The effect of silicate ions on proliferation, osteogenic differentiation and cell signalling pathways (WNT and SHH) of bone marrow stromal cells

Silicon (Si) is a trace element, which plays an important role in human bone growth. Si has been incorporated into biomaterials for bone regeneration in order to improve their osteogenic potential, both in vitro and in vivo. Little is known, however, as to how Si ions elicit their biological response on bone-forming cells. The aim of this study was to investigate the effect of Si ions on the proliferation, differentiation, bone-related gene expression and cell signalling pathways of bone marrow stromal cells (BMSCs) by comparing the BMSC responses to different concentrations of NaCl and Na2SiO3, while taking into account and excluding the effect of Na ions. Our study showed that Si ions at a concentration of 0.625 mM significantly enhanced the proliferation, mineralization nodule formation, bone-related gene expression (OCN, OPN and ALP) and bone matrix proteins (ALP and OPN) of BMSCs. Furthermore, Si ions at 0.625 mM could counteract the effect of the WNT inhibitor (W.I.) cardamonin on the osteogenic genes expression, (OPN, OCN and ALP), WNT and SHH signalling pathway-related genes in BMSCs. These results suggest that Si ions by themselves play an important role in regulating the proliferation and osteogenic differentiation of BMSCs, with the involvement of WNT and SHH signalling pathways. Our study provides evidence to explain possible molecular mechanisms whereby Si ions released from Si-containing biomaterials can acquire enhanced bioactivity at desired concentration.

Kallikrein 14 is down-regulated by androgen receptor signalling and harbours genetic variation that is associated with prostate tumour aggressiveness

Kallikrein 14 (KLK14) has been proposed as a useful prognostic marker in prostate cancer, with expression reported to be associated with tumour characteristics such as higher stage and Gleason score. KLK14 tumour expression has also shown the potential to predict prostate cancer patients at risk of disease recurrence after radical prostatectomy. The KLKs are a remarkably hormone-responsive family of genes, although detailed studies of androgen regulation of KLK14 in prostate cancer have not been undertaken to date. Using in vitro studies, we have demonstrated that unlike many other prostatic KLK genes that are strictly androgen responsive, KLK14 is more broadly expressed and inversely androgen regulated in prostate cancer cells. Given these results and evidence that KLK14 may play a role in prostate cancer prognosis, we also investigated whether common genetic variants in the KLK14 locus are associated with risk and/or aggressiveness of prostate cancer in approximately 1200 prostate cancer cases and 1300 male controls. Of 41 single nucleotide polymorphisms assessed, three were associated with higher Gleason score (≥7): rs17728459 and rs4802765, both located upstream of KLK14, and rs35287116, which encodes a p.Gln33Arg substitution in the KLK14 signal peptide region. Our findings provide further support for KLK14 as a marker of prognosis in prostate cancer.

Relationships and sexual health promotion project for QUT international students

International students may experience a variety of sexual health problems which include unplanned pregnancies, abortions and sexually transmitted diseases. These are often because of limited knowledge of sexual health matters and lack of sexual health education and/or access to health services in their home country. A study was undertaken to identify the concerns of international students and how to provide culturally appropriate promotion of sexual health for international students at Queensland University of Technology (QUT). The project included consultations with stakeholders, interviews with key informants, an online survey and focus group discussions with international students. The project found that sexual health is a concern for international students, particularly in developing relationships and when becoming sexually active in Australia, and there is a perceived lack of access to health services and insufficient knowledge on sexual health matters. Preferred methods of dissemination of sexual health information included use of student mentors, web-based online resources, brochures and confidential on-line advice.

Allegations of child sexual abuse in family court cases : a qualitative analysis of psychiatric evidence

Allegations of child sexual abuse in Family Court cases have gained increasing attention. The study investigates factors involved in Family Court cases involving allegations of child sexual abuse. A qualitative methodology was employed to examine Records of Judgement and Psychiatric Reports for 20 cases distilled from the data corpus of 102 cases. A seven-stage methodology was developed utilising a thematic analysis process informed by principles of grounded theory and phenomenology. The explication of eight thematic clusters was undertaken. The findings point to complex issues and dynamics in which child sexual abuse allegations have been raised. The alleging parent’s allegations of sexual abuse against their ex-partner may be: the expression of unconscious deep fears for their children’s welfare, or an action to meet their needs for personal affirmation in the context of the painful upheaval of a relationship break-up. Implications of the findings are discussed.

Stromal upregulation of lateral epithelial adhesions : gene expression analysis of signalling pathways in prostate epithelium

BACKGROUND: Stromal signalling increases the lateral cell adhesions of prostate epithelial cells grown in 3D culture. The aim of this study was to use microarray analysis to identify significant epithelial signalling pathways and genes in this process. METHODS: Microarray analysis was used to identify genes that were differentially expressed when epithelial cells were grown in 3D Matrigel culture with stromal co-culture compared to without stroma. Two culture models were employed: primary epithelial cells (ten samples) and an epithelial cell line (three experiments). A separate microarray analysis was performed on each model system and then compared to identify tissue-relevant genes in a cell line model. RESULTS: TGF beta signalling was significantly ranked for both model systems and in both models the TGF beta signalling gene SOX4 was significantly down regulated. Analysis of all differentially expressed genes to identify genes that were common to both models found several morphology related gene clusters; actin binding (DIAPH2, FHOD3, ABLIM1, TMOD4, MYH10), GTPase activator activity (BCR, MYH10), cytoskeleton (MAP2, MYH10, TMOD4, FHOD3), protein binding (ITGA6, CD44), proteinaceous extracellular matrix (NID2, CILP2), ion channel/ ion transporter activity (CACNA1C, CACNB2, KCNH2, SLC8A1, SLC39A9) and genes associated with developmental pathways (POFUT1, FZD2, HOXA5, IRX2, FGF11, SOX4, SMARCC1). CONCLUSIONS: In 3D prostate cultures, stromal cells increase lateral epithelial cell adhesions. We show that this morphological effect is associated with gene expression changes to TGF beta signalling, cytoskeleton and anion activity.

The cancer stem-cell hypothesis : its emerging role in lung cancer biology and its relevance for future therapy

The cancer stem-cell (CSC) hypothesis suggests that there is a small subset of cancer cells that are responsible for tumor initiation and growth, possessing properties such as indefinite self-renewal, slow replication, intrinsic resistance to chemotherapy and radiotherapy, and an ability to give rise to differentiated progeny. Through the use of xenotransplantation assays, putative CSCs have been identified in many cancers, often identified by markers usually expressed in normal stem cells. This is also the case in lung cancer, and the accumulated data on side population cells, CD133, CD166, CD44 and ALDH1 are beginning to clarify the true phenotype of the lung cancer stem cell. Furthermore, it is now clear that many of the pathways of normal stem cells, which guide cellular proliferation, differentiation, and apoptosis are also prominent in CSCs; the Hedgehog (Hh), Notch, and Wnt signaling pathways being notable examples. The CSC hypothesis suggests that there is a small reservoir of cells within the tumor, which are resistant to many standard therapies, and can give rise to new tumors in the form of metastases or relapses after apparent tumor regression. Therapeutic interventions that target CSC pathways are still in their infancy and clinical data of their efficacy remain limited. However Smoothened inhibitors, gamma-secretase inhibitors, anti-DLL4 antagonists, Wnt antagonists, and CBP/β-catenin inhibitors have all shown promising anticancer effects in early studies. The evidence to support the emerging picture of a lung cancer CSC phenotype and the development of novel therapeutic strategies to target CSCs are described in this review.

Framing sexual harassment through media representations

This article examines mainstream news media texts reporting sexual harassment in four industrialized countries. The study first identifies the aspects of sexual harassment cases considered newsworthy by asking how the media texts characterize such cases. Second, the study illuminates the discourses evident in these texts, which are theorized as a mode by which understandings of workplace gender (in)equality shape, and are shaped by, individuals, organizations and the community. The analysis reveals that the media most frequently reports “classic” sexual harassment and emphasizes scandalous allegations and overtly sexualized conduct. The hegemony of a discourse of sexual harassment as an individualized problem of inappropriate employee behavior is also evident. By contrast, discourses presenting sexual harassment as a systemic issue, or as symptomatic of broader gender inequality, are less frequent. We argue that these media representations limit opportunities to frame sexual harassment as dynamic, complex, and part of the practice of gendering in and beyond organizational boundaries.

Nagelschmidtite bioceramics with osteostimulation properties : material chemistry activating osteogenic genes and WNT signalling pathway of human bone marrow stromal cells

Bioactive materials with osteostimulation properties are of great importance to promote osteogenic differentiation of human bone marrow stromal cells (hBMSCs) for potential bone regeneration. We have recently synthesized nagelschmidtite (NAGEL, Ca7Si2P2O16) ceramic powders which showed excellent apatite-mineralization ability. The aim of this study was to investigate the interaction of hBMSCs with NAGEL bioceramic bulks and their ionic extracts, and to explore the osteostimulation properties of NAGEL bioceramics and the possible molecular mechanism. The cell attachment, proliferation, bone-related gene expression (ALP, OPN and OCN) and WNT signalling pathways (WNT3a, FZD6, AXIN2 and CTNNB) of hBMSCs cultured on NAGEL bioceramic disks were systematically studied. We further investigated the biological effects of ionic products from NAGEL powders on cell proliferation and osteogenic differentiation of hBMSCs by culturing cells with NAGEL extracts. Furthermore, the effect of NAGEL bioceramics on the osteogenic differentiation in hBMSCs was also investigated with the addition of cardamonin, a WNT inhibitor. The results showed that NAGEL bioceramic disks supported the attachment and proliferation of hBMSCs, and significantly enhanced the bone-related gene expression and WNT signalling pathway of hBMSCs, compared to conventional beta-tricalcium phosphate (β-TCP) bioceramic disks and blank controls. The ionic products from NAGEL powders also significantly promoted the proliferation, bone and WNT-related gene expression of hBMSCs. It was also identified that NAGEL bioceramics could bypass the action of the WNT inhibitor (10 μM) to stimulate the selected osteogenic genes in hBMSCs. Our results suggest that NAGEL bioceramics possess excellent in vitro osteostimulation properties. The possible mechanism for the osteostimulation may be directly related to the released Si, Ca and P-containing ionic products from NAGEL bioceramics which activate bone-related gene expression and WNT signalling pathway of hBMSCs. The present study suggests that NAGEL bioceramics are a potential bone regeneration material with significant osteostimulation capacity.

Clergy Sexual Abuse Litigation: Survivors Seeking Justice By Jennifer M. Balboni (Boulder: First Forum Press, 2011, 180pp. £43.77)

Balboni identifies her interest as being the processes of official disclosure and the path taken to civil litigation by survivors of child sexual abuse by Roman Catholic Clergy. The empirical data, on which this work is based, come in the form of in-depth face-to-face interviews with 22 survivors of clergy sexual abuse who have pursued litigation and 13 of their advocates. Balboni provides a space for survivors’ accounts of the ‘why’ behind their decision making and the impact of civil litigation on their lives to be heard, discussed and contextualized with both clarity and sensitivity. She acknowledges the breadth and depth of survivor responses, and the perspectives of their legal advocates, employing defiance theory, symbolic interaction and other points of analysis, to capture the journey of survivors towards litigation and beyond. Balboni’s work is deeply poignant in its recognition of survivors’ voices, the complex transformative capacity of litigation, the effects of community forming amongst survivors and the complex nature of ‘empowerment’ obtained by survivors through civil litigation. Acknowledging that, for many survivors, litigation becomes a means of identity change and truth telling, Balboni admits that ‘these survivors helped me understand that litigation is more about voice than monetary settlement’ (p. 149). This work is not deeply analytical or theoretically rich but privileges the voices of survivors and their advocates with sufficient frameworks to contextualize and explain participants’ perspectives and experiences.

A salutogenic approach to healing following child sexual assault

Decades of research has now produced a rich description of the destruction child sexual assault (CSA) can cause in an individual’s life. Post-Traumatic Stress Disorder (PTSD), Dissociative Identity Disorder, Borderline Personality Disorder, depression, anxiety, Panic Disorder, intimacy issues, substance abuse, self-harm, and suicidal ideation and attempts, are some of the negative outcomes that have been attributed to this type of traumatic experience. Psychology's tendency to dwell within a pathological paradigm, along with popular media who espouse a similar rhetoric, would lead to the belief that once exposed to CSA, an individual is forever at the mercy of dealing with a massive array of accompanying negative effects. While the possibility of these outcomes in those who have experienced CSA is not at all denied, it is also timely to consider an alternative paradigm that up until now has received a paucity of attention in the sexual assault literature. That is to say, not only do people have the ability to work through the painful and personal impacts of CSA, but for some people the process of recovery may provide a catalyst for positive life changes that have been termed post-traumatic growth (Tedeschi & Calhoun, 1995). To begin with in this chapter, the negative sequale’ of childhood sexual assault it discussed initially. Inherent to this discussion are questions of measurement and definitions of sexual assault. The chapter highlights ways in which the term CSA has been defined and hence operationalised in research, and the myriad problems, confusions, and inconclusive findings that have plagued the sexual assault literature. Following this is a review of the sparse literature that has conceptualised CSA from a more salutogenic (Antonovsky, 1979) theoretical orientation. It is argued that a salutogenic approach to intervention and to research in this area, provides a more useful way of promoting healing and the gaining of wisdom, but importantly does not negate the very real distress that may accompany growth. This chapter will then present a case study to elucidate the theoretical and empirical literature discussed using the words of a survivor. Finally, the chapter concludes with implications for therapeutic practice, which includes some practical ways in which to promote adaptation to life within the context of having survived this insidious crime.

Exploring the process of meaning making in healing after childhood sexual assault : a case study approach

Childhood sexual assault (CSA) is one of the most devastating of all traumatic experiences with population studies documenting survivors experiencing higher levels of pathology than general trends in survivors of other traumatic experiences. Yet recent research has demonstrated that far from being permanently crippled by their experiences, many adult survivors of CSA manage to heal and move forward in their lives to experience a rich and fulfilling existence. In this paper two case studies are presented to provide a detailed account of how a person who has experienced CSA may find a pathway to healing. Moreover, data demonstrates that meaning making, spiritual or otherwise, is a pivotal part of acceptance of CSA and ensuing growth. The case studies highlight the unique journeys of two women and the underlying similarities in their pathway to healing. Clinical implications of the research are discussed and specific strategies for encouraging healing and growth are outlined.

Regression and hypothesis tests for multivariate GNSS state time series

A satellite based observation system can continuously or repeatedly generate a user state vector time series that may contain useful information. One typical example is the collection of International GNSS Services (IGS) station daily and weekly combined solutions. Another example is the epoch-by-epoch kinematic position time series of a receiver derived by a GPS real time kinematic (RTK) technique. Although some multivariate analysis techniques have been adopted to assess the noise characteristics of multivariate state time series, statistic testings are limited to univariate time series. After review of frequently used hypotheses test statistics in univariate analysis of GNSS state time series, the paper presents a number of T-squared multivariate analysis statistics for use in the analysis of multivariate GNSS state time series. These T-squared test statistics have taken the correlation between coordinate components into account, which is neglected in univariate analysis. Numerical analysis was conducted with the multi-year time series of an IGS station to schematically demonstrate the results from the multivariate hypothesis testing in comparison with the univariate hypothesis testing results. The results have demonstrated that, in general, the testing for multivariate mean shifts and outliers tends to reject less data samples than the testing for univariate mean shifts and outliers under the same confidence level. It is noted that neither univariate nor multivariate data analysis methods are intended to replace physical analysis. Instead, these should be treated as complementary statistical methods for a prior or posteriori investigations. Physical analysis is necessary subsequently to refine and interpret the results.

An evaluation of the Australian Capital Territory Sexual Assault Reform Program (SARP): Final Report

In 2005 the Australian Capital Territory (ACT) Office of the Director of Public Prosecutions (DPP) and the Australian Federal Police (AFP) produced a report, Responding to sexual assault: The challenge of change (DPP & AFP 2005), which made 105 recommendations for reforming the way sexual offence cases are handled by the ACT’s criminal justice system. The Sexual Assault Reform Program (SARP) is one key initiative developed in response to these recommendations. Managed by the ACT Justice and Community Safety Directorate (JACS), SARP’s main objective is to improve aspects of the criminal justice system relating to: processes and support for victims of sexual offences as they progress through the system; attrition in sexual offence matters in the criminal justice system; and coordination and collaboration among the agencies involved. In November 2007 the ACT Attorney-General announced $4 million of funding for several SARP reforms. This funding provided for additional victim support staff; a dedicated additional police officer, prosecutor and legal policy officer; and an upgrade of equipment for the Supreme Court and Magistrates Court, including improvements in technology to assist witnesses in giving evidence, and the establishment of an off-site facility to allow witnesses to give evidence from a location outside of the court. In addition, the reform agenda included a number of legislative amendments that changed how evidence can be given by victims of sexual and family violence offences, children and other vulnerable witnesses. The primary objectives of these legislative changes are to provide an unintimidating, safe environment for vulnerable witnesses (including sexual offence complainants) to give evidence and to obtain prompt statements from witnesses to improve the quality of evidence captured (DPP 2009: 13). The current evaluation The funding for SARP reforms also provided for a preliminary evaluation of the reforms; this report outlines findings from the evaluation. The evaluation sought to address whether the program has met its key objectives: better support for victims, lower attrition rates and improved coordination and collaboration among agencies involved in administering SARP. The evaluation was conducted in two stages and involved a mixed-methods approach. During stage 1 key indicators for the evaluation were developed with stakeholders. During stage 2 quantitative data were collected by stakeholders and provided to the AIC for analysis. Qualitative interviews were also conducted with service delivery providers, and with a small number (n=5) of victim/survivors of sexual offences whose cases had recently been resolved in the ACT criminal justice system. The current evaluation is preliminary in nature. As the SARP reforms will take time to become entrenched within the ACT’s criminal justice system, some of the impacts of the reforms may not yet be evident. Nonetheless, this evaluation provides an insight into how well the SARP reforms have been implemented to date, as well as key areas that could be addressed in the future. Key findings from the preliminary evaluation are outlined briefly below.

The key regulatory roles of the PI3K/Akt signalling pathway in the functionalities of mesenchymal stem cells and applications in tissue regeneration

Mesenchymal stem cells (MSCs) are multi-potent cells that can differentiate into various cell types and have been used widely in tissue engineering application. In tissue engineering, a scaffold, MSCs and growth factors are used as essential components and their interactions have been regarded to be important for regeneration of tissues. A critical problem for MSCs in tissue engineering is their low survival ability and functionality. Most MSCs are going to be apoptotic after transplantation. Therefore, increasing MSC survival ability and functionalities is the key for potential applications of MSCs. Several approaches have been studied to increase MSC tissue forming capacity including application of growth factors, overexpression of stem cell regulatory genes and improvement of biomaterials for scaffolds. The effects of these approaches on MSCs have been associated with the activation of the PI3K/Akt signaling pathway. The pathway plays central regulatory roles in MSC survival, proliferation, migration, angiogenesis, cytokine production and differentiation. In this review, we summarize and discuss the literatures related to the roles of the PI3K/Akt pathway in the functionalities of MSCs and the involvement of the pathway in biomaterials-increased MSC functinalities. Biomaterials have been modified in their properties, surface structure and loaded with growth factors to increase MSC functionalities. Several studies demonstrated that the biomaterials-increased MSC functionalities are mediated by the activation of the PI3K/Akt pathway.

"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.