Development of lightweight aggregate concrete with high resistance to water and chloride-ion penetration

This paper presents an experimental study to evaluate the effect of coarse and fine LWA in concrete on its water absorption and permeability, and resistance to chloride-ion penetration. In additions, LWC with lower unit weight of about 1300 kg/m3 but high resistance to water and chloride-ion penetration was developed and evaluated. The results indicate that the incorporation of coarse LWA in concrete increases water sorptivity and permeability slightly compared to NWC of similar w/c. The resistance of the sand-LWC to chloride-ion penetration depends on porosity of the coarse LWA. Fine LWA has more influence on the transport proper-ties of concrete than coarse LWA. Use of lightweight crushed sand <1.18 mm reduced the resistance of the LWC to water and chloride-ion penetration to some extent. With low w/cm and silica fume, low unit weight LWC (~1300 kg/m3) was produced with higher resistance to water and chloride ion penetration compared with concretes of higher unit weights.

A practical comparison of manual and autonomous methods for acoustic monitoring

1. Autonomous acoustic recorders are widely available and can provide a highly efficient method of species monitoring, especially when coupled with software to automate data processing. However, the adoption of these techniques is restricted by a lack of direct comparisons with existing manual field surveys. 2. We assessed the performance of autonomous methods by comparing manual and automated examination of acoustic recordings with a field-listening survey, using commercially available autonomous recorders and custom call detection and classification software. We compared the detection capability, time requirements, areal coverage and weather condition bias of these three methods using an established call monitoring programme for a nocturnal bird, the little spotted kiwi(Apteryx owenii). 3. The autonomous recorder methods had very high precision (>98%) and required <3% of the time needed for the field survey. They were less sensitive, with visual spectrogram inspection recovering 80% of the total calls detected and automated call detection 40%, although this recall increased with signal strength. The areal coverage of the spectrogram inspection and automatic detection methods were 85% and 42% of the field survey. The methods using autonomous recorders were more adversely affected by wind and did not show a positive association between ground moisture and call rates that was apparent from the field counts. However, all methods produced the same results for the most important conservation information from the survey: the annual change in calling activity. 4. Autonomous monitoring techniques incur different biases to manual surveys and so can yield different ecological conclusions if sampling is not adjusted accordingly. Nevertheless, the sensitivity, robustness and high accuracy of automated acoustic methods demonstrate that they offer a suitable and extremely efficient alternative to field observer point counts for species monitoring.

Dosimetric effects of a high-density spinal implant

In this study, a treatment plan for a spinal lesion, with all beams transmitted though a titanium vertebral reconstruction implant, was used to investigate the potential effect of a high-density implant on a three-dimensional dose distribution for a radiotherapy treatment. The BEAMnrc/DOSXYZnrc and MCDTK Monte Carlo codes were used to simulate the treatment using both a simplified, recltilinear model and a detailed model incorporating the full complexity of the patient anatomy and treatment plan. The resulting Monte Carlo dose distributions showed that the commercial treatment planning system failed to accurately predict both the depletion of dose downstream of the implant and the increase in scattered dose adjacent to the implant. Overall, the dosimetric effect of the implant was underestimated by the commercial treatment planning system and overestimated by the simplified Monte Carlo model. The value of performing detailed Monte Carlo calculations, using the full patient and treatment geometry, was demonstrated.

The role for police in addressing alcohol-related harm inside and outside licensed premises

Alcohol consumption is enmeshed with Australian culture (Palk, 2008) and the use and misuse of alcohol contributes to considerable health and social harms (Barbor et al., 2010; English et al., 1995; Gutjahr, Gmel, & Rehm, 2001; Palk, 2008; Steenkamp, Harrison, & Allsop, 2002). Despite shifts in the way that alcohol is consumed and how it is used, it has been reported that one-third of all alcohol consumed is done so within licensed premises (Lang, Stockwell, Rydon, & Gamble, 1992). Consequently, licensed premises are over-represented as settings in which alcohol-related harms occur. These harms, particularly those related to violence, are associated with particular licensed premises operating in the night-time economy (Briscoe & Donnelly, 2001b; Chikritzhs, Stockwell, & Masters, 1997; Homel, Tomsen, & Thommeny, 1991; Stockwell, 1997). Police have a role in not only responding to the manifestation of harms, such as crime, injuries, assaults, domestic violence, stealing and sexual offences, but they also have a role in preventing problems, and thereby reducing alcohol and other drug-related harms (Doherty & Roche, 2003). Given the extent of alcohol consumption within licensed premises and the nature and extent of the harms, as well as the lack of opportunity to influence outcomes in other settings (e.g. the home), licensed premises offer police and other stakeholders a significant opportunity to influence positively the reduction of alcoholrelated harm. This research focuses specifically on the police role in policing licensed premises. Primarily, this research aims to investigate the factors which are relevant to why and how police officers respond to alcohol-related incidents inside and outside licensed premises. It examines the attitudes and beliefs of police and assesses their knowledge, capacity and ability to effectively police licensed premises. The research methodology uses three distinct surveys. Each contributes to understanding the motivations and practice of police officers in this important area of harm reduction. Study One involved a survey of police officers within a police district (Brisbane Central District) in Queensland, Australia and used a comprehensive questionnaire involving both quantitative and qualitative techniques. A key research outcome of Study One was the finding that officers had low levels of knowledge of the strategies that are effective in addressing alcohol-related harm both inside and outside licensed premises. Paradoxically, these officers also reported extensive recent experience in dealing with alcohol issues in these locations. In addition, these officers reported that alcohol was a significant contextual factor in the majority of matters to which they responded. Officers surveyed reported that alcohol increased the difficulty of responding to situations and that licensed premises (e.g. nightclubs, licensed clubs and hotels) were the most difficult contexts to police. Those surveyed were asked to self-assess their knowledge of the Liquor Act (Qld), which is the primary legislative authority in Queensland for regulating licensed premises. Surprisingly, well over half of the officers (65%) reported ‘no’ to ‘fair’ knowledge of the Act, despite officers believing that their skill level to police such premises was in the ‘good to very good range’. In an important finding, officers reported greater skill level to police outside licensed premises than inside such premises, indicating that officers felt less capable, from a skill perspective, to operate within the confines of a licensed premise than in the environment immediately outside such premises. Another key finding was that officers reported greater levels of training in responding to situations outside and around licensed premises than to situations inside licensed premises. Officers were also asked to identify the frequency with which they employed specified regulatory enforcement and community-based strategies. Irrespective of the type of response, ‘taking no action’ or passive policing interventions were not favoured by officers. The findings identified that officers favoured taking a range of strategies (sending home, releasing into the custody of friends, etc.) in preference to arrest. In another key finding, officers generally reported their support for operational stakeholder partnership approaches to policing licensed premises. This was evidenced by the high number of officers (over 90%) reporting that there should be shared responsibility for enforcing the provisions of the Liquor Act. Importantly, those surveyed also identified the factors which constrain or prevent them from policing licensed premises. Study Two involved interviewing a small but comprehensive group (n=11) of senior managers from within the Queensland Police Service (QPS) who have responsibility for setting operational and strategic policy. The aim of this study was to examine the attitudes, perceptions and influence that senior officers (at the strategy and policy-setting level) had on the officers at the operational level. This qualitative study was carried out using a purposive sampling (Denzin & Lincoln, 2005; Guba & Lincoln, 1989), focused interview and thematic analytic approach. The interview participants were drawn from three tiers of management at district, regional as well as the whole-of-organisational level. The first key theme emerging from the study related to role, in terms of both the QPS broader organisational role, and the individual officer role with respect to the policing of licensed premises. For the QPS organisational role, participants at all three strategic levels had a high degree of congruity as to the organisations service role; that is, to enhance public safety. With respect to participants’ beliefs as to whether police officers have knowledge and understanding of their individual roles concerning licensed premises (as opposed to the QPS role), participants reported most commonly that officers had a reasonable to clear understanding of their role. Participant comments also were supportive of the view that officers operating in the research area, Brisbane Central District (BCD), had a clearer understanding of their role than police operating in other locations. The second key theme to emerge identified a disparity between the knowledge and capability of specialist police, compared with general duties police, to police licensed premises. In fact, a number of the responses to a variety of questions differentiated specialist and general police in a range of domains. One such example related to the clarity of understanding of officer role. Participants agreed that specialist police (Liquor Enforcement & Proactive Strategies [LEAPS] officers) had more clarity of understanding in terms of their role than generalist police. Participants also were strongly of the opinion that specialist police had higher skill levels to deal with issues both inside and outside licensed premises. Some participants expressed the view that general duty police undertook purely response-related activities, or alternatively, dealt with lower order matters. Conversely, it was viewed that specialist police undertook more complex tasks because of their higher levels of knowledge and skill. The third key theme to emerge concerned the identification of barriers that serve to restrict or prevent police officers from policing licensed premises. Participant responses strongly indicated that there was a diversity of resourcing barriers that restrict police from undertaking their roles in licensed premises. Examples of such barriers were the lack of police and the low ratio of police to patrons, available officer time, and lack of organisational investment in skills and knowledge acquisition. However, some participants indicated that police resourcing in the BCD was appropriate and officers were equipped with sufficient powers (policy and legislation). Again, the issue of specialist police was raised by one participant who argued that increasing the numbers of specialist police would ameliorate the difficulties for police officers policing licensed premises. The fourth and last key theme to emerge from Study Two related to the perception of senior officers regarding the opportunity and capability of officers to leverage off external partnerships to reduce harms inside and outside licensed premises. Police working in partnership in BCD was seen as an effective harm reduction strategy and strongly supported by the participants. All participants demonstrated a high degree of knowledge as to who these partners were and could identify those government, non-government and community groups precisely. Furthermore, the majority of participants also held strong views that the partnerships were reasonably effective and worked to varying degrees depending on the nature of the partnership and issues such as resourcing. These senior officers identified better communication and coordination as factors that could potentially strengthen these partnerships. This research finding is particularly important for senior officers who have the capacity to shape the policy and strategic direction of the police service, not only in Queensland but throughout Australasia. Study Three examined the perceptions of those with links to the broader liquor industry (government, non-government and community but exclusive of police) concerning their understanding of the police role and the capacity of police to reduce alcohol-related harm inside and outside licensed premises, and their attitudes towards police. Participants (n=26) surveyed represented a range of areas including the liquor industry, business represenatives and government representatives from Queensland Fire and Rescue Service, Queensland Ambulance Service, Brisbane City Council and Queensland Health. The first key theme to emerge from Study Three related to participant understanding of the QPS organisational role, and importantly, individual officer role in policing licensed premises. In terms of participant understanding of the QPS role there was a clear understanding by the majority of participants that the police role was to act in ways consistent with the law and to otherwise engage in a range of enforcement-related activities. Participants saw such activities falling into two categories. The first category related to reactive policing, which included actions around responding to trouble in licensed premises, monitoring crowd controllers and removing trouble-makers. In the second category, proactive approaches, participants identified the following activities as consistent with that approach: early intervention with offenders, support of licensed premises operators and high visibility policing. When participants were asked about their understanding of individual officer roles in the policing of licensed premises, a range of responses were received but the consistent message that emerged was that there is a different role to be played by general duty (uniformed) police compared to specialist (LEAPS Unit) police, which reflects differences in knowledge, skill and capability. The second key theme that emerged from the data related to the external participants’ views of the knowledge and capability of specialist police, compared with general duty police, to police licensed premises. As noted in the first key theme, participants were universally of the view that the knowledge, skill and capability of police in specialist units (LEAPS Unit) was at a higher level than that of general duty police. Participants observed that these specialist officers were better trained than their colleagues in generalist areas and were therefore better able to intervene knowledgeably and authoritatively to deal with problems and issues as they emerged. Participants also reported that officers working within BCD generally had a positive attitude to their duties and had important local knowledge that they could use in the resolution of alcohol-related issues. Participants also commented on the importance of sound and effective QPS leadership, as well as the quality of the leadership in BCD. On both these measures, there was general consensus from participants, who reported positively on the importance and effectiveness of such leadership in BCD. The third key theme to emerge from Study Three concerned the identification of barriers that serve to restrict or prevent police officers from policing licensed premises. Overwhelmingly, external participants reported the lack of human resources (i.e. police officers) as the key barrier. Other resourcing limitations, such as available officer time, police computer systems, and the time taken to charge offenders, were identified as barriers. Some participants identified barriers in the liquor industry such as ‘dodgy operators’ and negative media attention as limitations. Other constraints to emerge related to government and policy barriers. These were reflected in comments about the collection by government of fees from licensees and better ‘powers’ for police to deal with offenders. The fourth and final key theme that emerged from Study Three related to the opportunities for and capability of police to leverage off external partnerships to reduce harms inside and outside licensed premises. Not surprisingly, participants had a comprehensive knowledge of a broad range of stakeholders, from a diversity of contexts, influential in addressing issues in licensed premises. Many participants reported their relationships with the police and other stakeholders as effective, productive and consistent with the objectives of partnering to reduce alcohol-related harm. On the other hand, there were those who were concerned with their relationship with other stakeholders, particularly those with a compliance function (e.g. Office of Liquor & Gaming Regulation [OLGR]). The resourcing limitations of partners and stakeholders were also raised as an important constraining factor in fulfilling the optimum relationship. Again, political issues were mentioned in terms of the impact on partnerships, with participants stating that there is at times political interference and that politicians complicate the relationships of stakeholders. There are some significant strengths with respect to the methodology of this research. The research is distinguished from previous work in that it examines these critical issues from three distinct perspectives (i.e. police officer, senior manager and external stakeholder). Other strengths relate to the strong theoretical framework that guides and informs the research. There are also some identified limitations, including the subjective nature of self-report data as well as the potential for bias by the author, which was controlled for using a range of initiatives. A further limitation concerns the potential for transferability and generalisability of the findings to other locations given the distinctive nature of the BCD. These limitations and issues of transferability are dealt with at length in the thesis. Despite a growing body of literature about contextual harms associated with alcohol, and specific research concerning police intervention in such contextual harms, there is still much to learn. While research on the subject of police engaging in alcohol-related incidents has focused on police behaviours and strategies in response to such issues, there is a paucity of research that focuses on the knowledge and understanding of officers engaged in such behaviours and practices. Given the scarcity of research dealing with the knowledge, skills and attitudes of police officers responding to harms inside and outside licensed premises, this research contributes significantly to what is a recent and growing body of research and literature in the field. The research makes a practical contribution to police agencies’ understanding of officer knowledge and police practice in ways that have the potential to shape education and training agendas, policy approaches around generalist versus specialist policing, strategic and operational strategy, as well as partnership engagements. The research also makes a theoretical contribution given that the research design is informed by the Three Circle

Mg-based nanocomposites with high capacity and fast kinetics for hydrogen storage

Magnesium and its alloys have shown a great potential in effective hydrogen storage due to their advantages of high volumetric/gravimetric hydrogen storage capacity and low cost. However, the use of these materials in fuel cells for automotive applications at the present time is limited by high hydrogenation temperature and sluggish sorption kinetics. This paper presents the recent results of design and development of magnesium-based nanocomposites demonstrating the catalytic effects of carbon nanotubes and transition metals on hydrogen adsorption in these materials. The results are promising for the application of magnesium materials for hydrogen storage, with significantly reduced absorption temperatures and enhanced ab/desorption kinetics. High level Density Functional Theory calculations support the analysis of the hydrogenation mechanisms by revealing the detailed atomic and molecular interactions that underpin the catalytic roles of incorporated carbon and titanium, providing clear guidance for further design and development of such materials with better hydrogen storage properties.

High altitude stereo visual odometry

Stereo visual odometry has received little investigation in high altitude applications due to the generally poor performance of rigid stereo rigs at extremely small baseline-to-depth ratios. Without additional sensing, metric scale is considered lost and odometry is seen as effective only for monocular perspectives. This paper presents a novel modification to stereo based visual odometry that allows accurate, metric pose estimation from high altitudes, even in the presence of poor calibration and without additional sensor inputs. By relaxing the (typically fixed) stereo transform during bundle adjustment and reducing the dependence on the fixed geometry for triangulation, metrically scaled visual odometry can be obtained in situations where high altitude and structural deformation from vibration would cause traditional algorithms to fail. This is achieved through the use of a novel constrained bundle adjustment routine and accurately scaled pose initializer. We present visual odometry results demonstrating the technique on a short-baseline stereo pair inside a fixed-wing UAV flying at significant height (~30-100m).

Australian adolescent perceptions of parental support: Can it predict self-esteem among high and low SES groups?

Aims Physical activity has been shown to increase adolescent self-esteem. The aim of this investigation was to assess adolescent perceptions of parental support for physical activity endeavours, and its relationship with self-esteem among high and low SES groups. Methods Perceptions of parental support, and Rosenberg’s self-esteem (1965) were derived from the Children’s Physical Activity Correlates questionnaire, with scores ranging from 1 (lowest) to 4 (highest). Independent sample t-tests were conducted and Levene’s test indicated homogenous group variance, while Pearson’s r was employed to assess relationships between perceptions of parental support, and self-esteem. Results Overall, 111 (89%) and 64 (55%) high and low SES participants had complete data and were included in the analysis. The high SES differed for self-esteem (M = 3.39, SE = .05) from the low SES group (M = 2.75, SE = .08), t (173) = 6.82, p < .05, with a medium effect size (ES) r = .46. The high SES group scored higher for perceptions of parental support (M = 2.95, SE = .06) than the low SES group (M = 2.71, SE = .07), t (173) = 2.58, p < .05, with a low ES r = .04. Self-esteem was significantly correlated with parental support in both high (r = .34) and low (r = .47) SES groups. Conclusion Results indicate that perceptions of parental support may be a stronger indicator of self-esteem for low, than for high SES adolescents. Future physical activity strategies to promote self-esteem should involve parents as active facilitators.

Bridging the gap: Wellness differences between high and low SES Australian adolescents

Aims Wellness assessments can determine adolescent lifestyle behaviors. A better understanding of wellness differences between high and low SES adolescents could assist policy makers to develop improved strategies to bridge the gap between these two groups. The aim of this investigation was to explore wellness differences between high and low SES adolescents. Methods In total, 241 (125 high and 116 low SES) adolescents completed the 5-Factor Wellness Inventory (5F-Wel). The 5F-Wel comprises 97 items contributing to 17 subscales, 5 dimensions, 4 contexts, total wellness, and a life satisfaction index, with scores ranging from 0-100. Independent sample t-tests were performed with Levene’s test of equality for variances, which checked the assumption of homogeneity of variances. Results Overall, 117 (94%) and 112 (97 %) high and low SES participants had complete data and were included in the analysis. The high SES group scored higher for total wellness (M = 81.09, SE = .61) than the low SES group (M = 75.73, SE = .99). This difference was significant t (186) = 4.635, p < .05, with a medium effect size r = .32. The high SES group scored higher on 23 of 27 scales (21 scales, p < .05), while the low SES group scored higher on the remaining 3 scales (all non-significant). Conclusion These results contribute empirical data to the body of literature, indicating a large wellness discrepancy between high and low SES youth. Deficient areas can be targeted by policymakers to assist in bridging the gap between these groups.

An in situ high pressure FT-IR study of CO2/H2 interactions with model ZnO/SiO2, Cu/SiO2 and Cu/ZnO/SiO2 methanol synthesis catalysts

In situ FT-IR spectroscopy allows the methanol synthesis reaction to be investigated under actual industrial conditions of 503 K and 10 MPa. On Cu/SiO2 catalyst formate species were initially formed which were subsequently hydrogenated to methanol. During the reaction a steady state concentration of formate species persisted on the copper. Additionally, a small quantity of gaseous methane was produced. In contrast, the reaction of CO2 and H2 on ZnO/SiO2 catalyst only resulted in the formation of zinc formate species: no methanol was detected. The interaction of CO2 and H2 with Cu/ZnO/SiO2 catalyst gave formate species on both copper and zinc oxide. Methanol was again formed by the hydrogenation of copper formate species. Steady-state concentrations of copper formate existed under actual industrial reaction conditions, and copper formate is the pivotal intermediate for methanol synthesis. Collation of these results with previous data on copper-based methanol synthesis catalysts allowed the formulation of a reaction mechanism

Yersinia high pathogenicity island genes modify the Escherichia coli primary metabolome independently of siderophore production

Bacterial siderophores may enhance pathogenicity by scavenging iron, but their expression has been proposed to exert a substantial metabolic cost. Here we describe a combined metabolomic-genetic approach to determine how mutations affecting the virulence-associated siderophore yersiniabactin affect the Escherichia coli primary metabolome. Contrary to expectations, we did not find yersiniabactin biosynthesis to correspond to consistent metabolomic shifts. Instead, we found that targeted deletion of ybtU or ybtA, dissimilar genes with similar roles in regulating yersiniabactin expression, were associated with a specific shift in arginine pathway metabolites during growth in minimal media. This interaction was associated with high arginine levels in the model uropathogen Escherichia coli UTI89 compared to its ybtU and ybtA mutants and the K12 strain MG1655, which lacks yersiniabactin-associated genes. Because arginine is not a direct yersiniabactin biosynthetic substrate, these findings show that virulence-associated secondary metabolite systems may shape bacterial primary metabolism independently of substrate consumption

Power converters design and analysis for high power piezoelectric ultrasonic transducers

High power piezoelectric ultrasonic transducers have been widely exploited in a variety of applications. The critical behaviour of a piezoelectric device is encapsulated in its resonant frequencies because of its maximum transmission performance at these frequencies. Therefore power electronic converters should be tuned at those resonant frequencies to transfer electrical power to mechanical power efficiently. However, structural and environmental changes cause variations in the device resonant frequencies which can degrade the system performance. Hence, estimating the device resonant frequencies within the incorporated setup can significantly improve the system performance. This paper proposes an efficient resonant frequency estimation approach to maintain the performance of high power ultrasonic applications using the employed power converter. Experimental validations indicate the effectiveness of the proposed method.

Pharmacokinetics of cimifugin in rat plasma after oral administration of the extract of Saposhnikovia divaricatae root : Determination of cimifugin by high performance liquid chromatography coupled with solid phase extraction

High performance liquid chromatography (HPLC) coupled with the solid phase extraction method was developed for determining cimifugin (a coumarin derivative; one of Saposhnikovia divaricatae's constituents) in rat plasma after oral administration of Saposhnikovia divaricatae extract (SDE), and the pharmacokinetics of cimifugin either in SDE or as a single compound was investigated. The HPLC analysis was performed on a commercially available column (4.6 mm x 200 mm, 5 pm) with the isocratic elution of solvent A (Methanol) and solvent B (Water) (A:B=60:40) and the detection wavelength was set at 250 nm. The calibration curve was linear over the range of 0.100-10.040 microg/mL. The limit of detection was 30 ng/mL. At the rat plasma concentrations of 0.402, 4.016, 10.040 microg/mL, the intra-day precision was 6.21%, 3.98%, and 2.23%; the inter-day precision was 7.59%, 4.26%, and 2.09%, respectively. The absolute recovery was 76.58%, 76.61%, and 77.67%, respectively. When the dosage of SDE was equal to the pure compound calculated by the amount of cimifugin, it was found to have two maximum peaks while the pure compound only showed one peak in the plasma concentration-time curve. The pharmacokinetic characteristics of SDE showed the superiority of the extract and the properties of traditional Chinese medicine.

High-resolution loss of heterozygosity screening implicates PTPRJ as a potential tumor suppressor gene that affects susceptibility to non-Hodgkin's Lymphoma

We employed a Hidden-Markov-Model (HMM) algorithm in loss of heterozygosity (LOH) analysis of high-density single nucleotide polymorphism (SNP) array data from Non-Hodgkin’s lymphoma (NHL) entities, follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). This revealed a high frequency of LOH over the chromosomal region 11p11.2, containing the gene encoding the protein tyrosine phosphatase receptor type J (PTPRJ). Although PTPRJ regulates components of key survival pathways in B-cells (i.e., BCR, MAPK, and PI3K signaling), its role in B-cell development is poorly understood. LOH of PTPRJ has been described in several types of cancer but not in any hematological malignancy. Interestingly, FL cases with LOH exhibited down-regulation of PTPRJ, in contrast no significant variation of expression was shown in DLBCLs. In addition, sequence screening in Exons 5 and 13 of PTPRJ identified the G973A (rs2270993), T1054C (rs2270992), A1182C (rs1566734), and G2971C (rs4752904) coding SNPs (cSNPs). The A1182 allele was significantly more frequent in FLs and in NHLs with LOH. Significant over-representation of the C1054 (rs2270992) and the C2971 (rs4752904) alleles were also observed in LOH cases. A haplotype analysis also revealed a significant lower frequency of haplotype GTCG in NHL cases, but it was only detected in cases with retention. Conversely, haplotype GCAC was over-representated in cases with LOH. Altogether, these results indicate that the inactivation of PTPRJ may be a common lymphomagenic mechanism in these NHL subtypes and that haplotypes in PTPRJ gene may play a role in susceptibility to NHL, by affecting activation of PTPRJ in these B-cell lymphomas.

Variants in the human potassium channel gene (KCNN3) are associated with migraine in a high risk genetic isolate

The calcium-activated potassium ion channel gene (KCNN3) is located in the vicinity of the familial hemiplegic migraine type 2 locus on chromosome 1q21.3. This gene is expressed in the central nervous system and plays a role in neural excitability. Previous association studies have provided some, although not conclusive, evidence for involvement of this gene in migraine susceptibility. To elucidate KCNN3 involvement in migraine, we performed gene-wide SNP genotyping in a high-risk genetic isolate from Norfolk Island, a population descended from a small number of eighteenth century Isle of Man ‘Bounty Mutineer’ and Tahitian founders. Phenotype information was available for 377 individuals who are related through the single, well-defined Norfolk pedigree (96 were affected: 64 MA, 32 MO). A total of 85 SNPs spanning the KCNN3 gene were genotyped in a sub-sample of 285 related individuals (76 affected), all core members of the extensive Norfolk Island ‘Bounty Mutineer’ genealogy. All genotyping was performed using the Illumina BeadArray platform. The analysis was performed using the statistical program SOLAR v4.0.6 assuming an additive model of allelic effect adjusted for the effects of age and sex. Haplotype analysis was undertaken using the program HAPLOVIEW v4.0. A total of four intronic SNPs in the KCNN3 gene displayed significant association (P < 0.05) with migraine. Two SNPs, rs73532286 and rs6426929, separated by approximately 0.1 kb, displayed complete LD (r 2 = 1.00, D′ = 1.00, D′ 95% CI = 0.96–1.00). In all cases, the minor allele led to a decrease in migraine risk (beta coefficient = 0.286–0.315), suggesting that common gene variants confer an increased risk of migraine in the Norfolk pedigree. This effect may be explained by founder effect in this genetic isolate. This study provides evidence for association of variants in the KCNN3 ion channel gene with migraine susceptibility in the Norfolk genetic isolate with the rarer allelic variants conferring a possible protective role. This the first comprehensive analysis of this potential candidate gene in migraine and also the first study that has utilised the unique Norfolk Island large pedigree isolate to implicate a specific migraine gene. Studies of additional variants in KCNN3 in the Norfolk pedigree are now required (e.g. polyglutamine variants) and further analyses in other population data sets are required to clarify the association of the KCNN3 gene and migraine risk in the general outbred population.