Low frequency of CHEK2 1100delC allele in Australian multiple-case breast cancer families : functional analysis in heterozygous individuals

A protein-truncating variant of CHEK2, 1100delC, is associated with a moderate increase in breast cancer risk. We have determined the prevalence of this allele in index cases from 300 Australian multiple-case breast cancer families, 95% of which had been found to be negative for mutations in BRCA1 and BRCA2. Only two (0.6%) index cases heterozygous for the CHEK2 mutation were identified. All available relatives in these two families were genotyped, but there was no evidence of co-segregation between the CHEK2 variant and breast cancer. Lymphoblastoid cell lines established from a heterozygous carrier contained approximately 20% of the CHEK2 1100delC mRNA relative to wild-type CHEK2 transcript. However, no truncated CHK2 protein was detectable. Analyses of expression and phosphorylation of wild-type CHK2 suggest that the variant is likely to act by haploinsufficiency. Analysis of CDC25A degradation, a downstream target of CHK2, suggests that some compensation occurs to allow normal degradation of CDC25A. Such compensation of the 1100delC defect in CHEK2 might explain the rather low breast cancer risk associated with the CHEK2 variant, compared to that associated with truncating mutations in BRCA1 or BRCA2.

'The black hole of our history' : a conversation with Louis Nowra

This is an edited version of an interview recorded for Canadian Theatre Review in 1992. By that time Nowra had established a reputation as one of Australia's foremost playwrights. Part of the generation which succeeded the New Wave of the late 1960s and early 1970s, Nowra became known for a stylistic inventiveness which placed him outside the tradition of realist playwriting in Australia. The international outlook in his early plays, and the fact that he was not exclusively preoccupied with Australian settings and subject matter, was often a focal point in critical accounts of his work. In this interview Nowra discusses his 'internationalism', and a range of topics including the playwriting process; the presence of landscape in his plays; and the autobiographical elements in his work.

Socially adaptable housing new housing model for families living with disability

In Australia as far back as 1993, researchers such as Baladin and Chapmen reported that "18% of the total Australian population and 51% of the population over 60 years of age were identified as having a disability" (2001; p38.2). Statistics such as these are not by any means astonishing, even to members of the general public, and it is widely understood that these are only to increase significantly in our near future. What is particularly surprising however is, in the face of such statistics, the lack of new and creative responses to this demographic shift, particularly by the architecture and construction industries. The common response from a range of sectors seems to be the repetition of a series of models which offer limited, and often undesirable, housing options. It is this against this backdrop, characterized by a lack of original options from mainstream practitioners and relevant government bodies, that the need has arisen to develop alternative models at grass-roots level. This paper reports primarily on the work of one group comprising a not-for-profit organization, a pro-bono design practice group and a local university working together to design a more holistic, emotionally sustainable independent living model of housing for families where a member of the family has a disability. This approach recognizes the limitations of universal design in that it often does not " ... meet all the housing needs that arise for people with moderate to severe disabilities" (Scotts, Margie et al, 2007; p.17). It is hoped that by examining the work of such a collective which is not driven by profit or policy, but rather born with the aim to address first and foremost individual and community need, that better insight can be gained into the real requirements of individuals and families as well as open up a view to new ways of fulfilling them.

Black v Garnock : implications for Queensland conveyancing practice

What was previously established as a fundamental principle, that a judgment creditor may take no interest beyond what the judgment debtor could give, has now been called into question by the decision of the High Court in Black v Garnock [2007] HCA 31. This article examines the implications of the decision of the High Court for conveyancing practice in Queensland. The relevant facts of Black v Garnock [2007] HCA 31 may be briefly stated: The Garnocks and the Luffs, as purchasers, entered a contract to purchase a rural property from Mrs Smith with settlement due on 24 August 2005. On 23 August 2005, a creditor obtained a writ against Mrs Smith from the District Court of New South Wales. No caveat was lodged on behalf of the purchasers prior to settlement (there being no equivalent, in New South Wales, of the Queensland settlement notice mechanism).

Home literacy education of Taiwanese Australian families : a sociological analysis

This research investigates home literacy education practices of Taiwanese families in Australia. As Taiwanese immigrants represent the largest ¡°Chinese Australian¡± subgroup to have settled in the state of Queensland, teachers in this state often face the challenges of cultural differences between Australian schools and Taiwanese homes. Extensive work by previous researchers suggests that understanding the cultural and linguistic differences that influence how an immigrant child views and interacts with his/her environment is a possible way to minimise the challenges. Cultural practices start from infancy and at home. Therefore, this study is focused on young children who are around the age of four to five. It is a study that examines the form of literacy education that is enacted and valued by Taiwanese parents in Australia. Specifically, this study analyses ¡°what literacy knowledge and skill is taught at home?¡±, ¡°how is it taught?¡± and ¡°why is it taught?¡± The study is framed in Pierre Bourdieu.s theory of social practice that defines literacy from a sociological perspective. The aim is to understand the practices through which literacy is taught in the Taiwanese homes. Practices of literacy education are culturally embedded. Accordingly, the study shows the culturally specialised ways of learning and knowing that are enacted in the study homes. The study entailed four case studies that draw on: observations and recording of the interactions between the study parent and child in their literacy events; interviews and dialogues with the parents involved; and a collection of photographs of the children.s linguistic resources and artefacts. The methodological arguments and design addressed the complexity of home literacy education where Taiwanese parents raise children in their own cultural ways while adapting to a new country in an immigrant context. In other words, the methodology not only involves cultural practices, but also involves change and continuity in home literacy practices. Bernstein.s theory of pedagogic discourse was used to undertake a detailed analysis of parents. selection and organisation of content for home literacy education, and the evaluative criteria they established for the selected literacy knowledge and skill. This analysis showed how parents selected and controlled the interactions in their child.s literacy learning. Bernstein.s theory of pedagogic discourse was used also to analyse change and continuity in home literacy practice, specifically, the concepts of ¡°classification¡± and ¡°framing¡±. The design of this study aimed to gain an understanding of parents. literacy teaching in an immigrant context. The study found that parents tended to value and enact traditional practices, yet most of the parents were also searching for innovative ideas for their adult-structured learning. Home literacy education of Taiwanese families in this study was found to be complex, multi-faceted and influenced in an ongoing way by external factors. Implications for educators and recommendations for future study are provided. The findings of this study offer early childhood teachers in Australia understandings that will help them build knowledge about home literacy education of Taiwanese Australian families.

Investigating the cost-effectiveness of video telephone based support for newly diagnosed paediatric oncology patients and their families: design of a randomised controlled trial

Background Providing ongoing family centred support is an integral part of childhood cancer care. For families living in regional and remote areas, opportunities to receive specialist support are limited by the availability of health care professionals and accessibility, which is often reduced due to distance, time, cost and transport. The primary aim of this work is to investigate the cost-effectiveness of videotelephony to support regional and remote families returning home for the first time with a child newly diagnosed with cancer Methods/design We will recruit 162 paediatric oncology patients and their families to a single centre randomised controlled trial. Patients from regional and remote areas, classified by Accessibility/Remoteness Index of Australia (ARIA+) greater than 0.2, will be randomised to a videotelephone support intervention or a usual support control group. Metropolitan families (ARIA+ ≤ 0.2) will be recruited as an additional usual support control group. Families allocated to the videotelephone support intervention will have access to usual support plus education, communication, counselling and monitoring with specialist multidisciplinary team members via a videotelephone service for a 12-week period following first discharge home. Families in the usual support control group will receive standard care i.e., specialist multidisciplinary team members provide support either face-to-face during inpatient stays, outpatient clinic visits or home visits, or via telephone for families who live far away from the hospital. The primary outcome measure is parental health related quality of life as measured using the Medical Outcome Survey (MOS) Short Form SF-12 measured at baseline, 4 weeks, 8 weeks and 12 weeks. The secondary outcome measures are: parental informational and emotional support; parental perceived stress, parent reported patient quality of life and parent reported sibling quality of life, parental satisfaction with care, cost of providing improved support, health care utilisation and financial burden for families. Discussion This investigation will establish the feasibility, acceptability and cost-effectiveness of using videotelephony to improve the clinical and psychosocial support provided to regional and remote paediatric oncology patients and their families.

Early intervention music therapy : reporting on a 3-year project to address needs with at-risk families

Sing & Grow is an early intervention music therapy project presented to families with additional needs, or those at risk of experiencing disadvantage due to social and/or economic circumstances that may impact on their parenting experiences. The aim of the project is to provide short term music therapy programs to families in communities where access to such services may be limited. The program is strengths-based and focuses on building upon a parent’s capacity to relate to and respond to their child’s emotional and developmental needs.

Reflections on music therapy with Indigenous families : cultural learning put into practice

This paper will describe the process of learning and development that occurred when the Sing & Grow prevention and early intervention project began to provide services to Indigenous families, a relatively new area or music therapy, particularly in Brisbane. The first attempt at establishing a weekly group music therapy program for Indigenous families was not as successful as anticipated; however through analysis of the contributing factors, guidelines were developed and implemented in the following program, which resulted in a positive learning experience for the families and therapists involved.

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.

Mutation analysis of the CDKN2A promoter in Australian melanoma families

Approximately 50% of all melanoma families worldwide show linkage to 9p21-22, but only about half of these have been shown to contain germ line CDKN2A mutations. It has been hypothesized that a proportion of these families carry mutations in the noncoding regions of CDKN2A. Several Canadian families have been reported to carry a mutation in the 5' UTR, at position -34 relative to the start site, which gives rise to a novel AUG translation initiation codon that markedly decreases translation from the wild-type AUG (Liu et al., 1999). Haplotype sharing in these Canadian families suggested that this mutation is of British origin. We sequenced 1,327 base pairs (bp) of CDKN2A, making up 1,116 bp of the 5' UTR and promoter, all of exon 1, and 61 bp of intron 1, in at least one melanoma case from 110 Australian families with three or more affected members known not to carry mutations within the p16 coding region. In addition, 431 bp upstream of the start codon was sequenced in an additional 253 affected probands from two-case melanoma families for which the CDKN2A mutation status was unknown. Several known polymorphisms at positions -33, -191, -493, and -735 were detected, in addition to four novel variants at positions 120, -252, -347, and -981 relative to the start codon. One of the probands from a two-case family was found to have the previously reported Q50R mutation. No family member was found to carry the mutation at position -34 or any other disease-associated mutation. For further investigation of noncoding CDKN2A mutations that may affect transcription, allele-specific expression analysis was carried out in 31 of the families with at least three affected members who showed either complete or "indeterminate" 9p haplotype sharing without CDKN2A exonic mutations. Reverse transcription polymerase chain reaction and automated sequencing showed expression of both CDKN2A alleles in all family members tested. The lack of CDKN2A promoter mutations and the absence of transcriptional silencing in the germ line of this cohort of families suggest that mutations in the promoter and 5' UTR play a very limited role in melanoma predisposition.