The human tissue kallikrein and kallikrein-related peptidase family

The human kallikrein-related peptidases are a subgroup of trypsin and chymotrypsin-like serine peptidases that are characterized by their homology to tissue kallikrein or kallikrein 1 (KLK1) encoded by the KLK1 gene (reviewed in[1-4]). The human KLK locus spans an approximately 320 kb region on chromosome 19q13.3-13.4 and contains fifteen genes encoding KLK1 and fourteen other kallikrein-related peptidases, KLK2-KLK15, which have been named contiguously in the locus in the order of their discovery [5-8] (Figure 606.1). It is the largest contiguous cluster of serine protease encoding genes in the human genome which has evolved from gene duplication of KLK1 and then subsequent reduplication of the newly evolved KLK genes [2]. The high conservation noted for KLK1-KLK3 (62-77%) reflects the proposed duplication of the KLK1 gene that produced the KLK2 gene which further generated the KLK3 gene. In contrast, the newer KLK4-KLK15 proteases share much less similarity, from 24-66%, although strong homology between KLK4 and KLK5, KLK9 and KLK11, and KLK10 and KLK12 suggests these genes are duplications of each other [2]...

Growth of confined cancer spheroids : a combined experimental marker, critical modelling approach

A critical step in the dissemination of ovarian cancer is the formation of multicellular spheroids from cells shed from the primary tumour. The objectives of this study were to apply bioengineered three-dimensional (3D) microenvironments for culturing ovarian cancer spheroids in vitro and simultaneously to build on a mathematical model describing the growth of multicellular spheroids in these biomimetic matrices. Cancer cells derived from human epithelial ovarian carcinoma were embedded within biomimetic hydrogels of varying stiffness and grown for up to 4 weeks. Immunohistochemistry, imaging and growth analyses were used to quantify the dependence of cell proliferation and apoptosis on matrix stiffness, long-term culture and treatment with the anti-cancer drug paclitaxel. The mathematical model was formulated as a free boundary problem in which each spheroid was treated as an incompressible porous medium. The functional forms used to describe the rates of cell proliferation and apoptosis were motivated by the experimental work and predictions of the mathematical model compared with the experimental output. This work aimed to establish whether it is possible to simulate solid tumour growth on the basis of data on spheroid size, cell proliferation and cell death within these spheroids. The mathematical model predictions were in agreement with the experimental data set and simulated how the growth of cancer spheroids was influenced by mechanical and biochemical stimuli including matrix stiffness, culture duration and administration of a chemotherapeutic drug. Our computational model provides new perspectives on experimental results and has informed the design of new 3D studies of chemoresistance of multicellular cancer spheroids.

Paclitaxel resistance and multicellular spheroid formation are induced by kallikrein-related peptidase 4 in serous ovarian cancer cells in an ascites mimicking microenvironment

High tumor kallikrein-related-peptidase 4 (KLK4) levels are associated with a poor outcome for women with serous epithelial ovarian cancer (EOC), for which peritoneal dissemination and chemoresistance are key events. To determine the role of KLK4 in these events, we examined KLK4-transfected SKOV-3 and endogenous KLK4 expressing OVCA432 cells in 3-dimensional (3D) suspension culture to mimic the ascites microenvironment. KLK4-SKOV-3 cells formed multicellular aggregates (MCAs) as seen in ascites, as did SKOV-3 cells treated with active KLK4. MCA formation was reduced by treatment with a KLK4 blocking antibody or the selective active site KLK4 sunflower trypsin inhibitor (SFTI-FCQR). KLK4-MCAs formed larger cancer cell foci in mesothelial cell monolayers than those formed by vector and native SKOV-3 cells, suggesting KLK4-MCAs are highly invasive in the peritoneal microenvironment. A high level of KLK4 is expressed by ascitic EOC cells compared to matched primary tumor cells, further supporting its role in the ascitic microenvironment. Interestingly, KLK4 transfected SKOV-3 cells expressed high levels of the KLK4 substrate, urokinase plasminogen activator (uPA), particularly in 3D-suspension, and high levels of both KLK4 and uPA were observed in patient cells taken from ascites. Importantly, the KLK4-MCAs were paclitaxel resistant which was reversed by SFTI-FCQR and to a lesser degree by the general serine protease inhibitor, Aprotinin, suggesting that in addition to uPA, other as yet unidentified substrates of KLK4 must be involved. Nonetheless, these data suggest that KLK4 inhibition, in conjunction with paclitaxel, may improve the outcome for women with serous epithelial ovarian cancer and high KLK4 levels in their tumors.

Genetic association of the KLK4 locus with risk of prostate cancer

The Kallikrein-related peptidase, KLK4, has been shown to be significantly overexpressed in prostate tumours in numerous studies and is suggested to be a potential biomarker for prostate cancer. KLK4 may also play a role in prostate cancer progression through its involvement in epithelial-mesenchymal transition, a more aggressive phenotype, and metastases to bone. It is well known that genetic variation has the potential to affect gene expression and/or various protein characteristics and hence we sought to investigate the possible role of single nucleotide polymorphisms (SNPs) in the KLK4 gene in prostate cancer. Assessment of 61 SNPs in the KLK4 locus (±10 kb) in approximately 1300 prostate cancer cases and 1300 male controls for associations with prostate cancer risk and/or prostate tumour aggressiveness (Gleason score <7 versus ≥7) revealed 7 SNPs to be associated with a decreased risk of prostate cancer at the Ptrend<0.05 significance level. Three of these SNPs, rs268923, rs56112930 and the HapMap tagSNP rs7248321, are located several kb upstream of KLK4; rs1654551 encodes a non-synonymous serine to alanine substitution at position 22 of the long isoform of the KLK4 protein, and the remaining 3 risk-associated SNPs, rs1701927, rs1090649 and rs806019, are located downstream of KLK4 and are in high linkage disequilibrium with each other (r2≥0.98). Our findings provide suggestive evidence of a role for genetic variation in the KLK4 locus in prostate cancer predisposition.

Preface to the proceedings of the 16th Computational Techniques and Applications Conference

CTAC2012 was the 16th biennial Computational Techniques and Applications Conference, and took place at Queensland University of Technology from 23 - 26 September, 2012. The ANZIAM Special Interest Group in Computational Techniques and Applications is responsible for the CTAC meetings, the first of which was held in 1981.

New graduate occupational therapists feelings of preparedness for practice in Australia and Aotearoa/New Zealand

Aim The development of competent future allied health professionals through academic programmes, professional support and practical education is continually evolving. The aim of this study was to explore the feelings of newly graduated occupational therapists in Australia and Aotearoa/New Zealand regarding their education and work preparedness. Methods Newly graduated occupational therapists from Australia (n = 178) and Aotearoa/New Zealand (n = 53) who had completed their occupational therapy studies in 2007 were recruited. Participants completed an online survey which explored their preparedness for work; based on professional competencies. Results Most newly graduated occupational therapists felt somewhat prepared for practice. However, only 17.1% of Australian new graduates, and even fewer (8.5%) of Aotearoa/New Zealand new graduates felt very well prepared. Participants felt more prepared for the competencies required for ‘managing inwards’ (including interpersonal skills) and less prepared for those required for ‘managing outwards’ (including evidence-based practice). Conclusions This study provides the first international comparison into the feelings of competence and preparedness for practice of new graduates of occupational therapy from Australia and Aotearoa/New Zealand. Given the importance of competencies, such as evidence-based practice to the progress of the profession, there is a need to further explore methods to increase feelings of preparedness in these areas.

The new normativity : the innovation imperative

At a quite fundamental level, the very way in which Public Service Broadcasting (PSB) may envisage its future usually captured in the semantic shift from PSB to Public Service Media (PSM) is at stake when considering the recent history of public value discourse and the public value test. The core Reithian PSB idea assumed that public value would be created through the application of core principles of universality of availability and appeal, provision for minorities, education of the public, distance from vested interests, quality programming standards, program maker independence, and fostering of national culture and the public sphere. On the other hand, the philosophical import of the public value test is that potentially any excursion into the provision of new media services needs to be justified ex ante. In this era of New Public Management, greater transparency and accountability, and the proposition that resources for public value deliverables be contestable and not sequestered in public sector institutions, what might be the new Archimedean point around which a contemporised normativity for PSM be built? This paper will argue for the innovation imperative as an organising principle for contemporary PSM. This may appear counterintuitive, as it is precisely PSB’s predilection for innovating in new media services (in online, mobile, and social media) that has produced the constraining apparatus of the ex ante/public value/Drei-Stufen-Test in Europe, based on principles of competitive neutrality and transparency in the application of public funds for defined and limited public benefit. However, I argue that a commitment to innovation can define as complementary to, rather than as competitive ‘crowding out’, the new products and services that PSM can, and should, be delivering into a post-scarcity, superabundant all-media marketplace. The evidence presented in this paper for this argument is derived mostly from analysis of PSM in the Australian media ecology. While no PSB outside Europe is subject to a formal public value test, the crowding out arguments are certainly run in Australia, particularly by powerful commercial interests for whom free news is a threat to monetising quality news journalism. Take right wing opinion leader, herself a former ABC Board member, Judith Sloan: ‘… the recent expansive nature of the ABC – all those television stations, radio stations and online offerings – is actually squeezing activity that would otherwise be undertaken by the private sector. From partly correcting market failure, the ABC is now causing it. We are now dealing with a case of unfair competition and wasted taxpayer funds’ (The Drum, 1 August http://www.abc.net.au/unleashed/2818220.html). But I argue that the crowding out argument is difficult to sustain in Australia because of the PSB’s non-dominant position and the fact that much of innovation generated by the two PSBs, the ABC and the SBS, has not been imitated by or competed for by the commercials. The paper will bring cases forward, such as SBS’ Go Back to Where you Came From (2011) as an example of product innovation, and a case study of process and organisational innovation which also has resulted in specific product and service innovation – the ABC’s Innovation Unit. In summary, at least some of the old Reithian dicta, along with spectrum scarcity and market failure arguments, have faded or are fading. Contemporary PSM need to justify their role in the system, and to society, in terms of innovation.

Hepatitis B knowledge, testing, and vaccination among Chinese and Vietnamese adults in Australia

Hepatitis B is a significant public health challenge within some subpopulations in Australia, including Chinese and Vietnamese migrants. There has been limited research on hepatitis B knowledge and actions in these communities. The authors conducted a self-administered survey among 442 Chinese and 433 Vietnamese in Brisbane. Generally, the knowledge is best described as “moderate.” One in 2 could not identify the sexual transmission risk and less than one third knew that sharing foods or drinks did not spread the disease. The majority of Vietnamese (80%) and 60% of Chinese respondents indicated prior testing. Vaccination was reported in 60% of the Vietnamese and in 52% of the Chinese. Knowledge was better among Chinese people who had been tested and vaccinated compared with those who were nontested and nonvaccinated. Only 3.5% of the Chinese, but 11.6% of the Vietnamese, indicated having a positive test result hepatitis B virus. This study helps identify strategies for programs targeting both communities and practitioners.

An informal community of practice : the case of the DEHub Virtual Worlds Working Group

The DEHub Virtual Worlds Working Group has an informal membership of nearly 200 members with an interest in education and virtual worlds within the Australian and New Zealand context. Members come from a variety of academic disciplines and may be teaching or research academics, Research Higher Degree candidates, project managers, virtual world builders and developers. The group acts as an informal Community of Practice, facilitating learning and the transfer of skills through social contact, opportunities to collaborate on projects and publications, and through the sharing of knowledge and experience. This poster provides a snapshot of the activity of this highly active group.

The OO files : providing online formative feedback on Contract Law learning in a narrative setting

Feedback, both formative and summative, enables students to reflect on their understandings and to restructure their thinking to develop their capabilities. It can also encourage positive motivation and help boost self-esteem. Online multiple choice questions can be an efficient and effective means of providing timely formative feedback. At the same time, locating learning in a narrative environment can facilitate engaging and effective learning experiences. Narratives can help learners to navigate through information and support cognitive and imaginative engagement. This article will discuss The 00 Files, an online suite of modules containing multiple choice questions situated in the narrative of a fictional law firm. It notes student responses to the program and discusses lessons that may be learnt from its development which may be of assistance to academics considering the development of similar programs for their courses.

Do cyberbullies suffer too? Cyberbullies' perceptions of the harm they cause to others and to their own mental health

While it is recognised that there are serious correlates for students who are victims of cyberbullying including depression, anxiety, lower self-esteem and social difficulties, there has been little research attention paid to the mental health of students who cyberbully. It is known that students who traditionally bully report they feel indifferent to their victims, showing a lack of empathy and that they themselves are at increased risk for psychosocial adjustment. However, there is scant research on the mental health associations of students who cyberbully or their awareness of their impact on others. The current study sought to ascertain from Australian students who reported cyberbullying others in years 6 to 12 (10-19 years of age), their perceptions of their mental health and the harm they caused to and the impact their actions had, on their victims. Most students who cyberbullied did not think that their bullying was harsh or had an impact on their victims. They reported more social difficulties and higher scores on stress, depression and anxiety scales than those students who were not involved in any bullying. The implications of these findings for the mental health of the cyberbullies and for psychologists in schools who assist them, are dis-cussed.

A leap into foodservice satisfaction in the private acute care setting

Monitoring foodservice satisfaction is a risk management strategy for malnutrition in the acute care sector, as low satisfaction may be associated with poor intake. This study aimed to investigate the relationship between age and foodservice satisfaction in the private acute care setting. Patient satisfaction was assessed using a validated tool, the Acute Care Hospital Foodservice Patient Satisfaction Questionnaire for data collected 2008–2010 (n = 779) at a private hospital, Brisbane. Age was grouped into three categories; <50 years, 51–70 years and >70 years. Fisher’s exact test assessed independence of categorical responses and age group; ANOVA or Kruskal–Wallis test was used for continuous variables. Dichotomised responses were analysed using logistic regression and odds ratios (95% confidence interval, p < 0.05). Overall foodservice satisfaction (5 point scale) was high (≥4 out of 5) and was independent of age group (p = 0.377). There was an increasing trend with age in mean satisfaction scores for individual dimensions of foodservice; food quality (p < 0.001), meal service quality (p < 0.001), staff service issues (p < 0.001) and physical environment (p < 0.001). A preference for being able to choose different sized meals (59.8% > 70 years vs 40.6% ≤50 years; p < 0.001) and response to ‘the foods are just the right temperature’ (55.3% >70 years vs 35.9% ≤50 years; p < 0.001) was dependent on age. For the food quality dimension, based on dichotomised responses (satisfied or not), the odds of satisfaction was higher for >70 years (OR = 5.0, 95% CI: 1.8–13.8; <50 years referent). These results suggest that dimensions of foodservice satisfaction are associated with age and can assist foodservices to meet varying generational expectations of clients.

Non-contact ACL injuries : association with clegg soil impact test values for sports fields, soil moisture and prevailing weather

Introduction: There is a recognised relationship between dry weather conditions and increased risk of anterior cruciate ligament (ACL) injury. Previous studies have identified 28 day evaporation as an important weather-based predictor of non-contact ACL injuries in professional Australian Football League matches. The mechanism of non-contact injury to the ACL is believed to increased traction and impact forces between footwear and playing surface. Ground hardness and the amount and quality of grass are factors that would most likely influence this and are inturn, related to the soil moisture content and prevailing weather conditions. This paper explores the relationship between soil moisture content, preceding weather conditions and the Clegg Soil Impact Test (CSIT) which is an internationally recognised standard measure of ground hardness for sports fields. Methodology: The 2.25 kg Clegg Soil Impact Test and a pair of 12 cm soil moisture probes were used to measure ground hardness and percentage moisture content. Five football fields were surveyed at 13 prescribed sites just before seven football matches from October 2008 to January 2009 (an FC Women’s WLeague team). Weather conditions recorded at the nearest weather station were obtained from the Bureau of Meteorology website and total rainfall less evaporation was calculated for 7 and 28 days prior to each match. All non-contact injuries occurring during match play and their location on the field were recorded. Results/conclusions: Ground hardness varied between CSIT 5 and 17 (x10G) (8 is considered a good value for sports fields). Variations within fields were typically greatest in the centre and goal areas. Soil moisture ranged from 3 to 40% with some fields requiring twice the moisture content of others to maintain similar CSIT values. There was a non-linear, negative relationship for ground hardness versus moisture content and a linear relationship with weather (R2, of 0.30 and 0.34, respectively). Three non-contact ACL injuries occurred during the season. Two of these were associated with hard and variable ground conditions.