The role of education and awareness in workplace alcohol and drug use in the Australian construction industry : proposed program of research and preliminary results

The main aim of this paper is to outline a proposed program of research which will attempt to quantify the extent of the problem of alcohol and other drugs in the Australian construction industry, and furthermore, develop an appropriate industry-wide policy and cultural change management program and implementation plan to address the problem. This paper will also present preliminary results from the study. The study will use qualitative and quantitative methods (in the form of interviews and surveys, respectively) to evaluate the extent of the problem of alcohol and other drug use in this industry, to ascertain the feasibility of an industry-wide policy and cultural change management program, and to develop an appropriate implementation plan. The study will be undertaken in several construction organisations, at selected sites in South Australia, Victoria and Northern Territory. It is anticipated that approximately 500 employees from the participating organisations across Australia will take part in the study. The World Health Organisation’s Alcohol Use Disorders Identification Test (AUDIT) will be used to measure the extent of alcohol use in the industry. Illicit drug use, ‘‘readiness to change’’, impediments to reducing impairment, feasibility of proposed interventions, and employee attitudes and knowledge regarding workplace AOD impairment, will also be measured through a combination of interviews and surveys. Among the preliminary findings, for 51% (n=127) of respondents, score on the AUDIT indicated alcohol use at hazardous levels. Of the respondents who were using alcohol at hazardous levels, 76% reported (n97) that they do not have a problem with drinking and 54% (n=68) reported that it would be easy to ‘‘cut down’’ or stop drinking. Nearly half (49%) of all respondents (n=122) had used marijuana/cannabis at some time prior to being surveyed. The use of other illicit substances was much less frequently reported. Preliminary interview findings indicated a lack of adequate employee knowledge regarding the physical effects of alcohol and other drugs in the workplace. As for conclusions, the proposed study will address a major gap in the literature with regard to the extent of the problem of alcohol and other drug use in the construction industry in Australia. The study will also develop and implement a national, evidence-based workplace policy, with the aim of mitigating the deleterious effects of alcohol and other drugs in this industry.

The identification of therapeutic targets in metastatic melanoma

Metastatic melanoma, a cancer historically refractory to chemotherapeutic strategies, has a poor prognosis and accounts for the majority of skin cancer related mortality. Although the recent approval of two new drugs combating this disease, Ipilimumab and Vemurafenib (PLX4032), has demonstrated for the first time in decades an improvement in overall survival; the clinical efficacy of these drugs has been marred by severe adverse immune reactions and acquired drug resistance in patients, respectively. Thus, understanding the etiology of metastatic melanoma will contribute to the improvement of current therapeutic strategies while leading to the development of novel drug approaches. In order to identify recurrently mutated genes of therapeutic relevance in metastatic melanoma, a panel of stage III local lymph node melanomas were extensively characterised using high-throughput genomic technologies. This led to the identification of mutations in TFG in 5% of melanomas from a candidate gene sequencing approach using SNP array analysis, 24% of melanomas with mutations in MAP3K5 or MAP3K9 though unbiased whole-exome sequencing strategies, and inactivating mutations in NF1 in BRAF/NRAS wild type tumours though pathway analysis. Lastly, this thesis describes the development of a melanoma specific mutation panel that can rapidly identify clinically relevant mutation profiles that could guide effective treatment strategies through a personalised therapeutic approach. These findings are discussed in respect to a number of important issues raised by this study including the current limitation of next-generation sequencing technology, the difficulty in identifying ‘driver’ mutations critical to the development of melanoma due to high carcinogenic exposure by UV radiation, and the ultimate application of mutation screening in a personalised therapeutic setting. In summary, a number novel genes involved in metastatic melanoma have been identified that may have relevance for current therapeutic strategies in treating this disease.

Identification of direct transcriptional targets of V600EBRAF/MEK signalling in melanoma

Oncogenic mutations in BRAF are common in melanoma and drive constitutive activation of the MEK/ERK pathway. To elucidate the transcriptional events downstream of V600EBRAF/MEK signalling we performed gene expression profiling of A375 melanoma cells treated with potent and selective inhibitors of V600EBRAF and MEK (PLX4720 and PD184352 respectively). Using a stringent Bayesian approach, we identified 69 transcripts that appear to be direct transcriptional targets of this pathway and whose expression changed after 6 h of pathway inhibition. We also identified several additional genes whose expression changed after 24 h of pathway inhibition and which are likely to be indirect transcriptional targets of the pathway. Several of these were confirmed by demonstrating their expression to be similarly regulated when BRAF was depleted using RNA interference, and by using qRT-PCR in other BRAF mutated melanoma lines. Many of these genes are transcription factors and feedback inhibitors of the ERK pathway and are also regulated by MEK signalling in NRAS mutant cells. This study provides a basis for understanding the molecular processes that are regulated by V600EBRAF/MEK signalling in melanoma cells.

Identification of a novel FGFRL1 MicroRNA target site polymorphism for bone mineral density in meta-analyses of genome-wide association studies

MicroRNAs (miRNAs) are critical post-transcriptional regulators. Based on a previous genome-wide association (GWA) scan, we conducted a polymorphism in microRNAs' Target Sites (poly-miRTS)-centric multistage meta-analysis for lumbar spine (LS)-, total hip (HIP)-, and femoral neck (FN)-bone mineral density (BMD). In stage I, 41,102 poly-miRTSs were meta-analyzed in 7 cohorts with a genome-wide significance (GWS) α=0.05/41,102=1.22×10-6. By applying α=5×10-5 (suggestive significance), 11 poly-miRTSs were selected, with FGFRL1 rs4647940 and PRR5 rs3213550 as top signals for FN-BMD (P-value=7.67×10-6 and 1.58×10-5) in gender-combined sample. In stage II in silico replication (two cohorts), FGFRL1 rs4647940 was the only signal marginally replicated for FN-BMD (P-value=5.08×10-3) at α=0.10/11=9.09×10-3. PRR5 rs3213550 was also selected based on biological significance. In stage III de novo genotyping replication (two cohorts), FGFRL1 rs4647940 was the only signal significantly replicated for FN-BMD (P-value=7.55×10-6) at α=0.05/2=0.025 in gender-combined sample. Aggregating three stages, FGFRL1 rs4647940 was the single stage I-discovered and stages II- and III-replicated signal attaining GWS for FN-BMD (P-value=8.87×10-12). Dual-luciferase reporter assays demonstrated that FGFRL1 3' untranslated region harboring rs4647940 appears to be hsa-miR-140-5p's target site. In a zebrafish microinjection experiment, dre-miR-140-5p is shown to exert a dramatic impact on craniofacial skeleton formation. Taken together, we provided functional evidence for a novel FGFRL1 poly-miRTS rs4647940 in a previously known 4p16.3 locus, and experimental and clinical genetics studies have shown both FGFRL1 and hsa-miR-140-5p are important for bone formation. © The Author 2015. Published by Oxford University Press. All rights reserved.

Texture for Script identification

The problem of determining the script and language of a document image has a number of important applications in the field of document analysis, such as indexing and sorting of large collections of such images, or as a precursor to optical character recognition (OCR). In this paper, we investigate the use of texture as a tool for determining the script of a document image, based on the observation that text has a distinct visual texture. An experimental evaluation of a number of commonly used texture features is conducted on a newly created script database, providing a qualitative measure of which features are most appropriate for this task. Strategies for improving classification results in situations with limited training data and multiple font types are also proposed.