Cigarette smoking in young adults : the influence of the HTR2A T102C polymorphism and punishment sensitivity

Background: The C allele of a common polymorphism of the serotonin 2A receptor (HTR2A) gene, T102C, results in reduced synthesis of 5-HT2A receptors and has been associated with current smoking status in adults. The -1438A/G polymorphism, located in the regulatory region of this gene, is in linkage disequilibrium with T102C, and the A allele is associated with increased promoter activity and with smoking in adult males. We investigated the contributions of the HTR2A gene, chronic psychological stress, and impulsivity to the prediction of cigarette smoking status and dependence in young adults. Methods: T102C and -1438A/G genotyping was conducted on 132 healthy Caucasian young adults (47 smokers) who completed self-report measures of chronic stress, depressive symptoms, impulsive personality and cigarette use. Results: A logistic regression analysis of current cigarette smoker user status, after adjusting for gender, depressive symptom severity and chronic stress, indicated that the T102C TT genotype relative to the CC genotype (OR = 7.53), and lower punishment sensitivity (OR = 0.91) were each significant predictive risk factors. However, for number of cigarettes smoked, only lower punishment sensitivity was a significant predictor (OR = 0.81). Conclusions: These data indicate the importance of the T102C polymorphism to tobacco use but not number of cigarettes smoked for Caucasian young adults. Future studies should examine whether this is explained by effects of nicotine on the serotonin system. Lower punishment sensitivity increased risk of both smoking and of greater consumption, perhaps via a reduced sensitivity to cigarette health warnings and negative physiological effects.

Inhibitors to optimal project portfolio selection

The selection of projects and programs of work is a key function of both public and private sector organisations. Ideally, projects and programs that are selected to be undertaken are consistent with strategic objectives for the organisation; will provide value for money and return on investment; will be adequately resourced and prioritised; will not compete with general operations for resources and not restrict the ability of operations to provide income to the organisation; will match the capacity and capability of the organisation to deliver; and will produce outputs that are willingly accepted by end users and customers. Unfortunately,this is not always the case. Possible inhibitors to optimal project portfolio selection include: processes that are inconsistent with the needs of the organisation; reluctance to use an approach that may not produce predetermined preferences; loss of control and perceived decision making power; reliance on quantitative methods rather than qualitative methods for justification; ineffective project and program sponsorship; unclear project governance, processes and linkage to business strategies; ignorance, taboos and perceived effectiveness; inadequate education and training about the processes and their importance.

Culture-fair assessment : challenging Indigenous students through effortful mathematics teaching

This paper reports on a mathematics education research project centred on teachers’ pedagogical practices and capacity to assess Indigenous Australian students in a culture-fair manner. The project has been funded by the Australian Research Council Linkage program and is being conducted in seven Catholic and Independent primary schools in north Queensland. Our Industry Partners are Catholic Education and the Association of Independent Schools, Queensland. The study aims to provide greater understanding about how to build more equitable assessment practices to address the issue of underperforming Aboriginal and Torres Strait Islander (ATSI) students in regional and remote Australia. The goal is to identify ways forward by attending to culture-fair assessment practice. The research is exploring the attitudes, beliefs and responses of Indigenous students to assessment in the context of mathematics learning with particular focus on teacher knowledge in these educational settings in relation to the design of assessment tasks that are authentic and engaging for these students in an accountability context. This approach highlights how teachers need to distinguish the ‘funds of knowledge’ (González, Moll, Floyd Tenery, Rivera, Rendón, Gonzales & Amanti, 2008) that Indigenous students draw on and how teachers need to be culturally responsive in their pedagogy to open up curriculum and assessment practice to allow for different ways of knowing and being

Linking ambulance, emergency department and hospital admissions data : understanding the emergency journey

Objective: to assess the accuracy of data linkage across the spectrum of emergency care in the absence of a unique patient identifier, and to use the linked data to examine service delivery outcomes in an emergency department setting. Design: automated data linkage and manual data linkage were compared to determine their relative accuracy. Data were extracted from three separate health information systems: ambulance, ED and hospital inpatients, then linked to provide information about the emergency journey of each patient. The linking was done manually through physical review of records and automatically using a data linking tool (Health Data Integration) developed by the CSIRO. Match rate and quality of the linking were compared. Setting: 10, 835 patient presentations to a large, regional teaching hospital ED over a two month period (August-September 2007). Results: comparison of the manual and automated linkage outcomes for each pair of linked datasets demonstrated a sensitivity of between 95% and 99%; a specificity of between 75% and 99%; and a positive predictive value of between 88% and 95%. Conclusions: Our results indicate that automated linking provides a sound basis for health service analysis, even in the absence of a unique patient identifier. The use of an automated linking tool yields accurate data suitable for planning and service delivery purposes and enables the data to be linked regularly to examine service delivery outcomes.

CRE workshop part I : comprehending the context

CRE (Corporate Real Estate) decisions should not simply deal with the management of individual facilities, but should especially be concerned with the relationships that a facility has with the corporate business strategy and with the larger real estate markets. Both the practice and the research of CRE management have historically tended to emphasize real estate issues and ignore the corporation’s business issues, causing real estate strategies to be disconnected from the goal and priorities of the corporation’s senior management. With regard to office cycles, a large number of econometric models have been proposed during the last 20 years. However, evidence from historical data and previous research in the field of real estate forecasting seem to agree only on one thing: the existence of interconnected property cycles that are concentrated on vacancy rates (demand). Vacancy also represents the linkage between the inadequacy of existing CRE strategies and the inability of existing econometric models to correctly forecast office rent cycles. Business cycles, across different industry sectors, have decreased from 5-7 years to 1-3 years today, yet corporations are still entering into leases of 5-10 years, causing hidden vacancy levels to rise. Possibly, once CRE strategies are totally in tune with the overall business, hidden vacancy will fade away providing forecasters with better quality data. The aim of this paper is not to investigate whether and when the supply-side will eventually evolve to provide flexible occupancy arrangements to accommodate corporate agility requirements, but rather to propose a general framework for corporations to improve the decision making process of their CRE executives, while emphasizing the importance of understanding the context as a precondition to effective real estate involvements.

Extending the task of diarization to speaker attribution

In this paper we extend the concept of speaker annotation within a single-recording, or speaker diarization, to a collection wide approach we call speaker attribution. Accordingly, speaker attribution is the task of clustering expectantly homogenous intersession clusters obtained using diarization according to common cross-recording identities. The result of attribution is a collection of spoken audio across multiple recordings attributed to speaker identities. In this paper, an attribution system is proposed using mean-only MAP adaptation of a combined-gender UBM to model clusters from a perfect diarization system, as well as a JFA-based system with session variability compensation. The normalized cross-likelihood ratio is calculated for each pair of clusters to construct an attribution matrix and the complete linkage algorithm is employed to conduct clustering of the inter-session clusters. A matched cluster purity and coverage of 87.1% was obtained on the NIST 2008 SRE corpus.

Bayesian methodology for genetics of complex diseases

Genetic research of complex diseases is a challenging, but exciting, area of research. The early development of the research was limited, however, until the completion of the Human Genome and HapMap projects, along with the reduction in the cost of genotyping, which paves the way for understanding the genetic composition of complex diseases. In this thesis, we focus on the statistical methods for two aspects of genetic research: phenotype definition for diseases with complex etiology and methods for identifying potentially associated Single Nucleotide Polymorphisms (SNPs) and SNP-SNP interactions. With regard to phenotype definition for diseases with complex etiology, we firstly investigated the effects of different statistical phenotyping approaches on the subsequent analysis. In light of the findings, and the difficulties in validating the estimated phenotype, we proposed two different methods for reconciling phenotypes of different models using Bayesian model averaging as a coherent mechanism for accounting for model uncertainty. In the second part of the thesis, the focus is turned to the methods for identifying associated SNPs and SNP interactions. We review the use of Bayesian logistic regression with variable selection for SNP identification and extended the model for detecting the interaction effects for population based case-control studies. In this part of study, we also develop a machine learning algorithm to cope with the large scale data analysis, namely modified Logic Regression with Genetic Program (MLR-GEP), which is then compared with the Bayesian model, Random Forests and other variants of logic regression.

The factor V HR2 haplotype: Prevalence and association of the A4070G and A6755G polymorphisms

Recently, a polymorphism was identified in exon 25 of the factor V gene that is possibly a functional candidate for the HR2 haplotype. This haplotype is characterized by a single base substitution named R2 (A4070G) in the B domain of the protein. A mutation (A6755G; 2194Asp→Gly) located near the C terminus has been hypothesized to influence protein folding and glycosylation, and might be responsible for the shift in factor V isoform (FV1 / FV2) ratio. This study investigated the prevalence of these two factor V HR2 haplotype polymorphisms in a cohort of normal blood donors, patients with osteoarthritis and women with complications during pregnancy, and in families of factor V Leiden individuals. A high allele frequency for the two polymorphisms was found in the blood donor group (6.2% R2, 5.6% A6755G). No significant difference in allele frequency was observed in the clinical groups (obstetric complications and osteoarthritis, 4.1-4.9% for the two polymorphisms) when compared with that of healthy blood donors. We confirm that the factor V A6755G polymorphism shows strong linkage to the R2 allele, although it is not exclusively inherited with the exon 13 A4070G variant and can occur independently. © 2001 Lippincott Williams & Wilkins.

Moderation and consistency of teacher judgement : teachers’ views

Major curriculum and assessment reforms in Australia have generated research interest in issues related to standards, teacher judgement and moderation. This article is based on one related inquiry of a large-scale Australian Research Council Linkage project conducted in Queensland. This qualitative study analysed interview data to identify teachers’ views on standards and moderation as a means to achieving consistency of teacher judgement. A complementary aspect of the research involved a blind review that was conducted to determine the degree of teacher consistency without the experience of moderation. Empirical evidence was gained that most teachers, of the total interviewed, articulated a positive attitude towards the use of standards in moderation and perceived that this process produces consistency in teachers’ judgements. Context was identified as an important influential factor in teachers’ judgements and it was concluded that teachers’ assessment beliefs, attitudes and practices impact on their perceptions of the value of moderation practice and the extent to which consistency can be achieved.

Exploiting the 1,2,3-triazolium motif in anion-templated formation of a bromide-selective rotaxane host assembly

Stimulated by the efficacy of copper (I) catalysed Huisgen-type 1,3-dipolar cycloaddition of terminal alkynes and organic azides to generate 1,4-disubstituted 1,2,3-triazole derivatives, the importance of ‘click’ chemistry in the synthesis of organic and biological molecular systems is ever increasing.[1] The mild reaction conditions have also led to this reaction gaining favour in the construction of interlocked molecular architectures.[2-4] In the majority of cases however, the triazole group simply serves as a covalent linkage with no function in the resulting organic molecular framework. More recently a renewed interest has been shown in the transition metal coordination chemistry of triazole ligands.[3, 5, 6] In addition novel aryl macrocyclic and acyclic triazole based oligomers have been shown to recognise halide anions via cooperative triazole C5-H….anion hydrogen bonds.[7] In light of this it is surprising the potential anion binding affinity of the positively charged triazolium motif has not, with one notable exception,[8] been investigated. With the objective of manipulating the unique topological cavities of mechanically bonded molecules for anion recognition purposes, we have developed general methods of using anions to template the formation of interpenetrated and interlocked structures.[9-13] Herein we report the first examples of exploiting the 1,2,3-triazolium group in the anion templated formation of pseudorotaxane and rotaxane assemblies. In an unprecedented discovery the bromide anion is shown to be a superior templating reagent to chloride in the synthesis of a novel triazolium axle containing [2]rotaxane. Furthermore the resulting rotaxane interlocked host system exhibits the rare selectivity preference for bromide over chloride...

Common variation in the fibroblast growth factor receptor 2 gene is not associated with endometriosis risk

BACKGROUND Endometriosis is a polygenic disease with a complex and multifactorial aetiology that affects 8-10% of women of reproductive age. Epidemiological data support a link between endometriosis and cancers of the reproductive tract. Fibroblast growth factor receptor 2 (FGFR2) has recently been implicated in both endometrial and breast cancer. Our previous studies on endometriosis identified significant linkage to a novel susceptibility locus on chromosome 10q26 and the FGFR2 gene maps within this linkage region. We therefore hypothesized that variation in FGFR2 may contribute to the risk of endometriosis. METHODS We genotyped 13 single nucleotide polymorphisms (SNPs) densely covering a 27 kb region within intron 2 of FGFR2 including two SNPs (rs2981582 and rs1219648) significantly associated with breast cancer and a total 40 tagSNPs across 150 kb of the FGFR2 gene. SNPs were genotyped in 958 endometriosis cases and 959 unrelated controls. RESULTS We found no evidence for association between endometriosis and FGFR2 intron 2 SNPs or SNP haplotypes and no evidence for association between endometriosis and variation across the FGFR2 gene. CONCLUSIONS Common variation in the breast-cancer implicated intron 2 and other highly plausible causative candidate regions of FGFR2 do not appear to be a major contributor to endometriosis susceptibility in our large Australian sample.

Association between polymorphisms in the progesterone receptor gene and endometriosis

The progesterone receptor (PR) is a candidate gene for the development of endometriosis, a complex disease with strong hormonal features, common in women of reproductive age. We typed the 306 base pair Alu insertion (AluIns) polymorphism in intron G of PR in 101 individuals, estimated linkage disequilibrium (LD) between five single-nucleotide polymorphisms (SNPs) across the PR locus in 980 Australian triads (endometriosis case and two parents) and used transmission disequilibrium testing (TDT) for association with endometriosis. The five SNPs showed strong pairwise LD, and the AluIns was highly correlated with proximal SNPs rs1042839 (Δ2 = 0.877, D9 = 1.00, P < 0.0001) and rs500760 (Δ2 = 0.438, D9 = 0.942, P < 0.0001). TDT showed weak evidence of allelic association between endometriosis and rs500760 (P = 0.027) but not in the expected direction. We identified a common susceptibility haplotype GGGCA across the five SNPs (P = 0.0167) in the whole sample, but likelihood ratio testing of haplotype transmission and non-transmission of the AluIns and flanking SNPs showed no significant pattern. Further, analysis of our results pooled with those from two previous studies suggested that neither the T2 allele of the AluIns nor the T1/T2 genotype was associated with endometriosis.

Domestication to crop improvement: Genetic resources for sorghum and saccharum (Andropogoneae)

Background Both sorghum (Sorghum bicolor) and sugarcane (Saccharum officinarum) are members of the Andropogoneae tribe in the Poaceae and are each other's closest relatives amongst cultivated plants. Both are relatively recent domesticates and comparatively little of the genetic potential of these taxa and their wild relatives has been captured by breeding programmes to date. This review assesses the genetic gains made by plant breeders since domestication and the progress in the characterization of genetic resources and their utilization in crop improvement for these two related species. Genetic Resources The genome of sorghum has recently been sequenced providing a great boost to our knowledge of the evolution of grass genomes and the wealth of diversity within S. bicolor taxa. Molecular analysis of the Sorghum genus has identified close relatives of S. bicolor with novel traits, endosperm structure and composition that may be used to expand the cultivated gene pool. Mutant populations (including TILLING populations) provide a useful addition to genetic resources for this species. Sugarcane is a complex polyploid with a large and variable number of copies of each gene. The wild relatives of sugarcane represent a reservoir of genetic diversity for use in sugarcane improvement. Techniques for quantitative molecular analysis of gene or allele copy number in this genetically complex crop have been developed. SNP discovery and mapping in sugarcane has been advanced by the development of high-throughput techniques for ecoTILLING in sugarcane. Genetic linkage maps of the sugarcane genome are being improved for use in breeding selection. The improvement of both sorghum and sugarcane will be accelerated by the incorporation of more diverse germplasm into the domesticated gene pools using molecular tools and the improved knowledge of these genomes.

Assessing the concordance of health and child protection data for 'maltreated' and 'unintentionally injured' children

Objectives: To quantify the concordance of hospital child maltreatment data with child protection service (CPS) records and identify factors associated with linkage. Methods: Multivariable logistic regression analysis was conducted following retrospective medical record review and database linkage of 884 child records from 20 hospitals and the CPS in Queensland, Australia. Results: Nearly all children with hospital assigned maltreatment codes (93.1%) had a CPS record. Of these, 85.1% had a recent notification. 29% of the linked maltreatment group (n=113) were not known to CPS prior to the hospital presentation. Almost 1/3 of children with unintentional injury hospital codes were known to CPS. Just over 24% of the linked unintentional injury group (n=34) were not known to CPS prior to the hospital presentation but became known during or after discharge from hospital. These estimates are higher than the 2006/07 annual rate of 2.39% of children being notified to CPS. Rural children were more likely to link to CPS, and children were over 3 times more likely to link if the index injury documentation included additional diagnoses or factors affecting their health. Conclusions: The system for referring maltreatment cases to CPS is generally efficient, although up to 1 in 15 children had codes for maltreatment but could not be linked to CPS data. The high proportion of children with unintentional injury codes who linked to CPS suggests clinicians and hospital-based child protection staff should be supported by further education and training to ensure children at risk are being detected by the child protection system.

Analysis of the CDKN2A, CDKN2B and CDK4 genes in 48 Australian melanoma kindreds

Germline mutations within the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene and one of its targets, the cyclin dependent kinase 4 (CDK4) gene, have been identified in a proportion of melanoma kindreds. In the case of CDK4, only one specific mutation, resulting in the substitution of a cysteine for an arginine at codon 24 (R24C), has been found to be associated with melanoma. We have previously reported the identification of germline CDKN2A mutations in 7/18 Australian melanoma kindreds and the absence of the R24C CDK4 mutation in 21 families lacking evidence of a CDKN2A mutation. The current study represents an expansion of these efforts and includes a total of 48 melanoma families from Australia. All of these families have now been screened for mutations within CDKN2A and CDK4, as well as for mutations within the CDKN2A homolog and 9p21 neighbor, the CDKN2B gene, and the alternative exon 1 (E1beta) of CDKN2A. Families lacking CDKN2A mutations, but positive for a polymorphism(s) within this gene, were further evaluated to determine if their disease was associated with transcriptional silencing of one CDKN2A allele. Overall, CDKN2A mutations were detected in 3/30 (10%) of the new kindreds. Two of these mutations have been observed previously: a 24 bp duplication at the 5' end of the gene and a G to C transversion in exon 2 resulting in an M531 substitution. A novel G to A transition in exon 2, resulting in a D108N substitution was also detected. Combined with our previous findings, we have now detected germline CDKN2A mutations in 10/48 (21%) of our melanoma kindreds. In none of the 'CDKN2A-negative' families was melanoma found to segregate with either an untranscribed CDKN2A allele, an R24C CDK4 mutation, a CDKN2B mutation, or an E1beta mutation. The last three observations suggest that these other cell cycle control genes (or alternative gene products) are either not involved at all, or to any great extent, in melanoma predisposition.