Partial agonists of the [alpha]3[beta]4[ast] neuronal nicotinic acetylcholine receptor reduce ethanol consumption and seeking in rats

Alcohol use disorders (AUDs) impact millions of individuals and there remain few effective treatment strategies. Despite evidence that neuronal nicotinic acetylcholine receptors (nAChRs) have a role in AUDs, it has not been established which subtypes of the nAChR are involved. Recent human genetic association studies have implicated the gene cluster CHRNA3-CHRNA5-CHRNB4 encoding the α3, α5, and β4 subunits of the nAChR in susceptibility to develop nicotine and alcohol dependence; however, their role in ethanol-mediated behaviors is unknown due to the lack of suitable and selective research tools. To determine the role of the α3, and β4 subunits of the nAChR in ethanol self-administration, we developed and characterized high-affinity partial agonists at α3β4 nAChRs, CP-601932, and PF-4575180. Both CP-601932 and PF-4575180 selectively decrease ethanol but not sucrose consumption and operant self-administration following long-term exposure. We show that the functional potencies of CP-601932 and PF-4575180 at α3β4 nAChRs correlate with their unbound rat brain concentrations, suggesting that the effects on ethanol self-administration are mediated via interaction with α3β4 nAChRs. Also varenicline, an approved smoking cessation aid previously shown to decrease ethanol consumption and seeking in rats and mice, reduces ethanol intake at unbound brain concentrations that allow functional interactions with α3β4 nAChRs. Furthermore, the selective α4β2(*) nAChR antagonist, DHβE, did not reduce ethanol intake. Together, these data provide further support for the human genetic association studies, implicating CHRNA3 and CHRNB4 genes in ethanol-mediated behaviors. CP-601932 has been shown to be safe in humans and may represent a potential novel treatment for AUDs.

Volcanology and petrology of submarine volcanoes of the New Hebrides island arc

The New Hebrides Island Arc, an intra-oceanic island chain in the southwest Pacific, is formed by subduction of the Indo-Australian Plate beneath the Pacific Plate. The southern end of the New Hebrides Island Arc is an ideal location to study the magmatic and tectonic interaction of an emerging island arc as this part of the island chain is less than 3 million years old. A tectonically complex island arc, it exhibits a change in relative subduction rate from ~12cm/yr to 6 cm/yr before transitioning to a left-lateral strike slip zone at its southern end. Two submarine volcanic fields, Gemini-Oscostar and Volsmar, occur at this transition from normal arc subduction to sinistral strike slip movement. Multi-beam bathymetry and dredge samples collected during the 2004 CoTroVE cruise onboard the RV Southern Surveyor help define the relationship between magmatism and tectonics, and the source for these two submarine volcanic fields. Gemini-Oscostar volcanic field (GOVF), dominated by northwest-oriented normal faults, has mature polygenetic stratovolcanoes with evidence for explosive subaqueous eruptions and homogeneous monogenetic scoria cones. Volsmar volcanic field (VVF), located 30 km south of GOVF, exhibits a conjugate set of northwest and eastwest-oriented normal faults, with two polygenetic stratovolcanoes and numerous monogenetic scoria cones. A deep water caldera provides evidence for explosive eruptions at 1500m below sea level in the VVF. Both volcanic fields are dominated by low-K island arc tholeiites and basaltic andesites with calcalkalic andesite and dacite being found only in the GOVF. Geochemical signatures of both volcanic fields continue the along-arc trend of decreasing K2O with both volcanic fields being similar to the New Hebrides central chain lavas. Lavas from both fields display a slight depletion in high field strength elements and heavy rare earth elements, and slight enrichments in large-ion lithophile elements and light rare earth elements with respect to N-MORB mantle. Sr and Nd isotope data correlate with heavy rare earth and high field strength element data to show that both fields are derived from depleted mantle. Pb isotopes define Pacific MORB mantle sources and are consistent with isotopic variation along the New Hebrides Island Arc. Pb isotopes show no evidence for sediment contamination; the subduction component enrichment is therefore a slab-derived enrichment. There is a subtle spatial variation in source chemistry which sees a northerly trend of decreasing enrichment of slab-derived fluids.

Haplotype analysis of two recurrent CDKN2A mutations in 10 melanoma families : evidence for common founders and independent mutations

Germ-line mutations in CDKN2A have been shown to predispose to cutaneous malignant melanoma. We have identified 2 new melanoma kindreds which carry a duplication of a 24bp repeat present in the 5' region of CDKN2A previously identified in melanoma families from Australia and the United States. This mutation has now been reported in 5 melanoma families from 3 continents: Europe, North America, and Australasia. The M53I mutation in exon 2 of CDKN2A has also been documented in 5 melanoma families from Australia and North America. The aim of this study was to determine whether the occurrence of the mutations in these families from geographically diverse populations represented mutation hotspots within CDKN2A or were due to common ancestors. Haplotypes of 11 microsatellite markers flanking CDKN2A were constructed in 5 families carrying the M53I mutation and 5 families carrying the 24bp duplication. There were some differences in the segregating haplotypes due primarily to recombinations and mutations within the short tandem-repeat markers; however, the data provide evidence to indicate that there were at least 3 independent 24bp duplication events and possibly only 1 original M53I mutation. This is the first study to date which indicates common founders in melanoma families from different continents.

Evidence for three tumor suppressor loci on chromosome 9p involved in melanoma development

Cytogenetic and loss of heterozygosity (LOH) studies have long indicated the presence of a tumor suppressor gene (TSG) on 9p involved in the development of melanoma. Although LOH at 9p has been reported in approximately 60% of melanoma tumors, only 5-10% of these tumors have been shown to carry CDKN2A mutations, raising the possibility that another TSG involved in melanoma maps to chromosome 9p. To investigate this possibility, a panel of 37 melanomas derived from 35 individuals was analyzed for CDKN2A mutations by single-strand conformation polymorphism analysis and sequencing. The melanoma samples were then typed for 15 markers that map to 9p13-24 to investigate LOH trends in this region. In those tumors demonstrating retention of heterozygosity at markers flanking CDKN2A and LOH on one or both sides of the gene, multiplex microsatellite PCR was performed to rule out homozygous deletion of the region encompassing CDKN2A. CDKN2A mutations were found in tumors from 5 patients [5 (14%) of 35], 4 of which demonstrated LOH across the entire region examined. The remaining tumor with no observed LOH carried two point mutations, one on each allele. Although LOH was identified at one or more markers in 22 (59%) of 37 melanoma tumors corresponding to 20 (57%) of 35 individuals, only 11 tumors from 9 individuals [9 (26%) of 35] demonstrated LOH at D9S942 and D9S1748 the markers closest to CDKN2A. Of the remaining 11 tumors with LOH 9 demonstrated LOH at two or more contiguous markers either centromeric and/or telomeric to CDKN2A while retaining heterozygosity at several markers adjacent to CDKN2A. Multiplex PCR revealed one tumor carried a homozygous deletion extending from D9S1748 to the IFN-alpha locus. In the remaining eight tumors, multiplex PCR demonstrated that the observed heterozygosity was not attributable to homozygous deletion and stromal contamination at D9S1748, D9S942, or D9S974, as measured by comparative amplification strengths, which indicates that retention of heterozygosity with flanking LOH does not always indicate a homozygous deletion. This report supports the conclusions of previous studies that a least two TSGs involved in melanoma development in addition to CDKN2A may reside on chromosome 9p.

Drinking and driving in Vietnam : perceptions and risk

Road traffic injuries are a major global public health problem but continue to receive inadequate attention. Alcohol influences both risk and consequence of road traffic injury but the scale of the problem is not well understood in many countries. In Vietnam, economic development has brought a substantial increase in the number of registered motorcycles as well as alcohol consumption. Traffic injury is among the leading causes of death in Vietnam but there is little local information regarding alcohol related traffic injuries. The primary goal of this study is to explore the drinking and driving patterns of males and their perceptions towards drink-driving and to determine the relationship between alcohol consumption and road traffic injuries. Furthermore, this thesis aims to present the situation analysis for choosing priority actions to reduce drinking and driving in Vietnam. The study is a combination of two cross-sectional surveys and a pilot study. The pilot study, involving 224 traffic injured patients, was conducted to test the tools and the feasibility of approach methods. In the first survey, male patrons (n=464) were randomly selected at seven restaurants. Face-to-face interviews were conducted when patrons just arrived and breath tests were collected when they were about to leave the restaurant. In the second survey, male patients admitted to hospital following a traffic injury (n=480, of which 414 were motorcycle or bicycle riders) were interviewed and their blood alcohol concentration (BAC) measured by breathalyzer. The results show broadly similar patterns of drinking and driving among male patrons and male traffic injured patients with a high frequency of drinking and drink-driving reported among the majority of the two groups. A high proportion of male patrons were leaving restaurants with a BAC over the legal limit. Factors that significantly associate with the number of drinks and BAC were age, hazardous drinking, frequency of drink-driving in the past year, self-estimated number of drinks consumed to drive legally, perceived family’s disapproval of drink-driving, and perceived legal risk and physical risk. The proportion of patrons and patients with BAC above the legal limit of 0.05 were 86.7% and 60.4% respectively, which was much higher than found in previous studies. In addition, both groups had a high prevalence of BAC over 0.15g/100ml (39.7% of patrons and 45.6% patients), a level that can seriously affect driving capacity. Results from the case-crossover analysis for patients indicate a dose-response relationship between alcohol consumption and the risk of traffic injury. The risk of traffic injury increased when alcohol was consumed before driving and there was a more than 13 fold increase when six or more drinks were consumed. Regarding perceptions towards drinking and driving, findings corroborate the low awareness among males in Vietnam, with a majority of respondents holding a low knowledge of safe and legally permissible alcohol use, and a low perceived risk of drinking and driving. The results also indicate a huge gap in prevention skills in terms of planning ahead or using alternative transport to avoid drink-driving and a perception by patrons and patients of a low rate of disapproval of drink-driving from peers and family. Findings in this study have considerable implications for national policy, injury prevention, clinical practice, reporting systems, and for further research. The low rate of compliance with existing laws and a generally low perceived legal risk toward drink-driving in this study call for the strengthening of enforcement along with mass media campaigns and news coverage in order to decrease the widespread perception of impunity and thereby, to reduce the level of drink-driving. In addition, no significant difference was found in this study on risk of traffic injuries between car drivers and motorcycle drivers. The current inconsistency between legal BAC for drivers of motorcycles, compared to cars, thus needs addressing. Furthermore, as drinking was found to be very common, rather than solely targeting drink-driving, it is important to call for a more strategic and comprehensive approach to alcohol policy in Viet Nam. This study also has considerable implications for clinical practice in terms of screening and brief interventions. Our study suggests that the short form of the AUDIT (AUDIT-C) screening tool is appropriate for use in busy emergency departments. The high proportion of traffic injured patients with evidence of alcohol abuse or hazardous drinking suggests that brief interventions by alcohol and drug counselors in emergency departments are a sensible option to addressing this important problem. The significance of this study is in the combination of the systematic collection of breath test and use of case-crossover design to estimate the risk of traffic injuries after alcohol consumption. The results provide convincing evidence to policy makers, health authorities and the media to help raise community awareness and policy advocacy toward the drinkdriving problem in Vietnam. The findings suggest an urgent need for a multi-sectoral approach to curtail drink-driving in Vietnam, especially programs to raise community awareness and effective legal enforcement. Furthermore, serving as a situation analysis, the thesis should inform the formulation of interventions designed to curtail drinking and driving in Vietnam and other developing countries.

Daily average temperature and mortality among the elderly : a meta-analysis and systematic review of epidemiological evidence

The impact of climate change on the health of vulnerable groups such as the elderly has been of increasing concern. However, to date there has been no meta-analysis of current literature relating to the effects of temperature fluctuations upon mortality amongst the elderly. We synthesised risk estimates of the overall impact of daily mean temperature on elderly mortality across different continents. A comprehensive literature search was conducted using MEDLINE and PubMed to identify papers published up to December 2010. Selection criteria including suitable temperature indicators, endpoints, study-designs and identification of threshold were used. A two-stage Bayesian hierarchical model was performed to summarise the percent increase in mortality with a 1°C temperature increase (or decrease) with 95% confidence intervals in hot (or cold) days, with lagged effects also measured. Fifteen studies met the eligibility criteria and almost 13 million elderly deaths were included in this meta-analysis. In total, there was a 2-5% increase for a 1°C increment during hot temperature intervals, and a 1-2 % increase in all-cause mortality for a 1°C decrease during cold temperature intervals. Lags of up to 9 days in exposure to cold temperature intervals were substantially associated with all-cause mortality, but no substantial lagged effects were observed for hot intervals. Thus, both hot and cold temperatures substantially increased mortality among the elderly, but the magnitude of heat-related effects seemed to be larger than that of cold effects within a global context.

Developing a model of embedding academic numeracy in university programs : a case study from nursing

This is a study of the academic numeracy of nursing students. This study develops a theoretical model for the design and delivery of university courses in academic numeracy. The following objectives are addressed: 1. To investigate nursing students' current knowledge of academic numeracy; 2. To investigate how nursing students’ knowledge and skills in academic numeracy can be enhanced using a developmental psychology framework; and 3. To utilise data derived from meeting objectives 1 and 2 to develop a theoretical model to embed academic numeracy in university programs. This study draws from Valsiner’s Human Development Theory (Valsiner, 1997, 2007). It is a quasi-experimental intervention case study (Faltis, 1997) and takes a multimethod approach using pre- and post-tests; observation notes; and semi-structured teaching sessions to document a series of microgenetic studies of student numeracy. Each microgenetic study is centered on the lived experience of students becoming more numerate. The method for this section is based on Vygotsky’s double stimulation (Valsiner, 2000a; 2007). Data collection includes interviews on students’ past experience with mathematics; their present feelings and experiences and how these present feelings and experiences are transformed. The findings from this study have provided evidence that the course developed for nursing students, underpinned by an appropriate framework, does improve academic numeracy. More specifically, students improved their content knowledge of and confidence in mathematics in areas that were directly related to their degree. The study used Valsiner’s microgenetic approach to development to trace the course as it was being taught and two students’ personal academic numeracy journeys. It highlighted particularly troublesome concepts, then outlined scaffolding and pathways used to develop understanding. This approach to academic numeracy development was summarised into a four-faceted model at the university, program, course and individual level. This model can be applied successfully to similar contexts. Thus the thesis advances both theory and practice in this under-researched and under-theorised area.

Corporate governance mechanisms and earnings management in transitional countries – evidence from Chinese listed firms

The objective of this thesis is to investigate whether the corporate governance practices adopted by Chinese listed firms are associated with the quality of earnings information. Based on a review of agency and institutional theory, this study develops hypotheses that predict the monitoring effectiveness of the board and the audit committee. Using a combination of univariate and multivariate analyses, the association between corporate governance mechanisms and earnings management are tested from 2004 to 2008. Through analysing the empirical results, a number of findings are summarised as below. First, board independence is weakened by the introduction of government officials as independent directors on the boards. Government officials acting as independent directors, claim that they meet the definition of independent director set by the regulation. However, they have some connection with the State, which is the controlling shareholder in listed SOEs affiliated companies. Consequently, the effect of the independent director’s expertise in constraining earnings management is mitigated as demonstrated by an insignificant association between board expertise and earnings management. An alternative explanation for the inefficiency of board independence may point to the pre-selection of independent directors by the powerful CEO. It is argued that a CEO can manipulate the board composition and choose the "desirable" independent directors to monitor themselves. Second, a number of internal mechanisms, such as board size, board activities, and the separation of the roles of the CEO and chair are found to be significantly associated with discretionary accruals. This result suggests that there are advantages in having a large and active board in the Chinese setting. This can offset the disadvantages associated with large boards, such as increased bureaucracy, and hence, increase the constraining effects of a large and resourceful board. Third, factor analysis identifies two factors: CEO power and board power. CEO power is the factor which consists of CEO duality and turnover, and board power is composed of board size and board activity. The results of CEO power show that if a Chinese listed company has CEO duality and turnover at the same time, it is more likely to have a high level of earnings management. The significant and negative relationship between board power and accruals indicate that large boards with frequent meetings can be associated with low level of earnings management. Overall, the factor analysis suggests that certain governance mechanisms complement each other to become more efficient monitors of opportunistic earnings management. A combination of board characteristics can increase the negative association with earnings management. Fourth, the insignificant results between audit committees and earnings management in Chinese listed firms suggests that the Chinese regulator should strengthen the audit committee functions. This thesis calls for listed firms to disclose more information on audit committee composition and activities, which can facilitate future research on the Chinese audit committee’s monitoring role. Fifth, the interactive results between State ownership and board characteristics show that dominant State ownership has a moderating effect on board monitoring power as the State totally controls 42% of the issued shares. The high percentage of State ownership makes it difficult for the non-controlling institutional shareholders to challenge the State’s dominant status. As a result, the association between non-controlling institutional ownership and earnings management is insignificant in most situations. Lastly, firms audited by the international Big4 have lower abnormal accruals than firms audited by domestic Chinese audit firms. In addition, the inverse U-shape relationship between audit tenure and earnings quality demonstrates the changing effects of audit quality after a certain period of appointment. Furthermore, this thesis finds that listing in Hong Kong Stock Exchanges can be an alternative governance mechanism to discipline Chinese firms to follow strict Hong Kong listing requirements. Management of Hong Kong listed companies are exposed to the scrutiny of international investors and Hong Kong regulators. This in turn reduces their chances of conducting self-interested earnings manipulation. This study is designed to fill the gap in governance literature in China that is related to earnings management. Previous research on corporate governance mechanisms and earnings management in China is not conclusive. The current research builds on previous literature and provides some meaningful implications for practitioners, regulators, academic, and international investors who have investment interests in a transitional country. The findings of this study contribute to corporate governance and earnings management literature in the context of the transitional economy of China. The use of alternative measures for earnings management yields similar results compared with the accruals models and produces additional findings.

The effectiveness of a short-term group music therapy intervention for young parents and their children

The quality of early life experiences are known to influence a child’s capacities for emotional, social, cognitive and physical competence throughout their life (Peterson, 1996; Zubrick et al., 2008). These early life experiences are directly affected by parenting and family environments. A lack of positive parenting has significant implications both for children, and the broader communities in which they live (Davies & Cummings, 1994; Dryfoos, 1990; Sanders, 1995). Young parents are known to be at risk of experiencing adverse circumstances that affect their ability to provide positive parenting to their children (Milan et al., 2004; Trad, 1995). There is a need to provide parenting support programs to young parents that offer opportunities for them to come together, support each other and learn ways to provide for their children’s developmental needs in a friendly, engaging and non-judgemental environment. This research project examines the effectiveness of a 10 week group music therapy program Sing & Grow as an early parenting intervention for 535 young parents. Sing & Grow is a national early parenting intervention program funded by the Australian Government and delivered by Playgroup Queensland. It is designed and delivered by Registered Music Therapists for families at risk of marginalisation with children aged from birth to three years. The aim of the program is to improve parenting skills and parent-child interactions, and increase social support networks through participation in a group that is strengths-based and structured in a way that lends itself to modelling, peer learning and facilitated learning. During the 10 weeks parents have opportunities to learn practical, hands-on ways to interact and play with their children that are conducive to positive parent-child relationships and ongoing child development. A range of interactive, nurturing, stimulating and developmental music activities provide the framework for parents to interact and play with their children. This research uses data collected through the Sing & Grow National Evaluation Study to examine outcomes for all participants aged 25 years and younger, who attended programs during the Sing & Grow pilot study and main study from mid-2005 to the end of 2007. The research examines the change from pre to post in self-reported parent behaviours, parent mental health and parent social support, and therapist observed parent-child interactions. A range of statistical analyses are used to address each Research Objective for the young parent population, and for subgroups within this population. Research Objective 1 explored the patterns of attendance in the Sing & Grow program for young parents, and for subgroups within this population. Results showed that levels of attendance were lower than expected and influenced by Indigenous status and source of family income. Patterns of attendance showed a decline over time and incomplete data rates were high which may indicate high dropout rates. Research Objective 2 explored perceived satisfaction, benefits and social support links made. Satisfaction levels with the program and staff were very high. Indigenous status was associated with lower levels of reported satisfaction with both the program and staff. Perceived benefits from participation in the program were very high. Employment status was associated with perceived benefits: parents who were not employed were more likely than employed parents to report that their understanding of child development had increased as a result of participation in the program. Social support connections were reported for participants with other professionals, services and parents. In particular, families were more likely to link up with playgroup staff and services. Those parents who attended six or more sessions were significantly more likely to attend a playgroup than those who attended five sessions or less. Social support connections were related to source of family income, level of education, Indigenous status and language background. Research Objective 3 investigated pre to post change on self-report parenting skills and parent mental health. Results indicated that participation in the Sing & Grow program was associated with improvements in parent mental health. No improvements were found for self-reported parenting skills. Research Objective 4 investigated pre to post change in therapist observation measures of parent-child interactions. Results indicated that participation in the Sing & Grow program was associated with large and significant improvements in parent sensitivity to, engagement with and acceptance of the child. There were significant interactions across time (pre to post) for the parent characteristics of Indigenous status, family income and level of education. Research Objective 5 explored the relationship between the number of sessions attended and extent of change on self-report outcomes and therapist observed outcomes, respectively. For each, an overall change score was devised to ascertain those parents who had made any positive changes over time. Results showed that there was no significant relationship between high attendance and positive change in either the self-report or therapist observed behavioural measures. A risk index was also constructed to test for a relationship between the risk status of the parent. Parents with the highest risk status were significantly more likely to attend six or more sessions than other parents, but risk status was not associated with any differences in parent reported outcomes or therapist observations. The results of this research study indicate that Sing & Grow is effective in improving outcomes for young parents’ mental health, parent-child interactions and social support connections. High attendance by families in the highest category for risk factors may indicate that the program is effective at engaging and retaining parents who are most at-risk and therefore traditionally hard to reach. Very high levels of satisfaction and perceived benefits support this. Further research is required to help confirm the promising evidence from the current study that a short term group music therapy program can support young parents and improve their parenting outcomes. In particular, this needs to address the more disappointing outcomes of the current research study to improve attendance and engagement of all young parents in the program and especially the needs of young Indigenous parents.

Breastfeeding self-efficacy and alternative techniques to overcome maternal or infant breastfeeding challenges : a retrospective descriptive study

Background: Breastfeeding is the internationally accepted ideal in infant feeding. Ensuring mothers and babies receive optimal benefits, in both the short and long term, is dependent upon the successful establishment of breastfeeding in the first week. Many maternal and infant challenges can occur during the establishment of breastfeeding (Lactogenesis II). There are also many methods and devices (alternative techniques) which can be used to help, but the majority do not have an evidence-base. The mother.s self-confidence (self-efficacy) can be challenged by these unexpected circumstances, but understanding of the relationship is unclear. Method: This descriptive study used mail survey (including the Breastfeeding Self-Efficacy Scale . Short Form) to obtain the mother.s reports of their self-efficacy and their breastfeeding experience during the first week following birth, as well as actual use of alternative techniques. This study included all mothers of full term healthy singleton infants from one private hospital in Brisbane who began any breastfeeding. The data collection took place from November 2008 to February 2009. Ethical approval was granted from the research site and QUT Human Research Ethics Committee. Results: A total of 128 questionnaires were returned, a response rate of 56.9%. The sample was dissimilar to the Queensland population with regard to age, income, and education level, all of which were higher in this study. The sample was similar to the Queensland population in terms of parity and marital status. The rate of use of alternative techniques was 48.3%. The mean breastfeeding self-efficacy score of those who used any alternative technique was 43.43 (SD=12.19), and for those who did not, it was 58.32 (SD=7.40). Kruskal-Wallis analysis identified that the median self efficacy score for those who used alternative techniques was significantly lower than median self efficacy scores for those who did not use alternative techniques. The reasons women used alternative techniques varied widely, and their knowledge of alternative techniques was good. Conclusion: This study is the first to document breastfeeding self-efficacy of women who used alternative techniques to support their breastfeeding goals in the first week postpartum. An individualised clinical intervention to develop women.s self-efficacy with breastfeeding is important to assist mother/infant dyads encountering challenges to breastfeeding in the first week postpartum.