treatments increased DM (p < 0.05) digestibility compared with the CON treatment throughout the experiment. The apparent total tract digestibility of N was (p < 0.05) increased by the dietary FGP throughout the experiment. Pigs fed FGP1 and FGP2 treatments increased the lymphocyte concentration (p < 0.05) and RBC concentration compared with the CON group. Dietary FGP decreased the blood total cholesterol (p < 0.05) in comparison with the CON group. The triglyceride (p < 0.05) concentration was decreased in FGP1 and FGP2 treatments compared with those in the CON treatment at the end of the experiment. Pigs fed FGP1 and FGP2 treatments had a lower number of Escherichia coli in faeces on 21 (p < 0.05) and 35 days (p = 0.05) than those in the CON treatment. In conclusion, dietary fermented garlic powder (0.5 g/kg) can improve ADG and ADFI in weanling pigs, but not at higher levels (1 and 2 g/kg). Dietary fermented garlic powder can also increase the nutrient digestibility, lymphocytes and RBC concentrations, but decrease the faecal E. coli concentration in weaning pigs.
KCNQ1 gene polymorphisms are associated with the therapeutic efficacy of repaglinide in Chinese Type 2 diabetic patients
Authors: Dai Xing‐Ping , Huang Qiong , Yin Ji‐Ye , Guo Yu , Gong Zhi‐Cheng , Lei Min‐Xiang , Jiang Tie‐Jian , Zhou Hong‐Hao , Liu Zhao‐Qian
Published: March 2012

The present study evaluated the effects of KCNQ1 rs2237892 and rs2237895 polymorphisms on repaglinide efficacy in Chinese patients with Type 2 diabetes mellitus (T2DM).

In all, 367 T2DM patients and 214 controls were genotyped. Forty of the T2DM patients were randomly selected to undergo 8 weeks repaglinide treatment.

The frequency of the rs2237892 allele was lower in the T2DM patients than in the control group (P < 0.05). The frequency of the rs2237895 C allele was higher in T2DM patients than in healthy control subjects (P < 0.05). Diabetic patients with the rs2237892 risk C allele had lower fasting insulin levels (P < 0.01) and homeostasis model assessment of insulin resistance (HOMA‐IR; P < 0.01) values than carriers of the T allele. Diabetic patients with the rs2237895 risk C allele had higher fasting plasma glucose (P < 0.01), postprandial plasma glucose (PPG) levels (P < 0.01) and HOMA‐IR values (P < 0.01) than those with the A allele.

Following repaglinide treatment, those T2DM patients with the rs2237892 T allele and rs2237895 C allele were more likely to have a positive response to repaglinide in terms of PPG levels (P < 0.05) than T2DM patients with the rs2237892 CC and rs2237895 AA genotypes.

In conclusion, KCNQ1 rs2237892 and rs2237895 polymorphisms were found to be associated with the therapeutic efficacy of repaglinide in Chinese T2DM patients.
Pathogenesis and management of pruritus in cholestatic liver disease
Authors: Imam Mohamad H , Gossard Andrea A , Sinakos Emmanouil , Lindor Keith D
Published: March 2012

Patients with cholestatic liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis and intrahepatic cholestasis of pregnancy commonly complain of pruritus. The underlying pathogenesis remains obscure with several mediators possibly playing an important role; these include lysophosphatidic acid, bile salts, opioids, histamine and progesterone metabolites. We describe in this review novel insights into the pathogenesis and management of pruritus in patients with cholestasis.
Prevalence and associated factors with esophageal varices in early primary biliary cirrhosis
Authors: Ikeda Fusao , Okamoto Ryoichi , Baba Nobuyuki , Fujioka Shin‐ichi , Shoji Bon , Yabushita Kazuhisa , Ando Masaharu , Matsumura Shuji , Kubota Junichi , Yasunaka Tetsuya , Miyake Yasuhiro , Iwasaki Yoshiaki , Kobashi Haruhiko , Okada Hiroyuki , Yamamoto Kazuhide
Published: March 2012

Background and Aims:  Recent routine testing for anti‐mitochondrial antibodies has increased the number of patients with early primary biliary cirrhosis (PBC). The prevalence and clinical significance of esophageal varices in those patients remains obscure.

Methods:  A systematic cohort analysis of 256 PBC patients was performed to clarify the prevalence, characteristics, and prognosis of the patients with early PBC and esophageal varices.

Results:  Twenty‐two patients had esophageal varices at the time of diagnosis: 5.5% (12/217) with early disease of histological stage 1 or 2, and 25.6% (10/39) with advanced disease of stage 3 or 4. Immediate treatments were required for two patients with early PBC: one for bleeding varices, and the other for large varices. The overall survival of the patients with early PBC and esophageal varices at diagnosis did not significantly differ from that of patients without esophageal varices (P = 0.66). High alkaline phosphatase (ALP) ratios (odds ratio = 2.3) and low platelet counts (odds ratio = 0.77) were significantly associated with the presence of esophageal varices in the patients with early PBC. Significant associations of these two factors with the development of esophageal varices during follow‐up were also revealed (odds ratio = 1.4 and 0.88, respectively). The patients with early PBC and high ALP ratios ≥ 1.9 had significantly high risks of developing esophageal varices during follow‐up (P = 0.022).

Conclusions:  High ALP ratios and low platelet counts at diagnosis and decreased platelet counts during follow‐up are useful predictors of esophageal varices in patients with early PBC.
Current status and future perspectives of leukocytapheresis for inflammatory bowel disease
Authors: Fukunaga Ken , Matsumoto Takayuki
Published: March 2012

Ulcerative colitis (UC) and Crohn's disease (CD) comprise the idiopathic inflammatory bowel diseases (IBD) of the gut. The etiology of IBD is poorly understood, but an autoimmune disturbance has been suggested to play an important role in this incurable disease. Extracorporeal leukocytapheresis (CAP) is an additional adjunct for IBD patients refractory to other conventional therapies, including steroids. The primary aim of CAP should be to suppress such unwanted immunological response by removing circulating inflammatory cells from the blood stream. The first decade has been passed since CAP was approved by Japanese social health insurance policy. It is therefore now an appropriate opportunity to upgrade and summarize our current understandings and/or future perspectives of this unique non‐pharmacological and non‐surgical strategy for IBD patients. According to several clinical and basic research reports, an early introduction of CAP should produce higher efficacy as compared with CAP applied sometime after a clinical relapse. Likewise, CAP therapy adjusted to patients' body‐weight as well as two treatment sessions per week (intensive regimen) should benefit the efficacy rate. The etiology of IBD is not fully elucidated yet. As a result, the major therapeutic strategies in the Western world have been immunosuppressive therapy, including biologics. CAP is an unusual treatment modality for IBD because it seems to have both effectiveness and safety, which should generally be balanced in this type of illness. We now have to develop future strategies with and without combining biologics to improve the quality of life of IBD patients.
Cholesteryl ester transfer protein gene polymorphisms increase the risk of fatty liver in females independent of adiposity
Authors: Adams Leon A , Marsh Julie A , Ayonrinde Oyekoya T , Olynyk John K , Ang Wei Q , Beilin Lawrence J , Mori Trevor , Palmer Lyle J , Oddy Wendy W , Lye Steven J , Pennell Craig E
Published: March 2012

Background and Aim:  Environmental factors including excessive caloric intake lead to disordered lipid metabolism and fatty liver disease (FLD). However, FLD demonstrates heritability suggesting genetic factors are also important. We aimed to use a candidate gene approach to examine the association between FLD and single nucleotide polymorphisms (SNPs) in lipid metabolism genes in the adolescent population‐based Western Australian Pregnancy (Raine) Cohort.

Methods:  A total 951 seventeen year‐olds underwent hepatic ultrasound, anthropometric and biochemical characterization, DNA extraction and genotyping for 57 SNPs in seven lipid metabolism genes (ApoB100, ATGL, ABHD5, MTTP, CETP, SREBP‐1c, PPARα). Associations were adjusted for metabolic factors and Bonferroni corrected.

Results:  The prevalence of FLD was 16.2% (11.4% male vs 21.2% female, P = 0.001). Multivariate analysis of metabolic factors found suprailiac skinfold thickness (SST) to be the major predictor of FLD in females and males (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.08‐1.15, P = 1.7 × 10−10 and OR 1.17, 95%CI 1.13–1.22, P = 2.4 × 10−11, respectively). In females, two SNPs in linkage disequilibrium from the CETP gene were associated with FLD: rs12447924 (OR 2.16, 95%CI 1.42–3.32, P = 0.0003) and rs12597002 (OR = 2.22, 95%CI 1.46–3.41 P = 0.0002). In lean homozygotes, the probability of FLD was over 30%, compared with 10–15% in lean heterozygotes and 3–5% in lean wild‐types. However, these associations were modified by SST, such that for obese individuals, the probability of FLD was over 30% in all genotype groups.

Conclusions:  Cholesteryl ester transfer protein gene polymorphisms are associated with an increased risk of FLD in adolescent females. The effect is independent of adiposity in homozygotes, thereby placing lean individuals at a significant risk of FLD.