bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of translation in cross-cultural knowledge transfer within a MNE’s business networks
Authors: Zhong Weihe , Chin Tachia
Published: November 2015

Purpose

– The purpose of this paper is to explore how translation activities influence knowledge transfer across cultures in Chinese multinational enterprises (MNEs). Although translation is recognized as a critical instrument for MNEs to enhance cross-national knowledge flow, scholars have not put much emphasis on the importance of translation in international business research.

Design/methodology/approach

– This paper proposes a novel hierarchical framework to delineate the five major boundary-spanning functions regarding translation for knowledge transfer in China (i.e. exchanging, linking, manipulating, facilitating and intervening). Due to the paucity of relevant literature, the authors used exploratory case studies investigating two large Chinese MNEs to illustrate how individuals as boundary spanners handle the translation requirements associated with cross-cultural knowledge transmission within a MNE’s business network. The data coding approach was used to examine the assumed model.

Findings

– The findings demonstrate that translators indeed play a vital role in cross-border knowledge exchanging, linking people with crucial knowledge, manipulating the flow of knowledge for protecting confidentiality, facilitating the cross-cultural interaction of various knowledge sources and intervening to prevent the occurrence of misunderstanding in MNE contexts. The authors also reveal how translators overcome the three constraints of language interpretation concerning knowledge transfer (i.e. lack of equivalence, cultural interference and ambiguity). The proposed research framework was fully supported.

Research limitations/implications

– The results provide insightful implications for MNEs to treat translation as a significant “re-codification” rather than a mundane task. Knowledge transfer within MNEs involves not only knowledge regarding products, technology and operations but also involves “whole organizations” including business models, organizational visions, missions and strategies.

Originality/value

– The main value of this paper is to propose a novel model regarding the role of translation in cross-cultural knowledge transfer in China. Language is a container of contexts; the translation procedure in MNEs is actually dynamic and contingent in nature and can be seen as an act of knowledge creation per se.
Knowledge creation and application in technology collaboration portfolio
Authors: Liu Yang , Ying Ying , Fagerlin Wen Pan
Published: November 2015

Purpose

– This study aims at developing a better understanding of the different mechanisms that affect technology collaboration portfolio management. How do firms manage their technology collaboration portfolio? Despite some thoughtful scholars have advanced the understanding of the phenomenon of technology collaboration portfolio, there is not much research that has been done in terms of understanding the endeavors of firms when they collectively use a range of actors for the best interests of the firms. Additionally, little attention has been paid to the trade-offs and managing mechanisms for the collaborations between different partners from a portfolio-level perspective, especially in emerging markets.

Design/methodology/approach

– A multiple-case study of two Chinese high-tech firms, an inductive approach.

Findings

– The authors identified three primary mechanisms that underlie successful knowledge creation and application in technology collaboration portfolio context: informally mobilizing boundary-spanning brokers for domestic academic collaborations, formally institutionalizing learning activities for industry collaborations and integrating formal and informal mechanisms for technology collaborations between focused firms and foreign organizations.

Originality/value

– The authors extend the line of organizational ambidexterity literature with a focus on strategic alliance, proposing that firms need to balance academic and industry collaborations from a portfolio level. Moreover, the authors intend to extend the literature of alliance portfolio by suggesting three different learning mechanisms of managing different technology collaborations for the purpose of balancing successful knowledge creation and application.
Cross-organizational knowledge creation theory from the perspective of I-Ching
Authors: Yao Wei , Han Xu , Li Yuxiang
Published: November 2015

Purpose

– This paper aims to refine cross-organizational knowledge creation theory by exploring the knowledge conversion process of University-Industry (U-I) collaboration in Chinese aerospace industry. An ancient Chinese philosophy named I-Ching is also introduced to illustrate dynamics of knowledge creation to achieve enlightenment.

Design/methodology/approach

– To describe the knowledge conversion tendency, a theoretical framework is developed by reference to Boisot’s (1995) Information Space. The application of the framework is described in the in-depth case study of micro-electrode manufacturing for aerospace vehicles. The dynamics of each stage in knowledge conversion is investigated with the implications from I-Ching.

Findings

– Analysis of the results suggests that seven certain stages can be especially indicative of cross-organizational knowledge creation, namely: demand codification; knowledge gain; knowledge digestion; knowledge sharing; knowledge propagation; knowledge spillover and knowledge degeneration. A knowledge gain, digestion, sharing and propagation (GDSP) knowledge creation theory is developed accordingly. The form of knowledge in different stages is variable, the change among various forms is effectively explained by I-Ching.

Research limitations/implications

– There is clearly a strong requirement to test the framework further with other cases, such as sampling cases from different industries and of different firm scales. Besides, the knowledge creation processes on the organizational level and the individual level are quite different, which call for further study.

Practical implications

– First, the theory helps firms to get a better understanding of the nature of U-I collaboration, that is to say, knowledge creation. That will, in turn, power the firm to take the initiative to participate in knowledge creation activities. Second, the illustration through I-Ching provides reasonable and easily understandable interpretations for Chinese corporate managers and executives. Traditional Chinese culture will be beneficial to make U-I collaborations more efficient and effective in China.

Originality/value

– A new “GDSP knowledge creation theory” which enriches and advances the typical socialization, externalization, combination and internalization (SECI) knowledge creation theory in some aspects is proposed. The theory is deeply grounded in Chinese culture. Furthermore, the conversion of different knowledge forms in the theory is considered from a totally new perspective of ancient Chinese philosophy: I-Ching.
Achieving digital literacy through game development: an authentic learning experience
Authors: Frydenberg Mark
Published: November 2015

Purpose

– This paper aims to argue that the process of making an original game develops digital literacy skills and provides an authentic learning experience as students create, publish and deploy interactive games. Teaching students to create computer games has become common in both K-12 and tertiary education to introducing programming concepts, increase student engagement and recruit majors and minors in technology fields. This study describes a project where first-year college students in an introductory technology concepts course use a visual game creation tool to develop original games to play on their computers and mobile devices.

Design/methodology/approach

– The author created a game development exercise which was implemented in three different sections of an introductory technology course. Students who participated were surveyed about their experiences. In addition, the author considers information technology (IT) skills and aspects of authentic learning which are achieved through this assignment.

Findings

– Initial findings suggest that students found the gaming assignment offers an opportunity for students with no prior programming skills to create software within a controlled and supportive environment. It allows them to demonstrate their understanding of coding principles, including identifying objects and interactions, and that creating software requires a developer to specify exact instructions for the computer to follow.

Research limitations/implications

– This study is limited to results from one semester and a small number of students participating. In addition, student frustration with the complicated process of publishing games online may have influenced student attitudes toward the assignment.

Practical implications

– Challenges of implementing this study on a larger scale are discussed.

Social implications

– Creating games encourages collaborative learning through trial and error, and students who share their games with friends to play on their devices achieve a sense of pride.

Originality/value

– While most studies of game development emphasize the programming skills that are developed through creating computer games, this paper looks at a larger scope of digital literacy and IT skills achieved, as well as opportunities to perform tasks often completed by IT professionals.
Learning through telepresence with iPads: placing schools in local/global communities
Authors: Meyer Bente
Published: November 2015

Purpose

– This study aims to present findings from an ongoing study in three rural schools in Denmark where videoconferences are used as part of the teaching at lower secondary level. The research focuses on how students learn from videoconferences that are both one-to-many and peer-to-peer. Videoconferencing, conceptualized by the schools in question as telepresence, is performed in a unique combination of desktop interaction through mobile devices (iPads) and studio-based large screen lectures and interaction.

Design/methodology/approach

– Data have been collected through multi-sited ethnography, which has contributed to mapping relationships between schools and studying their collaboration through telepresence. As collaboration between schools is built into the project, multi-sited ethnography has followed telepresence as a phenomenon that emerges within these collaborations, i.e. the idea is that looking at it from one locality is only seeing it partially.

Findings

– Preliminary results from the project suggest that schools need to work more on organizational frameworks for collaboration and that synchronous connections could be extended through asynchronous communication to support the potential of collaboration via telepresence with iPads.

Research limitations/implications

– The study has followed schools for two years in the initial development phase, but can be further qualified by following the next phase of the project, which will be initiated in the Autumn of 2015.

Practical implications

– The study has implications for the development of telepresence practices in which mobile devices are used in home classrooms and combined with stationary devices in auditoriums. In addition to this, the study provides examples of how schools can collaborate through telepresence activities in which both teacher-driven and student-driven activities are involved.

Originality/value

– The study fulfils a need for knowledge about ways in which telepresence and videoconferencing is used in elementary education and for different educational goals.
Sporting memories
&
the social inclusion of older people experiencing mental health problems
Authors: Clark Michael , Murphy Charlie , Jameson-Allen Tony , Wilkins Chris
Published: November 2015

Purpose

– Social exclusion and isolation of older people and their mental health are likely to be more significant, interlinked issues for society as countries experience an ageing demographic profile. The authors urgently need to identify effective ways of addressing these challenges that can be easily mobilised to meet diverse needs in different settings. The purpose of this paper is to explore the impact of sporting memories (SM) work as one approach to help meet this need. This SM work entails the use of sports-based reminiscence to engage with older people experiencing mental health problems. To date this has especially focused on people living with dementia in institutional and in community settings.

Design/methodology/approach

– The paper sets out the SM idea and discusses lessons learnt from case studies of its application to meet the inclusion and mental health needs of different older people in institutional and community settings.

Findings

– The evidence from the application of SM work to date is that it is an effective and flexible means of engaging people to improve their social inclusion and mental well-being. It can be readily deployed in various care and community settings.

Research limitations/implications

– The evidence to date is of case studies of the use of SM work, and, although these are now extensive case studies, further research is needed on the costs and impacts of SM work.

Practical implications

– SM work is a flexible and readily adoptable intervention to engage older people and help improve their social inclusion and mental well-being.

Social implications

– SM work can be an important part of meeting some of the challenges society faces with an ageing population profile.

Originality/value

– This is the first paper to set out the SM work.
“Broken homes and violent streets”: are there common factors which predispose girls and young women to become street sex workers?
Authors: Collinson Susan , Ash Anny
Published: November 2015

Purpose

– Street-based sex workers in the London Borough of Hackney have high levels of physical and mental ill-health, antisocial behaviour and substance misuse. This study interviewed sex workers at a local drop-in, in an attempt to understand the women’s family, social and educational backgrounds, and whether there were common factors that contributed to them becoming sex workers. The paper aims to discuss these issues.

Design/methodology/approach

– In total, 17 street sex workers were interviewed using semi-structured questions. The transcripts were examined methodologically using a conceptual content analysis approach in order to identify dominant themes.

Findings

– The women had very similar narratives of early physical and sexual abuse, negative parenting, poor impulse control and low levels of educational attainment, suggestive of conduct disorder, the aetiology of which involves an interaction of genetic, familial and social factors. Research suggests that multi-factorial early intervention to promote social and environmental development can significantly improve a child’s life chances and opportunities.

Research limitations/implications

– This study involved a very small number of women from a very defined inner-city area. Nearly all the women were UK born and local, and thus would have been through the local schools, social services and care system. These factors mean that it is not possible to generalise findings to a whole population.

Originality/value

– This study was the first piece of qualitative work carried out in the confidential drop-in setting used by this hard to reach group of women. Their narratives are valuable in terms of their impact, and that there were so many common themes, especially in relation to their early life experiences.
Epistemic asymmetries in psychotherapy interaction: therapists' practices for displaying access to clients' inner experiences
Authors: Weiste Elina , Voutilainen Liisa , Peräkylä Anssi
Published: November 2015

The relationship between a psychotherapist and a client involves a specific kind of epistemic asymmetry: in therapy sessions the talk mainly concerns the client's experience, which is unavailable, as such, to the therapist. This epistemic asymmetry is understood in different ways within different psychotherapeutic traditions. Drawing on a corpus of 70 audio‐recorded sessions of cognitive psychotherapy and psychoanalysis and using the method of conversation analysis, the interactional practices of therapists for dealing with this epistemic asymmetry are investigated. Two types of epistemic practices were found to be employed by therapists while formulating and interpreting the client's inner experience. In the formulations, the therapists and clients co‐described the client's experience, demonstrating that the client's inner experience was somewhat similarly available to both participants. In the interpretations, the therapists constructed an evidential foundation for the interpretation by summarising the client's talk and using the same descriptive terms as the client. Clients held therapists accountable for this epistemic work: if they failed to engage in such work, their right to know the client's inner experience was called into question.
Using Patient‐Reported Information to Improve Clinical Practice
Authors: Schlesinger Mark , Grob Rachel , Shaller Dale
Published: November 2015

Objective

To assess what is known about the relationship between patient experience measures and incentives designed to improve care, and to identify how public policy and medical practices can promote patient‐valued outcomes in health systems with strong financial incentives.

Data Sources/Study Setting

Existing literature (gray and peer‐reviewed) on measuring patient experience and patient‐reported outcomes, identified from Medline and Cochrane databases; evaluations of pay‐for‐performance programs in the United States, Europe, and the Commonwealth countries.

Study Design/Data Collection

We analyzed (1) studies of pay‐for‐performance, to identify those including metrics for patient experience, and (2) studies of patient experience and of patient‐reported outcomes to identify evidence of influence on clinical practice, whether through public reporting or private reporting to clinicians.

Principal Findings

First, we identify four forms of “patient‐reported information” (PRI), each with distinctive roles shaping clinical practice: (1) patient‐reported outcomes measuring self‐assessed physical and mental well‐being, (2) surveys of patient experience with clinicians and staff, (3) narrative accounts describing encounters with clinicians in patients' own words, and (4) complaints/grievances signaling patients' distress when treatment or outcomes fall short of expectations. Because these forms vary in crucial ways, each must be distinctively measured, deployed, and linked with financial incentives. Second, although the literature linking incentives to patients experience is limited, implementing pay‐for‐performance systems appears to threaten certain patient‐valued aspects of health care. But incentives can be made compatible with the outcomes patients value if: (a) a sufficient portion of incentives is tied to patient‐reported outcomes and experiences, (b) incentivized forms of PRI are complemented by other forms of patient feedback, and (c) health care organizations assist clinicians to interpret and respond to PRI. Finally, we identify roles for the public and private sectors in financing PRI and orchestrating an appropriate balance among its four forms.

Conclusions

Unless public policies are attentive to patients' perspectives, stronger financial incentives for clinicians can threaten aspects of care that patients most value. Certain policy parameters are already clear, but additional research is required to clarify how best to collect patient narratives in varied settings, how to report narratives to consumers in conjunction with quantified metrics, and how to promote a “culture of learning” at the practice level that incorporates patient feedback.
Policy‐Oriented Research on Improved Physician Incentives for Higher Value Health Care
Authors: Luft Harold S.
Published: November 2015

Policy makers (both public and private) are seeking ways to improve the value delivered within our health care system, that is, using fewer resources to provide the same benefit to patients, or using equivalent resources to provide more benefit. One strategy is to alter the predominant fee‐for‐service (FFS) economic incentives in the current system. To inform such policy changes, this paper identifies areas in which little is known about the effects of specific incentives (FFS, salary, etc.) on the two components of value: resource use and quality. Specific suggestions are offered regarding research that would be informative for policy makers, focusing on fundamental “building block” studies rather than overall evaluations of complex interventions, such as accountable care organizations. This research would better identify critical aspects of the FFS model and salary‐based payments that are particularly problematic, as well as situations in which FFS or salary may be less problematic. The research would also explore when alternatives, such as episode‐based payment might be feasible, or simply be hypothetical solutions. The availability of electronic health record‐based data in various delivery systems would allow many of these studies to be accomplished in 3–5 years with budgets manageable by public and private funding sources.
In‐Depth Analysis of Computer Memory Acquisition Software for Forensic Purposes
Authors: McDown Robert J. , Varol Cihan , Carvajal Leonardo , Chen Lei
Published: November 2015

The comparison studies on random access memory (RAM) acquisition tools are either limited in metrics or the selected tools were designed to be executed in older operating systems. Therefore, this study evaluates widely used seven shareware or freeware/open source RAM acquisition forensic tools that are compatible to work with the latest 64‐bit Windows operating systems. These tools' user interface capabilities, platform limitations, reporting capabilities, total execution time, shared and proprietary DLLs, modified registry keys, and invoked files during processing were compared. We observed that Windows Memory Reader and Belkasoft's Live Ram Capturer leaves the least fingerprints in memory when loaded. On the other hand, ProDiscover and FTK Imager perform poor in memory usage, processing time, DLL usage, and not‐wanted artifacts introduced to the system. While Belkasoft's Live Ram Capturer is the fastest to obtain an image of the memory, Pro Discover takes the longest time to do the same job.
Eggs of Ephestia kuehniella and Ceratitis capitata, and motile stages of the astigmatid mites Tyrophagus putrescentiae and Carpoglyphus lactis as factitious foods for Orius spp.
Authors: Bonte Jochem , Van de Walle Anaïs , Conlong Des , De Clercq Patrick
Published: November 2015

Several factitious foods were assessed for rearing the anthocorid predators Orius thripoborus (Hesse) and Orius naivashae (Poppius) (Hemiptera: Anthocoridae) in the laboratory. Developmental and reproductive traits of both Orius species were examined when offered frozen eggs of the Mediterranean flour moth, Ephestia kuehniella Zeller, frozen processed eggs of the medfly, Ceratitis capitata Wiedemann, or mixed motile stages of the astigmatid mites Tyrophagus putrescentiae (Schrank) or Carpoglyphus lactis (L). Whereas C. lactis and T. putresecentiae proved to be an inferior food for rearing O. thripoborus and O. naivashae, eggs of C. capitata fully supported development and reproduction of both predators. Results on medfly eggs were similar or slightly inferior to those on E. kuehniella eggs, which is the standard food for culturing these anthocorid bugs. O. thripoborus could be maintained for 4 consecutive generations on C. capitata eggs indicating that processed medfly eggs can be a suitable and cheaper alternative to E. kuehniella eggs for prolonged rearing of these Orius spp.
SIMR: an R package for power analysis of generalized linear mixed models by simulation
Authors: Green Peter , MacLeod Catriona J.
Published: November 2015

The r package simr allows users to calculate power for generalized linear mixed models from the lme4 package. The power calculations are based on Monte Carlo simulations.

It includes tools for (i) running a power analysis for a given model and design; and (ii) calculating power curves to assess trade‐offs between power and sample size.

This paper presents a tutorial using a simple example of count data with mixed effects (with structure representative of environmental monitoring data) to guide the user along a gentle learning curve, adding only a few commands or options at a time.
Failure to Obtain Computed Tomography Imaging in Head Trauma: A Review of Relevant Case Law
Authors: Lindor Rachel A. , Boie Eric T. , Campbell Ronna L. , Hess Erik P. , Sadosty Annie T.
Published: November 2015

Objectives

The objectives were to describe lawsuits against providers for failing to order head computed tomography (CT) in cases of head trauma and to determine the potential effects of available clinical decision rules (CDRs) on each lawsuit.

Methods

The authors collected jury verdicts, settlements, and court opinions regarding alleged malpractice for failure to order head CT in the setting of head trauma from 1972 through February 2014 from an online legal research tool (WestlawNext). Data were abstracted onto a standardized data form. The performance of five CDRs was evaluated.

Results

Sixty relevant cases were identified (52 adult, eight children). Of 48 cases with known outcomes, providers were found negligent in 10 cases (six adult, four pediatric), settled in 11 cases (nine adult, two pediatric), and were found not liable in 27 cases. In all 10 cases in which providers were found negligent, every applicable CDR studied would have indicated the need for head CT. In all eight cases involving children, the applicable CDR would have suggested the need for head CT or observation.

Conclusions

A review of legal cases reported in a major online legal research system revealed 60 lawsuits in which providers were sued for failing to order head CTs in cases of head trauma. In all cases in which providers were found negligent, CT imaging or observation would have been indicated by every applicable CDR.
Optimizing Patient‐centered Communication and Multidisciplinary Care Coordination in Emergency Diagnostic Imaging: A Research Agenda
Authors: Sabbatini Amber K. , Merck Lisa H. , Froemming Adam T. , Vaughan William , Brown Michael D. , Hess Erik P. , Applegate Kimberly E. , Comfere Nneka I.
Published: November 2015

Patient‐centered emergency diagnostic imaging relies on efficient communication and multispecialty care coordination to ensure optimal imaging utilization. The construct of the emergency diagnostic imaging care coordination cycle with three main phases (pretest, test, and posttest) provides a useful framework to evaluate care coordination in patient‐centered emergency diagnostic imaging. This article summarizes findings reached during the patient‐centered outcomes session of the 2015 Academic Emergency Medicine consensus conference “Diagnostic Imaging in the Emergency Department: A Research Agenda to Optimize Utilization.” The primary objective was to develop a research agenda focused on 1) defining component parts of the emergency diagnostic imaging care coordination process, 2) identifying gaps in communication that affect emergency diagnostic imaging, and 3) defining optimal methods of communication and multidisciplinary care coordination that ensure patient‐centered emergency diagnostic imaging. Prioritized research questions provided the framework to define a research agenda for multidisciplinary care coordination in emergency diagnostic imaging.
Cost‐effectiveness of motivational intervention with significant others for patients with alcohol misuse
Authors: Shepard Donald S. , Lwin Aung K. , Barnett Nancy P. , Mastroleo Nadine , Colby Suzanne M. , Gwaltney Chad , Monti Peter M.
Published: November 2015

Aims

To estimate the incremental cost, cost‐effectiveness and benefit–cost ratio of incorporating a significant other (SO) into motivational intervention for alcohol misuse.

Design

We obtained economic data from the one year with the intervention in full operation for patients in a recent randomized trial.

Setting

The underlying trial took place at a major urban hospital in the United States.

Participants

The trial randomized 406 (68.7% male) eligible hazardous drinkers (196 during the economic study) admitted to the emergency department or trauma unit.

Intervention

The motivational interview condition consisted of one in‐person session featuring personalized normative feedback. The significant other motivational interview condition comprised one joint session with the participant and SO in which the SO's perspective and support were elicited.

Measurements

We ascertained activities across 445 representative time segments through work sampling (including staff idle time), calculated the incremental cost in per patient of incorporating an SO, expressed the results in 2014 US$, incorporated quality and mortality effects from a closely related trial and derived the cost per quality‐adjusted life‐year (QALY) gained.

Findings

From a health system perspective, the incremental cost per patient of adding an SO was $341.09 [95% confidence interval (CI) = $244.44–437.74]. The incremental cost per year per hazardous drinker averted was $3623 (CI = $1777–22 709), the cost per QALY gained $32 200 (CI = $15 800–201 700), and the benefit–cost ratio was 4.73 (95% CI = 0.7–9.66). If adding an SO into the intervention strategy were concentrated during the hours with highest risk or in a trauma unit, it would become even more cost‐beneficial.

Conclusions

Using criteria established by the World Health Organization (cost‐effectiveness below the country's gross domestic product per capita), incorporating a significant other into a patient's motivational intervention for alcohol misuse is highly cost‐effective.
Results of radical surgery in women with stage IB2/IIA2 cervical cancer
Authors: Derks Marloes , Biewenga Petra , van der Velden Jacobus , Kenter Gemma G. , Stalpers Lukas J.A. , Buist Marrije R.
Published: November 2015

Introduction

There is ongoing discussion about the primary treatment of women with bulky early‐stage cervical cancer. Because of the high number of patients who need adjuvant (chemo)radiotherapy after initial surgical treatment, some state that primary (chemo)radiotherapy should be the treatment of choice to prevent morbidity. The aim of our study is to assess the results of radical surgery for women with bulky early‐stage cervical cancer in terms of recurrence patterns and survival.

Materials and methods

We conducted a retrospective cohort study. We included 129 women who underwent a radical hysterectomy with pelvic lymphadenectomy for stage IB2/IIA2 cervical cancer between 1984 and June 2010. Disease‐specific survival was measured using a Kaplan–Meier method and univariate and multivariate regression analyses were performed to determine prognostic factors associated with survival. A literature search was performed to analyze our data in the context of findings from the literature.

Results

Five‐year disease‐specific survival was 84%. Fifty percent of the women received adjuvant treatment. The pelvic recurrence rate was 8%. With our multivariate analysis we found that histology, tumor diameter, and parametrial involvement were independently associated with disease‐specific survival. Our literature search showed wide diversity in rates of adjuvant treatment after initial surgery as well as for survival and recurrence rates.

Conclusions

In the context of current knowledge about survival and side effects of various treatments for bulky early‐stage cervical cancer, radical surgery is a good treatment option in these patients. Depending on the type of surgery used, adjuvant radiotherapy can be minimized.
Immunocytochemical localization of sulfhydryl oxidase in mammalian epidermis suggests that the enzyme cross‐links keratins in the granular and transitional corneous layers
Authors: Alibardi Lorenzo
Published: November 2015

The epidermis of representative mammalian species including humans has been examined for the presence of sulfhydryl oxidase, an enzyme likely involved in the oxidation of corneous proteins containing sulfhydryl groups in the epidermis. A database search indicates that the enzyme shares common sequences in numerous mammalian species so that an antibody against the human sulfhydryl oxidase 2 has been utilized on other species. The immunofluorescent study on the epidermis of the platypus (monotreme), red kangaroo (marsupials), hamster and human (placentals) reveals a prevalent labelling in the granular, transitional and lowermost part of the stratum corneous layer. The detailed ultrastructural immunogold study of the human epidermis reveals a diffuse and uneven labelling in the paler component of the composite keratohyalin granules or among keratin filaments of the transitional layer while the labelling disappears in the corneous layer. The study supports the hypothesis of the participation of the enzyme in the oxidative process that determines the formation of stable disulphide groups among keratins and other corneous proteins of the stratum corneum. This process gives rise to the resistant cell corneous envelope of keratinocytes in addition to the isopeptide bonds that derive from the catalytic action of epidermal transglutaminase on several corneous proteins.
Antidepressants and antipsychotics classified with torsades de pointes arrhythmia risk and mortality in older adults ‐ a Swedish nationwide study
Authors: Danielsson Bengt , Collin Julius , Jonasdottir Bergman Gudrun , Borg Natalia , Salmi Peter , Fastbom Johan
Published: November 2015

Aim

The aim of the study was to examine mortality risk associated with use of antidepressants and antipsychotics classified with torsades de pointes (TdP) risk in elderly.

Methods

A matched case–control register study was conducted in people 65 years and older dying outside hospital from 2008–2013 (n = 286 092) and matched controls (n = 1 430 460). The association between prescription of antidepressants and antipsychotics with various TdP risk according to CredibleMeds (www.crediblemeds.org) and all‐cause mortality was studied by multivariate conditional logistic regression adjusted for comorbidity and several other confounders.

Results

Use of antidepressants classified with known or possible TdP risk, was associated with higher adjusted risk for mortality (OR 1.53, 95% CI 1.51, 1.56 and OR 1.63, 95% CI 1.61, 1.67, respectively) compared with antidepressants classified with conditional TdP risk (OR 1.25, 95% CI 1.22, 1.28) or without TdP classification (OR 0.99, 95% CI 0.94, 1.05). Antipsychotics classified with known TdP risk were associated with higher risk (OR 4.57, 95% CI 4.37, 4.78) than antipsychotics with possible risk (OR 2.58, 95% CI 2.52, 2.64) or without TdP classification (OR 2.14, 95% CI 2.03, 2.65). The following risk ranking was observed for commonly used antidepressants: mirtazapine > citalopram > sertraline > amitriptyline and for antipsychotics: haloperidol > risperidone >olanzapine > quetiapine.

Conclusion

The CredibleMeds system predicted drug‐associated risk for mortality in the elderly at the risk class level. Among antipsychotics, haloperidol, and among antidepressants, mirtazapine and citalopram, were associated with the highest risks. The results suggest that the TdP risk with antidepressants and antipsychotics should be taken into consideration when prescribing to the elderly.
4β‐hydroxycholesterol correlates with dose but not steady‐state concentration of carbamazepine: indication of intestinal CYP3A in biomarker formation?
Authors: Gjestad Caroline , Huynh Duy Khanh , Haslemo Tore , Molden Espen
Published: November 2015

Aim

4β‐hydroxycholesterol (4βOHC) is an endogenous CYP3A(4) biomarker, which is elevated by use of the CYP3A4 inducer carbamazepine. Our aim was to compare to what extent serum concentration of 4βOHC correlates with dose (presystemic exposure) and steady‐state concentration (systemic exposure) of carbamazepine.

Methods

The study was based on a therapeutic drug monitoring material, including information about daily doses and steady‐state concentrations (Css) of carbamazepine. 4βOHC concentrations were determined in residual serum samples of 55 randomly selected carbamazepine‐treated patients and 54 levetiracetam‐treated patients (negative controls) by UPLC‐APCI‐MS/MS after liquid–liquid extraction. Correlation analyses between 4βOHC concentration and daily dose and Css of carbamazepine, respectively, were performed by Spearman's tests. In addition, 4βOHC concentrations in females vs. males were compared in induced and non‐induced patients.

Results

Median 4βOHC concentration was ~10‐fold higher in carbamazepine‐ vs. levetiracetam‐treated patients (650 vs. 54 nmol l−1, P < 0.0001). There was a significant, positive correlation between carbamazepine dose and 4βOHC concentration (Spearman r = 0.53, 95% confidence interval [CI] 0.27, 0.72, P < 0.001). No significant correlation between carbamazepine Css and 4βOHC concentration was found (Spearman r = 0.14; 95% CI −0.14, 0.40, P = 0.3). Enzyme‐induced females had significantly higher 4βOHC concentrations than males (P < 0.001), while no significant gender difference was found in non‐induced patients (P = 0.52).

Conclusion

Serum concentrations of 4βOHC correlate with presystemic, but not systemic exposure of the CYP3A4 inducer carbamazepine. This suggests a stronger inductive effect of carbamazepine on presystemic than systemic CYP3A4 phenotype and might indicate a role of the intestine in 4βOHC formation. Moreover, CYP3A4 inducibility seems to be higher in females than males.
Cardiovascular Drugs and Metformin Drug Dosage According to Renal Function in Non‐Institutionalized Elderly Patients
Authors: Becquemont Laurent , Bauduceau Bernard , Benattar‐Zibi Linda , Al‐Salameh Abdallah , Berrut Gilles , Bertin Philippe , Bucher Sophie , Corruble Emmanuelle , Danchin Nicolas , Derumeaux Geneviève , Doucet Jean , Falissard Bruno , Forette Francoise , Hanon Olivier , Pasquier Florence , Pinget Michel , Ourabah Rissane , Piedvache Celine
Published: November 2015

Adaptation of drug dosage to kidney function is a common problem in general practice. The aim was to describe adaptation of cardiovascular drugs and metformin according to renal function and its association with mortality with regard to metformin in a cohort of elderly patients. This was an ancillary study to the S.AGES cohort made up of patients over 65 years of age managed by their general practitioner under real‐life conditions and followed up prospectively for 3 years. The medications studied were digoxin, spironolactone and metformin. Adaptation of their daily dose according to renal function (eGFR according to CKD/EPI) was compared to that recommended in the summaries of product characteristics (SPCs) or international scientific societies (ISS). A total of 900 patients were included, including 588 on metformin. At baseline, dose adjustment according to renal function was 100% and 87.6% (95% CI: 82.6–92.6) for patients on digoxin and spironolactone respectively. For metformin, only 71.3% (95% CI: 67.6–74.9) or 78.1% (95% CI: 74.7–81.4) of patients had their dosage adapted at inclusion according to their renal function depending on whether the SPCs or ISS recommendations were considered. During the 3‐year follow‐up period, 42/588 patients died (none from lactic acidosis). At inclusion, a metformin dosage not adapted for renal function according to ISS was not associated with an increase in all‐cause mortality (OR 1.7; 95% CI 0.6–5.0, p = 0.32). In conclusion, approximately one‐quarter of elderly patients treated with metformin do not have their dosage adapted for renal function according to ISS although there is no increase in mortality after follow‐up for 3 years.
Acetaminophen for Chronic Pain: A Systematic Review on Efficacy
Authors: Ennis Zandra Nymand , Dideriksen Dorthe , Vægter Henrik Bjarke , Handberg Gitte , Pottegård Anton
Published: November 2015

Acetaminophen (paracetamol) is the most commonly used analgesic worldwide and recommended as first‐line treatment in all pain conditions by WHO. We performed a systematic literature review to evaluate the efficacy of acetaminophen when used for chronic pain conditions. Applying three broad search strategies for acetaminophen use in chronic pain in both Embase and PubMed, 1551 hits were obtained. After cross‐reference searches of both trials and 38 reviews, seven studies comparing acetaminophen in continuous dosing regimens of more than 2 weeks with placebo were included. The review was conducted according to the PRISMA guidelines. All studies were conducted in patients with hip‐ or knee osteoarthritis and six of seven studies had observation periods of less than 3 months. All included studies showed no or little efficacy with dubious clinical relevance. In conclusion, there is little evidence to support the efficacy of acetaminophen treatment in patients with chronic pain conditions. Assessment of continuous efficacy in the many patients using acetaminophen worldwide is recommended.
Nonparametric Methods for Analyzing Recurrent Gap Time Data with Application to Infections After Hematopoietic Cell Transplant
Authors: Lee Chi Hyun , Luo Xianghua , Huang Chiung-Yu , DeFor Todd E. , Brunstein Claudio G. , Weisdorf Daniel J.
Published: November 2015

Infection is one of the most common complications after hematopoietic cell transplantation. Many patients experience infectious complications repeatedly after transplant. Existing statistical methods for recurrent gap time data typically assume that patients are enrolled due to the occurrence of an event of interest, and subsequently experience recurrent events of the same type; moreover, for one-sample estimation, the gap times between consecutive events are usually assumed to be identically distributed. Applying these methods to analyze the post-transplant infection data will inevitably lead to incorrect inferential results because the time from transplant to the first infection has a different biological meaning than the gap times between consecutive recurrent infections. Some unbiased yet inefficient methods include univariate survival analysis methods based on data from the first infection or bivariate serial event data methods based on the first and second infections. In this article, we propose a nonparametric estimator of the joint distribution of time from transplant to the first infection and the gap times between consecutive infections. The proposed estimator takes into account the potentially different distributions of the two types of gap times and better uses the recurrent infection data. Asymptotic properties of the proposed estimators are established.
A Rank-Sum Test for Clustered Data When the Number of Subjects in a Group within a Cluster is Informative
Authors: Dutta Sandipan , Datta Somnath
Published: November 2015

The Wilcoxon rank-sum test is a popular nonparametric test for comparing two independent populations (groups). In recent years, there have been renewed attempts in extending the Wilcoxon rank sum test for clustered data, one of which (Datta and Satten, 2005, Journal of the American Statistical Association  100, 908–915) addresses the issue of informative cluster size, i.e., when the outcomes and the cluster size are correlated. We are faced with a situation where the group specific marginal distribution in a cluster depends on the number of observations in that group (i.e., the intra-cluster group size). We develop a novel extension of the rank-sum test for handling this situation. We compare the performance of our test with the Datta–Satten test, as well as the naive Wilcoxon rank sum test. Using a naturally occurring simulation model of informative intra-cluster group size, we show that only our test maintains the correct size. We also compare our test with a classical signed rank test based on averages of the outcome values in each group paired by the cluster membership. While this test maintains the size, it has lower power than our test. Extensions to multiple group comparisons and the case of clusters not having samples from all groups are also discussed. We apply our test to determine whether there are differences in the attachment loss between the upper and lower teeth and between mesial and buccal sites of periodontal patients.
N‐terminally and C‐terminally truncated forms of glucose‐dependent insulinotropic polypeptide are high‐affinity competitive antagonists of the human GIP receptor
Authors: Hansen L S , Sparre‐Ulrich A H , Christensen M , Knop F K , Hartmann B , Holst J J , Rosenkilde M M
Published: November 2015

Background and Purpose

Glucose‐dependent insulinotropic polypeptide (GIP) affects lipid, bone and glucose homeostasis. High‐affinity ligands for the GIP receptor are needed to elucidate the physiological functions and pharmacological potential of GIP in vivo. GIP(1–30)NH2 is a naturally occurring truncation of GIP(1–42). Here, we have characterized eight N‐terminal truncations of human GIP(1–30)NH2.

Experimental Approach

COS‐7 cells were transiently transfected with human GIP receptors and assessed for cAMP accumulation upon ligand stimulation or competition binding with 125I‐labelled GIP(1–42), GIP(1–30)NH2, GIP(2–30)NH2 or GIP(3–30)NH2.

Key Results

GIP(1–30)NH2 displaced 125I‐GIP(1–42) as effectively as GIP(1–42) (Ki 0.75 nM), whereas the eight truncations displayed lower affinities (Ki 2.3–347 nM) with highest affinities for GIP(3–30)NH2 and GIP(5–30)NH2 (5–30)NH2. Only GIP(1–30)NH2 (Emax 100% of GIP(1–42)) and GIP(2–30)NH2 (Emax 20%) were agonists. GIP(2‐ to 9–30)NH2 displayed antagonism (IC50 12–450 nM) and Schild plot analyses identified GIP(3–30)NH2 and GIP(5–30)NH2 as competitive antagonists (Ki 15 nM). GIP(3–30) NH2 was a 26‐fold more potent antagonist than GIP(3–42). Binding studies with agonist (125I‐GIP(1–30)NH2), partial agonist (125I‐GIP(2–30)NH2) and competitive antagonist (125I‐GIP(3–30)NH2) revealed distinct receptor conformations for these three ligand classes.

Conclusions and Implications

The N‐terminus is crucial for GIP agonist activity. Removal of the C‐terminus of the endogenous GIP(3–42) creates another naturally occurring, more potent, antagonist GIP(3–30)NH2, which like GIP(5–30)NH2, was a high‐affinity competitive antagonist. These peptides may be suitable tools for basic GIP research and future pharmacological interventions.
Did Canadian welfare reform work? The effects of new reform strategies on social assistance participation
Authors: Berg Nathan , Gabel Todd
Published: November 2015

This paper measures the extent to which declines in social assistance (SA) participation were associated with novel and aggressive reforms referred to as new reform strategies: work requirements, diversion, earning exemptions and time limits. Controlling for province‐specific benefit levels, eligibility requirements, GDP growth, labour market conditions and demographics, SA participation rates were more than one percentage point lower (equivalent to a 13% decline) in provinces with new reforms. Work requirements with strong sanctions had the sharpest negative associations. New reform strategies explain at least 10% of observed declines in SA participation, twice that of benefit levels and eligibility requirements.