The role of immunoglobulins and their transporters in urogenital Chlamydial infections

Chlamydia trachomatis infections of the male and female reproductive tracts are the world's leading sexually transmitted bacterial disease, and can lead to damaging pathology, scarring and infertility. The resolution of chlamydial infection requires the development of adaptive immune responses to infection, and includes cell-mediated and humoral immunity. Whilst cluster of differentiation (CD)4+ T cells are known to be essential in clearance of infection [1], they are also associated with immune cell infiltration, autoimmunity and infertility in the testes [2-3]. Conversely, antibodies are less associated with inflammation, are readily transported into the reproductive tracts, and can offer lumenal neutralization of chlamydiae prior to infection. Antibodies, or immunoglobulins (Ig), play a supportive role in the resolution of chlamydial infections, and this thesis sought to define the function of IgA and IgG, against a variety of chlamydial antigens expressed during the intracellular and extracellular stages of the chlamydial developmental cycle. Transport of IgA and IgG into the mucosal lumen is facilitated by receptor-mediated transcytosis yet the expression profile (under normal conditions and during urogenital chlamydial infection) of the polymeric immunoglobulin receptor (pIgR) and the neonatal Fc receptor (FcRn) remains unknown. The expression profile of pIgR and FcRn in the murine male reproductive tract was found to be polarized to the lower and upper reproductive tract tissues respectively. This demonstrates that the two receptors have a tissue tropism, which must be considered when targeting pathogens that colonize different sites. In contrast, the expression of pIgR and FcRn in the female mouse was found to be distributed in both the upper and lower reproductive tracts. When urogenitally infected with Chlamydia muridarum, both male and female reproductive tracts up-regulated expression of pIgR and down-regulated expression of FcRn. Unsurprisingly, the up-regulation of pIgR increased the concentration of IgA in the lumen. However, down-regulation of FcRn, prevented IgG uptake and led to an increase or pooling of IgG in lumenal secretions. As previous studies have identified the importance of pIgR-mediated delivery of IgA, as well as the potential of IgA to bind and neutralize intracellular pathogens, IgA against a variety of chlamydial antigens was investigated. The protection afforded by IgA against the extracellular antigen major outer membrane protein (MOMP), was found to be dependent on pIgR expression in vitro and in vivo. It was also found that in the absence of pIgR, no protection was afforded to mice previously immunized with MOMP. The protection afforded from polyclonal IgA against the intracellular chlamydial antigens; inclusion membrane protein A (IncA), inclusion membrane proteins (IncMem) and secreted chlamydial protease-like activity factor (CPAF) were produced and investigated in vitro. Antigen-specific intracellular IgA was found to bind to the respective antigen within the infected cell, but did not significantly reduce inclusion formation (p > 0.05). This suggests that whilst IgA specific for the selected antigens was transported by pIgR to the chlamydial inclusion, it was unable to prevent growth. Similarly, immunization of male mice with intracellular chlamydial antigens (IncA or IncMem), followed by depletion CD4+ T cells, and subsequent urogenital C. muridarum challenge, provided minimal pIgR-mediated protection. Wild type male mice immunized with IncA showed a 57 % reduction (p < 0.05), and mice deficient in pIgR showed a 35 % reduction (p < 0.05) in reproductive tract chlamydial burden compared to control antigen, and in the absence of CD4+ T cells. This suggests that pIgR and secretory IgA (SIgA) were playing a protective role (21 % pIgR-mediated) in unison with another antigen-specific immune mechanism (36 %). Interestingly, IgA generated during a primary respiratory C. muridarum infection did not provide a significant amount of protection to secondary urogenital C. muridarum challenge. Together, these data suggest that IgA specific for an extracellular antigen (MOMP) can play a strong protective role in chlamydial infections, and that IgA targeting intracellular antigens is also effective but dependent on pIgR expression in tissues. However, whilst not investigated here, IgA targeting and blocking other intracellular chlamydial antigens, that are more essential for replication or type III secretion, may be more efficacious in subunit vaccines. Recently, studies have demonstrated that IgG can neutralize influenza virus by trafficking IgG-bound virus to lysosomes [4]. We sought to determine if this process could also traffic chlamydial antigens for degradation by lysosomes, despite Chlamydia spp. actively inhibiting fusion with the host endocytic pathway. As observed in pIgR-mediated delivery of anti-IncA IgA, FcRn similarly transported IgG specific for IncA which bound the inclusion membrane. Interestingly, FcRn-mediated delivery of anti-IncA IgG significantly decreased inclusion formation by 36 % (p < 0.01), and induced aberrant inclusion morphology. This suggests that unlike IgA, IgG can facilitate additional host cellular responses which affect the intracellular niche of chlamydial growth. Fluorescence microscopy revealed that IgG also bound the inclusion, but unlike influenza studies, did not induce the recruitment of lysosomes. Notably, anti-IncA IgG recruited sequestosomes to the inclusion membrane, markers of the ubiquitin/proteasome pathway and major histocompatibility complex (MHC) class I loading. To determine if the protection against C. muridarum infection afforded by IncA IgG in vitro translated in vivo, wild type mice and mice deficient in functional FcRn and MHC-I, were immunized, depleted of CD4+, and urogenitally infected with C. muridarum. Unlike in pIgR-deficient mice, the protection afforded from IncA immunization was completely abrogated in mice lacking functional FcRn and MHC-I/CD8+. Thus, both anti-IncA IgA and IgG can bind the inclusion in a pIgR and FcRn-mediated manner, respectively. However, only IgG mediates a higher reduction in chlamydial infection in vitro and in vivo suggesting more than steric blocking of IncA had occurred. Unlike anti-MOMP IgA, which reduced chlamydial infection of epithelial cells and male mouse tissues, IgG was found to enhance infectivity in vitro, and in vivo. Opsonization of EBs with MOMP-IgG enhanced inclusion formation of epithelial cells in a MOMP-IgG dose-dependent and FcRn-dependent manner. When MOMP-IgG opsonized EBs were inoculated into the vagina of female mice, a small but non-significant (p > 0.05) enhancement of cervicovaginal C. muridarum shedding was observed three days post infection in mice with functional FcRn. Interestingly, infection with opsonized EBs reduced the intensity of the peak of infection (day six) but protracted the duration of infection by 60 % in wild type mice only. Infection with EBs opsonized in IgG also significantly increased (p < 0.05) hydrosalpinx formation in the oviducts and induced lymphocyte infiltration uterine horns. As MOMP is an immunodominant antigen, and is widely used in vaccines, the ability of IgG specific to extracellular chlamydial antigens to enhance infection and induce pathology needs to be considered. Together, these data suggest that immunoglobulins play a dichotomous role in chlamydial infections, and are dependent on antigen specificity, FcRn and pIgR expression. FcRn was found to be highly expressed in upper male reproductive tract, whilst pIgR was dominantly expressed in the lower reproductive tract. Conversely, female mice expressed FcRn and pIgR in both the lower and upper reproductive tracts. In response to a normal chlamydial infection, pIgR is up-regulated increasing secretory IgA release, but FcRn is down-regulated preventing IgG uptake. Similarly to other studies [5-6], we demonstrate that IgA and IgG generated during primary chlamydial infections plays a minor role in recall immunity, and that antigen-specific subunit vaccines can offer more protection. We also show that both IgA and IgG can be used to target intracellular chlamydial antigens, but that IgG is more effective. Finally, IgA against the extracellular antigen MOMP can afford protection, whist IgG plays a deleterious role by increasing infectivity and inducing damaging immunopathology. Further investigations with additional antigens or combination subunit vaccines will enhance our understanding the protection afforded by antibodies against intracellular and extracellular pathogenic antigens, and help improve the development of an efficacious chlamydial vaccine.

Polyalanine repeat polymorphism in RUNX2 is associated with site-specific fracture in post-menopausal females

Runt related transcription factor 2 (RUNX2) is a key regulator of osteoblast differentiation. Several variations within RUNX2 have been found to be associated with significant changes in BMD, which is a major risk factor for fracture. In this study we report that an 18bp deletion within the polyalanine tract (17A>11A) of RUNX2 is significantly associated with fracture. Carriers of the 11A allele were found to be nearly twice as likely to have sustained fracture. Within the fracture category, there was a significant tendency of 11A carriers to present with fractures of bones of intramembranous origin compared to bones of endochondral origin (p=0.005). In a population of random subjects, the 11A allele was associated with decreased levels of serum collagen cross links (CTx, p=0.01), suggesting decreased bone turnover. The transactivation function of the 11A allele was quantitatively decreased. Interestingly, we found no effect of the 11A allele on BMD at multiple skeletal sites, although these were not the sites where a relationship with fracture was most evident. These findings suggest that the 11A allele is a biologically relevant polymorphism that influences serum CTx and confers enhanced fracture risk in a site-selective manner related to intramembranous bone ossification.

Do drinking and riding mix? Effects of legal doses of alcohol on balance ability in experienced motorcyclists

The appropriateness of applying drink driving legislation to motorcycle riding has been questioned as there may be fundamental differences in the effects of alcohol on these two activities. For example, while the distribution of blood alcohol content (BAC) levels among fatally injured male drivers compared to riders is similar, a greater proportion of motorcycle fatalities involve levels in the lower (0 to .10% BAC) range. Several psychomotor and higher-order cognitive skills underpinning riding performance appear to be significantly influenced by low levels of alcohol. For example, at low levels (.02 to .046% BAC), riders show significant increases in reaction time to hazardous stimuli, inattention to the riding task, performance errors such as leaving the roadway and a reduced ability to complete a timed course. It has been suggested that alcohol may redirect riders’ focus from higher-order cognitive skills to more physical skills such as maintaining balance. As part of a research program to investigate the potential benefits of introducing a zero, or reduced, BAC for all riders in Queensland regardless of their licence status, the effects of low doses of alcohol on balance ability were investigated in a laboratory setting. The static balance of ten experienced riders was measured while they performed either no secondary task, a visual search task, or a cognitive (arithmetic) task following the administration of alcohol (0; 0.02, and 0.05% BAC). Subjective ratings of intoxication and balance impairment increased in a dose-dependent manner; however, objective measures of static balance were negatively affected only at the .05% BAC dose. Performance on a concurrent secondary visual search task, but not a purely cognitive (arithmetic) task, improved postural stability across all BAC levels. Finally, the .05% BAC dose was associated with impaired performance on the cognitive (arithmetic) task, but not the visual search task, when participants were balancing, but neither task was impaired by alcohol when participants were standing on the floor. Implications for road safety and future ‘drink riding’ policy considerations are discussed.

Development and evaluation of a program to improve clinician and patient communication during a telehealth consultation : C.R.I.S.P. Telehealth

Introduction: The delivery of health care in the 21st century will look like no other in the past. The fast paced technological advances that are being made will need to transition from the information age into clinical practice. The phenomenon of e-Health is the over-arching form of information technology and telehealth is one arm of that phenomenon. The uptake of telehealth both in Australia and overseas, has changed the face of health service delivery to many rural and remote communities for the better, removing what is known as the tyranny of distance. Many studies have evaluated the satisfaction and cost-benefit analysis of telehealth across the organisational aspects as well as the various adaptations of clinical pathways and this is the predominant focus of most studies published to date. However, whilst comments have been made by many researchers about the need to improve and attend to the communication and relationship building aspects of telehealth no studies have examined this further. The aim of this study was to identify the patient and clinician experiences, concerns, behaviours and perceptions of the telehealth interaction and develop a training tool to assist these clinicians to improve their interaction skills. Methods: A mixed methods design combining quantitative (survey analysis and data coding) and qualitative (interview analysis) approaches was adopted. This study utilised four phases to firstly qualitatively explore the needs of clients (patients) and clinicians within a telehealth consultation then designed, developed, piloted and quantitatively and qualitatively evaluated the telehealth communication training program. Qualitative data was collected and analysed during Phase 1 of this study to describe and define the missing 'communication and rapport building' aspects within telehealth. This data was then utilised to develop a self-paced communication training program that enhanced clinicians existing skills, which comprised of Phase 2 of this study to develop the interactive program. Phase 3 included evaluating the training program with 26 clinicians and results were recorded pre and post training, whilst phase 4 was the pilot for future recommendations of this training program using a patient group within a Queensland Health setting at two rural hospitals. Results: Comparisons of pre and post training data on 1) Effective communication styles, 2) Involvement in communication training package, 3) satisfaction pre and post training, and 4) health outcomes pre and post training indicated that there were differences between pre and post training in relation to effective communication style, increased satisfaction and no difference in health outcomes between pre and post training for this patient group. The post training results revealed over half of the participants (N= 17, 65%) were more responsive to non-verbal cues and were better able to reflect and respond to looks of anxiousness and confusion from a 'patient' within a telehealth consultation. It was also found that during post training evaluations, clinicians had enhanced their therapeutic communication with greater detail to their own body postures, eye contact and presentation. There was greater time spent looking at the 'patient' with an increase of 35 second intervals of direct eye contact and less time spent looking down at paperwork which decreased by 20 seconds. Overall 73% of the clinicians were satisfied with the training program and 61% strongly agreed that they recognised areas of their communication that needed improving during a telehealth consultation. For the patient group there was significant difference post training in rapport with a mean score from 42 (SD = 28, n = 27) to 48 (SD = 5.9, n = 24). For communication comfort of the patient group there was a significant difference between the pre and post training scores t(10) = 27.9, p = .002, which meant that overall the patients felt less inhibited whilst talking to the clinicians and more understood. Conclusion: The aim of this study was to explore the characteristics of good patient-clinician communication and unmet training needs for telehealth consultations. The study developed a training program that was specific for telehealth consultations and not dependent on a 'trainer' to deliver the content. In light of the existing literature this is a first of its kind and a valuable contribution to the research on this topic. It was found that the training program was effective in improving the clinician's communication style and increased the satisfaction of patient's within an e-health environment. This study has identified some historical myths that telehealth cannot be part of empathic patient centred care due to its technology tag.

Algorithm clustering for multi-algorithm processor design

An Application Specific Instruction-set Processor (ASIP) is a specialized processor tailored to run a particular application/s efficiently. However, when there are multiple candidate applications in the application’s domain it is difficult and time consuming to find optimum set of applications to be implemented. Existing ASIP design approaches perform this selection manually based on a designer’s knowledge. We help in cutting down the number of candidate applications by devising a classification method to cluster similar applications based on the special-purpose operations they share. This provides a significant reduction in the comparison overhead while resulting in customized ASIP instruction sets which can benefit a whole family of related applications. Our method gives users the ability to quantify the degree of similarity between the sets of shared operations to control the size of clusters. A case study involving twelve algorithms confirms that our approach can successfully cluster similar algorithms together based on the similarity of their component operations.

Aqueous phase synthesis of copper nanoparticles : a link between heavy metal resistance and nanoparticle synthesis ability in bacterial systems

We demonstrate aqueous phase biosynthesis of phase-pure metallic copper nanoparticles (CuNPs) using a silver resistant bacterium Morganella morganii. This is particularly important considering that there has been no report that demonstrates biosynthesis and stabilization of pure copper nanoparticles in the aqueous phase. Electrochemical analysis of bacterial cells exposed to Cu2+ ions provides new insights into the mechanistic aspect of Cu2+ ion reduction within the bacterial cell and indicates a strong link between the silver and copper resistance machinery of bacteria in the context of metal ion reduction. The outcomes of this study take us a step closer towards designing rational strategies for biosynthesis of different metal nanoparticles using microorganisms.

Moderating teen drinking : combining social marketing and education

Purpose This paper outlines a pilot study that was undertaken in Australia in 2011 that combined social marketing with education. An intervention targeting 14-16 year olds to influence attitudes and behavioural intentions towards moderate drinking was developed and tested. Game On:Know alcohol (GO:KA) is a six-module intervention that is delivered to a year level cohort in an auditorium. GO:KA combines a series of online and offline experiential activities to engage (with) students. Design/methodology Following social marketing benchmark criteria, formative research and competitive analysis were undertaken to create, implement and evaluate an intervention. The intervention was delivered in one all boys' and one all girls' school in April and June 2011, respectively. A total of 223 Year 10 students participated in GO:KA with the majority completing both pre- and post-surveys. Paired samples t-tests and descriptive analysis were used to assess attitudinal and behavioural intention change. Findings Attitudinal change was observed in both schools while behavioural intentions changed for girls and not boys according to paired samples t-testing. Post hoc testing indicated gender differences. Research limitations The lack of a control group is a key limitation of the current research that can be overcome in the 20 school main study to be conducted in 2013-2015. Originality/value The current study provides evidence to suggest that a combined social marketing and education intervention can change teenage attitudes towards moderate drinking whilst only changing behavioural intentions for female teenagers. Analysis of the intervention provides insight into gender differences and highlights the need for a segmented approach.

Gifted students with a reading disability : the impact of lived experience

Gifted students who have a reading disability have learning characteristics that set them apart from their peers. The ability to read impacts upon all areas of the formal curriculum in which print-based texts are common. Therefore, the full intellectual development of gifted students with a reading disability can be repressed because their access to learning opportunities is reduced. When the different learning needs caused by concomitant giftedness and reading disability are not met, it can have serious implications for both academic achievement and the social-emotional wellbeing of these students. In order to develop a deeper understanding of this vulnerable group of students, this study investigated the learning characteristics of gifted students with a reading disability. Furthermore, it investigated how the learning characteristics of these students impact upon their lived experiences. Since achievement and motivation have been shown to be closely linked to self-efficacy, self-efficacy theory underpinned the conceptual framework of the study. The study used a descriptive case study approach to document the lived experiences of gifted students with a reading disability. Nine participants aged between 11 and 18, who were formally identified as gifted with a reading disability, took part in the study. Data sources in the case study database included: cognitive assessments, such as WISC assessments, Stanford Binet 5, or the Raven's Standard Progressive Matrices; the WIAT II reading assessment; the Reader Self-Perception Scale; document reviews; parent and teacher checklists designed to gain information about the students' learning characteristics; and semi-structured interviews with students. The study showed that gifted students with a reading disability display a complex profile of learning strengths and weaknesses. As a result, they face a daily struggle of trying to reconcile the confusion of being able to complete some tasks to a high level, while struggling to read. The study sheds light on the myriad of issues faced by the students at school. It revealed that when the particular learning characteristics and needs of gifted students with a reading disability are recognised and met, these students can experience academic success, and avoid the serious social-emotional complications cited in previous studies. Indeed, rather than suffering from depression, disengagement from learning, and demotivation, these students were described as resilient, independent, determined, goal oriented and motivated to learn and persevere. Notably, the students in the study had developed effective coping strategies for dealing with the daily challenges they faced. These strategies are outlined in the thesis together with the advice students offered for helping other gifted students with a reading disability to succeed. Their advice is significant for all teachers who wish to nurture the potential of those students who face the challenge of being gifted with a reading disability, and for the parents of these students. This research advances knowledge pertaining to the theory of self-efficacy, and self-efficacy in reading specifically, by showing that although gifted students with a reading disability have low self-efficacy, the level is not the same for all aspects of reading. Furthermore, despite low self-efficacy in reading these students remained motivated. The study also enhances existing knowledge in the areas of gifted education and special education because it documents the lived experience of gifted students with a specific learning disability in reading from the students' perspectives. Based on a synthesis of the literature and research findings, an Inclusive Pathway Model is proposed that describes a framework to support gifted students with a reading disability so that they might achieve, and remain socially and emotionally well-adjusted. The study highlights the importance of clear identification protocols (such as the use of a range of assessment sources, discussions with students and parents, and an awareness of the characteristics of gifted students with a reading disability) and support mechanisms for assisting students (for example, differentiated reading instruction and the use of assistive technology).

Othering the Malay in Malaysia : a planned consequence of politics?

This paper examines the rise in the politicisation of Islam in Malaysia and links it to the othering of the Malaysian Malay. It is my argument that both were “conquering” tools of Malaysia’s “Father of Modernisation”, Mahathir Mohamad, devised to win the support of the Malay Muslim majority in Malaysia. The many awards bestowed on Mahathir obscure the fact that he was instrumental in the systematic erosion of the power and roles of state institutions, especially at the Federal government level. This includes the significant loss of the independence of the Malaysian judiciary. Whilst per capita income in Malaysia may well have increased eight times under his 22-year leadership, this paper asks why is it that the majority of the Malays remain the largest number among the poor and the more disenfranchised of ethnicities in the country? Why have Malay and Muslim women suffered such a rapid decreasing ability to access justice? This paper examines existing research on the social and political changes Malaysia has experienced with Islamisation and under Mahathir’s rule, as well as studies on Malayness, Malay nationalism and Muslim Malay identity formation. The paper elaborates the othering of a majority people, the Malays in Malaysia, and how this othering has brought forth a fast-growing political power in the name of a supremacist Islam, a puritanical Sunni and Malay Islam. Specific events in the rise and rule of Mahathir as Malaysia’s then Prime Minister are reviewed, such as the banning of The Malay Dilemma, and the split in the United Malays National Organisation (UMNO) in 1987. Also examined is the varying emphasis between Muslim and race, and how during Mahathir’s rule, that strong misogynist and patriarchal attitudes took hold in Malay Muslim consciousness, a colonising consciousness that is othering the perceived cultural and genetic “impurities” within the Malay.

Development of a children's acute cough specific quality of life questionnaire (Pac-Qol)

The high burden of parental concern in children with chronic cough has been well documented. Acute cough in children (lasting less than 2 weeks) also has a significant impact on families, reflected by the number of doctor visits for cough. Currently there is no validated acute cough specific quality of life (QOL) measure for children. The objective of this study is to develop and validate an acute cough specific QOL questionnaire (PAC-QOL) for paediatric use. Here we present our data on item selection. Methods Two independent focus groups were conducted to determine relevant items. Parents discussed the impact of their child’s current or previous episodes of acute cough on their child, themselves and their family functioning. Transcripts were analyzed to determine whether discussions had reached an item saturation point. Items were also compared against our previously validated parent-centred children’s chronic cough specific QOL questionnaire (PC-QOL), which was used as a model. The newly developed acute cough specific QOL questionnaire is designed to assess the level of frequency of parents’ feelings and worry related to their child’s acute cough, using a 24-h time-point reference. Results Newly identified acute cough specific items include parental worry around whether or not they should take their child to a doctor or emergency department, and frequency of seeking assistance from friends and family. Conclusions While there are similarities between items identified for both acute and chronic cough, there are distinct features. Further data will be collected for item reduction and validation of this children’s acute cough specific QOL questionnaire.

A novel iterative method for simulating patient-specific optimal deformation and fit of fracture fixation plates

This paper proposes a new iterative method to achieve an optimally fitting plate for preoperative planning purposes. The proposed method involves integration of four commercially available software tools, Matlab, Rapidform2006, SolidWorks and ANSYS, each performing specific tasks to obtain a plate shape that fits optimally for an individual tibia and is mechanically safe. A typical challenge when crossing multiple platforms is to ensure correct data transfer. We present an example of the implementation of the proposed method to demonstrate successful data transfer between the four platforms and the feasibility of the method.

The multi-platform user engagement and data visualisation tool

The ability to identify and assess user engagement with transmedia productions is vital to the success of individual projects and the sustainability of this mode of media production as a whole. It is essential that industry players have access to tools and methodologies that offer the most complete and accurate picture of how audiences/users engage with their productions and which assets generate the most valuable returns of investment. Drawing upon research conducted with Hoodlum Entertainment, a Brisbane-based transmedia producer, this project involved an initial assessment of the way engagement tends to be understood, why standard web analytics tools are ill-suited to measuring it, how a customised tool could offer solutions, and why this question of measuring engagement is so vital to the future of transmedia as a sustainable industry. Working with data provided by Hoodlum Entertainment and Foxtel Marketing, the outcome of the study was a prototype for a custom data visualisation tool that allowed access, manipulation and presentation of user engagement data, both historic and predictive. The prototyped interfaces demonstrate how the visualization tool would collect and organise data specific to multiplatform projects by aggregating data across a number of platform reporting tools. Such a tool is designed to encompass not only platforms developed by the transmedia producer but also sites developed by fans. This visualisation tool accounted for multiplatform experience projects whose top level is comprised of people, platforms and content. People include characters, actors, audience, distributors and creators. Platforms include television, Facebook and other relevant social networks, literature, cinema and other media that might be included in the multiplatform experience. Content refers to discreet media texts employed within the platform, such as tweet, a You Tube video, a Facebook post, an email, a television episode, etc. Core content is produced by the creators’ multiplatform experiences to advance the narrative, while complimentary content generated by audience members offers further contributions to the experience. Equally important is the timing with which the components of the experience are introduced and how they interact with and impact upon each other. Being able to combine, filter and sort these elements in multiple ways we can better understand the value of certain components of a project. It also offers insights into the relationship between the timing of the release of components and user activity associated with them, which further highlights the efficacy (or, indeed, failure) of assets as catalysts for engagement. In collaboration with Hoodlum we have developed a number of design scenarios experimenting with the ways in which data can be visualised and manipulated to tell a more refined story about the value of user engagement with certain project components and activities. This experimentation will serve as the basis for future research.

Analysis of acute-phase proteins, AHSG, C3, CLI, HP and SAA, reveals distinctive expression patterns associated with breast, colorectal and lung cancer

Early detection, clinical management and disease recurrence monitoring are critical areas in cancer treatment in which specific biomarker panels are likely to be very important in each of these key areas. We have previously demonstrated that levels of alpha-2-heremans-schmid-glycoprotein (AHSG), complement component C3 (C3), clusterin (CLI), haptoglobin (HP) and serum amyloid A (SAA) are significantly altered in serum from patients with squamous cell carcinoma of the lung. Here, we report the abundance levels for these proteins in serum samples from patients with advanced breast cancer, colorectal cancer (CRC) and lung cancer compared to healthy controls (age and gender matched) using commercially available enzyme-linked immunosorbent assay kits. Logistic regression (LR) models were fitted to the resulting data, and the classification ability of the proteins was evaluated using receiver-operating characteristic curve and leave-one-out cross-validation (LOOCV). The most accurate individual candidate biomarkers were C3 for breast cancer [area under the curve (AUC) = 0.89, LOOCV = 73%], CLI for CRC (AUC = 0.98, LOOCV = 90%), HP for small cell lung carcinoma (AUC = 0.97, LOOCV = 88%), C3 for lung adenocarcinoma (AUC = 0.94, LOOCV = 89%) and HP for squamous cell carcinoma of the lung (AUC = 0.94, LOOCV = 87%). The best dual combination of biomarkers using LR analysis were found to be AHSG + C3 (AUC = 0.91, LOOCV = 83%) for breast cancer, CLI + HP (AUC = 0.98, LOOCV = 92%) for CRC, C3 + SAA (AUC = 0.97, LOOCV = 91%) for small cell lung carcinoma and HP + SAA for both adenocarcinoma (AUC = 0.98, LOOCV = 96%) and squamous cell carcinoma of the lung (AUC = 0.98, LOOCV = 84%). The high AUC values reported here indicated that these candidate biomarkers have the potential to discriminate accurately between control and cancer groups both individually and in combination with other proteins. Copyright © 2011 UICC.

The use of Facebook in tertiary education : case study of a unit-related Facebook page in a university justice class

Purpose – This study aims to evaluate the usefulness of a university unit Facebook page, which was established to support a first-year university justice unit. The study pays particular regard to the Facebook page's impact on students learning outcomes and communications amongst students and between students and teaching staff. Design/methodology/approach – All students enrolled in the unit were asked to complete an online survey, which sought to determine whether they used the unit Facebook page and if so, the nature and extent of their use. Findings – The study found that the unit Facebook page was useful in achieving most learning objectives for the unit. This included enhancing students' knowledge and understanding of unit content, as well as their ability to critically analyse unit materials. Students also indicated that they found the Facebook page better than the university's central learning management system across a range of areas. It was particularly useful for facilitating unit-related discussions. Research limitations/implications – The survey results reported in this paper are based on a relatively small sample of students (n=67) from a first-year university justice unit. Future studies should seek to garner evidence from broader and larger samples that transcend specific unit populations. However, the findings of this study do indicate further support for the use of Facebook as a supplementary tool in university education. Originality/value – This study focuses on two aspects of social networking technologies that have not been previously researched and thus contributes to the growing literature on the uses and benefits of Facebook in tertiary education.

Replicating satellite RNA induces sequence-specific DNA methylation and truncated transcripts in plants

Tobacco plants were transformed with a chimeric transgene comprising sequences encoding β-glucuronidase (GUS) and the satellite RNA (satRNA) of cereal yellow dwarf luteovirus. When transgenic plants were infected with potato leafroll luteovirus (PLRV), which replicated the transgene-derived satRNA to a high level, the satellite sequence of the GUS:Sat transgene became densely methylated. Within the satellite region, all 86 cytosines in the upper strand and 73 of the 75 cytosines in the lower strand were either partially or fully methylated. In contrast, very low levels of DNA methylation were detected in the satellite sequence of the transgene in uninfected plants and in the flanking nonsatellite sequences in both infected and uninfected plants. Substantial amounts of truncated GUS:Sat RNA accumulated in the satRNA-replicating plants, and most of the molecules terminated at nucleotides within the first 60 bp of the satellite sequence. Whereas this RNA truncation was associated with high levels of satRNA replication, it appeared to be independent of the levels of DNA methylation in the satellite sequence, suggesting that it is not caused by methylation. All the sequenced GUS:Sat DNA molecules were hypermethylated in plants with replicating satRNA despite the phloem restriction of the helper PLRV. Also, small, sense and antisense ∼22 nt RNAs, derived from the satRNA, were associated with the replicating satellite. These results suggest that the sequence-specific DNA methylation spread into cells in which no satRNA replication occurred and that this was mediated by the spread of unamplified satRNA and/or its associated 22 nt RNA molecules.