Pharmacogenetics of migraine : genetic variants and their potential role in migraine therapy

Migraine is a paroxysmal neurological disorder affecting up to 6% of males and 18% of females in the general population, and has been demonstrated to have a strong, but complex, genetic component. Genetic investigation of migraine provides hope that new targets for medications and individual specific therapy will be developed. The identification of polymorphisms or genetic biomarkers for disease susceptibility and treatment should aid in providing a better understanding of migraine pathology and, consequently, more appropriate and efficient treatment for migraineurs. In this review, we will discuss results investigating genetic biomarkers for migraine and their potential role in future therapy planning.

No role for estrogen receptor 1 gene intron 1 Pvu II and exon 4 C325G polymorphisms in migraine susceptibility

Background We have previously reported an association between the estrogen receptor 1 (ESR1) gene exon 8 G594A polymorphism and migraine susceptibility in two independent Australian cohorts. In this paper we report results of analysis of two further single nucleotide polymorphisms (SNPs) in the ESR1 gene in the same study group, the T/C Pvu II SNP in intron 1 and the C325G SNP in exon 4, as well as results of linkage disequilibrium (LD) analysis on these markers. Methods We investigated these variants by case-control association analysis in a cohort of 240 migraineurs and 240 matched controls. The SNPs were genotyped using specific restriction enzyme assays. Results were analysed using contingency table methods incorporating the chi-squared statistic. LD results are presented as D' statistics with associated P values. Results We found no evidence for association of the Pvu II T/C polymorphism and the C325G polymorphism and migraine susceptibility and no evidence for LD between these two SNPs and the previously implicated exon 8 G594A marker. Conclusion We have found no role for the polymorphisms in intron 1 and exon 4 with migraine susceptibility. To further investigate our previously implicated exon 8 marker, we suggest the need for studies with a high density of polymorphisms be undertaken, with particular focus on markers in LD with the exon 8 marker.

The role of vascular and hormonal genes in migraine susceptibility

Migraine is a primary headache disorder that involves both genetic and environmental components. Migraine is considered to be a polygenic disorder with a number of susceptibility genes having a minor but nonetheless significant impact on susceptibility. Migraine candidate gene studies have concentrated mainly on genes involved in neurotransmitter pathways, however evidence also exists for a role for alterations in vascular and hormonal function in migraine susceptibility. We present here a mini-review of genetic studies, investigating the potential role of vascular and hormonal gene variants, and discuss how vascular and hormonal dysfunction may impact on migraine susceptibility. We propose that the potential role of vascular and hormonal genes in this disorder warrants further investigation.

The role of adenosine-related genes variants in susceptibility to essential hypertension

OBJECTIVE: To test markers within adenosine-related genes: A1 and A2a receptors (ADORA1, ADORA2a) and adenosine deaminase (ADA) for potential involvement in essential hypertension (EH). DESIGN: Case-control association study investigating gene variants for the ADORA1, ADORA2a and ADA genes. PARTICIPANTS: The study used a cohort of 249 unrelated hypertensive individuals who were diagnosed with hypertension, and an age, sex and ethnically matched group of 249 normotensive controls. RESULTS: The association analysis indicated that both allele and genotype frequencies did not differ significantly between the case and control groups (P > 0.05) for any of the markers tested. CONCLUSION: The adenosine-related gene variants do not appear to alter susceptibility to the disease in this group of essential hypertensives. However, involvement of these genes and the adenosine system cannot be conclusively excluded from essential hypertension pathogenesis as other gene variants may still be involved.

The role of psychological and physiological factors in decision making under risk and in a dilemma

We study the difference in the result of two different risk elicitation methods by linking estimates of risk attitudes to gender, age, personality traits, a decision in a dilemma situation, and physiological states measured by heart rate variability (HRV). Our results indicate that differences between the methods can partly be explained by gender, but not by personality traits. Furthermore, HRV is linked to risktaking in the experiment for at least one of the methods, indicating that more stressed individuals display more risk aversion. Finally, we and that risk attitudes are not predictive of the ability to decide in a dilemma, but personality traits are. Surprisingly, there is also no apparent relationship between the physiological state during the dilemma situation and the ability to make a decision.

Role salience and support as moderators of demand/conflict relationships in China

This study examined the effects of role demand on both work–family conflict and family–work conflict, and the moderating effects of role salience and support on these relationships. Based on 391 dual-career (managerial and blue-collar employees) couples from a Taiwanese company in China, the results of this survey study showed clear gender differences in the patterns of relationships observed. For men, the most important demands that negatively impacted on work–family conflict were frequency of overtime and frequency of socializing for work purposes (yingchou), and supervisory support buffered the negative impact of frequent overtime. For women however, strong supervisory support and low work role salience were more important for reducing work–family conflict, and there was no significant main effect found for any of the role demand factors. Furthermore, women with high work role salience were more likely to feel the impact of yingchou on work–family conflict. In the family domain, the most influential demand for men was hours spent on household tasks, but for women, it was the frequency of family-related leave. Interestingly, males reported higher family role salience than females and spouse support intensified rather than buffered the positive impact of hours spent on household tasks on family–work conflict for males.

Evaluating patient presentations for care delivered by emergency nurse practitioners : a retrospective analysis of 12 months

Background The delivery of quality patient care in the emergency department (ED) is emerging as one of the most important service indicators to be measured in health services today. The emergency nurse practitioner role was implemented as a service innovation in a Emergency & Trauma Centre (ETC), Melbourne, Australia, in July 2004 .The primary aim of the role was intended to enhance healthcare services, improve the efficiency and timely delivery of high quality care to patients. Aim To conduct a retrospective study of patient presentations at the ETC to obtain a profile of the characteristics of patients managed by emergency nurse practitioners. Specifically the objectives of the study were to: 1) examine the demographics of the patient population 2) evaluate data on emergency department service indicators for this patient cohort Method All patients presenting to the ETC from January 01 2011 to December 31 2011 and managed by emergency nurse practitioners were included in the review. Data collection included baseline demographics, waiting times to be seen, length of stay, emergency department discharge diagnoses and referral patterns. Data were extracted and imported directly from the emergency department Patient Information System (Cerner log), for the specified time frame. Results A total of 5212 patients were reviewed in the study period. The median age of patients was 35 years and 61% of patients were male. The most common discharge diagnosis was open wounds to hand/wrist. Waiting times to be seen by the emergency nurse practitioner were 14 minutes and length of stay for patients with a discharge disposition of home were 122 minutes. Conclusions This study has provided information on patient baseline characteristics and performance on important service indicators for this patient sample that will inform further research to evaluate specific outcomes of the emergency nurse practitioner service.

Examination of the role of nitric oxide synthase and renal kallikrein as candidate genes for essential hypertension

Nitric oxide synthase and renal kallikrein are both involved in blood pressure regulation. Genes for these enzymes may, therefore, be considered candidates for hypertension pathogenesis. 2. In the present study, genotypes for nitric oxide synthase and renal kallikrein microsatellite markers were determined in a cross-sectional association analysis of hypertensive patients and normotensive control subjects. 3. Results from this study did not indicate an association of either of the candidate gene polymorphisms with essential hypertension. Hence, findings for this study do not support a role for these genes in human hypertension.

The biology of the glutamatergic system and potential role in migraine

Migraine is a common genetically linked neurovascular disorder. Approximately ~12% of the Caucasian population are affected including 18% of adult women and 6% of adult men (1, 2). A notable female bias is observed in migraine prevalence studies with females affected ~3 times more than males and is credited to differences in hormone levels arising from reproductive achievements. Migraine is extremely debilitating with wide-ranging socioeconomic impact significantly affecting people's health and quality of life. A number of neurotransmitter systems have been implicated in migraine, the most studied include the serotonergic and dopaminergic systems. Extensive genetic research has been carried out to identify genetic variants that may alter the activity of a number of genes involved in synthesis and transport of neurotransmitters of these systems. The biology of the Glutamatergic system in migraine is the least studied however there is mounting evidence that its constituents could contribute to migraine. The discovery of antagonists that selectively block glutamate receptors has enabled studies on the physiologic role of glutamate, on one hand, and opened new perspectives pertaining to the potential therapeutic applications of glutamate receptor antagonists in diverse neurologic diseases. In this brief review, we discuss the biology of the Glutamatergic system in migraine outlining recent findings that support a role for altered Glutamatergic neurotransmission from biochemical and genetic studies in the manifestation of migraine and the implications of this on migraine treatment.

Entrepreneurial growth : the role of international knowledge acquisition as moderated by firm age

In line with repeated recent calls for research on specific forms of growth rather than on an undifferentiated notion of “total growth,” our study contributes to the understanding of entrepreneurial growth. By this we mean growth through expansion into new geographic markets and/or via the introduction of new products or services. Building on Penrose's theory of the growth of the firm and on the research streams she has in part inspired, we investigate the impact of knowledge acquisition from international markets on entrepreneurial growth both at home and abroad. We further suggest that the effects of international knowledge acquisition on entrepreneurial growth will vary with firm age. Utilizing longitudinal data on 138 small and medium-sized enterprises (SMEs), we find that the acquisition of knowledge from international markets fuels growth through market development, and that this effect is stronger for international expansion than domestic expansion. Our results also show that firm age negatively moderates the relationship between international knowledge acquisition and entrepreneurial growth via the introduction of new products or services. Specifically, international knowledge acquisition has a positive effect on growth via new products/services development in young firms, but a negative effect in mature firms. We assume this reflects changes over time in how international knowledge is managed.

Role of hydraulic factors in constructed wetland and bioretention basin treatment performance

This research project contributed to the in-depth understanding of the influence of hydrologic and hydraulic factors on the stormwater treatment performance of constructed wetlands and bioretention basins in the "real world". The project was based on the comprehensive monitoring of a Water Sensitive Urban Design treatment train in the field and underpinned by complex multivariate statistical analysis. The project outcomes revealed that the reduction in pollutant concentrations were consistent in the constructed wetland, but was highly variable in the bioretention basin to a range of influential factors. However, due to the significant amount retention within the filter media, all pollutant loadings were reduced in the bioretention basin.

Local development planning and community empowerment in decentralised Indonesia : the role of local planning in improving self organising capabilities of local communities in Takalar, Indonesia

This study investigates the role of development planning in empowering rural communities in Indonesia’s decentralised era. Evidence is produced that the combination of procedural justice in planning development and social learning in its implementation can assist self-organisation and help empower local communities. Significant benefits are shown to result in: the acquisition and use of collective resources; the development of shared knowledge, skills, values and trust; community leadership; and the development of social networks. Two features of this empowerment model are community-based planning, utilising participatory rural appraisal at the level of the natural village, and the organisation of collective action. These are shown to be effective ways of incorporating procedural justice and social learning in self organisation and community empowerment.

Inside the research incubator : a case study of an intensive undergraduate research experience for nursing and midwifery students

Undergraduate research experiences are an increasing component of nursing and midwifery degrees. The Summer Research Scholarship Programme (SRSP) is a tertiary education initiative in Australia to provide an intensive undergraduate research experience. Between 2009 and 2010, six students and four academic faculty mentors in School of Nursing and Midwifery participated in an inaugural SRSP. This study explores the experiences of both students and faculty mentors to determine how this undergraduate research experience impacted student learning and interest in research. A qualitative case study approach was used to explore the research experiences of undergraduate student and faculty participants in an inaugural undergraduate research programme. Based on the results of two surveys four main themes were identified: (1) acquisition of research skills, (2) expectations, (3) academic engagement, and (4) continued interest in research. An intensive undergraduate research experience is a valuable component of student learning that has the capacity to contribute to immediate and longer-term learning and research outcomes.

The role of HRM practices in building intellectual capital in knowledge-based teams

In this paper, we investigate the ways HRM systems support development of intellectual capital in teams in three case studies of knowledge-intensive firms (KIFs) in Denmark. By focusing on team composition and structure, findings build on the rapidly growing body of literature on HRM’s role in supporting intellectual capital development. Specifically, we make a theoretical contribution to this literature by identifying three distinct ways KIFs develop intellectual capital: 1) through HRM development systems that build relationship-centric team-based intellectual capital by targeting development of social capital; 2) through HRM employee relations systems that build human-centric team based intellectual capital by targeting human capital; 3) through a balanced approach to HRM that builds polycentric team-based intellectual capital through focusing on all aspects of intellectual capital. The findings also have managerial implications regarding the need to align team composition and structure, HRM systems, and intellectual capital focus to support development of team-based intellectual capital.

International acclaim : the role(s) of the international film festival in supporting emerging women’s cinema

International Film Festivals act as important sites for the exhibition of contemporary world cinema. Film festivals represent an increasingly transnational film culture, where audiences, filmmakers, distributors, press, critics and academics come together from all over the world to discover new films, network with one another and debate about the past, present and future of cinema. This research project investigates the role that international film festivals play within the wider international film industry, with a specific focus on emerging women filmmakers. It therefore explores the arena of contemporary women.s cinema at its intersection with the international film festival industry. The significance and original contribution of the research is its intervention in the growing field of film festival studies through a specific investigation of how international film festivals support emerging women filmmakers. The positioning of the research at the intersection of feminist film theory and festival research within the broader context of transnational cinema allows the examination of each festival, the attending filmmakers and their films to be addressed within a more refined and nuanced lens. A core method for the thesis is the close textual analysis of particular emerging women filmmakers. films which are screened at the respective festivals. The research also utilises the qualitative research strategies of the case study and the interview to ¡°seek to understand the context or setting of the participants through visiting this context and gathering information personally¡± (Creswell 2003, 9). The textual analysis is used in dialogue with the interviews and the participant observational data gathering to provide a related context for understanding these films and their cultural meanings, both personally for the filmmaker and transnationally across the festival circuit. The focus of the case studies is the Brisbane International Film Festival, the International Film Festival Rotterdam and the Toronto International Film Festival. These three festivals were chosen for their distinct geographical locations in the Asia Pacific, Europe and North America, as well as for their varying size and influence on the international film festival circuit. Specifically, I investigate the reasons behind why the organisers of a particular festival have chosen a certain woman.s film, how it is then packaged or displayed within the programme, and how all of this impacts on the filmmaker herself. The focus of my research is to investigate film festivals and their .real-life. applications and benefits for the filmmakers being supported, both through the exhibition of their films and through their attendance as festival guests. The research finds that the current generation of emerging women filmmakers has varying levels of experience and success at negotiating the international film festival circuit. Each of the three festivals examined include and promote the films of emerging women filmmakers through a range of strategies, such as specific programming strands dedicated to showcasing emerging talent, financial support through festival funds, providing visibility within the programme, exposure to international audiences and networking opportunities with industry professionals and other filmmakers. Furthermore, the films produced by the emerging women filmmakers revealed a strong focus on women.s perspectives and experiences, which were explored through the interweaving of particular aesthetic and cinematographic conventions.