bluuebunny/crossref_metadata_2025 huggingface dataset:
Recombination between co-infecting herpesviruses occurs where replication compartments coalesce
Authors: Tomer Enosh , Cohen Efrat M. , Drayman Nir , Afriat Amichay , Weitzman Matthew D. , Zaritsky Assaf , Kobiler Oren
Published: June 2018

Homologous recombination (HR) is considered a major driving force of evolution since it generates and expands genetic diversity. Evidence of HR between co-infecting herpesvirus DNA genomes can be found frequently, bothin vitroand in clinical isolates. Each herpes simplex virus type 1 (HSV-1) replication compartment (RC) derives from a single incoming genome and maintains a specific territory within the nucleus. This raises intriguing questions about where and when co-infecting viral genomes interact. To study the spatiotemporal requirements for inter-genomic recombination, we developed an assay with dual-color fluorescencein situhybridization which enables detection of HR between different pairs of co-infecting HSV-1 genomes. Our results revealed that when viral RCs enlarge towards each other, there is detectable overlap between territories of genomes from each virus. Infection with paired viruses that allow visualization of HR correlates with increased overlap of RCs. Further, inhibition of RC movement reduces the rate of HR events among co-infecting viruses. Taken together, these findings suggest that inter-genomic HR events take place during replication of HSV-1 DNA and are mainly confined to the periphery of RCs when they coalesce. Our observations have implications on understanding the recombination restrictions of other DNA viruses and cellular DNA.
N1 component of event-related potential evoked by simple composite figures in the lateral occipital cortex
Authors: Uchiyama Hiroyuki , Iwashita Shoichi , Mitsui Takashi
Published: June 2018

Since Sugawara and Morotomi (1991) first reported that illusory contour (IC) figures, or Kanizsa square inducers (KSI), evoked a significant N1 component, the first visually evoked negative component of event-related potentials (ERPs), in the lateral occipital cortex (LO), many ERP studies have confirmed their finding, and these studies showed that Kanizsa-type inducers alone evoked a relatively large N1 in the LO, even when the inducers are oriented to not form an IC (see Murray and Herrmann, 2013). In the present study, we used non-IC simple composite figures composed of several elementary shapes (e.g., triplet squares or quadruplet circles) as visual stimuli, and found that the composite figures evoked a significant N1 comparable to that evoked by KSI in the anterior LO, whereas solitary elementary shapes did not. Thus, it appears that the LO is activated by not only an IC but also the compositeness of figures, which implies that the LO might analyze the geometrical relationships among multiple 2D shapes that compose a single composite figure.
Single cell functional genomics reveals the importance of mitochondria in cell-to-cell variation in proliferation, drug resistance and mutation outcome
Authors: Dhar Riddhiman , Missarova Alsu M , Lehner Ben , Carey Lucas B
Published: June 2018

Mutations frequently have outcomes that differ across individuals, even when these individuals are genetically identical and share a common environment. Moreover, individual microbial and mammalian cells can vary substantially in their proliferation rates, stress tolerance, and drug resistance, with important implications for the treatment of infections and cancer. To investigate the causes of cell-to-cell variation in proliferation, we developed a high-throughput automated microscopy assay and used it to quantify the impact of deleting >1,500 genes in yeast. Mutations affecting mitochondria were particularly variable in their outcome. In both mutant and wild-type cells mitochondria state – but not content – varied substantially across individual cells and predicted cell-to-cell variation in proliferation, mutation outcome, stress tolerance, and resistance to a clinically used anti-fungal drug. These results suggest an important role for cell-to-cell variation in the state of an organelle in single cell phenotypic variation.
Glucose signaling is important for nutrient adaptation during differentiation of pleomorphic African trypanosomes
Authors: Qiu Yijian , Milanes Jillian E. , Jones Jessica A. , Noorai Rooksana E. , Shankar Vijay , Morris James C.
Published: June 2018

The African trypanosome has evolved mechanisms to adapt to changes in nutrient availability that occur during its lifecycle. During transition from mammalian blood to insect vector gut, parasites experience a rapid reduction in environmental glucose. Here we describe how pleomorphic parasites respond to glucose depletion with a focus on parasite changes in energy metabolism and growth. Long slender bloodstream form parasites are rapidly killed as glucose concentrations fall, while the short stumpy bloodstream form parasites persist to differentiate into the insect stage procyclic form parasite. The rate of differentiation was slower than that triggered by other cues but reached physiological rates when combined with cold shock. Both differentiation and growth of resulting procyclic form parasites were inhibited by glucose and its non-metabolizable analogs in a concentration dependent manner. Procyclic form parasites differentiated from short stumpy form parasites in glucose depleted medium significantly upregulated gene expression of amino acid metabolic pathway components when compared to procyclic forms generated by cis-aconitate treatment. Additionally, growth of these parasite was inhibited by the presence of either glucose or 6-deoxyglucose. In summary, glucose transitions from the primary metabolite of the blood stage infection to a negative regulator of cell development and growth in the insect vector, suggesting that the hexose is not only a key metabolic agent but is also an important signaling molecule.

Author Summary

As the African trypanosome, Trypanosoma brucei, completes its lifecycle, it encounters many different environments. Adaptation to these environments includes modulation of metabolic pathways to parallel the availability of nutrients. Here, we describe how the blood-dwelling lifecycle stages of the African trypanosome, which consume glucose to meet their nutritional needs, respond differently to culture in the near absence of glucose. The proliferative long slender parasites rapidly die, while the non-dividing short stumpy remains viable and undergoes differentiation to the next lifecycle stage, the procyclic form parasite. Interestingly a sugar analog that cannot be used as an energy source inhibited the process. Furthermore, the growth of procyclic form parasite that resulted from the event was inhibited by glucose, a behavior that is similar to that of parasites isolated from tsetse flies. Our findings suggest that glucose sensing serves as an important modulator of nutrient adaptation in the parasite.
Sensitive periods for white matter plasticity and reading intervention
Authors: Yeatman Jason D. , Huber Elizabeth
Published: June 2018

As a child matures, some brain circuits stabilize while others remain plastic. However, the literature on maturational changes in the brain’s capacity for experience-dependent plasticity is primarily based on experiments in animals that mature over dramatically different time-scales than humans. Moreover, while principles of plasticity for sensory and motor systems might be conserved across species, the myriad of late-developing and uniquely human cognitive functions such as literacy cannot be studied with animal models. Here we use an intensive reading intervention program, in combination with longitudinal diffusion MRI measurements in school-aged children with dyslexia, to investigate the sensitive period for white matter plasticity and literacy learning. We find that the intervention induces large-scale changes in white matter diffusion properties, and improvements in reading scores, but that the magnitude and time-course of plasticity does not depend on the subject’s age. Thus, we conclude that, for the intensive, one-on-one reading intervention program employed here, if a sensitive period exists, it does not end before middle school.
Mapping the ligand binding landscape
Authors: Dickson Alex
Published: June 2018

The interaction between a ligand and a protein involves a multitude of conformational states. To achieve a particular deeply-bound pose the ligand must search across a rough free energy landscape, with many metastable minima. Creating maps of the ligand binding landscape is a great challenge, as binding and release events typically occur on timescales that are beyond the reach of molecular simulation. The WExplore enhanced sampling method is well-suited to build these maps, as it is designed to broadly explore free-energy landscapes, and is capable of simulating ligand release pathways that occur on timescales as long as minutes. WExplore also uses only unbiased trajectory segments, allowing for the construction of Markov state models (MSM) and conformation space networks that combine the results of multiple simulations. Here we use WExplore to study two bromodomain-inhibitor systems using multiple docked starting poses (Brd4-MS436 and Baz2B-ICR7), and synthesize our results using a series of MSMs using time-lagged independent component analysis. Ranking the starting poses by exit rate agrees with the crystal structure pose in both cases. We also predict the most stable pose using the equilibrium populations from the MSM, but find that the prediction is not robust as a function of MSM parameters. The simulated trajectories are synthesized into network models that visualize the entire binding landscape for each system, and we examine transition paths between deeply-bound stable states. We find that, on average, transitions between deeply bound states convert through the unbound state 81% of the time, implying a trial-and-error approach to ligand binding. We conclude with a discussion of the implications of this result for both kinetics-based drug discovery and virtual screening pipelines that incorporate molecular dynamics.
Resilience of Atlantic Slippersnail Crepidula fornicata Larvae in the Face of Severe Coastal Acidification
Authors: Kriefall Nicola G. , Pechenik Jan A. , Pires Anthony , Davies Sarah W.
Published: June 2018

Globally, average oceanic pH is dropping, and it will continue to decline into the foreseeable future. This ocean acidification (OA) will exacerbate the natural fluctuations in pH that nearshore ecosystems currently experience daily, potentially pushing marine organisms to their physiological limits. Adults of Crepidula fornicata (the Atlantic slippersnail) have proven remarkably resilient to many environmental changes, which is perhaps not surprising considering that they are common intertidally, have a geographically large native range, and have been extremely successful at invading coastal water in many other parts of the world. However, the larvae of C. fornicata have been shown to be somewhat more vulnerable than adults to the effects of reduced pH. Research to date has focused on the physiological impacts of OA on C. fornicata larvae; few studies have explored shifts in gene expression resulting from changes in pH. In the present study, we examined the response of young (4- day old) C. fornicata larvae to two extreme OA treatments (pH 7.5 and 7.6) relative to pH 8.0, documenting both phenotypic and genome-wide gene expression responses. We found that rearing larvae at reduced pH had subtle influences on gene expression, predominantly involving downregulation of genes related to growth and metabolism, accompanied by significantly reduced shell growth rates only for larvae reared at pH 7.5. Additionally, 10-day old larvae that had been reared at the two lower pH levels were far less likely to metamorphose within six hours when exposed to inducer. However, all larvae eventually reached similarly high levels of metamorphosis 24 hours after settlement induction. Finally, there were no observed impacts of OA on larval mortality. Taken together, our results indicate that far future OA levels have observable, but not severe, impacts on C. fornicata larvae, which is consistent with the resilience of this invasive snail across rapidly changing nearshore ecosystems. We propose that future work should delve further into the physiological and transcriptomic responses of all life history stages to gain a more comprehensive understanding of how OA impacts the intertidal gastropod C. fornicata.
A combinatorial extracellular code tunes the intracellular signaling network activity to distinct cellular responses
Authors: Kuchenov Dmitry , Ziebell Frederik , Salopiata Florian , Citir Mevlut , Klingmueller Ursula , Huber Wolfgang , Schultz Carsten
Published: June 2018

Cells constantly survey a complex set of inputs that is processed by the intracellular signaling network, but little is known of how cells integrate input information from more than one cue. We employed a FRET biosensor-based imaging platform to study the effect of combinatorial growth factor levels on the signaling network in human cells. We found that pairwise stimuli caused distinct concentration- and ratio-dependent signaling states through signaling signatures such as antagonism, additivity and synergy. The unique signaling states correlated with differential gene expression and non-additive transcription patterns. We further elucidated how a signal-rich environment can fine-tune the signaling network and adjust physiological outcomes, by kinase and phosphatase activity profiling. We describe how complex extracellular conditions affect phospho-turnover and the basal phosphorylation status. Thus, we provide mechanistic insights into cellular processing of multiple cues and explain part of the complexity of cellular adaptation to changes in the extracellular environment.
Evaluating predictive biomarkers for a binary outcome with linear versus logistic regression – Practical recommendations for the choice of the model
Authors: Gola Damian , Heßler Nicole , Schwaninger Markus , Ziegler Andreas , König Inke R.
Published: June 2018

A predictive biomarker can forecast whether a patient benefits from a specific treatment under study. To establish predictiveness of a biomarker, a statistical interaction between the biomarker status and the treatment group concerning the clinical outcome needs to be shown. In clinical trials looking at a binary outcome, linear or logistic regression models may be used to evaluate the interaction, but the effects in the two models are different and differently interpreted. Specifically, the effects are estimated as absolute risk reductions (ARRs) and odds ratios (ORs) in the linear and logistic model, thus measuring the effect on an additive and multiplicative scale, respectively.

We derived the relationship between the effects of the linear and the logistic regression model allowing for translations between the effect estimates between both models. In addition, we performed a comprehensive simulation study to compare the power of the two models under a variety of scenarios in different study designs. In general, the differences in power to detect interaction were minor, and visible differences were detected in rather unrealistic scenarios of effect size combinations and were usually in favor of the logistic model.

Based on our results and theoretical considerations, we recommend to 1) estimate logistic regression models because of their statistical properties, 2) test for interaction effects and 3) calculate and report both ARRs and ORs from these using the formulae provided.
Measures of Possible Allostatic Load in Comorbid Cocaine and Alcohol Use Disorder: Brain White Matter Integrity, Telomere Length, and Anti-Saccade Performance
Authors: Tannous Jonika , Mwangi Benson , Hasan Khader M. , Narayana Ponnada A. , Steinberg Joel L. , Walss-Bass Consuelo , Moeller F. Gerard , Schmitz Joy M. , Lane Scott D.
Published: June 2018

Chronic cocaine and alcohol use impart significant stress on biological and cognitive systems, resulting in changes consistent with an allostatic load model of neurocognitive impairment. The present study measured potential markers of allostatic load in individuals with comorbid cocaine/alcohol use disorders (CUD/AUD) and control subjects. Measures of brain white matter (WM) integrity, telomere length, and impulsivity/attentional bias were obtained. WM integrity (CUD/AUD only) was indexed by diffusion tensor imaging metrics, including radial diffusivity (RD) and fractional anisotropy (FA). Telomere length was indexed by T/S ratio. Impulsivity and attentional bias to drug cues were measured via eye-tracking, and were also modeled using the Hierarchical Diffusion Drift Model (HDDM). Average whole-brain RD and FA were associated with years of cocaine use (R2= 0.56 and 0.51, both p < .005) but not years of alcohol use. CUD/AUD subjects showed more anti-saccade errors (p < .01), greater attentional bias scores (p < .001), and higher HDDM drift rates on cocaine-cue trials (Bayesian probability CUD/AUD > control = p > 0.99). Telomere length was shorter in CUD/AUD, but the difference was not statistically significant. Within the CUD/AUD group, exploratory regression using an elastic-net model determined that more years of cocaine use, older age, larger HDDM drift rate differences and shorter telomere length were all predictive of white matter integrity as measured by RD (model R2= 0.79). Collectively, the results provide modest support linking CUD/AUD to putative markers of allostatic load.
TIAM-1/GEF can shape somatosensory dendrites independently of its GEF activity by regulating F-actin localization
Authors: Tang Leo T.H. , Díaz-Balzac Carlos A. , Rahman Maisha , Ramirez-Suarez Nelson J. , Salzberg Yehuda , Lázaro-Peñal María I. , Bülow Hannes E.
Published: June 2018

Development of dendritic arbors is crucial for nervous system assembly, but the intracellular mechanisms that govern these processes remain incompletely understood. Here we show that the complex dendritic trees of PVD somatosensory neurons inCaenorhabditis elegansare patterned by distinct pathways downstream of the DMA-1 leucine rich transmembrane (LRR-TM) receptor. The guanine nucleotide exchange factortiam-1/GEFandact-4/Actinfunction with the DMA-1/LRR-TM to pattern 4° higher order branches by localizing F-actin to the distal ends of developing dendrites. Biochemical experiments show that DMA-1/LRR-TM is part of a biochemical complex with TIAM-1/GEF and ACT-4/Actin. Surprisingly, TIAM-1/GEF appears to function independently of Rac1 guanine nucleotide exchange factor activity. Additionally, another pathway dependent on HPO-30/Claudin and TIAM-1/GEF is required for formation of 2° and 3° branches. Collectively, our experiments suggest that the DMA-1/LRR-TM receptor on PVD dendrites may control aspects of dendrite patterning by directly modulating F-actin dynamics, independently of TIAM-1/GEF enzymatic activity.
EPIGEN-Brazil Initiative resources: a Latin American imputation panel and the Scientific Workflow
Authors: Magalhães Wagner C.S. , Araujo Nathalia M. , Leal Thiago P. , Araujo Gilderlanio S. , Viriato Paula J.S. , Kehdy Fernanda S. , Costa Gustavo N. , Barreto Mauricio L. , Horta Bernardo L. , Lima-Costa Maria Fernanda , Pereira Alexandre C. , Tarazona-Santos Eduardo , Rodrigues Maíra R. ,   The Brazilian EPIGEN Consortium
Published: June 2018

EPIGEN-Brazil is one of the largest Latin American initiatives at the interface of human genomics, public health, and computational biology. Here, we present two resources to address two challenges to the global dissemination of precision medicine and the development of the bioinformatics know-how to support it. To address the underrepresentation of non-European individuals in human genome diversity studies, we present the EPIGEN-5M+1KGP imputation panel—the fusion of the public 1000 Genomes Project (1KGP) Phase 3 imputation panel with haplotypes derived from the EPIGEN-5M data set (a product of the genotyping of 4.3 million SNPs in 265 admixed individuals from the EPIGEN-Brazil Initiative). When we imputed a target SNPs data set (6487 admixed individuals genotyped for 2.2 million SNPs from the EPIGEN-Brazil project) with the EPIGEN-5M+1KGP panel, we gained 140,452 more SNPs in total than when using the 1KGP Phase 3 panel alone and 788,873 additional high confidence SNPs (info score ≥ 0.8). Thus, the major effect of the inclusion of the EPIGEN-5M data set in this new imputation panel is not only to gain more SNPs but also to improve the quality of imputation. To address the lack of transparency and reproducibility of bioinformatics protocols, we present a conceptual Scientific Workflow in the form of a website that models the scientific process (by including publications, flowcharts, masterscripts, documents, and bioinformatics protocols), making it accessible and interactive. Its applicability is shown in the context of the development of our EPIGEN-5M+1KGP imputation panel. The Scientific Workflow also serves as a repository of bioinformatics resources.
Investor relations – a systematic literature review
Authors: Hoffmann Christian Pieter , Tietz Sandra , Hammann Kerstin
Published: June 2018

Purpose

The purpose of this paper is to present a comprehensive, interdisciplinary review of international investor relations (IR) research published since 1990. It highlights the development of IR research, its disciplinary foundations and key areas of inquiry. Research is shown to reflect the rising importance of IR as a corporate communications function, its interdisciplinary character, and the recognition of its contribution to strategic management.

Design/methodology/approach

Findings are based on an interdisciplinary systematic literature review focusing on peer-reviewed journal articles published in English since 1990.

Findings

The authors differentiate five strands of research focusing on the organization, strategy, instruments, content and effects of IR. IR research is shown to have strong roots in the business and management, accounting and communications literature. The authors document a rising interest in the topic and a steady development beyond descriptive accounts of the function to distinctive lines of inquiry. The authors summarize the state of the field and derive a number of suggestions for future research.

Research limitations/implications

The review is limited in scope to the applied research process, including the choice of keywords, databases as well as peer-reviewed journal publications published in English since 1990.

Originality/value

This study contributes to the necessary structuration and consolidation of the emergent field of IR research by identify salient perspectives and common subfields. It provides both a comprehensive overview of the state of research and specific suggestions for future endeavors.
The significance of further education for black males
Authors: Peart Sheine
Published: June 2018

Purpose

The purpose of this paper is to explore the lived educational realities of black male students studying in further education (FE) colleges to understand how these experiences compare to their experiences of statutory education. It describes the way in which students perceived and received education in both sectors and highlights the similarities and variations between the two.

Design/methodology/approach

Ethnographic methods including focus groups, individual interviews and naturalistic observations were used to investigate black male students’ perceptions of FE. These accounts were compared to their memories of compulsory schooling experiences to establish differences and similarities between sectors and to determine which educational approaches black male students identified as most useful.

Findings

The research established black males perceived there were significant differences between the two sectors and these differences had impacted on their ability to learn. These findings provide a useful reference point for educators seeking to evaluate their organisation’s education provision for black male students.

Social implications

This paper provides suggestions on what sorts of educational opportunities are appropriate and accessible for black males and which approaches help to support their educational achievement.

Originality/value

There are little research data which specifically discuss black male students’ experience of the FE sector. This paper will help teachers and managers at all organisational levels in FE (and in schools) review their provision and consider adopting approaches that may help to enhance black students’ educational journeys.
Towards a well-functioning stock market in context
Authors: Haslam Jim , Ji Jiao , Sun Hanwen
Published: June 2018

Purpose

The purpose of this paper is to summarise and reflect upon key issues at the interface of prices, information and regulation with a focus upon the stock market in context. Reflecting upon academic research in the area of efficient markets, and regulatory policy, the concern is to discern issues in terms of policy and support for policy. What does the research imply for policy? Is it possible that the research, perhaps given its rhetoric, can be misinterpreted in relation to policy? The study is also concerned to develop avenues for future research based on these considerations.

Design/methodology/approach

The paper is an analytical and critical review and writing.

Findings

The reading of the research suggests a pragmatic regulatory policy that should be concerned to improve stock market functioning, including with respect to information, as well as the context of which this is part. At the same time, the literature may be read as promoting anti-regulatory policy.

Practical implications

On the one hand, these are consistent with the pragmatic policy referred to above. On the other hand, further research is suggested to explore substantively the rhetoric of the research and its interpretation and to explore understandings of the research and its implications amongst key constituencies in practice.

Originality/value

The concern is to bring key insights from the academic literature together with a view to promoting a pragmatic policy orientation, while cautioning in a critical perspective about how this academic literature and research might be interpreted from a policy perspective.
Audit fees via an indirect payment channel and professional skepticism
Authors: Kim Sanghun , Kim Taewoo , Pae Sujin , Kim Sangphill
Published: June 2018

Purpose

This paper aims to examine the merit of an indirect payment system for audit fees, a system where an intermediary collects fees from the auditee and then pays this audit fee to the auditor.

Design/methodology/approach

Big 4 auditors and professional analysts in South Korea participated in an experiment and survey to investigate whether the change in the payment channel (from direct to indirect) of audit fees positively impacts auditors’ decision-making.

Findings

The authors find evidence that the indirect payment of audit fees is positively associated with professional skepticism.

Research limitations/implications

This paper, by highlighting the potential for alternate auditor payment channels to improve the quality of auditor judgments, motivates future research in this area.

Practical implications

Qualified by the need for further research, the potential merit in an indirect payment system may have implications for audit regulators.

Social implications

An indirect payment channel has the potential to improve public perceptions of the audit function, thereby elevating society’s confidence in auditor opinions and improving the effectiveness and efficiency with which scarce resources are distributed within society.

Originality/value

This study is one of the first that looks into a systematic change in audit fee payment channel and how an indirect payment system of audit fees impacts professional skepticism.
Impact of CSR on learning outcomes
Authors: Sinha Shiv Nath , Chaudhari Tushar
Published: June 2018

Purpose

The purpose of this paper is to examine the impact of CSR initiative of ITC Limited on the stakeholders especially impact on the learning outcome of primary school students. The research further attempts to discover the level of impact of CSR on learning outcomes.

Design/methodology/approach

The data were collected from the rural areas of Pune in the state of Maharashtra and Mysuru in the state of Karnataka in India. The total number of data collected was 227. The data were collected with the help of self-administered questionnaires via personal visits to the schools using systematic random sampling method. Parametric test,t-test is used to test research hypothesis. Multiple linear regression analysis is performed to identify which aspects have better contribution towards overall impact level of the CSR program.

Findings

The study results clearly underscore the impact of firm’s CSR activities on the stakeholders. The study findings suggest a significant impact of CSR on the stakeholder, primarily on the learning outcome of the primary school students.

Practical implications

The study offers a new insight for the CSR heads of companies who are planning and implementing CSR initiatives of companies for widespread impact on the stakeholders. This study addresses the concerns of business managers and CSR heads to prove the potential of CSR initiatives and the measurement of the value generated for the society through CSR interventions.

Originality/value

The previously conducted research works have explored the impact of CSR on financial performance, organizational stability, employee turnover, customer retention, etc. This study advances existing body of knowledge beyond developed western economies by exploring the value of CSR in India and its impact on the stakeholders. This study finds the impact of CSR initiative on learning outcome. The study makes a novel contribution by not only determining the impact of CSR on learning outcome but also by going a step further to unfurl the various underlying factors which contribute towards the overall impact.
Development of a custom zygomatic implant using metal sintering
Authors: Meena Vijay Kumar , Gagandeep Gagandeep , Aneesh Aneesh , Rattan Vidya , Luthra Gaurav , Kalra Parveen
Published: June 2018

Purpose

The purpose of this paper is to design and development of a patient-specific implant for zygomatic area of a patient suffering from mucormycosis (fungal infection). The paper describes how integration of computer-aided design (CAD) and 3D printing can be successfully used for developing custom implants for the sites for which readymade optimal solutions are not available.

Design/methodology/approach

The CT scan data of the patient were used for the generation of a 3D model. The healthy side of skull was mirrored and copied on the infected part, which served as a base for designing the implant. The prototype of the implant was printed using fused deposition modelling before finally printing in Ti6Al4V alloy using direct metal laser sintering process.

Findings

The custom designed implant fitted well to the patient’s skull during surgery. Proper facial aesthetics were maintained post-surgery.

Originality/value

The work describes the application of CAD-based image processing software and additive manufacturing in the development of a custom implant for the sites for which no readymade optimal solution is available.
A new method for single-layer-part nesting in additive manufacturing
Authors: Zhang Yicha , Bernard Alain , Harik Ramy , Fadel Georges
Published: June 2018

Purpose

This paper aims to introduce a new nesting scheme to better describe and solve the single-layer-part packing problem in additive manufacturing (AM).

Design/methodology/approach

Parallel nesting scheme using two-dimensional (2D) changeable projection profiles is developed. At first, a feature-based orientation optimization method is used to identify a set of practical alternative build orientations for each part to ensure the part quality. Then, 2D polygons are used to represent each part’s projection profiles under its alternative build orientations. Finally, a parallel layout searching algorithm is developed to identify the optimal part layout by using 2D changeable projection profiles.

Findings

The proposed nesting scheme can both guarantee the production quality for each part and search the optimal part layout with larger probability but less computational time.

Originality/value

With the use of changeable 2D projection profiles, this method conducts 2D computation to solve the single-layer-part packing problem with five degrees of freedom, which saves much computation cost and, at the same time, guarantees the production quality of each part. By adding specific nesting objectives or constraints and heuristic searching knowledge to the proposed nesting scheme, practical nesting software can be developed to meet the specific nesting or packing requirements for industrial AM machines.
Smart destinations and tech-savvy millennial tourists: hype versus reality
Authors: Femenia-Serra Francisco , Perles-Ribes José F. , Ivars-Baidal Josep A.
Published: June 2018

Purpose

This paper aims to contrast the expectations placed on the smart destination as a theoretical management approach with the reality of emergent tech-savvy tourism demand by examining the response of this segment to three critical dimensions of technology use in the context of smart destinations. Tech-savvy tourists are here represented by highly educated Spanish millennial tourists.

Design/methodology/approach

Data were obtained through an online survey and analysed through descriptive techniques and exploratory factor analysis using SPSS. Literature review was critical for setting the foundations of the research in this novel context.

Findings

Results suggest the existence of a gap between the smart destination theoretical expectations and created hype and the real response of the examined demand in the three main scopes for this tourist-smart destination technology-based relationship, namely, mobile technology use, data sharing for personalised experiences and smart technologies for enhanced experiences.

Research limitations/implications

Convenience sampling was used, and the results of the study cannot be generalised to all millennial tourists. The research is a first approximation to the interrelationship between tourists and smart destinations.

Practical/implications

Tourists’ role and experiences mediated by information and communication technologies (ICTs) are decisive in smart destinations. Destination Management Organisations (DMOs), through their policies and actions, ought to take into account the limited predisposition of tourists in using mobile devices, sharing data and using smart technologies for their experiences. Privacy concerns appear to have special relevance for tourists and, therefore, for the future of smart destinations.

Originality/value

The findings offer relevant insights for smart destinations from a neglected angle hitherto, as they introduce several interesting nuances which do not match entirely the fast track taken by institutions, media and academia. This is critical for better understanding tourists in the current panorama, for DMOs and for the theoretical foundations of smart tourism. Besides, the exploratory data analysis reveals potential dimensions of millennials’ behaviour, which can be useful for further investigations.
Contribution of peroxisomal docking machinery to mycotoxin biosynthesis, pathogenicity and pexophagy in the plant pathogenic fungus Fusarium graminearum
Authors: Chen Yun , Zheng Shiyu , Ju Zhenzhen , Zhang Chengqi , Tang Guangfei , Wang Jing , Wen Ziyue , Chen Wei , Ma Zhonghua
Published: June 2018

Peroxisomal proliferation is highly stimulated during the biosynthesis of mycotoxins and plant infection by Fusarium graminearum. Currently, the functions of the peroxisome in these cellular processes are poorly understood. In this study, we applied genetic, cell biological and biochemical analyses to investigate the functions of the peroxisomes. We constructed targeted deletion of docking machinery components, including FgPex13, FgPex14 and the filamentous fungal specific peroxin FgPex33. Our results indicated that peroxisome dysfunction resulted in a shortage of acetyl‐CoA, the precursor of trichothecene biosynthesis, and subsequently decreased deoxynivalenol (DON) production. Deletion mutants of ΔFgPex13, ΔFgPex14 or ΔFgPex33 showed an increased accumulation of endogenous reactive oxygen species (ROS) and reduced phosphorylation of MAP (Mitogen‐Activated Protein) kinase FgMgv1. In addition, mutants of the docking peroxin exhibited increased sensitivity toward host oxidative bursts and cell wall integrity stress agents and reduced virulence on host plants. More importantly, we found for the first time that FgPex14 is required for pexophagy in F. graminearum. Overall, our study suggests that peroxisomes play critical roles in DON biosynthesis and virulence in F. graminearum.
Mortality in schizophrenia: 30‐year nationwide follow‐up study
Authors: Tanskanen A. , Tiihonen J. , Taipale H.
Published: June 2018

Objective

Recent reports suggest that the mortality gap between persons with schizophrenia and the general population is increasing. We investigated the mortality, age at death, and causes of death among persons diagnosed with schizophrenia and the general population in Finland during 1984–2014.

Methods

All persons with schizophrenia in Finland were identified from hospital discharge register, and compared with the Finnish population aged 16 years and older during 1984–2014, based on data from Statistics Finland. Age at death and standardized mortality ratio (SMR) were calculated for each follow‐up year.

Results

Mean age at death increased from 57.6 years in 1984 to 70.1 years in 2014 in persons with schizophrenia, and from 70.9 to 77.5 years in the general population. All‐cause SMR remained stable during the follow‐up (2.6 in 1984 and 2.7 in 2014). A major change was observed in SMR for suicides which decreased from 11.0 in 1984 to 6.6 in 2014 (−40%). The SMRs for cardiovascular and cancer deaths showed increasing trends.

Conclusion

The longevity of persons with schizophrenia is improving at approximately the same rate as the general population but suicide rates have declined substantially. However, there is still a major disparity in mortality compared with general population.
What defines a clinically meaningful outcome in the treatment of substance use disorders: reductions in direct consequences of drug use or improvement in overall functioning?
Authors: Kiluk Brian D. , Fitzmaurice Garrett M. , Strain Eric C. , Weiss Roger D.
Published: June 2018

Background

Sustained abstinence is currently the only accepted end‐point for pharmacotherapy trials for most substance use disorders (SUD), with the exception of alcohol. Despite recent efforts, the identification of a non‐abstinence alternative as a clinically meaningful end‐point for drug use trials has been elusive.

Argument and analysis

The current standard for establishing a clinically meaningful outcome in SUD trials is to demonstrate that a reduction in drug use is associated with improvement in long‐term functioning, but data indicate relatively weak associations between drug use and various psychosocial problem domains. This may be because assessments used most commonly to measure an individual's functioning do not specify whether aspects of functioning are a direct consequence of drug use. The acceptance of a non‐abstinence‐based end‐point for alcohol use disorder trials was supported in part through associations with reductions in alcohol‐related consequences, although measures designed to assess the direct consequences of drug use are rarely included in drug treatment efficacy trials.

Conclusions

The field of substance use disorders should include measures of negative psychosocial and health consequences of drug use, as opposed to overall functioning, in the effort to establish meaningful non‐abstinence‐based end‐points.
Contemporary prenatal aneuploidy screening practice in Australia: Frequently asked questions in the cell‐free DNA era
Authors: Rieder Wawrzyniec , White Scott , McGillivray George , Hui Lisa
Published: June 2018

Cell‐free DNA screening has quickly become established in Australia as an accurate – albeit costly – prenatal screening test for trisomy 21, 18 and 13. It is also commonly used for the detection of sex chromosome abnormalities. The increasing number of prenatal screening pathways available to women has increased the complexity of pretest counselling. Concurrent advances in diagnostic testing with the widespread use of chromosomal microarrays create further challenges for the continuing education of clinicians and health consumers. This article aims to answer common clinical questions in this rapidly evolving field and complements the recently updated Royal Australian and New Zealand College of Obstetricians and Gynaecologists Statement on Prenatal Screening for Fetal Chromosome and Genetic Conditions.
RAGE‐dependent VCAM‐1 expression in the lung endothelium mediates IL‐33‐induced allergic airway inflammation
Authors: Perkins T. N. , Oczypok E. A. , Milutinovic P. S. , Dutz R. E. , Oury T. D.
Published: June 2018

Background

The receptor for advanced glycation endproducts (RAGE) has been implicated as a critical molecule in the pathogenesis of experimental asthma/allergic airway inflammation (AAI). It has been previously shown that RAGE acts both upstream of interleukin‐33 (IL‐33) release and downstream of IL‐33 release via RAGE‐dependent IL‐33‐induced accumulation of type 2 innate lymphoid cells (ILC2s) in the lungs, which perpetuate type 2 inflammation and mucus metaplasia. However, the mechanism by which RAGE mediates downstream IL‐33‐induced type 2 inflammatory responses is unknown.

Objective

This study tested the hypothesis that ILC2s are recruited to the lungs via RAGE‐dependent vascular cell adhesion molecule 1 (VCAM‐1) expression on lung endothelial cells.

Methods

House dust mite extract, Alternaria alternata extract, or rIL‐33 was used to induce AAI/VCAM‐1 expression in wild‐type (WT) and RAGE‐knockout (RAGE‐KO) mice. Intravenous (i.v.) anti‐VCAM‐1 or intraperitoneal (i.p.) β7 blocking antibody administration was used to determine the role of VCAM‐1 in IL‐33‐induced AAI.

Results

Enhanced VCAM‐1 expression in the lungs by HDM, AA, or rIL‐33 exposure was found to be RAGE‐dependent. In addition, stimulation of primary mouse lung endothelial cells with IL‐33 induced VCAM‐1 expression in WT, but not RAGE‐KO cells. Administration of VCAM‐1 and β7‐integrin blocking antibodies reduced IL‐33‐induced eosinophilic inflammation, mucus metaplasia, and type 2 inflammatory responses.

Conclusion

This study demonstrates that allergen‐ and cytokine‐induced VCAM‐1 expression is RAGE‐dependent and contributes to lung ILC2 accumulation and downstream eosinophilic inflammation, mucus metaplasia, and type 2 inflammatory responses.
A qualitative study of midwives’ perceptions on using video‐calling in early labor
Authors: Spiby Helen , Faucher Mary Ann , Sands Gina , Roberts Julie , Kennedy Holly Powell
Published: June 2018

Background

Decisions made in early labor influence the outcomes of childbirth for women and infants. Telephone assessment during labor, the current norm in many settings, has been found to be a source of dissatisfaction for women and can present challenges for midwives. The aim of this qualitative study was to explore midwives’ views on the potential of video‐calling as a method for assessing women in early labor.

Methods

A series of 8 midwife focus groups (n = 45) and interviews (n = 4) in the Midlands region of England and the mid‐South and Northeast regions of the United States were completed. Audio recordings were transcribed verbatim and coded using content analysis. Coding diagrams were used to help develop major themes in the data.

Results

Midwives were generally positive about the potential of video‐calling in early labor and using visual cues to make more accurate assessments and to enhance trust. Some midwives expressed concerns about privacy, both for themselves and for women, and issues of accessibility. They suggested strategies for implementation and further research, such as the need for a private space in birth facilities and training for both staff and service users.

Conclusions

Video‐calling was seen as a viable option for assessment of women in early labor with some particular challenges related to implementation. This research focused on midwives’ views; the views of women and their families should also be considered. There is a lack of evidence on the clinical and cost effectiveness of video‐calling in maternity care and further research is warranted.
L'emprunt de termes génériques français dans la toponymie des États‐Unis d'Amérique, un état des lieux
Authors: Léonard Carol J. , Díez González Estrella
Published: June 2018

Messages clés

Nous avons identifié sept lexies empruntées à la langue française par l'anglo‐américain dont le nombre d'occurrences est suffisant pour témoigner de la réalité de L'emprunt.

Ces lexies empruntées qui œuvrent en tant que génériques toponymiques sont : butte, chute, coulée/coulee, plateau, portage, prairie et rapid/rapids.

La région du Nord‐Est des États‐Unis se distingue de toutes les autres en cela qu'un seul des termes génériques étudiés s'y retrouve dans les toponymes hybrides identifiés.
Use of point‐of‐care HbA1c measurement to estimate the level of undiagnosed diabetes mellitus among 67‐year‐old participants in a cardiovascular screening programme in the municipality of Viborg, Denmark
Authors: Andersen J. W. , Dahl M. , Yderstraede K. B. , Hoegh A.
Published: June 2018

Aims

To determine the prevalence of unidentified diabetes mellitus among 67‐year‐olds in Denmark participating in a screening programme focusing on cardiovascular disease and diabetes, and to describe glycaemic levels in individuals according to point‐of‐care HbA1c combined with self‐reported diabetes status.

Methods

In this cross‐sectional, retrospective, population‐based study, all people aged 67 years living in the Viborg municipality were invited to take part in the Viborg Inter‐sectorial Screening Programme (VISP), which focuses on cardiovascular disease and diabetes. The VISP study was initiated in August 2014 and is ongoing. During the first 2 years of the programme, we stratified participants into groups based on their self‐reported diabetes status and a single HbA1c measurement.

Results

A total of 1802 individuals were invited to participate, and 1501 consented, seven of whom were excluded because of missing data (HbA1c or diabetes status), resulting in an 82.9% participation rate (n=1494). Among those reporting not to have diabetes, 3.3% (n=45) had an HbA1c level ≥48 mmol/mol (6.5%). In the same group, 16.7% (n=226) had an HbA1c level of 41–48 mmol/mol (5.9–6.5%). Among those self‐reporting the presence of diabetes, 30.1% (n=43) had an HbA1c level ≥58 mmol/mol (7.5%).

Conclusions

The prevalence of unidentified diabetes was 3.3% based on a single HbA1c measurement. Furthermore, 16.7% of those reporting not to have diabetes had an HbA1c level of 41–48 mmol/mol (5.9–6.5%), representing a subgroup with an increased risk of developing diabetes. Among those with self‐reported diabetes, 30.1% had an HbA1c level ≥58 mmol/mol (7.5%) and 6.3% had a level >74 mmol/mol (8.9%).
Appropriate application of information from biodiversity databases is critical when investigating species distributions and diversity: a comment on Dallas et al. ()
Authors: Knouft Jason H.
Published: June 2018

Using data from biodiversity informatics resources, Dallas et al. (Ecol. Lett., 20, 2017, 1526–1533) suggested limited relationships between climate and local abundance among several taxonomic groups. Investigation of a subset of these data suggests that their results may be misleading due to inappropriate application of the biodiversity data.