CDKN2A is not the principal target of deletions on the short arm of chromosome 9 in neuroendocrine (Merkel cell) carcinoma of the skin

The majority of small-cell lung cancers (SCLCs) express p16 but not pRb. Given our previous study showing loss of pRb in Merkel cell carcinoma (MCC)/neuroendocrine carcinoma of the skin and the clinicopathological similarities between SCLC and MCC, we wished to determine if this was also the case in MCC. Twenty-nine MCC specimens from 23 patients were examined for deletions at 10 loci on 9p and 1 on 9q. No loss of heterozygosity (LOH) was seen in 9 patients including 2 for which tumour and cell line DNAs were examined. Four patients had LOH for all informative loci on 9p. Ten tumours showed more limited regions of loss on 9p, and from these 2 common regions of deletion were determined. Half of all informative cases had LOH at D9S168, the most telomeric marker examined, and 3 specimens showed loss of only D9S168. A second region (IFNA-D9S126) showed LOH in 10 (44%) cases, and case MCC26 showed LOH for only D9S126, implicating genes centromeric of the CDKN2A locus. No mutations in the coding regions of p16 were seen in 7 cell lines tested, and reactivity to anti-p16 antibody was seen in all 11 tumour specimens examined and in 6 of 7 cell lines from 6 patients. Furthermore, all cell lines examined reacted with anti-p14(ARF) antibody. These results suggest that neither transcript of the CDKN2A locus is the target of deletions on 9p in MCC and imply the existence of tumour-suppressor genes mapping both centromeric and telomeric of this locus.

Queensland floods anniversary : Angela Emmerson

"We're marking the anniversary of the destructive floods that hit Queensland a year ago this week with our series of interviews from survivors. Today's story is from Helidon teenager and university student Angela Emmerson, who tells Amanda Gearing how she and her sister scrambled to the roof to escape the dangerous flash flood which suddenly engulfed their house on the 10th of January last year. Tomorrow we'll hear from Grantham resident Rob Wilkin who rescued 31 local people using his car and boat. He helped them escape to safety as 138 houses in the town were destroyed. To mark the anniversary of the floods in Queensland, ABC Open has compiled Aftermath, an extensive look at the Queensland floods as well as floods in NSW, Victoria and remote Western Australia; Cyclone Yasi and the 2009 Victorian 'Black Saturday' bushfires. Australia certainly has been hit by a few disasters in the past two or so years. The site has a timeline showing content from these six disasters, with links to about 40 people effected by these disasters. If you go to that site you will be able to choose a person to watch videos about them."

Fine-needle aspiration cytology of Merkel cell carcinoma-A review of 69 cases

Background This study reviewed the clinical presentation, cytologic findings and the immunophenotype of 69 Merkel Cell Carcinoma (MCC) cases sampled by FNA. Methods Demographic and clinical data, the cytology findings and results of ancillary testing were reviewed. Results Median patient age was 78 years (37 – 104) with a 1:1.8 female to male ratio. The most common FNA sites sampled included lymph nodes in the neck, the axillary region, the inguinal region and the parotid gland. Most patients had a history of MCC (68%) &/or non-MCC malignancy (70%). The common cytologic pattern was a cellular smear with malignant cells arranged in a dispersed pattern with variable numbers of disorganised groups of cells. Cytoplasm was scant or absent and nuclei showed mild to moderate anisokaryosis, stippled chromatin, inconspicuous nucleoli and nuclear molding. Numerous apoptotic bodies were often present. Cell block samples (28 cases) were usually positive for cytokeratins in a perinuclear dot pattern, including 88% of cases with CK20 positivity. CD56 was the most sensitive (95%) neuroendocrine marker on cell blocks and was also positive with flow cytometry in 9 cases tested. Conclusions MCC is most commonly seen in FNA specimens from the head and neck of elderly patients, often with a history of previous skin lesions. Occasional cases present in younger patients and some may be mistaken for other round blue cell tumors, such as lymphoma. CD 56 may be a useful marker in cell block preparations and in flow cytometric analysis of MCC.

Multiple primary cancers associated with Merkel cell carcinoma in Queensland, Australia, 1982-2011

The relatively high incidence of Merkel cell carcinoma (MCC) in Queensland provides a valuable opportunity to examine links with other cancers. A retrospective cohort study was performed using data from the Queensland Cancer Registry. Standardized incidence ratios (SIRs) were used to approximate the relative risk of being diagnosed with another primary cancer either following or prior to MCC. Patients with an eligible first primary MCC (n=787) had more than double the expected number of subsequent primary cancers (SIR=2.19, 95% confidence interval (CI)=1.84–2.60; P<0.001). Conversely, people who were initially diagnosed with cancers other than MCC were about two and a half times more likely to have a subsequent primary MCC (n=244) compared with the general population (SIR=2.69, 95% CI=2.36–3.05; P<0.001). Significantly increased bi-directional relative risks were found for melanoma, lip cancer, head and neck cancer, lung cancer, myelodysplastic diseases, and cancer with unknown primary site. In addition, risks were elevated for female breast cancer and kidney cancer following a first primary MCC, and for subsequent MCCs following first primary colorectal cancer, prostate cancer, non-Hodgkin lymphoma, or lymphoid leukemia. These results suggest that several shared pathways are likely for MCC and other cancers, including immunosuppression, UV radiation, and genetics.

Developing a vision for an nD modelling tool

The design of a building is a complicated process, having to formulate diverse components through unique tasks involving different personalities and organisations in order to satisfy multi-faceted client requirements. To do this successfully, the project team must encapsulate an integrated design that accommodates various social, economic and legislative factors. Therefore, in this era of increasing global competition integrated design has been increasingly recognised as a solution to deliver value to clients.----- The ‘From 3D to nD modelling’ project at the University of Salford aims to support integrated design; to enable and equip the design and construction industry with a tool that allows users to create, share, contemplate and apply knowledge from multiple perspectives of user requirements (accessibility, maintainability, sustainability, acoustics, crime, energy simulation, scheduling, costing etc.). Thus taking the concept of 3-dimensional computer modelling of the built environment to an almost infinite number of dimensions, to cope with whole-life construction and asset management issues in the design of modern buildings. This paper reports on the development of a vision for how integrated environments that will allow nD-enabled construction and asset management to be undertaken. The project is funded by a four-year platform grant from the Engineering and Physical Sciences Research Council (EPSRC) in the UK; thus awarded to a multi-disciplinary research team, to enable flexibility in the research strategy and to produce leading innovation. This paper reports on the development of a business process and IT vision for how integrated environments will allow nD-enabled construction and asset management to be undertaken. It further develops many of the key issues of a future vision arising from previous CIB W78 conferences.

The effectiveness of designated driver programs

Designated driver programs aim to reduce alcohol related crashes by encouraging and facilitating a safe means of transport for those who have been drinking and by influencing attitudes and knowledge. This review discusses the use and effectiveness of designated driver programs in preventing drink driving and ultimately reducing alcohol related road trauma. The limitations of studies examining designated driver programs and recommendations for further research are also discussed. The available evidence suggests that while designated driver campaigns can successfully increase the awareness and use of designated drivers, it is less clear whether these programs lead to a reduction in drink driving and/or alcohol related crashes. Differences in the way that designated driver programs have historically been implemented may account for the inconsistent evidence for their effectiveness in reducing drink driving. There are also a variety of methodological problems relating to the evaluation of designated driver programs which need to be addressed by future research.

Built environment procurement practice: Impediments to innovation and opportunities for changes

This report was commissioned by the Built Environment Industry Innovation Council and funded by the Australian Government Department of Innovation, Industry, Science and Research.

Nonfatal heroin overdoses in Queensland, Australia : an analysis of ambulance data

In the past decade, the utilization of ambulance data to inform the prevalence of nonfatal heroin overdose has increased. These data can assist public health policymakers, law enforcement agencies, and health providers in planning and allocating resources. This study examined the 672 ambulance attendances at nonfatal heroin overdoses in Queensland, Australia, in 2000. Gender distribution showed a typical 70/30 male-to-female ratio. An equal number of persons with nonfatal heroin overdose were between 15 and 24 years of age and 25 and 34 years of age. Police were present in only 1 of 6 cases, and 28.1% of patients reported using drugs alone. Ambulance data are proving to be a valuable population-based resource for describing the incidence and characteristics of nonfatal heroin overdose episodes. Future studies could focus on the differences between nonfatal heroin overdose and fatal heroin overdose samples.

The efficacy of waste management plans in Australian commercial construction refurbishment projects

Renovation and refurbishment of the existing commercial building stock is a growing area of total construction activity and a significant generator of waste sent to landfill in Australia. A written waste management plan (WMP) is a widespread regulatory requirement for commercial office redevelopment projects. There is little evidence, however, that WMPs actually increase the quantity of waste that is ultimately diverted from landfill. Some reports indicate an absence of any formal verification or monitoring process by regulators to assess the efficacy of the plans. In order to gauge the extent of the problem a survey was conducted of twenty four consultants and practitioners involved in commercial office building refurbishment projects to determine the state of current practice with regard to WMPs and to elicit suggestions with regard to ways of making the process more effective. Considerable variation in commitment to recycling policies was encountered indicating a need to revisit waste minimisation practices if the environmental performance of refurbishment projects is to be improved.

Suicide plays

Suicide is a uniquely human behaviour and has always elicited strong - usually negative - opinions. Thus I would like to state from the very outset that this morbid collection of writing (all separately published elsewhere previously) should not be seen as an attempt to glamorise the act of felo-de-se. Nevertheless, one needs to recognise the inherent theatricality of suicide: too often it is a petulant, peevish performance intended to convey a bitter message to the audience of those left behind. Unfortunately, it is also a performance that many similarly unhappy souls try to emulate, and this phenomenon, known as “The Werther Effect”, is the subject of the first paper, which serves as a most appropriate introduction to the four plays that follow it. The first play, entitled “Hamlet + Ophelia = ?”, is deliberately provocative, and may easily be misunderstood as a call to commit self-murder. It is hoped, however, that the protagonists of this angry little piece are seen to be impetuous and childish, rather than noble or deep. The second play, “Games for Married Couples”, is less about seppuku than it is about the despair of child-less marriage. It is not much happier than the first, but may nevertheless raise a smile or two. “His ... or Her ... Suicide”, on the other hand, is utterly frivolous. I am sure no reader will take it seriously. Finally, and circuitously, is the stage adaptation (and translation) of Goethe’s classic 1774 novella "Die Leiden des jungen Werthers". This piece was produced as part of my 2005 Master of Creative Arts at the University of Melbourne in Australia. Many thanks must go to my supervisor, Associate Professor Angela O’Brien, for prodding and poking me until the thesis was of an acceptable standard.

A brief motivational intervention for substance misuse in recent-onset psychosis

Substance misuse is common in early psychosis, and impacts negatively on outcomes. Little is known about effective interventions for this population. We report a pilot study of brief intervention for substance misuse in early psychosis (Start Over and Survive: SOS), comparing it with Standard Care (SC). Twenty-five in-patients aged 18-35 years with early psychosis and current misuse of non-opioid drugs were allocated randomly to conditions. Substance use and related problems were assessed at baseline, 6 weeks and 3, 6 and 12 months. Final assessments were blind to condition. All 13 SOS participants who proceeded to motivational interviewing reported less substance use at 6 months, compared with 58% (7/12) in SC alone. Effects were well maintained to 12 months. However, more SOS participants lived with a relative or partner, and this also was associated with better outcomes. Engagement remained challenging: 39% (16/41) declined participation and 38% (5/13) in SOS only received rapport building. Further research will increase sample size, and address both engagement and potential confounds.

Start Over and Survive : A Brief Intervention For Substance Abuse in Early Psychosis

Over the last decade, brief intervention for alcohol problems has become a well-validated and accepted treatment, with bried interventions frequently showing equivalence in terms of outcome to more extended treatments (Bien et al, 1993). A recent review of this studies found that heavy drinkers who received interventions of less than 1 h were almost twice as likely to moderate their drinking over the following 6-12 months as did those not receiving intervention (Wilk etal, 1997).Some studies have used motivational interviewing (MI) strategies (Monti et al, 1999); others have simply given information ajnd advice to reduce drinking (Fleming et al, 1997). Leaflets or information on strategies to assist in the attempt or follow-up sessions are sometimes provided (Fleming et al, 1997). In general practice research, provision of one or more follow-up sessions increases the reliability of intake reductions across studies (Poikolainen, 1999).