A metastatic neuroendocrine anaplastic small cell tumor in a patient with multiple endocrine neoplasia type 1 syndrome : assessment of disease status and response to doxorubicin, cyclophosphamide, etoposide chemotherapy through scintigraphic imaging with 111In-pentetreotide

Extrapulmonary small cell and small cell neuroendocrine tumors of unknown primary site are, in general, aggressive neoplasms with a short median survival. Like small cell lung cancer (SCLC), they often are responsive to chemotherapy and radiotherapy. Small cell lung cancer and well differentiated neuroendocrine carcinomas of the gastrointestinal tract and pancreas tend to express somatostatin receptors. These tumors may be localized in patients by scintigraphic imaging using radiolabeled somatostatin analogues. A patient with an anaplastic neuroendocrine small cell tumor arising on a background of multiple endocrine neoplasia type 1 syndrome is reported. The patient had a known large pancreatic gastrinoma and previously treated parathyroid adenopathy. At presentation, there was small cell cancer throughout the liver and skeleton. Imaging with a radiolabeled somatostatin analogue, 111In- pentetreotide (Mallinckrodt Medical B. V., Petten, Holland), revealed all sites of disease detected by routine biochemical and radiologic methods. After six cycles of chemotherapy with doxorubicin, cyclophosphamide, and etoposide, there was almost complete clearance of the metastatic disease. 111In-pentetreotide scintigraphy revealed uptake consistent with small areas of residual disease in the liver, the abdomen (in mesenteric lymph nodes), and posterior thorax (in a rib). The primary gastrinoma present before the onset of the anaplastic small cell cancer showed no evidence of response to the treatment. The patient remained well for 1 year and then relapsed with brain, lung, liver, and skeletal metastases. Despite an initial response to salvage radiotherapy and chemotherapy with carboplatin and dacarbazine, the patient died 6 months later.

Prognostic value of biochemical liver parameters in neonatal sepsis-associated cholestasis

Aims The aim of the study was to evaluate the significance of total bilirubin, aspartate transaminase (AST), alanine transaminase and gamma-glutamyltransferase (GGT) for predicting outcome in sepsis-associated cholestasis. Methods: A retrospective cohort review of the hospital records was performed in 181 neonates admitted to the Neonatal Care Unit. A comparison was performed between subjects with low and high liver values based on cut-off values from ROC analysis. We defined poor prognosis to be when a subject had prolonged cholestasis of more than 3.5 months, developed severe sepsis, septic shock or had a fatal outcome. Results: The majority of the subjects were male (56%), preterm (56%) and had early onset sepsis (73%). The poor prognosis group had lower initial values of GGT compared with the good prognosis group (P = 0.003). Serum GGT (cut-off value of 85.5 U/L) and AST (cut-off value of 51 U/L) showed significant correlation with the outcome following multivariate analysis. The odds ratio (OR) of low GGT and high AST were OR 4.3 (95% CI:1.6 to11.8) and OR 2.9 (95% CI:1.1 to 8), respectively, for poor prognosis. In subjects with normal AST values, those with low GGT value had relative risk of 2.52 (95% CI:1.4 to 3.5) for poorer prognosis compared with those with normal or high GGT. Conclusion: Serum GGT and AST values can be used to predict the prognosis of patients with sepsis-associated cholestasis

Short-rib polydactyly and jeune syndromes are caused by mutations in WDR60

Short-rib polydactyly syndromes (SRPS I-V) are a group of lethal congenital disorders characterized by shortening of the ribs and long bones, polydactyly, and a range of extraskeletal phenotypes. A number of other disorders in this grouping, including Jeune and Ellis-van Creveld syndromes, have an overlapping but generally milder phenotype. Collectively, these short-rib dysplasias (with or without polydactyly) share a common underlying defect in primary cilium function and form a subset of the ciliopathy disease spectrum. By using whole-exome capture and massive parallel sequencing of DNA from an affected Australian individual with SRPS type III, we detected two novel heterozygous mutations in WDR60, a relatively uncharacterized gene. These mutations segregated appropriately in the unaffected parents and another affected family member, confirming compound heterozygosity, and both were predicted to have a damaging effect on the protein. Analysis of an additional 54 skeletal ciliopathy exomes identified compound heterozygous mutations in WDR60 in a Spanish individual with Jeune syndrome of relatively mild presentation. Of note, these two families share one novel WDR60 missense mutation, although haplotype analysis suggested no shared ancestry. We further show that WDR60 localizes at the base of the primary cilium in wild-type human chondrocytes, and analysis of fibroblasts from affected individuals revealed a defect in ciliogenesis and aberrant accumulation of the GLI2 transcription factor at the centrosome or basal body in the absence of an obvious axoneme. These findings show that WDR60 mutations can cause skeletal ciliopathies and suggest a role for WDR60 in ciliogenesis.

Risk factors for fatal crashes in rural Australia

This paper presents findings from the rural and remote road safety study, conducted in Queensland, Australia, from March 2004 till June 2007, and compares fatal crashes and non-fatal but serious crashes in respect of their environmental, vehicle and operator factors. During the study period there were 613 non-fatal crashes resulting in 684 hospitalised casualties and 119 fatal crashes resulting in 130 fatalities. Additional information from police sources was available on 103 fatal and 309 non-fatal serious crashes. Over three quarters of both fatal and hospitalised casualties were male and the median age in both groups was 34 years. Fatal crashes were more likely to involve speed, alcohol and violations of road rules and fatal crash victims were 2 and a 1/2 times more likely to be unrestrained inside the vehicle than non-fatal casualties, consistent with current international evidence. After controlling for human factors, vehicle and road conditions made a minimal contribution to the seriousness of the crash outcome. Targeted interventions to prevent fatalities on rural and remote roads should focus on reducing speed and drink driving and promoting seatbelt wearing.

EGFR expression : associations with outcome and clinicopathological variables in malignant pleural mesothelioma

Malignant mesothelioma (MM) is a fatal tumour of increasing incidence which is related to asbestos exposure. This work evaluated expression in MM of Epidermal Growth Factor Receptor (EGFR) by immunohistochemistry in 168 tumour sections and its correlations with clinicopathological and biological factors. The microvessel density (MVD) was derived from CD34 immunostained sections. Hematoxylin and eosin stained sections were examined for intratumoural necrosis. COX-2 protein expression was evaluated with semi-quantitative Western blotting of homogenised tumour supernatants (n = 45). EGFR expression was correlated with survival by Kaplan-Meier and log rank analysis. Univariate and multivariate Cox proportional hazards models were used to compare the effects of EGFR with clinicopathological and biological prognostic factors and prognostic scoring systems. EGFR expression was identified in 74 cases (44%) and correlated with epithelioid cell type (p < 0.0001), good performance status (p < 0.0001), the absence of chest pain (p < 0.0001) and the presence of TN (p = 0.004), but not MVD or COX-2. EGFR expression was a good prognostic factor in univariate analysis (p = 0.01). Independent indicators of poor prognosis in multivariate analysis were non-epithelioid cell type (p = 0.0001), weight loss, performance status and WBC > 8.3 × 10 9 L -1. EGFR status was not an independent prognostic factor. EGFR expression in MM correlates with epithelioid histology and TN. EGFR may be a target for selective therapies in MM. © 2006 Elsevier Ireland Ltd. All rights reserved.

Amblyopia treatment : an evidence-based approach to maximising treatment outcome

The basis of treatment for amblyopia (poor vision due to abnormal visual experience early in life) for 250 years has been patching of the unaffected eye for extended times to ensure a period of use of the affected eye. Over the last decade randomised controlled treatment trials have provided some evidence on how to tailor amblyopia therapy more precisely to achieve the best visual outcome with the least negative impact on the patient and the family. This review highlights the expansion of knowledge regarding treatment for amblyopia and aims to provide optometrists with a summary of research evidence to enable them to better treat amblyopia. Treatment for amblyopia is effective, as it reduces overall prevalence and severity of visual loss in this population. Correction of refractive error alone significantly improves visual acuity, sometimes to the point where further amblyopia treatment is not required. Atropine penalisation and patch occlusion are effective in treating amblyopia. Lesser amounts of occlusion or penalisation have been found to be just as effective as greater amounts. Recent evidence has highlighted that occlusion or penalisation in amblyopia treatment can create negative changes in behaviour in children and impact on family life. These complications should be considere when prescribing treatment because they can negatively affect compliance. Studies investigating the maximum age at which treatment of amblyopia can still be effective and the importance of near activities during occlusion are ongoing.

Multi-outcome construction policies : comparative analysis of western australian and queensland policies

This document provides an overview of the differences and similarities in the objectives and implementation frameworks of the training and employment policies applying to public construction projects in Western Australia and Queensland. The material in the document clearly demonstrates the extent to which approaches to the pursuit of training objectives in particular have been informed by the experiences of other jurisdictions. The two State governments now have very similar approaches to the promotion of training with the WA government basing a good part of its policy approach on the “Queensland model”. As the two States share many similar economic and other characteristics, and have very similar social and economic goals, this similarity is to be expected. The capacity to benefit from the experiences of other jurisdictions is to be welcomed. The similarity in policy approach also suggests a potential for ongoing collaborations between the State governments on research aimed at further improving training and employment outcomes via public construction projects.

Final report : feasibility study linking best value procurement assessment to outcome performance indicators

This feasibility study was established to investigate the application of the concept of ‘best value’ in construction procurement in Australia. In the case of ‘best value’ in the business enterprise, ‘best value’ is that which returns greatest value to the business enterprise’s shareholders. However, in the case of the public sector, ‘best value’ is more complex. For that reason, this research project focuses mainly on public sector construction project procurement.

Multi-Outcome Construction Policies : Industry-Focused Research Summary

The Multi-outcomes Construction Policies research project, funded by the Cooperative Research Centre for Construction Innovation (Project 2006-036-A), sought to explore the costs and benefits of leveraging social outcomes on public construction contracts. The context of the research project was the trend towards the contracting out of public construction works and the attempts that have been made to use new contractual arrangements with construction companies to construction achieve a wide range of social outcomes. In federal and state jurisdictions it is now common for governments to impose a range of additional requirements on public works contractors that relate to broad social/community objectives. These requirements include commitments to train apprentices and trainees; to provide local and/or indigenous employment opportunities; to buy local materials; and to include art works. The cost and benefits of using public construction contracts to achieve social/community goals have, to our knowledge, not been thoroughly researched in an Australian context. This is likely to reflect in large part the relatively short history of contracting out public works. As Jensen and Stonecash (2004) explain, most previous empirical studies of contracting out have attempted to measure the cost savings achieved through privatization, as this was the focus of policy debate in the 1980s and 1990s. Relatively few studies have addressed the ability of contracting arrangements to ensure the delivery of desired ‘quality’ outcomes1, or the costs of achieving these outcomes via contracting arrangements. One of the potential costs of attempting to leverage social/community outcomes on public construction projects is a reduction in the amount of competition for these projects, with obvious consequences for average bid prices and choice. In jurisdictions, such as Western Australia and Queensland, where currently construction market conditions are already

Fatal motorcycle crashes in north Queensland : characteristics and potential interventions

Aims: The Rural and Remote Road Safety Study (RRRSS) addresses a recognised need for greater research on road trauma in rural and remote Australia, the costs of which are disproportionately high compared with urban areas. The 5-year multi-phase study with whole-of-government support concluded in June 2008. Drawing on RRRSS data, we analysed fatal motorcycle crashes which occurred over 39 months to provide a description of crash characteristics, contributing factors and people involved. The descriptive analysis and discussion may inform development of tailored motorcycle safety interventions. Methods: RRRSS criteria sought vehicle crashes resulting in death or hospitalisation for 24 hours minimum of at least 1 person aged 16 years or over, in the study area defined roughly as the Queensland area north from Bowen in the east and Boulia in the west (excluding Townsville and Cairns urban areas). Fatal motorcycle crashes were selected from the RRRSS dataset. Analysis considered medical data covering injury types and severity, evidence of alcohol, drugs and prior medical conditions, as well as crash descriptions supplied by police to Queensland Transport on contributing circumstances, vehicle types, environmental conditions and people involved. Crash data were plotted in a geographic information system (MapInfo) for spatial analysis. Results: There were 23 deaths from 22 motorcycle crashes on public roads meeting RRRSS criteria. Of these, half were single vehicle crashes and half involved 2 or more vehicles. In contrast to general patterns for driver/rider age distribution in crashes, riders below 25 years of age were represented proportionally within the population. Riders in their thirties comprised 41% of fatalities, with a further 36% accounted for by riders in their fifties. 18 crashes occurred in the Far North Statistical Division (SD), with 2 crashes in both the Northern and North West SDs. Behavioural factors comprised the vast majority of contributing circumstances cited by police, with adverse environmental conditions noted in only 4 cases. Conclusions: Fatal motorcycle crashes were more likely to involve another vehicle and less likely to involve a young rider than non-fatal crashes recorded by the RRRSS. Rider behaviour contributed to the majority of crashes and should be a major focus of research, education and policy development, while other road users’ behaviour and awareness also remains important. With 68% of crashes occurring on major and secondary roads within a 130km radius of Cairns, efforts should focus on this geographic area.