Translating vision research into policy and practice to improve visibility, and hence safety, of road workers at night

This case study report describes the stages involved in the translation of research on night-time visibility into standards for the safety clothing worn by roadworkers. Vision research demonstrates that when lights are placed on the moveable joints of the body and the person moves in a dark setting, the phenomenon known as “biological motion or biomotion” occurs, enabling rapid and accurate recognition of the human form although only the lights can be seen. QUT was successful in gaining funding from the Australian Research Council for a Linkage grant due to the support of the predecessors of the Queensland Department of Transport and Main Roads (TMR) to research the biomotion effect in on-road settings using materials that feature in roadworker clothing. Although positive results were gained, the process of translating the research results into policy, practices and standards relied strongly on the supportive efforts of TMR staff engaged in the review and promulgation of national standards. The ultimate result was the incorporation of biomotion marking into AS/NZS 4602.1 2011. The experiences gained in this case provide insights into the processes involved in translating research into practice.

Critical Factors for Sustainable Post Natural Disaster Reconstruction : Chinese Data

While scientists continue to explore the level of climate change impact to new weather patterns and our environment in general, there have been some devastating natural disasters worldwide in the last two decades. Indeed natural disasters are becoming a major concern in our society. Yet in many previous examples, our reconstruction efforts only focused on providing short-term necessities. How to develop resilience in the long run is now a highlight for research and industry practice. This paper introduces a research project aimed at exploring the relationship between resilience building and sustainability in order to identify key factors during reconstruction efforts. From extensive literature study, the authors considered the inherent linkage between the two issues as evidenced from past research. They found that sustainability considerations can improve the level of resilience but are not currently given due attention. Reconstruction efforts need to focus on resilience factors but as part of urban development, they must also respond to the sustainability challenge. Sustainability issues in reconstruction projects need to be amplified, identified, processed, and managed properly. On-going research through empirical study aims to establish critical factors (CFs) for stakeholders in disaster prone areas to plan for and develop new building infrastructure through holistic considerations and balanced approaches to sustainability. A questionnaire survey examined a range of potential factors and the subsequent data analysis revealed six critical factors for sustainable Post Natural Disaster Reconstruction that include: considerable building materials and construction methods, good governance, multilateral coordination, appropriate land-use planning and policies, consideration of different social needs, and balanced combination of long-term and short-term needs. Findings from this study should have an influence on policy development towards Post Natural Disaster Reconstruction and help with the achievement of sustainable objectives.

Factors associated with suboptimal adherence to antiretroviral therapy in Viet Nam: A cross-sectional study using audio computer-assisted self-interview (ACASI)

Background: Optimal adherence to antiretroviral therapy (ART) is necessary for people living with HIV/AIDS (PLHIV). There have been relatively few systematic analyses of factors that promote or inhibit adherence to antiretroviral therapy among PLHIV in Asia. This study assessed ART adherence and examined factors associated with suboptimal adherence in northern Viet Nam. Methods: Data from 615 PLHIV on ART in two urban and three rural outpatient clinics were collected by medical record extraction and from patient interviews using audio computer-assisted self-interview (ACASI). Results: The prevalence of suboptimal adherence was estimated to be 24.9% via a visual analogue scale (VAS) of past-month dose-missing and 29.1% using a modified Adult AIDS Clinical Trial Group scale for on-time dose-taking in the past 4 days. Factors significantly associated with the more conservative VAS score were: depression (p < 0.001), side-effect experiences (p < 0.001), heavy alcohol use (p = 0.001), chance health locus of control (p = 0.003), low perceived quality of information from care providers (p = 0.04) and low social connectedness (p = 0.03). Illicit drug use alone was not significantly associated with suboptimal adherence, but interacted with heavy alcohol use to reduce adherence (p < 0.001). Conclusions: This is the largest survey of ART adherence yet reported from Asia and the first in a developing country to use the ACASI method in this context. The evidence strongly indicates that ART services in Viet Nam should include screening and treatment for depression, linkage with alcohol and/or drug dependence treatment, and counselling to address the belief that chance or luck determines health outcomes.

Improving the measurement and surveillance of child abuse in Queensland emergency departments

There are no population studies of prevalence or incidence of child maltreatment in Australia. Child protection data gives some understanding but is restricted by system capacity and definitional issues across jurisdictions. Child protection data currently suggests that numbers of reports are increasing yearly, and the child protection system then becomes focussed on investigating all reports and diluting available resources for those children who are most in need of intervention. A public health response across multiple agencies enables responses to child safety across the entire population. All families are targeted at the primary level; examples include ensuring all parents know the dangers of shaking a baby or teaching children to say no if a situation makes them uncomfortable. The secondary level of prevention targets families with a number of risk factors, for example subsidised child care so children aren't left unsupervised after school when both parents have to be at work or home visiting for drug-addicted parents to ensure children are cared for. The tertiary response then becomes the responsibility of the child protection system and is reserved for those children where abuse and neglect are identified. This model requires that child safety is seen in a broader context than just the child protection system, and increasingly health professionals are being identified as an important component in the public health framework. If all injury is viewed as preventable and considered along a continuum of 'accidental' through to 'inflicted', it becomes possible to conceptualise child maltreatment in an injury context. Parental intent may not be to cause harm to the child, but by lack of insight or concern about risk, the potential for injury is high. The mechanisms for unintentional and intentional injury overlap and some suggest that by segregating child abuse (with the possible exception of sexual abuse) from unintentional injury, child abuse is excluded from the broader injury prevention initiative that is gaining momentum in the community. This research uses a public health perspective, specifically that of injury prevention, to consider the problem of child abuse. This study employed a mixed method design that incorporates secondary data analysis, data linkage and structured interviews of different professional groups. Datasets from the Queensland Injury Surveillance Unit (QISU) and The Department of Child Safety (DCS) were evaluated. Coded injury data was grouped according to intent of injury according to those with a code that indicated the ED presentation was due to child abuse, a code indicating that the injury was possibly due to abuse or, in the third group, the intent code indicated that the injury was unintentional and not due to abuse. Primary data collection from ED records was undertaken and information recoded to assess reliability and completeness. Emergency department data (QISU) was linked to Department of Child Safety Data to examine concordance and data quality. Factors influencing the collection and collation of these data were identified through structured interview methodology and analysed using qualitative methods. Secondary analysis of QISU data indicated that codes lacking specific information on the injury event were more likely to also have an intent code indicating abuse than those records where there was specific information on the injury event. Codes for abuse appeared in only 1.2% of the 84,765 records analysed. Unintentional injury was the most commonly coded intent (95.3%). In the group with a definite abuse code assigned at triage, 83% linked to a record with DCS and cases where documentation indicated police involvement were significantly more likely to be associated with a DCS record than those without such documentation. In those coded with an unintentional injury code, 22% linked to a DCS record with cases assigned an urgent triage category more likely to link than those with a triage category for resuscitation and children who presented to regional or remote hospitals more likely to link to a DCS record than those presenting to urban hospitals. Twenty-nine per cent of cases with a code indicating possible abuse linked to a DCS record. In documentation that indicated police involvement in the case, a code for unspecified activity when compared to cases with a code indicating involvement in a sporting activity and children less than 12 months of age compared to those in the 13-17 year old age group were all variables significantly associated with linkage to a DCS record. Only 13% of records contained documentation indicating that child abuse and neglect were considered in the diagnosis of the injury despite almost half of the sample having a code of abuse or possible abuse. Doctors and nurses were confident in their knowledge of the process of reporting child maltreatment but less confident about identifying child abuse and neglect and what should be reported. Many were concerned about implications of reporting, for the child and family and for themselves. A number were concerned about the implications of not reporting, mostly for the wellbeing of the child and a few in terms of their legal obligations as mandatory reporters. The outcomes of this research will help improve the knowledge of barriers to effective surveillance of child abuse in emergency departments. This will, in turn, ensure better identification and reporting practises; more reliable official statistical collections and the potential of flagging high-risk cases to ensure adequate departmental responses have been initiated.

Environmental education through listening to children

Environmental education centres contribute to schools and communities in Environmental Education and Education for Sustainability through nature and urban -based, experiential learning and action learning approaches. An underlying assumption of these centres is that intensive, short-term, outdoor/environmental education experiences can change key attitudes and/or actions leading to positive environmental behaviour. This study reflects the interests of a researching professional who investigated aspects of a program that he designed and implemented as principal of an environmental education centre. Most evaluations of similar programs have used quasi-experimental designs to measure the program outcomes. However, this study considered the experiences of the program from the perspectives of a group of key stakeholders often overlooked in the literature; the children who participated in the program. This study examined children’s accounts of their own experiences in order to contribute new understandings of children’s perspectives and how they can be considered when designing and implementing environmental education programs. This research drew on key theoretical assumptions derived from the sociology of childhood. Within sociology of childhood, children are considered to be competent practitioners within their social worlds, who, through their talk and interaction, participate actively in the construction of their own social situations. This approach also views children as capable and competent learners who construct their knowledge through everyday participation in social experiences. This study set out to generate children’s own accounts of their experiences of a five day residential program at the Centre. In total, 54 children participated in the study that used a multi-faceted data collection approach that included conversations, drawings, photographs and journal writing. Using content analysis, data were analysed by means of an inductive approach to develop themes related to the children’s perspectives of their experiences. Three interrelated and co-dependent components of the experience emerged from the analysis; space and place; engagement and participation; and responsiveness and reflection. These components co-exist and construct the conditions for effective experiences in environmental education at the Centre. The first key finding was the emphasis that the children placed on being provided with somewhere where they could feel safe and comfortable to interact with their environment and engage in a range of outdoor experiences. The children identified that place was an outdoor classroom where they could participate in first-hand experiences and, at times, explore out-of-bound spaces; that is, a place where they had previously been limited, often by adults, in their opportunities to interact with nature. A second key finding was the emphasis that the children placed on engagement and participation in environmental experience. The children described participating in a range of new primary experiences that involved first-hand, experiences and also described participating in collaborative experiences that involved interacting with peers and with teachers, who appeared to behave differently to how they behaved at school. Finally, the children described a different type of interactional relationship with teachers, comparing the active educational role they played on camp to a more passive role at school where they sat at a table and the teacher wrote on the board. The final key finding was the emphasis that the children placed on responsiveness and reflection in the experience. In responding to their experiences, the children described the fun and excitement, confidence and satisfaction that they gained from the experience. The children also identified how their experiences contributed to the development of a caring-for-nature attitude and the value of a disorienting dilemma in promoting responsiveness to the environment. This disorienting dilemma was an event that caused the children to reassess their own beliefs and attitudes. From the three main findings, a theoretical framework that represented the children’s accounts of their experiences and a pedagogic approach that respected their accounts was developed. This pedagogic approach showed how a disorienting dilemma could create a disequilibrium in relation to a child’s existing ideas and experiences. As a result, children were challenged to reflect upon their existing environmental beliefs and practices. The findings of this research have implications for the field of environmental education. Adopting sociology of childhood provides an alternative foundation to research and can present a deeper understanding of what children believe, than an approach that relies solely on using scientific methods to undercover and analyse these understandings. This research demonstrates the value of gaining children’s accounts to assist educators to design environmental education programs as it can offer more than adult and educator perspectives. This study also provides understandings of environmental education practice by describing how the children engaged with informal learning situations. Finally, two sets of recommendations, drawn from this study, are made. The first set considers nine recommendations about and for future research and the second relates to redesigning of the environmental educational program at the research site, with six recommendations made.

Land use planning and the airport metropolis

Australian airports have emerged as important urban activity centres over the past decade as a result of privatisation. A range of reciprocal airport and regional impacts now pose considerable challenges for both airport operation and the surrounding urban and regional environment. The airport can no longer be managed solely as a specialised transport entity in isolation from the metropolis that it serves. In 2007 a multidisciplinary Australian Research Council Linkage Project (LP 0775225) was funded to investigate the changing role of airports in Australia. This thesis is but one component of this collaborative research effort. Here the issues surrounding the policy and practice of airport and regional land use planning are explored, analysed and detailed. This research, for the first time, assembles a distinct progression of the wider social, economic, technological and environmental roles of the airport within the Australian airport literature from 1914 – 2011. It recognises that while the list of airport and regional impacts has grown through time, treatment within practice and the literature has largely remained highly specialised and contained within disciplinary paradigms. The first publication of the thesis (Chapter 2) acknowledges that the changing role of airports demands the establishment of new models of airport planning and development. It argues that practice and research requires a better understanding of the reciprocal impacts of airports and their urban catchments. The second publication (Chapter 3) highlights that there is ad hoc examination and media attention of high profile airport and regional conflict, but little empirical analysis or understanding of the extent to which all privatised Australian airports are intending to develop. The conceptual and methodological significance of this research is the development of a national land use classification system for on-airport development. This paper establishes the extent of on-airport development in Australia, providing insight into the changing land use and economic roles of privatised airports. The third publication (Chapter 4) details new and significant interdependencies for airport and regional development in consideration of the progression of airports as activity centres. Here the model of an ‘airport metropolis’ is offered as an organising device and theoretical contribution for comprehending the complexity and planning of airport and regional development. It delivers a conceptual framework for both research and policy, which acknowledges the reciprocal impacts of economic development, land use, infrastructure and governance ‘interfaces’. In a timely and significant concurrence with this research the Australian Government announced and delivered a National Aviation Policy Review (2008 – 2009). As such the fourth publication (Chapter 5) focuses on the airport and urban planning aspects of the review. This paper also highlights the overall policy intention of facilitating broader airport and regional collaborative processes. This communicative turn in airport policy is significant in light of the communicative theoretical framework of the thesis. The fifth paper of the thesis (Chapter 6) examines three Australian case studies (Brisbane, Adelaide and Canberra) to detail the context of airport and regional land use planning and to apply the airport metropolis model as a framework for research. Through the use of Land Use Forums, over 120 airport and regional stakeholders are brought together to detail their perspectives and interactions with airport and regional land use planning. An inductive thematic analysis of the results identifies three significant themes which contribute to the fragmentation of airport and regional and land use planning: 1) inadequate coordination and disjointed decision-making; 2) current legislative and policy frameworks; and 3) competing stakeholder priorities and interests. Building on this new knowledge, Chapter 7 details the perceptions of airport and local, state and territory government stakeholders to land use relationships, processes and outcomes. A series of semi-structured interviews are undertaken in each of the case studies to inform this research. The potential implications for ongoing communicative practice are discussed in conclusion. The following thesis represents an incremental and cumulative research process which delivers new knowledge for the practical understanding and research interpretation of airport and regional land use planning practice and policy. It has developed and applied a robust conceptual framework which delivers significant direction for all stakeholders to better comprehend the relevance of airports in the urban character and design of our cities.

Robust automatic speaker linking and attribution

This research makes a major contribution which enables efficient searching and indexing of large archives of spoken audio based on speaker identity. It introduces a novel technique dubbed as “speaker attribution” which is the task of automatically determining ‘who spoke when?’ in recordings and then automatically linking the unique speaker identities within each recording across multiple recordings. The outcome of the research will also have significant impact in improving the performance of automatic speech recognition systems through the extracted speaker identities.

Understanding IT value : a multilevel, complex, and adaptive system perspective

One remaining difficulty in the Information Technology (IT) business value evaluation domain is the direct linkage between IT value and the underlying determinants of IT value or surrogates of IT value. This paper proposes a research that examines the interacting effects of the determinants of IT value, and their influences on IT value. The overarching research question is how those determinants interact with each other and affect the IT value at organizational value. To achieve this, this research embraces a multilevel, complex, and adaptive system view, where the IT value emerges from the interacting of underlying determinants. This research is theoretically grounded on three organizational theories – multilevel theory, complex adaptive systems theory, and adaptive structuration theory. By integrating those theoretical paradigms, this research proposes a conceptual model that focuses on the process where IT value is created from interactions of those determinants. To answer the research question, agent-based modeling technique is used in this research to build a computational representation based on the conceptual model. Computational experimentation will be conducted based on the computational representation. Validation procedures will be applied to consolidate the validity of this model. In the end, hypotheses will be tested using computational experimentation data.

Contributing factors to optimal project portfolio selection

A modified Delphi approach has been applied in this study to investigate best practice and to determine the factors that contribute to optimal selection of projects. There are various standards and practices that some may recognise as representing best practice in this area. Many of these have similar characteristics and this study has found no single best practice. The study identified the factors that contribute to the optimal selection of projects as: culture, process, knowledge of the business, knowledge of the work, education, experience, governance, risk awareness, selection of players, preconceptions, and time pressures. All these factors were found to be significant; to be appropriate to public sector organisations, private sector organisations and government owned corporations; and to have a strong linkage to research on strategic decision making. These factors can be consolidated into two underlying factors of organisation culture and leadership.

Gestational Diabetes Mellitus in Far North Queensland, Australia, 2004 to 2010 : midwives’ perinatal data most accurate source

Objectives: This study examines the accuracy of Gestational Diabetes Mellitus (GDM) case-ascertainment in routinely collected data. Methods: Retrospective cohort study analysed routinely collected data from all births at Cairns Base Hospital, Australia, from 1 January 2004 to 31 December 2010 in the Cairns Base Hospital Clinical Coding system (CBHCC) and the Queensland Perinatal Data Collection (QPDC). GDM case ascertainment in the National Diabetes Services Scheme (NDSS) and Cairns Diabetes Centre (CDC) data were compared. Results: From 2004 to 2010, the specificity of GDM case-ascertainment in the QPDC was 99%. In 2010, only 2 of 225 additional cases were identified from the CDC and CBHCC, suggesting QPDC sensitivity is also over 99%. In comparison, the sensitivity of the CBHCC data was 80% during 2004–2010. The sensitivity of CDC data was 74% in 2010. During 2010, 223 births were coded as GDM in the QPDC, and the NDSS registered 247 women with GDM from the same postcodes, suggesting reasonable uptake on the NDSS register. However, the proportion of Aboriginal and Torres Strait Islander women was lower than expected. Conclusion: The accuracy of GDM case ascertainment in the QPDC appears high, with lower accuracy in routinely collected hospital and local health service data. This limits capacity of local data for planning and evaluation, and developing structured systems to improve post-pregnancy care, and may underestimate resources required. Implications: Data linkage should be considered to improve accuracy of routinely collected local health service data. The accuracy of the NDSS for Aboriginal and Torres Strait Islander women requires further evaluation.

Studies on the pathophysiology and genetic basis of migraine

Migraine is a neurological disorder that affects the central nervous system causing painful attacks of headache. A genetic vulnerability and exposure to environmental triggers can influence the migraine phenotype. Migraine interferes in many facets of people’s daily life including employment commitments and their ability to look after their families resulting in a reduced quality of life. Identification of the biological processes that underlie this relatively common affliction has been difficult because migraine does not have any clearly identifiable pathology or structural lesion detectable by current medical technology. Theories to explain the symptoms of migraine have focused on the physiological mechanisms involved in the various phases of headache and include the vascular and neurogenic theories. In relation to migraine pathophysiology the trigeminovascular system and cortical spreading depression have also been implicated with supporting evidence from imaging studies and animal models. The objective of current research is to better understand the pathways and mechanisms involved in causing pain and headache to be able to target interventions. The genetic component of migraine has been teased apart using linkage studies and both candidate gene and genome-wide association studies, in family and case-control cohorts. Genomic regions that increase individual risk to migraine have been identified in neurological, vascular and hormonal pathways. This review discusses knowledge of the pathophysiology and genetic basis of migraine with the latest scientific evidence from genetic studies.

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.

An X chromosome association scan of the Norfolk Island genetic isolate provides evidence for a novel migraine susceptibility locus at Xq12

Migraine is a common and debilitating neurovascular disorder with a complex envirogenomic aetiology. Numerous studies have demonstrated a preponderance of women affected with migraine and previous pedigree linkage studies in our laboratory have identified susceptibility loci on chromosome Xq24-Xq28. In this study we have used the genetic isolate of Norfolk Island to further analyse the X chromosome for migraine susceptibility loci. An association approach was employed to analyse 14,124 SNPs spanning the entire X chromosome. Genotype data from 288 individuals comprising a large core-pedigree, of which 76 were affected with migraine, were analysed. Although no SNP reached chromosome-wide significance (empirical α = 1×10−5) ranking by P-value revealed two primary clusters of SNPs in the top 25. A 10 SNP cluster represents a novel migraine susceptibility locus at Xq12 whilst a 11 SNP cluster represents a previously identified migraine susceptibility locus at Xq27. The strongest association at Xq12 was seen for rs599958 (OR = 1.75, P = 8.92×10−4), whilst at Xq27 the strongest association was for rs6525667 (OR = 1.53, P = 1.65×10−4). Further analysis of SNPs at these loci was performed in 5,122 migraineurs from the Women’s Genome Health Study and provided additional evidence for association at the novel Xq12 locus (P<0.05). Overall, this study provides evidence for a novel migraine susceptibility locus on Xq12. The strongest effect SNP (rs102834, joint P = 1.63×10−5) is located within the 5′UTR of the HEPH gene, which is involved in iron homeostasis in the brain and may represent a novel pathway for involvement in migraine pathogenesis.

Functional analysis of missense variants in the TRESK (KCNK18) K+ channel

A loss of function mutation in the TRESK K2P potassium channel (KCNK18), has recently been linked with typical familial migraine with aura. We now report the functional characterisation of additional TRESK channel missense variants identified in unrelated patients. Several variants either had no apparent functional effect, or they caused a reduction in channel activity. However, the C110R variant was found to cause a complete loss of TRESK function, yet is present in both sporadic migraine and control cohorts, and no variation in KCNK18 copy number was found. Thus despite the previously identified association between loss of TRESK channel activity and migraine in a large multigenerational pedigree, this finding indicates that a single non-functional TRESK variant is not alone sufficient to cause typical migraine and highlights the genetic complexity of this disorder. Migraine is a common, disabling neurological disorder with a genetic, environmental and in some cases hormonal component. It is characterized by attacks of severe, usually unilateral and throbbing headache, can be accompanied by nausea, vomiting and photophobia and is clinically divided into two main subtypes, migraine with aura (MA) when a migraine is accompanied by transient and reversible focal neurological symptoms and migraine without aura (MO)1. The multifactorial and clinical heterogeneity of the disorder have considerably hindered the identification of common migraine susceptibility genes and most of our current understanding comes from the studies of familial hemiplegic migraine (FHM), a rare monogenic autosomal dominant form of MA2. So far, the three susceptibility genes that have been convincingly identified in FHM families all encode ion channels or transporters: CACNA1A encoding the α1 subunit of the Cav2.1 calcium channel3, SCN1A encoding the Nav1.1 sodium channel4 and ATP1A2 encoding the α2 subunit of the Na+/K+ pump5. It is believed that mutations in these genes may lead to increased efflux of glutamate and potassium in the synapse and thereby cause migraine by rendering the brain more susceptible to cortical spreading depression (CSD)6 which is thought to play a role in initiating a migraine attack7,8. However, these genes have not to date been implicated in common forms of migraine9. Nevertheless, current opinion suggests that typical migraine, like FHM, is also disorder of neuronal excitability, ion homeostasis and neurotransmitter release10,11,12. Mutations in the SLC4A4 gene encoding the sodium-bicarbonate cotransporter NBCe1, have recently been implicated in several different forms of migraine13, and a variety of genes involved in glutamate homeostasis (PGCP, MTDH14 and LRP115) and a cation channel (TRPM8)15 have also recently been implicated in migraine via genome-wide association studies. Ion channels are therefore highly likely to play an important role in the pathogenesis of typical migraine. TRESK (KCNK18), is a member of the two-pore domain (K2P) family of potassium channels involved in the control of cellular electrical excitability16. Regulation of TRESK activity by the calcium-dependent phosphatase calcineurin17, as well as its expression in dorsal root ganglia (DRG)18 and trigeminal ganglia (TG)19,20 has led to a proposed role for this channel in a variety of pain pathways. In a recent study, a frameshift mutation (F139Wfsx24) in TRESK was identified in a large multigenerational pedigree where it co-segregated perfectly with typical MA and a significant genome-wide linkage LOD score of 3.0. Furthermore, functional analysis revealed that this mutation caused a complete loss of TRESK function and that the truncated subunit was also capable of down regulating wild-type channel function. This therefore highlighted KCNK18 as potentially important candidate gene and suggested that TRESK dysfunction might play a possible role in the pathogenesis of familial migraine with visual aura20. Additional screening for KCNK18 mutations in unrelated sporadic migraine and control cohorts also identified a number of other missense variants; R10G, A34V, C110R, S231P and A233V20. The A233V variant was found only in the control cohort, whilst A34V was identified in a single Australian migraine proband for which family samples were not available, but it was not detected in controls. By contrast, the R10G, C110R, and S231P variants were found in both migraineurs and controls in both cohorts. In this study, we have investigated the functional effect of these variants to further probe the potential association of TRESK dysfunction with typical migraine.

Identification of molecular genetic factors that influence migraine

Migraine is a common neurological disorder with a strong genetic basis. However, the complex nature of the disorder has meant that few genes or susceptibility loci have been identified and replicated consistently to confirm their involvement in migraine. Approaches to genetic studies of the disorder have included analysis of the rare migraine subtype, familial hemiplegic migraine with several causal genes identified for this severe subtype. However, the exact genetic contributors to the more common migraine subtypes are still to be deciphered. Genome-wide studies such as genome-wide association studies and linkage analysis as well as candidate genes studies have been employed to investigate genes involved in common migraine. Neurological, hormonal and vascular genes are all considered key factors in the pathophysiology of migraine and are a focus of many of these studies. It is clear that the influence of individual genes on the expression of this disorder will vary. Furthermore, the disorder may be dependent on gene–gene and gene–environment interactions that have not yet been considered. In addition, identifying susceptibility genes may require phenotyping methods outside of the International Classification of Headache Disorders II criteria, such as trait component analysis and latent class analysis to better define the ambit of migraine expression.