The antihypertensive drug pindolol attenuates long-term but not short-term binge-like ethanol consumption in mice

Alcohol dependence is a debilitating disorder with current therapies displaying limited efficacy and/or compliance. Consequently, there is a critical need for improved pharmacotherapeutic strategies to manage alcohol use disorders (AUDs). Previous studies have shown that the development of alcohol dependence involves repeated cycles of binge-like ethanol intake and abstinence. Therefore, we used a model of binge-ethanol consumption (drinking-in-the-dark) in mice to test the effects of compounds known to modify the activity of neurotransmitters implicated in alcohol addiction. From this, we have identified the FDA-approved antihypertensive drug pindolol, as a potential candidate for the management of AUDs. We show that the efficacy of pindolol to reduce ethanol consumption is enhanced following long-term (12-weeks) binge-ethanol intake, compared to short-term (4-weeks) intake. Furthermore, pindolol had no effect on locomotor activity or consumption of the natural reward sucrose. Because pindolol acts as a dual beta-adrenergic antagonist and 5-HT1A/1B partial agonist, we examined its effect on spontaneous synaptic activity in the basolateral amygdala (BLA), a brain region densely innervated by serotonin- and norepinephrine-containing fibres. Pindolol increased spontaneous excitatory post-synaptic current frequency in BLA principal neurons from long-term ethanol consuming mice but not naïve mice. Additionally, this effect was blocked by the 5-HT1A/1B receptor antagonist methiothepin, suggesting that altered serotonergic activity in the BLA may contribute to the efficacy of pindolol to reduce ethanol intake following long-term exposure. Although further mechanistic investigations are required, this study demonstrates the potential of pindolol as a new treatment option for AUDs that can be fast-tracked into human clinical studies.

Influences on novice drivers' speed selection - a systematic review: Application and limitations of theory and methodology

Background Excessive speed is a primary contributing factor to young novice road trauma, including intentional and unintentional speeds above posted limits or too fast for conditions. The objective of this research was to conduct a systematic review of recent investigations into novice drivers��� speed selection, with particular attention to applications and limitations of theory and methodology. Method Systematic searches of peer-reviewed and grey literature were conducted during September 2014. Abstract reviews identified 71 references potentially meeting selection criteria of investigations since the year 2000 into factors that influence (directly or indirectly) actual speed (i.e., behaviour or performance) of young (age <25 years) and/or novice (recently-licensed) drivers. Results Full paper reviews resulted in 30 final references: 15 focused on intentional speeding and 15 on broader speed selection investigations. Both sets identified a range of individual (e.g., beliefs, personality) and social (e.g., peer, adult) influences, were predominantly theory-driven and applied cross-sectional designs. Intentional speed investigations largely utilised self-reports while other investigations more often included actual driving (simulated or ‘real world’). The latter also identified cognitive workload and external environment influences, as well as targeted interventions. Discussion and implications Applications of theory have shifted the novice speed-related literature beyond a simplistic focus on intentional speeding as human error. The potential to develop a ‘grand theory’ of intentional speeding emerged and to fill gaps to understand broader speed selection influences. This includes need for future investigations of vehicle-related and physical environment-related influences and methodologies that move beyond cross-sectional designs and rely less on self-reports.

Drink driving among indigenous people in Far North Queensland and Northern New South Wales: A summary of qualitative findings

In response to the threat that drink drivers pose to themselves and others, drink driving programs form an important part of a suite of countermeasures used in Australia and internationally. Unlike New Zealand/Aotearoa, United States and Canada that have programs catering for their First Peoples, all Australian programs are designed for the general driver population. The aim of this study was to identify the factors that contribute to Indigenous drink driving in order to inform appropriate recommendations related to developing a community-based program for Indigenous communities. Broader drivers licensing policy recommendations are also discussed. A sample of 73 Indigenous people from Queensland and in New South Wales with one or more drink driving convictions completed a semi-structured interview regarding their drink driving behaviour. Participants were asked to disclose information regarding their drink driving history, and alcohol and drug use. If participants self-reported no longer drink driving, they were probed about what factors had assisted them to avoid further offending. Key themes which emerged to maintain drink driving include motivations to drink and drive, and belief in the ability to manage the associated risks. Factors that appeared to support others from avoiding further offending include re-connecting with culture and family support. A range of recommendations regarding delivery and content of a program for regional and remote communities as well as other policy implications are discussed.

Chronic disease risks and use of a smartphone application during a physical activity and dietary intervention in Australian truck drivers

- Objective This study examined chronic disease risks and the use of a smartphone activity tracking application during an intervention in Australian truck drivers (April-October 2014). - Methods Forty-four men (mean age=47.5 [SD 9.8] years) completed baseline health measures, and were subsequently offered access to a free wrist-worn activity tracker and smartphone application (Jawbone UP) to monitor step counts and dietary choices during a 20-week intervention. Chronic disease risks were evaluated against guidelines; weekly step count and dietary logs registered by drivers in the application were analysed to evaluate use of the Jawbone UP. - Results Chronic disease risks were high (e.g. 97% high waist circumference [≥94 cm]). Eighteen drivers (41%) did not start the intervention; smartphone technical barriers were the main reason for drop out. Across 20-weeks, drivers who used the Jawbone UP logged step counts for an average of 6 [SD 1] days/week; mean step counts remained consistent across the intervention (weeks 1–4=8,743[SD 2,867] steps/day; weeks 17–20=8,994[SD 3,478] steps/day). The median number of dietary logs significantly decreased from start (17 [IQR 38] logs/weeks) to end of the intervention (0 [IQR 23] logs/week; p<0.01); the median proportion of healthy diet choices relative to total diet choices logged increased across the intervention (weeks 1–4=38[IQR 21]%; weeks 17–20=58[IQR 18]%). - Conclusions Step counts were more successfully monitored than dietary choices in those drivers who used the Jawbone UP. - Implications Smartphone technology facilitated active living and healthy dietary choices, but also prohibited intervention engagement in a number of these high-risk Australian truck drivers.

Drink driving among Indigenous Australians in outer regional and remote communities and development of a drink driving program: A summary of findings and recommendations

Drink driving is a leading cause of criminal justice system contact for Indigenous Australians. National and state strategies recommend Indigenous road safety initiatives are warranted. However, there is sparse evidence to inform drink driving-related preventive and treatment measures. Using quantitative and qualitative methods, the study examines the profile of Queensland’s Indigenous drink drivers using court convictions and identifies the contributing psycho-social, cultural and contextual factors through qualitative interviews.

Drug discovery approaches utilizing three-dimensional cell culture

Historically, two-dimensional (2D) cell culture has been the preferred method of producing disease models in vitro. Recently, there has been a move away from 2D culture in favor of generating three-dimensional (3D) multicellular structures, which are thought to be more representative of the in vivo environment. This transition has brought with it an influx of technologies capable of producing these structures in various ways. However, it is becoming evident that many of these technologies do not perform well in automated in vitro drug discovery units. We believe that this is a result of their incompatibility with high-throughput screening (HTS). In this study, we review a number of technologies, which are currently available for producing in vitro 3D disease models. We assess their amenability with high-content screening and HTS and highlight our own work in attempting to address many of the practical problems that are hampering the successful deployment of 3D cell systems in mainstream research.

Advancing initiatives in care of cognitively impaired patients in acute care settings

In November 2014, the Australian Commission on Safety and Quality in Health Care (ACSQHC) released “A better way to care: Safe and high quality care for patients with cognitive impairment (dementia and delirium) in hospital”. http://www.safetyandquality.gov.au/our-work/cognitive-impairment. The handbook is available as three separate resources for the three audiences: clinicians, service managers and consumers. These resources are designed to inform and guide improved care for older patients with cognitive impairment (CI) (dementia, delirium) in acute care settings. In particular, the service managers resource recommends that organisations comprehensively prepare themselves so that they are alert to delirium and the risk it poses for patients, that they can recognise and respond to patients with CI, and that they are able to provide safe and high quality care tailored to individual patient’s needs. Service managers and clinicians should carefully consider the information provided in the resources and judiciously explore how best to modify and adapt everyday care practices where appropriate. It is important that clinical teams respond to the available information as the ACSQHC identifies that dementia and/or delirium is associated with adverse outcomes, including functional decline, increased risk of falls, and increased morbidity and mortality...

Gap acceptance behavior of mobile phone distracted drivers at roundabouts

While mobile phones have become ubiquitous in modern society, the use of mobile phones while driving is increasing at an alarming rate despite the associated crash risks. A significant safety concern is that driving while distracted by a mobile phone is more prevalent among young drivers, a less experienced driving cohort with elevated crash risk. The objective of this study was to examine the gap acceptance behavior of distracted young drivers at roundabouts. The CARRS-Q Advanced Driving Simulator was used to test participants on a simulated gap acceptance scenario at roundabouts. Conflicting traffic from the right approach of a four-legged roundabout were programmed to have a series of vehicles having the gaps between them proportionately increased from two to six seconds. Thirty-two licensed young drivers drove the simulator under three phone conditions: baseline (no phone conversation), hands-free and handheld phone conversations. Results show that distracted drivers started responding to the gap acceptance scenario at a distance closer to the roundabout and approached the roundabout at slower speeds. They also decelerated at faster rates to reduce their speeds prior to gap acceptance compared to non-distracted drivers. Although accepted gap sizes were not significantly different across phone conditions, differences in the safety margins at various gap sizes—measured by Post Encroachment Time (PET) between the driven vehicle and the conflicting vehicle—were statistically significant across phone conditions. PETs for distracted drivers were smaller across different gap sizes, suggesting a lower safety margin taken by distracted drivers compared to non-distracted drivers. The results aid in understanding how cognitive distraction resulting from mobile phone conversations while driving influences driving behavior during gap acceptance at roundabouts.

Key drivers of the economic burden of community-associated Methicillin-resistant Staphylococcus aureus in Australia

Estimates of the economic cost of community-associated Methicillin-resistant Staphylococcus aureus(CA-MRSA) in the United States (US) are substantial, ranging from $1.4-13.8 billion. In Australia, it has been shown that rates of CA-MRSA are increasing, and individual studies have looked at the morbidity and mortality associated with CA-MRSA, however, it is not clear what is driving the economic burden of CA-MRSA at a national level. This study presents preliminary findings about the key drivers of the economic cost of CA-MRSA infections in Australia

Does family background impact driving attitudes and risky behaviours? - An investigation on Chinese young drivers

This thesis took a novel approach to examining factors associated with risky attitudes and risky road use in China by investigating the economic and political background status of a sample of young Chinese drivers. Using data from an online survey significant relationships are found between some family background factors and road safety variables. Correlation analysis, ANOVA, hierarchical regression analysis and structural equation modelling are applied in this study, with culture, personality and demographic variables as additional factors for a better understanding of the key findings. The findings are discussed in light of China's political management system and potential education opportunities for young drivers.

Association of FOXE1 Polyalanine Repeat Region with Papillary Thyroid Cancer

CONTEXT: Polyalanine tract variations in transcription factors have been identified for a wide spectrum of developmental disorders. The thyroid transcription factor forkhead factor E1 (FOXE1) contains a polymorphic polyalanine tract with 12-22 alanines. Single-nucleotide polymorphisms (SNP) close to this locus are associated with papillary thyroid cancer (PTC), and a strong linkage disequilibrium block extends across this region. OBJECTIVE: The objective of the study was to assess whether the FOXE1 polyalanine repeat region was associated with PTC and to assess the effect of polyalanine repeat region variants on protein expression, DNA binding, and transcriptional function on FOXE1-responsive promoters. DESIGN: This was a case-control study. SETTING: The study was conducted at a tertiary referral hospital. PATIENTS AND METHODS: The FOXE1 polyalanine repeat region and tag SNP were genotyped in 70 PTC, with a replication in a further 92 PTC, and compared with genotypes in 5767 healthy controls (including 5667 samples from the Wellcome Trust Case Control Consortium). In vitro studies were performed to examine the protein expression, DNA binding, and transcriptional function for FOXE1 variants of different polyalanine tract lengths. RESULTS: All the genotyped SNP were in tight linkage disequilibrium, including the FOXE1 polyalanine repeat region. We confirmed the strong association of rs1867277 with PTC (overall P = 1 × 10(-7), odds ratio 1.84, confidence interval 1.31-2.57). rs1867277 was in tight linkage disequilibrium with the FOXE1 polyalanine repeat region (r(2) = 0.95). FOXE1(16Ala) was associated with PTC with an odds ratio of 2.23 (confidence interval 1.42-3.50; P = 0.0005). Functional studies in vitro showed that FOXE1(16Ala) was transcriptionally impaired compared with FOXE1(14Ala), which was not due to differences in protein expression or DNA binding. CONCLUSIONS: We have confirmed the previous association of FOXE1 with PTC. Our data suggest that the coding polyalanine expansion in FOXE1 may be responsible for the observed association between FOXE1 and PTC.

Compound heterozygous mutations in RIPPLY2 associated with vertebral segmentation defects

Segmentation defects of the vertebrae (SDV) are caused by aberrant somite formation during embryogenesis and result in irregular formation of the vertebrae and ribs. The Notch signal transduction pathway plays a critical role in somite formation and patterning in model vertebrates. In humans, mutations in several genes involved in the Notch pathway are associated with SDV, with both autosomal recessive (MESP2, DLL3, LFNG, HES7) and autosomal dominant (TBX6) inheritance. However, many individuals with SDV do not carry mutations in these genes. Using whole-exome capture and massive parallel sequencing, we identified compound heterozygous mutations in RIPPLY2 in two brothers with multiple regional SDV, with appropriate familial segregation. One novel mutation (c.A238T:p.Arg80*) introduces a premature stop codon. In transiently transfected C2C12 mouse myoblasts, the RIPPLY2 mutant protein demonstrated impaired transcriptional repression activity compared with wild-type RIPPLY2 despite similar levels of expression. The other mutation (c.240-4T>G), with minor allele frequency <0.002, lies in the highly conserved splice site consensus sequence 5' to the terminal exon. Ripply2 has a well-established role in somitogenesis and vertebral column formation, interacting at both gene and protein levels with SDV-associated Mesp2 and Tbx6. We conclude that compound heterozygous mutations in RIPPLY2 are associated with SDV, a new gene for this condition. © The Author 2014.

Juggling priorities: Balancing economic and social drivers to address the LLN needs of students in the VET sector

Economic success, and a commitment to the social benefits of inclusive training opportunities are important goals for public vocational education and training (VET). Currently, in Australia, VET policy is a shared responsibility between the Commonwealth and the States and Territories. Priorities for investment are juggled between: a) improving efficiency and responsiveness; and b) providing societal prosperity. Amid recent VET educational reforms and policy directives the authors of this paper undertook a pilot study examining language, literacy and numeracy support and inclusive teaching and learning practices in a Diploma of Nursing course. The data highlighted implications arising from new market driven education reforms. This article reports on identified factors that influenced inclusive learning opportunities, noticeably associated with two recent policy developments: the release of the FSK Foundation Skills Training Package (IBSA 2014); and the Queensland's Higher Skills Program Policy 2014-15.

Prostate cancer organoids: A potential new tool for testing drug sensitivity

Recent technical advances have enabled for the first time, reliable in vitro culture of prostate cancer samples as prostate cancer organoids. This breakthrough provides the significant possibility of high throughput drug screening covering the spectrum of prostate cancer phenotypes seen clinically. These advances will enable precision medicine to become a reality, allowing patient samples to be screened for effective therapeutics ex vivo, with tailoring of treatments specific to that individual. This will hopefully lead to enhanced clinical outcomes, avoid morbidity due to ineffective therapies and improve the quality of life in men with advanced prostate cancer.