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    The purpose of this Thesis has been an exploration of the means of composing paintings that are personally expressive, meaningful in concept, and aesthetically exciting, while being structurally well designed and executed. An intensive search in the areas of concept, or idea development; design and composition; as well as the technical concerns in choosing media and the methodology of its use has resulted in growth, increased knowledge, and many new discoveries. Each area has been systematically explored in great depth in a productive and effective sequence. The process involved in the development of concept was researched through many avenues. The areas of art philosophy, human development, psychology, mythology, historic viewpoints, artist\u27s diaries and writings, artist\u27s biographies, interviews, and personal experience have been considered. The study of design and composition has been extensive. Both pictorial material, sculpture, and writings of theory have been studied. Investigation of varying media and techniques was undertaken to determine the best means of giving visible form to the concepts developed. This was done by researching along with a lot of trial and error. Each part of this investigation and working process has contributed to the body of work that evolved

    Odorants for surveillance and control of the Asian Citrus Psyllid (Diaphorina citri).

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    BackgroundThe Asian Citrus Psyllid (ACP), Diaphorina citri, can transmit the bacterium Candidatus Liberibacter while feeding on citrus flush shoots. This bacterium causes Huanglongbing (HLB), a major disease of citrus cultivation worldwide necessitating the development of new tools for ACP surveillance and control. The olfactory system of ACP is sensitive to variety of odorants released by citrus plants and offers an opportunity to develop new attractants and repellents.ResultsIn this study, we performed single-unit electrophysiology to identify odorants that are strong activators, inhibitors, and prolonged activators of ACP odorant receptor neurons (ORNs). We identified a suite of odorants that activated the ORNs with high specificity and sensitivity, which may be useful in eliciting behavior such as attraction. In separate experiments, we also identified odorants that evoked prolonged ORN responses and antagonistic odorants able to suppress neuronal responses to activators, both of which can be useful in lowering attraction to hosts. In field trials, we tested the electrophysiologically identified activating odorants and identified a 3-odor blend that enhances trap catches by ∼230%.ConclusionThese findings provide a set of odorants that can be used to develop affordable and safe odor-based surveillance and masking strategies for this dangerous pest insect

    Development of radioligand binding and functional assays for the characterization of dopamine D2-like receptor ligands

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    The family of dopamine D2-like receptors comprises the D2, D3 and D4 receptor, which exist in different isoforms, due to alternative splicing of the mRNA or polymorphisms in the coding sequence for the respective receptor. The D2-like receptors are implicated in various pathological conditions, such as schizophrenia, Parkinson’s disease, substance abuse or attention deficit hyperactivity disorder (ADHD) among others. This renders them an important target for the development of therapeutic drugs and pharmacological tools, facilitating the elucidation of distinct functions of the receptor subtypes. For the characterization of dopamine receptor ligands regarding their affinities to the receptor subtypes and their functional properties, a variety of technologies is available. This thesis aimed at the establishment of a radioligand binding assay to enable the investigation of ligand affinities at D2long, D3 and D4.4 receptors, the most commonly occurring isoforms. Further, providing a proximal functional readout that enables the determination of agonism or antagonism of ligands, a β-arrestin2 recruitment assay was established. The label-free DMR technology yields a distal readout, generated from the response of whole cells to stimulation of an expressed receptor and was chosen to extend the pharmacological toolbox for the characterization of ligands at D2 receptors. Label-free methods have the advantage of being less prone to false negatives regarding biased ligands since the whole cell response is detected, compared to the quantification of one distinct signaling event in more traditional functional assays. Unfortunately, it was not possible to establish the DMR assay for the D3R and the D4.4R. For the binding assay, the high affinity D2-like receptor antagonist [³H]N-methylspiperone was chosen as radioligand and binding to all three D2-like receptor subtypes was investigated using whole cells and homogenates prepared from the same cell lines. The utilization of homogenates appeared more useful, especially regarding the investigation of agonists. Agonists distinguish between high and low affinity states of the D2-like receptors, which appears undetectable when whole cell preparations are used. Further studies were carried out with cell homogenates. The binding kinetics of [³H]N-methylspiperone and the detectability of high affinity states of the D2longR, D3R and D4.4R were investigated. A library of well-known reference ligands was screened and obtained data was compared with literature reports, leading to the conclusion that the established method is a reliable tool for the determination of ligand affinities. Hence, several histamine H2 receptor agonists generated by our group could be tested for their affinities to the D2longR, D3R and D4.4R, supporting the development of histamine H2 receptor specific compounds. By developing a β-arrestin2 recruitment assay employing the split Emerald luciferase (ELuc) technique, agonist and antagonistic properties could be determined at the D2longR and the D3R. At the D4.4R, as described in the literature, no β-arrestin recruitment could be determined. Expression of the receptor and the β-arrestin2 fusion proteins with complementary fragments of the ELuc were confirmed by radioligand binding experiments and Western Blotting. Radioligand competition binding studies were performed and showed that the modification of the receptor does not impact the ligand affinities. β-Arrestin2 recruitment to the D2longR was distinct, yielded excellent signal-to-background ratios and could be monitored in real-time using whole cells. The D3R recruited β-arrestin2 in a less pronounced manner, but by performing lysis-based endpoint measurements, robust concentration-response and inhibition curves could still be generated. The DMR assay was established using CHO-K1 cells stably expressing the hD2longR, as CHO cells exhibit favorable adhesion properties. Assay conditions were optimized, regarding factors such as the cell seeding density or the assay temperature. Sets of reference (partial) agonists and antagonists were investigated using the DMR technique and the resulting potencies were compared to data obtained from other more conventional assays. Agonists, as well as antagonists exhibited the highest potencies in the DMR assay. The underlying reasons cannot fully be elucidated since different expression systems were used (HEK293T cells or CHO-K1 cells) for the performance of the different assays. However, the DMR assay provides a very distal readout, which is prone to signal amplification and may contribute to the comparably higher potencies. Investigations using pharmacological tools such as pertussis toxin, identified the Gi/o protein to be the main trigger of the cell response observed by DMR measurements. Altogether, the methods described in this thesis in combination with the mini-G protein recruitment assay provide a broad range of assays for the characterization of newly synthesized compounds regarding their affinities and functional properties

    Impaction of spray droplets on leaves: influence of formulation and leaf character on shatter, bounce and adhesion

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    This paper combines experimental data with simple mathematical models to investigate the influence of spray formulation type and leaf character (wettability) on shatter, bounce and adhesion of droplets impacting with cotton, rice and wheat leaves. Impaction criteria that allow for different angles of the leaf surface and the droplet impact trajectory are presented; their predictions are based on whether combinations of droplet size and velocity lie above or below bounce and shatter boundaries. In the experimental component, real leaves are used, with all their inherent natural variability. Further, commercial agricultural spray nozzles are employed, resulting in a range of droplet characteristics. Given this natural variability, there is broad agreement between the data and predictions. As predicted, the shatter of droplets was found to increase as droplet size and velocity increased, and the surface became harder to wet. Bouncing of droplets occurred most frequently on hard to wet surfaces with high surface tension mixtures. On the other hand, a number of small droplets with low impact velocity were observed to bounce when predicted to lie well within the adhering regime. We believe this discrepancy between the predictions and experimental data could be due to air layer effects that were not taken into account in the current bounce equations. Other discrepancies between experiment and theory are thought to be due to the current assumption of a dry impact surface, whereas, in practice, the leaf surfaces became increasingly covered with fluid throughout the spray test runs.Comment: 19 pages, 6 figures, accepted for publication by Experiments in Fluid

    Investigating the ligand agonism and antagonism at the D2long receptor by dynamic mass redistribution

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    The signalling of the D2 receptor (D2R), a G protein coupled receptor (GPCR), is a complex process consisting of various components. For the screening of D2R ligands, methods quantifying distinct second messengers such as cAMP or the interaction of the receptor with β-arrestin, are commonly employed. In contrast, a label-free biosensor technology like dynamic mass redistribution (DMR), where it is mostly unknown how the individual signalling pathways contribute to the DMR signal, provides a holistic readout of the complex cellular response. In this study, we report the successful application of the DMR technology to CHO-K1 cells stably expressing the human dopamine D2long receptor. In real-time kinetic experiments, studies of D2R reference compounds yielded results for agonists and antagonists that were consistent with those obtained by conventional methods and also allowed a discrimination between partial and full agonists. Furthermore, investigations on the signalling pathway in CHO-K1 hD2longR cells identified the Gαi/o protein as the main proximal trigger of the observed DMR response. The present study has shown that the DMR technology is a valuable method for the characterisation of putative new ligands and, due to its label-free nature, suggests its use for deorphanisation studies of GPCRs

    Additional years of Australian Rural Clinical School undergraduate training is associated with rural practice

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    BACKGROUND: To understand the influence of the number of years spent at an Australian rural clinical school (RCS) on graduate current, preferred current and intended location for rural workforce practice. METHODS: Retrospective online survey of medical graduates who spent 1–3 years of their undergraduate training in the University of New South Wales (UNSW) Rural Clinical School. Associations with factors (gender, rural versus non-rural entry, conscription versus non-conscript and number of years of RCS attendance) influencing current, preferred current and intended locations were assessed using χ2 test. Factors that were considered significant at P < 0.1 were entered into a logistic regression model for further analysis. RESULTS: 214 graduates responded to the online survey. Graduates with three years of previous RCS training were more likely to indicate rural areas as their preferred current work location, than their colleagues who spent one year at an RCS campus (OR = 3.0, 95% CI = 1.2-7.4, P = 0.015). Also RCS graduates that spent three years at an RCS were more likely to intend to take up rural medical practice after completion of training compared to the graduates with one year of rural placement (OR = 5.1, 95% CI = 1.8-14.2, P = 0.002). Non-rural medicine entry graduates who spent three years at rural campuses were more likely to take up rural practice compared to those who spent just one year at a rural campus (OR = 8.4, 95% CI = 2.1-33.5, P = 0.002). CONCLUSIONS: Increasing the length of time beyond a year at an Australian RCS campus for undergraduate medical students is associated with current work location, preferred current work location and intended work location in a rural area. Spending three years in a RCS significantly increases the likelihood of rural career intentions of non-rural students

    A descriptive study of mastitis in Australian breastfeeding women: incidence and determinants

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    <p>Abstract</p> <p>Background</p> <p>Mastitis is one of the most common problems experienced by women who are breastfeeding. Mastitis is an inflammation of breast tissue, which may or may not result from infection. The aims of this paper are to compare rates of mastitis in primiparous women receiving public hospital care (standard or birth centre) and care in a co-located private hospital, and to use multivariate analysis to explore other factors related to mastitis.</p> <p>Methods</p> <p>Data from two studies (a randomised controlled trial [RCT] and a survey) have been combined. The RCT (Attachment to the Breast and Family Attitudes to Breastfeeding, ABFAB) which was designed to test whether breastfeeding education in mid-pregnancy could increase breastfeeding duration recruited public patients at the Royal Women's Hospital at 18–20 weeks gestation. A concurrent survey recruited women planning to give birth in the Family Birth Centre (at 36 weeks gestation) and women in the postnatal wards of Frances Perry House (private hospital). All women were followed up by telephone at 6 months postpartum. Mastitis was defined as at least 2 breast symptoms (pain, redness or lump) AND at least one of fever or flu-like symptoms.</p> <p>Results</p> <p>The 6 month telephone interview was completed by 1193 women. Breastfeeding rates at 6 months were 77% in Family Birth Centre, 63% in Frances Perry House and 53% in ABFAB. Seventeen percent (n = 206) of women experienced mastitis. Family Birth Centre and Frances Perry House women were more likely to develop mastitis (23% and 24%) than women in ABFAB (15%); adjusted odds ratio (Adj OR) ~1.9. Most episodes occurred in the first 4 weeks postpartum: 53% (194/365). Nipple damage was also associated with mastitis (Adj OR 1.7, 95% CI, 1.14, 2.56). We found no association between breastfeeding duration and mastitis.</p> <p>Conclusion</p> <p>The prevention and improved management of nipple damage could potentially reduce the risk of lactating women developing mastitis.</p> <p>Trial registration</p> <p>Trial registration (ABFAB): Current Controlled Trials ISRCTN21556494</p

    The early postnatal period: Exploring women's views, expectations and experiences of care using focus groups in Victoria, Australia

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    Background: There is growing evidence from Australia and overseas that the care provided in hospital in the early postnatal period is less than ideal for both women and care providers. Many health services face increasing pressure on hospital beds and have limited physical space available to care for mothers and their babies. We aimed to gain a more in-depth understanding of women\u27s views, expectations and experiences of early postnatal care.Methods: We conducted focus groups in rural and metropolitan Victoria, Australia in 2006. Fifty-two people participated in eight focus groups and four interviews. Participants included eight pregnant women, of whom seven were pregnant with their first baby; 42 women who were in the postpartum period (some up to twelve months after the birth of their baby); and two partners. All participants were fluent in English. Focus group guides were developed specifically for the study and explored participants\u27 experiences and/or expectations of early postnatal care in hospital and at home, with an emphasis on length of hospital stay, professional and social support, continuity of care, and rest. Discussions were audio-taped and transcribed verbatim. A thematic network was constructed to describe and connect categories with emerging basic, organizing, and global themes.Results: Global themes that emerged were: anxiety and/or fear; and the transition to motherhood and parenting. The needs of first time mothers were considered to be different to the needs of women who had already experienced motherhood. The women in this study were generally concerned about the safety of their new baby, and lacked confidence in themselves as new mothers regarding their ability to care for their baby. There was a consistent view that the physical presence and availability of professional support helped alleviate these concerns, and this was especially the case for women having a first baby.Conclusion: Women have anxieties and fears around early parenting and their changing role, and may consider that the physical availability of professional care providers will help during this time. Care providers should be cognisant of these potential issues. It is crucial that women\u27s concerns and needs be considered when service delivery changes are planned. If anxiety around new parenting is a predominant view then care providers need to recognise this and ensure care is individualised to address each woman\u27s/families particular concerns.<br /

    Efficacy and safety of propranolol as first-line treatment for infantile hemangiomas

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    Beta-blockers are a highly promising treatment modality for complicated infantile hemangiomas (IH). However, data on propranolol as first-line treatment, objective outcome measures and impact on hemodynamics in young infants is limited. We retrospectively evaluated a homogenous group of infants with proliferating complicated IH treated with propranolol (2mg/kg/day). Outcome was assessed by blinded evaluation of clinical photographs by visual analogue scale (VAS), ultrasound examination and ophthalmological review (if appropriate). Tolerance and hemodynamic variables were recorded over time, including a 2-day in-patient observation at the initiation of therapy. Twenty-five infants (median age 3.6 (1.5-9.1) months) were included in the study. The median follow-up-time was 14 (9-20) months and 14 patients completed treatment at a median age of 14.3 (11.4-22.1) months, after a duration of 10.5 (7.5-16) months. In all patients, there was significant fading of colour (with a VAS of −9 (−6 to −9) after 7months) and significant decrease in size of the IH (with a VAS of −8 (−3 to −10) after 7months). Median thickness of the lesions assessed by ultrasound at baseline and after 1month was 14 (7-28) mm and 10 (5-23) mm, respectively (p < 0.01). In children with periocular involvement, astigmatism and amblyopia resolved rapidly within 8weeks. The overall tolerance of propranolol was good, and no relevant hemodynamic changes were noted. Conclusion: Our report supports the excellent effect and good tolerance of this novel therapy, and we propose the use of propranolol as first-line treatment for I

    Ringing up about breastfeeding: a randomised controlled trial exploring early telephone peer support for breastfeeding (RUBY) - trial protocol

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    BACKGROUND: The risks of not breastfeeding for mother and infant are well established, yet in Australia, although most women initiate breastfeeding many discontinue breastfeeding altogether and few women exclusively breastfeed to six months as recommended by the World Health Organization and Australian health authorities. We aim to determine whether proactive telephone peer support during the postnatal period increases the proportion of infants who are breastfed at six months, replicating a trial previously found to be effective in Canada. DESIGN/METHODS: A two arm randomised controlled trial will be conducted, recruiting primiparous women who have recently given birth to a live baby, are proficient in English and are breastfeeding or intending to breastfeed. Women will be recruited in the postnatal wards of three hospitals in Melbourne, Australia and will be randomised to peer support or to 'usual' care. All women recruited to the trial will receive usual hospital postnatal care and infant feeding support. For the intervention group, peers will make two telephone calls within the first ten days postpartum, then weekly telephone calls until week twelve, with continued contact until six months postpartum. Primary aim: to determine whether postnatal telephone peer support increases the proportion of infants who are breastfed for at least six months. HYPOTHESIS: that telephone peer support in the postnatal period will increase the proportion of infants receiving any breast milk at six months by 10% compared with usual care (from 46% to 56%).Outcome data will be analysed by intention to treat. A supplementary multivariate analysis will be undertaken if there are any baseline differences in the characteristics of women in the two groups which might be associated with the primary outcomes. DISCUSSION: The costs and health burdens of not breastfeeding fall disproportionately and increasingly on disadvantaged groups. We have therefore deliberately chosen trial sites which have a high proportion of women from disadvantaged backgrounds. This will be the first Australian randomised controlled trial to test the effectiveness and cost effectiveness of proactive peer telephone support for breastfeeding. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12612001024831
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