Prefrontal cortex involvement in selective letter generation: A functional magnetic resonance imaging study

Cerebral responses to alternating periods of a control task and a selective letter generation paradigm were investigated with functional Magnetic Resonance Imaging (fMRI). Subjects selectively generated letters from four designated sets of six letters from the English language alphabet, with the instruction that they were not to produce letters in alphabetical order either forward or backward, repeat or alternate letters. Performance during this condition was compared with that of a control condition in which subjects recited the same letters in alphabetical order. Analyses revealed significant and extensive foci of activation in a number of cerebral regions including mid-dorsolateral frontal cortex, inferior frontal gyrus, precuneus, supramarginal gyrus, and cerebellum during the selective letter generation condition. These findings are discussed with respect to recent positron emission tomography (PET) and fMRI studies of verbal working memory and encoding/retrieval in episodic memory.

The semantic interference effect in the picture-word paradigm: An event-related fMRI study employing overt responses

We used event-related functional magnetic resonance imaging (fMRI) to investigate neural responses associated with the semantic interference (SI) effect in the picture-word task. Independent stage models of word production assume that the locus of the SI effect is at the conceptual processing level (Levelt et al. [1999]: Behav Brain Sci 22:1-75), whereas interactive models postulate that it occurs at phonological retrieval (Starreveld and La Heij [1996]: J Exp Psychol Learn Mem Cogn 22:896-918). In both types of model resolution of the SI effect occurs as a result of competitive, spreading activation without the involvement of inhibitory links. These assumptions were tested by randomly presenting participants with trials from semantically-related and lexical control distractor conditions and acquiring image volumes coincident with the estimated peak hemodynamic response for each trial. Overt vocalization of picture names occurred in the absence of scanner noise, allowing reaction time (RT) data to be collected. Analysis of the RT data confirmed the SI effect. Regions showing differential hemodynamic responses during the SI effect included the left mid section of the middle temporal gyrus, left posterior superior temporal gyrus, left anterior cingulate cortex, and bilateral orbitomedial prefrontal cortex. Additional responses were observed in the frontal eye fields, left inferior parietal lobule, and right anterior temporal and occipital cortex. The results are interpreted as indirectly supporting interactive models that allow spreading activation between both conceptual processing and phonological retrieval levels of word production. In addition, the data confirm that selective attention/response suppression has a role in resolving the SI effect similar to the way in which Stroop interference is resolved. We conclude that neuroimaging studies can provide information about the neuroanatomical organization of the lexical system that may prove useful for constraining theoretical models of word production.

The future of roads: How road agencies are facing a conflicted future

Although road construction and use provides significant economic and social benefits, its environmental impact is of growing concern. Roads are one of the greatest greenhouse gas contributors, both directly through fossil energy consumed in mining, transporting, earthworks and paving work, and through the emissions from road use by vehicles. Further,according to the Australian Government, when combined with expected population growth and internal migration,expected changes in temperature and rainfall are expected to increase road maintenance costs. This discussion paper will outline opportunities within the Australian context for reducing environmental and carbon pressure from road building, and provide a framework for considering the potential pressures that will affect the resilience of roads to the impacts of climate change and oil vulnerability.

Reducing the environmental impact of road construction

The practice of road construction and maintenance is inherently lean and efficient; a result of the economic benefits that are gained by minimizing wasted resources. In this age of conservation and environmental management, the inbuilt sustainability of existing road construction practices is being developed and extended to produce variety of environmentally sustainable options. A new concept of a “sustainable road” has emerged through both academia and industry, and is defined to be a road that is: - constructed to reduce environmental impacts; - designed to optimise the alignment (vertical and horizontal including considerations of ecological constraints and operational use by vehicles); - resilient to future environmental and economic pressures (e.g. climate change and resource scarcity); - adaptable to changing uses including increased travel volumes, greater demand for public and active (cycling and walking) transport, and; - able to harvest the energy to power itself.

Scenario planning and emerging global trends for the future of roads and automobile transport

Roads and road infrastructure will be faced with multiple challenges over the coming decades – challenges that in many ways bear little resemblance to those previously faced - and as such will require new approaches. The opportunity exists to transform the way road infrastructure is conceived and constructed, as a key part of the process of assisting society to respond to climate change and reduce other environmental pressures. Innovations in road construction, use and management in order to manage these changes can now be seen. Scenario planning is one tool that can take into account emerging challenges, develop or adopt new approaches, and thus help this transformation to occur. The paper explores scenario planning methodologies, global innovations and trends in road construction and maintenance and the findings from stakeholder workshops in Brisbane and Perth. It highlights key opportunities for road agencies to use scenarios to enable planning that, in the face of future uncertainties, facilitates appropriate responses.

The impact of project announcements on property values: An empirical analysis

The study examines the property value impacts of an announcement of a project which has potential environmental impacts as distinct from other studies that address costs associated with under-construction and the operating impacts of developments. The hypothesis is that the announcement of a proposed project with potential environmental impact creates uncertainty in the property market of the affected area, and this impact is greater on properties closer to the project than those farther from it. The results of the study confirm the hypothesis and indicate that the marginal willingness to pay for properties within a 5 km distance declined by AU$17,020 per km proximity to the proposed heavy vehicle route, after the proposed route was announced. The results support the need for more holistic measurement of cost–benefit analysis of projects and provide a basis for improved consideration by policy makers of the rights of affected parties.

If you don’t know, you can’t help: A practical guide for alcohol and other drug screening in psychological services

Alcohol is implicated in over 60 diseases and injuries and accounted for 6.2 per cent of all male deaths globally in 2004 (WHO, 2011). Alcohol and other drug (AOD) abuse causes significant individual, family and social harms at all age levels and across all socioeconomic groups. These may result from intoxication (e.g., overdose, vulnerability to physical injury/trauma or death, consequences of impulsive behaviour, aggression and driving under the influence) and longer-term consequences (e.g., alcohol or drug-related brain injury, cardiovascular and liver diseases, blood borne viruses e.g., Chikritzhs et al., 2003, Roxburgh et al., 2013). Mental health problems may be triggered or exacerbated, and family breakdown, poor self-esteem, legal issues and lack of community engagement may also be evident. Despite the prevalence of substance use disorders and evident consequences for the individual, family and wider community, it would seem that health professionals, including psychologists, are reluctant to ask about substance use.

Estate contestation in Australia: An empirical study of a year of case law

This article reports on a study which reviewed all publicly available succession law judgments in Australia during a 12-month period. The article begins with a brief overview of the relevant Australian law and the method adopted for the case review to provide some context for the analysis that follows. It then shifts to its primary objective: to provide an overview of Australian estate litigation during this period with a particular focus on analysing the family provision contests, which comprised over half the cases in the sample. The article examines how many estates were subject to family provision claims, who were contesting them, and to what extent those challenges were successful. The article also considers variation in estate litigation across Australian states and the impact of estate size on contests. It concludes by identifying the themes that emerged from these judicial cases and outlines their significance for law and practice reform.

Key opportunities for the future of roads to contribute to Australia's climate change response

Road agencies face growing pressure to respond to a range of issues associated with climate change and the reliance on fossil fuels. A key part of this response will be to reduce the dependency on fossil fuel based energy (and the associated greenhouse gas emissions) of transport, both vehicles and infrastructure. This paper presents findings of investigations into three key areas of innovative technologies and processes, namely the inclusion of onsite renewable energy generation technologies as part of road and transport infrastructure, the potential for automated motorways to reduce traffic fuel consumption (referred to as 'Smart Roads'), and the reduction of energy demand from route and signal lighting. The paper then concludes with the recommendation for the engineering profession to embrace sustainability performance assessment and rating tools as the basis for enhancing and communicating the contribution to Australia's response to climate change. Such tools provide a rigorous structure that can standardise approaches to key issues across entire sectors and provide clarity on the evidence required to demonstrate leading performance. The paper has been developed with funding and support provided by Australia's Sustainable Built Environment National Research Centre (SBEnrc), working with partners including Main Roads Western Australia, NSW Roads and Maritime Services, Queensland Department of Transport and Main Roads, John Holland Group, the Infrastructure Sustainability Council of Australia, Roads Australia, and the CRC for Low Carbon Living.

WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk

We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ~2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of -0.11 standard deviations [SD] per C allele, P = 6.2×10-9). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (-0.14 SD per C allele, P = 2.3×10-12, and -0.16 SD per G allele, P = 1.2×10-15, respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3×10-9), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9×10-6 and rs2707466: OR = 1.22, P = 7.2×10-6). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16-/- mice had 27% (P<0.001) thinner cortical bones at the femur midshaft, and bone strength measures were reduced between 43%-61% (6.5×10-13<P<5.9×10-4) at both femur and tibia, compared with their wild-type littermates. Natural variation in humans and targeted disruption in mice demonstrate that WNT16 is an important determinant of CBT, BMD, bone strength, and risk of fracture. © 2012 Zheng et al.

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.

The effect of HLA-DR on susceptibility to rheumatoid arthritis is influenced by the associated lymphotoxin α-tumor necrosis factor haplotype

Objective. HLA-DRB1, a major genetic determinant of susceptibility to rheumatoid arthritis (RA), is located within 1,000 kb of the gene encoding tumor necrosis factor (TNF). Because certain HLA-DRB1*04 subtypes increase susceptibility to RA, investigation of the role of the TNF gene is complicated by linkage disequilibrium (LD) between TNF and DRB1 alleles. By adequately controlling for this LD, we aimed to investigate the presence of additional major histocompatibility complex (MHC) susceptibility genes. Methods. We identified 274 HLA-DRB1*04-positive cases of RA and 271 HLA-DRB1*04-positive population controls. Each subject was typed for 6 single-nucleotide polymorphisms within a 4.5-kb region encompassing TNF and lymphotoxin a (LTA). LTA-TNF haplotypes in these unrelated individuals were determined using a combination of family data and the PHASE software program. Results. Significant differences in LTA-TNF haplotype frequencies were observed between different subtypes of HLA-DRB1*04. The LTA-TNF haplotypes observed were very restricted, with only 4 haplotypes constituting 81% of all haplotypes present. Among individuals carrying DRB1*0401, the LTA-TNF 2 haplotype was significantly underrepresented in cases compared with controls (odds ratio 0.5 [95% confidence interval 0.3-0.8], P = 0.007), while in those with DRB1*0404, the opposite effect was observed (P = 0.007). Conclusion. These findings suggest that the MHC contains genetic elements outside the LTA-TNF region that modify the effect of HLA-DRB1 on susceptibility to RA.

Will-making prevalence and patterns in Australia: Keeping it in the family

This article provides evidence of the prevalence of wills and the principles underpinning the intended distribution of estates in Australia. Intentions around wealth transfers and the social norms that underpin them occur in the context of predicted extensive intergenerational transfers from the ageing baby boomer generation, policies of self provision and user pays for care in old age, broader views on what constitutes ‘family’, the increased importance of the not-for-profit sector in the delivery of services, and the related need for philanthropy. A national telephone survey conducted in 2012 with 2,405 respondents aged 18 and over shows that wills are predominantly used to distribute assets to partners and/or equally to immediate descendants. There is little evidence that will makers are recognising a wider group of relationships, obligations and entitlements outside the traditional nuclear family, or that wills are being replaced by other mechanisms of wealth transfer. Only a minority consider bequests to charities as important. These findings reflect current social norms about entitlements to ‘family’ money, a narrow view of what and who constitutes ‘family’, limited obligation for testators to recompense individuals or organisations for care and support provided, and limited commitment to charitable organisations and civil society.

Comparison of two pressurisers for cementation of the proximal femur

PURPOSE: To compare pressures generated by 2 different cement pressurisers at various locations in the proximal femur. METHODS: Two groups of 5 synthetic femurs were used, and 6 pressure sensors were placed in the femur at 20-mm intervals proximally to distally. Cement was filled into the femoral canal retrogradely using a cement gun with either the half-moon pressuriser or the femoral canal pressuriser. Maximum pressures and pressure time integrals (cumulative pressure over time) of the 2 pressurisers were compared. RESULTS: At all sensors, the half-moon pressuriser produced higher maximum pressures and pressure time integrals than the femoral canal pressuriser, but the difference was significant only at sensor 1 (proximal femur). This may result in reduced cement interdigitation in the proximal femur. CONCLUSION: The half-moon pressuriser produced higher maximum cementation pressures and pressure time integrals than the femoral canal pressuriser in the proximal femur region, which is critical for rotational stability of the implant and prevention of implant fracture. KEYWORDS: arthroplasty, replacement, hip; bone cements; femur

5-year Chlamydia vaccination programme could reverse disease-related koala population decline: Predictions from a mathematical model using field data

BACKGROUND Many koala populations around Australia are in serious decline, with a substantial component of this decline in some Southeast Queensland populations attributed to the impact of Chlamydia. A Chlamydia vaccine for koalas is in development and has shown promise in early trials. This study contributes to implementation preparedness by simulating vaccination strategies designed to reverse population decline and by identifying which age and sex category it would be most effective to target. METHODS We used field data to inform the development and parameterisation of an individual-based stochastic simulation model of a koala population endemic with Chlamydia. The model took into account transmission, morbidity and mortality caused by Chlamydia infections. We calibrated the model to characteristics of typical Southeast Queensland koala populations. As there is uncertainty about the effectiveness of the vaccine in real-world settings, a variety of potential vaccine efficacies, half-lives and dosing schedules were simulated. RESULTS Assuming other threats remain constant, it is expected that current population declines could be reversed in around 5-6 years if female koalas aged 1-2 years are targeted, average vaccine protective efficacy is 75%, and vaccine coverage is around 10% per year. At lower vaccine efficacies the immunological effects of boosting become important: at 45% vaccine efficacy population decline is predicted to reverse in 6 years under optimistic boosting assumptions but in 9 years under pessimistic boosting assumptions. Terminating a successful vaccination programme at 5 years would lead to a rise in Chlamydia prevalence towards pre-vaccination levels. CONCLUSION For a range of vaccine efficacy levels it is projected that population decline due to endemic Chlamydia can be reversed under realistic dosing schedules, potentially in just 5 years. However, a vaccination programme might need to continue indefinitely in order to maintain Chlamydia prevalence at a sufficiently low level for population growth to continue.