bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the Effectiveness of Case-Based Collaborative Learning via Randomized Controlled Trial
Authors: Krupat Edward , Richards Jeremy B. , Sullivan Amy M. , Fleenor Thomas J. , Schwartzstein Richard M.
Published: November 2015

Purpose

Case-based collaborative learning (CBCL) is a novel small-group approach that borrows from team-based learning principles and incorporates elements of problem-based learning (PBL) and case-based learning. CBCL includes a preclass readiness assurance process and case-based in-class activities in which students respond to focused, open-ended questions individually, discuss their answers in groups of 4, and then reach consensus in larger groups of 16. This study introduces CBCL and assesses its effectiveness in one course at Harvard Medical School.

Method

In a 2013 randomized controlled trial, 64 medical and dental student volunteers were assigned randomly to one of four 8-person PBL tutorial groups (control; n = 32) or one of two 16-person CBCL tutorial groups (experimental condition; n = 32) as part of a required first-year physiology course. Outcomes for the PBL and CBCL groups were compared using final exam scores, student responses to a postcourse survey, and behavioral coding of portions of video-recorded class sessions.

Results

Overall, the course final exam scores for CBCL and PBL students were not significantly different. However, CBCL students whose mean exam performance in prior courses was below the participant median scored significantly higher than their PBL counterparts on the physiology course final exam. The most common adjectives students used to describe CBCL were “engaging,” “fun,” and “thought-provoking.” Coding of observed behaviors indicated that individual affect was significantly higher in the CBCL groups than in the PBL groups.

Conclusions

CBCL is a viable, engaging, active learning method. It may particularly benefit students with lower academic performance.
A discrete spectral analysis for determining quasi-linear viscoelastic properties of biological materials
Authors: Babaei Behzad , Abramowitch Steven D. , Elson Elliot L. , Thomopoulos Stavros , Genin Guy M.
Published: November 2015

The viscoelastic behaviour of a biological material is central to its functioning and is an indicator of its health. The Fung quasi-linear viscoelastic (QLV) model, a standard tool for characterizing biological materials, provides excellent fits to most stress–relaxation data by imposing a simple form upon a material's temporal relaxation spectrum. However, model identification is challenging because the Fung QLV model's ‘box’-shaped relaxation spectrum, predominant in biomechanics applications, can provide an excellent fit even when it is not a reasonable representation of a material's relaxation spectrum. Here, we present a robust and simple discrete approach for identifying a material's temporal relaxation spectrum from stress–relaxation data in an unbiased way. Our ‘discrete QLV’ (DQLV) approach identifies ranges of time constants over which the Fung QLV model's typical box spectrum provides an accurate representation of a particular material's temporal relaxation spectrum, and is effective at providing a fit to this model. The DQLV spectrum also reveals when other forms or discrete time constants are more suitable than a box spectrum. After validating the approach against idealized and noisy data, we applied the methods to analyse medial collateral ligament stress–relaxation data and identify the strengths and weaknesses of an optimal Fung QLV fit.
Peridynamic simulations of brittle structures with thermal residual deformation: strengthening and structural reactivity of glasses under impacts
Authors: Jeon ByoungSeon , Stewart Ross J. , Ahmed Izhar Z.
Published: November 2015

In glass research, the effect and influence of pre-deformation by thermal or chemical treatment is of great importance when configuring different mechanical properties or scratch resistance on the surface of glasses. In particular, such pre-deformation affects dynamic fracture or damage evolution when glass structures are under impact or collision conditions. Peridynamics provides a seamless approach for the simulation of dynamic damage evolution of the system under aggressive environments. Revising the pair interaction of each material point, the effect of pre-deformation is implemented, and the corresponding damage evolution can be simulated conveniently. Our approach is composed of two steps: first, a static solution is found via energy minimization with thermal boundary conditions in the peridynamic platform. Second, comparing the initial and the pre-deformed structures from the energy minimization, the effect of residual deformation, strengthening and reactive behaviour of brittle structures are seamlessly simulated. The developed methods are applied to the Prince Rupert’s drop and Bologna vial, which are classic examples of strengthened glasses. This study reports the first complete and successful simulation of dynamic behaviour of strengthened glasses, and a significant contribution in simulating residual stress behaviour in any material.
An inverse method for determining the spatially resolved properties of viscoelastic–viscoplastic three-dimensional printed materials
Authors: Chen X. , Ashcroft I. A. , Wildman R. D. , Tuck C. J.
Published: November 2015

A method using experimental nanoindentation and inverse finite-element analysis (FEA) has been developed that enables the spatial variation of material constitutive properties to be accurately determined. The method was used to measure property variation in a three-dimensional printed (3DP) polymeric material. The accuracy of the method is dependent on the applicability of the constitutive model used in the inverse FEA, hence four potential material models: viscoelastic, viscoelastic–viscoplastic, nonlinear viscoelastic and nonlinear viscoelastic–viscoplastic were evaluated, with the latter enabling the best fit to experimental data. Significant changes in material properties were seen in the depth direction of the 3DP sample, which could be linked to the degree of cross-linking within the material, a feature inherent in a UV-cured layer-by-layer construction method. It is proposed that the method is a powerful tool in the analysis of manufacturing processes with potential spatial property variation that will also enable the accurate prediction of final manufactured part performance.
The Implications of Small Stem Cell Niche Sizes and the Distribution of Fitness Effects of New Mutations in Aging and Tumorigenesis
Authors: Cannataro Vincent L. , McKinley Scott A. , St. Mary Colette M.
Published: November 2015

Somatic tissue evolves over a vertebrate’s lifetime due to the accumulation of mutations in stem cell populations. Mutations may alter cellular fitness and contribute to tumorigenesis or aging. The distribution of mutational effects within somatic cells is not known. Given the unique regulatory regime of somatic cell division we hypothesize that mutational effects in somatic tissue fall into a different framework than whole organisms; one in which there are more mutations of large effect. Through simulation analysis we investigate the fit of tumor incidence curves generated using exponential and power law Distributions of Fitness Effects (DFE) to known tumorigenesis incidence. Modeling considerations include the architecture of stem cell populations, i.e., a large number of very small populations, and mutations that do and do not fix neutrally in the stem cell niche. We find that the typically quantified DFE in whole organisms is sufficient to explain tumorigenesis incidence. Further, due to the effects of small stem cell population sizes, i.e., strong genetic drift, deleterious mutations are predicted to accumulate, resulting in reduced tissue maintenance. Thus, despite there being a large number of stem cells throughout the intestine, its compartmental architecture leads to significant aging, a prime example of Muller’s Ratchet.
Leadership cultures and discursive hybridisation
Authors: Crevani Lucia , Ekman Marianne , Lindgren Monica , Packendorff Johann
Published: November 2015

Purpose

– The purpose of this paper is to explore the concept of leadership culture and analyse how leadership cultures are produced in higher education reforms, in a hybridised discursive context of traditional academic values and emerging managerialism and leaderism.

Design/methodology/approach

– Building on a perspective on leadership as a cultural phenomenon emerging in processes in which societal, sectorial and professional discursive resources are invoked, this study adds to earlier studies on how notions of leadership are involved in the transformation of higher education organisations. To this end, the method combines a traditional qualitative study of change initiatives over a long period of time with participative observation. Focusing on two vignettes, the analysis centres on how several discursive resources are drawn upon in daily interaction.

Findings

– The emergence of hybrid leadership cultures in which several discursive resources are drawn upon in daily interaction is illustrated. This paper emphasises how hybrid cultures develop through confirmation, re-formulation and rejection of discursive influences.

Research limitations/implications

– An extended empirical material would enable further understanding of what cultural constructions of leadership that become confirmed, re-formulated or rejected. International comparisons would also enrich the analysis.

Practical implications

– This paper may influence leadership, leadership development and change initiatives in higher education organisation.

Social implications

– Higher education organisations are crucial for societal development and this paper contributes to better understanding how they are changing.

Originality/value

– The perspective proposed builds on recent developments in leadership studies and expands the means for focusing on social processes rather than individuals.
Faith-based organizations and the challenges of public legitimation
Authors: Malmelin Karoliina , Malmelin Nando
Published: November 2015

Purpose

– The purpose of this paper is to identify and analyze the challenges of public legitimation faced by faith-based organizations (FBOs) today. The paper addresses a new approach to studying legitimation as a public and communicative process.

Design/methodology/approach

– FBOs ' public legitimation problems are discussed on the basis of a systematic literature review and the problematization method.

Findings

– The paper presents a novel typology of FBOs ' public legitimation problems, which are divided into the four categories of mission, brand and reputation, public relations and trust. It is suggested that research on FBOs and their legitimation should apply and develop the communication approach.

Originality/value

– The paper addresses a current gap in legitimation research by reviewing the literature on public legitimation and the legitimation problems faced by FBOs. It identifies the communication approach as a significant perspective for future studies of FBO public legitimation.
Application of the strain-based FAD to failure assessment of surface cracked components
Authors: Varfolomeev Igor , Windisch Michael , Sinnema Gerben
Published: November 2015

Purpose

– The purpose of this paper is to validate the strain-based failure assessment diagram (SB-FAD) approach for surface cracks in components subjected to displacement controlled boundary conditions.

Design/methodology/approach

– Numerical analyses are performed for several crack geometries and materials representative for aerospace applications. The performance of the SB-FAD is judged by comparing numerically calculated J-integrals to respective analytical estimates, using both Options 1 and 2 approximations.

Findings

– In the most cases, both Options 1 and 2 SB-FAD method results in reasonably conservative J-estimates. Exceptions are for surface cracks in a pressurized vessel made of a material with low-strain hardening, for which Option 2 assessment produces non-conservative results. In contrast, Option 1 assessment is conservative for all geometries considered. In general, Option 1 results in a considerable overestimation of the crack driving force, whereas Option 2 produces rather accurate results in many cases.

Originality/value

– The results demonstrate both the potential of the SB-FAD method and needs for its further improvements.
Fracture mechanical behaviour of laser beam-welded AA2198 butt joints and integral structures
Authors: Kashaev Nikolai , Riekehr Stefan , Erdmann Kay , Carvalho Alexandre Amorim , Nurgaliev Maxim , Alexopoulos Nikolaos , Karanika Alexandra
Published: November 2015

Purpose

– Composite materials and metallic structures already compete for the next generation of single-aisle aircraft. Despite the good mechanical properties of composite materials metallic structures offer challenging properties and high cost effectiveness via the automation in manufacturing, especially when metallic structures will be welded. In this domain, metallic aircraft structures will require weight savings of approximately 20 per cent to increase the efficiency and reduce the CO2emission by the same amount. Laser beam welding of high-strength Al-Li alloy AA2198 represents a promising method of providing a breakthrough response to the challenges of lightweight design in aircraft applications. The key factor for the application of laser-welded AA2198 structures is the availability of reliable data for the assessment of their damage tolerance behaviour. The paper aims to discuss these issues.

Design/methodology/approach

– In the presented research, the mechanical properties concerning the quasi-static tensile and fracture toughness (R-curve) of laser beam-welded AA2198 butt joints are investigated. In the next step, a systematic analysis to clarify the deformation and fracture behaviour of the laser beam-welded AA2198 four-stringer panels is conducted.

Findings

– AA2198 offers better resistance against fracture than the well-known AA2024 alloy. It is possible to weld AA2198 with good results, and the welds also exhibit a higher fracture resistance than AA2024 base material (BM). Welded AA2198 four-stringer panels exhibit a residual strength behaviour superior to that of the flat BM panel.

Originality/value

– The present study is undertaken on the third-generation airframe-quality Al-Li alloy AA2198 with the main emphasis to investigate the mechanical fracture behaviour of AA2198 BMs, laser beam-welded joints and laser beam-welded integral structures. Studies investigating the damage tolerance of welded integral structures of Al-Li alloys are scarce.
Multi-objective fatigue life optimization using Tabu Genetic Algorithms
Authors: Long Kim C. , Duff William S , Labadie John W , Stansloski Mitchell J , Sampath Walajabad S , Chong Edwin K.P.
Published: November 2015

Purpose

– The purpose of this paper is to present a real world application of an innovative hybrid system reliability optimization algorithm combining Tabu search with an evolutionary algorithm (TSEA). This algorithm combines Tabu search and Genetic algorithm to provide a more efficient search method.

Design/methodology/approach

– The new algorithm is applied to an aircraft structure to optimize its reliability and maintain its structural integrity. For retrofitting the horizontal stabilizer under severe stall buffet conditions, a decision support system (DSS) is developed using the TSEA algorithm. This system solves a reliability optimization problem under cost and configuration constraints. The DSS contains three components: a graphical user interface, a database and several modules to provide the optimized retrofitting solutions.

Findings

– The authors found that the proposed algorithm performs much better than state-of-the-art methods such as Strength Pareto Evolutionary Algorithms on bench mark problems. In addition, the proposed TSEA method can be easily applied to complex real world optimization problem with superior performance. When the full combination of all input variables increases exponentially, the DSS become very efficient.

Practical implications

– This paper presents an application of the TSEA algorithm for solving nonlinear multi-objective reliability optimization problems embedded in a DSS. The solutions include where to install doublers and stiffeners. Compromise programming is used to rank all non-dominant solutions.

Originality/value

– The proposed hybrid algorithm (TSEA) assigns fitness based upon global dominance which ensures its convergence to the non-dominant front. The high efficiency of this algorithm came from using Tabu list to guidance the search to the Pareto-optimal solutions.
Sensory Threshold Studies of Picrocrocin, the Major Bitter Compound of Saffron
Authors: Chrysanthou Andreas , Pouliou Evangelia , Kyriakoudi Anastasia , Tsimidou Maria Z.
Published: November 2015

This study is part of a wider project on the bitter taste of saffron and its preparations. A deeper knowledge on the taste perception of picrocrocin is necessary in order to develop products that satisfy consumer senses and provide them with adequate amounts of saffron major constituents, also appreciated for bioactivity. A systematic approach on the bitterness of picrocrocin, the major responsible compound, was conducted. A panel was trained specifically for the determination of taste detection and recognition thresholds of picrocrocin, which were found to be 5.34 and 7.26 mg/L, respectively, using the Ascending Forced Choice of Limits methodology. The threshold values were examined in water in absence and presence of other saffron constituents and ethanol and were found to decrease when served hot (61 ± 4 °C). Bitterness was enhanced in 40% (v/v) aqueous ethanol. In both aqueous and ethanol extracts, the presence of saffron volatiles improved bitterness perception. The usefulness of the study was tested in the case of commercial saffron based infusions.
Identification of Drivers of Liking for Bar‐Type Snacks Based on Individual Consumer Preference
Authors: Kim Mina K. , Greve Patrick , Lee Youngseung
Published: November 2015

Understanding consumer hedonic responses on food products are of greatest interests in global food industry. A global partial least square regression (GPLSR) had been well accepted method for understanding consumer preferences. Recently, individual partial least square regression (IPLSR) was accepted as an alternative method of predicting consumer preferences on given food product, because it utilizes the individual differences on product acceptability. To improve the understanding of what constitutes bar‐type snack preference, the relationship between sensory attributes and consumer overall liking for 12 bar‐type snacks was determined. Sensory attributes that drive consumer product likings were analyzed using averaged‐consumer data by GPLSR. To facilitate the interpretation of individual consumer liking, a dummy matrix for the significant weighted regression coefficients of each consumer derived from IPLSR was created. From the application of GPLSR and IPLSR, current study revealed that chocolate and cereal‐flavored bars were preferred over fruit‐flavored bars. Attributes connected to chocolate flavor positively influenced consumer overall likings on the global and individual consumer levels. Textural attributes affected liking only on the individual level. To fully capture the importance of sensory attributes on consumer preference, the use of GPLSR in conjunction with IPLSR is recommended.
‘Rip'ning buds in Freedom's field’: Staging Irish Improvement in the 1780s
Authors: O'Shaughnessy David
Published: November 2015

This article offers John O'Keeffe as a case study representing a network of Irish playwrights in 1780s London. The literary achievement of these writers, significantly underwritten in London theatre history, might be better understood against the backdrop of Irish patriotism of that period. This achievement was partly facilitated by the establishment of the Benevolent Society of St Patrick in 1783, ostensibly a charitable organisation but also a forum for Irish networking across professional and class boundaries. This article reads two of O'Keeffe's plays against this backdrop and argues that theatre is a crucial site of intersection for Irish patriotism and cosmopolitan ambition.
IL‐17A increases TNF‐α‐induced COX‐2 protein stability and augments PGE2 secretion from airway smooth muscle cells: impact on β2‐adrenergic receptor desensitization
Authors: Rumzhum N. N. , Patel B. S. , Prabhala P. , Gelissen I. C. , Oliver B. G. , Ammit A. J.
Published: November 2015

Background

IL‐17A plays an important role in respiratory disease and is a known regulator of pulmonary inflammation and immunity. Recent studies have linked IL‐17A with exacerbation in asthma and COPD. We have shown that the enzyme cyclooxygenase‐2 (COX‐2) and its prostanoid products, prostaglandin E2 (PGE2) in particular, are key contributors in in vitro models of infectious exacerbation; however, the impact of IL‐17A was not known.

Methods and Results

We address this herein and show that IL‐17A induces a robust and sustained upregulation of COX‐2 protein and PGE2 secretion from airway smooth muscle (ASM) cells. COX‐2 can be regulated at transcriptional, post‐transcriptional and/or post‐translational levels. We have elucidated the underlying molecular mechanisms responsible for the sustained upregulation of TNF‐α‐induced COX‐2 by IL‐17A in ASM cells and show that is not via increased COX‐2 gene expression. Instead, TNF‐α‐induced COX‐2 upregulation is subject to regulation by the proteasome, and IL‐17A acts to increase TNF‐α‐induced COX‐2 protein stability as confirmed by cycloheximide chase experiments. In this way, IL‐17A acts to amplify the COX‐2‐mediated effects of TNF‐α and greatly enhances PGE2 secretion from ASM cells.

Conclusion

As PGE2 is a multifunctional prostanoid with diverse roles in respiratory disease, our studies demonstrate a novel function for IL‐17A in airway inflammation by showing for the first time that IL‐17A impacts on the COX‐2/PGE2 pathway, molecules known to contribute to disease exacerbation.
Career Criminals and the Antisocial Life Course
Authors: DeLisi Matt
Published: November 2015

Career criminals account for more than half of the crime in society and an even larger proportion of the most violent offenses, including homicide. In recent years, biosocial criminologists have specified the etiological bases of pathological criminality using data from twin and genetic studies. Coupled with environmental factors, several endophenotypes (e.g., self‐regulation, self‐control, neuropsychological functioning, and temperament) connect biological vulnerabilities to behavioral phenotypes. The antisocial repertoire of career criminals is traceable across life as aggressive and antisocial conduct continues from early childhood through adolescence and into adulthood. Prevention programs and interventions can reduce the incidence of career criminality.
Evolving systemic targeted therapy strategies in uveal melanoma and implications for ophthalmic management: a review
Authors: Goh Amanda YL , Layton Christopher J
Published: November 2015

Uveal melanoma (UM) is the most common primary ocular tumour in adults. Despite good local control of the primary tumour with current methods, survival after the development of metastasis has remained poor over the last 30 years. After cutaneous melanoma, UM is the most common type of melanoma, and an ongoing debate exists regarding whether these conditions should be considered separate entities, particularly in the context of targeted therapy, where many of the initial trials for patients with metatatic cutaneous melanoma excluded metastatic UM. This paper will review the recent and ongoing investigations designed to validate systemic targeted therapy and immunotherapy in patients with metastatic UM and suggests ways in which these developments may affect management of UM by ophthalmologists in the near future.
Allogeneic adipose‐derived stem cells for the treatment of perianal fistula in Crohn's disease: a pilot clinical trial
Authors: Park K. J. , Ryoo S.‐B. , Kim J. S. , Kim T. I. , Baik S. H. , Kim H. J. , Lee K. Y. , Kim M. , Kim W. H.
Published: November 2015

Aim

Many perianal fistulae in Crohn's disease do not respond to conventional surgical and medical management and recurrence rates are high. The study evaluated the safety and feasibility of allogeneic adipose‐derived stem cells for the treatment of perianal fistula in Crohn's disease.

Method

A multicentre, open‐label, dose escalation pilot study was performed. The first three patients (group 1) were administered 1 × 107 cells/ml based on the size of the fistula tract. Four weeks later, after which time this dose had been confirmed to be safe, the next three patients (group 2) were administered 3 × 107 cells/ml. The end‐point was complete closure at 8 weeks after the injection. Patients who attended for the 8 week assessment were followed for an additional 6 months.

Results

There were no adverse events of Grade 3 or 4 severity and no adverse events related to the treatment with allogeneic adipose‐derived stem cells. Two patients in group 1 achieved complete closure of the fistula at month 4 and month 6, and one patient in group 2 achieved complete closure at 8 weeks. The closure was sustained up to month 8 in all three of those patients.

Conclusion

These data suggest that allogeneic adipose‐derived stem cells may be a feasible treatment option for perianal fistula in Crohn's disease.
Efficacy and safety of linagliptin as add‐on therapy to basal insulin and metformin in people with Type 2 diabetes
Authors: Durán‐Garcia S. , Lee J. , Yki‐Järvinen H. , Rosenstock J. , Hehnke U. , Thiemann S. , Patel S. , Woerle H.‐J.
Published: November 2015

Aim

To evaluate the efficacy and safety of linagliptin in people with Type 2 diabetes inadequately controlled on basal insulin and metformin.

Methods

This was a post hoc subanalysis of participants who received basal insulin and metformin in a global phase III study that randomized participants (1:1) to receive linagliptin 5 mg once daily or placebo for ≥52 weeks as add‐on therapy to basal insulin alone or in combination with metformin and/or pioglitazone. During the first 24 weeks, the background dose of basal insulin remained stable; thereafter, adjustments based on glucose concentrations were recommended. The primary endpoint of the subanalysis was the change from baseline in HbA1c after 24 weeks. The safety analysis incorporated data up to a maximum of 110 weeks.

Results

A total of 950 participants receiving background insulin and metformin were included in this subanalysis (linagliptin and placebo, both n = 475). At week 24, the placebo‐corrected adjusted mean (±se) change from baseline in HbA1c with linagliptin was –7 (±1) mmol/mol [–0.7 (±0.1) %; 95% CI –0.8, –0.6; P < 0.0001]. The overall frequency of drug‐related adverse events (linagliptin, 18.9%; placebo, 21.9%) and investigator‐reported hypoglycaemia (linagliptin, 30.7%; placebo, 31.6%) were similar in both groups at the end of treatment. The frequency of severe hypoglycaemia was low (linagliptin, 1.7%; placebo, 0.8%). No meaningful changes in mean (±sd) body weight were noted in either group [week 52: linagliptin, –0.5 (±3.2) kg; placebo, 0.0 (±3.1) kg].

Conclusions

Linagliptin added to basal insulin and metformin improved glycaemic control, without increasing the risk of hypoglycaemia or body weight gain.
Carotid stenosis and cognitive impairment amongst older Chinese adults living in a rural area: a population‐based study
Authors: Yan Z. , Liang Y. , Shi J. , Cai C. , Jiang H. , Song A. , Qiu C.
Published: November 2015

Background and purpose

The possible association between carotid stenosis and cognitive impairment in the Chinese population has been rarely investigated. The association between the severity of carotid stenosis and cognitive impairment amongst older Chinese people living in a rural area was assessed.

Methods

This cross‐sectional study included 1375 participants (age ≥60 years) from the Confucius Hometown Aging Project in Shandong. In 2010–2011, data were collected through interviews and clinical examinations. Carotid stenosis was assessed using ultrasonography. Cognitive impairment was defined according to the education‐specific cutoff scores of the Mini‐Mental State Examination. Data were analyzed using multinomial logistic models.

Results

The overall prevalence was 7.0% for moderate carotid stenosis, 2.0% for severe stenosis and 6.0% for cognitive impairment. The multi‐adjusted odds ratio of cognitive impairment was 1.43 (95% confidence interval 0.63–3.22) for moderate carotid stenosis and 3.75 (1.24–11.40) for severe carotid stenosis (Ptrend = 0.023). Similar results were obtained in people without a history of cerebrovascular disease.

Conclusions

Severe carotid stenosis, even asymptomatic, is associated with cognitive impairment independent of atherosclerotic risk factors and disorders amongst older Chinese people.
Pharmacokinetics, safety and tolerability of the novel, selective mineralocorticoid receptor antagonist finerenone – results from first‐in‐man and relative bioavailability studies
Authors: Lentini Silvia , Heinig Roland , Kimmeskamp‐Kirschbaum Nina , Wensing Georg
Published: November 2015

The safety, tolerability and pharmacokinetics of the selective nonsteroidal mineralocorticoid receptor antagonist finerenone were evaluated in healthy male volunteers in two randomized, single‐centre studies. Study 1 was a first‐in‐man, single‐blinded, placebo‐controlled, parallel‐group, dose‐escalation study. Fasted participants (n = 45) received single oral doses of finerenone 1–40 mg polyethylene glycol (PEG) solution or placebo. Study 2 was a relative bioavailability study comparing a finerenone 10 mg immediate‐release (IR) tablet with finerenone 10 mg PEG solution in the fasted state, investigating the effect of a high‐fat/high‐calorie meal on the pharmacokinetics of the IR tablet and assessing a further dose escalation to finerenone 80 mg (eight × finerenone 10 mg IR tablets), in an open‐label, fourfold crossover design (n = 15). Finerenone was rapidly absorbed from PEG solution (median time to maximum plasma concentration [tmax]: 0.500–1.00 h), exhibited dose‐linear pharmacokinetics and was rapidly eliminated from plasma (geometric mean terminal half‐life [t½]: 1.70–2.83 h). Finerenone IR tablets demonstrated similar pharmacokinetics (median tmax: 0.750–2.50 h; geometric mean t½: 1.89–4.29 h) with, however, enhanced bioavailability versus PEG solution (least‐squares mean tablet/solution ratio of 187% for area under the plasma–concentration curve [AUC] and maximum plasma concentration [Cmax]). High‐fat/high‐calorie food affected the rate but not the extent of finerenone absorption. Finerenone was well tolerated and did not influence clinical laboratory parameters, blood pressure, heart rate, urinary electrolytes or neurohormones, including serum aldosterone and angiotensin II. In conclusion, finerenone has favourable pharmacokinetics and tolerability in healthy men, and is suitable for dosing independent of food intake.
Development of a patient‐centred conceptual framework of health‐related quality of life in neuromyelitis optica: a qualitative study
Authors: Methley Abigail M. , Mutch Kerry , Moore Perry , Jacob Anu
Published: November 2015

Background

Neuromyelitis optica (NMO) is an auto‐immune disease that can cause severe visual and mobility impairments. Research on health‐related quality of life (HRQoL) in NMO is scarce, limiting knowledge on factors influencing HRQoL and support needs.

Aim

This study provides the first qualitative exploration of HRQoL in NMO, conducted to provide a conceptual framework for the development of an NMO patient‐reported outcome measure.

Method

Fifteen people with NMO (aged 18–74; 11 women, 4 men) participated in semi‐structured interviews; data were analysed using constant comparative analysis.

Results

HRQoL in NMO is a multifaceted concept incorporating highly subjective perceptions of normality and meaning. Four major themes were identified: impact of physical symptoms on daily living, utilizing support to achieve independence, expectations for life and meaningful roles in life and purpose.

Discussion

Themes highlighted the importance of perceived normality, and its relationship to attaining life goals comparable to peers, as underpinning evaluations of HRQoL. Many people with severe disability reported a high HRQoL, suggesting the inappropriateness of assuming a negative HRQoL on the basis of an individual's neurological impairment.

Conclusions

These findings further the conceptual understanding of HRQoL in NMO, informing patient‐care approaches and the development of an NMO‐specific patient‐reported outcome measure.
Regional challenges: evaluation of a hepatitis outreach programme using transient elastography (FibroScan) in Victoria
Authors: Thurnheer M. C. , Schulz T. R. , Nguyen T. , MacLachlan J. , Sasadeusz J.
Published: November 2015

Background

Evaluation of an outreach programme using a mobile transient elastography (TE) device (FibroScan) to improve liver disease assessment in different clinical settings.

Aims

To evaluate a programme of liver fibrosis assessment by TE and to compare fibrosis scores between different sites and patient groups.

Methods

Prospective cohort study. TE was conducted at a tertiary hospital and during outreach clinics in three different settings: community clinics, clinics for people who use drugs (PWUD) and regional clinics in rural Victoria. All patients referred for TE at the participating locations were eligible during the study period.

Results

A total of 200 of 623 patients was assessed and evaluated during outreach sessions (regional 100; PWUD 18; community 82). While the majority of patients in community centres were infected with hepatitis B (68%), most patients in regional clinics and in PWUD settings had hepatitis C virus (HCV) (81 and 100%, respectively). Significantly more patients assessed at regional clinics and PWUD settings presented with severe fibrosis (F3‐F4, F4): regional clinics 39%; PWUD 31%; tertiary 11%; community 7%, (P <0.001). Multivariable logistic regression analysis revealed that older age, alcohol consumption, male sex, increased alanine transferase levels, HCV infection and importantly, evaluation at regional sites were independently associated with severe fibrosis.

Conclusions

A TE‐based outreach programme allows for assessment of liver fibrosis in varied and regional populations. The finding that patients in regional settings and PWUD presented with more advanced fibrosis should prompt improvements in healthcare to improve access for these populations.
Production mondialisée et progrès social: le cas du textile et de l'habillement
Authors: GIMET Céline , GUILHON Bernard , ROUX Nathalie
Published: November 2015

La fragmentation de la production au sein de réseaux mondiaux n'obéit pas seulement à l'avantage comparatif, mais aussi aux décisions de localisation des entreprises dominantes en fonction de la capacité de négociation des producteurs locaux et du rôle qu'elles leur assignent dans la chaîne de production. Les auteurs examinent les conséquences de cette spécialisation dans le textile et l'habillement, pour vingt‐six pays où l'offre de main‐d'œuvre est abondante, sur la période 1990–2007. L'étude économétrique montre que le secteur ne tire pas toujours bénéfice de l'intégration commerciale: on observe plutôt une association négative entre spécialisation verticale et salaires réels.
Informality in a micro economy: Measurement, composition and consequences
Authors: BESIM Mustafa , EKICI Tufan , JENKINS Glenn P.
Published: November 2015

This article measures the extent of – and unrecorded income generated by – informal employment in a micro economy characterized by poor governance. Household survey and census data are used to estimate the number of informal workers in Northern Cyprus and analyse the characteristics of informal employment, for the period 2004–11. Informal workers are mostly comprised of citizens with no social security registration, illegally employed immigrants or second‐job holders who have not registered their second jobs. In terms of value added, the estimated size of the informal economy is 9.1 per cent and 12.2 per cent of GNP in 2006 and 2011, respectively.
The Relationship Between High‐Sensitivity C‐Reactive Protein Levels and Left Ventricular Hypertrophy in Patients With Newly Diagnosed Hypertension
Authors: Seyfeli Ergun , Sarli Bahadir , Saglam Hayrettin , Karatas Can Y. , Ozkan Eyup , Ugurlu Mehmet
Published: November 2015

The authors aimed to evaluate the relationship between high‐sensitivity C‐reactive protein (hs‐CRP) and presence of left ventricular hypertrophy and diastolic dysfunction in patients with hypertension. A total of 95 newly diagnosed hypertensive patients (mean age, 54±10 years) and 20 controls were included in this study. Patients were divided into four groups according to relative wall thickness as normal, concentric remodeling, concentric, and eccentric hypertrophy. hs‐CRP was measured in all patients and serum hs‐CRP level was shown to be increased in patients with hypertension compared with controls (0.57 mg/dL vs 0.25 mg/dL, respectively; P<.001). The hs‐CRP level was highest in patients with concentric hypertrophy. When compared with controls, serum hs‐CRP level was significantly higher in patients with concentric remodeling (0.61±0.3 mg/dL vs 0.43±0.5 mg/dL, P<.030) and concentric hypertrophy (0.69±0.3 mg/dL vs 0.43±0.5 mg/dL, P<.032). The present study shows that serum hs‐CRP is significantly associated with left ventricular diastolic function and concentric hypertrophy in patients with hypertension.
The Postcolonial has Moved into Europe: Bordering, Security and Ethno‐Cultural Belonging
Authors: Kinnvall Catarina
Published: November 2015

The legacy of European colonialisms and nationalisms has conditioned immigration and citizenship policies that inform the postcolonial move into Europe. This article questions the assumptions that undergird conceptions of boundary, territory and ethno‐cultural belonging in the constitution of Europe. In particular, it emphasizes how Europe and European integration must be read within the context of postcolonial globalization, migration and ethnicity in which the concept of postcolonialism is important not only for understanding how the idea of Europe was transferred to postcolonial societies, but also for arguing that colonialism never left Europe unaffected and is still part of European reality. Reading Europe and European integration through a postcolonial lens means taking seriously the challenges involved in the re‐assertion of national identities. It also provides a novel attempt to conceptualize the current economic crisis as being as much about contesting (national) narratives of economic transformations as of contrasting material developments and processes.
The dipeptidyl peptidase IV inhibitor vildagliptin suppresses development of neuropathy in diabetic rodents: effects on peripheral sensory nerve function, structure and molecular changes
Authors: Tsuboi Kentaro , Mizukami Hiroki , Inaba Wataru , Baba Masayuki , Yagihashi Soroku
Published: November 2015

Incretin‐related therapy was found to be beneficial for experimental diabetic neuropathy, but its mechanism is obscure. The purpose of this study is to explore the mechanism through which dipeptidyl peptidase IV inhibitor, vildagliptin (VG), influences neuropathy in diabetic rodents. To this end, non‐obese type 2 diabetic Goto‐Kakizaki rats (GK) and streptozotocin (STZ)‐induced diabetic mice were treated with VG orally. Neuropathy was evaluated by nerve conduction velocity (NCV) in both GK and STZ‐diabetic mice, whereas calcitonin‐gene‐related peptide expressions, neuronal cell size of dorsal root ganglion (DRG) and intraepidermal nerve fiber density were examined in GK. DRG from GK and STZ‐diabetic mice served for the analyses of GLP‐1 and insulin signaling. As results, VG treatment improved glucose intolerance and increased serum insulin and GLP‐1 in GK accompanied by the amelioration of delayed NCV and neuronal atrophy, reduced calcitonin‐gene‐related peptide expressions and intraepidermal nerve fiber density. Diet restriction alone did not significantly influence these measures. Impaired GLP‐1 signals such as cAMP response element binding protein, protein kinase B/Akt (PKB/Akt) and S6RP in DRG of GK were restored in VG‐treated group, but the effect was equivocal in diet‐treated GK. Concurrently, decreased phosphorylation of insulin receptor substrate 2 in GK was corrected by VG treatment. Consistent with the effect on GK, VG treatment improved NCV in diabetic mice without influence on hyperglycemia. DRG of VG‐treated diabetic mice were characterized by correction of GLP‐1 signals and insulin receptor substrate 2 phosphorylation without effects on insulin receptor β expression. The results suggest close association of neuropathy development with impaired signaling of insulin and GLP‐1 in diabetic rodents.

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Diabetic neurons are resistant to insulin and such insulin resistance may contribute to development of neuropathy. DPP‐IV inhibitor, vildagliptin, corrected insulin resistance and improved neuropathy irrespective of blood glucose via augmented action of GLP‐1.
Effects of Light Color on Consumers’ Acceptability and Willingness to Eat Apples and Bell Peppers
Authors: Yang Famous Lue , Cho Sungeun , Seo Han‐Seok
Published: November 2015

This study aimed to determine whether ambient light colors affect consumers’ willingness to eat, sensory perceptions and hedonic impressions of foods. Sliced apples and red bell peppers were presented under five different colors of light: white, yellow, green, blue and red, respectively. Participants were asked to observe the presented food under these colored lights, to rate their willingness to eat and liking of food appearance. After tasting, participants were asked to rate intensities of flavor and crispness and rate overall impression of the food. When the food samples were presented under white or yellow light rather than blue light, participants not only wanted to eat more, but also liked the foods more. Participants were especially more willing to eat apples under yellow light than under white light commonly experienced in daily life. Flavor intensity of apples was found to be lower under blue light than under yellow, white or red light; this trend was not observed in flavor intensity of bell peppers. Crispness intensities were not different among the five light‐color conditions. In conclusion, our findings support and extend the notion that light colors modulate consumers’ willingness to eat and their hedonic impressions of foods, especially apples and bell peppers.

Practical Applications

As multicolored light‐emitting diode bulbs have become popular, foods and drinks are often displayed under colored light in restaurants and retail stores. The results of this study will provide sensory scientists and food‐service professionals with valuable insights as to how their consumers will most likely behave under colored lights in a given dining establishment. In addition, based on findings that participants’ appetites were significantly higher for apples under yellow light than under white light, yellow light might be used as a tool for encouraging people to consume more apples in everyday life.
Complete Genome Sequence of a Chinese Isolate of Melon Necrotic Spot Virus and its Phylogenetic Relationship
Authors: Wu Hui‐jie , Wen Shao‐hua , Hong Ni , Veronica Truniger , Gu Qin‐sheng
Published: November 2015

The full‐length nucleotide sequence and genomic organization of a melon necrotic spot virus isolate from Haimen, China (MNSV‐HM), were determined. The MNSV‐HM genome consists of a positive sense single‐stranded RNA, 4267 nt in length, with at least five open reading frames (ORFs) encoding p29, p89, p42, and two small 7‐kDa proteins (p7A and p7B). p89 shares a common start codon with p29 and continues through the amber stop codon of p29 to produce an 89‐kDa protein. The p7A ORF terminates in an amber codon whose read‐through could generate a 14‐kDa protein. Phylogenetic analyses based on the p42 amino acid sequence and complete genomic sequence placed MNSV‐HM and Spanish isolates of the virus in a major cluster, indicating a close genetic relationship. In conclusion, we report the full‐length sequence of MNSV‐HM and its translation strategy. The obtained genomic organization and phylogenetic trees indicate that MNSV‐HM belongs to the MNSV genus Carmovirus. To the best of our knowledge, this is the first demonstration of the complete nucleotide sequence of an MNSV isolate from China.
Subjective parameters markedly limit the referral of transplantation candidates to liver transplant centres
Authors: Vidal‐Trécan Gwenaëlle , Kone Victoria , Pilette Christophe , Nousbaum Jean‐Baptiste , Doll Jacques , Buffet Catherine , Eugene Claude , Podevin Philippe , Boutet Olivier , Puyeo Jacques , Conti Filomena , Calmus Yvon
Published: November 2015

Background & Aims

Equality of access to organ transplantation is a mandatory public health requirement. Referral from a local to a university hospital and then registration on the national waiting list are the two key steps enabling access to liver transplantation (LT). Although the latter procedure is well defined using the Model for End‐stage Liver Disease score that improves equality of access, the former is mostly reliant on the practices of referring physicians. The aim of this study was to clarify the factors determining this initial step.

Methods

This observational study included consecutive inpatients with cirrhosis of whatever origin in a cohort constituted between 2003 and 2008, using medical records and structured questionnaires concerning patient characteristics and the opinions of hospital clinicians. Candidates for LT were defined in line with these opinions.

Results

Four hundred and thirty‐three patients, mostly affected by alcoholic cirrhosis, were included, 21.0% of whom were considered to be candidates for LT. Factors independently associated with their candidature were: physician empathy [odds ratio (OR) = 10.8; 95% CI: 4.0–29.5], adherence to treatment (OR = 16.6; 95% CI: 3.7–75.2), geographical area (OR = 6.8; 95% CI: 2.2–21.3) and the patient's physiological age (OR = 2.3; 95% CI: 1.1–4.7).

Conclusions

Several subjective markers restrict the referral of patients from local hospitals to liver transplant centres. Their advancement to this second step is thus markedly weakened by initial subjectivity. The development of objective guidelines for local hospital physicians to assist them with their initial decision‐making on LT is now necessary.