bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequential acquisition of virulence and fluoroquinolone resistance has shaped the evolution ofEscherichia coliST131
Authors: Ben Zakour Nouri L. , Alsheikh-Hussain Areej S. , Ashcroft Melinda M. , Nhu Nguyen Thi Khanh , Roberts Leah W. , Stanton-Cook Mitchell , Schembri Mark A. , Beatson Scott A.
Published: February 2016

Escherichia coliST131 is the most frequently isolated fluoroquinolone resistant (FQR)E. coliclone worldwide and a major cause of urinary tract and bloodstream infections. Although originally identified through its association with the CTX-M-15 extended-spectrum β-lactamase resistance gene, global genomic epidemiology studies have failed to resolve the geographical and temporal origin of the ST131 ancestor. Here, we developed a framework for the reanalysis of publicly available genomes from different sources and used this dataset to reconstruct the evolutionary steps that led to the emergence of FQR ST131. Using Bayesian estimation, we show that point mutations in chromosomal genes that confer FQR coincide with the first clinical use of fluoroquinolone in 1986, and illustrate the impact of this pivotal event in the rapid population expansion of ST131 worldwide from an apparent origin in North America. Furthermore, we identify key virulence factor acquisition events that predate the development of FQR, suggesting that the gain of virulence-associated genes followed by the tandem development of antibiotic resistance primed the successful global dissemination of ST131.
FRETBursts: An Open Source Toolkit for Analysis of Freely-Diffusing Single-Molecule FRET
Authors: Ingargiola Antonino , Lerner Eitan , Chung SangYoon , Weiss Shimon , Michalet Xavier
Published: February 2016

Single-molecule Förster Resonance Energy Transfer (smFRET) allows probing intermolecular interactions and conformational changes in biomacromolecules, and represents an invaluable tool for studying cellular processes at the molecular scale. smFRET experiments can detect the distance between two fluorescent labels (donor and acceptor) in the 3–10 nm range. In the commonly employed confocal geometry, molecules are free to diffuse in solution. When a molecule traverses the excitation volume, it emits a burst of photons, which can be detected by single-photon avalanche diode (SPAD) detectors. The intensities of donor and acceptor fluorescence can then be related to the distance between the two fluorophores.

While recent years have seen a growing number of contributions proposing improvements or new techniques in smFRET data analysis, rarely have those publications been accompanied by so.ware implementation. In particular, despite the widespread application of smFRET, no complete so.ware package for smFRET burst analysis is freely available to date.

In this paper, we introduce FRETBursts, an open source software for analysis of freely-diffusing smFRET data. FRETBursts allows executing all the fundamental steps of smFRET bursts analysis using state-of-the-art as well as novel techniques, while providing an open, robust and welldocumented implementation. Therefore, FRETBursts represents an ideal platform for comparison and development of new methods in burst analysis.

We employ modern software engineering principles in order to minimize bugs and facilitate long-term maintainability. Furthermore, we place a strong focus on reproducibility by relying on Jupyter notebooks for FRETBursts execution. Notebooks are executable documents capturing all the steps of the analysis (including data files, input parameters, and results) and can be easily shared to replicate complete smFRET analyzes. Notebooks allow beginners to execute complex workflows and advanced users to customize the analysis for their own needs. By bundling analysis description, code and results in a single document, FRETBursts allows to seamless share analysis workflows and results, encourages reproducibility and facilitates collaboration among researchers in the single-molecule community.
Singing above the chorus: cooperative Princess cichlid fish (Neolamprologus pulcher) has high pitch
Authors: Spinks Rachel K. , Muschick Moritz , Salzburger Walter , Gante Hugo F.
Published: February 2016

Teleost fishes not only communicate with well-known visual cues, but also olfactory and acoustic signals. Communicating with sound has advantages, as signals propagate fast, omnidirectionally, around obstacles, and over long distances. Heterogeneous environments might favour multimodal communication, especially in socially complex species, as combination of modalities’ strengths helps overcome their individual limitations. Cichlid fishes are known to be vocal, but a recent report suggests that this is not the case for the socially complex Princess cichlidNeolamprologus pulcherfrom Lake Tanganyika. Here we further investigated acoustic communication in this species. Wild and captiveN. pulcherproduced high frequency sounds (mean: 12 kHz), when stimulated by mirror images. In laboratory experiments,N. pulcherproduced distinct two-pulsed calls mostly, but not exclusively, associated with agonistic displays. Our results suggest that maleN. pulcherproduce more sounds at greater durations than females. Thus, we confirm that the Princess cichlid does not produce low frequency sounds, but does produce high frequency sounds, both in combination with and independent from visual displays, suggesting that sounds are not a by-product of displays. Further studies on the hearing abilities ofN. pulcherare needed to clarify if the high-frequency sounds are used in intra-or inter-specific communication.
Audit quality within adverse selection markets
Authors: Sarath Bharat
Published: February 2016

Purpose

– Auditing may be viewed as an arrangement for reducing inefficiencies arising from the fundamental market conflict between a seller who wants as high a price as possible and a buyer who wants to pay as low a price as possible. In more general terms, sellers prefer policies that boost the stock price in the short run whereas buyers would prefer the price to peak when they are ready to sell some time in the future. By framing audited financial reports within this context, the purpose of this paper is to provide some insights regarding both audit institutions and audit regulation.

Design/methodology/approach

– This paper relies on conceptual arguments and a simple analytical model.

Findings

– The basic findings are that a unique definition of audit quality is not compatible with the economics of a market where there are conflicts across traders as well a possibility that some traders hold superior information to others. Even an identification of quality with accuracy fails in this setting of conflict. The inference is that audit quality should be approached from a multi-dimensional perspective rather than a unique measure.

Research limitations/implications

– While the paper points out difficulties in constructing measures of audit quality extant in the literature, it does not provide any clear empirical suggestions for better measures.

Originality/value

– The paper brings back into focus issues from information economics that form the bedrock for the study of audited financial statements in equity markets. While the paper is partially a survey and synthesis of some of the latest empirical findings, it describes them within the context of a rational economic market where traders may possess private information. Within such a market, the paper outlines both the conflicts and the benefits inherent to the current institutional arrangements where auditors are paid by incumbent shareholders and overseen by regulators.
The mediating effects of customers’ intimacy perceptions on the trust-commitment relationship
Authors: Ponder Nicole , Bugg Holloway Betsy , Hansen John D.
Published: February 2016

Purpose

This paper aims to draw from intimacy theory in examining the mediating effects of interactive communication and social bonds on the trust–commitment relationship.

Design/methodology/approach

The study is conducted in the professional services context. Qualitative and quantitative data are gathered from respondents engaged in attorney–client and real estate–client relationships. Unstructured, in-depth interviews are first conducted for use in model development. Study hypotheses are examined and mediation tests are conducted utilizing the serial multiple mediator model proposed by Hayes (2013).

Findings

Study findings indicate that intimate relationships in the professional services context are characterized by interactive communication and social bonds, and that the variables act as full mediators of the trust–commitment relationship. Though trust has a positive and significant effect on commitment in isolation, this relationship becomes nonsignificant when simultaneously accounting for the effects of the two variables.

Practical/implications

Study findings suggest a need for programs designed to assist professional service providers in the development of intimate customer relationships. The importance of interactive communications and social bonding should be emphasized in these programs.

Originality/value

The study is one of the few empirical papers to investigate the role of intimacy in service relationships and the first to illustrate its mediating effects on the trust–commitment relationship.
Revisiting “big ideas in services marketing” 30 years later
Authors: Berry Leonard L.
Published: February 2016

Purpose

“Big Ideas in Services Marketing”, published in 1987, identified seven precepts fundamental to the just emerging field; this paper aims to explore the relevance of these ideas three decades later and discuss what should be changed and what should be added.

Design/methodology/approach

Deep reflection on the central ideas proposed in a paper written 30 years ago through the lens of the author’s personal research and learning journey was the basis for preparing this retrospective essay.

Findings

The seven ideas presented in the original paper have stood the test of time although one of the seven “services branding” was incompletely developed. After 30 years, four more ideas need to be added, i.e. competing on value, meeting and exceeding customers’ expectations, saving customers’ time and effort, and generosity.

Originality/value

The proposals in the 1987 paper offered an early framework for consideration by scholars who have produced a worthy body of work and brought services marketing into its own as a legitimate discipline.
Retrospective: compatibility management: customer-to-customer relationships in service environments
Authors: Martin Charles L.
Published: February 2016

Purpose

This paper aims to revisit Martin and Pranter’s (1989) Journal of Services Marketing article, “Compatibility Management […]”, and by doing so, heighten service scholars’ and practitioners’ awareness of the historical and ongoing relevance of customer-to-customer (C2C) encounters, the challenges C2C encounters pose and the opportunities for future research.

Design/methodology/approach

A combination of review and commentary approaches is taken to summarize the 1989 article, the circumstances of its conception, the topic’s intersection with contemporary service topics and to illustrate the multi-faceted nature of C2C encounters and the challenges faced in their management.

Findings

Investigated in a number of service contexts, C2C encounters continue to be relevant in a multitude of service environments where customers converge.

Research limitations/implications

Because the evolution of service scholarship and practice is collectively shaped by an infinite number of people, events and sources, the attribution of effects to only one or a few influences is a highly subjective matter of interpretation.

Practical implications

Because C2C encounters are part of customers’ service experiences and can affect their satisfaction and patronage behaviors, service organizations can benefit by their efforts to influence C2C encounters.

Social implications

The criteria customers use to react to other customers and the bases used by service organizations/personnel to manage C2C encounters may not always be morally, ethically or legally defensible. For example, the Napa Valley Wine Train incident of 2015 involved allegations of racial discrimination and intentional infliction of emotional distress.

Originality/value

The retrospective analysis contributes to the field’s understanding of the historical development of services marketing and provides fodder for future research.
Nitrogen loads influence trophic organization of estuarine fish assemblages
Authors: Warry Fiona Y. , Reich Paul , Cook Perran L. M. , Mac Nally Ralph , Thomson James R. , Woodland Ryan J.
Published: February 2016

Nutrient (N and P) loading may affect functioning in aquatic ecosystems by restructuring producer assemblages with flow‐on effects to consumers. Trophic niche occupancy and trophic organization of consumers are key components of ecosystem function that have been increasingly investigated using quantitative isotopic niche indices. These indices are based on the premise that the isotopic values of consumer tissues indicate their assimilated diet. Typically, isotopic niche indices are calculated using only consumer isotope data, which limit their application for spatial and temporal comparisons because consumer isotopic niches depend on isotopic variability of available autotrophs.

We used measures of isotopic variability of autotrophs to standardize isotopic niche indices, which enabled us to compare trophic organization of fish assemblages in nine estuaries spanning a broad range of nutrient loading. We related standardized isotopic niche indices of fish assemblages to nitrogen and phosphorous loads and hydrological flushing of the estuaries in autumn and spring.

The estuarine fish assemblages studied here showed greater trophic diversity and less redundancy given moderate to high inorganic nitrogen loading. Taxonomic richness partly influenced three isotopic niche indices measuring trophic diversity, but not measures of redundancy. Similar patterns may occur in other systems in which nitrogen loads have increased but the diversity of primary producers has not been reduced to a single dominant source.

Our results demonstrate bottom‐up controls of estuarine food webs. Effects of inorganic nitrogen loading were transmitted upwards through the food web to affect the trophic organization of higher trophic levels, demonstrating the crucial role of nitrogen for estuarine trophic dynamics.
Fungal effects on plant–plant interactions contribute to grassland plant abundances: evidence from the field
Authors: Bennett Jonathan A. , Cahill James F.
Published: February 2016

Plant–fungal interactions can have strong effects on plant abundances, both through direct effects on plant performance and indirect effects on competition and facilitation. Most evidence linking fungi to plant abundances derives from direct fungal effects on initial growth, with little evidence linking fungal effects on plant–plant interactions in intact communities to plant abundances for any plant life‐history stage.

We transplanted 4320 individuals belonging to 18 plant species into plots where we removed neighbouring vegetation and suppressed fungi using fungicide in a factorial design. We monitored plant survival and growth for 3 years, using these data to test whether fungi had net effects on how plant–plant interactions affected different plant life‐history components (initial survival/growth, adult survival/growth). We then tested whether these indirect fungal effects or direct fungal effects on plant performance best explained plant commonness (frequency of occurrence) and local density (per cent cover). Finally, we measured differences in root‐associated fungi following fungal suppression and associated these differences with fungal effects on plant performance.

Overall, fungi increased competitive effects on survival (i.e. lower survival with fungi intact), but reduced competitive effects on growth of adult plants (i.e. higher growth when fungi intact). Among the focal species, these indirect fungal effects increased survival for more common species relative to rarer species. However, indirect fungal effects on adult growth benefitted rarer species more than common species. Local plant densities were unassociated with indirect fungal effects, but were negatively associated with direct fungal effects on survival and adult growth. This suggests that fungi limit local dominance, thereby indirectly increasing the establishment of common species and the growth of rare species.

Synthesis. Using a variety of plant species and suppressing both fungi and neighbours, we show that fungi have net indirect effects, through plant–plant interactions, within intact plant communities. Variation among species in both direct and indirect fungal effects contributed to plant abundances, yet fungal effects did not consistently benefit either common or rare species. However, regardless of commonness, fungi directly reduced growth and survival for species with high local densities, consistent with plant–soil feedbacks limiting species dominance.
Marginal abatement costs of greenhouse gas emissions: broadacre farming in the Great Southern Region of Western Australia
Authors: Tang Kai , Hailu Atakelty , Kragt Marit E. , Ma Chunbo
Published: February 2016

Broadacre agriculture is a major emitter of greenhouse gases (GHG). To improve efficiency of climate change policies, we need to know the marginal abatement costs of agricultural GHG. This article combines calculations of on‐farm GHG emissions with an input‐based distance function approach to estimate the marginal abatement costs for a broadacre farming system in the Great Southern Region of Western Australia. The results show that, in the study region, the average marginal abatement cost for the 1998–2005 periods was $29.3 per tonne CO2‐e. Farms with higher crop output shares were found to have higher marginal abatement costs. Overall, our results indicate that broadacre agriculture is among the lowest cost sources of GHG mitigation.
Habitus: beyond Sociology
Authors: Silva Elizabeth B.
Published: February 2016

This paper presents a contribution of a set of interrelated innovative thinking to revitalize the sociological understanding of the notion of the habitus. It discusses contributions by sociologists exploring the sources of Bourdieu's inspiration from psychology and psychoanalysis to the development of the concept, and brings in new thinking inspired by authors and frameworks that branch out of sociology to bring into sociology fresher thinking. Three areas of concern about habitus are focused on: firstly, the objectivism and subjectivism dichotomy; secondly, the plasticity or rigidity of the concept; and thirdly, the implications of intangibles attached to the notion. The paper introduces a Special Section including five articles on theoretical and empirical explorations bringing exciting perspectives to creative and critical sociology.
Conflicts in the Habitus: The Emotional Work of Becoming Modern
Authors: Aarseth Helene , Layton Lynne , Nielsen Harriet Bjerrum
Published: February 2016

This article argues that Bourdieu's concept of habitus, and, in particular, the way habitus is transmitted intergenerationally, can be enhanced by considering conflictual conscious and unconscious processes that emerge in relationships. We suggest that Christopher Bollas's discussions of the ‘unthought known’ and of ‘transformational objects’ add relational depth to the concept of habitus and thus contribute to developing a more psycho-social understanding of the relation between agency and change. Drawing on in-depth interviews with a socially mobile chain of a middleclass grandmother, mother and daughter in a period of rapid change, we describe how conflicts in the habitus are produced relationally and can either impede or motivate desires for change. Relational and object relational psychoanalytic theories offer a way to move beyond what we consider a problem in Bourdieu's theory of habitus that derives from his assumption of a subject who either consciously opts for change in habitus when faced with new social demands or non-consciously and unconflictually reproduces habitus.
A non‐invasive magnetic resonance imaging‐based model predicts portal venous pressure
Authors: Zhang Qian Wen , Wang Yi , Wang Jian , Zhao Hong Bo , Yu Hong , Liu Shi Yuan , Zeng Xin , Chen Qi , Hu Zhi Qian , Guo Wen Yuan , Fu Zhi Ren , Ding Guo Shan , Shi Xue Yin , Xie Wei Fen
Published: February 2016

Objective

To establish a non‐invasive model for the assessment of portal venous pressure (PVP) based on the magnetic resonance (MR) parameters.

Methods

In this prospective study, contrast‐enhanced magnetic resonance imaging (MRI) scan was performed in 109 patients indicated for upper abdominal surgeries after their written consents were obtained, and intraoperative PVP measurements were completed in 92 patients. Altogether 17 patients were excluded for not undergoing surgery or unsuccessful catheterization. A linear model was constructed for estimating PVP levels in 56 patients and further validation was conducted in the other 36 patients.

Results

The PVP levels were significantly correlated with MR parameters, including splenic volume (SV), splenic venous diameter (SVD), liver/splenic volume ratio, portal venous diameter, hepatic diameter, portal venous cross‐sectional area, ascites, varices and arterial portal shunts. A linear model was established as follows: PVP (mmHg) = 2.529 + 1.572 × SVD (mm) + 0.231 × SV/body mass index (× 104 cm5/kg) + 3.44 × aspartate aminotransferase‐to‐platelet ratio index. This model showed excellent accuracy in the detection of portal hypertension, with the area under the receiver operating characteristic curve (AUROC) of 0.945 (95% CI 0.867–1.000), with the sensitivity and specificity of 91.7% and 93.7%, respectively. The agreement analysis revealed that the predictive value using this formula closely reflected the patients’ actual PVP level. Moreover, the validation confirmed the accuracy of this model for the assessment of portal hypertension [AUROC 0.935 (95% CI 0.856–1.000)].

Conclusions

The MRI‐based formula has great potential for detecting portal hypertension. As a non‐invasive measurement, it may be clinically accepted for the replacement of invasive modalities after further refinement.
Methylene blue attenuates mitochondrial dysfunction of rat kidney during experimental acute pancreatitis
Authors: Kuliaviene Irma , Baniene Rasa , Virketyte Simona , Kincius Marius , Jansen Eugene , Gulbinas Antanas , Kupcinskas Limas , Trumbeckaite Sonata , Borutaite Vilmante
Published: February 2016

Objective

The disturbance of mitochondrial functions has been considered as one of the mechanisms of pathogenesis of acute pancreatitis (AP) followed by kidney failure. This study was aimed to investigate the effects of methylene blue (MB) on pancreas and kidney mitochondrial respiratory functions during experimental acute pancreatitis in rats.

Methods

AP was induced by administrating sodium taurocholate into the pancreatic duct of male Wistar rats. The rats were divided into three groups: the MB group, MB (5 mg/kg) was injected intravenously 10 min prior to AP induction; the AP group, saline solution was injected intravenously 10 min prior to AP induction; and the sham operation group, isotonic sodium chlorine was used instead of sodium taurocholate. The animals were sacrificed after 24 h. The pancreas and kidney were removed for mitochondrial assay by oxygraphic and spectrophotometric methods.

Results

Intravenous injection of MB did not prevent AP‐induced inhibition of pancreatic mitochondrial respiration; however, MB significantly improved kidney mitochondrial respiratory functions with complex I‐dependent substrates glutamate and malate. The activity of complex I of mitochondria isolated from AP‐damaged kidney was increased after pretreatment with MB. However, MB did not affect AP‐inhibited kidney mitochondrial respiration with succinate. MB had no protective effects on amylase activity or on urea content in serum in AP.

Conclusion

The disturbances of kidney mitochondrial energy metabolism in experimental model of severe AP can be ameliorated by MB administration.
Alcohol withdrawal induces long‐lasting spatial working memory impairments: relationship with changes in corticosterone response in the prefrontal cortex
Authors: Dominguez Gaelle , Belzung Catherine , Pierard Christophe , David Vincent , Henkous Nadia , Decorte Laurence , Mons Nicole , Beracochea Daniel
Published: February 2016

This study intends to determine whether long‐lasting glucocorticoids (GCs) dysregulation in the prefrontal cortex (PFC) or the dorsal hippocampus (dHPC) play a causal role in the maintenance of working memory (WM) deficits observed after alcohol withdrawal. Here, we report that C57/BL6 male mice submitted to 6 months alcohol consumption (12 percent v/v) followed by 1 (1W) or 6 weeks (6W) withdrawal periods exhibit WM deficits in a spatial alternation task and an exaggerated corticosterone rise during and after memory testing in the PFC but not the dHPC. In contrast, emotional reactivity evaluated in a plus‐maze is altered only in the 1W group. No behavioral alterations are observed in mice still drinking alcohol. To determine the causal role of corticosterone in the withdrawal‐associated long‐lasting WM deficits, we further show that a single intraperitoneal injection injection of metyrapone (an inhibitor of corticosterone synthesis) 30 minutes before testing, prevents withdrawal‐associated WM deficits and reestablishes PFC activity, as assessed by increased phosphorylated C‐AMP Response Element‐binding protein (CREB) immunoreactivity in withdrawn mice. Finally, we show that intra‐PFC blockade of mineralocorticoid receptors by infusion of spironolactone and, to a lesser extent, of GCs receptors by injection of mifepristone reverses the WM deficits induced by withdrawal whereas the same injections into the dHPC do not. Overall, our study evidences that long‐lasting GCs dysfunction selectively in the PFC is responsible for the emergence and maintenance of WM impairments after withdrawal and that blocking prefrontal mineralocorticoid receptors receptors restores WM in withdrawn animals.
White matter alterations in cocaine users are negatively related to the number of additionally (ab)used substances
Authors: Kaag Anne Marije , van Wingen Guido A. , Caan Matthan W. A. , Homberg Judith R. , van den Brink Wim , Reneman Liesbeth
Published: February 2016

Diffusion tensor imaging studies have provided evidence for white matter (WM) alterations in cocaine users. While polysubstance use is a widespread phenomenon among cocaine users, its role in WM alterations in cocaine users is currently unknown. This study examined the relation between the number of substances that are used(cocaine, alcohol and marijuana) and WM alterations in 67 male non‐drug users and 67 male regular cocaine users, who were classified into five groups based on the number of used substances. Diffusion‐weighted images were acquired on a 3.0 T magnetic resonance imaging scanner. Using tract‐based spatial statistics we demonstrated that there was a negative relation between the number of used substances and fractional anisotropy, a global measure of WM integrity. Also, we demonstrated a positive relation between the number of used substance and radial diffusivity within the prefrontal lobe, suggesting an increase in demyelination with the number of used substances. We did not find a dose‐effect between the level of substance use and WM alterations. The results of the current study may reflect the presence of a pre‐existing vulnerability to polysubstance use resulting from prefrontal WM abnormalities and related impaired cognitive control although WM alterations because of polysubstance use cannot be fully excluded. This study is an important first step in understanding the problems related to polysubstance use among cocaine users.
Effect of monoclonal antibodies to PCSK9 on high‐sensitivity C‐reactive protein levels: a meta‐analysis of 16 randomized controlled treatment arms
Authors: Sahebkar Amirhossein , Di Giosia Paolo , Stamerra Cosimo Andrea , Grassi Davide , Pedone Claudio , Ferretti Gianna , Bacchetti Tiziana , Ferri Claudio , Giorgini Paolo
Published: February 2016

Aims

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are an emerging class of low‐density lipoprotein cholesterol (LDL‐C)‐lowering agents. In spite of their known effects on lipids, the impact of these drugs on systemic inflammation is less known. We aimed to investigate the effect of PCSK9 inhibitors on high‐sensitivity C‐reactive protein (hs‐CRP) levels through a meta‐analysis of randomized controlled trials (RCTs).

Methods

A systematic literature search of Medline, SCOPUS and Google Scholar was conducted up to December 2015 to identify RCTs assessing changes in hs‐CRP concentrations during treatment with PCSK9 inhibitors. Quantitative data synthesis was performed using a random‐effects model, with weighed mean difference (WMD) and 95% confidence interval (CI) as summary statistics.

Results

Sixteen treatment arms, with a total of 2546 participants, were included. Random‐effects meta‐analysis did not show any significant effect of PCSK9 inhibitors on hs‐CRP levels (WMD: 0.002 mg l–1, CI: –0.017, 0.021; P = 0.807; I2 = 37.26%). This effect size was robust, not sensitive to any single study, and not affected by the type of PCSK9 inhibitor (evolocumab: WMD: 0.002 mg l–1, CI: –0.02, 0.02; P = 0.855; alirocumab WMD: 0.15 mg l–1, CI: –0.11, 0.40; P = 0.259; I2 = 0%), or dosing frequency (biweekly: WMD: 0.13 mg l–1, CI: –0.20, 0.46; P = 0.433; I2 = 55.19%; monthly: WMD: 0.003 mg l–1, CI: –0.01, 0.01; P = 0.59; I2 = 0%). Random‐effects meta‐regression did not suggest any association of changes in hs‐CRP levels with changes in plasma LDL‐C concentrations (P = 0.697) or cumulative dosage of the drug (P = 0.980).

Conclusions

This meta‐analysis of RCTs did not suggest an effect of PCSK9 inhibitors on hs‐CRP concentrations.
Interagency collaboration in children and young people's mental health: a systematic review of outcomes, facilitating factors and inhibiting factors
Authors: Cooper M. , Evans Y. , Pybis J.
Published: February 2016

Background

In the UK and internationally, there have been increasing calls for interagency collaboration across mental health services for children and young people. However, it is not clear whether such practices do, indeed, have a positive impact and, if so, what factors facilitate and inhibit collaboration across agencies.

Methods

Electronic searches were carried out on seven key computerized bibliographic databases. For inclusion in the review, studies needed to report on close working by two or more services that provided mental health support for children and/or young people and that had some systematic collection of qualitative and/or quantitative data. Outcomes were analysed narratively, and facilitating and inhibiting factors were examined using thematic analysis.

Results

A final sample of 33 studies was identified from 4136 initial records. Outcomes were mixed, with some findings indicating that interagency collaboration was associated with greater service use and equity of service provision, but other suggesting negative outcomes on service use and quality. However, interagency collaboration was perceived as helpful and important by both service users and professionals, and collaborative initiatives were evaluated positively. The factors most commonly identified as facilitating interagency collaboration were good interagency communication, joint trainings, good understandings across agencies, mutual valuing across agencies, senior management support, protocols on interagency collaboration and a named link person. The most commonly perceived barriers to interagency collaboration were inadequate resourcing, poor interagency communication, lack of valuing across agencies, differing perspectives, poor understandings across agencies and confidentiality issues.

Conclusions

The results are consistent with findings from previous reviews of interagency collaboration across adult and child services: there were some indications of benefit; and facilitating and inhibiting factors involved working relationships and multi‐agency processes, resources and management. The identification of these factors has implications for practitioners, service managers, trainers, commissioners and researchers.
Differences in hospital attendance for anaphylaxis between immigrants and non‐immigrants: a cohort study
Authors: Norredam M. , Sheikh A. , Dynnes Svendsen K. , Holm Petersen J. , Garvey L. H. , Kristiansen M.
Published: February 2016

Background

The impact of migration on the risk of anaphylaxis remains unknown. We hypothesized that non‐Western immigrants have a lower incidence of anaphylaxis compared to Danish‐born. We investigated variations in hospital attendance for anaphylaxis between immigrants and Danish‐born including time‐ and age‐ trends.

Methods

A register‐based, historical prospective cohort design. Refugees or family reunified immigrants (n = 127 250) who, between January 1, 1994 and December 31, 2010, obtained residency permits in Denmark were included and matched in a 1 : 6 ratio on age and sex with Danish‐born individuals (n = 740 600). Personal identification numbers were cross‐linked to the Danish National Patient Registry identifying all first‐time hospital attendances for anaphylaxis from January 1, 1994 and December 31, 2010. Incidence rate ratios were estimated, stratified for sex and region of birth, adjusting for age using a Cox regression model including the influence of duration of residence and age when residence was obtained.

Results

In total 1053 hospital attendances for anaphylaxis were identified: 89 among non‐Western immigrants, 9 among Western immigrants and 955 among Danish‐born patients. Both male (RR = 0.65; 95%CI: 0.46;0.90) and female (RR = 0.64; 95%CI: 0.48;0.85) non‐Western immigrants had a significantly lower risk ratio of hospital attendance for anaphylaxis compared to Danish‐born. Compared to Danish‐born, non‐Western immigrants living in Denmark during the entire follow‐up period also showed a decreased risk (RR = 0.65; 95%CI: 0.34;1.25). Compared to Danish‐born, non‐Western immigrants who obtained residence permission as children had a decreased risk of hospital attendance for anaphylaxis (RR = 0.48; 95%CI: 0.25;0.91).

Conclusion

This Danish register‐based study using nationwide data revealed fewer hospital attendances for anaphylaxis among non‐Western immigrants compared to Danish‐born; however this protection was lost over time.
Human islets and dendritic cells generate post-translationally modified islet autoantigens
Authors: McLaughlin R J , de Haan A , Zaldumbide A , de Koning E J , de Ru A H , van Veelen P A , van Lummel M , Roep B O
Published: February 2016

The initiation of type 1 diabetes (T1D) requires a break in peripheral tolerance. New insights into neoepitope formation indicate that post-translational modification of islet autoantigens, for example via deamidation, may be an important component of disease initiation or exacerbation. Indeed, deamidation of islet autoantigens increases their binding affinity to the T1D highest-risk human leucocyte antigen (HLA) haplotypes HLA-DR3/DQ2 and -DR4/DQ8, increasing the chance that T cells reactive to deamidated autoantigens can be activated upon T cell receptor ligation. Here we investigated human pancreatic islets and inflammatory and tolerogenic human dendritic cells (DC and tolDC) as potential sources of deamidated islet autoantigens and examined whether deamidation is altered in an inflammatory environment. Islets, DC and tolDC contained tissue transglutaminase, the key enzyme responsible for peptide deamidation, and enzyme activity increased following an inflammatory insult. Islets treated with inflammatory cytokines were found to contain deamidated insulin C-peptide. DC, heterozygous for the T1D highest-risk DQ2/8, pulsed with native islet autoantigens could present naturally processed deamidated neoepitopes. HLA-DQ2 or -DQ8 homozygous DC did not present deamidated islet peptides. This study identifies both human islets and DC as sources of deamidated islet autoantigens and implicates inflammatory activation of tissue transglutaminase as a potential mechanism for islet and DC deamidation.
Detecting Change over Time: A Comparison of the SLUMS Examination and the MMSE in Older Adults at Risk for Cognitive Decline
Authors: Howland Molly , Tatsuoka Curtis , Smyth Kathleen A. , Sajatovic Martha
Published: February 2016

Aims

To directly compare the 1‐year stability of Mini‐Mental State Examination (MMSE) score and Saint Louis University Mental Status (SLUMS) examination score and correlate score changes with demographic variables, clinical factors, and functional domains.

Methods

A sample of 304 study participants was recruited from residential and clinical settings in Ohio. Follow‐up assessments were administered after 1 year with a retention rate of 92% (n = 281). Functional domains included the Instrumental Activities of Daily Living (IADL) scale.

Results

MMSE and SLUMS scores correlated with each other (r = 0.65, P < 0.001) and with two functional measures, including the IADL (r = 0.27, r = 0.24, P < 0.001). However, the MMSE and SLUMS frequently placed the same subject into different categories. Rates of reversion and conversion varied between the two tests. The 1‐year changes in MMSE raw score correlated with changes in three functional domains as well as age (P < 0.05), while SLUMS raw score changes did not correlate with any functional measures.

Conclusion

Our large, longitudinal data set allowed us to compare the tests' stability, which differed between the SLUMS and MMSE. The MMSE may be more sensitive than the SLUMS to 1‐year cognitive changes influencing functional abilities.
DopAmide: Novel, Water‐Soluble, Slow‐Release l‐dihydroxyphenylalanine (l‐DOPA) Precursor Moderates l‐DOPA Conversion to Dopamine and Generates a Sustained Level of Dopamine at Dopaminergic Neurons
Authors: Atlas Daphne
Published: February 2016

Background

Long‐term l‐dihydroxyphenylalanine (l‐DOPA) treatment of Parkinson's disease (PD) is associated with motor complications known as l‐DOPA‐induced dyskinesias (LID) and on/off fluctuations, which are linked to unsteady pulsatile dopaminergic stimulation.

Aim

The objective of this study was to improve l‐DOPA treatment by slowing and stabilizing dopamine (DA) production in the brain and increasing water solubility to provide a rescue therapy for PD.

Results

We synthesized l‐DOPA‐amide, a novel l‐DOPA precursor called DopAmide. DopAmide is water soluble and, as a prodrug, requires hydrolysis prior to decarboxylation by the aromatic l‐amino acid decarboxylase (EC 4.1.1.28; AAAD). In the 6‐OH‐dopamine (6‐OHDA)‐lesioned rats, DopAmide maintained steady rotations for up to 4 h compared with 2 h by l‐DOPA, suggesting that this rate‐limiting step generated a sustained level of DA at dopaminergic neurons. Pharmacokinetic studies showed elimination half‐life of l‐DOPA in the plasma after DopAmide treatment of t1/2 = 4.1 h, significantly longer than t1/2 = 2.9 h after treatment with l‐DOPA, consistent with the 6‐OHDA results.

Conclusions

The slow conversion of DopAmide to l‐DOPA provides a sustained level of DA in the dopaminergic cells, shown by the long 6‐OHDA steady rotations. The water solubility and improved bioavailability may help reduce medication frequency associated with l‐DOPA treatment of PD. Sustained levels of DA might lower the super‐sensitization of DA signaling and potentially attenuate l‐DOPA adverse effects.
Can protected areas mitigate the impacts of climate change on bird's species and communities?
Authors: Gaüzère Pierre , Jiguet Frédéric , Devictor Vincent
Published: February 2016

Aim

Protected areas (PAs) are the mainstay of our conservation strategies. While they may succeed in locally preventing species and habitat degradation due to human activities, their ability to mitigate the impacts of climate change on biodiversity is still debated. We assessed whether community and species responses to climate change were related to PAs by testing three main predictions: (1) the thermal adjustment of community composition to temperature changes should be positively related to the proportion of PAs, (2) the species that benefit most from PAs should be less impacted by temperature change, and (3) the species a priori considered the most vulnerable to global change should be even more sensitive to the mitigating effect of PAs.

Location

Mainland France.

Methods

Data from a long‐term, large‐scale standardized monitoring programme, recording annual changes in the abundance of 116 breeding bird species in France between 2001 and 2012, were used. Local temporal trends in spring temperature, community reshuffling and bird populations over the country were estimated with a moving window approach (2094 spatial windows). Generalized additive mixed models were then performed to relate these responses to the local proportion of PAs.

Results

Most PAs promote community adjustment to temperature changes. At the species scale, our results show that the more a species benefited from PAs, the less vulnerable it was to temperature changes. PAs were also more effective in mitigating the impact of climate change on the less common and northernmost birds.

Main conclusion

Protected areas do seem to mitigate climate change impacts on species and communities. Our study argues for the use of integrative frameworks at different biological scales to assess the usefulness and relevance of PAs faced with climate change and suggests that PAs remain key effective conservation strategies in a changing climatic world.
Prognostic factors for cerebral palsy and motor impairment in children born very preterm or very low birthweight: a systematic review
Authors: Linsell Louise , Malouf Reem , Morris Joan , Kurinczuk Jennifer J , Marlow Neil
Published: February 2016

Aim

There is a large literature reporting risk factor analyses for poor neurodevelopment in children born very preterm (VPT: ≤32wks) or very low birthweight (VLBW: ≤1250g), which to date has not been formally summarized. The aim of this paper was to identify prognostic factors for cerebral palsy (CP) and motor impairment in children bornVPT/VLBW.

Method

A systematic review was conducted using Medline, Embase, and Pyscinfo databases to identify studies published between 1 January 1990 and 1 June 2014 reporting multivariable prediction models for poor neurodevelopment inVPT/VLBWchildren (registration numberCRD42014006943). Twenty‐eight studies for motor outcomes were identified.

Results

There was strong evidence that intraventricular haemorrhage and periventricular leukomalacia, and some evidence that the use of postnatal steroids and non‐use of antenatal steroids, were prognostic factors forCP. Male sex and gestational age were of limited use as prognostic factors forCPin cohorts restricted to ≤32 weeks gestation; however, in children older than 5 years with no major disability, there was evidence that male sex was a predictive factor for motor impairment.

Interpretation

This review has identified factors which may be of prognostic value forCPand motor impairment inVPT/VLBWchildren and will help to form the basis of future prognostic research.
Diagnostic accuracy of the clinical feeding evaluation in detecting aspiration in children: a systematic review
Authors: Calvo Irene , Conway Aifric , Henriques Filipa , Walshe Margaret
Published: February 2016

The aim of this systematic review is to determine the diagnostic accuracy of clinical feeding evaluation (CFE) compared to instrumental assessments in detecting oropharyngeal aspiration (OPA) in children. This is important to support clinical decision‐making and to provide safe, cost‐effective, higher quality care. All published and unpublished studies in all languages assessing the diagnostic accuracy of CFE compared to videofluoroscopic swallowing study (VFSS) and/or fibre‐optic endoscopic examination of swallowing (FEES) in detecting OPA in paediatric populations were sought. Databases were searched from inception to April 2015. Grey literature, citations, and references were also searched. Two independent reviewers extracted and analysed data. Accuracy estimates were calculated. Research reports were translated into English as required. Six studies examining the diagnostic accuracy of CFE using VFSS and/or FEES were eligible for inclusion. Sample sizes, populations studied, and CFE characteristics varied widely. The overall methodological quality of the studies, assessed with QUADAS‐2, was considered ‘low’. Results suggested that CFEs trialling liquid consistencies might provide better accuracy estimates than CFEs trialling solids exclusively. This systematic review highlights the critical lack of evidence on the accuracy of CFE in detecting OPA in children. Larger well‐designed primary diagnostic test accuracy studies in this area are needed to inform dysphagia assessment in paediatrics.
Utility of combined gray‐scale and perflubutane contrast‐enhanced ultrasound for diagnosing early hepatocellular carcinomas: Comparison of well differentiated and distinctly nodular types
Authors: Tada Toshifumi , Kumada Takashi , Toyoda Hidenori , Sone Yasuhiro , Kaneoka Yuji , Maeda Atsuyuki , Okuda Seiji , Otobe Katsuhiko , Tsuji Nozomi
Published: February 2016

Aim

To clarify the value of gray‐scale ultrasound (US) combined with contrast‐enhanced US (CEUS) with perflubutane in diagnosing early hepatocellular carcinoma (HCC).

Methods

A total of 57 surgically resected, well differentiated HCCs were analyzed. Hepatocellular carcinomas were macroscopically diagnosed as vaguely nodular or distinctly nodular types, which correspond to early HCC or progressed HCC, respectively. Gray‐scale US findings were evaluated in terms of shape (round or roundish, or irregular), border and contour (well‐defined and smooth, or poorly defined), and intratumor echo levels (hyper, hypo, iso, heterogeneous, or mosaic). Contrast‐enhanced US findings were evaluated during the arterial phase (vascularity [finely homogeneous, dendritic, or chaotic] and perfusion enhancement [homogeneous or heterogeneous]), portal phase (presence or absence of washout), and post‐vascular phase (echo intensity level [defect, incomplete defect, or iso‐enhancing]).

Results

Eighteen HCCs were categorized as early HCCs and the remaining 39 were categorized as progressed HCCs. Receiver operating characteristic curve analysis for the diagnosis of early HCC yielded area under the receiver operating characteristic curve (Az) values for border and contour on gray‐scale US and echo intensity level in the CEUS post‐vascular phase of 0.782 and 0.828, respectively. Multiple logistic regression analysis also indicated that both of these gray‐scale US and CEUS findings were independently associated with early HCC. The Az value for the combination of border and contour and echo intensity for the diagnosis of early HCC was 0.907, corresponding to a high diagnostic value.

Conclusion

The combination of gray‐scale US and CEUS can provide high‐quality imaging assessment for diagnosing early HCC.