bluuebunny/crossref_metadata_2025 huggingface dataset:
Severe Thrombocytopenia in Adults with Severe Acute Respiratory Distress Syndrome: Impact of Extracorporeal Membrane Oxygenation Use
Authors: Dzierba Amy L. , Roberts Russel , Muir Justin , Alhammad Abdullah , Schumaker Greg , Clark Jacqueline , Ruthazer Robin , Devlin John W.
Published: July 2016

Extracorporeal membrane oxygenation (ECMO) use is perceived to cause thrombocytopenia (T), but the role of non-ECMO factors in the development of T remains unclear. We sought to evaluate the incidence and factors associated with severe T (platelet count ≤ 50,000/μl) in adults with severe acute respiratory distress syndrome (ARDS) managed with or without ECMO. The ECMO (n = 32) versus the non-ECMO (n = 53) groups had a similar baseline platelet count (214,000 vs. 179,000/μl), Acute Physiology and Chronic Health Evaluation (APACHE) II score (p = 0.13), unfractionated heparin (UFH) exposure (p = 0.62), and severe T incidence (25 vs. 19%, p = 0.5). Although the APACHE II score (p = 0.01), presence of liver failure (p = 0.08), and platelet transfusion (p = 0.0009) were different between the severe T (18/85 [21%]) and non-severe T groups (67/85 [79%]), the incidence of septic shock (p = 0.64), heparin infusion use (p = 0.41), exposure to non-heparin T-causing medications (p = 0.77) and ECMO use (p = 0.5) were not. An adjusted multivariate linear regression model revealed that only the APACHE II score was independently associated with the development of severe T (p = 0.01) but use of ECMO was not (p = 0.32) ECMO use may not affect the incidence of severe T among adults with severe ARDS. Larger studies that are prospective in nature are required to confirm this finding.
How much do we really know about von Willebrand disease?
Authors: Swystun Laura L. , Lillicrap David
Published: July 2016

Purpose of review

In the last nine decades, large advances have been made toward the characterization of the pathogenic basis and clinical management of von Willebrand disease (VWD), the most prevalent inherited bleeding disorder. Pathological variations at the von Willebrand factor (VWF) locus present as a range of both quantitative and qualitative abnormalities that make up the complex clinical spectrum of VWD. This review describes the current understanding of the pathobiological basis of VWD.

Recent findings

The molecular basis of type 2 (qualitative abnormalities) and type 3 VWD (total quantitative deficiency) have been well characterized in recent decades. However, knowledge of type 1 VWD (partial quantitative deficiency) remains incomplete because of the allelic and locus heterogeneity of this trait, and is complicated by genetic variability at the VWF gene, interactions between the VWF gene and the environment, and the involvement of external modifying loci. Recent genome wide association studies and linkage analyses have sought to identify additional genes that modify the type 1 VWD phenotype.

Understanding the pathogenic basis of VWD will facilitate the development of novel treatment regimens for this disorder, and improve the ability to provide complementary molecular diagnostics for type 1 VWD.
Independent origins of parasitism in Animalia
Authors: Weinstein Sara B. , Kuris Armand M.
Published: July 2016

Nearly half of all animals may have a parasitic lifestyle, yet the number of transitions to parasitism and their potential for species diversification remain unresolved. Based on a comprehensive survey of the animal kingdom, we find that parasitism has independently evolved at least 223 times in just 15 phyla, with the majority of identified independent parasitic groups occurring in the Arthropoda, at or below the level of Family. Metazoan parasitology is dominated by the study of helminthes; however, only 20% of independently derived parasite taxa belong to those groups, with numerous transitions also seen in Mollusca, Rotifera, Annelida and Cnidaria. Parasitism is almost entirely absent from deuterostomes, and although worm-like morphology and host associations are widespread across Animalia, the dual symbiotic and trophic interactions required for parasitism may constrain its evolution from antecedent consumer strategies such as generalist predators and filter feeders. In general, parasitic groups do not differ from their free-living relatives in their potential for speciation. However, the 10 largest parasitic clades contain 90% of described parasitic species, or perhaps 40% of all animal species. Hence, a substantial fraction of animal diversity on the Earth arose following these few transitions to a parasitic trophic strategy.
Elastic membranes in confinement
Authors: Bostwick J. B. , Miksis M. J. , Davis S. H.
Published: July 2016

An elastic membrane stretched between two walls takes a shape defined by its length and the volume of fluid it encloses. Many biological structures, such as cells, mitochondria and coiled DNA, have fine internal structure in which a membrane (or elastic member) is geometrically ‘confined’ by another object. Here, the two-dimensional shape of an elastic membrane in a ‘confining’ box is studied by introducing a repulsive confinement pressure that prevents the membrane from intersecting the wall. The stage is set by contrasting confined and unconfined solutions. Continuation methods are then used to compute response diagrams, from which we identify the particular membrane mechanics that generate mitochondria-like shapes. Large confinement pressures yield complex response diagrams with secondary bifurcations and multiple turning points where modal identities may change. Regions in parameter space where such behaviour occurs are then mapped.
Revealing neuro-computational mechanisms of reinforcement learning and decision-making with the hBayesDM package
Authors: Ahn Woo-Young , Haines Nathaniel , Zhang Lei
Published: July 2016

Reinforcement learning and decision-making (RLDM) provide a quantitative framework and computational theories, with which we can disentangle psychiatric conditions into basic dimensions of neurocognitive functioning. RLDM offer a novel approach to assess and potentially diagnose psychiatric patients, and there is growing enthusiasm on RLDM and Computational Psychiatry among clinical researchers. Such a framework can also provide insights into the brain substrates of particular RLDM processes as exemplified by model-based functional magnetic resonance imaging (fMRI) or electroencephalogram (EEG). However, many researchers often find the approach too technical and have difficulty adopting it for their research. Thus, there remains a critical need to develop a user-friendly tool for the wide dissemination of computational psychiatric methods. We introduce an R package called hBayesDM (hierarchicalBayesian modeling ofDecision-Making tasks), which offers computational modeling on an array of RLDM tasks and social exchange games. The hBayesDM package offers state-of-the-art hierarchical Bayesian modeling, where both individual and group parameters (i.e., posterior distributions) are estimated simultaneously in a mutually constraining fashion. At the same time, it is extremely user-friendly: users can perform computational modeling, output visualization, and Bayesian model comparisons–each with a single line of coding. Users can also extract trial-by-trial latent variables (e.g., prediction errors) required for model-based fMRI/EEG. With the hBayesDM package, we anticipate that anyone with minimal knowledge of programming can take advantage of cutting-edge computational modeling approaches and investigate the underlying processes of and interactions between multiple decision-making (e.g., goal-directed, habitual, and Pavlovian) systems. In this way, it is our expectation that the hBayesDM package will contribute to the dissemination of advanced modeling approaches and enable a wide range of researchers to easily perform computational psychiatric research within their populations.
A scored human protein-protein interaction network to catalyze genomic interpretation
Authors: Li T , Wernersson R , Hansen RB , Horn H , Mercer JM , Slodkowicz G , Workman CT , Rigina O , Rapacki K , Stærfeldt HH , Brunak S , Jensen TS , Lage K
Published: July 2016

Human protein-protein interaction networks are critical to understanding cell biology and interpreting genetic and genomic data, but are challenging to produce in individual large-scale experiments. We describe a general computational framework that through data integration and quality control provides a scored human protein-protein interaction network (InWeb_IM). Juxtaposed with five comparable resources, InWeb_IM has 2.8 times more interactions (~585K) and a superior functional signal showing that the added interactions reflect real cellular biology. InWeb_IM is a versatile resource for accurate and cost-efficient functional interpretation of massive genomic datasets illustrated by annotating candidate genes from >4,700 cancer genomes and genes involved in neuropsychiatric diseases.
Genome urbanization: Clusters of topologically co-regulated genes delineate functional compartments in the genome ofS. cerevisiae
Authors: Tsochatzidou Maria , Malliarou Maria , Papanikolaou Nikolas , Roca Joaquim , Nikolaou Christoforos
Published: July 2016

The eukaryotic genome evolves under the dual constraint of maintaining co-ordinated gene transcription and performing effective DNA replication and cell division, the coupling of which brings about inevitable DNA topological tension. DNA supercoiling is resolved and, in some cases, even harnessed by the genome through the function of DNA topoisomerases, as has been shown in the concurrent transcriptional activation and suppression of genes upon transient deactivation of topoisomerase II (topoII). By analyzing a genome wide run-on experiment upon thermal inactivation of topoII inS.cerevisiae. we were able to define 116 gene clusters of consistent response (either positive or negative) to topological stress. A comprehensive analysis of these topologically co-regulated gene clusters revealed pronounced preferences regarding their functional, regulatory and structural attributes. Genes that negatively respond to topological stress, are positioned in gene-dense pericentromeric regions, are more conserved and associated to essential functions, while up-regulated gene clusters are preferentially located in the gene-sparse nuclear periphery, associated with secondary functions and under complex regulatory control. We propose that evolves with a core of essential genes occupying a compact genomic “old town”, whereas more recently acquired, condition-specific genes tend to be located in a more spacious “suburban” genomic periphery.
Resolution and reconciliation of non-binary gene trees with transfers, duplications and losses
Authors: Jacox Edwin , Weller Mathias , Tannier Eric , Scornavacca Celine
Published: July 2016

Motivation

Gene trees reconstructed from sequence alignments contain poorly supported branches when the phylogenetic signal in the sequences is weak. When a species tree is available, the signal of gains and losses of genes can be used to correctly resolve the unsupported parts of the gene history. Unfortunately, finding the best (i.e. most parsimonious) resolution has been shown to be NP-hard if transfers are considered as possible gene scale events, in addition to gene originations, duplications and losses.

Results

We propose an exact, parameterized algorithm solving this problem in single-exponential time, where the parameter is the number of connected branches of the gene tree that show low support from the sequence alignment or, equivalently, the maximum number of children of any node of the gene tree once the low-support branches have been collapsed. We propose a way to choose among optimal solutions based on the available information. We show the usability of this principle on several simulated and biological data sets. The results show a comparable or better quality than several other tested methods having similar goals, but with a lower running time and a guarantee on the optimality of the solution.

Availability

Our algorithm has been integrated into the ecceTERA phylogeny package, available athttp://mbb.univ-montp2.fr/MBB/download_sources/16_ecceTERAand which can be run online athttp://mbb.univ-montp2.fr/MBB/subsection/softExec.php?soft=eccetera.

Contact

celine.scornavacca@umontpellier.fr
Maternal immune activation dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorder
Authors: Lombardo Michael V. , Moon Hyang Mi , Su Jennifer , Palmer Theo D. , Courchesne Eric , Pramparo Tiziano
Published: July 2016

Maternal immune activation (MIA) via infection during pregnancy is known to increase risk for autism spectrum disorder (ASD). However, it is unclear how MIA disrupts fetal brain gene expression in ways that may explain this increased risk. Here we examine how MIA dysregulates fetal brain gene expression near the end of the first trimester of human gestation in ways relevant to ASD-associated pathophysiology. MIA downregulates expression of ASD-associated genes, with the largest enrichments in genes known to harbor rare highly penetrant mutations. MIA also downregulates expression of many genes also known to be persistently downregulated in ASD cortex later in life and which are canonically known for roles in affecting prenatally-late developmental processes at the synapse. Transcriptional and translational programs that are downstream targets of highly ASD-penetrantFMR1andCHD8genes are also heavily affected by MIA. MIA strongly upregulates expression of a large number of genes involved in translation initiation, cell cycle, DNA damage, and proteolysis processes that affect multiple key neural developmental functions. Upregulation of translation initiation is common to and preserved in gene network structure with the ASD cortical transcriptome throughout life and has downstream impact on cell cycle processes. The cap-dependent translation initiation gene,EIF4E, is one of the most MIA-dysregulated of all ASD-associated genes and targeted network analyses demonstrate prominent MIA-induced transcriptional dysregulation ofmTORandEIF4E-dependent signaling. This dysregulation of translation initiation via alteration of theTsc2-mTor-Eif4e-axis was further validated across MIA rodent models. MIA may confer increased risk for ASD by dysregulating key aspects of fetal brain gene expression that are highly relevant to pathophysiology affecting ASD.
Identification of a novel putative interaction partner of the nucleoporin ALADIN
Authors: Jühlen Ramona , Landgraf Dana , Huebner Angela , Koehler Katrin
Published: July 2016

It has been shown that the nucleoporin ALADIN employs a significant role in the redox homeostasis of the cell but the function in steroidogenesis contributing to adrenal atrophy in triple A syndrome remains largely unknown. In an attempt to identify new interaction partners of ALADIN, co-immunoprecipitation followed by proteome analysis was conducted in different expression models using the human adrenocortical tumour cell line NCI-H295R. Our results suggest an interaction of ALADIN with the microsomal protein PGRMC2. PGRMC2 is shown to be activity regulator of CYP P450 enzymes and therefore, to be a possible target for adrenal dysregulation in triple A syndrome. We show that there is a sexual dimorphism regarding the expression ofPgrmc2in adrenals and gonads of WT andAaasKO mice. FemaleAaasKO mice are sterile due to delayed oocyte maturation and meiotic spindle assembly. A participation in meiotic spindle assembly confirms the recently investigated involvement of ALADIN in mitosis and emphasises an interaction with PGRMC2 which is a regulator of cell cycle. By identification of a novel interaction partner of ALADIN we provide novel aspects for future research of the function of ALADIN during cell cycle and for new insights into the pathogenesis of triple A syndrome.
Ethological principles predict the neuropeptides co-opted to influence parenting
Authors: Cunningham Christopher B. , Badgett Majors J. , Meagher Richard B. , Orlando Ron , Moore Allen J.
Published: July 2016

Ethologists predicted that parental care evolves by modifying suitable behavioural precursors in the asocial ancestor, such as nest building, defensive and aggressive behaviours, and potentially shared resources. From this, we predicted that the evolved mechanistic changes would reside in genetic pathways underlying these behavioural precursors. We tested this by measuring differential expression of neuropeptides in femaleNicrophorus vespilloidesParenting in this species is extensive and complex as caring adults regurgitate food to begging, dependent offspring. We identified neuropeptides associated with mating, feeding, aggression, and social interactions by sampling females in different behavioural states: solitary, actively parenting, or post-parenting and solitary. We measured peptide abundance in adult female brains and identified 130 peptides belonging to 17 neuropeptides. Of these 17, seven were differentially expressed. Six of the seven were up-regulated during parenting. None of the identified neuropeptides have previously been associated with parental care, but all have known roles in the behavioural precursors. Two, tachykinin and sulfakinin, influence multiple pathways. Our study supports the prediction that appropriate behavioural precursors are likely targets of selection during the evolution of parenting. Evolutionary principles predicted neuropeptides influencing social behaviour, and our results provide several new candidate neuropeptides underpinning parenting.
6-Propyl-2-thiouracilversus6-methoxymethyl-2-thiouracil: enhancing the hydrogen-bonded synthon motif by replacement of a methylene group with an O atom
Authors: Hützler Wilhelm Maximilian , Egert Ernst , Bolte Michael
Published: July 2016

The understanding of intermolecular interactions is a key objective of crystal engineering in order to exploit the derived knowledge for the rational design of new molecular solids with tailored physical and chemical properties. The tools and theories of crystal engineering are indispensable for the rational design of (pharmaceutical) cocrystals. The results of cocrystallization experiments of the antithyroid drug 6-propyl-2-thiouracil (PTU) with 2,4-diaminopyrimidine (DAPY), and of 6-methoxymethyl-2-thiouracil (MOMTU) with DAPY and 2,4,6-triaminopyrimidine (TAPY), respectively, are reported. PTU and MOMTU show a high structural similarity and differ only in the replacement of a methylene group (–CH2–) with an O atom in the side chain, thus introducing an additional hydrogen-bond acceptor in MOMTU. Both molecules contain anADAhydrogen-bonding site (A= acceptor andD= donor), while the coformers DAPY and TAPY both show complementaryDADsites and therefore should be capable of forming a mixedADA/DADsynthon with each other,i.e. N—H...O, N—H...N and N—H...S hydrogen bonds. The experiments yielded one solvated cocrystal salt of PTU with DAPY, four different solvates of MOMTU, one ionic cocrystal of MOMTU with DAPY and one cocrystal salt of MOMTU with TAPY, namely 2,4-diaminopyrimidinium 6-propyl-2-thiouracilate–2,4-diaminopyrimidine–N,N-dimethylacetamide–water (1/1/1/1) (the systematic name for 6-propyl-2-thiouracilate is 6-oxo-4-propyl-2-sulfanylidene-1,2,3,6-tetrahydropyrimidin-1-ide), C4H7N4+·C7H9N2OS−·C4H6N4·C4H9NO·H2O, (I), 6-methoxymethyl-2-thiouracil–N,N-dimethylformamide (1/1), C6H8N2O2S·C3H7NO, (II), 6-methoxymethyl-2-thiouracil–N,N-dimethylacetamide (1/1), C6H8N2O2S·C4H9NO, (III), 6-methoxymethyl-2-thiouracil–dimethyl sulfoxide (1/1), C6H8N2O2S·C2H6OS, (IV), 6-methoxymethyl-2-thiouracil–1-methylpyrrolidin-2-one (1/1), C6H8N2O2S·C5H9NO, (V), 2,4-diaminopyrimidinium 6-methoxymethyl-2-thiouracilate (the systematic name for 6-methoxymethyl-2-thiouracilate is 4-methoxymethyl-6-oxo-2-sulfanylidene-1,2,3,6-tetrahydropyrimidin-1-ide), C4H7N4+·C6H7N2O2S−, (VI), and 2,4,6-triaminopyrimidinium 6-methoxymethyl-2-thiouracilate–6-methoxymethyl-2-thiouracil (1/1), C4H8N5+·C6H7N2O2S−·C6H8N2O2S, (VII). Whereas in (I) only anAA/DDhydrogen-bonding interaction was formed, the structures of (VI) and (VII) both display the desiredADA/DADsynthon. Conformational studies on the side chains of PTU and MOMTU also revealed a significant deviation for cocrystals (VI) and (VII), leading to the desired enhancement of the hydrogen-bond pattern within the crystal.
Social marketing’s consumer myopia
Authors: Brennan Linda , Previte Josephine , Fry Marie-Louise
Published: July 2016

Purpose

Addressing calls for broadening social marketing thinking beyond “individualistic” parameters, this paper aims to describe a behavioural ecological systems (BEM) approach to enhance understanding of social markets.

Design/methodology/approach

A conceptual framework – the BEM – is presented and discussed within a context of alcohol social change.

Findings

The BEM emphasises the relational nature of behaviour change, where individuals are embedded in an ecological system that involves the performances of behaviour and social change within historical, social, cultural, physical and environmental settings. Layers of influence on actors are characterised as macro (distant, large in scale), exo (external, remote from individuals), meso (between the individual and environments) and micro (the individual within their social setting). The BEM can be applied to guide social marketers towards creating solutions that focus on collaboration amongst market actors rather than among consumers.

Practical implications

The BEM contributes to a broader holistic view of social ecologies and behaviour change; emphasises the need for social marketers to embrace systems thinking; and recognises that relationships between actors at multiple layers in social change markets are interactive, collaborative and embedded in dynamic social contexts. Importantly, a behavioural ecological systems approach enables social marketers to develop coherent, integrated and multi-dimensional social change programmes.

Originality/value

The underlying premise of the BEM brings forward relational logic as the foundation for future social marketing theory and practice. Taking this approach to social market change focuses strategy on the intangible aspects of social offerings, inclusive of the interactions and processes of value creation (and/or destruction) within a social marketing system to facilitate collaboration and interaction across a network of actors so as to overcome barriers and identify solutions to social problems.
Welfare Nationalism and Popular Support for Raising the Child Allowance: Evidence from a Norwegian Survey Experiment
Authors: Bay Ann‐Helen , Finseraas Henning , Pedersen Axel West
Published: July 2016

Refugee and labour immigration have placed the issue of immigrants’ access to welfare benefits high on the political agenda. This article explores how voter preferences for increases in the child benefit change when respondents are reminded about immigrants’ access to benefits. The survey experiment shows that information about newly arrived immigrants’ access to child benefit has only a small impact on support for increasing the child allowance. By contrast, information about labour migrants’ access to benefits for children living in another European Union country has a strong impact, and the observed sensitivity to this cue is not to the same extent confined to respondents who otherwise support welfare dualism.
Trust and Safety in the Segregated City: Contextualizing the Relationship between Institutional Trust, Crime‐related Insecurity and Generalized Trust
Authors: Berg Monika , Johansson Tobias
Published: July 2016

Trust is a crucial asset for any society, and the quest to generate and uphold trust is as crucial as ever. Several contemporary societal developments are proposed as being particularly challenging for upholding and restoring the levels of trust in society, including increasing ethnic diversity, rising inequality and the related geographical segregation. It has been convincingly argued that democratic institutions may generate trust by neutralizing some of these effects. This article explores how the mechanisms of trust differ in segregated, disadvantaged neighbourhoods as opposed to the surrounding general society. The empirical material consists of individual‐level data from a segregated neighbourhood (Vivalla) in a medium‐sized city in Sweden (Örebro), with a random sample from the population of the city (the Vivalla area excluded) as the comparison reference point, representing the general society. In the article, perceived safety is introduced as an important mediator between trust in legal and government institutions and generalized trust, through which the differing mechanisms become evident. In the disadvantaged neighbourhood, it is shown that trust in government institutions has the function of primarily decreasing crime‐related insecurity, which in its turn affects generalized trust. Thus, the relationship is indirect. In the city population, the effect instead goes directly from trust in government institutions to generalized trust. The results suggest that the potentials of different means to build and restore trust are dependent on local context.
Development and validation of the Dietetic Confidence Scale for working with clients experiencing psychological issues
Authors: Buttenshaw Kerryn , Ash Susan , Shakespeare‐Finch Jane
Published: July 2016

Aim

A standardised tool was needed to measure a generalist dietitian's confidence about working with clients experiencing psychological issues in order to effectively evaluate mental health‐related professional development activities. The aim of this study was to develop, pilot and validate a robust instrument that measures a generalist dietitian's professional confidence for working with clients experiencing psychological issues.

Methods

The Dietetic Confidence Scale (DCS) was developed. Two cross‐sectional samples of practicing dietitians (n = 185; 458) from various settings and locations were recruited. Study 1: principal components analysis (PCA) helped refine scale items and derive a model, which was then validated using confirmatory factor analysis (CFA, Study 2). Cronbach's alpha estimated scale reliability. Correlations assessed associations between factors.

Results

Study 1: A 13‐item, two‐factor solution accounted for 69.1% of the total variance. Total Cronbach's α = 0.92. Dietetic confidence was associated with: (i) Confidence using the Nutrition Care Process and (ii) Confidence Advocating for Self care and Client care. Study 2: The CFA supported the proposed scale and model. A Good Fit Index of 0.95 indicated a strong fit. Item‐factor correlations ranged from r = 0.50 to 0.91. The final scale showed good reliability (α = 0.93).

Conclusions

This is the first self‐efficacy scale for dietetic practitioners subjected to PCA and CFA using two independent samples. The DCS is a psychometrically robust instrument with strong internal consistency. It can be used to measure dietetic confidence about working with clients experiencing psychological issues and to highlight areas where additional support or training may be needed. Further validity and reliability testing is needed to enhance scale generalisability and use.
The Agnotology of Eviction in South Lebanon's Palestinian Gatherings: How Institutional Ambiguity and Deliberate Ignorance Shape Sensitive Spaces
Authors: Stel Nora
Published: July 2016

A significant part of Lebanon's Palestinian refugees live in unofficial camps, so‐called “gatherings”, where they reside on Lebanese land. Many of these gatherings are now threatened with eviction. By means of two qualitative case studies this article explores responses to such eviction threats. Residents, it turns out, engage in deliberate disinformation and stalling tactics and invoke both a professed and real ignorance about their situation. In contrast to dominant discourses that project Palestinian refugees as illicit and sovereignty undermining, I explain these tactics as a reaction to, and duplication of, a “politics of uncertainty” implemented by Lebanese authorities. Drawing on agnotology theory, and reconsidering the gatherings as sensitive spaces subjected to aleatory governance, I propose that residents’ responses to the looming evictions are a manifestation of the deliberate institutional ambiguity that Lebanese authorities impose on the gatherings. As such, the article contributes to understanding the spatial dimensions of strategically imposed ignorance.
c‐Jun N‐terminal Kinase mediates prostaglandin‐induced sympathoexcitation in rats with chronic heart failure by reducing GAD1 and GABRA1 expression
Authors: Wang R. , Zhang W. , Dong Z. , Qi Y. , Hultström M. , Zhou X. , Lai E. Y.
Published: July 2016

Aim

Prostaglandin E2 mediates sympathoexcitation in chronic heart failure (CHF) through EP3 receptors (PTGER3) in the paraventricular nucleus (PVN). The aim of this study was to investigate the role of c‐Jun N‐terminal kinase (JNK) in expressional regulation of gamma‐aminobutyric acid signalling in PVN in CHF rats.

Methods

Chronic heart failure was induced by left coronary ligation in Wistar rats. Renal sympathetic nerve discharge (RSND) and mean arterial pressure (MAP) responses to the PVN infusion were determined in anaesthetized rats. Osmotic minipumps were used for chronic PVN infusion. PTGER3 expression was examined with immunofluorescence staining, quantitative real‐time PCR and Western blot.

Results

Chronic heart failure rats had increased JNK activation and decreased glutamate decarboxylase 1 (GAD1) and GABAA receptor alpha 1 subunit (GABRA1) expression in the PVN. PVN infusion of the PTGER3 agonist SC‐46275 caused sympathoexcitation in sham‐operated control (Sham) rats and increased it further in CHF. The PTGER3 antagonist L798106 reduced sympathoexcitation and cardiac dysfunction in CHF. PVN infusion of EP1 receptor antagonist SC‐19220, EP2 receptor antagonist AH6809 or EP4 receptor antagonist L‐161982 had no effect on sympathoexcitation. The JNK inhibitor SP600125 normalized sympathoexcitation and GAD1 and GABRA1 expression in PVN in CHF rats. Both the p44/42 and p38 mitogen‐activated protein kinase inhibitors PD98059 and SB203580 could not prevent the downregulation of GAD1 and GABRA1 expression in PVN in CHF. PTGER3 agonist activated JNK but downregulated GAD1 and GABRA1 expression in NG108 neuronal cells.

Conclusion

Prostaglandin signalling through upregulated PTGER3 activates JNK which reduces GAD1 and GABRA1 expression in the PVN, and contributes to sympathoexcitation in CHF.
Ordinal Probability Effect Measures for Group Comparisons in Multinomial Cumulative Link Models
Authors: Agresti Alan , Kateri Maria
Published: July 2016

We consider simple ordinal model-based probability effect measures for comparing distributions of two groups, adjusted for explanatory variables. An “ordinal superiority” measure summarizes the probability that an observation from one distribution falls above an independent observation from the other distribution, adjusted for explanatory variables in a model. The measure applies directly to normal linear models and to a normal latent variable model for ordinal response variables. It equals for the corresponding ordinal model that applies a probit link function to cumulative multinomial probabilities, for standard normal cdf and effect that is the coefficient of the group indicator variable. For the more general latent variable model for ordinal responses that corresponds to a linear model with other possible error distributions and corresponding link functions for cumulative multinomial probabilities, the ordinal superiority measure equals with the log–log link and equals approximately with the logit link, where is the group effect. Another ordinal superiority measure generalizes the difference of proportions from binary to ordinal responses. We also present related measures directly for ordinal models for the observed response that need not assume corresponding latent response models. We present confidence intervals for the measures and illustrate with an example.
Efficacy and safety of ipragliflozin as add‐on therapy to insulin in Japanese patients with type 2 diabetes mellitus (IOLITE): a multi‐centre, randomized, placebo‐controlled, double‐blind study
Authors: Ishihara Hisamitsu , Yamaguchi Susumu , Nakao Ikko , Okitsu Akira , Asahina Seitaro
Published: July 2016

Aims

To examine the efficacy and safety of add‐on ipragliflozin in Japanese patients with type 2 diabetes in the early stage of insulin therapy.

Methods

Patients treated with insulin (bolus component <30% of total daily dose) with/without a dipeptidyl peptidase‐4 (DPP‐4) inhibitor were randomized to receive placebo (n = 87) or ipragliflozin (n = 175) for 16 weeks. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline. Secondary endpoints included changes in fasting plasma glucose (FPG) and metabolic hormones. Safety endpoints were also examined.

Results

The changes in HbA1c were 0.27% and −0.79% (2.9 and −8.7 mmol/mol) in the placebo and ipragliflozin groups, respectively (baseline: 8.62% vs 8.67% [70.8 vs 71.2 mmol/mol]), corresponding to an adjusted mean difference of −1.07% (95% confidence interval −1.24, −0.91) or −11.7 mmol/mol (−13.5, −9.9), p < .001. Ipragliflozin reduced FPG and serum C‐peptide levels and body weight (all p < .001), and increased serum adiponectin levels (p = .022). There was a statistically significant interaction for use/non‐use of a DPP‐4 inhibitor × treatment group for the change in HbA1c (p = .042). Hypoglycaemia was the only treatment‐related adverse event reported in >5% of patients (14.9% vs 29.1%). Events consistent with urinary tract infection (placebo 1.1% vs ipragliflozin 2.3%) or genital infection (0.0% and 4.0%, respectively) occurred in <5% of patients.

Conclusion

Ipragliflozin was well tolerated and effective in insulin‐treated patients, especially when used with a DPP‐4 inhibitor.
Rapid faecal tests for detecting disease activity in colonic inflammatory bowel disease
Authors: Puolanne Anna‐Maija , Kolho Kaija‐Leena , Alfthan Henrik , Ristimäki Ari , Mustonen Harri , Färkkilä Martti
Published: July 2016

Background

Increasing numbers of patients with inflammatory bowel disease (IBD) have raised the need for a rapid noninvasive means to monitor disease activity. We validated two rapid tests for faecal calprotectin and one for faecal lactoferrin and compared them to the most common clinical and endoscopic scores, enzyme‐linked immunosorbent assay (ELISA) calprotectin test and systemic inflammation markers.

Materials and methods

The clinical and endoscopic disease activity of 72 patients with colonic IBD, who underwent ileocolonoscopy, was determined. The patients provided stool samples to measure calprotectin and lactoferrin, and blood samples to measure systemic inflammation markers.

Results

Rapid calprotectin tests correlated significantly with clinical and endoscopic indices and standard ELISA calprotectin in ulcerative colitis, but not in Crohn's disease. CalDetect correlated more closely with ELISA calprotectin than CerTest FC in concentrations exceeding 200 μg/g. CalDetect was also more sensitive in indicating histological remission or mild disease than was CerTest FC at cut‐off of 200 μg/g. CerTest Lactoferrin was comparable to CalDetect in their correlation with clinical, endoscopic and histological scores.

Conclusions

These rapid tests are suitable for identifying patients with inactive or mildly active disease, but as semiquantitative or qualitative tests, they cannot totally replace ELISA calprotectin in decision‐making related to therapy.
You'll Never Lobby Alone. Explaining the Participation of Sub‐national Authorities in the European Commission's Open Consultations
Authors: Van Hecke Matti , Bursens Peter , Beyers Jan
Published: July 2016

The multi‐level system of the EU (European Union) constrains the institutionalized representation of the regional tier of government. Consequently, SNAs (sub‐national authorities) seek to represent their interests through various lobbying practices, including taking part in the European Commission's open consultations. In this article, we argue that varying levels with which SNAs take part in open consultations cannot be adequately explained by regional‐level conditions such as resources or autonomy. Instead, we hypothesize that the specific policy context strongly affects regional involvement in open consultations. We test our hypotheses with evidence of the participation pattern of 296 SNAs in eight online consultations situated in five policy areas: CAP (Common Agricultural Policy), EAP (Environment Action Programme), Horizon 2020, COH (Cohesion Policy) and TEN‐T (Trans‐European Network for Transport). Our analysis demonstrates that the probability that SNAs take part in open consultations increases significantly when private interests of the same region and/or other SNAs of the same country participate in the same consultation.
Prediction of Lethality by Nonlinear Artificial Neural Network Modeling
Authors: Guldas Metin , Kurtulmus Ferhat , Gurbuz Ozan
Published: July 2016

In this research, the aim was to predict F value (lethality or sterilization value) of canned peas by using a nonlinear auto‐regressive artificial neural network model with exogenous input (NARX‐ANN). During the model testing, training, validation and reliability steps were followed, respectively. It was found that the model tested was a useful tool to predict the F value for the canned foods with high reliability. Cross‐validation rules were performed for training and testing of the model. F value of the 5 kg canned peas could be predicted with a high degree of accuracy (R2 = 0.9982, mean square error (MSE) = 0.1088) using training the data yielded from 0.5 kg canned peas despite huge mass differences between cross‐validated data sets. When the same data sets were trained and tested inversely, a high degree of prediction accuracy (R2 = 0.9914, MSE = 0.6262) was also observed. The model is also significant in terms of reducing the operational costs due to the fact that higher temperatures and longer process times lead to increased energy costs.

Practical Applications

In this research, it was found that nonlinear auto‐regressive artificial neural network model with exogenous input is a reliable model for the prediction of lethality rate (F value) in canned food factories. It also provides the advantage of estimating process time more accurately in the retort and thus, reducing operational costs.
Specific aspects of a combined approach to male face correction: botulinum toxin A and volumetric fillers
Authors: Scherer Max‐Adam
Published: July 2016

Cosmetologists in the last decade face a permanently increasing number of male patients. The necessity of a gender‐adjusted approach in treatment of this patient category is obvious. An adequate correction requires consideration of the anatomic and physiologic features of male faces together with a whole set of interrelated aspects of psychologic perception of the male face esthetics, socially formed understanding of masculine features and appropriate emotional expressions, also of the motivations and expectations of men coming to a cosmetologist. The author explains in detail the elaborated out of own vast experience methods of complex male face correction using the above‐mentioned gender‐specific approach to create a naturally looking and harmonic facial expression and appearance. The presented botulinum therapy specifics concern the injection point location and toxin doses for every point. As a result, a rather distinct smoothening of the skin profile without detriment to the facial expressiveness and gender‐related features is achieved. The importance and methods of an extremely delicate approach to volumetric plasty with stabilized hyaluronic acid‐based fillers in men for avoiding hypercorrection and retaining the gender‐specific features are discussed.
Developing a play‐based communication assessment through collaborative action research with teachers in northern Canadian indigenous communities
Authors: Stagg Peterson Shelley
Published: July 2016

With the goal of developing culturally appropriate approaches for assessing and supporting children's language use, teachers of 4‐to 6‐year‐old children in northern Canadian rural and Indigenous communities are involved in a 6‐year collaborative action research project. Teachers video record children's interactions during dramatic and construction play and then meet with university researchers to carry out inductive analyses of ways in which children use language to achieve social purposes. From these analyses, a Play‐based Communication Assessment has been created. Examples from two teachers' classrooms in one Indigenous community are used to show how play contexts and the still‐evolving play‐based communication assessment provide opportunities for teachers to recognise and build upon the linguistic and cultural resources that children bring to classrooms. Through the play‐based assessment and action research processes, teachers have come to recognise the richness of children's language when they are engaged in play and have gained understandings of their community's culture. Teachers and researchers are exploring ways to capture children's non‐verbal communication abilities through this assessment approach.
The current state of knowledge about shatter cones: Introduction to the special issue
Authors: Baratoux David , Reimold Wolf Uwe
Published: July 2016

Shatter cones are a fracture phenomenon that is exclusively associated with shock metamorphism and has also been produced in the laboratory in several shock experiments. The occurrence of shatter cones is the only accepted meso‐ to macroscopic recognition criterion for impact structures. Shatter cones exhibit a number of geometric characteristics (orientation, apical angles, striation angles, sizes) that can be best described as varied, from case to case. Possible links between geometric properties with impact or crater parameters have remained controversial and the lack of understanding of the mechanism of formation of shatter cones does not offer a physical framework to discuss or understand them. A database of shatter cone occurrences has been produced for this introduction paper to the special issue of Meteoritics and Planetary Science on shatter cones. Distribution of shatter cones with respect to crater size and lithology suggests that shatter cones do not occur in impact craters less than a few kilometers in diameter, with a few, currently questionable exceptions. All pertinent hypotheses of formation are presented and discussed. Several may be discarded in light of the most recent observations. The branching fracture mechanism and the interference models proposed, respectively, by Sagy et al. (2002) and Baratoux and Melosh (2003) require further evaluation. New observations, experiments, or theoretical considerations presented in this special issue promise an important step forward, based on a renewed effort to resolve the enigmatic origin of these important features.
Humpback whales interfering when mammal‐eating killer whales attack other species: Mobbing behavior and interspecific altruism?
Authors: Pitman Robert L. , Deecke Volker B. , Gabriele Christine M. , Srinivasan Mridula , Black Nancy , Denkinger Judith , Durban John W. , Mathews Elizabeth A. , Matkin Dena R. , Neilson Janet L. , Schulman‐Janiger Alisa , Shearwater Debra , Stap Peggy , Ternullo Richard
Published: July 2016

Humpback whales (Megaptera novaeangliae) are known to interfere with attacking killer whales (Orcinus orca). To investigate why, we reviewed accounts of 115 interactions between them. Humpbacks initiated the majority of interactions (57%vs. 43%;n= 72), although the killer whales were almost exclusively mammal‐eating forms (MEKWs, 95%)vs. fish‐eaters (5%;n= 108). WhenMEKWs approached humpbacks (n= 27), they attacked 85% of the time and targeted only calves. When humpbacks approached killer whales (n= 41), 93% wereMEKWs, and ≥87% of them were attacking or feeding on prey at the time. When humpbacks interacted with attackingMEKWs, 11% of the prey were humpbacks and 89% comprised 10 other species, including three cetaceans, six pinnipeds, and one teleost fish. Approaching humpbacks often harassed attackingMEKWs (≥55% of 56 interactions), regardless of the prey species, which we argue was mobbing behavior. Humpback mobbing sometimes allowedMEKWprey, including nonhumpbacks, to escape. We suggest that humpbacks initially responded to vocalizations of attackingMEKWs without knowing the prey species targeted. Although reciprocity or kin selection might explain communal defense of conspecific calves, there was no apparent benefit to humpbacks continuing to interfere when other species were being attacked. Interspecific altruism, even if unintentional, could not be ruled out.
A Usage‐Based Investigation of L2 Lexical Acquisition: The Role of Input and Output
Authors: CROSSLEY SCOTT , KYLE KRISTOPHER , SALSBURY THOMAS
Published: July 2016

This study investigates relations between second language (L2) lexical input and output in terms of word information properties (i.e., lexical salience; Ellis, 2006a). The data for this study come from a longitudinal corpus of naturalistic spoken data between L2 learners and first language (L1) interlocutors collected over a year's time. The corpus was analyzed using word information properties related to concreteness, familiarity, and meaningfulness to examine word repetitions between input and output, correlations between the input and the output, linear trends over time, and whether lexical properties in the output were predictive of growth in TOEFL scores. The results indicate that L2 learners are more likely to repeat word types found in L1 input and that L1 interlocutors and L2 learners follow similar linear trends over time such that words with lower concreteness, lower familiarity, and lower meaningfulness were produced over the course of the study in both the input and output. A linear mixed model analysis showed that decreases in concreteness scores explained significant gains in TOEFL scores over time. The findings from the study indicate strong associations between L2 input and output and provide evidence linking development in word information properties to development in academic English proficiency.
A novel leucine‐rich repeat protein, CaLRR51, acts as a positive regulator in the response of pepper toRalstonia solanacearuminfection
Authors: Cheng Wei , Xiao Zhuoli , Cai Hanyang , Wang Chuanqing , Hu Yang , Xiao Yueping , Zheng Yuxing , Shen Lei , Yang Sheng , Liu Zhiqin , Mou Shaoliang , Qiu Ailian , Guan Deyi , He Shuilin
Published: July 2016

The leucine‐rich repeat (LRR) proteins play important roles in the recognition of corresponding ligands and signal transduction networks in plant defence responses. Herein, a novel LRR protein fromCapsicum annuum, CaLRR51, was identified and characterized. It was localized to the plasma membrane and transcriptionally up‐regulated byRalstonia solanacearuminfection (RSI), as well as the exogenous application of salicylic acid (SA), jasmonic acid (JA) and ethephon (ETH). Virus‐induced gene silencing ofCaLRR51significantly increased the susceptibility of pepper to RSI. By contrast, transient overexpression ofCaLRR51in pepper plants activated hypersensitive response (HR)‐like cell death, and up‐regulated the defence‐related marker genes, includingPO2,HIR1,PR1,DEF1andACO1. Moreover, ectopic overexpression ofCaLRR51in transgenic tobacco plants significantly enhanced the resistance to RSI. Transcriptional expression of the corresponding defence‐related marker genes in transgenic tobacco plants was also found to be enhanced by the overexpression ofCaLRR51, which was potentiated by RSI. These loss‐ and gain‐of‐function assays suggest that CaLRR51 acts as a positive regulator in the response of pepper to RSI. In addition, the putative signal peptide and transmembrane region were found to be required for plasma membrane targeting of CaLRR51, which is indispensable for the role of CaLRR51 in plant immunity.