Evaluation of the alkaline comet assay and urinary 3-methyladenine excretion for monitoring DNA damage in melanoma patients treated with dacarbazine and tamoxifen

Purpose: To develop, using dacarbazine as a model, reliable techniques for measuring DNA damage and repair as pharmacodynamic endpoints for patients receiving chemotherapy. Methods: A group of 39 patients with malignant melanoma were treated with dacarbazine 1 g/m2 i.v. every 21 days. Tamoxifen 20 mg daily was commenced 24 h after the first infusion and continued until 3 weeks after the last cycle of chemotherapy. DNA strand breaks formed during dacarbazine-induced DNA damage and repair were measured in individual cells by the alkaline comet assay. DNA methyl adducts were quantified by measuring urinary 3-methyladenine (3-MeA) excretion using immunoaffinity ELISA. Venous blood was taken on cycles 1 and 2 for separation of peripheral blood lymphocytes (PBLs) for measurement of DNA strand breaks. Results: Wide interpatient variation in PBL DNA strand breaks occurred following chemotherapy, with a peak at 4 h (median 26.6 h, interquartile range 14.75- 40.5 h) and incomplete repair by 24 h. Similarly, there was a range of 3-MeA excretion with peak levels 4-10 h after chemotherapy (median 33 nmol/h, interquartile range 20.448.65 nmol/h). Peak 3-MeA excretion was positively correlated with DNA strand breaks at 4 h (Spearman's correlation coefficient, r = 0.39, P = 0.036) and 24 h (r = 0.46, P = 0.01). Drug-induced emesis correlated with PBL DNA strand breaks (Mann Whitney U-test, P = 0.03) but not with peak 3-MeA excretion. Conclusions: DNA damage and repair following cytotoxic chemotherapy can be measured in vivo by the alkaline comet assay and by urinary 3-MeA excretion in patients receiving chemotherapy.

A stepped-wedge cluster randomised controlled trial for evaluating rates of falls among inpatients in aged care rehabilitation units receiving tailored multimedia education in addition to usual care : a trial protocol

Introduction Falls are the most frequent adverse event reported in hospitals. Approximately 30% of in-hospital falls lead to an injury and up to 2% result in a fracture. A large randomised trial found that a trained health professional providing individualised falls prevention education to older inpatients reduced falls in a cognitively intact subgroup. This study aims to investigate whether this efficacious intervention can reduce falls and be clinically useful and cost-effective when delivered in the real-life clinical environment. Methods A stepped-wedge cluster randomised trial will be used across eight subacute units (clusters) which will be randomised to one of four dates to start the intervention. Usual care on these units includes patient's screening, assessment and implementation of individualised falls prevention strategies, ongoing staff training and environmental strategies. Patients with better levels of cognition (Mini-Mental State Examination >23/30) will receive the individualised education from a trained health professional in addition to usual care while patient's feedback received during education sessions will be provided to unit staff. Unit staff will receive training to assist in intervention delivery and to enhance uptake of strategies by patients. Falls data will be collected by two methods: case note audit by research assistants and the hospital falls reporting system. Cluster-level data including patient's admissions, length of stay and diagnosis will be collected from hospital systems. Data will be analysed allowing for correlation of outcomes (clustering) within units. An economic analysis will be undertaken which includes an incremental cost-effectiveness analysis. Ethics and dissemination The study was approved by The University of Notre Dame Australia Human Research Ethics Committee and local hospital ethics committees. Results The results will be disseminated through local site networks, and future funding and delivery of falls prevention programmes within WA Health will be informed. Results will also be disseminated through peer-reviewed publications and medical conferences.

Efficient top-k retrieval with signatures

This paper describes a new method of indexing and searching large binary signature collections to efficiently find similar signatures, addressing the scalability problem in signature search. Signatures offer efficient computation with acceptable measure of similarity in numerous applications. However, performing a complete search with a given search argument (a signature) requires a Hamming distance calculation against every signature in the collection. This quickly becomes excessive when dealing with large collections, presenting issues of scalability that limit their applicability. Our method efficiently finds similar signatures in very large collections, trading memory use and precision for greatly improved search speed. Experimental results demonstrate that our approach is capable of finding a set of nearest signatures to a given search argument with a high degree of speed and fidelity.

Effects of wireless sensor network uncertainties on output-only modal-based damage identification

The use of Wireless Sensor Networks (WSNs) for Structural Health Monitoring (SHM) has become a promising approach due to many advantages such as low cost, fast and flexible deployment. However, inherent technical issues such as data synchronization error and data loss have prevented these distinct systems from being extensively used. Recently, several SHM-oriented WSNs have been proposed and believed to be able to overcome a large number of technical uncertainties. Nevertheless, there is limited research examining effects of uncertainties of generic WSN platform and verifying the capability of SHM-oriented WSNs, particularly on demanding SHM applications like modal analysis and damage identification of real civil structures. This article first reviews the major technical uncertainties of both generic and SHM-oriented WSN platforms and efforts of SHM research community to cope with them. Then, effects of the most inherent WSN uncertainty on the first level of a common Output-only Modal-based Damage Identification (OMDI) approach are intensively investigated. Experimental accelerations collected by a wired sensory system on a benchmark civil structure are initially used as clean data before being contaminated with different levels of data pollutants to simulate practical uncertainties in both WSN platforms. Statistical analyses are comprehensively employed in order to uncover the distribution pattern of the uncertainty influence on the OMDI approach. The result of this research shows that uncertainties of generic WSNs can cause serious impact for level 1 OMDI methods utilizing mode shapes. It also proves that SHM-WSN can substantially lessen the impact and obtain truly structural information without having used costly computation solutions.

Phytophotodermatitis : case reports of children presenting with blistering after preparing lime juice

Letter to the Editor We read with interest the case report entitled ‘‘Contact with fig tree sap: An unusual cause of burn injury’’ by Mandalia et al. [1] and would like to report our similar experience with phytophotodermatitis caused by lime juice. Phototoxic dermatitis is understandably easily confused with a burn, particularly when a patient presents with large blisters of unknown mechanism. At the Royal Children’s Hospital Burns Centre, this injury was treated in the same manner as a burn and is described here...

Modelling for the electricity distribution network

Global awareness for cleaner and renewable energy is transforming the electricity sector at many levels. New technologies are being increasingly integrated into the electricity grid at high, medium and low voltage levels, new taxes on carbon emissions are being introduced and individuals can now produce electricity, mainly through rooftop photovoltaic (PV) systems. While leading to improvements, these changes also introduce challenges, and a question that often rises is ‘how can we manage this constantly evolving grid?’ The Queensland Government and Ergon Energy, one of the two Queensland distribution companies, have partnered with some Australian and German universities on a project to answer this question in a holistic manner. The project investigates the impact the integration of renewables and other new technologies has on the physical structure of the grid, and how this evolving system can be managed in a sustainable and economical manner. To aid understanding of what the future might bring, a software platform has been developed that integrates two modelling techniques: agent-based modelling (ABM) to capture the characteristics of the different system units accurately and dynamically, and particle swarm optimization (PSO) to find the most economical mix of network extension and integration of distributed generation over long periods of time. Using data from Ergon Energy, two types of networks (3 phase, and Single Wired Earth Return or SWER) have been modelled; three-phase networks are usually used in dense networks such as urban areas, while SWER networks are widely used in rural Queensland. Simulations can be performed on these networks to identify the required upgrades, following a three-step process: a) what is already in place and how it performs under current and future loads, b) what can be done to manage it and plan the future grid and c) how these upgrades/new installations will perform over time. The number of small-scale distributed generators, e.g. PV and battery, is now sufficient (and expected to increase) to impact the operation of the grid, which in turn needs to be considered by the distribution network manager when planning for upgrades and/or installations to stay within regulatory limits. Different scenarios can be simulated, with different levels of distributed generation, in-place as well as expected, so that a large number of options can be assessed (Step a). Once the location, sizing and timing of assets upgrade and/or installation are found using optimisation techniques (Step b), it is possible to assess the adequacy of their daily performance using agent-based modelling (Step c). One distinguishing feature of this software is that it is possible to analyse a whole area at once, while still having a tailored solution for each of the sub-areas. To illustrate this, using the impact of battery and PV can have on the two types of networks mentioned above, three design conditions can be identified (amongst others): · Urban conditions o Feeders that have a low take-up of solar generators, may benefit from adding solar panels o Feeders that need voltage support at specific times, may be assisted by installing batteries · Rural conditions - SWER network o Feeders that need voltage support as well as peak lopping may benefit from both battery and solar panel installations. This small example demonstrates that no single solution can be applied across all three areas, and there is a need to be selective in which one is applied to each branch of the network. This is currently the function of the engineer who can define various scenarios against a configuration, test them and iterate towards an appropriate solution. Future work will focus on increasing the level of automation in identifying areas where particular solutions are applicable.

The epidemiology of basal cell carcinoma

Basal cell carcinoma (BCC) is a skin cancer of particular importance to the Australian community. Its rate of occurrence is highest in Queensland, where 1% to 2% of people are newly affected annually. This is an order of magnitude higher than corresponding incidence estimates in European and North American populations. Individuals with a sun-sensitive complexion are particularly susceptible because sun exposure is the single most important causative agent, as shown by the anatomic distribution of BCC which is in general consistent with the levels of sun exposure across body sites. A distinguishing feature of BCC is the occurrence of multiple primary tumours within individuals, synchronously or over time, and their diagnosis and treatment costs contribute substantially to the major public health burden caused by BCC. A primary knowledge gap about BCC pathogenesis however was an understanding of the true frequency of multiple BCC occurrences and their body distribution, and why a proportion of people do develop more than one BCC in their life. This research project sought to address this gap under an overarching research aim to better understand the detailed epidemiology of BCC with the ultimate goal of reducing the burden of this skin cancer through prevention. The particular aim was to document prospectively the rate of BCC occurrence and its associations with constitutional and environmental (solar) factors, all the while paying special attention to persons affected by more than one BCC. The study built on previous findings and recent developments in the field but set out to confirm and extend these and propose more adequate theories about the complex epidemiology of this cancer. Addressing these goals required a new approach to researching basal cell carcinoma, due to the need to account for the phenomenon of multiple incident BCCs per person. This was enabled by a 20 year community-based study of skin cancer in Australians that provided the methodological foundation for this thesis. Study participants were originally randomly selected in 1986 from the electoral register of all adult residents of the subtropical township of Nambour in Queensland, Australia. On various occasions during the study, participants were fully examined by dermatologists who documented cumulative photodamage as well as skin cancers. Participants completed standard questionnaires about skin cancer-related factors, and consented to have any diagnosed skin cancers notified to the investigators by regional pathology laboratories in Queensland. These methods allowed 100% ascertainment of histologically confirmed BCCs in this study population. 1339 participants had complete follow-up to the end of 2007. Statistical analyses in this thesis were carried out using SAS and SUDAAN statistical software packages. Modelling methods, including multivariate logistic regressions, allowed for repeated measures in terms of multiple BCCs per person. This innovative approach gave new findings on two levels, presented in five chapters as scientific papers: 1. Incidence of basal cell carcinoma multiplicity and detailed anatomic distribution: longitudinal study of an Australian population The incidence of people affected multiple times by BCC was 705 per 100,000 person years compared to an incidence rate of people singly affected of 935 per 100,000 person years. Among multiply and singly affected persons alike, site-specific BCC incidence rates were far highest on facial subsites, followed by upper limbs, trunk, and then lower limbs 2. Melanocytic nevi and basal cell carcinoma: is there an association? BCC risk was significantly increased in those with forearm nevi (Odds Ratios (OR) 1.43, 95% Confidence Intervals (CI) 1.09-1.89) compared to people without forearm nevi, especially among those who spent their time mainly outdoors (OR 1.6, 95%CI 1.1-2.3) compared to those who spent their time mainly indoors. Nevi on the back were not associated with BCC. 3. Clinical signs of photodamage are associated with basal cell carcinoma multiplicity and site: a 16-year longitudinal study Over a 16-year follow-up period, 58% of people affected by BCC developed more than one BCC. Among these people 60% developed BCCs across different anatomic sites. Participants with high numbers of solar keratoses, compared to people without solar keratoses, were most likely to experience the highest BCC counts overall (OR 3.3, 95%CI 1.4-13.5). Occurrences of BCC on the trunk (OR 3.3, 95%CI 1.4-7.6) and on the limbs (OR 3.7, 95%CI 2.0-7.0) were strongly associated with high numbers of solar keratoses on these sites. 4. Occurrence and determinants of basal cell carcinoma by histological subtype in an Australian community Among 1202 BCCs, 77% had a single growth pattern and 23% were of mixed histological composition. Among all BCCs the nodular followed by the superficial growth patterns were commonest. Risk of nodular and superficial BCCs on the head was raised if 5 or more solar keratoses were present on the face (OR 1.8, 95%CI 1.2-2.7 and OR 4.5, 95%CI 2.1-9.7 respectively) and similarly on the trunk in the presence of multiple solar keratoses on the trunk (OR 4.2, 95%CI 1.5-11.9 and OR 2.2, 95%CI 1.1-4.4 respectively). 5. Basal cell carcinoma and measures of cumulative sun exposure: an Australian longitudinal community-based study Dermal elastosis was more likely to be seen adjacent to head and neck BCCs than trunk BCCs (p=0.01). Severity of dermal elastosis increased on each site with increasing clinical signs of cutaneous sun damage on that site. BCCs that occurred without perilesional elastosis per se, were always found in an anatomic region with signs of photodamage. This thesis thus has identified the magnitude of the burden of multiple BCCs. It does not support the view that people affected by more than one BCC represent a distinct group of people who are prone to BCCs on certain body sites. The results also demonstrate that BCCs regardless of site, histology or order of occurrence are strongly associated with cumulative sun exposure causing photodamage to the skin, and hence challenge the view that BCCs occurring on body sites with typically low opportunities for sun exposure or of the superficial growth pattern are different in their association with the sun from those on typically sun-exposed sites, or nodular BCCs, respectively. Through dissemination in the scientific and medical literature, and to the community at large, these findings can ultimately assist in the primary and secondary prevention of BCC, perhaps especially in high-risk populations.

Levels of social trust among men from refugee backgrounds after the 2011 Queensland floods

Purpose This paper examines the relationship between flood exposure and levels of social trust among a cohort of adult men from refugee backgrounds who were affected by the 2011 Queensland floods in Australia. Design/methodology/approach A quantitative questionnaire was administered to 141 men from refugee backgrounds almost two years after the 2011 Queensland floods. The survey was administered in person by trained peer in-terviewers, and included a number of standardised instruments assessing respondents’ so-cio-demographic characteristics, levels of social trust towards and from neighbours, the police, the wider Australian community, and the media, and exposure to and impact of the floods. Multiple logistic regression analyses were used to assess the relationship between flood exposure and social trust adjusting for pre-disaster levels of trust and other potentially confounding variables. Findings Participants with higher levels of flood exposure were significantly more likely to report greater levels of trust both towards and from their neighbours, the wider Australian community, and the media, and they were also more likely to believe that most people can be trusted. Research limitations/implications Although the study reports on data collected two years after the floods, the analysis has adjusted for pre-disaster measures of social trust and other socio-demographic variables. Originality/value Our paper has highlighted the important place of social trust and social capital for refugee communities in a post-disaster setting. Disaster responses that support social capital among marginalised populations are critical to increasing community resilience and supporting recovery.

Sustainable development as a meta-context for engineering education

At the end of the first decade of the twenty-first century, there is unprecedented awareness of the need for a transformation in development, to meet the needs of the present while also preserving the ability of future generations to meet their own needs. However, within engineering, educators still tend to regard such development as an ‘aspect’ of engineering rather than an overarching meta-context, with ad hoc and highly variable references to topics. Furthermore, within a milieu of interpretations there can appear to be conflicting needs for achieving sustainable development, which can be confusing for students and educators alike. Different articulations of sustainable development can create dilemmas around conflicting needs for designers and researchers, at the level of specific designs and (sub-) disciplinary analysis. Hence sustainability issues need to be addressed at a meta-level using a whole of system approach, so that decisions regarding these dilemmas can be made. With this appreciation, and in light of curriculum renewal challenges that also exist in engineering education, this paper considers how educators might take the next step to move from sustainable development being an interesting ‘aspect’ of the curriculum, to sustainable development as a meta-context for curriculum renewal. It is concluded that capacity building for such strategic considerations is critical in engineering education.

Sustainable development as a meta-context for engineering education

At the end of the first decade of the twenty-first century, there is unprecedented awareness of the need for a transformation in development, to meet the needs of the present while also preserving the ability of future generations to meet their own needs. However, within engineering, educators still tend to regard such development as an ‘aspect’ of engineering rather than an overarching meta-context, with ad hoc and highly variable references to topics. Furthermore, within a milieu of interpretations there can appear to be conflicting needs for achieving sustainable development, which can be confusing for students and educators alike. Different articulations of sustainable development can create dilemmas around conflicting needs for designers and researchers, at the level of specific designs and (sub-) disciplinary analysis. Hence sustainability issues need to be addressed at a meta-level using a whole of system approach, so that decisions regarding these dilemmas can be made. With this appreciation, and in light of curriculum renewal challenges that also exist in engineering education, this paper considers how educators might take the next step to move from sustainable development being an interesting ‘aspect’ of the curriculum, to sustainable development as a meta-context for curriculum renewal. It is concluded that capacity building for such strategic considerations is critical in engineering education.

Estimating present day extreme water level exceedance probabilities around the coastline of Australia : tides, extra-tropical storm surges and mean sea level

The occurrence of extreme water levels along low-lying, highly populated and/or developed coastlines can lead to considerable loss of life and billions of dollars of damage to coastal infrastructure. Therefore it is vitally important that the exceedance probabilities of extreme water levels are accurately evaluated to inform risk-based flood management, engineering and future land-use planning. This ensures the risk of catastrophic structural failures due to under-design or expensive wastes due to over-design are minimised. This paper estimates for the first time present day extreme water level exceedence probabilities around the whole coastline of Australia. A high-resolution depth averaged hydrodynamic model has been configured for the Australian continental shelf region and has been forced with tidal levels from a global tidal model and meteorological fields from a global reanalysis to generate a 61-year hindcast of water levels. Output from this model has been successfully validated against measurements from 30 tide gauge sites. At each numeric coastal grid point, extreme value distributions have been fitted to the derived time series of annual maxima and the several largest water levels each year to estimate exceedence probabilities. This provides a reliable estimate of water level probabilities around southern Australia; a region mainly impacted by extra-tropical cyclones. However, as the meteorological forcing used only weakly includes the effects of tropical cyclones, extreme water level probabilities are underestimated around the western, northern and north-eastern Australian coastline. In a companion paper we build on the work presented here and more accurately include tropical cyclone-induced surges in the estimation of extreme water level. The multi-decadal hindcast generated here has been used primarily to estimate extreme water level exceedance probabilities but could be used more widely in the future for a variety of other research and practical applications.

Apple skin patterning is associated with differential expression of MYb10

Background Some apple (Malus × domestica Borkh.) varieties have attractive striping patterns, a quality attribute that is important for determining apple fruit market acceptance. Most apple cultivars (e.g. 'Royal Gala') produce fruit with a defined fruit pigment pattern, but in the case of 'Honeycrisp' apple, trees can produce fruits of two different kinds: striped and blushed. The causes of this phenomenon are unknown. Results Here we show that striped areas of 'Honeycrisp' and 'Royal Gala' are due to sectorial increases in anthocyanin concentration. Transcript levels of the major biosynthetic genes and MYB10, a transcription factor that upregulates apple anthocyanin production, correlated with increased anthocyanin concentration in stripes. However, nucleotide changes in the promoter and coding sequence of MYB10 do not correlate with skin pattern in 'Honeycrisp' and other cultivars differing in peel pigmentation patterns. A survey of methylation levels throughout the coding region of MYB10 and a 2.5 Kb region 5' of the ATG translation start site indicated that an area 900 bp long, starting 1400 bp upstream of the translation start site, is highly methylated. Cytosine methylation was present in all three contexts, with higher methylation levels observed for CHH and CHG (where H is A, C or T) than for CG. Comparisons of methylation levels of the MYB10 promoter in 'Honeycrisp' red and green stripes indicated that they correlate with peel phenotypes, with an enrichment of methylation observed in green stripes. Conclusions Differences in anthocyanin levels between red and green stripes can be explained by differential transcript accumulation of MYB10. Different levels of MYB10 transcript in red versus green stripes are inversely associated with methylation levels in the promoter region. Although observed methylation differences are modest, trends are consistent across years and differences are statistically significant. Methylation may be associated with the presence of a TRIM retrotransposon within the promoter region, but the presence of the TRIM element alone cannot explain the phenotypic variability observed in 'Honeycrisp'. We suggest that methylation in the MYB10 promoter is more variable in 'Honeycrisp' than in 'Royal Gala', leading to more variable color patterns in the peel of this cultivar.

Alterations in cervical muscle activity in functional and stressful tasks in female office workers with neck pain

This study determined differences between computer workers with varying levels of neck pain in terms of work stressors, employee strain, electromyography (EMG) amplitude and heart rate response to various tasks. Participants included 85 workers (33, no pain; 38, mild pain; 14, moderate pain) and 22 non-working controls. Work stressors evaluated were job demands, decision authority, and social support. Heart rate was recorded during three tasks: copy-typing, typing with superimposed stress and a colour word task. Measures included electromyography signals from the sternocleidomastoid (SCM), anterior scalene (AS), cervical extensor (CE) and upper trapezius (UT) muscles bilaterally. Results showed no difference between groups in work stressors or employee strain measures. Workers with and without pain had higher measured levels of EMG amplitude in SCM, AS and CE muscles during the tasks than controls (all P < 0.02). In workers with neck pain, the UT had difficulty in switching off on completion of tasks compared with controls and workers without pain. There was an increase in heart rate, perceived tension and pain and decrease in accuracy for all groups during the stressful tasks with symptomatic workers producing more typing errors than controls and workers without pain. These findings suggest an altered muscle recruitment pattern in the neck flexor and extensor muscles. Whether this is a consequence or source of the musculoskeletal disorder cannot be determined from this study. It is possible that workers currently without symptoms may be at risk of developing a musculoskeletal disorder.

Factors associated with physical activity in children attending family child care homes

Objective To determine the relationship between family child care home (FCCH) practices and characteristics, and objectively measured physical activity (PA) among children attending FCCHs. Methods FCCH practices and characteristics were assessed in 45 FCCHs in Oregon (USA) in 2010-2011 using the Nutrition and Physical Activity Self-Assessment for Child Care Instrument. Within the 45 FCCHs, 136 children between ages 2 and 5. years wore an accelerometer during child care attendance over a one-week period. Time spent in light, moderate, and vigorous PA per hour was calculated using intensity-related cut-points (Pate et al., 2006). Results FCCH characteristics and practices associated with higher levels of PA (min/h; p < 0.05) included provision of sufficient outdoor active play [32.2 (1.0) vs. 28.6 (1.3)], active play using portable play equipment [31.7 (1.0) vs. 29.3 (1.4)], the presence of a variety of fixed play equipment [32.2 (1.0) vs. 28.9 (1.3)], and suitable indoor play space [32.2 (1.0) vs. 28.6 (1.3)], engaging in active play with children [32.1 (1.1) vs. 29.6 (1.2)], and receiving activity-related training [33.1 (1.2) vs. 30.3 (1.1)]. Conclusions This is the first study to identify practices and characteristics of FCCHs that influence children's PA. These data should be considered when developing programs and policies to promote PA in FCCHs.

The role of biological extracellular matrix scaffolds in vascularized three-dimensional tissue growth in vivo

An in vivo murine vascularized chamber model has been shown to generate spontaneous angiogenesis and new tissue formation. This experiment aimed to assess the effects of common biological scaffolds on tissue growth in this model. Either laminin-1, type I collagen, fibrin glue, hyaluronan, or sea sponge was inserted into silicone chambers containing the epigastric artery and vein, one end was sealed with adipose tissue and the other with bone wax, then incubated subcutaneously. After 2, 4, or 6 weeks, tissue from chambers containing collagen I, fibrin glue, hyaluronan, or no added scaffold (control) had small amounts of vascularized connective tissue. Chambers containing sea sponge had moderate connective tissue growth together with a mild "foreign body" inflammatory response. Chambers containing laminin-1, at a concentration 10-fold lower than its concentration in Matrigel™, resulted in a moderate adipogenic response. In summary, (1) biological hydrogels are resorbed and gradually replaced by vascularized connective tissue; (2) sponge-like matrices with large pores support connective tissue growth within the pores and become encapsulated with granulation tissue; (3) laminin-containing scaffolds facilitate adipogenesis. It is concluded that the nature and chemical composition of the scaffold exerts a significant influence on the amount and type of tissue generated in this in vivo chamber model.