bluuebunny/crossref_metadata_2025 huggingface dataset:
Linking fashion consciousness with Gen Y attitude towards prestige brands
Authors: Casidy Riza , Nuryana Asti Nafia , Hati Sri Rahayu Hijrah
Published: May 2015

Purpose

– The purpose of this paper is to examine the relationship between fashion self-congruity (FSC), fashion consciousness (FC), and attitude towards prestige brands (ATT) among Generation Y (Gen Y) consumers. The study aims to expand the scope of fashion marketing research by validating the self-congruence theory within the context of Indonesian prestige brand market.

Design/methodology/approach

– The paper opted for a descriptive study involving 210 undergraduate students from a top-ranked university in Indonesia. Data were collected using anonymous self-administered questionnaire. Structural equation modelling were employed to test the research hypotheses.

Findings

– The study found that FC performs a full mediating role on the relationship between fashion self-congruence and ATT.

Research limitations/implications

– The homogenous nature of the respondents have limited the generalisability of the findings. Future research could replicate this study using a sample of wider population.

Practical implications

– The paper includes implications for fashion marketers to effectively target fashion-conscious consumers by developing a brand positioning strategy that is consistent with consumers’ self-concept.

Originality/value

– This paper extends the empirical model of FC by incorporating fashion self-congruence as an antecedent of ATT. With limited academic research on Indonesian consumers in mind, this is the first empirical study to examine the antecedents of Indonesian consumers’ attitude towards prestige fashion brands.
Hidden in practice: the management activities that foster employee learning
Authors: Cohen Jay Andrew
Published: May 2015

Purpose

– The purpose of this paper is in providing guidance to human resource development and frontline managers in shaping employee learning at work.

Design/methodology/approach

– This paper takes a viewpoint approach.

Findings

– This paper builds on recent discussions on the inseparable nature of working and learning: peripheral management practice that facilitates employee learning (Cohen, 2014) to focus on the practical activities that frontline managers can do to promote and facilitate employee learning.

Originality/value

– To the best of my knowledge and belief, this paper contains no material previously published or written by any other person, except where due reference is given in the text.
The elite education of Lieutenant Arthur Wheen, MM
Authors: Ramsland John
Published: May 2015

Purpose

– The purpose of this paper is to explore the educative experiences of Arthur Wesley Wheen – his socialisation and indoctrination within a devout family, on the one hand, and his elite classical schooling on the other hand. Such influences laid the seeds of internal conflict and were compounded at Teachers College, the Arts Faculty of the University of Sydney and at New College Oxford. It is argued that profound educative influences and the trauma of First World War shaped and redefined his life, work and personality as a scholar, cultural critic and translator. The impact of the curriculum and ethos of elite schooling on life interests is a major theme. Attempts will be made to discover from the vast mosaic of classical learning what eventually became inscribed on Wheen’s psyche.

Design/methodology/approach

– In this paper the author uses a critical biographical and life-study approach in the broad parameters of historical research by a close examination of primary and secondary sources including a rich vein of correspondence and related unpublished writings; school, teachers college and university records, battalion and personal war records and published literature, frequently contemporary in nature. In design subtle iconographic and psychoanalytic nuances will be drawn from the raw material of history.

Findings

– This research is intended to demonstrate how the traumatic requirements of a frontline soldier affected a profound disillusionment with imperial institutions. The study attempts to show how Wheen lost his religious convictions in the heat of total war and later became a passionate expatriate pacifist, social theorist and scholar. It is intended to reveal the complex layers of personal conviction. The author glances at the literary impact of AW Wheen’s translation of Erich Maria Remarque’s All Quiet on the Western Front and the Hollywood film version in terms of his contribution that has not been well recognised.

Originality/value

– The paper demonstrates how educative experiences led to significant literary outcomes and how elite classical educative forces shaped style and scholarly endeavour. It draws from history, theology, education and cultural studies and synthesises them.
Prophet or fool? The professional position and role of historians of education
Authors: Dorn Sherman
Published: May 2015

Purpose

– The purpose of this paper is to explore the professional dilemmas of historians of education in the USA.

Design/methodology/approach

– This paper uses historiographical analysis.

Findings

– While some aspects of both “prophet” and “fool” cultural archetypes fit some historians of education, neither archetype is a useful model for discussing the possible professional positions and roles of new scholars. Instead, “border-crossing” is an appropriate metaphor for new scholars in the history of education.

Originality/value

– This manuscript addresses a topic of concern to many historians of education in multiple countries. It moves beyond material concerns of intellectuals to discuss the cultural archetypes that may be at play.
The great unraveling; restructuring and reorganising education and schooling in Victoria, 1980-1992
Authors: Pardy John , Preston Lesley  F.
Published: May 2015

Purpose

– The purpose of this paper is to trace the restructure of the Victorian Education Department in Australia during the years 1980-1992. It examines how the restructuring of the department resulted in a generational reorganization of secondary schooling. This reorganization culminated in the closure of secondary technical schools that today continues to have enduring effects on access and equity to different types of secondary schooling.

Design/methodology/approach

– The history is based on documentary and archival research and draws on publications from the State government of Victoria, Education Department/Ministry of Education Annual Reports and Ministerial Statements and Reviews, Teacher Union Archives, Parliamentary Debates and unpublished theses and published works.

Findings

– As an outcome the restructuring of the Victorian Education Department, schools and the reorganization of secondary schooling, a dual system of secondary schools was abolished. The introduction of a secondary colleges occurred through a process of rationalization of schools and what secondary schooling would entail.

Originality/value

– This study traces how, over a decade, eight ministers of education set about to reform education by dismantling and undoing the historical development of Victoria’s distinctive secondary schools system.
Emergence of common tacit knowledge in an international IT project
Authors: Nishinaka Miwa , Umemoto Katsuhiro , Kohda Youji
Published: May 2015

Purpose

– The purpose of this paper is to examine knowledge processes in an international IT outsourcing project between two countries when knowledge is transferred from one country to the other due to business situations. A theoretical model is presented regarding knowledge processes in international projects which explains emergence of international common understanding as one of the solutions for knowledge-related challenges in international projects.

Design/methodology/approach

– The empirical study was conducted at the headquarters of a chemical company in Japan and its subsidiary in Singapore. The study employed a qualitative analysis method. Interviews were conducted in these companies and the results were analyzed according to grounded theory.

Findings

– The authors propose ARC Model of Knowledge Management in International IT Outsourcing Projects, which is a new theoretical model of project knowledge management in international settings, with a view of localization into knowledge processes. International common understanding will emerge from an understanding of thinking of each locale that brings a project to a successful conclusion.

Research limitations/implications

– This research might be subject to limitations regarding the data and results. Data were collected from particular companies, thus reducing the ability to generalize the results. Further research is required to verify the model with an additional empirical study.

Practical implications

– Project managers and other managers utilize the theoretical model as a base theory for the implementation of high quality localization that is managed by the locals themselves with common knowledge.

Originality/value

– The study proposes the theoretical model with the empirical analysis of the international project, which synthesizes project knowledge management and cross-cultural knowledge management in a novel way and expands the role of knowledge management.
Transaction cost analysis of public infrastructure delivery
Authors: De Schepper Steven , Haezendonck Elvira , Dooms Michaël
Published: May 2015

Purpose

– The purpose of this paper is to offer a systematic assessment of the magnitude of transaction costs of public infrastructure delivery, based on the three attributes of transaction costs, being the asset specificity, uncertainty and frequency of a transaction.

Design/methodology/approach

– Non-parametric tests were used to test the transaction cost differences between different procurement types.

Findings

– The authors find empirical support, based on a sample of 172 public infrastructure projects in Belgium, that construction firms make higher relation specific investments to their transaction partners under a public-private partnership (PPP) than a under a traditional public procurement (TPP). In addition, the authors found that PPP transactions are burdened by a greater uncertainty and a less mature market than TPP transactions.

Research limitations/implications

– Given the complexity of this research, the scope is limited to: a strict distinction between two procurement types, one geographical area, a limited time scope and a focus on the private sector. Hence, the authors suggest that further research broadens the scope of either one of these aspects in order to get a better understanding of the total transaction cost burden of the public infrastructure market.

Practical implications

– This study offers policy makers form a better understanding of the transaction cost implications when evaluating different procurement types.

Originality/value

– This paper serves as one of the first systematic comparative analyses of the magnitude and determinants of transaction costs for the delivery of public infrastructure.
User engagement in living lab field trials
Authors: Georges Annabel , Schuurman Dimitri , Baccarne Bastiaan , Coorevits Lynn
Published: May 2015

Purpose

– The purpose of this paper is to reflect on the factors playing a role in the engagement of end-users to participate in Living Lab field trials.

Design/methodology/approach

– Multiple case study analysis of three Living Lab cases in which field trials were organized.

Findings

– Based on academic literature on field trials, user engagement and the technology acceptance model, the authors argue that several factors play a role in the participation of users in field trials. An influential factor that emerged is the functional maturity of the innovation, the extent to which a prototype resembles the functionalities and the processes of the final, go-to-market product at the moment of the field trial. Within this exploratory paper, we propose the “user engagement model for field trials” to explain the factors that play a role in the engagement of end-users in field trials.

Research limitations/implications

– The methodological limitations of a case study design make it difficult to extrapolate the findings toward a larger sample. Therefore, this paper focuses on making an in-depth analysis rather than making general claims. However, the insights regarding user engagement for participation pave the way for future validation on a larger scale and suggest future research directions.

Practical implications

– The findings of this paper suggest that Living Lab field trials should carefully take into account the (perceived) functional maturity of the innovation and the specific characteristics of the innovation when engaging end-users for field trials. Interaction and trust between the test-users and the other stakeholders is of great importance for the active engagement of test-users during field trials.

Originality/value

– This exploratory paper adds to a general understanding of end-user involvement in innovation development processes and suggests guidelines to engage end-users to participate in field trials. In addition, it introduces the concept of functional maturity of innovations and the user-engagement model for field trials.
Citizenship-behavior, cooperation and job satisfaction of medical and nursing teams in an Israeli hospital
Authors: Shetach Ana , Marcus Ohad
Published: May 2015

Purpose

– The purpose of this paper is to investigate into the relationships among citizenship behavior within medical and nursing teams, cooperation among these teams within hospital units and job satisfaction of members of those teams.

Design/methodology/approach

– Data were gathered via questionnaires, administered to 107 doctors and nurses of a small hospital in Israel, regarding their job satisfaction, their evaluation of the citizenship behavior within their own professional team (medical or nursing) and the extent of cooperation of their own team with the other professional team. Preacher and Hayes’s mediation analyses were carried out on the data.

Findings

– The findings show that medical–nursing cooperation mediates the relationship between citizenship behavior within the professional team (medical or nursing) and job satisfaction. When analyzed separately for doctors and nurses, results show that job satisfaction is predicted by the cooperation between the medical and nursing staff within hospital units, for nurses only. Citizenship behavior is shown to predict job satisfaction for each of the two professional sectors. Although for nurses, both factors affect their levels of job satisfaction, whereas for the doctors, cooperation affects citizenship behavior within the medical team, which, in turn, affects their job satisfaction.

Research limitations/implications

– The research sample is small and culturally specific, thus limiting the generalization potential of this study.

Originality/value

– The unique nature of teamwork within hospital departments is hereby investigated. The findings shed light on a critical issue of hospital human resource management, which has not been previously investigated, and may have practical implications regarding hospitals’ overall management policies.
Tools to support the development of a quality culture in a learning organisation
Authors: Gillies Alan Cameron
Published: May 2015

Purpose

– The purpose of this paper is to show how a systematic approach and supporting tools can support the development of a quality culture, and align cultural change with process improvement goals.

Design/methodology/approach

– The paper describes the development and deployment of a systematic approach to developing a quality culture, achieved through a structured approach to mentoring and supporting learning techniques including algorithmic matching of mentors to mentees and a structured mentoring journey built around goals and milestones.

Findings

– A structured approach to mentoring can deliver significant enhancements to a quality culture, complementing structured approaches to process improvement allowing alignment of cultural and process goals.

Research limitations/implications

– The approach has been applied in a relatively small number of organisations (eight) at the time of writing.

Originality/value

– The use of a structured approach to learning enables establishment of a quality culture to be part of a structured quality plan.
Identifying effective actions to guide volunteer‐based and nationwide conservation efforts for a ground‐nesting farmland bird
Authors: Santangeli Andrea , Arroyo Beatriz , Millon Alexandre , Bretagnolle Vincent
Published: May 2015

Modern farming practices threaten wildlife in different ways, and failure to identify the complexity of multiple threats acting in synergy may result in ineffective management. To protect ground‐nesting birds in farmland, monitoring and mitigating impacts of mechanical harvesting is crucial.

Here, we use 6 years of data from a nationwide volunteer‐based monitoring scheme of the Montagu's harrier, a ground‐nesting raptor, in French farmlands. We assess the effectiveness of alternative nest protection measures and map their potential benefit to the species.

We show that unprotected nests in cultivated land are strongly negatively affected by harvesting and thus require active management. Further, we show that protection from harvesting alone (e.g. by leaving a small unharvested buffer around the nest) is impaired by post‐harvest predation at nests that become highly conspicuous after harvest. Measures that simultaneously protect from harvesting and predation (by adding a fence around the nest) significantly enhance nest productivity.

The map of expected gain from nest protection in relation to available volunteers' workforce pinpoints large areas of high expected gain from nest protection that are not matched by equally high workforce availability. This mismatch suggests that the impact of nest protection can be further improved by increasing volunteer efforts in key areas where they are low relative to the expected gain they could have.

Synthesis and applications. This study shows that synergistic interplay of multiple factors (e.g. mechanical harvesting and predation) may completely undermine the success of well‐intentioned conservation efforts. However, identifying areas where the greatest expected gains can be achieved relative to effort expended can minimize the risk of wasted volunteer actions. Overall, this study underscores the importance of citizen science for collecting large‐scale data useful for producing science and ultimately informs large‐scale evidence‐based conservation actions within an adaptive management framework.
The Effect of Testosterone and Fenofibrate, Administered Alone or in Combination, on Cardiometabolic Risk Factors in Men with Late‐Onset Hypogonadism and Atherogenic Dyslipidemia
Authors: Krysiak Robert , Gilowski Wojciech , Okopien Bogusław
Published: May 2015

Introduction

Oral testosterone was found to reduce plasma levels of HDL cholesterol. No previous study has examined the effect of fibrates, known to increase HDL cholesterol, in patients with low testosterone levels requiring testosterone replacement.

Aims

The study included three age‐, weight‐, and lipid‐matched groups of older men with atherogenic dyslipidemia and late‐onset hypogonadism, treated with oral testosterone undecanoate (120 mg daily, n = 15), micronized fenofibrate (200 mg daily, n = 15), or testosterone plus fenofibrate (n = 18). Plasma lipids, glucose homeostasis markers, as well as plasma levels of androgens, uric acid, high‐sensitivity C‐reactive protein (hsCRP), homocysteine, and fibrinogen were assessed before and after 16 weeks of therapy.

Results

Apart from an increase in plasma testosterone and a reduction in HDL cholesterol, testosterone undecanoate tended to decrease hsCRP and to improve insulin sensitivity. Fenofibrate administered alone increased HDL cholesterol, reduced triglycerides, decreased insulin resistance, reduced circulating levels of uric acid, hsCRP, and fibrinogen, as well as increased plasma levels of homocysteine. The strongest effect on testosterone, HOMA1‐IR, uric acid, hsCRP, and fibrinogen was observed if fenofibrate was administered together with testosterone. Testosterone–fenofibrate combination therapy was also devoid of unfavorable effect on HDL cholesterol and homocysteine.

Conclusions

Our study shows that fenofibrate produces a stronger effect on cardiometabolic risk factors in men with late‐onset hypogonadism and atherogenic dyslipidemia than oral testosterone undecanoate. The obtained results suggest that this group of patients may benefit the most from the combined treatment with oral testosterone undecanoate and micronized fenofibrate.
Three of a Kind? The Special Case of Australia's Island Councils
Authors: Sinnewe Elisabeth , Kortt Michael A. , Dollery Brian , Hayward Philip
Published: May 2015

In common with many other countries, Australian local government policy‐makers have focussed heavily on improving financial sustainability and operational efficiency through structural change and other modes of systemic reform. However, this system‐wide approach cannot adequately deal with small island councils due to their sui generis characteristics. In an effort to fill this gap in the literature, this article examines the financial sustainability of Australia's three island councils – Flinders, Kangaroo and King – over the period 2008–2013 in order to determine whether alternative organisational arrangements may be better suited to their unique circumstances. In so doing, our study contributes to the literature by providing the first empirical analysis of the financial viability of Australia's island councils while considering the need for an alternative organisation entity in an effort to enhance their long‐term financial sustainability.
Examining the Impact of Separate Components of a Multicomponent Intervention Designed to Reduce At‐Risk Drinking Among Older Adults: The Project SHARE Study
Authors: Duru Obidiugwu K. , Xu Haiyong , Moore Alison A. , Mirkin Michelle , Ang Alfonso , Tallen Louise , Tseng Chi‐Hong , Ettner Susan L.
Published: May 2015

Background

Health promotion interventions often include multiple components and several patient contacts. The objective of this study was to examine how participation within a multicomponent intervention (Project SHARE) is associated with changes in at‐risk drinking among older adults.

Methods

We analyzed observational data from a cluster‐randomized trial of 31 primary care physicians and their patients aged ≥60 years, at a community‐based practice with 7 clinics. Recruitment occurred between 2005 and 2007. At‐risk drinkers in a particular physician's practice were randomly assigned as a group to usual care (n = 640 patients) versus intervention (n = 546 patients). The intervention included personalized reports, educational materials, drinking diaries, in‐person physician advice, and telephone counseling by health educators (HEs). The primary outcome was at‐risk drinking at follow‐up, defined by scores on the Comorbidity Alcohol Risk Evaluation Tool (CARET). Predictors included whether a physician–patient alcohol risk discussion occurred, HE call occurred, drinking agreement with the HE was made, and patients self‐reported keeping a drinking diary as suggested by the HE.

Results

At 6 months, there was no association of at‐risk drinking with having had a physician–patient discussion. Compared to having had no HE call, the odds of at‐risk drinking at 6 months were lower if an agreement was made or patients reported keeping a diary (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.37 to 0.90), or if an agreement was made and patients reported keeping a diary (OR 0.52, CI 0.28 to 0.97). At 12 months, a physician–patient discussion (OR 0.61, CI 0.38 to 0.98) or an agreement and reported use of a diary (OR 0.45, CI 0.25) were associated with lower odds of at‐risk drinking.

Conclusions

Within the Project SHARE intervention, discussing alcohol risk with a physician, making a drinking agreement, and/or self‐reporting the use of a drinking diary were associated with lower odds of at‐risk drinking at follow‐up. Future studies targeting at‐risk drinking among older adults should consider incorporating both intervention components.
Injury‐Related Mortality Over 12 Years in a Cohort of Patients with Alcohol Use Disorders: Higher Mortality Among Young People and Women
Authors: Guitart Anna M. , Espelt Albert , Castellano Yolanda , Suelves Josep M. , Villalbí Joan R. , Brugal M. Teresa
Published: May 2015

Background

The goal of this study was to estimate excess death due to external causes among 18‐ to 64‐year‐olds with alcohol use disorder (AUD) who were treated at public outpatient treatment centers, and the time elapsed from treatment initiation to death.

Methods

We conducted a retrospective longitudinal study among 7,012 outpatients aged 18 to 64 years who began treatment for AUD between 1997 and 2007. Deaths due to external causes (intentional and unintentional injuries) were monitored until the end of 2008. Person‐years (PY) of follow‐up and crude mortality rates (CMRs) were calculated for all study variables, for each sex, and for 2 age groups (18 to 34 and 35 to 64 years). Standardized mortality ratios (SMRs) were estimated by age group and sex. Survival was analyzed using the Kaplan–Meier method and Cox regression.

Results

We recorded 114 deaths due to external causes. The CMR was 2.7 per 1,000 PY (95% confidence interval [CI]: 2.2 to 3.2), with significant gender differences only among younger individuals (CMR for males = 3.9 per 1,000 PY [95% CI: 2.2 to 5.5] and CMR for females = 2.8 per 1,000 PY [95% CI: 0.1 to 5.6]). Unintentional injury was the most common cause of death (n = 65), of which acute poisoning (n = 25; 38.5%) and traffic accidents (n = 15; 23.1%) were the most prevalent. Suicide accounted for 91.8% (n = 49) of deaths from intentional injuries. The excess of mortality between the AUD group and the general population (SMR) was 9.5 higher than in the general population (95% CI: 7.9 to 11.4), with significant differences between genders (SMR = 6.1 [95% CI: 4.9 to 7.5] in males and SMR = 20.4 [95% CI: 13.9 to 29.9] in females). Approximately 35% of deaths among individuals aged <35 years and 60% among women occurred within a year of initiating treatment.

Conclusions

This study highlights the importance of excess of mortality among people with AUD and patients' vulnerability during the initial years of treatment. Preventing premature deaths due to external causes among women and younger patients with AUD is a priority.
Estimating theAboriginal Population in Early ColonialAustralia: The Role of Chickenpox Reconsidered
Authors: Hunter Boyd H. , Carmody John
Published: May 2015

NoelButlin radically altered the debate about the pre‐colonialAboriginal population when he provided a set of hypothetical demographic scenarios, which nonetheless were both grounded in economic theory or human ecological considerations and broadly consistent with what we know about the historical record. This research builds onButlin's legacy by exploring how his scenarios are consistent with both the medical understandings of the infectiousness and mortality of various diseases and the history of settlement. Another contribution from this paper is to highlight the possible role of chickenpox in theAboriginal depopulation in the early colonial period.
What are VBAC Women Seeking and Sharing? A Content Analysis of Online Discussion Boards
Authors: Konheim‐Kalkstein Yasmine L. , Whyte Rosemarie , Miron‐Shatz Talya , Stellmack Mark A.
Published: May 2015

Background

In the United States, one‐third of pregnancies result in a cesarean delivery. In subsequent pregnancies, mothers must decide whether to pursue a vaginal birth after a cesarean (VBAC) or a repeat cesarean delivery. Pregnant women frequently turn to the Internet for support and information.

Methods

We analyzed 300 posts from a popular online discussion board created for pregnant women who are in the process of deciding to have a VBAC and compared them to 300 posts from a discussion board for pregnant women in general.

Results

Women contemplating a VBAC sought more information on health care providers, more information about labor and delivery, and actively sought birth narratives from other women. Over one‐third of VBAC posters shared a birth story, whereas this activity was rare on the general discussion board. Activity on the VBAC board suggested more involvement in the online community (longer entries and more feedback).

Conclusions

Many women considering VBAC seek a substantial amount of information and emotional support from online discussion boards. Knowledge of information sought can assist health care providers in more fully meeting the needs of VBAC candidates.
Risk Factors for Severe Secondary Postpartum Hemorrhages: A Historical Cohort Study
Authors: Debost‐Legrand Anne , Rivière Olivier , Dossou Mathieu , Vendittelli Françoise
Published: May 2015

Background

The predictive factors of secondary postpartum hemorrhage (PPH) are little known. Our principal objective was to determine if immediate PPH is a risk factor for severe secondary PPH. We also sought to identify other factors associated with severe secondary PPH.

Methods

Our historical cohort study included all women who gave birth (≥ 22 weeks) in our level III hospital from 2004 through 2013. The hospital discharge database enabled us to identify all women readmitted during the 42‐day postpartum period or who underwent a surgical, medical, or interventional radiology procedure during their immediate postpartum hospitalization. We then examined all medical records to identify the cases involving severe secondary PPH. We studied the known risk factors of secondary PPH and assessed other potential ones: maternal age, multiple pregnancy, induction of labor, cesarean birth, preterm birth, and stillbirth.

Results

The study included 63 women with a severe secondary PPH and 25,696 women without a secondary PPH. Immediate PPH (aOR 2.7 [95% CI 1.3–5.6]) and maternal age ≥ 35 years (aOR 2.0 [95% CI 1.1–3.7]) were the only factors associated with severe secondary PPH.

Discussion

This cohort study confirms that immediate PPH is a risk factor for severe secondary PPH and reports for the first time an association between secondary PPH and advanced maternal age. It is likely that risk factors for immediate PPH are also risk factors for severe secondary PPH and thus that immediate PPH may be an intermediate factor between its own known risk factors and secondary PPH.
The Akt inhibitor, triciribine, ameliorates chronic hypoxia‐induced vascular pruning and TGFβ‐induced pulmonary fibrosis
Authors: Abdalla Maha , Sabbineni Harika , Prakash Roshini , Ergul Adviye , Fagan Susan C , Somanath Payaningal R
Published: May 2015

Background and Purpose

Interstitial lung disease accounts for a group of chronic and progressive disorders associated with severe pulmonary vascular remodelling, peripheral vascular rarefaction and fibrosis, thus limiting lung function. We have previously shown that Akt is necessary for myofibroblast differentiation, a critical event in organ fibrosis. However, the contributory role of the Akt‐mTOR pathway in interstitial lung disease and the therapeutic benefits of targeting Akt and mTOR remain unclear.

Experimental Approach

We investigated the role of the Akt‐mTOR pathway and its downstream molecular mechanisms in chronic hypoxia‐ and TGFβ‐induced pulmonary vascular pruning and fibrosis in mice. We also determined the therapeutic benefits of the Akt inhibitor triciribine and the mTOR inhibitor rapamycin for the treatment of pulmonary fibrosis in mice.

Key Results

Akt1−/− mice were protected from chronic hypoxia‐induced peripheral vascular pruning. In contrast, hyperactivation of Akt1 induced focal fibrosis similar to TGFβ‐induced fibrosis. Pharmacological inhibition of Akt, but not the Akt substrate mTOR, inhibited hypoxia‐ and TGFβ‐induced pulmonary vascular rarefaction and fibrosis. Mechanistically, we found that Akt1 modulates pulmonary remodelling via regulation of thrombospondin1 (TSP1) expression. Hypoxic Akt1−/− mice lungs expressed less TSP1. Moreover, TSP1−/− mice were resistant to adMyrAkt1‐induced pulmonary fibrosis.

Conclusions and Implications

Our study identified Akt1 as a novel target for the treatment of interstitial lung disease and provides preclinical data on the potential benefits of the Akt inhibitor triciribine for the treatment of interstitial lung disease.
Quinazoline‐4‐piperidine sulfamides are specific inhibitors of human NPP1 and prevent pathological mineralization of valve interstitial cells
Authors: Shayhidin Elnur Elyar , Forcellini Elsa , Boulanger Marie‐Chloé , Mahmut Ablajan , Dautrey Sébastien , Barbeau Xavier , Lagüe Patrick , Sévigny Jean , Paquin Jean‐François , Mathieu Patrick
Published: May 2015

Background and Purpose

Ectonucleotide pyrophosphatase/PDE1 (NPP1) is an ectoenzyme, which plays a role in several disorders including calcific aortic valve disease (CAVD). So far, compounds that have been developed as inhibitors of NPP1 lack potency and specificity. Quinazoline‐4‐piperidine sulfamides (QPS) have been described as potent inhibitors of NPP1. However, their mode of inhibition as well as their selectivity and capacity to modify biological processes have not been investigated.

Experimental Approach

In the present series of experiments, we have evaluated the efficacy of two derivatives, QPS1‐2, in inhibiting human NPP1, and we have evaluated the effect of the most potent derivative (QPS1) on other ectonucleotidases as well as on the ability of this compound to prevent phosphate‐induced mineralization of human primary aortic valve interstitial cells (VICs).

Key Results

The QPS1 derivative is a potent (Ki 59.3 ± 5.4 nM) and selective non‐competitive inhibitor of human NPP1. Moreover, QPS1 also significantly inhibited the K121Q NPP1 gene variant (Ki 59.2 ± 14.5 nM), which is prevalent in the general population. QPS1 did not significantly alter the activity of other nucleotide metabolizing ectoenzymes expressed at the cell surface, namely NPP3, NTPDases (1–3), ecto‐5′‐nucleotidase and ALP. Importantly, QPS1 in the low micromolar range (≤10 μM) prevented phosphate‐induced mineralization of VICs and lowered the rise of osteogenic genes as expected for NPP1 inhibition.

Conclusions and Implications

We have provided evidence that QPS1 is a potent and selective non‐competitive inhibitor of NPP1 and that it prevented pathological mineralization in a cellular model.
Constrictor prostanoids and uridine adenosine tetraphosphate: vascular mediators and therapeutic targets in hypertension and diabetes
Authors: Matsumoto Takayuki , Goulopoulou Styliani , Taguchi Kumiko , Tostes Rita C , Kobayashi Tsuneo
Published: May 2015

Vascular dysfunction plays a pivotal role in the development of systemic complications associated with arterial hypertension and diabetes. The endothelium, or more specifically, various factors derived from endothelial cells tightly regulate vascular function, including vascular tone. In physiological conditions, there is a balance between endothelium‐derived factors, that is, relaxing factors (endothelium‐derived relaxing factors; EDRFs) and contracting factors (endothelium‐derived contracting factors; EDCFs), which mediate vascular homeostasis. However, in disease states, such as diabetes and arterial hypertension, there is an imbalance between EDRF and EDCF, with a reduction of EDRF signalling and an increase of EDCF signalling. Among EDCFs, COX‐derived vasoconstrictor prostanoids play an important role in the development of vascular dysfunction associated with hypertension and diabetes. Moreover, uridine adenosine tetraphosphate (Up4A), identified as an EDCF in 2005, also modulates vascular function. However, the role of Up4A in hypertension‐ and diabetes‐associated vascular dysfunction is unclear. In the present review, we focused on experimental and clinical evidence that implicate these two EDCFs (vasoconstrictor prostanoids and Up4A) in vascular dysfunction associated with hypertension and diabetes.
Sex hormones regulate cerebral drug metabolism via brain miRNAs: down‐regulation of brain CYP2D by androgens reduces the analgesic effects of tramadol
Authors: Li Jie , Xie Mengmeng , Wang Xiaoshuang , Ouyang Xiufang , Wan Yu , Dong Guicheng , Yang Zheqiong , Yang Jing , Yue Jiang
Published: May 2015

Background and Purpose

Brain cytochrome P450 2D (CYP2D) metabolises exogenous neurotoxins, endogenous substances and neurotransmitters. Brain CYP2D can be regulated in an organ‐specific manner, but the possible regulatory mechanisms are poorly understood. We investigated the involvement of miRNAs in the selective regulation of brain CYP2D by testosterone and the corresponding alteration of the pharmacological profiles of tramadol by testosterone.

Experimental Approach

The regulation of CYP2D and brain‐enriched miRNAs by testosterone was investigated using SH‐SY5Y cells, U251 cells, and HepG2 cells as well as orchiectomized growth hormone receptor knockout (GHR‐KO) mice and rats. Concentration–time curves of tramadol in rat brain were determined using a microdialysis technique. The analgesic action of tramadol was assessed by the tail‐flick test in rats.

Key Results

miR‐101 and miR‐128‐2 bound the 3′‐untranslated region of the CYP2D6 mRNA and decreased its level. Testosterone decreased CYP2D6 catalytic function via the up‐regulation of miR‐101 and miR‐128‐2 in SH‐SY5Y and U251 cells, but not in HepG2 cells. Orchiectomy decreased the levels of miR‐101 and miR‐128‐2 in the hippocampus of male GHR‐KO mice, indicating that androgens regulate miRNAs directly, not via the alteration of growth hormone secretion patterns. Changes in the pharmacokinetic and pharmacodynamic profiles of tramadol by orchiectomy was attenuated by either testosterone supplementation or a specific brain CYP2D inhibitor.

Conclusions and Implications

The selective regulation of brain CYP2D via brain‐enriched miRNAs, following changes in androgen levels, such as in testosterone therapy, androgen deprivation therapy and/or ageing may alter the response to centrally active substances.
Evaluation of drug‐induced QT interval prolongation in animal and human studies: a literature review of concordance
Authors: Vargas Hugo M , Bass Alan S , Koerner John , Matis‐Mitchell Sherri , Pugsley Michael K , Skinner Matthew , Burnham Matthew , Bridgland‐Taylor Matthew , Pettit Syril , Valentin Jean‐Pierre
Published: May 2015

Evaluating whether a new medication prolongs QT intervals is a critical safety activity that is conducted in a sensitive animal model during non‐clinical drug development. The importance of QT liability detection has been reinforced by non‐clinical [International Conference on Harmonization (ICH) S7B] and clinical (ICH E14) regulatory guidance from the International Conference on Harmonization. A key challenge for the cardiovascular safety community is to understand how the finding from a non‐clinical in vivo QT assay in animals predicts the outcomes of a clinical QT evaluation in humans. The Health and Environmental Sciences Institute Pro‐Arrhythmia Working Group performed a literature search (1960–2011) to identify both human and non‐rodent animal studies that assessed QT signal concordance between species and identified drugs that prolonged or did not prolong the QT interval. The main finding was the excellent agreement between QT results in humans and non‐rodent animals. Ninety‐one percent (21 of 23) of drugs that prolonged the QT interval in humans also did so in animals, and 88% (15 of 17) of drugs that did not prolong the QT interval in humans had no effect on animals. This suggests that QT interval data derived from relevant non‐rodent models has a 90% chance of predicting QT findings in humans. Disagreement can occur, but in the limited cases of QT discordance we identified, there appeared to be plausible explanations for the underlying disconnect between the human and non‐rodent animal QT outcomes.
Measuring genetic knowledge: a brief survey instrument for adolescents and adults
Authors: Fitzgerald‐Butt S. M. , Bodine A. , Fry K. M. , Ash J. , Zaidi A. N. , Garg V. , Gerhardt C. A. , McBride K. L.
Published: May 2015

Basic knowledge of genetics is essential for understanding genetic testing and counseling. The lack of a written, English language, validated, published measure has limited our ability to evaluate genetic knowledge of patients and families. Here, we begin the psychometric analysis of a true/false genetic knowledge measure. The 18‐item measure was completed by parents of children with congenital heart defects (CHD) (n = 465) and adolescents and young adults with CHD (age: 15–25, n = 196) with a mean total correct score of 12.6 [standard deviation (SD) = 3.5, range: 0–18]. Utilizing exploratory factor analysis, we determined that one to three correlated factors, or abilities, were captured by our measure. Through confirmatory factor analysis, we determined that the two factor model was the best fit. Although it was necessary to remove two items, the remaining items exhibited adequate psychometric properties in a multidimensional item response theory analysis. Scores for each factor were computed, and a sum‐score conversion table was derived. We conclude that this genetic knowledge measure discriminates best at low knowledge levels and is therefore well suited to determine a minimum adequate amount of genetic knowledge. However, further reliability testing and validation in diverse research and clinical settings is needed.
Long‐term isolation and endemicity of Neotropical aquatic insects limit the community responses to recent amphibian decline
Authors: Múrria Cesc , Rugenski Amanda T. , Whiles Matt R. , Vogler Alfried P.
Published: May 2015

Aim

Neotropical highland streams have shown diminished ecosystem functioning after amphibian extirpation infected by the chytrid fungus Batrachochytrium dendrobatidis. The loss of amphibians could affect communities of aquatic insects co‐occurring in these streams in various ways. We examined patterns of species and genetic diversity of these communities and their evolutionary history along the chytrid expansion gradient to elucidate potential community responses.

Location

Six streams over a 320‐km transect in Panama affected by chytrid expansion from west to east for up to 14 years, and two apparently chytrid‐free streams in the east.

Methods

Patterns of α‐ and β‐diversity were investigated at three hierarchical levels: genus, species and haplotypes. Genus identification was based on morphology, and putative species were inferred by grouping the DNA barcodes (749 cox1 sequences) with the GMYC method on all collected individuals of Ephemeroptera, Trichoptera, Coleoptera and Plecoptera.

Results

A total of 96 genera in 43 families (9 orders) of insects were encountered. Genus‐level α‐diversity was higher in the easternmost streams, possibly due to a separate biogeographical history, whereas β‐diversity was constant along the chytrid expansion gradient. Community DNA barcoding resulted in 426 cox1 haplotypes and 154 putative species, most of them limited to single sites. High β‐diversity along the gradient at both species and haplotype levels argues against community homogenization by migration in the wake of amphibian declines. In contrast, phylo‐β‐diversity was low, indicating community similarity at deep levels.

Main conclusions

Aquatic insect communities in this region are influenced by long‐term limited dispersion that generated high endemicity. The pattern persists mostly unperturbed after disease‐driven amphibian declines; hence, if indeed insects fill the niches vacated by tadpoles, they would originate from local communities rather than immigration. Given the unique evolutionary history and physical isolation of local assemblages, the ecosystem deterioration carries the risk of losing unique diversity.
Women with an HbA1c of 41–49 mmol/mol (5.9–6.6%): a higher risk subgroup that may benefit from early pregnancy intervention
Authors: Rowan J. A. , Budden A. , Ivanova V. , Hughes R. C. , Sadler L. C.
Published: May 2015

Aims

To examine whether women with an HbA1c of 41–49 mmol/mol (5.9–6.6%) at diagnosis of gestational diabetes are higher risk than women with an HbA1c of < 41 mmol/mol (5.9%) and whether pregnancy outcomes are improved if treated at < 24 weeks' gestation.

Methods

This was an observational study of women with gestational diabetes diagnosed by early HbA1c screening or subsequent oral glucose tolerance test at < 34 weeks' gestation who delivered at National Women's Health, Auckland, from July 2012 to June 2014. Data were extracted from the hospital database. Women with HbA1c 41–49 mmol/mol (5.9–6.6%) were divided into those seen < 24 weeks (Early, n = 134) and those seen ≥ 24 weeks (Later, n = 151). Those with HbA1c < 41 mmol/mol (5.9%) were labelled Other GDM (n = 661).

Results

The Early and Later groups, compared with Other GDM, had more Polynesian and fewer (non‐Indian) Asian women, higher BMI and more required medication (P < 0.001). More were smokers (P = 0.007, 0.02) and more had chronic hypertension (P < 0.001, 0.02). There were higher rates of adverse outcomes in the Later group than the Other GDM group (pre‐eclampsia 8.0% vs. 2.4%, P = 0.001, preterm birth 16.6% vs. 8.2%, P = 0.002, neonatal admission 15.5% vs. 9.2%, P = 0.02). Outcomes were similar between the Early group and Other GDM group (pre‐eclampsia 1.5% vs. 2.4%, P = 0.5, preterm birth 10.5% vs. 8.2% P = 0.4, neonatal admission 13.6% vs. 9.2%, P = 0.12). Comparing the Early and Later groups, the Early group had less pre‐eclampsia, 1.5% vs. 8.0%, adjusted P = 0.03. Other outcomes were not statistically different.

Conclusions

An HbA1c of 41–49 mmol/mol (5.9–6.7%) identifies a higher‐risk group of women with gestational diabetes. Overall, our data support early treatment of women with an HbA1c ≥ 41 mmol/mol (5.9%).
On the Relationship between Accounting Risk and Return: Is There a (Bowman) Paradox?
Authors: Brick Ivan E. , Palmon Oded , Venezia Itzhak
Published: May 2015

Bowman's (1980, 1982, 1984) finding of a negative relationship between the means and variances of accounting returns (the Bowman Paradox) spurred a considerable literature analyzing this phenomenon. The sign of the relationship between the mean return on equity (ROE) and its standard deviation remains unresolved. Concerns were raised about ROE measurement and statistical techniques used in establishing the paradox. The papers critiquing (and supporting) it were mostly limited in scope, studied only short periods of time and provided limited robustness checks. In addition, no paper considered the effect of issuances and repurchase of stocks on the measurement of ROE. This study revisits the Paradox and addresses the above mentioned deficiencies in prior research. We use data from longer periods, control for size and leverage and provide additional robustness checks. We conclude that a positive relationship between mean ROE and its standard deviation is far more likely than a negative one.