Hydrogen peroxide-mediated neuronal cell death induced by an endogenous neurotoxin, 3-hydroxykynurenine.

3-Hydroxykynurenine (3-HK) is a tryptophan metabolite whose level in the brain is markedly elevated under several pathological conditions, including Huntington disease and human immunodeficiency virus infection. Here we demonstrate that micromolar concentrations (1-100 microM) of 3-HK cause cell death in primary neuronal cultures prepared from rat striatum. The neurotoxicity of 3-HK was blocked by catalase and desferrioxamine but not by superoxide dismutase, indicating that the generation of hydrogen peroxide and hydroxyl radical is involved in the toxicity. Measurement of peroxide levels revealed that 3-HK caused intracellular accumulation of peroxide, which was largely attenuated by application of catalase. The peroxide accumulation and cell death caused by 1-10 microM 3-HK were also blocked by pretreatment with allopurinol or oxypurinol, suggesting that endogenous xanthine oxidase activity is involved in exacerbation of 3-HK neurotoxicity. Furthermore, NADPH diaphorase-containing neurons were spared from toxicity of these concentrations of 3-HK, a finding reminiscent of the pathological characteristics of several neurodegenerative disorders such as Huntington disease. These results suggest that 3-HK at pathologically relevant concentrations renders neuronal cells subject to oxidative stress leading to cell death, and therefore that this endogenous compound should be regarded as an important factor in pathogenesis of neurodegenerative disorders.

Oxidative stress is involved in heat-induced cell death in Saccharomyces cerevisiae.

The cause for death after lethal heat shock is not well understood. A shift from low to intermediate temperature causes the induction of heat-shock proteins in most organisms. However, except for HSP104, a convincing involvement of heat-shock proteins in the development of stress resistance has not been established in Saccharomyces cerevisiae. This paper shows that oxidative stress and antioxidant enzymes play a major role in heat-induced cell death in yeast. Mutants deleted for the antioxidant genes catalase, superoxide dismutase, and cytochrome c peroxidase were more sensitive to the lethal effect of heat than isogenic wild-type cells. Overexpression of catalase and superoxide dismutase genes caused an increase in thermotolerance. Anaerobic conditions caused a 500- to 20,000-fold increase in thermotolerance. The thermotolerance of cells in anaerobic conditions was immediately abolished upon oxygen exposure. HSP104 is not responsible for the increased resistance of anaerobically grown cells. The thermotolerance of anaerobically grown cells is not due to expression of heat-shock proteins. By using an oxidation-dependent fluorescent molecular probe a 2- to 3-fold increase in fluorescence was found upon heating. Thus, we conclude that oxidative stress is involved in heat-induced cell death.

Proteolytic activation of the cell death protease Yama/CPP32 by granzyme B.

The serine protease granzyme B, which is secreted by cytotoxic cells, is one of the major effectors of apoptosis in susceptible targets. To examine the apoptotic mechanism of granzyme B, we have analyzed its effect on purified proteins that are thought to be components of death pathways inherent to cells. We demonstrate that granzyme B processes interleukin 1beta-converting enzyme (ICE) and the ICE-related protease Yama (also known as CPP32 or apopain) by limited proteolysis. Processing of ICE does not lead to activation. However, processing by granzyme B leads directly to the activation of Yama, which is now able to bind inhibitors and cleave the substrate poly(ADP-ribose) polymerase whose proteolysis is a marker of apoptosis initiated by several other stimuli. Thus ICE-related proteases can be activated by serine proteases that possess the correct specificity. Activation of pro-Yama by granzyme B is within the physiologic range. Thus the cytotoxic effect of granzyme B can be explained by its activation of an endogenous protease component of a programmed cell death pathway.

Mortality and perinatal infectious complications following home birth in Washington State: 2003-2013

Thesis (Master's)--University of Washington, 2016-06

Co-existing conditions for deaths from infectious and parasitic diseases in Australia

Objective: To examine the frequency distribution of co-existing conditions for deaths where the underlying cause was infectious and parasitic diseases. Materials and methods: Besides the underlying cause of death, the distributions of co-existing conditions for deaths from infectious and parasitic diseases were examined in total and by various age and sex groups, at individual and chapter levels, using 1998 Australian mortality data. Results: In addition to the underlying cause of death, the average number of reported co-existing conditions for a single infectious and parasitic death was 1.62. The most common co-existing conditions were respiratory failure, acute renal failure non-specific causes, ischaemic heart disease, pneumonia and diabetes. When studying the distribution of co-existing conditions at the ICD-9 chapter level, it was found that the circulatory system diseases were the most important. There was an increasing trend in the number of reported co-existing conditions from 60 years of age upwards. Gender differences existed in the frequency of some reported co-existing conditions. The most common organism types of co-existing conditions were other bacterial infection and other viruses. Conclusions: The study indicated that the quality of death certificates is less than satisfactory for the 1998 Australian mortality data. The findings may be helpful in clarifying the ICD coding rules and the development of disease prevention strategies. (C) 2003 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Tissue transglutaminase and the stress response

The expression of the protein crosslinking enzyme tissue transglutaminase (TG2, tTG), the ubiquitous member of transglutaminase family, can be regulated by multiple factors. Although it has been suggested that TG2 can be involved in apoptotic cell death, high levels of enzyme have also been associated with cell survival in response to different stimuli. Furthermore, evidence indicates that increases in TG2 production cause enzyme translocation to cell membrane. Cell stress can also lead to TG2 accumulation on the cell surface and in the extracellular matrix resulting in changes in cell-matrix interactions. Here, we discuss the underlying mechanisms of TG2 up-regulation induced by various stimuli including glutamate exposure, calcium influx, oxidative stress, UV, and inflammatory cytokines. These findings agree with a postulated role for transglutaminases in molecular mechanisms involved in several diseases suggesting that cross-linking reactions could be a relevant part of the biochemical changes observed in pathological conditions. © 2007 Springer-Verlag.

‘Death talk’, ‘loss talk’ and identification in the process of ageing

In this paper, we examine the injunction issued by the prominent politician, broadcaster and older people's advocate, Baroness Joan Bakewell, to engage in ‘death talk’. We see positive ethical potential in this injunction, insofar as it serves as a call to confront more directly the prospects of death and dying, thereby releasing creative energies with which to change our outlook on life and ageing more generally. However, when set against a culture that valorises choice, independence and control, the positive ethical potential of such injunctions is invariably thwarted. We illustrate this with reference to one of Bakewell's interventions in a debate on scientific innovation and population ageing. In examining the context of her intervention, we affirm her intuition about its positive ethical potential, but we also point to an ambivalence that accompanies the formulation of the injunction – one that ultimately blunts the force and significance of her intuition. We suggest that Gilleard and Higgs' idea of the third age/fourth age dialectic, combined with the psycho-analytic concepts of fantasy and mourning, allow us to express this intuition better. In particular, we argue that the expression ‘loss talk’ (rather than ‘death talk’) better captures the ethical negotiations that should ultimately underpin the transformation processes associated with ageing, and that our theoretical contextualisation of her remarks can help us see this more clearly. In this view, deteriorations in our physical and mental capacities are best understood as involving changes in how we see ourselves, i.e. in our identifications, and so what is at stake are losses of identity and the conditions under which we can engage in new processes of identification.

DATA DRIVEN APPROACHES TO IDENTIFY DETERMINANTS OF HEART DISEASES AND CANCER RESISTANCE

Cancer and cardio-vascular diseases are the leading causes of death world-wide. Caused by systemic genetic and molecular disruptions in cells, these disorders are the manifestation of profound disturbance of normal cellular homeostasis. People suffering or at high risk for these disorders need early diagnosis and personalized therapeutic intervention. Successful implementation of such clinical measures can significantly improve global health. However, development of effective therapies is hindered by the challenges in identifying genetic and molecular determinants of the onset of diseases; and in cases where therapies already exist, the main challenge is to identify molecular determinants that drive resistance to the therapies. Due to the progress in sequencing technologies, the access to a large genome-wide biological data is now extended far beyond few experimental labs to the global research community. The unprecedented availability of the data has revolutionized the capabilities of computational researchers, enabling them to collaboratively address the long standing problems from many different perspectives. Likewise, this thesis tackles the two main public health related challenges using data driven approaches. Numerous association studies have been proposed to identify genomic variants that determine disease. However, their clinical utility remains limited due to their inability to distinguish causal variants from associated variants. In the presented thesis, we first propose a simple scheme that improves association studies in supervised fashion and has shown its applicability in identifying genomic regulatory variants associated with hypertension. Next, we propose a coupled Bayesian regression approach -- eQTeL, which leverages epigenetic data to estimate regulatory and gene interaction potential, and identifies combinations of regulatory genomic variants that explain the gene expression variance. On human heart data, eQTeL not only explains a significantly greater proportion of expression variance in samples, but also predicts gene expression more accurately than other methods. We demonstrate that eQTeL accurately detects causal regulatory SNPs by simulation, particularly those with small effect sizes. Using various functional data, we show that SNPs detected by eQTeL are enriched for allele-specific protein binding and histone modifications, which potentially disrupt binding of core cardiac transcription factors and are spatially proximal to their target. eQTeL SNPs capture a substantial proportion of genetic determinants of expression variance and we estimate that 58% of these SNPs are putatively causal. The challenge of identifying molecular determinants of cancer resistance so far could only be dealt with labor intensive and costly experimental studies, and in case of experimental drugs such studies are infeasible. Here we take a fundamentally different data driven approach to understand the evolving landscape of emerging resistance. We introduce a novel class of genetic interactions termed synthetic rescues (SR) in cancer, which denotes a functional interaction between two genes where a change in the activity of one vulnerable gene (which may be a target of a cancer drug) is lethal, but subsequently altered activity of its partner rescuer gene restores cell viability. Next we describe a comprehensive computational framework --termed INCISOR-- for identifying SR underlying cancer resistance. Applying INCISOR to mine The Cancer Genome Atlas (TCGA), a large collection of cancer patient data, we identified the first pan-cancer SR networks, composed of interactions common to many cancer types. We experimentally test and validate a subset of these interactions involving the master regulator gene mTOR. We find that rescuer genes become increasingly activated as breast cancer progresses, testifying to pervasive ongoing rescue processes. We show that SRs can be utilized to successfully predict patients' survival and response to the majority of current cancer drugs, and importantly, for predicting the emergence of drug resistance from the initial tumor biopsy. Our analysis suggests a potential new strategy for enhancing the effectiveness of existing cancer therapies by targeting their rescuer genes to counteract resistance. The thesis provides statistical frameworks that can harness ever increasing high throughput genomic data to address challenges in determining the molecular underpinnings of hypertension, cardiovascular disease and cancer resistance. We discover novel molecular mechanistic insights that will advance the progress in early disease prevention and personalized therapeutics. Our analyses sheds light on the fundamental biological understanding of gene regulation and interaction, and opens up exciting avenues of translational applications in risk prediction and therapeutics.

Friedreich Ataxia

Friedreich's ataxia (FRDA) is the most common autosomal recessive hereditary ataxia in Caucasians. Neurological symptoms dominate the clinical picture. The underlying neuropathology affects the dorsal root ganglia, the spinal cord, and the deep cerebellar nuclei. In addition, most cases present a hypertrophic cardiomyopathy that may cause premature death. Other problems include a high risk of diabetes, skeletal abnormalities such as kyphoscoliosis, and pes cavus. Most patients carry a homozygous expansion of GAA trinucleotide repeat within the first intron of the FXN gene, leading to repressed transcription through epigenetic mechanisms. The encoded protein, frataxin, is localized in mitochondria and participates in the biogenesis of iron-sulfur clusters. Frataxin deficiency leads to mitochondrial dysfunction, altered iron metabolism, and oxidative damage. Thanks to progress in understanding pathogenesis and to the development of animal and cellular models, therapies targeted to correct frataxin deficiency or its downstream consequences are being developed and tested in clinical trials.

Factores asociados a la mortalidad en el síndrome de Sjögren

Antecedentes: El síndrome de Sjögren (SS) es una patología crónica, autoinmune, de características multifactoriales en su etiología. También es conocida como una epitelitis autoinmune, caracterizada por síntomas secos como xeroftalmia y xerostomía, pero que también puede tener compromiso sistémico, dado por manifestaciones extra-glandulares. En la actualidad es poco reconocida como tal, y por lo tanto, la tasa de sobrevida en estos pacientes se encuentra disminuida pero poco tenida en cuenta a la hora de la valoración de ellos. Este trabajo describe la evidencia encontrada acerca de las causas de mortalidad y sus factores asociados luego de realizar una revisión sistemática de la literatura. Objetivos: El objetivo de este estudio fue reunir de forma exhaustiva y sistemática toda la evidencia empírica, publicada o no, que cumpla los criterios de búsqueda y elegibilidad sobre factores asociados al incremento de la mortalidad o disminución en la sobrevida de los pacientes con diagnóstico de SS. Métodos: Se realizó una revisión sistemática de la literatura mediante una búsqueda exhaustiva de todos los estudios publicados en las bases de datos electrónicas preestablecidas, hasta abril de 2015, con el fin de determinar las causas más frecuentes de mortalidad en pacientes con SS y los factores asociados a ella. Resultados: Se encontraron 4,654 resultados que coincidían con los criterios de búsqueda establecidos; de estos, 33 cumplieron con los criterios de inclusión y se distribuyeron de la siguiente forma: el 66.6% (22/33) correspondieron a estudios de corte cohorte, 30.3% (10/33) a estudios de corte transversal y el 3.03% (1/33) a estudios casos y controles. Se obtuvieron resultados en cuanto a frecuencias de mortalidad, razón estandarizada de mortalidad, tasas de supervivencia, causas más frecuentes de mortalidad y sus factores asociados. Conclusiones: La mortalidad reportada en los diferentes estudios fue entre el 1.2% hasta el 30%. Aquellos estudios que reportaron una tasa de mortalidad inferior al 5%, tuvieron un tiempo de seguimiento menor 8 años [1,7,33,60,64,86]. La mayoría de los casos sigue un curso relativamente estable, pero hay un porcentaje importante que presenta otras manifestaciones sistémicas con mayor frecuencia de complicaciones durante la evolución del SS. Por tanto, son los que requieren un seguimiento más estrecho, debido a una mayor necesidad de tratamiento sistémico y al mayor riesgo de ingreso hospitalario y de mortalidad, especialmente por el desarrollo de procesos linfoproliferativos B. La presencia de factores pronósticos en el paciente con SS obligará a realizar un seguimiento clínico e inmunológico mucho más estrecho, lo cual permitirá identificar lo antes posible las complicaciones que puedan aparecer e instaurar las correspondientes medidas terapéuticas, para aumentar las tasas de supervivencia.

Injury prevention in Queensland : report to Queensland Injury Prevention Council

Injury is the fourth leading cause of death in Australia. Injury rates in Queensland are amongst the highest in Australia and 21.5% of people surveyed for this research reported that their lifestyle or that of an immediate family member had been permanently affected by injury. Injury results in over 40,000 hospital admissions and 200,000 attendances at hospital Emergency Departments in Queensland each year. Queensland's death rate from injuries is higher than the national average, with consistently higher rates of deaths related to transport injuries. Queensland statistics also show higher than national average rates of injuries due to falls, homicide and accidental drowning. (Pike, Muller, Baade & Ward, 2000) In 2000-01 injuries represented over $4 billion (or 8%) of total health system expenditure, and 185,000 disability-adjusted life years (DALYs), or 7% of the total morbidity burden of disease and injury in Australia in 2003. (Begg, Vos, Barker, Stevenson, Stanley & Lopez, 2007). Injury is one of seven key health areas identified by the Commonwealth, state and territory governments for priority attention as National Health Priority Areas

Membrane associated transporter protein gene (SLC45A2) and the genetic basis of normal human pigmentation variation

This work is concerned with the genetic basis of normal human pigmentation variation. Specifically, the role of polymorphisms within the solute carrier family 45 member 2 (SLC45A2 or membrane associated transporter protein; MATP) gene were investigated with respect to variation in hair, skin and eye colour ― both between and within populations. SLC45A2 is an important regulator of melanin production and mutations in the gene underly the most recently identified form of oculocutaneous albinism. There is evidence to suggest that non-synonymous polymorphisms in SLC45A2 are associated with normal pigmentation variation between populations. Therefore, the underlying hypothesis of this thesis is that polymorphisms in SLC45A2 will alter the function or regulation of the protein, thereby altering the important role it plays in melanogenesis and providing a mechanism for normal pigmentation variation. In order to investigate the role that SLC45A2 polymorphisms play in human pigmentation variation, a DNA database was established which collected pigmentation phenotypic information and blood samples of more than 700 individuals. This database was used as the foundation for two association studies outlined in this thesis, the first of which involved genotyping two previously-described non-synonymous polymorphisms, p.Glu272Lys and p.Phe374Leu, in four different population groups. For both polymorphisms, allele frequencies were significantly different between population groups and the 272Lys and 374Leu alleles were strongly associated with black hair, brown eyes and olive skin colour in Caucasians. This was the first report to show that SLC45A2 polymorphisms were associated with normal human intra-population pigmentation variation. The second association study involved genotyping several SLC45A2 promoter polymorphisms to determine if they also played a role in pigmentation variation. Firstly, the transcription start site (TSS), and hence putative proximal promoter region, was identified using 5' RNA ligase mediated rapid amplification of cDNA ends (RLM-RACE). Two alternate TSSs were identified and the putative promoter region was screened for novel polymorphisms using denaturing high performance liquid chromatography (dHPLC). A novel duplication (c.–1176_–1174dupAAT) was identified along with other previously described single nucleotide polymorphisms (c.–1721C>G and c.–1169G>A). Strong linkage disequilibrium ensured that all three polymorphisms were associated with skin colour such that the –1721G, +dup and –1169A alleles were associated with olive skin in Caucasians. No linkage disequilibrium was observed between the promoter and coding region polymorphisms, suggesting independent effects. The association analyses were complemented with functional data, showing that the –1721G, +dup and –1169A alleles significantly decreased SLC45A2 transcriptional activity. Based on in silico bioinformatic analysis that showed these alleles remove a microphthalmia-associated transcription factor (MITF) binding site, and that MITF is a known regulator of SLC45A2 (Baxter and Pavan, 2002; Du and Fisher, 2002), it was postulated that SLC45A2 promoter polymorphisms could contribute to the regulation of pigmentation by altering MITF binding affinity. Further characterisation of the SLC45A2 promoter was carried out using luciferase reporter assays to determine the transcriptional activity of different regions of the promoter. Five constructs were designed of increasing length and their promoter activity evaluated. Constitutive promoter activity was observed within the first ~200 bp and promoter activity increased as the construct size increased. The functional impact of the –1721G, +dup and –1169A alleles, which removed a MITF consensus binding site, were assessed using electrophoretic mobility shift assays (EMSA) and expression analysis of genotyped melanoblast and melanocyte cell lines. EMSA results confirmed that the promoter polymorphisms affected DNA-protein binding. Interestingly, however, the protein/s involved were not MITF, or at least MITF was not the protein directly binding to the DNA. In an effort to more thoroughly characterise the functional consequences of SLC45A2 promoter polymorphisms, the mRNA expression levels of SLC45A2 and MITF were determined in melanocyte/melanoblast cell lines. Based on SLC45A2’s role in processing and trafficking TYRP1 from the trans-Golgi network to stage 2 melanosmes, the mRNA expression of TYRP1 was also investigated. Expression results suggested a coordinated expression of pigmentation genes. This thesis has substantially contributed to the field of pigmentation by showing that SLC45A2 polymorphisms not only show allele frequency differences between population groups, but also contribute to normal pigmentation variation within a Caucasian population. In addition, promoter polymorphisms have been shown to have functional consequences for SLC45A2 transcription and the expression of other pigmentation genes. Combined, the data presented in this work supports the notion that SLC45A2 is an important contributor to normal pigmentation variation and should be the target of further research to elucidate its role in determining pigmentation phenotypes. Understanding SLC45A2’s function may lead to the development of therapeutic interventions for oculocutaneous albinism and other disorders of pigmentation. It may also help in our understanding of skin cancer susceptibility and evolutionary adaptation to different UV environments, and contribute to the forensic application of pigmentation phenotype prediction.

Extreme sports as a facilitator of ecocentricity and positive life changes

Extreme sports and extreme sports participants have been most commonly explored from a negative perspective, for example the 'need to take unnecessary risks'. This study reports on findings that indicate a more positive experience. A phenomenological method was used via unstructured interviews with 15 extreme sports participants and other first hand accounts. The extreme sports included B.A.S.E. jumping, big wave surfing, extreme skiing, waterfall kayaking, extreme mountaineering and solo rope-free climbing. Results indicate that participating in activities that involve a real chance of death, fear and the realisation that nature in its extreme is far greater and more powerful than humanity triggers positive life changes, and an eco-centric standpoint.

Rural and remote road safety study : final report

• Introduction: Concern and action for rural road safety is relatively new in Australia in comparison to the field of traffic safety as a whole. In 2003, a program of research was begun by the Centre for Accident Research and Road Safety - Queensland (CARRS-Q) and the Rural Health Research Unit (RHRU) at James Cook University to investigate factors contributing to serious rural road crashes in the North Queensland region. This project was funded by the Premier’s Department, Main Roads Department, Queensland Transport, QFleet, Queensland Rail, Queensland Ambulance Service, Department of Natural Resources and Queensland Police Service. Additional funding was provided by NRMA Insurance for a PhD scholarship. In-kind support was provided through the four hospitals used for data collection, namely Cairns Base Hospital, The Townsville Hospital, Mount Isa Hospital and Atherton Hospital.----- The primary aim of the project was to: Identify human factors related to the occurrence of serious traffic incidents in rural and remote areas of Australia, and to the trauma suffered by persons as a result of these incidents, using a sample drawn from a rural and remote area in North Queensland.----- The data and analyses presented in this report are the core findings from two broad studies: a general examination of fatalities and casualties from rural and remote crashes for the period 1 March 2004 until 30 June 2007, and a further linked case-comparison study of hospitalised patients compared with a sample of non-crash-involved drivers.----- • Method: The study was undertaken in rural North Queensland, as defined by the Australian Bureau of Statistics (ABS) statistical divisions of North Queensland, Far North Queensland and North-West Queensland. Urban areas surrounding Townsville, Thuringowa and Cairns were not included. The study methodology was centred on serious crashes, as defined by a resulting hospitalisation for 24 hours or more and/or a fatality. Crashes meeting this criteria within the North Queensland region between 1 March 2004 and 30 June 2007 were identified through hospital records and interviewed where possible. Additional data was sourced from coroner’s reports, the Queensland Transport road crash database, the Queensland Ambulance Service and the study hospitals in the region.----- This report is divided into chapters corresponding to analyses conducted on the collected crash and casualty data.----- Chapter 3 presents an overview of all crashes and casualties identified during the study period. Details are presented in regard to the demographics and road user types of casualties; the locations, times, types, and circumstances of crashes; along with the contributing circumstances of crashes.----- Chapter 4 presents the results of summary statistics for all casualties for which an interview was able to be conducted. Statistics are presented separately for drivers and riders, passengers, pedestrians and cyclists. Details are also presented separately for drivers and riders crashing in off-road and on-road settings. Results from questionnaire data are presented in relation to demographics; the experience of the crash in narrative form; vehicle characteristics and maintenance; trip characteristics (e.g. purpose and length of journey; periods of fatigue and monotony; distractions from driving task); driving history; alcohol and drug use; medical history; driving attitudes, intentions and behaviour; attitudes to enforcement; and experience of road safety advertising.----- Chapter 5 compares the above-listed questionnaire results between on-road crash-involved casualties and interviews conducted in the region with non-crash-involved persons. Direct comparisons as well as age and sex adjusted comparisons are presented.----- Chapter 6 presents information on those casualties who were admitted to one of the study hospitals during the study period. Brief information is given regarding the demographic characteristics of these casualties. Emergency services’ data is used to highlight the characteristics of patient retrieval and transport to and between hospitals. The major injuries resulting from the crashes are presented for each region of the body and analysed by vehicle type, occupant type, seatbelt status, helmet status, alcohol involvement and nature of crash. Estimates are provided of the costs associated with in-hospital treatment and retrieval.----- Chapter 7 describes the characteristics of the fatal casualties and the nature and circumstances of the crashes. Demographics, road user types, licence status, crash type and contributing factors for crashes are presented. Coronial data is provided in regard to contributing circumstances (including alcohol, drugs and medical conditions), cause of death, resulting injuries, and restraint and helmet use.----- Chapter 8 presents the results of a comparison between casualties’ crash descriptions and police-attributed crash circumstances. The relative frequency of contributing circumstances are compared both broadly within the categories of behavioural, environmental, vehicle related, medical and other groupings and specifically for circumstances within these groups.----- Chapter 9 reports on the associated research projects which have been undertaken on specific topics related to rural road safety.----- Finally, Chapter 10 reports on the conclusions and recommendations made from the program of research.---- • Major Recommendations : From the findings of these analyses, a number of major recommendations were made: + Male drivers and riders - Male drivers and riders should continue to be the focus of interventions, given their very high representation among rural and remote road crash fatalities and serious injuries.----- - The group of males aged between 30 and 50 years comprised the largest number of casualties and must also be targeted for change if there is to be a meaningful improvement in rural and remote road safety.----- + Motorcyclists - Single vehicle motorcycle crashes constitute over 80% of serious, on-road rural motorcycle crashes and need particular attention in development of policy and infrastructure.----- - The motorcycle safety consultation process currently being undertaken by Queensland Transport (via the "Motorbike Safety in Queensland - Consultation Paper") is strongly endorsed. As part of this process, particular attention needs to be given to initiatives designed to reduce rural and single vehicle motorcycle crashes.----- - The safety of off-road riders is a serious problem that falls outside the direct responsibility of either Transport or Health departments. Responsibility for this issue needs to be attributed to develop appropriate policy, regulations and countermeasures.----- + Road safety for Indigenous people - Continued resourcing and expansion of The Queensland Aboriginal Peoples and Torres Strait Islander Peoples Driver Licensing Program to meet the needs of remote and Indigenous communities with significantly lower licence ownership levels.----- - Increased attention needs to focus on the contribution of geographic disadvantage (remoteness) factors to remote and Indigenous road trauma.----- + Road environment - Speed is the ‘final common pathway’ in determining the severity of rural and remote crashes and rural speed limits should be reduced to 90km/hr for sealed off-highway roads and 80km/hr for all unsealed roads as recommended in the Austroads review and in line with the current Tasmanian government trial.----- - The Department of Main Roads should monitor rural crash clusters and where appropriate work with local authorities to conduct relevant audits and take mitigating action. - The international experts at the workshop reviewed the data and identified the need to focus particular attention on road design management for dangerous curves. They also indicated the need to maximise the use of audio-tactile linemarking (audible lines) and rumble strips to alert drivers to dangerous conditions and behaviours.----- + Trauma costs - In accordance with Queensland Health priorities, recognition should be given to the substantial financial costs associated with acute management of trauma resulting from serious rural and remote crashes.----- - Efforts should be made to develop a comprehensive, regionally specific costing formula for road trauma that incorporates the pre-hospital, hospital and post-hospital phases of care. This would inform health resource allocation and facilitate the evaluation of interventions.----- - The commitment of funds to the development of preventive strategies to reduce rural and remote crashes should take into account the potential cost savings associated with trauma.----- - A dedicated study of the rehabilitation needs and associated personal and healthcare costs arising from rural and remote road crashes should be undertaken.----- + Emergency services - While the study has demonstrated considerable efficiency in the response and retrieval systems of rural and remote North Queensland, relevant Intelligent Transport Systems technologies (such as vehicle alarm systems) to improve crash notification should be both developed and evaluated.----- + Enforcement - Alcohol and speed enforcement programs should target the period between 2 and 6pm because of the high numbers of crashes in the afternoon period throughout the rural region.----- + Drink driving - Courtesy buses should be advocated and schemes such as the Skipper project promoted as local drink driving countermeasures in line with the very high levels of community support for these measures identified in the hospital study.------ - Programs should be developed to target the high levels of alcohol consumption identified in rural and remote areas and related involvement in crashes.----- - Referrals to drink driving rehabilitation programs should be mandated for recidivist offenders.----- + Data requirements - Rural and remote road crashes should receive the same quality of attention as urban crashes. As such, it is strongly recommended that increased resources be committed to enable dedicated Forensic Crash Units to investigate rural and remote fatal and serious injury crashes.----- - Transport department records of rural and remote crashes should record the crash location using the national ARIA area classifications used by health departments as a means to better identifying rural crashes.----- - Rural and remote crashes tend to be unnoticed except in relatively infrequent rural reviews. They should receive the same level of attention and this could be achieved if fatalities and fatal crashes were coded by the ARIA classification system and included in regular crash reporting.----- - Health, Transport and Police agencies should collect a common, minimal set of data relating to road crashes and injuries, including presentations to small rural and remote health facilities.----- + Media and community education programmes - Interventions seeking to highlight the human contribution to crashes should be prioritised. Driver distraction, alcohol and inappropriate speed for the road conditions are key examples of such behaviours.----- - Promotion of basic safety behaviours such as the use of seatbelts and helmets should be given a renewed focus.----- - Knowledge, attitude and behavioural factors that have been identified for the hospital Brief Intervention Trial should be considered in developing safety campaigns for rural and remote people. For example challenging the myth of the dangerous ‘other’ or ‘non-local’ driver.----- - Special educational initiatives on the issues involved in rural and remote driving should be undertaken. For example the material used by Main Roads, the Australian Defence Force and local initiatives.

Safer construction : the development of a voluntary code of practice to improve safety performance in the Australian construction industry

In Australia, between 1994 and 2000, 50 construction workers were killed each year as a result of their work, the industry fatality rate, at 10.4 per 100,000 persons, is similar to the national road toll fatality rate and the rate of serious injury is 50% higher than the all industries average. This poor performance represents a significant threat to the industry’s social sustainability. Despite the best efforts of regulators and policy makers at both State and Federal levels, the incidence of death, injury and illness in the Australian construction industry has remained intransigently high, prompting an industry-led initiative to improve the occupational health and safety (OHS) performance of the Australian construction industry. The ‘Safer Construction’ project involves the development of an evidence-based Voluntary Code of Practice for OHS in the industry.