Evaluating parent-child group music therapy programmes: challenges and successes for Sing & Grow

Sing & Grow is an early intervention music therapy programme for families with children from birth to 3 years of age, who are socially, economically, or physically disadvantaged. It aims to improve parenting skills and confidence, promote positive parent–child interactions, stimulate child development, and provide social networking opportunities. Music and song activities are used in a therapeutic context to enhance parenting skills, improve parent–child interactions, provide essential developmental stimulation for children, promote social support for parenting, and strengthen links between parents and community services.

CDKN2A/p16 is inactivated in most melanoma cell lines

The CDKN2A gene maps to chromosome 9p21-22 and is responsible for melanoma susceptibility in some families. Its product, p16, binds specifically to CDK4 and CDK6 in vitro and in vivo, inhibiting their kinase activity. CDKN2A is homozygously deleted or mutated in a large proportion of tumor cell lines and some primary tumors, including melanomas. The aim of this study was to investigate the involvement of CDKN2A and elucidate the mechanisms of p16 inactivation in a panel of 60 cell lines derived from sporadic melanomas. Twenty-six (43%) of the melanoma lines were homozygously deleted for CDKN2A, and an additional 15 (25%) lines carried missense, nonsense, or frameshift mutations. All but one of the latter group were shown by microsatellite analysis to be hemizygous for the region of 9p surrounding CDKN2A. p16 was detected by Western blotting in only five of the cell lines carrying mutations. Immunoprecipitation of p16 in these lines, followed by Western blotting to detect the coprecipitation of CDK4 and CDK6, revealed that p16 was functionally compromised in all cell lines but the one that carried a heterozygous CDKN2A mutation. In the remaining 19 lines that carried wild-type CDKN2A alleles, Western blot analysis and immunoprecipitation indicated that 11 cell lines expressed a wild-type protein. Northern blotting was performed on the remaining eight cell lines and revealed that one cell line carried an aberrantly sized RNA transcript, and two other cell lines failed to express RNA. The promoter was found to be methylated in five cell lines that expressed CDKN2A transcript but not p16. Presumably, the message seen by Northern blotting in these cell lines is the result of cross-hybridization of the total cDNA probe with the exon 1beta transcript. Microsatellite analysis revealed that the majority of these cell lines were hemi/homozygous for the region surrounding CDKN2A, indicating that the wild-type allele had been lost. In the 11 cell lines that expressed functional p16, microsatellite analysis revealed loss of heterozygosity at the markers immediately surrounding CDKN2A in five cases, and the previously characterized R24C mutation of CDK4 was identified in one of the remaining 6 lines. These data indicate that 55 of 60 (92%) melanoma cell lines demonstrated some aberration of CDKN2A or CDK4, thus suggesting that this pathway is a primary genetic target in melanoma development.

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.

High frequency of BRAF mutations in nevi

To evaluate the timing of mutations in BRAF (v-raf murine sarcoma viral oncogene homolog B1) during melanocytic neoplasia, we carried out mutation analysis on microdissected melanoma and nevi samples. We observed mutations resulting in the V599E amino-acid substitution in 41 of 60 (68%) melanoma metastases, 4 of 5 (80%) primary melanomas and, unexpectedly, in 63 of 77 (82%) nevi. These data suggest that mutational activation of the RAS/RAF/MAPK pathway in nevi is a critical step in the initiation of melanocytic neoplasia but alone is insufficient for melanoma tumorigenesis.

Computational approaches for modelling intrinsic noise and delays in genetic regulatory networks

This chapter focuses on the interactions and roles between delays and intrinsic noise effects within cellular pathways and regulatory networks. We address these aspects by focusing on genetic regulatory networks that share a common network motif, namely the negative feedback loop, leading to oscillatory gene expression and protein levels. In this context, we discuss computational simulation algorithms for addressing the interplay of delays and noise within the signaling pathways based on biological data. We address implementational issues associated with efficiency and robustness. In a molecular biology setting we present two case studies of temporal models for the Hes1 gene (Monk, 2003; Hirata et al., 2002), known to act as a molecular clock, and the Her1/Her7 regulatory system controlling the periodic somite segmentation in vertebrate embryos (Giudicelli and Lewis, 2004; Horikawa et al., 2006).

Evolving noisy oscillatory dynamics in genetic regulatory networks

We introduce a genetic programming (GP) approach for evolving genetic networks that demonstrate desired dynamics when simulated as a discrete stochastic process. Our representation of genetic networks is based on a biochemical reaction model including key elements such as transcription, translation and post-translational modifications. The stochastic, reaction-based GP system is similar but not identical with algorithmic chemistries. We evolved genetic networks with noisy oscillatory dynamics. The results show the practicality of evolving particular dynamics in gene regulatory networks when modelled with intrinsic noise.

A mathematical model for genetic regulation of the lactose operon

In this paper we construct a mathematical model for the genetic regulatory network of the lactose operon. This mathematical model contains transcription and translation of the lactose permease (LacY) and a reporter gene GFP. The probability of transcription of LacY is determined by 14 binding states out of all 50 possible binding states of the lactose operon based on the quasi-steady-state assumption for the binding reactions, while we calculate the probability of transcription for the reporter gene GFP based on 5 binding states out of 19 possible binding states because the binding site O2 is missing for this reporter gene. We have tested different mechanisms for the transport of thio-methylgalactoside (TMG) and the effect of different Hill coefficients on the simulated LacY expression levels. Using this mathematical model we have realized one of the experimental results with different LacY concentrations, which are induced by different concentrations of TMG.

Quality of life and genetics in men with prostate cancer

As family history has been established as a risk factor for prostate cancer, attempts have been made to isolate predisposing genetic variants that are related to hereditary prostate cancer. With many genetic variants still to be identified and investigated, it is not yet possible to fully understand the impact of genetic variants on prostate cancer development. The high survival rates among men with prostate cancer have meant that other issues, such as quality of life (QoL), have also become important. Through their effect on a person’s health, a range of inherited genetic variants may potentially influence QoL in men with prostate cancer, even prior to treatment. Until now, limited research has been conducted on the relationship between genetics and QoL. Thus, this study contributes to an emerging field by aiming to identify certain genetic variants related to the QoL found in men with prostate cancer. It is hoped that this study may lead to future research that will identify men who have an increased risk of a poor QoL following prostate cancer treatment, which will aid in developing treatments that are individually tailored to support them. Previous studies have established that genetic variants of Vascular Endothelial Growth Factor (VEGF) and Insulin-like Growth Factor 1 (IGF-1) may play a role in prostate cancer development. VEGF and IGF-1 have also been reported to be associated with QoL in people with ovarian cancer and colorectal cancer, respectively. This study completed a series of secondary analyses using two major data-sets (from 850 men newly diagnosed with prostate cancer, and approximately 550 men from the general Queensland population), in which genetic variants of VEGF and IGF-1 were investigated for associations with prostate cancer susceptibility and QoL. The first aim of this research was to investigate genetic variants in the VEGF and IGF-I gene for an association with the risk of prostate cancer. It was found that one IGF-1 genetic variant (rs35765) had a statistically significant association with prostate cancer (p = 0.04), and one VEGF genetic variant (rs2146323) had a statistically significant association with advanced prostate cancer (p = 0.02). The estimates suggest that carriers of the CA and AA genotype for rs35765 may have a reduced risk of developing prostate cancer (Odds Ratio (OR) = 0.72, 95% Confidence Interval (CI) = 0.55, 0.95, OR = 0.60, 95% CI = 0.26, 1.39, respectively). Meanwhile, carriers of the CA and AA genotype for rs2146323 may be at increased risk of advanced prostate cancer, which was determined by a Gleason score of above 7 (OR = 1.72, 95% CI = 1.12, 2.63, OR = 1.90, 95% CI = 1.08, 3.34, respectively). Utilising the widely used short-form health survey, the SF-36v2, the second aim of this study was to investigate the relationship between prostate cancer and QoL prior to treatment. Assessing QoL at this time-point was important as little research has been conducted to evaluate if prostate cancer affects QoL regardless of treatment. The analyses found that mean SF-36v2 scale scores related to physical health were higher by at least 0.3 Standard Deviations (SD) among men with prostate cancer than the general population comparison group. This difference was considered clinically significant (defined by group differences in mean SF-36v2 scores by at least 0.3 SD). These differences were also statistically significant (p<0.05). Mean QoL scale scores related to mental health were similar between men with prostate cancer and those from the general population comparison group. The third aim of this study was to investigate genetic variants in the VEGF and IGF-1 gene for an association with QoL in prostate cancer patients prior to their treatment. It was essential to evaluate these relationships prior to treatment, before the involvement of these genes was potentially interrupted by treatment. The analyses found that some genetic variants had a small clinically significant association (0.3 SD) to some QoL domains experienced by these men. However, most relationships were not statistically significant (p>0.05). Most of the associations found identified that a small sub-group of men with prostate cancer (approximately 2%) reported, on average, a slightly better QoL than the majority of the prostate cancer patients. The fourth aim of this research was to investigate whether associations between genetic variants in VEGF and IGF-1 and QoL were specific to men with prostate cancer, or were also applicable to the general male population. It was found that twenty out of one-hundred relationships between the genetic variants of VEGF and IGF-1 and QoL health-measures and scales examined differed between these groups. In the majority of the relationships involving VEGF SNPs that differed, a clinically significant difference (0.3 or more SD) between mean scores among the genotype groups in prostate cancer patients was found, while mean scores among men from the general-population comparison group were similar. For example, prostate cancer participants who carried at least one T allele (CT or TT genotype) for rs3024994 had a clinically significant higher (0.3 SD) mean QoL score in terms of the role-physical scale, than participants who carried the CC genotype. This was not seen among men from the general population sample, as the mean score was similar between genotype groups. The opposite was seen in regards to the IGF-1 SNPs examined. Overall, these relationships were not considered to directly impact on the clinical options for men with prostate cancer. As this study utilised secondary data from two separate studies, there are a number of important limitations that should be acknowledged including issues of multiple comparisons, power, and missing or unavailable data. It is recommended that this study be replicated as a better-designed study that takes greater consideration of the many factors involved in prostate cancer and QoL. Investigation into other genetic variants of VEGF or IGF-1 is also warranted, as is consideration of other genes and their relationship with QoL. Through identifying certain genetic variants that have a modest association to prostate cancer, this project adds to the knowledge surrounding VEGF and IGF-1 and their role in prostate cancer susceptibility. Importantly, this project has also introduced the potential role genetics plays in QoL, through investigating the relationships between genetic variants of VEGF and IGF-1 and QoL.

Evolving genetic regulatory networks performing as stochastic switches

Recent studies have shown that small genetic regulatory networks (GRNs) can be evolved in silico displaying certain dynamics in the underlying mathematical model. It is expected that evolutionary approaches can help to gain a better understanding of biological design principles and assist in the engineering of genetic networks. To take the stochastic nature of GRNs into account, our evolutionary approach models GRNs as biochemical reaction networks based on simple enzyme kinetics and simulates them by using Gillespie’s stochastic simulation algorithm (SSA). We have already demonstrated the relevance of considering intrinsic stochasticity by evolving GRNs that show oscillatory dynamics in the SSA but not in the ODE regime. Here, we present and discuss first results in the evolution of GRNs performing as stochastic switches.

QoS-aware web service composition using genetic algorithms

Web service technology is increasingly being used to build various e-Applications, in domains such as e-Business and e-Science. Characteristic benefits of web service technology are its inter-operability, decoupling and just-in-time integration. Using web service technology, an e-Application can be implemented by web service composition — by composing existing individual web services in accordance with the business process of the application. This means the application is provided to customers in the form of a value-added composite web service. An important and challenging issue of web service composition, is how to meet Quality-of-Service (QoS) requirements. This includes customer focused elements such as response time, price, throughput and reliability as well as how to best provide QoS results for the composites. This in turn best fulfils customers’ expectations and achieves their satisfaction. Fulfilling these QoS requirements or addressing the QoS-aware web service composition problem is the focus of this project. From a computational point of view, QoS-aware web service composition can be transformed into diverse optimisation problems. These problems are characterised as complex, large-scale, highly constrained and multi-objective problems. We therefore use genetic algorithms (GAs) to address QoS-based service composition problems. More precisely, this study addresses three important subproblems of QoS-aware web service composition; QoS-based web service selection for a composite web service accommodating constraints on inter-service dependence and conflict, QoS-based resource allocation and scheduling for multiple composite services on hybrid clouds, and performance-driven composite service partitioning for decentralised execution. Based on operations research theory, we model the three problems as a constrained optimisation problem, a resource allocation and scheduling problem, and a graph partitioning problem, respectively. Then, we present novel GAs to address these problems. We also conduct experiments to evaluate the performance of the new GAs. Finally, verification experiments are performed to show the correctness of the GAs. The major outcomes from the first problem are three novel GAs: a penaltybased GA, a min-conflict hill-climbing repairing GA, and a hybrid GA. These GAs adopt different constraint handling strategies to handle constraints on interservice dependence and conflict. This is an important factor that has been largely ignored by existing algorithms that might lead to the generation of infeasible composite services. Experimental results demonstrate the effectiveness of our GAs for handling the QoS-based web service selection problem with constraints on inter-service dependence and conflict, as well as their better scalability than the existing integer programming-based method for large scale web service selection problems. The major outcomes from the second problem has resulted in two GAs; a random-key GA and a cooperative coevolutionary GA (CCGA). Experiments demonstrate the good scalability of the two algorithms. In particular, the CCGA scales well as the number of composite services involved in a problem increases, while no other algorithms demonstrate this ability. The findings from the third problem result in a novel GA for composite service partitioning for decentralised execution. Compared with existing heuristic algorithms, the new GA is more suitable for a large-scale composite web service program partitioning problems. In addition, the GA outperforms existing heuristic algorithms, generating a better deployment topology for a composite web service for decentralised execution. These effective and scalable GAs can be integrated into QoS-based management tools to facilitate the delivery of feasible, reliable and high quality composite web services.

The influence of conformity and group identity on drink walking intentions : comparing intentions to drink walk across risky pedestrian crossing scenarios

Despite the dangers associated with drink walking, limited research is currently available regarding the factors which influence individuals to engage in this risky behaviour. This study examined the influence of psychosocial factors upon individuals’ intentions to drink walk across four experimental scenarios (and a control condition). Specifically, a 2 × 2 repeated measures design was utilised in which all of the scenarios incorporated a risky pedestrian crossing situation (i.e., a pedestrian crossing against a red man signal) but differed according to the level of group identity (i.e., low/strangers and high/friends) and conformity (low and high). Individuals were assessed for their intentions to drink walk within each of these different scenarios. Undergraduate students (N = 151), aged 17–30 years, completed a questionnaire. Overall, most of the study's hypotheses were supported with individuals reporting the highest intentions to drink walk when in the presence of friends (i.e., high group identity) and their friends were said to be also crossing against the red man signal (i.e., high conformity). The findings may have significant implications for the design of countermeasures to reduce drink walking. For instance, the current findings would suggest that potentially effective strategies may be to promote resilience to peer influence as well as highlight the negative consequences associated with following the behaviour of other intoxicated pedestrians who are crossing against a red signal.

An improved genetic algorithm and graph theory based method for optimal sectionalizer switch placement in distribution networks with DG

In this paper a new graph-theory and improved genetic algorithm based practical method is employed to solve the optimal sectionalizer switch placement problem. The proposed method determines the best locations of sectionalizer switching devices in distribution networks considering the effects of presence of distributed generation (DG) in fitness functions and other optimization constraints, providing the maximum number of costumers to be supplied by distributed generation sources in islanded distribution systems after possible faults. The proposed method is simulated and tested on several distribution test systems in both cases of with DG and non DG situations. The results of the simulations validate the proposed method for switch placement of the distribution network in the presence of distributed generation.

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.

Impacts of traditional husbandry practices on exploitable levels of genetic diversity in cultured 'Tra' catfish (Pangasianodon hypophthalmus) in the Mekong Delta, Vietnam

Sutchi catfish (Pangasianodon hypophthalmus) – known more universally by the Vietnamese name ‘Tra’ is an economically important freshwater fish in the Mekong Delta in Vietnam that constitutes an important food resource. Artificial propagation technology for Tra catfish has only recently been developed along the main branches of the Mekong River where more than 60% of the local human population participate in fishing or aquaculture. Extensive support for catfish culture in general, and that of Tra (P. hypophthalmus) in particular, has been provided by the Vietnamese government to increase both the scale of production and to develop international export markets. In 2006, total Vietnamese catfish exports reached approximately 286,602 metric tons (MT) and were valued at 736.87 $M with a number of large new export destinations being developed. Total value of production from catfish culture has been predicted to increase to approximately USD 1 billion by 2020. While freshwater catfish culture in Vietnam has a promising future, concerns have been raised about long-term quality of fry and the effectiveness of current brood stock management practices, issues that have been largely neglected to date. In this study, four DNA markers (microsatellite loci: CB4, CB7, CB12 and CB13) that were developed specifically for Tra (P. hypophthalmus) in an earlier study were applied to examine the genetic quality of artificially propagated Tra fry in the Mekong Delta in Vietnam. The goals of the study were to assess: (i) how well available levels of genetic variation in Tra brood stock used for artificial propagation in the Mekong Delta of Vietnam (breeders from three private hatcheries and Research Institute of Aquaculture No2 (RIA2) founders) has been conserved; and (ii) whether or not genetic diversity had declined significantly over time in a stock improvement program for Tra catfish at RIA2. A secondary issue addressed was how genetic markers could best be used to assist industry development. DNA was extracted from fins of catfish collected from the two main branches of the Mekong River inf Vietnam, three private hatcheries and samples from the Tra improvement program at RIA2. Study outcomes: i) Genetic diversity estimates for Tra brood stock samples were similar to, and slightly higher than, wild reference samples. In addition, the relative contribution by breeders to fry in commercial private hatcheries strongly suggest that the true Ne is likely to be significantly less than the breeder numbers used; ii) in a stock improvement program for Tra catfish at RIA2, no significant differences were detected in gene frequencies among generations (FST=0.021, P=0.036>0.002 after Bonferroni correction); and only small differences were observed in alleles frequencies among sample populations. To date, genetic markers have not been applied in the Tra catfish industry, but in the current project they were used to evaluate the levels of genetic variation in the Tra catfish selective breeding program at RIA2 and to undertake genetic correlations between genetic marker and trait variation. While no associations were detected using only four loci, they analysis provided training in the practical applications of the use of molecular markers in aquaculture in general, and in Tra culture, in particular.