bluuebunny/crossref_metadata_2025 huggingface dataset:
Nucleosome dynamics of human iPSC during the early stages of neurodevelopment
Authors: Harwood Janet C , Kent Nicholas A , Allen Nicholas D , Harwood Adrian J
Published: August 2018

Regulation of nucleosome positioning is important for neurodevelopment, and mutation of genes mediating chromatin remodelling are strongly associated with human neurodevelopmental disorders. Unicellular organisms possess arrays of highly positioned nucleosomes within their chromatin, occupying up to 80% of their genomes. These span gene-coding and regulatory regions, and can be associated with local changes of gene transcription. In the much larger genome of human cells, the roles of nucleosome positioning are less clear, and this raises questions of how nucleosome dynamics interfaces with human neurodevelopment.

We have generated genome-wide nucleosome maps from an undifferentiated human induced pluripotent stem cell (hiPSC) line and after its differentiation to the neuronal progenitor cell (NPC) stage. We found that approximately 3% of nucleosomes are highly positioned in NPC. In contrast, there are 8-fold less positioned nucleosomes in pluripotent cells, with the majority arisingde novoor relocating during cell differentiation. Positioned nucleosomes do not directly correlate with active chromatin or gene transcription, such as marking Transcriptional Start Sites (TSS). Unexpectedly, we find a small population of nucleosomes that remain positioned after differentiation, occupying similar positions in pluripotent and NPC cells. They flank the binding sites of the key gene regulators NRSF/REST and CTCF, but remain in place whether or not their regulatory complexes are present. Together, these results present an alternative view in human cells, where positioned nucleosomes are sparse and dynamic, but act to alter gene expression at a distance via structural conformation at sites of chromatin regulation, not local changes in gene organisation.
Epigenomic and functional characterization of a core DNA methyltransferase in the human pathogenClostridium difficile
Authors: Oliveira Pedro H. , Ribis John W. , Garrett Elizabeth M. , Trzilova Dominika , Kim Alex , Sekulovic Ognjen , Mead Edward A. , Pak Theodore , Zhu Shijia , Deikus Gintaras , Touchon Marie , Beckford Colleen , Zeitouni Nathalie E. , Altman Deena , Webster Elizabeth , Oussenko Irina , Bunyavanich Supinda , Aggarwal Aneel K. , Bashir Ali , Patel Gopi , Hamula Camille , Huprikar Shirish , Schadt Eric E. , Sebra Robert , van Bakel Harm , Kasarskis Andrew , Tamayo Rita , Shen Aimee , Fang Gang
Published: August 2018

Clostridioides difficileis a leading cause of health care-associated infections. Although significant progress has been made in the understanding of its genome, the epigenome ofC. difficileand its functional impact has not been systematically explored. Here, we performed the first comprehensive DNA methylome analysis ofC. difficileusing 36 human isolates and observed great epigenomic diversity. We discovered an orphan DNA methyltransferase with a well-defined specificity whose corresponding gene is highly conserved across our dataset and in all ~300 globalC. difficilegenomes examined. Inactivation of the methyltransferase gene negatively impacted sporulation, a key step inC. difficiledisease transmission, consistently supported by multi-omics data, genetic experiments, and a mouse colonization model. Further experimental and transcriptomic analysis also suggested that epigenetic regulation is associated with cell length, biofilm formation, and host colonization. These findings open up a new epigenetic dimension to characterize medically relevant biological processes in this critical pathogen. This work also provides a set of methods for comparative epigenomics and integrative analysis, which we expect to be broadly applicable to bacterial epigenomics studies.
Thalamo-cortical interactions define functional dissociations across the macaque attention network
Authors: Fiebelkorn Ian C. , Pinsk Mark A. , Kastner Sabine
Published: August 2018

Spatial attention is discontinuous, sampling behaviorally relevant locations in theta-rhythmic cycles (3–6 Hz). Underlying this rhythmic sampling are intrinsic theta oscillations in frontal and parietal cortices that provide a clocking mechanism for two alternating attentional states that are associated with either engagement at the presently attended location (and enhanced perceptual sensitivity) or disengagement (and diminished perceptual sensitivity). It has remained unclear, however, how these theta-dependent states are coordinated across the large-scale network that directs spatial attention. The pulvinar is a candidate for such coordination, having been previously shown to regulate cortical activity. We therefore examined pulvino-cortical interactions during theta-rhythmic sampling by simultaneously recording from FEF, LIP, and the pulvinar. Neural activity propagated from (i) pulvinar to cortex during periods of engagement and (ii) from cortex to pulvinar during periods of disengagement. A rhythmic reweighting of pulvino-cortical interactions thus defines functional dissociations in the macaque attention network.
On the feasibility of saltational evolution
Authors: Katsnelson Mikhail I. , Wolf Yuri I. , Koonin Eugene V.
Published: August 2018

One of the key tenets of Darwin’s theory that was inherited by the Modern Synthesis of evolutionary biology is gradualism, that is, the notion that evolution proceeds gradually, via accumulation of “infinitesimally small” heritable changes1,2. However, some of the most consequential evolutionary changes, such as, for example, the emergence of major taxa, seem to occur abruptly rather than gradually, as captured in the concepts of punctuated equilibrium3,4and evolutionary transitions5,6. We examine a mathematical model of an evolutionary process on a rugged fitness landscape7,8and obtain analytic solutions for the probability of multi-mutational leaps, that is, several mutations occurring simultaneously, within a single generation in one genome, and being fixed all together in the evolving population. The results indicate that, for typical, empirically observed combinations of the parameters of the evolutionary process, namely, effective population size, mutation rate, and distribution of selection coefficients of mutations, the probability of a multi-mutational leap is low, and accordingly, their contribution to the evolutionary process is minor at best. However, such leaps could become an important factor of evolution in situations of population bottlenecks and elevated mutation rates, such as stress-induced mutagenesis in microbes or tumor progression, as well as major evolutionary transitions and evolution of primordial replicators.
Long-read Sequencing Uncovers a Complex Transcriptome Topology in Varicella Zoster Virus
Authors: Prazsák István , Moldován Norbert , Tombácz Dóra , Megyeri Klára , Szűcs Attila , Csabai Zsolt , Boldogkői Zsolt
Published: August 2018

Background

Varicella zoster virus (VZV) is a human pathogenic alphaherpesvirus harboring a relatively large DNA molecule. The VZV transcriptome has already been analyzed by microarray and short-read sequencing analyses. However, both approaches have substantial limitations when used for structural characterization of transcript isoforms, even if supplemented with primer extension or other techniques. Among others, they are inefficient in distinguishing between embedded RNA molecules, transcript isoforms, including splice and length variants, as well as between alternative polycistronic transcripts. It has been demonstrated in several studies that long-read sequencing is able to circumvent these problems.

Results

In this work, we report the analysis of VZV lytic transcriptome using the Oxford Nanopore Technologies sequencing platform. These investigations have led to the identification of 114 novel transcripts, including mRNAs, non-coding RNAs, polycistronic RNAs and complex transcripts, as well as 10 novel spliced transcripts and 27 novel transcription start site isoforms and transcription end site isoforms. A novel class of transcripts, the nroRNAs are described in this study. These transcripts are encoded by the genomic region located in close vicinity to the viral replication origin. We also show that the VZV latency transcript (VLT) exhibits a more complex structural variation than formerly believed. Additionally, we have detected RNA editing in a novel non-coding RNA molecule.

Conclusions

Our investigations disclosed a composite transcriptomic architecture of VZV, including the discovery of novel RNA molecules and transcript isoforms, as well as a complex meshwork of transcriptional read-throughs and overlaps. The results represent a substantial advance in the annotation VZV transcriptome and in understanding the molecular biology of the herpesviruses in general.
Kinpute: Using identity by descent to improve genotype imputation
Authors: Abney Mark , El Sherbiny Aisha
Published: August 2018

1

Motivation

Genotype imputation, though generally accurate, often results in many genotypes being poorly imputed, particularly in studies where the individuals are not well represented by standard reference panels. When individuals in the study share regions of the genome identical by descent (IBD), it is possible to use this information in combination with a study specific reference panel (SSRP) to improve the imputation results. Kinpute uses IBD information—due to either recent, familial relatedness or distant, unknown ancestors— in conjunction with the output from linkage disequilibrium (LD) based imputation methods to compute more accurate genotype probabilities. Kinpute uses a novel method for IBD imputation, which works even in the absence of a pedigree, and results in substantially improved imputation quality.

Results

Given initial estimates of average IBD between subjects in the study sample, Kinpute uses a novel algorithm to select an optimal set of individuals to sequence and use as an SSRP. Kinpute is designed to use as input both this SSRP and the genotype probabilities output from other LD based imputation software, and uses a new method to combine the LD imputed genotype probabilities with IBD configurations to substantially improve imputation. We tested Kinpute on a human population isolate where 98 individuals have been sequenced. In half of this sample, whose sequence data was masked, we used Impute2 to perform LD based imputation and Kinpute was used to obtain higher accuracy genotype probabilities. Measures of imputation accuracy improved significantly, particularly for those genotypes that Impute2 imputed with low certainty.

Availability

Kinpute is an open-source and freely available C++ software package that can be downloaded from https://github.com/markabney/Kinpute/releases.
Selection methods and diversity preservation in many-objective evolutionary algorithms
Authors: Martí Luis , Segredo Eduardo , Sánchez-Pi Nayat , Hart Emma
Published: August 2018

Purpose

One of the main components of multi-objective, and therefore, many-objective evolutionary algorithms, is the selection mechanism. It is responsible for performing two main tasks simultaneously. First, it has to promote convergence by selecting solutions which are as close as possible to the Pareto optimal set. And second, it has to promote diversity in the solution set provided. In the current work, an exhaustive study that involves the comparison of several selection mechanisms with different features is performed. Particularly, Pareto-based and indicator-based selection schemes, which belong to well-known multi-objective optimisers, are considered. The paper aims to discuss these issues.

Design/methodology/approach

Each of those mechanisms is incorporated into a common multi-objective evolutionary algorithm framework. The main goal of the study is to measure the diversity preserved by each of those selection methods when addressing many-objective optimisation problems. The Walking Fish Group test suite, a set of optimisation problems with a scalable number of objective functions, is taken into account to perform the experimental evaluation.

Findings

The computational results highlight that the the reference-point-based selection scheme of the Non-dominated Sorting Genetic Algorithm III and a modified version of the Non-dominated Sorting Genetic Algorithm II, where the crowding distance is replaced by the Euclidean distance, are able to provide the best performance, not only in terms of diversity preservation, but also in terms of convergence.

Originality/value

The performance provided by the use of the Euclidean distance as part of the selection scheme indicates this is a promising line of research and, to the best of the knowledge, it has not been investigated yet.
A review of non-specialised, group-based mental health and psychosocial interventions in displaced populations
Authors: Wood Benjamin Mitchell , Kallestrup Per
Published: August 2018

Purpose

The purpose of this paper is to describe non-specialised, group-based interventions in displaced populations from reviewed literature, and to explore their outcomes.

Design/methodology/approach

A literature review was conducted using the PubMed database, Web of Science, The Cochrane Library of Systematic Reviews, and defined “grey literature”. Characteristics of the interventions were summarised into a table under key categories such as targeted persons, study setting, level of evidence, outcome measures, assessment tools used and summary of results.

Findings

In total, 11 articles were identified stemming from nine separate interventions. Three of these were considered level 1 evidence as they were randomised controlled trials. The described interventions were markedly heterogeneous in nature and produced diverse findings. There were noted methodological issues in the majority of interventions reviewed.

Originality/value

This original research has demonstrated clear need for research that uses robust methodology accounting for the complex and challenging nature of this context.
E-mail load, workload stress and desired e-mail load: a cybernetic approach
Authors: Stich Jean-Francois , Tarafdar Monideepa , Stacey Patrick , Cooper Cary L.
Published: August 2018

Purpose

Using e-mail is a time-consuming activity that can increase workload stress. The purpose of this paper is to investigate the relationship between the individual’s e-mail load, workload stress and desired e-mail load, drawing from the cybernetic theory of stress.

Design/methodology/approach

Based on prior theory, the authors first hypothesized relationships among e-mail load, workplace stress and desired e-mail load. The authors then tested these relationships on a sample of 504 full-time workers in the USA, using survey data and covariance-based structural equation modeling techniques.

Findings

The authors find that higher e-mail load is associated with higher workload stress; higher workload stress is associated with lower desired e-mail load; lower desired e-mail load is associated with lower e-mail load; and higher workload stress is associated with higher psychological strain, higher negative emotions and lower organizational commitment.

Originality/value

The study provides a novel understanding of workload stress due to e-mail load, through the lens of cybernetic theory. It contributes to the e-mail overload and technostress literatures by conceptualizing desired e-mail load as a potential outcome of workplace stress and as a regulator for e-mail load. For practitioners, the study highlights the importance of managing employees’ e-mail load to prevent the negative effects of workplace stress and associated strains.
Race/ethnicity, discrimination, and confidence in order institutions
Authors: Wu Yuning , Cao Liqun
Published: August 2018

Purpose

The purpose of this paper is to propose and test a conceptual model that explains racially/ethnically differential confidence in order institutions through a mediating mechanism of perception of discrimination.

Design/methodology/approach

This study relies on a nationally representative sample of 1,001 respondents and path analysis to test the relationships between race/ethnicity, multiple mediating factors, and confidence in order institutions.

Findings

Both African and Latino Americans reported significantly lower levels of confidence compared to White Americans. People who have stronger senses of being discriminated against, regardless of their races, have reduced confidence. A range of other cognitive/evaluative variables have promoted or inhibited people’s confidence in order institutions.

Research limitations/implications

This study relies on cross-sectional data which preclude definite inferences regarding causal relationships among the variables. Some measures are limited due to constraint of data.

Practical implications

To lessen discrimination, both actual and perceived, officials from order institutions should act fairly and impartially, recognize citizen rights, and treat people with respect and dignity. In addition, comprehensive measures involving interventions throughout the entire criminal justice system to reduce racial inequalities should be in place.

Social implications

Equal protection and application of the law by order institutions are imperative, so are social policies that aim to close the structural gaps among all races and ethnicities.

Originality/value

This paper takes an innovative effort of incorporating the currently dominant group position perspective and the injustice perspective into an integrated account of the process by which race and ethnicity affect the perception of discrimination, which, in turn, links to confidence in order institutions.
Going to the dogs? Police, donations, and K9s
Authors: Walby Kevin , Luscombe Alex , Lippert Randy K.
Published: August 2018

Purpose

Most existing literature on K9 units has focused on the relationship between police handler and canine, or questions about use of force. The purpose of this paper is to explore the relationship between private donations to public police departments, an increasingly accepted institutional practice in the policing world, and K9 units. Specifically, the authors examine rationales for sponsoring and financially supporting K9 units in Canada and the USA.

Design/methodology/approach

The authors focus on four main themes that emerged in analysis of media articles, interview transcripts, and the results of freedom of information requests.

Findings

These four rationales or repertoires of discourse are: police dogs as heroes; dogs as crime fighters; cute K9s; and police dogs as uncontroversial donation recipients.

Originality/value

After drawing attention to the expanding role of police foundations in these funding endeavors, the authors reflect on what these findings mean for understanding private sponsorship of public police as well as K9 units in North America and elsewhere. The authors draw attention to the possibility of perceived and actual corruption when private, corporate monies become the main channel through which K9 and other police units are funded.
News media and perceptions of police: a state-of-the-art-review
Authors: Graziano Lisa M.
Published: August 2018

Purpose

The purpose of this paper is to provide a systematic review of the literature examining the role of news media consumption and awareness in shaping public attitudes about police.

Design/methodology/approach

A comprehensive, systematic search of multiple academic databases (e.g. EBSCO Host) was undertaken, supplemented by the use of Google Scholar to search among journals indicated as having cited the articles found in the databases.

Findings

A total of 42 studies were identified that met the selection criteria for this meta-review and examined exposure to high-profile incidents involving police, awareness of negative news coverage of police, and/or consumption of specific news mediums (e.g. newspapers). Overall, research supports a relationship between negative perceptions of police and both exposure to high-profile incidents and awareness of negative coverage. Some support for the influence of consuming television news on attitudes exists, but more research is needed on the role of different news sources in shaping perceptions. Future research should also include determining causal pathways and how news about police is selected.

Originality/value

This is the first meta-review of the research examining how news media and attitudes about police are related. This study will provide a useful resource for those researchers wishing to continue to examine different aspects of news media consumption as a predictor of perceptions.
How commitment and satisfaction explain leave intention in police force?
Authors: Ahmad Rashid , Islam Talat , Saleem Saima
Published: August 2018

Purpose

The purpose of this paper is to investigate the impact of professional commitment and job satisfaction on leave intention considering alternative job opportunities as a moderator.

Design/methodology/approach

The authors collected data from 147 patrolling police officers on the basis of convenience sampling using a questionnaire-based survey.

Findings

The study noted that professionally committed and satisfied police officers are less likely to leave their organization. In addition, alternative job opportunities strengthen the negative association of professional commitment and job satisfaction with leave intention.

Research limitations/implications

This study was conducted at one point of time and the majority of the respondents were male, therefore, the results might be gender biased. This study has implications for policymakers and HR managers.

Practical implications

Law enforcement agencies and organizations should develop and sustain workplace environments where professional commitment and job satisfaction can positively influence the leave intentions of their employees. More specifically, it provides insight to the managers to retain talented and commitment employees in their organizations.

Originality/value

This study adds to the scant literature on professional commitment and alternative job opportunity in the context of police.
Career choice of real estate students in Nigeria
Authors: Ayodele Timothy Oluwafemi
Published: August 2018

Purpose

The purpose of this paper is to examine the career preferences of real estate students and the predisposing factors influencing the choice of career. The study also analysed the gender and socioeconomic variations with respect to the career preferences and factors influencing the career choice of real estate students in an emergent market like Nigeria.

Design/methodology/approach

Closed-ended questionnaires were administered on final year real estate students in the three Federal universities offering real estate in Southwestern Nigeria. Data were analysed using frequency counts, percentages, mean ranking, independent t-test, analysis of variance and correlation analysis.

Findings

The findings showed that the predominant individual factors influencing career choice of real estate students were personal career interest, the magnitude of initial salary, future financial prospects and job security. Furthermore, while intrinsic and economic/financial factors were the major themes influencing respondents’ career choice, the influence of a third party was less a likely determinant. Analysis of gender differences showed that there was a statistical difference between the male and female respondents with respect to the intrinsic and career exposure factors.

Research limitations/implications

The study has implications for real estate students, career advisers/academic counsellors, organisations employing the services of real estate graduates, and educational institutions and policy stakeholders in the real estate sector. The study also has implication for real estate professional bodies in Nigeria and other emergent markets.

Originality/value

This is perhaps the first attempt that examined the factors influencing the career choice of real estate students in an emergent market like Nigeria, especially from the perspectives of gender and socioeconomic variations.
The Intergovernmental Panel on Climate Change and the Science‐Diplomacy Nexus
Authors: Ruffini Pierre‐Bruno
Published: August 2018

In this article, we address the climate change issue through the lens of science diplomacy. We contribute to analyzing the mechanisms by which, in the international climate regime, the issues of science intermingle with those of diplomacy. We use the term ‘nexus’ to designate the interactions between the dynamics of science itself and the dynamics of diplomacy. We focus on the critical role played by the IPCC in the formation of this nexus. We argue that the extent to which diplomats understand and use scientific knowledge as well as that the clashing of national interests during major negotiations can jeopardize science diplomacy effectiveness. We thus explain why the large consensus that exists among scientists about the origins and long‐term risks of climate change does not translate into a consensus among diplomats over an appropriate course of action. These findings illustrate the limits of ‘science in diplomacy’.
Remittances and Protest in Dictatorships
Authors: Escribà‐Folch Abel , Meseguer Covadonga , Wright Joseph
Published: August 2018

Remittances—money migrant workers send back home—are the second largest source of international financial flows in developing countries. As with other sources of international finance, such as foreign direct investment and foreign aid, worker remittances shape politics in recipient countries. We examine the political consequences of remittances by exploring how they influence antigovernment protest behavior. While recent research argues that remittances have a pernicious effect on politics by contributing to authoritarian stability, we argue the opposite: Remittances increase political protest in nondemocracies by augmenting the resources available to potential political opponents. Using cross‐national data on a latent measure of antigovernment political protest, we show that remittances increase protest. To explore the mechanism linking remittances to protest, we turn to individual‐level data from eight nondemocracies in Africa to show that remittance receipt increases protest in opposition areas but not in progovernment regions.
The Effects of US Presidential Elections on Work Engagement and Job Performance
Authors: Beck James W. , Shen Winny
Published: August 2018

We predicted that presidential election results would spill over to influence the work domain. Individuals who voted for the winning candidate were expected to experience increased engagement, whereas individuals who voted for the losing candidate were expected to experience decreased engagement. We tested these predictions within the context of the 2016 US presidential election. Using a sample of 232 working Americans, work engagement and job performance were assessed one week prior to the election, the day after the election, and one week after the election. Contrary to our prediction, individuals who voted for Trump (the winning candidate) did not report increased work engagement, thereby providing no evidence of positive spillover. However, individuals who voted for Clinton (the losing candidate) were less engaged on the day after the election compared to baseline, demonstrating negative spillover. Downstream, work engagement was positively related to job performance. However, these effects were relatively short‐lived, as engagement returned to baseline levels within one week following the election. Our results suggest that elections can have important implications for work‐related outcomes. From a practical perspective we suggest that to the extent possible it may be prudent to avoid scheduling important work tasks for the days following presidential elections.
Recognising knowledge transfers in ‘unskilled’ and ‘low‐skilled’ international migration: Insights from Pacific Island seasonal workers in rural Australia
Authors: Dun Olivia , Klocker Natascha , Head Lesley
Published: August 2018

This article explores knowledge transfers in international migration and development through insights from Pacific Island seasonal workers participating in Australia's Seasonal Worker Programme (SWP). We discuss actual and potential horticultural knowledge transfers that are enabled when circular migrants are engaged in agriculture in their place of migration origin and destination. Transfers identified by seasonal workers themselves include: technologies to improve horticultural production, exposure to different crop types, and techniques to improve crop yields. We argue that SWP migrants should be reframed as knowledge holders (not ‘unskilled’ or ‘low‐skilled’ labourers), and reflect on how knowledge transfers can be better supported to enable benefits for communities of origin and destination.
Tetrahydrocurcumin, a major metabolite of curcumin, ameliorates allergic airway inflammation by attenuating Th2 response and suppressing the IL‐4Rα‐Jak1‐STAT6 and Jagged1/Jagged2 ‐Notch1/Notch2 pathways in asthmatic mice
Authors: Chen Bin Lin , Chen Yan Qiu , Ma Bai Hui , Yu Si Fei , Li Li Yue , Zeng Qing Xiang , Zhou Yu Tao , Wu Yin Fan , Liu Wen long , Wan Jian Bo , Yang Yan , Li Chun Wei
Published: August 2018

Background

Curcumin (Cur), derived from Curcuma species, exhibits anti‐inflammatory, antioxidant, and anticancer effects. Although Cur has some beneficial effects on asthma, its clinical application is limited by its low bioavailability. Tetrahydrocurcumin (THC), the major active metabolite of Cur, has multiple biological functions, similarly to Cur, and importantly, it showed enhanced bioavailability in tissues and plasma. However, the effect of THC on asthma has not been reported.

Objective

The current study sought to investigate the efficacy of dietary THC on allergic asthma compared to that of Cur in an animal model.

Methods

The anti‐inflammatory effects of Cur and THC were evaluated in an ovalbumin‐induced asthmatic mouse model. The nasal symptoms, pathological alterations of the lung tissues, oxidants and antioxidants, cytokine production, T cell subsets, and Th2‐related signalling pathway activity were assessed.

Results

Both THC and Cur had beneficial effects on asthmatic mice with regard to nasal symptoms, pathological changes (eosinophils and mucus hyper‐production), oxidative stress (malondialdehyde), cytokine production (IL‐13), Th17 and cytotoxic T cell subsets, and Th2 signalling pathway (IL‐4Rα‐Jak1‐STAT6 and Jagged1/Jagged2‐Notch1/Notch2 axis) activity. THC was more effective than Cur in suppressing tissue eosinophilia, mucus production, and IL‐4Rα/Jak1/STAT6 pathway activity. Furthermore, only THC inhibited peripheral eosinophil levels, Th2 cytokines (IL‐4 and IL‐5), and Th2 cell subsets and enhanced an antioxidant enzyme (glutathione).

Conclusion and Clinical Relevance

The above results demonstrated for the first time that THC was superior to Cur in modulating allergic asthmatic phenotypes, especially attenuating the Th2 response. THC might be a potentially effective agent for asthma treatment.
Changes in anti-citrullinated protein antibody isotype levels in relation to disease activity and response to treatment in early rheumatoid arthritis
Authors: Kastbom A , Roos Ljungberg K , Ziegelasch M , Wetterö J , Skogh T , Martinsson K
Published: August 2018

Rheumatoid arthritis (RA) is a chronic inflammatory disease where serum analysis of anti-citrullinated peptide/protein antibodies (ACPA) is an important diagnostic/prognostic tool. Levels and changes of ACPA in RA patients have been studied previously in relation to disease course and therapy response, but less is known regarding ACPA isotype changes in early RA. Hence, recent-onset RA patients (n = 231) were subjected to a 3-year clinical and radiological follow-up. Serum samples were serially collected and ACPA isotypes were analysed using the second-generation cyclic citrullinated peptide (CCP) as capture antigen. Changes in ACPA isotype levels and status were related to disease course and pharmacotherapy. At inclusion, 74% of the patients tested positive for ACPA IgG; 55% for immunoglobulin (Ig)A, 37% for secretory IgA (SIgA) and 35% for IgM. The proportion of positive patients decreased significantly at follow-up regarding ACPA SIgA, IgM and IgA. During the initial 3 months, reduction of the 28-joint disease activity score (DAS28) correlated with reduced levels of ACPA IgG (Rho = 0·242, P = 0·003), IgA (Rho = 0·260, P = 0·008), IgM (Rho = 0·457, P < 0·001) and SIgA (Rho = 0·402, P < 0·001). Levels of ACPA SIgA (P = 0·008) and IgM (P = 0·021) decreased significantly among patients with good response to treatment, which was not seen regarding ACPA IgA or IgG. Changes in ACPA isotype levels were not associated with radiographic damage. In conclusion, ACPA SIgA and IgM declined rapidly upon anti-rheumatic therapy and correlated with decreased disease activity in recent-onset RA. This may indicate that down-regulation of mucosal immunity to citrullinated proteins/peptides and recruitment of new B cells are key features of therapy responses in early RA.
Building a System of Indicators to Evaluate the Right of a Child to Play
Authors: Payà Rico Andrés , Bantulà Janot Jaume
Published: August 2018

This study presents the results of a research project whose objective is to propose measures to evaluate the right of children to engage in play, as recognised in the Convention on the Rights of the Child. After exhausting documentation and statistical sources, a lack of measures related to this right was clear. This led to the formation of discussion groups about play with schools, families and social agents. From this, an initial matrix was developed and submitted to experts who selected the most suitable measures. This resulted in the SIDERJU matrix, composed of measures for the structure, process and result.
Transcutaneous Baha Attract system: Long‐term outcomes of the French multicenter study
Authors: Nevoux Jérôme , Coudert Cyrille , Boulet Marc , Czajka Cécile , Tavernier Laurent , Daval Mary , Ayache Denis , Meller Renaud , Rossetto Stéphane , Papon Jean‐François , Deveze Arnaud
Published: August 2018

Background

Bone conduction implants based on abutment‐driven acoustic transmission result in good hearing outcomes; however, skin complications impact the quality of life (QOL) and possibly the viability of the device for many patients. The transcutaneous magnetic Baha® Attract technology was developed with the goal of minimising skin complications.

Objectives

To analyse surgical, auditory and QOL outcomes for patients implanted with the Baha® Attract.

Design

Prospective multicentre cohort study.

Setting

Four French tertiary referral centres.

Participants

Thirty‐two patients implanted with the Baha® Attract, including 25 with conductive and mixed hearing loss and 7 with single‐sided deafness.

Main outcome measures

Postoperative follow‐up involved the visual analysis of soft tissue adaptation and sound processor magnet strength measurement. The audiometric outcomes were evaluated in quiet and noise, and the QOL was assessed using three different questionnaires.

Results

After 12 months of use, soft tissue was thinner, and mean magnet strength was significantly decreased (3.7‐3.1, P < 0.05) relative to measures during surgery. The speech recognition threshold in quiet significantly improved compared to unaided situation (73‐44 dB HL respectively, P < 0.001) as did functional gain in noise (+2.8). All QOL scores improved, and the APHAB questionnaire score correlated with the audiometric outcomes.

Conclusions

The Baha® Attract technology results in significant hearing gain and improves QOL. Skin complications were not observed, although surgeons, audiologists and patients should be aware of soft tissue evolution during the first postoperative year. The reversibility of this implant is a major advantage that allows switching to another system if hearing degrades.
Evaluation of Pharmacokinetics and Pharmacodynamics of BI 425809, a Novel GlyT1 Inhibitor: Translational Studies
Authors: Rosenbrock Holger , Desch Michael , Kleiner Oliver , Dorner‐Ciossek Cornelia , Schmid Bernhard , Keller Sascha , Schlecker Christina , Moschetti Viktoria , Goetz Sophia , Liesenfeld Karl‐Heinz , Fillon Gwenaelle , Giovannini Riccardo , Ramael Steven , Wunderlich Glen , Wind Sven
Published: August 2018

BI 425809 is a potent and selective glycine transporter 1 (GlyT1) inhibitor being developed for the treatment of cognitive impairment in Alzheimer disease and schizophrenia. Translational studies evaluated the effects of BI 425809 on glycine levels in rat and human cerebrospinal fluid (CSF). Oral administration of BI 425809 in rats induced a dose‐dependent increase of glycine CSF levels from 30% (0.2 mg/kg, not significant) to 78% (2 mg/kg, P < 0.01), relative to vehicle. Similarly, oral administration of BI 425809 in healthy volunteers resulted in a dose‐dependent increase in glycine CSF levels at steady state, with a mean 50% increase at doses as low as 10 mg. The peak plasma concentration (Cmax) of BI 425809 was achieved earlier in plasma than in CSF (tmax 3–5 vs. 5–8 hours, respectively). Generally, BI 425809 was safe and well tolerated. These data provide evidence of functional target engagement of GlyT1 by BI 425809.
25 Years of Real Option Empirical Research in Management
Authors: Ipsmiller Edith , Brouthers Keith D. , Dikova Desislava
Published: August 2018

For several decades, management scholars have extolled the virtues of using real option logic when making decisions under uncertainty. Real option logic suggests that in such situations, firms might be better off deferring or staging investments, reducing potential financial losses, while at the same time securing an option to grow (or abandon) the investment when uncertainty abates. Our analysis of the empirical research published in leading management journals over the past 25 years suggests that while some progress has been made, much more work needs to be done. We still do not have the answers to critical questions such as: Which entrepreneurial/managerial traits impact the identification or exploitation of real options? Do multiple types of uncertainties interact with each other and influence real option decisions? Addressing these and other issues identified in our study can help improve our understanding of the usefulness of real option logic in management.
Gelatin as a convenient surrogate protein to model the in vitro effects of advanced glycation end‐product formation
Authors: Pringle Nadine A. , van de Venter Maryna , Koekemoer Trevor C.
Published: August 2018

Protein glycation has been implicated in skin ageing and several other disease states; however, the slow rate of glycation end‐product formation makes in vitro studies challenging and often impractical. Gelatin, a denatured form of collagen, was identified as a convenient glycation surrogate amenable to cell culture conditions. The suitability of glycated gelatin to model the effects of AGE formation was verified using RAW 264.7 macrophages which revealed a remarkable correlation to previously documented effects. Effects of glycated gelatin on the central role of NF‐ĸB and its downstream consequences (COX‐2 and CD86) confirmed the pro‐inflammatory nature of advanced glycation end‐products. Together, these findings provide confidence that this model could prove a valuable tool to study the poorly understood mechanisms characterizing cellular dysfunction in response to AGE accumulation.
Headache Characteristics in Children With Pseudotumor Cerebri Syndrome, Elevated Opening Pressure Without Papilledema, and Normal Opening Pressure: A Retrospective Cohort Study
Authors: Hamedani Ali G. , Witonsky Kailyn F.R. , Cosico Mahgenn , Rennie Robert , Xiao Riu , Sheldon Claire A. , Paley Grace L. , McCormack Shana E. , Liu Geraldine W. , Friedman Deborah I. , Liu Grant T. , Szperka Christina L.
Published: August 2018

Background

Certain headache characteristics and associated symptoms are commonly attributed to increased intracranial pressure, but they have not been systematically studied among children in the context of revised diagnostic criteria for pseudotumor cerebri syndrome (PTCS).

Methods

We performed a retrospective cohort study of patients treated for suspected or confirmed PTCS. Charts were reviewed for PTCS and headache diagnostic criteria and associated characteristics. Chi‐squared or Fisher’s exact tests were used to compare the frequency of headache characteristics between groups.

Results

One hundred and twenty‐seven individuals were identified: 61 had definite PTCS, 10 had probable PTCS, 31 had elevated opening pressure (OP) without papilledema, and 25 had normal OP without papilledema. Eleven children had no headache (6 with definite PTCS, 5 with probable PTCS). Headache pattern was episodic in 49% (95% CI: 34–64%) of those with definite PTCS, 18% (95% CI 6–37%) of those with elevated OP without papilledema, and 16% (5–36%) of those with normal OP without papilledema. Headache location was more likely to involve the head along with neck or shoulders in those with definite PTCS compared with elevated OP without papilledema (OR = 7.2, 95% CI: 1.9–27.6) and normal OP (OR = 4.5, 95% CI: 1.3–15.6) groups.

Discussion

While missing data and small cohort size are limitations, this study suggests that headache in PTCS is more likely to involve the head along with neck/shoulders, and that headache in PTCS may be episodic or constant. Headache is occasionally absent in PTCS.
TESTING THE QUANTAL RESPONSE HYPOTHESIS
Authors: Melo Emerson , Pogorelskiy Kirill , Shum Matthew
Published: August 2018

We develop a nonparametric test for consistency of player behavior with the quantal response equilibrium (QRE). The test exploits a characterization of the equilibrium choice probabilities in any structural QRE as the gradient of a convex function; thereby, QRE‐consistent choices satisfy the cyclic monotonicity inequalities. Our testing procedure utilizes recent econometric results for moment inequality models. We assess our test using lab experimental data from a series of generalized matching pennies games. We reject the QRE hypothesis in the pooled data but cannot reject individual‐level quantal response behavior for over half of the subjects.
Incidence and risk of vaginal candidiasis associated with sodium–glucose cotransporter 2 inhibitors in real‐world practice for women with type 2 diabetes
Authors: Yokoyama Hiroki , Nagao Ami , Watanabe Sanae , Honjo Jun
Published: August 2018

Aims/Introduction

The prevalence and risk of vaginal candidiasis before and after initiating sodium–glucose cotransporter 2 (SGLT2) inhibitors, although some clinical trials have been carried out, have not been adequately shown in real‐world practice. We investigated the incidence of vaginal Candida colonization and symptomatic vaginitis, and the clinical risk factors including diabetic microvascular complications.

Materials and Methods

The participants were 114 women with type 2 diabetes who were free of vaginitis symptoms and started SGLT2 inhibitors. Vaginal candidiasis tests through self‐administered swabs were carried out at baseline, 6 and 12 months.

Results

Before starting SGLT2 inhibitors, 17 participants (14.9%) had positive vaginal Candida colonization. Younger age and the presence of microangiopathy were significantly associated with the positive colonization in multivariate analysis. Among all participants, 23 (20.2%, 8 because of vaginitis and 15 for other reasons) discontinued SGLT2 inhibitors before reaching the 6‐month test. Of 65 participants who were negative for Candida at baseline and received the 6‐month test, 24 (36.9%) converted to a positive culture, and multivariate analysis showed older age as an independent risk for developing Candida colonization. There were 18 participants (15.8%) who developed symptomatic vaginitis, and they showed similar characteristics to the 24 participants. Most of those with negative cultures at 6 months showed negative results at 12 months and vice versa.

Conclusions

The rates of developing positive colonization and symptomatic vaginitis after starting SGLT2 inhibitors appear to be higher in real‐world practice than the rates of 31% and 5–10% in clinical trials, respectively. Risk factors of vaginal Candida colonization might be different before and after taking SGLT2 inhibitors.
Using the SSU, ITS, and Ribosomal DNA Operon Arrangement to Characterize Two Microsporidia Infecting Bruce Spanworm, Operophtera bruceata (Lepidoptera: Geometridae)
Authors: Donahue Katelyn L. , Broadley Hannah J. , Elkinton Joseph S. , Burand John P. , Huang Wei‐Fone , Andersen Jeremy C.
Published: August 2018

Research pertaining to the two closely‐related microsporidian genera Nosema and Vairimorpha is hindered by inconsistencies in species differentiation within and between the two clades. One proposal to better delimit these genera is to restructure the Nosema around a “True Nosema” clade, consisting of species that share a characteristic reversed ribosomal DNA operon arrangement and small subunit (SSU) ribosomal DNA sequences similar to that of the Nosema type species, N. bombycis. Using this framework, we assess two distinct microsporidia recovered from the forest insect Bruce spanworm (Operophtera bruceata) by sequencing their SSU and internal transcribed spacer regions. Phylogenetic analyses place one of our isolates within the proposed True Nosema clade close to N. furnacalis and place the other in the broader Nosema/Vairimorpha clade close to N. thomsoni. We found that 25% of Bruce spanworm cadavers collected over the four‐year study period were infected with microsporidia, but no infections were detected in cadavers of the Bruce spanworm's invasive congener, the winter moth (O. brumata), collected over the same period. We comment on these findings as they relate to the population dynamics of the Bruce spanworm‐winter moth system in this region, and more broadly, on the value of ribosomal DNA operon arrangement in Nosema systematics.
Integrated Memory Care Clinic: Design, Implementation, and Initial Results
Authors: Clevenger Carolyn K. , Cellar Janet , Kovaleva Mariya , Medders Laura , Hepburn Kenneth
Published: August 2018

The Integrated Memory Care Clinic (IMCC) is a patient‐centered medical home as defined by the National Committee for Quality Assurance directed by advanced practice registered nurses (APRNs) caring for persons living with dementia (PLWD); physicians provide specialty consultation but do not direct care or care planning. The IMCC incorporates geriatric nursing, social work, and APRNs from neurology, gerontology, palliative care, and geriatric psychiatry. APRNs provide comprehensive, coordinated primary care for dementia, other chronic conditions, and minor acute illnesses. Partnering with PLWD and families and taking a palliative‐oriented, dementia‐informed medical home approach, the IMCC aims to reduce dementia burden. This study describes the first 12 months of IMCC's operation with 139 enrolled PLWD‐caregiver dyads. All patients have a diagnosis of dementia or mild cognitive impairment; most have Alzheimer's disease (53.2%). Patients have an average of 5.8 medical conditions and 6.9 prescriptions; 38.1% have an advanced directive, a medical power of attorney, or a living will. Mean age is 78.6, 63.3% are female, and 30.9% are African American. Mean Montreal Cognitive Assessment score is 12.6. Most require assistance in activities of daily living. Many display neuropsychiatric symptoms. The most prevalent comorbidities are hypertension, dyslipidemia, and depression. The rate of ambulatory‐sensitive hospitalizations declined from 6.7% in December 2015 to less than 1% in May 2016. Caregivers were highly satisfied. We observed nonsignificant improvements in neuropsychiatric symptom severity (p=.07), caregiver distress (p=.69), and caregiver competence (p=.18). IMCC is a novel care model for PLWD and their caregivers and may be a more sustainable model than traditional primary care for this growing vulnerable population. J Am Geriatr Soc 66:2401–2407, 2018.