bluuebunny/crossref_metadata_2025 huggingface dataset:
Trading direct for indirect defense? Phytochrome B inactivation in tomato attenuates direct anti‐herbivore defenses whilst enhancing volatile‐mediated attraction of predators
Authors: Cortés Leandro E. , Weldegergis Berhane T. , Boccalandro Hernán E. , Dicke Marcel , Ballaré Carlos L.
Published: October 2016

Under conditions of competition for light, which lead to the inactivation of the photoreceptor phytochrome B (phyB), the growth of shade‐intolerant plants is promoted and the accumulation of direct anti‐herbivore defenses is down‐regulated. Little is known about the effects of phyB on emissions of volatile organic compounds (VOCs), which play a major role as informational cues in indirect defense.

We investigated the effects of phyB on direct and indirect defenses in tomato (Solanum lycopersicum) using two complementary approaches to inactivate phyB: illumination with a low red to far‐red ratio, simulating competition, and mutation of the two PHYB genes present in the tomato genome.

Inactivation of phyB resulted in low levels of constitutive defenses and down‐regulation of direct defenses induced by methyl jasmonate (MeJA). Interestingly, phyB inactivation also had large effects on the blends of VOCs induced by MeJA. Moreover, in two‐choice bioassays using MeJA‐induced plants, the predatory mirid bug Macrolophus pygmaeus preferred VOCs from plants in which phyB was inactivated over VOCs from control plants.

These results suggest that, in addition to repressing direct defense, phyB inactivation has consequences for VOC‐mediated tritrophic interactions in canopies, presumably attracting predators to less defended plants, where they are likely to find more abundant prey.
Design and Simulation of Passive Thermal Management System for Lithium-Ion Battery Packs on an Unmanned Ground Vehicle
Authors: Parsons Kevin K. , Mackin Thomas J.
Published: October 2016

The transient thermal response of a 15-cell, 48 V, lithium-ion battery pack for an unmanned ground vehicle (UGV) was simulated using ANSYS fluent. Heat generation rates and specific heat capacity of a single cell were experimentally measured and used as input to the thermal model. A heat generation load was applied to each battery, and natural convection film boundary conditions were applied to the exterior of the enclosure. The buoyancy-driven natural convection inside the enclosure was modeled along with the radiation heat transfer between internal components. The maximum temperature of the batteries reached 65.6 °C after 630 s of usage at a simulated peak power draw of 3600 W or roughly 85 A. This exceeds the manufacturer's maximum recommended operating temperature of 60 °C. We present a redesign of the pack that incorporates a passive thermal management system consisting of a composite expanded graphite (EG) matrix infiltrated with a phase-changing paraffin wax. The redesigned battery pack was similarly modeled, showing a decrease in the maximum temperature to 50.3 °C after 630 s at the same power draw. The proposed passive thermal management system kept the batteries within their recommended operating temperature range.
Dye-Sensitized Solar Cell Using Saffron Petal Extract as a Novel Natural Sensitizer
Authors: Hosseinpanahi Kambiz , Abbaspour-Fard Mohammad Hossein , Feizy Javad , Reza Golzarian Mahmood
Published: October 2016

Natural dye extract of the saffron petal, purified by solid-phase extraction (SPE) technique, has been studied as a novel sensitizing dye to fabricate TiO2 nanoparticles-based dye-sensitized solar cells (DSSC). The extract was characterized using ultraviolet–visible (UV–Vis) and Fourier transform infrared (FTIR) spectroscopies to confirm the presence of anthocyanins in saffron petals. The typical current–voltage and the incident photon to current efficiency (IPCE) curves were also provided for the fabricated cell. The saffron petal extract exhibited an open-circuit voltage (Voc) of 0.397 V, short circuit current density (Jsc) of 2.32 mA/cm2, fill factor (FF) of 0.71, and conversion efficiency of 0.66%, which are fairly good in comparison with the other similar natural dye-sensitized solar cells. These are mainly due to the improved charge transfer between the dye extract of saffron petal and the TiO2 anode surface. Considering these results, it can be concluded that the use of saffron petal dye as a sensitizer in DSSC is a promising method for providing clean energy from performance, environmental friendliness, and cost points of view.
Design Optimization of a Sorption Integrated Sydney Type Vacuum Tube Collector
Authors: Hallström Olof
Published: October 2016

In order to reach the targets on emissions set by the European Commission, both new and existing buildings must reduce their fossil fuel inputs. Solar thermal cooling supplying on-site renewable heating and cooling could potentially contribute toward this goal. In this paper, a novel concept for solar thermal cooling providing efficient coproduction of cooling and heating based on sorption integrated vacuum tube collectors is proposed. A prototype collector has been constructed and tested in a solar laboratory based on a method developed specifically for sorption integrated collectors. From the test results, the key performance parameters have been determined and used to calibrate a mathematical model for trnsys environment. System simulation has been conducted to optimize the collector and sorption module configuration by performing a parametric study where different vacuum tube center–center (C–C) distances and sorption module designs are tested for a generic hotel in Ankara, Turkey. The parametric study showed that the heating and cooling output per year can be as high as 1000 kWh/m2 for solar fractions above 50%, and that the output per sorption module compared to the prototype can more than double with an optimized design. Furthermore, cooling conversion efficiencies defined as total cooling output per total solar insolation can be as high as 26% while simultaneously converting 35–40% of the incident solar energy into useful hot water.
Geoacoustic inversion using low frequency broadband acoustic measurements from L-shaped arrays in the Shallow Water 2006 Experiment
Authors: Wan Lin , Badiey Mohsen , Knobles David P.
Published: October 2016

When using geoacoustic inversion methods, one objective function may not result in a unique solution of the inversion problem because of the ambiguity among the unknown parameters. This paper utilizes acoustic normal mode dispersion curves, mode shapes, and modal-based longitudinal horizontal coherence to define a three-objective optimization problem for geoacoustic parameter estimation. This inversion scheme is applied to long-range combustive sound source data obtained from L-shaped arrays deployed on the New Jersey continental shelf in the summer of 2006. Based on the sub-bottom layering structure from the Compressed High-Intensity Radiated Pulse reflection survey at the experimental site, a two-layer (sand ridge overlaying a half-space basement) range-independent sediment model is utilized. The ambiguities of the sound speed, density, and depth of the sand ridge layer are partially removed by minimizing these objective functions. The inverted seabed sound speed over a frequency range of 15–170 Hz is comparable to the ones from direct measurements and other inversion methods in the same general area. The inverted seabed attenuation shows a nonlinear frequency dependence expressed as αb=0.26f1.55(dB/m) from 50 to 500 Hz or αb=0.32f1.65(dB/m) from 50 to 250 Hz, where f is in kHz.
High Prevalence of Dehydration and Inadequate Nutritional Knowledge Among University and Club Level Athletes
Authors: Magee Pamela Jane , Gallagher Alison M. , McCormack Jacqueline M.
Published: October 2016

Although dehydration of ≥ 2% body weight (BW) loss significantly impairs endurance performance, dehydration remains prevalent among athletes and may be owing to a lack of knowledge in relation to fluid requirements. The aim of this study was to assess the hydration status of university/club level athletes (n = 430) from a range of sports/activities (army officer cadet training; bootcamp training; cycling; Gaelic Athletic Association camogie, football and hurling; golf; hockey; netball; rugby; running (sprinting and endurance); Shotokan karate and soccer) immediately before and after training/competition and to assess their nutritional knowledge. Urine specific gravity (USG) was measured immediately before and after exercise and BW loss during exercise was assessed. Nutritional knowledge was assessed using a validated questionnaire. 31.9% of athletes commenced exercise in a dehydrated state (USG >1.020) with 43.6% of participants dehydrated posttraining/competition. Dehydration was particularly prevalent (>40% of cohort) among karateka, female netball players, army officer cadets, and golfers. Golfers that commenced a competitive 18 hole round dehydrated took a significantly higher number of strokes to complete the round in comparison with their euhydrated counterparts (79.5 ± 2.1 vs. 75.7 ± 3.9 strokes, p = .049). Nutritional knowledge was poor among participants (median total score [IQR]; 52.9% [46.0, 59.8]), albeit athletes who were euhydrated at the start of exercise had a higher overall score in comparison with dehydrated athletes (55.2% vs. 50.6%, p = .001). Findings from the current study, therefore, have significant implications for the education of athletes in relation to their individual fluid requirements around exercise.
Dietary Protein Intake and Distribution Patterns of Well-Trained Dutch Athletes
Authors: Gillen Jenna B. , Trommelen Jorn , Wardenaar Floris C. , Brinkmans Naomi Y.J. , Versteegen Joline J. , Jonvik Kristin L. , Kapp Christoph , de Vries Jeanne , van den Borne Joost J.G.C. , Gibala Martin J. , van Loon Luc J.C.
Published: October 2016

Dietary protein intake should be optimized in all athletes to ensure proper recovery and enhance the skeletal muscle adaptive response to exercise training. In addition to total protein intake, the use of specific proteincontaining food sources and the distribution of protein throughout the day are relevant for optimizing protein intake in athletes. In the present study, we examined the daily intake and distribution of various proteincontaining food sources in a large cohort of strength, endurance and team-sport athletes. Well-trained male (n=327) and female (n=226) athletes completed multiple web-based 24-hr dietary recalls over a 2-4 wk period. Total energy intake, the contribution of animal- and plant-based proteins to daily protein intake, and protein intake at six eating moments were determined. Daily protein intake averaged 108±33 and 90±24 g in men and women, respectively, which corresponded to relative intakes of 1.5±0.4 and 1.4±0.4 g/kg. Dietary protein intake was correlated with total energy intake in strength (r=0.71, p <.001), endurance (r=0.79, p <.001) and team-sport (r=0.77, p <.001) athletes. Animal and plant-based sources of protein intake was 57% and 43%, respectively. The distribution of protein intake was 19% (19±8 g) at breakfast, 24% (25±13 g) at lunch and 38% (38±15 g) at dinner. Protein intake was below the recommended 20 g for 58% of athletes at breakfast, 36% at lunch and 8% at dinner. In summary, this survey of athletes revealed they habitually consume > 1.2 g protein/kg/d, but the distribution throughout the day may be suboptimal to maximize the skeletal muscle adaptive response to training.
Dietary Intake, Body Composition, and Nutrition Knowledge of Australian Football and Soccer Players: Implications for Sports Nutrition Professionals in Practice
Authors: Devlin Brooke L. , Leveritt Michael D , Kingsley Michael , Belski Regina
Published: October 2016

Sports nutrition professionals aim to influence nutrition knowledge, dietary intake and body composition to improve athletic performance. Understanding the interrelationships between these factors and how they vary across sports has the potential to facilitate better-informed and targeted sports nutrition practice. This observational study assessed body composition (DXA), dietary intake (multiple-pass 24-hr recall) and nutrition knowledge (two previously validated tools) of elite and subelite male players involved in two team-based sports; Australian football (AF) and soccer. Differences in, and relationships between, nutrition knowledge, dietary intake and body composition between elite AF, subelite AF and elite soccer players were assessed. A total of 66 (23 ± 4 years, 82.0 ± 9.2 kg, 184.7 ± 7.7 cm) players participated. Areas of weaknesses in nutrition knowledge are evident (57% mean score obtained) yet nutrition knowledge was not different between elite and subelite AF and soccer players (58%, 57% and 56%, respectively, p > .05). Dietary intake was not consistent with recommendations in some areas; carbohydrate intake was lower (4.6 ± 1.5 g/kg/day, 4.5 ± 1.2 g/kg/day and 2.9 ± 1.1 g/kg/day for elite and subelite AF and elite soccer players, respectively) and protein intake was higher (3.4 ± 1.1 g/kg/day, 2.1 ± 0.7 g/kg/day and 1.9 ± 0.5 g/kg/day for elite and subelite AF and elite soccer players, respectively) than recommendations. Nutrition knowledge was positively correlated with fat-free soft tissue mass (n = 66; r2 = .051, p = .039). This insight into known modifiable factors may assist sports nutrition professionals to be more specific and targeted in their approach to supporting players to achieve enhanced performance.
Battle over rare disease drug ensnares NIH
Authors: Wadman Meredith
Published: October 2016

Firms and parents of kids with fatal condition clash over drug delivery and role of agency.
European XFEL to shine as brightest, fastest x-ray source
Authors: Cartlidge Edwin
Published: October 2016

Free electron laser's rapid-fire pulses will probe free-floating molecules in their natural habitat.
First Polynesians launched from East Asia to settle Pacific
Authors: Gibbons Ann
Published: October 2016

“Game-changing” study of ancient genomes traces Polynesian roots solely to East Asian farmers.
Great apes anticipate that other individuals will act according to false beliefs
Authors: Krupenye Christopher , Kano Fumihiro , Hirata Satoshi , Call Josep , Tomasello Michael
Published: October 2016

Apes understand false beliefs

We humans tend to believe that our cognitive skills are unique, not only in degree, but also in kind. The more closely we look at other species, however, the clearer it becomes that the difference is one of degree. Krupenye
et al.
show that three different species of apes are able to anticipate that others may have mistaken beliefs about a situation (see the Perspective by de Waal). The apes appear to understand that individuals have different perceptions about the world, thus overturning the human-only paradigm of the theory of mind.

Science
, this issue p.
110
; see also p.
39
The methanogenic CO
2
reducing-and-fixing enzyme is bifunctional and contains 46 [4Fe-4S] clusters
Authors: Wagner Tristan , Ermler Ulrich , Shima Seigo
Published: October 2016

The long and winding road to methane

The process by which archaea make methane involves a series of reactions and enzymes. First, CO
2
and methanofuran (MFR) are reduced to formyl-MFR by an as yet unresolved mechanism. Wagner
et al.
solved the x-ray crystal structure of a tungsten-containing formyl-MFR dehydrogenase complex. Two active sites in the complex are separated by a 43-Å tunnel, which is responsible for transferring the formate made after CO
2
reduction. The complex also contains a chain of 46 iron-sulfur clusters. Although the exact function of this chain is unclear, it may electronically couple the four tungsten redox centers.

Science
, this issue p.
114
An artificial metalloenzyme with the kinetics of native enzymes
Authors: Dydio P. , Key H. M. , Nazarenko A. , Rha J. Y.-E. , Seyedkazemi V. , Clark D. S. , Hartwig J. F.
Published: October 2016

Something like the real thing

Artificial metalloenzymes ideally combine the favorable properties of natural enzymes with the high efficiency of synthetic catalysts. Inserting new metal groups into existing native proteins, however, often leads to poorer overall catalytic efficiency. To break through this limitation, Dydio
et al.
replaced the iron in the heme group of cytochrome P450 with iridium and subjected it to directed evolution. The enzyme catalyzed a range of reactions with kinetics similar to those of the native enzyme. It was also able to functionalize fully unactivated C-H bonds, a reaction that previously has only been mediated by synthetic catalysts. Moreover, the artificial enzyme was stable across temperatures and scales that are used industrially.

Science
, this issue p.
102
Growing a synthetic mollusk shell
Authors: Barthelat Francois
Published: October 2016

Three-dimensional organic templates control calcium carbonate precipitation

[Also see Report by

Mao
et al.

]
Quantifying culture
Living by Numbers In Defence of Quantity
Steven Connor
Reaktion Books, 2016. 296 pp.
Authors: Phillips Christopher J.
Published: October 2016

A humanist's ode to mathematics reveals how numbers underlie literature, art, and music
A pragmatic way forward?
Authors: Powell-Jackson Timothy
Published: October 2016

Training of informal providers may improve the quality of primary health care in rural India

[Also see Research Article by

Das
et al.

]
Shigella Vaccine Development: Finding the Path of Least Resistance
Authors: Chen Wilbur H. , Kotloff Karen L.
Published: October 2016

Shigella
spp. represent the second most common etiologic pathogen causing childhood diarrhea in developing countries. There are no licensed
Shigella
vaccines, and progress for such vaccines has been limited. In this issue of
Clinical and Vaccine Immunology
, Riddle and colleagues (M. S. Riddle, R. W. Kaminski, C. Di Paolo, C. K. Porter, R. L. Gutierrez, et al., Clin Vaccine Immunol 23:908–917, 2016,
http://dx.doi.org/10.1128/CVI.00224-16
) report results from a phase I study of a parenterally administered monovalent O-polysaccharide “bioconjugate” directed against
Shigella flexneri
2a. Ultimately, the goal is to develop a broad-spectrum
Shigella
vaccine to address this public health concern. A parenteral
Shigella
vaccine capable of eliciting protection in children of developing countries would be an important tool to reach this goal.
Development and Evaluation of a Molecular Diagnostic Method for Rapid Detection of Histoplasma capsulatum var. farciminosum, the Causative Agent of Epizootic Lymphangitis, in Equine Clinical Samples
Authors: Scantlebury C. E. , Pinchbeck G. L. , Loughnane P. , Aklilu N. , Ashine T. , Stringer A. P. , Gordon L. , Marshall M. , Christley R. M. , McCarthy A. J.
Published: October 2016

Histoplasma capsulatum
var.
farciminosum
, the causative agent of epizootic lymphangitis (EZL), is endemic in parts of Africa. Diagnosis based on clinical signs and microscopy lacks specificity and is a barrier to further understanding this neglected disease. Here, a nested PCR method targeting the internal transcribed spacer (ITS) region of the rRNA operon was validated for application to equine clinical samples. Twenty-nine horses with signs of EZL from different climatic regions of Ethiopia were clinically examined. Blood samples and aspirates of pus from cutaneous nodules were taken, along with blood from a further 20 horses with no cutaneous EZL lesions. Among the 29 horses with suspected cases of EZL,
H. capsulatum
var.
farciminosum
was confirmed by extraction of DNA from pus and blood samples from 25 and 17 horses, respectively. Positive PCR results were also obtained with heat-inactivated pus (24 horses) and blood (23 horses) spotted onto Whatman FTA cards. Two positive results were obtained among blood samples from 20 horses that did not exhibit clinical signs of EZL. These are the first reports of the direct detection of
H. capsulatum
var.
farciminosum
in equine blood and at high frequency among horses exhibiting cutaneous lesions. The nested PCR outperformed conventional microscopic diagnosis, as characteristic yeast cells could be observed only in 14 pus samples. The presence of
H. capsulatum
var.
farciminosum
DNA was confirmed by sequencing the cloned PCR products, and while alignment of the ITS amplicons showed very little sequence variation, there was preliminary single nucleotide polymorphism-based evidence for the existence of two subgroups of
H. capsulatum
var.
farciminosum
. This molecular diagnostic method now permits investigation of the epidemiology of EZL.
Chlorhexidine versus Tincture of Iodine for Reduction of Blood Culture Contamination Rates: a Prospective Randomized Crossover Study
Authors: Story-Roller Elizabeth , Weinstein Melvin P.
Published: October 2016

Blood cultures (BCs) are the standard method for diagnosis of bloodstream infections (BSIs). However, the average BC contamination rate (CR) in U.S. hospitals is 2.9%, potentially resulting in unnecessary antibiotic use and excessive therapy costs. Several studies have compared various skin antisepsis agents without a clear consensus as to which agent is most effective in reducing contamination. A prospective, randomized crossover study directly comparing blood culture contamination rates using chlorhexidine versus iodine tincture for skin antisepsis was performed at Robert Wood Johnson University Hospital (RWJUH). Eight nursing units at RWJUH were provided with blood culture kits containing either chlorhexidine (CH) or iodine tincture (IT) for skin antisepsis prior to all blood culture venipunctures, which were obtained by nurses or clinical care technicians. At quarterly intervals, the antiseptic agent used on each nursing unit was switched. Analyses of positive BCs were performed to distinguish true BSIs from contaminants. Of the 6,095 total BC sets obtained from the participating nursing units, 667 (10.94%) were positive and 238 (3.90%) were judged by the investigators to be contaminated. Of the 3,130 BCs obtained using IT, 340 (10.86%) were positive and 123 (3.93%) were contaminated. Of 2,965 BCs obtained using CH, 327 (11.03%) were positive and 115 (3.88%) were contaminated. The rates of contaminated BCs were not statistically significant between the two antiseptic agents (
P
= 1.0). We conclude that CH and IT are equivalent agents for blood culture skin antisepsis.
HIV-1 Glycan Density Drives the Persistence of the Mannose Patch within an Infected Individual
Authors: Coss Karen P. , Vasiljevic Snezana , Pritchard Laura K. , Krumm Stefanie A. , Glaze Molly , Madzorera Sharon , Moore Penny L. , Crispin Max , Doores Katie J.
Published: October 2016

The HIV envelope glycoprotein (Env) is extensively modified with host-derived N-linked glycans. The high density of glycosylation on the viral spike limits enzymatic processing, resulting in numerous underprocessed oligomannose-type glycans. This extensive glycosylation not only shields conserved regions of the protein from the immune system but also acts as a target for anti-HIV broadly neutralizing antibodies (bnAbs). In response to the host immune system, the HIV glycan shield is constantly evolving through mutations affecting both the positions and numbers of potential N-linked glycosylation sites (PNGSs). Here, using longitudinal Env sequences from a clade C-infected individual (CAP256), we measured the impact of the shifting glycan shield during HIV infection on the abundance of oligomannose-type glycans. By analyzing the intrinsic mannose patch from a panel of recombinant CAP256 gp120s displaying high protein sequence variability and changes in PNGS number and positioning, we show that the intrinsic mannose patch persists throughout the course of HIV infection and correlates with the number of PNGSs. This effect of the glycan density on the processing state was also supported by the analysis of a cross-clade panel of recombinant gp120 glycoproteins. Together, these observations underscore the importance of glycan clustering for the generation of carbohydrate epitopes for anti-HIV bnAbs. The persistence of the intrinsic mannose patch over the course of HIV infection further highlights this epitope as an important target for HIV vaccine strategies.

IMPORTANCE
Development of an HIV vaccine is critical for control of the HIV pandemic, and elicitation of broadly neutralizing antibodies (bnAbs) is likely to be a key component of a successful vaccine response. The HIV envelope glycoprotein (Env) is covered in an array of host-derived N-linked glycans often referred to as the glycan shield. This glycan shield is a target for many of the recently isolated anti-HIV bnAbs and is therefore under constant pressure from the host immune system, leading to changes in both glycan site frequency and location. This study aimed to determine whether these genetic changes impacted the eventual processing of glycans on the HIV Env and the susceptibility of the virus to neutralization. We show that despite this variation in glycan site positioning and frequency over the course of HIV infection, the mannose patch is a conserved feature throughout, making it a stable target for HIV vaccine design.
The Tetherin Antagonism of the Ebola Virus Glycoprotein Requires an Intact Receptor-Binding Domain and Can Be Blocked by GP1-Specific Antibodies
Authors: Brinkmann Constantin , Nehlmeier Inga , Walendy-Gnirß Kerstin , Nehls Julia , González Hernández Mariana , Hoffmann Markus , Qiu Xiangguo , Takada Ayato , Schindler Michael , Pöhlmann Stefan
Published: October 2016

The glycoprotein of Ebola virus (EBOV GP), a member of the family
Filoviridae
, facilitates viral entry into target cells. In addition, EBOV GP antagonizes the antiviral activity of the host cell protein tetherin, which may otherwise restrict EBOV release from infected cells. However, it is unclear how EBOV GP antagonizes tetherin, and it is unknown whether the GP of Lloviu virus (LLOV), a filovirus found in dead bats in Northern Spain, also counteracts tetherin. Here, we show that LLOV GP antagonizes tetherin, indicating that tetherin may not impede LLOV spread in human cells. Moreover, we demonstrate that appropriate processing of N-glycans in tetherin/GP-coexpressing cells is required for tetherin counteraction by EBOV GP. Furthermore, we show that an intact receptor-binding domain (RBD) in the GP1 subunit of EBOV GP is a prerequisite for tetherin counteraction. In contrast, blockade of Niemann-Pick disease type C1 (NPC1), a cellular binding partner of the RBD, did not interfere with tetherin antagonism. Finally, we provide evidence that an antibody directed against GP1, which protects mice from a lethal EBOV challenge, may block GP-dependent tetherin antagonism. Our data, in conjunction with previous reports, indicate that tetherin antagonism is conserved among the GPs of all known filoviruses and demonstrate that the GP1 subunit of EBOV GP plays a central role in tetherin antagonism.

IMPORTANCE
Filoviruses are reemerging pathogens that constitute a public health threat. Understanding how Ebola virus (EBOV), a highly pathogenic filovirus responsible for the 2013-2016 Ebola virus disease epidemic in western Africa, counteracts antiviral effectors of the innate immune system might help to define novel targets for antiviral intervention. Similarly, determining whether Lloviu virus (LLOV), a filovirus detected in bats in northern Spain, is inhibited by innate antiviral effectors in human cells might help to determine whether the virus constitutes a threat to humans. The present study shows that LLOV, like EBOV, counteracts the antiviral effector protein tetherin via its glycoprotein (GP), suggesting that tetherin does not pose a defense against LLOV spread in humans. Moreover, our work identifies the GP1 subunit of EBOV GP, in particular an intact receptor-binding domain, as critical for tetherin counteraction and provides evidence that antibodies directed against GP1 can interfere with tetherin counteraction.
Glycaemic control and antidiabetic treatment trends in primary care centres in patients with type 2 diabetes mellitus during 2007–2013 in Catalonia: a population-based study
Authors: Mata-Cases Manel , Franch-Nadal Josep , Real Jordi , Mauricio Dídac
Published: October 2016

Objectives

To assess trends in prescribing practices of antidiabetic agents and glycaemic control in patients with type 2 diabetes mellitus (T2DM).

Design

Cross-sectional analysis using yearly clinical data and antidiabetic treatments prescribed obtained from an electronic population database.

Setting

Primary healthcare centres, including the entire population attended by the Institut Català de la Salut in Catalonia, Spain, from 2007 to 2013.

Participants

Patients aged 31–90 years with a diagnosis of T2DM.

Results

The number of registered patients with T2DM in the database was 257 072 in 2007, increasing up to 343 969 in 2013. The proportion of patients not pharmacologically treated decreased by 9.7% (95% CI −9.48% to −9.92%), while there was an increase in the percentage of patients on monotherapy (4.4% increase; 95% CI 4.16% to 4.64%), combination therapy (2.8% increase; 95% CI 2.58% to 3.02%), and insulin alone or in combination (increasing 2.5%; 95% CI 2.2% to 2.8%). The use of metformin and dipeptidyl peptidase-IV inhibitors increased gradually, while sulfonylureas, glitazones and α-glucosidase inhibitors decreased. The use of glinides remained stable, and the use of glucagon-like peptide-1 receptor agonists was still marginal. Regarding glycaemic control, there were no relevant differences across years: mean glycated haemoglobin (HbA1c) value was around 7.2%; the percentage of patients reaching an HbA1c≤7% target ranged between 52.2% and 55.6%; and those attaining their individualised target from 72.8% to 75.7%.

Conclusions

Although the proportion of patients under pharmacological treatment increased substantially over time and there was an increase in the use of combination therapies, there have not been relevant changes in glycaemic control during the 2007–2013 period in Catalonia.
Examination of psychosocial predictors of Chinese hospital pharmacists' intention to provide clinical pharmacy services using the theory of planned behaviour: a cross-sectional questionnaire study
Authors: He Yuan , Yang Fan , Mu Dongqin , Xing Yuan , Li Xin
Published: October 2016

Objectives

Main study aim was as follows: (1) to explore the usefulness of the theory of planned behaviour (TPB) model in predicting Chinese hospital pharmacists' intention to provide clinical pharmacy services (CPSs), including auxiliary CPSs and core CPSs; (2) to identify the main factors affecting the Chinese hospital pharmacists' intention to provide core CPSs based on TPB quantitatively.

Design

Cross-sectional questionnaire study.

Setting

The study was conducted in 22 general hospitals in seven cities located in the eastern and western part of China.

Participants

416 hospital pharmacists (292 (70.2%) female) entered and completed the study.

Primary and secondary outcome measures

Quantitative responses with hospital pharmacists' intention, attitude, subjective norms (SNs) and perceived behavioural control (PBC) over provision of CPSs and their past behaviour (PB)-related CPSs.

Results

The structural equation model analysis found that attitude (p=0.0079, β=0.12), SN (p=0.038, β=0.10) and the pharmacists' intention to provide auxiliary CPSs (p=0.0001, β=0.63) significantly predicted of their intention to provide core CPSs, accounting for 54.0% of its variance. Attitude (p=0.0001, β=0.35), PBC (p=0.0182, β=0.12) and PB (p=0.0009, β=0.15) are significant predictors of pharmacists' intention, accounting for 21% of the variance in pharmacists' intention to provide auxiliary CPSs.

Conclusions

The TPB with the addition of PB is a useful framework for predicting pharmacists' intention to provide CPSs in Chinese hospital care context. Strategies to improve hospital pharmacists' intention to provide CPSs should focus on helping the individuals related medical care see the value of CPSs, altering their perception of social pressure towards core CPSs and the removal of obstacles that impede the translation of intentions into behaviour.
An ED paradox: patients who arrive by ambulance and then leave without consulting an ED provider
Authors: Doupe Malcolm B , Day Suzanne , Palatnick Wes , Chochinov Alecs , Chateau Dan , Snider Carolyn , Lobato de Faria Ricardo , Weldon Erin , Derksen Shelley
Published: October 2016

Background

Scientists have called for strategies to identify ED patients with unmet needs. We identify the unique profile of ED patients who arrive by ambulance and subsequently leave without consulting a provider (ie, a paradoxical visit, PV).

Methods

Using a retrospective cohort design, administrative data from Winnipeg, Manitoba were interrogated to identify all ED patients 17+ years old as having zero, single or multiple PVs in 2012/2013. Analyses compare the sociodemographic, physical (eg, arthritis), mental (eg, substance abuse) and concurrent healthcare use profile of non-PV, single and multiple PV patients.

Results

The study cohort consisted of 122 639 patients with 250 754 ED visits. Across all ED sites, 2.3% of patients (N=2815) made 3387 PVs, comprising 1.4% of all ED visits. Descriptively, more single versus non-PV patients lived in urban core and lowest-income areas, were frequent ED users generally, were substance abusers and had seven plus primary care physician visits. Multiple PV patients had a similar but more extreme profile versus their single PV counterparts (eg, 54.7% of multiple vs 27.4% of single PV patients had substance abuse challenges). From multivariate statistics, single versus non-PV patients are defined uniquely by their frequent ED use, by their substance abuse, as living in a core and low income area, and as having multiple visits with primary care physicians.

Conclusions

PV patients have needs that do not align with the acute model of ED care. These patients may benefit from a more integrated care approach likely involving allied health professionals.
Benchmarking a large regional UK HER2 testing service against current practice guidelines
Authors: Thomas Jeremy , Loane Joseph , Matthews Richard , Maxwell Scott , Ingman Tim , Beesley Mathew , Ferrigan Lynda
Published: October 2016

Aims

To critically evaluate HER2 testing data for 3500 consecutive cases over 28 months for a single laboratory and review these findings in the light of current UK reporting guidelines.

Methods

We have reviewed all data relating to the HER2 testing service including reagents and analytical machine, HER2 immunohistochemistry (IHC) and fluorescentin situhybridisation (FISH) scoring profiles. We have examined the place of double counting and rapid screening of FISH and when it is and is not safe to do so. This analysis has been facilitated greatly by the inclusion of custom scripts embedded in a spreadsheet used for recording the data.

Results

There were no differences in scoring profiles in relation to testing machine or reagent batch for both HER2 IHC and FISH. There was excellent concordance in scoring by the biomedical scientists and pathologists providing the service. There is a significant difference between the proximity of scores in double-scored cases with HER2 copy number >6.0 compared with those with copy number <6.00. It is safe to single score with rapid screening of HER2 FISH following a first count with a HER2/CEP17 ratio <1.5 and a HER2 copy number <3.5.

Conclusions

Single counting of HER2 FISH supported by a second rapid screen is safe and practicable within strict parameters. Any assessment of proximity of scores in double-scored cases should take into account the HER2 copy number, with greater spreads experienced at higher copy numbers. Centralising HER2 testing in a regional centre allows detailed audit of the entire analytical process.
Measuring impairments of functioning and health in patients with axial spondyloarthritis by using the ASAS Health Index and the Environmental Item Set: translation and cross-cultural adaptation into 15 languages
Authors: Kiltz U , van der Heijde D , Boonen A , Bautista-Molano W , Burgos-Vargas R , Chiowchanwisawakit P , Duruoz T , El-Zorkany B , Essers I , Gaydukova I , Géher P , Gossec L , Grazio S , Gu J , Khan M A , Kim T J , Maksymowych W P , Marzo-Ortega H , Navarro-Compán V , Olivieri I , Patrikos D , Pimentel-Santos F M , Schirmer M , van den Bosch F , Weber U , Zochling J , Braun J
Published: October 2016

Introduction

The Assessments of SpondyloArthritis international society Health Index (ASAS HI) measures functioning and health in patients with spondyloarthritis (SpA) across 17 aspects of health and 9 environmental factors (EF). The objective was to translate and adapt the original English version of the ASAS HI, including the EF Item Set, cross-culturally into 15 languages.

Methods

Translation and cross-cultural adaptation has been carried out following the forward–backward procedure. In the cognitive debriefing, 10 patients/country across a broad spectrum of sociodemographic background, were included.

Results

The ASAS HI and the EF Item Set were translated into Arabic, Chinese, Croatian, Dutch, French, German, Greek, Hungarian, Italian, Korean, Portuguese, Russian, Spanish, Thai and Turkish. Some difficulties were experienced with translation of the contextual factors indicating that these concepts may be more culturally-dependent. A total of 215 patients with axial SpA across 23 countries (62.3% men, mean (SD) age 42.4 (13.9) years) participated in the field test. Cognitive debriefing showed that items of the ASAS HI and EF Item Set are clear, relevant and comprehensive. All versions were accepted with minor modifications with respect to item wording and response option. The wording of three items had to be adapted to improve clarity. As a result of cognitive debriefing, a new response option ‘not applicable’ was added to two items of the ASAS HI to improve appropriateness.

Discussion

This study showed that the items of the ASAS HI including the EFs were readily adaptable throughout all countries, indicating that the concepts covered were comprehensive, clear and meaningful in different cultures.
D2R2: an evidence‐based decision support tool to aid prioritisation of animal health issues for government funding
Authors: Gibbens J. C. , Frost A. J. , Houston C. W. , Lester H. , Gauntlett F. A.
Published: October 2016

An evidence‐based decision support tool, ‘D2R2’, has been developed by Defra. It contains a wide range of standardised information about exotic and endemic diseases held in ‘disease profiles’. Each profile includes 40 criteria used for scoring, enabling D2R2 to provide relative priority rankings for every disease profiled. D2R2 also provides a range of reports for each disease and the functionality to explore the impact of changes in any criterion or weighting on a disease's ranking. These outputs aid the prioritisation and management of animal diseases by government. D2R2 was developed with wide stakeholder engagement and its design was guided by clear specifications. It uses the weighted scores of a limited number of criteria to generate impact and risk scores for each disease, and relies on evidence drawn from published material wherever possible and maintained up to date. It allows efficient use of expertise, as maintained disease profiles reduce the need for on call, reactive, expert input for policy development and enables rapid simultaneous access to the same information by multiple parties, for example during exotic disease outbreaks. The experience in developing D2R2 has been shared internationally to assist others with their development of disease prioritisation and categorisation systems.
Intracerebroventricular tempol administration in older rats reduces oxidative stress in the hypothalamus but does not change STAT3 signalling or SIRT1/AMPK pathway
Authors: Toklu Hale Z. , Scarpace Philip J. , Sakarya Yasemin , Kirichenko Nataliya , Matheny Michael , Bruce Erin B. , Carter Christy S. , Morgan Drake , Tümer Nihal
Published: October 2016

Hypothalamic inflammation and increased oxidative stress are believed to be mechanisms that contribute to obesity. 4-Hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol), a free radical scavenger, has been shown to reduce inflammation and oxidative stress. We hypothesized that brain infusion of tempol would reduce oxidative stress, and thus would reduce food intake and body weight and improve body composition in rats with age-related obesity and known elevated oxidative stress. Furthermore, we predicted an associated increase in markers of leptin signalling, including the silent mating type information regulator 2 homolog 1 (SIRT1)/5′AMP-activated protein kinase (AMPK) pathway and the signal transducer and activator of transcription 3 (STAT3) pathway. For this purpose, osmotic minipumps were placed in the intracerebroventricular region of young (3 months) and aged (23 months) male Fischer 344 x Brown Norway rats for the continuous infusion of tempol or vehicle for 2 weeks. Tempol significantly decreased (p < 0.01) nicotinamide adenine dinucleotide phosphate oxidase activity in the hypothalamus but failed to reduce food intake or weight gain and did not alter body composition. SIRT1 activity and Acetyl p53 were decreased and phosphorylation of AMPK was increased with age, but they were unchanged with tempol. Basal phosphorylation of STAT3 was unchanged with age or tempol. These results indicate that tempol decreases oxidative stress but fails to alter feeding behaviour, body weight, or body composition. Moreover, tempol does not modulate the SIRT1/AMPK/p53 pathway and does not change leptin signalling. Thus, a reduction in hypothalamic oxidative stress is not sufficient to reverse age-related obesity.
Geological significance of 40Ar/39Ar mica dates across a mid-crustal continental plate margin, Connemara (Grampian orogeny, Irish Caledonides), and implications for the evolution of lithospheric collisions
Authors: Friedrich Anke M. , Hodges Kip V.
Published: October 2016

The Connemara region is a world-class example of a regional-scale, high-temperature metamorphic terrain. Its rock record documents formation of a bi-vergent orogenic wedge and associated calkalkaline magmatism in a an arc–continent collisional setting (Grampian orogeny), for which a protracted evolution was inferred based on a >75 Ma spread in U–Pb, Rb–Sr, and K–Ar mineral ages. In contrast, geological field observations imply a simple relationship between syntectonic magmatism, bi-vergent deformation, and Barrovian-type metamorphism. We explore the significance of the spread in apparent cooling ages using 40Ar/39Ar mica thermochronometers of varying grain sizes and composition, collected across metamorphic grades ranging from staurolite to upper sillimanite. We integrated geological and previously published geochronological evidence to identify a 32 Ma range (ca. 475–443 Ma) of permissible cooling ages and distinguished them from those dates not related to cooling after high-temperature metamorphism. Variations in 40Ar/39Ar dates at a single locality are ≤10 Ma, implying rapid cooling (≥6–26 °C/Ma) following metamorphism and deformation. A distinct cooling age variation (≥15 Ma) occurs on the regional scale, consistent with spatial differences in the metamorphic, magmatic, and deformational evolution across Connemara. This cooling record relates to a lateral thermal gradient (30 °C/km) in an evolving arc–continent collision, rather than to differential unroofing of the orogen. Our results imply that the large (≥50 Ma) spread in thermochronometers commonly observed in orogens does not automatically translate into a protracted cooling history, but that only a small number of thermochronometers supply permissible cooling ages.
The multiple applications of DNA barcodes in avian evolutionary studies
Authors: Barreira Ana S. , Lijtmaer Darío A. , Tubaro Pablo L.
Published: October 2016

DNA barcodes of birds are currently available for 41% of known species and for many different geographic areas; therefore, they are a rich data source to answer evolutionary questions. We review studies that have used DNA barcodes to investigate evolutionary processes in birds using diverse approaches. We also review studies that have investigated species in depth where taxonomy and DNA barcodes present inconsistencies. Species that showed low genetic interspecific divergence and lack of reciprocal monophyly either are the result of recent radiation and (or) hybridize, while species with large genetic splits in their COI sequences were determined to be more than one independent evolutionary unit. In addition, we review studies that employed large DNA barcode datasets to study the molecular evolution of mitochondrial genes and the biogeography of islands, continents, and even at a multi-continental scale. These studies showed that DNA barcodes offer high-quality data well beyond their main purpose of serving as a molecular tool for species identification.
He–McKellar–Wilkens-type effect, quantum holonomies and Aharonov–Bohm-type effect for bound states from the Lorentz symmetry breaking effects
Authors: de Lima A. G. , Belich H. , Bakke K.
Published: October 2016

From the effects of the Lorentz symmetry violation in the CPT-even gauge sector of the Standard Model Extension determined by a tensor background [Formula: see text], we establish a possible scenario where an analogue of the He–McKellar–Wilkens effect can stem from. Besides, we build quantum holonomies associated with the analogue of the He–McKellar–Wilkens effect and discuss a possible analogy with the geometric quantum computation. Finally, we investigate the dependence of the energy levels on the He–McKellar–Wilkens geometric phase induced by Lorentz symmetry breaking effects when the particle is confined to a hard-wall confining potential.
Distribution of periodic trajectories of C-K systems MIXMAX pseudorandom number generator
Authors: Görlich Andrzej , Kalomenopoulos Marios , Savvidy Konstantin , Savvidy George
Published: October 2016

We are considering the hyperbolic C-K systems of Anosov–Kolmogorov which are defined on high dimensional tori and are used to generate pseudorandom numbers for Monte-Carlo simulations. All trajectories of the C-K systems are exponentially unstable and pseudorandom numbers are represented in terms of coordinates of very long chaotic trajectories. The C-K systems on a torus have countable set of everywhere dense periodic trajectories and their distribution play a crucial role in coding and implementation of the pseudorandom number generator. The asymptotic distribution of chaotic trajectories of C-K systems with periods less than a given number is well known in mathematical literature, but a deviation from its asymptotic behavior is unknown. Using analytical and computer calculations, we are studying a distribution function of periodic trajectories and their deviation from asymptotic behavior. The corresponding MIXMAX generator has the best combination of speed, size of the state and is currently available generator.
Nonclassicality versus entanglement in a noncommutative space
Authors: Dey Sanjib , Fring Andreas , Hussin Véronique
Published: October 2016

Nonclassicality is an interesting property of light having applications in many different contexts of quantum optics, quantum information and computation. Nonclassical states produce substantial amount of reduced noise in optical communications. Furthermore, they often behave as sources of entangled quantum states, which are the most elementary requirement for quantum teleportation. We study various nonclassical properties of coherent states and Schrödinger cat states in a setting of noncommutative space resulting from the generalized uncertainty relation, first, in a complete analytical fashion and, later, by computing their entanglement entropies, which in turn provide supporting arguments behind our analytical results. By using standard theoretical frameworks, they are shown to produce considerably improved squeezing and nonclassicality and, hence, significantly higher amount of entanglement in comparison to the usual quantum mechanical models. Both the nonclassicality and the entanglement can be enhanced further by increasing the noncommutativity of the underlying space. In addition, we find as a by-product some rare explicit minimum uncertainty quadrature and number squeezed states, i.e., ideal squeezed states.