Target acquired: Progress and promise of targeted therapeutics in the treatment of prostate cancer

Cancer is fundamentally a genomic disease caused by mutations or rearrangements in the DNA or epigenetic machinery of a patient. An emerging field in cancer treatment targets key aberrations arising from the mutational landscape of an individual patient’s disease rather than employing a cancer-wide cytotoxic therapy approach. In prostate cancer in particular, where there is an observed variation in response to standard treatments between patients with disease of a similar pathological stage and grade, mutationdirected treatment may grow to be a viable tool for clinicians to tailor more effective treatments. This review will describe a number of mutations across multiple forms of cancer that have been successfully antagonised by targeted therapeutics including their identification, the development of targeted compounds to combat them and the development of resistance to these therapies. This review will continue to examine these same mutations in the treatment and management of prostate cancer; the prevalence of targetable mutations in prostate cancer, recent clinical trials of targeted-agents and the potential or limitations for their use.

Speeding through roadworks: Understanding driver speed profiles and ways to reduce speeding

Poor compliance with speed limits is a serious safety concern at roadworks. While considerable research has been undertaken worldwide to understand drivers’ speeding behaviour at roadworks and to identify treatments for improving compliance with speed limits, little is known about the speeding behaviour of drivers at Australian roadworks and how their compliance rates with speed limits could be improved. This paper presents findings from two Queensland studies targeted at 1) examining drivers’ speed profiles at three long-term roadwork sites, and 2) understanding the effectiveness of speed control treatments at roadworks. The first study analysed driver speeds at various locations in the sites using a Tobit regression model. Results show that the probability of speeding was higher for light vehicles and their followers, for leaders of platoons with larger front gaps, during late afternoon and early morning, when higher proportions of surrounding vehicles were speeding, and at the upstream of work areas. The second study provided a comprehensive understanding of the effectiveness of various speed control treatments used at roadworks by undertaking a critical review of the literature. Results showed that enforcement has the greatest effects on reducing speeds among all treatments, while the roadwork signage and information-related treatments have small to moderate effects on speed reduction. Findings from the studies have potential for designing programs to effectively improve speed limit compliance at Australian roadworks.

Osmolality electrolyte and carbohydrate type and oral rehydration solutions: A controlled study to compare the efficacy of two commercially available solutions (osmolalities 240 mmol/L and 340 mmol/L)

An open-label, inpatient study was undertaken to compare the efficacy of two oral rehydration solutions (ORS) given randomly to children aged 1-10 years who had acute gastroenteritis with mild or moderate dehydration (n = 45). One solution contained 60 mmol/L sodium and 1.8% glucose, total osmolality 240 mosm/l (gastrolyte, Rhone-poulenc, Rorer) and the other contained 26 mmol/l sodium, 2.7% glucose and 3.6% sucrose, total osmolality 340 mOsm/l (Glucolyte, Gilseal). Analysis of data indicated that Gastrolyte therapy resulted in significantly fewer episodes and volume of vomiting over all time periods in comparison to Glucolyte and significantly less stool volume during the first 8 h and in the 0-24 h period. The differences between treatments in degree of dehydration at each follow-up period, duration of diarrhea, and duration of hospital stay were not significant. No adverse drug reactions occurred. Six patients received intravenous rehydration treatment and were considered treatment failures. We conclude that oral rehydration therapy is safe and efficacious in the management of dehydration in acute diarrhoea and that the lower osmolar rehydration solution has clinically marginal advantages.

Early detection of melanoma metastases using microRNAs as novel biomarkers

Early detection of melanoma skin cancer, prior to metastatic spread, is critical to improve survival outcomes in patients. This study identified a melanoma-related panel of blood markers that can detect the presence of melanoma with high sensitivity and accuracy which is superior to currently used markers for melanoma progression, recurrence, and survival. Overall, the findings discussed in this thesis may lead to more precise measurement of disease progression allowing for better treatments and an increase in overall survival.