Understanding PK/PD

Pharmacology is the science underpinning dosing, mechanisms of action and effectiveness of drugs. Central to pharmacology, are the studies of pharmacokinetics (PK) and pharmacodynamics (PD). On one hand, PK defines the time-course of drug concentrations in the body and incorporates the broad concepts of drug absorption, distribution, metabolism and elimination. On the other hand, PD describes the relationship between drug concentrations and pharmacological effects. In practice, PK is often referred as “what the body does to the drug” whilst PD as “what the drug does to the body”. Thus, PK/PD describes the relationship between drug dose and pharmacological effects with changes in drug concentrations leading to different pharmacological effects.

Cultural factors: Understanding culture to design organisation structures and systems to optimise safety

Safety culture is a term with numerous definitions in the literature. Many authors advocate a prescriptive approach to safety culture in which if an organisation has certain levels of externally prescribed systems and structures in place it has a “good safety culture”. Conversely, other researchers suggest an anthropological approach of exploring deep meanings and understandings present within an organisation’s workforce. In a recent published review, the authors presented an alternative view to safety culture, in which the anthropological aspects of safety culture interact with the structures and systems in place within an organisation to result in behavioural patterns. This can be viewed as a human factors approach to safety culture in which, through understanding the specific interactions between the culture of a workforce and external organisational elements, organisational structures and systems can be optimised in order to shape worker behaviour and improve safety. This paper presents findings from a recent investigation of safety culture in the Australian heavy vehicle (transport) industry. Selected results are discussed to explore how understanding culture can provide direction to the optimisation of organisational structures and systems to match worker culture and thus improve safety. Specifically the value placed on personal experience and stories, as well as on both time and money are discussed, and interventions that are suited to these aspects of the culture are discussed. These findings demonstrate the importance of shifting beyond mere prescriptive and interpretive approaches to safety culture and instead to focus on the interaction between cultural and contextual elements to optimise organisational structures and systems.

Barriers to good occupational health and safety (OHS) practices by small construction firms

The construction industry has long been considered to have unacceptably high injury and fatality rates. Previous research has shown that small construction companies sustain higher injury rates than large companies. However, despite the industry being dominated by a very large number of such small companies, little is known of their occupational health and safety (OHS) needs, practices and constraints. This paper takes a first step in aiming to identify the principal barriers that affect good OHS performance of small construction companies so that effective OHS practices can be developed to improve this in future. The contents of the literature are first summarised, in which three critical barriers to good OHS practice in small construction firms are proposed. They are : cost, time, lack of safety awareness and concern. The results of a questionnaire survey carried out with South East Queensland construction personnel are presented, which largely confirm what is suggested by the literature research and also succeed in providing an indication of their ranking in terms of importance and suggestions for overcoming these barriers. The research results provide a better understanding of the issues that restrict good OHS practice in small construction companies and potential measures for improvement.

Comparison of the effects of litigation and ADR in South-East Queensland

Alternative dispute resolution (ADR) methods, such as arbitration, are often used instead of litigation to resolve construction disputes, as industry folklore considers litigation overly expensive and time-consuming. But is this actually the case? Do the people most involved in construction dispute resolution agree? What are the real advantages and disadvantages of using litigation or ADR? When, if ever, is litigation the most appropriate way of resolving construction disputes? To answer these questions, this paper first provides a review of the literature on the use of litigation and ADR for construction dispute resolution. This is followed by the results of a survey of construction and legal personnel with moderate to extensive experience of dispute resolution in the Australian South-East Queensland construction industry. The main results of this are that, in addition to litigation being more expensive in money and time than ADR methods, the nature of the existing relationship between the parties has an important effect on the resolution process, what happens after an unsuccessful ADR and, if adversarial, is more likely to lead to litigation. The results are then validated and verified by one of the most experienced practitioners in claims and disputes in the whole of Australia.

Mutations in the gene encoding IFT dynein complex component WDR34 cause jeune asphyxiating thoracic dystrophy

Bidirectional (anterograde and retrograde) motor-based intraflagellar transport (IFT) governs cargo transport and delivery processes that are essential for primary cilia growth and maintenance and for hedgehog signaling functions. The IFT dynein-2 motor complex that regulates ciliary retrograde protein transport contains a heavy chain dynein ATPase/motor subunit, DYNC2H1, along with other less well functionally defined subunits. Deficiency of IFT proteins, including DYNC2H1, underlies a spectrum of skeletal ciliopathies. Here, by using exome sequencing and a targeted next-generation sequencing panel, we identified a total of 11 mutations in WDR34 in 9 families with the clinical diagnosis of Jeune syndrome (asphyxiating thoracic dystrophy). WDR34 encodes a WD40 repeat-containing protein orthologous to Chlamydomonas FAP133, a dynein intermediate chain associated with the retrograde intraflagellar transport motor. Three-dimensional protein modeling suggests that the identified mutations all affect residues critical for WDR34 protein-protein interactions. We find that WDR34 concentrates around the centrioles and basal bodies in mammalian cells, also showing axonemal staining. WDR34 coimmunoprecipitates with the dynein-1 light chain DYNLL1 in vitro, and mining of proteomics data suggests that WDR34 could represent a previously unrecognized link between the cytoplasmic dynein-1 and IFT dynein-2 motors. Together, these data show that WDR34 is critical for ciliary functions essential to normal development and survival, most probably as a previously unrecognized component of the mammalian dynein-IFT machinery.

Arson-associated homicide in Australia: A five year follow-up

Arson homicides are rare, representing only two percent of all homicides in Australia each year. In this study, data was collected from the AIC’s National Homicide Monitoring Program (NHMP) to build on previous research undertaken into arson-associated homicides (Davies & Mouzos 2007) and to provide more detailed analysis of cases and offenders. Over the period 1989 to 2010, there were 123 incidents of arson-associated homicide, involving 170 unique victims and 131 offenders. The majority of incidents (63%) occurred in the victim’s home and more than half (57%) of all victims were male. It was found that there has been a 44 percent increase in the number of incidents in the past decade. It is evident that a considerable proportion of the identified arson homicides involved a high degree of premeditation and planning. These homicides were commonly committed by an offender who was well known to the victim, with over half of the victims (56%) specifically targeted by the offender. This paper therefore provides a valuable insight into the nature of arson homicides and signposts areas for further investigation.

Impulsivity-related cognition in alcohol dependence: Is it moderated by DRD2/ANKK1 gene status and executive dysfunction?

Perceived impaired control over alcohol use is a key cognitive construct in alcohol dependence that has been related prospectively to treatment outcome and may mediate the risk for problem drinking conveyed by impulsivity in non-dependent drinkers. The aim of the current study was to investigate whether perceived impaired control may mediate the association between impulsivity-related measures (derived from the Short-form Eysenck Personality Questionnaire-Revised) and alcohol-dependence severity in alcohol-dependent drinkers. Furthermore, the extent to which this hypothesized relationship was moderated by genetic risk (Taq1A polymorphism in the DRD2/ANKK1 gene cluster) and verbal fluency as an indicator of executive cognitive ability (Controlled Oral Word Association Test) was also examined. A sample of 143 alcohol-dependent inpatients provided an extensive clinical history of their alcohol use, gave 10ml of blood for DNA analysis, and completed self-report measures relating to impulsivity, impaired control and severity of dependence. As hypothesized, perceived impaired control (partially) mediated the association between impulsivity-related measures and alcohol-dependence severity. This relationship was not moderated by the DRD2/ANKK1 polymorphism or verbal fluency. These results suggest that, in alcohol dependence, perceived impaired control is a cognitive mediator of impulsivity-related constructs that may be unaffected by DRD2/ANKK1 and neurocognitive processes underlying the retrieval of verbal information

Social influences on risky driving behaviours among young drivers in Oman

Young drivers represent approximately 20% of the Omani population, yet account for over one third of crash injuries and fatalities on Oman's roads. Internationally, research has demonstrated that social influences play an important role within young driver safety, however, there is little research examining this within Arab gulf countries. This study sought to explore young driver behaviour using Akers' social learning theory. A self-report survey was conducted by 1319 (72.9% male and 27.1% female) young drivers aged 17-25 years. A hierarchical regression model was used to investigate the contribution of social learning variables (norms and behaviour of significant others, personal attitudes towards risky behaviour, imitation of significant others, beliefs about the rewards and punishments offered by risky behaviour), socio-demographic characteristics (age and gender), driving experience (initial training, time driving and previous driving without supervision) and sensitivity to rewards and punishments upon the self-reported risky driving behaviours of young drivers. It was found that 39.6% of the young drivers reported that they have been involved in at least one crash since the issuance of their driving licence and they were considered ‘at fault’ in 60.7% of these crashes. The hierarchical multiple regression models revealed that socio-demographic characteristics and driving experience alone explained 14.2% of the variance in risky driving behaviour. By introducing social learning factors into the model a further 37.0% of variance was explained. Finally, 7.9% of the variance in risky behaviour could be explained by including individual sensitivity to rewards and punishments. These findings and the implications are discussed.

Socio-cultural influences on vehicle defects in the Omani heavy vehicle industry

With recent economic growth in Oman there is increased use of heavy vehicles, presenting an increase in heavy vehicle crashes, associated fatalities and injuries. Vehicle defects cause a significant number of heavy vehicle crashes in Oman and increase the likelihood of fatalities. The aim of this study is to explore factors contributing to driving with vehicle defects in the Omani heavy vehicle industry. A series of qualitative participants observations were conducted in Oman with 49 drivers. These observations also involved discussion and interviews with drivers. The observations occurred at two road-side locations where heavy vehicle drivers gather for eating, resting, vehicle check-up, etc. Data collection was conducted over a three week period. The data was analysed using thematic analysis. A broad number of factors were identified as contributing to the driving of vehicles with defects. Participants indicated that tyres and vehicle mechanical faults were a common issue in the heavy vehicle industry. Participants regularly reported that their companies use cheap, poor quality standards parts and conducted minimal maintenance. Drivers also indicated that they felt powerless to resist company pressure to drive vehicles with known faults. In addition, drivers reported that traffic police were generally in effective and lacked skill to appropriately conduct roadside inspection on trucks. Further, participants stated that it was possible for companies to avoid being fined during annual or roadside vehicle inspections if members of the company knew the traffic police officer conducting the inspection. Moreover, fines issued by police are generally directed to the individual driver rather than being applied to the company, thus providing no incentive for companies to address vehicle faults. The implications of the findings are discussed.

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1–3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region4, 5, 6, 7, 8, 9, 10, 11. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods—recursive partitioning and regression...

Policing of road safety in Oman: Perceptions and beliefs of traffic police officers

With increasing motorisation, road safety has become a major concern within Oman. Internationally, traffic policing plays a major role in improving road safety. Within Oman, the Royal Oman Police's (ROP) Directorate General of Traffic is responsible for policing traffic laws. Many common enforcement approaches originate from culturally different jurisdictions. The ROP is a relatively young policing force and may have different operational practices. Prior to applying practices from other jurisdictions it is important to understand the beliefs and expectations within the Directorate General of Traffic. Further, there is a need for individuals to understand their role and what is expected of them. Therefore, it is important to explore the agreement between levels of the ROP to determine how strategies and expectations transfer within the organisation. Interviews were conducted with 19 police officers from various levels of the ROP. A number of themes and findings emerged. Individuals at the upper level of the traffic police had a clear knowledge of the role of the ROP, believed that traffic police know what is expected of them, are well trained in their role and can have a very positive influence on road safety. These beliefs were less certain lower within the organisations with traffic officers having little knowledge of the role of the ROP or what was expected of them, felt undertrained, and believed their peers have little positive impact on road safety. There is a need to address barriers within the ROP in order to positively impact road safety.

Safety culture and speeding in the Australian heavy vehicle industry

Inappropriate speed and speeding are among the highest causes of crashes in the heavy vehicle industry. Truck drivers are subjected to a broad range of influences on their behaviour including industrial pressures, company monitoring and police enforcement. Further, drivers have a high level of autonomy over their own behaviour. As such it is important to understand how these external influences interact with commonly shared beliefs, attitudes and values of heavy vehicle drivers to influence their behaviour. The present study uses a re-conceptualisation of safety culture to explore the behaviours of driving at an inappropriate speed and speeding in the heavy vehicle industry. A series of case studies, consisting of interviews and ride-along observations, were conducted with three transport organisations to explore the effect of culture on safety in the heavy vehicle industry. Results relevant to inappropriate speed are reported and discussed. It was found that organisational management through monitoring, enforcement and payment, police enforcement, customer standards and vehicle design factors could all reduce the likelihood of driving at inappropriate speeds under some circumstances. However, due to weaknesses in the ability to accurately monitor appropriate speed, this behaviour was primarily influenced by cultural beliefs, attitudes and values. Truck drivers had a tendency to view speeding as relatively safe, had a desire to speed to save time and increase personal income, and thus often attempted to speed without detection. When drivers saw speeding as dangerous, however, they were more likely to drive safely. Implications for intervention are discussed.

Prevalence and characteristics of road traffic injuries among young drivers in Oman, 2009-2011

Objectives Studies from different parts of the world have indicated that the impact of road traffic incidents disproportionally affects young adults. Few known studies have been forthcoming from Arabian Gulf countries. Within Oman, a high proportion of the population is under the age of 20. Coupled with the drastic increase of motorization in recent years there is a need to understand the state of road safety among young people in Oman. The current research aimed to explore the prevalence and characteristics of road traffic injuries among young drivers aged 17-25 years. Methods Crash data from 2009-2011 was extracted from the Directorate General of Traffic, Royal Oman Police (ROP) database in Oman. The data was analyzed to explore the impact of road crashes on young people (17-25 years), the characteristics of young driver crashes and how these differ from older drivers and to identify key predictors of fatalities in young driver crashes. Results Overall, young people were over-represented in injuries and fatalities within the sample time period. While it is true that many young people in crashes were driving at the time, it was also evident that young people were often a victim in a crash caused by someone else. Thus, to reduce the impact of road crashes on young people, there is a need to generally address road safety within Oman. When young drivers were involved in crashes they were predominantly male. The types of crashes these drivers have can be broadly attributed to risk taking and inexperience. Speeding and night time driving were the key risk factors for fatalities. Conclusion The results highlight the need to address young driver safety in Oman. From these findings, the introduction of a graduated driver licensing system with night time driving restrictions could significantly improve young driver safety.

State-formation, teaching techniques, and globalization as aporia

Eleanor Smith [pseudonym], teacher : I was talking to the kids about MacDonalds*/I forget exactly what the context was*/I said ‘‘ah, the Americans call them French fries, and, you know, MacDonalds is an American chain and they call them French fries because the Americans call them French fries’’, and this little Australian kid in the front row, very Australian child, said to me, ‘‘I call them French fries!’’ . . . Um, a fourth grade boy whom I taught in 1993 at this school, the world basketball championships were on . . . Americans were playing their dream machine and the Boomers were up against them . . . and, ah, this boy was very interested in basketball . . . but it’s not in my blood, not in the way cricket is for example . . . Um, Um, and I said to this fellow, ‘‘um, well’’, I said, ‘‘Australia’s up against Dream Machine tomorrow’’. He [Jason, pseudonym] said, ‘‘Ah, you know, Boomers probably won’t win’’. . . . I said, ‘‘Well that’s sport, mate’’. I said, ‘‘You never know in sport. Australia might win’’. And he looked at me and he said, ‘‘I’m not going for Australia, I’m going for America’’. This is from an Australian boy! And I thought so strong is the hype, so strong is the, is the, power of the media, etc., that this boy is not [pause], I can’t tell you how outraged I was. Here’s me as an Australian and I don’t even support basketball, it’s not even my sport, um, but that he would respond like that because of the power of the American machine that’s converting kids’ minds, the way they think, where they’re putting their loyalties, etc. I was just appalled, but that’s where he was. And when I asked kids for their favourite place, he said Los Angeles.

Statistical modelling and power analysis for detecting trends in total suspended sediment loads

The export of sediments from coastal catchments can have detrimental impacts on estuaries and near shore reef ecosystems such as the Great Barrier Reef. Catchment management approaches aimed at reducing sediment loads require monitoring to evaluate their effectiveness in reducing loads over time. However, load estimation is not a trivial task due to the complex behaviour of constituents in natural streams, the variability of water flows and often a limited amount of data. Regression is commonly used for load estimation and provides a fundamental tool for trend estimation by standardising the other time specific covariates such as flow. This study investigates whether load estimates and resultant power to detect trends can be enhanced by (i) modelling the error structure so that temporal correlation can be better quantified, (ii) making use of predictive variables, and (iii) by identifying an efficient and feasible sampling strategy that may be used to reduce sampling error. To achieve this, we propose a new regression model that includes an innovative compounding errors model structure and uses two additional predictive variables (average discounted flow and turbidity). By combining this modelling approach with a new, regularly optimised, sampling strategy, which adds uniformity to the event sampling strategy, the predictive power was increased to 90%. Using the enhanced regression model proposed here, it was possible to detect a trend of 20% over 20 years. This result is in stark contrast to previous conclusions presented in the literature. (C) 2014 Elsevier B.V. All rights reserved.