bluuebunny/crossref_metadata_2025 huggingface dataset:
Alleviating feature fatigue in product development based on the bass model
Authors: Wu Mingxing , Wang Liya , Li Ming , Long Huijun
Published: June 2015

Purpose

– This paper aims to propose a novel method to predict and alleviate feature fatigue. Many products now are loaded with an extensive number of features. Adding more features to one product generally makes the product more attractive on the one hand but, on the other hand, may result in increasing difficulty to use the product. This phenomenon is called “feature fatigue”, which will lead to dissatisfaction and negative word-of-mouth (WOM). Feature fatigue will damage the brand’s long-term profit, and ultimately decrease the manufacturer’s customer equity. Thus, a problem of balancing the benefit of increasing “attractiveness” with the cost of decreasing “usability” exists.

Design/methodology/approach

– A novel method based on the Bass model is proposed to predict and alleviate feature fatigue. Product capability, usability and WOM effects are integrated into the Bass model to predict the impacts of adding features on customer equity in product development, thus helping designers alleviate feature fatigue. A case study of mobile phone development based on survey data is presented to illustrate and validate the proposed method.

Findings

– The results of the case study demonstrate that adding more features indeed increases initial sales; however, adding too many features ultimately decreases customer equity due to usability problems. There is an optimal feature combination a product should include to balance product capability with usability. The proposed method makes a trade-off between initial sales and long-term profits to maximize customer equity.

Originality/value

– The proposed method can help designers predict the impacts of adding features on customer equity in the early stages of product development. It can provide decision supports for designers to decide what features should be added to maximize customer equity, thus alleviating feature fatigue.
Economic growth and cost stickiness: evidence from Egypt
Authors: Ibrahim Awad Elsayed Awad
Published: June 2015

Purpose

– This paper aims to examine whether costs respond asymmetrically to demand change, and examine the influence of economic growth on cost stickiness, in the pre- and post-2008 financial crisis periods.

Design/methodology/approach

– This study uses multiple regression models to investigate the behavior of three costs: selling, general and administrative (SG & A), cost of goods sold (COGS) and operating costs (OCs) for the 2004-2011 period. Moreover, the study compares cost stickiness during the economic prosperity period (2006-2008) with cost stickiness during the economic recession period (2009-2011).

Findings

– The results reveal that SG & A increased by 0.38 per cent but decreased by 0.08 per cent, and COGS increased by 1.02 per cent but decreased by 0.57 per cent for a 1 per cent demand change, which proves cost stickiness. However, OC increased by 0.91 per cent, but decreased by 1.03 per cent for a 1 per cent demand change, which proves cost anti-stickiness. Moreover, SG & As were sticky during the prosperity period, but anti-sticky during the recession period. COGSs were sticky in both periods; however, the extent of cost stickiness is larger in the prosperity period. In contrast, OC were statistically insignificant in both periods.

Originality/value

– The results imply that managers should not use the same cost model all the time, as the economic growth fluctuations were found to affect the nature and extent of cost behavior. In addition, researchers should provide a modified cost model that considers the nonlinearity of correlation between costs and activity.
Ask me anything: what is Reddit?
Authors: Anderson Katie Elson
Published: June 2015

Purpose

– This article aims to provide an overview of the popular website Reddit.

Design/methodology/approach

– In many cases, items that are popular on Reddit become viral, appearing on other social media sites and in the news several days later.

Findings

– The site’s content is supplied by its users, and the popularity of that content is also determined by the membership. While the site can be described simply as an aggregator of user provided content, this simple description does not adequately capture the essence of the Reddit community and the impact of that community and its generated content on society.

Originality/value

– Librarians should be aware of this impact and the potential that Reddit possesses for connecting with a number of different communities.
Conference report of INTED 2015, the International Technology and Education for Development Conference
Authors: Kesselman Martin
Published: June 2015

Purpose

– This article is a conference report dealing with instructional technology.

Design/methodology/approach

– The methodology adopted is an overview of a conference report.

Findings

– There is much to take away from INTED2015.

Originality/value

– This article is the only report of INTED2015.
Disturbance alters beta‐diversity but not the relative importance of community assembly mechanisms
Authors: Myers Jonathan A. , Chase Jonathan M. , Crandall Raelene M. , Jiménez Iván
Published: June 2015

Ecological disturbances are often hypothesized to alter community assembly processes that influence variation in community composition (β‐diversity). Disturbance can cause convergence in community composition (low β‐diversity) by increasing niche selection of disturbance‐tolerant species. Alternatively, disturbance can cause divergence in community composition (high β‐diversity) by increasing habitat filtering across environmental gradients. However, because disturbance may also influence β‐diversity through random sampling effects owing to changes in the number of individuals in local communities (community size) or abundances in the regional species pool, observed patterns of β‐diversity alone cannot be used to unambiguously discern the relative importance of community assembly mechanisms.

We compared β‐diversity of woody plants and inferred assembly mechanisms among unburned forests and forests managed with prescribed fires in the Missouri Ozarks, USA. Using a null‐model approach, we compared how environmental gradients influenced β‐diversity after controlling for differences in local community size and regional species abundances between unburned and burned landscapes.

Observed β‐diversity was higher in burned landscapes. However, this pattern disappeared or reversed after controlling for smaller community size in burned landscapes.

β‐diversity was higher than expected by chance in both landscapes, indicating an important role for processes that create clumped species distributions. Moreover, fire appeared to decrease clumping of species at broader spatial scales, suggesting homogenization of community composition through niche selection of disturbance‐tolerant species. Environmental variables, however, explained similar amounts of variation in β‐diversity in both landscapes, suggesting that disturbance did not alter the relative importance of habitat filtering.

Our results indicate that contingent responses of communities to fire reflect a combination of fire‐induced changes in local community size and scale‐dependent effects of fire on species clumping across landscapes.

Synthesis. Although niche‐based mechanisms of community assembly are often invoked to explain changes in community composition following disturbance, our results suggest that these changes also arise through random sampling effects owing to the influence of disturbance on community size. Comparative studies of these processes across disturbed ecosystems will provide important insights into the ecological conditions that determine when disturbance alters the interplay of deterministic and stochastic processes in natural and human‐modified landscapes.
Nominating women for Europe: Exploring the role of political parties' recruitment procedures for European Parliament elections
Authors: Fortin‐Rittberger Jessica , Rittberger Berthold
Published: June 2015

Drawing on an original dataset covering more than 100 political parties in over 20 European Union Member States, this article analyses how political recruitment procedures affect the proportion of women nominated on party lists in the context of the 2009 European Parliament elections. The findings show that the inclusiveness of the selectorates in the early stage of candidate selection processes is a key determinant of the representativeness of lists regarding their gender composition. Moreover, it is found that neither territorial centralisation nor the inclusiveness of the selectorate in the later stage of candidate selection play a significant role. The key to the puzzle, therefore, lies in the composition of the initial pool of potential candidates and those who make initial nominations.
Are Employee Selection and Incentive Contracts Complements or Substitutes?
Authors: ABERNETHY MARGARET A. , DEKKER HENRI C. , SCHULZ AXEL K‐D.
Published: June 2015

There is a debate in the literature as to whether employee selection is a substitute or complement to incentive contracting. We argue that incentive contracts and selection can be both complements and substitutes conditional on the contracting difficulty faced by the firm. We examine these control choices in a setting where contracting difficulties arise due to the firm's choice of strategy and from the volatility created by the firm's external environment. We select a firm's commitment to organizational learning (OL) as our strategic choice variable as this provides a useful proxy for identifying settings where explicit incentive contracting is difficult. The results show that, as firms become increasingly committed to OL, incentive contracts and employee selection operate as complements. However, with a high commitment to OL and an increasing level of external volatility, contracting on performance measures will become less effective. In this context, our results indicate that there is a substitution effect toward employee selection.
Action research and reducing the vulnerability of peri‐urban agriculture: a case study from the Montreal Region
Authors: Bryant Christopher Robin , Chahine Ghalia
Published: June 2015

Important pressures still increase the vulnerability of peri‐urban farming despite initiatives to protect agricultural land and activities since the mid‐1960s in several jurisdictions in the USA and Canada. Often, farmland is still removed from agricultural reserves for the ‘good of society’ (for example, creating industrial parks). In 2008, an action research project was initiated to attempt to reduce agricultural vulnerability in several peri‐urban and rural areas near Montreal by emphasising the importance of the appropriation of the value of these farmlands by non‐farm citizens and actors. The action research roles involved accompanying the farmers, facilitating meetings, mobilising non‐farm actors, and informing farmers of possibilities when asked to do so. In this article, one specific project is analysed in Senneville (in the west of Montreal Island). While the project was initiated by the farmers to guarantee their long‐term future, they also sought to involve other, mostly non‐agricultural, actors. In a colloquium, a collective vision for the project was constructed, integrating other functions of farmland such as conservation and leisure activities. Many meetings were organised over a three‐year period and formal presentations were made to the municipality. The project is ongoing, including new farm operations and the reinforcement of local markets for marketing mainly organic produce. The area is now an integral part of an emerging ‘green belt’ of the Montreal agglomeration and is already part of a ‘green coalition’ of both urban and peri‐urban actors (farmers and non‐farmers), and an emerging food system movement which represents a more holistic approach to food production.
Amur tiger conservation education program: A pilot study on program effectiveness
Authors: MUKHACHEVA Anna S. , DERUGINA Vasilissa V. , MAKSIMOVA Galina D. , SOUTYRINA Svetlana V.
Published: June 2015

Anthropogenic impacts are the primary threats to Amur tigers (Panthera tigris altaica) and their habitat. Villagers living in proximity to tigers tend to view them negatively and, often, as a source of revenue on black markets. We aim to reduce human–tiger conflict by working with young students of Ternei County in the heart of tiger habitat in Primorskii Krai (Province). To inform and influence Ternei County's future decision‐makers, we developed “Safe Conduct”, a year‐long education program held in 6 villages, culminating in a multi‐school conference. We tested the efficacy of Safe Conduct as a potential model for tiger conservation educational programs. We measured levels of student knowledge about tiger ecology, their attitude towards tigers, and their willingness to engage in tiger conservation activites prior to, immediately after and 6 months following the completion of our program. Results supported the fundamental premise of Safe Conduct that knowledge and attitude towards tigers are correlated. Knowledge of tiger ecology and attitude towards tigers increased by the project's completion; both remained high after 6 months. However, commitment to participation in conservation efforts rose temporarily post‐program and then dropped. Results varied by village. We recommend that the reasons for the high performance measures of students in 2 villages be investigated, and that lessons learned be applied to villages that underperformed. Safe Conduct represents a potential model for environmental education programs in Ternei County and elsewhere to educate future generations, to eventually develop a strong commitment to Amur tiger conservation at the community level.
Identifying ecological corridors for Amur tigers (Panthera tigris altaica) and Amur leopards (Panthera pardus orientalis)
Authors: MIQUELLE Dale G. , ROZHNOV Vyachaslav V. , ERMOSHIN Victor , MURZIN Andre A. , NIKOLAEV Igor G. , HERNANDEZ‐BLANCO Jose A. , NAIDENKO Sergie V.
Published: June 2015

The rapid explosion of human populations and the associated development of human‐dominated landscapes have drastically reduced and fragmented habitat for tigers (Panthera tigris) and leopards (Panthera pardus) across Asia, resulting in multiple small populations. However, Amur tiger (Panthera tigris altaica) habitat in Russia has remained largely interconnected, except for a break between tigers in southwest Primorye and the southern Sikhote‐Alin Mountains. This habitat patch in southwest Primorye also retains the last population of Amur leopards (Panthera pardus orientalis). Genetic differentiation of tigers in southwest Primorye and the Sikhote‐Alin Mountains along with survey data suggest that habitat fragmentation is limiting movement of tigers and leopards across the Razdolnaya River basin. We looked at historical and recent survey data on tigers and leopards and mapped existing cover types to examine land‐use patterns of both large felids and humans in the development strip along the Razdolnaya River. We then used least‐cost distance analyses to identify the most effective potential corridor to retain connectivity for large felids between Land of the Leopard National Park and Ussuriskii Zapovednik (Reserve). We identified a single potential corridor that still exists with a total distance of 62.5 km from Land of the Leopard National Park to Ussuriskii Zapovednik, mostly (93%) through forested habitat. We recommend formal recognition of a Razdolnaya ecological corridor and provide specific recommendations for each of 3 proposed management sections.
Mortality of Amur tigers: The more things change, the more they stay the same
Authors: ROBINSON Hugh S. , GOODRICH John M. , MIQUELLE Dale G. , MILLER Clayton S. , SERYODKIN Ivan V.
Published: June 2015

Poaching as well as loss of habitat and prey are identified as causes of tiger population declines. Although some studies have examined habitat requirements and prey availability, few studies have quantified cause‐specific mortality of tigers. We used cumulative incidence functions (CIFs) to quantify cause‐specific mortality rates of tigers, expanding and refining earlier studies to assess the potential impact of a newly emerging disease. To quantify changes in tiger mortality over time, we re‐examined data first collected by Goodrich et al. (; study period 1: 1992–2004) as well as new telemetry data collected since January 2005 (study period 2: 2005–2012) using a total of 57 tigers (27 males and 30 females) monitored for an average of 747 days (range 26–4718 days). Across the entire study period (1992 to 2012) we found an estimated average annual survival rate of 0.75 for all tigers combined. Poaching was the primary cause of mortality during both study periods, followed by suspected poaching, distemper and natural/unknown causes. Since 2005, poaching mortality has remained relatively constant and, if combined with suspected poaching, may account for a loss of 17–19% of the population each year. Canine distemper virus (CDV) may be an additive form of mortality to the population, currently accounting for an additional 5%. Despite this relatively new source of mortality, poaching remains the main threat to Amur tiger survival and, therefore, population growth.
Evaluation of the effect of a 1‐day interventional workshop on recovery from job stress for radiation therapists and oncology nurses: A randomised trial
Authors: Poulsen Anne A. , Sharpley Christopher F , Baumann Kathryn C , Henderson Julie , Poulsen Michael G
Published: June 2015

Introduction

Cancer care workers experience high levels of occupational stress that can have adverse mental and physical health consequences. Educating health professionals about self‐care practices throughout their careers can potentially build resilience. Our study aimed to evaluate the effects of an educational intervention to improve recovery from job stress, increase satisfaction with current self‐care practices and improve sleep quality.

Methods

An equivalent, randomised comparison, pretest–post‐test intervention design was used to investigate the effects of a 1‐day workshop (plus educational material) compared with written educational material alone, on measures of recovery experiences (i.e. psychological detachment from work, relaxation, mastery experiences and control over leisure), satisfaction with recovery‐related self‐care practices and perceived sleep quality of 70 cancer care workers.

Results

Workshop participants reported greater mean changes 6 weeks post‐workshop for total recovery experiences (F(1,69) = 8.145, P = .008), self‐care satisfaction (F(1,69) = 8.277, P = .005) and perceived sleep quality (F(1,69) = 9.611, P = .003). There was a decline in the scores of the control group over the 6‐week period for all measures. Workshop participants not only avoided this decline, but demonstrated increased mean scores, with a significant main effect 6 weeks post‐workshop, compared with the control group (F(3,63) = 4.262, P = .008).

Conclusions

A 1‐day intervention workshop improved recovery skills, satisfaction with self‐care practices and perceived sleep quality of oncology nurses and radiation therapists. Outcomes were enhanced when participants actively participated in experiential group‐based learning compared with receiving written material alone. This intervention has the potential to enhance resilience and prevent burnout at different points in a cancer worker's career.
A Comparison of the Tax‐Motivated Income Shifting of Multinationals in Territorial and Worldwide Countries
Authors: Markle Kevin
Published: June 2015

This paper tests for differences in the tax‐motivated income‐shifting behaviors of multinationals subject to different systems of taxing foreign earnings. I find that, on average, multinationals subject to territorial tax regimes shift more income than those subject to worldwide tax regimes. The difference in shifting, however, is driven by a difference in the subset of shifting that involves the parent country; multinationals in the two groups appear to shift equally among their foreign affiliates. In additional tests, I find that the shifting of worldwide firms is sensitive to reinvestment in the recipient countries, while that of territorial firms is not.
mvmorph: an r package for fitting multivariate evolutionary models to morphometric data
Authors: Clavel Julien , Escarguel Gilles , Merceron Gildas
Published: June 2015

We present mvmorph, a package of multivariate phylogenetic comparative methods for the r statistical environment. mvmorph is freely available on the cran package repository (http://cran.r-project.org/web/packages/mvMORPH/).

mvmorph allows fitting a range of multivariate evolutionary models under a maximum‐likelihood criterion. Initially developed in the context of phylogenetic analysis of multiple morphometric traits, its use can be extended to any biological data set with one or multiple covarying continuous traits. All the fitting models include the possibility to use simmap‐like mapping, which may be useful for fitting changes along lineages at a given point in time. All models provide diagnostic metrics for convergence and reliability of estimates, as well as the possibility to include trait measurement errors in model estimates.

New features provided by the mvmorph package include the possibility of fitting models with changes in the mode of evolution along the phylogeny, which will be particularly meaningful in comparative analyses that include extinct taxa, for example when testing changes in evolutionary mode associated with global biotic/abiotic events.

We briefly describe the models already included in mvmorph and provide some demonstration of the use of the package with two simulated worked examples.
Causation and Validation of Nursing Diagnoses: A Middle Range Theory
Authors: de Oliveira Lopes Marcos Venícios , da Silva Viviane Martins , Herdman T. Heather
Published: June 2015

Purpose

To describe a predictive middle range theory (MRT) that provides a process for validation and incorporation of nursing diagnoses in clinical practice.

Data Sources

Literature review.

Data Synthesis

The MRT includes definitions, a pictorial scheme, propositions, causal relationships, and translation to nursing practice.

Conclusions

The MRT can be a useful alternative for education, research, and translation of this knowledge into practice.

Implications for Nursing Practice

This MRT can assist clinicians in understanding clinical reasoning, based on temporal logic and spectral interaction among elements of nursing classifications. In turn, this understanding will improve the use and accuracy of nursing diagnosis, which is a critical component of the nursing process that forms a basis for nursing practice standards worldwide.
LEARNING POWER
Authors: Coomber Steve
Published: June 2015

Companies from developing markets have learnt quickly; their counterparts in the developed world need to start doing so to compete
THE SCIENCE OF FORGIVENESS
Authors: Coomber Steve
Published: June 2015

Steve Coomber seeks forgiveness by investigating new research by Gabrielle Adams
TRUST US
Authors: Crainer Stuart
Published: June 2015

New research by Randall S Peterson sheds fresh light on how trust works in small groups
RISING TO THE CHALLENGE
Authors: Peters Georgina
Published: June 2015

Thomas Philippon looks at why finance firms need to be more productive
THE INNOVATIVE ARCHER
Authors: Crainer Stuart
Published: June 2015

Bow & Arrow offers a distinctive new take on management consulting. Stuart Crainer takes aim
OFFICE SPACE
Authors: Franck Tatyana
Published: June 2015

Tatyana Franck gives us a glimpse inside Musée d'Elysée in Lausanne
THREE REASONS WHY MANAGERS DON'T KNOW WHAT THEY'RE DOING
Authors: Vermeulen Freek
Published: June 2015

Freek Vermeulen navigates the managerial future
MORAL INC.
Authors: Goddard Jules
Published: June 2015

As people want and need far more from their work than earlier generations, Jules Goddard explores the growing need for corporations to be reincarnated as moral communities
Growing Incomes, Growing People in Nineteenth‐Century Tasmania
Authors: Inwood Kris , Maxwell‐Stewart Hamish , Oxley Deborah , Stankovich Jim
Published: June 2015

The earliest measures of well‐being for Europeans born in the Pacific region are heights and wages in Tasmania. Evidence of rising stature in middle decades of the nineteenth century survives multiple checks for measurement, compositional, and selection bias. The challenge to health and stature seen in other settler societies (the ‘antebellum paradox’) is not visible here. We sketch an interpretation for the simultaneous rise of Tasmanian stature and per capita gross domestic product based on relatively slow population growth and urbanisation, a decline in food cost per family member available from a worker's wage, and early recognition of the importance of public health.
On the Strong Consistency of M‐Estimates in Linear Models for Negatively Superadditive Dependent Errors
Authors: Wang Xinghui , Hu Shuhe
Published: June 2015

In this paper we discuss the strong consistency of M‐estimates of the regression parameters in a linear model with negatively superadditive dependent (NSD) random errors. The result improves the moment condition and generalises the case of independent random errors to that of NSD random errors.
An interdisciplinary specialist team leads to improved diagnostics and treatment for paediatric patients with vascular anomalies
Authors: Mattila Katariina A. , Kervinen Kaisa , Kalajoki‐Helmiö Teija , Lappalainen Kimmo , Vuola Pia , Lohi Jouko , Rintala Risto J. , Pitkäranta Anne , Salminen Päivi
Published: June 2015

Aim

Patients with vascular anomalies are often misdiagnosed, leading to delayed or improper treatment. The aim of this study was to evaluate the impact of an interdisciplinary team on the diagnosis and treatment of paediatric patients with vascular anomalies.

Methods

We reviewed the paediatric patients evaluated by our interdisciplinary team between 2002 and 2012, analysing the referral diagnosis, final diagnosis, patient age, sex, clinical history, laboratory tests, imaging studies and treatments.

Results

Of the 480 patients who were evaluated, 435 (90.6%) had a vascular anomaly: 30.7% of all patients had a tumour and 55.2% had a malformation. Haemangiomas comprised 93.2% of all tumours, while malformations included capillary (9.8%), lymphatic (30.1%), venous (36.8%), arteriovenous (3.8%) and combined slow–flow (7.9%) malformations. Tumours were initially diagnosed correctly in 89.2% of the patients, but only 38.0% of the malformations were diagnosed correctly. Improper treatment was given to 1.4%, due to incorrect diagnoses.

Conclusion

This study showed that haemangiomas were likely to be diagnosed correctly, but other tumours and vascular malformations were likely to be misdiagnosed. Misdiagnosis seldom led to improper treatment, but probably led to delayed treatment in many cases. The interdisciplinary approach led to improved diagnostics and treatment.
Malnutrition is common in Ugandan children with cerebral palsy, particularly those over the age of five and those who had neonatal complications
Authors: Kakooza‐Mwesige Angelina , Tumwine James K. , Eliasson Ann‐Christin , Namusoke Hanifa K. , Forssberg Hans
Published: June 2015

Aim

Poor growth and malnutrition are frequently reported in children with cerebral palsy in developed countries, but there is limited information from developing countries. We investigated the nutritional status of Ugandan children with cerebral palsy and described the factors associated with poor nutrition.

Methods

We examined 135 children from two to 12 years with cerebral palsy, who attended Uganda's national referral hospital. A child was considered underweight, wasted, stunted or thin if the standard deviation scores for their weight for age, weight for height, height for age and body mass index for age were ≤−2.0 using World Health Organization growth standards. Multivariable logistic regression identified the factors associated with nutritional indicators.

Results

Over half (52%) of the children were malnourished, with underweight (42%) being the most common category, followed by stunting (38%), thinness (21%) and wasting (18%). Factors that were independently associated with being malnourished were as follows: presence of cognitive impairment, with an adjusted odds ratio (aOR) of 4.5, being 5 years or older (aOR = 3.4) and feeding difficulties in the perinatal period (aOR = 3.2).

Conclusion

Malnutrition was common in Ugandan children with cerebral palsy and more likely if they were 5 years or more or had experienced neonatal complications.
Feasibility of thoracoscopic thymectomy for treatment of early‐stage thymoma
Authors: Odaka Makoto , Shibasaki Takamasa , Asano Hisatoshi , Marushima Hideki , Yamashita Makoto , Morikawa Toshiaki
Published: June 2015

Introduction

The objective of this study was to evaluate the feasibility of thoracoscopic thymectomy (TT) for treatment of early‐stage thymoma and to compare the outcomes with those after open thymectomy (OT).

Methods

A retrospective review of 98 patients who underwent TT or OT of Masaoka stage I‐II thymoma without thymic cancer between 1996 and 2013 was performed.

Results

Thoracoscopic thymectomy was performed in 67 patients, and OT was performed in 31 patients. The intraoperative blood loss amounts differed significantly between the TT group and OT group (100 vs 185 mL, P = 0.0070). The postoperative hospital stay was significantly shorter in the TT group than in the OT group (4 vs 12 days, P < 0.0001). No patient in the TT group underwent conversion to open surgery, and no surgical complications, such as massive bleeding, were observed. Two patients experienced recurrence in the TT group during the median postoperative follow‐up period of 65 months. No significant differences were found in the 5‐year disease‐free survival rates between the two groups. There were no significant differences in disease‐free survival as classified by Masaoka stage, World Health Organization type, and the extent of resection of the thymus.

Conclusion

Our outcome showed that TT largely reduced the degree of invasiveness. The outcome was not inferior to that of OT. The results primarily demonstrated the feasibility of TT for treatment of early‐stage thymoma.
The effect of atorvastatin treatment on serum oxysterol concentrations and cytochrome P450 3A4 activity
Authors: Hukkanen Janne , Puurunen Johanna , Hyötyläinen Tuulia , Savolainen Markku J. , Ruokonen Aimo , Morin‐Papunen Laure , Orešič Matej , Piltonen Terhi , Tapanainen Juha S.
Published: June 2015

Aims

Atorvastatin is known to both inhibit and induce the cytochrome P450 3A4 (CYP3A4) enzyme in vitro. Some clinical studies indicate that atorvastatin inhibits CYP3A4 but there are no well‐controlled longer term studies that could evaluate the inducing effect of atorvastatin. We aimed to determine if atorvastatin induces or inhibits CYP3A4 activity as measured by the 4β‐hydroxycholesterol to cholesterol ratio (4βHC : C).

Methods

In this randomized, double‐blind, placebo‐controlled 6 month study we evaluated the effects of atorvastatin 20 mg day−1 (n = 15) and placebo (n = 14) on oxysterol concentrations and determined if atorvastatin induces or inhibits CYP3A4 activity as assessed by the 4βHC : C index. The respective 25‐hydroxycholesterol and 5α,6α‐epoxycholesterol ratios were used as negative controls.

Results

Treatment with atorvastatin decreased 4βHC and 5α,6α‐epoxycholesterol concentrations by 40% and 23%, respectively. The mean 4βHC : C ratio decreased by 13% (0.214 ± 0.04 to 0.182 ± 0.04, P = 0.024, 95% confidence interval (CI) of the difference –0.0595, –0.00483) in the atorvastatin group while no significant change occurred in the placebo group. The difference in change of 4βHC : C between study arms was statistically significant (atorvastatin –0.032, placebo 0.0055, P = 0.020, 95% CI of the difference –0.069, –0.0067). The ratios of 25‐hydroxycholesterol and 5α,6α‐epoxycholesterol to cholesterol did not change.

Conclusions

The results establish atorvastatin as an inhibitor of CYP3A4 activity. Furthermore, 4βHC : C is a useful index of CYP3A4 activity, including the conditions with altered cholesterol concentrations.
Racial and Ethnic Differences in the Likelihood of Vaginal Birth After Cesarean Delivery
Authors: Cheng Erika R. , Declercq Eugene R. , Belanoff Candice , Iverson Ronald E. , McCloskey Lois
Published: June 2015

Background

A major contributor to the increase in cesarean deliveries over recent decades is the decline in vaginal births after cesarean (VBAC). Racial and ethnic disparities in other perinatal outcomes are widely recognized, but few studies have been directed toward racial/ethnic differences in VBAC rates.

Methods

We used the population‐based Massachusetts Pregnancy to Early Life (PELL) database to investigate racial/ethnic differences in rates of VBAC for Massachusetts residents with one prior cesarean from 1998 to 2008.

Results

The overall VBAC rate was 17.3 percent. After adjusting for demographic, behavioral, and medical risk factors, non‐Hispanic Asian mothers had a greater likelihood of VBAC than non‐Hispanic white mothers (adjusted risk ratio 1.31 [95% CI 1.23–1.39]). No other racial/ethnic group was significantly different from non‐Hispanic whites in adjusted analyses. The likelihood of VBAC also decreased with increasing maternal age.

Discussion

Non‐Hispanic Asian women are significantly more likely to have VBAC than non‐Hispanic white women. Efforts to reduce cesarean delivery rates in the United States should address these disparities. Future research should investigate factors underlying these differences to ensure that all women have access to appropriate maternity care services.
Seven basic dimensions of personality pathology and their clinical consequences: Are all personalities equally harmful?
Authors: Vall Gemma , Gutiérrez Fernando , Peri Josep M. , Gárriz Miguel , Ferraz Liliana , Baillés Eva , Obiols Jordi E.
Published: June 2015

Objectives

Dimensional pathology models are increasingly being accepted for the assessment of disordered personalities, but their ability to predict negative outcomes is yet to be studied. We examine the relative clinical impact of seven basic dimensions of personality pathology through their associations with a wide range of clinical outcomes.

Methods

A sample of 960 outpatients was assessed through a 7‐factor model integrating the Cloninger, the Livesley, and the DSM taxonomies. Thirty‐six indicators of clinical outcome covering three areas – dissatisfaction, functional difficulties, and clinical severity – were also assessed. The unique contribution of each personality dimension to clinical outcome was estimated through multiple regressions.

Results

Overall, personality dimensions explained 17.6% of the variance of clinical outcome, but varied substantially in terms of their unique contributions. Negative Emotionality had the greatest impact in all areas, contributing 43.9% of the explained variance. The remaining dimensions led to idiosyncratic patterns of clinical outcomes but had a comparatively minor clinical impact. A certain effect was also found for combinations of dimensions such as Negative Emotionality × Impulsive Sensation Seeking, but most interactions were clinically irrelevant.

Conclusions

Our findings suggest that the most relevant dimensions of personality pathology are associated with very different clinical consequences and levels of harmfulness.

Practitioner points

The relative clinical impact of seven basic dimensions of personality pathology is examined.

Negative Emotionality (Neuroticism) is 6–14 times as harmful as other pathological dimensions.

The remaining dimensions and their interactions have very specific and comparatively minor clinical consequences.

Limitations

We examine only a handful of clinical outcomes. Our results may not be generalizable to other clinical or life outcomes.

Our variables are self‐reported and hence susceptible to bias.

Our design does not allow us to establish causal relationships between personality and clinical outcomes.
Adolescent reading skill and engagement with digital and traditional literacies as predictors of reading comprehension
Authors: Duncan Lynne G. , McGeown Sarah P. , Griffiths Yvonne M. , Stothard Susan E. , Dobai Anna
Published: June 2015

This study investigates the concurrent predictors of adolescent reading comprehension (literal, inferential) for fiction and non‐fiction texts. Predictors were examined from the cognitive (word identification, reading fluency), psychological (gender), and ecological (print exposure) domains. Print exposure to traditional and digital texts was surveyed using a diary method of reading habits. A cross‐sectional sample of 312 students in early (11–13 years) or middle adolescence (14–15 years) participated from a range of SES backgrounds. Word identification emerged as a strong predictor of reading comprehension across adolescence and text genres. Gender effects favouring female students were evident for reading frequency but not for reading skill itself. Reading habits also differed, and comprehension advantages were observed among females for fiction and males for non‐fiction. Age effects emerged for reading frequency, which was lower in middle adolescence. Although more time was spent on digital than on traditional texts, traditional extended text reading was the only reading habit to predict inference‐making in comprehension and to distinguish skilled from less skilled comprehenders. The theoretical and educational implications of these results are discussed.
Structural and functional analysis of tunneling nanotubes (TnTs) using gCW STED and gconfocal approaches
Authors: Bénard Magalie , Schapman Damien , Lebon Alexis , Monterroso Baptiste , Bellenger Marine , Le Foll Frank , Pasquier Jennifer , Vaudry Hubert , Vaudry David , Galas Ludovic
Published: June 2015

Background information

Tunneling nanotubes (TnTs) are thin plasma membrane bridges mediating transfers of materials and signals between cells. Heterogeneity of heterocellular and homocellular TnTs is largely described but ultrafine imaging of these light‐sensitive floating nanometric structures represents a real challenge in microscopy. We propose here imaging strategies designed to dissect structural and dynamic aspects of TnT formation and function in fixed or living PC12 cells.

Results

Through time‐gated Continuous Wave STimulated Emission Depletion (gCW STED) nanoscopy associated with deconvolution, we provided nanoscale details of membrane and cytoskeleton organisations in two subtypes of TnTs, namely type 1 TnT (TnT1) and type 2 TnT (TnT2). In fixed PC12 cells, TnT1 (length, several tens of micrometres; diameter, 100–650 nm) exhibited a large trumpet‐shaped origin, a clear cytosolic tunnel and different bud‐shaped connections from closed‐ended to open‐ended tips. TnT1 contained both actin and tubulin. TnT2 (length, max 20 μm, diameter, 70–200 nm) only contained actin without clear cytosolic tunnel. In living PC12 cells, we observed through gCW STED additional details, unrevealed so far, including a filament spindle emerging from an organising centre at the origin of TnT1 and branched or bulbous attachments of TnT2. However, the power of depletion laser in STED nanoscopy was deleterious for TnTs and prolonged time‐lapse experiments were almost prohibited. By circumventing the hazard of photoxicity, we were able to monitor dynamics of bud‐shaped tips and intercellular transfer of wheat germ agglutinin labelled cellular elements through time‐gated confocal microscopy.

Conclusions

Our work identified new structural characteristics of two subtypes of TnTs in PC12 cells as well as dynamics of formation and transfer through complementary imaging methods combined with image processing. Therefore, we could achieve maximum lateral resolution and sample preservation during acquisitions to reveal new insights into TnT studies.

Significance

Due to large disparity of TnT‐like structures in neuronal, immune, cancer or epithelial cells, high‐ and superresolution approaches can be utilised for full characterisation of these yet poorly understood routes of cell‐to‐cell communication.
Mortalin is Expressed by Astrocytes and Decreased in the Midbrain of Parkinson's Disease Patients
Authors: Cook Travis J. , Hoekstra Jake G. , Eaton David L. , Zhang Jing
Published: June 2015

Mortalin, an essential mitochondrial chaperone protein, has previously been implicated in the pathogenesis of a wide array of diseases, including neurodegenerative conditions such as Parkinson's disease (PD) and Alzheimer's disease. Previous reports have consistently described mortalin protein levels to be lower in the brain tissue of patients with neurodegenerative disease, with expression demonstrated to be lower in neurons of post‐mortem PD brain specimens. However, to date, mortalin expression has not yet been evaluated in astrocytes of post‐mortem brain tissue from either normal or PD subjects. Mortalin expression was demonstrated in mouse primary astrocyte cultures by Western blot and quantitative polymerase chain reaction (PCR). Furthermore, confocal microscopy studies in human post‐mortem tissue indicated co‐localization of mortalin within astrocytes. Utilizing a quantitative immunofluorescence staining approach, the protein was found to be moderately reduced (∼35%) in this cell type in the substantia nigra pars compacta, but not structures of the corpus striatum, in PD subjects as compared to age‐/gender‐matched controls. These findings highlight the potential contribution of disrupted astroglial function in the pathogenesis of PD.
Astrocyte Dysfunction Induced by Alcohol in Females but Not Males
Authors: Wilhelm Clare J. , Hashimoto Joel G. , Roberts Melissa L. , Bloom Shelley H. , Andrew Melissa R. , Wiren Kristine M.
Published: June 2015

Chronic alcohol abuse is associated with brain damage in a sex‐specific fashion, but the mechanisms involved are poorly described and remain controversial. Previous results have suggested that astrocyte gene expression is influenced by ethanol intoxication and during abstinence in vivo. Here, bioinformatic analysis of astrocyte‐enriched ethanol‐regulated genes in vivo revealed ubiquitin pathways as an ethanol target, but with sexually dimorphic cytokine signaling and changes associated with brain aging in females and not males. Consistent with this result, astrocyte activation was observed after exposure in female but not male animals, with reduced S100β levels in the anterior cingulate cortex and increased GFAP+ cells in the hippocampus. In primary culture, the direct effects of chronic ethanol exposure followed by recovery on sex‐specific astrocyte function were examined. Male astrocyte responses were consistent with astrocyte deactivation with reduced GFAP expression during ethanol exposure. In contrast, female astrocytes exhibited increased expression of Tnf, reduced expression of the neuroprotective cytokine Tgfb1, disrupted bioenergetics and reduced excitatory amino acid uptake following exposure or recovery. These results indicate widespread astrocyte dysfunction in ethanol‐exposed females and suggest a mechanism that may underlie increased vulnerability to ethanol‐induced neurotoxicity in females.
Afatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non‐small cell lung cancer harboring activating EGFR mutations: Subgroup analysis of LUX‐Lung 3
Authors: Kato Terufumi , Yoshioka Hiroshige , Okamoto Isamu , Yokoyama Akira , Hida Toyoaki , Seto Takashi , Kiura Katsuyuki , Massey Dan , Seki Yoko , Yamamoto Nobuyuki
Published: June 2015

In LUX‐Lung 3, afatinib significantly improved progression‐free survival (PFS) versus cisplatin/pemetrexed in EGFR mutation‐positive lung adenocarcinoma patients and overall survival (OS) in Del19 patients. Preplanned analyses in Japanese patients from LUX‐Lung 3 were performed. Patients were randomized 2:1 to afatinib or cisplatin/pemetrexed, stratified by mutation type (Del19/L858R/Other). Primary endpoint was PFS (independent review). Secondary endpoints included OS, objective response, and safety. Median PFS (data cut‐off: February 2012) for afatinib versus cisplatin/pemetrexed was 13.8 vs 6.9 months (hazard ratio [HR], 0.38; 95% confidence interval [CI], 0.20–0.70; P = 0.0014) in all Japanese patients (N = 83), with more pronounced improvements in those with common mutations (Del19/L858R; HR, 0.28; 95% CI, 0.15–0.52; P < 0.0001) and Del19 mutations (HR, 0.16; 95% CI, 0.06–0.39; P < 0.0001). PFS was also improved in L858R patients (HR, 0.50; 95% CI, 0.20–1.25; P = 0.1309). Median OS (data cut‐off: November 2013) with afatinib versus cisplatin/pemetrexed was 46.9 vs 35.8 months (HR, 0.75; 95% CI, 0.40–1.43; P = 0.3791) in all Japanese patients, with greater benefit in patients with common mutations (HR, 0.57; 95% CI, 0.29–1.12; P = 0.0966) and Del19 mutations (HR, 0.34; 95% CI, 0.13–0.87; P = 0.0181); OS was not significantly different in L858R patients (HR, 1.13; 95% CI, 0.40–3.21; P = 0.8212). Following study treatment discontinuation, most patients (93.5%) received subsequent anticancer therapy. The most common treatment‐related adverse events were diarrhea, rash/acne, nail effects and stomatitis with afatinib and nausea, decreased appetite, neutropenia, and leukopenia with cisplatin/pemetrexed. Afatinib significantly improved PFS versus cisplatin/pemetrexed in Japanese EGFR mutation‐positive lung adenocarcinoma patients and OS in Del19 but not L858R patients (www.clinicaltrials.gov; NCT00949650).
Ghrelin administration suppresses inflammation‐associated colorectal carcinogenesis in mice
Authors: Kawaguchi Makiko , Kanemaru Ai , Fukushima Tsuyoshi , Yamamoto Koji , Tanaka Hiroyuki , Haruyama Yukihiro , Itoh Hiroshi , Matsumoto Nobuhiro , Kangawa Kenji , Nakazato Masamitsu , Kataoka Hiroaki
Published: June 2015

Ghrelin is a 28‐amino‐acid peptide that stimulates the release of pituitary growth hormone. Because of its orexigenic effects, ghrelin is being developed as a therapeutic option for postoperative support and treatment of anorexia‐cachexia syndrome of cancer patients. However, ghrelin has a multiplicity of physiological functions, and it also affects cell proliferation. Therefore, the effects of ghrelin administration on carcinogenesis and cancer progression in patients susceptible to cancer should be clarified. In this study, we examined the effects of ghrelin on cancer promotion in vivo using murine intestinal carcinogenesis models. Intestinal tumorigenesis was examined to determine the effects of either exogenous ghrelin administration or ghrelin deficiency following deletion of the Ghrl gene. Two murine intestinal tumorigenesis models were used. The first was the azoxymethane (AOM)/dextran sodium sulfate (DSS)‐induced inflammation‐associated colon carcinogenesis model and the second was the ApcMin/+ genetic cancer susceptibility model. In AOM/DSS‐treated mice, administration of ghrelin significantly suppressed tumor formation in the colon. In contrast, ghrelin administration did not affect the number of intestinal tumors formed in ApcMin/+ mice. The absence of endogenous ghrelin did not affect the incidence of intestinal tumors in either AOM/DSS‐treated mice or ApcMin/+ mice, though tumor size tended to be larger in Ghrl−/− colons in the AOM/DSS model. No tumor‐promoting effect was observed by ghrelin administration in either tumorigenesis model. In summary, this study provides in vivo experimental evidence for the usefulness of ghrelin administration in the chemoprevention of inflammation‐associated colorectal carcinogenesis and may suggest its safety in patients under colitis‐associated cancer susceptibility conditions.