bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of ethical behaviors in corporate governance
Authors: Lopez Eduardo V. , Medina Alicia
Published: May 2015

Purpose

– The purpose of this paper is to provide a summary of key aspects of a recently defended PhD thesis. It enables readers who may be interested in the thesis topic to gain an overview of that work and a link to the entire thesis through a URL linkwww.dropbox.com/s/1gikjlh6qw0v26u/Dissertation_Eduardo_Lopez_03122015.pdf?dl=0. The second purpose of this Thesis Research Note (TRN) is to explain the thesis author’s doctoral journey.

Design/methodology/approach

– The methodology was rooted in critical realism using mixed research methods. The approach for the paper is to provide a reflective narrative to explain the lived experience of the authors throughout the candidate’s doctoral journey.

Findings

– The theoretical implications of this study are the introduction of two new constructs (The Small Sins Allowed (SSA) and the Line of Impunity (LoI)) and the definition of these constructs as variables that affect corporate governance.

Research limitations/implications

– Although this study was intended to collect feedback regardless of geographical location, over 91 percent of responses came from the USA, Canada, and Latin America. For this reason, generalization beyond these boundaries requires further analysis.

Practical implications

– The practical implications are related to the application of the two constructs (SSA and the LoI) into the daily corporate governance activities.

Social implications

– SSA and LoI, can be the foundation for renewed and vigorous corporate governance. SSA helps to establish a level above which adherence to ethical standards is expected. LoI aids in identifying ethical fault lines. Together they help to keep unethical behaviors under control.

Originality/value

– The TRN provides a highly individualized account of a doctoral journey but it is intended to contribute to the growing body of TRNs published in this journal that in turn may inform decisions relating to candidates embarking on a doctoral journey.
Assessing the quality of collaboration towards the achievement of Sustainable Energy Innovation in PFI school projects
Authors: Badi Sulafa M. , Pryke Stephen D
Published: May 2015

Purpose

– The purpose of this paper is to examine the quality of collaboration towards Sustainable Energy Innovation (SEI) in Private Finance Initiative (PFI) projects. While the capacity of PFI to encourage collaboration towards innovation is largely advocated by its proponents; however, it remains to be supported by empirical evidence.

Design/methodology/approach

– Adopting the Complex Product System (CoPS) innovation management model, the authors assess the quality of collaboration at the interface between the innovation superstructure of public sector clients and users, and the innovation infrastructure of private sector designers, contractors and operators. Two interactional elements are examined upon which the quality of collaboration is assessed: openness of communication and alignment of objectives. The authors apply the model to four new-built PFI school projects within the context of the UK government Building Schools for the Future Programme. Semi-structured interviews with total of 50 key stakeholders were used as the primary data collection method.

Findings

– PFI has introduced a number of problematic issues weakening collaborative efforts towards innovation in the project environment. Particularly, the study underlines the restricting internal contractual relationships within the integrated Project Company and the misalignment of Design-Construction-Operation sustainability objectives. It also highlights ineffective communication with public sector clients and users brought in by the restricted nature of PFI engagement processes as well as the misalignment of public sector-private sector sustainability objectives.

Research limitations/implications

– The qualitative nature of the chosen research methodology limits the ability to generalise. The research findings need to be confirmed or rejected by means of quantitative research as representative of all PFI projects.

Practical implications

– The study emphasizes the public authority’s role in relation to providing the necessary conditions for the creation of a collaborative environment conducive to SEI in PFI projects.

Originality/value

– The study was able to expand the understanding of innovation and collaboration management processes in PFI projects in three respects: First, addressing the limited attention to innovation in PFI research, the study is the first to examine the quality of collaboration in PFI projects towards the implementation SEI. Second, examining the quality of collaboration in PFI projects through the lens of CoPS provides a new understanding of sustainability innovation and strongly indicates that the CoPS model should be expanded to account for the dynamics of innovation processes in the procurement of sustainable CoPS. Third, the explorative nature of the study was useful in generating research hypotheses that can form the basis for future research on SEI in PFI projects.
Framework for enhanced third-party relationships in project networks
Authors: Sariola Rami , Martinsuo Miia Maarit
Published: May 2015

Purpose

– This paper investigates third-party relationships in project networks in the construction industry and seeks increased understanding on how such relationships can be strengthened. The purpose of this paper is to develop a framework and propositions on enhanced relationship strength between component suppliers and designers as third parties.

Design/methodology/approach

– A conceptual approach is used in this paper. Previous empirical research on business relationships, project networks and relationship strength is reviewed systematically, to identify factors required for strengthening the relationship in project networks.

Findings

– Cooperative practices needed for strengthening the relationships in project networks were identified. The framework on how such practices are associated with relationship strength between supplier and designers was developed. Propositions on strengthening the relationship between component suppliers and designers were stated. These propositions can be developed further and tested in a hypothetic-deductive study.

Research limitations/implications

– The research was delimited by the choice of designers as third parties. The authors used some excerpts from the earlier interview study with over 20 designers, to illustrate the issues. Empirical analysis was not included in this paper which causes an evident limitation to validity. Additional research is proposed on analyzing the contractors’ and suppliers’ viewpoints to third-party relationships.

Practical implications

– The paper suggests cooperative practices for construction component suppliers to enhance their relationship strength with third parties in project networks.

Originality/value

– Limited research attention has been directed at the third-party relationships of suppliers in project networks. This paper offers important knowledge about these less salient relationships in project networks, beyond a simple dyadic relationship in the direct supply chain.
Top management support in software cost estimation
Authors: Rahikkala Jurka , Leppänen Ville , Ruohonen Jukka , Holvitie Johannes
Published: May 2015

Purpose

– A cost estimate is considered to have a high impact on software project success. Because of this, different methodologies for creating an accurate estimate have been studied over decades. Many methodologies produce accurate results, when used properly. However, software projects still suffer from inaccurate estimates. The disparity may result from organisational hindrances. This paper focuses on top management support (TMS) for software cost estimation (SCE). The purpose of this paper is to identify current practices and attitudes of top management involvement in SCE, and to analyse the relationship between these two and project success.

Design/methodology/approach

– A list of 16 TMS practices for SCE has been developed. A survey was conducted to capture the frequency of use and the experienced importance of support practices. Data has been collected from 114 software professionals in Finland. Correlations between the frequency of use, attitudes and project success were analysed.

Findings

– Top management invests a significant amount of attention in SCE. The extent of use and experienced importance do not correlate strongly with each other or project success.

Research limitations/implications

– The results may lack generalisability. Researchers are encouraged to validate the results with further studies.

Practical implications

– Software professionals invite senior managers to participate in SCE. A list of practices for participating is provided.

Originality/value

– This paper suggests a list of 16 TMS practices for SCE. The paper also reports on the extent of use and experienced importance of practices, and the correlations between these two and project success.
Nursing governance and clinical error control
Authors: Tuan Luu Trong
Published: May 2015

Purpose

– This study aims to fathom the role of nursing governance as a mechanism to activate the chain effect from corporate social responsibility (CSR) through psychological contract to knowledge sharing, which in turn reduces clinical errors in hospitals in the Vietnam context. Clinical errors not merely result from human factors but also from mechanisms which influence human factors.

Design/methodology/approach

– The clues for the research model were established through structural equation modeling-based analysis of cross-sectional data from 233 nurses of Vietnam-based hospitals.

Findings

– Research findings unveiled the positive correlation between nursing governance and ethical CSR as well as the negative correlations between nursing governance and legal CSR or economic CSR. Ethical CSR was found to have positive effect on psychological contract, whereas legal or economic CSR was found to have negative effect on psychological contract. The chain effects from psychological contract through knowledge sharing to clinical error control were also attested in this inquiry.

Originality/value

– Research results have contributed to literature in some ways, for example, expanding health-care quality and patient safety literature through the chain of antecedents (nursing governance, CSR, psychological contract and knowledge sharing) to clinical error control, underscoring the role of psychological contract in cultivating knowledge sharing and adding organizational outcomes such as knowledge sharing and clinical error control to the nursing governance literature.
Attitudes toward acupuncture in Hong Kong
Authors: Chan Kara , Tsang Lennon , Fung Timothy K.F.
Published: May 2015

Purpose

– This paper aims at describing and exploring how consumers perceive acupuncture as a medical treatment in relation to biomedicine.

Design/methodology/approach

– Data were collected through an online survey using quota sampling. The attitudes of 879 Hong Kong residents aged 20 or above were surveyed. Questions were generated from a previous focus group study.

Findings

– Factor analysis found that attitude toward acupuncture consisted of five underlying dimensions, including trust in biomedicine, risks versus benefits, cure and effectiveness, qualification and skills of acupuncturists, side effects and costs and severe aftereffects. Lack of trust in acupuncturists and perceived inferiority of acupuncture to biomedicine were the major barriers of public acceptance of acupuncture. Perceived strengths of acupuncture identified were not involving taking medicine, fewer side effects and being good for preventive care.

Research limitations/implications

– This study used a convenience sample recruited through personal networks, so the findings cannot automatically be generalized to the rest of the population.

Practical implications

– There is a need to build trust in the therapy and the reputation of acupuncturists through better communication of the profession’s qualification and accreditation system, as well as dissemination of clinical evidence on a long-term basis. Consumers need to be better educated about the sensations to be expected during acupuncture and the criteria for selecting an acupuncturist.

Originality/value

– This has been the first quantitative study focusing on Hong Kong consumers’ perceptions of acupuncture.
Striving for excellence: the role of top management team diversity in universities
Authors: Hattke Fabian , Blaschke Steffen
Published: May 2015

Purpose

– The purpose of this paper is to evaluate the influence of top management team diversity on academic excellence in universities. Academic excellence is conceptualized as successfully gaining funds for inter-organizational research collaborations, interdisciplinary graduate schools and high-ranked scientific reputation.

Design/methodology/approach

– The study applies upper echelon theory to universities. Three hypotheses are developed: (overall) top management team heterogeneity is positively associated with successful funding of excellence clusters, (overall) top management team heterogeneity is positively associated with successful funding of graduate schools and (overall) top management team heterogeneity is positively associated with academic reputation. The empirical study is based on a cross-sectional dataset with a time lag, covering characteristics of 75 German public universities from 2008 to 2013. Multiple-regression analysis is applied to test the hypotheses.

Findings

– Our results indicate that disciplinary and educational diversity of upper echelons has a positive effect on the outcomes. Other top management team characteristics (age, gender, etc.) show no significant effects. Besides top management team composition, we find that a high number of faculties and a broad inclusion of internal status groups (students, tenured faculty, academic and administrative staff) and external stakeholders in decision making processes may enhance academic excellence of universities.

Research limitations/implications

– First, the study contributes to the body of literature concerned with higher education. It is situated at the crossroads of management studies and higher education research, unlocking strategic management theorizing for the public context. Furthermore, the study contributes to the body of literature on strategic leadership in pluralistic organizations. It highlights the importance of heterogeneous governance structures and modular organization designs for achieving academic excellence.

Practical implications

– The paper may inform practitioners in administrative or leading positions and policy-makers concerned with higher education. The more diverse a top management team is in terms of multiple disciplinary backgrounds, the more likely they succeed in driving the university toward academic excellence.

Originality/value

– The study is among the first to evaluate the influence of top management teams in universities with a quantitative research design.
Examining teamwork and leadership in the fields of public administration, leadership, and management
Authors: Chin Roger J.
Published: May 2015

Purpose

– The purpose of this paper is to provide a systematic review of papers in ten top scholarly journals to determine their overall examination of leadership in teams and to identify which models of teamwork and leadership have been most explored by researchers.

Design/methodology/approach

– This paper reaches its findings through content analysis of 80 journal papers published in top academic journals from 1999 through 2012. Coding based on categories of teams, leadership and leadership styles conformed to forced choice and latent coding; two independent reviewers managed the subjectivity of the coding.

Findings

– Sixty per cent of the papers studied explored a group of workers whose teamwork was expected to be permanent, which receives a strong direction from a designated leader; almost that many (58.75 per cent) explored a group working with formal leadership by the worker’s supervisor; almost 50 per cent of papers explored leadership that combined two or more leadership styles simultaneously. This heavy concentration of the literature in a few areas suggests that research on other types of teamwork and leadership is minimal.

Research limitations/implications

– This particular research utilized the latent coding method of content analysis and forced choice in the selections. Even though content analysis has many strengths, the latent coding method of content analysis and forced choice selections require the researcher to examine the overall content to determine whether certain variables were present or absent. After the examination of the overall content, a subjective interpretation of the data is needed from the researcher. Other researchers that look at the same data may interpret the data differently.

Practical implications

– This research provides researchers, academics and practitioners with a comprehensive analysis on teamwork and leadership. The extensive investigation presents a pivotal starting point for further developments in this emerging area. The content analysis found a proliferation of diverse organizations utilizing teamwork, and this subject should be researched more vigorously. As organizations continue to embrace, pursue and promote teamwork, understanding the current state of the field will assist in having better understanding on how to develop effective teams.

Originality/value

– This paper contributes to the field by creating taxonomy to categorize the types of leaders and teams and presenting an explanation on the distinction between traditional and horizontal style of leadership. In identifying major trends in the existent literature, this examination provides valuable information for researchers.
Doctors’ functional leadership in psychiatric healthcare teams – a reversible leadership logic
Authors: Berlin Johan M.
Published: May 2015

Purpose

– The purpose of this paper was to study how psychiatric doctors practise leadership in multidisciplinary healthcare teams. The paper seeks to answer the question: How do psychiatric doctors lead multidisciplinary teams during treatment conferences?

Design/methodology/approach

– Six psychiatric teams were studied at a university hospital. Each team was observed over a period of 18 months, and data were collected during four years (2008-2011). Data were collected through interviews with doctors (n= 19) and observations (n= 30) of doctors’ work in multidisciplinary psychiatric teams.

Findings

– Doctors in a multidisciplinary team use either self-imposed or involuntary leadership style. Oscillating between these two extremes was a strategy for handling the internal tensions of the team.

Research limitations/implications

– The study was a case study, performed during treatment conferences at psychiatric wards in a university hospital. This limitation means that there is cause for some caution in generalising the results.

Practical implications

– The results are useful for understanding leadership in multidisciplinary medical teams. By understanding the reversible logic of leadership, cooperation and knowledge sharing can be gained, which means that a situation of mere peaceful coexistence can be avoided. Understanding the importance of the informal contract makes it possible to switch leadership among team members. A reversible leadership with an informal contract makes the team less vulnerable. The team’s professionals can thus easily handle difficult situations and internal tensions, facilitating leadership and management of multidisciplinary teams.

Originality/value

– Doctors in multidisciplinary psychiatric teams use reversible leadership logic.
When Siberia came to the Netherlands: the response of continental black‐tailed godwits to a rare spring weather event
Authors: Senner Nathan R. , Verhoeven Mo A. , Abad‐Gómez José M. , Gutiérrez Jorge S. , Hooijmeijer Jos C. E. W. , Kentie Rosemarie , Masero José A. , Tibbitts T. Lee , Piersma Theunis
Published: May 2015

Extreme weather events have the potential to alter both short‐ and long‐term population dynamics as well as community‐ and ecosystem‐level function. Such events are rare and stochastic, making it difficult to fully document how organisms respond to them and predict the repercussions of similar events in the future.

To improve our understanding of the mechanisms by which short‐term events can incur long‐term consequences, we documented the behavioural responses and fitness consequences for a long‐distance migratory bird, the continental black‐tailed godwit Limosa limosa limosa, resulting from a spring snowstorm and three‐week period of record low temperatures.

The event caused measurable responses at three spatial scales – continental, regional and local – including migratory delays (+19 days), reverse migrations (>90 km), elevated metabolic costs (+8·8% maintenance metabolic rate) and increased foraging rates (+37%).

There were few long‐term fitness consequences, however, and subsequent breeding seasons instead witnessed high levels of reproductive success and little evidence of carry‐over effects.

This suggests that populations with continued access to food, behavioural flexibility and time to dissipate the costs of the event can likely withstand the consequences of an extreme weather event. For populations constrained in one of these respects, though, extreme events may entail extreme ecological consequences.
Conceptualising professionalism in occupational therapy through a Western lens
Authors: Hordichuk Chelsea J. , Robinson Allison J. , Sullivan Theresa M.
Published: May 2015

Introduction

The term professionalism is embedded within curriculum and occupational therapy documents, yet, explicit discussion of the concept is lacking in the literature. This paper strives for a greater understanding of how professionalism is currently conceptualised within Western occupational therapy literature.

Methods

A broad literature search was conducted and included international peer‐reviewed and grey literature from Western cultures including Australia, Canada, New Zealand, the United Kingdom and the United States. To enrich understanding, some documents from medicine were also included.

Findings

Professionalism is widely upheld as a core construct of occupational therapy. However, an evidence‐based consensus of the specific elements of professionalism guiding occupational therapy practice is lacking. Currently, understanding of professionalism is largely based on multiple, isolated concepts presented in Western professional association documents.

Relevance to Clinical Practice

Acknowledging the multifaceted and multicultural nature of professionalism is essential to begin systematically delineating and conceptualising elements of professionalism specific to occupational therapy.

Limitations

This review has been conducted from a solely Western cultural lens.

Recommendations for Further Research

Additional work to highlight differences specific to international contexts, cultures, and societal influences is needed to enrich the understanding of professionalism in occupational therapy practice.
Symptoms and side effects in chronic non‐cancer pain patients: clinical implications and development of new assessment tools
Authors: Olsen T. S. , Jonsson T. , Højsted J. , Sjøgren P. , Christrup L.
Published: May 2015

Objective

To improve a 41‐item screening tool evaluated in our previous study by making it more simple and convenient to patients and at the same time maintain the level of information and the sensitivity.

Methods

In a prospective, two‐period questionnaire study, patients suffering from chronic pain of non‐cancer origin for more than 6 months, were asked to fill in two questionnaires: QSSE‐41 or QSSE‐33 and SF‐36. The first part of the study (QSSE‐41) included an age‐ and sex‐matched control group.

Results

A total of 67 patients were included in QSSE‐41 and 60 patients in QSSE‐33. In QSSE‐41, the mean number of symptoms reported by the patient group (12.3) was significantly higher than those reported by the controls (6.8) (P < 0.001). Out of the total number of symptoms, 40.3% were reported to be side effects caused by analgesics, and out of those 61.3% were reported as acceptable and 38.7% as unacceptable side effects. In the QSSE‐33, the mean number of symptoms reported by the patient group was 13.6. Out of the total number of symptoms, 46.3% were reported to be side effects caused by analgesics, and out of those 56.4% were reported as acceptable and 43.6% as unacceptable side effects.

Conclusions

This new and shorter screening tool QSSE‐33 may substitute the original QSSE‐41 and in clinical use, contribute substantially to a more comprehensive and detailed understanding of symptoms/side effects and may consequently lead to improved therapies.
Interactive and Indirect Effects of Anxiety and Negative Urgency on Alcohol‐Related Problems
Authors: Menary Kyle R. , Corbin William R. , Leeman Robert F. , Fucito Lisa M. , Toll Benjamin A. , DeMartini Kelly , O'Malley Stephanie S.
Published: May 2015

Background

Although drinking for tension reduction has long been posited as a risk factor for alcohol‐related problems, studies investigating anxiety in relation to risk for alcohol problems have returned inconsistent results, leading researchers to search for potential moderators. Negative urgency (the tendency to become behaviorally dysregulated when experiencing negative affect) is a potential moderator of theoretical interest because it may increase risk for alcohol problems among those high in negative affect. This study tested a cross‐sectional mediated moderation hypothesis whereby an interactive effect of anxiety and negative urgency on alcohol problems is mediated through coping‐related drinking motives.

Methods

The study utilized baseline data from a hazardously drinking sample of young adults (N = 193) evaluated for participation in a randomized controlled trial of naltrexone and motivational interviewing for drinking reduction.

Results

The direct effect of anxiety on physiological dependence symptoms was moderated by negative urgency such that the positive association between anxiety and physiological dependence symptoms became stronger as negative urgency increased. Indirect effects of anxiety and negative urgency on alcohol problems (operating through coping motives) were also observed.

Conclusions

Although results of the current cross‐sectional study require replication using longitudinal data, the findings suggest that the simultaneous presence of anxiety and negative urgency may be an important indicator of risk for alcohol use disorders via both direct interactive effects and indirect additive effects operating through coping motives. These findings have potentially important implications for prevention/intervention efforts for individuals who become disinhibited in the context of negative emotional states.
The effects of proton pump inhibition on patient‐reported severity of dyspepsia when receiving dual anti‐platelet therapy with clopidogrel and low‐dose aspirin: analysis from the Clopidogrel and the Optimization of Gastrointestinal Events Trial
Authors: Vardi M. , Cryer B. L. , Cohen M. , Lanas A. , Schnitzer T. J. , Lapuerta P. , Goldsmith M. A. , Laine L. , Doros G. , Liu Y. , McIntosh A. I. , Cannon C. P. , Bhatt D. L.
Published: May 2015

Background

Dual anti‐platelet therapy with clopidogrel and low‐dose aspirin increases the risk for gastrointestinal clinical events. Omeprazole has been shown to significantly reduce these events without compromising cardiovascular safety in patients treated with dual anti‐platelet therapy. Whether or not omeprazole improves patient‐reported outcomes is undetermined.

Aim

To assess the impact of prophylactic omeprazole with background dual anti‐platelet therapy on patient‐reported symptoms of dyspepsia compared to placebo.

Methods

We analysed results of the Severity of Dyspepsia Assessment questionnaires collected in the Clopidogrel and the Optimization of Gastrointestinal Events Trial.

Results

Patient‐reported outcome data from 3759 subjects were available for analysis. At 4 weeks, the mean scores of pain intensity and nonpain symptoms were lower in the omeprazole group (5.61 ± 0.17 vs. 6.40 ± 0.17, P = 0.001, and 10.61 ± 0.07 vs. 11.00 ± 0.07, P < 0.001 respectively). These differences were maintained at 24 weeks (5.91 ± 0.35 vs. 7.10 ± 0.37, P = 0.020 for pain intensity; 10.36 ± 0.12 vs. 10.93 ± 0.13, P = 0.001 for nonpain symptoms). After adjusting for covariates there were no statistically significant differences between the groups in the percent of patients with dyspepsia during follow‐up.

Conclusions

In addition to reducing the risk of gastrointestinal bleeding, statistically significant benefits with prophylactic omeprazole use on both pain and nonpain symptoms were evident at 4 weeks and sustained through 24 weeks. The clinical significance of these overall results is unclear, but greater in patients with pain at baseline.
Myopathy in older people receiving statin therapy: a systematic review and meta‐analysis
Authors: Iwere Roli B. , Hewitt Jonathan
Published: May 2015

Objective

The aim of the present study was to determine the risk of myopathy in older people receiving statin therapy.

Methods

Eligible studies were identified searching Ovid Medline, EMBASE, Scopus, CINAHL, Cochrane and PSYCHINFO databases (1987 to July 2014). The selection criteria comprised randomized controlled studies that compared the effects of statin monotherapy and placebo on muscle adverse events in the older adult (65+ years). Data were extracted and assessed for validity by the authors. Odds ratios and 95% confidence intervals (CIs) were used to calculate binary outcomes. Evidence from included studies were pooled in a meta‐analysis using Revman 5.3.

Results

The trials assessed in the systematic review showed little or no evidence of a difference in risks between treatment and placebo groups, with myalgia [odds ratio (OR) 1.03, 95% CI 0.90, 1.17; I2 = 0%; P = 0.66] and combined muscle adverse events (OR 1.03, 95% CI 0.91, 1.18; I2 = 0%; P = 0.61) (myopathy). No evidence was found for an increased risk of rhabdomyolysis (OR 2.93, 95% CI 0.30, 28.18; I2 = 0%; P = 0.35) in the seven trials that reported this. No trials reported mortality due to a muscle‐related event. Discontinuations due to an adverse effect were reduced in the treatment group compared with placebo (OR 0.74, 95% CI 0.50, 1.09; I2 = 0%; P = 0.13).

Conclusion

The results obtained from the present review suggest that statins are relatively safe, even in older people. There was no evidence to suggest an increased risk of myopathy in older adults receiving statin therapy. There is slightly increased seen with rhabdomyolysis when compared with the general population, although the event is relatively rare. Statins should be prescribed to elderly people who need it, and not withheld, as its myopathy safety profile is tolerable.
The FNTB promoter polymorphism rs11623866 as a potential predictive biomarker for lonafarnib treatment of ovarian cancer patients
Authors: Bachmann Hagen Sjard , Meier Werner , du Bois Andreas , Kimmig Rainer , Kuhlmann Jan Dominik , Siffert Winfried , Sehouli Jalid , Wollschlaeger Kerstin , Huober Jens , Hillemanns Peter , Burges Alexander , Schmalfeldt Barbara , Aminossadati Behnaz , Wimberger Pauline
Published: May 2015

Aim

Despite promising preclinical findings regarding clinical utility of farnesyltransferase inhibitors (FTI), such as lonafarnib, success of clinical trials is limited. A multicentre AGO‐OVAR‐15 phase II trial reported an unfavourable effect of lonafarnib on the outcome of patients with advanced ovarian cancer. This study was performed as a genetic subgroup analysis of the AGO‐OVAR‐15 trial, and investigated the utility of the promoter polymorphism rs11623866 of the farnesyltransferase ß‐subunit gene (FNTB) in predicting the clinical effectiveness of lonafarnib.

Methods

The influence of rs11623866 (c.‐609G > C) on FNTB promoter activity was investigated by electrophoretic‐mobility‐shift assay, luciferase‐reporter assay and RT‐qPCR. A total of 57 out of 105 patients from the AGO‐OVAR‐15 trial, treated with carboplatin and paclitaxel ± lonafarnib, was genotyped for rs11623866 by restriction fragment length polymorphism analysis. Genotype‐dependent survival analysis was performed by Kaplan–Meier analysis.

Results

The presence of the G allele was associated with increased FNTB promoter activity compared with the C allele. An unfavourable effect of lonafarnib was limited to patients carrying a GG genotype (HRPFS 6.2, 95%CI = 2.01, 19.41, P = 0.002; HROS 9.6, 95%CI = 1.89, 48.54, P = 0.006). Median progression free survival (PFS) for patients with the GG genotype in the lonafarnib treated arm was 10 months, whereas median PFS without FTI‐treatment was 40 months. Median overall survival (OS) in the lonafarnib‐treated group was 19 months, whereas median OS was not reached in the untreated group.

Conclusions

Discrepancies between preclinical success and clinical failure may be due to the patients' genetic variability of FNTB. Therefore, our results may encourage retrospective evaluation of FNTB polymorphisms in previous FTI studies, especially those reporting positive FTI response.
Clinicopathologic and molecular characteristics of gastric cancer showing gastric and intestinal mucin phenotype
Authors: Oue Naohide , Sentani Kazuhiro , Sakamoto Naoya , Yasui Wataru
Published: May 2015

Gastric cancer (GC), one of the most common human cancers, can be classified into gastric or intestinal phenotype according to mucin expression. TP53 mutation, allelic deletion of the APC gene and nuclear staining of β‐catenin are frequently detected in the intestinal phenotype of GC, whereas CDH1 gene mutation, microsatellite instability and DNA hypermethylation of MLH1 are common events in the gastric phenotype of GC. Our Serial Analysis of Gene Expression (SAGE) and Escherichia coli ampicillin secretion trap (CAST) analyses revealed that CDH17, REG4, OLFM4, HOXA10, DSC2, TSPAN8 and TM9SF3 are upregulated in GC and that CLDN18 is downregulated in GC. Expression of CDH17, REG4, HOXA10 and DSC2 and downregulation of CLDN18 are observed in the intestinal phenotype of GC. In contrast, OLFM4 is expressed in the gastric phenotype of GC. Expression of TSPAN8, TM9SF3 and HER2 are not associated with either gastric or intestinal phenotypes. Ectopic CDX2 expression plays a key function in the GC intestinal phenotype. MUC2, CDH17, REG4, DSC2 and ABCB1 are direct targets of CDX2. Importantly, these genes encode transmembrane/secretory proteins, indicating that the microenvironment as well as cancer cells are also different between gastric and intestinal phenotypes of GC.
Temperature rises in the round window caused by various light sources during insertion of rigid endoscopes: an experimental animal study
Authors: Dundar R. , Bulut H. , Yükkaldiran A. , Güler O.K. , Demirtaş Y. , Iynen İ. , Bozkuş F. , Soy F.K.
Published: May 2015

Objectives

The instruments used in endoscopic surgery include rigid endoscopes of different diameters and angles, sources of light and monitors. In this study, we explored temperature rises in the round window caused by insertion of rigid endoscopes of different diameters into the middle ear; the endoscopes were fitted with different light sources.

Design

An experimental animal study.

Setting

We subjected seven guinea pigs to simulate otological surgery at room temperature. We monitored body temperatures, along with temperature rises caused by the use of 0° rigid endoscopes of diameters 3 or 4 mm, fitted with light sources including a halogen light, a light‐emitting diode (LED) and a xenon light. Data were collected every second from a sensor placed in the round window.

Participants

An experimental study on 7 guinea pigs.

Main Outcome Measures

Rise of the temperature on round window.

Results

Rigid endoscopes caused the temperature of the tympanum to rise when xenon and halogen light sources were used, regardless of endoscope diameter. However, the temperature rise was less when a LED light source was employed.

Conclusion

The endoscopic instruments used in middle ear surgery caused the temperature of the round window to rise. The rise varied with endoscope diameter and the type of light source used.
Charcot neuroarthropathy after simultaneous pancreas–kidney transplantation: risk factors, prevalence, and outcome
Authors: García Barrado Fernando , Kuypers Dirk R. , Matricali Giovanni A.
Published: May 2015

We retrospectively analyzed outcome and risk factors of developing Charcot foot (CF) in 100 patients with type 1 diabetes mellitus who underwent a simultaneous pancreas–kidney (SPK) transplantation. Patients who developed CF after SPK transplantation had significantly higher mortality (56% vs. 18%) and more frequently graft failure (44% vs. 13%). Recipients with CF also experienced acute rejections more frequently (78% vs. 41%). They furthermore had higher pre‐transplant values of HbA1c, received cyclosporine and azathioprine more often, and had significantly higher cumulative corticosteroid use. Patients transplanted in an earlier era (1992–1998) received cyclosporine and azathioprine more often and had a significantly higher cumulative corticosteroid use with the higher prevalence of CF. Conversely, patients with diabetes transplanted more recently (1999–2012) received lower doses of corticosteroids as part of their tacrolimus‐based immunosuppressive therapy, resulting in fewer CF attacks. In conclusion, development of CF after SPK is associated with poor patient and graft outcome. Poor pre‐transplant diabetic control and the use of high‐dose corticosteroids are risk factors for the development of CF. We recommend reduction in or even total avoidance of corticosteroids after SPK transplantation. Given the importance of the diagnosis of CF on outcome, a systematic examination of SPK patients' feet is recommended.
Self‐reported diabetes self‐management competence and support from healthcare providers in achieving autonomy are negatively associated with diabetes distress in adults with Type 1 diabetes
Authors: Mohn J. , Graue M. , Assmus J. , Zoffmann V. , B. Thordarson H. , Peyrot M. , Rokne B.
Published: May 2015

Aim

To investigate the associations of self‐perceived competence in diabetes management and autonomy support from healthcare providers with diabetes distress in adults with Type 1 diabetes mellitus that is not optimally controlled [HbA1c ≥ 64 mmol/mol (8.0%)].

Methods

This cross‐sectional study comprised blood sampling and three self‐report questionnaires, the Problem Areas in Diabetes scale, the Perceived Competence in Diabetes Scale and a measure of autonomy support by healthcare providers, the Health Care Climate Questionnaire. We fitted blockwise linear regression models to assess the associations between Problem Areas in Diabetes score and the variables of interest (autonomy support and perceived diabetes competence), controlling for clinical and sociodemographic variables.

Results

Of the study sample [n = 178; mean age 36.7 (±10.7) years], 31.5% had long‐term complications and 43.2% reported elevated (≥40) Problem Areas in Diabetes scores. A significant negative association was found between autonomy support and Problem Areas in Diabetes score (B = ‐3.61, P = 0.001), indicating that lower autonomy support was associated with greater diabetes distress. When perceived competence was controlled, it mediated the association of autonomy support with diabetes distress, reducing it to non‐significance. There was a significant negative association between perceived competence and Problem Areas in Diabetes score (B = ‐8.89, P < 0.001), indicating that lower perceived competence was associated with greater perceived distress.

Conclusions

There was an indirect (fully mediated) relationship between autonomy support and diabetes distress; autonomy support was associated with increased perceived competence, which, in turn, was associated with reduced distress. Healthcare providers' communication styles enhancing perceived competence through autonomy support may contribute to effective treatment for people with Type 1 diabetes and suboptimum glycaemic control.
A novel mutation of the hGR gene causing Chrousos syndrome
Authors: Nicolaides Nicolas C. , Geer Eliza B. , Vlachakis Dimitrios , Roberts Michael L. , Psarra Anna‐Maria G. , Moutsatsou Paraskevi , Sertedaki Amalia , Kossida Sophia , Charmandari Evangelia
Published: May 2015

Background

Natural mutations in the human glucocorticoid receptor (hGR, NR3C1) gene cause Chrousos syndrome, a rare condition characterized by generalized, partial, target‐tissue insensitivity to glucocorticoids.

Objective

To present a new case of Chrousos syndrome caused by a novel mutation in the hGR gene, and to elucidate the molecular mechanisms through which the natural mutant receptor affects glucocorticoid signal transduction.

Design and Results

The index case presented with hirsutism, acne, alopecia, anxiety, fatigue and irregular menstrual cycles, but no clinical manifestations suggestive of Cushing's syndrome. Endocrinologic evaluation revealed elevated 08:00 h plasma adrenocorticotropic hormone, serum cortisol and androstenedione concentrations and increased urinary free cortisol excretion. The patient harbored a novel A > G transition at nucleotide position 2177, which resulted in histidine (H) to arginine (R) substitution at amino acid position 726 of the receptor (c.2177A > G, p.H726R). Compared with the wild‐type receptor, the mutant receptor hGRαH726R demonstrated decreased ability to transactivate glucocorticoid‐responsive genes and to transrepress the nuclear factor‐κB signalling pathway, displayed 55% lower affinity for the ligand and a four‐fold delay in nuclear translocation, and interacted with the glucocorticoid receptor‐interacting protein 1 coactivator mostly through its activation function‐1 domain. Finally, a 3‐dimensional molecular modelling study of the H726R mutation revealed a significant structural shift in the rigidity of helix 10 of the receptor, which resulted in reduced flexibility and decreased affinity of the mutant receptor for binding to the ligand.

Conclusions

The natural mutant receptor hGRαH726R impairs multiple steps of glucocorticoid signal transduction, thereby decreasing tissue sensitivity to glucocorticoids.
Factors influencing recruitment of walleye and white bass to three distinct early ontogenetic stages
Authors: DeBoer Jason A. , Pope Kevin L.
Published: May 2015

Determining the factors that influence recruitment to sequential ontogenetic stages is critical for understanding recruitment dynamics of fish and for effective management of sportfish, particularly in dynamic and unpredictable environments. We sampled walleye (Sander vitreus) and white bass (Morone chrysops) at 3 ontogenetic stages (age 0 during spring: ‘age‐0 larval’; age 0 during autumn: ‘age‐0 juvenile’; and age 1 during autumn: ‘age‐1 juvenile’) from 3 reservoirs. We developed multiple linear regression models to describe factors influencing age‐0 larval, age‐0 juvenile and age‐1 juvenile walleye and white bass abundance indices. Our models explained 40–80% (68 ± 9%; mean ± SE) and 71%–97% (81 ± 6%) of the variability in catch for walleye and white bass respectively. For walleye, gizzard shad were present in the candidate model sets for all three ontogenetic stages we assessed. For white bass, there was no unifying variable in all three stage‐specific candidate model sets, although walleye abundance was present in two of the three white bass candidate model sets. We were able to determine several factors affecting walleye and white bass year‐class strength at multiple ontogenetic stages; comprehensive analyses of factors influencing recruitment to multiple early ontogenetic stages are seemingly rare in the literature. Our models demonstrate the interdependency among early ontogenetic stages and the complexities involved with sportfish recruitment.
Fish species incidence patterns in naturally fragmented Chihuahuan Desert streams
Authors: Miyazono Seiji , Taylor Christopher M.
Published: May 2015

We investigated how stream fragmentation affects local fish species persistence and extinction from three Rio Grande systems (Texas, USA) stream reaches with different levels of natural fragmentation. We examined species–volume (SV) relationships of fish assemblages in 42 pools across the watersheds and predicted greater fragmentation would correspond to an increase in the slope of the SV relationship due to decreased within‐reach rescue effects. In addition, we examined relationships among tributary‐specific nested subset patterns, local habitat features and spatial position of the reaches relative to the Rio Grande mainstem to better understand the importance of local and regional processes on fish species richness patterns in the stream reaches. Slopes of the SV curves did not differ among the stream reaches, but the intercepts of the SV curves were significantly different. These results indicated rescue effects among habitats within a stream reach were not apparent; however, rescue effects from the mainstem largely determined the species richness of a given stream reach. The nested subset patterns in all stream reaches were related to several local environmental factors, and large, deep pools provided important aquatic refugia in all three systems. We suggest declines in mainstem and tributary flows will likely continue to impact local and regional fish assemblage attributes. High flow events are important for dispersal and can reset tributary fish communities for the next extinction‐driven, successional cycle.
The GIRK2 subunit is involved in IS‐like seizures induced by GABAB receptor agonists
Authors: Blichowski Monica , Shephard Alexander , Armstrong Jessica , Shen Liqing , Cortez Miguel A. , Eubanks James H. , Snead O. Carter
Published: May 2015

Objective

Infantile spasms (or IS) is a catastrophic childhood epilepsy that is particularly prevalent in children with Down syndrome. Previously, we have shown that the Ts65Dn (Ts) mouse model of Down syndrome is a useful substrate upon which to develop an animal model of infantile spasms. Specifically, the Ts mouse is exquisitely sensitive to the electroencephalography (EEG) and behavioral effects of γ‐aminobutyric acid (GABA) B receptor (GABABR) agonists with a resultant phenotype that bears behavioral, EEG, and pharmacologic semblance to infantile spasms in humans. The G protein–coupled inward rectifying potassium channel subunit 2 (GIRK2) gene, KCNJ6, is overexpressed in Ts mice, and the GABABR‐mediated GIRK2 current is significantly increased in these mutant animals as well. Therefore, we formulated the hypothesis that the GIRK2 channel plays a significant role in the behavioral (measured by acute extensor spasms quantification) and EEG (measured by the electrodecremental response duration) phenotype induced in the Ts mice by GABABR agonists.

Methods

GIRK2−/−, +/−, and +/+ mice were treated with γ‐butyrolactone (GBL), a pro‐drug of the GABABR agonist γ‐hydroxybutyric acid, and the specific GABABR agonist baclofen (BAC) under continuous EEG monitoring. These drugs induce epileptiform bursts, extensor spasms, and an electrodecremental response (EDR) in Ts mice at low doses, and in wild‐type mice at high doses. A dose–response curve was ascertained with two treatment groups: GBL (100, 200, and 400 mg/kg) and BAC (4, 8, 12, and 16 mg/kg). We determined the baseline, the presence and duration of electrodecremental epochs (EDEs), and quantified acute epileptic extensor spasms.

Results

Analysis of EEG and behavior of GIRK2−/−, +/−, and +/+ mice after treatment with GABABR agonists and antagonists, indicate that GIRK2−/− mice are highly resistant to GABABR agonist–induced EEG and behavioral changes.

Significance

These data increase the possibility that GIRK2 channel function plays a major role in the genesis of infantile spasms.