bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep tunneling in the unimolecular decay of CH3CHOO Criegee intermediates to OH radical products
Authors: Fang Yi , Liu Fang , Barber Victoria P. , Klippenstein Stephen J. , McCoy Anne B. , Lester Marsha I.
Published: December 2016

Unimolecular decay of Criegee intermediates produced in alkene ozonolysis is known to be a significant source of OH radicals in the troposphere. In this work, unimolecular decay of the methyl-substituted Criegee intermediate, syn-CH3CHOO, to OH products is shown to occur at energies significantly below the transition state barrier for a 1,4 hydrogen transfer that leads to these products [Y. Fang et al., J. Chem. Phys. 144, 061102 (2016)]. The rate of appearance of OH products arising from tunneling through the barrier is obtained through direct time-domain measurements following the vibrational activation of syn-CH3CHOO. IR excitation of syn-CH3CHOO at energies nearly 2000 cm−1 below the barrier is achieved through combination bands involving CH stretch and another lower frequency mode, and the resultant OH products are detected by UV laser-induced fluorescence. The observed syn-CH3CHOO combination bands in the 4100–4350 cm−1 region are identified by comparison with the computed IR absorption spectrum. The experimental decay rates are found to be ca. 106 s−1 in this deep tunneling regime, which is approximately 100-times slower than that in the vicinity of the barrier.The experimental results are consistent with statistical Rice-Ramsperger-Kassel-Marcus (RRKM) calculations of the microcanonical decay rates with tunneling through the barrier, and notable deviations may originate from the sparsity in the density of states for syn-CH3CHOO at lower energies. Thermal unimolecular decay of syn-CH3CHOO is predicted to have significant contribution from microcanonical rates at energies that are much below the barrier.
Naturally occurring branched-chain polyamines induce a crosslinked meshwork structure in a giant DNA
Authors: Muramatsu Akira , Shimizu Yuta , Yoshikawa Yuko , Fukuda Wakao , Umezawa Naoki , Horai Yuhei , Higuchi Tsunehiko , Fujiwara Shinsuke , Imanaka Tadayuki , Yoshikawa Kenichi
Published: December 2016

We studied the effect of branched-chain polyamines on the folding transition of genome-sized DNA molecules in aqueous solution by the use of single-molecule observation with fluorescence microcopy. Detailed morphological features of polyamine/DNA complexes were characterized by atomic force microscopy (AFM). The AFM observations indicated that branched-chain polyamines tend to induce a characteristic change in the higher-order structure of DNA by forming bridges or crosslinks between the segments of a DNA molecule. In contrast, natural linear-chain polyamines cause a parallel alignment between DNA segments. Circular dichroism measurements revealed that branched-chain polyamines induce the A-form in the secondary structure of DNA, while linear-chain polyamines have only a minimum effect. This large difference in the effects of branched- and linear-chain polyamines is discussed in relation to the difference in the manner of binding of these polyamines to negatively charged double-stranded DNA.
Zintl layer formation during perovskite atomic layer deposition on Ge (001)
Authors: Hu Shen , Lin Edward L. , Hamze Ali K. , Posadas Agham , Wu HsinWei , Smith David J. , Demkov Alexander A. , Ekerdt John G.
Published: December 2016

Using in situ X-ray photoelectron spectroscopy, reflection high-energy electron diffraction, and density functional theory, we analyzed the surface core level shifts and surface structure during the initial growth of ABO3 perovskites on Ge (001) by atomic layer deposition, where A = Ba, Sr and B = Ti, Hf, Zr. We find that the initial dosing of the barium- or strontium-bis(triisopropylcyclopentadienyl) precursors on a clean Ge surface produces a surface phase that has the same chemical and structural properties as the 0.5-monolayer Ba Zintl layer formed when depositing Ba by molecular beam epitaxy. Similar binding energy shifts are found for Ba, Sr, and Ge when using either chemical or elemental metal sources. The observed germanium surface core level shifts are consistent with the flattening of the initially tilted Ge surface dimers using both molecular and atomic metal sources. Similar binding energy shifts and changes in dimer tilting with alkaline earth metal adsorption are found with density functional theory calculations. High angle angular dark field scanning transmission microscopy images of BaTiO3, SrZrO3, SrHfO3, and SrHf0.55Ti0.45O3 reveal the location of the Ba (or Sr) atomic columns between the Ge dimers. The results imply that the organic ligands dissociate from the precursor after precursor adsorption on the Ge surface, producing the same Zintl template critical for perovskite growth on Group IV semiconductors during molecular beam epitaxy.
Picosecond time resolved conductance measurements of redox molecular junctions
Authors: Arielly Rani , Nachman Nirit , Zelinskyy Yaroslav , May Volkhard , Selzer Yoram
Published: December 2016

Due to bandwidth limitations of state of the art electronics, the transient transport properties of molecular junctions are experimentally a terra incognita, which can only be explored if novel picosecond current-probing techniques are developed. Here we demonstrate one such approach: the laser pulse-pair sequence scheme. The method is used to monitor in picosecond resolution the oxidation state of a redox molecule, 6-ferrocenyl-1-hexanethiol, within a junction and to quantify its redox rate constant, which is found to be (80 ps)−1.
A new method of probing mechanical losses of coatings at cryogenic temperatures
Authors: Galliou Serge , Deléglise Samuel , Goryachev Maxim , Neuhaus Leonhard , Cagnoli Gianpietro , Zerkani Salim , Dolique Vincent , Bon Jérémy , Vacheret Xavier , Abbé Philippe , Pinard Laurent , Michel Christophe , Karassouloff Thibaut , Briant Tristan , Cohadon Pierre-François , Heidmann Antoine , Tobar Michael E. , Bourquin Roger
Published: December 2016

A new method of probing mechanical losses and comparing the corresponding deposition processes of metallic and dielectric coatings in 1-100 MHz frequency range and cryogenic temperatures is presented. The method is based on the use of high-quality quartz acoustic cavities whose internal losses are orders of magnitude lower than any available coating nowadays. The approach is demonstrated for chromium, chromium/gold, and multilayer tantala/silica coatings. The Ta2O5/SiO2 coating has been found to exhibit a loss angle lower than 1.6 × 10−5 near 30 MHz at 4 K. The results are compared to the previous measurements.
Route toward high-speed nano-magnonics provided by pure spin currents
Authors: Divinskiy B. , Demidov V. E. , Demokritov S. O. , Rinkevich A. B. , Urazhdin S.
Published: December 2016

We study experimentally the possibility to utilize pulses of pure spin current, produced via the nonlocal spin injection mechanism, to generate short packets of spin waves propagating in nanoscale magnetic waveguides. Spatially and time-resolved micro-focus Brillouin light scattering spectroscopy measurements demonstrate that the excitation by spin current results in extremely fast transient response, enabling efficient generation of short spin-wave packets with duration down to a few nanoseconds. The proposed method opens a route for the implementation of high-speed magnonic systems for transmission and processing of information on the nanoscale.
Artifacts reduction in VIR/Dawn data
Authors: Carrozzo F. G. , Raponi A. , De Sanctis M. C. , Ammannito E. , Giardino M. , D’Aversa E. , Fonte S. , Tosi F.
Published: December 2016

Remote sensing images are generally affected by different types of noise that degrade the quality of the spectral data (i.e., stripes and spikes). Hyperspectral images returned by a Visible and InfraRed (VIR) spectrometer onboard the NASA Dawn mission exhibit residual systematic artifacts. VIR is an imaging spectrometer coupling high spectral and spatial resolutions in the visible and infrared spectral domain (0.25–5.0 μm). VIR data present one type of noise that may mask or distort real features (i.e., spikes and stripes), which may lead to misinterpretation of the surface composition. This paper presents a technique for the minimization of artifacts in VIR data that include a new instrument response function combining ground and in-flight radiometric measurements, correction of spectral spikes, odd-even band effects, systematic vertical stripes, high-frequency noise, and comparison with ground telescopic spectra of Vesta and Ceres. We developed a correction of artifacts in a two steps process: creation of the artifacts matrix and application of the same matrix to the VIR dataset. In the approach presented here, a polynomial function is used to fit the high frequency variations. After applying these corrections, the resulting spectra show improvements of the quality of the data. The new calibrated data enhance the significance of results from the spectral analysis of Vesta and Ceres.
Nonvolatile transtance change random access memory based on magnetoelectric P(VDF-TrFE)/Metglas heterostructures
Authors: Lu Peipei , Shang Dashan , Shen Jianxin , Chai Yisheng , Yang Chuansen , Zhai Kun , Cong Junzhuang , Shen Shipeng , Sun Young
Published: December 2016

Transtance change random access memory (TCRAM) is a type of nonvolatile memory based on the nonlinear magnetoelectric coupling effects of multiferroics. In this work, ferroelectric P(VDF-TrFE) thin films were prepared on Metglas foil substrates by the sol-gel technique to form multiferroic heterostructures. The magnetoelectric voltage coefficient of the heterostructure can be switched reproducibly to different levels between positive and negative values by applying selective electric-field pulses. Compared with bulk multiferroic heterostructures, the polarization switching voltage was reduced to 7 V. Our facile technological approach enables this organic magnetoelectric heterostructure as a promising candidate for the applications in multilevel TCRAM devices.
Modulation of graphene field effect by heavy charged particle irradiation
Authors: Cazalas Edward , Sarker Biddut K. , Childres Isaac , Chen Yong P. , Jovanovic Igor
Published: December 2016

Device architectures based on the two-dimensional material graphene can be used for sensing of electromagnetic and particle radiation. The sensing mechanism may be direct, by absorbance of radiation by the graphene or the immediately adjacent material, and indirect, via the field effect principle, whereby the change in conductivity within a semiconducting absorber substrate induces electric field change at graphene. Here, we report on a graphene field effect transistor (GFET) sensitive to heavy charged particle radiation (α particles) at MeV energies by use of the indirect sensing mechanism. Both the continuous and discrete changes of graphene are observed, and the latter are attributed to single α particle interactions with the GFET. While this study provides the basis for understanding of the irradiation effects, it also opens prospects for the use of GFETs as heavy charged particle detectors.
Electrostatic electron-doping yields superconductivity in LaOBiS2
Authors: Uesugi Eri , Nishiyama Saki , Goto Hidenori , Ota Hiromi , Kubozono Yoshihiro
Published: December 2016

Electrostatic carrier-doping is attracting serious attention as a meaningful technique for producing interesting electronic states in two-dimensional (2D) layered materials. Ionic-liquid gating can provide the critical carrier density required to induce the metal-insulator transition and superconductivity. However, the physical properties of only a few materials have been controlled by the electrostatic carrier-doping during the past decade. Here, we report an observation of superconductivity in a 2D layered material, LaOBiS2, achieved by the electrostatic electron-doping. The electron doping of LaOBiS2 induced metallic conductivity in the normally insulating LaOBiS2, ultimately led to superconductivity. The superconducting transition temperature, Tc, was 3.6 K, higher than the 2.7 K seen in LaO1-xFxBiS2 with an electron-doped BiS2 layer. A rapid drop in resistance (R) was observed at low temperature, which disappeared with the application of high magnetic fields, implying a superconducting state. This study reveals that electron-doping is an important technique for inducing superconductivity in 2D layered BiS2 materials.
N-channel field-effect transistors with an organic-inorganic layered perovskite semiconductor
Authors: Matsushima Toshinori , Mathevet Fabrice , Heinrich Benoît , Terakawa Shinobu , Fujihara Takashi , Qin Chuanjiang , Sandanayaka Atula S. D. , Ribierre Jean-Charles , Adachi Chihaya
Published: December 2016

Large electron injection barriers and electrode degradation are serious issues that need to be overcome to obtain n-channel operation in field-effect transistors with an organic-inorganic layered perovskite (C6H5C2H4NH3)2SnI4 semiconductor. By employing low-work-function Al source/drain electrodes and by inserting C60 layers between the perovskite semiconductor and the Al electrodes to reduce the injection barrier and to suppress the electrode degradation, we demonstrate n-channel perovskite transistors with electron mobilities of up to 2.1 cm2/V s, the highest value ever reported in spin-coated perovskite transistors. The n-channel transport properties of these transistors are relatively stable in vacuum but are very sensitive to oxygen, which works as electron traps in perovskite and C60 layers. In addition, grazing-incidence X-ray scattering and thermally stimulated current measurements revealed that crystallite size and electron traps largely affect the n-channel transport properties.
Communication: Trapping a proton in argon: Spectroscopy and theory of the proton-bound argon dimer and its solvation
Authors: McDonald D. C. , Mauney D. T. , Leicht D. , Marks J. H. , Tan J. A. , Kuo J.-L. , Duncan M. A.
Published: December 2016

Ion-molecule complexes of the form H+Arn are produced in pulsed-discharge supersonic expansions containing hydrogen and argon. These ions are analyzed and mass-selected in a reflectron spectrometer and studied with infrared laser photodissociation spectroscopy. Infrared spectra for the n = 3–7 complexes are characterized by a series of strong bands in the 900–2200 cm−1 region. Computational studies at the MP2/aug-cc-pVTZ level examine the structures, binding energies, and infrared spectra for these systems. The core ion responsible for the infrared bands is the proton-bound argon dimer, Ar–H+–Ar, which is progressively solvated by the excess argon. Anharmonic vibrational theory is able to reproduce the vibrational structure, identifying it as arising from the asymmetric proton stretch in combination with multiple quanta of the symmetric argon stretch. Successive addition of argon shifts the proton vibration to lower frequencies, as the charge is delocalized over more ligands. The Ar–H+–Ar core ion has a first solvation sphere of five argons.
Virtual Issue in Australian Journal of Botany: rare and threatened plant conversation and recovery
Authors: Broadhurst Linda , Coates David , Hoebee Susan , Edwards Trevor , Morgan John
Published: December 2016

Virtual Issues consist of previously published papers that are repackaged into an online themed collection. With appropriate marketing, and making them free for a limited time, these issues are a powerful tool that allow all readers to rediscover and access content already published. Release of this Virtual Issue of Australian Journal of Botany was timed to coincide with the 11th Australasian Plant Conservation Conference (APCC11), held on 14–18 November at the Royal Botanic Gardens, Melbourne. For more information, please visit: http://www.publish.csiro.au/bt/content/VirtualIssues.
For a radically usage-based diachronic construction grammar
Authors: Noël Dirk
Published: December 2016

This squib first sketches the state-of-the-art in diachronic construction grammar by tracing it back to two strands of research which it distinguishes as historical construction grammar and constructionist grammaticalization theory. It then differentiates between usage-based work in diachronic construction grammar that focuses on (frequency of) use and work that centres on knowledge. It is posited that, to arrive at truly (radically) usage-based models of change, one should separate individual knowledge, or internal systems/constructicons, from assumed-to-be-shared knowledge, or external systems/constructicons. Two us-age-based models of constructional change, “Traugott/Trousdale” and “Fischer”, are assessed against this criterion. While the former explicitly distinguishes between individual and “community” knowledge, it is judged to confuse these by assigning a central role to reanalysis/neoanalysis. The latter model revolves around the role of analogy and is less confined to a semasiological account of the linear developments dictated by an external outlook.
Modelling pronominal gender agreement in Dutch
Authors: Rădulescu Roxana , Beuls Katrien
Published: December 2016

In the context of cultural evolution, we propose a multi-agent model that allows, through pair-wise interactions between homogeneous individuals of a population, to simulate the shift from a syntactic towards a semantic pronominal agreement system. We explore various gender mapping and learning mechanisms that can allow the agents to form a new agreement system using their semantic knowledge about the world. We investigate whether our strategies can yield cohesive clusterings over the semantic space. We notice that the system reaches full convergence in terms of gender preference at population level and that there are multiple successful ways of dividing the semantic space, including one that reflects the so-calledindividuation hierarchy, a case attested by a study of a spoken language data.
Heidegger and post-colonial fascism
Authors: Love Jeff , Meng Michael
Published: December 2016

Alexander Dugin is considered a fringe figure in contemporary Russia. Yet, his writings exert considerable influence and develop a virulent nationalism that exploits the vocabulary of post-colonial resistance in an unaccustomed way. Dugin should not be ignored, and this article gives a brief account of Dugin's peculiar brand of post-colonial thinking by reference to its central source: Martin Heidegger. Specifically, the article examines how Dugin adapts the anti-metaphysical thinking of Heidegger's most radical work of the 1930s – a thinking that seeks to renew Western thought in an other beginning – to the context of modern Russia as it tries to free itself from Western (American) domination. Dugin aims at nothing less than the creation of a new Russian identity and destiny that will not only save Russia but also, in a nod to Heidegger, renew the Western tradition itself from the “outside.” If Dugin's political project is ambitious, so is his interpretation of Heidegger which attempts to bring out the full radicality of Heidegger's thinking, both as philosophy and as politics.
Active Vertex Model for Cell-Resolution Description of Epithelial Tissue Mechanics
Authors: Barton Daniel L. , Henkes Silke , Weijer Cornelis J. , Sknepnek Rastko
Published: December 2016

We introduce an Active Vertex Model (AVM) for cell-resolution studies of the mechanics of confluent epithelial tissues consisting of tens of thousands of cells, with a level of detail inaccessible to similar methods. The AVM combines the Vertex Model for confluent epithelial tissues with active matter dynamics. This introduces a natural description of the cell motion and accounts for motion patterns observed on multiple scales. Furthermore, cell contacts are generated dynamically from positions of cell centres. This not only enables efficient numerical implementation, but provides a natural description of the T1 transition events responsible for local tissue rearrangements. The AVM also includes cell alignment, cell-specific mechanical properties, cell growth, division and apoptosis. In addition, the AVM introduces a flexible, dynamically changing boundary of the epithelial sheet allowing for studies of phenomena such as the fingering instability or wound healing. We illustrate these capabilities with a number of case studies.
Investigating telemonitoring practice: a proposed work-applied methodology
Authors: Jurman Paul , Shafei Ingy
Published: December 2016

Purpose

Diabetes is regarded as a global epidemic with 382 million people globally suffering from diabetes. It also has major implications on patients’ quality of life. There are also high cost of treatment associated with diabetes for both patient and healthcare provider. Telemonitoring represents an excellent technology opportunity to redefine health care delivery. Using technology for home-based care promises the ability to deliver more cost effective care whilst also enhancing quality of care and patient satisfaction. The paper aims to discuss these issues.

Design/methodology/approach

The current research aims to contribute to the methodological design of action research projects in their use to implementation health technologies such as telemonitoring. In particular, it seeks create a model which can be used to demonstrate the efficacy of the use of the action research method as a viable alternative to the traditional randomised control trials methodology currently employed in healthcare.

Findings

The paper contributes towards the methodological design to investigate the area of practice making use of the telemonitoring programme within a Victorian Health Services Network using action research.

Originality/value

It intends to address the research problem of the low utilisation of telemonitoring within Monash Health as a whole, and more specifically within the diabetes unit. In this context the research intends to utilise the benefits of telemonitoring to improve clinical outcomes of patients by increasing insulin stabilisation. It is also intended the research organisation benefits by increased efficiency by decreasing clinical workforce time spent on managing patient insulin data.
A radical agenda for enabling organisation transformation through work-applied learning
Authors: Critten Peter
Published: December 2016

Purpose

The purpose of this paper is to challenge how we have traditionally thought about organisations and introduce two frameworks to enable us to understand how change in organisations might be facilitated better.

Design/methodology/approach

The paper discusses organisations as complex adaptive systems and uses complexity theory to inform two new frameworks for facilitating organisational learning and change.

Findings

In order for organisational learning to occur we need to change our mind-set of how we see organisations and to think of learning not just as individual but also as generative “communicative action” that emerge out of collaborative relationships.

Research limitations/implications

The frameworks proposed are grounded in organisational learning literature and the experience of the author. The proposed agenda for organisational learning has yet to be acted upon and evaluated.

Practical implications

The frameworks can be used to enhance understanding of learning and change in organisations. The agenda for enabling organisational transformation identifies key steps to put the ideas developed in the paper into practice.

Social implications

The approach advocated for use within organisations is one of empowerment and collaboration rather than top down direction.

Originality/value

The paper introduces new frameworks and a practical agenda to bring about organisational transformation through work-applied learning.
Reviving the ubuntu spirit in landscapes of practice: evidence from deep within the forest
Authors: Wall Tony
Published: December 2016

Purpose

The purpose of this paper is to offer a humanistic perspective on practice and prompts us to think about some of the implications for a more connected perspective on work and learning.

Design/methodology/approach

This paper takes literary and metaphoric approach to discussion to evoke and engage the audience. It uses the primary device of the thriving of forests to prompt reflection.

Findings

This paper prioritises concepts of sustainability and responsibility and aims to prompt the reader in thinking about connectedness in relation to their own life and work.

Originality/value

This paper attempts to challenge an overly economic concept of work and learning, and offers an alternative humanistic metaphor to evoke and engage the reader. It values and encourages an experimental form of writing.
Factitious Disorder in a Patient Claiming to be a Sexually Sadistic Serial Killer
Authors: Fischer Christopher A. , Beckson Mace , Dietz Park
Published: December 2016

Factitious disorder involves the conscious simulation of psychological or physiological symptoms of illness, for the purpose of fulfilling the unconscious desire to be taken care of or to assume the “sick role.” Typically patients with factitious disorder simulate conditions that are designed to arouse feelings of empathy in care providers with the intention to engage them in caretaking. However, patients might also simulate conditions that arouse revulsion or rejection and still meet full diagnostic criteria for factitious disorder. In this case report, we present a patient who fabricated an elaborate history of being a sexually sadistic serial killer with homicidal ideation with the intention of obtaining personal attention, nurturance, and empathy from his psychotherapist. However, given the nature of his feigned condition, the patient frightened the very person whom he sought to engage in caretaking.
Bioactive secondary metabolites with multiple activities from a fungal endophyte
Authors: Bogner Catherine W. , Kamdem Ramsay S.T. , Sichtermann Gisela , Matthäus Christian , Hölscher Dirk , Popp Jürgen , Proksch Peter , Grundler Florian M.W. , Schouten Alexander
Published: December 2016

In order to replace particularly biohazardous nematocides, there is a strong drive to finding natural product‐based alternatives with the aim of containing nematode pests in agriculture. The metabolites produced by the fungal endophyte Fusarium oxysporum 162 when cultivated on rice media were isolated and their structures elucidated. Eleven compounds were obtained, of which six were isolated from a Fusarium spp. for the first time. The three most potent nematode‐antagonistic compounds, 4‐hydroxybenzoic acid, indole‐3‐acetic acid (IAA) and gibepyrone D had LC50 values of 104, 117 and 134 μg ml−1, respectively, after 72 h. IAA is a well‐known phytohormone that plays a role in triggering plant resistance, thus suggesting a dual activity, either directly, by killing or compromising nematodes, or indirectly, by inducing defence mechanisms against pathogens (nematodes) in plants. Such compounds may serve as important leads in the development of novel, environmental friendly, nematocides.
Efficacy of anakinra in an adult patient with recurrent pericarditis and cardiac tamponade as initial manifestations of tumor necrosis factor receptor‐associated periodic syndrome due to the R92Q TNFRSF1A variant
Authors: Camprubí Daniel , Mitjavila Francesca , Arostegui Juan I. , Corbella Xavier
Published: December 2016

Tumor necrosis factor receptor‐associated periodic syndrome (TRAPS) is a dominantly inherited autoinflammatory disease caused by TNFRSF1A mutations. Patients with TRAPS suffer from recurrent, long episodes with fever, arthralgia/arthritis, migratory myalgias, abdominal pain, serositis, conjunctivitis and migratory erythematous skin rash. More than 70 different TNFRSF1A mutations have been reported to date, and as consequence of its genetic heterogeneity, TRAPS shows a variable phenotypic expression. Among TNFRSF1A variants, the low‐penetrance p.Arg92Gln variant represents the most commonly detected, and is typically associated with mild and short episodes, with a higher tendency to spontaneous resolution, and less familial association than the structural TNFRSF1A mutations. Pericardial involvement is rare but a well‐known clinical feature of TRAPS, with a significant increased rate in those adult patients in whom the onset of the disease occurred during adulthood. Moreover, idiopathic recurrent acute pericarditis has also been occasionally described as a clinical presentation of TRAPS. However, cardiac tamponade is an unusual initial manifestation of the disease. Herein, we present a brief review based on the description of the exceptional case of a 35‐year‐old female patient who presented with recurrent pericardial effusions and cardiac tamponade. TNFRSF1A analyses showed a heterozygous genotype for the low‐penetrance p.Arg92Gln variant. Due to disease severity, the patient was treated with the anti‐interleukin‐1 drug anakinra, showing a prompt resolution of her clinical manifestations.
The Impact of Peer Substance Use and Polygenic Risk on Trajectories of Heavy Episodic Drinking Across Adolescence and Emerging Adulthood
Authors: Li James J. , Cho Seung Bin , Salvatore Jessica E. , Edenberg Howard J. , Agrawal Arpana , Chorlian David B. , Porjesz Bernice , Hesselbrock Victor ,   COGA Investigators, Dick Danielle M.
Published: December 2016

Background

Heavy episodic drinking is developmentally normative among adolescents and young adults, but is linked to adverse consequences in later life, such as drug and alcohol dependence. Genetic and peer influences are robust predictors of heavy episodic drinking in youth, but little is known about the interplay between polygenic risk and peer influences as they impact developmental patterns of heavy episodic drinking.

Methods

Data were from a multisite prospective study of alcohol use among adolescents and young adults with genome‐wide association data (n = 412). Generalized linear mixed models were used to characterize the initial status and slopes of heavy episodic drinking between age 15 and 28. Polygenic risk scores (PRS) were derived from a separate genome‐wide association study for alcohol dependence and examined for their interaction with substance use among the adolescents’ closest friends in predicting the initial status and slopes of heavy episodic drinking.

Results

Close friend substance use was a robust predictor of adolescent heavy episodic drinking, even after controlling for parental knowledge and peer substance use in the school. PRS were predictive of the initial status and early patterns of heavy episodic drinking in males, but not in females. No interaction was detected between PRS and close friend substance use for heavy episodic drinking trajectories in either males or females.

Conclusions

Although substance use among close friends and genetic influences play an important role in predicting heavy episodic drinking trajectories, particularly during the late adolescent to early adult years, we found no evidence of interaction between these influences after controlling for other social processes, such as parental knowledge and broader substance use among other peers outside of close friends. The use of longitudinal models and accounting for multiple social influences may be crucial for future studies focused on uncovering gene–environment interplay. Clinical implications are also discussed.
Establishment of in vitro model of erectile dysfunction for the study of high‐glucose‐induced angiopathy and neuropathy
Authors: Yin G. N. , Park S.‐H. , Song K.‐M. , Limanjaya A. , Ghatak K. , Minh N. N. , Ock J. , Ryu J.‐K. , Suh J.‐K.
Published: December 2016

Penile erection requires complex interaction between vascular endothelial cells, smooth muscle cells, pericytes, and autonomic nerves. Diabetes mellitus is one of the most common causes of erectile dysfunction (ED) and multiple pathogenic factors, such as cavernous angiopathy and autonomic neuropathy, are associated with diabetic ED. Although a variety of animal models of diabetic ED play an important role in understanding pathophysiologic mechanisms of diabetes‐induced ED, these animal models have limitations for addressing the exact cellular or molecular mechanisms involved in ED. Therefore, we established an in vitro model of ED for the study of high‐glucose‐induced angiopathy and neuropathy. We successfully isolated and cultivated mouse cavernous endothelial cells (MCECs) and mouse cavernous pericytes (MCPs). The cells were exposed to the normal‐glucose (5 mmoL) or high‐glucose (30 mmoL) condition for 48 h. In vitro matrigel assay revealed impairments in tube formation in primary cultured MCECs or MCPs exposed to high‐glucose condition. To study cellular interaction between MCECs and MCPs, co‐culture systems including indirect contact, indirect non‐contact, and direct mixed co‐culture system, were established. We observed impaired tube formation and increased permeability in MCECs‐MCPs co‐culture exposed to high‐glucose condition. To evaluate the effect of high‐glucose on neurite sprouting, the mouse major pelvic ganglion (MPG) tissue was harvested and cultivated in matrigel. Neurite outgrowth and nNOS‐positive nerve fibers were significantly lower in MPG tissues exposed to the high‐glucose condition than in the tissues exposed to the normal‐glucose condition. We believe that in vitro model of ED will aid us to understand the role of each cellular component in the pathogenesis of diabetic ED, and also be a useful tool for determining the efficacy of candidate therapeutics targeting vascular or neuronal function. This model would present a new avenue for drug discovery and development of novel therapeutic modalities for erectile dysfunction.
The Fertility Assessment and Counseling Clinic – does the concept work? A prospective 2‐year follow‐up study of 519 women
Authors: Birch Petersen Kathrine , Maltesen Thomas , Forman Julie L. , Sylvest Randi , Pinborg Anja , Larsen Elisabeth C. , Macklon Kirsten T. , Nielsen Henriette S. , Hvidman Helene W. , Nyboe Andersen Anders
Published: December 2016

Introduction

The Fertility Assessment and Counseling (FAC) Clinic was initiated to provide women with information about their current fertility status to prevent infertility and smaller families than desired. The aim was to study the predictive value of a risk assessment score based on known fertility risk factors in terms of time to pregnancy.

Material and methods

Prospective cohort study of the first 570 women attending the FAC Clinic from 2011 to 2013 at Rigshospitalet, Denmark. A consultation included: risk assessment score sheet with items on infertility risk factors, anti‐Müllerian hormone and ultrasound. The risk score was categorized as low, medium or high. After 2 years an email‐based questionnaire was distributed regarding subsequent pregnancies.

Results

The follow‐up questionnaire was answered by 519 women (91.1%). The mean age was 35 years and 38% were single at inclusion. The majority (67.8%, 352/519) tried to conceive within 2 years after attending the FAC Clinic. At follow up, 73.6% (259/352) had achieved a pregnancy, 21% (74/352) were still trying and 5.4% (19/352) had given up. Two‐thirds (65%) with only low risk scores conceived spontaneously within 12 months, although this figure was only 32% for women with at least one high risk score (n = 82). Accordingly, presence of at least one high risk score reduced the odds of achieving a pregnancy within 12 months by 75% (OR 0.25, 95% CI 0.12–0.52).

Conclusion

The new FAC Clinic concept seems usable and offers a tool for fertility experts to guide women on how to fulfill their reproductive life‐plan.
Area‐based study shows most parents follow advice to reduce risk of sudden infant death syndrome
Authors: Strömberg Celind Frida , Wennergren Göran , Möllborg Per , Goksör Emma , Alm Bernt
Published: December 2016

Aim

Guidance on reducing the risk of sudden infant death syndrome (SIDS) was successfully introduced to a number of countries in the early 1990s. The most important recommendations were supine sleeping for infants and non‐smoking for mothers. This 2012–2014 study examined adherence to the national Swedish SIDS advice.

Methods

We asked 1000 parents with infants registered at child healthcare centres in western Sweden to complete a questionnaire on infant care from birth to 12 months of age.

Results

We analysed 710 responses and found that, in the first three months, 1.3% of the infants were placed in the prone sleeping position and 14.3% were placed on their side. By three to five months, this had risen to 5.6% and 23.6%. In the first three months, 83.1% were breastfed, 84.1% used a pacifier and 44.2% shared their parents' bed, while 5.8% slept in another room. Bed sharing was more likely if infants were breastfed and less likely if they used pacifiers. During pregnancy, 2.8% of the mothers smoked and the mothers who had smoked during pregnancy were less likely to bed share.

Conclusion

Overall adherence to the SIDS advice was good, but both prone and side sleeping practices should be targeted.
Are behaviour problems in extremely low‐birthweight children related to their motor ability?
Authors: Danks Marcella , Cherry Kate , Burns Yvonne R. , Gray Peter H.
Published: December 2016

Aim

To investigate whether behaviour problems are independently related to mild motor impairment in 11–13‐year‐old children born preterm with extremely low birthweight (ELBW).

Methods

The cross‐sectional study included 48 (27 males) non‐disabled, otherwise healthy ELBW children (<1000 g) and 55 (28 males) term‐born peers. Parents reported behaviour using the Child Behaviour Checklist (CBCL). Children completed the Movement Assessment Battery for Children (Movement ABC).

Results

Extremely low birthweight children had poorer behaviour scores (CBCL Total Problem T score: mean difference = 5.89, 95% confidence interval = 10.29, 1.49, p = 0.009) and Movement ABC Total Motor Impairment Scores (ELBW group median = 17.5, IQR = 12.3; term‐born group median = 7.5, IQR = 9, p < 0.01) than term‐born peers. Behaviour was related to motor score (regression coefficient 2.16; 95% confidence interval 0.34, 3.97, p = 0.02) independent of gender, socio‐economic factors or birthweight. Motor score had the strongest association with attention (ρ = 0.51; p < 0.01) and social behaviours (ρ = 0.50; p < 0.01).

Conclusion

Behaviour problems of otherwise healthy 11‐ to 13‐year‐old ELBW children are not related to prematurity independent of their motor difficulties. Supporting improved motor competence in ELBW preteen children may support improved behaviour, particularly attention and social behaviours.
Effectiveness of the repeated administration of scopolamine ointment on clozapine‐induced hypersalivation in patients with treatment‐resistant schizophrenia: A preliminary study
Authors: Takeuchi Ippei , Hanya Manako , Uno Junji , Fujita Kiyoshi , Kamei Hiroyuki
Published: December 2016

Introduction

This study investigated the efficacy of scopolamine (an anticholinergic agent) ointment against clozapine‐induced hypersalivation.

Methods

The patients enrolled in this study consisted of 10 clozapine‐treated schizophrenia patients and 10 healthy adult men. A prospective, randomized, double‐blind, crossover, placebo‐controlled clinical trial was designed.

Results

A total of 10 patients and 10 healthy adult men completed the study. No significant reduction in the saliva production of the clozapine‐treated patients was observed; however, that of the healthy adult men decreased significantly.

Discussion

Scopolamine ointment was not effective against clozapine‐induced hypersalivation. A further study is necessary for confirming its effect.
Molecular typing for blood group antigens within 40 min by direct polymerase chain reaction from plasma or serum
Authors: Wagner Franz F. , Flegel Willy A. , Bittner Rita , Döscher Andrea
Published: December 2016

Determining blood group antigens by serological methods may be unreliable in certain situations, such as in patients after chronic or massive transfusion. Red cell genotyping offers a complementary approach, but current methods may take much longer than conventional serological typing, limiting their utility in urgent situations. To narrow this gap, we devised a rapid method using direct polymerase chain reaction (PCR) amplification while avoiding the DNA extraction step. DNA was amplified by PCR directly from plasma or serum of blood donors followed by a melting curve analysis in a capillary rapid‐cycle PCR assay. We evaluated the single nucleotide polymorphisms underlying the clinically relevant Fya, Fyb, Jka and Jkb antigens, with our analysis being completed within 40 min of receiving a plasma or serum sample. The positive predictive value was 100% and the negative predictive value at least 84%. Direct PCR with melting point analysis allowed faster red cell genotyping to predict blood group antigens than any previous molecular method. Our assay may be used as a screening tool with subsequent confirmatory testing, within the limitations of the false‐negative rate. With fast turnaround times, the rapid‐cycle PCR assay may eventually be developed and applied to red cell genotyping in the hospital setting.
Phase II clinical trial of peptide cocktail therapy for patients with advanced pancreatic cancer: VENUS‐PC study
Authors: Suzuki Nobuaki , Hazama Shoichi , Iguchi Haruo , Uesugi Kazuhiro , Tanaka Hiroaki , Hirakawa Kosei , Aruga Atsushi , Hatori Takashi , Ishizaki Hidenobu , Umeda Yuzo , Fujiwara Toshiyoshi , Ikemoto Tetsuya , Shimada Mitsuo , Yoshimatsu Kazuhiko , Shimizu Ryoichi , Hayashi Hiroto , Sakata Koichiro , Takenouchi Hiroko , Matsui Hiroto , Shindo Yoshitaro , Iida Michihisa , Koki Yasunobu , Arima Hideki , Furukawa Hiroyuki , Ueno Tomio , Yoshino Shigefumi , Nakamura Yusuke , Oka Masaaki , Nagano Hiroaki
Published: December 2016

We previously conducted a phase I clinical trial combining the HLA‐A*2402‐restricted KIF20A‐derived peptide vaccine with gemcitabine for advanced pancreatic cancer (PC) and confirmed its safety and immunogenicity in cancer patients. In this study, we conducted a multicenter, single‐armed, phase II trial using two antiangiogenic cancer vaccines targeting VEGFR1 and VEGFR2 in addition to the KIF20A peptide. We attempted to evaluate the clinical benefit of the cancer vaccination in combination with gemcitabine. Chemotherapy naïve PC patients were enrolled to evaluate primarily the 1‐year survival rate, and secondarily overall survival (OS), progression free survival (PFS), response rate (RR), disease control rate (DCR) and the peptide‐specific immune responses. All enrolled patients received therapy without the HLA‐A information, and the HLA genotypes were used for classification of the patients. Between June 2012 and May 2013, a total of 68 patients were enrolled. No severe systemic adverse effects of Grade 3 or higher related to these three peptides were observed. The 1‐year survival rates between the HLA‐A*2402‐matched and ‐unmatched groups were not significantly different. In the HLA‐A*2402 matched group, patients showing peptide‐specific CTL induction for KIF20A or VEGFR1 showed a better prognosis compared to those without such induction (P = 0.023, P = 0.009, respectively). In the HLA‐A*2402‐matched group, the patients who showed a strong injection site reaction had a better survival rate (P = 0.017) compared to those with a weak or no injection site reaction. This phase II study demonstrated that this therapeutic peptide cocktail might be effective in patients who demonstrate peptide‐specific immune reactions although predictive biomarkers are needed for patient selection in its further clinical application.
Concomitant alterations of metabolic parameters, cardiovascular risk factors and altered cortisol secretion in patients with adrenal incidentalomas during prolonged follow‐up
Authors: Papanastasiou Labrini , Alexandraki Krystallenia Ι. , Androulakis Ioannis I. , Fountoulakis Stelios , Kounadi Theodora , Markou Athina , Tsiavos Vaios , Samara Christianna , Papaioannou Theodoros G. , Piaditis George , Kaltsas Gregory
Published: December 2016

Objective

Adrenal incidentalomas (AI) are associated with metabolic and hormonal abnormalities, most commonly autonomous cortisol secretion (ACS). Data regarding alterations of insulin resistance (IR) and ACS after prolonged follow‐up are limited. We investigated the evolution of IR, cortisol secretion and ACS development in patients with AI during prolonged follow‐up.

Design

Prospective study in a tertiary hospital.

Patients and measurements

Seventy‐one patients with AI [51 nonfunctioning (NFAI) and 20 ACS] and 5·54 ± 1·7 years follow‐up underwent testing for ACS and oral glucose tolerance test to determine IR indices and adrenal imaging.

Results

At follow‐up, 16/51 (31%) NFAI patients converted to ACS, while two with previous ACS reverted to NFAI; 21% (7/33) of patients who did not covert to ACS exhibited high urinary‐free cortisol (H‐UFC) levels. All AI patients developed deterioration of IR irrespective of their cortisol secretory status. Eight patients developed newly diagnosed type 2 diabetes (9·8% NFAI and 15% ACS, respectively) and 14 IR (17·6% NFAI and 25% ACS, respectively). Adenoma size increased from 2·1 ± 0·8 to 2·3 ± 0·8 cm, whereas IR correlated with postdexamethasone cortisol level and adenoma size increase. IR showed an incremental continuum trend from normal UFC (Ν‐UFC), to H‐UFC, C‐ACS and ACS patients.

Conclusions

New‐onset ACS developed in 31% patients with NFAI, whereas 21% of NFAI patients had H‐UFC levels. All AI patients as a group and the subgroups of N‐UFC, H‐UFC, C‐ACS and ACS patients developed deterioration of metabolic parameters during follow‐up that was more prominent in ACS patients.
‘En face’ ex vivo reflectance confocal microscopy to help the surgery of basal cell carcinoma of the eyelid
Authors: Espinasse Marine , Cinotti Elisa , Grivet Damien , Labeille Bruno , Prade Virginie , Douchet Catherine , Cambazard Frédéric , Thuret Gilles , Gain Philippe , Perrot Jean Luc
Published: December 2016

Background

Ex vivo confocal microscopy is a recent imaging technique for the perioperative control of skin tumour margins. Up to date, it has been used in the fluorescence mode and with vertical sections of the specimen margins. The aim of this study was to evaluate its use in the reflectance mode and with a horizontal (‘en face’) scanning of the surgical specimen in a series of basal cell carcinoma of the eyelid.

Design

Prospective consecutive cohort study was performed at the University Hospital of Saint‐Etienne, France.

Participants

Forty‐one patients with 42 basal cell carcinoma of the eyelid participated in this study.

Methods

Basal cell carcinomas were excised with a 2‐mm‐wide clinically safe margin. The surgical specimens were analysed under ex vivo confocal microscopy in the reflectance mode and with an en face scanning in order to control at a microscopic level if the margins were free from tumour invasion. Histopathogical examination was later performed in order to compare the results.

Main Outcome Measures

Sensitivity and specificity of ex vivo confocal microscopy for the presence of tumour‐free margins.

Results

Ex vivo confocal microscopy results were consistent with histopathology in all cases (tumour‐free margins in 40 out of 42 samples; sensitivity and specificity of 100%).

Conclusions

Ex vivo confocal microscopy in the reflectance mode with an ‘en face’ scanning can control tumour margins of eyelid basal cell carcinomas and optimize their surgical management. This procedure has the advantage on the fluorescent mode of not needing any contrast agent to examine the samples.