bluuebunny/crossref_metadata_2025 huggingface dataset:
Bilingual education in the UAE: factors, variables and critical questions
Authors: Gallagher Kay
Published: February 2011

Purpose

The purpose of this paper is to analyse the macro‐factors and contextual variables surrounding the recent introduction of compulsory bilingual schooling in Abu Dhabi in the United Arab Emirates, in order to generate informed discussion, and in order for stakeholders to understand the sociocultural, linguistic and pedagogical issues involved.

Design/methodology/approach

This paper is an analytic one which examines language‐in‐education in Abu Dhabi through a framework of the operational, situational and outcomes factors involved in bilingual education, as identified by Spolskyet al.and Beardsmore. Insights gained from international empirical research into bilingual education are applied to the Abu Dhabi context, and key questions about the specific model of bilingual education selected are posed for future local research to answer.

Findings

The paper concludes that bilingual education is likely to confer linguistic, academic and socioeconomic benefits on future generations of Emirati school leavers. However, the acquisition of biliteracy is likely to be challenging because of the diglossic features of Arabic, as well as the linguistic distance between Arabic and English. Because of the ambiguity of international research findings with regard to the appropriate age to begin second language learning, as well as uncertainty about the merits of simultaneous versus sequential teaching of biliteracy, research must be undertaken in Abu Dhabi schools into the effects of bilingual education under conditions of early Arabic/English immersion.

Originality/value

This paper is timely given the recent announcement of compulsory and universal bilingual state schooling from an early age in Abu Dhabi, and necessary given the dearth of discussion and research on language‐in‐education matters in the Arab world. While the paper is contextualised within the school system of Abu Dhabi, it has resonance for adjacent Gulf States and for the many expatriates from across the Middle East who teach and study in Abu Dhabi's schools.
The theory of attractive quality and experience offerings
Authors: Högström Claes
Published: February 2011

Purpose

The aim of this paper is to discuss the use of the theory of attractive quality and the Kano methodology in an experience context in order to understand how different experienced attributes contribute to delight and satisfaction among customers.

Design/methodology/approach

The study applied theoretical and quantitative approaches in order to examine the theory of attractive quality and the Kano methodology. A total of 270 respondents responded to the survey instrument, which was based on qualitative interviews.

Findings

The research showed that existing questions and answering alternatives included in the Kano methodology must be adapted to the nature of experiences. The paper contributes in the form of a new evaluation table, having shown that existing tables were invalid in relation to the importance rating and the Must‐Be>One‐dimensional>Attractive>Indifferent evaluation rule. Finally, the paper also shows how hedonic attributes create delight and utilitarian attributes create satisfaction, which contributes to a holistic offering.

Practical implications

Managers should address the fact that simply including an attribute is not sufficient; they must also consider its nature and how it performs and attach to the offering when studying experiences to understand how it contributes to either delight or satisfaction.

Originality/value

To date, few studies have addressed or discussed the consequences of applying the theory of attractive quality and the Kano model – including its rules for classification – to experience‐based offerings. The present article does this and also offers a theoretical extension of the theory of attractive quality and service marketing in terms of how customers holistically consider value and how Kano survey results should be analysed.
Attractive quality for requirement assessment during the front‐end of innovation
Authors: Ben Rejeb Helmi , Boly Vincent , Morel‐Guimaraes Laure
Published: February 2011

Purpose

The purpose of this paper is to provide a new decision‐aided tool for selecting customer needs during the new product development process.

Design/methodology/approach

The study started by examining the principles of attractive quality and its limits. The theory of attractive quality developed by Kano was used to conduct a requirement assessment and classification within four categories. The study also proposed a new method for needs analysis and, finally, an experiment with a case study was carried out for new self‐directed learning software.

Findings

This paper proposes a methodology involving the three following steps: identifying customers' needs, classifying and evaluating them, and comparing several concepts of new products. The paper proposes a matrix modeling that is based on the Kano model, which results in an analytical approach of the attractive quality theory. This enables the selection of innovative concepts and new ideas through the evaluation of their impact on needs satisfaction.

Research limitations/implications

Future research is required in order to study the impact of the vocabulary used in the Kano questionnaire; misunderstanding these needs could lead to incorrect classification. Moreover, future work could consider other technical criteria for concept selection, including technical feasibility and cost constraints.

Practical implications

The formality of the model (clear steps and matrix modeling) and its graphical aspect (decision made based on graphical mappings) makes it a simple decision tool. It can be used by design teams during the Front‐End phases and in activities coming upstream from the more formal and well‐structured New Product Development Process (NPDP).

Originality/value

A major concern for companies during an innovation process is to discover users' needs. This paper presents an integrated method for customer environment analysis, needs identification, needs classification, and new concept selection. The most interesting concepts – those that yield satisfaction – will then continue through the innovation process.
Theory of attractive quality and life cycles of quality attributes
Authors: Löfgren Martin , Witell Lars , Gustafsson Anders
Published: February 2011

Purpose

The purpose of this study is to shed further light on the dynamics of quality attributes, as suggested by the theory of attractive quality. The study aims to investigate the existence of the life cycle for successful quality attributes and to identify alternative life cycles of quality attributes.

Design/methodology/approach

The research is based on two surveys in which a total of 1,456 customers (708 in 2003 and 748 in 2009) participated in the classification of quality attributes. In particular, the study investigated how customers perceived 24 particular packaging attributes at two points in time, in 2003 and 2009.

Findings

The study identified three life cycles of quality attributes: successful quality attributes, flavor‐of‐the‐month quality attributes, and stable quality attributes. The research also extends the theory of attractive quality by identifying the reverse movement of certain quality attributes; that is, that a quality attribute can take a step backwards in the life cycle of successful quality attributes through, for instance, a change in design.

Originality/value

The paper provides empirical evidence for the existence of several alternative life cycles of quality attributes. The results of the empirical investigation increase the validity of the theory of attractive quality, which is important, given the limited amount of research that has attempted to validate the fundamentals of the theory of attractive quality.
Strategic aspects of innovation and internationalization in higher education
Authors: Li‐Hua Richard , Wilson John , Aouad Ghassan , Li Xiang
Published: February 2011

Purpose

As globalization increasingly affects the university sector around the world, there is a great advantage being placed on those universities that can respond timely and flexibly with appropriate innovation and internationalization strategies. The purpose of this paper is to review the literature of strategic aspects of innovation and internationalization in higher education. Based upon the premises of the Salford Prime Minister's Initiative 2 (PMI2) project, this paper aims to develop a theoretical framework which demonstrates how various objectives of innovation and internationalization can be translated and achieved in a learning organization context.

Design/methodology/approach

Theoretical analysis supported by empirical experiences. The paper explores the ideas and links between globalization and innovation/internationalization in higher education. The main concern of the paper is the implementation strategy of innovation and internationalization rather than the concepts and process of innovation and internationalization in higher education.

Findings

With examination of the impact of globalization upon higher education and strategic aspects of innovation and internationalization, this paper focuses on the implementation of innovation and internationalization and how to translate the overall institutional strategy into managed objectives. Organizational learning not only asserts and promotes organizational outcome and improved performance but also plays a significant role in achieving innovation and internationalization, e.g. staff engagement, staff motivation, empowerment, leadership and configuration. Furthermore, the paper identifies a number of strategic elements which are crucial to the successful implementation strategy of innovation and internationalization. The paper is based on the Salford PMI2 project and how various objectives were implemented which demonstrates the significance of collaboration in higher education between China and the UK.

Originality/value

Based on a comprehensive examination of the theoretical elements on innovation and internationalization and critical analysis of the Salford PMI2 project, adapting a typology of learning organizational framework, this study emphasizes the significance of incorporating both cultural and organizational learning factors. The paper develops a theoretical framework which enables policy makers and decision makers to make appropriate arrangements in designing international development strategy. Furthermore, the paper addresses the appropriateness and effectiveness of knowledge transfer, individual and organizational learning during the implementation of the internationalization strategy.
Embedding employability in the curriculum
Authors: Sun Qian
Published: February 2011

Purpose

The purpose of this paper is to draw on the experience of students, employers, and tutors in the two product design degree programmes, respectively, delivered at the University of Salford in the UK and at Shanghai Jiao Tong University, China, to examine the differences in employer engagement embedded within the curriculum.

Design/methodology/approach

Two in‐depth case studies supported by interviews have been conducted, which are represented as two distinctive employer engagement models. These two models are compared in terms of context, employer perception, curriculum development, and challenges for sustainability.

Findings

An understanding has been generated of the differences and suggests a collaborative framework between these two programmes, which draws the advantages of both sides together. The findings also shed light on the development of curriculum to engage employers, recognise a move away from “teaching” towards “managing learning opportunities” and the complexities of employer engagement, and explore how this may be embedded.

Originality/value

To address employability agenda, one of the main problems faced by higher education institutions is the content of curriculum and its relevance to the employment market. Engaging employers in the curriculum becomes key in addressing this issue, and this is especially typical for the design industry, given its unique characteristics. However, little has been researched as to how universities across different cultures achieve employer engagement. Understanding of the differences helps universities from different regions to seek potential sustainability solutions that may be bred on the basis of collaboration.
Leader political skill and team performance: a moderated mediation model
Authors: Liu Jun , Wang Wei , Cao Kun‐peng
Published: February 2011

Purpose

Drawing on the political theory of leadership and the input‐process‐output model the purpose of this paper is to examine the link between leader political skill and team performance by focusing on the mediating role of team communication and the moderating role of team task interdependence.

Design/methodology/approach

The authors collected three waves of data from 80 teams across four business units and employed hierarchical regression modeling and the moderated path analysis approach suggested by Edwards and Lambert to test the moderated mediation model.

Findings

Leader political skill was found to positively influence team performance via promoting the quality of team communication. Moreover, team task interdependence moderates the relationship between leader political skill and team communication, such that the relationship is stronger when team task interdependence is high rather than low.

Research limitations/implications

First, the paper adopts the measuring scales developed in the western organizational context to investigate the relations and phenomena existing in the Chinese organizational context. Future research should adopt the indigenous measuring scales to investigate the relations and phenomena existing in the Chinese organizational context. Second, both political skill and team performance were reported by the team leader, which might lead to common source bias. Future research should allow team members to rate leaders' political skill and the team leaders' supervisors to provide evaluation of team performance.

Practical implications

Owing to its importance to team performance, political skill is one of the critical skills that leaders should make efforts to develop. When companies recruit leaders for work teams, they should put more attention on the political skills of the candidates. Moreover, companies should cultivate a cooperative team climate to facilitate team communication.

Originality/value

Although Ahearn et al. suggested that leader political skill has positive effect on team performance, they did not empirically examine the specific process and mechanism through which the positive effect occurs. This study argues team communication is a critical mechanism that bridges leader political skill and team operations and outcomes as well. The study adopts longitudinal research design and collects multi‐source data to test the authors' model. The study also complements past research by investigating both the mediating and moderating mechanisms in the leader political‐team performance linkage.
Accounting conservatism and stock pricing: an analysis based on China's split‐stock reform
Authors: Zhu Song , Xia Donglin
Published: February 2011

Purpose

China's securities market is growing gradually as well as the investors, analysts, intermediates and regulation authorities. Accounting earnings is a key determinant among the factors influencing stock prices, which even overreacts to earnings. Split‐stock reform (all‐circulation reform) in China provides a chance for investors to revaluate the stock prices. The purpose of this paper is to investigate the market reaction during the reform from the perspective of accounting conservatism.

Design/methodology/approach

Using the data of companies completing the split‐stock reform, this paper empirically investigates how the accounting conservatism influences the market reaction around re‐open day after the reform.

Findings

Accounting information plays its role on stock pricing through the reform of split‐stock reform in the China securities market, evident in the significantly positive relation between the proxies of accounting conservatism and cumulative abnormal returns for one day, three days, ten days and 30 days around re‐open day after the reform. Also, the profitability of listed firms in the past will further improve the positive relation between conservatism and market reaction.

Originality/value

There is ample theoretical work on stock pricing of accounting conservatism but empirical work is scarce, so this paper provides more evidence for the role of stock pricing of accounting conservatism, especially in emerging markets. Second, current research on accounting conservatism in China is focusing on whether conservatism exists and how the conservatism varies; this paper further extends the research field of conservatism from the pricing perspective. Third, researches based on the determinants of stock compensation and market reaction on stock reform lack theoretical analysis, while this paper provides a theory basis for the market reaction during the stock reform.
Effects of new product preannouncement on purchase intention
Authors: Zhang Lijun , Su Meng
Published: February 2011

Purpose

Although consumers are viewed as one of the important target groups of new product preannouncements (NPPs), little existing literature focuses on the NPP's consequences from consumer perspective. To fill up this research gap, this paper explores how a NPP signal influences consumer purchase intention and how its influences vary across consumers.

Design/methodology/approach

Based on a scenario‐based survey with different new cellular phone preannouncement contexts, this paper examines impacts of brand, prior vaporware history, and innovativeness conveyed by NPP signals, as well as consumer characteristics, on purchase intentions. A logit regression and a hierarchical Bayesian Logit regression are applied to test effects of NPP signal and consumer factors, respectively.

Findings

The empirical results show that consumers may mainly rely on brand and prior vaporware history to decide whether to purchase this new product after it is launched. They are more likely to purchase a preannounced new product with strong brand, or from a company without prior vaporware. The results also demonstrate that the brand and vaporware impacts on purchase intention are moderated by consumer product knowledge, NPP experience, and risk attitude.

Originality/value

Following the competitive signal interpretation process model in signaling theory, this paper first provides and empirically examines an overall framework of NPP impacts on purchase intentions from the consumer perspective, which may contribute to the preannouncement literature. The findings also provide useful insights to help companies to make right NPP decisions.
Play as a Resource for Children Facing Adversity: An Exploration of Indicative Case Studies
Authors: Fearn Maggie , Howard Justine
Published: February 2011

In this paper, we suggest that the ability and opportunity to play affords children a natural resource to meet intellectual and emotional challenge. Analysis of case studies focusing on interventions with children caught in the bombing of Beirut, children abandoned to the state system in Romania, and the street children in Rio de Janeiro and Cali is used to support this view. When resources are in deficit, challenge is more likely to become adversity. The impact of adversity is particular to context, but comparison across contexts also shows connections between children’s disparate experiences. Analysis confirms that given the opportunity, children interact with and influence their environment through play and that this process provides a resource to meet the challenge of adversity.
Three years’ experience of focused cardiovascular ultrasound in the peri‐operative period
Authors: Cowie B.
Published: February 2011

Ultrasound applications in peri‐operative medicine have become common place in modern anaesthesia practice. Anaesthetists have performed transoesophageal echocardiography in cardiac and selected non‐cardiac surgery for over two decades. We aimed to assess the indications, impact on clinical management and accuracy of focused cardiovascular ultrasound performed by anaesthetists in the peri‐operative period. One hundred and seventy patients over a 3‐year period had a focused transthoracic echocardiogram. Adequate images to answer the clinical question were obtained in 167 out of 170 patients (98%). The undifferentiated systolic murmur was the commonest indication (98 out of 170, 58%). Some degree of aortic stenosis was present in 47 out of 170 (26%) of patients; mitral valve disease (30 out of 170 (18%)) and pulmonary hypertension (25 out of 170 (14%)) were also common. Changes in peri‐operative management occurred in 140 out of 170 (82%) patients and major findings correlated with a formal cardiology transthoracic echocardiogram in 52 out of 57 (92%) patients. Focused cardiovascular ultrasound performed by anaesthetists in the peri‐operative period accurately detects major cardiac pathology and significantly alters peri‐operative management.
Reduction of intra‐ocular pressure by ocular compression before combined peri‐ and retrobulbar block
Authors: Kallio H. , Harju M. P. , Ihanamäki T. , Vesti E. T. , Kivelä T.
Published: February 2011

The intra‐ocular pressure immediately before glaucoma surgery can be raised. We wished to investigate if ocular compression for 20 min before a combined peri‐ and retrobulbar injection would result in a lower pressure after the block. Sixty consecutive patients scheduled for filtration surgery were randomly assigned to receive ocular compression using an external pressure device for 20 min before combined peri‐ and retrobulbar injection (intervention group, who also received compression after the block) or to a control group in whom pressure was applied only after the block was completed. The intra‐ocular pressure was measured at baseline, after the 20‐min pre‐injection compression (intervention group), after injecting the block, and after the 10‐min post‐injection compression. The pressure did not differ between groups at baseline, after the block or after the post‐injection compression. In the intervention group, the compression before the block reduced the median (IQR [range]) pressure from 21.0 (17.0–25.0 [12.0–40.0]) mmHg to 16.8 (12.5–22.5 [7.5–33.5]) mmHg (p < 0.001). We conclude that external ocular compression reduces the intra‐ocular pressure, but applying an additional compression for 20 min before injecting the block is not beneficial.
Ultrasound‐guided supra‐inguinal fascia iliaca block: a cadaveric evaluation of a novel approach
Authors: Hebbard P. , Ivanusic J. , Sha S.
Published: February 2011

Existing descriptions of ultrasound‐guided fascia iliaca block focus on injection of local anaesthetic inferior to the inguinal ligament, relying on supra‐inguinal spread to block the lateral femoral cutaneous nerve in the iliac fossa. In this study, we explored injectate spread and nerve involvement in a cadaveric dye‐injection model, using a supra‐inguinal ultrasound‐guided technique that places local anaesthetic directly into the iliac fossa. Bilateral injections of 20 ml 0.25% aniline blue dye were made in six unembalmed cadavers. The femoral nerve was stained by the dye in all twelve injections. The lateral femoral cutaneous nerve was stained bilaterally in five cadavers, but the nerve was absent on both sides in the sixth cadaver. The ilio‐inguinal nerve passed into the iliac fossa over the iliacus muscle in eight of the hemi‐pelvi and was stained in seven of these occasions. We have performed more than 150 blocks in patients using this approach without complications. Injection using this technique in cadavers leads to extensive fluid spread throughout the iliac fossa. In patients this approach may allow a lower volume block of the femoral nerve and lateral femoral cutaneous nerve while still injecting at a distance from the femoral nerve.
Evaluation of a single‐use intubating videoscope (Ambu aScopeTM) in three airway training manikins for oral intubation, nasal intubation and intubation via three supraglottic airway devices
Authors: Scutt S. , Clark N. , Cook T. M. , Smith C. , Christmas T. , Coppel L. , Crewdson K.
Published: February 2011

We compared the Ambu aScope™ with a conventional fibrescope in two simulated settings. First, 22 volunteers performed paired oral and nasal fibreoptic intubations in three different manikins: the Laerdal Airway Trainer, Bill 1 and the Airsim (a total of 264 intubations). Second, 21 volunteers intubated the Airway Trainer manikin via three supraglottic airways: classic and intubating laryngeal mask airways and i‐gel (a total of 66 intubations). Performance of the aScope was good with few failures and infrequent problems. In the first study, choice of fibrescope had an impact on the number of user‐reported problems (p = 0.004), and user‐assessed ratings of ease of endoscopy (p < 0.001) and overall usefulness (p < 0.001), but not on time to intubate (p = 0.19), or ease of railroading (p = 0.72). The manikin chosen and route of endoscopy had more consistent effects on performance: best performance was via the nasal route in the Airway Trainer manikin. In the second study, the choice of fibrescope did not significantly affect any performance outcome (p = 0.3), but there was a significant difference in the speed of intubation between the devices (p = 0.02) with the i‐gel the fastest intubation conduit (mean (SD) intubation time i‐gel 18.5 (6.8) s, intubating laryngeal mask airway = 24.1 (11.2) s, classic laryngeal mask airway = 31.4 (32.5) s, p = 0.02). We conclude that the aScope performs well in simulated fibreoptic intubation and (if adapted for untimed use) would be a useful training tool for both simulated fibreoptic intubation and conduit‐assisted intubation. The choice of manikin and conduit are also important in the success of such training. This manikin study does not predict performance in humans and a clinical study is required.
Comparison of pharmacokinetic variability of fesoterodine vs. tolterodine extended release in cytochrome P450 2D6 extensive and poor metabolizers
Authors: Malhotra Bimal , Darsey Edress , Crownover Penelope , Fang Juanzhi , Glue Paul
Published: February 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Tolterodine and 5‐hydroxymethyl tolterodine (5‐HMT) are equipotent active moieties of tolterodine; 5‐HMT is the singular active moiety of fesoterodine. The formation of 5‐HMT from tolterodine occurs via CYP2D6, and some subjects are poor metabolizers CYP2D6. On the other hand, the formation of 5‐HMT from fesoterodine occurs via ubiquitous esterases. Cross‐study comparisons of data from phase 1 studies suggest that active moiety exposures are considerably more variable following tolterodine extended release vs. fesoterodine.

WHAT THIS STUDY ADDS

• This head‐to‐head study confirmed the findings of reduced pharmacokinetic variability of fesoterodine and further delineates that tolterodine, and not 5‐HMT, was the principal source of variability after administration of tolterodine extended release. The data suggest that fesoterodine delivers 5‐HMT consistently, regardless of CYP2D6 status, with up to 40% higher bioavailability compared with tolterodine.

AIMS Tolterodine and 5‐hydroxymethyl tolterodine (5‐HMT) are equipotent active moieties of tolterodine; 5‐HMT is the singular active moiety of fesoterodine. Formation of 5‐HMT from fesoterodine and tolterodine occurs via esterases and CYP2D6 respectively. This randomized, crossover, open‐label, multiple‐dose study in CYP2D6 extensive metabolizers (EMs) and poor metabolizers (PMs) compared the pharmacokinetics of fesoterodine vs. tolterodine extended release (ER).

METHODS Subjects received fesoterodine and tolterodine ER with a ≥3‐day washout period. Treatment comprised 4‐mg once daily doses for 5 days escalated to 8‐mg once daily for 5 days. Pharmacokinetics of active moieties were compared by drug, dose and genotype.

RESULTS Active moiety exposures following fesoterodine and tolterodine ER increased proportional to dose in EMs and PMs. In EMs only, coefficients of variation for AUC and Cmax following fesoterodine (up to 46% and 48% respectively) were lower than those following tolterodine ER (up to 87% and 87% respectively). Following fesoterodine and tolterodine ER administration, active moiety exposures ranged up to sevenfold and 40‐fold respectively. Mean urinary excretion of 5‐HMT following fesoterodine 4 and 8 mg, respectively, was 0.44 and 0.89 mg in EMs and 0.60 and 1.32 mg in PMs. Following tolterodine ER 4 and 8 mg, it was 0.38 and 0.71 mg respectively (EMs only). Renal clearance was similar regardless of administered drug, dose or genotype.

CONCLUSIONS Tolterodine, not 5‐HMT, was the principal source of variability after tolterodine ER administration. Fesoterodine delivers 5‐HMT with less variability than tolterodine, regardless of CYP2D6 status, with up to 40% higher bioavailability. The pharmacokinetics of fesoterodine were considerably less variable than TER.
Variability in response to clopidogrel: how important are pharmacogenetics and drug interactions?
Authors: Ma Terry K. W. , Lam Yat‐Yin , Tan Victoria P. , Yan Bryan P.
Published: February 2011

Clopidogrel is a pro‐drug which is converted to an active metabolite that selectively blocks ADP‐dependent platelet activation and aggregation. The main enzyme responsible for activating clopidogrel is the cytochrome P450 (CYP) isoenzyme CYP2C19, which is polymorphic. There is a growing body of literature showing that carriers of variant CYP2C19 alleles have impaired ability to metabolize clopidogrel (i.e. poor metabolizers), which is associated with decreased inhibition of platelet aggregation and increased cardiovascular risk. Some proton pump inhibitors are also metabolized by the CYP2C19 enzyme and often given together with clopidogrel to reduce gastrointestinal side effects. In particular, omeprazole has been shown to inhibit the CYP‐mediated metabolism of clopidogrel, and some studies have shown that the combination was associated with a higher incidence of cardiovascular adverse reactions than clopidogrel given alone. However, a recent randomized controlled trial demonstrated no significant difference in adverse cardiovascular events for patients on the combination of clopidogrel and omeprazole compared with clopidogrel alone. This current review aims to summarize the role of pharmacogenetics and drug interactions in determining variability in response to clopidogrel.
Methaemoglobinaemia associated with the use of cocaine and volatile nitrites as recreational drugs: a review
Authors: Hunter Laura , Gordge Laura , Dargan Paul I. , Wood David M.
Published: February 2011

Methaemoglobinaemia can cause significant tissue hypoxia, leading to severe, potentially life‐threatening clinical features and/or death. Over recent years there have been increasing reports of methaemoglobinaemia related to recreational drug use. There have been 25 articles describing methaemoglobinaemia related to recreational use of volatile nitrites (poppers) and more recently, four reports of methaemoglobinaemia in association with recreational cocaine use. In this article we discuss the mechanisms by which methaemoglobinaemia occurs in relation to the use of both volatile nitrites and cocaine, and summarize the published cases of recreational drug‐related methaemoglobinaemia. The volatile nitrites can cause methaemoglobinaemia directly through their activity as oxidizing agents. However, with cocaine, methaemoglobinaemia is related to adulterants such as local anaesthetics or phenacetin, rather than to the cocaine itself. Clinicians managing patients with acute recreational drug toxicity should be aware of the potential for methaemoglobinaemia in these patients, particularly in patients with cyanosis or unexplained low oxygen saturations on pulse oximetry, and ensure that appropriate and timely management is provided, including, where appropriate, the use of methylthioninium chloride (methylene blue).
Dasatinib inhibits B cell receptor signalling in chronic lymphocytic leukaemia but novel combination approaches are required to overcome additional pro‐survival microenvironmental signals
Authors: MCCaig Alison M. , Cosimo Emilio , Leach Michael T. , Michie Alison M.
Published: February 2011

As antigenic stimulation of the B cell antigen receptor (BCR) is key to chronic lymphocytic leukaemia (CLL) pathogenesis, targeting dysregulated kinases involved in BCR signalling is an attractive therapeutic approach. We studied the effects of the Src/c‐Abl tyrosine kinase inhibitor dasatinib on BCR signal transduction in CLL cells. Treatment of CLL cells with 100 nmol/l dasatinib induced apoptosis by an average reduction in viability of 33·7% at 48 h, with dasatinib sensitivity correlating with inhibition of SykY348 phosphorylation. Dasatinib inhibited calcium flux, phosphatidylinositol‐3‐kinase and mitogen‐activated protein kinase activation following BCR crosslinking, and blocked the Mcl‐1‐dependent increase in CLL cell survival on prolonged BCR stimulation. However, the pro‐apoptotic effect of dasatinib was abrogated by stromal cell contact alone or in the presence of CD154 and interleukin (IL)‐4 (CD154L/IL‐4 system). Whilst dasatinib retained the ability to sensitize CLL cells in stromal co‐culture to both fludarabine and chlorambucil, the addition of CD154 and IL‐4 rendered cells resistant to these drug combinations. We demonstrate that the HSP90 inhibitor 17‐DMAG exhibited synergy with dasatinib in vitro, and moreover, induced apoptosis of CLL cells in the CD154L/IL‐4 system. Our data provide evidence that dasatinib would be most clinically effective in combination with agents able to target antigen‐independent microenvironmental signals.
A pilot study evaluating the safety and CD34+ cell mobilizing activity of escalating doses of plerixafor in healthy volunteers
Authors: Lemery Steven J. , Hsieh Matthew M. , Smith Aleah , Rao Sheila , Khuu Hanh M. , Theresa Donohue , Viano Jennifer M. , Cook Lisa , Goodwin Rose , Boss Carol , Calandra Gary , Geller Nancy , Tisdale John , Childs Richard
Published: February 2011

This study evaluated the safety and CD34+ cell mobilizing activity of escalating doses of plerixafor in healthy volunteers. Three cohorts of six subjects received two different doses of plerixafor separated by at least 2 weeks to allow for adequate pharmacodynamic wash‐out. The following dosing cohorts were evaluated: 0·24 and 0·32 mg/kg (Cohort 1); 0·32 and 0·40 mg/kg (Cohort 2); and 0·40 and 0·48 mg/kg (Cohort 3). Circulating CD34+ cells were measured 0, 2, 4, 6, 8, 10, 12, 14, 18 and 24 h after each dose. Blood colony‐forming units were measured at baseline and 6 h after each dose. Common adverse events were diarrhoea, injection site erythema, perioral numbness, sinus tachycardia, headache, nausea, abdominal distention and injection site pain. No dose limiting toxicities occurred. When higher doses of plerixafor were administered, there was a trend towards higher peak CD34+ counts and CD34+ area under the curves, although these differences did not achieve statistical significance, perhaps due to intra‐subject variability. Together, these data show that the higher doses of plerixafor evaluated in this study are reasonably safe and suggest that a larger study should be performed to definitively answer whether increased numbers of CD34+ cell are mobilized with higher doses of plerixafor.
CD4+ T cells from HIV-1-infected patients recognize wild-type and mutant human immunodeficiency virus-1 protease epitopes
Authors: Muller N G , Alencar R , Jamal L , Hammer J , Sidney J , Sette A , Brindeiro R M , Kalil J , Cunha-Neto E , Moraes S L
Published: February 2011

Human immunodeficiency virus (HIV)-1 protease is a known target of CD8+ T cell responses, but it is the only HIV-1 protein in which no fully characterized HIV-1 protease CD4 epitopes have been identified to date. We investigated the recognition of HIV-1 protease by CD4+ T cells from 75 HIV-1-infected, protease inhibitor (PI)-treated patients, using the 5,6-carboxyfluorescein diacetate succinimidyl ester-based proliferation assay. In order to identify putative promiscuous CD4+ T cell epitopes, we used the TEPITOPE algorithm to scan the sequence of the HXB2 HIV-1 protease. Protease regions 4–23, 45–64 and 73–95 were identified; 32 sequence variants of the mentioned regions, encoding frequent PI-induced mutations and polymorphisms, were also tested. On average, each peptide bound to five of 15 tested common human leucocyte antigen D-related (HLA-DR) molecules. More than 80% of the patients displayed CD4+ as well as CD8+ T cell recognition of at least one of the protease peptides. All 35 peptides were recognized. The response was not associated with particular HLA-DR or -DQ alleles. Our results thus indicate that protease is a frequent target of CD4+ along with CD8+ proliferative T cell responses by the majority of HIV-1-infected patients under PI therapy. The frequent finding of matching CD4+ and CD8+ T cell responses to the same peptides may indicate that CD4+ T cells provide cognate T cell help for the maintenance of long-living protease-specific functional CD8+ T cells.
Adenovirus-mediated overexpression of soluble ST2 provides a protective effect on lipopolysaccharide-induced acute lung injury in mice
Authors: Yin H , Li X Y , Yuan B H , Zhang B B , Hu S L , Gu H B , Jin X B , Zhu J Y
Published: February 2011

Acute lung injury is characterized by a diffuse inflammatory parenchymal process, implicated in the context of significant morbidity and mortality. Previously, we have reported that soluble ST2 (sST2), a member of the Toll-interleukin (IL)-1 receptor (TIR) superfamily, represses proinflammatory cytokine production of macrophage exposed to lipopolysaccharide (LPS). In this study, we examined the possibility of modulating LPS-induced murine inflammatory pulmonary damage by recombinant adenovirus-mediated sST2-Fc (Ad-sST2-Fc) gene transfer. Single intranasal administration of Ad-sST2-Fc led to a profound decrease in LPS-induced bronchoalveolar lavage leucocyte exudation and lung tissue myeloperoxidase activity (reflecting phagocyte infiltration). Histological examination revealed alveolitis with inflammatory cell infiltration and alveolar haemorrhage in the alveolar airspace was less severe in Ad-sST2-Fc-treated mice when compared with control groups. In addition, high levels of sST2-Fc in vivo reduced the transcription of tumour necrosis factor-α, IL-6 and Toll-like receptor-4 gene remarkably, and suppressed the nuclear translocation of nuclear factor-κB in lung tissues in response to LPS challenge. Taken together, these results suggested that administration of Ad-sST2-Fc gene transfer may have therapeutic potential for the immunomodulatory treatment of LPS-mediated inflammatory lung injury.
A soluble thymic stromal lymphopoietin (TSLP) antagonist, TSLPR-immunoglobulin, reduces the severity of allergic disease by regulating pulmonary dendritic cells
Authors: Zhang F , Huang G , Hu B , Song Y , Shi Y
Published: February 2011

Recent studies show that thymic stromal lymphopoietin (TSLP) plays a critical role in the upstream phase of the allergic cascade to induce T helper type 2 cell (Th2)-dominant allergic diseases. However, the effect of blocking TSLP signalling with the soluble TSLP receptor (TSLPR), TSLPR-immunoglobulin (Ig), on asthma development needs further investigation. Here, we examined the effects of TSLPR-Ig on asthmatic airway inflammation and dendritic cell (DC) function. TSLPR-Ig (comprising the extracellular domain of murine TSLPR and an IgG2a Fc tail) purified from transfected COS-7 cells reduced the expression of CD40, CD80 and CD86 on TSLP-activated DCs in vitro. We also investigated the mechanisms underlying TSLPR-Ig-mediated amelioration of allergic airway inflammation in a murine asthma model. When TSLP signalling was blocked by intratracheal administration of TSLPR-Ig prior to sensitization, allergen-specific serum IgE levels, airway tissue inflammation, inflammatory cell infiltration and Th2 cytokine levels in the bronchiolar lavage fluid (BALF) were reduced significantly. This was because of the TSLP-Ig-mediated down-regulation of co-stimulatory molecule expression on pulmonary DCs. We also transferred bone marrow-derived mature DCs (mDCs) into the airways of asthmatic mice. Intratracheal administration of TSLPR-Ig prior to the transfer of mDCs reduced eosinophilic airway inflammation and Th2 differentiation significantly. Collectively, these data suggest that local use of TSLPR-Ig prevents airway inflammation, at least in part, by regulating DC function, and that blocking TSLP signalling using TSLPR-Ig may be a novel strategy for the treatment of asthma bronchiale.
Incomplete activation of peripheral blood dendritic cells during healthy human pregnancy
Authors: Della Bella S , Giannelli S , Cozzi V , Signorelli V , Cappelletti M , Cetin I , Villa M L
Published: February 2011

Successful pregnancy relies on the adaptation of immune responses that allow the fetus to grow and develop in the uterus despite being recognized by maternal immune cells. Dendritic cells (DCs) are central to the control of immune tolerance, and their state of activation at the maternal–decidual interface is critical to the feto–maternal immunological equilibrium. So far, the involvement of circulating DCs has been investigated poorly. Therefore, in this study we investigated whether, during healthy human pregnancy, peripheral blood DCs (PBDCs) undergo changes that may be relevant to the adaptation of maternal immune responses that allow fetal tolerance. In a cross-sectional study, we analysed PBDCs by six-colour flow cytometry on whole blood samples from 47 women during healthy pregnancy progression and 24 non-pregnant controls. We demonstrated that both myeloid and plasmacytoid PBDCs undergo a state of incomplete activation, more evident in the third trimester, characterized by increased expression of co-stimulatory molecules and cytokine production but lacking human leucocyte antigen (HLA)-DR up-regulation. To investigate the contribution of soluble circulating factors to this phenomenon, we also performed culture experiments showing that sera from pregnant women added to control DCs conditioned a similar incomplete activation that was associated with reduced DC allostimulatory capacity, supporting the in vivo relevance of our findings. We also obtained evidence that the glycoprotein hormone activin-A may contribute to DC incomplete activation. We suggest that the changes of PBDCs occurring during late pregnancy may aid the comprehension of the immune mechanisms operated by the maternal immune system to maintain fetal tolerance.
What is the best approach to suspected cyclical Cushing syndrome? Strategies for managing Cushing’s syndrome with variable laboratory data
Authors: Atkinson Brew , Mullan Karen R.
Published: February 2011

Cyclical Cushing’s syndrome is a pattern of hypercortisolism in which the biochemistry of cortisol production fluctuates rhythmically. This syndrome is often associated with fluctuating symptoms and signs. It is now being increasingly recognized. The phenomenon is important because it can, if not recognized, lead to errors in diagnosis and differential diagnosis of the syndrome and in assessment of therapeutic outcomes. The techniques and criteria, protocols and dynamic biochemical tools to detect cycling in patients with hypercortisolism are discussed as are the strategies for diagnosing and managing this important subgroup of patients with hypercortisolism.
Artificial immune systems for the detection of credit card fraud: an architecture, prototype and preliminary results
Authors: Wong Nicholas , Ray Pradeep , Stephens Greg , Lewis Lundy
Published: February 2011

Some biological phenomena offer clues to solving real‐life, complex problems. Researchers have been studying techniques such as neural networks and genetic algorithms for computational intelligence and their applications to such complex problems. The problem of security management is one of the major concerns in the development of eBusiness services and networks. Recent incidents have shown that the perpetrators of cybercrimes are using increasingly sophisticated methods. Hence, it is necessary to investigate non‐traditional mechanisms, such as biological techniques, to manage the security of evolving eBusiness networks and services. Towards this end, this paper investigates the use of an Artificial Immune System (AIS). The AIS emulates the mechanism of human immune systems that save human bodies from complex natural biological attacks. The paper discusses the use of AIS on one aspect of security management, viz. the detection of credit card fraud. The solution is illustrated with a case study on the management of frauds in credit card transactions, although this technique may be used in a range of security management applications in eBusiness.
Perceived discontinuities and constructed continuities in virtual work
Authors: Watson‐Manheim Mary Beth , Chudoba Katherine M. , Crowston Kevin
Published: February 2011

Boundaries such as time, distance, organisation and culture have been a useful conceptual tool for researchers to unpack changes in the virtual work environment, moving from a dichotomous perspective that contrasts face‐to‐face and virtual work to a more nuanced hybrid perspective. However, researchers may tacitly assume that all members of a virtual team and virtual teams collectively will respond to a boundary in a similar way. We posit instead that boundaries are a dynamic phenomenon and may have different consequences under different circumstances. We offer organisational discontinuity theory as a tool for more focused investigation of the virtual work environment. Discontinuities and continuities describe the setting in which individuals in a virtual team operate, both actual work practices and the perceptions of the individuals in the virtual work environment. The terms offer a starting point to identify and understand what may otherwise seem to be paradoxical differences in how virtual team members respond to boundaries.
Survival of biogenic amine‐producing dairy LAB strains at pasteurisation conditions
Authors: Ladero Victor , Sánchez‐Llana Esther , Fernández María , Alvarez Miguel A.
Published: February 2011

Biogenic amines (BAs) are low molecular weight organic bases with biological activity, synthesised by the microbial decarboxylation of precursor amino acids such as histidine, tyrosine or arginine. The consumption of food and beverages containing large amounts of BA can have toxicological effects. This paper reports the resistance of aminogenic lactic acid bacteria strains to pasteurisation (63 °C for 30 min). Skimmed milk inoculated with histamine‐ and tyramine‐producing strains of Enterococcus and Lactobacillus was subjected to pasteurisation. The viable number of Enterococcus durans IPLA 655 was reduced by 1 log, while that of Enterococcus faecalis BA64 was reduced by 3 logs. Lactobacillus brevis CECT 3810 did not survive pasteurisation, while the other Lactobacillus strains examined were more resistant; their viable numbers were reduced by about 2 logs. The two most resistant strains, E. durans IPLA 655 and Lactobacillus curvatus VI6, were subjected to higher temperatures. Enterococcus durans was completely inactivated at 78 °C, while some live cells of Lb. curvatus were observed. These results show that some native, metabolically active BA producers could be found in pasteurised milk owing to their resistance to the thermal treatment; their presence could have a negative impact on the final content of BAs in dairy products made from such milk.