bluuebunny/crossref_metadata_2025 huggingface dataset:
Animal model of methylphenidate's long-term memory-enhancing effects
Authors: Carmack Stephanie A. , Howell Kristin K. , Rasaei Kleou , Reas Emilie T. , Anagnostaras Stephan G.
Published: January 2014

Methylphenidate (MPH), introduced more than 60 years ago, accounts for two-thirds of current prescriptions for attention deficit hyperactivity disorder (ADHD). Although many studies have modeled MPH's effect on executive function, almost none have directly modeled its effect on long-term memory (LTM), even though improvement in LTM is a critical target of therapeutic intervention in ADHD. We examined the effects of a wide range of doses of MPH (0.01–10 mg/kg, i.p.) on Pavlovian fear learning, a leading model of memory. MPH's effects were then compared to those of atomoxetine (0.1–10 mg/kg, i.p.), bupropion (0.5–20 mg/kg, i.p.), and citalopram (0.01–10 mg/kg, i.p.). At low, clinically relevant doses, MPH enhanced fear memory; at high doses it impaired memory. MPH's memory-enhancing effects were not confounded by its effects on locomotion or anxiety. Further, MPH-induced memory enhancement seemed to require both dopamine and norepinephrine transporter inhibition. Finally, the addictive potential of MPH (1 mg/kg and 10 mg/kg) was compared to those of two other psychostimulants, amphetamine (0.005 mg/kg and 1.5 mg/kg) and cocaine (0.15 mg/kg and 15 mg/kg), using a conditioned place preference and behavioral sensitization paradigm. We found that memory-enhancing effects of psychostimulants observed at low doses are readily dissociable from their reinforcing and locomotor activating effects at high doses. Together, our data suggest that fear conditioning will be an especially fruitful platform for modeling the effects of psychostimulants on LTM in drug development.
Tetrakis(dipropylammonium) tetrakis(oxalato-κ2O1,O2)stannate(IV) monohydrate: a complex with an eight-coordinate SnIVatom
Authors: Gueye Ndongo , Diop Libasse , Stoeckli-Evans Helen
Published: January 2014

In the title salt, [(CH3CH2CH2)2NH2]4[Sn(C2O4)4]·H2O, the SnIVatom of the stannate anion is located on a special position with -42msymmetry. It is eight-coordinated by four chelating oxalate anions. The dipropylammonium cation possesses mirror symmetry while the lattice water molecule is disordered about a position with -42msymmetry and has an occupancy of 0.25. In the crystal, the anions and cations are linked by N—H...O hydrogen bonds, forming a three-dimensional network. This network is futher stabilized by weak O—H...O hydrogen bonds involving the water molecules and oxalate O atoms. The crystal studied was refined as an inversion twin.
Adenin-1-ium hydrogen isophthalate dimethylformamide monosolvate
Authors: Koteswara Rao Vandavasi , Siddiqui Tausif , Zeller Matthias , Lovelace-Cameron Sherri R.
Published: January 2014

In the title proton-transfer organic salt, C5H6.3N5+·C8H4.7O4−·C3H7NO, the adeninium moiety is protonated at the N atom in the 1-position of the 6-amino-7H-purin-1-ium (adeninium) cation. In the solid state, the second acidic proton of isophthalic acid is partially transferred to the imidazole N atom of the adeninium cation [refined O—HversusN—H ratio = 0.70 (11):0.30 (11)]. Through the partially transferred proton, the adeninium cation is strongly hydrogen bonded (N—H...O/O—H...N) to the isophthalate anion. This strong interaction is assisted by another N—H...O hydrogen bond originating from the adeninium NH2group towards the isophthalate keto O atom, with anR22(8) graph-set motif. This arrangement is linkedviaN—H...O hydrogen bonds to the O atoms of the carboxylate group of an isophthalate anion. Together, these hydrogen bonds lead to the formation criss-cross zigzag isophthalate...adeninium chains lying parallel to (501) and (50-1). The adeninium cations and the isophthalate anions are arranged in infinite π stacks that extend along thec-axis direction [interplanar distance = 3.305 (3) Å]. Molecules are inclined with respect to this direction and within the stacks they are offset by ca. half a molecule each. Combination of the N—H...O and O—H...N hydrogen bonds with the π–π interactions forms infinitely stacked isophthalate...adeninium chains, thus leading to a two-dimensional supramolecular structure with parallel interdigitating layers formed by theπstacked isophthalate...adeninium chains. The DMF molecules of crystallization are bonded to the adeninium cations through strong N—H...O hydrogen bonds and project into the lattice space in between the anions and cations. There are also C—H...O hydrogen bonds present which, combined with the other interactions, form a three-dimensional network. The crystal under investigation was found to be split and was handled as if non-merohedrally twinned.
(4S)-5′-Chloro-3,7,7-trimethyl-5,6,7,8-tetrahydro-4H-spiro[1,2-oxazolo[5,4-b]quinoline-4,3′-indole]-2′,5-dione
Authors: Govindan E. , Yuvaraj PanneerSelvam , Reddy Boreddy Siva Rami , Premalatha K. , SubbiahPandi A.
Published: January 2014

In the title compound, C20H18ClN3O3, the five- and six-membered heterocycles fused through a spiro C atom are inclined to each other at an angle of 87.4 (1)°. In the tricyclic ring system, the cyclohexene ring adopts an envelope conformation with the spiro atom as the flap. In the crystal, two sets of N—H...O hydrogen bonds link the molecules into columns containing centrosymmetricR22(7) ring motifs and propagating along theb-axis direction.
Bis(1,10-phenanthrolin-1-ium) tetrachloridozincate monohydrate
Authors: Govindan E. , Thirumurugan Subramani , Ganeshraja Ayyakannu Sundaram , Anbalagan Krishnamoorthy , SubbiahPandi A.
Published: January 2014

In the crystal structure of the title compound, (C12H9N2)2[ZnCl4]·H2O, the two independent 1,10-phenanthrolinium cations are bridged by the water molecule and the tetrahedral tetrachloridozincate anionviaN—H...O, O—H...Cl and N—H...Cl hydrogen bonds, forming chains along [100]. The chains are linkedviaC—H...Cl hydrogen bonds and a number of π–π interactions [centroid–centroid distances vary from 3.5594 (14) to 3.7057 (13) Å], forming a three-dimensional network. In each 1,10-phenanthrolinium cation, there is a short N—H...N interaction.
2-(2-Amino-4-nitrophenyl)-7-nitro-4H-3,1-benzoxazin-4-one
Authors: Tiekink Edward R. T. , Wardell James L.
Published: January 2014

In the title compound, C14H8N4O6, the benzoxazin-4-one fused-ring system (r.m.s. deviation = 0.018 Å) is coplanar with the attached benzene ring [dihedral angle = 0.81 (4)°], there being an intramolecular N—H...N hydrogen bond between them. Each nitro group is twisted out of the plane of the attached benzene ring [O—N—C—C torsion angles = 167.94 (11) and 170.38 (11)°]. In the crystal, amine–nitro N—H...O hydrogen bonds lead to centrosymmetric dimeric aggregates that are connected into a three-dimensional architecture by oxazinyl–nitro C—H...O and π–π interactions [inter-centroid distance between the oxazinyl and terminal benzene rings = 3.5069 (7) Å].
1-(6-Chloro-1-methyl-1H-imidazo[4,5-c]pyridin-4-yl)-3-(2-chlorophenyl)urea
Authors: Devaru Venkatesh B. , Vinduvahini M. , Madaiah M. , Revanasiddappa H. D. , Devarajegowda H. C.
Published: January 2014

In the title compound, C14H11Cl2N5O, the plane of the 1H-imidazo[4,5-c]pyridine ring system [r.m.s. deviation = 0.087 (19) Å] makes a dihedral angle of 4.87 (10)° with the terminal phenyl ring. An intramolecular N—H...N hydrogen bond stabilizes the molecular conformation. In the crystal, N—H...O hydrogen bonds link the molecules into inversion dimers. These dimers are connected by π–π interactions between imidazole rings [shortest centroid–centroid distance = 3.4443 (14) Å].
cis-Triaqua[1,1′-(propane-1,3-diyl)bis(pyridin-1-ium-4-carboxylato)-κO]bis(thiocyanato-κN)manganese(II) dihydrate
Authors: Tan Qing-Hua , Wang Yan-Qin
Published: January 2014

In the title compound, [Mn(NCS)2(C15H14N2O4)(H2O)3]·2H2O, the metal ion is octahedrally coordinated by three water molecules, one carboxylate O atom from a 1,1′-(propane-1,3-diyl)bis(pyridinium-4-carboxylate) ligand and two N atoms from two thiocyanate anions incispositions, forming a mononuclear complex molecule. In the crystal, molecules are connected into a three-dimensional architecture through O—H...O hydrogen bonds involving water molecules and carboxylate groups.
Tetrakis(μ3-2-{[1,1-bis(hydroxymethyl)-2-oxidoethyl]iminomethyl}-6-nitrophenolato)tetracopper(II)
Authors: Chygorin Eduard N. , Smal Yuri O. , Kokozay Vladimir N. , Omelchenko Irina V.
Published: January 2014

The title cluster, [Cu4(C11H12N2O6)4], was obtained from the Cu0–FeCl2·4H2O–H4L–Et3N–DMF reaction system (in air), where H4Lis 2-hydroxymethyl-2{[(2-hydroxy-3-nitrophenyl)methylidene]amino}propane-1,3-diol and DMF is dimethylformamide. The asymmetric unit consists of one Cu2+ion and one dianionic ligand; a -4 symmetry element generates the cluster, which contains a {Cu4O4} cubane-like core. The metal ion has an elongated square-based pyramidal CuNO4coordination geometry with the N atom in a basal site. An intramolecular O—H...O hydrogen bond is observed. The solvent molecules were found to be highly disordered and their contribution to the scattering was removed with the SQUEEZE procedure inPLATON[Spek (2009).Acta Cryst. D65, 148–155], which indicated a solvent cavity of volume 3131 Å3containing approximately 749 electrons. These solvent molecules are not considered in the given chemical formula.
Poly[μ5-{hydrogen bis[(E)-cinnamato]}-caesium]
Authors: Smith Graham
Published: January 2014

In the structure of the title polymeric complex, [Cs(C9H7O2)(C9H8O2)]n, a caesium salt oftrans-cinnamic acid, the Cs+ions of the two individual irregular CsO8coordination polyhedra lie on twofold rotation axes and are linked by four bridging carboxyl O-atom donors from two cinnamate ligand species. These two ligand components are interlinked through a delocalized H atom within a short O...H...O hydrogen bond. Structure extension gives a two-dimensional coordination polymer which lies parallel to (001). The structure was determined from a crystal twinned by non-merohedry, with a twin component ratio of approximately 1:1.
Butane-1,4-diammonium hexafluorosilicate
Authors: Ouasri Ali , Rhandour Ali , Saadi Mohamed , El Ammari Lahcen
Published: January 2014

The title compound, [NH3(CH2)4NH3]2+·SiF62−, is a hybrid built from an organic butane-1,4-diammonium dication linked to a hexafluorosilicate mineral anion. Both ions posses inversion symmetry. In the anion the Si atom is located on an inversion center, while in the cation the center of inversion is situated at the mid-point of the central —CH2—CH2— bond. The Si atom is surrounded by six F atoms, forming a slightly distorted SiF62−octahedron. These octahedra are linked to the organic cations through N—H...F hydrogen bonds, forming a three-dimensional network.
GrainSpotter: a fast and robust polycrystalline indexing algorithm
Authors: Schmidt Søren
Published: January 2014

A new approach for indexing multigrain diffraction data is presented. It is based on the use of a monochromatic beam simultaneously illuminating all grains. By operating in sub-volumes of Rodrigues space, a powerful vertex-finding algorithm can be applied, with a running time that is compatible with online analysis. The resulting program,GrainSpotter, is sufficiently fast to enable online analysis during synchrotron sessions. The program applies outlier rejection schemes, leading to more robust and accurate data. By simulations it is shown that several thousand grains can be retrieved. A new method to derive partial symmetries, called pseudo-twins, is introduced. Uniquely,GrainSpotterincludes an analysis of pseudo-twins, which is shown to be critical to avoid erroneous grains resulting from the indexing.
A high-pressure and high-temperature gas-loading system for the study of conventional to real industrial sized samples in catalysed gas/solid and liquid/solid reactions
Authors: Andrieux Jerome , Chabert Christophe , Mauro Anthony , Vitoux Hugo , Gorges Bernard , Buslaps Thomas , Honkimäki Veijo
Published: January 2014

A high-pressure–high-temperature gas-loading system (GLS) is described for combinedoperandoX-ray diffraction and mass spectrometry investigations during catalysed gas/solid or liquid/solid reactions. The pressure cell consists of a single-crystal sapphire tube which serves as both high-pressure container and reaction cell, with up to 6 mm inner diameter. The system can operate in two different configurations, under either static high pressure or dynamic pressurized flow. The transportable reaction cell can be filled under inert atmosphere inside a glove box, enabling studies with oxygen-sensitive compounds to be conducted. The five main benefits of this system can be summarized as follows: (i) the temperature, pressure and gas-flow ranges of 298–1273 K, 10−3 mbar–200 bar (0.1–2 × 107 Pa) and 0–1 l min−1, respectively, (ii) the combination of different gases, (iii) the flexibility of the cell design, (iv) the full rotation of the pressurized cell, and (v) the combination of X-ray diffraction and mass spectrometry as analytical tools. These key points open new possibilities for studying the evolution of catalysts or compounds from a fundamental point of view as well as for industrial applications, in both cases inoperandoconditions.
A new time-of-flight small-angle scattering instrument at the Helmholtz-Zentrum Berlin: V16/VSANS
Authors: Vogtt Karsten , Siebenbürger Miriam , Clemens Daniel , Rabe Christian , Lindner Peter , Russina Margarita , Fromme Michael , Mezei Ferenc , Ballauff Matthias
Published: January 2014

Small-angle scattering methods have become routine techniques for the structural characterization of macromolecules and macromolecular assemblies like polymers, (block) copolymers or micelles in the spatial range from a few to hundreds of nanometres. Neutrons are valuable scattering probes, because they offer freedom with respect to scattering length density contrast and isotopic labelling of samples. In order to gain maximum benefit from the allotted experiment time, the instrumental setup must be optimized in terms of statistics of scattered intensity, resolution and accessible range in momentum transferQ. The new small-angle neutron scattering instrument V16/VSANS at the Helmholtz-Zentrum in Berlin, Germany, augments neutron guide collimation and pinhole optics with time-of-flight data recording and flexible chopper configuration. Thus, the availableQrange and the respective instrumental resolution in the intermediate and high momentum transfer regions can be adjusted and balanced to the individual experimental requirements. This renders V16/VSANS a flexible and versatile instrument for soft-matter research.
Single-mode dynamic X-ray diffraction for Si and Si nanowires on Si
Authors: Chen Hsin-Yi , Chu Pei-Tzi , Chang Shih-Lin
Published: January 2014

A method is reported of realizing single-mode diffraction using singly polarized X-ray wide-angle incidence and grazing-emergence diffraction from a bare Si substrate and from Si nanowires on an Si substrate. For a bare Si substrate, the surface-diffracted and specularly reflected beams of single-mode excitation are separated owing to the extremely asymmetric diffraction at grazing emergence. For Si wires on Si, single-mode diffraction is achieved by tuning the X-ray energy or the azimuthal angle under the conditions of total reflection. This finding opens up new opportunities for using crystal diffraction, in addition to optical reflection or refraction, for the design of coherent X-ray optics.
Bench-top X-ray microtomography complemented with spatially localized X-ray scattering experiments
Authors: Suuronen Jussi-Petteri , Kallonen Aki , Hänninen Ville , Blomberg Merja , Hämäläinen Keijo , Serimaa Ritva
Published: January 2014

This article describes a novel experimental setup that combines X-ray microtomography (XMT) scans within situX-ray scattering experiments in a laboratory setting. Combining these two methods allows the characterization of both the micrometre-scale morphology and the crystallographic properties of the sample without removing it from the setup. Precise control of the position of the sample allows an accurate choice of the scattering beam path through the sample and facilitates the performance of X-ray scattering experiments on submillimetre-sized samples. With the present setup, a voxel size of less than 0.5 µm is achievable in the XMT images, and scattering experiments can be carried out with a beam size of approximately 200 × 200 µm. The potential of this setup is illustrated with the analysis of micrometeorite crystal structure and diffraction tomographic imaging of a silver behenate phantom as example applications.
Short communication radiation effects on MHD free convection flow of a
gas past a semi—infinite vertical plate
Authors: Takhar H.S. , Subba Reddy Gorla Rama , Soundalgekar V.M.
Published: January 2014

Free convection heat transfer due to the simultaneous action of
buoyancy, radiation and transverse magnetic field is investigated for a
semi‐infinite vertical plate. Solutions are derived by expanding the stream
function and the temperature into a series in terms of the parameter ζ =
x1/2 L–1/2, where L is the length of the plate. Velocity and
temperature functions are shown on graphs and the numerical values of
functions affecting the shear stress and the rate of heat transfer are
entered in a table. The effects of the magnetic field parameter λ and the
radiation parameter F on these functions are discussed.
Reading self‐help literature inRussia: governmentality, psychology and subjectivity
Authors: Salmenniemi Suvi , Vorona Mariya
Published: January 2014

Self‐help has become a booming business over the past decades and an increasingly visible part of popular media culture worldwide. The paper analyzes the arrival and effects of this cultural technology in post‐SovietRussia after more than seventy years of socialism. It examines how Russians are engaging with popular psychology self‐help as a technology of the self and how they are making it meaningful in their lives. Drawing on a set of one‐to‐one and focus group interviews conducted with self‐help readers, it examines how these individuals negotiate the new ethics and the normative models of personhood put forward by the self‐help genre. It argues that popular psychology has offered a new language for making sense of the self and the social world, and highlights how the readers critically engage with the normalizing power of popular psychology by drawing on a number of local historically sedimented discourses.
A comparative study of the prevalence of domestic violence in women requesting a termination of pregnancy and those attending the antenatal clinic
Authors: Wokoma TT , Jampala M , Bexhell H , Guthrie K , Lindow S
Published: January 2014

Objective

To compare the prevalence of domestic violence (DV) in women requesting antenatal care (ANC) and termination of pregnancy (TOP) in North East England.

Design

This was a cross‐sectional comparative prevalence study using self‐administered questionnaires, with women selected as opportunistic samples over a concurrent period.

Setting

The participants were screened anonymously and confidentially in the ANC and TOP clinics.

Sample

Pregnant women in the first trimester requesting a TOP or ANC.

Methods

The participants were screened for a history of DV using a modified version of the Abuse Assessment Screening tool.

Main outcome measures

Prevalence of DV between ANC and TOP populations, and any differences in the characteristics of the women, such as age, level of education, or marital status. We aimed to determine the reasons for requesting a TOP.

Results

There were 507 respondents, with 233 attending ANC and 274 requesting a TOP. Of the ANC population, 219 completed the questionnaire. In the TOP population, all the questionnaires were fully or partially completed. Women requesting a TOP were six times as likely to suffer physical abuse in the current relationship (5.8 versus 0.9%; χ2 = 10.2 (2); P < 0.05), and were five times as likely to suffer emotional abuse (9.9 versus 1.8%; χ2 = 13.6 (2); P < 0.0001), than those attending ANC. Of the 274 women requesting a TOP, only ten mentioned DV as a contributing factor.

Conclusions

There is a higher prevalence of DV in the TOP population than in the ANC population, but very few women stated that DV influenced their request for a TOP.
Who is responsible for selecting children's fast food meals, and what impact does this have on energy content of the selected meals?
Authors: Wellard Lyndal , Chapman Kathy , Wolfenden Luke , Dodds Pennie , Hughes Clare , Wiggers John
Published: January 2014

Aim

The present study aimed to: (i) document the role of parents in children's fast food meal selection; (ii) determine whether parental demographics, weight status or fast food consumption frequency were associated with who selects children's fast food meals; and (iii) determine whether the total energy content of children's meals selected from a hypothetical fast food menu was associated with selection responsibility.

Methods

A cross‐sectional survey of 477 parents of children aged 3–12 years in New South Wales, Australia, was conducted. Participants completed two computer‐assisted telephone interviews. The first collected demographic and anthropometric data including height and weight. Participants were subsequently mailed a hypothetical fast food menu. The second interview asked who was responsible for selecting their children's fast food meals, and what items would be chosen. Energy content of the selections was examined.

Results

Most parents (60%) stated that they shared meal selection responsibility with their children. Parents with higher education levels (P < 0.01) or younger children (P < 0.01) were more likely to take responsibility for meal selection. When parents stated that children were responsible, they chose fast food meals with significantly higher energy content than when responsibility was shared (P < 0.01).

Conclusions

The present study shows that parents are influential in children's fast food intake. Parents should be encouraged to play an active role in assisting children to make healthier fast food choices, to reduce the impact of high‐energy meals on their overall diets.
A New Type of Dual Atrioventricular Nodal Nonreentrant Tachycardia
Authors: Kaczmarek Krzysztof , Ruta Jan , Wranicz Jerzy , Ptaszynski Pawel
Published: January 2014

Dual atrioventricular nodal nonreentrant tachycardia (DAVNNT) is very rarely observed clinically. The first review of this arrhythmia was published in 2011 by Wang, where four types of DAVNNT were described. Our case report presents a phenomenon that has never been published before. We revealed a very specific sequence of double fire phenomenon, 1:1 atrioventricular (AV) conduction and AV block.
Urban Community Gardens as Spaces of Citizenship
Authors: Ghose Rina , Pettygrove Margaret
Published: January 2014

A growing body of literature conceptualizes urban agriculture and community gardens as spaces of democratic citizenship and radical political practice. Urban community gardens are lauded as spaces through which residents can alleviate food insecurity and claim rights to the city. However, discussions of citizenship practice more broadly challenge the notion that citizen participation is inherently transformative or empowering, particularly in the context of neoliberal economic restructuring. This paper investigates urban community gardens as spaces of citizenship through a case study of Milwaukee, Wisconsin. It examines the impacts of community gardens on citizenship practice and the effects of volunteerism on the development of community gardens. It explores how grassroots community gardens simultaneously contest and reinforce local neoliberal policies. This research contributes empirically and theoretically to scholarship on urban food movements, neoliberal urbanization, collaborative governance, and citizenship practice.
Renal denervation restores the baroreflex control of renal sympathetic nerve activity and heart rate in Wistar‐Kyoto rats with cisplatin‐induced renal failure
Authors: Khan S. A. , Sattar M. A. , Rathore H. A. , Abdulla M. H. , ud din Ahmad F. , Ahmad A. , Afzal S. , Abdullah N. A. , Johns E. J.
Published: January 2014

Aim

There is evidence that in chronic renal failure, the sympathetic nervous system is activated. This study investigated the role of the renal innervation in suppressing high‐ and low‐pressure baroreflex control of renal sympathetic nerve activity and heart rate in cisplatin‐induced renal failure.

Methods

Renal failure was induced using cisplatin (5 mg kg−1, i.p.) and the rats used 7 days later. Groups of rats were anaesthetized and prepared for measurement of renal sympathetic nerve activity and heart rate. Acute unilateral or bilateral renal denervation was performed, and renal sympathetic nerve activity and heart rate baroreflex gain curves were generated while the cardiopulmonary receptors were stimulated using an acute saline volume load.

Results

Cisplatin administration reduced (P < 0.05) glomerular filtration rate by 27%, increased sodium fractional excretions fourfold, plasma creatinine and kidney index by 39 and 30% respectively, (all P < 0.05) compared with control rats. In the renal failure rats, baroreflex sensitivity for renal sympathetic nerve activity and heart rate was reduced (P < 0.05) by 29% and 27% (both P < 0.05) compared with control animals. Bilateral, but not unilateral, renal denervation restored baroreflex sensitivity to normal values. Volume expansion reduced (P < 0.05) renal sympathetic nerve activity by 34% in control rats, but remained unchanged in the renal failure rats. Unilateral and bilateral renal denervation progressively restored the volume expansion induced renal sympathoinhibition to control values.

Conclusion

These findings reveal a significant role of the renal sensory innervation in cisplatin‐damaged kidneys which blunt the normal baroreflex control of renal sympathetic nerve activity.
Improving antibiotic prescribing for children in the resource‐poor setting
Authors: Le Doare Kirsty , Barker Charlotte I. S. , Irwin Adam , Sharland Mike
Published: January 2014

Antibiotics are a critically important part of paediatric medical care in low‐ and middle‐income countries (LMICs), where infectious diseases are the leading cause of child mortality. The World Health Organization estimates that >50% of all medicines are prescribed, dispensed or sold inappropriately and that half of all patients do not take their medicines correctly. Given the rising prevalence of antimicrobial resistance globally, inappropriate antibiotic use is of international concern, and countries struggle to implement basic policies promoting rational antibiotic use. Many barriers to rational paediatric prescribing in LMICs persist. The World Health Organization initiatives, such as ‘Make medicines child size’, the Model List of Essential Medicines for Children and the Model Formulary for Children, have been significant steps forward. Continued strategies to improve access to appropriate drugs and formulations, in conjunction with improved evidence‐based clinical guidelines and dosing recommendations, are essential to the success of such initiatives on both a national and an international level. This paper provides an overview of these issues and considers future developments that may improve LMIC antibiotic prescribing.
Population pharmacokinetic approach to evaluate the effect of CYP2D6, CYP3A, ABCB1, POR and NR1I2 genotypes on donepezil clearance
Authors: Noetzli Muriel , Guidi Monia , Ebbing Karsten , Eyer Stephan , Wilhelm Laurence , Michon Agnès , Thomazic Valérie , Stancu Ioana , Alnawaqil Abdel‐Messieh , Bula Christophe , Zumbach Serge , Gaillard Michel , Giannakopoulos Panteleimon , von Gunten Armin , Csajka Chantal , Eap Chin B.
Published: January 2014

Aims

A large interindividual variability in plasma concentrations has been reported in patients treated with donepezil, the most frequently prescribed antidementia drug. We aimed to evaluate clinical and genetic factors influencing donepezil disposition in a patient population recruited from a naturalistic setting.

Methods

A population pharmacokinetic study was performed including data from 129 older patients treated with donepezil. The patients were genotyped for common polymorphisms in the metabolic enzymes CYP2D6 and CYP3A, in the electron transferring protein POR and the nuclear factor NR1I2 involved in CYP activity and expression, and in the drug transporter ABCB1.

Results

The average donepezil clearance was 7.3 l h−1 with a 30% interindividual variability. Gender markedly influenced donepezil clearance (P < 0.01). Functional alleles of CYP2D6 were identified as unique significant genetic covariate for donepezil clearance (P < 0.01), with poor metabolizers and ultrarapid metabolizers demonstrating, respectively, a 32% slower and a 67% faster donepezil elimination compared with extensive metabolizers.

Conclusion

The pharmacokinetic parameters of donepezil were well described by the developed population model. Functional alleles of CYP2D6 significantly contributed to the variability in donepezil disposition in the patient population and should be further investigated in the context of individual dose optimization to improve clinical outcome and tolerability of the treatment.
Is intermittent androgen‐deprivation therapy beneficial for patients with advanced prostate cancer?
Authors: Wolff Johannes M. , Abrahamsson Per‐Anders , Irani Jacques , Calais da Silva Fernando
Published: January 2014

Use of intermittent androgen‐deprivation therapy (IADT) in patients with prostate cancer has been evaluated in several studies, in an attempt to delay the development of castration resistance and reduce side‐effects associated with ADT. However it is still not clear whether survival is adversely affected in patients treated with IADT. In this review, we explore the available data in an attempt to identify the most suitable candidate patients for IADT, and discuss factors that may inform appropriate patient stratification. ADT is first‐line treatment for advanced/metastatic prostate cancer and is also recommended for use with definitive radiotherapy for high‐risk localised prostate cancer. The changes in hormone levels induced by ADT can lead to short‐ and long‐term side‐effects which, although treatable in most cases, can significantly reduce the tolerability of ADT treatment. IADT has been investigated in several phase II and phase III studies in patients with locally advanced or metastatic prostate cancer, in an attempt to delay time to tumour progression and reduce the side‐effect burden of ADT. In selected patient groups IADT is no less effective than continuous ADT, ameliorating the impact of ADT‐related side‐effects, and, to a degree, their impact on patient health‐related quality of life (HRQL). Further comparative study is required, particularly in relation to HRQL and long‐term complications associated with ADT.
Greater India's northern margin prior to its collision with Asia
Authors: Ali J. R. , Aitchison J. C.
Published: January 2014

Greater India's northern edge prior to collision with Asia is typically modelled as a rifted passive margin. We argue for a quite different geometry as a consequence of two tectonic episodes that happened sometime before the main impact. Whilst the western segment of India's northern boundary had formed in the Late Triassic as a rifted margin, the central and eastern portions developed between 132 and 110 Ma when the sub‐continent separated from Australia–Antarctica as the inner wall of a dextral ‘scything’ transform fault along the Wallaby–Zenith Fracture Zone off western Australia. Key features would have been (i) the very narrow (20–30 km wide) ocean–continent transition zone marking the sub‐continent's eastern northern boundary, and (ii) similar to the region offshore South Africa's Garden Route coast, Greater India's NE corner may have developed a series of ‘perched’ half grabens due to shearing related to its motion along the Wallaby–Zenith Fracture Zone, from initial break‐up until it passed the Zenith Plateau (ca. 110 Ma). Differences in the development of NW Greater India may be reflected in restriction of ultra‐high pressure metamorphic rocks to the western Himalaya where late Paleocene subduction of the rifted passive margin occurred at sub‐equatorial latitudes beneath the intra‐Tethyan arc. Further east, where the margin developed along the scything transform, the continent–ocean boundary would have been more abrupt and probably less strongly welded. Ophiolite emplacement appears to have been penecontemporaneous along the margin. A subsequent slab break‐off episode then eliminated the original plate boundary. Thereafter, remaining oceanic lithosphere north of the arc sutured to the sub‐continent, albeit rather weakly, was consumed beneath Eurasia, culminating in India–Asia collision.
Sediment storage and reworking on the shelf and in the Canyon of the Indus River‐Fan System since the last glacial maximum
Authors: Clift Peter D. , Giosan Liviu , Henstock Timothy J. , Tabrez Ali R.
Published: January 2014

The transport of sediment from the mouth of the Indus River on to the deep‐water submarine fan is complicated by temporary storage within large clinoforms on the shelf on either side of the submarine canyon, where most of the sedimentation since the start of the Holocene has occurred. In contrast, shelf edge clinoform deltas represent the products of forced regression and not the progradation of highstand clinoforms as far as the shelf edge. Clinoform sediments have a mixed provenance that involves significant reworking of older sediment deposited during or before the last glacial maximum. Recent sedimentation in the canyon head has been very rapid in the last few centuries (ca. 10 cm year−1), but has been starved of sand probably because of 20th century damming. Sandy layers appear to represent annual monsoonal floods with a particularly large flood every 50–70 years. This canyon head sediment is also reworked by currents flowing along the canyon axis before being deposited deeper into the canyon. The last sandy sediment to reach the mid‐canyon (ca. 1300 m depth) was transported around 7000 year BP at a time of rising sea‐levels, and might reflect reworking by the transgression, or local slumping from the walls of the canyon. Dating of the uppermost in a series of terraces in the mid‐canyon area suggests that the canyon may have been partly filled and emptied of sediment at least three times since ca. 50 ka. We conclude from the Holocene record that sediment flux to the deep‐water fan experiences major buffering, reworking and recycling both on the shelf and within the submarine canyon prior to its deposition, so that turbidite sands in the deep Arabian Sea cannot be used to correlate with climatic or tectonic events onshore over timescales of 103–105 years.
Hedgehog signaling pathway is a potential therapeutic target for gallbladder cancer
Authors: Matsushita Shojiro , Onishi Hideya , Nakano Kenji , Nagamatsu Iori , Imaizumi Akira , Hattori Masami , Oda Yoshinao , Tanaka Masao , Katano Mitsuo
Published: January 2014

Gallbladder cancer (GBC) is a particularly deadly type of cancer with a 5‐year survival rate of only 10%. New effective therapeutic strategies are greatly needed. Recently, we have shown that Hedgehog (Hh) signaling is reactivated in various types of cancer and is a potential therapeutic target. However, little is known about the biological significance of Hh signaling in human GBC. In this study, we determined whether Hh signaling could be a therapeutic target in GBC. The Hh transcription factor Gli1 was detected in the nucleus of GBC cells but not in the nucleus of normal gallbladder cells. The expression levels of Sonic Hh (Shh) and Smoothened (Smo) in human GBC specimens (n = 37) were higher than those in normal gallbladder tissue. The addition of exogenous Shh ligand augmented the anchor‐dependent and anchor‐independent proliferation and invasiveness of GBC cells in vitro. In contrast, inhibiting the effector Smo decreased the anchor‐dependent and anchor‐independent proliferation. Furthermore, the suppression of Smo decreased GBC cell invasiveness through the inhibition of MMP‐2 and MMP‐9 expression and inhibited the epithelial–mesenchymal transition. In a xenograft model, tumor volume in Smo siRNA‐transfected GBC cells was significantly lower than in control tumors. These results suggest that Hh signaling is elevated in GBC and may be involved in the acquisition of malignant phenotypes, and that Hh signaling may be a potential therapeutic target for GBC.
Acid‐sensing Ion Channels Activation and Hypoxia Upregulate Homer1a Expression
Authors: Su Jing‐Jing , Pan Hui , Zhou Hou‐Guang , Tang Yu‐Ping , Dong Qiang , Liu Jian‐Ren
Published: January 2014

Background

Recent studies have indicated that dynamic alterations in the structure of postsynaptic density (PSD) are involved in the pathogenesis of many central nervous system disorders, including ischemic stroke. Homer is the newly identified scaffolding protein located at PSD and regulates synaptic function. Homer1a, an immediate early gene, has been shown to be induced by several stimulations, such as glutamate, brain‐derived neurotrophic factor, and trauma. However, whether acidosis mediated by acid‐sensing ion channels (ASICs) and hypoxia during cerebral ischemia can change Homer1a expression remains to be determined.

Results

We investigated that acidosis and hypoxia selectively and rapidly upregulated Homer1a expression, but not Homer1b/c in cultured cortical neurons. We also found that Homer1a exhibited induction expression in brain cortex of the middle cerebral artery occlusion (MCAO) rats. Additionally, acid‐evoked Homer1a mRNA induction depended on extracellular signal‐regulated kinase1/2 (ERK1/2) and Akt activity, and ASIC1a‐mediated calcium influx whereas hypoxia depended only on ERK1/2 activity. Also, we demonstrated that continuous acidosis and hypoxia resulted in pronounced cell injury and Homer1a knockdown with small interfering RNA aggravated this damage induced by 3 h acid and hypoxia incubation in neuro‐2a cells.

Conclusion

Homer1a might act as an activity‐dependent regulator responding to extracellular stimuli during cerebral ischemia.
Oculomotor assessment and cognitive functions in children after traumatic brain injury
Authors: Castelli Enrico
Published: January 2014

This paper is on the article by Phillipou et al. on pages 337–345 of this issue.
Short‐term Type‐1 diabetes differentially modulates 14‐3‐3 proteins in rat brain and liver
Authors: Taurino Federica , Stanca Eleonora , Vonghia Luisa , Siculella Luisa , Sardanelli Anna Maria , Papa Sergio , Zanotti Franco , Gnoni Antonio
Published: January 2014

Background

The 14‐3‐3 proteins family consists of seven proteins that are highly conserved molecular chaperones with roles in the regulation of metabolism, signal transduction, cell cycle control, protein trafficking and apoptosis. Their role in several pathologies has been reported. In this study, we investigated the mRNA and protein expression of the 14‐3‐3s in rat brain and liver in the early stage of Type‐1 diabetes (T1D).

Material and methods

Diabetes was induced by a single intraperitoneal injection (70 mg/kg bw) of freshly prepared streptozotocin (STZ), and, after 3 weeks of treatment, brain and liver nuclei and cytosolic extracts were prepared. Quantitative real‐time PCR and Western blotting analyses were performed to evaluate mRNA and protein expression for each of the seven 14‐3‐3s.

Results

In nondiabetic control rats, the expression profile of 14‐3‐3s revealed a tissue‐specific distribution, and the expression level of each isoform was found higher in the brain than in the liver. In the diabetic brain, mRNA and protein levels of the 14‐3‐3β, ε, ζ, η and θ were lower; 14‐3‐3σ mRNA significantly increased while its protein level decreased. In the diabetic liver, the mRNA of 14‐3‐3γ, 14‐3‐3θ and 14‐3‐3σ significantly increased, but only the 14‐3‐3γ protein level increased. Overall, in diabetic animals, the changes in the expression levels of brain 14‐3‐3s were much more pronounced than in the liver.

Conclusion

Our results indicate that during the early phase of STZ‐induced T1D, the 14‐3‐3 proteins are affected in an isoform‐ and tissue‐specific way.
The Dynamic of Aggression: How Individual and Group Factors Affect the Long‐Term Interspecific Aggression Between Two Sympatric Species of Dolphin
Authors: Cusick Jessica A. , Herzing Denise L.
Published: January 2014

Interspecific aggression, similar to intergroup conspecific aggression, has been observed in a variety of taxa. The dominant group or individual is determined by multiple aggressive events and can be influenced by the size, age, or group size of the participating individuals. Interspecific aggression between Atlantic bottlenose (Tursiops truncatus) and spotted (Stenella frontalis) dolphins, both resident and sympatric to Little Bahama Bank, the Bahamas has been consistently observed for over two decades. However, it is unclear whether one species is more dominant and little is known about the factors that influence the progression of aggression. For this study, underwater video recordings of 32 aggressive encounters composed of 451 aggressive behavioural events were analysed over a 12‐yr period (1993–2004). These were used to describe the interspecific aggression observed and quantify which factors (the species and age class of the participants or the group size and behaviour of spotted dolphin groups) had the strongest impact on the progression and outcome of aggression. Over the long term, interspecific aggression was bidirectional with neither species being more dominant. During a single encounter, spotted dolphin group synchrony had the strongest impact on the dynamic of aggression, specifically impacting which group (1) initiated aggression, (2) the direction of aggression and (3) the occurrence of dynamic shifts or dominance reversals. This is the first study to quantify the dynamic of aggression for this population, to document bidirectional aggression and dynamic shifts during long‐term interspecific aggression in free‐ranging delphinids, and this study quantifies the role of synchrony during interspecific aggression using underwater observations.
A critical role of the small GTPase Rac1 in Akt2‐mediated GLUT4 translocation in mouse skeletal muscle
Authors: Takenaka Nobuyuki , Izawa Rumi , Wu Junyuan , Kitagawa Kaho , Nihata Yuma , Hosooka Tetsuya , Noguchi Tetsuya , Ogawa Wataru , Aiba Atsu , Satoh Takaya
Published: January 2014

Insulin promotes glucose uptake in skeletal muscle by inducing the translocation of the glucose transporter GLUT4 to the plasma membrane. The serine/threonine kinase Akt2 has been implicated as a key regulator of this insulin action. However, the mechanisms whereby Akt2 regulates multiple steps of GLUT4 translocation remain incompletely understood. Recently, the small GTPase Rac1 has been identified as a skeletal muscle‐specific regulator of insulin‐stimulated glucose uptake. Here, we show that Rac1 is a critical downstream component of the Akt2 pathway in mouse skeletal muscle as well as cultured myocytes. GLUT4 translocation induced by constitutively activated Akt2 was totally dependent on the expression of Rac1 in L6 myocytes. Moreover, we observed the activation of Rac1 when constitutively activated Akt2 was ectopically expressed. Constitutively activated Akt2‐triggered Rac1 activation was diminished by knockdown of FLJ00068, a guanine nucleotide exchange factor for Rac1. Knockdown of Akt2, on the other hand, markedly reduced Rac1 activation by a constitutively activated mutant of phosphoinositide 3–kinase. In mouse skeletal muscle, constitutively activated mutants of Akt2 and phosphoinositide 3‐kinase, when ectopically expressed, induced GLUT4 translocation. Muscle‐specific rac1 knockout markedly diminished Akt2‐ or phosphoinositide 3‐kinase‐induced GLUT4 translocation, highlighting a crucial role of Rac1 downstream of Akt2. Taken together, these results strongly suggest a novel regulatory link between Akt2 and Rac1 in insulin‐dependent signal transduction leading to glucose uptake in skeletal muscle.
Simulation of ductile crack propagation and determination of CTOAs in pipeline steels using cohesive zone modelling
Authors: Dunbar A. , Wang X. , Tyson W. R. , Xu S.
Published: January 2014

This paper presents recent results of numerical studies on stable crack extension of high toughness steels typical of those in modern gas pipelines using cohesive zone modelling (CZM). The main focus of the work is on the determination of crack‐tip opening angles (CTOAs) of these steels from CZM. Two sets of materials are modelled. The first material set models a typical structural steel, with variable toughness described by four traction–separation (TS) laws. The second set models an X70 pipe steel, with three different TS laws. For each TS law, there are three defining parameters: the maximum cohesive strength, the final separation and the work of separation. The specimens analysed include a crack in an infinite plate (small‐scale yielding, SSY) and a standard drop‐weight tear test (DWTT). Fracture propagation characteristics and values of CTOA are obtained from these two types of specimens. It is shown that cohesive zone models can be successfully used to simulate ductile crack propagation and to numerically measure CTOAs. The ductile crack propagation characteristics and CTOAs obtained from SSY and DWTT specimens are compared for each set of steels. In addition, the CTOA results from numerical CZM of DWTT specimens of X70 steel are compared with those from laboratory tests.
Underwater repair of fatigue cracks by gas tungsten arc welding process
Authors: Rodriguez‐Sanchez J. E. , Perez‐Guerrero F. , Liu S. , Rodriguez‐Castellanos A. , Albiter‐Hernandez A.
Published: January 2014

A fatigue crack repair method for offshore jacket tubular joints is presented. This method is applicable for fatigue cracks detected and sized by regular inspection techniques such as magnetic particle inspection up to a crack depth in the range of 5 mm. The main advantage of the method relies on its easy implementation allowing to be applied immediately after the crack is detected because equipment required is easy to transport and operate; so, it can be on board of a regular inspection campaign ship. A welding procedure specification has to be prepared and qualified prior to implementation of the repair method, considering particular parameters of the jacket fleet and selecting the welding equipment to be used. The proposed method could reinstall the original fatigue life in early stages of growth avoiding the need of more expensive procedures of repair such as joint clamping.
The Effects of Corporate Social Performance on the Cost of Corporate Debt and Credit Ratings
Authors: Oikonomou Ioannis , Brooks Chris , Pavelin Stephen
Published: January 2014

This study investigates the differential impact that various dimensions of corporate social performance have on the pricing of corporate debt as well as the assessment of the credit quality of specific bond issues. The empirical analysis, based on an extensive longitudinal data set, suggests that overall, good performance is rewarded and corporate social transgressions are penalized through lower and higher corporate bond yield spreads, respectively. Similar conclusions can be drawn when focusing on either the bond rating assigned to a specific debt issue or the probability of it being considered to be an asset of speculative grade.
Managerial Behavior and the Link between Stock Mispricing and Corporate Investments: Evidence from Market‐to‐Book Ratio Decomposition
Authors: Alzahrani Mohammed , Rao Ramesh P.
Published: January 2014

We examine the impact of mispricing on corporate investments and its components: capital expenditures, research and development, acquisitions, and asset sales. By decomposing the market‐to‐book ratio into mispricing and growth components, we show that corporate investments are linked to mispricing through market‐timing and catering, after controlling for growth and financial slack. This investment‐mispricing link is more pronounced in financially constrained firms and in firms with short‐horizon shareholders. Overall, our study indicates that the sensitivity of investments to mispricing is a function of the nature of mispricing, the type of investment, and the firm's characteristics.