bluuebunny/crossref_metadata_2025 huggingface dataset:
Order effects and multi-city visits: tour guides’ perspectives
Authors: Zare Samira , Pearce Philip
Published: March 2018

Purpose

The purpose of this paper is to examine the influence of the order in which a set of cities are visited to ascertain the effects of position on group tourists’ recall and evaluations.

Design/methodology/approach

Using a questionnaire, the views of highly experienced tour guides were analysed to provide preliminary insights about the likely occurrence of position effects. The topic was studied in Iran where a natural variation in the order of visiting cities on guided tours exists.

Findings

Credible and consistent evidence was found for the perceived effects of recency when considering tourists’ recall and evaluations. In particular, the influence was seen as clearly enhancing the recall and positive evaluation for the most high profile cities in the set of visited locations.

Research limitations/implications

Replications of the position effect in other countries and for other kinds of tourism cities needs to be pursued, desirably by direct assessments of tourist’ views to buttress the present views held by guides.

Practical implications

Designing itineraries by making imaginative use of the effects of order on the tourists’ sequence of city visits should facilitate the memorability of destinations for tourists and benefit businesses.

Originality/value

Empirical evidence about order effects in multi-city tour itineraries has never been established. The study provides foundation evidence for such influences through a non-reactive and naturalistic assessment by tour guides who are in contact with varied itineraries and who regularly consider the experiences of diverse and large numbers of tourists.
Clique and elite: inter-organizational knowledge sharing across five star hotels in the Saudi Arabian religious tourism and hospitality industry
Authors: Idrees Inaam Altayeb , Vasconcelos Ana Cristina , Ellis David
Published: March 2018

Purpose

The purpose of this study is to offer a theoretical and practical explanation for the nature and reasons for inter-organizational knowledge sharing across an informal clique of competing five-star hotels in the Saudi Arabian religious tourism and hospitality industry.

Design/methodology/approach

The methodology is an adapted form of the grounded theory approach deploying a four-stage research design using qualitative interviews with key players in the industry to inform the analysis of the knowledge sharing approaches.

Findings

The findings illustrate the features of the knowledge sharing approaches across the five-star hotels studied. In particular, the findings highlight the existence of a cooperative-competitive tension in the relationships and knowledge sharing between the hotels. This illustrates the existence of a tacit strategy that cooperation can lead to long-term benefits for the competitor hotels.

Originality/value

The study is unique in its focus on the cooperative-competitive tension of five-star hotels in the Saudi Arabian religious tourism and hospitality industry and on this influence on the inter-organizational knowledge sharing across hotels within an oligopolistic market structure. The study also has value in using elements of oligopoly theory and of game theory, particularly, the prisoner’s dilemma, in explaining how inter-organizational knowledge sharing occurs within this market context.
Servicization with skill premium in the digital economy
Authors: Yoon Sang-Chul
Published: March 2018

Purpose

The purpose of this paper is to examine an endogenous growth model, as a component of a broader study of servicization with skill premium and its policy implications in the evolving digital economy.

Design/methodology/approach

This paper develops a two-sector endogenous growth model which allows for the observed characteristics of digitally empowered structural changes. Specifically, the driving force of economic growth is the expanding variety of intermediate services as a consequence of innovation in services. The introduction of new intermediate services specifically contributes to total factor productivity in the production of service sector, and thus an uneven growth path with skill premium toward a service economy generally exists.

Findings

The principal finding of this paper is that the digitally empowered expanding variety of intermediate services due to innovation contributes significantly to total factor productivity in the production of service sector, and thus a servicization with skill premium generally exists along a steady-state path. In addition, this paper derives an optimal innovation policy to rule out the market failures due to innovation externality and market power in monopolistic competition conditions, and shows the Rybczynski effects of exogenous endowment changes in the evolving digital economy.

Originality/value

The principal contribution of this paper is to determine how unbalanced endogenous growth along a steady-state path is linked with a service economy with skill premium in the evolving digital economy. In addition to this analysis, this paper provides policy implications – namely, that a positive but finite innovation subsidy can achieve the social optimum in the digital economy, and that an exogenous increase in high-skilled labor can speed up a digitally empowered economic growth.
Flying asset
Authors: Martinetti Alberto , Schakel Erik Jan , van Dongen Leo A.M.
Published: March 2018

Purpose

The purpose of this paper is to create a framework to provide a scalable maintenance program for unmanned aircraft systems (UAS) in order to choose the most suitable and feasible maintenance strategy in terms of reliability.

Design/methodology/approach

The paper opted for a reliability-centered maintenance-based approach to develop the framework using a UAS as the starting point of the research. A linear and user-friendly design of the methodology based on a Boolean flowchart was chosen in order to lead the analyst through the process avoiding as much as possible subjectivity decision-making issues. Finally, the framework was, on the component level, performed by a UAS company gathering feedback on its applicability.

Findings

An agile and structured decision-making framework for developing scalable maintenance program of UAS is provided. The proposed solution gives the opportunity to tailor the maintenance strategy to the technical characteristics, considering not only the single component but also situations and conditions in which the machine will operate.

Research limitations/implications

Because of the chosen research approach, the framework is potentially applicable to every UAS. A first trial of the method was run on a multirotor vehicle equipped with eight electric brushless motors. Further studies focused on different UAS will be mandatory in order to obtain comparable and robust findings and a reliable approach.

Practical implications

This study offers a different scheme to elaborate a specific maintenance solution related to the characteristics of the system. It strives to remedy the drawbacks of the traditional approach for a manned aircraft not completely suitable for systems with such different functions, features and tasks. The authors believe that the method presented in this paper will provide a new selection tool for choosing maintenance actions based on the features of the UAS.

Originality/value

This paper provides a new and usable solution to include the maintenance actions in the management of pioneering products. In spite of the maintenance program representing an essential aspect to provide reliable assets, frameworks to create programs and to help manufacturers and users are still difficult to find or to apply to different UAS. This gap enhances the misunderstanding that the maintenance is not required or essential for the unmanned aircrafts management.
Trade credit in times of crisis: evidence from European SMEs
Authors: Bussoli Candida , Marino Francesca
Published: March 2018

Purpose

The purpose of this paper is to investigate the use of trade credit in a sample of small and medium enterprises in Europe, before and after the outbreak of the subprime financial crisis and the sovereign debt crisis (2006-2013). This study aims to verify whether trade credit is an alternative source of funding compared to other sources of financing. In addition, it tests whether firms that grant extended payment terms to their customers demand delayed accounts payable terms from their suppliers.

Design/methodology/approach

The empirical analysis is conducted on a sample of European SMEs that were observed over the period immediately before and after the outbreak of the subprime crisis (2008) and the sovereign debt crisis (2010-2011). A panel data analysis is conducted using the generalized method of moment.

Findings

The results suggest that SMEs with a high probability of insolvency use trade credit more extensively. Distressed and weaker SMEs are less able to match accounts receivable to accounts payable. Finally, the evidence suggests that during the financial crises, the substitution hypothesis is weakened and liquidity shocks are propagated through trade credit channels.

Originality/value

This study contributes to the extant literature as very few studies have analyzed intercompany financing for European SMEs during periods of financial crisis. The results suggest that supporting trade credit channels, through timely injections of liquidity to companies, could reduce the impact of both financial and intercompany credit crunch on SMEs.
Imagining with the body in analytical psychology. Movement as active imagination: an interdisciplinary perspective from philosophy and neuroscience
Authors: Deligiannis Ana
Published: March 2018

This article explores how the body and imagination operate as pathways of knowledge through the use of Movement as Active Imagination in clinical practice. This method activates the transcendent function, thus encouraging new therapeutic responses. A philosophical perspective (Spinoza, Nietzsche, Merleau‐Ponty) and some concepts from neuroscience (embodied cognition, somatic markers, image schema, mirror neurons, neuronal plasticity) will accompany us throughout this work, illustrated with a clinical vignette. Three levels of integration: 1) body, 2) body‐emotion, 3) body‐emotion‐imagination are proposed: these mark a progressive sense of articulation and complexity. Finally the relation between creativity and neuronal plasticity will be considered.
Overexpression of long non‐coding RNA KCNQ1OT1 is related to good prognosis via inhibiting cell proliferation in non‐small cell lung cancer
Authors: Sun Xiao , Xin Yanlu , Wang Maolong , Li Shicheng , Miao Shuncheng , Xuan Yunpeng , Wang Yuanyong , Lu Tong , Liu Jia , Jiao Wenjie
Published: March 2018

Background

Lung cancer (LC) is the most common malignancy in the world. Many long non‐coding RNAs (lncRNAs) have been reported to be associated with LC; however, the function of KCNQ1OT1 in LC requires exploration.

Methods

We conducted in silico analysis with data from The Cancer Genome Atlas to investigate the association between KCNQ1OT1 and LC. A Kaplan–Meier plotter was used to analyze the function of KCNQ1OT1 on LC patient prognosis. Quantitative reverse transcription‐PCR (qRT‐PCR) was performed to confirm previous results. An A549 lung cancer cell was transfected with pcDNA‐KCNQ1OT1, and methyl thiazolyl tetrazolium assay was performed to investigate the function of KCNQ1OT1 on cell proliferation. in vivo assay was performed with nude mice.

Results

Bioinformatics analysis and qRT‐PCR indicated that KCNQ1OT1 expression was higher in stage I LC patients (P < 0.01), and survival analysis showed that high expression of KCNQ1OT1 in LC patients was associated with better prognosis (P < 0.05). qRT‐PCR showed a negative correlation between KCNQ1OT1 and Ki67 expression and tumor size (P < 0.01), which indicated that KCNQ1OT1 is associated with tumor growth in LC. There was no significant correlation between KCNQ1OT1 level and lymph node metastasis (P > 0.05). KCNQ1OT1 overexpression significantly inhibited cell proliferation and tumor growth in vitro and in vivo (P < 0.05).

Conclusion

Our preliminary data showed that KCNQ1OT1 is overexpressed in early stage LC and is correlated with better prognosis in LC patients, possibly by suppressing cell proliferation.
Trends in the incidence rate of lung cancer by histological type and gender in Sichuan, China, 1995–2015: A single‐center retrospective study
Authors: Zhang Xiaoxuan , Wu Li , Xu Yong , Zhang Benxia , Wu Xueqian , Wang Yongsheng , Pang Zongguo
Published: March 2018

Background

In recent years, lung cancer incidence has been increasing; however the impact of different histological types of lung cancer is not yet clear.

Methods

Trends in the lung cancer incidence rate by histological type were examined based on data of 36 658 primary lung cancer patients from West China Hospital between 1995 and 2015.

Results

The most common histological type of lung cancer in our hospital was adenocarcinoma (ADC) in both genders, followed by squamous cell carcinoma (SQCC), and small cell carcinoma (SCLC), which is consistent with general worldwide trends. The proportion of young patients with SCLC showed a downward trend. In the overall population with lung cancer, the number of elderly patients with lung cancer increased significantly, while the proportion of elderly patients increased gradually. The mean age at diagnosis also increased. The number of women with ADC increased sharply in recent years, especially in young patients, and the incidence rate in women is now greater than in men.

Conclusion

Significant increases in the number of patients with ADC and the rate of lung cancer in women over recent years were observed, indicating that research on the pathogenesis of disease in these patients is urgent.
Pitching research: ‘qualitative cousins’ and the ‘extended family’
Authors: Faff Robert
Published: March 2018

This study has two related goals – one very specific and one more general. The specific goal is to constructively engage with Lodhia (2017) on the issue of whether and to what extent ‘qualitative cousins’ are well served by Faff's (2015) original pitching research (PR) template. Using this ‘cousins’ focus as a primer, the more general goal is to update the agenda created by Faff (2015) and in so doing, explore the ‘extended family’ of PR work/resources now available.
Water and cattle shape habitat selection by wild herbivores at the edge of a protected area
Authors: Valls‐Fox H. , Chamaillé‐Jammes S. , de Garine‐Wichatitsky M. , Perrotton A. , Courbin N. , Miguel E. , Guerbois C. , Caron A. , Loveridge A. , Stapelkamp B. , Muzamba M. , Fritz H.
Published: March 2018

Understanding the spatiotemporal dynamics of human‐wildlife interfaces is important for the sustainable management of protected areas and wildlife conservation. We investigated the drivers of domestic and wild herbivore habitat selection at the edge of an unfenced protected area adjacent to Hwange National Park, Zimbabwe. We used GPS data to quantify the movement patterns of elephant bulls, buffalo and cattle at multiple scales and according to seasonal changes of surface water availability. Cattle, elephant and buffalo prefer open grassland habitats found close to water but elephant and buffalo avoid cattle differently. During the rainy season, cattle enter the protected area daily; buffalo avoid cattle completely at the home range scale, whereas elephant bulls avoid cattle at finer scales by favoring temporal niche shift. Elephant bulls avoid direct encounters with cattle (or people) during the day but come closer to the boundary and to water at night when cattle are kept in enclosures close to the homesteads. During the dry season, when cattle range further into the protected area in search of forage, buffalo and cattle spatial overlap increases as water dependence takes precedence over avoidance. Elephant bulls range closer to the boundary at night and increase the number of excursions into the Communal Area. Cattle herding creates a buffer zone between wildlife areas and human settlements because wild herbivores strongly avoid livestock and people. However, avoidance only lasts as long as resources are abundant. Our study suggests that long‐term planning of both artificial water provisioning and traditional cattle herding practices could help maintaining spatial segregation and thus mitigate conservation conflicts such as pathogen transmission, crop raiding or livestock depredation.
Pharmacogenetics of Dopamine β‐Hydroxylase in cocaine dependence therapy with doxazosin
Authors: Zhang Xuefeng , Nielsen David A. , Domingo Coreen B. , Shorter Daryl I. , Nielsen Ellen M. , Kosten Thomas R.
Published: March 2018

The α1‐adrenergic antagonist, doxazosin, has improved cocaine use disorder (CUD) presumably by blocking norepinephrine (NE) stimulation and reward from cocaine‐induced NE increases. If the NE levels for release were lower, then doxazosin might more readily block this NE stimulation and be more effective. The NE available for release can be lower through a genetic polymorphism in dopamine β‐hydroxylase (DBH) (C‐1021T, rs1611115), which reduces DβH's conversion of dopamine to NE. We hypothesize that doxazosin would be more effective in CUD patients who have these genetically lower DβH levels. This 12‐week, double‐blind, randomized, placebo‐controlled trial included 76 CUD patients: 49 with higher DβH levels from the DBH CC genotype and 27 with lower DβH levels from T‐allele carriers (CT or TT). Patients were randomized to doxazosin (8 mg/day, N = 47) or placebo (N = 29) and followed with thrice weekly urine toxicology and once weekly cognitive behavioral psychotherapy. Cocaine use was reduced at a higher rate among patients in the doxazosin than in the placebo arm. We found significantly lower cocaine use rates among patients carrying the T‐allele (CT/TT) than the CC genotype. The percentage of cocaine positive urines was reduced by 41 percent from baseline in the CT/TT group with low DβH and NE levels, as compared with no net reduction in the CC genotype group with normal DβH and NE levels. The DBH polymorphism appears play an important role in CUD patients' response to doxazosin treatment, supporting a pharmacogenetic association and potential application for personalized medicine.
Examining clinicians’ perceptions of head and neck cancer (HNC) information
Authors: Jabbour Joe , Wykes James , Milross Chris , Sundaresan Puma , Ebrahimi Ardalan , Shepherd Heather L. , Dhillon Haryana M. , Clark Jonathan R.
Published: March 2018

Background

Providing appropriate educational resources to patients with head and neck cancer (HNC) is important but challenging. The aim of this study was to determine Australian clinicians’ perceptions of currently used HNC information resources.

Methods

A purpose‐designed questionnaire was disseminated electronically to clinician members of the Australian and New Zealand Head and Neck Cancer Society (ANZHNCS) and The Australian Society of Otolaryngology Head and Neck Surgery (ASOHNS).

Results

Of the 648 clinicians invited, 112 responded to the survey (17.3% response rate). Overall, 85% utilized written information as their primary mode of patient education and 49% received information on treatment details. Areas for improvement include information provision, pain management, emerging risk factors, survivorship and side effects. The majority (66%) of clinicians had a preference for internet patient education materials.

Conclusions

Clinicians predominantly utilized written HNC information rather than multimedia or interactive resources. However, they expressed the desire to be able to deliver HNC information resources via an internet‐based platform covering the psychosocial effects of treatment.
Readmissions for surgical site infections following caesarean section
Authors: El‐Achi Vanessa , Wan King Man , Brown James , Marshall Drew , McGee Therese
Published: March 2018

This retrospective study was conducted to identify the incidence and characteristics associated with readmissions for surgical site infections following caesarean section in a tertiary hospital from 2012 to 2015. Of 6334 patients who underwent caesarean section, 165 (2.6%) were readmitted, most commonly for surgical site infection (25.5%, n = 42). Thirty‐seven of these patients (88%) had an emergency caesarean compared to five (12%) following an elective caesarean section. Of the women with surgical site infections, 69% were overweight and 14% had diabetes. Emergency caesarean sections were responsible for the majority of readmissions, particularly in women with co‐morbidities that predisposed them to infection.
EAA clinical guideline on management of bone health in the andrological outpatient clinic
Authors: Rochira V. , Antonio L. , Vanderschueren D.
Published: March 2018

Male osteoporosis is now a well‐recognized medical disorder with established clinical guidelines for both diagnosis and management. Prevention as well as management of osteoporosis in men consulting the andrological outpatient clinic because of low testosterone, however, is not well established. This gap of knowledge is—at least partly—explained by the controversy with respect to the threshold of testosterone needed for skeletal maintenance. However, testosterone deficiency may be clearly associated with bone loss as well as frailty in men. If anything, andrologists should therefore be aware of the potential silent presence of osteoporosis in men with confirmed hypogonadism. Therefore, the management of patients with potential hypogonadism should include a complete bone health assessment, besides clinical and biochemical evaluation of gonadal status. Such bone health assessment should include specific items in medical history and physical examination related to fracture risk. Furthermore, dual‐energy absorptiometry is indicated to evaluate fracture risk in men with confirmed clinical hypogonadism. Regarding treatment, besides general measures to prevent or manage male osteoporosis testosterone replacement can be initiated (as described in guidelines for hypogonadism), but data on its efficacy in preventing fractures are lacking. Thus, additional anti‐osteoporotic may be needed, especially in men with very low testosterone who are at high risk of bone loss and/or in men not able to receive testosterone replacement.
Optical coherence tomography angiography in patients with retinitis pigmentosa who have normal visual acuity
Authors: Takagi Seiji , Hirami Yasuhiko , Takahashi Masayo , Fujihara Masashi , Mandai Michiko , Miyakoshi Chisato , Tomita Goji , Kurimoto Yasuo
Published: March 2018

Purpose

To investigate flow area changes measured using optical coherence tomography angiography (OCTA; RTVue XR Avanti®) in patients with retinitis pigmentosa (RP) with preserved visual acuity (VA).

Methods

This was an age‐ and refraction‐matched case–control study. Consecutive patients with a best‐corrected visual acuity (BCVA) of ≥20/20 and normal subjects were recruited. Fifty eyes (32 patients) and 22 eyes (12 controls) were included. The flow area and foveal avascular zone (FAZ) were measured in both superficial and deep layers within a 3 × 3 mm central area of the fovea. Association between OCTA parameters and the length of the inner segment ellipsoid (ISe) and external limiting membrane (ELM), the area without abnormal fluorescence in fundus autofluorescence (normal FAF area ratio) and the area of I‐2e of the Goldmann perimeter were analysed using mixed‐effects regression analysis.

Results

Foveal avascular zones were significantly smaller in patients with RP than in controls in superficial (p = 0.004) but not in deep layers (p = 0.25). The flow area in superficial (p = 0.007) and deep layers (p = 0.004) was significantly smaller in patients with RP than in controls. In patients with RP, flow areas in the superficial layers, but not in the deep layers, were significantly associated with the lengths of ISe (p = 0.001) and ELM (p = 0.002) and the I‐2e area (p = 0.036), but not with the normal FAF area ratio (p = 0.399).

Conclusion

Optical coherence tomography angiography (OCTA)‐measured flow area in superficial layers gradually reduced with RP progression and may be a useful parameter of RP pathogenesis.
Wisdom of the social versus non‐social crowd in face identification
Authors: Jeckeln Géraldine , Hahn Carina A. , Noyes Eilidh , Cavazos Jacqueline G. , O'Toole Alice J.
Published: March 2018

Face identification is more accurate when people collaborate in social dyads than when they work alone (Dowsett & Burton, 2015, Br. J. Psychol., 106, 433). Identification accuracy is also increased when the responses of two people are averaged for each item to create a ‘non‐social’ dyad (White, Burton, Kemp, & Jenkins, 2013, Appl. Cogn. Psychol., 27, 769; White et al., 2015, Proc. R. Soc. B Biol. Sci., 282, 20151292). Does social collaboration add to the benefits of response averaging for face identification? We compared individuals, social dyads, and non‐social dyads on an unfamiliar face identity‐matching test. We also simulated non‐social collaborations for larger groups of people. Individuals and social dyads judged whether face image pairs depicted the same‐ or different identities, responding on a 5‐point certainty scale. Non‐social dyads were constructed by averaging the responses of paired individuals. Both social and non‐social dyads were more accurate than individuals. There was no advantage for social over non‐social dyads. For larger non‐social groups, performance peaked at near perfection with a crowd size of eight participants. We tested three computational models of social collaboration and found that social dyad performance was predicted by the decision of the more accurate partner. We conclude that social interaction does not bolster accuracy for unfamiliar face identity matching in dyads beyond what can be achieved by averaging judgements.
Impact of hospital volume and surgeon volume on robot‐assisted partial nephrectomy outcomes: a multicentre study
Authors: Peyronnet Benoît , Tondut Lauranne , Bernhard Jean‐Christophe , Vaessen Christophe , Doumerc Nicolas , Sebe Philippe , Pradere Benjamin , Guillonneau Bertrand , Khene Zine‐Eddine , Nouhaud Francois‐Xavier , Brichart Nicolas , Seisen Thomas , Alimi Quentin , Beauval Jean‐Baptiste , Mathieu Romain , Rammal Adham , de la Taille Alexandre , Baumert Herve , Droupy Stéphane , Bruyere Franck , Rouprêt Morgan , Mejean Arnaud , Bensalah Karim ,   The members of the French Committee of Urologic Oncology (CCAFU)
Published: March 2018

Objective

To assess the impact of hospital volume (HV) and surgeon volume (SV) on perioperative outcomes of robot‐assisted partial nephrectomy (RAPN).

Patients and Methods

All consecutive patients who underwent a RAPN from 2009 to 2015, at 11 institutions, were included in a retrospective study. To evaluate the impact of HV, we divided RAPN into four quartiles according to the caseload per year: low HV (<20/year), moderate HV (20–44/year), high HV (45–70/year), and very high HV (>70/year). The SV was also divided into four quartiles: low SV (<7/year), moderate SV (7–14/year), high SV (15–30/year), and very high SV (>30/year). The primary endpoint was the Trifecta defined as the following combination: no complications, warm ischaemia time (WIT) <25 min, and negative surgical margins.

Results

In total, 1 222 RAPN were included. The mean (sd) caseload per hospital per year was 44.9 (26.7) RAPNs and the mean (sd) caseload per surgeon per year was 19.2 (14.9) RAPNs. The Trifecta achievement rate increased significantly with SV (69.9% vs 72.8% vs 73% vs 86.1%; P < 0.001) and HV (60.3% vs 72.3% vs 86.2% vs 82.4%; P < 0.001). The positive surgical margins (PSM) rate (P = 0.02), length of hospital stay (LOS; P < 0.001), WIT (P < 0.001), and operative time (P < 0.001), all decreased significantly with increasing SV. The PSM rate (P = 0.02), LOS (P < 0.001), WIT (P < 0.001), operative time (P < 0.001), and major complications rate (P = 0.01), all decreased significantly with increasing HV. In multivariate analysis adjusting for HV and SV (model 3), HV remained the main predictive factor of Trifecta achievement (odds ratio [OR] 3.70 for very high vs low HV; P < 0.001), whereas SV was not associated with Trifecta achievement (OR 1.58 for very high vs low SV; P = 0.34).

Conclusion

In this multicentre study HV and SV both greatly influenced RAPN perioperative outcomes, but HV appeared to have a greater impact than SV.
Human secreted proteins SLURP‐1 and SLURP‐2 control the growth of epithelial cancer cells via interactions with nicotinic acetylcholine receptors
Authors: Lyukmanova E N , Bychkov M L , Sharonov G V , Efremenko A V , Shulepko M A , Kulbatskii D S , Shenkarev Z O , Feofanov A V , Dolgikh D A , Kirpichnikov M P
Published: March 2018

Background and Purpose

Nicotinic acetylcholine receptors (nAChRs) are a promising target for development of new anticancer therapies. Here we have investigated the effects of the endogenous human proteins SLURP‐1 and SLURP‐2, antagonists of nAChRs, on human epithelial cancer cells.

Experimental Approach

Growth of epithelial cancer cells (A431, SKBR3, MCF‐7, A549, HT‐29) exposed to SLURP‐1, SLURP‐2, mecamylamine, atropine, timolol and gefitinib was measured by the WST‐1 test. Expression levels of SLURP‐1, α7‐nAChR and EGF receptors and their distribution in cancer cells were studied by confocal microscopy and flow cytometry. Secretion of endogenous SLURP‐1 by A431 cells under treatment with recombinant SLURP‐1 was analysed by Western‐blotting.

Key Results

SLURP‐1 and SLURP‐2 significantly inhibited growth of A431, SKBR3, MCF‐7 and HT‐29 cells at concentrations above 1 nM, to 40–70% of the control, in 24 h. Proliferation of A549 cells was inhibited only by SLURP‐1. The anti‐proliferative activity of SLURPs on A431 cells was associated with nAChRs, but not with β‐adrenoceptors or EGF receptors. Action of gefitinib and SLURPs was additive and resulted almost complete inhibition of A431 cell proliferation during 24 h. Exposure of A431 cells to recombinant SLURP‐1 down‐regulated α7‐nAChR expression and induced secretion of endogenous SLURP‐1 from intracellular depots, increasing its concentration in the extracellular media.

Conclusions and Implications

SLURPs inhibit growth of epithelial cancer cells in vitro and merit further investigation as potential agents for anticancer therapy.

Linked Articles

This article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc
Function and underlying mechanisms of seasonal colour moulting in mammals and birds: what keeps them changing in a warming world?
Authors: Zimova Marketa , Hackländer Klaus , Good Jeffrey M. , Melo‐Ferreira José , Alves Paulo Célio , Mills L. Scott
Published: March 2018

Animals that occupy temperate and polar regions have specialized traits that help them survive in harsh, highly seasonal environments. One particularly important adaptation is seasonal coat colour (SCC) moulting. Over 20 species of birds and mammals distributed across the northern hemisphere undergo complete, biannual colour change from brown in the summer to completely white in the winter. But as climate change decreases duration of snow cover, seasonally winter white species (including the snowshoe hare Lepus americanus, Arctic fox Vulpes lagopus and willow ptarmigan Lagopus lagopus) become highly contrasted against dark snowless backgrounds. The negative consequences of camouflage mismatch and adaptive potential is of high interest for conservation. Here we provide the first comprehensive review across birds and mammals of the adaptive value and mechanisms underpinning SCC moulting. We found that across species, the main function of SCC moults is seasonal camouflage against snow, and photoperiod is the main driver of the moult phenology. Next, although many underlying mechanisms remain unclear, mammalian species share similarities in some aspects of hair growth, neuroendocrine control, and the effects of intrinsic and extrinsic factors on moult phenology. The underlying basis of SCC moults in birds is less understood and differs from mammals in several aspects. Lastly, our synthesis suggests that due to limited plasticity in SCC moulting, evolutionary adaptation will be necessary to mediate future camouflage mismatch and a detailed understanding of the SCC moulting will be needed to manage populations effectively under climate change.
Searching for strategy: Value for Money (VFM) audit choice in the new public management era
Authors: Adi Sana , Dutil Patrice
Published: March 2018

Value for Money (VFM) audits are now critical aspects of accountability in Westminster systems, based on the assumption that ministries are systematically examined. This study explores the VFM inquiries of the Auditor General of Ontario (AGO) between 1997 and 2014 as a case study to uncover trends of consistency of approach under the flourishing “new public management” philosophy of cutting costs and raising efficiencies. It asks three broad questions: does the frequency and intensity of VFM audits correlate with the financial importance of the ministries? Do political controversies affect the choice of what will be subject to a VFM audit? Finally, do Auditors General make a personal difference in what ministries will be audited through a VFM framework? The findings demonstrate a pattern of over‐auditing of some ministries while important ministries are consistently under‐audited.
Non‐invasive estimation of 10B‐4‐borono‐L‐phenylalanine‐derived boron concentration in tumors by PET using 4‐borono‐2‐18F‐fluoro‐phenylalanine
Authors: Yoshimoto Mitsuyoshi , Honda Natsuki , Kurihara Hiroaki , Hiroi Kenta , Nakamura Satoshi , Ito Masashi , Shikano Naoto , Itami Jun , Fujii Hirofumi
Published: March 2018

In boron neutron capture therapy (BNCT), 10B‐4‐borono‐L‐phenylalanine (BPA) is commonly used as a 10B carrier. PET using 4‐borono‐2‐18F‐fluoro‐phenylalanine (18F‐FBPA PET) has been performed to estimate boron concentration and predict the therapeutic effects of BNCT; however, the association between tumor uptake of 18F‐FBPA and boron concentration in tumors remains unclear. The present study investigated the transport mechanism of 18F‐FBPA and BPA, and evaluated the utility of 18F‐FBPA PET in predicting boron concentration in tumors. The transporter assay revealed that 2‐aminobicyclo‐(2.2.1)‐heptane‐2‐carboxylic acid, an inhibitor of the L‐type amino acid transporter, significantly inhibited 18F‐FBPA and 14C‐4‐borono‐L‐phenylalanine (14C‐BPA) uptake in FaDu and LN‐229 human cancer cells. 18F‐FBPA uptake strongly correlated with 14C‐BPA uptake in 7 human tumor cell lines (r = .93; P < .01). PET experiments demonstrated that tumor uptake of 18F‐FBPA was independent of the administration method, and uptake of 18F‐FBPA by bolus injection correlated well with BPA uptake by continuous intravenous infusion. The results of this study revealed that evaluating tumor uptake of 18F‐FBPA by PET was useful for estimating 10B concentration in tumors.
Periostin antisense oligonucleotide suppresses bleomycin‐induced formation of a lung premetastatic niche for melanoma
Authors: Semba Takashi , Sugihara Eiji , Kamoshita Nagisa , Ueno Sayaka , Fukuda Keitaro , Yoshino Masafumi , Takao Kazumasa , Yoshikawa Kazunori , Izuhara Kenji , Arima Yoshimi , Suzuki Makoto , Saya Hideyuki
Published: March 2018

Metastasis is the leading cause of cancer death. A tumor‐supportive microenvironment, or premetastatic niche, at potential secondary tumor sites plays an important role in metastasis, especially in tumor cell colonization. Although a fibrotic milieu is known to promote tumorigenesis and metastasis, the underlying molecular contributors to this effect have remained unclear. Here we show that periostin, a component of the extracellular matrix that functions in tissue remodeling, has a key role in formation of a fibrotic environment that promotes tumor metastatic colonization. We found that periostin was widely expressed in fibrotic lesions of mice with bleomycin‐induced lung fibrosis, and that up‐regulation of periostin expression coincided with activation of myofibroblasts positive for α‐smooth muscle actin. We established a lung metastasis model for B16 murine melanoma cells and showed that metastatic colonization of the lung by these cells was markedly promoted by bleomycin‐induced lung fibrosis. Inhibition of periostin expression by giving an intratracheal antisense oligonucleotide targeting periostin mRNA was found to suppress bleomycin‐induced lung fibrosis and thereby to attenuate metastatic colonization of the lung by melanoma cells. Our results indicate that periostin is a key player in the development of bleomycin‐induced fibrosis and consequent enhancement of tumor cell colonization in the lung. Our results therefore implicate periostin as a potential target for prevention or treatment of lung metastasis.
Clinical outcomes after Descemet’s stripping endothelial keratoplasty using donor corneas from children younger than 3 years
Authors: Peng Rong‐mei , Guo Yu‐xin , Qiu Yuan , Hong Jing , Xiao Ge‐ge , Qu Hong‐qiang
Published: March 2018

Importance

There is limited literature on paediatric donors in endothelial keratoplasty.

Background

This study investigated the efficacy of and appropriate paediatric donor age for Descemet’s stripping endothelial keratoplasty (DSEK).

Design

Retrospective and observational case series.

Participants

Thirty‐eight consecutive patients underwent DSEK with paediatric donor corneas.

Methods

The age of the donors ranged from 32 weeks gestation (premature neonate) to 3 years old. All donor consents were obtained from the parents. The causes of donor death included traffic accident, congenital heart disease and neonatal respiratory distress syndrome.

Main Outcome Measures

The outcome measures included best‐corrected visual acuity, endothelial cell loss and complications.

Results

Best‐corrected visual acuity at last follow‐up was >20/40 in 28 of 38 eyes (73.7%). The mean preoperative endothelial cell density of donor corneas was 4682 ± 520 cells/mm2. The mean endothelial cell density of grafts was 3977 ± 556 cells/mm2 at 18 months postoperatively. Three lenticules from premature neonate donors exhibited severe contraction postoperatively. The edge of six lenticules from donors <1‐year‐old exhibited contraction in the early postoperative period and gradually flattened spontaneously. Graft detachment occurred in one patient.

Conclusions and Relevance

DSEK with paediatric donor corneas can achieve good clinical outcomes. The corneal lenticules from 1‐ to 3‐year‐ old donors are suitable for DSEK while those from donors <1‐year‐old are less suitable due to the possibility of severe postoperative graft contraction.
DECREASING CAMPUS SMOKING WITH PUNISHMENTS AND SOCIAL PRESSURES
Authors: Clemons Kaytlynn , Johnson David B. , Kiger Amy , Putnam Janice
Published: March 2018

This paper reports the effectiveness of a Midwest state university's “100% tobacco‐free” policy. The policy used social pressures and punishments to incentivize tobacco users to no longer consume tobacco on campus. The policy had three distinct periods (Pre‐Promotion, Post‐Promotion, and Post‐Policy). Social pressures and punishments were introduced during the Post‐Promotion and Post‐Policy periods, respectively. Changes in cigarette consumption were inferred by counting the number of cigarette butts found at various locations on campus. A statistically significant decrease in the number of cigarette butts was observed during the Post‐Promotion period. After the initial drop, tobacco use remained constant for the remainder of the period. An additional decrease was observed once punishments were introduced in the third period. However, the number of cigarette butts observed on campus remained significantly above zero. Further research is needed to understand how smokers substitute across time, location, and tobacco products after the implementation of similar policies. (JEL I11, C99, I12)
Fak‐Mapk, Hippo and Wnt signalling pathway expression and regulation in distraction osteogenesis
Authors: Song Jian , Ye Bin , Liu Hanghang , Bi Ruiye , Zhang Nian , Hu Jing , Luo En
Published: March 2018

Objectives

To investigate the mechanism of mechanical stimulation in bone formation and regeneration during distraction osteogenesis.

Materials and methods

In this study, microarray technology was used to investigate the time course of bone‐related molecular changes in distraction osteogenesis in rats. Real‐timePCRand Western‐blot analyses were used to confirm the expression of genes identified in microarrays. Meanwhile, we used a lentivirus vector to inhibit Fak expression, in order to identify the osteogenic effect of Fak and Fak‐Mapk pathway during distraction osteogenesis.

Results

Several components of the Wnt and Hippo pathways were found to be up‐ or down‐regulated during distraction osteogenesis by microarray. Meanwhile, it was found that Fak, Src, Raf‐1, Erk1, Jnk and p38‐Mapk were up‐regulated during gradual distraction, compared with consolidation. To further determine whether Fak‐Mapk pathway played an important role in distraction osteogenesis, Fak was disrupted with a lentivirus vector. The expressions levels of p‐Fak, p‐Erk1/2, p‐JNKand p‐p38Mapk were decreased. Meanwhile, a poor early and late osteogenesis effect was found in the shRNA‐Fak group.

Conclusion

It was inferred that the mechanical stimulus induces increased expression of Fak and activates Fak‐Mapk pathway, by activation of Erk, Jnk and p38‐Mapk pathway, and that Fak at least, in part, plays an important role in maintaining osteogenic effect by activating Fak‐Mapk pathway during distraction osteogenesis.
Antibiotic resistance evolution of Pseudomonas aeruginosa in cystic fibrosis patients (2010‐2013)
Authors: Lucca Francesca , Guarnieri Margherita , Ros Mirco , Muffato Giovanna , Rigoli Roberto , Da Dalt Liviana
Published: March 2018

Introduction

Pseudomonas aeruginosa is the predominant pathogen responsible of chronic colonization of the airways in cystic fibrosis (CF) patients. There are few European data about antibiotic susceptibility evolution of P aeruginosa in CF patients.

Objectives

The aim of this study is to evaluate the evolution of antibiotic resistance in the period 2010‐2013 in CF patients chronically colonized by P aeruginosa and to highlight the characteristics of this evolution in patients younger than 20 years.

Methods

Clinical and microbiological data were extracted from two electronic databases and analyzed. Antibiotic resistance was defined according to European Committee of Antimicrobial Susceptibility Testing for levofloxacin, ciprofloxacin, meropenem, amikacin and ceftazidime. The between‐group comparison was drawn with the Chi‐square test for proportions, with the T‐test for unpaired samples for normally distributed data and with Mann‐Whitney test for non‐normally distributed data. Significancy was defined by P < .05.

Results

Fifty‐seven CF patients, including thirteen subjects aged less than 20 years, were enrolled. P.. aeruginosa antibiotic sensitivity decreased significantly for fluoroquinolones, mainly in patients aged <20 years, while it increased for amikacin and colistin. The analysis of minimum inhibitory concentration confirmed these trends. In pediatric patients treated with more than three antibiotic cycles per year, greater resistance was found, except for amikacin and colistin.

Conclusion

An evolution in P aeruginosa antibiotic resistances is observed in the 4‐year period studied. Responsible and informed use of antibiotics is mandatory in CF.
Cardio‐hepatic risk assessment by CMR imaging in liver transplant candidates
Authors: Reddy Sahadev T. , Thai Ngoc L. , Oliva Jose , Tom Kusum B. , Dishart Michael K. , Doyle Mark , Yamrozik June A. , Williams Ronald B. , Shah Moneal , Wani Adil , Singh Anil , Maheswary Rishi , Biederman Robert W.W.
Published: March 2018

Background

The preoperative workup of orthotopic liver transplantation (OLT) patients is practically complex given the need for multiple imaging modalities. We recently demonstrated in our proof‐of‐concept study the value of a one‐stop‐shop approach using cardiovascular MRI (CMR) to address this complex problem. However, this approach requires further validation in a larger cohort, as detection of hepatocellular carcinoma (HCC) as well as cardiovascular risk assessment is critically important in these patients. We hypothesized that coronary risk assessment and HCC detectability is acceptable using the one‐stop‐shop CMR approach.

Methods

In this observational study, patients underwent CMRI evaluation including cardiac function, stress CMR, thoracoabdominal MRA, and abdominal MRI on a standard MRI scanner in one examination.

Results

Over 8 years, 252 OLT candidates underwent evaluation in the cardiac MRI suit. The completion rates for each segment of the CMR examination were 99% for function, 95% completed stress CMR, 93% completed LGE for viability, 85% for liver MRI, and 87% for MRA. A negative CMR stress examination had 100% CAD event‐free survival at 12 months. A total of 63 (29%) patients proceeded to OLT. Explant pathology confirmed detection/exclusion of HCC.

Conclusions

This study further defines the population suitable for the one‐stop‐shop CMR concept for preop evaluation of OLT candidates providing a road map for integrated testing in this complex patient population for evaluation of cardiac risk and detection of HCC lesions.
Early development of letter specialization in left fusiform is associated with better word reading and smaller fusiform face area
Authors: Centanni Tracy M , Norton Elizabeth S , Park Anne , Beach Sara D , Halverson Kelly , Ozernov‐Palchik Ola , Gaab Nadine , Gabrieli John DE
Published: March 2018

A functional region of left fusiform gyrus termed “the visual word form area” (VWFA) develops during reading acquisition to respond more strongly to printed words than to other visual stimuli. Here, we examined responses to letters among 5‐ and 6‐year‐old early kindergarten children (N = 48) with little or no school‐based reading instruction who varied in their reading ability. We used functional magnetic resonance imaging (fMRI) to measure responses to individual letters, false fonts, and faces in left and right fusiform gyri. We then evaluated whether signal change and size (spatial extent) of letter‐sensitive cortex (greater activation for letters versus faces) and letter‐specific cortex (greater activation for letters versus false fonts) in these regions related to (a) standardized measures of word‐reading ability and (b) signal change and size of face‐sensitive cortex (fusiform face area or FFA; greater activation for faces versus letters). Greater letter specificity, but not letter sensitivity, in left fusiform gyrus correlated positively with word reading scores. Across children, in the left fusiform gyrus, greater size of letter‐sensitive cortex correlated with lesser size of FFA. These findings are the first to suggest that in beginning readers, development of letter responsivity in left fusiform cortex is associated with both better reading ability and also a reduction of the size of left FFA that may result in right‐hemisphere dominance for face perception.