A pharmacogenomic evaluation of migraine therapy

Migraine is a common idiopathic primary headache disorder with significant mental, physical and social health implications. Accompanying an intense unilateral pulsating head pain other characteristic migraine symptoms include nausea, emesis, phonophobia, photophobia and in approximately 20-30% of migraine cases, neurologic disturbances associated with the aura phase. Although selective serotonin (5-HT) receptor agonists (i.e., 5-HT(1B/1D)) are successful in alleviating migrainous symptoms in < or = 70% of known sufferers, for the remaining 30%, additional migraine abortive medications remain unsuccessful, not tested or yet to be identified. Genetic characterization of the migrainous disorder is making steady progress with an increasing number of genomic susceptibility loci now identified on chromosomes 1q, 4q, 5q, 6p, 11q, 14q, 15q, 17p, 18q, 19p and Xq. The 4q, 5q, 17p and 18q loci involve endophenotypic susceptibility regions for various migrainous symptoms. In an effort to develop individualized pharmacotherapeutics, the identification of these migraine endophenotypic loci may well be the catalyst needed to aid in this goal. In this review the authors discuss the present treatment of migraine, known genomic susceptibility regions and results from migraine (genetic) association studies. The authors also discuss pharmacogenomic considerations for more individualized migraine prophylactic treatments.

The valuation of long life mines : current issues and methodologies

The past decade has seen an increasing focus on the mining and extractive industries in Australia. The significant increases in both new mines, commodity prices and employment opportunities has lead to considerable discussion on the value of this industry and the contribution that the industry makes to exports, GDP and the public in general. This debate has resulted in the introduction of the Mineral Resources Rent Tax being introduced in 2012. An issue that follows from the introduction of these taxes is the current exposure of property valuers to mine and extractive industry valuations and the most appropriate method that should be employed for valuing long life mines for rating and taxing purposes, finance and accounting purposes. This paper will provide a detailed review of past and current valuation methods for long life mines and will highlight the current issues and problem facing valuers who are currently working in or intend to carry out valuation work in this industry.

The Effective and The Evocative : A Spectrum of Creative Practice Research

In the expanding literature on creative practice research, art and design are often described as a unified field. They are bracketed together (art-and-design), referred to as interchangeable terms (art/design), and nested together, as if the practices of one domain encompass the other. However it is possible to establish substantial differences in research approaches. In this chapter we argue that core distinctions arise out of the goals of the research, intentions invested in the resulting “artefacts” (creative works, products, events), and the knowledge claims made for the research outcomes. Moreover, these fundamental differences give rise to a number of contingent attributes of the research such as the forming contexts, methodological approaches, and ways of evidencing and reporting new knowledge. We do not strictly ascribe these differences to disciplinary contexts. Rather, we use the terms effective practice research and evocative practice research to describe the spirit of the two distinctive research paradigms we identify. In short, effective practice research (often pursued in design fields) seeks a solution (or resolution) to a problem identified with a particular community, and it produces an artefact that addresses this problem by effecting change (making a situation, product or process more efficient or effective in some way). On the other hand, evocative practice research (often pursued by creative arts fields) is driven by individual pre-occupations, cultural concerns or human experience more broadly. It produces artefacts that evoke affect and resonance, and are poetically irreducible in meaning. We cite recent examples of creative research projects that illustrate the distinctions we identify. We then go on to describe projects that integrate these modes of research. In this way, we map out a creative research spectrum, with distinct poles as well as multiple hybrid possibilities. The hybrid projects we reference are not presented as evidence an undifferentiated field. Instead, we argue that they integrate research modes in deliberate, purposeful and distinctive ways: employing effective practice research methods in the production of evocative artefacts or harnessing evocative (as well as effective) research paradigms to effect change.

Comparison of historic exploration with contemporary space policy suggests a retheorisation of settings

The 2008 NASA Astrobiology Roadmap provides one way of theorising this developing field, a way which has become the normative model for the discipline: science-and scholarship-driven funding for space. By contrast, a novel re-evaluation of funding policies is undertaken in this article to reframe astrobiology, terraforming and associated space travel and research. Textual visualisation, discourse and numeric analytical methods, and value theory are applied to historical data and contemporary sources to re-investigate significant drivers and constraints on the mechanisms of enabling space exploration. Two data sets are identified and compared: the business objectives and outcomes of major 15th-17th century European joint-stock exploration and trading companies and a case study of a current space industry entrepreneur company. Comparison of these analyses suggests that viable funding policy drivers can exist outside the normative science and scholarship-driven roadmap. The two drivers identified in this study are (1) the intrinsic value of space as a territory to be experienced and enjoyed, not just studied, and (2) the instrumental, commercial value of exploiting these experiences by developing infrastructure and retail revenues. Filtering of these results also offers an investment rationale for companies operating in, or about to enter, the space business marketplace.

Gelatine

A Social Public Display to Facilitate Shared Encounters in Coworking Spaces The idea behind ‘Gelatine’ is a system that facilitates shared encounters between coworkers and library users by allowing them to digitally ‘check in’ at a work space. Gelatine displays skills, areas of interest, and needs of currently present coworkers on a public screen. The system provides an online / mobile website for users to create a personal profile with keywords (‘tags’) that describe their skills, areas of interests, as well as areas that they have a problem in or want to learn more about. This profile information is linked to their RFID membership card, which they can swipe at one of the ‘checkin-points’ at the entrance or specific sub locations such as individual desks or coffee kiosk to confirm their presence in the space.

“Conversations Before the End of Time” : Refuturing Applications of a New Media Praxis

This chapter examines how the methods, outcomes and transformative potentials of my new media arts praxis have been understood by a range of critical commentators from disciplinary perspectives outside of my own ‘home territory’ of media arts. By drawing upon perspectives from Human Computer Interface Design, Engineering, Sustainability Design, Tertiary Education, Communication Design and Public Librarianship I demonstrate how ideas from my arts disciplines have had tangible ‘external’ significance and application.

Practice as Method : The Ex/centric Fixations Project

In this chapter, I consider the efficacy of creative practice as a research method, concentrating specifically on its applications in the performing arts, using one of my own recent projects, The Ex/centric Fixations Project (2009), as an example.

Genetic variants underlying risk of endometriosis: Insights from meta-analysis of eight genome-wide association and replication datasets

BACKGROUND Endometriosis is a heritable common gynaecological condition influenced by multiple genetic and environmental factors. Genome-wide association studies (GWASs) have proved successful in identifying common genetic variants of moderate effects for various complex diseases. To date, eight GWAS and replication studies from multiple populations have been published on endometriosis. In this review, we investigate the consistency and heterogeneity of the results across all the studies and their implications for an improved understanding of the aetiology of the condition. METHODS Meta-analyses were conducted on four GWASs and four replication studies including a total of 11 506 cases and 32 678 controls, and on the subset of studies that investigated associations for revised American Fertility Society (rAFS) Stage III/IV including 2859 cases. The datasets included 9039 cases and 27 343 controls of European (Australia, Belgium, Italy, UK, USA) and 2467 cases and 5335 controls of Japanese ancestry. Fixed and Han and Elkin random-effects models, and heterogeneity statistics (Cochran's Q test), were used to investigate the evidence of the nine reported genome-wide significant loci across datasets and populations. RESULTS Meta-analysis showed that seven out of nine loci had consistent directions of effect across studies and populations, and six out of nine remained genome-wide significant (P < 5 × 10(-8)), including rs12700667 on 7p15.2 (P = 1.6 × 10(-9)), rs7521902 near WNT4 (P = 1.8 × 10(-15)), rs10859871 near VEZT (P = 4.7 × 10(-15)), rs1537377 near CDKN2B-AS1 (P = 1.5 × 10(-8)), rs7739264 near ID4 (P = 6.2 × 10(-10)) and rs13394619 in GREB1 (P = 4.5 × 10(-8)). In addition to the six loci, two showed borderline genome-wide significant associations with Stage III/IV endometriosis, including rs1250248 in FN1 (P = 8 × 10(-8)) and rs4141819 on 2p14 (P = 9.2 × 10(-8)). Two independent inter-genic loci, rs4141819 and rs6734792 on chromosome 2, showed significant evidence of heterogeneity across datasets (P < 0.005). Eight of the nine loci had stronger effect sizes among Stage III/IV cases, implying that they are likely to be implicated in the development of moderate to severe, or ovarian, disease. While three out of nine loci were inter-genic, the remaining were in or near genes with known functions of biological relevance to endometriosis, varying from roles in developmental pathways to cellular growth/carcinogenesis. CONCLUSIONS Our meta-analysis shows remarkable consistency in endometriosis GWAS results across studies, with little evidence of population-based heterogeneity. They also show that the phenotypic classifications used in GWAS to date have been limited. Stronger associations with Stage III/IV disease observed for most loci emphasize the importance for future studies to include detailed sub-phenotype information. Functional studies in relevant tissues are needed to understand the effect of the variants on downstream biological pathways.

Who owns your body? Patricia Piccinini and the future of bioethics

This article analyses some popular cultural representations of biotechnology, especially the artistic work of the Australian artist Patricia Piccinini to reflect on the role of law, technology and ethics in relation to bodily material. Her view that "with creation...comes an obligation to care for the result", so evident in her poignant pictures, is a sober reminder to us of our responsibilities in regulating new technologies.

The attack of the clones: Patent law and stem cell research

This article considers the integral role played by patent law in respect of stem cell research. It highlights concerns about commercialization, access to essential medicines and bioethics. The article maintains that there is a fundamental ambiguity in the Patents Act 1990 (Cth) as to whether stem cell research is patentable subject matter. There is a need to revise the legislation in light of the establishment of the National Stem Cell Centre and the passing of the Research Involving Embryos Act 2002 (Cth). The article raises concerns about the strong patent protection secured by the Wisconsin Alumni Research Foundation and Geron Corporation in respect of stem cell research in the United States. It contends that a number of legal reforms could safeguard access to stem cell lines, and resulting drugs and therapies. Finally, this article explores how ethical concerns are addressed within the framework of the European Biotechnology Directive. It examines the decision of the European Patent Office in relation to the so-called Edinburgh patent, and the inquiry of the European Group on Ethics in Science and New Technologies into The Ethical Aspects of Patenting Involving Human Stem Cells.

Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk

Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55-85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or -4.0 to -1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD-associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies. © 2011 Duncan et al.

Positive development and assessment

Purpose – There has been a tendency in sustainability science to be passive. The purpose of this paper is to introduce an alternative positive framework for a more active and direct approach to sustainable design and assessment that de-couples environmental impacts and economic growth. Design/methodology/approach – This paper deconstructs some systemic gaps that are critical to sustainability in built environment management processes and tools, and reframes negative “sustainable” decision making and assessment frameworks into their positive counterparts. In particular, it addresses the omission of ecology, design and ethics in development assessment. Findings – Development can be designed to provide ecological gains and surplus “eco-services,” but assessment tools and processes favor business-as-usual. Despite the tenacity of the dominant paradigm (DP) in sustainable development institutionalized by the Brundtland Report over 25 years ago, these omissions are easily corrected. Research limitations/implications – The limitation is that the author was unable to find exceptions to the omissions cited here in the extensive literature on urban planning and building assessment tools. However, exceptions prove the rule. The implication is that it is not too late for eco-positive retrofitting of cities to increase natural and social capital. The solutions are just as applicable in places like China and India as the USA, as they pay for themselves. Originality/value – Positive development (PD) is a fundamental paradigm shift that reverses the negative models, methods and metrics of the DP of sustainable development. This paper provides an example of how existing “negative” concepts and practices can be converted into positive ones through a PD prism. Through a new form of bio-physical design, development can be a sustainability solution.

Genome-wide association analysis identifies susceptibility loci for migraine without aura

Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants associated with this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch individuals with migraine without aura and 4,580 population-matched controls. We selected SNPs from 12 loci with 2 or more SNPs associated with P values of <1 x 10(-5) for replication testing in 2,508 individuals with migraine without aura and 2,652 controls. SNPs at two of these loci showed convincing replication: at 1q22 (in MEF2D; replication P = 4.9 x 10(-4); combined P = 7.06 x 10(-11)) and at 3p24 (near TGFBR2; replication P = 1.0 x 10(-4); combined P = 1.17 x 10(-9)). In addition, SNPs at the PHACTR1 and ASTN2 loci showed suggestive evidence of replication (P = 0.01; combined P = 3.20 x 10(-8) and P = 0.02; combined P = 3.86 x 10(-8), respectively). We also replicated associations at two previously reported migraine loci in or near TRPM8 and LRP1. This study identifies the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder.

Veterans' Health

The Australian veteran population can be loosely grouped into the younger veterans that are currently serving in, or returned from recent conflicts, to the ‘young elderly’ (65 to 74 years of age) from the Cold War era, to the near centenarians and centenarians from the earlier conflicts of World War 1 and 2. In 2013, 58.2% of veterans receiving medical treatment under the Gold or White cards were males being on average 71.3 years of age, while the average age of females was 83.4 years. Overall, 51.5% were 80+ years of age (ranging from <30, to 90+ years of age)...

The effectiveness of SMS reminders on appointment attendance: A meta-analysis

Objective To identify the efficacy of short message service (SMS) reminders in health care appointment attendance. Materials and Methods A systematic review was undertaken to identify studies published between 2005 and 2015 that compared the attendance rates of patients receiving SMS reminders compared to patients not receiving a reminder. Each article was examined for information regarding the study design, sample size, population demographics and intervention methods. A meta-analysis was used to calculate a pooled estimate odds ratio. Results Twenty-eight (28) studies were included in the review, including 13 (46%) randomized controlled trials. The pooled odds ratio of the randomized control trials was 1.62 (1.35 – 1.94). Half of the studies reviewed sent the reminder within 48 hour prior to the appointment time, yet no significant subgroups differences with respect to participant age, SMS timing, rate or type, setting or specialty was detectable. Discussion All studies, except one with a small sample size, demonstrated a positive OR, indicating SMS reminders were an effective means of improving appointment attendance. There was no significant difference in OR when controlling for when the SMS was sent, the frequency of the reminders or the content of the reminder. Conclusion SMS appointment reminders are an effective and operative method in improving appointment attendance in a health care setting and this effectiveness has improved over the past five years. Further research is required to identify the optimal SMS reminder timing and frequency, specifically in relation to the length of time since the appointment.