Common Alzheimer's disease risk variant within the CLU gene affects white matter microstructure in young adults

There is a strong genetic risk for late-onset Alzheimer's disease (AD), but so far few gene variants have been identified that reliably contribute to that risk. A newly confirmed genetic risk allele C of the clusterin (CLU) gene variant rs11136000 is carried by ~88% of Caucasians. The C allele confers a 1.16 greater odds of developing late-onset AD than the T allele. AD patients have reductions in regional white matter integrity. We evaluated whether the CLU risk variant was similarly associated with lower white matter integrity in healthy young humans. Evidence of early brain differences would offer a target for intervention decades before symptom onset. We scanned 398 healthy young adults (mean age, 23.6 ± 2.2 years) with diffusion tensor imaging, a variation of magnetic resonance imaging sensitive to white matter integrity in the living brain. We assessed genetic associations using mixed-model regression at each point in the brain to map the profile of these associations with white matter integrity. Each C allele copy of the CLUvariant was associated with lower fractional anisotropy-a widely accepted measure of white matter integrity-in multiple brain regions, including several known to degenerate in AD. These regions included the splenium of the corpus callosum, the fornix, cingulum, and superior and inferior longitudinal fasciculi in both brain hemispheres. Young healthy carriers of the CLU gene risk variant showed a distinct profile of lower white matter integrity that may increase vulnerability to developing AD later in life.

Brain structure in healthy adults is related to serum transferrin and the H63D polymorphism in the HFE gene

Control of iron homeostasis is essential for healthy central nervous system function: iron deficiency is associated with cognitive impairment, yet iron overload is thought to promote neurodegenerative diseases. Specific genetic markers have been previously identified that influence levels of transferrin, the protein that transports iron throughout the body, in the blood and brain. Here, we discovered that transferrin levels are related to detectable differences in the macro- and microstructure of the living brain. We collected brain MRI scans from 615 healthy young adult twins and siblings, of whom 574 were also scanned with diffusion tensor imaging at 4 Tesla. Fiber integrity was assessed by using the diffusion tensor imaging-based measure of fractional anisotropy. In bivariate genetic models based on monozygotic and dizygotic twins, we discovered that partially overlapping additive genetic factors influenced transferrin levels and brain microstructure. We also examined common variants in genes associated with transferrin levels, TF and HFE, and found that a commonly carried polymorphism (H63D at rs1799945) in the hemochromatotic HFE gene was associated with white matter fiber integrity. This gene has a well documented association with iron overload. Our statistical maps reveal previously unknown influences of the same gene on brain microstructure and transferrin levels. This discovery may shed light on the neural mechanisms by which iron affects cognition, neurodevelopment, and neurodegeneration.

Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity

Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer's disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, highangular resolution diffusion MRI. We adapted GWASs to screen the brain's connectivity pattern, allowing us to discover genetic variants that affect the human brain's wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer's disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism (MACROD2), development (NEDD4), and mental retardation (UBE2A) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases.

New England Youth Speeding Project: A pilot study of young drivers and risky driving: Effective strategies for preventing speeding amongst young Australians aged 16-25 years in the New England Region

Young Australian drivers aged 17 – 25 years are overwhelmingly represented in road fatalities where speed is a factor. In the combined LGAs of Armidale Dumaresq, Guyra, Uralla and Walcha in the 5 years 1999-2003 inclusive, 43% of speeding related casualty crashes involved a young driver aged less than 25 years. This is despite the fact that the 17-25 age group account for only 25% of the driving population in this area. Young male drivers account for the majority of these crashes and also tend to have a higher number of driving offences and accrue more penalties for road traffic offences, especially speeding. By analysing data from questionnaires by male and female participants this research project has been able to evaluate road safety advertisements to determine which ones are most effective to young drivers, what features of these advertisements are effective, how males differ from females in their receptiveness and preferences for road safety advertisements and specifically how to target young people especially young men in conveying road safety messages. Finally this research project has identified factors that are important in the production of media road safety advertisements and has made recommendations for how best to convey effective road safety messages to young Australian drivers in rural areas.

Disorderly categories in picture postcards from colonial Papua and New Guinea

At the turn of the century in Melbourne, a notice typed on the verso of a postcard stated that the South Yarra Baptist Young Men's class was meeting on the following Sunday at 2.45 p.m. The card, published in the United Kingdom, was numbered 51828 in the Valentine series of Papuan postcards.1 The image, a photograph of Hanuabada village taken in the early 1880s, and the text, written early in 1900, are contradictory and constitute separate realms of evidence that invite a renegotiation of meaning, analysis, and interpretation of the relationships between images, tourism, colonial rule, and ethnographic knowing. The visual evidence suggests the postcard may have played an ethnographic, educative role in the public understanding of Papua, which had just become an Australian Territory and was not yet well known. It is also suggestive of educative roles related to mission endeavours, subimperialist ambitions and the new tourist traffic through the ports of Port Moresby, Samarai, and Rabaul.

Substance misuse in patients with schizophrenia : Epidemiology and management

Substance misuse in individuals with schizophrenia is very common, especially in young men, in communities where use is frequent and in people receiving inpatient treatment. Problematic use occurs at very low intake levels, so that most affected people are not physically dependent (with the exception of nicotine). People with schizophrenia and substance misuse have poorer symptomatic and functional outcomes than those with schizophrenia alone. Unless there is routine screening, substance misuse is often missed in assessments. Service systems tend to be separated, with poor inter-communication, and affected patients are often excluded from services because of their comorbidity. However, effective management of these disorders requires a fully integrated approach because of the close inter-relationship of the disorders. Use of atypical antipsychotics may be especially important in this population because of growing evidence (especially on clozapine and risperidone) that nicotine smoking, alcohol misuse and possibly some other substance misuse is reduced. Several pharmacotherapies for substance misuse can be used safely in people with schizophrenia, but the evidence base is small and guidelines for their use are necessarily derived from experience in the general population.

Plasma ATP concentration and venous oxygen content in the forearm during dynamic handgrip exercise

Background: It has been proposed that adenosine triphosphate (ATP) released from red blood cells (RBCs) may contribute to the tight coupling between blood flow and oxygen demand in contracting skeletal muscle. To determine whether ATP may contribute to the vasodilatory response to exercise in the forearm, we measured arterialised and venous plasma ATP concentration and venous oxygen content in 10 healthy young males at rest, and at 30 and 180 seconds during dynamic handgrip exercise at 45% of maximum voluntary contraction (MVC). Results: Venous plasma ATP concentration was elevated above rest after 30 seconds of exercise (P < 0.05), and remained at this higher level 180 seconds into exercise (P < 0.05 versus rest). The increase in ATP was mirrored by a decrease in venous oxygen content. While there was no significant relationship between ATP concentration and venous oxygen content at 30 seconds of exercise, they were moderately and inversely correlated at 180 seconds of exercise (r = -0.651, P = 0.021). Arterial ATP concentration remained unchanged throughout exercise, resulting in an increase in the venous-arterial ATP difference. Conclusions: Collectively these results indicate that ATP in the plasma originated from the muscle microcirculation, and are consistent with the notion that deoxygenation of the blood perfusing the muscle acts as a stimulus for ATP release. That ATP concentration was elevated just 30 seconds after the onset of exercise also suggests that ATP may be a contributing factor to the blood flow response in the transition from rest to steady state exercise.

Selective effects of acute exercise and breakfast interventions on mood and motivation to eat

The effects of exercise and breakfast manipulations on mood and motivation to eat were assessed in 11 healthy females who were regular exercisers and habitual breakfast eaters. The study involved a two by two repeated-measures design, with exercise (or no exercise) and a high-energy breakfast (or low-energy breakfast) as the repeated measures. The exercise or no-exercise session (0800 h) was followed by consumption of the low- or high-energy breakfast (0900 h). An ad libitum lunch test meal was provided 4 hours after the beginning of the exercise session (1200 h). Mood and motivation to eat were continuously tracked from 0800 until 1700 h by an electronic appetite ratings system (EARS). In general, morning subjective mood states (e.g., contentment) were significantly lower in the low-energy breakfast condition, but exercise reversed this effect. Exercise also significantly decreased feelings of lethargy, independent of the breakfast condition. Desire-to-eat and fullness ratings were significantly increased in the low-energy breakfast and high-energy breakfast conditions, respectively. Impairments of mood disappeared in the afternoon after consumption of an ad libitum lunch. In these healthy young adults, the condition inducing the largest energy deficit (exercise and low-energy breakfast) was not associated with the lowest mental states.

Mild systemic hypoxia and photopic visual field sensitivity

Purpose: Flickering stimuli increase the metabolic demand of the retina,making it a sensitive perimetric stimulus to the early onset of retinal disease. We determine whether flickering stimuli are a sensitive indicator of vision deficits resulting from to acute, mild systemic hypoxia when compared to standard static perimetry. Methods: Static and flicker visual perimetry were performed in 14 healthy young participants while breathing 12% oxygen (hypoxia) under photopic illumination. The hypoxia visual field data were compared with the field data measured during normoxia. Absolute sensitivities (in dB) were analysed in seven concentric rings at 1°, 3°, 6°, 10°, 15°, 22° and 30° eccentricities as well as mean defect (MD) and pattern defect (PD) were calculated. Preliminary data are reported for mesopic light levels. Results: Under photopic illumination, flicker and static visual field sensitivities at all eccentricities were not significantly different between hypoxia and normoxia conditions. The mean defect and pattern defect were not significantly different for either test between the two oxygenation conditions. Conclusion: Although flicker stimulation increases cellular metabolism, flicker photopic visual field impairment is not detected during mild hypoxia. These findings contrast with electrophysiological flicker tests in young participants that show impairment at photopic illumination during the same levels of mild hypoxia. Potential mechanisms contributing to the difference between the visual fields and electrophysiological flicker tests including variability in perimetric data, neuronal adaptation and vascular autoregulation, are considered. The data have implications for the use of visual perimetry in the detection of ischaemic/hypoxic retinal disorders under photopic and mesopic light levels.

Sacked! Workplace dismissals amongst youth employees

Limited academic attention has been afforded to young workers relative to their adult counterparts. This study addresses a phase of the employment relationship for young people that is very infrequently examined - during or around the time when the relationship ends. It examines the relative frequency of different forms of dismissal and the circumstances preceding the dismissals via a content analysis of 1259 cases of employee enquiries to a community advocacy organisation in Australia. Results indicate that dismissal was most commonly associated with bullying, harassment, and taking personal leave. Young men, compared to young women, were disproportionately likely to report allegations of misconduct as preceding dismissal, while females experienced higher rates of sexual harassment and discrimination. The research highlights the types and circumstances of dismissal across a range of employment contexts and reveals the complexities of youth employment relationships which may differ from those of the general workforce.

Offending Youth : Crime, Sex and Justice

Rates of female delinquency, especially for violent crimes, are increasing in most common law countries. At the same time the growth in cyber-bullying, especially among girls, appears to be a related global phenomenon. While the gender gap in delinquency is narrowing in Australia, United States, Canada and the United Kingdom, boys continue to dominate the youth who commit crime and have a virtual monopoly over sexually violent crimes. Indigenous youth continue to be vastly over-represented in the juvenile justice system in every Australian jurisdiction. The Indigenisation of delinquency is a persistent problem in other countries such as Canada and New Zealand. Young people who gather in public places are susceptible to being perceived as somehow threatening or riotous, attracting more than their share of public order policing. Professional football has been marred by repeated scandals involving sexual assault, violence and drunkenness. Given the cultural significance of footballers as role models to thousands, if not millions, of young men around the world, it is vitally important to address this problem. Offending Youth explores these key contemporary patterns of delinquency, the response to these by the juvenile justice agencies and moreover what can be done to address these problems. The book also analyses the major policy and legislative changes from the nineteenth to twenty first centuries, chiefly the shift the penal welfarism to diversion and restorative justice. Using original cases studied by Carrington twenty years ago, Offending Youth illustrates how penal welfarism criminalised young people from socially marginal backgrounds, especially Aboriginal children, children from single parent families, family-less children, state wards and young people living in poverty or in housing commission estates. A number of inquiries in Australia and the United Kingdom have since established that children committed to these institutions, supposedly for their own good, experienced systemic physical, sexual and psychological abuse during their institutionalisation. The book is dedicated to the survivors of these institutions who only now are receiving official recognition of the injustices they suffered. The underlying philosophy of juvenile justice has fundamentally shifted away from penal welfarism to embrace positive policy responses to juvenile crime, such as youth conferencing, cautions, warnings, restorative justice, circle sentencing and diversion examined in the concluding chapter. Offending Youth is aimed at a broad readership including policy makers, juvenile justice professionals, youth workers, families, teachers, politicians as well as students and academics in criminology, policing, gender studies, masculinity studies, Indigenous studies, justice studies, youth studies and the sociology of youth and deviance more generally.-- [from publisher website]

Effects of enhanced somatosensory information on postural stability in older people and people with Parkinson’s disease

The somatosensory system plays an important role in balance control and age-related changes to this system have been implicated in falls. Parkinson’s disease (PD) is a chronic and progressive disease of the brain, characterized by postural instability and gait disturbance. Previous research has shown that deficiencies in somatosensory feedback may contribute to the poorer postural control demonstrated by PD individuals. However, few studies have comprehensively explored differences in somatosensory function and postural control between PD participants and healthy older individuals. The soles of the feet contain many cutaneous mechanoreceptors that provide important somatosensory information sources for postural control. Different types of insole devices have been developed to enhance this somatosensory information and improve postural stability, but these devices are often too complex and expensive to integrate into daily life. Textured insoles provide a more passive intervention that may be an inexpensive and accessible means to enhance the somatosensory input from the plantar surface of the feet. However, to date, there has been little work conducted to test the efficacy of enhanced somatosensory input induced by textured insoles in both healthy and PD populations during standing and walking. Therefore, the aims of this thesis were to determine: 1) whether textured insole surfaces can improve postural stability by enhancing somatosensory information in younger and older adults, 2) the differences between healthy older participants and PD participants for measures of physiological function and postural stability during standing and walking, 3) how changes in somatosensory information affect postural stability in both groups during standing and walking; and 4), whether textured insoles can improve postural stability in both groups during standing and walking. To address these aims, Study 1 recruited seven older individuals and ten healthy young controls to investigate the effects of two textured insole surfaces on postural stability while performing standing balance tests on a force plate. Participants were tested under three insole surface conditions: 1) barefoot; 2) standing on a hard textured insole surface; and 3), standing on a soft textured insole surface. Measurements derived from the centre of pressure displacement included the range of anterior-posterior and medial-lateral displacement, path length and the 90% confidence elliptical area (C90 area). Results of study 1 revealed a significant Group*Surface*Insole interaction for the four measures. Both textured insole surfaces reduced postural sway for the older group, especially in the eyes closed condition on the foam surface. However, participants reported that the soft textured insole surface was more comfortable and, hence, the soft textured insoles were adopted for Studies 2 and 3. For Study 2, 20 healthy older adults (controls) and 20 participants with Parkinson’s disease were recruited. Participants were evaluated using a series of physiological assessments that included touch sensitivity, vibratory perception, and pain and temperature threshold detection. Furthermore, nerve function and somatosensory evoked potentials tests were utilized to provide detailed information regarding peripheral nerve function for these participants. Standing balance and walking were assessed on different surfaces using a force plate and the 3D Vicon motion analysis system, respectively. Data derived from the force plate included the range of anterior-posterior and medial-lateral sway, while measures of stride length, stride period, cadence, double support time, stance phase, velocity and stride timing variability were reported for the walking assessment. The results of this study demonstrated that the PD group had decrements in somatosensory function compared to the healthy older control group. For electrodiagnosis, PD participants had poorer nerve function than controls, as evidenced by slower nerve conduction velocities and longer latencies in sural nerve and prolonged latency in the P37 somatosensory evoked potential. Furthermore, the PD group displayed more postural sway in both the anterior-posterior and medial-lateral directions relative to controls and these differences were increased when standing on a foam surface. With respect to the gait assessment, the PD group took shorter strides and had a reduced stride period compared with the control group. Furthermore, the PD group spent more time in the stance phase and had increased cadence and stride timing variability than the controls. Compared with walking on the firm surface, the two groups demonstrated different gait adaptations while walking on the uneven surface. Controls increased their stride length and stride period and decreased their cadence, which resulted in a consistent walking velocity on both surfaces. Conversely, while the PD patients also increased their stride period and decreased their cadence and stance period on the uneven surface, they did not increase their stride length and, hence walked slower on the uneven surface. In the PD group, there was a strong positive association between decreased somatosensory function and decreased clinical balance, as assessed by the Tinetti test. Poorer somatosensory function was also strongly positively correlated with the temporospatial gait parameters, especially shorter stride length. Study 3 evaluated the effects of manipulating the somatosensory information from the plantar surface of the feet using textured insoles in the same populations assessed in Study 2. For this study, participants performed the standing and walking balance tests under three footwear conditions: 1) barefoot; 2) with smooth insoles; and 3), with textured insoles. Standing balance and walking were evaluated using a force plate and a Vicon motion analysis system and the data were analysed in the same way outlined for Study 2. The findings showed that the smooth and textured insoles caused different effects on postural control during both the standing and walking trials. Both insoles decreased medial-lateral sway to the same level on the firm surface. The greatest benefits were observed in the PD group while wearing the textured insole. When standing under a more challenging condition on the foam surface with eyes closed, only the textured insole decreased medial-lateral sway in the PD group. With respect to the gait trials, both insoles increased walking velocity, stride length and stride time and decreased cadence, but these changes were more pronounced for the textured insoles. The effects of the textured insoles were evident under challenging conditions in the PD group and increased walking velocity and stride length, while decreasing cadence. Textured insoles were also effective in reducing the time spent in the double support and stance phases of the gait cycle and did not increase stride timing variability, as was the case for the smooth insoles for the PD group. The results of this study suggest that textured insoles, such as those evaluated in this research, may provide a low-cost means of improving postural stability in high-risk groups, such as people with PD, which may act as an important intervention to prevent falls.

Pregnancy loss and mental health

Between 8 and 20 percent of depression in young men and women aged 18-23 is associated with pregnancy loss, according to a recent analysis of the 30 year Mater Hospital longitudinal study of mothers and children. Dr Kaeleen Dingle from the University of Queensland explains the study and discusses the implications for both men and women.

Alcohol-related violence presenting to the emergency department : is ‘glassing’ the big issue?

Objective Describe the characteristics of patients presenting to Emergency Departments (EDs) within Queensland, Australia with injuries due to assault with a glass implement (‘glassing’) and to set this within the broader context of presentations due to alcohol-related violence. Methods Analysis of prospectively collected ED injury surveillance data collated by the Queensland Injury Surveillance Unit (QISU) between 1999 and 2011. Cases of injury due to alcohol-related violence were identified and analysed using coded fields supplemented with qualitative data contained within the injury description text. Descriptive statistics were used to assess the characteristics of injury presentations due to alcohol-related violence. Violence included interpersonal violence and aggression (verbal aggression and object violence). Results A total of 4629 cases were studied. The study population was predominantly male (72%) and aged 18 to 24 (36%), with males in this age group comprising more than a quarter of the study population (28%). Nine percent of alcohol-related assault injuries were a consequence of ‘glassing’. The home was the most common location for alcohol-related violence (31%) and alcohol-related ‘glassings’ (33%). Overall, the most common glass object involved was a bottle (75%), however, within licensed venues an even mix of a drinking glass (44%) and glass bottle (45%) were identified. Conclusions Contrary to public perception generated by media, ‘glassing’ incidents, particularly at licensed venues, constitute a relatively small proportion of all alcohol-related violence. The current study highlights the predominance of young men injured following alcohol-related violence, demonstrating a key focus area within the population for aiming prevention strategies.

Analysis of Sdhd and Mmp12 in an affected solar keratosis and control cohort

The incidence of Squamous Cell Carcinoma (SCG) is growing in certain populations to the extent that it is now the most common skin lesion in young men and women in high ultraviolet exposure regions such as Queensland. In terms of incidence up to 40% of the Australian population over 40 years of age is thought to possess the precancerous Solar Keratosis (SK) lesion and with a small, but significant, chance of progression into SCC, understanding the genetic events that play a role in this process is essential. The major aims of this study were to analyse whole blood derived samples for DNA aberrations in genes associated with tumour development and cellular maintenance, with the ultimate aim of identifying genes associated with non-melanoma skin cancer development. More specifically the first aim of this project was to analyse the SDHD and MMP12 genes via Dual-Labelled Probe Real-Time PCR for copy number aberrations in an affected Solar Keratosis and control cohort. It was found that 12 samples had identifiable copy-number aberrations in either the SDHD or MMP12 gene (this means that a genetic section of either of these two genes is aberrantly amplified or deleted), with five of the samples exhibiting aberrations in both genes. The significance of this study is the contribution to the knowledge of the genetic pathways that are malformed in the progression and development of the pre-cancerous skin lesion Solar Keratosis. © 2008 Springer Science+Business Media, LLC.