Submission to the inquiry into the high level of involvement of Indigenous juveniles and young adults in the criminal justice system

Introduction • The Australian Institute of Criminology (AIC) is Australia's national research and knowledge centre on crime and justice. • The Institute seeks to promote justice and reduce crime by undertaking and communicating evidence-based research to inform policy and practice. • The AIC is governed by the Criminology Research Act and has been in operation since 1973. • The AIC is pleased to have the opportunity to contribute to the Committee's Inquiry into the high level of involvement of Indigenous juveniles and young adults in the criminal justice system. • There is a great deal of evidence to demonstrate that Indigenous young people are significantly over-represented at every stage of the criminal justice system in Australia.

Mechanical stimulation of the pro-angiogenic capacity of human fracture haematoma: Involvement of VEGF mechano-regulation

Compromised angiogenesis appears to be a major limitation in various suboptimal bone healing situations. Appropriate mechanical stimuli support blood vessel formation in vivo and improve healing outcomes. However, the mechanisms responsible for this association are unclear. To address this question, the paracrine angiogenic potential of early human fracture haematoma and its responsiveness to mechanical loading, as well as angiogenic growth factors involved, were investigated in vitro. Human haematomas were collected from healthy patients undergoing surgery within 72. h after bone fracture. The haematomas were embedded in a fibrin matrix, and cultured in a bioreactor resembling the in vivo conditions of the early phase of bone healing (20 compression, 1. Hz) over 3. days. Conditioned medium (CM) from the bioreactor was then analyzed. The matrices were also incubated in fresh medium for a further 24. h to evaluate the persistence of the effects. Growth factor (GF) concentrations were measured in the CM by ELISAs. In vitro tube formation assays were conducted on Matrigel with the HMEC-1 cell line, with or without inhibition of vascular endothelial growth factor receptor 2 (VEGFR2). Cell numbers were quantified using an MTS test. In vitro endothelial tube formation was enhanced by CM from haematomas, compared to fibrin controls. The angiogenesis regulators, vascular endothelial growth factor (VEGF) and transforming growth factor β1 (TGF-β1), were released into the haematoma CM, but not angiopoietins 1 or 2 (Ang1, 2), basic fibroblast growth factor (bFGF) or platelet-derived growth factor (PDGF). Mechanical stimulation of haematomas, but not fibrin controls, further increased the induction of tube formation by their CM. The mechanically stimulated haematoma matrices retained their elevated pro-angiogenic capacity for 24. h. The pro-angiogenic effect was cancelled by inhibition of VEGFR2 signalling. VEGF concentrations in CM tended to be elevated by mechanical stimulation; this was significant in haematomas from younger, but not from older patients. Other GFs were not mechanically regulated. In conclusion, the paracrine pro-angiogenic capacity of early human haematomas is enhanced by mechanical stimulation. This effect lasts even after removing the mechanical stimulus and appears to be VEGFR2-dependent.

Investigating the individual and organisational predictors of work-related driving crash involvement in Ethiopia

The rate of road traffic injury and death in Ethiopia is at a critical level when compared to rates in high-income countries. Considering the enormity of this issue, research is to identify groups of high-risk road users and the factors contributing to their crash involvement. This study focuses on work-related drivers. This study explores driving behaviour as a mediator of the relationship between organisational and individual attribute factors and self-reported crashes in a sample of 213 work-related drivers in Addis Ababa, Ethiopia. The hypothesised framework identifies driving behaviour as the most proximal determinant of self-reported crashes, and safety values, role overload and self-efficacy as antecedents of driving behaviour. With the exception of the relationship between self-efficacy and driving behaviour, all the hypothesised relationships were supported. We make recommendations for intervention approaches that are theoretically focused and sensitive to the cultural context.

A comparison of methods to identify alcohol involvement in youth injury-related emergency department presentation data

Aims: To compare different methods for identifying alcohol involvement in injury-related emergency department presentation in Queensland youth, and to explore the alcohol terminology used in triage text. Methods: Emergency Department Information System data were provided for patients aged 12-24 years with an injury-related diagnosis code for a 5 year period 2006-2010 presenting to a Queensland emergency department (N=348895). Three approaches were used to estimate alcohol involvement: 1) analysis of coded data, 2) mining of triage text, and 3) estimation using an adaptation of alcohol attributable fractions (AAF). Cases were identified as ‘alcohol-involved’ by code and text, as well as AAF weighted. Results: Around 6.4% of these injury presentations overall had some documentation of alcohol involvement, with higher proportions of alcohol involvement documented for 18-24 year olds, females, indigenous youth, where presentations occurred on a Saturday or Sunday, and where presentations occurred between midnight and 5am. The most common alcohol terms identified for all subgroups were generic alcohol terms (eg. ETOH or alcohol) with almost half of the cases where alcohol involvement was documented having a generic alcohol term recorded in the triage text. Conclusions: Emergency department data is a useful source of information for identification of high risk sub-groups to target intervention opportunities, though it is not a reliable source of data for incidence or trend estimation in its current unstandardised form. Improving the accuracy and consistency of identification, documenting and coding of alcohol-involvement at the point of data capture in the emergency department is the most desirable long term approach to produce a more solid evidence base to support policy and practice in this field.

Phenytoin metabolism by human cytochrome P450 : involvement of P450 3A and 2C forms in secondary metabolism and drug-protein adduct formation

The anticonvulsant phenytoin (5,5-diphenylhydantoin) provokes a skin rash in 5 to 10% of patients, which heralds the start of an idiosyncratic reaction that may result from covalent modification of normal self proteins by reactive drug metabolites. Phenytoin is metabolized by cytochrome P450 (P450) enzymes primarily to 5-(p-hydroxyphenyl-),5-phenylhydantoin (HPPH), which may be further metabolized to a catechol that spontaneously oxidizes to semiquinone and quinone species that covalently modify proteins. The aim of this study was to determine which P450s catalyze HPPH metabolism to the catechol, proposed to be the final enzymatic step in phenytoin bioactivation. Recombinant human P450s were coexpressed with NADPH-cytochrome P450 reductase in Escherichia coli. Novel bicistronic expression vectors were constructed for P450 2C19 and the three major variants of P450 2C9, i.e., 2C9*1, 2C9*2, and 2C9*3. HPPH metabolism and covalent adduct formation were assessed in parallel. P450 2C19 was the most effective catalyst of HPPH oxidation to the catechol metabolite and was also associated with the highest levels of covalent adduct formation. P450 3A4, 3A5, 3A7, 2C9*1, and 2C9*2 also catalyzed bioactivation of HPPH, but to a lesser extent. Fluorographic analysis showed that the major targets of adduct formation in bacterial membranes were the catalytic P450 forms, as suggested from experiments with human liver microsomes. These results suggest that P450 2C19 and other forms from the 2C and 3A subfamilies may be targets as well as catalysts of drug-protein adduct formation from phenytoin.

Nedd4-2functionally interacts with ClC-5: involvement in constitutive albumin endocytosis in proximal tubule cells

Constitutive albumin uptake by the proximal tubule is achieved by a receptor-mediated process in which the Cl– channel, ClC-5, plays an obligate role. Here we investigated the functional interaction between ClC-5 and ubiquitin ligases Nedd4 and Nedd4-2 and their role in albumin uptake in opossum kidney proximal tubule (OK) cells. In vivo immunoprecipitation using an anti-HECT antibody demonstrated that ClC-5 bound to ubiquitin ligases, whereas glutathione S-transferase pull-downs confirmed that the C terminus of ClC-5 bound both Nedd4 and Nedd4-2. Nedd4-2 alone was able to alter ClC-5 currents in Xenopus oocytes by decreasing cell surface expression of ClC-5. In OK cells, a physiological concentration of albumin (10 μg/ml) rapidly increased cell surface expression of ClC-5, which was also accompanied by the ubiquitination of ClC-5. Albumin uptake was reduced by inhibiting either the lysosome or proteasome. Total levels of Nedd4-2 and proteasome activity also increased rapidly in response to albumin. Overexpression of ligase defective Nedd4-2 or knockdown of endogenous Nedd4-2 with small interfering RNA resulted in significant decreases in albumin uptake. In contrast, pathophysiological concentrations of albumin (100 and 1000 μg/ml) reduced the levels of ClC-5 and Nedd4-2 and the activity of the proteasome to the levels seen in the absence of albumin. These data demonstrate that normal constitutive uptake of albumin by the proximal tubule requires Nedd4-2, which may act via ubiquitination to shunt ClC-5 into the endocytic pathway.

Internal audit involvement in enterprise risk management

Purpose The paper examines the impact of internal auditors’ involvement in Enterprise Risk Management (ERM) on perceptions of their willingness to report a breakdown in risk procedures and whether a strong relationship with the audit committee affects such willingness to report. The study also investigates the use of ERM and the role of internal audit in ERM in Australian private and public sector entities. Design/methodology/approach The study uses an experimental design, manipulating (i) the internal auditor’s involvement in ERM and (ii) the strength of the relationship between internal audit and the audit committee. Participants are 117 certified internal auditors. The study also gathers descriptive data on the use of ERM. Findings The study indicates that a high involvement in ERM impacts the perceptions of internal auditors’ willingness to report a breakdown in risk procedures to the audit committee. However, a strong relationship with the audit committee does not appear to affect their perceived willingness to report. The study also finds that the majority of organisations have recently adopted ERM. Internal auditors are involved in ERM assurance activities but some also engage in activities that could compromise objectivity.

Improving construction management : an investigation into the influences of effective stakeholder involvement on project quality outcomes

This research has developed a framework to improve the effectiveness and efficiency of stakeholder involvement during the early planning stages of residential construction projects, in order to improve many of the quality issues that occur during the construction phases of such projects. A mixed methods approach (survey, interviews and case studies) was employed to collect the required data. It is expected that with development, this framework can bring some significant benefits to future construction projects in terms of reducing rework and wastage, improving timely delivery and avoiding disputes. The research is also anticipated to produce three high impact journal articles.

Involvement of focal adhesion kinase in inhibition of motility of human breast cancer cells by sphingosine 1-phosphate

Sphingosine 1-phosphate (SPP), a bioactive sphingolipid metabolite, inhibits chemoinvasiveness of the aggressive, estrogen-independent MDA-MB-231 human breast cancer cell line. As in many other cell types, SPP stimulated proliferation of MDA-MB-231 cells, albeit to a lesser extent. Treatment of MDA-MB-231 cells with SPP had no significant effect on their adhesiveness to Matrigel, and only high concentrations of SPP partially inhibited matrix metalloproteinase-2 activation induced by Con A. However, SPP at a concentration that strongly inhibited invasiveness also markedly reduced chemotactic motility. To investigate the molecular mechanisms by which SPP interferes with cell motility, we examined tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin, which are important for organization of focal adhesions and cell motility. SPP rapidly increased tyrosine phosphorylation of FAK and paxillin and of the paxillin-associated protein Crk. Overexpression of FAK and kinase-defective FAK in MDA-MB-231 cells resulted in a slight increase in motility without affecting the inhibitory effect of SPP, whereas expression of FAK with a mutation of the major autophosphorylation site (F397) abolished the inhibitory effect of SPP on cell motility. In contrast, the phosphoinositide 3'-kinase inhibitor, wortmannin, inhibited chemotactic motility in both vector and FAK-F397- transfected cells. Our results suggest that autophosphorylation of FAK on Y397 may play an important role in SPP signaling leading to decreased cell motility.

Selective involvement of TIMP-2 in the second activational cleavage of pro-MMP-2 : refinement of the pro-MMP-2 activation mechanism

A tissue inhibitor of metalloproteinases-2 (TIMP-2)-independent mechanism for generating the first activational cleavage of pro-matrix metalloproteinase-2 (MMP-2) was identified in membrane type-1 MMP (MT1-MMP)-transfected MCF-7 cells and confirmed in TIMP-2-deficient fibroblasts. In contrast, the second MMP-2-activational step was found to be TIMP-2 dependent in both systems. MMP-2 hemopexin C-terminal domain was found to be critical for the first step processing, confirming a need for membrane tethering. We propose that the intermediate species of MMP-2 forms the well-established trimolecular complex (MT1-MMP/TIMP-2/MMP-2) for further TIMP-2-dependent autocatalytic cleavage to the fully active species. This alternate mechanism may supplement the traditional TIMP-2-mediated first step mechanism.

An empirical study of the factors impacting on the involvement of clients in Saudi Arabian construction projects

This thesis is an empirical study of the factors impacting on the client involvement in Saudi Arabian construction government projects. The study investigated the impact of some factors that limited the client involvement and developed a framework called "client involvement interactive" to improve the client involvement practices in Saudi Arabian construction projects through the implementation of an implementable strategy elaborated.

Value management in design planning : a systems-based framework for multi-disciplinary team involvement

This thesis investigates the Value Management processes used by construction project clients that effects project team involvement in VM workshops during the design stage of the projects. It is based on five case studies of the Malaysian international airport construction project packages. The focus of the research is on how issues related to infrastructure design that can improve construction processes on-site are being identified, analysed and resolved through multi-disciplinary team participation. The degrees of interaction, diversity of visualisation aids, certain cultural dimensions and the system thinking approach are found to have significant influence in maximizing participation among project team members during the entire VM workshop process.

The influence of families on early adolescent school connectedness : evidence that this association varies with adolescent involvement in peer drinking networks

School connectedness is central to the long term well-being of adolescents, and high quality parent-child relationships facilitate school connectedness. This study examined the extent to which family relationship quality is associated with the school connectedness of pre- and early teenagers, and how this association varies with adolescent involvement in peer drinking networks. The sample consisted of 7,372 10-14 year olds recruited from 231 schools in 30 Australian communities. Participants completed the Communities that Care youth survey. A multi-level model of school connectedness was used, with a random term for school-level variation. Key independent variables included family relationship quality, peer drinking networks, and school grade. Control variables included child gender, sensation seeking, depression, child alcohol use, parent education, and language spoken at home. For grade 6 students, the association of family relationship quality and school connectedness was lower when peer drinking networks were present, and this effect was nonsignificant for older (grade 8) students. Post hoc analyses indicated that the effect for family relationship quality on school connectedness was nonsignificant when adolescents in grade 6 reported that the majority of friends consumed alcohol. The results point to the importance of familyschool partnerships in early intervention and prevention.

The driving visual field and a history of motor vehicle collision involvement in older drivers: A population-based examination

Purpose We designed a visual field test focused on the field utilized while driving to examine associations between field impairment and motor vehicle collision involvement in 2,000 drivers ≥70 years old. Methods The "driving visual field test" involved measuring light sensitivity for 20 targets in each eye, extending 15° superiorly, 30° inferiorly, 60° temporally and 30° nasally. The target locations were selected on the basis that they fell within the field region utilized when viewing through the windshield of a vehicle or viewing the dashboard while driving. Monocular fields were combined into a binocular field based on the more sensitive point from each eye. Severe impairment in the overall field or a region was defined as average sensitivity in the lowest quartile of sensitivity. At-fault collision involvement for five years prior to enrollment was obtained from state records. Poisson regression was used to calculate crude and adjusted rate ratios examining the association between field impairment and at-fault collision involvement. Results Drivers with severe binocular field impairment in the overall driving visual field had a 40% increased rate of at-fault collision involvement (RR 1.40, 95%CI 1.07-1.83). Impairment in the lower and left fields was associated with elevated collision rates (RR 1.40 95%CI 1.07-1.82 and RR 1.49, 95%CI 1.15-1.92, respectively), whereas impairment in the upper and right field regions was not. Conclusions Results suggest that older drivers with severe impairment in the lower or left region of the driving visual field are more likely to have a history of at-fault collision involvement.

Crash involvement patterns of unlicensed drivers and riders in Queensland. Report to Queensland Department of Transport and Main Roads

Unlicensed driving remains a serious problem for road safety, despite ongoing improvements in traffic law enforcement practices and technology. While it does not play a direct causative role in road crashes, unlicensed driving undermines the integrity of the driver licensing system and is associated with a range of high-risk behaviours. This report examines official road crash data from Queensland for the years 2003-08 to compare the crash involvement patterns of unlicensed drivers with those of licensed drivers and explore the scope and nature of unlicensed driving. This study replicates and extends upon two previous studies examining the involvement of unlicensed drivers in crashes in Queensland (Watson, 2004a; 2004b; Watson & Steinhardt, 2006).