bluuebunny/crossref_metadata_2025 huggingface dataset:
Perceptions of fine dining restaurants in Pakistan
Authors: Shahzadi Mariam , Malik Shahab Alam , Ahmad Mansoor , Shabbir Asma
Published: January 2018

Purpose

The purpose of this paper is to explore the relationship between restaurant key attributes, customer satisfaction and behavioral intentions. The mediating role of customer satisfaction is assessed between restaurants’ key attributes of service quality and behavioral intentions.

Design/methodology/approach

Data were collected from a sample of 296 customers dining in the fine dining restaurants of Pakistan through a self-administered questionnaire. The data were then analyzed through regression analysis and gap analysis. Model fitness was checked in SPSS AMOS through CFA.

Findings

The findings suggest that the key restaurant attributes have a significant positive effect on behavioral intentions. Customer satisfaction partially mediates the relationship between key restaurant attributes and behavioral intentions. The findings also suggest that there is a significant gap between the perceptions of customers regarding the importance and performance of key restaurant attributes.

Practical implications

The result indicates that food taste and environmental cleanliness are the cornerstones of fine dining restaurants’ success in Pakistan and are among the strongest predictor of customer satisfaction and behavioral intentions; while improvement efforts should be made in four key areas, i.e., healthy food option, food freshness, food safety and fair price.

Originality/value

No comparative study has been directed in fine dining restaurants of Pakistan with respect to the key restaurants attributes, i.e., food quality attributes, service quality attributes, atmospheric quality attributes, and other attributes which have been analyzed in the current study. This research was conducted to investigate the perceptions of customers toward the fine dining restaurants of Pakistan to measure the key restaurants’ attributes that influence customers’ satisfaction and their post-dining behavioral intentions. This study will facilitate restaurants’ managers to understand the stronger and as well as the weaker aspects of service quality and permit them to investigate the factors which contribute toward customers’ satisfaction and their post-dining behavioral intentions in order to build and maintain long-term relationship between restaurants and customers.
Remodelling urban planning education for sustainable development: the case of Serbia
Authors: Maruna Marija , Milovanovic Rodic Danijela , Colic Ratka
Published: January 2018

Purpose

The paper aims to present a pedagogical model tailored to the development of key competences in the urban planning profession in post-socialist transitional countries that is based on the creation of an integrated platform for dialogue and the development of professional competences as part of the process, whereby students produce their final projects.

Design/methodology/approach

The pedagogical model is based on the principles of education for sustainable development and focuses on the establishment of a repeatable platform for dialogue between students and mentors, members of the mentoring team, the local community, external members of the consulting team of experts and foreign master’s degree programmes, in the process of producing students’ projects. The proposed method addresses several dimensions, including: the education of students, teachers, professionals and local experts, the establishment of a network for cooperation and collaboration and the delivery of practical and usable results.

Findings

The paper provides a comparative overview of the pedagogical model’s application in producing the final master’s degree projects of three generations of students, as well as its alignment with the needs of re-defining the role and reach of the profession of urban planner in an environment of post-socialist transition. The model was improved, enhanced and optimised through this process and then corroborated with its practical implementation.

Originality/value

The innovative pedagogical model comprises an instrument to enhance the professional capacities of all participants in the production of final master’s projects: academics, practitioners and future professionals/students, through discussions of topical issues, innovative modes of work and new professional responses grounded in the local context and tested by a broad range of stakeholders. It is of particular importance for countries in transition experiencing a shift in the paradigm of professional action, especially as the proposed pedagogical model establishes a problem-solving platform that surpasses academia.
The heart of music classification: toward a model of classifying musical medium
Authors: Lee Deborah , Robinson Lyn
Published: January 2018

Purpose

The purpose of this paper is to understand the classification of musical medium, which is a critical part of music classification. It considers how musical medium is currently classified, provides a theoretical understanding of what is currently problematic, and proposes a model which rethinks the classification of medium and resolves these issues.

Design/methodology/approach

The analysis is drawn from existing classification schemes, additionally using musicological and knowledge organization literature where relevant. The paper culminates in the design of a model of musical medium.

Findings

The analysis elicits sub-facets, orders and categorizations of medium: there is a strict categorization between vocal and instrumental music, a categorization based on broad size, and important sub-facets for multiples, accompaniment and arrangement. Problematically, there is a mismatch between the definitiveness of library and information science vocal/instrumental categorization and the blurred nature of real musical works; arrangements and accompaniments are limited by other categorizations; multiple voices and groups are not accommodated. So, a model with a radical new structure is proposed which resolves these classification issues.

Research limitations/implications

The results could be used to further understanding of music classification generally, for Western art music and other types of music.

Practical implications

The resulting model could be used to improve and design new classification schemes and to improve understanding of music retrieval.

Originality/value

Deep theoretical analysis of music classification is rare, so this paper’s approach is original. Furthermore, the paper’s value lies in studying a vital area of music classification which is not currently understood, and providing explanations and solutions. The proposed model is novel in structure and concept, and its original structure could be adapted for other knotty subjects.
Examining consumers’ attitude towards purchase of counterfeit fashion products
Authors: Bhatia Vinita
Published: January 2018

Purpose

This paper aims to investigate the factors affecting consumers’ attitude towards counterfeit fashion products and the relationship of consumers’ attitude towards counterfeit fashion products with purchase intention.

Design/methodology/approach

A conceptual model is proposed and validated by following the various studies on counterfeit products. A survey of 382 respondents was conducted in the Mumbai city. The researcher has used structural equation modelling to test the causal relationships among the constructs.

Findings

The results of the study indicate that value consciousness, materialism and social influence positively relate to consumers’ attitude towards counterfeit fashion products which eventually leads to purchase intention. Brand consciousness and perceived risk have no significant relationship with consumers’ attitude towards counterfeit fashion products. Low-income group consumers are value conscious and brand conscious and perceive a low risk which influences their attitude towards counterfeit fashion products.

Research limitations/implications

The study uses a self-reported measure to collect the data through email, and a printed copy of the questionnaire was circulated. Also, the method of sample selection was not random. These two aspects could limit the generalizability of the results.

Practical implications

The paper provides assistance to the manufacturers and the retailers of genuine brand products to formulate better marketing strategies for attracting new customers.

Originality/value

The study aims to investigate the factors affecting Indian consumers’ attitude towards counterfeit fashion products which is not much analysed. The factors were carefully chosen so as to meet the requirements of the study. Income is taken as a moderator for studying the relationship between factors and attitude towards counterfeit fashion products.
The patchwork of alcohol-free zones and alcohol-prohibited areas in New South Wales (Australia)
Authors: Fisher Daren G. , Wadds Phillip , Clancey Garner
Published: January 2018

Purpose

Developing policies to curb public alcohol consumption is a priority for governments. In the Australian state of New South Wales (NSW), local governments have introduced alcohol-free zones (AFZs) and alcohol-prohibited areas (APAs) to prohibit the public consumption of alcohol and reduce crime stemming from intoxication. Previous studies, however, argue that these policies are driven by stakeholder desire rather than alcohol-related crime and may result in increased criminal justice contact for vulnerable populations. The purpose of this paper is to estimate the number of AFZs and APAs in NSW and examine the extent to which these policies are connected to the frequency of alcohol-related crime.

Design/methodology/approach

Examining the 152 local government areas (LGAs) of NSW, the authors analysed whether the implementation of AFZs and APAs were linked to the frequency of liquor offences and assaults using group-based trajectory models.

Findings

The authors found that AFZs and APAs were often not advertised nor inconsistently implemented both across and within jurisdictions. Group-based trajectory models indicated that AFZs were more common in low liquor offence LGAs than high liquor offences LGAs, but were more frequently implemented in high assault LGAs compared to low assault LGAs. APAs were more common in the lowest crime LGAs compared to those LGAs that experienced higher levels of recorded crime.

Originality/value

These analyses demonstrate how widespread AFZs and APAs have become and provides evidence that the implementation of is only tenuously linked to the frequency of crime.
Anthropogenic disturbance of tropical forests threatens pollination services to açaí palm in the Amazon river delta
Authors: Campbell Alistair John , Carvalheiro Luísa Gigante , Maués Marcia Motta , Jaffé Rodolfo , Giannini Tereza Cristina , Freitas Madson Antonio Benjamin , Coelho Beatriz Woiski Texeira , Menezes Cristiano
Published: January 2018

The açaí palm Euterpe oleracea Mart. in the Amazon river delta has seen rapid expansion to meet increased demand for its fruit. This has been achieved by transforming lowland forest habitats (floodplains) into simplified agroforests and intensive plantation in upland areas. As açaí palm makes an important contribution to the economy and food security of local communities, identifying management approaches that support biodiversity and ecosystem processes that underpin fruit production on açaí farms is essential.

We compared flower‐visitor communities and açaí fruit production in floodplain forests and upland plantations, across gradients of local management intensity (i.e. açaí density per ha) and surrounding forest cover. The relative contribution of biotic pollination and degree of pollen limitation were assessed using insect exclusion and hand‐pollination experiments.

We found that açaí flower visitors are highly diverse (c. 200 distinct taxa) and had variable responses to disturbance. Bee visitation was higher in floodplains and positively related to surrounding forest cover, but other flower visitors, including specialised curculionid beetles, were unresponsive to changes in surrounding forest cover. However, intensive management practices (i.e. high açaí palm densities) in floodplains and uplands had contrasting effects on flower‐visitor communities, with flower‐visitor richness being lower on intensively managed floodplain farms and ant densities being higher on intensive upland farms.

Pollination experiments revealed açaí palm to be highly dependent on biotic pollination. Fruit set in open‐pollinated inflorescences was positively related to flower‐visitor richness and specialised curculionid beetle visitation, whereas the presence of ants on inflorescences had a negative effect.

Synthesis and applications. Our study shows that pollinators are essential for açaí fruit production, but that intensive farming practices have eroded the relationship between surrounding forest cover and ecosystem function in floodplains (i.e. conversion of native forest into simplified agroforests) and increased the frequency of antagonistic interactions in uplands (e.g. high ant densities). These findings underline the value of extensive management practices, such as the maintenance of other tree species within farms and adjacent unmanaged forest patches, to ensure the long‐term sustainability of açaí fruit production in the Amazon river delta.
Responses of macroinvertebrate communities to small dam removals: Implications for bioassessment and restoration
Authors: Carlson Peter Erich , Donadi Serena , Sandin Leonard
Published: January 2018

Small dam removals are increasing on a global scale; yet, general predictions of organism response to dam removal are constrained by heterogeneity of study designs, implementation strategies, geographies, and characteristics of dams and their removals.

Macroinvertebrate data extracted from 29 studies including 34 small dam removals over a broad geographical range were re‐analysed utilizing dam removal effect sizes (a quantified change from before to after removal). Effect sizes of 10 metrics of community structure were calculated to investigate the spatiotemporal extent of small dam removal effects and if responses differ with characteristics of the dam and environmental settings.

We found that dam removal had initial negative effects on total macroinvertebrate density and Ephemeroptera, Plecoptera and Trichoptera (EPT) density, both downstream and upstream; however, recovery to pre‐removal values was reached and exceeded after c. 15–20 months. Mean annual discharge, land use in the catchment and distance from the dam affected the magnitude and direction of responses of four community metrics: total density, EPT density, %EPT density and family biotic index.

Synthesis and applications. Our study provides evidence that macroinvertebrate community recovery from dam removal is mediated by catchment characteristics and system size, which may correlate with sediment flushing efficiency. Negative impacts were observed in smaller systems or those with a high percentage of undisturbed catchment areas, conditions that may benefit from sediment management prior to dam removal. Significant responses in reaches upstream of the impoundment clearly indicate that caution be applied to interpretations of response in sampling designs that utilize upstream sites for reference condition.
Pre‐retirement job and the work‐to‐retirement occupational transition process in Australia: A review
Authors: Eagers Jackie , Franklin Richard C. , Yau Matthew K. , Broome Kieran
Published: January 2018

Background

The transition from work to retirement is a complex process and unique experience with a relationship existing between work and retirement with implications for health in later life. This review explored the relationship between pre‐retirement job and participation in the work‐to‐retirement transition process in Australia by exploring: (i) factors influencing retirement in relation to pre‐retirement job; (ii) how jobs are classified; (iii) the effect of pre‐retirement job (based on categories) on this occupational transition; and (iv) the potential role for occupational therapy in this occupational transition.

Method

An integrative literature review was completed. PRISMA guidelines were used. Study designs were analysed for methodological quality using the National Health and Medical Research Council levels of evidence. Thematic analysis determined retirement factors which were used to compare differences between jobs.

Results

This review included 15 papers. There were two Level III‐2, one Level III‐3 and 13 Level IV studies. Factors influencing retirement related to the stages of work, preparation, transition and retired. White collar and blue collar was the most common job classification system. Although white collar and blue collar worker definitions utilised were inconsistent, differences between the two groups were still determined in all stages.

Conclusion

Differences in the work‐to‐retirement transition process, based on pre‐retirement job, are evident. Understanding differences by job groupings may assist occupational therapists to understand individualised needs during this occupational transition and subsequent tailoring of interventions (both individual and group based) to enable engagement in meaningful occupation in the work‐to‐retirement occupational transition to effect active healthy ageing.
Management of gout and hyperuricemia: Multidisciplinary consensus in Taiwan
Authors: Yu Kuang‐Hui , Chen Der‐Yuan , Chen Jiunn‐Horng , Chen Shih‐Yang , Chen Shyh‐Ming , Cheng Tien‐Tsai , Hsieh Song‐Chou , Hsieh Tsu‐Yi , Hsu Pai‐Feng , Kuo Chang‐Fu , Kuo Mei‐Chuan , Lam Hing‐Chung , Lee I‐Te , Liang Toong‐Hua , Lin Hsiao‐Yi , Lin Shih‐Chang , Tsai Wen‐Pin , Tsay Gregory J. , Wei James Cheng‐Chung , Yang Chung‐Han , Tsai Wen‐Chan
Published: January 2018

Gout is an inflammatory disease manifested by the deposition of monosodium urate (MSU) crystals in joints, cartilage, synovial bursa, tendons or soft tissues. Gout is not a new disease, which was first documented nearly 5,000 years ago. The prevalence of gout has increased globally in recent years, imposing great disease burden worldwide. Moreover, gout or hyperuricemia is clearly associated with a variety of comorbidities, including cardiovascular diseases, chronic kidney disease, urolithiasis, metabolic syndrome, diabetes mellitus, thyroid dysfunction, and psoriasis. To prevent acute arthritis attacks and complications, earlier use of pharmacotherapeutic treatment should be considered, and patients with hyperuricemia and previous episodes of acute gouty arthritis should receive long‐term urate‐lowering treatment. Urate‐lowering drugs should be used during the inter‐critical and chronic stages to prevent recurrent gout attacks, which may elicit gradual resolution of tophi. The goal of urate‐lowering therapy should aim to maintain serum uric acid (sUA) level <6.0 mg/dL. For patients with tophi, the initial goal can be set at lowering sUA to <5.0 mg/dL to promote tophi dissolution. The goal of this consensus paper was to improve gout and hyperuricemia management at a more comprehensive level. The content of this consensus paper was developed based on local epidemiology and current clinical practice, as well as consensuses from two multidisciplinary meetings and recommendations from Taiwan Guideline for the Management of Gout and Hyperuricemia.
Acute brain lesions on magnetic resonance imaging in relation to neurological outcome after cardiac arrest
Authors: Wallin E. , Larsson I.‐M. , Kristofferzon M.‐L. , Larsson E.‐M. , Raininko R. , Rubertsson S.
Published: January 2018

Background

Magnetic resonance imaging (MRI) of the brain including diffusion‐weighted imaging (DWI) is reported to have high prognostic accuracy in unconscious post‐cardiac arrest (CA) patients. We documented acute MRI findings in the brain in both conscious and unconscious post‐CA patients treated with target temperature management (TTM) at 32–34°C for 24 h as well as the relation to patients’ neurological outcome after 6 months.

Methods

A prospective observational study with MRI was performed regardless of the level of consciousness in post‐CA patients treated with TTM. Neurological outcome was assessed using the Cerebral Performance Categories scale and dichotomized into good and poor outcome.

Results

Forty‐six patients underwent MRI at 3–5 days post‐CA. Patients with good outcome had minor, mainly frontal and parietal, lesions. Acute hypoxic/ischemic lesions on MRI including DWI were more common in patients with poor outcome (P = 0.007). These lesions affected mostly gray matter (deep or cortical), with or without involvement of the underlying white matter. Lesions in the occipital and temporal lobes, deep gray matter and cerebellum showed strongest associations with poor outcome. Decreased apparent diffusion coefficient, was more common in patients with poor outcome.

Conclusions

Extensive acute hypoxic/ischemic MRI lesions in the cortical regions, deep gray matter and cerebellum detected by visual analysis as well as low apparent diffusion coefficient values from quantitative measurements were associated with poor outcome. Patients with good outcome had minor hypoxic/ischemic changes, mainly in the frontal and parietal lobes.
Bridge flap repair for central nasal dorsum defect
Authors: Salmon Paul JM , El‐Khayat Rami H
Published: January 2018

Surgery of the nose to remove skin cancer often requires the use of local flaps. We present a defect after the extirpation of a previously incompletely excised infiltrative squamous cell carcinoma, which we repaired with a Bridge flap, a bipedicled and subcutaneous islanded flap whose excellent vascularity allows reliable reconstruction and rapid mobilisation, with dependable results.
Financialisation as Monopoly Profit: The Case of US Banking
Authors: Christophers Brett
Published: January 2018

Different economic measures afford different ways of seeing processes of financialisation. In the prototypical case of the US economy, the most compelling evidence of post‐1970s financialisation is found in corporate profits measures. This much has been clear for at least a decade. What remains much less clear, however, is the explanation for the long‐term maintenance and amplification of extreme financial‐sector profitability that financialisation in the United States has and continues to entail. With a specific focus on banking, this article turns to post‐Marxian scholarship on profit rate trends to explain this phenomenon. It argues that limited and declining levels of competition within the US banking sector during recent decades—rooted in high levels of industry concentration, collusive behaviour, and substantial entry barriers—have contributed to sustaining and boosting abnormal sectoral profitability. In doing so, the article theorises financialisation in the United States explicitly in terms of monopoly profit.
Tactile stimulation during neonatal transition and its effect on vital parameters in neonates during neonatal transition
Authors: Baik‐Schneditz Nariae , Urlesberger Berndt , Schwaberger Bernhard , Mileder Lukas , Schmölzer Georg , Avian Alexander , Pichler Gerhard
Published: January 2018

Aim

This study analysed tactile stimulation during neonatal transition and resuscitation in preterm and term neonates born by Caesarean delivery. It examined the frequency, location and body region, duration and possible effects of stimulation on heart rate and arterial oxygen saturation (SpO2).

Methods

Two independent investigators analysed video recordings of tactile stimulation on term and preterm neonates during neonatal transition from January 2012 to December 2014. They were recorded during a prospective observational study and randomised controlled trial at a tertiary centre, the Medical University of Graz, Austria. SpO2 and heart rate were continuously recorded. Data on the frequency, body region and duration of stimulation were collected. To investigate the possible effects of stimulation, SpO2 and heart rate were compared before and after stimulation.

Results

Term infants received tactile stimulation more than once, and it tended to start later, last longer and be applied in more locations than in preterm infants. Only preterm infants showed a significant increase in SpO2 after stimulation and heart rates did not show any significant changes in either group.

Conclusion

Tactile stimulation was applied in different ways to preterm and term infants during neonatal transition and SpO2 showed a significant increase in preterm infants.
Inactivated antithombin as anticoagulant reversal in a rat model of cardiopulmonary bypass: a potent and potentially safer alternative to protamine
Authors: Bianchini Elsa P. , Sebestyen Alexandre , Abache Toufik , Bourti Yasmine , Fontayne Alexandre , Richard Vincent , Tamion Fabienne , Plantier Jean‐Luc , Doguet Fabien , Borgel Delphine
Published: January 2018

Heparin anticoagulation followed by protamine reversal is commonly used in cardiopulmonary bypass (CPB). As an alternative to protamine, a recombinant inactive antithrombin (riAT) was designed as an antidote to heparin and was previously shown to be as potent as protamine in‐vitro. In the present study, riAT was assessed for its ability to neutralize heparin after CPB in a rat model. After 60 min of CPB under heparin, rats received 5 mg/kg protamine, 37.5 mg/kg riAT or phosphate buffered saline (PBS) as placebo. Residual anticoagulant activity was assessed using the activated partial thromboplastin time assay before, and 10–30 min after reversion. Haemodynamic monitoring was performed and plasma histamine concentration was also measured. In this model, riAT appeared to be as efficient as protamine in neutralizing heparin. Ten minutes after injection, riAT and protamine both decreased heparin activity, to 1.8 ± 1.3 and 4.5 ± 1.4 u/ml, respectively (23.1 ± 5.1 u/ml in placebo group). Furthermore, evolution of mean carotid arterial pressure, heart rate and plasma histamine levels was comparable in rats treated with PBS or riAT, while protamine exhibited haemodynamic side effects and increased histamine plasma concentration. Thus, riAT could represent an advantage over protamine in CPB because it efficiently reverses heparin activity without negative effects on haemodynamic parameters and plasma histamine level.
Exploration of differentially expressed plasma proteins in patients with lung adenocarcinoma using iTRAQ‐coupled 2D LC‐MS/MS
Authors: Li Wentao , Zheng Houwen , Qin Huichan , Liu Guangnan , Ke Lan , Li Yu , Li Na , Zhong Xiaoning
Published: January 2018

Background

Lung adenocarcinoma is characterized by early asymptomatic progression and metastasis. Appearance of respiratory symptoms usually means the disease is aggravated. The aim of this study was to identify the protein profile in plasma of lung adenocarcinoma of stages I‐IV, and look for novel diagnostic biomarkers.

Methods

Isobaric tags for relative and absolute quantification (iTRAQ) coupled with two dimensional liquid chromatography ‐ tandem mass spectrometry technology (2D LC‐MS/MS) was applied to separate and identify differential expression of proteins in plasma specimens from 10 healthy individuals, 10 patients with pneumonia, 7 patients with lung adenocarcinoma of stages I‐II, respectively, and 10 patients with lung adenocarcinoma of stages III‐IV, then analyze the functions of the differential expression of proteins by bioinformatics.

Results

ADAMTS‐like protein 4, Fibrinogen‐like protein 1 precursor, secretoglobin family 3A member 2 and haptoglobin were up‐regulated in patients with lung adenocarcinoma by proteomics analysis, and the expression levels of SCGB3A2 and Hp by ELISA were consistent. Pathway analysis of identified differential expression of proteins showed they were mainly involved in chemokine/p53/TGF‐beta signaling pathway.

Conclusions

Plasma SCGB3A2 is a potential maker for diagnosis of primary pulmonary adenocarcinoma. Abnormal post‐translational protein modification may be associated with the progression of lung cancer.
A Combined test using both cell sediment and supernatant cell‐free DNA in pleural effusion shows increased sensitivity in detecting activating EGFR mutation in lung cancer patients
Authors: Kawahara A. , Fukumitsu C. , Azuma K. , Taira T. , Abe H. , Takase Y. , Murata K. , Sadashima E. , Hattori S. , Naito Y. , Akiba J.
Published: January 2018

Introduction

The aim of this study was to examine whether a combined test using both cell sediment and supernatant cytology cell‐free DNA (ccfDNA) is more useful in detecting EGFR mutation than using cell sediment DNA or supernatant ccfDNA alone in pleural effusion of lung cancer patients.

Methods

A total of 74 lung adenocarcinoma patients with paired samples between primary tumour and corresponding metastatic tumour with both cell sediment and supernatant ccfDNA of pleural effusion cytology were enrolled in this study. Cell sediment and supernatant ccfDNA were analysed separately for EGFR mutations by polymerase chain reaction.

Results

Out of 45 patients with mutant EGFR in primary tumours, EGFR mutations were detected in 23 cell sediments of corresponding metastases (sensitivity; 51.1%) and 20 supernatant ccfDNA corresponding metastases (sensitivity; 44.4%). By contrast, the combined test detected EGFR mutations in 27 corresponding metastases (sensitivity; 60.0%), and had a higher sensitivity than the cell sediment or the supernatant ccfDNA alone (P < .05). Out of 45 patients with mutant EGFR, 24, three and 18 were cytologically diagnosed as positive, atypical or negative, respectively. The detection rate in the combined test was highest (95.8%) in the positive group, and mutant EGFR was also detected in four of 18 samples (22.2%) in the negative group.

Conclusions

A combined test using both cell sediment DNA and supernatant ccfDNA samples increases the concordance rate of EGFR mutations between primary tumour and corresponding metastases. Our findings indicate that supernatant ccfDNA is useful even in cases where the cytological diagnosis is negative.
Biosimilars in Dermatology – theory becomes reality
Authors: Gerdes Sascha , Mrowietz Ulrich , Augustin Matthias , Ralph von Kiedrowski  , Enk Alexander , Strömer Klaus , Schön Michael P. , Radtke Marc A.
Published: January 2018

Biosimilars are biological medicines that are analogues of a specific reference product. Biosimilars of the tumor necrosis factor alpha inhibitors infliximab and etanercept are already approved and available for dermatological indications. Regulatory agencies require in‐depth analysis of physicochemical and functional properties of these highly complex molecules as well as clinical data on their similarity regarding efficacy and safety in at least one clinical trial in a sensitive and homogeneous population. Thus, it must be shown that biosimilars are essentially the same as the originator product if they are to be licensed in regulated drug markets. As a consequence, these data are extrapolated from one molecule (the originator) to another (biosimilar) resulting in an approval that includes the same indications as the originator product. While extrapolation is well accepted and regulated, clear recommendations regarding the interchangeability of originators and biosimilars as well as data on multiple consecutive switching are missing. Current scientific knowledge does not argue against the use of biosimilars for dermatological indications, but sequential switching of biosimilars should be considered carefully. To increase confidence and enhance evidence for biosimilars, accurate documentation of the specific products given to each patient is essential and should preferably be included in patient registries.
When trade liberalization is self‐fulfilling: Population aging and uncertainty
Authors: Kishishita Daiki
Published: January 2018

Expectation about future trade liberalization induces sectoral adjustment in advance. As a result, the extent of opposition to trade liberalization decreases, and liberalization becomes self‐fulfilling. We analyze this mechanism from two aspects: population aging and uncertainty. Then, we show that (1) the effect of expectation formation is non‐monotonic across ages, and (2) the effect of population aging of workforce varies depending on its driving force. In addition, we analyze uncertainty about future trade liberalization. Then, we show that (3) the mechanism cannot work due to strategic delay even under small uncertainty, but (4) a subsidy scheme can resolve this problem.
Genome‐wide single nucleotide polymorphism‐based autozygosity mapping facilitates identification of mutations in consanguineous families with epidermolysis bullosa
Authors: Vahidnezhad Hassan , Youssefian Leila , Saeidian Amir Hossein , Zeinali Sirous , Touati Andrew , Abiri Maryam , Sotoudeh Soheila , Norouz‐zadeh Sara , Amirinezhad Niloufar , Mozafari Nikoo , Daneshpazhooh Maryam , Mahmoudi Hamidreza , Hamid Mohammad , Bradfield Jonathan P. , Kim Cecilia E. , Hakonarson Hakon , Uitto Jouni
Published: January 2018

Autozygosity mapping (AM) is a technique utilised for mapping homozygous autosomal recessive (AR) traits and facilitation of genetic diagnosis. We investigated the utility of AM for the molecular diagnosis of heterogeneous AR disorders, using epidermolysis bullosa (EB) as a paradigm. We applied this technique to a cohort of 46 distinct EB families using both short tandem repeat (STR) and genome‐wide single nucleotide polymorphism (SNP) array‐based AM to guide targeted Sanger sequencing of EB candidate genes. Initially, 39 of the 46 cases were diagnosed with homozygous mutations using this method. Independently, 26 cases, including the seven initially unresolved cases, were analysed with an EB‐targeted next‐generation sequencing (NGS) panel. NGS identified mutations in five additional cases, initially undiagnosed due to the presence of compound heterozygosity, deep intronic mutations or runs of homozygosity below the set threshold of 2 Mb, for a total yield of 44 of 46 cases (95.7%) diagnosed genetically.
Mexican‐Origin Parents’ Stress and Satisfaction: The Role of Emotional Support
Authors: Popp Tierney K. , Delgado Melissa Y. , Wheeler Lorey A.
Published: January 2018

Guided by a process model of parenting and the integrative model, this study examined sources of emotional support (i.e., partner, maternal, paternal) as related to stress and satisfaction resulting from the parenting role in a sample of Mexican‐origin young adult parents who participated in the National Longitudinal Study of Adolescent to Adult Health (Add Health) during Wave IV. Participants were male and female parents (26–35 years of age; 59% female; N = 737) who had children and a partner. Results from structural equation modeling revealed support from mothers as salient; high levels of maternal support were associated with high levels of parenting satisfaction. Tests of indirect effects suggested that parenting satisfaction played an intervening role in the link between maternal support and parenting stress. The pattern of results held across levels of linguistic acculturation but varied by gender. Understanding the mechanisms that predict parenting stress and satisfaction within the Mexican‐origin population may help in the identification of culturally sensitive intervention strategies.
Attachment Versus Differentiation: The Contemporary Couple Therapy Debate
Authors: Hardy Nathan R. , Fisher Adam R.
Published: January 2018

This paper reviews the current debate between differentiation and attachment in treating couples through exploring the tenets of crucible therapy (Schnarch, 1991) and emotionally focused couple therapy (Johnson, 2004). We provide a review of the two theories—as well as the two “pure form” example models—and explore the debate in light of the integrative movement in couple and family therapy (Lebow, 2014). We also examine points of convergence of the two theories and models, and provide clinicians and researchers with an enhanced understanding of their divergent positions. Both differentiation and attachment are developmental theories that highlight the human experience of balancing individuality and connection in adulthood. The two models converge in terms of metaconcepts that pervade their respective theories and approach. Both models capitalize on the depth and importance of the therapeutic relationship, and provide rich case conceptualization and processes of therapy. However, they substantially differ in terms of how they view the fundamental aspects of adult development, have vastly divergent approaches to how a therapist intervenes in the room, and different ideas of how a healthy couple should function. In light of the deep polarization of the two models, points of integration—particularly between the broader theories of attachment and differentiation—are offered for therapists to consider.
Effectiveness of supplementary irrigant agitation with the Finisher GF Brush on the debridement of oval root canals instrumented with the Gentlefile or nickel titanium rotary instruments
Authors: Neelakantan P. , Khan K. , Li K. Y. , Shetty H. , Xi W.
Published: January 2018

Aim

To examine the efficacy of a novel supplementary irrigant agitating brush (Finisher GF Brush, MedicNRG, Kibbutz Afikim, Israel) on the debridement of root canals prepared with a novel stainless steel rotary instrumentation system (Gentlefile; MedicNRG), or nickel titanium rotary instruments in oval root canals.

Methodology

Mandibular premolars (n = 72) were selected and divided randomly into three experimental groups (n = 24) after microCT scanning: group 1, canal preparation to rotary NiTi size 20, .04 taper (R20); group 2, rotary NiTi to size 25, .04 taper (R25) and group 3, Gentlefile size 23, .04 taper (GF). Specimens were subdivided into two subgroups: subgroup A, syringe‐and‐needle irrigation (SNI); subgroup B, Finisher GF Brush (GB). Ten untreated canals served as controls. Specimens were processed for histological evaluation, and the remaining pulp tissue (RPT) was measured. Data were analysed using Mann–Whitney and Kruskal–Wallis tests (P = 0.05).

Results

All experimental groups had significantly less RPT than the control (P < 0.05). Group 3B (GF‐GB) had significantly less RPT than groups 1B (R20‐GB) and 2B (R25‐GF; P < 0.05). When irrigated with SNI, there was no significant difference in the RPT between the three groups (P > 0.05). When instrumented with R20, there was no significant difference between SNI and GF (P < 0.05) whilst GB had significantly less RPT than SNI for R25 (P < 0.05).

Conclusions

Supplementary irrigant agitation with the Finisher GF Brush improved the debridement of canals prepared with Gentlefile and size 25, .04 taper rotary NiTi. Root canal debridement did not significantly differ between the instruments when syringe irrigation was used.
The role of nailfold capillary dropout on mortality in systemic sclerosis
Authors: Tieu Joanna , Hakendorf Paul , Woodman Richard J. , Patterson Karen , Walker Jenny , Roberts‐Thomson Peter
Published: January 2018

Background

Semi‐quantitative wide‐field nailfold capillaroscopy (NFC) is a simple technique with proven utility in the early diagnosis of systemic sclerosis (SSc). Its role in prognosis, however, remains uncertain.

Aim

To investigate the possible utility of NFC in predicting survival.

Methods

Patients with SSc listed on the South Australian Scleroderma Register (SASR) with prior NFC performed at Flinders Medical Centre from 1991 to 2015 were included in this study. Baseline demographic data, diagnosis, scleroderma antibody status and mortality status were also collected for each patient.

Results

The cohort consisted of 99 patients with limited cutaneous SSc, 30 patients with diffuse cutaneous SSc and 23 with an overlap scleroderma syndrome. Fifty‐six patients died during the period of study (censured end June 2015).

Patients with diffuse scleroderma had significantly greater capillary dropout compared with limited and overlap scleroderma (P < 0.001). In univariate analysis, both capillary dropout scores (log‐rank χ2 = 8.75, P = 0.003) and antibody status (log‐rank χ2 = 13.94, P = 0.003) were associated with mortality. ANOVA showed a significant association between antibody status and capillary dropout (P < 0.001). In Cox regression, adjustment for capillary dropout attenuated the impact of autoantibody group on survival.

Conclusions

Nailfold capillary dropout was significantly associated with mortality and the severity of dropout attenuates survival dictated by antibody status. Together these observations support the hypothesis that capillary dropout is on the causal pathway between induction of scleroderma associated autoantibodies and mortality.
miR‐15b‐5p facilitates the tumorigenicity by targeting RECK and predicts tumour recurrence in prostate cancer
Authors: Chen Ran , Sheng Lu , Zhang Hao‐Jie , Ji Ming , Qian Wei‐Qing
Published: January 2018

MicroRNAs (miRNAs) have been reported to participate in many biological behaviours of multiple malignancies. Recent studies have shown that miR‐15b‐5p (miR‐15b) exhibits dual roles by accelerating or blocking tumour progression. However, the molecular mechanisms by which miR‐15b contributes to prostate cancer (PCa) are still elusive. Here, miR‐15b expression was found significantly up‐regulated in PCa in comparison with the normal samples and was positively correlated with age and Gleason score in patients with PCa. Notably, PCa patients with miR‐15b high expression displayed a higher recurrence rate than those with miR‐15b low expression (P = 0.0058). Knockdown of miR‐15b suppressed cell growth and invasiveness in 22RV1 and PC3 cells, while overexpression of miR‐15b reversed these effects. Then, we validated that RECK acted as a direct target of miR‐15b by dual‐luciferase assay and revealed the negative correlation of RECK with miR‐15b expression in PCa tissues. Ectopic expression of RECK reduced cell proliferation and invasive potential and partially abrogated the tumour‐promoting effects caused by miR‐15b overexpression. Additionally, miR‐15b knockdown inhibited tumour growth activity in a mouse PCa xenograft model. Taken together, our findings indicate that miR‐15b promotes the progression of PCa cells by targeting RECK and represents a potential marker for patients with PCa.
ACE2‐EPC‐EXs protect ageing ECs against hypoxia/reoxygenation‐induced injury through the miR‐18a/Nox2/ROS pathway
Authors: Zhang Cheng , Wang Jinju , Ma Xiaotang , Wang Wenjun , Zhao Bin , Chen Yanfang , Chen Can , Bihl Ji C.
Published: January 2018

Oxidative stress is one of the mechanisms of ageing‐associated vascular dysfunction. Angiotensin‐converting enzyme 2 (ACE2) and microRNA (miR)‐18a have shown to be down‐regulated in ageing cells. Our previous study has shown that ACE2‐primed endothelial progenitor cells (ACE2‐EPCs) have protective effects on endothelial cells (ECs), which might be due to their released exosomes (EXs). Here, we aimed to investigate whether ACE2‐EPC‐EXs could attenuate hypoxia/reoxygenation (H/R)‐induced injury in ageing ECs through their carried miR‐18a. Young and angiotensin II‐induced ageing ECs were subjected to H/R and co‐cultured with vehicle (medium), EPC‐EXs, ACE2‐EPCs‐EXs, ACE2‐EPCs‐EXs + DX600 or ACE2‐EPCs‐EXs with miR‐18a deficiency (ACE2‐EPCs‐EXsanti‐miR‐18a). Results showed (1) ageing ECs displayed increased senescence, apoptosis and ROS production, but decreased ACE2 and miR‐18a expressions and tube formation ability; (2) under H/R condition, ageing ECs showed higher rate of apoptosis, ROS overproduction and nitric oxide reduction, up‐regulation of Nox2, down‐regulation of ACE2, miR‐18a and eNOS, and compromised tube formation ability; (3) compared with EPC‐EXs, ACE2‐EPC‐EXs had better efficiencies on protecting ECs from H/R‐induced changes; (4) The protective effects were less seen in ACE2‐EPCs‐EXs + DX600 and ACE2‐EPCs‐EXsanti‐miR‐18a groups. These data suggest that ACE‐EPCs‐EXs have better protective effects on H/R injury in ageing ECs which could be through their carried miR‐18a and subsequently down‐regulating the Nox2/ROS pathway.
SRRintronic variation inhibits expression of its neighbouringSMG6 gene and protects against temporal lobe epilepsy
Authors: Tao Hua , Zhou Xu , Xie Qian , Ma Zhonghua , Sun Fuhai , Cui Lili , Cai Yujie , Ma Guoda , Fu Jiawu , Liu Zhou , Li You , Zhou Haihong , Zhao Jianghao , Chen Yanyan , Mai Hui , Chen Ying , Chen Jun , Qi Wei , Sun Chaowen , Zhao Bin , Li Keshen
Published: January 2018

D‐serine is a predominant N‐methyl‐D‐aspartate receptor co‐agonist with glutamate, and excessive activation of the receptor plays a substantial role in epileptic seizures. Serine racemase (SRR) is responsible for transforming L‐serine to D‐serine. In this study, we aimed to investigate the genetic roles ofSRRand a neighbouring gene, nonsense‐mediatedmRNAdecay factor (SMG6), in temporal lobe epilepsy (TLE). Here, a total of 496TLEpatients and 528 healthy individuals were successfully genotyped for threeSRRtag single nucleotide polymorphisms. The frequencies of theGGgenotype at rs4523957 T > G were reduced in theTLEcases in the initial cohort (cohort 1) and were confirmed in the independent cohort (cohort 2). An analysis of allTLEcases in cohort 1 + 2 revealed that the seizure frequency and drug‐resistant incidence were significantly decreased in carriers of theGGgenotype at rs4523957. Intriguingly, the activity of theSMG6 promoter with the mutant allele at rs4523957 decreased by 22% in the dual‐luciferase assay, and up‐regulated expression ofSMG6 was observed in an epilepsy rat model. This study provides the first demonstration that theGGgenotype is a protective marker againstTLE. In particular, variation at rs4523957 likely inhibitsSMG6 transcription and plays a key role against susceptibility to and severity ofTLE. The significance ofSMG6 hyperfunction in epileptic seizures deserves to be investigated in future studies.
Honokiol inhibits in vitro and in vivo growth of oral squamous cell carcinoma through induction of apoptosis, cell cycle arrest and autophagy
Authors: Huang Kao‐Jean , Kuo Chin‐Ho , Chen Shu‐Hsin , Lin Ching‐Yen , Lee Ying‐Ray
Published: January 2018

Honokiol, an active natural product derived from Magnolia officinalis, exerted anticancer effects through a variety of mechanisms on multiple types of cancers. In this study, the molecular mechanisms of honokiol in suppressing the human oral squamous cell carcinoma (OSCC) cells were evaluated. Treatment of two OSCC cell lines with honokiol resulted in reducing the cell proliferation and arresting the cell cycle at G1 stage which was correlated with the down‐regulation of Cdk2 and Cdk4 and the up‐regulation of cell cycle suppressors, p21 and p27. In addition, the caspase‐dependent programmed cell death was substantially detected, and the autophagy was induced as the autophagosome formation and autophagic flux proceeded. Modulation of autophagy by autophagic inducer, rapamycin or inhibitors, 3‐MA or bafilomycin, potentiated the honokiol‐mediated anti‐OSCC effects where honokiol exerted multiple actions in suppression of MAPK pathway and regulation of Akt/mTOR or AMPK pathways. As compared to clinical therapeutic agent, 5‐FU, honokiol exhibited more potent activity against OSCC cells and synergistically enhanced the cytotoxic effect of 5‐FU. Furthermore, orally administrated honokiol exerted effective antitumour activity in vivo in OSCC‐xenografted mice. Thus, this study revealed that honokiol could be a promising candidate in preventing human OSCCs.