Synthesis of an erodible biomimetic hydrogel for drug delivery using native chemical ligation

Hydrogels are hydrophilic, three dimensional polymers that imbibe large quantities of water while remaining insoluble in aqueous solutions due to chemical or physical cross-linking. The polymers swell in water or biological fluids, immobilizing the bioactive agent, leading to drug release in a well-defined specific manner. Thus the hydrogels’ elastic properties, swellability and biocompatibility make them excellent formulations for drug delivery. Currently, many drug potencies and therapeutic effects are limited or otherwise reduced because of the partial degradation that occurs before the administered drug reaches the desired site of action. On the other hand, sustained release medications release drugs continually, rather than providing relief of symptoms and protection solely when necessary. In fact, it would be much better if drugs could be administered in a manner that precisely matches physiological needs at desired times and at the desired site (site specific targeting). There is therefore an unmet need to develop controlled drug delivery systems especially for delivery of peptide and protein bound drugs. The purpose of this project is to produce hydrogels for structural drug delivery and time-dependent sustained release of drugs (bioactive agents). We use an innovative polymerisation strategy based on native chemical ligation (NCL) to covalently cross-link polymers to form hydrogels. When mixed in aqueous solution, four armed (polyethylene glycol) amine (PEG-4A) end functionalised with thioester and four branched Nterminal cysteine peptide dendrimers spontaneously conjugated to produce biomimetic hydrogels. These hydrogels showed superior resistance to shear stress compared to an equivalent PEG macromonomer system and were shown to be proteolytically degradable with concomitant release of a model payload molecule. This is the first report of a peptide dendrimers/PEG macromonomer approach to hydrogel production and opens up the prospect of facile hydrogel synthesis together with tailored payload release.

Advanced Bioactive Inorganic Materials for Bone Regeneration and Drug Delivery

Bioceramics play an important role in repairing and regenerating bone defects. Annually, more than 500,000 bone graft procedures are performed in the United states and approximately 2.2 million are conducted worldwide. The estimated cost of these procedures approaches $2.5billion per year. Around 60% of the bone graft substitutes available on the market involve bioceramics. It is reported that bioceramics in the world market increase by 9% per year. For this reason, the research of bioceramics has been one of the most active areas during, the past several years. Considering the significant importance of bioceramics, our goal was to compile this book to review the latest research advances in the field of bioceramics. The text also summarizes our work during the past 10 years in an effort to share innovative concepts, design of bioceramisc, and methods for material synthesis and drug delivery. We anticipate that this text will provide some useful information and guidance in the bioceramics field for biomedical engineering researchers and material scientists. Information on novel mesoporous bioactive glasses and silicate-based ceramics for bone regeneration and drug delivery are presented. Mesoporous bioactive glasses have shown multifunctional characteristics of bone regeneration and drug delivery due to their special mesopore structures,whereas silicated-based bioceramics, as typical third-generation biomaterials,possess significant osteostimulation properties. Silica nanospheres with a core-shell structure and specific properties for controllable drug delivery have been carefully reviewed-a variety of advanced synthetic strategies have been developed to construct functional mesoporous silica nanoparticles with a core-shell structure, including hollow, magnetic, or luminescent, and other multifunctional core-shell mesoporous silica nanoparticles. In addition, multifunctional drug delivery systems based on these nanoparticles have been designed and optimized to deliver the drugs into the targeted organs or cells,with a controllable release fashioned by virtue of various internal and external triggers. The novel 3D-printing technique to prepare advanced bioceramic scaffolds for bone tissue engineering applications has been highlighted, including the preparation, mechanical strength, and biological properties of 3D-printed porous scaffolds of calcium phosphate cement and silicate bioceramics. Three-dimensional printing techniques offer improved large-pore structure and mechanical strength. In addition , biomimetic preparation and controllable crystal growth as well as biomineralization of bioceramics are summarized, showing the latest research progress in this area. Finally, inorganic and organic composite materials are reviewed for bone regeneration and gene delivery. Bioactive inorganic and organic composite materials offer unique biological, electrical, and mechanical properties for designing excellent bone regeneration or gene delivery systems. It is our sincere hope that this book will updated the reader as to the research progress of bioceramics and their applications in bone repair and regeneration. It will be the best reward to all the contributors of this book if their efforts herein in some way help reader in any part of their study, research, and career development.

"They did not believe me" : Adult survivors' perspectives of child sexual abuse by personnel in Christian Institutions

Executive Summary Child sexual abuse (CSA) in Christian Institutions continues to be of serious concern in public, criminal justice and institutional discourse. This study was conducted in conjunction with Project Kidsafe Foundation and sought the perspectives of Australian survivors of CSA by Personnel in Christian Institutions (PICIs). In total, 81 individual survivors responded to an online survey which asked them a range of questions about their current and childhood life circumstance; the nature, extent and location of abuse; grooming strategies utilised by perpetrators; their experiences of disclosure; and outcomes of official reporting to both criminal justice agencies and also official processes Christian institutions. Survey participants were given the option to further participate in a qualitative interview with the principal researcher. These interviews are not considered within this report. In summary, survey data examined here indicate that: • Instances of abuse included a range of offences from touching outside of clothing to serious penetrative offences. • The onset of abuse occurred at a young age: between 6 and 10 years for most female participants, and 11 and 13 years for male participants. • In the majority of cases the abuse ceased because of actions by survivors, not by adults within families or the Christian institution. • Participants waited significant time before disclosing their abuse, with many waiting 20 years or more. • Where survivors disclosed to family members or PICIs, they were often met with disbelief and unhelpful responses aimed at minimising the harm. • Where an official report was made, it was most often made to police. In these cases 53% resulted in an official investigations. • The primary reasons for reporting were to protect others from the perpetrator and make the Christian institution accountable to an external agency. • Where reports to Christian institutions were made, most survivors were dissatisfied with outcomes, and a smaller majority was extremely dissatisfied. This report reflects the long-held understanding that responding to CSA is a complex and difficult task. If effective and meaningful responses are not made, however, trauma to the survivor is most often compounded and recovery delayed. This report demonstrates the need for further independent analysis and oversight of responses made to CSA by both criminal justice, religious and social institutions. Meaningful change will only be accessible, however, if family, community and institutional environments are safe places for survivors to disclose their experiences of abuse and begin to seek ways of healing. There is much to be learnt from survivors that have already made this journey.

Identity, forgiveness and power in the management of child sexual abuse by personnel in Christian Institutions

The ongoing crises of child sexual abuse by Christian institutions leaders across the Anglophone world continue to attract public attention and public inquiries. The pervasiveness of this issue lends credence to the argument that the prevailing ethos functioning within some Christian Institutions is one which exercises influence to repeatedly mismanage allegations of child sexual abuse by Church leaders. This work draws on semistructured interviews conducted with 15 Personnel in Christian Institutions (PICIs) in Australia who were identified as being pro-active in their approach to addressing child sexual abuse by PICIs. From these data, themes of power and forgiveness are explored through a Foucaultian conceptualising of pastoral power and ‘truth’ construction. Forgiveness is viewed as a discourse which can have the power effect of either silencing or empowering victim/survivors. The study concludes that individual PICIs’ understandings of the role ofpower in their praxis influences outcomes from the deployment of forgiveness.

Child sexual abuse prevention education : A review of school policy and curriculum provision in Australia

The past four decades have seen increasing public and professional awareness of child sexual abuse. Congruent with public health approaches to prevention, efforts to eliminate child sexual abuse have inspired the emergence of prevention initiatives which can be provided to all children as part of their standard school curriculum. However, relatively little is known about the scope and nature of child sexual abuse prevention efforts in government school systems internationally. This paper assesses and compares the policies and curriculum initiatives for child sexual abuse prevention education in primary (elementary) schools across state and territory Departments of Education in Australia. Using publicly available electronic data, a deductive qualitative content analysis of policy and curriculum documents was undertaken to examine the characteristics of child sexual abuse prevention education in these school systems. It was found that the system-level provision of child sexual abuse prevention education occurs unevenly across state and territory jurisdictions. This results in the potential for substantial inequity in Australian children’s access to learning opportunities in child abuse prevention education as a part of their standard school curriculum. In this research, we have developed a strategy for generating a set of theoretically-sound empirical criteria that may be more extensively applied in comparative research about prevention initiatives internationally.

Mathematical modelling of controlled drug release from polymer micro-spheres : incorporating the effects of swelling, diffusion and dissolution via moving boundary problems

Controlled drug delivery is a key topic in modern pharmacotherapy, where controlled drug delivery devices are required to prolong the period of release, maintain a constant release rate, or release the drug with a predetermined release profile. In the pharmaceutical industry, the development process of a controlled drug delivery device may be facilitated enormously by the mathematical modelling of drug release mechanisms, directly decreasing the number of necessary experiments. Such mathematical modelling is difficult because several mechanisms are involved during the drug release process. The main drug release mechanisms of a controlled release device are based on the device’s physiochemical properties, and include diffusion, swelling and erosion. In this thesis, four controlled drug delivery models are investigated. These four models selectively involve the solvent penetration into the polymeric device, the swelling of the polymer, the polymer erosion and the drug diffusion out of the device but all share two common key features. The first is that the solvent penetration into the polymer causes the transition of the polymer from a glassy state into a rubbery state. The interface between the two states of the polymer is modelled as a moving boundary and the speed of this interface is governed by a kinetic law. The second feature is that drug diffusion only happens in the rubbery region of the polymer, with a nonlinear diffusion coefficient which is dependent on the concentration of solvent. These models are analysed by using both formal asymptotics and numerical computation, where front-fixing methods and the method of lines with finite difference approximations are used to solve these models numerically. This numerical scheme is conservative, accurate and easily implemented to the moving boundary problems and is thoroughly explained in Section 3.2. From the small time asymptotic analysis in Sections 5.3.1, 6.3.1 and 7.2.1, these models exhibit the non-Fickian behaviour referred to as Case II diffusion, and an initial constant rate of drug release which is appealing to the pharmaceutical industry because this indicates zeroorder release. The numerical results of the models qualitatively confirms the experimental behaviour identified in the literature. The knowledge obtained from investigating these models can help to develop more complex multi-layered drug delivery devices in order to achieve sophisticated drug release profiles. A multi-layer matrix tablet, which consists of a number of polymer layers designed to provide sustainable and constant drug release or bimodal drug release, is also discussed in this research. The moving boundary problem describing the solvent penetration into the polymer also arises in melting and freezing problems which have been modelled as the classical onephase Stefan problem. The classical one-phase Stefan problem has unrealistic singularities existed in the problem at the complete melting time. Hence we investigate the effect of including the kinetic undercooling to the melting problem and this problem is called the one-phase Stefan problem with kinetic undercooling. Interestingly we discover the unrealistic singularities existed in the classical one-phase Stefan problem at the complete melting time are regularised and also find out the small time behaviour of the one-phase Stefan problem with kinetic undercooling is different to the classical one-phase Stefan problem from the small time asymptotic analysis in Section 3.3. In the case of melting very small particles, it is known that surface tension effects are important. The effect of including the surface tension to the melting problem for nanoparticles (no kinetic undercooling) has been investigated in the past, however the one-phase Stefan problem with surface tension exhibits finite-time blow-up. Therefore we investigate the effect of including both the surface tension and kinetic undercooling to the melting problem for nanoparticles and find out the the solution continues to exist until complete melting. The investigation of including kinetic undercooling and surface tension to the melting problems reveals more insight into the regularisations of unphysical singularities in the classical one-phase Stefan problem. This investigation gives a better understanding of melting a particle, and contributes to the current body of knowledge related to melting and freezing due to heat conduction.

Understanding the operational structure of Southeast Asian drug trafficking groups in Australia

This thesis examined the operational structure of Southeast Asian drug trafficking groups operating on the eastern seaboard of Australia by testing the validity and application of organised crime and drug trafficking typologies using data obtained from 159 drug trafficking cases in three Australian states: New South Wales; Queensland; and Victoria. Key findings indicated that the usefulness of typologies is limited when classifying and analysing organised crime groups. In particular, Southeast Asian drug trafficking groups operated largely in small, informal, family-based hierarchies or groups that were better conceptualised using theoretical perspectives from network and cultural studies. The study recommended that replicating previous empirical research in the field is an effective approach that will contribute towards building a cumulative body of knowledge on organised crime structures.

The role for police in addressing alcohol-related harm inside and outside licensed premises

Alcohol consumption is enmeshed with Australian culture (Palk, 2008) and the use and misuse of alcohol contributes to considerable health and social harms (Barbor et al., 2010; English et al., 1995; Gutjahr, Gmel, & Rehm, 2001; Palk, 2008; Steenkamp, Harrison, & Allsop, 2002). Despite shifts in the way that alcohol is consumed and how it is used, it has been reported that one-third of all alcohol consumed is done so within licensed premises (Lang, Stockwell, Rydon, & Gamble, 1992). Consequently, licensed premises are over-represented as settings in which alcohol-related harms occur. These harms, particularly those related to violence, are associated with particular licensed premises operating in the night-time economy (Briscoe & Donnelly, 2001b; Chikritzhs, Stockwell, & Masters, 1997; Homel, Tomsen, & Thommeny, 1991; Stockwell, 1997). Police have a role in not only responding to the manifestation of harms, such as crime, injuries, assaults, domestic violence, stealing and sexual offences, but they also have a role in preventing problems, and thereby reducing alcohol and other drug-related harms (Doherty & Roche, 2003). Given the extent of alcohol consumption within licensed premises and the nature and extent of the harms, as well as the lack of opportunity to influence outcomes in other settings (e.g. the home), licensed premises offer police and other stakeholders a significant opportunity to influence positively the reduction of alcoholrelated harm. This research focuses specifically on the police role in policing licensed premises. Primarily, this research aims to investigate the factors which are relevant to why and how police officers respond to alcohol-related incidents inside and outside licensed premises. It examines the attitudes and beliefs of police and assesses their knowledge, capacity and ability to effectively police licensed premises. The research methodology uses three distinct surveys. Each contributes to understanding the motivations and practice of police officers in this important area of harm reduction. Study One involved a survey of police officers within a police district (Brisbane Central District) in Queensland, Australia and used a comprehensive questionnaire involving both quantitative and qualitative techniques. A key research outcome of Study One was the finding that officers had low levels of knowledge of the strategies that are effective in addressing alcohol-related harm both inside and outside licensed premises. Paradoxically, these officers also reported extensive recent experience in dealing with alcohol issues in these locations. In addition, these officers reported that alcohol was a significant contextual factor in the majority of matters to which they responded. Officers surveyed reported that alcohol increased the difficulty of responding to situations and that licensed premises (e.g. nightclubs, licensed clubs and hotels) were the most difficult contexts to police. Those surveyed were asked to self-assess their knowledge of the Liquor Act (Qld), which is the primary legislative authority in Queensland for regulating licensed premises. Surprisingly, well over half of the officers (65%) reported ‘no’ to ‘fair’ knowledge of the Act, despite officers believing that their skill level to police such premises was in the ‘good to very good range’. In an important finding, officers reported greater skill level to police outside licensed premises than inside such premises, indicating that officers felt less capable, from a skill perspective, to operate within the confines of a licensed premise than in the environment immediately outside such premises. Another key finding was that officers reported greater levels of training in responding to situations outside and around licensed premises than to situations inside licensed premises. Officers were also asked to identify the frequency with which they employed specified regulatory enforcement and community-based strategies. Irrespective of the type of response, ‘taking no action’ or passive policing interventions were not favoured by officers. The findings identified that officers favoured taking a range of strategies (sending home, releasing into the custody of friends, etc.) in preference to arrest. In another key finding, officers generally reported their support for operational stakeholder partnership approaches to policing licensed premises. This was evidenced by the high number of officers (over 90%) reporting that there should be shared responsibility for enforcing the provisions of the Liquor Act. Importantly, those surveyed also identified the factors which constrain or prevent them from policing licensed premises. Study Two involved interviewing a small but comprehensive group (n=11) of senior managers from within the Queensland Police Service (QPS) who have responsibility for setting operational and strategic policy. The aim of this study was to examine the attitudes, perceptions and influence that senior officers (at the strategy and policy-setting level) had on the officers at the operational level. This qualitative study was carried out using a purposive sampling (Denzin & Lincoln, 2005; Guba & Lincoln, 1989), focused interview and thematic analytic approach. The interview participants were drawn from three tiers of management at district, regional as well as the whole-of-organisational level. The first key theme emerging from the study related to role, in terms of both the QPS broader organisational role, and the individual officer role with respect to the policing of licensed premises. For the QPS organisational role, participants at all three strategic levels had a high degree of congruity as to the organisations service role; that is, to enhance public safety. With respect to participants’ beliefs as to whether police officers have knowledge and understanding of their individual roles concerning licensed premises (as opposed to the QPS role), participants reported most commonly that officers had a reasonable to clear understanding of their role. Participant comments also were supportive of the view that officers operating in the research area, Brisbane Central District (BCD), had a clearer understanding of their role than police operating in other locations. The second key theme to emerge identified a disparity between the knowledge and capability of specialist police, compared with general duties police, to police licensed premises. In fact, a number of the responses to a variety of questions differentiated specialist and general police in a range of domains. One such example related to the clarity of understanding of officer role. Participants agreed that specialist police (Liquor Enforcement & Proactive Strategies [LEAPS] officers) had more clarity of understanding in terms of their role than generalist police. Participants also were strongly of the opinion that specialist police had higher skill levels to deal with issues both inside and outside licensed premises. Some participants expressed the view that general duty police undertook purely response-related activities, or alternatively, dealt with lower order matters. Conversely, it was viewed that specialist police undertook more complex tasks because of their higher levels of knowledge and skill. The third key theme to emerge concerned the identification of barriers that serve to restrict or prevent police officers from policing licensed premises. Participant responses strongly indicated that there was a diversity of resourcing barriers that restrict police from undertaking their roles in licensed premises. Examples of such barriers were the lack of police and the low ratio of police to patrons, available officer time, and lack of organisational investment in skills and knowledge acquisition. However, some participants indicated that police resourcing in the BCD was appropriate and officers were equipped with sufficient powers (policy and legislation). Again, the issue of specialist police was raised by one participant who argued that increasing the numbers of specialist police would ameliorate the difficulties for police officers policing licensed premises. The fourth and last key theme to emerge from Study Two related to the perception of senior officers regarding the opportunity and capability of officers to leverage off external partnerships to reduce harms inside and outside licensed premises. Police working in partnership in BCD was seen as an effective harm reduction strategy and strongly supported by the participants. All participants demonstrated a high degree of knowledge as to who these partners were and could identify those government, non-government and community groups precisely. Furthermore, the majority of participants also held strong views that the partnerships were reasonably effective and worked to varying degrees depending on the nature of the partnership and issues such as resourcing. These senior officers identified better communication and coordination as factors that could potentially strengthen these partnerships. This research finding is particularly important for senior officers who have the capacity to shape the policy and strategic direction of the police service, not only in Queensland but throughout Australasia. Study Three examined the perceptions of those with links to the broader liquor industry (government, non-government and community but exclusive of police) concerning their understanding of the police role and the capacity of police to reduce alcohol-related harm inside and outside licensed premises, and their attitudes towards police. Participants (n=26) surveyed represented a range of areas including the liquor industry, business represenatives and government representatives from Queensland Fire and Rescue Service, Queensland Ambulance Service, Brisbane City Council and Queensland Health. The first key theme to emerge from Study Three related to participant understanding of the QPS organisational role, and importantly, individual officer role in policing licensed premises. In terms of participant understanding of the QPS role there was a clear understanding by the majority of participants that the police role was to act in ways consistent with the law and to otherwise engage in a range of enforcement-related activities. Participants saw such activities falling into two categories. The first category related to reactive policing, which included actions around responding to trouble in licensed premises, monitoring crowd controllers and removing trouble-makers. In the second category, proactive approaches, participants identified the following activities as consistent with that approach: early intervention with offenders, support of licensed premises operators and high visibility policing. When participants were asked about their understanding of individual officer roles in the policing of licensed premises, a range of responses were received but the consistent message that emerged was that there is a different role to be played by general duty (uniformed) police compared to specialist (LEAPS Unit) police, which reflects differences in knowledge, skill and capability. The second key theme that emerged from the data related to the external participants’ views of the knowledge and capability of specialist police, compared with general duty police, to police licensed premises. As noted in the first key theme, participants were universally of the view that the knowledge, skill and capability of police in specialist units (LEAPS Unit) was at a higher level than that of general duty police. Participants observed that these specialist officers were better trained than their colleagues in generalist areas and were therefore better able to intervene knowledgeably and authoritatively to deal with problems and issues as they emerged. Participants also reported that officers working within BCD generally had a positive attitude to their duties and had important local knowledge that they could use in the resolution of alcohol-related issues. Participants also commented on the importance of sound and effective QPS leadership, as well as the quality of the leadership in BCD. On both these measures, there was general consensus from participants, who reported positively on the importance and effectiveness of such leadership in BCD. The third key theme to emerge from Study Three concerned the identification of barriers that serve to restrict or prevent police officers from policing licensed premises. Overwhelmingly, external participants reported the lack of human resources (i.e. police officers) as the key barrier. Other resourcing limitations, such as available officer time, police computer systems, and the time taken to charge offenders, were identified as barriers. Some participants identified barriers in the liquor industry such as ‘dodgy operators’ and negative media attention as limitations. Other constraints to emerge related to government and policy barriers. These were reflected in comments about the collection by government of fees from licensees and better ‘powers’ for police to deal with offenders. The fourth and final key theme that emerged from Study Three related to the opportunities for and capability of police to leverage off external partnerships to reduce harms inside and outside licensed premises. Not surprisingly, participants had a comprehensive knowledge of a broad range of stakeholders, from a diversity of contexts, influential in addressing issues in licensed premises. Many participants reported their relationships with the police and other stakeholders as effective, productive and consistent with the objectives of partnering to reduce alcohol-related harm. On the other hand, there were those who were concerned with their relationship with other stakeholders, particularly those with a compliance function (e.g. Office of Liquor & Gaming Regulation [OLGR]). The resourcing limitations of partners and stakeholders were also raised as an important constraining factor in fulfilling the optimum relationship. Again, political issues were mentioned in terms of the impact on partnerships, with participants stating that there is at times political interference and that politicians complicate the relationships of stakeholders. There are some significant strengths with respect to the methodology of this research. The research is distinguished from previous work in that it examines these critical issues from three distinct perspectives (i.e. police officer, senior manager and external stakeholder). Other strengths relate to the strong theoretical framework that guides and informs the research. There are also some identified limitations, including the subjective nature of self-report data as well as the potential for bias by the author, which was controlled for using a range of initiatives. A further limitation concerns the potential for transferability and generalisability of the findings to other locations given the distinctive nature of the BCD. These limitations and issues of transferability are dealt with at length in the thesis. Despite a growing body of literature about contextual harms associated with alcohol, and specific research concerning police intervention in such contextual harms, there is still much to learn. While research on the subject of police engaging in alcohol-related incidents has focused on police behaviours and strategies in response to such issues, there is a paucity of research that focuses on the knowledge and understanding of officers engaged in such behaviours and practices. Given the scarcity of research dealing with the knowledge, skills and attitudes of police officers responding to harms inside and outside licensed premises, this research contributes significantly to what is a recent and growing body of research and literature in the field. The research makes a practical contribution to police agencies’ understanding of officer knowledge and police practice in ways that have the potential to shape education and training agendas, policy approaches around generalist versus specialist policing, strategic and operational strategy, as well as partnership engagements. The research also makes a theoretical contribution given that the research design is informed by the Three Circle

Youth Alcohol and Drug Practice Guide 3 : Practice Strategies and Interventions

This guide canvasses a range of practice strategies and interventions utilised by workers and services who engage with young people experiencing problematic AOD use whilst also exploring the many and varied challenges associated with this type of work.

FP01-5 Pregnancy loss and psychiatric disorders in young men and women : results from Australian longitudinal cohort study

Recent evidence has linked induced abortion with later adverse psychiatric outcomes in young women. Little is known about later adverse psychiatric outcomes in young men whose partners have fallen pregnant and either go on to have a child, have an abortion or miscarry. 1223 women and 1159 men, from an Austrailan cohort born between 1981 and 1984, were assessed at 21 years for psychiatric and substance misuse and lifetime pregnancy histories. Young women reporting a pregnancy loss (either miscarriage or abortion) had nearly three times the odds of experiencing a illicit drug disorder (excluding cannabis), and nearly twice the odds of an alcohol misuse compared to never pregnant women. Young men whose partner had an abortion, but not a miscarriage, had nearly twice the odds of cannabis disorder, illicit drug disorder, and mood disorder compared to men that had never fathered a pregnancy. Young women who have lost a pregnancy have an increased risk of developing alcohol or substance abuse in later life. Young men whose partner aborted a pregnancy only had an increased of substance abuse and mood disorder in later life. These findings add to the growing body of evidence suggesting that pregnancy loss per se increases the risk of a range of substance use disorders in young women. The findings for young men are novel and raise the possibility that the associations measured may be due to common unmeasured factors associated with early pregnancy in young people rather than pregnancy loss.

Metabolomics coupled with proteomics advancing drug discovery toward more agile development of targeted combination therapies

To enhance the therapeutic efficacy and reduce the adverse effects of traditional Chinese medicine, practitioners often prescribe combinations of plant species and/or minerals, called formulae. Unfortunately, the working mechanisms of most of these compounds are difficult to determine and thus remain unknown. In an attempt to address the benefits of formulae based on current biomedical approaches, we analyzed the components of Yinchenhao Tang, a classical formula that has been shown to be clinically effective for treating hepatic injury syndrome. The three principal components of Yinchenhao Tang are Artemisia annua L., Gardenia jasminoids Ellis, and Rheum Palmatum L., whose major active ingredients are 6,7-dimethylesculetin (D), geniposide (G), and rhein (R), respectively. To determine the mechanisms underlying the efficacy of this formula, we conducted a systematic analysis of the therapeutic effects of the DGR compound using immunohistochemistry, biochemistry, metabolomics, and proteomics. Here, we report that the DGR combination exerts a more robust therapeutic effect than any one or two of the three individual compounds by hitting multiple targets in a rat model of hepatic injury. Thus, DGR synergistically causes intensified dynamic changes in metabolic biomarkers, regulates molecular networks through target proteins, has a synergistic/additive effect, and activates both intrinsic and extrinsic pathways.

Pharmacokinetic studies of a Chinese triple herbal drug formula

Yin Chen Hao Tang preparation (YCHTP) is a classic traditional Chinese medicine formula, which is commonly used for clinical treatment of hepatological diseases. In this study, a rapid and validated high-performance liquid chromatography (HPLC) method was developed to simultaneously identify 6,7-dimethylesculetin and geniposide in rat plasma. This assay was performed on a Dikma Diamonsil RP(18) column (200 mmx4.6 mm, 5 mum) with acetonitrile-methanol-water (0.1% formic acid) as the mobile phase, showing acceptable linearity, intra- and inter-day precision and accuracy (R.S.D.=5%), and absolute recovery for two analytes (74%); the limits of quantitation were 0.4 and 1.12 mug/ml, and the limits of detection were 0.06 and 0.09 mug/ml for two analytes. The developed method was successfully applied to study the effect of formula compatibility on the pharmacokinetics of 6,7-dimethylesculetin and geniposide in YCHTP when orally administrating an effective human daily dose of YCHTP to rats. We surmise that formula compatibility can significantly influence the pharmacokinetics of YCHTP, and we have elucidated and validated the compatible administration of YCHTP.

The next generation health intervention tool - Can smart phone applications help young people track and moderate alcohol use and potential harms?

Whilst alcohol is a common feature of many social gatherings, there are numerous immediate and long-term health and social harms associated with its abuse. Alcohol consumption is the world’s third largest risk factor for disease and disability with almost 4% of all deaths worldwide attributed to alcohol. Not surprisingly, alcohol use and binge drinking by young people is of particular concern with Australian data reporting that 39% of young people (18-19yrs) admitted drinking at least weekly and 32% drank to levels that put them at risk of alcohol-related harm. The growing market penetration and connectivity of smartphones may be an opportunities for innovation in promoting health-related self-management of substance use. However, little is known about how best to harness and optimise this technology for health-related intervention and behaviour change. This paper explores the utility and interface of smartphone technology as a health intervention tool to monitor and moderate alcohol use. A review of the psychological health applications of this technology will be presented along with the findings of a series of focus groups, surveys and behavioural field trials of several drink-monitoring applications. Qualitative and quantitative data will be presented on the perceptions, preferences and utility of the design, usability and functionality of smartphone apps to monitoring and moderate alcohol use. How these findings have shaped the development and evolution of the OnTrack app will be specifically discussed, along with future directions and applications of this technology in health intervention, prevention and promotion.

Current status of pharmacogenomics testing for anti-tumor drug therapies : approaches to non-melanoma skin cancer

Skin cancer is one of the most commonly occurring cancer types, with substantial social, physical, and financial burdens on both individuals and societies. Although the role of UV light in initiating skin cancer development has been well characterized, genetic studies continue to show that predisposing factors can influence an individual's susceptibility to skin cancer and response to treatment. In the future, it is hoped that genetic profiles, comprising a number of genetic markers collectively involved in skin cancer susceptibility and response to treatment or prognosis, will aid in more accurately informing practitioners' choices of treatment. Individualized treatment based on these profiles has the potential to increase the efficacy of treatments, saving both time and money for the patient by avoiding the need for extensive or repeated treatment. Increased treatment responses may in turn prevent recurrence of skin cancers, reducing the burden of this disease on society. Currently existing pharmacogenomic tests, such as those that assess variation in the metabolism of the anticancer drug fluorouracil, have the potential to reduce the toxic effects of anti-tumor drugs used in the treatment of non-melanoma skin cancer (NMSC) by determining individualized appropriate dosage. If the savings generated by reducing adverse events negate the costs of developing these tests, pharmacogenomic testing may increasingly inform personalized NMSC treatment.