SNP technologies for drug discovery : a current review

Single nucleotide polymorphisms (SNPs) are unique genetic differences between individuals that contribute in significant ways to the determination of human variation including physical characteristics like height and appearance as well as less obvious traits such as personality, behaviour and disease susceptibility. SNPs can also significantly influence responses to pharmacotherapy and whether drugs will produce adverse reactions. The development of new drugs can be made far cheaper and more rapid by selecting participants in drug trials based on their genetically determined response to drugs. Technology that can rapidly and inexpensively genotype thousands of samples for thousands of SNPs at a time is therefore in high demand. With the completion of the human genome project, about 12 million true SNPs have been identified to date. However, most have not yet been associated with disease susceptibility or drug response. Testing for the appropriate drug response SNPs in a patient requiring treatment would enable individualised therapy with the right drug and dose administered correctly the first time. Many pharmaceutical companies are also interested in identifying SNPs associated with polygenic traits so novel therapeutic targets can be discovered. This review focuses on technologies that can be used for genotyping known SNPs as well as for the discovery of novel SNPs associated with drug response.

Aging in China and its impact on vehicle design

This study contributes to the growth of design knowledge in China, where vehicle design for the local, older user is in its initial developmental stages. Therefore, this research has explored the travel needs of older Chinese vehicle users in order to assist designers to better understand users’ current and future needs. A triangulation method consisting of interviews, logbook and co-discovery was used to collect multiple forms of data and so explore the research question. Grounded theory has been employed to analyze the research data. This study found that users’ needs are reflected through various ‘meanings’ that they attach to vehicles – meanings that give a tangible expression to their experiences. This study identified six older-user need categories: (i) safety, (ii) utility, (iii) comfort, (iv) identity, (v) emotion and (vi) spirituality. The interrelationships among these six categories are seen as an interactive structure, rather than as a linear or hierarchical arrangement. Chinese cultural values, which are generated from particular local context and users’ social practice, will play a dynamic role in linking and shaping the travel needs of older vehicle users in the future. Moreover, this study structures the older-user needs model into three levels of meaning, to give guidance to vehicle design direction: (i) the practical meaning level, (ii) the social meaning level and (ii) the cultural meaning level. This study suggests that a more comprehensive explanation exists if designers can identify the vehicle’s meaning and property associated with the fulfilled older users’ needs. However, these needs will vary, and must be related to particular technological, social, and cultural contexts. The significance of this study lies in its contributions to the body of knowledge in three areas: research methodology, theory and design. These theoretical contributions provide a series of methodological tools, models and approaches from a vehicle design perspective. These include a conditional/consequential matrix, a travel needs identification model, an older users’ travel-related needs framework, a user information structure model, and an Older-User-Need-Based vehicle design approach. These models suggest a basic framework for the new design process which might assist in the design of new vehicles to fulfil the needs of future, aging Chinese generations. The models have the potential to be transferred to other design domains and different cultural contexts.

Adolescent protective behaviour to reduce drug and alcohol use, alcohol-related harm and interpersonal violence

Typically adolescents' friends are considered a risk factor for adolescent engagement in risk-taking. This study took a more novel approach, by examining adolescent friendship as a protective factor. In particular it investigated friends' potential to intervene to reduce risk-taking. 540 adolescents (mean age 13.47 years) were asked about their intention to intervene to reduce friends' alcohol, drug and alcohol-related harms and about psychosocial factors potentially associated with intervening. More than half indicated that they would intervene in friends' alcohol, drug use, alcohol-related harms and interpersonal violence. Intervening was associated with being female, having friends engage in overall less risk-taking and having greater school connectedness. The findings provide an important understanding of increasing adolescent protective behavior as a potential strategy to reduce alcohol and drug related harms.

Development of a particle number and particle mass vehicle emissions inventory for an urban fleet

Motor vehicles are major emitters of gaseous and particulate pollution in urban areas, and exposure to particulate pollution can have serious health effects, ranging from respiratory and cardiovascular disease to mortality. Motor vehicle tailpipe particle emissions span a broad size range from 0.003-10µm, and are measured as different subsets of particle mass concentrations or particle number count. However, no comprehensive inventories currently exist in the international published literature covering this wide size range. This paper presents the first published comprehensive inventory of motor vehicle tailpipe particle emissions covering the full size range of particles emitted. The inventory was developed for urban South-East Queensland by combining two techniques from distinctly different disciplines, from aerosol science and transport modelling. A comprehensive set of particle emission factors were combined with traffic modelling, and tailpipe particle emissions were quantified for particle number (ultrafine particles), PM1, PM2.5 and PM10 for light and heavy duty vehicles and buses. A second aim of the paper involved using the data derived in this inventory for scenario analyses, to model the particle emission implications of different proportions of passengers travelling in light duty vehicles and buses in the study region, and to derive an estimate of fleet particle emissions in 2026. It was found that heavy duty vehicles (HDVs) in the study region were major emitters of particulate matter pollution, and although they contributed only around 6% of total regional vehicle kilometres travelled, they contributed more than 50% of the region’s particle number (ultrafine particles) and PM1 emissions. With the freight task in the region predicted to double over the next 20 years, this suggests that HDVs need to be a major focus of mitigation efforts. HDVs dominated particle number (ultrafine particles) and PM1 emissions; and LDV PM2.5 and PM10 emissions. Buses contributed approximately 1-2% of regional particle emissions.

Fusion of in-vehicle sensor data to develop Intelligent Driver Training System (IDTS)

The over represented number of novice drivers involved in crashes is alarming. Driver training is one of the interventions aimed at mitigating the number of crashes that involve young drivers. To our knowledge, Advanced Driver Assistance Systems (ADAS) have never been comprehensively used in designing an intelligent driver training system. Currently, there is a need to develop and evaluate ADAS that could assess driving competencies. The aim is to develop an unsupervised system called Intelligent Driver Training System (IDTS) that analyzes crash risks in a given driving situation. In order to design a comprehensive IDTS, data is collected from the Driver, Vehicle and Environment (DVE), synchronized and analyzed. The first implementation phase of this intelligent driver training system deals with synchronizing multiple variables acquired from DVE. RTMaps is used to collect and synchronize data like GPS, vehicle dynamics and driver head movement. After the data synchronization, maneuvers are segmented out as right turn, left turn and overtake. Each maneuver is composed of several individual tasks that are necessary to be performed in a sequential manner. This paper focuses on turn maneuvers. Some of the tasks required in the analysis of ‘turn’ maneuver are: detect the start and end of the turn, detect the indicator status change, check if the indicator was turned on within a safe distance and check the lane keeping during the turn maneuver. This paper proposes a fusion and analysis of heterogeneous data, mainly involved in driving, to determine the risk factor of particular maneuvers within the drive. It also explains the segmentation and risk analysis of the turn maneuver in a drive.

Unusual hydrate stabilization in the two-dimensional layered structure of quinacrinium bis(2-carboxy-4,5-dichlorobenzoate) tetrahydrate, a proton-transfer compound of the drug quinacrine

The crystal structure of the hydrated proton-transfer compound of the drug quinacrine [rac-N'-(6-chloro-2-methoxyacridin-9-yl)-N,N-diethylpentane-1,4-diamine] with 4,5-dichlorophthalic acid, C23H32ClN3O2+ . 2(C8H3Cl2O4-).4H2O (I), has been determined at 200 K. The four labile water molecules of solvation form discrete ...O--H...O--H... hydrogen-bonded chains parallel to the quinacrine side chain, the two N--H groups of which act as hydrogen-bond donors for two of the water acceptor molecules. The other water molecules, as well as the acridinium H atom, also form hydrogen bonds with the two anion species and extend the structure into two-dimensional sheets. Between these sheets there are also weak cation--anion and anion--anion pi-pi aromatic ring interactions. This structure represents only the third example of a simple quinacrine derivative for which structural data are available but differs from the other two in that it is unstable in the X-ray beam due to efflorescence, probably associated with the destruction of the unusual four-membered water chain structures.

Increasing socio-economic inequalities in drug-induced deaths in Australia : 1981-2002

Introduction and Aims: Since the 1990s illicit drug use death rates in Australia have increased markedly. There is a notable gap in knowledge about changing socio-economic inequalities in drug use death rates. Some limited Australian and overseas data point to higher rates of drug death in the lowest socio-economic groups, but the paucity of available studies and their sometimes conflicting findings need to be addressed. Design and Methods: This paper uses data obtained from the Australian Bureau of Statistics (ABS) to examine changes in age-standardised drug-induced mortality rates for Australian males over the period 1981 – 2002. Socio-economic status was categorised as manual or non-manual work status. Results: With the rapid increase in drug-induced mortality rates in the 1990s, there was a parallel increase in socio-economic inequalities in drug-induced deaths. The decline in drug death rates from 2000 onwards was associated with a decline in socio-economic inequalities. By 2002, manual workers had drug death rates well over twice the rate of non-manual workers. Discussion: Three factors are identified which contribute to these socio-economic inequalities in mortality. First, there has been an age shift in deaths evident only for manual workers. Secondly, there has been an increase in availability until 1999 and a relative decline in the cost of the drug, which most often leads to drug death (heroin). Thirdly, there has been a shift to amphetamine use which may lead to significant levels of morbidity, but few deaths. [Najman JM, Toloo G, Williams GM. Increasing socio-economic inequalities in drug-induced deaths in Australia: 1981–2002.

Determining heavy vehicle suspension health from vibratory wheel loads

A low-cost test bed was made from a modified heavy vehicle (HV) brake tester. By rotating a test HV’s wheel on an eccentric roller, a known vibration was imparted to the wheel under test. A control case for dampers in good condition was compared with two test cases of ineffective shock absorbers. Measurement of the forces at the bearings of the roller provided an indication of the HV wheel-forces. Where the level of serviceability of the shock absorbers varied, differences in wheel load provided a quality indicator corresponding to a change of damper characteristic. Conclusions regarding the levels of damper maintenance beyond which HV suspensions cause road damage and dynamic wheel forces at the threshold of tyre wear at which HV shock absorbers are normally replaced are presented.

All-terrain vehicle crashes and associated injuries in North Queensland : findings from the Rural and Remote Road Safety Study

Objective: To define characteristics of all-terrain vehicle (ATV) crashes occurring in north Queensland from March 2004 till June 2007 with the exploration of associated risk factors. Design: Descriptive analysis of ATV crash data collected by the Rural and Remote Road Safety Study. Setting: Rural and remote north Queensland. Participants: Forty-two ATV drivers and passengers aged 16 years or over hospitalised at Atherton, Cairns, Mount Isa or Townsville for at least 24 hours as a result of a vehicle crash. Main outcome measures: Demographics of participants, reason for travel, nature of crash, injuries sustained and risk factors associated with ATV crash. Results: The majority of casualties were men aged 16–64. Forty-one per cent of accidents occurred while performing agricultural tasks. Furthermore, 39% of casualties had less than one year’s experience riding ATVs. Over half the casualties were not wearing a helmet at the time of the crash. Common injuries were head and neck and upper limb injuries. Rollovers tended to occur while performing agricultural tasks and most commonly resulted in multiple injuries. Conclusions: Considerable trauma results from ATV crashes in rural and remote north Queensland. These crashes are not included in most general vehicle crash data sets, as they are usually limited to events occurring on public roads. Minimal legislation and regulation currently applies to ATV use in agricultural, recreational and commercial settings. Legislation on safer design of ATVs and mandatory courses for riders is an essential part of addressing the burden of ATV crashes on rural and remote communities.

Vision, functional and cognitive determinants of motor vehicle incidents in older drivers

Background: The proportion of older individuals in the driving population is predicted to increase in the next 50 years. This has important implications for driving safety as abilities which are important for safe driving, such as vision (which accounts for the majority of the sensory input required for driving), processing ability and cognition have been shown to decline with age. The current methods employed for screening older drivers upon re-licensure are also vision based. This study, which investigated social, behavioural and professional aspects involved with older drivers, aimed to determine: (i) if the current visual standards in place for testing upon re-licensure are effective in reducing the older driver fatality rate in Australia; (ii) if the recommended visual standards are actually implemented as part of the testing procedures by Australian optometrists; and (iii) if there are other non-standardised tests which may be better at predicting the on-road incident-risk (including near misses and minor incidents) in older drivers than those tests recommended in the standards. Methods: For the first phase of the study, state-based age- and gender-stratified numbers of older driver fatalities for 2000-2003 were obtained from the Australian Transportation Safety Bureau database. Poisson regression analyses of fatality rates were considered by renewal frequency and jurisdiction (as separate models), adjusting for possible confounding variables of age, gender and year. For the second phase, all practising optometrists in Australia were surveyed on the vision tests they conduct in consultations relating to driving and their knowledge of vision requirements for older drivers. Finally, for the third phase of the study to investigate determinants of on-road incident risk, a stratified random sample of 600 Brisbane residents aged 60 years and were selected and invited to participate using an introductory letter explaining the project requirements. In order to capture the number and type of road incidents which occurred for each participant over 12 months (including near misses and minor incidents), an important component of the prospective research study was the development and validation of a driving diary. The diary was a tool in which incidents that occurred could be logged at that time (or very close in time to which they occurred) and thus, in comparison with relying on participant memory over time, recall bias of incident occurrence was minimised. Association between all visual tests, cognition and scores obtained for non-standard functional tests with retrospective and prospective incident occurrence was investigated. Results: In the first phase,rivers aged 60-69 years had a 33% lower fatality risk (Rate Ratio [RR] = 0.75, 95% CI 0.32-1.77) in states with vision testing upon re-licensure compared with states with no vision testing upon re-licensure, however, because the CIs are wide, crossing 1.00, this result should be regarded with caution. However, overall fatality rates and fatality rates for those aged 70 years and older (RR=1.17, CI 0.64-2.13) did not differ between states with and without license renewal procedures, indicating no apparent benefit in vision testing legislation. For the second phase of the study, nearly all optometrists measured visual acuity (VA) as part of a vision assessment for re-licensing, however, 20% of optometrists did not perform any visual field (VF) testing and only 20% routinely performed automated VF on older drivers, despite the standards for licensing advocating automated VF as part of the vision standard. This demonstrates the need for more effective communication between the policy makers and those responsible for carrying out the standards. It may also indicate that the overall higher driver fatality rate in jurisdictions with vision testing requirements is resultant as the tests recommended by the standards are only partially being conducted by optometrists. Hence a standardised protocol for the screening of older drivers for re-licensure across the nation must be established. The opinions of Australian optometrists with regard to the responsibility of reporting older drivers who fail to meet the licensing standards highlighted the conflict between maintaining patient confidentiality or upholding public safety. Mandatory reporting requirements of those drivers who fail to reach the standards necessary for driving would minimise potential conflict between the patient and their practitioner, and help maintain patient trust and goodwill. The final phase of the PhD program investigated the efficacy of vision, functional and cognitive tests to discriminate between at-risk and safe older drivers. Nearly 80% of the participants experienced an incident of some form over the prospective 12 months, with the total incident rate being 4.65/10 000 km. Sixty-three percent reported having a near miss and 28% had a minor incident. The results from the prospective diary study indicate that the current vision screening tests (VA and VF) used for re-licensure do not accurately predict older drivers who are at increased odds of having an on-road incident. However, the variation in visual measurements of the cohort was narrow, also affecting the results seen with the visual functon questionnaires. Hence a larger cohort with greater variability should be considered for a future study. A slightly lower cognitive level (as measured with the Mini-Mental State Examination [MMSE]) did show an association with incident involvement as did slower reaction time (RT), however the Useful-Field-of-View (UFOV) provided the most compelling results of the study. Cut-off values of UFOV processing (>23.3ms), divided attention (>113ms), selective attention (>258ms) and overall score (moderate/ high/ very high risk) were effective in determining older drivers at increased odds of having any on-road incident and the occurrence of minor incidents. Discussion: The results have shown that for the 60-69 year age-group, there is a potential benefit in testing vision upon licence renewal. However, overall fatality rates and fatality rates for those aged 70 years and older indicated no benefit in vision testing legislation and suggests a need for inclusion of screening tests which better predict on-road incidents. Although VA is routinely performed by Australian optometrists on older drivers renewing their licence, VF is not. Therefore there is a need for a protocol to be developed and administered which would result in standardised methods conducted throughout the nation for the screening of older drivers upon re-licensure. Communication between the community, policy makers and those conducting the protocol should be maximised. By implementing a standardised screening protocol which incorporates a level of mandatory reporting by the practitioner, the ethical dilemma of breaching patient confidentiality would also be resolved. The tests which should be included in this screening protocol, however, cannot solely be ones which have been implemented in the past. In this investigation, RT, MMSE and UFOV were shown to be better determinants of on-road incidents in older drivers than VA and VF, however, as previously mentioned, there was a lack of variability in visual status within the cohort. Nevertheless, it is the recommendation from this investigation, that subject to appropriate sensitivity and specificity being demonstrated in the future using a cohort with wider variation in vision, functional performance and cognition, these tests of cognition and information processing should be added to the current protocol for the screening of older drivers which may be conducted at licensing centres across the nation.

Correlating eye gaze direction, depth and vehicle information on an interactive map for driver training

The over represented number of novice drivers involved in crashes is alarming. Driver training is one of the interventions aimed at mitigating the number of crashes that involve young drivers. Experienced drivers have better hazard perception ability compared to inexperienced drivers. Eye gaze patterns have been found to be an indicator of the driver's competency level. The aim of this paper is to develop an in-vehicle system which correlates information about the driver's gaze and vehicle dynamics, which is then used to assist driver trainers in assessing driving competency. This system allows visualization of the complete driving manoeuvre data on interactive maps. It uses an eye tracker and perspective projection algorithms to compute the depth of gaze and plots it on Google maps. This interactive map also features the trajectory of the vehicle and turn indicator usage. This system allows efficient and user friendly analysis of the driving task. It can be used by driver trainers and trainees to understand objectively the risks encountered during driving manoeuvres. This paper presents a prototype that plots the driver's eye gaze depth and direction on an interactive map along with the vehicle dynamics information. This prototype will be used in future to study the difference in gaze patterns in novice and experienced drivers prior to a certain manoeuvre.

Friends looking out for friends as an intervention strategy for young adults' risky driving

Young adults are at the greatest risk of experiences road trauma disproportionately to those in other age groups. While the influence of peers is commonly associated with motor vehicle crashes and injury few studies examine whether their influence can be positive. In particular friends may be able to actively intervene to reduce the likelihood of risky driving (e.g. speeding, drink driving or drug driving) and alcohol use. The aim of this paper is to conduct a systematic review on intervening in risky driving behaviour including the situations in which it is likely or unlikely to occur, factors associated with individuals who might or report having intervened and any evaluated programs that make use of such strategies. In addition a study was conducted with 247 first year university students (32% males) to examine whether young adults report engaging in protective behaviour with their peers in South-east Queensland. In particular, if they intervene if their friends are about to drive after drinking, drive after taking illicit drugs or when speeding. It examines any differences in reported likelihood of discouraging such illegal and dangerous behaviour (in the past 12 months prior to the survey). Findings showed that young adults (17-25 years) did indeed report protective behaviour in relation to friends’ drink driving, drug driving, speeding and binge drinking. Conclusions will be drawn regarding important considerations in developing positive strategies and advertising campaigns that encourage positive behaviours (e.g. ‘don’t let mates drink and drive’).

In-vehicle driver distractions : characteristics underlying drivers' risk perceptions

Driver distraction continues to receive considerable research interest but the drivers‟ perspective is less well documented. The current research focussed on identifying features that are salient to drivers in their risk perception judgements for 19 in-vehicle distractions. Both technological (e.g. mobile phones) and non technological (e.g. eating) distractions were considered. Analysis identified that males and females were rating 7 of the 19 distractions differently. The current paper presents the data for the female participants (n = 84). Multidimensional scaling analysis identified three main dimensions contributing to female drivers‟ risk perception judgements. Qualitative characteristics such as the level of exposure to a distraction were identified as significant contributors to drivers‟ risk perception as well as features inherent in the distractions such as distractions being related to communication. This exploratory work contributes to better understanding female drivers‟ perceptions of risk associated with in-vehicle distractions. Understanding the drivers‟ perspective can help guide the development of road safety messages and ultimately improve the impact of such messages.

Applying Stafford and Warr’s Reconceptualization of Deterrence Theory to drug driving : can it predict those likely to offend?

In December 2007, random roadside drug testing commenced in Queensland, Australia. Subsequently, the aim of this study was to explore the preliminary impact of Queensland’s drug driving legislation and enforcement techniques by applying Stafford and Warr’s [Stafford, M. C., & Warr, M. (1993). A reconceptualization of general and specific deterrence. Journal of Research in Crime and Delinquency, 30, 123-135] reconceptualization of deterrence theory. Completing a comprehensive drug driving questionnaire were 899 members of the public, university students, and individuals referred to a drug diversion program. Of note was that approximately a fifth of participants reported drug driving in the past six months. Additionally, the analysis indicated that punishment avoidance and vicarious punishment avoidance were predictors of the propensity to drug drive in the future. In contrast, there were indications that knowing of others apprehended for drug driving was not a sufficient deterrent. Sustained testing and publicity of the legislation and countermeasure appears needed to increase the deterrent impact for drug driving.

A Vision Based Target Detection System for Docking of an Autonomous Underwater Vehicle

This paper describes the development and preliminary experimental evaluation of a visionbased docking system to allow an Autonomous Underwater Vehicle (AUV) to identify and attach itself to a set of uniquely identifiable targets. These targets, docking poles, are detected using Haar rectangular features and rotation of integral images. A non-holonomic controller allows the Starbug AUV to orient itself with respect to the target whilst maintaining visual contact during the manoeuvre. Experimental results show the proposed vision system is capable of robustly identifying a pair of docking poles simultaneously in a variety of orientations and lighting conditions. Experiments in an outdoor pool show that this vision system enables the AUV to dock autonomously from a distance of up to 4m with relatively low visibility.