Quantification of gammaH2AX foci in response to ionising radiation

DNA double-strand breaks (DSBs), which are induced by either endogenous metabolic processes or by exogenous sources, are one of the most critical DNA lesions with respect to survival and preservation of genomic integrity. An early response to the induction of DSBs is phosphorylation of the H2A histone variant, H2AX, at the serine-139 residue, in the highly conserved C-terminal SQEY motif, forming gammaH2AX(1). Following induction of DSBs, H2AX is rapidly phosphorylated by the phosphatidyl-inosito 3-kinase (PIKK) family of proteins, ataxia telangiectasia mutated (ATM), DNA-protein kinase catalytic subunit and ATM and RAD3-related (ATR)(2). Typically, only a few base-pairs (bp) are implicated in a DSB, however, there is significant signal amplification, given the importance of chromatin modifications in DNA damage signalling and repair. Phosphorylation of H2AX mediated predominantly by ATM spreads to adjacent areas of chromatin, affecting approximately 0.03% of total cellular H2AX per DSB(2,3). This corresponds to phosphorylation of approximately 2000 H2AX molecules spanning approximately 2 Mbp regions of chromatin surrounding the site of the DSB and results in the formation of discrete gammaH2AX foci which can be easily visualized and quantitated by immunofluorescence microscopy(2). The loss of gammaH2AX at DSB reflects repair, however, there is some controversy as to what defines complete repair of DSBs; it has been proposed that rejoining of both strands of DNA is adequate however, it has also been suggested that re-instatement of the original chromatin state of compaction is necessary(4-8). The disappearence of gammaH2AX involves at least in part, dephosphorylation by phosphatases, phosphatase 2A and phosphatase 4C(5,6). Further, removal of gammaH2AX by redistribution involving histone exchange with H2A.Z has been implicated(7,8). Importantly, the quantitative analysis of gammaH2AX foci has led to a wide range of applications in medical and nuclear research. Here, we demonstrate the most commonly used immunofluorescence method for evaluation of initial DNA damage by detection and quantitation of gammaH2AX foci in gamma-irradiated adherent human keratinocytes(9)

Out of the Box Festival for 3 to 8 year olds (Artistic Director)

The Out of the Box Festival was founded in 1994 by the Queensland Performing Arts Centre and has been held biannually ever since both within and around the centre in what is now known as the Cultural Precinct at Southbank. It is unique in Australia in that it caters entirely to children aged 8 years and under, with a highly curated program of ticketed performance events, workshops and free arts-based events. It is attended by school and kindergarten groups and by families, and besides engaging children in high quality arts experiences, the festival is also a platform for advocating the developmental and educational benefits of the arts for children. Dr Mark Radvan was the artistic director of the 2008 festival, with responsibility for developing the curatorial direction of each festival, for creating and programming its events, and for working with festival partners The Queensland Art Gallery, The Queensland Museum, The State Library of Queensland and The Queensland Theatre Company. Radvan designed selected and commissioned works to demonstrate how the arts create memorable, celebratory and immersive experiences that stimulate children’s imagination, their curiosity and confidence about the material world and the cultures of its people. A core event was an outdoor music and dance performance space featuring entirely Indigenous performers that was not only the beating heart of the festival, but served to underlie the importance of mainstreaming awareness of our first peoples in the increasingly culturally diverse communities of children attending.

Destined to design? How and why Australian women choose to study industrial design

Despite over three decades of legislation and initiatives designed to tackle the traditional gender divide in the science, technology and design fields, only a quarter of the registered architects in Australia are women. There are no statistics available for other design disciplines, with little known about why women choose design as a career path and who or what influences this decision. This qualitative research addresses this knowledge gap, through semi-structured in-depth interviews conducted with 19 Australian women who completed an industrial (product) design degree. Thematic analysis revealed three key themes: childhood aptitude and exposure; significant experiences and people; and design as a serendipitous choice. The findings emphasise the importance of early exposure to design as a potential career choice, highlighting the critical role played by parents, teachers, professionals and social networks.

Pituitary volume and early treatment response in drug-naïve first-episode psychosis patients

BACKGROUND: An early response to antipsychotic treatment in patients with psychosis has been associated with a better course and outcome. However, factors that predict treatment response are not well understood. The onset of schizophrenia and related disorders has been associated with increased levels of stress and hyper-activation of the hypothalamic-pituitary-adrenal (HPA) axis. This study examined whether pituitary volume at the onset of psychosis may be a potential predictor of early treatment response in first-episode psychosis (FEP) patients. METHODS: We investigated the relationship between baseline pituitary volume and symptomatic treatment response over 12 weeks using mixed model analysis in a sample of 42 drug-naïve or early treated FEP patients who participated in a controlled dose-finding study of quetiapine fumarate. Logistic regression was used to examine predictors of treatment response. Pituitary volume was measured from magnetic resonance imaging scans that were obtained upon entry into the trial. RESULTS: Larger pituitary volume was associated with less improvement in overall psychotic symptoms (Brief Psychiatric Rating Scale (BPRS) P=0.031) and positive symptoms (BPRS positive symptom subscale P=0.010). Regardless of gender, patients with a pituitary volume at the 25th percentile (413 mm(3)) were approximately three times more likely to respond to treatment by week 12 than those at the 75th percentile (635 mm(3)) (odds ratio=3.07, CI: 0.90-10.48). CONCLUSION: The association of baseline pituitary volumes with early treatment response highlights the importance of the HPA axis in emerging psychosis. Potential implications for treatment strategies in early psychosis are discussed.

Optimum position of steel outrigger system for high rise composite buildings subjected to wind loads

The responses of composite buildings under wind loads clearly become more critical as the building becomes taller, less stiff and more lightweight. When the composite building increases in height, the stiffness of the structure becomes more important factor and introduction to belt truss and outrigger system is often used to provide sufficient lateral stiffness to the structure. Most of the research works to date is limited to reinforced concrete building with outrigger system of concrete structure, simple building plan layout, single height of a building, one direction wind and single level of outrigger arrangement. There is a scarcity in research works about the effective position of outrigger level on composite buildings under lateral wind loadings when the building plan layout, height and outrigger arrangement are varied. The aim of this paper is to determine the optimum location of steel belt and outrigger systems by using different arrangement of single and double level outrigger for different size, shape and height of composite building. In this study a comprehensive finite element modelling of composite building prototypes is carried out, with three different layouts (Rectangular, Octagonal and L shaped) and for three different storey (28, 42 and 57-storey). Models are analysed for dynamic cyclonic wind loads with various combination of steel belt and outrigger bracings. It is concluded that the effectiveness of the single and double level steel belt and outrigger bracing are varied based on their positions for different size, shape and height of composite building.

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.

War and Revolution in St. Petersburg : Modernist Links in the Poetry of Edith Södergran and Anna Andreevna Akhmatova

Important modernists in their own countries, Anna Akhmatova and Edith Södergran are compared in this dissertation as poets whose poetry reflects the climactic events of the early twentieth century in Finland and Russia. A comparatist, biographical and historical approach is used to uncover the circumstances surrounding these events. First the poets’ early works are reviewed and their contemporaries are mentioned to provide a poetic context. Then a brief review of Finnish and Russian history situates them historically. Next, the rich literary diversity of St. Petersburg’s Silver Age is presented and the work of the poets is viewed in context before their poetry is compared, as the First World War, October Revolution and subsequent Finnish Civil War impact their writing. While biography is not the primary focus, it becomes important as inevitably the writers’ lives are changed by cataclysmic events and the textual analysis of the poems in Swedish, Russian and English shows the impact of war on their poetry. These two poets have not been compared before in a critical review in English and this work contributes to needed work in English. They share certain common modernist traits: attention to the word, an intimate, unconventional voice, and a concern with audience. In addition, they both reject formal traditions while they adopt new forms and use modern, outside influences such as art, architecture and philosophy as subject matter and a lens through which to focus their poetry. While it may seem that Anna Akhmatova was the most socially aware poet, because of the censorship she endured under Stalin, my research has revealed that actually Edith Södergran showed the most social consciousness. Thus, a contrast of the poets’ themes reveals these differences in their approaches. Both poets articulated a vibrant response to war and revolution becoming modernists in the process. In their final works created in the years before their deaths, they reveal the solace they found in nature as well as final mentions of the violent events of their youth. Keywords: St. Petersburg, Modernism, Symbolism, Acmeism, Silver Age, Finland-Swedish literature

Language in Acquisition : Early Lexical Development and Associations between Lexicon and Grammar Findings from Full-Term and Very-Low-Birth-Weight Finnish Children

The aim was to analyse the growth and compositional development of the receptive and expressive lexicons between the ages 0,9 and 2;0 in the full-term (FT) and the very-low-birth-weight (VLBW) children who are acquiring Finnish. The associations between the expressive lexicon and grammar at 1;6 and 2;0 in the FT children were also studied. In addition, the language skills of the VLBW children at 2;0 were analysed, as well as the predictive value of early lexicon to the later language performance. Four groups took part in the studies: the longitudinal (N = 35) and cross-sectional (N = 146) samples of the FT children, and the longitudinal (N = 32) and cross-sectional (N = 66) samples of VLBW children. The data was gathered by applying of the structured parental rating method (the Finnish version of the Communicative Development Inventory), through analysis of the children´s spontaneous speech and by administering a a formal test (Reynell Developmental Language Scales). The FT children acquired their receptive lexicons earlier, at a faster rate and with larger individual variation than their expressive lexicons. The acquisition rate of the expressive lexicon increased from slow to faster in most children (91%). Highly parallel developmental paths for lexical semantic categories were detected in the receptive and expressive lexicons of the Finnish children when they were analysed in relation to the growth of the lexicon size, as described in the literature for children acquiring other languages. The emergence of grammar was closely associated with expressive lexical growth. The VLBW children acquired their receptive lexicons at a slower rate and had weaker language skills at 2;0 than the full-term children. The compositional development of both lexicons happened at a slower rate in the VLBW children when compared to the FT controls. However, when the compositional development was analysed in relation to the growth of lexicon size, this development occurred qualitatively in a nearly parallel manner in the VLBW children as in the FT children. Early receptive and expressive lexicon sizes were significantly associated with later language skills in both groups. The effect of the background variables (gender, length of the mother s basic education, birth weight) on the language development in the FT and the VLBW children differed. The results provide new information of early language acquisition by the Finnish FT and VLBW children. The results support the view that the early acquisition of the semantic lexical categories is related to lexicon growth. The current findings also propose that the early grammatical acquisition is closely related to the growth of expressive vocabulary size. The language development of the VLBW children should be followed in clinical work.

Systematic analysis of changes in cannabis use among participants in control conditions of randomised controlled trials

Introduction Cannabis remains the most used illegal substance across the globe, and negative outcomes and disorders are common. A spotlight therefore falls on reductions in cannabis use in people with cannabis use disorder. Current estimates of unassisted cessation or reduction in cannabis use rely on community surveys, and few studies focus on individuals with disorder. A key interest of services and researchers is to estimate effect size of reductions in consumption among treatment seekers who do not obtain treatment. Effects within waiting list or information-only control conditions of randomised controlled trials offer an opportunity to study this question. Method This paper examines the extent of reductions in days of cannabis use in the control groups of randomised controlled trials on treatment of cannabis use disorders. A systematic literature search was performed to identify trials that reported days of cannabis use in the previous 30 (or equivalent). Results Since all but one of the eight identified studies had delayed treatment controls, results could only be summarised across 2–4 months. Average weighted days of use in the previous 30 days fell from 24.5 to 19.9, and a meta-analysis using a random effects model showed an average reduction of 0.442 SD. However, every study had at least one significant methodological issue. Conclusions While further high-quality data is needed to confirm the observed effects, these results provide a baseline from which researchers and practitioners can estimate the extent of change required to detect effects of cannabis treatments in services or treatment trials.

Smoking from Adolescence to Adulthood : A 15-year Follow-up of the North Karelia Youth Project

The aim of the study was to examine the effects of a smoking prevention program and smoking from early adolescence to early adulthood by using longitudinal data. In addition, predictors of smoking, smoking cessation, and associations of smoking with socio-economic factors and other health behaviours were assessed. The data was gathered in connection with the North Karelia Youth Project follow-up study during 15 years. A two-year cardiovascular disease risk factor prevention program was carried out among students from grades seven to nine in four schools in North Karelia. Two schools were selected from Kuopio province for the control schools. The North Karelia Project, a community-based cardiovascular disease prevention program, was implemented in the same area. At the baseline in 1978 the subjects were 13-year-olds (n=903) and in the following surveys 15-, 16-, 17-, 21- and 28-year-olds. The parents of the subjects were studied twice, in 1978 and 1980. A two-year intervention based on social influence approach prevented the onset of smoking for several years. The continuity of smoking from adolescence to adulthood was strong: most adolescent smokers were still smoking in adulthood. Moreover, approximately half of the 28-year-old smokers had started smoking after the age of 15. Previous smoking status and smoking by friends were the most important predictors of smoking. One third of all adolescent smokers had stopped smoking before the age of 28, averaging at 2.3 % annual decline. The socioeconomic status of the subject and, especially, education were strongly related to smoking, the lower socioeconomic groups smoking the most. Parental socioeconomic status and intergenerational social mobility were not significantly related to the smoking of the subject in adolescence or adulthood. Smoking was associated positively with the use of alcohol and negatively with physical activity from adolescence to adulthood. The results support the feasibility of a school-based social influence program with a community-based program in smoking prevention among adolescents. Strong continuity of smoking from adolescence to adulthood supports the importance of preventing the onset of smoking in adolescence. It would be useful to continue prevention programs also after the comprehensive school, since so many young start smoking after that. It would likewise be important to develop cessation programs tailor-made for adolescents and young adults. Additionally, the results support the importance of using methods based on social influence in smoking prevention and cessation programs, targeting especially such risk groups as those with low socioeconomic status as well as those with other unhealthy behaviours.

Macadamia Regional Variety Trials Series 3 - Phase 2

Regional variety trials (RVT) established in 1983 and again in 1997 identified superior varieties for the macadamia industry. From the 1983 trials, guidelines were developed to assist growers to select the most appropriate new varieties for their particular orchards and many of these superior varieties have been enthusiastically adopted by industry. This is also being done for varieties in the 1997 trials. Many of the best cultivars have already been adopted by growers on the basis of annual reports of yield and quality. Industry development over the next 10 to 20 years will be largely dependent on new, superior varieties selected in these RVT5, including new selections from the macadamia industry breeding program.

Remote sensing to implement an effective pest management strategy for canegrubs

Develop a remote-sensing system that can identify canegrub infestations and provide early- warning to growers via the internet.

Comparison of treatment effect sizes associated with surrogate and final patient relevant outcomes in randomised controlled trials: meta-epidemiological study

Objective To quantify and compare the treatment effect and risk of bias of trials reporting biomarkers or intermediate outcomes (surrogate outcomes) versus trials using final patient relevant primary outcomes. Design Meta-epidemiological study. Data sources All randomised clinical trials published in 2005 and 2006 in six high impact medical journals: Annals of Internal Medicine, BMJ, Journal of the American Medical Association, Lancet, New England Journal of Medicine, and PLoS Medicine. Study selection Two independent reviewers selected trials. Data extraction Trial characteristics, risk of bias, and outcomes were recorded according to a predefined form. Two reviewers independently checked data extraction. The ratio of odds ratios was used to quantify the degree of difference in treatment effects between the trials using surrogate outcomes and those using patient relevant outcomes, also adjusted for trial characteristics. A ratio of odds ratios >1.0 implies that trials with surrogate outcomes report larger intervention effects than trials with patient relevant outcomes. Results 84 trials using surrogate outcomes and 101 using patient relevant outcomes were considered for analyses. Study characteristics of trials using surrogate outcomes and those using patient relevant outcomes were well balanced, except for median sample size (371 v 741) and single centre status (23% v 9%). Their risk of bias did not differ. Primary analysis showed trials reporting surrogate endpoints to have larger treatment effects (odds ratio 0.51, 95% confidence interval 0.42 to 0.60) than trials reporting patient relevant outcomes (0.76, 0.70 to 0.82), with an unadjusted ratio of odds ratios of 1.47 (1.07 to 2.01) and adjusted ratio of odds ratios of 1.46 (1.05 to 2.04). This result was consistent across sensitivity and secondary analyses. Conclusions Trials reporting surrogate primary outcomes are more likely to report larger treatment effects than trials reporting final patient relevant primary outcomes. This finding was not explained by differences in the risk of bias or characteristics of the two groups of trials.

Reconstructions of past climates from documentary and natural sources in Finland since the 18th century

In this paper both documentary and natural proxy data have been used to improve the accuracy of palaeoclimatic knowledge in Finland since the 18th century. Early meteorological observations from Turku (1748-1800) were analyzed first as a potential source of climate variability. The reliability of the calculated mean temperatures was evaluated by comparing them with those of contemporary temperature records from Stockholm, St. Petersburg and Uppsala. The resulting monthly, seasonal and yearly mean temperatures from 1748 to 1800 were compared with the present day mean values (1961-1990): the comparison suggests that the winters of the period 1749-1800 were 0.8 ºC colder than today, while the summers were 0.4 ºC warmer. Over the same period, springs were 0.9 ºC and autumns 0.1 ºC colder than today. Despite their uncertainties when compared with modern meteorological data, early temperature measurements offer direct and daily information about the weather for all months of the year, in contrast with other proxies. Secondly, early meteorological observations from Tornio (1737-1749) and Ylitornio (1792-1838) were used to study the temporal behaviour of the climate-tree growth relationship during the past three centuries in northern Finland. Analyses showed that the correlations between ring widths and mid-summer (July) temperatures did not vary significantly as a function of time. Early (June) and late summer (August) mean temperatures were secondary to mid-summer temperatures in controlling the radial growth. According the dataset used, there was no clear signature of temporally reduced sensitivity of Scots pine ring widths to mid-summer temperatures over the periods of early and modern meteorological observations. Thirdly, plant phenological data with tree-rings from south-west Finland since 1750 were examined as a palaeoclimate indicator. The information from the fragmentary, partly overlapping, partly nonsystematically biased plant phenological records of 14 different phenomena were combined into one continuous time series of phenological indices. The indices were found to be reliable indicators of the February to June temperature variations. In contrast, there was no correlation between the phenological indices and the precipitation data. Moreover, the correlations between the studied tree-rings and spring temperatures varied as a function of time and hence, their use in palaeoclimate reconstruction is questionable. The use of present tree-ring datasets for palaeoclimate purposes may become possible after the application of more sophisticated calibration methods. Climate variability since the 18th century is perhaps best seen in the fourth paper study of the multiproxy spring temperature reconstruction of south-west Finland. With the help of transfer functions, an attempt has been made to utilize both documentary and natural proxies. The reconstruction was verified with statistics showing a high degree of validity between the reconstructed and observed temperatures. According to the proxies and modern meteorological observations from Turku, springs have become warmer and have featured a warming trend since around the 1850s. Over the period of 1750 to around 1850, springs featured larger multidecadal low-frequency variability, as well as a smaller range of annual temperature variations. The coldest springtimes occurred around the 1840s and 1850s and the first decade of the 19th century. Particularly warm periods occurred in the 1760s, 1790s, 1820s, 1930s, 1970s and from 1987 onwards, although in this period cold springs occurred, such as the springs of 1994 and 1996. On the basis of the available material, long-term temperature changes have been related to changes in the atmospheric circulation, such as the North Atlantic Oscillation (February-June).

The Distribution of Juvenile Fishes in Maryland Coastal Bays in Relation to Environmental Factors: a Multivariate Analysis

Fish assemblage structure of Maryland's coastal lagoon complex was analyzed for spatial and seasonal patterns for the period 1991-2000. Data was made available by Maryland Department of Natural Resources from their MD Coastal Bays Finfish Survey. Dominant species from separate trawl and wiw surveys included blue crab Callinectes sapidus (erroneously included here as a "fish" due to its dominance and commercial importance), bay anchovy Anchoa mitchilli, spot Leiostomous xanthurus, silver perch Bairdiella ehrysoura, and Atlantic menhaden Brevwrtia tyrannus. Ninety-four fish species were identified in the two surveys, a diversity substantially higher than other survey records for Middle Atlantic Bight estuarine and lagoon systems (richness=26 to 78 species). Total species richness for the trawl survey was highest in Chincoteague and lowest in Assawoman and Sinepuxent. On the other hand, mean richness per tow (-area) and related Shannon Weiner Diversity Index were significantly higher in the northern two bays (Assawoman and Isle of Wight Bays) than in the two southern bays (Chincoteague or Sinepuxent Bays). For the seine survey, effort-adjusted diversity indices were significantly lower for Chincoteague Bay than for the other three bays. Higher relative abundances were observed in the northern bays than in the southern bays. The trawl survey exhibited the lowest catch-per-site in Sinepuxent Bay and the highest in Assawoman Bay. The seine survey had the lowest catch-per-site in Chincoteague Bay while the other three embayments were of similar magnitude. There was clear seasonality in assemblage structure with peak abundance and diversity in the summer compared to other seasons. Blue crabs in particular showed a c. 2-fold decline in relative abundance from early summer to fall, which is likely attributable to harvest removals (i.e., an exploitation rate of c. 50%). Seagrass coverage, although increasing over the course of the 10 year survey, did not have obvious effects on species diversity and abundance across or within the embayments, although it did have positive associations with two important species: bay anchovy and summer flounder Pavalich thys dentatus. Atlantic menhaden were most dominant in Assawoman Bay, which could be related to higher primary production typically observed in this Bay in comparison to the other three. (PDF contains 99 pages)