Unique X-linked familial FSGS with co-segregating heart block disorder is associated with a mutation in the NXF5 gene

Focal segmental glomerulosclerosis (FSGS) is the consequence of a disease process that attacks the kidney's filtering system, causing serious scarring. More than half of FSGS patients develop chronic kidney failure within 10 years, ultimately requiring dialysis or renal transplantation. There are currently several genes known to cause the hereditary forms of FSGS (ACTN4, TRPC6, CD2AP, INF2, MYO1E and NPHS2). This study involves a large, unique, multigenerational Australian pedigree in which FSGS co-segregates with progressive heart block with apparent X-linked recessive inheritance. Through a classical combined approach of linkage and haplotype analysis, we identified a 21.19 cM interval implicated on the X chromosome. We then used a whole exome sequencing approach to identify two mutated genes, NXF5 and ALG13, which are located within this linkage interval. The two mutations NXF5-R113W and ALG13-T141L segregated perfectly with the disease phenotype in the pedigree and were not found in a large healthy control cohort. Analysis using bioinformatics tools predicted the R113W mutation in the NXF5 gene to be deleterious and cellular studies support a role in the stability and localization of the protein suggesting a causative role of this mutation in these co-morbid disorders. Further studies are now required to determine the functional consequence of these novel mutations to development of FSGS and heart block in this pedigree and to determine whether these mutations have implications for more common forms of these diseases in the general population.

A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura

Migraine with aura is a common, debilitating, recurrent headache disorder associated with transient and reversible focal neurological symptoms. A role has been suggested for the two-pore domain (K2P) potassium channel, TWIK-related spinal cord potassium channel (TRESK, encoded by KCNK18), in pain pathways and general anaesthesia. We therefore examined whether TRESK is involved in migraine by screening the KCNK18 gene in subjects diagnosed with migraine. Here we report a frameshift mutation, F139WfsX24, which segregates perfectly with typical migraine with aura in a large pedigree. We also identified prominent TRESK expression in migraine-salient areas such as the trigeminal ganglion. Functional characterization of this mutation demonstrates that it causes a complete loss of TRESK function and that the mutant subunit suppresses wild-type channel function through a dominant-negative effect, thus explaining the dominant penetrance of this allele. These results therefore support a role for TRESK in the pathogenesis of typical migraine with aura and further support the role of this channel as a potential therapeutic target.

Shouting from the ivory tower : a marketing approach to improve communication of academic research to entrepreneurs

Evidence-based practice in entrepreneurship requires effective communication of research findings. We focus on how research synopses can “promote” research to entrepreneurs. Drawing on marketing communications literature, we examine how message characteristics of research synopses affect their appeal. We demonstrate the utility of conjoint analysis in this context and find message length, media richness and source credibility to have positive influences. We find mixed support for a hypothesized negative influence of jargon, and for our predictions that participants’ involvement with academic research moderates these effects. Exploratory analyses reveal latent classes of entrepreneurs with differing preferences, particularly for message length and jargon.

No mutations detected in the INSR gene in a chromosome 19p13 linked migraine pedigree

The aim of this study was to investigate through direct sequencing the insulin receptor (INSR) gene in DNA samples from a migraine affected family previously showing linkage to chromosome 19p13 in an attempt to detect disease associated mutations. Migraine is a common debilitating disorder with a significant genetic component. At present, the number and type of genes involved in the common forms of migraine are not clear. The INSR gene on chromosome 19p13.3-13.2 is a gene of interest since a number of single nucleotide polymorphisms (SNPs) located within the gene have been implicated in migraine with (MA) and without aura (MO). Six DNA samples obtained from non-founding migraine affected members of migraine family 1 (MF1) were used in this study. Genomic DNA was sequenced for the INSR gene in exons 1-22 and the promoter region. In the six migraine family member samples, previously reported SNPs were detected within two exonic DNA coding regions of the INSR gene. These SNPs, in exons 13 and 17, do not alter the normal INSR polypeptide sequence. In addition, intron 7 also revealed a DNA base sequence variation. For the 5' untranslated promoter region of the gene, no mutations or polymorphisms were detected. In conclusion, this study detected no INSR mutations in affected members of a chromosome 19 linked migraine pedigree. Hence, migraine linkage to this chromosomal region may involve other candidate genes.

An analysis of clinical characteristics in genetically linked migraine-affected pedigrees

Migraine is a common complex disorder characterized by severe recurrent headache and usually accompanied by nausea and vomiting. Previous studies in our laboratory have utilized three large multigenerational Australian pedigrees affected with migraine to indicate that the disease is genetically heterogeneous, with linkage results implicating genomic susceptibility regions on both chromosomes 19p and Xq. The present study explores the possibility of a correlation between genetic and clinical heterogeneity in these affected pedigrees. Specifically, the clinical characteristics of migraine including subtype, age of onset, frequency, duration, and disease symptoms were compared between the migraine pedigrees, and gender differences were also assessed. Our exploratory analyses revealed no significant differences in any of the clinical characteristics tested between the chromosome 19-linked family and the two X-linked families. Also, we did not detect any differences in male vs. female clinical features for these pedigrees. In conclusion, migraine is considered to be a clinically and genetically heterogeneous disorder; however, our study provided no conclusive evidence that variation in genomic susceptibility region is related to heterogeneity at the clinical level in these migraine-affected pedigrees.

Consumer acceptance of m-wellbeing services : a social marketing perspective

Purpose This study aims to employ the Model of Goal-Directed Behaviour (MGB) to examine the consumer acceptance of technology-based self-service (TBSS) for a credence service instrumental to a social goal. Credence services are increasingly delivered via self-service technology and in social marketing, the achievement of social goals can be contingent on consumer acceptance of these services. However, little is known about the determinants of acceptance and extant marketing literature fails to account for emotional and goal influences which are likely to be important. Design/methodology/approach The authors interviewed 30 young adults with self-reported stress, anxiety or depression as potential users of a self-help mental health service delivered via mobile phone. The data were analysed deductively and inductively with the assistance of NVivo. Findings The findings generally support using the MGB to enhance understanding of consumers' acceptance of TBSS. The paper also found evidence of the importance of maintenance self-efficacy, the self-evaluation of the ability to continue using the service, and a previously ignored element of consumer level competition that arises between alternatives that achieve the same goal. Originality/value This study is the first to examine factors that influence consumers' acceptance of TBSS for credence services aimed at achieving a social goal. It builds on understanding of consumer decision making in social marketing, particularly the influence of self-efficacy and competition. It also contributes to attitudinal research by providing initial evidence for deepening and broadening the MGB in the context of TBSSs.

Evidence for an X-linked genetic component in familial typical migraine

Migraine is a common complex disorder that shows strong familial aggregation. There is a general increased prevalence of migraine in females compared with males, with recent studies indicating that migraine affects 18% of females compared with 6% of males. This preponderance of females among migraine sufferers coupled with evidence of an increased risk of migraine in first degree relatives of male probands but not in relatives of female probands suggests the possibility of an X-linked dominant gene. We report here the localization of a typical migraine susceptibility locus to the X chromosome. Of three large multigenerational migraine pedigrees two families showed significant excess allele sharing to Xq markers (P = 0.031 and P = 0.012). Overall analysis of data from all three pedigrees gave significant evidence in support of linkage and heterogeneity (HLOD = 3.1). These findings provide conclusive evidence that familial typical migraine is a heterogeneous disorder. We suggest that the localization of a migraine susceptibility locus to the X chromosome could in part explain the increased risk of migraine in relatives of male probands and may be involved in the increased female prevalence of this disorder.

The B subunit of coagulation factor XIII is linked to renin and the Duffy blood group to α-spectrin on human chromosome 1

Family linkage studies were used to detect two linkage relationships on human chromosome 1. The B subunit of coagulation factor XIII showed significant linkage to renin with a maximum lod score of 5.071 at a distance of 10 cM. Significant linkage was also shown between the Duffy blood group and α-spectrin with linkage results giving a combined lod score of 3.194 at 5 cM.

An introduction to the application of (case 1) best–worst scaling in marketing research

We review and discuss recent developments in best–worst scaling (BWS) that allow researchers to measure items or objects on measurement scales with known properties. We note that BWS has some distinct advantages compared with other measurement approaches, such as category rating scales or paired comparisons. We demonstrate how to use BWS to measure subjective quantities in two different empirical examples. One of these measures preferences for weekend getaways and requires comparing relatively few objects; a second measures academics' perceptions of the quality of academic marketing journals and requires comparing a significantly large set of objects. We conclude by discussing some limitations and future research opportunities related to BWS.

Destination marketing organizations and destination marketing : a narrative analysis of the literature

This article presents the first narrative analysis of the areas of research that have developed within the destination marketing field since its commencement in 1973. Given the broad extent of the field, and the absence of any previous reviews in four decades, a key challenge is in providing a focus for such a disparate body of knowledge. The review is structured around one principal question: ‘To what extent is the Destination Marketing Organisation (DMO) responsible for the competitiveness of the destination’? In pursuit of this underlying question, we address a number of themes including nomenclature and the DMO, the evolution of the destination marketing literature, competitiveness as the DMO reason d’être, and DMO effectiveness including issues of branding and positioning, and future research themes in the field.

Cross-linked poly(trimethylene carbonate-co-L-lactide) as a biodegradable, elastomeric scaffold for vascular engineering applications

A series of copolymers of trimethylene carbonate (TMC) and l-lactide (LLA) were synthesized and evaluated as scaffolds for the production of artificial blood vessels. The polymers were end-functionalized with acrylate, cast into films, and cross-linked using UV light. The mechanical, degradation, and biocompatibility properties were evaluated. High TMC polymers showed mechanical properties comparable to human arteries (Young’s moduli of 1.2–1.8 MPa and high elasticity with repeated cycling at 10% strain). Over 84 days degradation in PBS, the modulus and material strength decreased gradually. The polymers were nontoxic and showed good cell adhesion and proliferation over 7 days using human mesenchymal stem cells. When implanted into the rat peritoneal cavity, the polymers elicited formation of tissue capsules composed of myofibroblasts, resembling immature vascular smooth muscle cells. Thus, these polymers showed properties which were tunable and favorable for vascular tissue engineering, specifically, the growth of artificial blood vessels in vivo.

Buzz in motion pictures : what is buzz and how can marketing create it?

In the movie industry, the extraordinarily successful theatrical performance of certain films is largely attributed to buzz. Despite longstanding commentary about the role of buzz in successful movie marketing and the belief that it accelerates new product diffusion, limited scholarly evidence exists to support these assertions. This is primarily due to the lack of conceptual distinction of buzz from word-of-mouth, which is often used as the main basis for conceptualising buzz. However, word-of-mouth does not fully explain the buzz surrounding films such as 'Gone With The Wind', 'The Dark Knight' and 'Avatar'. Informed by valuable insights from key experts who have launched some of the most successful movies in box office history, as well as a range of moviegoers, this thesis developed a deeper understanding of what buzz is and how it is created. This thesis concludes that buzz is not the same as word-of-mouth.

Fresh ideas : services thinking for social marketing

Purpose The social marketing literature tends to focus on upstream marketing (policy) and downstream (individual behaviour change) and has a limited view on midstream (working with partners and community groups) social marketing. The paper proposes midstream social marketing should also include an understanding of how services and service employees influence and support individual behaviour change goals. The paper presents four key services marketing principles - derived from services theory and thinking - which the paper believes to be essential for implementing effective midstream social marketing. Design/methodology/approach This is a conceptual paper that uses service theory and case-examples to show how service thinking can be used as a midstream social marketing approach. Findings For effective uptake and impact of social marketing services amongst people and populations, social marketers need to design programs that consider the service experience, the service employee, service quality/customer value and the active role of the customer in value creation. Research limitations/implications Services marketing is a well-established sub-discipline of marketing which, until recently, has not interacted with social marketing. The extension and application of services theory for social marketing can enrich and propel the social marketing discipline forward. Further research is recommended to evaluate how service principles can be applied in practice. Social implications Given that social marketing services tend not to be accessed in sufficient numbers by the people who most need them, social marketers need to think beyond the technical, cognitive, and organisational-focused goals when designing social services. Originality/value This paper identifies key service theories that social marketers should understand and use and is thus a source of fresh ideas for theory and practice.

The value of health and wellbeing : an empirical model of value creation in social marketing

Purpose The purpose of this paper is to investigate the role of multiple actors in the value creation process for a preventative health service, and observe the subsequent impact on key service outcomes of satisfaction and customer behaviour intentions to use a preventative health service again in the future. Design/methodology/approach An online self-completion survey of Australian women (n=797) was conducted to test the proposed framework in the context of a free, government-provided breastscreening service. Data were analysed using Structural Equation Modelling (SEM). Findings The findings indicate that functional and emotional value are created from organisational and customer resources. These findings indicate that health service providers and customers are jointly responsible for the successful creation of value, leading to desirable outcomes for all stakeholders. Practical implications The results highlight to health professionals the aspects of service that can be managed in order to create value with target audiences. The findings also indicate the importance of the resources provided by users in the creation of value, signifying the importance of customer education and management. Originality/value This study provides a significant contribution to social marketing through the provision of an empirically validated model of value creation in a preventative health service. The model demonstrates how the creation and provision of value can lead to the achievement of desirable social behaviours - a key aim of social marketing.

Moderating teen drinking : combining social marketing and education

Purpose This paper outlines a pilot study that was undertaken in Australia in 2011 that combined social marketing with education. An intervention targeting 14-16 year olds to influence attitudes and behavioural intentions towards moderate drinking was developed and tested. Game On:Know alcohol (GO:KA) is a six-module intervention that is delivered to a year level cohort in an auditorium. GO:KA combines a series of online and offline experiential activities to engage (with) students. Design/methodology Following social marketing benchmark criteria, formative research and competitive analysis were undertaken to create, implement and evaluate an intervention. The intervention was delivered in one all boys' and one all girls' school in April and June 2011, respectively. A total of 223 Year 10 students participated in GO:KA with the majority completing both pre- and post-surveys. Paired samples t-tests and descriptive analysis were used to assess attitudinal and behavioural intention change. Findings Attitudinal change was observed in both schools while behavioural intentions changed for girls and not boys according to paired samples t-testing. Post hoc testing indicated gender differences. Research limitations The lack of a control group is a key limitation of the current research that can be overcome in the 20 school main study to be conducted in 2013-2015. Originality/value The current study provides evidence to suggest that a combined social marketing and education intervention can change teenage attitudes towards moderate drinking whilst only changing behavioural intentions for female teenagers. Analysis of the intervention provides insight into gender differences and highlights the need for a segmented approach.