bluuebunny/crossref_metadata_2025 huggingface dataset:
Spillover effects of a firm's relationship marketing orientation in the logistics triad
Authors: Rossiter Hofer Adriana , J. Smith Ronn , R. Murphy Paul
Published: July 2014

Purpose

– The central tenet of this paper is that a firm's efforts to nurture a long-term relationship with a third-party logistics (3PLs) will be influenced by its strategic orientation toward its own customers. The purpose of this paper is to propose that there will be a spillover effect of a firm's relationship marketing orientation (RMO) toward its customers on the nature of a firm's relationship with its 3PL, positively impacting its logistics performance.

Design/methodology/approach

– A survey was administered to logistics managers in Brazilian firms that employ the services of a large 3PL. The model was tested via structural equation modeling.

Findings

– Results of this research suggest that a firm's RMO toward its customers has a positive impact on the long-term orientation (LTO) toward the relationship with its 3PL, ultimately improving the firm's operations performance. Additionally, the findings reveal that the positive effect of RMO on LTO is stronger for higher levels of a firm's dependence on its 3PL.

Research limitations/implications

– The results provide initial evidence that when a RMO is embedded in a firm's strategies toward its customers, there will be spillover effects on both the nature and outcomes of relationships with other partners, such as 3PLs. Research limitations include the survey implementation in an emerging market, and surveying clients of a single 3PL.

Practical implications

– From the perspective of the 3PL, when selecting new clients, it is important to investigate how these potential clients relate to their own customers. In other words, 3PLs should investigate whether these potential clients embrace RMO toward their downstream customers. If that is the case, the client will be more likely to have LTO with the 3PLs with which it works.

Originality/value

– While most studies in logistics outsourcing demonstrate that interorganizational conditions are key determinants of long-term and collaborative relationships with 3PLs, this study provides initial evidence that when a strategic orientation – RMO – is embedded in a firm's strategies and operations toward its customers, there will be spillover effects on both the nature and outcomes of relationships with 3PLs as well.
Reverse logistics in the pharmaceuticals industry: a systemic analysis
Authors: A. Narayana Sushmita , A. Elias Arun , K. Pati Rupesh
Published: July 2014

Purpose

– The purpose of this paper is to present a systemic analysis of the complex interaction of factors affecting the reverse logistics (RL) processes in a pharmaceutical supply chain (PSC).

Design/methodology/approach

– This study uses a systems thinking approach. Initial problem structuring involved the analysis of behavior-over-time of main variables and incorporated stakeholder analysis. Further, a participative group model building process was used to develop a systems model.

Findings

– The model was analysed to identify a set of feedback loops operating in the system responsible for the complexities of the problem. To address this, the stakeholders identified three strategic interventions. The first intervention relates to returns avoidance by alleviating market flooding of medicines, second intervention aims at improving the infrastructure for quality and performance management and the third targets balanced risk sharing between the main stakeholders involved in the supply chain. The findings suggest strong linkage between RL network design and key activities in returns management. The study lays a platform for developing a simulation model.

Research limitations/implications

– Data collection was confined to stakeholders belonging to a PSC based in the South Indian state of Kerala and excluded the participation of doctors due to practical constraints. The application of systems thinking and modelling was limited to the qualitative phases of the methodology.

Practical implications

– The study illustrates a participative process capable of revealing the differing viewpoints of multiple stakeholders involved in a PSC.

Originality/value

– It provides a holistic approach based on the systems thinking and modelling methodology for analysing the complexities related to RL in the Indian pharmaceutical industry.
Sales promotion influencing consumer brand preferences/purchases
Authors: E. Schultz Don , P. Block Martin
Published: July 2014

Purpose

– This paper aims to investigate whether or not ongoing sales promotion contributed to the declines in “no brand preference” (NBP). Part of an ongoing series investigating the growth of US consumer’s responses of NBP for more than 1,500 frequently purchased consumer product brands. Data were drawn from responses to a very large (1.1 million) online longitudinal consumer questionnaire during 2002-2012.

Design/methodology/approach

– Additional research, combining this data set with two other major US longitudinal studies, confirmed results. This study focused on determining reasons for NBP increase. Initial data set included use of and influence of 23 in-store promotional tools. These were investigated to determine impact and effect.

Findings

– Four leading sales promotional tools, based on consumer influence, were coupons, home samples, in-store samples and retail shopper cards. Shopper cards had most influence on purchase of secondary, not primary brands in categories. Shopper cards are a clearly underused promotional tool in building brand preference and sales.

Research limitations/implications

– Limited to US consumer products only. No attempt made to connect media advertising and in-store media impact or effect.

Practical implications

– Future investigation should focus on other geographies, synergy between media advertising and promotional techniques. Also, the study is all aggregated data; individual brand investigations should be made. Shopper cards appear to be a major opportunity for secondary brands. More focus on cooperative activities between brands and retailers would benefit both.

Originality/value

– Paucity of longitudinal customer-view research on shopper cards identifies both manufacturer and retailer opportunities, particularly secondary brands.
Self-efficacy as an antecedent of cognition and affect in technology acceptance
Authors: Kulviwat Songpol , C. Bruner II Gordon , P. Neelankavil James
Published: July 2014

Purpose

– This paper aims to examine whether self-efficacy plays an important role in shaping the effect of cognition and affects in high technology adoption. It also examines whether cognition and affect mediate the effect of self-efficacy on attitude toward adoption.

Design/methodology/approach

– Using an experimental survey to collect data, subjects performed two different tasks (utilitarian and hedonic) to make sure that they had cognitive and affective experiences to draw upon as they developed attitudes toward the focal innovation. Structural equation modeling was used to analyze the model.

Findings

– The result shows that self-efficacy influenced cognitive perceptions and emotional reactions. Specifically, self-efficacy was found to play a substantive role in shaping individuals’ attitudes via a cognitive route (perceived usefulness and ease-of-use) and an affective one (pleasure, arousal and dominance).

Research limitations/implications

– The study of self-efficacy as an external variable provides further insights into the process and is expected to increase the explained variance of the theoretical model.

Practical implications

– This study confirms that a belief about something besides the product also plays a key role; it is the confidence consumers have in their own abilities to understand and effectively use a new piece of technology.

Originality/value

– The research makes important contributions to our understanding of technology acceptance and has implications for marketing managers.
Do females in advertisements reflect adolescents’ ideal female images?
Authors: Leung Ng Yu , Chan Kara
Published: July 2014

Purpose

– The purpose of this study was to investigate how Chinese adolescent girls and boys construct their own ideal female images in response to gendered advertisements based on Arnett’s (1995) theory of self-socialization and Hirschman and Thompson’s (1997) three interpretive strategies. A qualitative interview study was conducted for this purpose.

Design/methodology/approach

– Altogether, 32 adolescents aged 15-19 living in 16 different provinces in China were recruited for a face-to-face interview. Three advertisements were shown depicting an elegant woman, an urban sophisticated female and a strong woman, and interviewees were asked to describe the appearance, the personality and the work and family life of the female character in each advertisement. They were asked to choose one of them as most closely representing their ideal female image.

Findings

– The interviewees constructed their ideal female images from the advertisement that best suited their ideal appearance, personality and work and family life. Female interviewees aspired to be like the elegant woman, identified with the urban sophisticated female and rejected the strong woman in the ads. Male interviewees appreciated the urban sophisticated female but rejected the strong woman.

Research limitations/implications

– With just 32 interviewees, the generalizability of the findings is limited.

Practical implications

– Female central characters in advertisements should be pilot-tested among the target audience to maximize levels of aspiration and identification.

Originality/value

– This is the first study to examine ideal female images from gendered advertisements among adolescent boys and girls in China.
A novel multi‐strain probiotic and synbiotic supplement for prevention of Clostridium difficile infection in a murine model
Authors: Kondepudi Kanthi Kiran , Ambalam Padma , Karagin Peren H. , Nilsson Ingrid , Wadström Torkel , Ljungh Åsa
Published: July 2014

The protective effect of a multi‐strain probiotic and synbiotic formulation was evaluated in C57BL/6 mice infected with Clostridium difficile (CD) NAP1/027. Antibiotic‐treated mice were divided into the following four groups: Group 1, fed with a synbiotic formulation consisting of Lactobacillus plantarum F44, L. paracasei F8, Bifidobacterium breve 46, B. lactis 8:8, galacto‐oligosaccharides, isomalto‐oligosaccharides, and resistant starch; Group 2, fed with the same four probiotic strains as Group 1; Group 3, fed with the same prebiotic supplements as Group 1 for 7 days before CD infection; and Group 4 (control group) antibiotic treated and infected with NAP1/027 strain. Feces and cecal contents were collected for microbial cell viability, quantitative PCR (qPCR), toxin analyses and histopathology. Synbiotics‐ and probiotics‐fed mice showed a significant increase in total bifidobacteria (P < 0.05). The total lactobacilli count was increased in Group 1. Tests for cecal toxins were negative in Group 2 mice, whereas one sample each from Group 1 and 3 was positive. qPCR of cecal contents showed significant reduction in NAP1/027 DNA copies in Groups 1 and 2 and significantly higher numbers of B. breve 46, L. plantarum F44, and L. paracasei F8 in Groups 1 and 2 (P < 0.05); these changes were much less pronounced in Groups 3 and 4. Our findings indicate that the newly developed synbiotic or multi‐strain probiotic formulation confers protection against NAP1/027 infection in C57BL/6 mice. This holds promise for performing human studies.
Using manipulation of density‐dependent fecundity to recover an endangered species: the bearded vulture Gypaetus barbatus as an example
Authors: Ferrer Miguel , Newton Ian , Muriel Roberto , Báguena Gerardo , Bustamante Javier , Martini Matilde , Morandini Virginia
Published: July 2014

Endangered species subjected to reintroduction programmes often occur as small and isolated populations with local high density and depressed fecundity. Variation in territory quality may lead to this low fecundity owing to increasing occupation of suboptimal territories as population density grows, known as the habitat heterogeneity hypothesis (HHH). In this context, food supplementation in poor territories may be used to produce extra young which could be allocated to reintroduction programmes.

We analyse the density‐dependent fecundity pattern and the underlying mechanism in a small population of bearded vultures Gypaetus barbatus in Aragón (northeast Spain). We then use population simulations to examine the viability of a hypothetical reintroduction programme using extra young produced by supplementary feeding on poor‐quality territories and the effect on the donor population. We also compare the economic cost of such a reintroduction programme in relation to the cost of a traditional captive breeding programme.

The wild population showed clear negative, density‐dependent fecundity regulation driven by the HHH mechanism. Simulations showed that extractions for translocations had no relevant long‐term effects on the donor population viability, but a marked population reduction during the extraction period. However, the implementation of supplementary feeding to produce extra young for translocation lessened significantly this expected initial population reduction.

Analyses showed that the annual budget of a captive breeding programme for this species could be seven times more expensive than the translocation of extra young produced by food supplementation.

Synthesis and applications. Reintroduction programmes based on translocation of wild‐reared individuals, after a supplementary feeding programme oriented to poor‐quality territories, provide a source of young at least seven times cheaper than those from captive breeding programmes. The use of this approach would decrease initial effects on donor population avoiding public criticism. Increasing the number of young released during the first years of the reintroduction decreases total financial cost and increases the final population size in the new area.
The meningococcal autotransporter AutA is implicated in autoaggregation and biofilm formation
Authors: Arenas Jesús , Cano Sara , Nijland Reindert , van Dongen Vérène , Rutten Lucy , van der Ende Arie , Tommassen Jan
Published: July 2014

Autotransporters (ATs) are proteins secreted by Gram‐negative bacteria that often play a role in virulence. Eight different ATs have been identified in Neisseria meningitidis, but only six of them have been characterized. AutA is one of the remaining ATs. Its expression remains controversial. Here, we show that the autA gene is present in many neisserial species, but its expression is often disrupted by various genetic features; however, it is expressed in certain strains of N. meningitidis. By sequencing the autA gene in large panels of disease isolates and Western blot analysis, we demonstrated that AutA expression is prone to phase variation at AAGC nucleotide repeats located within the DNA encoding the signal sequence. AutA is not secreted into the extracellular medium, but remains associated with the bacterial cell surface. We further demonstrate that AutA expression induces autoaggregation in a process that, dependent on the particular strain, may require extracellular DNA (eDNA). This property influences the organization of bacterial communities like lattices and biofilms. In vitro assays evidenced that AutA is a self‐associating AT that binds DNA. We suggest that AutA‐mediated autoaggregation might be particularly important for colonization and persistence of the pathogen in the nasopharynx of the host.
Mary and the Catholic Church in England, 1854–1893
Authors: Leighton Cadoc D. A.
Published: July 2014

The article offers description of the Marianism of the English Catholic Church — in particular as manifested in the celebration of the definition of the doctrine of the Immaculate Conception in 1854 and the solemn consecration of England to the Virgin in 1893 — in order to comment on the community's (and more particularly, its leadership's) changing perception of its identity and situation over the course of the later nineteenth century. In doing so, it places particular emphasis on the presence of apocalyptic belief, reflective and supportive of a profound alienation from contemporary English society, which was fundamental in shaping the Catholic body's modern history.
The Use of Tooth Crown Measurements in the Assessment of Ancestry
Authors: Pilloud Marin A. , Hefner Joseph T. , Hanihara Tsunehiko , Hayashi Atsuko
Published: July 2014

As the hardest tissue in the body, teeth have the potential to offer a wealth of biological information to the forensic anthropologist, which can include the assessment of ancestry. Using a large data set of dental measurements, the efficacy of mesiodistal and buccolingual tooth dimensions to discriminate between broad, geographically based groups is explored. A general pattern is identified: African populations have the largest teeth, Asians possess teeth of intermediate size, and Europeans have the smallest teeth. In a discriminant function analysis using crown measurements of all teeth (mandibular and maxillary and excluding the third molar), individuals were correctly classified in 71.3% of cases. When the sex of the individual is known, classification is improved up to 88.1% in females and 71.9% of males (cross‐validated). Based on these results, we argue that dental metrics can be regularly employed as part of the development of the biological profile.
Child Sexual Abuse in Turkey: An Analysis of 1002 Cases
Authors: Aydin Berna , Akbas Seher , Turla Ahmet , Dundar Cihad , Yuce Murat , Karabekiroglu Koray
Published: July 2014

This study investigated the characteristics of abuse suffered by children, the dimensions of the psychiatric effects associated with abuse, and the factors affecting these. One thousand two cases aged under 18, exposed to sexual abuse, and referred over a 7‐year period were assessed. Girls represented 80.8% of cases, and the numbers rose with age. The aggressors were all male, and 88.2% were known to their victim. Approximately half the children were exposed to sexual abuse involving penetration. Psychological pathology was identified in 62.1%. Female gender, the presence of penetration, physical violence, and incest significantly increased the development of psychological pathology. Levels of awareness in people close to and trusted by the child must be raised to minimize the adverse effects of trauma in the long term, preventive measures must be taken, and medical and social support units from which victims can receive assistance need to be established.
Sensitivity of TATP to a TASER Electrical Output
Authors: Gerber Michael , Walsh Graham , Hopmeier Mike
Published: July 2014

A series of experiments were performed to evaluate and document the effect of a TASER (“stun gun”) on triacetone triperoxide (TATP), an easily manufactured explosive used often in IEDs and suicide bombing vests. TATP samples were synthesized and subjected to several tests of their sensitivity. These samples were run through a BAM Friction test with a result of <0.5 N, Impact Test with a result of 5.8 ± 0.4 cm, and Electrostatic Discharge test with a result of 0.073 ± 0.018 J. In addition, TATP was shocked with a TASER in a variety of configurations. The TATP reacted in 17/17 tests when the TASER arced through the TATP and 0/4 times when the TATP was configured in such a way that the TATP was not subjected to the electrical arc. Based on the experimental data, TATP will readily explode in a variety of configurations by a TASER or similar device. Testing should be expanded, as the data presented here are limited to a single formulation of TATP. Just one of a large array of TASER‐like devices by a single manufacturer were tested; other devices, scenarios and formulations of TATP and other likely threat materials should be assessed.
Market structure and the competitive effects of vertical integration
Authors: Loertscher Simon , Reisinger Markus
Published: July 2014

We analyze the competitive effects of backward vertical integration when firms exert market power upstream and compete in quantities downstream. Contrasting with previous literature, a small degree of vertical integration is always procompetitive because efficiency gains dominate foreclosure effects, and vertical integration even to full foreclosure can be procompetitive. Interestingly, vertical integration is more likely to be procompetitive if the industry is otherwise more concentrated. Extensions analyze welfare effects of integration and the incentives to integrate. Our analysis suggests that antitrust authorities should be wary of vertical integration when the integrating firm faces many competitors and should be permissive otherwise.
Search for differentiated products: identification and estimation
Authors: Koulayev Sergei
Published: July 2014

When consumers search for differentiated products, a given search decision can be explained either by low search cost or by low tastes for the set of products already found. We propose an identification strategy that allows to estimate the search cost distribution in the presence of unobserved tastes. The required data takes the form of conditional search decisions: observations of search actions combined with previously observed product displays. We develop an application using clickstream data from a hotel search platform. Estimates of price elasticity of demand in the search model differ from those in the static model, reflecting the bias due to endogeneity of search‐generated choice sets.
Integration and search engine bias
Authors: de Cornière Alexandre , Taylor Greg
Published: July 2014

We study the effects of integration between a search engine and a publisher. In a model in which the search engine (i) allocates users across publishers and (ii) competes with publishers to attract advertisers, we find that the search engine is biased against publishers that display many ads – even without integration. Integration can (but need not) lead to own‐content bias. It can also benefit consumers by reducing the nuisance costs due to excessive advertising. Advertisers are more likely to suffer from integration than consumers. On net, the welfare effects of integration are ambiguous.
Fibrinogen concentrate for bleeding – a systematic review
Authors: LUNDE J. , STENSBALLE J. , WIKKELSØ A. , JOHANSEN M. , AFSHARI A.
Published: July 2014

Fibrinogen concentrate as part of treatment protocols increasingly draws attention. Fibrinogen substitution in cases of hypofibrinogenaemia has the potential to reduce bleeding, transfusion requirement and subsequently reduce morbidity and mortality. A systematic search for randomised controlled trials (RCTs) and non‐randomised studies investigating fibrinogen concentrate in bleeding patients was conducted up to November 2013. We included 30 studies of 3480 identified (7 RCTs and 23 non‐randomised). Seven RCTs included a total of 268 patients (165 adults and 103 paediatric), and all were determined to be of high risk of bias and none reported a significant effect on mortality. Two RCTs found a significant reduction in bleeding and five RCTs found a significant reduction in transfusion requirements. The 23 non‐randomised studies included a total of 2825 patients, but only 11 of 23 studies included a control group. Three out of 11 found a reduction in transfusion requirements while mortality was reduced in two and bleeding in one. In the available RCTs, which all have substantial shortcomings, we found a significant reduction in bleeding and transfusions requirements. However, data on mortality were lacking. Weak evidence from RCTs supports the use of fibrinogen concentrate in bleeding patients, primarily in elective cardiac surgery, but a general use of fibrinogen across all settings is only supported by non‐randomised studies with serious methodological shortcomings. It seems pre‐mature to conclude whether fibrinogen concentrate has a routine role in the management of bleeding and coagulopathic patients. More RCTs are urgently warranted.
Neuronal glycogen synthesis contributes to physiological aging
Authors: Sinadinos Christopher , Valles‐Ortega Jordi , Boulan Laura , Solsona Estel , Tevy Maria F. , Marquez Mercedes , Duran Jordi , Lopez‐Iglesias Carmen , Calbó Joaquim , Blasco Ester , Pumarola Marti , Milán Marco , Guinovart Joan J.
Published: July 2014

Glycogen is a branched polymer of glucose and the carbohydrate energy store for animal cells. In the brain, it is essentially found in glial cells, although it is also present in minute amounts in neurons. In humans, loss‐of‐function mutations in laforin and malin, proteins involved in suppressing glycogen synthesis, induce the presence of high numbers of insoluble polyglucosan bodies in neuronal cells. Known as Lafora bodies (LBs), these deposits result in the aggressive neurodegeneration seen in Lafora's disease. Polysaccharide‐based aggregates, called corpora amylacea (CA), are also present in the neurons of aged human brains. Despite the similarity of CA to LBs, the mechanisms and functional consequences of CA formation are yet unknown. Here, we show that wild‐type laboratory mice also accumulate glycogen‐based aggregates in the brain as they age. These structures are immunopositive for an array of metabolic and stress‐response proteins, some of which were previously shown to aggregate in correlation with age in the human brain and are also present in LBs. Remarkably, these structures and their associated protein aggregates are not present in the aged mouse brain upon genetic ablation of glycogen synthase. Similar genetic intervention in Drosophila prevents the accumulation of glycogen clusters in the neuronal processes of aged flies. Most interestingly, targeted reduction of Drosophila glycogen synthase in neurons improves neurological function with age and extends lifespan. These results demonstrate that neuronal glycogen accumulation contributes to physiological aging and may therefore constitute a key factor regulating age‐related neurological decline in humans.
Depletion of Rictor, an essential protein component of mTORC2, decreases male lifespan
Authors: Lamming Dudley W. , Mihaylova Maria M. , Katajisto Pekka , Baar Emma L. , Yilmaz Omer H. , Hutchins Amanda , Gultekin Yetis , Gaither Rachel , Sabatini David M.
Published: July 2014

Rapamycin, an inhibitor of the mechanistic target of rapamycin (mTOR), robustly extends the lifespan of model organisms including mice. We recently found that chronic treatment with rapamycin not only inhibits mTOR complex 1 (mTORC1), the canonical target of rapamycin, but also inhibits mTOR complex 2 (mTORC2) in vivo. While genetic evidence strongly suggests that inhibition of mTORC1 is sufficient to promote longevity, the impact of mTORC2 inhibition on mammalian longevity has not been assessed. RICTOR is a protein component of mTORC2 that is essential for its activity. We examined three different mouse models of Rictor loss: mice heterozygous for Rictor, mice lacking hepatic Rictor, and mice in which Rictor was inducibly deleted throughout the body in adult animals. Surprisingly, we find that depletion of RICTOR significantly decreases male, but not female, lifespan. While the mechanism by which RICTOR loss impairs male survival remains obscure, we find that the effect of RICTOR depletion on lifespan is independent of the role of hepatic mTORC2 in promoting glucose tolerance. Our results suggest that inhibition of mTORC2 signaling is detrimental to males, which may explain in part why interventions that decrease mTOR signaling show greater efficacy in females.
Adherence to adrenal incidentaloma guidelines is influenced by radiology report recommendations
Authors: Wickramarachchi Binula N. , Meyer‐Rochow Goswin Y. , McAnulty Kim , Conaglen John V. , Elston Marianne S.
Published: July 2014

Introduction

Approximately 5% of all abdominal computed tomography (CT) and magnetic resonance imaging (MRI) scans reveal an adrenal incidentaloma. Although most adrenal incidentalomas are benign non‐functioning adenomas, lesions may be hormonally active and/or malignant. The aim of this study was to determine adherence to recommended international guidelines and potential influencing factors when an adrenal incidentaloma is identified in routine clinical practice.

Methods

A retrospective study was performed of all CT and MRI reports from December 2009 to December 2011 using a key phrase search to identify patients with an incidental adrenal lesion.

Results

A total of 125 patients with incidental adrenal lesions were identified, of which 74 patients were considered appropriate for further endocrine/radiological workup. Of the 74 patients, only 19 (26%) were initially referred to the endocrine service for investigation; 21/74 (28%) had complete biochemical workup and 24/74 (32%) had imaging follow‐up arranged. The reporting radiologist provided advice for follow‐up in 31/74 (42%), and action was more likely to be taken when this recommendation was given. Follow‐up of the patients who had not received investigation was attempted resulting in assessment of a further 23 patients. Of the 44 patients who have undergone full assessment, four patients were found to have clinically significant lesions (one each of: Cushing's syndrome, phaeochromocytoma, Conn's syndrome and plasmacytoma).

Conclusion

This study suggests that the majority of adrenal incidentalomas may not be investigated according to current international guidelines. The recommendations by the reporting radiologist appear to influence whether a patient is referred for further investigation.
Small‐size platelet microparticles trigger platelet and monocyte functionality and modulate thrombogenesis via P‐selectin
Authors: Montoro‐García Silvia , Shantsila Eduard , Hernández‐Romero Diana , Jover Eva , Valdés Mariano , Marín Francisco , Lip Gregory Y. H.
Published: July 2014

This study aimed to examine the mechanisms of cellular activation by small‐size platelet microparticles (sPMP) and to present the performance of high‐resolution flow cytometry for the analysis of subcellular entities from different origins. Plasma counts of sPMP were analysed in coronary artery disease patients (n = 40) and healthy controls (n = 40). The effect of sPMP and platelet debris (PD) in pathophysiologically relevant doses on platelet and monocyte activation parameters and thrombogenesis was investigated via flow cytometry and thromboelastometry. New generation flow cytometry identifies differences in size, levels and surface molecules of sPMP derived in the absence of stimulus, thrombin activation and platelet disruption. Addition of sPMP resulted in platelet degranulation and P‐selectin redistribution to the membrane (P = 0·019) in a dose and time‐dependent manner. Blood clotting time decreased after addition of sPMP (P = 0·005), but was not affected by PD. Blocking P‐selectin (CD62P) in sPMP markedly reverted the effect on thrombus kinetics (P = 0·035). Exposure to sPMP stimulated monocyte expression of intercellular adhesion molecule‐1 (P < 0·03) and decreased monocyte interleukin‐6 receptor density (P < 0·01). These results implicate sPMP as a direct source of downstream platelet and monocyte activation. In pathological coronary artery disease conditions, higher levels of sPMP favour a prothrombotic state, partly through P‐selectin expression.
The treatment of penile carcinoma in situ (CIS) within a UK supra‐regional network
Authors: Lucky Marc , Murthy Kusuma V.R. , Rogers Beverley , Jones Stephen , Lau Maurice W. , Sangar Vijay K. , Parr Nigel J.
Published: July 2014

Objectives

To review outcomes of the treatment of carcinoma in situ (CIS) of the penis at a large supra‐regional penile cancer network, where centralisation has permitted greater experience with treatment outcomes, and suggest treatment strategies.

Patients and Methods

The network penile cancer database, which details presentation, treatment and complications was analysed from 2003 to 2010, identifying patients with CIS, with a minimum follow‐up of 2 years, looking at treatments administered and outcomes.

Results

In all, 57 patients with mean (range) age of 61 (34–91) years were identified. In all, 18 were treated by circumcision only, 20 by circumcision and local excision (LE) and 19 by circumcision and 5‐flurouracil (5‐FU). The mean (range) follow‐up was 3.5 (2–8) years. Of those treated by circumcision none subsequently developed CIS on the glans. For those who underwent circumcision + LE, five of 20 (25%) developed recurrence requiring further treatment. Of those treated by circumcision + 5‐FU, 14/19 (73.7%) completely responded. Of the five incomplete responders, two had focal invasive malignancy at repeat biopsy. One incomplete responder underwent glansectomy and four grafting. No complete responders relapsed. Complications of 5‐FU included significant inflammatory response in seven (36.8%), with two requiring hospital admission and one neo‐phimosis (5.3%).

Conclusion

This study suggests that patients undergoing circumcision for isolated CIS and complete responders to 5‐FU may require only short‐term follow‐up, as recurrence is unlikely, whereas longer follow up is required for all other patients. However, numbers in this study are small and larger studies are needed to support this. An incomplete response to 5‐FU dictates immediate re‐biopsy, as it carries a significant chance of previously undetected invasive disease.
Characteristics of hyperparathyroid states in the Canadian multicentre osteoporosis study (CaMos) and relationship to skeletal markers
Authors: Berger C. , Almohareb O. , Langsetmo L. , Hanley D.A. , Kovacs C.S. , Josse R.G. , Adachi J.D. , Prior J.C. , Towheed T. , Davison K.S. , Kaiser S.M. , Brown J.P. , Goltzman D. ,   the CaMos Research Group
Published: July 2014

Context

PTH is an essential regulator of mineral metabolism; PTH hypersecretion may result in hyperparathyroidism including normocalcaemic, primary and secondary hyperparathyroidism.

Objective

To examine the characteristics of participants with hyperparathyroid states and the relationship to bone mineral density (BMD).

Design and participants

A cross‐sectional study of 1872 community‐dwelling men and women aged 35+ years (mostly Caucasian) with available serum PTH from Year 10 Canadian Multicentre Osteoporosis Study follow‐up (2005–07). PTH was determined using a second‐generation chemiluminescence immunoassay.

Outcome measures

L1‐L4, femoral neck and total hip BMD.

Results

We established a PTH reference range (2·7–10·2 pmol/l) based on healthy participants (i.e. normal serum calcium, serum 25‐hydroxyvitamin D, kidney function and body mass index, who were nonusers of antiresorptives, glucocorticoids and diuretics and not diagnosed with diabetes or thyroid disease). Participants with PTH levels in the upper reference range (5·6–10·2 pmol/l), representing a prevalence of 10·7%, had lower femoral neck and total hip BMD, by 0·030 g/cm2 [95% confidence interval: 0·009; 0·051] and 0·025 g/cm2 (0·001; 0·049), respectively, than those with levels 2·7–5·6 pmol/l. Participants with normocalcaemic and secondary hyperparathyroidism also had lower total hip BMD than those with levels 2·7–5·6 pmol/l, and CaMos prevalences of normocalcaemic, primary and secondary hyperparathyroidism were 3·3%, 1·4% and 5·2%, respectively.

Conclusion

We found reduced BMD in participants with accepted hyperparathyroid states but also a notable proportion of other participants that might benefit from having lower PTH levels.
Children's agency in interprofessional collaborative meetings in child welfare work
Authors: Bolin Anette
Published: July 2014

The concept of children's agency can be used to understand how children actively shape their lives. While in social work there is a growing body of research on how children experience meetings that involve collaborating professionals, little is known about the ways in which they exert an influence. The purpose of the study is, in a Swedish context, to investigate children's perceptions of their agentic capacity in regulating participation and exerting an influence on outcomes in interprofessional collaborative meetings. Interviews were carried out with 28 children in receipt of social services support. Findings revealed that children perceive professionals' talk as restricting opportunities for input. They also perceive that they have the capacity to exercise agency by (i) conforming to expectations by feigning boredom and seeming disengaged, but at the same time paying close attention; (ii) by using exit strategies; and (iii) by developing ‘in‐situ’ strategies to end meetings. Rather than, as previously suggested, being powerless in such circumstances, the children tell how they carefully assess situations, and, from a position of apparent subordination, talk of ways of acting that reveal their agentic capacity. These insights are of importance for practitioners who are encouraged to look beyond behaviours that first meet the eye.
Detailed characterization of MLH1 p.D41H and p.N710D variants coexisting in a Lynch syndrome family with conserved MLH1 expression tumors
Authors: Pineda M. , González‐Acosta M. , Thompson B.A. , Sánchez R. , Gómez C. , Martínez‐López J. , Perea J. , Caldés T. , Rodríguez Y. , Landolfi S. , Balmaña J. , Lázaro C. , Robles L. , Capellá G. , Rueda D.
Published: July 2014

Lynch syndrome (LS) is an autosomal dominant cancer‐susceptibility disease caused by inactivating germline mutations in mismatch repair (MMR) genes. Variants of unknown significance (VUS) are often detected in mutational analysis of MMR genes. Here we describe a large family fulfilling Amsterdam I criteria carrying two rare VUS in the MLH1 gene: c.121G > C (p.D41H) and c.2128A > G (p.N710D). Collection of clinico‐pathological data, multifactorial analysis, in silico predictions, and functional analyses were used to elucidate the clinical significance of the identified MLH1 VUS. Only the c.121G > C variant cosegregated with LS‐associated tumors in the family. Diagnosed colorectal tumors were microsatellite unstable although immunohistochemical staining revealed no loss of MMR proteins expression. Multifactorial likelihood analysis classified c.2128A > G as a non‐pathogenic variant and c.121G > C as pathogenic. In vitro functional tests revealed impaired MMR activity and diminished expression of c.121G > C. Accordingly, the N710 residue is located in the unconserved MLH1 C‐terminal domain, whereas D41 is highly conserved and located in the ATPase domain. The obtained results will enable adequate genetic counseling of c.121G > C and c.2128A > G variant carriers and their families. Furthermore, they exemplify how cumulative data and comprehensive analyses are mandatory to refine the classification of MMR variants.
Strategies for recruitment of relatives of BRCA mutation carriers to a genetic testing program in the Bahamas
Authors: Trottier M. , Lunn J. , Butler R. , Curling D. , Turnquest T. , Royer R. , Akbari M.R. , Donenberg T. , Hurley J. , Narod S.A.
Published: July 2014

The prevalence of BRCA1 and BRCA2 mutations among unselected breast cancer patients in the Bahamas is 23%. It is beneficial to advise relatives of mutation carriers that they are candidates for genetic testing. Women who test positive are then eligible for preventive interventions, such as oophorectomy. It is not clear how often relatives of women with a mutation in the Bahamas wish to undergo genetic testing for the family mutation. Furthermore, it is not clear how best to communicate this sensitive information to relatives in order to maximize patient compliance. We offered genetic testing to 202 first‐degree relatives of 58 mutation carriers. Of 159 women who were contacted by the proband or other family member, only 14 made an appointment for genetic testing (9%). In contrast, among 32 relatives who were contacted directly by the genetic counselor, 27 came for an appointment (84%). This study suggests that for recruitment of relatives in the Bahamas, direct contact by counselor is preferable to using the proband as an intermediary.
Negative outcomes after liver transplantation in patients with alcoholic liver disease beyond the fifth post‐transplant year
Authors: Grąt Michał , Lewandowski Zbigniew , Grąt Karolina , Wronka Karolina Maria , Krasnodębski Maciej , Barski Krzysztof , Zborowska Hanna , Patkowski Waldemar , Zieniewicz Krzysztof , Krawczyk Marek
Published: July 2014

Although up to 50% of patients with alcoholic liver disease (ALD) resume alcohol consumption after liver transplantation (LT), numerous studies indicate that long‐term results are not compromised. This study focused on evaluating the impact of ALD on outcomes up to and beyond the fifth year after LT. Among the 432 primary LT recipients included in this study, 97 underwent transplantation for ALD. Alcohol relapse rate at 10 yr was 33.5%, with younger recipient age being the only independent predictor (p = 0.019). Survival of patients with ALD (77.0%) was similar to those without (79.0%) up to the fifth post‐transplant year (p = 0.655) but worse during the five subsequent years among the five‐yr survivors (70.6% vs. 92.9%; p = 0.002). ALD was an independent risk factor for poorer survival beyond the fifth post‐transplant year (p = 0.049), but not earlier (p = 0.717). Conversely, alcohol relapse increased the risk of death only during the first five post‐transplant years (p = 0.039). There were no significant differences regarding graft failure incidence between ALD and non‐ALD recipients up to the fifth post‐transplant year (7.3% vs. 11.6%; p = 0.255) and beyond (12.9% vs. 5.0%; p = 0.126). In conclusion, pre‐transplant diagnosis of ALD yields negative effects on post‐transplant outcomes beyond the fifth post‐transplant year, not attributable to recidivism.
Developing a web‐based intervention to increase motivation to change and encourage uptake of specialist face‐to‐face treatment by hospital inpatients: Change Drinking
Authors: Bewick Bridgette M. , Rumball Katrina , Birtwistle Jacqueline C. , Shaw Joseph R. , Johnson Owen , Raistrick Duncan , Tober Gillian
Published: July 2014

Introduction and Aim

Problem drinking is rarely identified unless health‐care professionals are specifically instructed to assess alcohol consumption. Individualised web‐based alcohol interventions provide opportunities to enhance screening and early identification. We aimed to create a web‐based brief personalised feedback intervention to enable client‐centred screening and self‐referral by problem drinkers recently admitted to hospital.

Design and Methods

To increase transparency of the development process, this short report describes the theoretical underpinnings and development of ChangeDrinking including identification of needs and matching with resources, screening tool selection, and look and feel.

Results

The website structure and content was modelled on motivational dialogue. ChangeDrinking is closely coupled to an independent questionnaire management system; this architecture enables internal logic to allow branching based on dynamic user inputs. The motivational underpinnings led to development of personalised predetermined dialogue with strong theory–practice links. Applying principles of conveying empathy and reflection was challenging within the confines of a predetermined dialogue. Reflective listening in ChangeDrinking does not extend to inviting statements of resistance to be entered.

Discussion and Conclusions

ChangeDrinking has become an optional component of routine treatment for patients with an alcohol‐related admission in two large UK National Health Service general hospitals. [Bewick BM, Rumball K, Birtwistle JC, Shaw JR, Johnson O, Raistrick D, Tober G. Developing a web‐based intervention to increase motivation to change and encourage uptake of specialist face‐to‐face treatment by hospital inpatients: Change Drinking. Drug Alcohol Rev 2014;33:674–7]
Crack pipe sharing among street‐involved youth in a Canadian setting
Authors: Cheng Tessa , Wood Evan , Nguyen Paul , Montaner Julio , Kerr Thomas , DeBeck Kora
Published: July 2014

Introduction and Aims

Crack pipe sharing is a risky practice that has been associated with the transmission of hepatitis C and other harms. While previous research has exclusively focused on this phenomenon among adults, this study examines crack pipe sharing among street‐involved youth.

Design and Methods

From May 2006 to May 2012, data were collected from the At‐Risk Youth Study, a cohort of street‐involved youth aged 14–26 in Vancouver, Canada. Survey data from active crack smokers were analysed using generalised estimating equations logistic regression.

Results

Over the study period, 567 youth reported smoking crack cocaine and contributed 1288 observations, among which 961 (75%) included a report of crack pipe sharing. In multivariate analysis, factors that were associated with crack pipe sharing included difficulty accessing crack pipes [adjusted odds ratio (AOR) = 1.58, 95% confidence interval (CI) 1.13–2.20]; homelessness (AOR = 1.87, 95% CI 1.43–2.44); regular employment (AOR = 1.53, 95% CI 1.15–2.04); daily non‐injection crystal methamphetamine use (AOR = 2.04, 95% CI 1.11–3.75); daily crack smoking (AOR = 1.37, 95% CI 1.01–1.85); encounters with the police (AOR = 1.42, 95% CI 1.01–1.99); and reporting unprotected sex (AOR = 1.95, 95% CI 1.47–2.58).

Discussion and Conclusions

The prevalence of crack pipe sharing was high among our sample and independently associated with structural factors including difficulty accessing crack pipes and homelessness. Crack pipe sharing was also associated with high‐intensity drug use and a number of other markers of risk and vulnerability. Collectively, these findings highlight opportunities for health services to better engage with this vulnerable group and reduce this risky behaviour.
Two novel glucagon receptor antagonists prove effective therapeutic agents in high‐fat‐fed and obese diabetic mice
Authors: O'Harte F. P. M. , Franklin Z. J. , Irwin N.
Published: July 2014

Aims

To examine the effect of two novel, enzymatically stable, glucagon receptor peptide antagonists, on metabolic control in two mouse models of obesity/diabetes.

Method

The effects of twice daily i.p. administration of desHis1Pro4Glu9‐glucagon or desHis1Pro4Glu9Lys12FA‐glucagon for 10 days on metabolic control in high‐fat‐fed (HFF; 45% fat) and obese diabetic (ob/ob) mice were compared with saline‐treated controls.

Results

Neither analogue altered body weight or food intake in either model over 10 days; however, treatment with each peptide restored non‐fasting blood glucose towards normal control values in HFF mice. Basal glucose was also reduced (p < 0.01) in desHis1Pro4Glu9Lys12FA‐glucagon treated ob/ob mice by day 10, coinciding with increases (p < 0.001) in circulating insulin. At the end of the treatment period, both analogues significantly (p < 0.05–0.01) improved oral and i.p. glucose tolerance (p < 0.05) and peripheral insulin sensitivity, increased pancreatic insulin and glucagon content (p < 0.05–0.01) and decreased (p < 0.05) cholesterol levels in HFF mice. Similarly beneficial metabolic effects on oral glucose tolerance (p < 0.01) and pancreatic insulin content (p < 0.05) were observed in ob/ob mice, especially after desHis1Pro4Glu9Lys12FA‐glucagon treatment. No significant differences in circulating triglycerides or aspects of indirect calorimetry were noted between peptide treatment groups and respective control HFF and ob/ob mice. Finally, glucagon‐mediated elevations of glucose and insulin were significantly (p < 0.05–0.01) annulled after 10 days of desHis1Pro4Glu9‐glucagon or desHis1Pro4Glu9Lys12FA‐glucagon treatment in both animal models.

Conclusion

These data indicate that peptide‐based glucagon receptor antagonists can reverse aspects of genetically and dietary‐induced obesity‐related diabetes.