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.

A novel immunodeficiency disorder characterized by genetic amplification of interleukin 25

Many primary immunodeficiency disorders of differing etiologies have been well characterized, and much understanding of immunological processes has been gained by investigating the mechanisms of disease. Here, we have used a whole-genome approach, employing single-nucleotide polymorphism and gene expression microarrays, to provide insight into the molecular etiology of a novel immunodeficiency disorder. Using DNA copy number profiling, we define a hyperploid region on 14q11.2 in the immunodeficiency case associated with the interleukin (IL)-25 locus. This alteration was associated with significantly heightened expression of IL25 following T-cell activation. An associated dominant type 2 helper T cell bias in the immunodeficiency case provides a mechanistic explanation for recurrence of infections by pathogens met by Th1-driven responses. Furthermore, this highlights the capacity of IL25 to alter normal human immune responses.

Variation in the vitamin D receptor gene is associated with multiple sclerosis in an Australian population

Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) resulting in accumulating neurological disability. The disorder is more prevalent at higher latitudes. To investigate VDR gene variation using three intragenic restriction fragment length polymorphisms (Apa I, Taq I and Fok I) in an Australian MS case-control population. One hundred and four Australian MS patients were studied with patients classified clinically as Relapsing Remitting MS (RR-MS), Secondary Progressive MS (SP-MS) or Primary Progressive MS (PP-MS). Also, 104 age-, sex-, and ethnicity-matched controls were investigated as a comparative group. Our results show a significant difference of genotype distribution frequency between the case and control groups for the functional exon 9 VDR marker Taq I (p(Gen) = 0.016) and interestingly, a stronger difference for the allelic frequency (p(All) = 0.0072). The Apa I alleles were also found to be associated with MS (p(All) = 0.04) but genotype frequencies were not significantly different from controls (p(Gen) = 0.1). The Taq and Apa variants are in very strong and significant linkage disequilibrium (D' = 0.96, P < 0.0001). The genotypic associations are strongest for the progressive forms of MS (SP-MS and PP-MS). Our results support a role for the VDR gene increasing the risk of developing multiple sclerosis, particularly the progressive clinical subtypes of MS.

Large-scale association study identifies ICAM gene region as breast and prostate cancer susceptibility locus

We conducted a large-scale association study to identify genes that influence nonfamilial breast cancer risk using a collection of German cases and matched controls and >25,000 single nucleotide polymorphisms located within 16,000 genes. One of the candidate loci identified was located on chromosome 19p13.2 [odds ratio (OR) = 1.5, P = 0.001]. The effect was substantially stronger in the subset of cases with reported family history of breast cancer (OR = 3.4, P = 0.001). The finding was subsequently replicated in two independent collections (combined OR = 1.4, P < 0.001) and was also associated with predisposition to prostate cancer in an independent sample set of prostate cancer cases and matched controls (OR = 1.4, P = 0.002). High-density single nucleotide polymorphism mapping showed that the extent of association spans 20 kb and includes the intercellular adhesion molecule genes ICAM1, ICAM4, and ICAM5. Although genetic variants in ICAM5 showed the strongest association with disease status, ICAM1 is expressed at highest levels in normal and tumor breast tissue. A variant in ICAM5 was also associated with disease progression and prognosis. Because ICAMs are suitable targets for antibodies and small molecules, these findings may not only provide diagnostic and prognostic markers but also new therapeutic opportunities in breast and prostate cancer.

Percutaneous coronary intervention with drug-eluting stents or coronary artery bypass surgery in subjects with type 2 diabetes : evaluation of: Farkouth ME, Domanski M, Sleeper LA, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med 2012;367(25):2375-84, and Contini GA, Nicolini F, Fortuna D, et al. Five-year outcomes of surgical or percutaneous myocardial revascularization in diabetic patients. Int J Cardiol 2012. [Epub ahead of print]

There is debate as to whether percutaneous coronary intervention (PCI) with drug-eluting stents or coronary artery bypass surgery (CABG) is the best procedure for subjects with type 2 diabetes and coronary artery disease requiring revascularization. There is some evidence that following these procedures there is less further revascularization with CABG than PCI in subjects with diabetes. Two recent studies; the FREEDOM (Future Revascularization Evaluation in patients with Diabetes mellitus: Optimal Management of Multivessel Disease) trial, and a trial using a real world diabetic population from a Registry, have shown that the benefits of CABG over PCI in subjects with type 2 diabetes extends to lower rates of death and myocardial infarct, in addition to lower rates of revascularization. However, the rates of stroke may be higher with CABG than PCI with drug-eluting stents in this population. Thus, if CABG is going to be preferred to PCI in subjects with type 2 diabetes and multivessel coronary disease, consideration should be given to how to reduce the rates of stroke with CABG.

Sterilizing tissue-materials using pulsed power plasma

This paper investigates the potential of pulsed power to sterilize hard and soft tissues and its impact on their physico-mechanical properties. It hypothesizes that pulsed plasma can sterilize both vascular and avascular tissues and the transitive layers in between without deleterious effects on their functional characteristics. Cartilage/bone laminate was chosen as a model to demonstrate the concept, treated at low temperature, at atmospheric pressure, in short durations and in buffered environment using a purposed-built pulsed power unit. Input voltage and time of exposure were assigned as controlling parameters in a full factorial design of experiment to determine physical and mechanical alteration pre- and post-treatment. The results demonstrated that, discharges of 11 kV sterilized samples in 45 s, reducing intrinsic elastic modules from 1.4 ± 0.9 to 0.9 ± 0.6 MPa. There was a decrease of 14.1 % in stiffness and 27.8 % in elastic-strain energy for the top quartile. Mechanical impairment was directly proportional to input voltage (P value < 0.05). Bacterial inactivation was proportional to treatment time for input voltages above 32 V (P < 0.001; R Sq = 0.98). Thermal analysis revealed that helix-coil transition decelerated with exposure time and collagen fibrils were destabilized as denaturation enthalpy reduced by 200 μV. We concluded by presenting a safe operating threshold for pulsed power plasma as a feasible protocol for effective sterilization of connective tissues with varying level of loss in mechanical robustness which we argue to be acceptable in certain medical and tissue engineering application.

The changing face of contact lens wearers over 25 years

A combination of factors has dictated patterns of prescribing to contact lens wearers in different age groups over time, such as the evolution of manufacturing technology in bringing better lens designs and replacement frequency options; the aging population demographic; and the knowledge and attitudes of practitioners. Here we explore evolving lens fitting practices at the opposite poles of the age spectrum—children and presbyopes.

The Nagle Royal Commission 25 years on : gaining perspective on two and a half decades of NSW prison reform

This article attempts an audit of changes in the NSW penal system over the last nearly 30 years. Taking the 1978 Nagle Royal Commission findings and analysis as the starting point a comparison is made between the Nagle era and the contemporary scene across a range of practices including imprisonment rates, violence, drug use, deaths in custody, prison conditions, prisoners rights, legal regulation, and others. It is suggested that developments since Nagle are mixed and cannot be attributed to a single logic or force. Major changes include a doubling of imprisonment rates, significant increases in Indigenous and women's imprisonment rates, the apparent ending of institutionalised bashings and the centrality of drug use to imprisonment and to the culture, health and security practices which characterise the current prison experience. The article may constitute a useful starting point for broader attempts to relate current penal practices to far wider changes in the conditions of life under late modernity.

Antecedents of consumer brand loyalty in the Australian wine industry

The wine industry has become fiercely competitive worldwide and as a result, consumers are increasingly exposed to a wider range of wines in retail outlets. This expanding consumer choice means that there is a need for Australian wineries to develop and build consumer loyalty toward their brands. This paper aims to empirically examine the factors influencing consumer loyalty to wine brands. Using data from Australian wine consumers, the authors empirically test a model of antecedents of wine brand loyalty. The model considers wine brand trust, wine brand satisfaction, wine knowledge, and wine experience. Hypotheses were tested with structural equation modeling. The findings of this study show that wine knowledge and wine experience affect wine brand loyalty indirectly through wine brand trust and wine brand satisfaction. In addition, it is demonstrated that consumer satisfaction with a wine brand is the strongest driver of wine brand loyalty. The result of this study has value for Australian wineries, wine retailers, and wine marketers.

Gel dosimetry—it’s been the next big thing in radiotherapy for the past 25 years

Gel dosimetry and plastic chemical dosimeters such as PresageTM are capable of very accurately mapping dose distributions in three dimensions. Combined with their near tissue equivalence one would expect that after several decades of development they would be the dosimeter of choice for dosimetry, however they have not achieve widespread clinical use. This presentation will include a brief description and history of developments in gels and 3D plastics for dosimetry, the limitations and advantages, and their role in the future.

Inactivation of a 25.5 µm Enterococcus faecalis biofilm by a room-temperature, battery-operated, handheld air plasma jet

Effective biofilm inactivation using a handheld, mobile plasma jet powered by a 12 V dc battery and operated in open air without any external gas supply is reported. This cold, room-temperature plasma is produced in self-repetitive nanosecond discharges with current pulses of ~100 ns duration, current peak amplitude of ~6 mA and repetition rate of ~20 kHz. It is shown that the reactive plasma species penetrate to the bottom layer of a 25.5 µm-thick Enterococcus faecalis biofilm and produce a strong bactericidal effect. This is the thickest reported biofilm inactivated using room-temperature air plasmas.

Serum 25-hydroxy vitamin D concentrations are more deficient/insufficient in peritoneal dialysis than haemodialysis patients in a sunny climate

Background Research has identified associations between serum 25(OH)D and a range of clinical outcomes in chronic kidney disease and wider populations. The present study aimed to investigate vitamin D deficiency/insufficiency in dialysis patients and the relationship with vitamin D intake and sun exposure. Methods A cross-sectional study was used. Participants included 30 peritoneal dialysis (PD) (43.3% male; 56.87 ± 16.16 years) and 26 haemodialysis (HD) (80.8% male; 63.58 ± 15.09 years) patients attending a department of renal medicine. Explanatory variables were usual vitamin D intake from diet/supplements (IU day−1) and sun exposure (min day−1). Vitamin D intake, sun exposure and ethnic background were assessed by questionnaire. Weight, malnutrition status and routine biochemistry were also assessed. Data were collected during usual department visits. The main outcome measure was serum 25(OH)D (nm). Results Prevalence of inadequate/insufficient vitamin D intake differed between dialysis modality, with 31% and 43% found to be insufficient (<50 nm) and 4% and 33% found to be deficient (<25 nm) in HD and PD patients, respectively (P < 0.001). In HD patients, there was a correlation between diet and supplemental vitamin D intake and 25(OH)D (ρ = 0.84, P < 0.001) and average sun exposure and 25(OH)D (ρ = 0.50, P < 0.02). There were no associations in PD patients. The results remained significant for vitamin D intake after multiple regression, adjusting for age, gender and sun exposure. Conclusions The results highlight a strong association between vitamin D intake and 25(OH)D in HD but not PD patients, with implications for replacement recommendations. The findings indicate that, even in a sunny climate, many dialysis patients are vitamin D deficient, highlighting the need for exploration of determinants and consequences.

A sunburnt country – storms, surges and sea levels : of insurance and flooding rains

Increasing population pressures and life-style choices are resulting in more people living in areas that are at risk of inundation from rising sea levels and flooding. However, following natural disaster events, such as the 2011 Queensland floods, many Australians discovered they were uninsured. Either their insurance policies did not cover flood; or multiple (and confusing) water-related definitions led them to believe they had cover when they did not. Several theories are analysed to try to explain what is a world-wide underinsurance problem but these do not provide an answer to the problem. This research focuses on uncovering the reasons consumers fail to adequately insure for flood and other water-related events. Recent Australian legislative attempts to overcome insureds’ confusion of water related definitions are examined for this purpose. The authors conclude that Australian and other) legislators should set a maximum premium for a minimum amount of flood and sea related cover; and restrict the building and style of homes in flood prone areas.

The first 25 years of the Queensland Rugby Football League: Claims to legitimacy in annual reports

Despite the cultural importance of sporting organisations, little academic attention has been paid to the legitimising role of their annual reports. In this paper we examine the role of annual reports in establishing the legitimacy of a new organisation, the Queensland Rugby Football League (QRFL), founded in 1908. Contextualised with media reports from newspapers of the day, twelve annual reports from QRFL’s first 25 years are analysed and interpreted using insights from legitimacy theory. Through the presentation of audited financial statements and persuasive narrative accounts of its operations and success, QRFL made claims to pragmatic, moral and cognitive legitimacy as it sought to establish a niche as a new football code and organisation. This contextualised study situates the annual reports in their historical landscape, providing insights about how they contributed to QRFL’s efforts in overcoming the liability of newness in a competitive sports environment.

Key beliefs influencing young drivers' engagement with social interactive technology on their Smartphones: A qualitative study

Objective The main aim of this study was to identify young drivers' underlying beliefs (i.e., behavioral, normative, and control) regarding initiating, monitoring/reading, and responding to social interactive technology (i.e., functions on a Smartphone that allow the user to communicate with other people). Method This qualitative study was a beliefs elicitation study in accordance with the Theory of Planned Behavior and sought to elicit young drivers' behavioral (i.e., advantages, disadvantages), normative (i.e., who approves, who disapproves), and control beliefs (i.e., barriers, facilitators) which underpin social interactive technology use while driving. Young drivers (N = 26) aged 17 to 25 years took part in an interview or focus group discussion. Results While differences emerged between the three behaviors of initiating, monitoring/reading, and responding for each of the behavioral, normative, and control belief categories, the strongest distinction was within the behavioral beliefs category (e.g., communicating with the person that they were on the way to meet was an advantage of initiating; being able to determine whether to respond was an advantage of monitoring/reading; and communicating with important people was an advantage of responding). Normative beliefs were similar for initiating and responding behaviors (e.g., friends and peers more likely to approve than other groups) and differences emerged for monitoring/reading (e.g., parents were more likely to approve of this behavior than initiating and responding). For control beliefs, there were differences between the beliefs regarding facilitators of these behaviors (e.g., familiar roads and conditions facilitated initiating; having audible notifications of an incoming communication facilitated monitoring/reading; and receiving a communication of immediate importance facilitated responding); however, the control beliefs that presented barriers were consistent across the three behaviors (e.g., difficult traffic/road conditions). Conclusion The current study provides an important addition to the extant literature and supports emerging research which suggests initiating, monitoring/reading, and responding may indeed be distinct behaviors with different underlying motivations.