bluuebunny/crossref_metadata_2025 huggingface dataset:
The molecular charge distribution, the hydration shell, and the unique properties of liquid water
Authors: Tan Ming-Liang , Cendagorta Joseph R. , Ichiye Toshiko
Published: December 2014

The most essential features of a water molecule that give rise to its unique properties are examined using computer simulations of different water models. The charge distribution of a water molecule characterized by molecular multipoles is quantitatively linked to the liquid properties of water via order parameters for the degree (S2) and symmetry (ΔS2) of the tetrahedral arrangement of the nearest neighbors, or “hydration shell.” ΔS2 also appears to determine the long-range tetrahedral network and interfacial structure. From the correlations, some models are shown to be unable to reproduce certain properties due to the limitations of the model itself rather than the parameterization, which indicates that they are lacking essential molecular features. Moreover, since these properties depend not only on S2 but also on ΔS2, the long-range structure in these models may be incorrect. Based on the molecular features found in the models that are best able to reproduce liquid properties, the most essential features of a water molecule in liquid water appear to be a charge distribution with a large dipole, a large quadrupole, and negative charge out of the molecular plane, as well as a symmetrically ordered tetrahedral hydration shell that results from this charge distribution. The implications for modeling water are also discussed.
Simple bond-order-type interatomic potential for an intermixed Fe-Cr-C system of metallic and covalent bondings in heat-resistant ferritic steels
Authors: Kumagai Tomohisa , Nakamura Kaoru , Yamada Susumu , Ohnuma Toshiharu
Published: December 2014

It is known that M23C6(M = Cr/Fe) behavior in heat-resistant ferritic steels affects the strength of the material at high temperature. The ability to garner direct information regarding the atomic motion using classical molecular dynamics simulations is useful for investigating the M23C6 behavior in heat-resistant ferritic steels. For such classical molecular dynamics calculations, a suitable interatomic potential is needed. To satisfy this requirement, an empirical bond-order-type interatomic potential for Fe-Cr-C systems was developed because the three main elements to simulate the M23C6 behavior in heat-resistant ferritic steels are Fe, Cr, and C. The angular-dependent term, which applies only in non-metallic systems, was determined based on the similarity between a Finnis-Sinclair-type embedded-atom-method interatomic potential and a Tersoff-type bond-order potential. The potential parameters were determined such that the material properties of Fe-Cr-C systems were reproduced. These properties include the energy and lattice constants of 89 crystal structures; the elastic constants of four realistic precipitates; the bulk moduli of B1, B2, and B3 crystals; the surface energies of B1 and B2 crystals; and the defect-formation energies and atomic configurations of 66 Fe-Cr-C complexes. Most of these material properties were found to be reproduced by our proposed empirical bond-order potentials. The formation energies and lattice constants of randomly mixed Fe-Cr alloys calculated using the interatomic potentials were comparable to those obtained through experiments and first-principles calculations. Furthermore, the energies and structures of interfaces between Cr carbide and α-Fe as predicted through first-principles calculations were well reproduced using these interatomic potentials.
First-principle calculation of core level binding energies of LixPOyNz solid electrolyte
Authors: Guille Émilie , Vallverdu Germain , Baraille Isabelle
Published: December 2014

We present first-principle calculations of core-level binding energies for the study of insulating, bulk phase, compounds, based on the Slater-Janak transition state model. Those calculations were performed in order to find a reliable model of the amorphous LixPOyNz solid electrolyte which is able to reproduce its electronic properties gathered from X-ray photoemission spectroscopy (XPS) experiments. As a starting point, Li2PO2N models were investigated. These models, proposed by Du et al. on the basis of thermodynamics and vibrational properties, were the first structural models of LixPOyNz. Thanks to chemical and structural modifications applied to Li2PO2N structures, which allow to demonstrate the relevance of our computational approach, we raise an issue concerning the possibility of encountering a non-bridging kind of nitrogen atoms (=N−) in LixPOyNz compounds.
Note: Liquid chemical sensing by emission spectroscopy with a nanosecond pin-hole discharge in water
Authors: Xia H. , Yang Y.
Published: December 2014

This paper presents a simple yet effective method for chemical detection by emission spectroscopy using a nanosecond pin-hole discharge in water. The discharge was produced in a 200-μm-diameter microchannel in water without electrode contact. The simultaneous detection of multiple mineral ions was demonstrated by measuring the intensity of Na and Ca emission lines at different concentrations. The device can be further scaled down to be integrated with microfluidic systems for monitoring water contamination or hazardous materials in other aqueous solutions.
Formation of GeSn alloy on Si(100) by low-temperature molecular beam epitaxy
Authors: Talochkin A. B. , Mashanov V. I.
Published: December 2014

GeSn alloys grown on Si(100) by the low-temperature (100 °C) molecular beam epitaxy are studied using scanning tunneling microscopy and Raman spectroscopy. It is found that the effect of Sn as a surfactant modifies substantially the low-temperature growth mechanism of Ge on Si. Instead of the formation of small Ge islands surrounded by amorphous Ge, in the presence of Sn, the growth of pure Ge islands appears via the Stranski-Krastanov growth mode, and a partially relaxed Ge1−xSnx alloy layer with the high Sn-fraction up to 40 at. % is formed in the area between them. It is shown that the observed growth mode induced by high surface mobility of Sn and the large strain of the pseudomorphic state of Ge to Si ensures the minimum elastic-strain energy of the structure.
Photoelectric properties and charge dynamics in ZnO nanowires/Cu4Bi4S9 and ZnO nanowires/In2O3/Cu4Bi4S9 heterostructures
Authors: Liu Xiangyang , Wang Shun , Zhang Jingwei , Zhang Jiwei , Gu Yuzong
Published: December 2014

ZnO nanowires arrays were preformed in a horizontal double-tube system. Two types of heterostructures (ZnO nanowires/Cu4Bi4S9 and ZnO nanowires/In2O3/Cu4Bi4S9) and three-dimensional solar cells were fabricated with ZnO nanowires arrays as working electrode, In2O3 as buffer layer, and Cu4Bi4S9 as inorganic dye and hole collector. It is suggested that two types of heterostructures have the similar absorption properties with single Cu4Bi4S9. However, the results of steady state and electric field-induced surface photovoltage indicate that ZnO nanowires/In2O3/Cu4Bi4S9 exhibits the higher photovoltaic response than ZnO nanowires/Cu4Bi4S9. Using the transient surface photovoltage spectroscopy, we further studied the separation and transport mechanism of photogenerated charges. Furthermore, Cu4Bi4S9/In2O3/ZnO cells presents the better performance than Cu4Bi4S9/ZnO cells and the highest efficiencies are about 6.4% and 5.2%, respectively. It is suggested that direct paths, interface barrier, built-in electric field, and double energy level matchings between conduction bands (Cu4Bi4S9 and In2O3, In2O3 and ZnO) have obvious effect on the separation of photogenerated charges. Then we discussed the synthetic action on the charge dynamics from these factors.
Band offsets of n-type electron-selective contacts on cuprous oxide (Cu2O) for photovoltaics
Authors: Brandt Riley E. , Young Matthew , Park Helen Hejin , Dameron Arrelaine , Chua Danny , Lee Yun Seog , Teeter Glenn , Gordon Roy G. , Buonassisi Tonio
Published: December 2014

The development of cuprous oxide (Cu2O) photovoltaics (PVs) is limited by low device open-circuit voltages. A strong contributing factor to this underperformance is the conduction-band offset between Cu2O and its n-type heterojunction partner or electron-selective contact. In the present work, a broad range of possible n-type materials is surveyed, including ZnO, ZnS, Zn(O,S), (Mg,Zn)O, TiO2, CdS, and Ga2O3. Band offsets are determined through X-ray photoelectron spectroscopy and optical bandgap measurements. A majority of these materials is identified as having a negative conduction-band offset with respect to Cu2O; the detrimental impact of this on open-circuit voltage (VOC) is evaluated through 1-D device simulation. These results suggest that doping density of the n-type material is important as well, and that a poorly optimized heterojunction can easily mask changes in bulk minority carrier lifetime. Promising heterojunction candidates identified here include Zn(O,S) with [S]/[Zn] ratios >70%, and Ga2O3, which both demonstrate slightly positive conduction-band offsets and high VOC potential. This experimental protocol and modeling may be generalized to evaluate the efficiency potential of candidate heterojunction partners for other PV absorbers, and the materials identified herein may be promising for other absorbers with low electron affinities.
The effects of tungsten concentration on crystalline structure and perpendicular magnetic anisotropy of Co-W films
Authors: Yin S. Q. , Wu Y. , Xu X. G. , Wang H. , Wang J.P. , Jiang Y.
Published: December 2014

In this study, Co-W thin films deposited by DC magnetron sputtering were demonstrated to be perpendicular magnetic anisotropic with large magnetocrystalline anisotropy energy (MAE). Thermodynamic calculations based on Miedema’s semi-empirical model have been used to estimate the phase in this binary alloy system. Based on the thermodynamic calculations results, a series of Co-W thin films were deposited on amorphous Ta underlayer with different tungsten concentrations. According to the X-ray diffraction results, the crystal structure of Co-W thin films is consistent well with that of thermodynamic calculations. Large MAE of Co-W thin films can be obtained with Ku over 2.1 × 105 J/m3 after vacuum annealing. The perpendicular coercivity (Hc) of Co-W thin film reaches 9.1 × 104 A/m. Therefore, the Co-W thin film is considered as a potential choice of high-density magnetic recording media materials.
An unshielded radio-frequency atomic magnetometer with sub-femtoTesla sensitivity
Authors: Keder David A. , Prescott David W. , Conovaloff Adam W. , Sauer Karen L.
Published: December 2014

We demonstrate a radio-frequency potassium-vapor magnetometer operating with sensitivities of 0.3 fT/Hz at 0.5 MHz and 0.9 fT/Hz at 1.31 MHz in the absence of radio-frequency and mu-metal or magnetic shielding. The use of spatially separated magnetometers, two voxels within the same cell, permits for the subtraction of common mode noise and the retention of a gradient signal, as from a local source. At 0.5 MHz the common mode noise was white and measured to be 3.4 fT/Hz; upon subtraction the noise returned to the values observed when the magnetometer was shielded. At 1.31 MHz, the common mode noise was from a nearby radio station and was reduced by a factor of 33 upon subtraction, limited only by the radio signal picked up by receiver electronics. Potential applications include in-the-field low-field magnetic resonance, such as the use of nuclear quadrupole resonance for the detection of explosives.
Role of an encapsulating layer for reducing resistance drift in phase change random access memory
Authors: Jin Bo , Kim Jungsik , Pi Dong-Hai , Kim Hyoung Seop , Meyyappan M. , Lee Jeong-Soo
Published: December 2014

Phase change random access memory (PCRAM) devices exhibit a steady increase in resistance in the amorphous phase upon aging and this resistance drift phenomenon directly affects the device reliability. A stress relaxation model is used here to study the effect of a device encapsulating layer material in addressing the resistance drift phenomenon in PCRAM. The resistance drift can be increased or decreased depending on the biaxial moduli of the phase change material (YPCM) and the encapsulating layer material (YELM) according to the stress relationship between them in the drift regime. The proposed model suggests that the resistance drift can be effectively reduced by selecting a proper material as an encapsulating layer. Moreover, our model explains that reducing the size of the phase change material (PCM) while fully reset and reducing the amorphous/crystalline ratio in PCM help to improve the resistance drift, and thus opens an avenue for highly reliable multilevel PCRAM applications.
Improving the efficiency of copper indium gallium (Di-)selenide (CIGS) solar cells through integration of a moth-eye textured resist with a refractive index similar to aluminum doped zinc oxide
Authors: Burghoorn M. , Kniknie B. , van Deelen J. , Xu M. , Vroon Z. , van Ee R. , van de Belt R. , Buskens P.
Published: December 2014

Textured transparent conductors are widely used in thin-film silicon solar cells. They lower the reflectivity at interfaces between different layers in the cell and/or cause an increase in the path length of photons in the Si absorber layer, which both result in an increase in the number of absorbed photons and, consequently, an increase in short-circuit current density (Jsc) and cell efficiency. Through optical simulations, we recently obtained strong indications that texturing of the transparent conductor in copper indium gallium (di-)selenide (CIGS) solar cells is also optically advantageous. Here, we experimentally demonstrate that the Jsc and efficiency of CIGS solar cells with an absorber layer thickness (dCIGS) of 0.85 μm, 1.00 μm and 2.00 μm increase through application of a moth-eye textured resist with a refractive index that is sufficiently similar to AZO (nresist = 1.792 vs. nAZO = 1.913 at 633 nm) to avoid large optical losses at the resist-AZO interface. On average, Jsc increases by 7.2%, which matches the average reduction in reflection of 7.0%. The average relative increase in efficiency is slightly lower (6.0%). No trend towards a larger relative increase in Jsc with decreasing dCIGS was observed. Ergo, the increase in Jsc can be fully explained by the reduction in reflection, and we did not observe any increase in Jsc based on an increased photon path length.
The strain capacitor: A novel energy storage device
Authors: Deb Shuvra Pranoy , McNamara Shamus
Published: December 2014

A novel electromechanical energy storage device is reported that has the potential to have high energy densities. It can efficiently store both mechanical strain energy and electrical energy in the form of an electric field between the electrodes of a strain-mismatched bilayer capacitor. When the charged device is discharged, both the electrical and mechanical energy are extracted in an electrical form. The charge-voltage profile of the device is suitable for energy storage applications since a larger portion of the stored energy can be extracted at higher voltage levels compared to a normal capacitor. Its unique features include the potential for long lifetime, safety, portability, wide operating temperature range, and environment friendliness. The device can be designed to operate over varied operating voltage ranges by selecting appropriate materials and by changing the dimensions of the device. In this paper a finite element model of the device is developed to verify and demonstrate the potential of the device as an energy storage element. This device has the potential to replace conventional energy storage devices.
Enhancement of a robust arcuate GABAergic input to gonadotropin-releasing hormone neurons in a model of polycystic ovarian syndrome
Authors: Moore Aleisha M. , Prescott Mel , Marshall Christopher J. , Yip Siew Hoong , Campbell Rebecca E.
Published: December 2014

Significance

Polycystic ovarian syndrome (PCOS) is the leading cause of anovulatory infertility. Although the etiology of PCOS is unclear, disrupted central mechanisms mediating steroid hormone feedback to gonadotropin-releasing hormone (GnRH) neurons have been suggested. We describe here, in a mouse model reflecting the clinical neuroendocrine phenotype of PCOS, evidence for disordered progesterone (P4)-sensitive GABAergic input to GnRH neurons, originating specifically within the arcuate nucleus. These discoveries define a previously unidentified neuronal pathway, potentially critical for the steroid hormone feedback control of fertility. Of clinical relevance, our findings help explain the impact of GABA agonist drugs on menstrual cycle irregularity and interference with oral contraceptives and could be the basis for understanding clinical therapies of PCOS.
Subunit determination of the conductance of hair-cell mechanotransducer channels
Authors: Beurg Maryline , Xiong Wei , Zhao Bo , Müller Ulrich , Fettiplace Robert
Published: December 2014

Significance

Cochlear hair cells are sensory receptors of the inner ear that detect sound via opening of mechanically sensitive transduction channels at the tips of the eponymous hairs. The conductance of the channel increases two-fold along the cochlea, but neither its molecular structure nor mechanism of tonotopic variation is known. We show that when either of two deafness-linked proteins, transmembrane channel-like protein isoform 1 (TMC1) and tetraspan membrane protein of hair cell stereocilia (TMHS, also known as lipoma HMGIC fusion partner-like 5, LHFPL5) is knocked out, the conductance variation is lost. Furthermore, the effect of LHFPL5 is attributable to down-regulation of TMC1, suggesting that titrating the TMC1 content of the channel modulates its conductance. Evidence indicates that both proteins interact with the mechanotransduction channel and also with protocadherin-15, a component of the extracellular tip link that applies force to the channel.
Expected Problem Drinker Possible Self: Predictor of Alcohol Problems and Tobacco use in Adolescents
Authors: Lee Chia-Kuei , Corte Colleen , Stein Karen F. , Finnegan Lorna , McCreary Linda L. , Park Chang G.
Published: December 2014

Background

Alcohol and tobacco use commonly co-occur in adolescents. According to the cross-substance facilitation of information processing hypothesis, cognitive structures related to one substance increase use of another related substance through enhanced cognitive processing. In this study, the authors test this hypothesis by determining whether a problem drinker “possible self” in 8th grade predicts alcohol and tobacco use in 9th grade.

Methods

A secondary data analysis of a 12-month longitudinal dataset was conducted. The outcome variables were alcohol consumption, alcohol problems, and tobacco use in 9th grade. The main predictor of interest was presence of an expected problem drinker possible self in 8th grade. Zero-inflated gamma regression, zero-inflated negative binomial regression, and logistic regression were used.

Results

Among 137 adolescents, controlling for known family, parent, and peer determinants, and corresponding 8th grade behavior, having an expected problem drinker possible self in 8th grade predicted alcohol problems, but not level of alcohol consumption in 9th grade. Moreover, the expected problem drinker possible self in 8th grade predicted tobacco use in 9th grade, controlling for known determinants and concurrent alcohol problems.

Conclusions

Findings provide support for the cross-substance facilitation hypothesis, suggesting that interventions designed to modify the expected problem drinker possible self may reduce not only adolescent alcohol use but also tobacco use. Further studies are needed to determine whether smoking content is embedded in a drinking cognition or 2 separate but related drinking and smoking cognitions account for the association between alcohol and tobacco use.
Corporate Social Responsibility: A Very Short Introduction
Authors: Moon Jeremy
Published: December 2014

Corporate social responsibility (CSR) has been defined as ‘the responsibility of enterprises for their impacts on society’. Is CSR a contradiction in terms? Corporate Social Responsibility: A Very Short Introduction shows that CSR holds much more value than it first appears, and shows how it has come of age in recent years. Illustrating the sorts of CSR investments companies make, the ways in which they practice CSR, and the challenges this brings, it considers how the principles migrated from their US roots to become a global business phenomenon. Exploring the place of CSR in different economic, social, political, and managerial contexts, this VSI considers the many positives that CSR can present.
A Nested Parallel Experiment Demonstrates Differences in Intensity-Dependence Between RNA-Seq and Microarrays
Authors: Robinson David G. , Wang Jean , Storey John D.
Published: December 2014

Understanding the differences between microarray and RNA-Seq technologies for measuring gene expression is necessary for informed design of experiments and choice of data analysis methods. Previous comparisons have come to sometimes contradictory conclusions, which we suggest result from a lack of attention to the intensity-dependent nature of variation generated by the technologies. To examine this trend, we carried out a parallel nested experiment performed simultaneously on the two technologies that systematically split variation into four stages (treatment, biological variation, library preparation, and chip/lane noise), allowing a separation and comparison of the sources of variation in a well-controlled cellular system,Saccharomyces cerevisiae. With this novel dataset, we demonstrate that power and accuracy are more dependent on per-gene read depth in RNA-Seq than they are on fluorescence intensity in microarrays. However, we carried out qPCR validations which indicate that microarrays may demonstrate greater systematic bias in low-intensity genes than in RNA-seq.
Anticancer activity using positron emission tomography‐computed tomography and pharmacokinetics of β‐eudesmol in human cholangiocarcinoma xenografted nude mouse model
Authors: Plengsuriyakarn Tullayakorn , Karbwang Juntra , Na‐Bangchang Kesara
Published: December 2014

Cholangiocarcinoma (CCA) is an important public health problem in several parts of South East Asia, particularly in Thailand. The limited availability of effective diagnostic tools for early stage CCA, including chemotherapeutic options, constitutes a major problem for treatment and control of CCA. The aim of the present study was to assess the anti‐CCA activity and pharmacokinetics of β‐eudesmol in CCA‐xenografted nude mouse model and healthy mice. Positron emission tomography‐computed tomography (PET‐CT) with 18F‐fluorodeoxyglucose was used for detecting and monitoring tumour development, and PET‐CT with technetium‐99m was used to investigate its pharmacokinetics property. Results support the role of PET‐CT as a potential tool for detecting and monitoring the progress of lung metastasis. Tumour size and lung metastasis were significantly inhibited by 91.6% (of baseline) and 95% (of total lung mass), respectively, following treatment with high‐dose β‐eudesmol (100 mg/kg body weight for 30 days). Survival time was prolonged by 64.4% compared with untreated controls. Systemic clearance of the compound was rapid, particularly during the first 60 min. The compound was distributed to the vital organs at maximum levels 2 h after oral administration and 15 min after intravenous injection. Results from the present study suggest the potential of β‐eudesmol as a promising candidate for further development as an anti‐CCA drug with respect to its pharmacodynamics and pharmacokinetic properties. PET‐CT, with radiotracers 18F‐fluorodeoxyglucose and technetium‐99m, was shown to be a reliable tool in the investigation of anti‐CCA and pharmacokinetic properties of β‐eudesmol in CCA‐xenografted and healthy mice.
Communication between nurses and physicians: Strategies to surviving in the emergency department trenches
Authors: Abourbih Daniel , Armstrong Sherry , Nixon Kirsty , Ackery Alun D
Published: December 2014

The emergency department (ED) is a challenging and stressful work environment where communication lapses can lead to negative health outcomes. This article offers strategies to Emergency Medicine residents, nurses and staff physicians on how to improve communication to optimize patient care.
Optimization of colorectal cancer vaccine candidate protein GA733‐Fc expression in a baculovirus–insect cell system
Authors: Kim Deuk‐Su , Qiao Lu , Lee Kyung‐Jin , Ko Kisung
Published: December 2014

The baculovirus–insect cell expression system has been used to produce functional recombinant proteins. The antigen GA733 is a cell‐surface glycoprotein highly expressed on most human colorectal carcinoma cells. Conditions for the expression of GA733 fused to the human immunoglobulin IgG Fc fragment (GA733‐Fc) were optimized in the baculovirus expression system. Several variable factors were adjusted to optimize expression, including the cell line (Sf9 and High Five), multiplicity of infection (MOI) value (0.05, 0.1, 0.5, 1 and 3), post‐infection time (48, 72 and 96 h) and harvested sample (cell culture media (CM) or cell lysate (CL)). In addition, two pFastBac Dual vectors carrying the GA733‐Fc gene were constructed to express GA733‐Fc with or without an endoplasmic reticulum (ER) retention sequence KDEL and used to generate recombinant baculoviruses. Western blot showed that expression depended on the conditions used to express the recombinant proteins. The protein production level and secretion capability differed in each cell line. In Sf9 cells, the highest expression in the CM and CL was obtained with GA733‐Fc at 96 h post‐infection at 0.1 MOI and with GA733‐FcK at 96 h post‐infection at 3 MOI, respectively. In High Five cells, the highest expression in the CM and CL was obtained with GA733‐Fc at 48 h post‐infection at 1 MOI and with GA733‐FcK at 48 h post‐infection at 3 MOI, respectively. These results suggest that the MOI value, post‐infection time and subcellular localization affect expression, and that these conditions can be modified to optimize protein expression in the baculovirus–insect cell system.
Mal de Meleda in Indonesia: Mutations in the SLURP1 gene appear to be ubiquitous
Authors: Taylor Jessica A , Bondavalli Davide , Monif Mastura , Yap Lee Mei , Winship Ingrid
Published: December 2014

Mal de Meleda is a rare autosomal recessive genodermatosis caused by mutations in the ARS B (SLURP1) gene, with possible founder effects in the Mediterranean and Adriatic regions. We report an affected individual from Indonesia without known consanguinity in the family, suggesting that SLURP1 gene mutations are ubiquitous. Recognition of the phenotype can be confirmed by genetic testing, thus facilitating genetic counselling.
Multiple clustered dermatofibroma presenting in a segmental distribution
Authors: Bhabha Friyana K. , Magee Jill , Ng Su Yuen , Grills Claire Elizabeth , Su John , Orchard David
Published: December 2014

Multiple dermatofibromas is a rare entity consisting of more than fifteen lesions. Multiple clustered dermatofibroma is a distinct variant of multiple dermatofibromas and is defined as a well‐demarcated plaque composed of individual dermatofibromas. We report a 16‐year‐old boy with multiple clustered dermatofibroma in a segmental distribution, which has previously not been reported in the literature.
Bioequivalence of 0.1% mometasone furoate lotion to 0.1% mometasone furoate hydrogel
Authors: Greive Kerryn A. , Barnes Tanya M.
Published: December 2014

Background/Objectives

Vehicles used for topical therapy can affect drug delivery and patient adherence. This study compared the bioequivalence of 0.1% mometasone furoate lotion (reference) and 0.1% mometasone furoate hydrogel (test). Moisturising capacity and sensitivity/irritancy potential were also determined.

Methods

Bioequivalence was assessed by vasoconstriction assay and analysis of area under the effect curve (AUEC0–24) according to the Food and Drug Administration (FDA) guidance. In total, 131 individuals were screened in a pilot dose duration‐response study, and 90 responders enrolled. For the pivotal study, lotion and hydrogel (5 mg/cm2) were applied in a double‐blind manner. Vasoconstriction was evaluated by chromameter at 0, 2, 4, 6, 19 and 24 h following lotion and hydrogel removal. Barrier function was measured by assessment of transepidermal water loss (TEWL) and skin hydration. Sensitivity/irritancy potential was assessed by repeat insult patch tests.

Results

The mean AUEC0–24 of the test hydrogel and reference lotion were −18.200 and −18.953, respectively, with test/reference = 96%, with 90% confidence interval (0.81, 1.12), which was within FDA guidance limits. TEWL was found to significantly decrease by 43 and 29% after 2 and 24 h, respectively, while skin hydration significantly increased by 38% after 24 h following a single application of hydrogel. The hydrogel was also found to be non‐irritating and non‐sensitising. No adverse events were observed.

Conclusions

Mometasone furoate hydrogel is bioequivalent to mometasone furoate lotion. This novel hydrogel formulation provides effective drug delivery, increases moisturisation and affords greater ease and tolerability of application, improving patients' adherence to therapy.
Cisplatin resistance in germ cell tumours: models and mechanisms
Authors: Jacobsen C. , Honecker F.
Published: December 2014

Recent years have led to a better understanding of the mechanisms underlying cisplatin response and resistance in germ cell tumours (GCT), and several promising targets have been identified. Two main mechanisms of the responsiveness to DNA damaging agents have been postulated. Firstly, GCT readily activate a DNA damage response, but show deficits in several damage repair pathways. In particular, they have been found to have defects in interstrand crosslink repair and in homologous recombination (HR). Secondly, GCT, especially embryonal carcinoma (EC) cells, show a hypersensitive apoptotic response to DNA damage, which activates p53, and leads to up‐regulation of the pro‐apoptotic factors Noxa, Puma and Fas in non‐resistant EC. These cells fail to activate p21 which induces a G1/S arrest, but accumulate in G2/M phase. In the absence of functional p53, family members like p73 and GTAp63 might be important in initiating this response. Mechanisms involved in cisplatin resistance are as follows: down‐regulation of Oct4 (e.g. as a result of hypoxia, treatment with retinoic acid or exposure to cisplatin) and failure to induce Puma and Noxa; changes in the expression levels of micro‐RNAs such as miR‐17/‐106b, miR‐302a, or miR‐371 to ‐373; elevated levels of MDM2 and cytoplasmic translocation of p21 by phosphorylation; and activation of the PDGFRβ/PI3K/pAKT pathway. Several approaches to overcome resistance have been successfully examined in vitro and in vivo, including PARP inhibitors, especially in cells showing deficient HR‐repair; stabilization of p53 using nutlin‐3; inhibition of several components of the PI3K/pAKT pathway using small molecules; and DNA demethylation by 5‐azacytidine or 5‐aza‐deoxy‐cytidine, among others. Many of these substances deserve further exploration, alone or in combination with DNA damaging agents, and the most promising approaches should be taken forward to clinical testing. Targeted therapy based on mechanistic insights holds the promise to turn cisplatin‐resistant GCT into a curable disease.
Short‐term outcomes of combined implantation of diffractive multifocal intraocular lenses with different addition power
Authors: Hayashi Ken , Yoshida Motoaki , Hirata Akira , Yoshimura Koichi
Published: December 2014

Purpose

To compare short‐term binocular visual function between patients implanted with diffractive multifocal intraocular lenses (MIOLs) of different near addition powers in each eye or the same MIOLs bilaterally.

Methods

Seventy patients scheduled for implantation of diffractive MIOLs were divided into two groups: (i) mix and match group, a MIOL with +3.0 dioptre (D) addition power implanted in the dominant eye (Alcon SN60D1) and a MIOL with +4.0D power implanted in the non‐dominant eye (SN60D3) or (ii) same MIOL group, same MIOL (SN60D1) implanted bilaterally. At 3 months postoperatively, we examined binocular visual acuity (VA) at various distances, binocular contrast VA and that with a glare (glare VA), and near stereoacuity.

Results

Mean binocular uncorrected (UNVA) or corrected near VA (CNVA) at 0.3 m was significantly better in the mix and match group than in the same MIOL group (p ≤ 0.0066). Binocular uncorrected and distance‐corrected VA at other distances was similar. Binocular UNVA of 0.8 or better was achieved in 77.1% of patients in the mix and match group and 45.7% in the same MIOL group (p = 0.0144). Binocular contrast and glare VA, and stereoacuity did not significantly differ between groups. Spectacle independence and patient satisfaction with near vision were significantly better in the mix and match group (p ≤ 0.0195).

Conclusion

Mix and match implantation of diffractive MIOLs with different addition power provides a better binocular VA curve and spectacle independence than bilateral implantation of the same MIOLs, without compromising contrast sensitivity and stereopsis.
Enhanced depth imaging–optical coherence tomography of the choroid in moderate and severe primary angle‐closure glaucoma
Authors: Li Zheng , Wang Wei , Zhou Minwen , Huang Wenbin , Chen Shida , Li Xingyi , Gao Xinbo , Wang Jiawei , Du Shaolin , Zhang Xiulan
Published: December 2014

Purpose

To compare the choroidal thickness (CT) in eyes with moderate and severe primary angle‐closure glaucoma (PACG) with the eyes of healthy controls.

Methods

Fifty‐nine patients (59 eyes) with PACG and 56 age‐matched normal subjects underwent macular CT scanning using enhanced depth imaging–optical coherence tomography. The subjects with PACG were further classified as having moderate [−12 dB ≤ visual field mean deviation (VF‐MD) ≤ −6 dB] or severe (VF‐MD < −12 dB) glaucoma. The average CT of the PACG eyes at each location was compared to that of normal eyes.

Results

The CT was significantly increased in moderate and severe PACG eyes compared with the normal eyes at all nine macular locations, with the exception of 1 and 3 mm superior to the fovea. The mean CT under the fovea was 292.0 ± 48.2 μm in the moderate PACG eyes, 277.1 ± 58.3 μm in the severe PACG eyes and 249.9 ± 72.1 μm in the normal eyes, respectively. There were no significant differences between the macular CTs in the eyes with moderate PACG and those in severe PACG eyes (all p > 0.05). Factors associated with a thinner choroid were ageing (p < 0.001), female (p = 0.036) and increasing axial length (p = 0.021). Neither the VF‐MD nor pattern standard deviation was found to be associated with CT.

Conclusions

The CT is greater in patients with PACG, but it does not differ between moderate and severe PACG, suggesting a lack of relationship between CT and the progression of glaucoma based on EDI‐OCT measurements.
The homeostatic role of neuropeptide Y in immune function and its impact on mood and behaviour
Authors: Farzi A. , Reichmann F. , Holzer P.
Published: December 2014

Neuropeptide Y (NPY), one of the most abundant peptides in the nervous system, exerts its effects via five receptor types, termed Y1, Y2, Y4, Y5 and Y6. NPY's pleiotropic functions comprise the regulation of brain activity, mood, stress coping, ingestion, digestion, metabolism, vascular and immune function. Nerve‐derived NPY directly affects immune cells while NPY also acts as a paracrine and autocrine immune mediator, because immune cells themselves are capable of producing and releasing NPY. NPY is able to induce immune activation or suppression, depending on a myriad of factors such as the Y receptors activated and cell types involved. There is an intricate relationship between psychological stress, mood disorders and the immune system. While stress represents a risk factor for the development of mood disorders, it exhibits diverse actions on the immune system as well. Conversely, inflammation is regarded as an internal stressor and is increasingly recognized to contribute to the pathogenesis of mood and metabolic disorders. Intriguingly, the cerebral NPY system has been found to protect against distinct disturbances in response to immune challenge, attenuating the sickness response and preventing the development of depression. Thus, NPY plays an important homeostatic role in balancing disturbances of physiological systems caused by peripheral immune challenge. This implication is particularly evident in the brain in which NPY counteracts the negative impact of immune challenge on mood, emotional processing and stress resilience. NPY thus acts as a unique signalling molecule in the interaction of the immune system with the brain in health and disease.
The effectiveness of pharmaceutical interventions for obesity: weight loss with orlistat and sibutramine in a United Kingdom population‐based cohort
Authors: Douglas Ian J. , Bhaskaran Krishnan , Batterham Rachel L. , Smeeth Liam
Published: December 2014

Aims

Drug treatments for obesity have proven efficacy from randomized trials, but their effectiveness in routine clinical practice is unknown. We assessed the effects on weight and body mass index (BMI) of orlistat and sibutramine when delivered in routine primary care.

Methods

We used United Kingdom data from the Clinical Practice Research Datalink to estimate the effects of orlistat or sibutramine on weight and BMI over 3 years following treatment initiation. For comparison, we matched each patient with up to five obese patients receiving neither drug. Mixed effects linear regression with splines was used to model change in weight and BMI. Mean change with 95% confidence intervals (CI) was estimated.

Results

We identified 100 701 patients receiving orlistat, 15 355 receiving sibutramine and 508 140 non‐intervention patients, with body mass index of 37.2, 36.6 and 33.2 kg m−2, respectively. Patients receiving orlistat lost, on average, 0.94 kg month−1 (0.93 to 0.95) over the first 4 months. Weight gain then occurred, although weight remained slightly below baseline at 3 years. Patients receiving sibutramine lost, 1.28 kg month−1 (1.26 to 1.30) over the first 4 months, but by 3 years had exceeded baseline weight. Non‐intervention patients had slight increases in weight throughout the 3 year period, with gains ranging between 0.01 and 0.06 kg month−1.

Conclusions

Orlistat and sibutramine had early effects on weight loss, not sustained over 3 years. As new treatments for obesity are approved, their effectiveness should be measured in routine clinical practice, as effectiveness may be considerably less than seen in randomized trials.
Exploring the Tension between Clarity and Ambiguity in Goal Setting for Innovation
Authors: Stetler Katarina Lund , Magnusson Mats
Published: December 2014

In this article we analyse the role of goal setting for innovation in an R&D context. The literature on goal setting for innovation is inconclusive; some scholars claim that goals should be ambiguous in order to inspire novel ideas, but others claim that clear project goals are important in order to undertake innovation projects in an efficient manner. We aim to explain this inconsistency by taking a more fine‐grained view of innovation where we study goal setting in relation to exploratory aspects such as idea generation separately from exploitatory aspects such as idea implementation. The results from an empirical survey study in the R&D department of an automotive company reveal that a general ambition to be innovative is positively related to all phases of innovation, but the effects of clear project goals are more complex. We found that idea novelty increases under conditions of either high or low levels of goal clarity, whereas mid‐range levels of goal clarity are related to fewer novel ideas. These findings inform existing knowledge about goal setting and innovation, and in particular challenge the body of literature showing that only high levels of ambiguity in goal setting are a fruitful means for innovation.
Population‐based cohort studies of type 2 diabetes and stomach cancer risk in Chinese men and women
Authors: Xu Hong‐Li , Tan Yu‐Ting , Epplein Meira , Li Hong‐Lan , Gao Jing , Gao Yu‐Tang , Zheng Wei , Shu Xiao‐Ou , Xiang Yong‐Bing
Published: December 2014

Although positive associations have been found for diabetes and a number of cancer sites, investigations of stomach cancer are limited and the results lack consistency. In this prospective study we investigated the relationship between type 2 diabetes mellitus (T2DM) and stomach cancer risk in mainland China. We assessed the associations among T2DM, T2DM duration, and stomach cancer risk in two prospective population‐based cohorts, the Shanghai Women's Health Study and the Shanghai Men's Health Study. Included in the study were 61 480 men and 74 941 women. Stomach cancer cases were identified through annual record linkage to the Shanghai Cancer Registry, and verified through home visits and review of medical charts. After a median follow‐up of 7.5 years for the Shanghai Men's Health Study and 13.2 years for the Shanghai Women's Health Study, a total of 755 incident cases of stomach cancer (376 men and 379 women) were identified through to September 2013. Overall, we did not find any evidence that T2DM was associated with an increased risk of stomach cancer either in men (multi‐adjusted hazard ratio = 0.83, 95% confidence interval, 0.59–1.16) or in women (multi‐adjusted hazard ratio = 0.92, 95% confidence interval, 0.68–1.25). Our findings from two large prospective population‐based cohorts suggest that T2DM was not associated with stomach cancer risk.
Effects of testosterone treatment on glucose metabolism and symptoms in men with type 2 diabetes and the metabolic syndrome: a systematic review and meta‐analysis of randomized controlled clinical trials
Authors: Grossmann Mathis , Hoermann Rudolf , Wittert Gary , Yeap Bu B.
Published: December 2014

Context

The effects of testosterone treatment on glucose metabolism and other outcomes in men with type 2 diabetes (T2D) and/or the metabolic syndrome are controversial.

Objective

To perform a systematic review and meta‐analysis of placebo‐controlled double‐blind randomized controlled clinical trials (RCT) of testosterone treatment in men with T2D and/or the metabolic syndrome.

Data sources

A systematic search of RCTs was conducted using Medline, Embase and the Cochrane Register of controlled trials from inception to July 2014 followed by a manual review of the literature.

Study selection

Eligible studies were published placebo‐controlled double‐blind RCTs published in English.

Data extraction

Two reviewers independently selected studies, determined study quality and extracted outcome and descriptive data.

Data synthesis

Of the 112 identified studies, seven RCTs including 833 men were eligible for the meta‐analysis. In studies using a simple linear equation to calculate the homeostatic model assessment of insulin resistance (HOMA1), testosterone treatment modestly improved insulin resistance, compared to placebo, pooled mean difference (MD) −1·58 [−2·25, −0·91], P < 0·001. The treatment effect was nonsignificant for RCTs using a more stringent computer‐based equation (HOMA2), MD −0·19 [−0·86, 0·49], P = 0·58). Testosterone treatment did not improve glycaemic (HbA1c) control, MD −0·15 [−0·39, 0·10], P = 0·25, or constitutional symptoms, Aging Male Symptom score, MD −2·49 [−5·81, 0·83], P = 0·14).

Conclusions

This meta‐analysis does not support the routine use of testosterone treatment in men with T2D and/or the metabolic syndrome without classical hypogonadism. Additional studies are needed to determine whether hormonal interventions are warranted in selected men with T2D and/or the metabolic syndrome.
Prevalence of parathyroid carcinoma in 348 patients with multiple endocrine neoplasia type 1 – case report and review of the literature
Authors: Singh Ospina Naykky , Sebo Thomas J. , Thompson Geoffrey B. , Clarke Bart L. , Young William F.
Published: December 2014

Objective

To report the prevalence of parathyroid carcinoma (PC) in patients with multiple endocrine neoplasia type 1 (MEN1) and review of the literature.

Background

Primary hyperparathyroidism (PHP) is the most common manifestation of MEN1. The occurrence of PC in patients with MEN1 is rare and the literature regarding the clinical manifestations – including the prevalence of the disease – is scarce.

Context

Single tertiary care centre experience from 1977 to 2013.

Design

Electronic search of the medical records to identify a cohort of patients with MEN1. Literature review based on current case reports.

Patients

Single case of PC in a cohort of 348 patients with MEN1. Ten cases of PC in patients with MEN1 reported in the literature.

Measurement

Clinical features of PC in patients with MEN1.

Results

The prevalence of PC in 348 patients with MEN1 was found to be 0·28% (95% CI, 0–1·4%). Based on the current published cases of PC in patients with MEN1, 54·5% were women, mean age at diagnosis was 48·3 years, and the serum PTH concentrations at least four times the upper limit of the reference range in 73% of the cases.

Conclusion

PC in patients with MEN 1 is rare with a prevalence of 0·28%, and the clinical features are similar to PC in patients without MEN1.
Safety, sterility and stability of direct‐from‐vial multiple dosing intravitreal injection of bevacizumab
Authors: Das Taraprasad , Volety Srinivas , Ahsan Saad M , Thakur Abhay K , Sharma Savitri , Padhi Tapas R , Basu Soumyava , Rao Ch Mohan
Published: December 2014

Background

This study aims to determine the stability, sterility and safety of bevacizumab multiple dosing from a single vial without prior aliquoting.

Methods

In‐vitro and human study. Six bevacizumab vials, used in multiple patients on a single day by direct withdrawal from the vial, and stored in 4°C up to a variable period, were tested for stability (high‐performance liquid chromatography; [HPLC]), sterility (culture), conformational stability by circular dichroism and fluorescence spectroscopy and the rubber cork structural integrity (electron microscopy [EM]).

Results

HPLC of all six samples of used bevacizumab and the control bevacizumab sample were similar; culture was negative; and the EM of rubber corks did not show an open communication. Spectroscopic studies indicated drug conformational stability. Further, there was no infection or inflammation in 221 consecutive patients (973 injections) when bevacizumab was stored at 4°C and used for one week.

Conclusion

Bevacizumab does not lose stability when stored at 4°C. It may be used for a week by direct withdrawal from the vial without fear of infection or inflammation if all standard precautions related to intravitreal injection are adhered to.