bluuebunny/crossref_metadata_2025 huggingface dataset:
Trophic state changes can affect the importance of methane-derived carbon in aquatic food webs
Authors: Schilder Jos , van Hardenbroek Maarten , Bodelier Paul , Kirilova Emiliya P. , Leuenberger Markus , Lotter André F. , Heiri Oliver
Published: June 2017

Methane-derived carbon, incorporated by methane-oxidizing bacteria, has been identified as a significant source of carbon in food webs of many lakes. By measuring the stable carbon isotopic composition (δ13C values) of particulate organic matter, Chironomidae andDaphniaspp. and their resting eggs (ephippia), we show that methane-derived carbon presently plays a relevant role in the food web of hypertrophic Lake De Waay, The Netherlands. Sediment geochemistry, diatom analyses and δ13C measurements of chironomid andDaphniaremains in the lake sediments indicate that oligotrophication and re-eutrophication of the lake during the twentieth century had a strong impact on in-lake oxygen availability. This, in turn, influenced the relevance of methane-derived carbon in the diet of aquatic invertebrates. Our results show that, contrary to expectations, methane-derived relative to photosynthetically produced organic carbon became more relevant for at least some invertebrates during periods with higher nutrient availability for algal growth, indicating a proportionally higher use of methane-derived carbon in the lake's food web during peak eutrophication phases. Contributions of methane-derived carbon to the diet of the investigated invertebrates are estimated to have ranged from 0–11% during the phase with the lowest nutrient availability to 13–20% during the peak eutrophication phase.
Higher-order neural processing tunes motion neurons to visual ecology in three species of hawkmoths
Authors: Stöckl A. L. , O'Carroll D. , Warrant E. J.
Published: June 2017

To sample information optimally, sensory systems must adapt to the ecological demands of each animal species. These adaptations can occur peripherally, in the anatomical structures of sensory organs and their receptors; and centrally, as higher-order neural processing in the brain. While a rich body of investigations has focused on peripheral adaptations, our understanding is sparse when it comes to central mechanisms. We quantified how peripheral adaptations in the eyes, and central adaptations in the wide-field motion vision system, set the trade-off between resolution and sensitivity in three species of hawkmoths active at very different light levels: nocturnalDeilephila elpenor,crepuscularManduca sexta, and diurnalMacroglossum stellatarum.Using optical measurements and physiological recordings from the photoreceptors and wide-field motion neurons in the lobula complex, we demonstrate that all three species use spatial and temporal summation to improve visual performance in dim light. The diurnalMacroglossumrelies least on summation, but can only see at brighter intensities.Manduca,with large sensitive eyes, relies less on neural summation than the smaller eyedDeilephila, but both species attain similar visual performance at nocturnal light levels. Our results reveal how the visual systems of these three hawkmoth species are intimately matched to their visual ecologies.
Evidence for “inter- and intraspecific horizontal genetic transfers” between anciently asexual bdelloid rotifers is explained by cross-contamination
Authors: Wilson Christopher G. , Nowell Reuben W. , Barraclough Timothy G.
Published: June 2017

Bdelloid rotifers are microscopic invertebrates thought to have evolved for millions of years without sexual reproduction. They have attracted the attention of biologists puzzled by the maintenance of sex among nearly all other eukaryotes. Bdelloid genomes have an unusually high proportion of horizontally acquired non-metazoan genes. This well-substantiated finding has invited speculation that homologous horizontal transfer between rotifers also may occur, perhaps even 'replacing' sex. A 2016 study inCurrent Biologyclaimed to supply evidence for this hypothesis. The authors sampled rotifers of the genusAdinetafrom natural populations and sequenced one mitochondrial and four nuclear loci. For several samples, species assignments were incongruent among loci, which the authors interpreted as evidence of "interspecific genetic exchanges". Here, we use sequencing chromatograms supplied by the authors to demonstrate that samples treated as individuals actually contained two or more divergent mitochondrial and ribosomal sequences, indicating contamination with DNA from additional animals belonging to the supposed “donor species”. We also show that “exchanged” molecules share only 75% sequence homology, a degree of divergence incompatible with established mechanisms of recombination and genomic features ofAdineta. These findings are parsimoniously explained by cross-contamination of tubes with animals or DNA from different species. Given the proportion of tubes contaminated in this way, we show by calculation that evidence for "intraspecific horizontal exchange" in the same dataset is explained by contamination with conspecific DNA. On the clear evidence of these analyses, the 2016 study provides no reliable support for the hypothesis of horizontal genetic transfer between or within these bdelloid species.
A Guide to Robust Statistical Methods in Neuroscience
Authors: Wilcox Rand R. , Rousselet Guillaume A.
Published: June 2017

There is a vast array of new and improved methods for comparing groups and studying associations that offer the potential for substantially increasing power, providing improved control over the probability of a Type I error, and yielding a deeper and more nuanced understanding of neuroscience data. These new techniques effectively deal with four insights into when and why conventional methods can be unsatisfactory. But for the non-statistician, the vast array of new and improved techniques for comparing groups and studying associations can seem daunting, simply because there are so many new methods that are now available. The paper briefly reviews when and why conventional methods can have relatively low power and yield misleading results. The main goal is to suggest some general guidelines regarding when, how and why certain modern techniques might be used.
Size control in mammalian cells involves modulation of both growth rate and cell cycle duration
Authors: Cadart Clotilde , Monnier Sylvain , Grilli Jacopo , Attia Rafaele , Terriac Emmanuel , Baum Buzz , Cosentino-Lagomarsino Marco , Piel Matthieu
Published: June 2017

Despite decades of research, it remains unclear how mammalian cell growth varies with cell size and across the cell division cycle to maintain size control. Answers have been limited by the difficulty of directly measuring growth at the single cell level. Here we report direct measurement of single cell volumes over complete cell division cycles. The volume added across the cell cycle was independent of cell birth size, a size homeostasis behavior called “adder”. Single-cell growth curves revealed that the homeostatic behavior relied on adaptation of G1 duration as well as growth rate modulations. We developed a general mathematical framework that characterizes size homeostasis behaviors. Applying it on datasets ranging from bacteria to mammalian cells revealed that a near-adder is the most common type of size control, but only mammalian cells achieve it using modulation of both cell growth rate and cell-cycle progression.
Specter: linear deconvolution as a new paradigm for targeted analysis of data-independent acquisition mass spectrometry proteomics
Authors: Peckner Ryan , Myers Samuel A , Egertson Jarrett D , Johnson Richard S , Abelin Jennifer G. , Carr Steven A , MacCoss Michael J , Jaffe Jacob D
Published: June 2017

Mass spectrometry with data-independent acquisition (DIA) has emerged as a promising method to greatly improve the comprehensiveness and reproducibility of targeted and discovery proteomics, in theory systematically measuring all peptide precursors within a biological sample. Despite the technical maturity of DIA, the analytical challenges involved in discriminating between peptides with similar sequences in convoluted spectra have limited its applicability in important cases, such as the detection of single-nucleotide polymorphisms and alternative site localizations in phosphoproteomics data. We have developed Specter, an open-source software tool that uses linear algebra to deconvolute DIA mixture spectra directly in terms of a spectral library, circumventing the problems associated with typical fragment correlation-based approaches. We validate the sensitivity of Specter and its performance relative to other methods by means of several complex datasets, and show that Specter is able to successfully analyze cases involving highly similar peptides that are typically challenging for DIA analysis methods.
RAPGEF5 regulates nuclear translocation of β-catenin
Authors: Griffin John N. , Viso Florencia del , Duncan Anna R. , Robson Andrew , Kulkarni Saurabh , Liu Karen J. , Khokha Mustafa K.
Published: June 2017

Canonical Wnt signaling coordinates many critical aspects of embryonic development, while dysregulated Wnt signaling contributes to common diseases, including congenital malformations and cancer. The nuclear localization of β-catenin is the defining step in pathway activation. However, despite intensive investigation, the mechanisms regulating β-catenin nuclear transport remain undefined. In a patient with congenital heart disease and heterotaxy, a disorder of left-right patterning, we previously identified the guanine nucleotide exchange factor, RAPGEF5. Here, we demonstrate that RAPGEF5 regulates left-right patterning via Wnt signaling. In particular, RAPGEF5, regulates the nuclear translocation of β-catenin independently of both β-catenin cytoplasmic stabilization and the importin β1/Ran mediated transport system. We propose a model whereby RAPGEF5 activates the nuclear GTPases, Rap1/2, to facilitate the nuclear transport of β-catenin, defining a parallel nuclear transport pathway to Ran. Our results suggest new targets for modulating Wnt signaling in disease states.
Emergent properties in complex synthetic bacterial promoters
Authors: Monteiro Lummy Maria Oliveira , Arruda Letícia Magalhães , Silva-Rocha Rafael
Published: June 2017

Regulation of gene expression in bacteria results from the interplay between transcriptional factors (TFs) at target promoters, and how the arrangement of binding sites determines the regulatory logic of promoters is not well known. Here, we generated and fully characterized a library of synthetic complex promoters for the global regulators, CRP and IHF, inEscherichia coli, formed by a weak -35/-10 consensus sequence preceded by four combinatorial binding sites for these TFs. We found that whilecis-elements for CRP preferentially activate promoters when located immediately upstream of the promoter consensus, binding sites for IHF mainly function as “UP” elements and stimulate transcription in several different architectures in the absence of this protein. However, the combination of CRP- and IHF-binding sites resulted in emergent properties in these complex promoters, where the activity of combinatorial promoters cannot be predicted from the individual behavior of its components. Taken together, the results presented here add to the information on architecture-logic of complex promoters in bacteria.
Mechanical mismatch between Ras transformed and untransformed epithelial cells
Authors: Gullekson Corinne , Cojoc Gheorghe , Schürmann Mirjam , Guck Jochen , Pelling Andrew
Published: June 2017

The organization of the actin cytoskeleton plays a key role in regulating cell mechanics. It is fundamentally altered during transformation, affecting how cells interact with their environment. We investigated mechanical properties of cells expressing constitutively active, oncogenic Ras (RasV12) in adherent and suspended states. To do this, we utilized atomic force microscopy and a microfluidic optical stretcher. We found that adherent cells stiffen and suspended cells soften with the expression of constitutively active Ras. The effect on adherent cells was reversed when contractility was inhibited with the ROCK inhibitor Y-27632, resulting in softer RasV12cells. Our findings suggest that increased ROCK activity as a result of Ras has opposite effects on suspended and adhered cells. Our results also establish the importance of the activation of ROCK by Ras and its effect on cell mechanics.
Effect of swap disorder on the physical properties of the quaternary Heusler alloy PdMnTiAl: a first-principles study
Authors: Qin Guanhua , Wu Wei , Hu Shunbo , Tao Yongxue , Yan Xiaoyan , Jing Chao , Li Xi , Gu Hui , Cao Shixun , Ren Wei
Published: June 2017

Heusler alloys crystallize in a close-packed cubic structure, having a four-atom basis forming a face-centred cubic lattice. By selecting different composite elements, Heusler alloys provide a large family of members for frontier research of spintronics and magnetic materials and devices. In this paper, the structural, electronic and magnetic properties of a novel quaternary Heusler alloy, PdMnTiAl, have been investigated using a first-principles computational materials calculation. It was found that the stable ordered structure is a non-magneticY-type1, in good agreement with the Slater–Pauling rule. From the band structure and the density of states, it is predicted that thisY-type1 configuration is a new gapless semi-metal material. Furthermore, it was discovered that the Pd–Mn swap-disordered structure is more stable than theY-type1 structure. The present work provides a guide for experiments to synthesize and characterize this Heusler alloy.
Hard-sphere displacive model of deformation twinning in hexagonal close-packed metals. Revisiting the case of the (56°,a) contraction twins in magnesium
Authors: Cayron Cyril
Published: June 2017

Contraction twinning in magnesium alloys leads to new grains that are misoriented from the parent grain by a rotation (56°,a). The classical shear theory of deformation twinning does not specify the atomic displacements and does not explain why contraction twinning is less frequent than extension twinning. The paper proposes a new displacive model in line with our previous work on martensitic transformations and extension twinning. A continuous angular distortion matrix that transforms the initial hexagonal close-packed (h.c.p.) crystal into a final h.c.p. crystal is determined such that the atoms move as hard spheres and reach the final positions expected by the orientation relationship. The calculations prove that the distortion is not a simple shear when it is considered in its continuity. The ({0{\overline 1}1}) plane is untilted and restored, but it is not fully invariant because some interatomic distances in this plane evolve during the distortion process; the unit volume also increases up to 5% before coming back to its initial value when the twinning distortion is complete. Then, the distortion takes the form of a simple shear on the ({0{\overline 1}1}) plane with a shear along the direction [{18,{\overline 5},{\overline 5}}] of amplitude 0.358. Experiments are proposed to validate or disprove the model.
Effect of ownership structure and board structure on firm value: evidence from India
Authors: Mishra Rakesh , Kapil Sheeba
Published: June 2017

Purpose

This paper aims to explore the relationship of promoter ownership and board structure with firm performance for Indian companies.

Design/methodology/approach

Corporate governance structures of 391 Indian companies out of CRISIL NSE Index (CNX) 500 companies listed on national stock exchange (NSE) have been studied for their impact on performance of companies. Panel data regression methodology has been used on data for five financial years from 2010 to 2014 for the selected companies. Performance measures considered are market-based measure (Tobin’s Q) and accounting-based measure (return on assets [ROA]).

Findings

The empirical findings indicate that market-based measure (Tobin’s Q) is more impacted by corporate governance than accounting-based measure. There is significant positive association between promoter ownership and firm performance. It is also indicated that the relationship between promoter ownership and firm performance is different at different levels of promoter ownership. Board size is found to be positively related to ROA; however, board independence is not found to be related to any of the performance measures.

Research limitations/implications

Limitations of the study are in terms of data methodology and possible omission of some variables. It is felt that endogeneity and reverse causality might be better addressed using simultaneous equation methodology.

Originality/value

The paper adds to the emerging body of literature on corporate governance performance relationship in Indian context using a reasonably wider and newer data set.
Identifying the factors determining cooperative innovation effect in emerging economies
Authors: Xie Xuemei , Zeng Saixing , Zang Zhipeng , Zou Hailiang
Published: June 2017

Purpose

The purpose of this study is to identify the factors determining collaborative innovation effect of manufacturing firms in emerging economies.

Design/methodology/approach

Based on a survey of 1,206 Chinese manufacturing firms and using structural equation modelling, this study explores the factors determining the effect of collaborative innovation among manufacturing firms (namely, internal capabilities, government policies, collaboration mechanisms and social networks) and examines the relationship between collaborative innovation effect and innovation performance.

Findings

The study finds that there are significantly positive relationships between firms’ internal capabilities, government policies, collaboration mechanisms and social networks and collaborative innovation effect among firms.

Practical implications

These findings reveal that policymakers should create an effective institutional culture and market environment to facilitate firms’ collaborative innovation.

Originality/value

This paper draws on the resource-based view of firms and contributes to understanding of how the development of factors determining firms’ collaborative innovation effect can improve innovation performance. This study extends established frameworks on collaborative innovation in relation to four dimensions, namely, firms’ internal capabilities, government policies, collaboration mechanisms and social networks, uniquely identifying the limits of specific dimensions. Moreover, this study addresses government policies and “Guanxi culture” specific to China that provide new insights into how firms’ collaborative innovation is improved from the perspectives of business–governmental relations and social networks.
The mediating effect of LMX in the relationship between school bureaucratic structure and teachers’ proactive behavior
Authors: Cerit Yusuf
Published: June 2017

Purpose

The purpose of this paper is to examine the mediating effect of leader-member exchange on school bureaucratic structure and teachers’ proactive behavior.

Design/methodology/approach

The study was carried out in elementary schools in Turkey. Classroom teachers proactive behavior was measured using the taking charge scale developed by Morrison and Phelps (1999), school bureaucratic structure was measured using enabling school structure scale developed by Hoy and Sweetland (2000), and LMX quality was measured using the seven-item LMX scale developed by Graen ve Uhl-bien (1995).

Findings

It was found that school bureaucratic structure had both directly and indirectly effect on teachers proactive behavior via leader-member exchange.

Research limitations/implications

This study contributes to complete proactive behavior literature by investigating how such behavior is related to the quality of LMX relationships and school bureaucratic structure. The investigation of these relationships is likely to advance understanding of the consequences of teachers’ proactive behavior.

Originality/value

This research combines prior research streams by jointly exploring bureaucratic school structure and the quality of LMX relationships as predictors of teachers’ proactive behaviors.
Keratitis–ichthyosis–deafness syndrome accompanied by disseminated cutaneous fungal infection
Authors: Ma Han , Liang Panpan , Chen Jian , Feng Peiying , Lai Wei
Published: June 2017

Keratitis–ichthyosis–deafness (KID) syndrome is a rare genodermatosis. It is mostly associated with mutations of the connexin 26 gene, resulting in keratitis, erythrokeratoderma and neurosensory deafness. In addition to the clinical triad, the KID syndrome patients are at high risk for infectious complications, while the mechanisms are poorly understood. In the present article, we described an Asian case of KID syndrome accompanied by fungal infection. The present study was designed to define the mutation type, and further to explore the interaction between the innate immunity response and the infectious complication of KID syndrome. Genomic DNA was extracted from peripheral blood for mutation analysis. Isolation and identification of the species were carried out to confirm the infectious microorganism. Three biopsy specimens from different parts of the body (right thigh, abdomen and forehead, respectively) were carried out for histopathological and immunohistochemical analysis. Furthermore, quantitative polymerase chain reaction (PCR) was carried out to study the expression of Toll‐like receptor 2 (TLR2) on the epidermis of the right thigh. We identified a mutation (p.G12R) in the GJB2 gene in this patient with Trichophyton rubrum infection. Immunohistochemistry staining revealed a lower expression of TLR2 and no significant difference in TLR4. Meanwhile, PCR showed a relatively slight increase of TLR2 RNA expression. These results indicated that GJB2 mutation (p.G12R) in this case of KID syndrome, which was susceptible to T. rubrum infection, might be attributed to a limited native immune response.
Efficacy and safety of ixekizumab treatment in Japanese patients with moderate‐to‐severe plaque psoriasis: Subgroup analysis of a placebo‐controlled, phase 3 study (UNCOVER‐1)
Authors: Imafuku Shinichi , Torisu‐Itakura Hitoe , Nishikawa Atsushi , Zhao Fangyi , Cameron Gregory S. ,   the Japanese UNCOVER‐1 Study Group
Published: June 2017

The present study describes a subgroup analysis of 33 Japanese patients participating in UNCOVER‐1, an international, placebo‐controlled, phase 3 study of ixekizumab in patients with moderate‐to‐severe psoriasis. Patients were randomized to a placebo (n = 13) or ixekizumab 80 mg every 4 (IXEQ4W, n = 12) or 2 (IXEQ2W, n = 8) weeks, from week 0–12. At week 12, ixekizumab‐treated patients with a static Physician Global Assessment score 0 or 1 (sPGA [0,1]; n = 16) were re‐randomized to a placebo (n = 6), ixekizumab 80 mg every 12 (IXEQ12W, n = 5) or 4 (IXEQ4W, n = 5) weeks, from week 12–60. At week 12, more ixekizumab‐treated versus placebo‐treated patients achieved sPGA (0,1) (≥66.7% vs 0%), ≥75% improvement in Psoriasis Area and Severity Index (≥75% vs 0%), and sPGA (0) or 100% improvement in Psoriasis Area and Severity Index (both ≥33.3% vs 0%), with improved symptoms and quality of life. At week 60, 100% (IXEQ4W), 40.0% (IXEQ12W) and 16.7% (placebo) had maintained sPGA (0,1). From week 0–12, treatment‐emergent adverse events were 76.9% (placebo), 75.0% (IXEQ4W) and 87.5% (IXEQ2W), and from week 12–60 were 66.7% (placebo) and 100% (IXEQ12W, IXEQ4W). Ixekizumab‐treated patients had no severe treatment‐emergent adverse events, and one serious TEAE (IXEQ4W); infection was the most frequent treatment‐emergent adverse event. In conclusion, ixekizumab for 60 weeks was effective and safe for Japanese patients with moderate‐to‐severe psoriasis, in line with the overall findings from UNCOVER‐1.
Special education and subject teachers’ self‐perceived readiness to teach mathematics to low‐performing middle school students
Authors: Ekstam Ulrika , Korhonen Johan , Linnanmäki Karin , Aunio Pirjo
Published: June 2017

Educational reforms during the last decade have led to a more inclusive environment for students with different needs and have placed demands on teachers’ readiness to instruct diverse students in the general classroom. Previous research has ascertained that student achievement is correlated with teacher quality and teachers’ efficacy beliefs. Today, basic competence in mathematics is more important than ever for managing routine day‐to‐day activities and therefore, identifying and educationally supporting students with low performance in mathematics is necessary. The aim of the study was to investigate the perceived teacher efficacy beliefs of special education and mathematics teachers when teaching mathematics to low‐performing middle school students. Results indicated that special education teachers had higher teacher efficacy beliefs than mathematics teachers. Teacher experience, certification or gender had no effect on teachers’ efficacy beliefs. Furthermore, subject teachers reported high pedagogical knowledge for teaching low‐performing students, and special education teachers reported having moderate mathematical subject knowledge.
Development of advanced practice competency standards for dietetics in Australia
Authors: Palermo Claire , Capra Sandra , Beck Eleanor J , Dart Janeane , Conway Jane , Ash Susan
Published: June 2017

Aim

This study aimed to explore the work roles, major tasks and core activities of advanced practice dietitians in Australia to define the Competency Standards for advanced practice.

Methods

A qualitative approach was used to review advanced dietetic practice in Australia involving experienced professionals, mostly dietitians. Four focus groups were conducted with a total of 17 participants and an average of 20 years experience: 15 dietitian practitioners plus 2 employers (1 dietitian and 1 non‐dietitian). The focus groups explored the key purpose, roles and outcomes of these practitioners. Data from the focus groups were confirmed with in‐depth interviews about their core activities with a purposive sample of 10 individuals recently recognised as Advanced Accredited Practising Dietitians. Data from both focus groups and interviews were analysed adductively to identify key themes.

Results

The key theme that emerged to define advanced dietetics practice was leadership, with four subthemes that described in more detail the major work roles and outcomes of advanced practice. These subthemes identified that advanced practitioners were (i) outcome‐focused, having impact; (ii) influence others and advocate; (iii) innovate and embrace change; and (iv) inspire others and are recognised for their practice. These outcomes were conceptualised within a broad generalist framework to generate revised Competency Standards.

Conclusions

This study confirmed that leadership rather than specialist practice skills is the key determinant of advanced practice.
Sulforaphane protection against the development of doxorubicin‐induced chronic heart failure is associated with Nrf2 Upregulation
Authors: Bai Yang , Chen Qiang , Sun Yun‐Peng , Wang Xuan , Lv Li , Zhang Li‐Ping , Liu Jin‐Sha , Zhao Song , Wang Xiao‐Lu
Published: June 2017

Background

Doxorubicin (DOX) is an anthracycline antitumor drug. However, its clinical use is limited by dose‐dependent cardiotoxicity and even progresses to chronic heart failure (CHF).

Objective

This study aims to investigate whether the Nrf2 activator, sulforaphane (SFN), can prevent DOX‐induced CHF.

Methods

Male Sprague‐Dawley rats which received treatment for 6 weeks were divided into four groups (n=30 per group): control, SFN, DOX and DOX plus SFN group.

Results

Results revealed that DOX induced progressive cardiac damage as indicated by increased cardiac injury markers, cardiac inflammation, fibrosis and oxidative stress. SFN significantly prevented DOX‐induced progressive cardiac dysfunction between 2‐6 weeks and prevented DOX‐induced cardiac function deterioration. Furthermore, it significantly decreased ejection fraction and increased the expression of brain natriuretic peptide. SFN also almost completely prevented DOX‐induced cardiac oxidative stress, inflammation and fibrosis. SFN upregulated NF‐E2‐related factor 2 (Nrf2) expression and transcription activity, which was reflected by the increased mRNA expression of Nrf2 and its downstream genes. Furthermore, in cultured H9c2 cardiomyocytes, the protective effect of SFN against DOX‐induced fibrotic and inflammatory responses was abolished by Nrf2 silencing.

Conclusion

We arrived at the conclusion that DOX‐induced CHF can be prevented by SFN through the upregulation of Nrf2 expression and transcriptional function.
A farewell to the sum of Akaike weights: The benefits of alternative metrics for variable importance estimations in model selection
Authors: Galipaud Matthias , Gillingham Mark A. F. , Dechaume‐Moncharmont François‐Xavier
Published: June 2017

In a previous article, we advocated against using the sum of Akaike weights (SW) as a metric to distinguish between genuine and spurious variables in Information Theoretic (IT) statistical analyses. A recent article (Giam & Olden, Methods in Ecology and Evolution, 2016, 7, 388) criticises our finding and instead argues in favour of SW. It points out that (1) we performed a biased data‐generation procedure and (2) we erroneously evaluated SW on its capacity to estimate the proportion of variance in the data explained by a variable. We here respond to these points.

Giam and Olden's first concern is unfounded. When using the data‐generating code they proposed, SW remains very imprecise. To respond to their second concern, we first list the meanings taken by a variable's importance in the context of IT. Although, SW is presented as an estimate of variable relative importance in methodological textbooks (i.e. a variable's rank in importance or its relative contribution to the variance in the data), it is also used as a metric of variable absolute importance (i.e. a variable's absolute effect size or its statistical significance). We then compare SW to alternative metrics on its ability to estimate variable absolute or relative importance.

SW values have low repeatability across analyses. As a result, based on SW, it is hard to distinguish between variables with weak and large effects. For estimations of variable absolute importance, experimenters should prefer model‐averaged parameter estimates and/or compare nested models based on evidence ratios. Sum of Akaike weights is also a poor metric of variable relative importance. We showed that correct variable ranking in importance was generally more frequent when using model‐averaged standardised parameter estimates, than when using SW.

To avoid recurrent errors in ecology and evolution, we therefore warn against the use of SW for estimations of variable absolute and relative importance and we propose that experimenters should instead use model‐averaged standardised parameter estimates for statistical inferences.
JUXTAPOSING LITERARY AND DOCUMENTARY EVIDENCE: A NEW COPY OF THE SO-CALLED HELIODOROS STELE AND THE CORPUS INSCRIPTIONUM IUDAEAE/PALAESTINAE (CIIP)
Authors: COTTON-PALTIEL HANNAH M. , ECKER AVNER , GERA DOV
Published: June 2017

This article was prompted by the recent discovery of two more copies of the so-called ‘Heliodoros Stele’ from Maresha. A second one from Byblos was published in 2015. The third one, re-discovered recently and published here for the first time, also comes from Maresha. The steles bear Seleukos IV's epistolary prostagma from 178 bc to his vizier Heliodoros, and forwarded to other officials with the instruction to display it in public. It contains an appointment of one Olympiodoros to be high priest in Koele Syria and Phoenicia. Both Seleukos IV and Heliodoros also appear in the story of the plundering of the Temple related in II Maccabees 3. The existence of multiple copies, though hardly surprising, made us suspect the king's apologetic tone and identify the ‘reform’ as an attempt to embellish the withdrawal of previously bestowed privileges on the Jews (so Josephus) as well as on others.
Selective laser trabeculoplasty as replacement therapy in medically controlled glaucoma patients
Authors: De Keyser Myrjam , De Belder Maya , De Belder Jonas , De Groot Veva
Published: June 2017

Purpose

We examined selective laser trabeculoplasty (SLT) as a replacement therapy for medically controlled open‐angle glaucoma (OAG) or ocular hypertensive patients.

Methods

A prospective randomized interventional clinical trial on 143 glaucoma patients. Patients were randomized to either receiving SLT or to the control group that continued on pressure lowering medication. Data were recorded 1 hr, 1 week, 1, 3, 6, 12 and 18 months after SLT. Primary outcome was number of medications at 12 and 18 months while maintaining a predetermined target intraocular pressure (IOP).

Results

Selective laser trabeculoplasty (SLT) reduced number of medications from a mean of 1.5 at baseline, to 0.35 after 12 months and 0.29 after 18 months. Meanwhile, SLT achieved more than 20% IOP lowering in 95% of eyes and more than 30% IOP lowering in 86% of eyes after 18 months. Seventy‐seven per cent of our eyes no longer needed any medication after SLT at 18 months.

Conclusion

Selective laser trabeculoplasty (SLT) enabled a reduction in number of medications while maintaining good IOP control. Selective laser trabeculoplasty (SLT) was able to completely replace medical therapy in 77% of eyes after 18 months. Selective laser trabeculoplasty (SLT) as replacement therapy may reduce local and systemic side‐effects and prevent adherence issues.
The Effect of Genetic Polymorphisms in SLCO2B1 on the Lipid‐Lowering Efficacy of Rosuvastatin in Healthy Adults with Elevated Low‐Density Lipoprotein
Authors: Kim Tae‐Eun , Shin Dongseong , Gu Namyi , Jung Byung Hwa , Kim Jayoun , Cho Young Min , Yu Kyung‐Sang , Cho Joo‐Youn
Published: June 2017

Rosuvastatin is an HMG‐CoA reductase inhibitor widely used for treating hypercholesterolaemia. We investigated whether genetic polymorphisms in solute carrier organic anion transporter 2B1 (SLCO2B1) affect the lipid‐lowering effect of rosuvastatin in healthy adults with elevated low‐density lipoprotein (LDL). This study included 18 volunteers with LDL levels above 130 mg/dL. Rosuvastatin (20 mg) was administered once a day for 8 weeks. Blood samples were drawn before and after the 8‐week treatment to measure changes in lipid levels. The presence of single nucleotide polymorphisms (SNPs) of SLCO2B1 (c.935G>A and c.1457C>T), SLCO1B1 (c.521C>T, c.388A>G and c.‐11187G>A) and ABCG2 (c.421C>A) was determined by genotyping. Responses to rosuvastatin were compared between wild‐type and variant genotypes using permutation test on each polymorphism. In volunteers with SLCO2B1 c.935G>A (rs12422149) variant, rosuvastatin was less effective at lowering LDL (mean % decrease: GG 62.8% GA 50.6% AA 49.3%, p = 0.012) and apoprotein B (mean % decrease: GG 52.1% GA 42.8% AA 42.8%, p = 0.036). Regarding SLCO2B1 c.1457C>T (rs2306168) SNP, there was no significant difference between wild‐type and variant genotypes. This study demonstrated that SLCO2B1 c.935G>A (rs12422149) polymorphism influenced the lipid‐lowering effects of rosuvastatin in volunteers with hypercholesterolaemia.
Communautés francophones minoritaires : Le territoire influence‐t‐il l'identité linguistique ?
Authors: Charron Mathieu
Published: June 2017

Messages clés

Le territoire joue un rôle dans la construction de l'identité linguistique des francophones en situation minoritaire.

L'impact du territoire est cependant plus important sur la perception de la vitalité linguistique et les pratiques linguistiques.

Les technologies d'information et de communication pourraient modifier le rôle du territoire dans la construction identitaire.
RNA‐dependent RNA polymerase: Addressing Zika outbreak by a phylogeny‐based drug target study
Authors: Stephen Preyesh , Lin Sheng‐Xiang
Published: June 2017

Since the first major outbreak of Zika virus (ZIKV) in 2007, ZIKV is spreading explosively through South and Central America, and recent reports in highly populated developing countries alarm the possibility of a more catastrophic outbreak. ZIKV infection in pregnant women leads to embryonic microcephaly and Guillain–Barré syndrome in adults. At present, there is limited understanding of the infectious mechanism, and no approved therapy has been reported. Despite the withdrawal of public health emergency, the WHO still considers the ZIKV as a highly significant and long‐term public health challenge that the situation has to be addressed rapidly. Non‐structural protein 5 is essential for capping and replication of viral RNA and comprises a methyltransferase and RNA‐dependent RNA polymerase (RdRp) domain. We used molecular modeling to obtain the structure of ZIKV RdRp, and by molecular docking and phylogeny analysis, we here demonstrate the potential sites for drug screening. Two metal binding sites and an NS3‐interacting region in ZIKV RdRp are demonstrated as potential drug screening sites. The docked structures reveal a remarkable degree of conservation at the substrate binding site and the potential drug screening sites. A phylogeny‐based approach is provided for an emergency preparedness, where similar class of ligands could target phylogenetically related proteins.
pH‐dependent general base catalyzed activation rather than isocyanate liberation may explain the superior anticancer efficacy of laromustine compared to related 1,2‐bis(methylsulfonyl)‐1‐(2‐chloroethyl)hydrazine prodrugs
Authors: Penketh Philip G. , Finch Richard A. , Sauro Rachel , Baumann Raymond P. , Ratner Elena S. , Shyam Krishnamurthy
Published: June 2017

Laromustine (also known as cloretazine, onrigin, VNP40101M, 101M) is a prodrug of 90CE, a short‐lived chloroethylating agent with anticancer activity. The short half‐life of 90CE necessitates the use of latentiated prodrug forms for in vivo treatments. Alkylaminocarbonyl‐based prodrugs such as laromustine exhibit significantly superior in vivo activity in several murine tumor models compared to analogs utilizing acyl, and alkoxycarbonyl latentiating groups. The alkylaminocarbonyl prodrugs possess two exclusive characteristics: (i) They are primarily unmasked by spontaneous base catalyzed elimination; and (ii) they liberate a reactive carbamoylating species. Previous speculations as to the therapeutic superiority of laromustine have focused upon the inhibition of enzymes by carbamoylation. We have investigated the therapeutic interactions of analogs with segregated chloroethylating and carbamoylating activities (singly and in combination) in the in vivo murine L1210 leukemia model. The combined treatment with chloroethylating and carbamoylating prodrugs failed to result in any synergism and produced a reduction in the therapeutic efficacy compared to the chloroethylating prodrug alone. Evidence supporting an alternative explanation for the superior tumor selectivity of laromustine is presented that is centered upon the high pH sensitivity of its base catalyzed activation, and the more alkaline intracellular pH values commonly found within tumor cells.
Listening to Young People with Learning Disabilities Who Have Experienced, or Are at Risk of, Child Sexual Exploitation in the UK
Authors: Franklin Anita , Smeaton Emilie
Published: June 2017

This paper reports on a UK study which examined the identification of, and support for young people with learning disabilities who experience, or are at risk of, child sexual exploitation (CSE). CSE has received considerable attention in the UK, with evidence suggesting an increased risk for young people with learning disabilities. However, no study has specifically focused on this group, and their voices remain largely unheard. In‐depth interviews with 27 young people with learning disabilities were undertaken to explore how to meet their needs. This paper presents the young people's voices and identifies areas for improvements in policy and practice.
The length of patient and primary care time interval in the pathways to treatment in symptomatic oral cancer. A quantitative systematic review
Authors: Varela‐Centelles P. , Seoane J. , Lopez‐Cedrun J.L. , Fernandez‐Sanroman J. , García‐Martin J.M. , Takkouche B. , Alvarez‐Novoa P. , Seoane‐Romero J.M.
Published: June 2017

Objectives

To examine the relative length of the patient and primary care intervals in symptomatic oral cancer.

Design

Quantitative systematic review. Search strategy: Oral cancer OR oral squamous cell carcinoma OR oropharyngeal cancer AND time interval OR diagnostic delay.

Setting

Primary and secondary care.

Participants

Oral and oropharyngeal cancer patients.

Main outcome measures

We computed five measures (patient, primary care, diagnosis, total diagnosis and total treatment intervals). Most studies did not provide any dispersion measure. We then used the sample size of each study to compute a weighted average of the mean intervals. When the median was provided, we assumed normality of the distribution of the means and used the median as a proxy of the mean.

Results

A total of 1089 articles were identified, and 22 met the inclusion criteria, reporting on 2710 patients from Europe, USA, India, Australia, Japan, Argentina and Iran. The weighted average of patient interval was 80.3 days. Primary care interval was five times shorter: 15.8 days. The diagnostic interval was appreciably shorter (47.9 days) when compared with the patient interval during symptomatic period.

Conclusions

Patient interval represents the major component of waiting times since the detection of the first signs/symptoms to the definitive diagnosis of oral cancer. Thus, strategies focused on high‐risk patients should be prioritised. Interventions aimed at optimising the health systems should be implemented by monitoring and facilitating diagnostic and treatment pathways of patients with oral cancer.
The role of long‐term physical exercise on performance and brain activation during the Stroop colour word task in fibromyalgia patients
Authors: Martinsen S. , Flodin P. , Berrebi J. , Löfgren M. , Bileviciute‐Ljungar I. , Mannerkorpi K. , Ingvar M. , Fransson P. , Kosek E.
Published: June 2017

The Stroop colour word test (SCWT) has been widely used to assess changes in cognitive performance such as processing speed, selective attention and the degree of automaticity. Moreover, the SCWT has proven to be a valuable tool to assess neuronal plasticity that is coupled to improvement in performance in clinical populations. In a previous study, we showed impaired cognitive processing during SCWT along with reduced task‐related activations in patients with fibromyalgia. In this study, we used SCWT and functional magnetic resonance imagingFMRI to investigate the effects of a 15‐week physical exercise intervention on cognitive performance, task‐related cortical activation and distraction‐induced analgesia (DIA) in patients with fibromyalgia and healthy controls. The exercise intervention yielded reduced fibromyalgia symptoms, improved cognitive processing and increased task‐related activation of amygdala, but no effect on DIA. Our results suggest beneficial effects of physical exercise on cognitive functioning in FM.
The real thing: preschoolers prefer actual activities to pretend ones
Authors: Taggart Jessica , Heise Megan J. , Lillard Angeline S.
Published: June 2017

Pretend play is a quintessential activity of early childhood, and adults supply children with many toys to encourage it. Do young children actually prefer to pretend, or do they do it because they are unable to engage in some activities for real? Here we examined, for nine different activities, American middle‐class preschoolers' preferences for pretend and real activities. The 100 children we tested (M = 58.5 months, range 36 to 82 months) overwhelmingly preferred real activities to pretend ones, and this preference increased from age 3 to age 4, then remained steady through age 6. Children provided cogent justifications for their preferences. The results are discussed with reference to other domains in which children show reality preferences and with respect to the content of preschool curricula.
Successful management of refractory diabetic gastroparesis with long‐term Aprepitant treatment
Authors: Fountoulakis N. , Dunn J. , Thomas S. , Karalliedde J.
Published: June 2017

Background

People with gastroparesis who develop treatment‐resistant (refractory) disease pose a difficult challenge, especially in the setting of end‐stage renal disease (ESRD) or post pancreas transplant. Aprepitant (a neurokinin‐receptor antagonist) is licensed for the short‐term treatment of chemotherapy‐induced nausea. There is lack of information on its long‐term efficacy and safety in people with diabetic gastroparesis.

Case report

Case 1 was 73‐year‐old man with Type 2 diabetes of 25 years’ duration and ESRD requiring dialysis. He was referred to our unit as his severe symptoms of gastroparesis had failed to respond to multiple medications and resulted in frequent hospital admissions. Aprepitant, which can be used in ESRD, resulted in significant improvement in his symptoms of nausea and vomiting within weeks, and he remained on this long term (18 months) with continued benefits and had no further gastroparesis‐related hospital admissions. Case 2 was a 44‐year‐old man with Type 1 diabetes of 41 years’ duration with a history of severe hypoglycaemic events that required a pancreas transplant. Despite normoglycaemia, his symptoms of gastroparesis persisted and failed to respond to multiple medications and frequent botulinum toxin injections. He was commenced on aprepitant with significant improvement in symptoms and has remained on treatment for 12 months with sustained benefits.

Conclusion

We describe two cases in which long‐term aprepitant treatment proved effective in alleviating severe symptoms of gastroparesis that had failed to respond to conventional first‐line medical treatments. Our cases highlight the need for novel treatments for managing refractory diabetic gastroparesis.
Fetal overnutrition and offspring insulin resistance and β‐cell function: the Exploring Perinatal Outcomes among Children (EPOCH) study
Authors: Sauder K. A. , Hockett C. W. , Ringham B. M. , Glueck D.H. , Dabelea D.
Published: June 2017

Aims

To examine the associations of intrauterine exposure to maternal diabetes and obesity with offspring insulin resistance, β‐cell function and oral disposition index in a longitudinal observational study of ethnically diverse offspring.

Methods

A total of 445 offspring who were exposed (n=81) or not exposed (n=364) to maternal diabetes in utero completed two fasting blood measurements at mean (sd) ages of 10.5 (1.5) and 16.5 (1.2) years, respectively, and an oral glucose tolerance test at the second visit. We used linear mixed models and general linear univariate models to evaluate the associations of maternal diabetes and pre‐pregnancy BMI with offspring outcomes.

Results

Maternal diabetes in utero predicted increased insulin resistance [18% higher updated homeostatic model assessment of insulin resistance (HOMA2‐IR), P=0.01; 19% lower Matsuda index, P=0.01 and 9% greater updated homeostatic model assessment of β‐cell function (HOMA2‐β), P=0.04]. Each 5‐kg/m2 increase in pre‐pregnancy BMI predicted increased insulin resistance (11% greater HOMA2‐IR, P<0.001; 10% lower Matsuda index, P<0.001; 6% greater HOMA2‐β, P<0.001). Similar results were obtained in a combined model with both exposures. After adjustment for offspring BMI, only maternal diabetes was associated with higher HOMA2‐IR (β=1.12, P=0.03) and lower Matsuda index (β=0.83, P=0.01). Neither exposure was associated with early insulin response or oral disposition index.

Conclusions

Intrauterine exposure to diabetes or obesity is associated with greater offspring insulin resistance than non‐exposure, supporting the hypothesis that fetal overnutrition results in metabolic abnormalities during childhood and adolescence.