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.

Microarray expression profiling in melanoma reveals a BRAF mutation signature

We have used microarray gene expression profiling and machine learning to predict the presence of BRAF mutations in a panel of 61 melanoma cell lines. The BRAF gene was found to be mutated in 42 samples (69%) and intragenic mutations of the NRAS gene were detected in seven samples (11%). No cell line carried mutations of both genes. Using support vector machines, we have built a classifier that differentiates between melanoma cell lines based on BRAF mutation status. As few as 83 genes are able to discriminate between BRAF mutant and BRAF wild-type samples with clear separation observed using hierarchical clustering. Multidimensional scaling was used to visualize the relationship between a BRAF mutation signature and that of a generalized mitogen-activated protein kinase (MAPK) activation (either BRAF or NRAS mutation) in the context of the discriminating gene list. We observed that samples carrying NRAS mutations lie somewhere between those with or without BRAF mutations. These observations suggest that there are gene-specific mutation signals in addition to a common MAPK activation that result from the pleiotropic effects of either BRAF or NRAS on other signaling pathways, leading to measurably different transcriptional changes.

Melanoma cell invasiveness is regulated by miR-211 suppression of the BRN2 transcription factor

To identify microRNAs potentially involved in melanomagenesis, we compared microRNA expression profiles between melanoma cell lines and cultured melanocytes. The most differentially expressed microRNA between the normal and tumor cell lines was miR-211. We focused on this pigment-cell-enriched miRNA as it is derived from the microphthalmia-associated transcription factor (MITF)-regulated gene, TRPM1 (melastatin). We find that miR-211 expression is greatly decreased in melanoma cells and melanoblasts compared to melanocytes. Bioinformatic analysis identified a large number of potential targets of miR-211, including POU3F2 (BRN2). Inhibition of miR-211 in normal melanocytes resulted in increased BRN2 protein, indicating that endogenous miR-211 represses BRN2 in differentiated cells. Over-expression of miR-211 in melanoma cell lines changed the invasive potential of the cells in vitro through directly targeting BRN2 translation. We propose a model for the apparent non-overlapping expression levels of BRN2 and MITF in melanoma, mediated by miR-211 expression.

The politicization of youth crime in Scotland and the rise of the 'Burberry Court'

In 2003, the youth justice system in Scotland entered a new phase with the introduction of a pilot youth court. The processing of persistent 16 and 17 year old (and serious 15 year olds) represented a stark deviation from a ‘child centred’ and needs-oriented state apparatus for dealing with young offenders to one based on deeds and individual responsibility. This article, based on an evaluation funded by the Scottish Executive, is the first to provide a critical appraisal of this youth justice reform. It examines the views of the judiciary and young offenders and reveals that the pilot youth court in Scotland represents a punitive excursion that poses serious concerns for due process, human rights and net widening.

Transferring knowledge through peer-reviewed assessment : the creation of a community of practice and the threats to its survival

While it is generally accepted in the learning and teaching literature that assessment is the single biggest influence on how students approach their learning, assessment methods within higher education are generally conservative and inflexible. Constrained by policy and accreditation requirements and the need for the explicit articulation of assessment standards for public accountability purposes, assessment tasks can fail to engage students or reflect the tasks students will face in the world of practice. Innovative assessment design can simultaneously deliver program objectives and active learning through a knowledge transfer process which increases student participation. This social constructivist view highlights that acquiring an understanding of assessment processes, criteria and standards needs active student participation. Within this context, a peer-assessed, weekly, assessment task was introduced in the first “serious” accounting subject offered as part of an undergraduate degree. The positive outcomes of this assessment innovation was that student failure rates declined 15%, tutorial participation increased fourfold, tutorial engagement increased six-fold and there was a 100% approval rating for the retention of the assessment task. In contributing to the core conference theme of “seismic” shifts within higher education, in stark contrast to the positive student response, staff-related issues of assessment conservatism and the necessity of meeting increasing research commitments, threatened the assessment task’s survival. These opposing forces to change have the potential to weaken the ability of higher education assessment arrangements to adequately serve either a new generation of students or the sector's community stakeholders.

Transferring knowledge through peer-reviewed assessment : the creation of a community of practice and the threats to its survival

While it is generally accepted in the learning and teaching literature that assessment is the single biggest influence on how students approach their learning, assessment methods within higher education are generally conservative and inflexible. Constrained by policy and accreditation requirements and the need for the explicit articulation of assessment standards for public accountability purposes, assessment tasks can fail to engage students or reflect the tasks students will face in the world of practice. Innovative assessment design can simultaneously deliver program objectives and active learning through a knowledge transfer process which increases student participation. This social constructivist view highlights that acquiring an understanding of assessment processes, criteria and standards needs active student participation. Within this context, a peer-assessed, weekly, assessment task was introduced in the first “serious” accounting subject offered as part of an undergraduate degree. The positive outcomes of this assessment innovation was that student failure rates declined 15%, tutorial participation increased fourfold, tutorial engagement increased six-fold and there was a 100% approval rating for the retention of the assessment task. In contributing to the core conference theme of “seismic” shifts within higher education, in stark contrast to the positive student response, staff-related issues of assessment conservatism and the necessity of meeting increasing research commitments, threatened the assessment task’s survival. These opposing forces to change have the potential to weaken the ability of higher education assessment arrangements to adequately serve either a new generation of students or the sector's community stakeholders.

Helping undergraduate students across disciplines and cultures actively engage and collaborate as equal members of a community of scholars : peer review within an e-learning environment

At the international level, the higher education sector is currently being subjected to increased calls for public accountability and the current move by the OECD to rank universities based on the quality of their teaching and learning outcomes. At the national level, Australian universities and their teaching staff face numerous challenges including financial restrictions, increasing student numbers and the reality of an increasingly diverse student population. The Australian higher education response to these competing policy and accreditation demands focuses on precise explicit systems and procedures which are inflexible and conservative and which ignore the fact that assessment is the single biggest influence on how students approach their learning. By seriously neglecting the quality of student learning outcomes, assessment tasks are often failing to engage students or reflect the tasks students will face in the world of practice. Innovative assessment design, which includes new paradigms of student engagement and learning and pedagogically based technologies have the capacity to provide some measure of relief from these internal and external tensions by significantly enhancing the learning experience for an increasingly time-poor population of students. That is, the assessment process has the ability to deliver program objectives and active learning through a knowledge transfer process which increases student participation and engagement. This social constructivist view highlights the importance of peer review in assisting students to participate and collaborate as equal members of a community of scholars with both their peers and academic staff members. As a result of increasing the student’s desire to learn, peer review leads to more confident, independent and reflective learners who also become more skilled at making independent judgements of their own and others' work. Within this context, in Case Study One of this project, a summative, peer-assessed, weekly, assessment task was introduced in the first “serious” accounting subject offered as part of an undergraduate degree. The positive outcomes achieved included: student failure rates declined 15%; tutorial participation increased fourfold; tutorial engagement increased six-fold; and there was a 100% student-based approval rating for the retention of the assessment task. However, in stark contrast to the positive student response, staff issues related to the loss of research time associated with the administration of the peer-review process threatened its survival. This paper contributes to the core conference topics of new trends and experiences in undergraduate assessment education and in terms of innovative, on-line, learning and teaching practices, by elaborating the Case Study Two “solution” generated to this dilemma. At the heart of the resolution is an e-Learning, peer-review process conducted in conjunction with the University of Melbourne which seeks to both create a virtual sense of belonging and to efficiently and effectively meet academic learning objectives with minimum staff involvement. In outlining the significant level of success achieved, student-based qualitative and quantitative data will be highlighted along with staff views in a comparative analysis of the advantages and disadvantages to both students and staff of the staff-led, peer review process versus its on-line counterpart.

Documentary as history, memory, dream and film

A century ago, as the Western world embarked on a period of traumatic change, the visual realism of photography and documentary film brought print and radio news to life. The vision that these new mediums threw into stark relief was one of intense social and political upheaval: the birth of modernity fired and tempered in the crucible of the Great War. As millions died in this fiery chamber and the influenza pandemic that followed, lines of empires staggered to their fall, and new geo-political boundaries were scored in the raw, red flesh of Europe. The decade of 1910 to 1919 also heralded a prolific period of artistic experimentation. It marked the beginning of the social and artistic age of modernity and, with it, the nascent beginnings of a new art form: film. We still live in the shadow of this violent, traumatic and fertile age; haunted by the ghosts of Flanders and Gallipoli and its ripples of innovation and creativity. Something happened here, but to understand how and why is not easy; for the documentary images we carry with us in our collective cultural memory have become what Baudrillard refers to as simulacra. Detached from their referents, they have become referents themselves, to underscore other, grand narratives in television and Hollywood films. The personal histories of the individuals they represent so graphically–and their hope, love and loss–are folded into a national story that serves, like war memorials and national holidays, to buttress social myths and values. And, as filmic images cross-pollinate, with each iteration offering a new catharsis, events that must have been terrifying or wondrous are abstracted. In this paper we first discuss this transformation through reference to theories of documentary and memory–this will form a conceptual framework for a subsequent discussion of the short film Anmer. Produced by the first author in 2010, Anmer is a visual essay on documentary, simulacra and the symbolic narratives of history. Its form, structure and aesthetic speak of the confluence of documentary, history, memory and dream. Located in the first decade of the twentieth century, its non-linear narratives of personal tragedy and poetic dreamscapes are an evocative reminder of the distance between intimate experience, grand narratives, and the mythologies of popular films. This transformation of documentary sources not only played out in the processes of the film’s production, but also came to form its theme.

The Road to Whatever: Middle Class Cultgure and the Crisis of Adolescence

In this groundbreaking book, acclaimed sociologist and Pulitzer Prize finalist Elliott Currie draws on years of interviews to offer a profound investigation of what has gone wrong for so many “mainstream” American adolescents. Rejecting such predictable answers as TV violence, permissiveness, and inherent evil, Currie links this crisis to a pervasive “culture of exclusion” fostered by a society in which medications trump guidance and a punitive “zero tolerance” approach to adolescent misbehavior has become the norm. Broadening his inquiry, he dissects the changes in middle-class life that stratify the world into "winners" and "losers," imposing an extraordinarily harsh culture—and not just on kids. Vivid, compelling, and deeply empathetic, The Road to Whatever is a stark indictment of a society that has lost the will—or the capacity—to care.

Victims Speak: Comparing Child Sexual Abusers and Their Victims Accounts of Offence Circumstances

This article presents findings from a longitudinal study. The research aimed to explore the effectiveness of a treatment program for offenders which lasted for three years. The research design was structured around the program with interviews and psychometric testing undertaken at key points in time with the same group of respondents. View all notes that sought to evaluate a treatment program for child sexual abusers. A triangulated methodological approach was adopted drawing upon quantitative and qualitative methodological techniques. The focus here is upon one element of this research. 2 2The quantitative element of this research will be published shortly but is referred to in the following reports Davidson 2000, 2003 [research funded by the National Probation Service]. Psychometric testing was undertaken over a four-year period with the men attending the treatment program to explore shifts in the extent of denial, blame attribution, and victim empathy over time. Offender cognitive distortions, general health, and self-esteem were also explored via psychometric testing. An interview-administered survey was undertaken with all sex offenders registered with the Probation Service (those on probation and in custody) in order to gather demographic data, and 117 of 150 offenders responded. View all notes Ninety-one in-depth interviews were conducted over a four-year period with a small, nonrandom sample of twenty-one male offenders who had been convicted of sexual offenses against children. All of the men were subject to probation orders with a psychiatric condition (Criminal Justice Act, 1991). One of the aims of this element of the research was to explore the extent to which evidence of denial could be found in offenders’ accounts of offense circumstance and also to explore the extent to which offenders minimized the nature and extent of abuse perpetrated. Offenders’ accounts of offense circumstances were compared to victim statements, and stark differences emerge. These findings have considerable implications for treatment practice with sex offenders, where victims’ perceptions could be used to directly confront offender denial and minimization.

Does the effect of weight lifting on lymphedema following breast cancer differ by diagnostic method: results from a randomized controlled trial

The lymphedema diagnostic method used in descriptive or intervention studies may influence results found. The purposes of this work were to compare baseline lymphedema prevalence in the physical activity and lymphedema (PAL) trial cohort and to subsequently compare the effect of the weight-lifting intervention on lymphedema, according to four standard diagnostic methods. The PAL trial was a randomized controlled intervention study, involving 295 women who had previously been treated for breast cancer, and evaluated the effect of 12 months of weight lifting on lymphedema status. Four diagnostic methods were used to evaluate lymphedema outcomes: (i) interlimb volume difference through water displacement, (ii) interlimb size difference through sum of arm circumferences, (iii) interlimb impedance ratio using bioimpedance spectroscopy, and (iv) a validated self-report survey. Of the 295 women who participated in the PAL trial, between 22 and 52% were considered to have lymphedema at baseline according to the four diagnostic criteria used. No between-group differences were noted in the proportion of women who had a change in interlimb volume, interlimb size, interlimb ratio, or survey score of ≥5, ≥5, ≥10%, and 1 unit, respectively (cumulative incidence ratio at study end for each measure ranged between 0.6 and 0.8, with confidence intervals spanning 1.0). The variation in proportions of women within the PAL trial considered to have lymphoedema at baseline highlights the potential impact of the diagnostic criteria on population surveillance regarding prevalence of this common morbidity of treatment. Importantly though, progressive weight lifting was shown to be safe for women following breast cancer, even for those at risk or with lymphedema, irrespective of the diagnostic criteria used.

Fear, voice, and the environment in Sonya Hartnett's Forerst and The Midnight Zoo

Subtle is not a word that is normally associated with Sonya Hartnett’s style. Rather, she is known for her stark, bold approach. However, when it comes to the Australian environment, Hartnett is indeed subtle in her approach. Hartnett has set in play a new, almost posthumanist style of writing about the nonhuman. The Australian landscape and environment has always figured prominently in Australian literature for both adults and children but Hartnett has taken this writing in a totally different direction. This article looks at two of Hartnett's novels, Forest and The Midnight Zoo, and examines how Hartnett offers new and exciting avenues of thought regarding the place of humans in that environment.

Plant made anti-HIV microbicides-A field of opportunity

HIV remains a significant global burden and without an effective vaccine, it is crucial to develop microbicides to halt the initial transmission of the virus. Several microbicides have been researched with various levels of success. Amongst these, the broadly neutralising antibodies and peptide lectins are promising in that they can immediately act on the virus and have proven efficacious in in vitro and in vivo protection studies. For the purpose of development and access by the relevant population groups, it is crucial that these microbicides be produced at low cost. For the promising protein and peptide candidate molecules, it appears that current production systems are overburdened and expensive to establish and maintain. With recent developments in vector systems for protein expression coupled with downstream protein purification technologies, plants are rapidly gaining credibility as alternative production systems. Here we evaluate the advances made in host and vector system development for plant expression as well as the progress made in expressing HIV neutralising antibodies and peptide lectins using plant-based platforms. © 2012 Elsevier Inc.

The minority report : disproportionate representation in Australia’s largest education system

The overrepresentation of students from minority ethnic groups in separate special education settings has been extensively documented in North America, yet little research exists for Australian school systems. To address this gap, we systematically analyzed 13 years of enrolment data from the state of New South Wales. Stark differences are seen in patterns of enrolment between Indigenous students, students from a Language Background Other than English (LBOTE), and non-Indigenous English speaking students. Moreover, these differences are increasing. While enrollments of Indigenous students in separate settings increased faster across time than did enrollments of Indigenous students in mainstream, enrollments of LBOTE students in mainstream increased faster than did enrollments of LBOTE students in separate settings.