bluuebunny/crossref_metadata_2025 huggingface dataset:
Entrepreneurial self-efficacy and intention: do entrepreneurial creativity and education matter?
Authors: Shahab Yasir , Chengang Ye , Arbizu Angel David , Haider Muhammad Jamal
Published: June 2018

Purpose

The purpose of this paper is to present a “moderated-mediation model” covering the nexus between entrepreneurial self-efficacy (ESE) and entrepreneurial intentions (EIs) by comparing an emerging market (China) and a mature market (Spain). By drawing on the theory of planned behaviour and self-efficacy, this study theorizes that entrepreneurial creativity (EC) and attitudes towards entrepreneurship (ATE) mediate the relationship between ESI and EIs; moreover, entrepreneurial education (EE) moderates these relationships.

Design/methodology/approach

This research employs a survey-based methodology and uses a 37-item questionnaire for a total sample of 808 student respondents from both countries. Further, the study employs the structural equation modelling and confirmatory factor analysis to test the proposed hypotheses.

Findings

The results indicate that EC and ATE positively mediate the relationship between ESI and EI. Further, with EE, individuals can efficiently develop EC to successfully nurture their EIs, regardless of their countries’ economic maturity.

Practical implications

Being able to identify the importance of EC and education for future entrepreneurs is of definite concern for all the business eco-system: from intentions of young entrepreneurs to governments; new levers, facilitators and approaches, e.g. policies will be able to be adopted.

Originality/value

This research provides valuable insights on the importance of EC and education in the determination of EIs in two very distinct markets for the first time.
The obstacles to cold chain implementation in developing countries: insights from Vietnam
Authors: Gligor David , Tan Albert , Nguyen Thi Nha Trang
Published: June 2018

Purpose

The purpose of this paper is to identify the obstacles that impede cold chain implementation in developing countries.

Design/methodology/approach

A grounded theory methodology was employed to execute this research. Eight semi-structured, in-depth interviews were conducted with senior managers in Vietnam. In addition, consistent with grounded theory guidelines, the authors utilized archival data to facilitate theory development.

Findings

The results of the analysis revealed a total of ten key obstacles: deficient professional skills, lack of quality and safety-control measures, high concentration of intermediaries, poor infrastructure, lack of information systems, high cost of installation and operation, inadequate education and training at farmer level, deficiency of standardization, lack of government support for local businesses and social norms.

Originality/value

Although many authors have recognized the enormity of food wastage and limited employment of cold chain in developing countries compared to developed countries, few efforts have been made to explore the reasons for the limited use of cold chains in developing countries. There are several noteworthy theoretical and managerial contributions that emerged from addressing this gap.
Witness interview strategy for critical incidents (WISCI)
Authors: Smith Kevin , Milne Becky
Published: June 2018

Purpose

High-profile critical incidents involving multiple witnesses, particularly terrorist attacks, have increased over the years. The purpose of this paper is to describe the components of a witness interview strategy for this type of investigation. Central to these cases is a need for a triage system which deals with a large number of witness/victim interviews that must be conducted fast time.

Design/methodology/approach

This paper was developed based on the experience of the authors who provide practical advice and support to these types of investigations and a dialogue with police interview advisers involved in developing this type of strategy.

Findings

A witness interview strategy for critical incidents involving multiple witnesses should be set within a framework that covers initial contact with the witnesses, the interview process and post-interview processes.

Practical implications

It is important that a witness interview strategy is developed for any critical incident involving multiple witnesses to ensure that what could otherwise be a chaotic process is effectively managed.

Originality/value

No other papers have been published that consider the development of witness interview-strategies for multiple-witnesses in critical incidents.
Understanding mobile augmented reality adoption in a consumer context
Authors: Paulo Maria Madalena , Rita Paulo , Oliveira Tiago , Moro Sérgio
Published: June 2018

Purpose

The purpose of this paper is to further our knowledge of what influences users to adopt mobile augmented reality in tourism (MART). A conceptual model is proposed, combining the extension of Unified Theory of Acceptance and Usage of Technology (UTAUT2) with task technology fit (TTF), to explain behavioural intention and user behaviour of MART adopters.

Design/methodology/approach

A questionnaire was completed by a sample of 335 respondents in Portugal. Both UTAUT2 and TTF were combined into a new model from which several hypotheses were drawn based upon the literature.

Findings

The results have shown that the model explains 72 per cent of the variance in behaviour intention to use MART and 45 per cent of the variance in user behaviour.

Originality/value

MART is becoming increasingly known to travellers as it provides the user diverse and useful information with a real relationship with the world. By studying behaviour and what influences consumers to use MART, this study aims to advance the research into new technologies in tourism.
Critical success factors of small and medium-sized enterprises in Palestine
Authors: Alfoqahaa Sam
Published: June 2018

Purpose

The purpose of this paper is to investigate the success of small and medium enterprises (SMEs) in Palestine, and thus to contribute to the existing knowledge on the critical success factors (CSFs) of SMEs in the Palestinian context, especially in the West Bank.

Design/methodology/approach

The study is comprised a survey of a convenience sample of 370 SMEs operating in the West Bank, Palestine. It uses a multiple regression analysis to examine the effect of a set of CSFs, namely, reputation of the brand, excellence of customer services, reliable delivery and product innovation on the success of SMEs.

Findings

The results show that brand reputation, excellence of customer of services and reliable delivery strongly influence SME success, while innovation is weakly associated with SME success. These results imply that success is tied to customers and competition more than to production, structures or finance. That is, reputable brands, excellent customer service and reliable delivery are means to success according to the results of this research.

Practical implications

The study emphasizes the need for Palestinian SMEs to maintain and develop their brand reputation, institutionalize customer service and develop its logistical systems and practices. Generally, the study suggests that there are specific investment areas for SMEs that can contribute to achieving success. Specifically, excellence in customer service was found to be the factor most linked to the success of SMEs, followed by reliable delivery and then by brand reputation and innovation.

Originality/value

While plenty of research has been done on what contributes to the failure or success of SMEs, research on CSFs for SMEs is limited. The study combines four CSFs not previously used in combination to model the successful performance of SMEs in general and in the Palestinian context in particular. Only some specific factors are critical to the success of SMEs and should be the focal point of SMEs’ efforts as long as they are consistent with their nature as small economic entities competing with big companies in small markets. Thus, instead of using general factors of SME success, the study explains how success becomes more possible through specifying areas for decision-making or activities for the entrepreneurs to undertake, keeping in mind that there is a mechanism by which these factors work together toward the success of the SME.
What explains student’s intentions to pursue a certified professional accountancy qualification?
Authors: Owusu Godfred Matthew Yaw , Obeng Victoria Asantewaa , Ofori Charles Gyamfi , Ossei Kwakye Teddy , Bekoe Rita Amoah
Published: June 2018

Purpose

This study examines the factors that explain Ghanaian business students’ intentions to pursue a Certified Professional Accounting (CPA) qualification.

Design/methodology/approach

The study uses survey method of research and mainly used questionnaires as data collection instrument to elicit information from the respondent group. Using a total of 641 business students from the University of Ghana Business School, a mixture of factor analysis and logistic regression analysis techniques was used in investigating the study objectives.

Findings

Results from the regression analysis demonstrate that students’ preference and beliefs about accounting professional qualification, academic major and grade point average are significantly associated with their intentions to pursue a CPA qualification. Moreover, majority of the sampled respondents (47.9 per cent) with the desire to pursue a CPA qualification prefer to be affiliated with the Association of Chartered Certified Accountants, 27.2 per cent prefer the Institute of Charted Accountant Ghana qualification, while only 7 per cent of the students prefer to be affiliated with the Chartered Institute of Management Accountant.

Research limitations/implications

The findings from this study have important implications for the various professional accountancy bodies, accounting educators and other stakeholders interested in promoting the choice of accounting as a career path among university students.

Practical implications

The results indicate that, as part of the broader strategy to increase the number of professional accountants in Ghana, there is the need to promote the study of accounting at the undergraduate level in the various universities in the country.

Originality/value

This study uniquely uses the behavioral decision theory to explain the dominant factors associated with students’ intentions to pursue a CPA qualification.
Brinkman-Forchheimer flow of SWCNT and MWCNT magneto-nanoliquids in a microchannel with multiple slips and Joule heating aspects
Authors: N.S. Shashikumar , B.J. Gireesha , Mahanthesh B. , B.C. Prasannakumara
Published: June 2018

Purpose

The microfluidics has a wide range of applications, such as micro heat exchanger, micropumps, micromixers, cooling systems for microelectronic devices, fuel cells and microturbines. However, the enhancement of thermal energy is one of the challenges in these applications. Therefore, the purpose of this paper is to enhance heat transfer in a microchannel flow by utilizing carbon nanotubes (CNTs). MHD Brinkman-Forchheimer flow in a planar microchannel with multiple slips is considered. Aspects of viscous and Joule heating are also deployed. The consequences are presented in two different carbon nanofluids.

Design/methodology/approach

The governing equations are modeled with the help of conservation equations of flow and energy under the steady-state situation. The governing equations are non-dimensionalized through dimensionless variables. The dimensionless expressions are treated via Runge-Kutta-Fehlberg-based shooting scheme. Pertinent results of velocity, skin friction coefficient, temperature and Nusselt number for assorted values of physical parameters are comprehensively discussed. Also, a closed-form solution is obtained for momentum equation for a particular case. Numerical results agree perfectly with the analytical results.

Findings

It is established that multiple slip effect is favorable for velocity and temperature fields. The velocity field of multi-walled carbon nanotubes (MWCNTs) nanofluid is lower than single-walled carbon nanotubes (SWCNTs)-nanofluid, while thermal field, Nusselt number and drag force are higher in the case of MWCNT-nanofluid than SWCNT-nanofluid. The impact of nanotubes (SWCNTs and MWCNTs) is constructive for thermal boundary layer growth.

Practical implications

This study may provide useful information to improve the thermal management of microelectromechanical systems.

Originality/value

The effects of CNTs in microchannel flow by utilizing viscous dissipation and Joule heating are first time investigated. The results for SWCNTs and MWCNTs have been compared.
Bulk and block holders herding behaviour
Authors: R. Ganesh , Gopal Naresh , S. Thiyagarajan
Published: June 2018

Purpose

The purpose of this paper is to examine industry herding among the institutional investors and to find whether their herding behaviour is intentional or unintentional.

Design/methodology/approach

The study uses Lakonishok et al. (1992) model to examine the presence of industry herding behaviour among institutional investors. To determine whether the herding observed is intentional or unintentional, herding measure is regressed with volatility, volume, beta and return. The period of the study is from 1 April 2005-31 March 2015.

Findings

The findings of the study showed that though institutional investors have herding tendency towards most of the industries, in the overall period industry herding was not significant. The herding found in some industrial sectors was linked to economic performance of those sectors in India during the period of study and hence the herding was unintentional in nature.

Research limitations/implications

This is the first attempt to study industry herding among institutional investors and their intent in Indian market ever since the country opened its market to foreign investors in a big way. Present study is limited to the use of only bulk/block data instead of the entire trading data for the period.

Originality/value

This study is the first attempt to investigate industry herding behaviour of institutional investors in the market using their bulk and block trading data. The herding observed in well performing industries has been shown to be unintentional and hence rational. The results indicate that the entry of big institutional investors, including foreign institutions into the Indian market has not destabilised the market by irrational herding.
Intransitivity increases plant functional diversity by limiting dominance in drylands worldwide
Authors: Saiz Hugo , Le Bagousse‐Pinguet Yoann , Gross Nicolas , Maestre Fernando T.
Published: June 2018

Biotic interactions are key determinants of plant community structure. Indirect interactions such as intransitivity (i.e., the absence of competitive hierarchies among species) have been hypothesized to benefit diversity within plant communities. However, their effect on functional diversity remains scarcely explored in real communities. Here, we develop a novel approach to infer intransitivity from plant spatial patterns and functional traits (height and specific leaf area) and quantify its effect on different components of plant diversity along environmental gradients in 100 drylands from all continents except Antarctica.

We first calculated the spatial association pattern for all perennials to infer competition between species. Trait values were used as a proxy of competitive hierarchies to infer the direction of these interactions. We used multiple regression models to evaluate how intransitivity responds to environmental variables (mean annual temperature and precipitation, precipitation seasonality, soil pH, sand content and woody cover). We also used confirmatory path analysis to evaluate the effects of intransitivity on species richness and evenness, trait dispersion and functional diversity.

Intransitivity mostly responded to climatic variables and significantly increased with precipitation scarcity and seasonality. We found that intransitivity had significant effects on functional diversity, mostly by promoting plant community evenness. However, the dominance of woody vegetation (steppes versus shrublands) modulated this effect.

Synthesis. Intransitivity increased the functional diversity of drylands, particularly under high rainfall seasonality, by limiting functionally dominant species. Our findings specify how intransitivity structures the functional diversity of dryland vegetation worldwide. Intransitivity may be particularly important in ecosystems where the availability of abiotic resources changes over time, thereby breaking down inherent competitive hierarchies between plant species. Neglecting intransitivity will bias our estimation of the impacts of biotic interactions on plant communities, a fundamental issue to fully understand how plant communities will respond to ongoing environmental changes.
Service delivery and intervention intensity for phonology‐based speech sound disorders
Authors: Sugden Eleanor , Baker Elise , Munro Natalie , Williams A. Lynn , Trivette Carol M.
Published: June 2018

Background

When planning evidence‐based intervention services for children with phonology‐based speech sound disorders (SSD), speech and language therapists (SLTs) need to integrate research evidence regarding service delivery and intervention intensity within their clinical practice. However, relatively little is known about the optimal intensity of phonological interventions and whether SLTs’ services align with the research evidence.

Aims

The aims are twofold. First, to review external evidence (i.e., empirical research evidence external to day‐to‐day clinical practice) regarding service delivery and intervention intensity for phonological interventions. Second, to investigate SLTs’ clinical practice with children with phonology‐based SSD in Australia, focusing on service delivery and intensity. By considering these complementary sources of evidence, SLTs and researchers will be better placed to understand the state of the external evidence regarding the delivery of phonological interventions and appreciate the challenges facing SLTs in providing evidence‐based services.

Methods & Procedures

Two studies are presented. The first is a review of phonological intervention research published between 1979 and 2016. Details regarding service delivery and intervention intensity were extracted from the 199 papers that met inclusion criteria identified through a systematic search. The second study was an online survey of 288 SLTs working in Australia, focused on the service delivery and intensity of intervention provided in clinical practice.

Main Contributions

There is a gap between the external evidence regarding service delivery and intervention intensity and the internal evidence from clinical practice. Most published intervention research has reported to provide intervention two to three times per week in individual sessions delivered by an SLT in a university clinic, in sessions lasting 30–60 min comprising 100 production trials. SLTs reported providing services at intensities below that found in the literature. Further, they reported workplace, client and clinician factors that influenced the intensity of intervention they were able to provide to children with phonology‐based SSD.

Conclusions & Implications

Insufficient detail in the reporting of intervention intensity within published research coupled with service delivery constraints may affect the implementation of empirical evidence into everyday clinical practice. Research investigating innovative solutions to service delivery challenges is needed to provide SLTs with evidence that is relevant and feasible for clinical practice.
Arbuscular mycorrhizal fungi stimulate organic phosphate mobilization associated with changing bacterial community structure under field conditions
Authors: Zhang Lin , Shi Ning , Fan Jiequn , Wang Fei , George Timothy S. , Feng Gu
Published: June 2018

The extraradical hyphae of arbuscular mycorrhizal fungi (AMF) harbour and interact with a microbial community performing multiple functions. However, how the AMF‐microbiome interaction influences the phosphorus (P) acquisition efficiency of the mycorrhizal pathway is unclear. Here we investigated whether AMF and their hyphal microbiome play a role in promoting organic phosphorus (P) mineralizing under field conditions. We developed an AMF hyphae in‐growth core system for the field using PVC tubes sealed with membrane with different size of pores (30 or 0.45 μm) to allow or deny AMF hyphae access to a patch of organic P in root‐free soil. AMF and their hyphae associated microbiome played a role in enhancing soil organic P mineralization in situ in the field, which was shown to be a function of the change in bacteria community on the hyphae surface. The bacterial communities attached to the AMF hyphae surface were significantly different from those in the bulk soil. Importantly, AMF hyphae recruited bacteria that produced alkaline phosphatase and provided a function that was absent from the hyphae. These results demonstrate the importance of understanding trophic interactions to be able to gain insight into the functional controls of nutrient cycles in the rhizosphere.
Casting a Wide Net for Innovation: Mediating Effect of R&D Human and Social Capital to Unlock the Value from Alliance Portfolio Diversity
Authors: Garcia Martinez Marian , Zouaghi Ferdaous , Sanchez Garcia Mercedes
Published: June 2018

This paper examines the performance effects associated with different alliance portfolio configurations in terms of geographical location and partner type. Based on these distinctions, the authors hypothesize that more diverse alliance portfolios enable firms to gain and exploit innovation opportunities. Additionally, the mediating effects of R&D human and social capital on the R&D alliance portfolio diversity–innovation performance relationship are explored. The authors reason that the absorptive capacity of R&D intellectual capital determines a firm's potential gains from highly diverse alliance portfolios. From panel data of manufacturing firms in Spain for the period 2008–2013, the results confirm the inverted U‐shaped relationship between alliance portfolio diversity and firm innovation performance, implying that both insufficient and excessive alliance portfolio diversity may be detrimental to firm innovativeness. Additionally, R&D human and social capital partially mediates the R&D alliance diversity–innovation performance relationship, emphasizing the importance of internal capabilities to leverage the benefits of highly diverse alliance portfolios. These findings add a dynamic dimension to the conceptualization of alliance portfolios and how firms create value by balancing explorative and exploitative alliances.
Smallholder participation in vegetable exports and age‐disaggregated labor allocation in Northern Tanzania
Authors: Benali Marwan , Brümmer Bernhard , Afari‐Sefa Victor
Published: June 2018

Modern agricultural supply chains have been playing an increasingly important role in developing countries and have had significant effects on rural labor markets. This article analyses the effects of smallholder farmer participation in export vegetable supply chains in Northern Tanzania on both household hired labor demand and off‐farm labor supply, using an age‐disaggregated approach. In our sample, neither separability nor exogeneity of smallholder farmer participation in export supply chains can be rejected. Hence, we apply lognormal double‐hurdle models and find that participation in export supply chains positively affects households’ decision to hire labor from all age groups. We also find that it increases the unconditional overall level of hired labor demand, while the age‐disaggregated analysis shows that these effects mostly benefit rural youth. However, our sample does not allow us to establish statistically significant evidence of an effect on household off‐farm labor supply although the point estimates point to nonnegligible positive effect sizes.
Are maize marketers averse to quality loss in supplies? A case study from Ghana
Authors: Bassey Nkoyo Etim , Kuhn Arnim , Storm Hugo
Published: June 2018

To ensure sustainable post‐harvest loss reduction, markets that are averse to quality loss and provide incentives for farmers to supply high quality produce are crucial. Such markets will be averse to quality loss, offering distinct prices and substantial rewards to farmers for the supply of quality produce. Farmers in sub‐Saharan Africa (SSA), where informal markets exist, have often assessed the rewards for the supply of quality produce as inadequate. Hence, this study investigates if intermediary buyers are actually indifferent to quality loss in supplies based on two scenarios—the informal market scenario and a hypothesized grade scenario. The analysis builds on survey data from marketers in two informal maize markets in Ghana. For the hypothesized grade scenario, random effect regression was used to examine the influence of marketer‐specific characteristics on premiums offered to farmers over different quality levels. The findings suggest that although informal markets seem not to adequately value loss reduction, investing in institutional infrastructures, such as grades and standards can change this. Furthermore, interaction among marketers and association participation positively influences the value marketers place on quality loss reduction. The result highlights the importance of standard grading systems and collaborating with market groups in minimizing quality loss.
Association ofABCG2polymorphisms with ischemic stroke in a Chinese population
Authors: Liu Tonghanyu , Jiang Feng , Liu Xin , Zhang Hongye , Wang Lefeng , Liu Wenzhi , Wang Xingyu
Published: June 2018

ATP‐binding cassette, superfamily G, member 2 (ABCG2) has been shown to play an important role in the development of ischemic stroke in European and African American populations. The aim of the present study is to test the hypothesis that there are associations betweenABCG2polymorphisms and ischemic stroke risk in a Chinese population. We conducted a case–control study including 967 participants with ischemic stroke and 939 stroke‐free controls. The rs2231137C > T and rs2231142G > T were genotyped using a TaqMan real‐time polymerase chain reaction assay. We found the rs2231137C > T and rs2231142G > T inABCG2were significantly associated with ischemic stroke (sex‐, age‐, BMI‐, SBP‐, DBP‐adjusted OR = 1.252; 95% CI, 1.035–1.515;P‐value = 0.021 and OR = 1.526; 95% CI, 1.085–2.146;P‐value = 0.015, respectively). By haplotype analyses, the haplotype T‐G still had a strongly significant association with ischemic stroke (OR = 0.806; 95% CI, 0.692–0.939;P‐value = 0.00568). Our findings identified the rs2231137C > T and rs2231142G > T polymorphisms of theABCG2as risk factors for ischemic stroke in a Chinese population.
End‐of‐life care of oncology inpatients: Are we getting it right?
Authors: Batten Monique , Nguyen Bella , Burke Brandon , Harryanto Hilman , Mitchell Imogen , Davis Alison
Published: June 2018

Aim

To examine the current patterns of end‐of‐life care of medical oncology patients dying in an Australian tertiary acute hospital setting in order to determine potential areas for improvement.

Methods

A retrospective observational study was undertaken of 295 consecutive adult medical oncology inpatients dying between 2010 and 2015. Charts were reviewed for evidence of (1) resuscitation plans, (2) acute interventions in the 48‐h period prior to death, (3) palliative care involvement and (4) recognition of the dying patient and comfort care plans.

Results

At the time of death, 98% of patients had a resuscitation plan, 71% of which were completed by the medical oncology team. Fifty‐nine percent of medical emergency team reviews occurred in patients without a documented resuscitation plan. Within 48 h of death, active interventions were still being given to 64% of patients in the total patient population. Comfort care plans were documented in 86% of patients; however, 62% of these were only documented within 48 h of death and 20% of patients with a documented comfort care plan still received noncomfort measures.

Conclusion

There was a high level of documented resuscitation plans, comfort care plans and recognition of dying. However, active interventions were common within 48 h of death, and comfort care plans and recognition of dying often occurred late. These data indicate a gap between documenting a resuscitation plan and providing timely and appropriate end‐of‐life care. Understanding the gaps in delivering appropriate care provides an opportunity for improving end‐of‐life care.
Role of serum biomarkers to optimise a validated clinical risk prediction tool for gestational diabetes
Authors: Abell Sally K. , Shorakae Soulmaz , Boyle Jacqueline A. , De Courten Barbora , Stepto Nigel K. , Teede Helena J. , Harrison Cheryce L.
Published: June 2018

Background

Clinical risk prediction tools for gestational diabetes (GDM) may be enhanced by measuring biomarkers in early pregnancy.

Aim

To evaluate a two‐step GDM risk prediction tool incorporating fasting glucose (FG) and serum biomarkers in early pregnancy.

Materials and methods

High molecular weight (HMW) adiponectin, omentin‐1 and interleukin‐6 (IL‐6) were measured at 12–15 weeks gestation in women with high risk of GDM from a randomised trial using a clinical risk prediction tool. GDM diagnosis (24–28 weeks) was evaluated using 1998 Australian Diabetes in Pregnancy (ADIPS) criteria and newer International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria. Associations between biomarkers and development of GDM were examined using multivariable regression analysis. Area under the receiver‐operator curve (AUC), sensitivity and specificity were calculated to determine classification ability of each model compared to FG and maternal characteristics.

Results

HMW adiponectin improved prediction of ADIPS GDM (AUC 0.85, sensitivity 50%, specificity 96.2%, P = 0.04), compared to FG and maternal factors (0.78, 35% and, 98.1%, respectively). HMW adiponectin <1.53 μg/mL further improved the model (AUC 0.87, sensitivity 75%, specificity 88.2%, P = 0.01). HMW adiponectin did not improve prediction of IADPSG GDM (AUC 0.84, sensitivity 64%, specificity 97.9%, P = 0.22) compared to FG and maternal factors (0.79, 56%, 93.8%). Omentin‐1 and IL‐6 did not significantly improve classification ability for GDM.

Conclusions

A two‐step approach combining FG and HMW adiponectin to a validated clinical risk prediction tool improved sensitivity and predictive ability for ADIPS GDM. Further research is required to enhance GDM prediction using IADPSG criteria for application in clinical practice.
In vivo affinity and target engagement in skin and blood in a first‐time‐in‐human study of an anti‐oncostatin M monoclonal antibody
Authors: Reid Juliet , Zamuner Stefano , Edwards Ken , Rumley Sally‐Anne , Nevin Katherine , Feeney Maria , Zecchin Chiara , Fernando Disala , Wisniacki Nicolas
Published: June 2018

Aims

The oncostatin M (OSM) pathway drives fibrosis, inflammation and vasculopathy, and is a potential therapeutic target for inflammatory and fibrotic diseases. The aim of this first‐time‐in‐human experimental medicine study was to assess the safety, tolerability, pharmacokinetics and target engagement of single subcutaneous doses of GSK2330811, an anti‐OSM monoclonal antibody, in healthy subjects.

Methods

This was a phase I, randomized, double‐blind, placebo‐controlled, single‐dose escalation, first‐time‐in‐human study of subcutaneously administered GSK2330811 in healthy adults (NCT02386436). Safety and tolerability, GSK2330811 pharmacokinetic profile, OSM levels in blood and skin, and the potential for antidrug antibody formation were assessed. The in vivo affinity of GSK2330811 for OSM and target engagement in serum and skin blister fluid (obtained via a skin suction blister model) were estimated using target‐mediated drug disposition (TMDD) models in combination with compartmental and physiology‐based pharmacokinetic (PBPK) models.

Results

Thirty subjects were randomized to receive GSK2330811 and 10 to placebo in this completed study. GSK2330811 demonstrated a favourable safety profile in healthy subjects; no adverse events were serious or led to withdrawal. There were no clinically relevant trends in change from baseline in laboratory values, with the exception of a reversible dose‐dependent reduction in platelet count. GSK2330811 exhibited linear pharmacokinetics over the dose range 0.1–6 mg kg–1. The estimated in vivo affinity (nM) of GSK2330811 for OSM was 0.568 [95% confidence interval (CI) 0.455, 0.710] in the compartmental with TMDD model and 0.629 (95% CI 0.494, 0.802) using the minimal PBPK with TMDD model.

Conclusions

Single subcutaneous doses of GSK2330811 were well tolerated in healthy subjects. GSK2330811 demonstrated sufficient affinity to achieve target engagement in systemic circulation and target skin tissue, supporting the progression of GSK2330811 clinical development.
Integrin β1 is an essential factor in vasculogenic mimicry of human cancer cells
Authors: Kawahara Ryota , Niwa Yuki , Simizu Siro
Published: June 2018

Vasculogenic mimicry (VM) formation by cancer cells is known to play a crucial role in tumor progression, but its detailed mechanism is unclear. In the present study, we focused on integrin β1 (ITGB1) and assessed the role of ITGB1 in VM formation. We used in vitro methods to seed cancer cells on Matrigel to evaluate the capability of VM formation. We carried out ITGB1 gene deletion using the CRISPR/Cas9 system, and these ITGB1‐knockout cells did not show a VM‐like network formation. Further, reintroduction of ITGB1 rescued VM‐like network formation in ITGB1‐knockout cells. In conclusion, ITGB1 is a critical factor in VM of human cancer cells, and inhibition of ITGB1 may be a novel therapeutic approach for malignant cancer.
Autophagy inhibition synergizes with calcium mobilization to achieve efficient therapy of malignant gliomas
Authors: Vu Ha Thi , Kobayashi Masahiko , Hegazy Ahmed M. , Tadokoro Yuko , Ueno Masaya , Kasahara Atsuko , Takase Yusuke , Nomura Naho , Peng Hui , Ito Chiaki , Ino Yasushi , Todo Tomoki , Nakada Mitsutoshi , Hirao Atsushi
Published: June 2018

Autophagy plays a critical role in tumorigenesis, but how autophagy contributes to cancer cells’ responses to chemotherapeutics remains controversial. To investigate the roles of autophagy in malignant gliomas, we used CRISPR/CAS9 to knock out the ATG5 gene, which is essential for autophagosome formation, in tumor cells derived from patients with glioblastoma. While ATG5 disruption inhibited autophagy, it did not change the phenotypes of glioma cells and did not alter their sensitivity to temozolomide, an agent used for glioblastoma patient therapy. Screening of an anticancer drug library identified compounds that showed greater efficacy to ATG5‐knockout glioma cells compared to control. While several selected compounds, including nigericin and salinomycin, remarkably induced autophagy, potent autophagy inducers by mTOR inhibition did not exhibit the ATG5‐dependent cytoprotective effects. Nigericin in combination with ATG5 deficiency synergistically suppressed spheroid formation by glioma cells in a manner mitigated by Ca2+ chelation or CaMKK inhibition, indicating that, in combination with autophagy inhibition, calcium‐mobilizing compounds contribute to efficient anticancer therapeutics. ATG5‐knockout cells treated with nigericin showed increased mitochondria‐derived reactive oxygen species and apoptosis compared to controls, indicating that autophagy protects glioma cells from mitochondrial reactive oxygen species‐mediated damage. Finally, using a patient‐derived xenograft model, we demonstrated that chloroquine, a pharmacological autophagy inhibitor, dramatically enhanced the efficacy of compounds selected in this study. Our findings propose a novel therapeutic strategy in which calcium‐mobilizing compounds are combined with autophagy inhibitors to treat patients with glioblastoma.
NLRP3 inflammasome: A likely target for the treatment of allergic diseases
Authors: Xiao Yichen , Xu Wenna , Su Wenru
Published: June 2018

Allergic diseases, such as asthma, rhinitis, dermatitis, conjunctivitis, and anaphylaxis, have recently become a global public health concern. According to previous studies, the NLRP3 inflammasome is a multi‐protein complex known to be associated with many inflammatory conditions. In response to allergens or allergen/damage‐associated molecular signals, NLRP3 changes its conformation to allow the assembly of the NLRP3 inflammasome complex and activates caspase‐1, which is an evolutionarily conserved enzyme that proteolytically cleaves other proteins, such as the precursors of the inflammatory cytokines IL‐1β and IL‐18. Subsequently, active caspase‐1 cleaves pro‐IL‐1 and pro‐IL‐18. Recently, accumulating human and mouse experimental evidence has demonstrated that the NLRP3 inflammasome, IL‐1β, and IL‐18 are critically involved in the development of allergic diseases. Furthermore, the application of specific NLRP3 inflammasome inhibitors has been demonstrated in animal models. Therefore, these inhibitors may represent potential therapeutic methods for the management of clinical allergic disorders. This review summarizes findings related to the NLRP3 inflammasome and its related factors and concludes that specific NLRP3 inflammasome inhibitors may be potential therapeutic agents for allergic diseases.
Exploring what motivates and sustains support group engagement amongst young people with allergies: A qualitative study
Authors: Jones C. J. , Sommereux L. A. , Smith H. E.
Published: June 2018

Background

Positive self‐care behaviours are more likely in young people who engage with allergy support groups, but reasons for this association are not well understood.

Objectives

This study explored how and why young people engage with allergy support groups to identify what activities and resources are beneficial.

Methods

In‐depth, semistructured interviews were conducted with young people aged 12‐21 years who reported engaging with allergy support groups (in person or online). Interviews were audiotaped, transcribed verbatim and analysed using thematic content analysis.

Results

The 21 participants had a range of allergies; initially, most joined support groups on suggestion of their parent/carer although older participants sought groups independently. Feeling included and sharing experiences with people with similar problems/challenges were highly valued. Through membership, young people reported improved self‐esteem and confidence in both managing their allergies and lives generally. Information, such as allergy alerts and hard‐hitting video campaigns, were reported to positively influence adherence to self‐care behaviours such as carrying medication. Participants wanted greater availability of allergy support groups, and higher profiles in health care and educational settings, as well as through social media.

Conclusions and Clinical Relevance

Participants valued the psychological and practical support of networking with others with allergies, and described how membership improved their confidence. This study also provides insight into the ways support groups improve young people's adherence to medical advice and positive self‐care behaviours; participants responded well to hard‐hitting video campaigns which appeared to emphasize the severity and susceptibility of anaphylaxis. Participants identified the need for more active promotion of support groups amongst young people and their clinicians, as well as making them available in more localities.
Preconception folic acid supplementation use and the occurrence of neural tube defects in Japan: A nationwide birth cohort study of the Japan Environment and Children's Study
Authors: Nishigori Hidekazu , Obara Taku , Nishigori Toshie , Ishikuro Mami , Sakurai Kasumi , Hoshiai Tetsuro , Saito Masatoshi , Fujiwara Ikuma , Arima Takahiro , Nakai Kunihiko , Kuriyama Shinichi , Mano Nariyasu , Metoki Hirohito , Yaegashi Nobuo ,   Japan Environment & Children's Study Group
Published: June 2018

We evaluated the relationship between preconception folic acid supplementation and the occurrence of neural tube defects (NTDs) in offspring, using data from the Japan Environment and Children's Study (a nationwide prospective birth cohort study) database. Of 92 269 participants with single pregnancies, 74 cases (offspring or fetuses) had NTDs, including 32 cases of spina bifida, 24 cases of anencephaly, and 19 cases of encephalocele. A total of 7634 participants (8.27%) used preconception folic acid supplementation, and of these, 621 (0.67%) also took in dietary folic acid at ≥480 μg/day. Multivariate logistic regression analyses demonstrated no association between preconception folic acid supplementation and NTDs in offspring or fetuses (odds ratio [OR] 0.622; 95% confidence interval [CI]: 0.226‐1.713). Moreover, the participants who combined preconception folic acid supplement use with dietary folic acid intake ≥480 μg/day demonstrated no incidence of NTDs in offspring or fetuses. Our analysis is limited by the absence of the data on the daily amount of supplementary folic acid intake, requiring careful attention to the interpretation. Additional surveys are required in Japan to resolve those limitations for further comprehensive assessment.
Direct activation of tachykinin receptors within baroreflex afferent pathway and neurocontrol of blood pressure regulation
Authors: Yuan Mei , Ma Mei‐Na , Wang Ting‐Yu , Feng Yan , Chen Pei , He Chao , Liu Sijie , Guo Yun‐Xia , Wang Yue , Fan Yao , Wang Lu‐Qi , E Xiao‐Qiang , Qiao Guo‐Fen , Li Bai‐Yan
Published: June 2018

Aim

Substance P (SP) causes vasodilation and blood pressure (BP) reduction. However, the involvement of tachykinin receptors (NKRs) within baroreflex afferent pathway in SP‐mediated BP regulation is largely unknown.

Methods

Under control and hypertensive condition, NKRs’ expressions were evaluated in nodose (NG) and nucleus of tractus solitary (NTS) of male, female, and ovariectomized (OVX) rats; BP was recorded after microinjection of SP and NKRs agonists into NG; Baroreceptor sensitivity (BRS) was tested as well.

Results

Immunostaining and immunoblotting data showed that NK1R and NK2R were estrogen‐dependently expressed on myelinated and unmyelinated afferents in NG. A functional study showed that BP was reduced dose‐dependently by SP microinjection, which was more dramatic in males and can be mimicked by NK1R and NK2R agonists. Notably, further BP elevation and BRS dysfunction were confirmed in desoxycorticosterone acetate (DOCA)‐salt model in OVX compared with DOCA‐salt model in intact female rats. Additionally, similar changes in NKRs’ expression in NG were also detected using DOCA‐salt and SHR. Compared with NG, inversed expression profiles of NKRs were also found in NTS with either gender.

Conclusion

The estrogen‐dependent NKRs’ expression in baroreflex afferent pathway participates at least partially in sexual‐dimorphic and SP‐mediated BP regulation under physiological and hypertensive conditions.
How the Abstract Becomes Concrete: Irrational Numbers Are Understood Relative to Natural Numbers and Perfect Squares
Authors: Patel Purav , Varma Sashank
Published: June 2018

Mathematical cognition research has largely emphasized concepts that can be directly perceived or grounded in visuospatial referents. These include concrete number systems like natural numbers, integers, and rational numbers. Here, we investigate how a more abstract number system, the irrationals denoted by radical expressions like , is understood across three tasks. Performance on a magnitude comparison task suggests that people interpret irrational numbers (specifically, the radicands of radical expressions) as natural numbers. Strategy self‐reports during a number line estimation task reveal that the spatial locations of irrationals are determined by referencing neighboring perfect squares. Finally, perfect squares facilitate the evaluation of arithmetic expressions. These converging results align with a constellation of related phenomena spanning tasks and number systems of varying complexity. Accordingly, we propose that the task‐specific recruitment of more concrete representations to make sense of more abstract concepts (referential processing) is an important mechanism for teaching and learning mathematics.
Probing Representations of Gymnastics Movements: A Visual Priming Study
Authors: Calmels Claire , Elipot Marc , Naccache Lionel
Published: June 2018

In this study, we designed a visual short‐term priming paradigm to investigate the mechanisms underlying the priming of movements and to probe movement representations in motor experts and matched controls. We employed static visual stimuli that implied or not human whole‐body movements, that is, gymnastics movements and static positions. Twelve elite female gymnasts and twelve matched controls performed a speeded two‐choice response time task. The participants were presented with congruent and incongruent prime‐target pairs and had to decide whether the target stimulus represented a gymnastics movement or a static position. First, a visual priming effect was observed in the two groups. Second, a stimulus–response rote association could not easily account for our results. Novel primes never presented as targets could also prime the targets. Third, by manipulating three levels of prime‐target relations in moving congruent pairs, we demonstrated that the more similar prime‐target pairs, the greater the facilitation in target. Lastly, gymnastics motor expertise impacted on priming effects.
Alcohol industry involvement in science: A systematic review of the perspectives of the alcohol research community
Authors: McCambridge Jim , Mialon Melissa
Published: June 2018

Issues

Alcohol companies have recently invested large sums of money in answering research questions to which they have clear vested interests in the outcomes. There have been extensive concerns about corporate influence on public health sciences, following the experience with the tobacco industry.

Approach

This systematic review aims to investigate the perspectives of researchers on the activities of alcohol industry actors in relation to science, in order to guide future research. All data published in peer‐reviewed journals (including commentaries, opinion pieces, editorials and letters as well as research reports) were eligible for inclusion. This analysis focuses on the manifest rather than latent content of the articulated views, and accordingly adopts a thematic analysis using an inductive approach to the generation of themes.

Key Findings

There are serious concerns identified in three main areas, principally defined by where the impacts of industry scientific activities occur; on evidence informed policy making (instrumental uses of research by industry actors), on the content of the scientific evidence base itself (industry funding as a source of bias); and on the processes of undertaking research (transgressions of basic scientific norms). There are also opposing views which provide a useful critique. The evidence‐base on the validity of all concerns has been slow to develop.

Implications

The concerns are extensive, longstanding and unresolved and high quality investigations are needed.

Conclusion

This study informs the detailed content of the research needed to address the concerns identified here.