bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural diversity in vegetative and reproductive investments of perennial ryegrass is shaped by the climate at the place of origin
Authors: Barre P. , Ruttink T. , Muylle H. , Lootens P. , Sampoux J.‐P. , Rohde A. , Combes D. , Roldán‐Ruiz I.
Published: July 2017

In forage grasses, vegetative and reproductive investments are major determinants of yield and persistence. A survey of the diversity of vegetative and reproductive investment traits was carried out on 213 perennial ryegrass genotypes, representing 51 natural European accessions. Plants were phenotyped for traits related to leaf elongation, tillering, reproductive investment and heading date, at two locations with markedly different climates. Strong genetic effects for all traits were found. Interactions between genotype and location were moderate. Plants showed stronger spring leaf growth, lower numbers of tillers and higher reproductive investments at Lusignan (France) than at Melle (Belgium). Plant growth rate and tillering capacity were genetically nearly independent suggesting breeding for both traits simultaneously and independently should be possible. A high genetic diversity was observed for all traits. This diversity was structured in three main clusters. One cluster comprised early‐flowering genotypes with high reproductive investments and high spring growth rates. The remaining genotypes fell into two clusters based on differences in tillering capacity. Clear links were found between traits and the climatic conditions of the region of origin of the accessions. Autumn growth rate was positively correlated with solar radiation at the region of origin in October and February.
Service user involvement in the coproduction of a mental health nursing metric: The Therapeutic Engagement Questionnaire
Authors: Chambers Mary , McAndrew Susan , Nolan Fiona , Thomas Ben , Watts Paul , Kantaris Xenya
Published: July 2017

Service users’ involvement in mental health service research is increasingly acknowledged as important, yet, whilst involving users of mental health services as research participants is commonplace, seeking out their experience and indeed their “expertise” to facilitate the development of tools to be used within mental health services is in its infancy. This article describes the involvement and views of service users in the development of a nursing metric—the Therapeutic Engagement Questionnaire. It presents their role in the three stages of development: generation, statement reduction and authentication.
The medline UK filter: development and validation of a geographic search filter to retrieve research about the UK from OVID medline
Authors: Ayiku Lynda , Levay Paul , Hudson Tom , Craven Jenny , Barrett Elizabeth , Finnegan Amy , Adams Rachel
Published: July 2017

Background

A validated geographic search filter for the retrieval of research about the United Kingdom (UK) from bibliographic databases had not previously been published.

Objectives

To develop and validate a geographic search filter to retrieve research about the UK from OVID medline with high recall and precision.

Methods

Three gold standard sets of references were generated using the relative recall method. The sets contained references to studies about the UK which had informed National Institute for Health and Care Excellence (NICE) guidance. The first and second sets were used to develop and refine the medline UK filter. The third set was used to validate the filter. Recall, precision and number‐needed‐to‐read (NNR) were calculated using a case study.

Results

The validated medline UK filter demonstrated 87.6% relative recall against the third gold standard set. In the case study, the medline UK filter demonstrated 100% recall, 11.4% precision and a NNR of nine.

Conclusion

A validated geographic search filter to retrieve research about the UK with high recall and precision has been developed. The medline UK filter can be applied to systematic literature searches in OVID medline for topics with a UK focus.
Traces of the Trinity in the Old Testament: From Individual Texts to the Nature of Revelation
Authors: Huijgen Arnold
Published: July 2017

This article uncovers traces of the Trinity in the Old Testament. Different from traditional exegesis, it is argued that alleged allusions to God's plurality in specific texts, and examples of personified agents such as the Angel of the Lord, are less important and often inconclusive. The nature of Old Testament ‘monotheism’, however, supports trinitarian logic, and important traces of the Trinity are demonstrated in in‐depth structures of Old Testament theology: the anthropomorphic character of revelation, the second commandment, God's name as narrative self‐identification and the tendency of God's coming to his people.
Psychosis: an autoimmune disease?
Authors: Al‐Diwani Adam A. J. , Pollak Thomas A. , Irani Sarosh R. , Lennox Belinda R.
Published: July 2017

Psychotic disorders are common and disabling. Overlaps in clinical course in addition to epidemiological and genetic associations raise the possibility that autoimmune mechanisms may underlie some psychoses, potentially offering novel therapeutic approaches. Several immune loci including the major histocompatibility complex and B‐cell markers CD19 and CD20 achieve genome‐wide significance in schizophrenia. Emerging evidence suggests a potential role via neurodevelopment in addition to classical immune pathways. Additionally, lymphocyte biology is increasingly investigated. Some reports note raised peripheral CD19+ and reduced CD3+ lymphocyte counts, with altered CD4 : CD8 ratios in acute psychosis. Also, post‐mortem studies have found CD3+ and CD20+ lymphocyte infiltration in brain regions that are of functional relevance to psychosis. More specifically, the recent paradigm of neuronal surface antibody‐mediated (NSAb) central nervous system disease provides an antigen‐specific model linking adaptive autoimmunity to psychopathology. NSAbs bind extracellular epitopes of signalling molecules that are classically implicated in psychosis such as NMDA and GABA receptors. This interaction may cause circuit dysfunction leading to psychosis among other neurological features in patients with autoimmune encephalitis. The detection of these cases is crucial as autoimmune encephalitis is ameliorated by commonly available immunotherapies. Meanwhile, the prevalence and relevance of these antibodies in people with isolated psychotic disorders is an area of emerging scientific and clinical interest. Collaborative efforts to achieve larger sample sizes, comparison of assay platforms, and placebo‐controlled randomized clinical trials are now needed to establish an autoimmune contribution to psychosis.
The Drosophila simulans Y chromosome interacts with the autosomes to influence male fitness
Authors: Archer C. R. , Stephens R. M. , Sharma M. D. , Hosken D. J.
Published: July 2017

The Y chromosome should degenerate because it cannot recombine. However, male‐limited transmission increases selection efficiency for male‐benefit alleles on the Y, and therefore, Y chromosomes should contribute significantly to variation in male fitness. This means that although the Drosophila Y chromosome is small and gene‐poor, Y‐linked genes are vital for male fertility in Drosophila melanogaster and the Y chromosome has large male fitness effects. It is unclear whether the same pattern is seen in the closely related Drosophila simulans. We backcrossed Y chromosomes from three geographic locations into five genetic backgrounds and found strong Y and genetic background effects on male fertility. There was a significant Y‐background interaction, indicating substantial epistasis between the Y and autosomal genes affecting male fertility. This supports accumulating evidence that interactions between the Y chromosome and the autosomes are key determinants of male fitness.
Evolutionary allometry reveals a shift in selection pressure on male horn size
Authors: Tidière M. , Lemaître J.‐F. , Pélabon C. , Gimenez O. , Gaillard J.‐M.
Published: July 2017

How selection pressures acting within species interact with developmental constraints to shape macro‐evolutionary patterns of species divergence is still poorly understood. In particular, whether or not sexual selection affects evolutionary allometry, the increase in trait size with body size across species, of secondary sexual characters, remains largely unknown. In this context, bovid horn size is an especially relevant trait to study because horns are present in both sexes, but the intensity of sexual selection acting on them is expected to vary both among species and between sexes. Using a unique data set of sex‐specific horn size and body mass including 91 species of bovids, we compared the evolutionary allometry between horn size and body mass between sexes while accounting for both the intensity of sexual selection and phylogenetic relationship among species. We found a nonlinear evolutionary allometry where the allometric slope decreased with increasing species body mass. This pattern, much more pronounced in males than in females, suggests either that horn size is limited by some constraints in the largest bovids or is no longer the direct target of sexual selection in very large species.
Is bigger better? The relationship between size and reproduction in female Asian elephants
Authors: Crawley J. A. H. , Mumby H. S. , Chapman S. N. , Lahdenperä M. , Mar K. U. , Htut W. , Thura Soe A. , Aung H. H. , Lummaa V.
Published: July 2017

The limited availability of resources is predicted to impose trade‐offs between growth, reproduction and self‐maintenance in animals. However, although some studies have shown that early reproduction suppresses growth, reproduction positively correlates with size in others. We use detailed records from a large population of semi‐captive elephants in Myanmar to assess the relationships between size (height and weight), reproduction and survival in female Asian elephants, a species characterized by slow, costly life history. Although female height gain during the growth period overlapped little with reproductive onset in the population, there was large variation in age at first reproduction and only 81% of final weight had been reached by peak age of reproduction at the population level (19 years). Those females beginning reproduction early tended to be taller and lighter later in life, although these trends were not significant. We found that taller females were more likely to have reproduced by a given age, but such effects diminished with age, suggesting there may be a size threshold to reproduction which is especially important in young females. Because size was not linked with female survival during reproductive ages, the diminishing effect of height on reproduction with age is unlikely to be due to biased survival of larger females. We conclude that although reproduction may not always impose significant costs on growth, height may be a limiting factor to reproduction in young female Asian elephants, which could have important implications considering their birth rates are low and peak reproduction is young – 19 years in this population.
Choosing not to compete: Can firms maintain high prices by confusing consumers?
Authors: Crosetto Paolo , Gaudeul Alexia
Published: July 2017

Firms with very similar products often present their products in different ways. This makes it difficult for consumers to find out which product fits their needs best, or which one is the cheapest. Why is there no convergence toward common ways to present products? Is it possible for firms to maintain high prices by confusing consumers? We run a market experiment to investigate those questions. In our market, firms choose how to present their products in addition to choosing their price. We find that firms maintain different ways to present their products and that this allows them to maintain high prices. This behavior is not consistent with competitive behavior, such as when firms adopt best responses to each other, imitate the most successful firm, or learn the best strategy over time. Rather, our results are only consistent with cooperation between firms. Firms cooperate by not imitating the way other firms present their products. Cooperation is maintained by the threat of tough competition if a firm makes its product easy to compare with others. Firms are all the more likely to maintain such cooperation if their products do not actually differ much. This is because in that case, maintaining differences in the presentation of their products is the only way to maintain profits.
The recent colonization of south Brazil by the Azores chromis Chromis limbata
Authors: Anderson A. B. , Salas E. M. , Rocha L.A. , Floeter S. R.
Published: July 2017

The damselfish Chromis limbata is native to the Macaronesian Archipelagos (Azores, Madeira and Canaries) and the western coast of Africa between Senegal and Angola. During the austral summers of 2008 and 2009 the species was recorded for the first time in the south‐western Atlantic Ocean around Campeche and Xavier Islands, in Florianópolis, Santa Catarina State, Brazil. Here, the progression of C. limbata in southern Brazilian waters is described using visual counts and genetic surveys and changes in the density of the native congener Chromis multilineata were also investigated. Underwater visual censuses of both Chromis species were carried out from 2009 to 2014. Chromis limbata tissue samples were collected and the mtDNA control region was sequenced and compared with mtDNA haplotypes from the natural range to confirm species identity, compare genetic diversity and to infer connectivity between newly established Brazilian populations. The Brazilian population of C. limbata increased significantly over the past 5 years and the effect on C. multilineata is still an open question, longer time‐series data will be necessary to clarify possible interactions. The molecular analyses confirmed species identity, revealed strong haplotype connectivity among Brazilian study sites and showed a low genetic diversity in Brazil when compared with the native populations, suggesting few individuals started the invasion. Four hypotheses could explain this colonizing event: C. limbata was released by aquarium fish keepers; larvae or juveniles were transported via ship ballast water; the species has rafted alongside oil rigs; they crossed the Atlantic Ocean through normal larval dispersal or naturally rafting alongside drifting objects. The rafting hypotheses are favoured, but all four possibilities are plausible and could have happened in combination.
Occurrence of sympatric charr groups, Salvelinus, Salmonidae, in the lakes of Kamchatka: a legacy of the last glaciations
Authors: Esin E. V. , Bocharova E. S. , Mugue N. S. , Markevich G. N.
Published: July 2017

Six postglacial lakes were studied along both sides of the Kamchatka central mountain range, Russia. Pairs of local morphotypes of species of Arctic charrs, Salvelinus spp., have previously been described from the southernmost lakes while the fish fauna of the four northernmost lakes was studied here for the first time. Phenotypic data support the division of Kamchatkan lacustrine charrs into two groups according to the number of gill rakers and pyloric caeca, as well as snout–dorsal and snout–ventral distances (MANOVA, P < 0·001). These groups respectively correspond to phenotypes commonly referred to as Salvelinus malma and Salvelinus taranetzi. To clarify the identity of these groups, D‐loop and cytochrome b (cytb) region sequences were analysed. Haplotype network analysis of mtDNA shows the salmonids inhabiting four lakes on the south and north are phylogenetically close to either Beringian S. malma or to S. taranetzi from the Chukotka and Kolyma River basins (the mean ± s.e. pairwise per cent sequence divergence is 0·006 ± 0·001). Phenotype–genotype discordance suggests that mitochondrial introgression between species has occurred in the two smallest lakes (<0·5 km2) in the central part of the peninsula. Identical haplotypes of D‐loop and cytb regions were found for the populations of S. taranetzi from the most distant southern and northern lakes, indicating all lakes were colonized by both species simultaneously after the last glacial maximum. Salvelinus taranetzi may have colonized the Kamchatka peninsula from one or both of two different source regions: the Arctic Beringia and the northern coast of the Okhotsk Sea.
Introduction to anatomy on Wikipedia
Authors: Ledger Thomas Stephen
Published: July 2017

Wikipedia (www.wikipedia.com) is the largest encyclopaedia in existence. Of over five million English‐language articles, about 6000 relate to Anatomy, which are viewed roughly 30 million times monthly. No work parallels the amount of attention, scope or interdisciplinary layout of Wikipedia, and it offers a unique opportunity to improve the anatomical literacy of the masses. Anatomy on Wikipedia is introduced from an editor's perspective. Article contributors, content, layout and accuracy are discussed, with a view to demystifying editing for anatomy professionals. A final request for edits or on‐site feedback from anatomy professionals is made.
Current treatments of acne: Medications, lights, lasers, and a novel 650‐μs 1064‐nm Nd: YAG laser
Authors: Gold Michael H , Goldberg David J , Nestor Mark S
Published: July 2017

The treatment of acne, especially severe acne, remains a challenge to dermatologists. Therapies include retinoids, antibiotics, hormones, lights, lasers, and various combinations of these modalities. Acne is currently considered a chronic rather than an adolescent condition. The appropriate treatment depends on the patient and the severity of disease. The purpose of this study was to review current therapies for acne of all severities and to introduce the 650‐μs 1064‐nm laser for the treatment of acne.
Light‐based devices in the treatment of cutaneous vascular lesions: An updated review
Authors: Garden Benjamin C. , Garden Jerome M. , Goldberg David J.
Published: July 2017

Background

Light‐based devices have been used to treat cutaneous vascular lesions almost since the original development of the laser. After the introduction of the initial continuous wave and pulsed laser systems, the pulsed lasers became the gold standard device. Since then, new devices and methods to treat patients have been introduced.

Objective

To review and summarize the current literature specific to treatment of cutaneous vascular lesions with light‐based devices.

Methods

A review of the current literature of light‐based devices used for the treatment of vascular lesions.

Results and conclusions

New systems continue to be developed to treat vascular lesions with advantages and disadvantages compared to older devices. Nonlaser sources such as intense pulsed light and radiofrequency devices can also be used in the treatment of these patients. Newer approaches may lead to even better results.
Chronic Diarrhea in Dogs – Retrospective Study in 136 Cases
Authors: Volkmann M. , Steiner J.M. , Fosgate G.T. , Zentek J. , Hartmann S. , Kohn B.
Published: July 2017

Background

Chronic diarrhea (CD) is common in dogs, and information on frequency and distribution of primary and secondary causes is lacking.

Objectives

To evaluate underlying causes and predictors of outcome in dogs withCD.

Animals

One hundred and thirty‐six client‐owned dogs withCD(≥3 weeks duration).

Methods

Retrospective review of medical records (Small Animal Clinic, Freie Universität Berlin, Germany, 09/2009‐07/2011). Quantification of final diagnoses and comparison of clinical aspects including disease severity and clinicopathological abnormalities among dogs with clinical remission (either complete [gastrointestinal signs absent] or partial [clinical improvement of gastrointestinal signs and reduced episodes with shortened duration]), and those without recovery.

Results

Ninety percent of dogs were diagnosed with a primary enteropathy: inflammatory (71%; of those 66% dietary responsive, 23% idiopathic, 11% antibiotic responsive), infectious (13%), neoplastic (4%), and in one dog each mechanical disease or systemic vasculitis. Secondary causes were diagnosed in 10% of dogs: exocrine pancreatic (6%), endocrine (2%), and in one dog each hepatic, renal, and cardiac disease. In total, 87% of dogs had clinical remission, whereas 13% died or did not respond to treatment: Lack of recovery was frequently recorded for dogs with primary inflammatory (idiopathic) or neoplastic disease and was significantly associated with increased disease severity scores (P= .005), anemia (hematocrit < 40%,P< .001), severe hypoalbuminemia (serum albumin <2.0 g/dL,P= .008), and severe hypocobalaminemia (serum cobalamin concentration <200 pg/mL,P= .006).

Conclusions and clinical importance

Inflammatory enteropathies and particularly those of dietary origin were the most common causes ofCDin dogs. Findings support the usefulness of hematocrit, and serum albumin and cobalamin concentration as prognostic markers in dogs withCD.
Coronary artery calcification score and common iliac artery calcification score in non‐dialysis CKD patients
Authors: Mizuiri Sonoo , Nishizawa Yoshiko , Yamashita Kazuomi , Mizuno Kenji , Ishine Masahiro , Doi Shigehiro , Masaki Takao , Shigemoto Kenichiro
Published: July 2017

Summary at a Glance

Vascular calcification is a major contributor to morbidity and mortality in patients with CKD, although the optimal method and site for measurement of vascular calcification have not been determined. This study assesses and compares coronary artery calcification and common iliac artery calcification determined by CT in a cohort of non‐dialysis CKD patients and reports on associated variables and outcomes.
An autopsy case of Creutzfeldt‐Jakob disease with a prion protein gene codon 180 mutation presenting with pathological laughing and an exaggerated startle reaction
Authors: Iwasaki Yasushi , Mori Keiko , Ito Masumi , Akagi Akio , Mimuro Maya , Kitamoto Tetsuyuki , Yoshida Mari
Published: July 2017

A 78‐year‐old Japanese woman presented with slow progressive disorientation and memory disturbances. Pathological laughing was observed at an early disease stage and continued for several months. Around the same time, the patient began to exhibit an exaggerated startle reaction and mild myoclonus. The pathological laughing and startle reaction disappeared before the patient reached an akinetic mutism state approximately 16 months after symptom onset. MRI showed extensive hyperintensity of the cerebral cortex and striatum on diffusion‐weighted images, and swelling in the cerebral cortex on T2‐weighted and fluid attenuated inversion recovery images. A prion protein (PrP) gene analysis revealed a V180I mutation with methionine homozygosity at codon 129. Neuropathological examination showed extensive spongiform changes with characteristic various‐sized and non‐confluent (VaSNoC) vacuoles in the cerebral neocortex and striatum. Gliosis and hypertrophic astrocytosis were generally mild in character. Neurons were relatively preserved in number. We believe that pathological laughing and an exaggerated startle reaction are possible pathognomonic findings of V180I genetic Creutzfeldt‐Jakob disease. Based on the pathological findings of the present case, the presence of the VaSNoC‐type spongiform changes with relative preservation of the neurons in the cerebral cortex and a lack of apparent brainstem involvement are associated at least in part with the pathological laughing and startle reaction.
Genetic changes in a novel breeding population of Brassica napus synthesized from hundreds of crosses between B. rapa and B. carinata
Authors: Zou Jun , Hu Dandan , Mason Annaliese S. , Shen Xueqi , Wang Xiaohua , Wang Nian , Grandke Fabian , Wang Meng , Chang Shihao , Snowdon Rod J. , Meng Jinling
Published: July 2017

Introgression of genomic variation between and within related crop species is a significant evolutionary approach for population differentiation, genome reorganization and trait improvement. Using the Illumina Infinium Brassica 60K SNP array, we investigated genomic changes in a panel of advanced generation new‐type Brassica napus breeding lines developed from hundreds of interspecific crosses between 122 Brassica rapa and 74 Brassica carinata accessions, and compared them with representative accessions of their three parental species. The new‐type B. napus population presented rich genetic diversity and abundant novel genomic alterations, consisting of introgressions from B. rapa and B. carinata, novel allelic combinations, reconstructed linkage disequilibrium patterns and haplotype blocks, and frequent deletions and duplications (nonrandomly distributed), particularly in the C subgenome. After a much shorter, but very intensive, selection history compared to traditional B. napus, a total of 15 genomic regions with strong selective sweeps and 112 genomic regions with putative signals of selective sweeps were identified. Some of these regions were associated with important agronomic traits that were selected for during the breeding process, while others were potentially associated with restoration of genome stability and fertility after interspecific hybridization. Our results demonstrate how a novel method for population‐based crop genetic improvement can lead to rapid adaptation, restoration of genome stability and positive responses to artificial selection.
Phototherapy in systemic sclerosis: Review
Authors: Chaowattanapanit Suteeraporn , Choonhakarn Charoen , Foocharoen Chingching , Julanon Narachai
Published: July 2017

Systemic scleroderma—also known as systemic sclerosis (SSc)—is a chronic systemic connective tissue disease characterized by collagen deposition in cutaneous and internal organs, leading to skin sclerosis and multiple organ fibrosis. The pathogenesis is complex and remains poorly understood. Treatment is based on organ involvement and requires a multidisciplinary approach. Skin sclerosis can cause disability, leading to decreasing quality of life. Various systemic antifibrotic therapies have been used; however, most have unsatisfactory results. Recently, phototherapy and in particular ultraviolet A (UVA) has been used to treat skin sclerosis in SSc patients with satisfactory results. The main mechanisms include lymphocyte apoptosis, cytokine alteration, inhibition of collagen synthesis and increased collagenase production, and neovascularization, leading to the breakdown of collagen fibrils resulting in skin softening or even healing digital ulcers. Most studies reported that psoralen plus UVA (PUVA) and UVA1 phototherapy improved clinical outcomes vis‐à‐vis skin sclerosis, joint mobility, ulcers, and histopathology. PUVA and UVA1 phototherapy therefore have potential as an alternative or adjunctive therapy for patients with SSc.
Ascaris suum infection modulates inflammation: Implication of CD4+ CD25high Foxp3+ T cells and IL‐10
Authors: Titz T. de O. , de Araújo C. A. A. , Enobe C. S. , Rigato P. O. , Oshiro T. M. , de Macedo‐Soares M. F.
Published: July 2017

Helminth infections have the ability to modulate host's immune response through mechanisms that allow the chronic persistence of the worms in the host. Here, we investigated the mechanisms involved on the suppressive effect of Ascaris suum infection using a murine experimental model of LPS‐induced inflammation. We found that infection with A. suum markedly inhibited leucocyte influx induced by LPS into air pouches, suppressed secretion of pro‐inflammatory cytokines (IL‐1β, TNF‐α and IL‐6) and induced high levels of IL‐10 and TGF‐β. Augmented frequency of CD4+ CD25high Foxp3+ T cells was observed in the mesenteric lymph nodes of infected mice. Adoptive transfer of purified CD4+ CD25+ T cells to recipient uninfected mice demonstrated that these cells were able to induce a suppressive effect in the LPS‐induced inflammation in air pouch model. In addition, adoptive transfer of CD4+ CD25+ T cells derived from IL‐10 knockout mice suggests that this suppressive effect of A. suum infection involves IL‐10 cytokine. In conclusion, our results demonstrated that A. suum experimental infection was capable of suppressing LPS‐induced inflammation by mechanisms, which seem to be dependent on responses of CD4+ CD25+ T cells and secretion of IL‐10 cytokine.
The yielding and the linear-to-nonlinear viscoelastic transition of an elastoviscoplastic material
Authors: Fernandes Rubens R. , Andrade Diogo E. V. , Franco Admilson T. , Negrão Cezar O. R.
Published: July 2017

Elastoviscoplastic materials present a transition from a gel-like to a liquidlike state induced by shearing: While the first is primarily elastic, the second is predominantly viscous. The point that characterizes this transition is usually known as the yield point, which is associated to critical quantities such as yield stress and/or yield strain. Another characteristic of elastoviscoplastic materials is the transition from linear to nonlinear viscoelasticity. In the current work, a commercial hair gel, which is an elastoviscoplastic material, was tested in two rotational rheometers in order to evaluate these two transition points. Stress oscillatory amplitude sweeps at different frequencies were performed and a Fourier-Transform analysis was applied to the results in order to determine the linear viscoelastic limit. The linear viscoelastic limit stresses and strains at different frequencies were then compared to quantities that are usually associated to the yield point: The extrapolated zero-shear-rate stress obtained from the equilibrium flow curve, the minimum stress required to start up flows in creep experiments, the stress overshoot reached in constant shear rate experiments and the G′-and-G″ crossover stress determined through oscillatory amplitude sweeps. The results showed that the stresses and strains obtained as the linear viscoelastic limits were smaller than the critical quantities associated to the yield point for all evaluated cases. Although the critical quantities depend on the experimental condition, the linear viscoelastic limit strain was remarkably constant. Additionally, the linear viscoelastic limit strain was found to be in the same order of magnitude of the strain that characterizes the onset of plastic behavior in recovery experiments. This suggests that the beginning of the transition from a completely structured state of elastoviscoplastic materials to an unstructured state might be associated to the threshold of nonlinear viscoelasticity.
Distinct distributed patterns of neural activity are associated with two languages in the bilingual brain
Authors: Xu Min , Baldauf Daniel , Chang Chun Qi , Desimone Robert , Tan Li Hai
Published: July 2017

This fMRI study using MVPA reveals separated neural patterns for the first and second languages.
Carbapenemase Detection among Carbapenem-Resistant Glucose-Nonfermenting Gram-Negative Bacilli
Authors: Simner Patricia J. , Opene Belita N. A. , Chambers Krizia K. , Naumann Matthew E. , Carroll Karen C. , Tamma Pranita D.
Published: July 2017

Accurate detection of carbapenemase-producing glucose-nonfermenting Gram-negative bacilli (CPNFs), including
Pseudomonas aeruginosa
and
Acinetobacter baumannii
, is necessary to prevent their dissemination within health care settings. We performed a method comparison study of 11 phenotypic carbapenemase detection assays to evaluate their accuracy for the detection of CPNFs. A total of 96 carbapenem-resistant glucose-nonfermenting isolates were included, of which 29% produced carbapenemases. All CPNFs were molecularly characterized to identify β-lactamase genes. A total of 86% of the carbapenemase-producing
P. aeruginosa
isolates produced class B carbapenemases. Several assays performed with a sensitivity of >90% for the detection of carbapenemase-producing
P. aeruginosa
, including all rapid chromogenic assays and the modified carbapenem inactivation method. Most included assays, with the exception of the Manual Blue Carba assay, the Modified Carba NP assay, the boronic acid synergy test, and the metallo-β-lactamase Etest, had specificities of >90% for detecting carbapenemase-producing
P. aeruginosa
. Class D carbapenemases were the most prevalent carbapenemases among the carbapenemase-producing
A. baumannii
strains, with 60% of the carbapenemase-producing
A. baumannii
isolates producing acquired OXA-type carbapenemases. Although several assays achieved >90% specificity in identifying carbapenemase-producing
A. baumannii
, no assays achieved a sensitivity of greater than 90%. Our findings suggest that the available phenotypic tests generally appear to have excellent sensitivity and specificity for detecting carbapenemase-producing
P. aeruginosa
isolates. However, further modifications to existing assays or novel assays may be necessary to accurately detect carbapenemase-producing
A. baumannii
.
Experimental Transmission of the Chronic Wasting Disease Agent to Swine after Oral or Intracranial Inoculation
Authors: Moore S. Jo , West Greenlee M. Heather , Kondru Naveen , Manne Sireesha , Smith Jodi D. , Kunkle Robert A. , Kanthasamy Anumantha , Greenlee Justin J.
Published: July 2017

Chronic wasting disease (CWD) is a naturally occurring, fatal neurodegenerative disease of cervids. The potential for swine to serve as hosts for the agent of CWD is unknown. The purpose of this study was to investigate the susceptibility of swine to the CWD agent following experimental oral or intracranial inoculation. Crossbred piglets were assigned to three groups, intracranially inoculated (
n
= 20), orally inoculated (
n
= 19), and noninoculated (
n
= 9). At approximately the age at which commercial pigs reach market weight, half of the pigs in each group were culled (“market weight” groups). The remaining pigs (“aged” groups) were allowed to incubate for up to 73 months postinoculation (mpi). Tissues collected at necropsy were examined for disease-associated prion protein (PrP
Sc
) by Western blotting (WB), antigen capture enzyme immunoassay (EIA), immunohistochemistry (IHC), and
in vitro
real-time quaking-induced conversion (RT-QuIC). Brain samples from selected pigs were also bioassayed in mice expressing porcine prion protein. Four intracranially inoculated aged pigs and one orally inoculated aged pig were positive by EIA, IHC, and/or WB. By RT-QuIC, PrP
Sc
was detected in lymphoid and/or brain tissue from one or more pigs in each inoculated group. The bioassay was positive in four out of five pigs assayed. This study demonstrates that pigs can support low-level amplification of CWD prions, although the species barrier to CWD infection is relatively high. However, detection of infectivity in orally inoculated pigs with a mouse bioassay raises the possibility that naturally exposed pigs could act as a reservoir of CWD infectivity.

IMPORTANCE
We challenged domestic swine with the chronic wasting disease agent by inoculation directly into the brain (intracranially) or by oral gavage (orally). Disease-associated prion protein (PrP
Sc
) was detected in brain and lymphoid tissues from intracranially and orally inoculated pigs as early as 8 months of age (6 months postinoculation). Only one pig developed clinical neurologic signs suggestive of prion disease. The amount of PrP
Sc
in the brains and lymphoid tissues of positive pigs was small, especially in orally inoculated pigs. Regardless, positive results obtained with orally inoculated pigs suggest that it may be possible for swine to serve as a reservoir for prion disease under natural conditions.
Structural and Functional Basis for an EBNA1 Hexameric Ring in Epstein-Barr Virus Episome Maintenance
Authors: Deakyne Julianna S. , Malecka Kimberly A. , Messick Troy E. , Lieberman Paul M.
Published: July 2017

Epstein-Barr virus (EBV) establishes a stable latent infection that can persist for the life of the host. EBNA1 is required for the replication, maintenance, and segregation of the latent episome, but the structural features of EBNA1 that confer each of these functions are not completely understood. Here, we have solved the X-ray crystal structure of an EBNA1 DNA-binding domain (DBD) and discovered a novel hexameric ring oligomeric form. The oligomeric interface pivoted around residue T585 as a joint that links and stabilizes higher-order EBNA1 complexes. Substitution mutations around the interface destabilized higher-order complex formation and altered the cooperative DNA-binding properties of EBNA1. Mutations had both positive and negative effects on EBNA1-dependent DNA replication and episome maintenance with OriP. We found that one naturally occurring polymorphism in the oligomer interface (T585P) had greater cooperative DNA binding
in vitro
, minor defects in DNA replication, and pronounced defects in episome maintenance. The T585P mutant was compromised for binding to OriP
in vivo
as well as for assembling the origin recognition complex subunit 2 (ORC2) and trimethylated histone 3 lysine 4 (H3K4me3) at OriP. The T585P mutant was also compromised for forming stable subnuclear foci in living cells. These findings reveal a novel oligomeric structure of EBNA1 with an interface subject to naturally occurring polymorphisms that modulate EBNA1 functional properties. We propose that EBNA1 dimers can assemble into higher-order oligomeric structures important for diverse functions of EBNA1.

IMPORTANCE
Epstein-Barr virus is a human gammaherpesvirus that is causally associated with various cancers. Carcinogenic properties are linked to the ability of the virus to persist in the latent form for the lifetime of the host. EBNA1 is a sequence-specific DNA-binding protein that is consistently expressed in EBV tumors and is the only viral protein required to maintain the viral episome during latency. The structural and biochemical mechanisms by which EBNA1 allows the long-term persistence of the EBV genome are currently unclear. Here, we have solved the crystal structure of an EBNA1 hexameric ring and characterized key residues in the interface required for higher-order complex formation and long-term plasmid maintenance.
McKenzie Method of Mechanical Diagnosis and Therapy was slightly more effective than placebo for pain, but not for disability, in patients with chronic non-specific low back pain: a randomised placebo controlled trial with short and longer term follow-up
Authors: Garcia Alessandra Narciso , Costa Lucíola da Cunha Menezes , Hancock Mark J , Souza Fabrício Soares de , Gomes Geórgia Vieira Freschi de Oliveira , Almeida Matheus Oliveira de , Costa Leonardo Oliveira Pena
Published: July 2017

Background

The McKenzie Method of Mechanical Diagnosis and Therapy (MDT) is one of the exercise approaches recommended by low back pain (LBP) guidelines. We investigated the efficacy of MDT compared with placebo in patients with chronic LBP.

Methods

This was a prospectively registered, two-arm randomised placebo controlled trial, with a blinded assessor. A total of 148 patients seeking care for chronic LBP were randomly allocated to either MDT (n=74) or placebo (n=74). Patients from both groups received 10 treatment sessions over 5 weeks. Patients from both groups also received an educational booklet. Clinical outcomes were obtained at the end of treatment (5 weeks) and 3, 6 and 12 months after randomisation. Primary outcomes were pain intensity and disability at the end of treatment (5 weeks). We also conducted a subgroup analysis to identify potential treatment effect modifiers that could predict a better response to MDT treatment.

Results

The MDT group had greater improvements in pain intensity at the end of treatment (mean difference (MD) −1.00, 95% CI −2.09 to −0.01) but not for disability (MD −0.84, 95% CI −2.62 to 0.93). We did not detect between-group differences for any secondary outcomes, nor were any treatment effect modifiers identified. Patients did not report any adverse events.

Conclusion

We found a small and likely not clinically relevant difference in pain intensity favouring the MDT method immediately at the end of 5 weeks of treatment but not for disability. No other difference was found for any of the primary or secondary outcomes at any follow-up times.

Trial registration number

ClinicalTrials.gov (NCT02123394)
Maternal alcohol use disorder and child school attendance outcomes for non-Indigenous and Indigenous children in Western Australia: a population cohort record linkage study
Authors: Hafekost Katherine , Lawrence David , O’Leary Colleen , Bower Carol , Semmens James , Zubrick Stephen R
Published: July 2017

Objectives

Examine the relationship between maternal alcohol use disorder and child school attendance outcomes for non-Indigenous and Indigenous children in Western Australia.

Design

Population cohort study.

Setting

Routinely collected linked administrative health, education and child protection data.

Participants

Those in-scope for the study were women with a birth recorded on the Western Australian Midwives Notification System (1989–2007). Women who had an alcohol-related diagnosis (International Classification of Diseases Revisions 9/10) recorded on the Hospital Morbidity, Mental Health Inpatients and Outpatients, and Drug and Alcohol Office data sets formed the exposed group. The comparison cohort was frequency-matched to the exposed cohort based on maternal age within Indigenous status and child’s year of birth.

Primary outcome measure

Child’s school attendance was obtained from the Department of Education (2008–2012). Poor attendance was defined as <80% attendance for non-Indigenous children and <60% attendance for Indigenous children.

Results

11 430 exposed children and 26 850 unexposed children had a linked attendance record. Maternal alcohol use disorder was significantly associated with increased odds of poor attendance (non-Indigenous: OR=1.61, 95% CI 1.50 to 1.74; Indigenous: OR=1.66, 95% CI 1.54 to 1.79). With adjustment for maternal and child factors, there was no significant difference between the timing of alcohol diagnosis relative to pregnancy and attendance outcomes. The population attributable fraction was higher in the Indigenous cohort than the non-Indigenous cohort (6.0% vs 1.3%).

Conclusions

Maternal alcohol use disorder was associated with a significantly increased odds of poor school attendance for non-Indigenous and Indigenous children. There was no significant difference between the timing of diagnoses and odds of poor school attendance. This suggests that the effect of maternal alcohol use disorder may not be driven by the neurodevelopmental effects of alcohol exposure in utero, but may be mediated through family or social factors for which we were unable to adjust.
The effect of blinding on estimates of mortality in randomised clinical trials of intensive care interventions: protocol for a systematic review and meta-analysis
Authors: Anthon Carl Thomas , Granholm Anders , Perner Anders , Laake Jon Henrik , Møller Morten Hylander
Published: July 2017

Introduction

Evidence exists that unblinded randomised clinical trials (RCTs) overestimate intervention effects compared with blinded RCTs. It has been suggested that this is less pronounced for objective (ie, not subject to interpretation) outcome measures, including mortality. This may not apply in the intensive care unit (ICU), as most deaths are preceded by decisions to withhold or withdraw treatments. Lack of blinding of physicians in RCTs of ICU interventions may potentially influence the decision towards a higher threshold for discontinuing treatment in patients who receive the investigational treatment and/or a lower threshold for discontinuing treatment in patients who receive the comparator (control). This may have important implications for patients, caregivers, researchers and society. Accordingly, we aim to assess whether lack of blinding affects mortality effect estimates in RCTs of ICU interventions.

Methods and analysis

We will conduct a systematic review with meta-analyses and assess the effect of blinding versus no blinding on mortality effect estimates in RCTs of interventions used in adult ICU patients.

We will systematically search the Cochrane Library for systematic reviews reporting mortality effect estimates of any intervention used in adult ICU patients which includes at least one RCT with ‘low risk of bias’ in the bias domains ‘blinding of participants and personnel’ and/or ‘blinding of outcome assessment’ and one RCT with ‘unclear’ or ‘high risk of bias’ in the same bias domain(s). For each intervention, we will compare summary mortality effect estimates in blinded versus unblinded trials.

Ethics and dissemination

This research does not require ethical approval as we will use summary data from trials already approved by relevant ethical institutions. We will report the results in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement and submit the final paper to an international peer-reviewed journal.

Trial registration number

PROSPERO, registration number: CRD42017056212.
A directly comparative two-gate case–control diagnostic accuracy study of the pure tone screen and HearCheck screener tests for identifying hearing impairment in school children
Authors: Ukoumunne Obioha C , Hyde Chris , Ozolins Mara , Zhelev Zhivko , Errington Sam , Taylor Rod S , Benton Claire , Moody Joanne , Cocking Laura , Watson Julian , Fortnum Heather
Published: July 2017

Objectives

This study directly compared the accuracy of two audiometry-based tests for screening school children for hearing impairment: the currently used test, pure tone screen and a device newly applied to children, HearCheck Screener.

Design

Two-gate case–control diagnostic test accuracy study.

Setting and participants

Hearing impaired children (‘intended cases’) aged 4–6 years were recruited between February 2013 and August 2014 from collaborating audiology services. Children with no previously identified impairment (‘intended controls’) were recruited from Foundation and Year 1 of schools between February 2013 and June 2014 in central England. The reference standard was pure tone audiometry. Tests were administered at Nottingham Hearing Biomedical Research Unit or, for some intended cases only, in the participant’s home.

Main outcome measures

Sensitivity and specificity of the pure tone screen and HearCheck tests based on pure tone audiometry result as reference standard.

Results

315 children (630 ears) were recruited; 75 from audiology services and 240 from schools. Full test and reference standard data were obtained for 600 ears; 155 ears were classified as truly impaired and 445 as truly hearing based on the pure tone audiometry assessment. Sensitivity was estimated to be 94.2% (95% CI 89.0% to 97.0%) for pure tone screen and 89.0% (95% CI 82.9% to 93.1%) for HearCheck (difference=5.2% favouring pure tone screen; 95% CI 0.2% to 10.1%; p=0.02). Estimates for specificity were 82.2% (95% CI 77.7% to 86.0%) for pure tone screen and 86.5% (95% CI 82.5% to 89.8%) for HearCheck (difference=4.3% favouring HearCheck; 95% CI0.4% to 8.2%; p=0.02).

Conclusion

Pure tone screen was better than HearCheck with respect to sensitivity but inferior with respect to specificity. As avoiding missed cases is arguably of greater importance for school entry screening, pure tone screen is probably preferable in this context.

Study registration number

Current controlled trials:ISRCTN61668996.
TIGHTER BOUNDS FOR IMPLIED VOLATILITY
Authors: GATHERAL JIM , MATIĆ IVAN , RADOIČIĆ RADOŠ , STEFANICA DAN
Published: July 2017

We establish bounds on Black–Scholes implied volatility that improve on the uniform bounds previously derived by Tehranchi. Our upper bound is uniform, while the lower bound holds for most options likely to be encountered in practical applications. We further demonstrate the practical effectiveness of our new bounds by showing how the efficiency of the bisection algorithm is improved for a snapshot of SPX option quotes.