bluuebunny/crossref_metadata_2025 huggingface dataset:
CRISPR-Cas9 targeted deletion of theC9orf72repeat expansion mutation corrects cellular phenotypes in patient-derived iPS cells
Authors: Pribadi Mochtar , Yang Zhongan , Kim Tanya S. , Swartz Elliot W. , Huang Alden Y. , Chen Jason A. , Dokuru Deepika , Baek Jaeyun , Gao Fuying , Fua Andrea T. , Wojta Kevin , Wang Qing , Karydas Anna , Fong Jamie , Lezcano Ed , Ng Stephanie , Chehab Farid F. , Vinters Harry V. , Miller Bruce L. , Coppola Giovanni
Published: May 2016

The large hexanucleotide (GGGGCC) repeat expansion in the non-coding promoter region ofC9orf72is the leading cause of Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS). Mechanisms underlying neurodegeneration are not clear, and both a C9orf72 loss of function and a gain of toxicity, in the form of RNA foci or dipeptide repeat deposition, are implicated. CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9-mediated genome editing is an attractive strategy for disease modeling and therapeutic intervention. Here we show that this system can be utilized to completely remove the large repeat expansion mutation withinC9orf72in patient-derived induced pluripotent stem (iPS) cells. Removal of the mutation prevented RNA foci formation and promoter hypermethylation, two phenotypes of theC9orf72mutation. Interestingly, these changes did not significantly alter C9orf72 expression at the mRNA or protein level. This work provides a proof-of-principle for the use of CRISPR-Cas9-mediated excision of the pathogenicC9orf72repeat expansion as a therapeutic strategy in FTD/ALS.

One Sentence Summary

CRISPR-Cas9-mediated excision of the largeC9orf72repeat expansion mutation rescues RNA foci formation and promoter hypermethylation without altering C9orf72 transcript and protein expression.
The genetic basis of natural variation inC. eleganstelomere length
Authors: Cook D.C. , Zdraljevic S. , Tanny R.E. , Seo B. , Riccardi D.D. , Noble L.M. , Rockman M.V. , Alkema M.J. , Braendle C. , Kammenga J.E. , Wang J. , Kruglyak L. , Félix M.A. , Lee J. , Andersen E.C.
Published: May 2016

Telomeres are involved in the maintenance of chromosomes and the prevention of genome instability. Despite this central importance, significant variation in telomere length has been observed in a variety of organisms. The genetic determinants of telomere-length variation and their effects on organismal fitness are largely unexplored. Here, we describe natural variation in telomere length across theCaenorhabditis elegansspecies. We identify a large-effect variant that contributes to differences in telomere length. The variant alters the conserved oligosaccharide/oligonucleotide-binding fold of POT-2, a homolog of a human telomere-capping shelterin complex subunit. Mutations within this domain likely reduce the ability of POT-2 to bind telomeric DNA, thereby increasing telomere length. We find that telomere-length variation does not correlate with offspring production or longevity inC. eleganswild isolates, suggesting that naturally long telomeres play a limited role in modifying fitness phenotypes inC. elegans.
Optimizing multiplex CRISPR/Cas9-based genome editing for wheat
Authors: Wang Wei , Akhunova Alina , Chao Shiaoman , Akhunov Eduard
Published: May 2016

Background

CRISPR/Cas9-based genome editing holds great promise to accelerate the development of new crop varieties by providing a powerful tool to modify the genomic regions controlling major agronomic traits. To diversify the set of tools available for wheat genome engineering, we have established a tRNA-based multiplex gene editing strategy for hexaploid wheat.

Results

The functionality of the various CRISPR/Cas9 components was assessed using the transient expression in the wheat protoplasts followed by next-generation sequencing (NGS) of the targeted genomic regions. The efficiency of wheat codon-optimized Cas9 for targeted gene editing in wheat was validated. Multiple single guide RNAs (gRNAs) were evaluated for the ability to edit the homoeologous copies of four genes affecting some important agronomic traits in wheat. Low correspondence was found between the gRNA efficiency predicted bioinformatically and that assessed in the transient expression assay. A multiplex gene editing construct with several gRNA-tRNA units under the control of a single promoter for the RNA polymerase III generated indels at the targets sites with the efficiency comparable to that obtained for a single gRNA construct.

Conclusions

By integrating the protoplast transformation assay with multiplexed NGS, it is possible to perform fast functional screens for a large number of gRNAs and to optimize constructs for effective editing of multiple independent targets in the wheat genome. The multiplexing capacity of the tandemly arrayed tRNA–gRNA construct is well suited for the simultaneous editing of the redundant gene copies in the allopolyploid genomes or genomic regions beneficially affecting multiple agronomic traits. A polycistronic gene construct that can be quickly assembled using the Golden Gate reaction along with the wheat codon optimized Cas9 will further expand the set of tools available for engineering the wheat genome.
Transcriptome Analysis Reveals Skin Lipid Metabolism Related to Wool Diameter in Sheep
Authors: Fu Shaoyin , Qi YunXia , He Xiaolong , Da Lai , Wang biao , Te rigele , Wu jianghong , Yang ding , Liu yongbin , Zhang wengguang
Published: May 2016

Wool is one of the most important animal fibers in the textile industry and the diameter directly affects its economic value. However, the molecular mechanisms underlying the wool diameter have not been fully elucidated. In the present study, high-throughput RNA-Seq technology was employed to explore the skin transcriptome using 3 sheep with fine wool (fiber diameter, FD<21.0μm) and 3 sheep with coarse wool (fiber diameter, FD>27.0μm). In total, 28,607,228 bp clean reads were obtained, and 78.88%+/-3.84% was uniquely aligned to the reference genome across the six samples. In total, 19,914 mRNA transcripts were expressed (FPKM>0) in the six skin samples, among which there were certain well-known genes affecting the skin hair cycle, such as KRTAP7-1, KRT14, Wnt10b, Wnt2b, β-catenin, and FGF5. Furthermore, 467 expressed genes were significantly differentially expressed between the two groups, including 21 genes up-regulated and 446 genes down-regulated in the sheep with the smaller fiber diameter. To verify the results, 13 differentially expressed genes were randomly selected to validate the expression patterns using qRT-PCR, and the correlation between the mRNA expression level from qRT-PCR and RNA-Seq data was 0.999 ( P<0.05). These differentially expressed genes were particularly enriched in GO processes related to lipid metabolism, skin development, differentiation, and immune function (P<0.05). The biological processes were involved in collagen catabolism, negative regulation of macromolecule metabolism, steroid hormone stimulation and lipid metabolism. A significant KEGG pathway involving the “metabolism of lipids and lipoproteins” was also enriched. This study revealed that the lipid metabolism might constitute one of the major factors related to wool diameter.
Spatially Explicit Models to Investigate Geographic Patterns in the Distribution of Forensic STRs
Authors: Messina Francesco , Finocchio Andrea , Akar Nejat , Loutradis Aphrodite , Michalodimitrakis Emmanuel I. , Brdicka Radim , Jodice Carla , Novelletto Andrea
Published: May 2016

Human forensic STRs are used for individual identification but have been reported to have little power for inter-population analyses. Several methods have been developed which incorporate information on the spatial distribution of individuals to arrive at a description of the arrangement of diversity. We genotyped at 16 forensic STRs a large population sample obtained from many locations in Italy, Greece and Turkey, i.e. three countries seldom represented together in previous studies. Using spatial PCA on the full dataset, we detected patterns of population affinities in the area similar to those of genome-wide SNP and STR studies. Additionally, we devised objective criteria to reduce the overall complexity into reduced datasets. Independent spatially explicit methods applied to these latter datasets converged in showing that the extraction of information on long-to medium-range geographical trends and structuring from the overall diversity is possible. All analyses returned the picture of a background clinal variation, with regional discontinuities captured by each of the reduced datasets. These coincided with the main bodies of water, i.e. the Adriatic/Ionian and the Aegean Seas. High levels of gene flow were inferred within the main continental areas by coalescent simulations. These results are promising in a microevolutionary perspective, in view of the fast pace at which forensic data are being accumulated for many locales. It is foreseeable that this will allow the exploitation of an invaluable genotypic resource, assembled for other (forensic) purposes, to clarify important aspects in the formation of local gene pools.
Identifying dimensions of employer attractiveness in Indian universities: an approach towards scale development
Authors: Priyadarshini Chetna , Mamidenna Sireesha , Sayeed O.B.
Published: May 2016

Purpose

As the global war of talent is prevalent across different industries, universities are also facing an acute shortage of faculty members because of massification of higher education system in the past two decades. The tremendous increase in the number of higher education institutions has made attracting talented professors a challenging necessity for the university management as employers. The present study, therefore, carries out a scale development exercise and explores the attractive dimensions of Indian universities as employers.

Design/methodology/approach

With the help of principle component analysis, exploratory factor analysis was carried out to obtain five significant constructs of employer attractiveness in Indian universities.

Findings

The dimensions identified in the study includes fairness and work–life balance; teaching environment and compensation and benefits; research resources and career development; organizational integrity and commitment to quality; and organizational culture consisting of respect and recognition.

Practical implications

The finding provides valuable insights for the university management and government bodies and posits to assist them in formulating policies with regard to attracting competent teaching staff.

Originality/value

Although employer attractiveness has gained scholarly attention in the past two decades, study exploring the dimensionality of employer attractiveness in the context of academic institutions and universities has not been conducted so far. The present study, therefore, is one of the pioneers in this realm.
Impact of R&D on profitability in the pharma sector: an empirical study from India
Authors: Jaisinghani Dinesh
Published: May 2016

Purpose

The purpose of the current paper is to examine the nature of profit persistence and to estimate the dynamic relationship between research and development (R&D) intensity and firm profitability in the Indian pharmaceutical industry.

Design/methodology/approach

A dynamic panel data model with generalized methods of moments (GMMs) technique has been deployed to estimate the relationship between R&D intensity and performance. Arellano and Bond (1991) estimation methodology has been used to generate the estimates. A sample of 55 publicly listed firms operating in the Indian pharmaceutical industry for the period 2005-2014 has been considered.

Findings

The study finds moderate to heavy profit persistence in the Indian pharmaceutical industry. The study also finds that there exists a positive relationship between R&D intensity and performance for the Indian pharmaceutical Industry. The results hold even after considering two separate measures of profitability – return on assets and return on sales. The results also hint at a possible non-linear relationship between R&D intensity and profitability.

Research limitations/implications

The results highlight positive profit persistence among pharmaceutical firms. The results also highlight the need for a sustained investment in R&D, as its benefits are driven in the long run. Thus, managers should devise proper policies R&D investments. Also, prospective entrants should properly study the existing entry barriers before deciding upon the mode and timing of entry.

Originality/value

The degree of profit persistence and the dynamic nature of relationship between R&D intensity and firm performance in the Indian pharmaceutical sector has not been studied. Thus, this paper fills this gap and also highlights the impact of certain firm- and industry-specific variables on profitability.
Determinants of a successful cross-border knowledge transfer in franchise networks
Authors: Khan Zaheer
Published: May 2016

Purpose

Previous research on service multinational corporations (SMNCs) has mainly focused on the entry mode decisions in foreign markets. The purpose of this paper is to examine the cross-border knowledge transfer in franchisee networks in Pakistan.

Design/methodology/approach

The qualitative semi-structure interviews approach is used to study the cross-border knowledge transfer from a franchisor to two local franchisee networks in Pakistan.

Findings

The results show that both explicit and tacit knowledge are transferred in cross-border franchise networks. The transfer of the knowledge from a franchisor to a franchisee is facilitated through the use of a variety of transfer mechanisms – both hard and soft transfer mechanisms, that is, video conferencing, emails, phone calls, seminars, meetings, documents and franchisor agents’ visits. The knowledge sharing in cross-border franchise networks in Pakistan shows numerous similarities with that occurring in manufacturing industries. The prior experience of the franchisee and the regional and local franchisors’ agents – their role as knowledge transfer agents (intermediaries) – facilitate the acquisition and assimilation of knowledge from the franchisor to a franchisee in the developing economies.

Practical implications

The paper discusses relevant implications for managers of franchisor and franchisee networks by focusing on the need to engage with both explicit and tacit knowledge transfer. The experience of the franchisee is important for the acquisition and assimilation of knowledge.

Originality/value

This paper is the first in the context of cross-border knowledge transfer from a franchisor to a franchisee in the Pakistani context. The author highlights the important role of prior experience of the franchisee and the regional and local agents of the franchisor in the transfer of cross-border knowledge transfer under the franchising arrangements.
Sustainability practices and web-based communication
Authors: Da Giau Alessandro , Macchion Laura , Caniato Federico , Caridi Maria , Danese Pamela , Rinaldi Rinaldo , Vinelli Andrea
Published: May 2016

Purpose

– The purpose of this paper is to examine which environmental and social sustainability practices companies in the Italian fashion industry adopt and how these companies communicate their sustainability commitment through their corporate websites.

Design/methodology/approach

– The multiple case studies approach was selected and the practices of 12 companies in the Italian fashion industry were investigated.

Findings

– The findings showed that four different approaches in the field of sustainability practices and web-based communication are available within the Italian fashion industry (i.e. low commitment, high commitment, low disclosure, high marketing) by highlighting the alignment (i.e. fit or misfit) among these dimensions and by discussing the practices as well as the drivers/barriers of each approach.

Originality/value

– The paper contributes to the literature by deepening the understanding of both the environmental and social dimensions of the sustainability issue. Moreover, the work investigates the relationship between sustainability practices and web-based sustainability communication, a topic that has not yet been addressed in the current literature.
Media influence, fashion, and shopping: a gender perspective
Authors: Shephard Arlesa , Pookulangara Sanjukta , Kinley Tammy R. , Josiam Bharath M.
Published: May 2016

Purpose

– Promotional media and gender have been shown to influence purchase and shopping channel choice. The purpose of this paper is to better understand the role of media influence, fashion consciousness, and fashion leadership on shopping channel choice in regard to gender.

Design/methodology/approach

– A survey was administered using a convenience sample of male and female students at a Southwestern University in the USA. A total of 408 surveys were used for analysis. The data were factor analyzed using Statistical Package for the Social Sciences (SPSS) statistical software and a structural equation model was developed to test the hypotheses.

Findings

– The results indicate that while the media influence factor of mass media positively influences fashion consciousness for both males and females, personalized media only indicated significant influence on male fashion leaders. In addition, both male and female consumers indicated that fashion leadership influenced non-traditional over traditional retail channels.

Originality/value

– This research uses social cognitive theory and the theory of symbolic interaction to better understand the impact of media and fashion on shopping behavior. This paper addresses the changing media types and how they impact behavior for both men and women.
Negotiating Muslim masculinity: androgynous spaces within feminized fashion
Authors: Al-Mutawa Fajer Saleh
Published: May 2016

Purpose

– The purpose of this paper is to explore how Muslim men in Kuwait negotiate their luxury fashion consumption (considered a feminized practice in Kuwait) without compromising their masculine identity.

Design/methodology/approach

– The data were collected through 108 qualitative questionnaires and two unstructured in-depth interviews. Non-participant observations and informal conversations took place as part of an ongoing ethnographic study on luxury fashion consumption in Kuwait.

Findings

– Within the feminized space of fashion, accessories (such as shoes, wallets, watches, sunglasses, etc.) seem to allow Muslim men an androgynous space (consumer constructions of gendered spaces to be equally masculine and feminine) to be fashionable yet maintain a masculine identity.

Research limitations/implications

– Further research may explore the negotiation of androgyny among men who consume luxury fashion clothing or conspicuously feminized fashion (such as jewellery and handbags) in highly gendered societies. Limitations include reliance on questionnaire data (lacks depth insights) and narrow consumer (Muslim men in Kuwait).

Practical implications

– Marketers of luxury fashion brands in Kuwait should focus on fashion accessories when targeting males. Advertising needs to shift gender perceptions of traditionally feminine fashion (such as handbags or jewellery) towards androgyny to attract male consumers. Religiosity of consumers is an important segmentation basis, and Muslim men who are less religious may be more open towards fashion consumption.

Originality/value

– This research proposes the notion of androgynous spaces, contributing to gender within marketing theory and practice.
Temporal changes in the vegetation of Italian coastal dunes: identifying winners and losers through the lens of functional traits
Authors: Prisco Irene , Carboni Marta , Jucker Tommaso , Acosta Alicia T. R.
Published: May 2016

Plant communities of coastal dunes are highly biodiverse and greatly valued for the services they provide, yet they are also threatened by global change and are often neglected in conservation planning. To determine the long‐term effectiveness of conservation actions on Mediterranean coastal dunes, here we focus on Italy's coastline and (i) assess how the vegetation cover of the major psammophilous habitats and species has changed since the 1960s, (ii) identify which ecological strategies have been most successful in the face of global change and (iii) evaluate the efficacy of the protected areas network for safeguarding plant communities of coastal dunes.

We compiled 2583 geo‐located vegetation relevés spanning over half a century and covering the entire length of Italy's sandy coastline. Using this data base, we developed statistical models to test whether the vegetation cover of both individual species and habitats has changed over time. We then tested whether species‐level changes in vegetation cover through time could be explained by species’ functional traits and ecological strategy. Finally, we assessed the efficacy of current conservation measures by exploring how vegetation cover responded following the expansion of the protected areas network.

Our results indicate that, where protected, plant communities have generally increased in vegetation cover in recent years. The strongest increase in cover occurred in the wooded dune habitats, where late‐successional, tall‐growing and large‐seeded species show the clearest signs of recovery. However, this has come in part at the expense of dune grasslands, which thrive under natural disturbance and have declined since the 1960s. The Natura 2000 network seems to have played a central role in this recovery process, as the cumulative coastal land area under protection has tripled since the network was first established.

Synthesis and applications. Our results suggest that protected areas can play an important role in safeguarding coastal dune plant communities against land‐use transformations. In this context, functional traits can be a powerful tool in guiding conservation planning, helping to identify groups of species most at risk of population declines. Nonetheless, future conservation interventions need to be mindful to ensure that the natural disturbance regime of dune ecosystems is not disrupted.
Taxonomic and functional diversity in Mediterranean pastures: insights on the biodiversity–productivity trade‐off
Authors: Rolo Victor , Rivest David , Lorente Miren , Kattge Jens , Moreno Gerardo
Published: May 2016

Agricultural intensification is one of the main causes of biodiversity loss world‐wide. The inclusion of semi‐natural features in agricultural landscapes is suggested as a means of enhancing farm biodiversity, but this practice may have potential negative effects on yield production. Moreover, little evidence exists for effects of semi‐natural features on other components of biodiversity, such as functional diversity. Yet this could provide a more comprehensive understanding of biodiversity–productivity trade‐offs.

Here, we report the effects of semi‐natural woody vegetation on taxonomic and functional diversity, and biomass production of herbaceous species at the field and farm scales by sampling 50 fields, ranging from 0 to 90% woody vegetation cover, on nine similarly managed farms in central‐western Spain.

We found significant differences in herbaceous species richness among farms. Both taxonomic and functional β‐diversity exhibited significant negative relationships with herbage production, highlighting the trade‐off between biodiversity and productivity in these agroecosystems.

Woody vegetation cover had a significant negative relationship with biomass production and a unimodal relationship with species richness at the field scale. At high values of woody vegetation cover, species richness and functional diversity indices were decoupled, suggesting that at this extreme of the woody vegetation gradient, only herbaceous species with contrasting trait values were present. Our results showed both convergent and divergent patterns of trait values, suggesting that different assembly processes are acting concurrently along the gradient of woody vegetation.

Synthesis and applications. Our result indicates that management of woody vegetation may indeed increase both taxonomic and functional diversity, but this may come at the expense of key ecosystem services or other management goals, namely herbage production. Optimization of the trade‐off between herbage diversity and productivity can be reached with a woody vegetation cover of c. 30% at the field scale.
Spatio‐temporal modelling of auk abundance after the Erika oil spill and implications for conservation
Authors: Le Rest Kévin , Certain Grégoire , Debétencourt Benjamin , Bretagnolle Vincent
Published: May 2016

Species distribution models are widely used in applied ecology and conservation. While accounting for spatial dependences is now the rule, temporal dependences have rarely been dealt with explicitly. In this study, we analyse wintering auk distribution in the Bay of Biscay and English Channel and estimate changes in abundance within and between years while accounting for space–time dependencies. We then propose a retrospective estimate of the impact of the Erika oil spill that occurred in December 1999.

Two series of extensive aerial surveys, repeated at intervals of 1–2 months, were carried out at a 10‐year interval off the French Atlantic coast (2001–2002 and 2011–2012). Spatially and temporally explicit Bayesian models were fitted to these data to provide spatio‐temporal predictions of auk abundance. These were then used to compare abundances within the area affected by the Erika oil spill two and twelve years after the catastrophe.

The results showed that 1·55 million auks wintered in the study area in 2011–2012. The main wintering area was the English Channel (more than one million auks) but the Bay of Biscay also became an important area in the middle of winter (470 000 auks) owing to a strong southward shift in auk distribution.

Two years after the catastrophe (2001–2002), the area affected by the Erika oil spill hosted a small proportion of auks of the Bay of Biscay – about 80 000 individuals. This number increased by more than three times 10 years later and reached 270 000 individuals, whereas no significant change was detected elsewhere. We suggest that it could result from a recovery after the extra‐mortality induced by the Erika oil spill.

Policy implications. This study identified major auk wintering areas, with abundances much higher than previously realized. Oil spills have occurred regularly in these areas, with major delayed impacts on auk breeding populations. The worst case scenario would be if a major oil spill occurred in the English Channel in February, when abundance reaches one million auks. Although such a disaster has not so far occurred, stricter policies on the transport of hydrocarbons should be implemented to prevent such a possibility.
Occupational experiences of forced migrants: A scoping review
Authors: Huot Suzanne , Kelly Erin , Park Soo Jin
Published: May 2016

Background/aim

International or internal migration as a result of unexpected circumstances, such as that experienced by forced migrants (i.e. refugees, asylum seekers and internally displaced persons), can disrupt established occupations. Occupational therapists have the potential to improve quality of life by re‐establishing lost occupations. Research on forced migrants has been increasing within the occupation‐based literature and has the potential to inform practice with this population. Our aim was to identify and synthesise current knowledge of the occupational experiences of forced migrants.

Methods

This scoping review was conducted using the framework articulated by Arksey and O’Malley (International Journal of Social Research Methodology, 2005; 8, 19). Inclusion criteria for selected articles included peer‐reviewed articles published in English between 2003 and 2014 that focussed on forced migrant populations and that were written from an occupational perspective. Exclusion criteria consisted of grey literature as well as articles focussed more broadly on immigrants in general, and that failed to adopt occupation as a central construct.

Results

Based on a total of 320 studies that were identified, 24 met the inclusion criteria. Six themes emerged as a result of the data extraction and synthesis process: occupational deprivation, occupational imbalance, occupational adaptation, occupational change, efforts to maintain and re‐establish identity, and outlook for the future.

Conclusions and significance of the study

This scoping review outlines key factors that affect forced migrants’ occupational experiences and highlights gaps in the current literature. The results point towards potential practice implications for occupational therapists working with forced migrant populations to help promote culturally safe approaches.
The ‘Proper’ Way to Spread Ideas through Social Media: Exploring the Affordances and Constraints of Different Social Media Platforms as Perceived by Italian Activists
Authors: Comunello Francesca , Mulargia Simone , Parisi Lorenza
Published: May 2016

Social media have become a relevant arena for different forms of civic engagement and activism. This article focuses on the affordances and constraints of different social media platforms as they are perceived by Italian activists. Instead of focusing on single protest movements, or on single platforms, we adopt a media ecological approach and consider a variety of environments where people can choose to express protest-related content. Our main goal is to explore whether, and how, the affordances and constraints of different social media platforms are perceived by users, and how such perceived differences are integrated in everyday social media activities. To this end, we combined in-depth interviews with an adapted version of the cognitive walkthrough and thinking aloud techniques. Respondents reported that they act on social media platforms according to specific representations of what each platform ‘is’, and how it works. Such perceptions affect users' protest-related social media practices. Although they perceive major social media platforms filtering strategies and are aware, to different extents, of their commodified nature, they report continuing to use them for activism-related communication, often adopting an instrumental approach.
The Humanitarian Initiative on Nuclear Weapons: An Introduction to Global Policy's Special Section
Authors: Bolton Matthew , Minor Elizabeth
Published: May 2016

The dominant paradigm of international relations theory has long seen influence over nuclear arsenals as the preserve of presidents, premiers and generals of the world's great powers, not underfunded activists, feminist campaigners, radical nuns or even diplomats of small states. The approach of this special section could not be more different. In fact, we have intentionally curated a collection of articles that try to ‘de‐center’ the academic conversation about nuclear weapons. The inspiration for our approach comes from the Humanitarian Initiative on Nuclear Weapons, which since its emergence after the 2010 Review Conference of the Nuclear Non‐Proliferation Treaty, has dramatically reshaped the diplomatic discussions on nuclear disarmament, led by small states and middle powers. The shift in discourse has been accelerated by revitalized civil society action, represented by the International Campaign to Abolish Nuclear Weapons, a global NGO coalition, as well as renewed calls for disarmament from religious leaders – most notably Pope Francis. This special section, written from the perspective of scholars and practitioners associated with the Humanitarian Initiative, examines its dimensions and its potential impact on global policy making.
The Impact of Renal Failure and Renal Replacement Therapy on Outcome During Extracorporeal Membrane Oxygenation Therapy
Authors: Antonucci Elio , Lamanna Irene , Fagnoul David , Vincent Jean‐Louis , De Backer Daniel , Silvio Taccone Fabio
Published: May 2016

Acute kidney injury (AKI) is common in patients treated with veno‐arterial (VA‐) or veno‐venous (VV‐) extracorporeal membrane oxygenation (ECMO). In this setting, the use of continuous renal replacement therapy (CRRT) can help to optimize fluid status but may also negatively impact on patients' outcome. In contrast, the relationship between AKI, CRRT, and survival in critically ill adult patients receiving ECMO is not well defined. The institutional ECMO database (n = 162) from November 2008 to December 2013, excluding patients with ICU survival <24 hours was reviewed. Demographics, co‐morbidities, and concomitant therapies for all patients were collected. AKI was defined according to the Acute Kidney Injury Network (AKIN) criteria. ICU mortality was noted. Data were retrieved for 135 patients (79 with VA‐ECMO and 56 with VV‐ECMO). Of these, 95 developed AKI, 63 (47%) of whom required CRRT; thus three groups of patients were identified: (a) no AKI; (b) AKI without CRRT (AKINOCRRT); and (c) CRRT with AKI (AKICRRT). AKINOCCRT patients were more likely to have preexisting heart disease, to be more severely ill, and to be treated with VA‐ECMO than those without AKI. AKICRRT patients were also more likely to be treated with VA‐ECMO, had more organ dysfunction at the time of ECMO insertion, and needed more transfusions and inotropic agents than patients without AKI. ICU mortality was 53% (72/135) and was similar in the three groups, even when different AKI stages or VA/VV‐ECMO were analyzed separately. In this study, the use of CRRT was not associated with an increased mortality in an adult population of patients treated with ECMO, even after adjustment for confounders.
Are augmented reality picture books magic or real for preschool children aged five to six?
Authors: Yilmaz Rabia M. , Kucuk Sevda , Goktas Yuksel
Published: May 2016

The aim of this study is to determine preschool children's attitudes towards augmented reality picture books (ARPB), their story comprehension performance (SCP) and the relationships between these variables. The sample consisted of 92 five‐ and six‐year‐olds (49 boys, 43 girls). An attitude form, story comprehension test and interview form were used as data collection tools. Most of the children reported feeling “very happy” with the activity and enjoyed using the ARPB, which they found interesting and fun. The children also delivered strong story SCP. Their happiness was found to affect their SCP, while their enjoyment did not. ARPB are attractive and evocative for children, who perceive them as magic and more enjoyable than conventional books. This study demonstrates how they can be used as effective educational tools to improve preschool children's cognition and listening skills.
Epilepsy‐related sudden unexpected death: targeted molecular analysis of inherited heart disease genes using next‐generation DNA sequencing
Authors: Hata Yukiko , Yoshida Koji , Kinoshita Koshi , Nishida Naoki
Published: May 2016

Inherited heart disease causing electric instability in the heart has been suggested to be a risk factor for sudden unexpected death in epilepsy (SUDEP). The purpose of this study was to reveal the correlation between epilepsy‐related sudden unexpected death (SUD) and inherited heart disease. Twelve epilepsy‐related SUD cases (seven males and five females, aged 11–78 years) were examined. Nine cases fulfilled the criteria of SUDEP, and three cases died by drowning. In addition to examining three major epilepsy‐related genes, we used next‐generation sequencing (NGS) to examine 73 inherited heart disease‐related genes. We detected both known pathogenic variants and rare variants with minor allele frequencies of <0.5%. The pathogenicity of these variants was evaluated and graded by eight in silico predictive algorithms. Six known and six potential rare variants were detected. Among these, three known variants of LDB3, DSC2 and KCNE1 and three potential rare variants of MYH6, DSP and DSG2 were predicted by in silico analysis as possibly highly pathogenic in three of the nine SUDEP cases. Two of three cases with desmosome‐related variants showed mild but possible significant right ventricular dysplasia‐like pathology. A case with LDB3 and MYH6 variants showed hypertrabeculation of the left ventricle and severe fibrosis of the cardiac conduction system. In the three drowning death cases, one case with mild prolonged QT interval had two variants in ANK2. This study shows that inherited heart disease may be a significant risk factor for SUD in some epilepsy cases, even if pathological findings of the heart had not progressed to an advanced stage of the disease. A combination of detailed pathological examination of the heart and gene analysis using NGS may be useful for evaluating arrhythmogenic potential of epilepsy‐related SUD.
Intergenerational Transmission of Educational Attitudes in Chinese American Families: Interplay of Socioeconomic Status and Acculturation
Authors: Shen Yishan , Kim Su Yeong , Wang Yijie
Published: May 2016

This longitudinal study examined the influence of parents' educational attitudes on adolescents' educational attitudes and identified antecedents (i.e., parent education, family income, and parent acculturation), consequences (i.e., academic achievement and engagement), and a potential moderator (i.e., adolescent acculturation) of the transmission process. The sample was 444 Chinese American mothers, fathers, and adolescents (12–15 at W1). Using path analysis, this study found significant two‐way interactions among parent education, income, and acculturation in predicting parents' concurrent positive educational attitudes, which, in turn, predicted adolescents' attitudes at W2. The latter link was further moderated by W1 and W2 adolescent acculturation for mother–adolescent and father–adolescent dyads. Adolescents' positive educational attitudes at W2, in turn, were positively associated with their concurrent academic achievement and engagement.
Important non‐disease‐related determinants of exhaled nitric oxide levels in mild asthma – results from the Swedish GA2LEN study
Authors: Al‐shamkhi N. , Alving K. , Dahlen S. E. , Hedlin G. , Middelveld R. , Bjerg A. , Ekerljung L. , Olin A. C. , Sommar J. , Forsberg B. , Janson C. , Malinovschi A.
Published: May 2016

Background

Fractional exhaled nitric oxide (FeNO) has a potential clinical role in asthma management. Constitutive factors such as age, height and gender, as well as individual characteristics, such as IgE sensitization and smoking, affect the levels of FeNO in population‐based studies. However, their effect on FeNO in subjects with asthma has been scarcely studied.

Objective

To study the effects on FeNO of these commonly regarded determinants, as demonstrated in healthy subjects, as well as menarche age and parental smoking, in a population of asthmatics.

Material and Methods

Fractional exhaled nitric oxide was measured in 557 subjects with asthma from the Swedish GA2LEN study. Allergic sensitization was assessed by skin prick tests to most common aeroallergens. Upper airway comorbidities, smoking habits, smoking exposure during childhood and hormonal status (for women) were questionnaire‐assessed.

Results

Male gender (P < 0.001), greater height (P < 0.001) and sensitization to both perennial allergens and pollen (P < 0.001) are related to higher FeNO levels. Current smoking (P < 0.001) and having both parents smoking during childhood, vs. having neither (P < 0.001) or only one parent smoking (P = 0.002), are related to lower FeNO. Women with menarche between 9 and 11 years of age had lower FeNO than those with menarche between 12 and 14 years of age (P = 0.03) or 15 and 17 years of age (P = 0.003).

Conclusions and Clinical relevance

Interpreting FeNO levels in clinical practice is complex, and constitutional determinants, as well as smoking and IgE sensitisation, are of importance in asthmatic subjects and should be accounted for when interpreting FeNO levels. Furthermore, menarche age and parental smoking during childhood and their effects on lowering FeNO deserve further studies.
Follicular helper T cells are responsible for IgE responses to Der p 1 following house dust mite sensitization in mice
Authors: Noble A. , Zhao J.
Published: May 2016

Background

Th2 cells have long been considered responsible for the switching of B cells to production of IgE during cognate interaction, primarily due to their expression of CD40L and secretion of IL‐4. This concept has been challenged by the more recent definition of follicular helper T cells (Tfh) as the key T cell subset in B cell isotype switching, due to their physical location at the boundary of T cell:B cell areas in lymphoid follicles and ability to express IL‐4 and CD40L.

Objective

To determine whether Tfh cells are responsible for IgE responses to Der p 1 allergen after house dust mite (HDM)‐induced allergic sensitization.

Methods

Mice deficient in Tfh cells were sensitized to HDM and Der p 1‐specific IgE measured by ELISA.

Results

Mice with a mutation in T cell‐expressed IL‐6R were unable to expand Tfh populations after HDM sensitization, and their anti‐Der p 1 IgE, IgG1 and total IgE responses were reduced by 80–90% compared with wild‐type mice. These animals displayed unaltered lung Th2 and eosinophilic responses after intranasal HDM challenge and normal IL‐4 production, but B cell infiltration of the airways was abrogated.

Conclusions and Clinical Relevance

Our data indicate that Tfh cells are largely responsible for switching B cells to IgE synthesis, most likely via an IgG1+ intermediate. However, Th2 cells are the major source of IL‐4 during HDM sensitization and this might contribute to IgE synthesis at a stage distal to Tfh‐mediated isotype switching. The IL‐6/follicular helper T cell pathway is a potential therapeutic target in allergic disease.
Morphological and Functional Attenuation of Degeneration of Peripheral Neurons by Mesenchymal Stem Cell‐Conditioned Medium in Spinocerebellar Ataxia Type 1‐Knock‐in Mice
Authors: Suto Nana , Mieda Tokue , Iizuka Akira , Nakamura Kazuhiro , Hirai Hirokazu
Published: May 2016

Aims

Spinocerebellar ataxia type 1 (SCA1) is caused by the ataxin‐1 protein (ATXN1) with an abnormally expanded polyglutamine tract and is characterized by progressive neurodegeneration. We previously showed that intrathecal injection of mesenchymal stem cells (MSCs) during the nonsymptomatic stage mitigates the degeneration of the peripheral nervous system (PNS) neurons in SCA1‐knock‐in (SCA1‐KI) mice. We tested in this study whether the therapeutic effects of MSCs in SCA1‐KI mice could be reproduced with MSC‐releasing factor(s).

Methods

To test the effects of MSC‐releasing factor(s), we used MSC‐conditioned medium (MSC‐CM). MSC‐CM was intrathecally and/or intravenously injected into young SCA1‐KI mice, and the therapeutic effects were assessed in the PNS at later ages using immunostaining, electrophysiology, and behavioral tests.

Results

MSC‐CM attenuated the degeneration of axons and myelin of spinal motor neurons. Consequently, the injected SCA1‐KI mice exhibited smaller reductions in nerve conduction velocity in spinal motor neurons and reduced motor incoordination than the untreated mice.

Conclusions

These results suggest that factors released from MSC mitigate the morphological and functional abnormalities in the PNS that are observed in SCA1‐KI mice in a paracrine manner.
Anti‐HLA sensitization after kidney allograft nephrectomy: changes one year post‐surgery and beneficial effect of intravenous immunoglobulin
Authors: Matignon Marie , Leibler Claire , Moranne Olivier , Salomon Laurent , Charron Dominique , Lang Philippe , Jacquelinet Christian , Suberbielle Caroline , Grimbert Philippe
Published: May 2016

The analysis of anti‐HLA sensitization at the time of and following allograft nephrectomy may help clinicians to define better both the indications for nephrectomy and preventive therapeutic strategies. We carried out a retrospective analysis of anti‐HLA antibodies in 63 clinically indicated nephrectomies (baseline and three and 12 months after) according to the time elapsed since transplantation (six months) and clinical background. An intervention study included 10 patients without donor‐specific antibodies (DSA) at the time of nephrectomy treated with high‐dose intravenous immunoglobulin (IVIG) (1.5 g/kg). Early nephrectomies were performed in 15 patients (24%). Among the late nephrectomies, 14 patients (22%) were asymptomatic and 34 (54%) had graft intolerance syndrome (GIS). At baseline, anti‐HLA sensitization was significantly lower in the early and late asymptomatic groups than in the GIS group, but increased considerably within the three months following surgery. In the group of 10 patients treated with IVIG, only the number of class I non‐DSA increased in the three months after surgery, whereas in the control group (N = 13), all anti‐HLA variables increased significantly. All patients undergoing a clinically indicated allograft nephrectomy become highly sensitized within the 12 months after surgery. In patients without DSA before nephrectomy, high doses of IVIG may prevent anti‐HLA sensitization.
Skype clinics after intestinal transplantation – follow‐up beyond post codes
Authors: Gerlach Undine A. , Vrakas Georgios , Holdaway Lydia , O'Connor Marion , Macedo Rubens , Reddy Srikanth , Friend Peter J. , Giele Henk , Vaidya Anil
Published: May 2016

The follow‐up after intestinal transplantation (ITX) is complex and limited to specialized centers. ITX recipients often travel all over the country to be seen in the outpatient clinic of specialized centers which is costly and time‐consuming. Videoconferences through Skype have been implemented to eliminate travel time, costs, and to improve patient compliance without jeopardizing safety. Eighteen of 19 patients followed up after ITX or modified multivisceral transplantation (MMVTX) in conventional outpatient clinics in Oxford agreed to attend additional Skype clinics. All patients who were followed up through Skype clinics after ITX/MMVTX received a questionnaire to measure their satisfaction with methods and technical aspects of videoconferencing as well as time/mode of traveling, travel expenses/costs, waiting time in outpatient clinic and patients' satisfaction. Mean travel distance to Oxford was 236 ± 168 miles, mean travel time was 277 ± 175 min, and mean travel cost was 200 ± 56 Great Britain Pounds. A total of 56% had to take time off work and/or find child/family care for the time spent in travel. These patients reported a satisfaction score of 4.38 ± 0.77 of 5 points as opposed to 2.88 ± 0.90 for attending the conventional outpatient clinic. Skype clinics have been proven successful and feasible in highly specialized fields like ITX in eligible patients.