Surrogacy and IVF

While in the past surrogacy was illegal in Queensland, since June 2010 the Surrogacy Act 2010 (Qld) (“the Act”) has made altruistic surrogacy arrangements lawful in Queensland. In addition, it provides a mechanism for transfer of legal parentage from the surrogate to the person(s) wishing to have a child (the intended parent(s)). Commercial surrogacy – where a payment, reward or other material benefit of advantage (other than the reimbursement of the “birth mother’s surrogacy costs” (s11 of the Act) is made for entering into a surrogacy arrangement – remains unlawful. The paramount guiding principle underpinning the Act is that of the wellbeing and best interests of a child born as a result of surrogacy. The Surrogacy Act 2010 (Qld) allows a single person or a couple (heterosexual or same sex couples) to enter into an agreement with a woman, and her partner (if she has one), to become pregnant with the intention that the child will be relinquished to the intended parent(s). The Act also provides a mechanism for the intended parent(s) to be legally recognised as the parent(s) of the child. In order for the intended parent(s) to be legally recognised (via a parentage order, discussed below) it must be shown that the surrogacy arrangement was entered into when all the parties were over 25 years of age and the intended parent(s) are male or, in a heterosexual or lesbian couple the female(s) are not likely to conceive or give birth to a healthy child due to medical reasons. The arrangement must be entered into before the surrogate becomes pregnant and all parties must have obtained independent legal advice and counselling about the proposed arrangement, and evidence of this is required at the time a parentage order is applied for. For the purposes of the Act it does not matter how the surrogate conceives the child or if the child is genetically related to the parties. During the period of the pregnancy, the surrogate has the right to manage her pregnancy in the way she wishes. Although she cannot profit from acting as a surrogate, section 11 states that she is entitled to surrogacy costs. These include, for example, reasonable medical costs related to pregnancy and the birth of the child; counselling and legal costs associated with the surrogacy arrangement; actual lost earnings because of leave taken during pregnancy or following birth and any reasonable travel expenses incurred. The surrogacy arrangement itself is not legally enforceable; however, obligations to pay a surrogate’s surrogacy costs are enforceable unless she chooses not to relinquish the child to the intending parents. While the Act does not specifically deal with the situation where the surrogate decides she is unprepared to relinquish the child to the intended parents, there have been examples where parties have entered into these kinds of arrangements, and the arrangements have become difficult. For example, the Family Court case of Re Evelyn (1998) FLC 92–807 involved a child born to a surrogate mother who decided not to surrender her. The child was the genetic child of the surrogate mother and the husband of the couple who had contracted with the surrogate mother. Both sets of parents brought proceedings in the court, seeking that the child live with them. In hearing the application, the court applied the paramount principle of the ‘best interests of the child’. The court made clear that there is no presumption in favour of the birth mother, although in this case the court found that the child may be better placed with the surrogate mother’s family.

Automated recognition of drunk driving on highways from video sequences

A new method for the detection of abnormal vehicle trajectories is proposed. It couples optical flow extraction of vehicle velocities with a neural network classifier. Abnormal trajectories are indicative of drunk or sleepy drivers. A single feature of the vehicle, eg., a tail light, is isolated and the optical flow computed only around this feature rather than at each pixel in the image.

Surrogacy - A Path of Obstacles

Surrogacy has become an effective and accepted form of reproductive technology. It enables couples, regardless of gender or sexuality, to achieve the dream of becoming a parent in circumstances where other forms of reproductive technology and adoption are either not possible or have failed. To its credit, the Queensland parliament has recently brought this state up to date by enacting surrogacy laws that are in line with the majority of statutes implemented throughout the country. The Surrogacy Act 2010 (Qld) allows for the court to make a parentage order in certain circumstances where parties have entered into a surrogacy arrangement. A parentage order effectively transfers parental rights from the birth mother (and her spouse or de facto if there is one) to the intended parents. The requirements which must be satisfied to obtain a parenting order are comprehensive and onerous, making the path to parenthood through a surrogacy arrangement by no means easy. At the heart of the surrogacy issue lies a question, the answer to which has shifted and continues to shift as reproductive technologies continue to increase in success, method and popularity - what is a parent? A recent decision of the Administrative Appeals Tribunal, Hudson v Minister for Immigration and Citizenship, brought to attention the meaning of the word ‘parent’ as it appears in s 16(2) Australian Citizenship Act 2007 (Cth) (‘the Act’). Section 16(2) deals with citizenship by descent and provides that a person born outside Australia may make an application to the Minister to become an Australian citizen if a parent of the person was an Australian citizen at the time of the birth.

Support for energy-oriented design in the Australian context

There is a need for decision support tools that integrate energy simulation into early design in the context of Australian practice. Despite the proliferation of simulation programs in the last decade, there are no ready-to-use applications that cater specifically for the Australian climate and regulations. Furthermore, the majority of existing tools focus on achieving interaction with the design domain through model-based interoperability, and largely overlook the issue of process integration. This paper proposes an energy-oriented design environment that both accommodates the Australian context and provides interactive and iterative information exchanges that facilitate feedback between domains. It then presents the structure for DEEPA, an openly customisable system that couples parametric modelling and energy simulation software as a means of developing a decision support tool to allow designers to rapidly and flexibly assess the performance of early design alternatives. Finally, it discusses the benefits of developing a dynamic and concurrent performance evaluation process that parallels the characteristics and relationships of the design process.

Closing the loop of design and analysis : Parametric modelling tools for early decision support

There is a growing need for parametric design software that communicates building performance feedback in early architectural exploration to support decision-making. This paper examines how the circuit of design and analysis process can be closed to provide active and concurrent feedback between architecture and services engineering domains. It presents the structure for an openly customisable design system that couples parametric modelling and energy analysis software to allow designers to assess the performance of early design iterations quickly. Finally, it discusses how user interactions with the system foster information exchanges that facilitate the sharing of design intelligence across disciplines.

Microbial colonisation of human follicular fluid and adverse in vitro fertilisation outcomes

This study, investigating 263 women undergoing trans-vaginal oocyte retrieval for in vitro fertilisation (IVF) found that microorganisms colonising follicular fluid contributed to adverse IVF (pre-implantation) and pregnancy (post-implantation) outcomes including poor quality embryos, failed pregnancy and early pregnancy loss (< 37 weeks gestation). Some microorganisms also showed in vitro growth patterns in liquid media that appeared to be enhanced by the hormonal stimulation protocol used for oocyte retrieval. Elaborated cytokines within follicular fluid were also associated with adverse IVF outcomes. This study is imperative because infertility affects 16% of the human population and the numbers of couples needing assistance continues to increase. Despite significant improvements in the technical aspects of assisted reproductive technologies (ART), the live birth rate has not increased proportionally. Overt genital tract infection has been associated with both infertility and adverse pregnancy outcomes (including miscarriage and preterm birth) as a direct result of the infection or the host response to it. Importantly, once inflammation had become established, medical treatment often failed to prevent these significant adverse outcomes. Current evaluations of fertility focus on the ovary as a site of steroid hormone production and ovulation. However, infertility as a result of subclinical colonisation of the ovary has not been reported. Furthermore, identification of the microorganisms present in follicular fluid and the local cytokine profile may provide clinicians with an early indication of the prognosis for IVF treatment in infertile couples, thus allowing antimicrobial treatment and/or counselling about possible IVF failure. During an IVF cycle, multiple oocytes undergo maturation in vivo in response to hormonal hyperstimulation. Oocytes for in vitro insemination are collected trans-vaginally. The follicular fluid that bathes the maturing oocyte in vivo, usually is discarded as part of the IVF procedure, but provides a unique opportunity to investigate microbial causes of adverse IVF outcomes. Some previous studies have identified follicular fluid markers that predict IVF pregnancy outcomes. However, there have not been any detailed microbiological studies of follicular fluid. For this current study, paired follicular fluid and vaginal secretion samples were collected from women undergoing IVF cycles to determine whether microorganisms in follicular fluid were associated with adverse IVF outcomes. Microorganisms in follicular fluid were regarded as either "colonisers" or "contaminants"; colonisers, if they were unique to the follicular fluid sample, and contaminants if the same microorganisms were detected in the vaginal and follicular fluid samples indicating that the follicular fluid was merely contaminated during the oocyte retrieval process. Quite unexpectedly, by these criteria, we found that follicular fluid from approximately 30% of all subjects was colonised with bacteria. Fertile and infertile women with colonised follicular fluid had decreased embryo transfer rates and decreased pregnancy rates compared to women with contaminated follicular fluids. The observation that follicular fluid was not always sterile, but contained a diverse range of microorganisms, is novel. Many of the microorganisms we detected in follicular fluid are known opportunistic pathogens that have been detected in upper genital tract infections and are associated with adverse pregnancy outcomes. Bacteria were able to survive for at least 28 weeks in vitro, in cultures of follicular fluid. Within 10 days of establishing these in vitro cultures, several species (Lactobacillus spp., Bifidobacterium spp., Propionibacterium spp., Streptococcus spp. and Salmonella entericus) had formed biofilms. Biofilms play a major role in microbial pathogenicity and persistence. The propensity of microbial species to form biofilms in follicular fluid suggests that successful treatment of these infections with antimicrobials may be difficult. Bifidobacterium spp. grew, in liquid media, only if concentrations of oestradiol and progesterone were similar to those achieved in vivo during an IVF cycle. In contrast, the growth of Streptococcus agalactiae and Escherichia coli was inhibited or abolished by the addition of these hormones to culture medium. These data suggest that the likelihood of microorganisms colonising follicular fluid and the species of bacteria involved is influenced by the stage of the menstrual cycle and, in the case of IVF, the nature and dose of steroid hormones administered for the maturation of multiple oocytes in vivo. Our findings indicate that the elevated levels of steroid hormones during an IVF cycle may influence the microbial growth within follicular fluid, suggesting that the treatment itself will impact on the microflora present in the female upper genital tract during pre-conception and early post-conception phases of the cycle. The effect of the host immune response on colonising bacteria and on the outcomes of IVF also was investigated. White blood cells reportedly compose between 5% and 15% of the cell population in follicular fluid. The follicular membrane is semi-permeable and cells are actively recruited as part of the normal menstrual cycle and in response to microorganisms. A previous study investigated follicular fluid cytokines from infertile women and fertile oocyte donors undergoing IVF, and concluded that there were no significant differences in the cytokine concentrations between the two groups. However, other studies have reported differences in the follicular fluid cytokine levels associated with infertile women with endometriosis or polycystic ovary syndrome. In this study, elevated levels of interleukin (IL)-1 á, IL-1 â and vascular endothelial growth factor (VEGF) in vaginal fluid were associated with successful fertilisation, which may be useful marker for successful fertilisation outcomes for women trying to conceive naturally or prior to oocyte retrieval for IVF. Elevated levels of IL-6, IL-12p40, granulocyte colony stimulating factor (GCSF) and interferon-gamma (IFN ã) in follicular fluid were associated with successful embryo transfer. Elevated levels of pro-inflammatory IL-18 and decreased levels of anti-inflammatory IL-10 were identified in follicular fluid from women with idiopathic infertility. Successful fertilisation and implantation is dependent on a controlled pro-inflammatory environment, involving active recruitment of pro-inflammatory mediators to the genital tract as part of the menstrual cycle and early pregnancy. However, ongoing pregnancy requires an enhanced anti-inflammatory environment to ensure that the maternal immune system does not reject the semi-allergenic foetus. The pro-inflammatory skew in the follicular fluid of women with idiopathic infertility, correlates with normal rates of fertilisation, embryo discard and embryo transfer, observed for this cohort, which were similar to the outcomes observed for fertile women. However, their pregnancy rate was reduced compared to fertile women. An altered local immune response in follicular fluid may provide a means of explaining infertility in this cohort, previously defined as 'idiopathic'. This study has found that microorganisms colonising follicular fluid may have contributed to adverse IVF and pregnancy outcomes. Follicular fluid bathes the cumulus oocyte complex during the in vivo maturation process, and microorganisms in the fluid, their metabolic products or the local immune response to these microorganisms may result in damage to the oocytes, degradation of the cumulus or contamination of the IVF culture system. Previous studies that have discounted bacterial contamination of follicular fluid as a cause of adverse IVF outcomes failed to distinguish between bacteria that were introduced into the follicular fluid at the time of trans-vaginal oocyte retrieval and those that colonised the follicular fluid. Those bacteria that had colonised the fluid may have had time to form biofilms and to elicit a local immune response. Failure to draw this distinction has previously prevented consideration of bacterial colonisation of follicular fluid as a cause of adverse IVF outcomes. Several observations arising from this study are of significance to IVF programs. Follicular fluid is not always sterile and colonisation of follicular fluid is a cause of adverse IVF and pregnancy outcomes. Hormonal stimulation associated with IVF may influence whether follicular fluid is colonised and enhance the growth of specific species of bacteria within follicular fluid. Bacteria in follicular fluid may form biofilms and literature has reported that this may influence their susceptibility to antibiotics. Monitoring the levels of selected cytokines within vaginal secretions may inform fertilisation outcomes. This study has identified novel factors contributing to adverse IVF outcomes and that are most likely to affect also natural conception outcomes. Early intervention, possibly using antimicrobial or immunological therapies may reduce the need for ART and improve reproductive health outcomes for all women.

Acculturation stress in South Sudanese refugees : impact on marital relationships

A qualitative approach was used to explore the impact of acculturation stress on the marital relationships of South Sudanese refugees settled in Brisbane, Australia. Thirteen refugees, who were currently or previously married, participated in three gender specific focus groups. The perceived causes and possible solutions of conflict were thoroughly explored. Hypothetical scenarios were used to facilitate group discussion. Major issues causing conflict between couples were identified as: the management of finances and lack of family and social support. Several other areas of acculturation stress also emerged as factors associated with marital stress. There was a dissonance regarding the adherence to cultural gender roles. Freedom provided to women in Australia caused tension between the couples. Law enforcement officers were perceived as lacking cultural understanding and misinterpreting the couple distress. Finally, limited information provided to refugees pre and post migration was considered to hinder adjustment. The participants suggested a number of practical solutions to these issues which are potentially useful in guiding future refugee settlement programs.

Evaluating responses to land degradation mitigation measures in Southern Italy

The main factors affecting environmental sensitivity to degradation are soil, vegetation, climate and management, through either their intrinsic characteristics or by their interaction on the landscape. Different levels of degradation risks may be observed in response to particular combinations of the aforementioned factors. For instance, the combination of inappropriate management practices and intrinsically weak soil conditions will result in a severe degradation of the environment, while the combination of the same type of management with better soil conditions may lead to negligible degradation.The aim of this study was to identify factors and their impact on land degradation processes in three areas of the Basilicata region (southern Italy) using a procedure that couples environmental indices, GIS and crop-soil simulation models. Areas prone to desertification were first identified using the Environmental Sensitive Areas (ESA) procedure. An analysis for identifying the weight that each of the contributing factor (climate, soil, vegetation, management) had on the ESA was carried out using GIS techniques. The SALUS model was successfully executed to identify the management practices that could lead to better soil conditions to enhance land use sustainability. The best management practices were found to be those that minimized soil disturbance and increased soil organic carbon. Two alternative scenarios with improved soil quality and subsequently improving soil water holding capacity were used as mitigation measures. The ESA were recalculated and the effects of the mitigation measures suggested by the model were assessed. The new ESA showed a significant reduction on land degradation.

An Economic Exclusion/Male Peer Support Model Looks at 'Wedfare' and Woman Abuse

In recent years ‘‘welfare reform’’ has become a vehicle for many neo-conservative social commentators to invoke marriage vows as a cure for poverty and the abuse of poor women. Their basic claim is that cohabiting relationships are not only more violent than marriages, but that married couples are happier, healthier, and wealthier than cohabiting ones. A policy then of encouraging cohabitants to marry, they claim, would lead to increased family wealth and decreased family violence. We examine these claims in this article, along with the alternative argument that marriage per se is not a solution to these problems. Alternatively we propose an economic exclusion/male peer support model that explains why many cohabiting men abuse women in intimate relationships. If forcing these couples to marry is not a solution, then structural solutions are necessary, along with progressive policy suggestions that address the antecedents of poverty and abuse.

Men, wage work and family

In the last two decades there has been a plethora of research on a range of subjects collectively and rhetorically known as ‘work-life balance’. The bulk of this research, which spans disciplines including feminist sociology, industrial relations and management, has focused on the significant concerns of employed women and/or dual career couples. Less attention has been devoted to scholarship which explicitly examines men and masculinities in this context. Meanwhile, public and organizational discourse is largely espoused in gender neutral terms, often neglecting salient gendered issues which differentially impact the ability of women and men to successfully integrate their work and non-work lives. This edited book brings together empirical studies of the work-life nexus with a specific focus on men’s working time arrangements, how men navigate and traverse paid work and family commitments, and the impact of public and organizational policies on men’s participation in work, leisure, and other life domains. The book is innovative in that it presents both macro (institutional, how policy affects practice) and micro (individual, from men’s own perspectives) level studies, allowing for a rich and contrasting exploration of how men’s participation in paid work and other domains is divided, conflicted, or integrated. The essays in this volume address issues of fundamental social, labor market, and economic change which have occurred over the last 20 years and which have profoundly affected the way work, care, leisure and community have evolved in different contexts. Taking an international focus, Men, Wage Work and Family contrasts various public and organizational policies and how these policies impact men’s opportunities and participation in paid work and non-work domains in industrialised countries in Europe, North America, and Australia.

Introduction. Locating men in the work-life nexus

In the last two decades there has been a plethora of research on a range of subjects collectively and rhetorically known as ‘work-life balance’. The bulk of this research, which spans disciplines including feminist sociology, industrial relations and management, has focused on the significant concerns of employed women and/or dual career couples. Less attention has been devoted to scholarship which explicitly examines men and masculinities in this context. Meanwhile, public and organizational discourse is largely espoused in gender neutral terms, often neglecting salient gendered issues which differentially impact the ability of women and men to successfully integrate their work and non-work lives. This edited book brings together empirical studies of the work-life nexus with a specific focus on men’s working time arrangements, how men navigate and traverse paid work and family commitments, and the impact of public and organizational policies on men’s participation in work, leisure, and other life domains. The book is innovative in that it presents both macro (institutional, how policy affects practice) and micro (individual, from men’s own perspectives) level studies, allowing for a rich and contrasting exploration of how men’s participation in paid work and other domains is divided, conflicted, or integrated. The essays in this volume address issues of fundamental social, labor market, and economic change which have occurred over the last 20 years and which have profoundly affected the way work, care, leisure and community have evolved in different contexts. Taking an international focus, Men, Wage Work and Family contrasts various public and organizational policies and how these policies impact men’s opportunities and participation in paid work and non-work domains in industrialised countries in Europe, North America, and Australia.

Surrogacy laws in Queensland: one step forward and two steps back?

This short article summarises some of the proposed reforms to surrogacy laws in Queensland, suggested by the Liberal National Party in 2012. The paper outlines some of the main objections that could be voiced in response to the proposed changes to the law.

A dual-scale modelling approach for drying hygroscopic porous media

A new dualscale modelling approach is presented for simulating the drying of a wet hygroscopic porous material that couples the porous medium (macroscale) with the underlying pore structure (microscale). The proposed model is applied to the convective drying of wood at low temperatures and is valid in the so-called hygroscopic range, where hygroscopically held liquid water is present in the solid phase and water exits only as vapour in the pores. Coupling between scales is achieved by imposing the macroscopic gradients of moisture content and temperature on the microscopic field using suitably-defined periodic boundary conditions, which allows the macroscopic mass and thermal fluxes to be defined as averages of the microscopic fluxes over the unit cell. This novel formulation accounts for the intricate coupling of heat and mass transfer at the microscopic scale but reduces to a classical homogenisation approach if a linear relationship is assumed between the microscopic gradient and flux. Simulation results for a sample of spruce wood highlight the potential and flexibility of the new dual-scale approach. In particular, for a given unit cell configuration it is not necessary to propose the form of the macroscopic fluxes prior to the simulations because these are determined as a direct result of the dual-scale formulation.

In vitro and in vivo studies on protease-activated receptor-2

Protease-activated receptor-2 (PAR2) is a G protein coupled receptor (GPCR) that is activated by proteolytic cleavage of its amino terminal domain by trypsin-like serine proteases. Cleavage of this receptor exposes a neoepitope, termed the tethered ligand (TL), which binds intramolecularly within the receptor to stimulate signal transduction via coupled G proteins. PAR2-mediated signal transduction is also experimentally stimulated by hexapeptides (agonist peptides; APs) that are homologous to the TL sequence. Due to the irreversible nature of PAR2 proteolysis, downstream signal transduction is tightly regulated. Following activation, PAR2 is rapidly uncoupled from downstream signalling by the post-translational modifications phosphorylation and ubiquination which facilitate interactions with â- arrestin. This scaffolding protein couples PAR2 to the internalisation machinery initiating its desensitisation and trafficking through the early and late endosomes followed by receptor degradation. PAR2 is widely expressed in mammalian tissues with key roles for this receptor in cardiovascular, respiratory, nervous and musculoskeletal systems. This receptor has also been linked to pathological states with aberrant expression and signalling noted in several cancers. In prostate cancer, PAR2 signalling induces migration and proliferation of tumour derived cell lines, while elevated receptor expression has been noted in malignant tissues. Importantly, a role for this receptor has also been suggested in prostate cancer bone metastasis as coexpression of PAR2 and a proteolytic activator has been demonstrated by immunohistochemical analysis. Based on these data, the primary focus of this project has been on two aspects of PAR2 biology. The first is characterisation of cellular mechanisms that regulate PAR2 signalling and trafficking. The second aspect is the role of this receptor in prostate cancer bone metastasis. In addition, to permit these studies, it was first necessary to evaluate the specificity of the commercially available anti-PAR2 antibodies SAM11, C17, N19 and H99. The evaluation of the four commercially available antibodies was assessed using four techniques: immunoprecipitation; Western blot analysis; immunofluorescence; and flow cytometry. These approaches demonstrated that three of the antibodies efficiently detect ectopically expressed PAR2 by each of these techniques. A significant finding from this study was that N19 was the only antibody able to specifically detect N-glycosylated endogenous PAR2 by Western blot analysis. This analysis was performed on lysates from prostate cancer derived cell lines and tissue derived from wildtype and PAR2 knockout mice. Importantly, further evaluation demonstrated that this antibody also efficiently detects endogenous PAR2 at the cell surface by flow cytometry. The anti-PAR2 antibody N19 was used to explore the in vitro role of palmitoylation, the post-translational addition of palmitate, in PAR2 signalling, trafficking, cell surface expression and desensitization. Significantly, use of the palmitoylation inhibitor 2-bromopalmitate indicated that palmitate addition is important in trafficking of PAR2 endogenously expressed by prostate cancer cell lines. This was supported by palmitate labelling experiments using two approaches which showed that PAR2 stably expressed by CHO cells is palmitoylated and that palmitoylation occurs on cysteine 361. Another key finding from this study is that palmitoylation is required for optimal PAR2 signalling as Ca2+ flux assays indicated that in response to trypsin agonism, palmitoylation deficient PAR2 is ~9 fold less potent than wildtype receptor with a reduction of about 33% in the maximum signal induced via the mutant receptor. Confocal microscopy, flow cytometry and cell surface biotinylation analyses demonstrated that palmitoylation is required for efficient cell surface expression of PAR2. Importantly, this study also identified that palmitoylation of this receptor within the Golgi apparatus is required for efficient agonist-induced rab11amediated trafficking of PAR2 to the cell surface. Interestingly, palmitoylation is also required for receptor desensitization, as agonist-induced â-arrestin recruitment and receptor degradation were markedly reduced in CHO-PAR2-C361A cells compared with CHO-PAR2 cells. Collectively, these data provide new insights on the life cycle of PAR2 and demonstrate that palmitoylation is critical for efficient signalling, trafficking, cell surface localization and degradation of this receptor. This project also evaluated PAR2 residues involved in ligand docking. Although the extracellular loop (ECL)2 of PAR2 is known to be required for agonist-induced signal transduction, the binding pocket for receptor agonists remains to be determined. In silico homology modelling, based on a crystal structure for the prototypical GPCR rhodopsin, and ligand docking were performed to identify PAR2 transmembrane (TM) amino acids potentially involved in agonist binding. These methods identified 12 candidate residues that were mutated to examine the binding site of the PAR2 TL, revealed by trypsin cleavage, as well as of the soluble ligands 2f-LIGRLO-NH2 and GB110, which are both structurally based on the AP SLIGRLNH2. Ligand binding was evaluated from the impact of the mutated residues on PAR2-mediated calcium mobilisation. An important finding from these experiments was that mutation of residues Y156 and Y326 significantly reduced 2f-LIGRLO-NH2 and GB110 agonist activity. L307 was also important for GB110 activity. Intriguingly, mutation of PAR2 residues did not alter trypsin-induced signalling to the same extent as for the soluble agonists. The reason for this difference remains to be further examined by in silico and in vitro experimentation and, potentially, crystal structure studies. However, these findings identified the importance of TM domains in PAR2 ligand docking and will enhance the design of both PAR2 agonists and potentially agents to inhibit signalling (antagonists). The potential importance of PAR2 in prostate cancer bone metastasis was examined using a mouse model. In patients, prostate cancer bone metastases cause bone growth by disrupting bone homeostasis. In an attempt to mimic prostate cancer growth in bone, PAR2 responsive 22Rv1 prostate cancer cells, which form mixed osteoblastic and osteolytic lesions, were injected into the proximal aspect of mouse tibiae. A role for PAR2 was assessed by treating these mice with the recently developed PAR2 antagonist GB88. As controls, animals bearing intra-tibial tumours were also treated with vehicle (olive oil) or the prostate cancer chemotherapeutic docetaxel. The effect of these treatments on bone was examined radiographically and by micro-CT. Consistent with previous studies, 22Rv1 tumours caused osteoblastic periosteal spicule formation and concurrent osteolytic bone loss. Significantly, blockade of PAR2 signalling reduced the osteoblastic and osteolytic phenotype of 22Rv1 tumours in bone. No bone defects were detected in mice treated with docetaxel. These qualitative data will be followed in the future by quantitative micro-CT analysis as well as histology and histomorphometry analysis of already collected tissues. Nonetheless, these preliminary experiments highlight a potential role for PAR2 in prostate cancer growth in bone. In summary, in vitro studies have defined mechanisms regulating PAR2 activation, downstream signalling and trafficking and in vivo studies point to a potential role for this receptor in prostate cancer bone metastasis. The outcomes of this project are that a greater understanding of the biology of PAR2 may lead to the development of strategies to modulate the function of this receptor in disease.