bluuebunny/crossref_metadata_2025 huggingface dataset:
The use of longitudinal case studies and semiotics for analysing brand development as process of assimilation or accommodation
Authors: Veg-Sala Nathalie
Published: October 2014

Purpose

– The purpose of this paper is to define and understand the different models of brand development, according to the evolution of a brand’s identity and the introduction of brand extensions, starting from the premise that brands must be managed in a consistent way over time, but also need to be expanded. The second aim of this article is to introduce a specific methodology for studying the development of brands with a long-term approach.

Design/methodology/approach

– The concepts of assimilation and accommodation as defined by Piaget (1983) provide an in-depth understanding of how and why brands evolve. This article is based on a multiple case study approach. Four luxury brands were studied longitudinally. Brand chronologies were drawn and images of brand communications and brand extensions were gathered. Structural semiotic analysis was then used to highlight the different processes of brand development. In addition, qualitative interviews with two experts were conducted.

Findings

– Hermès and Louis Vuitton develop their brands according to the assimilation model. Gucci and Dolce & Gabbana follow the accommodation model. There is a link between the brand’s identity type (symbolic/functional) and the model used for brand development. A detailed analysis of each model is presented highlighting the main features.

Research limitations/implications

– To reinforce the distinction between the two models of brand development, it would be interesting to look at other brands. The choice of these brands depends on their country of origin and their age.

Originality/value

– The main contributions of this paper are the dynamic and longitudinal analyses of brand development and the introduction of the assimilation and accommodation concepts. The use of semiotics constitutes another original feature of this research.
Benchmarking desired corporate brand image in relation to stakeholders: a managerial perspective
Authors: Anisimova Tatiana
Published: October 2014

Purpose

– The purpose of this paper is to use managerial vision of corporate brand in relation to consumers, dealers and frontline employees to generate brand benchmarks. These benchmarks are sets of perceptions on how managers envision corporate brand to be positioned in minds of consumers, dealers and frontline employees. Additionally, this study explores managerial views concerning the importance of corporate branding in relation to an organization and its stakeholders. One of the most important strategic decisions that managers make concerns positioning of a corporate brand in the minds of key internal and external stakeholders.

Design/methodology/approach

– Insights are drawn from the in-depth semi-structured interviews with 22 senior managers from the three car manufacturers based in Australia and engaged in the corporate branding strategy.

Findings

– Although managers viewed corporate brand as a “strategic tool” and “the DNA” of an organization, the findings suggest that corporate brand strategy is ultimately driven by consumers rather than multiple stakeholders. Practical (utilitarian) components of the brand value were emphasized by the managers as key brand benefits communicated to consumers and also to dealers and frontline employees. Although managers recognized the importance of being seen as a “trustworthy partner” by dealer principals and customer-facing staff, the idea of dealer networks playing a role of a “supportive mechanism” for enhancing consumer experience, was domineering.

Research limitations/implications

– The views expressed by the interviewees in this paper may not fully reflect the views of the whole organization regarding the corporate brand. As this study is conducted in the car manufacturing industry, its findings may not be directly applicable in other industries. As corporate branding a relatively new area, organizations do not always appreciate its scope and what such a branding strategy involves. However, organizations need to move beyond a “product branding thinking” to a strategic perspective as corporate brands build the images formed and held by key external and internal stakeholders.

Practical implications

– Generating benchmarks for corporate brands using top management’s aspirations can assist organizations in generating focused and more nuanced understanding of how they wish corporate brand to be perceived by the key stakeholders and effectively build corporate brand.

Originality/value

– Managerial vision of corporate brand was used as a starting point in developing reference points (i.e. benchmarks) for the desired brand identity, which may potentially be developed into relevant standards and best practices in corporate branding within an organization.
Corporate impression formation in online communities: a qualitative study
Authors: Hallier Willi Christine , Nguyen Bang , Melewar T.C. , Dennis Charles
Published: October 2014

Purpose

– This study aims to evaluate elements of corporate communication in online communities (OCs) and their influence on corporate impression formation. Interactive online platforms such as OCs are growing. Companies are discovering their importance and increasingly include OCs in their communication activities. The present study identifies the underlying components relevant to successful corporate communication in OCs, and further explore if and how online community members (OCMs) expect companies to communicate with them, explaining how corporate impressions are formed.

Design/methodology/approach

– A qualitative research method was chosen, consisting of two stages. In stage one, 17 expert interviews with academics and practitioners were conducted, and in stage two, 12 OCMs were interviewed to clarify the concepts and gain new insights.

Findings

– The study gains new knowledge relating to corporate communication in OCs and image formation. Specifically, the authors identify and confirm important key constructs in corporate impression formation in OCs, namely, relevance of messages, communication style, social context cues, affiliation, perceived similarity, source credibility and interpersonal communication. Furthermore, a conceptual model is proposed on the relationship between communication elements relevant in online communities and their influence on corporate impression.

Practical implications

– The study helps to refine existing concepts of corporate impression formation in OCs. It is suggested that understanding how corporate impression is formed in OCs helps companies to participate in virtual networks, improving their corporate impression.

Originality/value

– This study extends prior findings on word-of-mouth on the Internet (word-of-mouse) to demonstrate that communication among virtual community (VC) members can influence the image formation process, such that positive word-of-mouse has a positive effect on corporate image.
Reshaping the Village Test for investigating service brand attachment
Authors: Mzahi Chourouk
Published: October 2014

Purpose

– The purpose of this paper is to demonstrate the use of an investigative technique which has until now only been used in the field of psychology, namely, the Village Test. The new version of the Village Test proposed in this paper aims to explore service brand attachment.

Design/methodology/approach

– Village Tests were administered over 9 months, including two pre-test phases, followed by a series of 21 final tests. Two main types of analytical procedures were used in the interpretation of our data: procedures used for textual data analyses and procedures used for non-textual data analyses.

Findings

– The spatially oriented attachment toward service brands is sustained by three service experience axes. The first axis involves the ritualized aspects of consumer experience. The second axis takes into account the congruence between the servicescape associations and the brand associations. The third axis is linked to the memorable nature of a previous consumer experience.

Research limitations/implications

– Despite the use of two pre-test periods, we believe that the technique could benefit from further improvement. For example, improvements could be made to the type of materials used. The material could also be improved by the addition of a more commercial nature models.

Practical implications

– The Village Test as a projective technique in qualitative market research has the potential to generate additional and insightful data that increase the understanding of service brand relationship through attachment bonds.

Originality/value

– The originality of this paper is to demonstrate the use of an investigative technique which has until now only been used in the field of psychology. A second methodological contribution of the paper lies in the transfer of analytical methods used in the field of psychology (within the framework of the original version of the Village Test), to research in marketing dealing with consumer behavior studies.
The Role of Task and Process Conflict in Strategizing
Authors: Lê Jane K. , Jarzabkowski Paula A.
Published: October 2014

The implementation of strategic initiatives is central to organizational success because it involves not just the execution of strategy, but also the formulation of strategy content. Yet, strategy implementation is complex, partially because it is critically affected by human dynamics. These dynamics are an integral but poorly understood aspect of how organizations negotiate multiple goals. Conflict is one dynamic that has received little attention in the context of strategy implementation. The authors address this gap by studying task and process conflict as a firm implements a strategy in real time. The study demonstrates that process conflict directs attention to problems with how to implement a strategy, while task conflict directs attention to problems with the content of the strategy. Critically, however, managers can only harness generative effects of conflict if they correctly diagnose process and task conflict, and respond to both forms of conflict. This requires an understanding of the entwined nature of task and process conflict, and highlights the necessity of aligning responses to these forms of conflict. Thus, this study offers conflict as one explanatory mechanism of how actors execute strategy and clarify strategy content.
Treatment of low back pain: First extended follow up of an original trial (NCT00600197) comparing a multidisciplinary group‐based rehabilitation program with oral drug treatment alone up to 24 months
Authors: Tavafian Sedigheh Sadat , Jamshidi Ahmad Reza , Shay Barbara
Published: October 2014

Background

This study aimed to examine the effects of the extended follow‐up of an original trial (NCT00600197) which has been published in The Clinical Journal of Pain.

Methods

Eighty‐three percent (165 of 197) of the original study, including 82 patients in intervention and 83 patients in the control group, provided extended 24‐month follow‐up data. The intervention was a group‐based multidisciplinary rehabilitation program which was continued by monthly motivational consultation. Data on measures of Short Form 36 (SF‐36), Quebec Disability Scale (QDS) and Ronald Morris Disability (RDQ) were collected at 12‐, 18‐ and 24‐month follow‐ups and analyzed through repeated measures analysis of variance.

Results

The patients who responded (n = 165) and who did not respond (n = 32) to the questionnaires were the same in terms of all baseline data except for physical function which was better for respondents (P < 0.05). Among the respondents, both intervention and control groups were the same at baseline except for education level and mental health which was better in the intervention group (P < 0.05). As a result, the intervention group had consistently better outcomes regarding all variables except for social function at all follow‐up times. Furthermore, in the intervention group only for mental health the interaction between time and group was significant (P = 0.01).

Discussion

The designed multidisciplinary program could improve health‐related quality of life and disability up to 24 months in chronic low back pain patients.
The Effect of Emergency Department Crowding on Reassessment of Children With Critically Abnormal Vital Signs
Authors: Depinet Holly E. , Iyer Srikant B. , Hornung Richard , Timm Nathan L. , Byczkowski Terri L.
Published: October 2014

Objectives

The objective was to determine whether several measures of emergency department (ED) crowding are associated with an important indicator of quality and safety: time to reevaluation of children with documented critically abnormal triage vital signs.

Methods

This was a retrospective cross‐sectional study of all patients with critically abnormal vital signs measured in triage over a 2.5‐year period (September 1, 2006, to May 1, 2009). Cox proportional hazard analysis was used to determine rate ratios for time to critically abnormal vital sign reassessment, when controlled for potential confounders.

Results

In this 2.5‐year sample, 9,976 patients with critically abnormal vital signs in triage (representing 3.9% of 253,408 visits) were placed in regular ED rooms with electronic alerts prompting vital sign reassessment after 1 hour. Overall, the mean time to reassessment was 84 minutes. The rate of vital sign reassessment was reduced by 31% for each additional 10 patients waiting for admission (adjusted odds ratio [OR] = 0.98; 95% confidence interval [CI] = 0.98 to 0.99), by 10% for every 10 patients in the lobby (adjusted OR = 0.94; 95% CI = 0.93 to 0.96), and by 6% for every additional 10 patients in the overall ED census (adjusted OR = 0.97; 95% CI = 0.97 to 0.98).

Conclusions

Emergency department crowding was associated with delay in the reassessment of critically abnormal vital signs in children; further work is needed to develop systems to mitigate these delays.
Predictive Value of the Heart‐type Fatty Acid–binding Protein and the Pulmonary Embolism Severity Index in Patients With Acute Pulmonary Embolism in the Emergency Department
Authors: Lauque Dominique , Maupas‐Schwalm Françoise , Bounes Vincent , Juchet Henry , Bongard Vanina , Roshdy Ashraf , Botella Jean Marie , Charpentier Sandrine
Published: October 2014

Objectives

Heart‐type fatty acid–binding protein (h‐FABP), sensitive troponins, natriuretic peptides, and clinical scores such as the Pulmonary Embolism Severity Index (PESI) are candidates for risk stratification of patients with acute pulmonary embolism (PE). The aim was to compare their respective prognostic values to predict an adverse outcome at 1 month.

Methods

The authors prospectively included 132 consecutive patients with confirmed acute PE. On admission to the emergency department (ED), plasma concentrations of h‐FABP, sensitive cardiac troponin I‐Ultra (cTnI‐Ultra), and brain natriuretic peptide (BNP) were measured and the PESI calculated in all patients. The combined 30‐day outcomes of interest were death, cardiac arrest, mechanical ventilation, use of catecholamines, and recurrence of acute PE.

Results

During the first 30 days, 14 (10.6%) patients suffered complications. Among the biomarkers, h‐FABP above 6 μg/L was a stronger predictor of an unfavorable outcome (odds ratio [OR] = 17.5, 95% confidence interval [CI] = 4.2 to 73.3) than BNP > 100 pg/mL (OR = 5.7, 95% CI = 1.6 to 20.4) or cTnI‐Ultra > 0.05 μg/L (OR = 3.4, 95% CI = 1.1 to 10.9). The PESI classified 83 of 118 patients (70.3%) with favorable outcomes and only one of 14 (7%) with adverse outcomes in low class I or II (OR = 30.8, 95% CI = 3.2 to 299.7). The areas under the receiver operating characteristic (ROC) curves (AUCs) were 0.90 (95% CI = 0.81 to 0.98) for h‐FABP, 0.89 (95% CI = 0.82 to 0.96) for PESI, 0.79 (95% CI = 0.67 to 0.90) for BNP, and 0.76 (95% CI = 0.64 to 0.87) for cTnI‐Ultra. The combination of h‐FABP with PESI was a particularly useful prognostic indicator because none of the 79 patients (59.8%) with h‐FABP < 6 ng/mL and PESI class < III had an adverse outcome.

Conclusions

h‐FABP and the PESI are superior to BNP and cTnI‐Ultra as markers for risk stratification of patients with acute PE. The high sensitivity of their combination identified a large number of low‐risk patients in the ED.
Increased prevalence of thyroid disorders in patients with new onset alopecia areata
Authors: Lyakhovitsky Anna , Shemer Avner , Amichai Boaz
Published: October 2014

Background

Several studies have revealed a high prevalence of thyroid disorders in patients with alopecia areata. The aim of the present study was to evaluate the frequency of thyroid function abnormalities and anti‐thyroid auto‐antibodies in patients with new onset alopecia areata on their first visit to a community dermatology clinic.

Methods

The study included 78 patients with new onset alopecia areata who visited a community dermatology clinic between 2007 and 2011. Every patient underwent a complete medical history, physical examination and laboratory testing consisting of thyroid function tests (serum levels of free triiodothyronine, free thyroxine and thyroid stimulating hormone) and anti‐thyroid auto‐antibodies (thyroglobulin antibodies and thyroid peroxidase antibodies).

Results

The 78 patients included 46 (59%) men and 32 (41%) women, with 1.44 male : female ratio and mean age of 32.7 +/− 3.09 years. Abnormal thyroid function and anti‐thyroid auto‐antibodies were detected in 19 (24%) patients. Of these, 12 (15%) patients were diagnosed with subclinical hypothyroidism, one (1%) with an overt hypothyroidism, one (1%) with an overt hyperthyroidism and four (5%) with euthyroid Hashimoto's thyroiditis.

Conclusion

The study revealed a significant association between alopecia areata and thyroid abnormalities. Screening for thyroid function and anti‐thyroid auto‐antibodies is advised in alopecia areata.
Erbium‐doped yttrium aluminium garnet ablative laser treatment for endogenous ochronosis
Authors: Chaptini Cassandra , Huilgol Shyamala C
Published: October 2014

Ochronosis is a rare disease characterised clinically by bluish‐grey skin discolouration and histologically by yellow‐brown pigment deposits in the dermis. It occurs in endogenous and exogenous forms. Endogenous ochronosis, also known as alkaptonuria, is an autosomal recessive disease of tyrosine metabolism, resulting in the accumulation and deposition of homogentisic acid in connective tissue. We report a case of facial endogenous ochronosis and coexistent photodamage, which was successfully treated with erbium‐doped yttrium aluminium garnet laser resurfacing and deep focal point treatment to remove areas of residual deep pigment.
Biology of childhood germ cell tumours, focussing on the significance of microRNAs
Authors: Murray M. J. , Nicholson J. C. , Coleman N.
Published: October 2014

Genomic and protein‐coding transcriptomic data have suggested that germ cell tumours (GCTs) of childhood are biologically distinct from those of adulthood. Global messenger RNA profiles segregate malignant GCTs primarily by histology, but then also by age, with numerous transcripts showing age‐related differential expression. Such differences are likely to account for the heterogeneous clinico‐pathological behaviour of paediatric and adult malignant GCTs. In contrast, as global microRNA signatures of human tumours reflect their developmental lineage, we hypothesized that microRNA profiles would identify common biological abnormalities in all malignant GCTs owing to their presumed shared origin from primordial germ cells. MicroRNAs are short, non‐protein‐coding RNAs that regulate gene expression via translational repression and/or mRNA degradation. We showed that all malignant GCTs over‐express the miR‐371–373 and miR‐302/367 clusters, regardless of patient age, histological subtype or anatomical tumour site. Furthermore, bioinformatic approaches and subsequent Gene Ontology analysis revealed that these two over‐expressed microRNAs clusters co‐ordinately down‐regulated genes involved in biologically significant pathways in malignant GCTs. The translational potential of this finding has been demonstrated with the detection of elevated serum levels of miR‐371–373 and miR‐302/367 microRNAs at the time of malignant GCT diagnosis, with levels falling after treatment. The tumour‐suppressor let‐7 microRNA family has also been shown to be universally down‐regulated in malignant GCTs, because of abundant expression of the regulatory gene LIN28. Low let‐7 levels resulted in up‐regulation of oncogenes including MYCN, AURKB and LIN28 itself, the latter through a direct feedback mechanism. Targeting LIN28, or restoring let‐7 levels, both led to effective inhibition of this pathway. In summary, paediatric malignant GCTs show biological differences from their adult counterparts at a genomic and protein‐coding transcriptome level, whereas they both display very similar microRNA expression profiles. These similarities and differences may be exploited for diagnostic and/or therapeutic purposes.
Extra‐hepatic manifestations of autochthonous hepatitis E infection
Authors: Woolson K. L. , Forbes A. , Vine L. , Beynon L. , McElhinney L. , Panayi V. , Hunter J. G. , Madden R. G. , Glasgow T. , Kotecha A. , Dalton H. C. , Mihailescu L. , Warshow U. , Hussaini H. S. , Palmer J. , Mclean B. N. , Haywood B. , Bendall R. P. , Dalton H. R.
Published: October 2014

Background

Autochthonous (locally acquired) hepatitis E is increasingly recognised in developed countries, and is thought to be a porcine zoonosis. A range of extra‐hepatic manifestations of hepatitis E infection have been described, but have never been systematically studied.

Aim

To report the extra‐hepatic manifestations of hepatitis E virus.

Methods

Retrospective review of data of 106 cases of autochthonous hepatitis E (acuten = 105, chronicn = 1).

Results

Eight (7.5%) cases presented with neurological syndromes, which included brachial neuritis, Guillain‐Barré syndrome, peripheral neuropathy, neuromyopathy and vestibular neuritis. Patients with neurological syndromes were younger (median age 40 years, range 34–92 years,P = 0.048) and had a more modest transaminitis (medianALT471 IU/L,P = 0.015) compared to cases without neurological symptoms [median age 64 years (range 18–88 years), medianALT1135 IU/L]. One patient presented with a cardiac arrhythmia,twelve patients (11.3%) presented with thrombocytopenia, fourteen (13.2%) with lymphocytosis and eight (7.5%) with a lymphopenia, none of which had any clinical consequence. Serum electrophoresis was performed in 65 patients at presentation, of whom 17 (26%) had a monoclonal gammopathy of uncertain significance. Two cases developed haematological malignancies, acute myeloid leukaemia and duodenal plasmacytoma, 18 and 36 months after presenting with acute hepatitis E infection.

Conclusions

A range of extra‐hepatic manifestations can occur with hepatitis E. Neurological and haematological features of hepatitis E infection are relatively frequent in thisUKcohort, and result in significant morbidity which warrants further study.
A Randomized Controlled Trial of a Psycho‐Education Intervention by Midwives in Reducing Childbirth Fear in Pregnant Women
Authors: Toohill Jocelyn , Fenwick Jennifer , Gamble Jenny , Creedy Debra K. , Buist Anne , Turkstra Erika , Ryding Elsa‐Lena
Published: October 2014

Background

Childbirth fear is associated with increased obstetric interventions and poor emotional and psychological health for women. The purpose of this study is to test an antenatal psycho‐education intervention by midwives in reducing women's childbirth fear.

Methods

Women (n = 1,410) attending three hospitals in South East Queensland, Australia, were recruited into the BELIEF trial. Participants reporting high fear were randomly allocated to intervention (n = 170) or control (n = 169) groups. All women received a decision‐aid booklet on childbirth choices. The telephone counseling intervention was offered at 24 and 34 weeks of pregnancy. The control group received usual care offered by public maternity services. Primary outcome was reduction in childbirth fear (WDEQ‐A) from second trimester to 36 weeks’ gestation. Secondary outcomes were improved childbirth self‐efficacy, and reduced decisional conflict and depressive symptoms. Demographic, obstetric & psychometric measures were administered at recruitment, and 36 weeks of pregnancy.

Results

There were significant differences between groups on postintervention scores for fear of birth (p < 0.001) and childbirth self‐efficacy (p = 0.002). Decisional conflict and depressive symptoms reduced but were not significant.

Conclusion

Psycho‐education by trained midwives was effective in reducing high childbirth fear levels and increasing childbirth confidence in pregnant women. Improving antenatal emotional well‐being may have wider positive social and maternity care implications for optimal childbirth experiences.
Redox signalling and cardioprotection: translatability and mechanism
Authors: Pagliaro P , Penna C
Published: October 2014

The morbidity and mortality from coronary artery disease (CAD) remain significant worldwide. The treatment for acute myocardial infarction has improved over the past decades, including early reperfusion of culprit coronary arteries. Although it is mandatory to reperfuse the ischaemic territory as soon as possible, paradoxically this leads to additional myocardial injury, namely ischaemia/reperfusion (I/R) injury, in which redox stress plays a pivotal role and for which no effective therapy is currently available. In this review, we report evidence that the redox environment plays a pivotal role not only in I/R injury but also in cardioprotection. In fact, cardioprotective strategies, such as pre‐ and post‐conditioning, result in a robust reduction in infarct size in animals and the role of redox signalling is of paramount importance in these conditioning strategies. Nitrosative signalling and cysteine redox modifications, such as S‐nitrosation/S‐nitrosylation, are also emerging as very important mechanisms in conditioning cardioprotection. The reasons for the switch from protective oxidative/nitrosative signalling to deleterious oxidative/nitrosative/nitrative stress are not fully understood. The complex regulation of this switch is, at least in part, responsible for the diminished or lack of cardioprotection induced by conditioning protocols observed in ageing animals and with co‐morbidities as well as in humans. Therefore, it is important to understand at a mechanistic level the reasons for these differences before proposing a safe and useful transition of ischaemic or pharmacological conditioning. Indeed, more mechanistic novel therapeutic strategies are required to protect the heart from I/R injury and to improve clinical outcomes in patients with CAD.

Linked Articles

This article is part of a themed section on Conditioning the Heart – Pathways to Translation. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue‐8
Unravelling the theories of pre‐eclampsia: are the protective pathways the new paradigm?
Authors: Ahmed Asif , Ramma Wenda
Published: October 2014

Pre‐eclampsia is a vascular disorder of pregnancy where anti‐angiogenic factors, systemic inflammation and oxidative stress predominate, but none can claim to cause pre‐eclampsia. This review provides an alternative to the ‘two‐stage model’ of pre‐eclampsia in which abnormal spiral arteries modification leads to placental hypoxia, oxidative stress and aberrant maternal systemic inflammation. Very high maternal soluble fms‐like tyrosine kinase‐1 (sFlt‐1 also known as sVEGFR) and very low placenta growth factor (PlGF) are unique to pre‐eclampsia; however, abnormal spiral arteries and excessive inflammation are also prevalent in other placental disorders. Metaphorically speaking, pregnancy can be viewed as a car with an accelerator and brakes, where inflammation, oxidative stress and an imbalance in the angiogenic milieu act as the ‘accelerator’. The ‘braking system’ includes the protective pathways of haem oxygenase 1 (also referred as Hmox1 or HO‐1) and cystathionine‐γ‐lyase (also known as CSE or Cth), which generate carbon monoxide (CO) and hydrogen sulphide (H2S) respectively. The failure in these pathways (brakes) results in the pregnancy going out of control and the system crashing. Put simply, pre‐eclampsia is an accelerator–brake defect disorder. CO and H2S hold great promise because of their unique ability to suppress the anti‐angiogenic factors sFlt‐1 and soluble endoglin as well as to promote PlGF and endothelial NOS activity. The key to finding a cure lies in the identification of cheap, safe and effective drugs that induce the braking system to keep the pregnancy vehicle on track past the finishing line.

Linked Articles

This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue‐6
Annexin A2 complexes with S100 proteins: structure, function and pharmacological manipulation
Authors: Liu Yidong , Myrvang Helene K , Dekker Lodewijk V
Published: October 2014

Annexin A2 (AnxA2) was originally identified as a substrate of the pp60v‐src oncoprotein in transformed chicken embryonic fibroblasts. It is an abundant protein that associates with biological membranes as well as the actin cytoskeleton, and has been implicated in intracellular vesicle fusion, the organization of membrane domains, lipid rafts and membrane‐cytoskeleton contacts. In addition to an intracellular role, AnxA2 has been reported to participate in processes localized to the cell surface including extracellular protease regulation and cell‐cell interactions. There are many reports showing that AnxA2 is differentially expressed between normal and malignant tissue and potentially involved in tumour progression. An important aspect of AnxA2 function relates to its interaction with small Ca2+‐dependent adaptor proteins called S100 proteins, which is the topic of this review. The interaction between AnxA2 and S100A10 has been very well characterized historically; more recently, other S100 proteins have been shown to interact with AnxA2 as well. The biochemical evidence for the occurrence of these protein interactions will be discussed, as well as their function. Recent studies aiming to generate inhibitors of S100 protein interactions will be described and the potential of these inhibitors to further our understanding of AnxA2 S100 protein interactions will be discussed.

Linked Articles

This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue‐7
Carboxylated Hydroxyethyl Starch: A novel Polysaccharide for the Delivery of Doxorubicin
Authors: Paleos Constantinos M. , Sideratou Zili , Theodossiou Theodossis A. , Tsiourvas Dimitris
Published: October 2014

Hydroxyethyl starch (HES) was interacted with succinic anhydride affording a carboxylated derivative which has proved to be a promising polymeric drug delivery system. Specifically, this polymer is conveniently prepared, is biodegradable, non‐immunogenic, and can encapsulate doxorubicin due to the protonation of the primary amino group of doxorubicin by the carboxylic group located on the branched scaffold of the polysaccharide. In addition, due to the polyhydroxylated character of the polysaccharide, the latter can act as a protective coating in an analogous manner to the PEG‐chains ensuring prolonged circulation in vivo. In vitro experiments showed controlled release of doxorubicin to the nuclei of DU145 prostate cancer cells when the anticancer drug is incorporated in the carboxylated hydroxyethyl starch.
Generation of β cell-specific human cytotoxic T cells by lentiviral transduction and their survival in immunodeficient human leucocyte antigen-transgenic mice
Authors: Babad J , Mukherjee G , Follenzi A , Ali R , Roep B O , Shultz L D , Santamaria P , Yang O O , Goldstein H , Greiner D L , DiLorenzo T P
Published: October 2014

Several β cell antigens recognized by T cells in the non-obese diabetic (NOD) mouse model of type 1 diabetes (T1D) are also T cell targets in the human disease. While numerous antigen-specific therapies prevent diabetes in NOD mice, successful translation of rodent findings to patients has been difficult. A human leucocyte antigen (HLA)-transgenic mouse model incorporating human β cell-specific T cells might provide a better platform for evaluating antigen-specific therapies. The ability to study such T cells is limited by their low frequency in peripheral blood and the difficulty in obtaining islet-infiltrating T cells from patients. We have worked to overcome this limitation by using lentiviral transduction to ‘reprogram’ primary human CD8 T cells to express three T cell receptors (TCRs) specific for a peptide derived from the β cell antigen islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP265–273) and recognized in the context of the human class I major histocompatibility complex (MHC) molecule HLA-A2. The TCRs bound peptide/MHC multimers with a range of avidities, but all bound with at least 10-fold lower avidity than the anti-viral TCR used for comparison. One exhibited antigenic recognition promiscuity. The β cell-specific human CD8 T cells generated by lentiviral transduction with one of the TCRs released interferon (IFN)-γ in response to antigen and exhibited cytotoxic activity against peptide-pulsed target cells. The cells engrafted in HLA-A2-transgenic NOD-scid IL2rγnull mice and could be detected in the blood, spleen and pancreas up to 5 weeks post-transfer, suggesting the utility of this approach for the evaluation of T cell-modulatory therapies for T1D and other T cell-mediated autoimmune diseases.
Occupational irritant contact dermatitis diagnosed by analysis of contact irritants and allergens in the work environment
Authors: Friis Ulrik F. , Menné Torkil , Schwensen Jakob F. , Flyvholm Mari‐Ann , Bonde Jens P. E. , Johansen Jeanne D.
Published: October 2014

Background

Irritant contact dermatitis (ICD) is a common diagnosis in patients with occupational contact dermatitis (OCD). Studies are lacking on the usefulness of material safety data sheets (MSDSs) in making the diagnosis of ICD.

Objective

To characterize irritant exposures leading to the diagnosis of occupational ICD (OICD), and to evaluate the occurrence of concomitant exposures to contact allergens.

Methods

We included 316 patients with suspected occupational hand dermatitis, referred to the Department of Dermato‐Allergology, Copenhagen University Hospital Gentofte, Denmark during January 2010–August 2011, in a programme consisting of a clinical examination, exposure assessment, and extensive patch/prick testing.

Results

OCD was diagnosed in 228 patients. Of these patients, 118 were diagnosed with OICD. The main irritant exposures identified were wet work (n = 64), gloves (n = 45), mechanical traumas (n = 19), and oils (n = 15). Exposure to specific irritant chemicals was found in 9 patients, and was identified from MSDSs/ingredients labelling in 8 of these patients. Review of MSDSs and ingredients labelling showed that 41 patients were exposed to 41 moderate to potent contact allergens, and 18 patients were exposed to 25 weak workplace contact allergens.

Conclusion

In the present study, the systematic exposure assessment did not reveal any new irritants. MSDSs have a limited role in the investigation of ICD.
Type of opioids injected: Does it matter? A multicentric cross‐sectional study of people who inject drugs
Authors: Ambekar Atul , Rao Ravindra , Mishra Ashwani Kumar , Agrawal Alok
Published: October 2014

Introduction and Aims

Injecting pharmaceutical opioids for non‐medical purposes is a major concern globally. Though pharmaceutical opioids injection is reported in India, the exact proportion of people who inject drugs (PWID) using pharmaceutical opioids is unknown. The objectives of this study were to describe the various types of drugs that are injected by people in India and to analyse the differences between the commonly injected drugs.

Design and Methods

A cross‐sectional, multicentric study covering 22 harm‐reduction sites from different regions of the country was conducted. First 50 subjects, chosen randomly from a list of PWIDs accessing services from each site and fulfilling study criteria, were interviewed using a structured questionnaire. Data from 902 male subjects are presented here.

Results

Pharmaceutical opioid injectors (POI) accounted for 65% of PWIDs (buprenorphine: 30.8%, pentazocine: 21.8% and dextropropoxyphene: 11.9%). Heroin, injected by 34.3%, was prevalent in most states surveyed. Buprenorphine and pentazocine were not injected in the north‐east region, whereas dextropropoxyphene was injected in the north‐east alone. Univariate and multivariate logistic regression showed that, compared with heroin injectors, the POI group was more likely to consume alcohol and pharmaceutical opioids orally, inject frequently, share needle/syringes and develop injection‐site complications. Among individual POIs, buprenorphine injectors had significantly higher proportion of subjects injecting frequently, sharing needle/syringes and developing local complications. Irrespective of the opioid type, majority of subjects were opioid dependent.

Discussion and Conclusions

Pharmaceutical opioids are the most common drugs injected in India currently and have greater injection‐related risks and complications. Significant differences exist between different pharmaceutical opioids, which would be important considerations for interventions. [Ambekar A, Rao R, Mishra AK, Agrawal A. Type of opioids injected: Does it matter? A multicentric cross‐sectional study of people who inject drugs. Drug Alcohol Rev 2015;34:97–104]
Implications of enrolment eligibility criteria in alcohol treatment outcome research: Generalisability and potential bias in 1‐ and 6‐year outcomes
Authors: Storbjörk Jessica
Published: October 2014

Introduction and Aims

It has been acknowledged that participants in clinical trials differ from real‐world service users, primarily due to the extensive use of research eligibility criteria (EC). Generalisability and outcome bias become pressing issues when evidence‐based treatment guidelines, crystallised from outcome research, influence treatment provision. This study reports on the effects of EC on generalisability and short‐ and long‐term outcomes among real‐world treatment‐seekers.

Design and Methods

Ten of the most commonly used EC were operationalised and applied to a large representative service user sample (n = 1125) from Stockholm County, Sweden, to determine the percentage of real‐world problem alcohol users that would have been excluded by each EC and the extent to which EC bias the 1 and 6‐year alcohol outcomes.

Results

Individual EC excluded between 5% and 80% of real‐world service users and 96% would have been excluded by at least one EC. Most of the EC introduced a positive/upwards bias in 1‐ and 6‐year outcomes. Most notably, the removal of the unmotivated/non‐compliant service users caused an upwards bias that would considerably boost estimates of treatment effectiveness. Other bias effects were smaller. Six‐year effects were generally higher than for 1 year.

Discussion and Conclusions

Outcome studies that exclude complex and non‐compliant cases are not representative of real‐world service users, and thus effectiveness estimates from clinical trials are biased by several commonly used EC. EC should be used judiciously and be taken into account in practice guidelines. This burgeoning research area should be further developed. [Storbjörk J. Implications of enrolment eligibility criteria in alcohol treatment outcome research: Generalisability and potential bias in 1‐ and 6‐year outcomes. Drug Alcohol Rev 2014;33:604–11]
Social skills in pediatric epilepsy: important but understudied
Authors: Caplan Rochelle
Published: October 2014

This commentary is on the original article by Lew et al. on pages 53–59 of this issue.
FIRM PRODUCTIVITY AND SALES DESTINATIONS: EVIDENCE FROM WITHIN CHINA
Authors: Huang Jiuli , Wang Yanling , Bao Qun
Published: October 2014

This paper builds on and extends the literature on the linkage between firm productivity and their export destinations to study the productivity of Chinese firms and their sales destinations in other provinces within China. Moving the study from international markets to domestic markets conveniently avoids the hard to control heterogeneity across different destination markets in international trade, as provincial markets within China are less heterogeneous than international markets but segmented by Chinese provincial borders. The paper explicitly controls the fact that many firms only sell in their home provinces by using the zero‐inflated negative binomial method. It finds that firms with higher productivity tend to sell in other provincial markets, and more productive firms enter more provincial markets. The results are robust. (JEL F15, D21, D24)
The effect of weightbearing and limb load cycling on equine lamellar perfusion and energy metabolism measured using tissue microdialysis
Authors: Medina‐Torres C. E. , Underwood C. , Pollitt C. C. , Castro‐Olivera E. M. , Hodson M. P. , Richardson D. W. , van Eps A. W.
Published: October 2014

Reasons for performing study

Lamellar perfusion is thought to be affected by weightbearing and limb load cycling; this may be critical in the development of supporting limb laminitis.

Objectives

To document the effects of unilateral weightbearing and altered limb load cycling on lamellar energy metabolism and perfusion.

Study design

Randomised, controlled (within subject), experimental trial.

Methods

Nine Standardbred horses were instrumented with microdialysis probes in the foot lamellar tissue and skin (over the tail base). Urea (20 mmol/l) was added to the perfusate. Samples were collected every 15 min for a 1 h control period, then during periods of unilateral weightbearing (opposite limb held off the ground for 1 h); enhanced static limb load cycling (instrumented limb lifted every 10 s for 30 min); reduced limb load cycling activity (i.v. detomidine sedation) and continuous walking (30 min). Dialysate concentrations of glucose, lactate, pyruvate and urea were measured and lactate:glucose (L:G) and lactate:pyruvate (L:P) ratios were calculated. For each intervention, values were compared with baseline using nonparametric statistical testing.

Results

Lamellar dialysate glucose increased andL:Gdecreased significantly during enhanced static limb load cycling. Glucose and pyruvate increased, andL:G,L:Pand urea decreased significantly during walking. Simultaneous skin dialysate values did not change significantly. There were no significant dialysate changes during unilateral weightbearing or after detomidine administration, but only the latter resulted in a significant decrease in limb load cycling frequency.

Conclusions

Increases in limb load cycling frequency (particularly walking) caused dialysate changes consistent with increased lamellar perfusion. Unilateral weightbearing (1 h) and a sedation‐induced reduction in limb load cycling frequency did not have a detectable effect on lamellar perfusion. More research is needed to confirm the role of hypoperfusion in supporting limb laminitis, but strategies to increase limb load cycling may be important for prevention.
Electric current‐induced lymphatic activation
Authors: Kajiya Kentaro , Matsumoto‐Okazaki Yuko , Sawane Mika , Fukada Kaedeko , Takasugi Yuya , Akai Tomonori , Saito Naoki , Mori Yuichiro
Published: October 2014

The lymphatic system in skin plays important roles in drainage of wastes and in the afferent phase of immune response. We previously showed that activation of vascular endothelial growth factor receptor (VEGFR), specifically the VEGFC/VEGFR‐3 pathway, attenuates oedema and inflammation by promoting lymphangiogenesis, suggesting a protective role of lymphatic vessels against skin inflammation. However, it remains unknown how physical stimuli promote lymphatic function. Here, we show that lymphatic endothelial cells (LECs) are activated by direct‐current (DC) electrical stimulation, which induced extension of actin filaments of LECs, increased calcium influx into LECs, and increased phosphorylation of p38 mitogen‐activated protein kinase (MAPK). An inhibitor of focal adhesion kinase, which plays a role in cellular adhesion and motility, diminished the DC‐induced extension of F‐actin and abrogated p38 phosphorylation. Time‐lapse imaging revealed that pulsed‐DC stimulation promoted proliferation and migration of LECs. Overall, these results indicate that electro‐stimulation activates lymphatic function by activating p38 MAPK.
DAMP molecules S100A9 and S100A8 activated by IL‐17A and house‐dust mites are increased in atopic dermatitis
Authors: Jin Shan , Park Chang Ook , Shin Jung U , Noh Ji Yeon , Lee Yun Sun , Lee Na Ra , Kim Hye Ran , Noh Seongmin , Lee Young , Lee Jeung‑Hoon , Lee Kwang Hoon
Published: October 2014

S100A9 and S100A8 are called damage‐associated molecular pattern (DAMP) molecules because of their pro‐inflammatory properties. Few studies have evaluated S100A9 and S100A8 function as DAMP molecules in atopic dermatitis (AD). We investigated how house‐dust mites affect S100A9 and S100A8 expression in Th2 cytokine‐ and Th17 cytokine‐treated keratinocytes, and how secretion of these molecules affects keratinocyte‐derived cytokines. Finally, we evaluated expression of these DAMP molecules in AD patients. S100A9 expression and S100A8 expression were strongly induced in IL‐17A‐ and Dermatophagoides (D.) farinae‐treated keratinocytes, respectively. Furthermore, co‐treatment with D. farinae and IL‐17A strongly increased expression of S100A9 and S100A8 compared with D. farinae‐Th2 cytokine co‐treatment. The IL‐33 mRNA level increased in a dose‐dependent manner in S100A9‐treated keratinocytes, but TSLP expression did not change. S100A8/A9 levels were also higher in the lesional skin and serum of AD patients, and correlated with disease severity. Taken together, S100A9 and S100A8 may be involved in inducing DAMP‐mediated inflammation in AD triggered by IL‐17A and house‐dust mites.