Integrated genomic characterization of endometrial carcinoma

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.

Book Review [White Bound: Nationalists, Antiracists, and the Shared Meanings of Race, by MW Hughey]

Dr Kathy A. Mills provides a critical synthesis and review of the new book by Matthew W. Hughey entitle: White Bound: Nationalists, Antiractists, and the Shared Meanings of Race, published by Standford University Press in 2012. A sample of Dr Mills' review reads: "The author positions race squarely at the center to challenge the shared assumptions of white supremacist logic on both sides of the debate. The clever thesis blurs the boundaries between “good whites” and “bad whites”, rendering the white reader intellectually stimulated, but existentially unchanged – White Bound – as the author ponders: “Perhaps we have met the enemy, and he [it] is us” (p.193)...The unanswered question that remains is: How do we resist the various “shades” of white supremacy to pursue counter-hegemonic practices?"

Prolegomenon to the study of the concepts of maturity and maturity model : from Black Horse to White Knight?

This paper takes its root in a trivial observation: management approaches are unable to provide relevant guidelines to cope with uncertainty, and trust of our modern worlds. Thus, managers are looking for reducing uncertainty through information’s supported decision-making, sustained by ex-ante rationalization. They strive to achieve best possible solution, stability, predictability, and control of “future”. Hence, they turn to a plethora of “prescriptive panaceas”, and “management fads” to bring simple solutions through best practices. However, these solutions are ineffective. They address only one part of a system (e.g. an organization) instead of the whole. They miss the interactions and interdependencies with other parts leading to “suboptimization”. Further classical cause-effects investigations and researches are not very helpful to this regard. Where do we go from there? In this conversation, we want to challenge the assumptions supporting the traditional management approaches and shed some lights on the problem of management discourse fad using the concept of maturity and maturity models in the context of temporary organizations as support for reflexion. Global economy is characterized by use and development of standards and compliance to standards as a practice is said to enable better decision-making by managers in uncertainty, control complexity, and higher performance. Amongst the plethora of standards, organizational maturity and maturity models hold a specific place due to general belief in organizational performance as dependent variable of (business) processes continuous improvement, grounded on a kind of evolutionary metaphor. Our intention is neither to offer a new “evidence based management fad” for practitioners, nor to suggest research gap to scholars. Rather, we want to open an assumption-challenging conversation with regards to main stream approaches (neo-classical economics and organization theory), turning “our eyes away from the blinding light of eternal certitude towards the refracted world of turbid finitude” (Long, 2002, p. 44) generating what Bernstein has named “Cartesian Anxiety” (Bernstein, 1983, p. 18), and revisit the conceptualization of maturity and maturity models. We rely on conventions theory and a systemic-discursive perspective. These two lenses have both information & communication and self-producing systems as common threads. Furthermore the narrative approach is well suited to explore complex way of thinking about organizational phenomena as complex systems. This approach is relevant with our object of curiosity, i.e. the concept of maturity and maturity models, as maturity models (as standards) are discourses and systems of regulations. The main contribution of this conversation is that we suggest moving from a neo-classical “theory of the game” aiming at making the complex world simpler in playing the game, to a “theory of the rules of the game”, aiming at influencing and challenging the rules of the game constitutive of maturity models – conventions, governing systems – making compatible individual calculation and social context, and possible the coordination of relationships and cooperation between agents with or potentially divergent interests and values. A second contribution is the reconceptualization of maturity as structural coupling between conventions, rather than as an independent variable leading to organizational performance.

The Norfolk Island Eye Study (NIES) : rationale, methodology and distribution of ocular biometry (Biometry of the Bounty)

Aim: To describe the recruitment, ophthalmic examination methods and distribution of ocular biometry of participants in the Norfolk Island Eye Study, who were individuals descended from the English Bounty mutineers and their Polynesian wives. Methods: All 1,275 permanent residents of Norfolk Island aged over 15 years were invited to participate, including 602 individuals involved in a 2001 cardiovascular disease study. Participants completed a detailed questionnaire and underwent a comprehensive eye assessment including stereo disc and retinal photography, ocular coherence topography and conjunctival autofluorescence assessment. Additionally, blood or saliva was taken for DNA testing. Results: 781 participants aged over 15 years were seen (54% female), comprising 61% of the permanent Island population. 343 people (43.9%) could trace their family history to the Pitcairn Islanders (Norfolk Island Pitcairn Pedigree). Mean anterior chamber depth was 3.32mm, mean axial length (AL) was 23.5mm, and mean central corneal thickness was 546 microns. There were no statistically significant differences in these characteristics between persons with and without Pitcairn Island ancestry. Mean intra-ocular pressure was lower in people with Pitcairn Island ancestry: 15.89mmHg compared to those without Pitcairn Island ancestry 16.49mmHg (P = .007). The mean keratometry value was lower in people with Pitcairn Island ancestry (43.22 vs. 43.52, P = .007). The corneas were flatter in people of Pitcairn ancestry but there was no corresponding difference in AL or refraction. Conclusion: Our study population is highly representative of the permanent population of Norfolk Island. Ocular biometry was similar to that of other white populations. Heritability estimates, linkage analysis and genome-wide studies will further elucidate the genetic determinants of chronic ocular diseases in this genetic isolate.

Familial typical migraine: Significant linkage and localization of a gene to Xq24-28

In a previous study we found evidence for an X-linked genetic component for familial typical migraine in two large Australian white pedigrees, designated MF7 and MF14. Significant excess allele sharing was indicated by nonparametric linkage (NPL) analysis using GENEHUNTER (P=0.031 and P=0.012, respectively), with a combined analysis of the two pedigrees showing further increased evidence for linkage, producing a maximum NPL score of 2.87 (P=0.011 ) at DXS 1123 on Xq27. The present study was aimed at refining the localization of the migraine X-chromosomal component by typing additional markers, performing haplotype analysis and applying a more powerful technique in the analysis of linkage data from these two pedigrees. Results from the haplotype analyses, coupled with linkage analyses that produced a peak GENEHUNTER-PLUS LOD* score of 2.388 (P=0.0005), provide compelling evidence for the presence of a migraine susceptibility locus on chromosome Xq24-28.

The null allele of GSTM1 does not affect susceptibility to solar keratoses in the Australian white population

Solar keratoses (SKs) are induced by exposure to UV radiation and are capable of undergoing transformation to squamous cell carcinoma (SCC).1 The two main factors influencing the occurrence of SK are the sensitivity of the skin to sunlight and the total duration of solar exposure. These factors are responsible for the high incidence of SK in Australia. Although the influence of genetic factors is not defined, there is evidence that the gene encoding the enzyme, glutathione S-transferase, may be implicated in cancer predisposition and therefore SK. Glutathione S-transferase Mu-1 (GSTM1) is an isoenzyme involved in the detoxification of carcinogens. The GSTM1 protein is completely absent in approximately 50% of white persons. This absence is caused by a homozygous gene deletion on chromosome 1p resulting in a null genotype.2 Katoh3 showed that the frequency of the GSTM1 null genotype was significantly higher in 85 patients with urothelial cancer (61.2%; p < 0.05), suggesting that the null genotype may increase cancer susceptibility. This finding was supported by Lafuente et al.4 who found evidence that persons who lack the GSTM1 gene have approximately twice the chance of experiencing malignant melanoma. Further research in the United Kingdom found that patients with two or more skin tumors of different types, basal cell carcinoma (BCC) and SCC, had a significantly higher frequency of GSTM1 null genotypes than controls (71%; p = 0.033). However the GSTM1 genotype in patients with only SCC was not excessive in this population.5 Persons residing in northern Australia have the highest incidence of nonmelanoma skin cancer (SCC and BCC) in the world6 and receive far greater solar exposure than persons residing in the United Kingdom. It is possible that the GSTM1 null genotype may affect susceptibility to SK, which may act as SCC precursors, in Australians exposed to these high levels of solar radiation.

White teachers at a discursive crossroad

This study explored the way white teachers speak about Indigenous students and communities. The accounts of teachers working in eight schools across Australia were analysed using Foucauldian discourse analysis. The research found that deficit and colour-blind discourses dominate the ways that white teachers "know" Indigenous students and families. The data indicates that colour-blind and compensatory pedagogies are employed heavily by teachers working with Indigenous students, and highlights the complexities and tensions that exist in schools. Although there is evidence of some disruption to dominant discourses, teachers' discursive resources are limited in terms of imagining and enacting more equitable pedagogies.

Testing second order cyclostationarity in the squared envelope spectrum of non-white vibration signals

Cyclostationary models for the diagnostic signals measured on faulty rotating machineries have proved to be successful in many laboratory tests and industrial applications. The squared envelope spectrum has been pointed out as the most efficient indicator for the assessment of second order cyclostationary symptoms of damages, which are typical, for instance, of rolling element bearing faults. In an attempt to foster the spread of rotating machinery diagnostics, the current trend in the field is to reach higher levels of automation of the condition monitoring systems. For this purpose, statistical tests for the presence of cyclostationarity have been proposed during the last years. The statistical thresholds proposed in the past for the identification of cyclostationary components have been obtained under the hypothesis of having a white noise signal when the component is healthy. This need, coupled with the non-white nature of the real signals implies the necessity of pre-whitening or filtering the signal in optimal narrow-bands, increasing the complexity of the algorithm and the risk of losing diagnostic information or introducing biases on the result. In this paper, the authors introduce an original analytical derivation of the statistical tests for cyclostationarity in the squared envelope spectrum, dropping the hypothesis of white noise from the beginning. The effect of first order and second order cyclostationary components on the distribution of the squared envelope spectrum will be quantified and the effectiveness of the newly proposed threshold verified, providing a sound theoretical basis and a practical starting point for efficient automated diagnostics of machine components such as rolling element bearings. The analytical results will be verified by means of numerical simulations and by using experimental vibration data of rolling element bearings.

Anglican Church knew clergyman Robert Waddington was a risk

AUSTRALIAN church officials knew of child-sex allegations in Britain against a senior clergymen when they pushed a victim into accepting a compensation payout on the basis that there was no evidence to back up his claims of abuse. Former Church of England investigator Ray Morris says he prepared a 2004 report about allegations in Britain and Australia - from the 1960s and 80s - against Robert Waddington. He sent it to north Queensland diocese officials, who were at the time involved in mediation with the Australian victim over his claims that he was abused weekly by Waddington between 1964 and 1968, who was headmaster of St Barnabas boarding school in Ravenshoe, southwest of Cairns.

Robert Waddington's cycle of abuse stretches beyond 50 years

THE Church of England banished serial pedophile priest Robert Waddington to Australia, where he abused children across a decade, after suspicions were raised about him molesting choirboys in his London parish. In an alleged church cover-up spanning almost 60 years, Waddington was suddenly and unexpectedly sent to a small school in regional Queensland in 1956 amid claims he was molesting the son of an English politician. Last month the Church of England ordered an independent inquiry into the handling of allegations against Waddington, after a joint investigation by The Australian and The Times of London. But it can now be revealed that Waddington - who died in 2007, facing allegations he abused students in Australia in the 1960s and English choirboys in the 80s and 90s - was molesting children as soon as he joined the church in 1953. The latest allegations have been made by Ray Munn, 70, who was recruited by Waddington, then a curate at St John's church in Bethnal Green, East London, to sing in the choir in 1953. He was almost immediately groomed by the Cambridge University-educated clergyman, who took him on holidays in the English countryside, before he began molesting the then 11-year-old.

Managing creativity on the margins : a comparative study of Beijing’s Songzhuang Art District and Hangzhou’s White Horse Lake Creative Eco-City

In the past decade the ‘creative cluster’ has become a driver of urban renewal in China. Many cluster developments attract human capital and investment to post-industrial spaces. This paper looks at two developments which are more post-agricultural than post-industrial: the first is Songzhuang, a large scale contemporary art community situated on the eastern fringe of Beijing, the second is Hangzhou’s White Horse Lake Creative Eco-City, a ‘mixed variety’ cluster model which integrates elements of art, fashion, design and animation. The common factor in both cases is how they came into existence. In both districts urban creative workers moved into a rural environment. Drawing on interviews with planners, officials, and residents we investigate the challenges of sustaining such fringe clusters.

Identification of Mendel's white flower character

Background The genetic regulation of flower color has been widely studied, notably as a character used by Mendel and his predecessors in the study of inheritance in pea. Methodology/Principal Findings We used the genome sequence of model legumes, together with their known synteny to the pea genome to identify candidate genes for the A and A2 loci in pea. We then used a combination of genetic mapping, fast neutron mutant analysis, allelic diversity, transcript quantification and transient expression complementation studies to confirm the identity of the candidates. Conclusions/Significance We have identified the pea genes A and A2. A is the factor determining anthocyanin pigmentation in pea that was used by Gregor Mendel 150 years ago in his study of inheritance. The A gene encodes a bHLH transcription factor. The white flowered mutant allele most likely used by Mendel is a simple G to A transition in a splice donor site that leads to a mis-spliced mRNA with a premature stop codon, and we have identified a second rare mutant allele. The A2 gene encodes a WD40 protein that is part of an evolutionarily conserved regulatory complex.