Mitogen-activated protein kinases (MAPKs) are modulated during in vitro and in vivo infection with the intracellular bacterium Burkholderia pseudomallei.

Burkholderia pseudomallei is a Gram-negative intracellular bacterium that causes the disease melioidosis. The disease can be fatal if left untreated or when antibiotic therapy is delayed and total clearance of the pathogen from the host is often not accomplished with current therapies. Thus, new therapeutic approaches for the treatment of infections caused by B. pseudomallei are required. To better understand host responses to B. pseudomallei infection, the activation of key proteins involved in the TLR inflammatory cascade was measured by western blotting. Activation of the mitogen-activated protein kinases (MAPKs) p38 and ERK were both significantly altered during both in vitro and in vivo infection. In considering an approach for therapy of B. pseudomallei infection the inhibition of ERK was achieved in vitro using the inhibitor PD0325901, along with decreased TNF-α production. However, the reduction in phosphorylated ERK and TNF-α release did not correspond with decreased bacterial replication or enhance clearance from infected macrophages. Despite this apparent lack of effect on the intracellular growth of B. pseudomallei in vitro, it is not clear what effect inhibition of ERK activation might have on outcome of disease in vivo. It may be that decreasing the levels of TNF-α in vivo could aid in reducing the overactive immune response that is known to ensue following B. pseudomallei infection, thereby increasing host survival.

Outcome evaluation of the p drivers Program: Randomised controlled trial of a program to improve safe driving among novice drivers.

BACKGROUND: Globally, road traffic crashes are the leading cause of death for young adults. The P Drivers Project was a trial of a behavioural change program developed for, and targeted at, young Australian drivers in their initial months of solo driving when crash risk is at its highest. METHODS: In a parallel group randomised controlled trial, drivers (N = 35,109) were recruited within 100 days of obtaining their probationary licence (allowing them to drive unaccompanied) and randomised to an intervention or control group. The intervention was a 3 to 6-week multi-stage driving behaviour change program (P Drivers Program). Surveys were administered at three time points (pre-Program, approximately one month post-Program and at 12 months after). The outcome evaluation employed an on-treatment analysis comprising the 2,419 intervention and 2,810 control participants who completed all required activities, comparing self-reported crashes and police-reported casualty crashes (primary outcome), infringements, self-reported attitudes and behaviours (secondary outcomes) between groups. RESULTS: The P Drivers Program improved awareness of crash risk factors and intentions to drive more safely, relative to the controls; effects were maintained after 12-months. However, the Program did not reduce self-reported crashes or police-reported casualty crashes. In addition, self-reported violations, errors and risky driving behaviours increased in the intervention group compared to the control group as did recorded traffic infringements. This suggests that despite the Program increasing awareness of risky behaviour in novice drivers, behaviour did not improve. This reinforces the need to collect objective measures to accompany self-reported behaviour and intentions. CONCLUSIONS: The P Drivers Program was successful in improving attitudes toward driving safety but the negative impact on behaviour, lack of effect on crashes, and the large loss to follow-up fail to support the use of a post-licensing behaviour change program to improve novice driver behaviour and reduce crashes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: 363,293 (ANZCTR, 2012).

Development and operation of the defence COVID-19 lab as a SARS-CoV-2 diagnostic screening capability for UK military personnel.

BACKGROUND: In the face of the COVID-19 pandemic, the Defence Science and Technology Laboratory (Dstl) and Defence Pathology combined to form the Defence Clinical Lab (DCL), an accredited (ISO/IEC 17025:2017) high-throughput SARS-CoV-2 PCR screening capability for military personnel. LABORATORY STRUCTURE AND RESOURCE: The DCL was modular in organisation, with laboratory modules and supporting functions combining to provide the accredited SARS-CoV-2 (envelope (E)-gene) PCR assay. The DCL was resourced by Dstl scientists and military clinicians and biomedical scientists. LABORATORY RESULTS: Over 12 months of operation, the DCL was open on 289 days and tested over 72 000 samples. Six hundred military SARS-CoV-2-positive results were reported with a median E-gene quantitation cycle (Cq) value of 30.44. The lowest Cq value for a positive result observed was 11.20. Only 64 samples (0.09%) were voided due to assay inhibition after processing started. CONCLUSIONS: Through a sustained effort and despite various operational issues, the collaboration between Dstl scientific expertise and Defence Pathology clinical expertise provided the UK military with an accredited high-throughput SARS-CoV-2 PCR test capability at the height of the COVID-19 pandemic. The DCL helped facilitate military training and operational deployments contributing to the maintenance of UK military capability. In offering a bespoke capability, including features such as testing samples in unit batches and oversight by military consultant microbiologists, the DCL provided additional benefits to the UK Ministry of Defence that were potentially not available from other SARS-CoV-2 PCR laboratories. The links between Dstl and Defence Pathology have also been strengthened, benefitting future research activities and operational responses.

Evaluation of the 30km/h speed limit trial in the City of Yarra, Melbourne, Australia.

OBJECTIVE: Safe vehicle speeds were identified as a key element in a safe system approach to road safety. The City of Yarra in Melbourne, Australia has a 40 km/h default speed limit across their municipality, but wished to reduce the speed limit in local residential streets to 30 km/h. The Monash University Accident Research Center provided Council with a design for a demonstration trial and agreed to evaluate its safety benefits over 12 months. The trial was expected to show significant reductions in speed and increased community support. METHOD: A before and after design was employed with a control (untreated) area to evaluate the safety outcomes of the trial. Speed limits were reduced to 30 km/h in the trial area for 12 months but kept at kept at the current 40 km/h (25 mph) limit in the control region. Vehicle speeds were measured at around 100 selected sites in the trial and control areas, and resident surveys were undertaken in both regions before and after the trial. RESULTS: The findings showed a small but modest reduction of 1.1% in average speed in the trial region but a surprising 2.7% in the control region. On further examination, significant reductions were observed in the percent of vehicles exceeding 40 km/h (25 mph) and 50 km/h (31 mph) in both the treated and control regions, but not at 30 km/h (19 mph). A regression analysis further showed a significant treatment effect of 11% at 40 km/h and 25% at 50 km/h when adjusting for differences between treated and controls. Among other findings, the survey results found increased support for the lower speed limit of 17% with little adverse consequences. CONCLUSION: The findings give support for the likely safety benefits of the 30 km/h trial with increased support from the residents. Speed reductions in the control region suggested a carry-over of the effects of the trial but also added support by local residents for reduced speed limits in the region. Potential injury savings were estimated at a 4% reduction in the risk of a pedestrian injury from the observed treatment effect in the trial region.

An index for rating the total secondary safety of vehicles from real world crash data.

This study proposes a total secondary safety index for light passenger vehicles that rates the relative performance of vehicles in protecting both their own occupants and other road users in the full range of real world crash circumstances. The index estimates the risk of death or serious injury to key road users in crashes involving light passenger vehicles across the full range of crash types. The proposed index has been estimated from real world crash data from Australasia and was able to identify vehicles that have superior or inferior total secondary safety characteristics compared with the average vehicle.

Overall impact of speed-related initiatives and factors on crash outcomes.

From December 2000 until July 2002 a package of speed-related initiatives and factors took place in Victoria, Australia. The broad aim of this study was to evaluate the overall impact of the package on crash outcomes. Monthly crash counts and injury severity proportions were assessed using Poisson and logistic regression models respectively. The model measured the overall effect of the package after adjusting as far as possible for non-speed road safety initiatives and socio-economic factors. The speed-related package was associated with statistically significant estimated reductions in casualty crashes and suggested reductions in injury severity with trends towards increased reductions over time. From December 2000 until July 2002, three new speed enforcement initiatives were implemented in Victoria, Australia. These initiatives were introduced in stages and involved the following key components: More covert operations of mobile speed cameras, including flash-less operations; 50% increase in speed camera operating hours; and lowering of cameras' speed detection threshold. In addition, during the period 2001 to 2002, the 50 km/h General Urban Speed Limit (GUSL) was introduced (January 2001), there was an increase in speed-related advertising including the "Wipe Off 5" campaign, media announcements were made related to the above enforcement initiatives and there was a speeding penalty restructure. The above elements combine to make up a package of speed-related initiatives and factors. The package represents a broad, long term program by Victorian government agencies to reduce speed based on three linked strategies: more intensive Police enforcement of speed limits to deter potential offenders, i.e. the three new speed enforcement initiatives just described - supported by higher penalties; a reduction in the speed limit on local streets throughout Victoria from 60 km/h to 50 km/h; and provision of information using the mass media (television, radio and billboard) to reinforce the benefits of reducing low level speeding - the central message of "Wipe Off 5". These strategies were implemented across the entire state of Victoria with the intention of covering as many road users as possible. This study aimed to evaluate the overall effectiveness of the speed-related package. The study objectives were: to document the increased speed camera activity in each speed limit zone and in Melbourne compared with the rest of Victoria; to evaluate the overall effect on crash outcomes of the package; to account as far as possible for the effect on crash outcomes of non-speed road safety initiatives and socio-economic factors, which would otherwise influence the speed-related package evaluation; and to examine speed trends in Melbourne and on Victorian rural highways, especially the proportions of vehicles travelling at excessive speeds. This paper presents the results of the evaluation of the overall impact on crash outcomes associated with the speed-related package, after adjusting as far as possible for the effect of non-speed road safety initiatives and socio-economic factors. D'Elia, Newstead and Cameron (2007) document the study results in full.

Real-world evaluation of the effectiveness of reversing camera and parking sensor technologies in preventing backover pedestrian injuries.

Backover injuries to pedestrians are a significant road safety issue, but their prevalence is underestimated as the majority of such injuries are often outside the scope of official road injury recording systems, which just focus on public roads. Based on experimental evidence, reversing cameras have been found to be effective in reducing the rate of collisions when reversing; the evidence for the effectiveness of reverse parking sensors has been mixed. The wide availability of these technologies in recent model vehicles provides impetus for real-world evaluations using crash data. A logistic model was fitted to data from crashes that occurred on public roads constituting 3172 pedestrian injuries in New Zealand and four Australian States to estimate the odds of backover injury (compared to other sorts of pedestrian injury crashes) for the different technology combinations fitted as standard equipment (both reversing cameras and sensors; just reversing cameras; just sensors; neither cameras nor sensors) controlling for vehicle type, jurisdiction, speed limit area and year of manufacture restricted to the range 2007-2013. Compared to vehicles without any of these technologies, reduced odds of backover injury were estimated for all three of these technology configurations: 0.59 (95% CI 0.39-0.88) for reversing cameras by themselves; 0.70 (95% CI 0.49-1.01) for both reversing cameras and sensors; 0.69 (95% CI 0.47-1.03) for reverse parking sensors by themselves. These findings are important as they are the first to our knowledge to present an assessment of real-world safety effectiveness of these technologies.

Exposure factors of Victoria's active motorcycle fleet related to serious injury crash risk.

OBJECTIVE: The purpose of this study was to describe the nature and extent of current powered 2-wheeler (PTW) risk exposures in order to support future efforts to improve safety for this mode of transport. METHODS: A cross-sectional analysis of the control arm of a population-based case-control study was conducted. The control sample was selected from 204 sites on public roads within 150 km of the city of Melbourne that were locations of recent serious injury motorcycle crashes. Traffic observations and measurements at each site were sampled for a mean of 2 h on the same type of day (weekday, Saturday, or Sunday) and within 1 h of the crash time. Photographs of passing riders during this observation period recorded data relating to characteristics of PTWs, age of riders, travel speed of PTWs and all vehicles, time gaps between vehicles, visibility, and protective clothing use. RESULTS: Motorcycles and scooters represented 0.6% of all traffic (compared with 4% of all vehicle registrations). Riders were significantly more likely to have larger time gaps in front and behind when compared to other vehicles. The average travel speed of motorcycles was not significantly different than the traffic, but a significantly greater proportion were exceeding the speed limit when compared to other vehicles (6 vs. 3%, respectively). The age of registered owners of passing motorcycles was 42 years. Over half of riders were wearing dark clothing with no fluorescent or reflective surfaces. One third of motorcyclists had maximum coverage of motorcycle-specific protective clothing. CONCLUSIONS: A very low prevalence of motorcyclists combined with relatively higher rates of larger time gaps to other vehicles around motorcycles may help explain their overrepresentation in injury crashes where another vehicle fails to give way. An increased risk of injury in the event of a crash exists for a small but greater proportion of motorcyclists (compared to other vehicle types) who were exceeding the speed limit. An apparent shift toward older age of the active rider population may be reducing injury crash risk relative to exposure time. There is significant scope to improve the physical conspicuity of motorcyclists and the frequency of motorcycle specific protective clothing use. These results can be used to inform policy development and monitor progress of current and future road safety initiatives.

A review of models relevant to road safety.

It is estimated that more than 1.2 million people die worldwide as a result of road traffic crashes and some 50 million are injured per annum. At present some Western countries' road safety strategies and countermeasures claim to have developed into 'Safe Systems' models to address the effects of road related crashes. Well-constructed models encourage effective strategies to improve road safety. This review aimed to identify and summarise concise descriptions, or 'models' of safety. The review covers information from a wide variety of fields and contexts including transport, occupational safety, food industry, education, construction and health. The information from 2620 candidate references were selected and summarised in 121 examples of different types of model and contents. The language of safety models and systems was found to be inconsistent. Each model provided additional information regarding style, purpose, complexity and diversity. In total, seven types of models were identified. The categorisation of models was done on a high level with a variation of details in each group and without a complete, simple and rational description. The models identified in this review are likely to be adaptable to road safety and some of them have previously been used. None of systems theory, safety management systems, the risk management approach, or safety culture was commonly or thoroughly applied to road safety. It is concluded that these approaches have the potential to reduce road trauma.

The source of belief bias effects in syllogistic reasoning.

In studies of the belief bias effect in syllogistic reasoning, an interaction between logical validity and the believability of the conclusion has been found; in essence, logic has a larger effect on unbelievable than on believable conclusions. Two main explanations have been proposed for this finding. The selective scrutiny account claims that people focus on the conclusion and only engage in logical processing if this is found to be unbelievable; while the misinterpreted necessity account claims that subjects misunderstand what is meant by logical necessity and respond on the basis of believability when indeterminate syllogisms are presented. Experiments 1 and 2 compared the predictions of these two theories by examining whether the interaction would disappear if only determinate syllogisms were used. It did, thus providing strong support for the misinterpreted necessity explanation. However, the results are also consistent with a version of the mental models theory, and so Experiment 3 was carried out to compare these two explanations. The mental models theory received strong support, as it did also in the follow-up Experiments 4 and 5. It is concluded that people try to construct a mental model of the premises but, if there is a believable conclusion consistent with the first model they produce, then they fail to construct alternative models.

The crash reduction effectiveness of a network-wide traffic police deployment system.

Random Road Watch (RRW) is a traffic policing program in operation in Queensland, Australia. It differs from conventional traffic policing in that an explicit resource management technique is used which randomly schedules low levels of police enforcement in a manner intended to provide long-term, widespread coverage of a road network and hence maximise road safety benefits. Implementation of the program studied in Queensland covered 55% of total crashes within the state. This study aimed to measure the crash effects of the RRW program in Queensland. A quasi-experimental study design was used for the evaluation incorporating Poisson regression statistical analysis techniques. Analysis of the effects of the Queensland RRW program on crash frequency has shown the program to be effective overall. Estimated program effects were largest on fatal crashes, with an estimated reduction of 31%. Estimated aggregate program crash effects reduced with crash severity and increased with time after program introduction. Crash reductions in the third year after program introduction translated into savings, at state level, of some 12% of the state's crashes of all severities and some 15% of the state's fatal road crashes. Overall, the program produced a significant 11% reduction in total crashes in areas outside of metropolitan Brisbane. The opportunity-cost benefit/cost ratio for the program was estimated to be 55:1.

Mandatory bicycle helmet use following a decade of helmet promotion in Victoria, Australia--an evaluation.

On July 1, 1990, a law requiring wearing of an approved safety helmet by all bicyclists (unless exempted) came into effect in Victoria, Australia. Some of the more important steps that paved the way for this important initiative (believed to be the first statewide legislation of its type in the world) are described, and the initiative's effects are analysed. There was an immediate increase in average helmet-wearing rates from 31% in March 1990 to 75% in March 1991, although teenagers continued to show lower rates than younger children and adults. The number of insurance claims from bicyclists killed or admitted to hospital after sustaining a head injury decreased by 48% and 70% in the first and second years after the law, respectively. Analysis of the injury data also showed a 23% and 28% reduction in the number of bicyclists killed or admitted to hospital who did not sustain head injuries in the first and second post-law years, respectively. For Melbourne, where regular annual surveys of helmet wearing have been conducted, it was possible to fit a logistic regression model that related the reduction in head injuries to increased helmet wearing. Surveys in Melbourne also indicated a 36% reduction in bicycle use by children during the first year of the law and an estimated increase in adult use of 44%.

PCDD/PCDF on land around an industrial site and identification of source.

Following the discovery of elevated levels of PCDD/PCDF in dairy products and in flue gases at a nearby industrial site, the levels and spatial distribution of these compounds on surrounding land were determined through soil monitoring. In mass terms, the levels in soil were excessive relative to the UK background but in terms of toxicity they were less significant. There were positive correlations between wind directions and deposition levels. The relative amounts of the prominent congeners/congener groups in the soil were similar to those in the flue gas but different from those in the background. An incinerator of chemical waste was identified as the likely source of the PCDD/PCDF.

A new approach to exploring biases in educational assessment.

This paper presents and illustrates an approach to the study of marking biases based on multi-sample confirmatory factor analysis. This is applied to the marks awarded by two independent markers to the final year dissertations of 197 female and 58 male psychology undergraduates. One of the two markers had supervised the work on which the dissertation was based on a one-to-one basis. The results suggest that about 30 per cent of the variance in the supervisor's mark is attributable to influences which are specific to the supervisor, orthogonal to the merit of the project as assessed by the two markers jointly, and general across each of the four marks awarded by the supervisor. The most plausible interpretation of these influences is that they represent a contamination of the supervisor's mark by personal knowledge of the student. These biases in the supervisor's marking were found to have more influence for male than for female students and to elevate the marks of males relative to those of females to a small but significant extent. It would be unwise to overgeneralize from these findings, but they demonstrate the potential value of this method of studying marking biases.

A study of two "quick-and-easy" methods of assessing individual differences in student learning.

A study is reported which examined the reliability and validity of two measures of individual differences in learning, a short form of the Approaches to Studying Inventory (Entwistle and Ramsden, 1983) and the Learning Style Inventory (Kolb, 1976). Both of these are short and easy to administer, making them attractive for use in the classroom. The Approaches to Studying Inventory was found to be a potentially useful measure: the predicted factors emerged, the scales were moderately reliable and those students adopting a deep approach to learning were more likely to be successful in their exams. The Learning Style Inventory, on the other hand, was relatively unreliable and the underlying factor structure did not correspond to what was predicted; there was, however, a correlation between scores on the active/passive dimension and academic success. It is concluded that the short form of the Approaches to Studying Inventory has some potential in assessing the learning styles of students, but that further refinement is required before it is adopted for general use.

The nature and development of student motivation.

AIM: The aim of the present series of studies was to investigate what motivates undergraduate students and how their motivation changes during their degree course. The present research investigated both subject specific and generic motivators by asking students what knowledge areas, skills and experiences were important to them. SAMPLE: Study 1: 336 prospective and current undergraduate psychology students at a university in southern England. Study 2: 57 year one psychology students from a university in the north of England. Study 3: 30 undergraduate psychology students from the university used in Study 1. METHOD: The studies used a modified version of the Radford and Holdstock (1993) scale to assess students' objectives in taking a degree programme, by rating the importance of knowledge areas, skills development and experiences. Study 1 used a cross-sectional design comparing responses of student by year of study. Study 2 compared responses of students in year one in Study 1 to students at a second university. Study 3 used a longitudinal design to investigate changes in values by year of study. RESULTS: The findings suggest that there are two types of students: those who are motivated by the discipline itself and those who are motivated by the acquisition of more general skills and experiences. The perceived importance of many aspects declines over the three years of the degree, and seems especially low in year two. However, some aspects, notably research methodology, and some skills and experiences show marked increases in the final year. CONCLUSIONS: Current theories of educational motivation need to be extended to account for the difference between subject-related and generic motives.

The interaction between speed camera enforcement and speed-related mass media publicity in Victoria, Australia.

The objective was to measure the presence of any interaction between the effect of mobile covert speed camera enforcement and the effect of intensive mass media road safety publicity with speed-related themes. During 1999, the Victoria Police varied the levels of speed camera activity substantially in four Melbourne police districts according to a systematic plan. Camera hours were increased or reduced by 50% or 100% in respective districts for a month at a time, during months when speed-related publicity was present and during months when it was absent. Monthly frequencies of casualty crashes, and their severe injury outcome, in each district during 1996-2000 were analysed to test the effects of the enforcement, publicity and their interaction. Reductions in crash frequency were associated monotonically with increasing levels of speed camera ticketing, and there was a statistically significant 41% reduction in fatal crash outcome associated with very high camera activity. High publicity awareness was associated with 12% reduction in crash frequency. The interaction between the enforcement and publicity was not statistically significant.

The effect of set size on the interpretation of quantifiers used in rating scales.

Two studies are reported which investigated how people interpret quantifiers of amount such as are commonly used in questionnaires and rating scales. The results indicated that the interpretation of certain quantifiers and rating scales. The results indicated that the interpretation of certain quantifiers varied depending on the context in which they occurred. Low-magnitude quantifiers (e g, 'few', 'several') seemed to signify a much greater proportion when they described small set sizes than when they described relatively large ones. This means that it will be virtually impossible to find quantifiers for use in rating scales which achieve the desirable property of interval scaling. Despite this, some quantifiers are clearly more consistent in their interpretation and more appropriate to use than others, and recommendations are made as to the best ones to use in different situations.

On the mental representation of conditional sentences.

Four experiments are reported which attempt to externalize subjects' mental representation of conditional sentences, using novel research methods. In Experiment 1, subjects were shown arrays of coloured shapes and asked to rate the degree to which they appeared to be true of conditional statements such as "If the figure is green then it is a triangle". The arrays contained different distributions of the four logically possible cases in which the antecedent or consequent is true or false: TT, TF, FT, and FF. For example, a blue triangle would be FT for the conditional quoted above. In Experiments 2 to 4, subjects were able to construct their own arrays to make conditional either true or false with any distribution of the four cases they wished to choose. The presence and absence of negative components was varied, as was the form of the conditional, being either "if then" as above or "only if": "The figure is green only if it is a triangle". The first findings was that subjects represent conditional in fuzzy way: conditional that include some counter-example TF cases (Experiment 1) may be rated as true, and such cases are often included when subjects construct an array to make the rule true (Experiments 2 to 4). Other findings included a strong tendency to include psychologically irrelevant FT and FF cases in constructed arrays, presumably to show that conditional statements only apply some of the time. A tendency to construct cases in line with the "matching bias" reported on analogous tasks in the literature was found, but only in Experiment 4, where the number of symbols available to construct each case was controlled. The findings are discussed in relation to the major contemporary theories of conditional reasoning based upon inference rules and mental models, neither of which can account for all the results.