The hedgehog pathway inhibitor GDC-0449 shows potential in skin and other cancers

Background: The hedgehog signaling pathway is vital in early development, but then becomes dormant, except in some cancer tumours. Hedgehog inhibitors are being developed for potential use in cancer. Objectives/Methods: The objective of this evaluation is to review the initial clinical studies of the hedgehog inhibitor, GDC-0449, in subjects with cancer. Results: Phase I trials have shown that GDC-0449 has benefits in subjects with metastatic or locally advanced basal-cell carcinoma and in one subjects with medulloblastoma. GDC-0449 was well tolerated. Conclusions: Long term efficacy and safety studies of GDC-0449 in these conditions and other solid cancers are now underway. These clinical trials with GDC-0449, and trials with other hedgehog inhibitors, will reveal whether it is beneficial and safe to inhibit the hedgehog pathway, in a wide range of solid tumours or not.

Does the p38 MAP kinase inhibitor pamapimod have potential for the treatment of rheumatoid arthritis?

Background: Methotrexate alone or in combination with other agents is the standard treatment for moderate-to-severe rheumatoid arthritis. As the biological agents are expensive, they are not usually used until methotrexate has failed to give a good response. Thus, there is scope for the development of cheaper drugs that can be used instead of methotrexate or in addition to methotrexate. Objectives/methods: Pamapimod is a p38α inhibitor being developed for use in the treatment of rheumatoid arthritis. The objective was to evaluate the recent clinical trials of pamapimod in subjects with rheumatoid arthritis. Results: There is no clear cut evidence that pamapimod alone or in the presence of methotrexate is efficacious in subjects with rheumatoid arthritis, but it does cause adverse effects. Conclusion: It is unlikely that pamapimod will be useful in the treatment of rheumatoid arthritis.

Modeling the stepped potential discharge of primary alkaline battery cathodes

A novel model for the potentiostatic discharge of primary alkaline battery cathodes is presented. The model is used to simulate discharges resulting from the stepped potential electrochemical spectroscopy (SPECS) of primary alkaline battery cathodes cathodes, and the results are validated with experimental data. We show that a model based on a single (or mean) reaction framework can be used to simulate multi-reaction discharge behaviour and we develop a consistent functional modification to the kinetic equation of the model that allows for this to occur. The model is used to investigate the effects that the initial exchange current density, i00, and the diffusion coefficient for protons in electrolytic manganese dioxide (EMD), DH+, have on SPECS discharge. The behaviour observed is consistent with the idea that individual reduction reactions, within the multi-reaction, reduction behaviour of EMD, have distinct i00 and DH+ values.

Automatic generation of assertions to detect potential security vulnerabilities in C programs that use union and pointer types

Type unions, pointer variables and function pointers are a long standing source of subtle security bugs in C program code. Their use can lead to hard-to-diagnose crashes or exploitable vulnerabilities that allow an attacker to attain privileged access over classified data. This paper describes an automatable framework for detecting such weaknesses in C programs statically, where possible, and for generating assertions that will detect them dynamically, in other cases. Exclusively based on analysis of the source code, it identifies required assertions using a type inference system supported by a custom made symbol table. In our preliminary findings, our type system was able to infer the correct type of unions in different scopes, without manual code annotations or rewriting. Whenever an evaluation is not possible or is difficult to resolve, appropriate runtime assertions are formed and inserted into the source code. The approach is demonstrated via a prototype C analysis tool.

Access to meaningful relationships through virtual instruments and ensembles

This workshop focuses upon research about the qualities of community in music and of music in community facilitated by technologically supported relationships. Generative media systems present an opportunity for users to leverage computational systems to form new relationships through interactive and collaborative experiences. Generative music and art are a relatively new phenomenon that use procedural invention as a creative technique to produce music and visual media. Early systems have demonstrated the potential to provide access to collaborative ensemble experiences for users with little formal musical or artistic expertise. This workshop examines the relational affordances of these systems evidenced by selected field data drawn from the Network Jamming Project. These generative performance systems enable access to unique ensembles with very little musical knowledge or skill and offer the possibility of interactive relationships with artists and musical knowledge through collaborative performance. In this workshop we will focus on data that highlights how these simulated experiences might lead to understandings that may be of social benefit. Conference participants will be invited to jam in real time using virtual interfaces and to evaluate purposively selected video artifacts that demonstrate different kinds of interactive relationship with artists, peers, and community and that enrich the sense of expressive self. Theoretical insights about meaningful engagement drawn from the longitudinal and cross cultural experiences will underpin the discussion and practical presentation.

Oxidative potential of logwood and pellet burning particles assessed by a novel profluorescent nitroxide probe

This study reports the potential toxicological impact of particles produced during biomass combustion by an automatic pellet boiler and a traditional logwood stove under various combustion conditions using a novel profluorescent nitroxide probe BPEAnit. This probe is weakly fluorescent, but yields strong fluorescence emission upon radical trapping or redox activity. Samples were collected by bubbling aerosol through an impinger containing BPEAnit solution, followed by fluorescence measurement. The fluorescence of BPEAnit was measured for particles produced during various combustion phases, at the beginning of burning (cold start), stable combustion after refilling with the fuel (warm start) and poor burning conditions. For particles produced by the logwood stove under cold-start conditions significantly higher amounts of reactive species per unit of particulate mass were observed compared to emissions produced during a warm start. In addition, sampling of logwood burning emissions after passing through a thermodenuder at 250oC resulted in an 80-100% reduction of the fluorescence signal of BPEAnit probe, indicating that the majority of reactive species were semivolatile. Moreover, the amount of reactive species showed a strong correlation with the amount of particulate organic material. This indicates the importance of semivolatile organics in particle-related toxicity. Particle emissions from the pellet boiler, although of similar mass concentration, were not observed to lead to an increase in fluorescence signal during any of the combustion phases.

Potential of St John's Wort for the treatment of depression : the economic perspective

The burden of rising health care expenditures has created a demand for information regarding the clinical and economic outcomes associated with complementary and alternative medicines. Meta-analyses of randomized controlled trials have found Hypericum perforatum preparations to be superior to placebo and similarly effective as standard antidepressants in the acute treatment of mild to moderate depression. A clear advantage over antidepressants has been demonstrated in terms of the reduced frequency of adverse effects and lower treatment withdrawal rates, low rates of side effects and good compliance, key variables affecting the cost-effectiveness of a given form of therapy. The most important risk associated with use is potential interactions with other drugs, but this may be mitigated by using extracts with low hyperforin content. As the indirect costs of depression are greater than five times direct treatment costs, given the rising cost of pharmaceutical antidepressants, the comparatively low cost of Hypericum perforatum extract makes it worthy of consideration in the economic evaluation of mild to moderate depression treatments.

Self-narratives of children : using digital journals

This paper takes the position that children are at risk of being marginalised when research methods are not tailored to their requirements. In particular, children who are negotiating early adolescence are presented as an ideal group for involvement with narrative research approaches that attempt to be flexible and creative. With the premise that the need to juggle multiple realities within complex societal structures is challenging and isolating for such children, narrative methods offer a promising mode of access to their individual realities. Children's own self-narratives in the form of email journal entries are proposed as research tools that can help to minimise issues arising from resistance to adults and problems of shared vocabulary that may occur using more traditional methods. Digital journaling, as a means of capturing self-narratives, can provide a convenient space for young people to generate and share their own personal accounts of their lives and their experiences that can also serve to inform others. Guidelines are offered for how to manage a journaling project that is not reliant on children's physical presence within school settings. Digital journals are thus described as multi-function mechanisms that can support personal growth as well as promote shared understandings and social fairness between adults and children.

A validated self-administered female pelvic floor questionnaire

Introduction and hypothesis: The aim of this study was to validate a self-administered version of the already validated interviewer-administered Australian pelvic floor questionnaire. Methods: The questionnaire was completed by 163 women attending an urogynecological clinic. Face and convergent validity was assessed. Reliability testing and comparison with the interviewer-administered version was performed in a subset of 105 patients. Responsiveness was evaluated in a subset of 73 women. Results: Missing data did not exceed 4% for any question. Cronbach’s alpha coefficients were acceptable in all domains. Kappa coefficients for the test–retest analyses varied from 0.64–1.0. Prolapse symptoms correlated significantly with the pelvic organ prolapse quantification. Urodynamics confirmed the reported symptom stress incontinence in 70%. The self and interviewer administered questionnaires demonstrated equivalence. Effect sizes ranged from 0.6 to 1.4. Conclusions: This self-administered pelvic floor questionnaire assessed pelvic floor function in a reproducible and valid fashion and due to its responsiveness, can be used for routine clinical assessment and outcome research.

Towards making a difference through a university-TAFE partnership : mentoring potential teacher aides

Universities promote partnerships as an investment of social capital that may benefit communities. Mentoring of university students in schools has become key to induction of education workplace practices. One such arrangement is the mentoring of students from TAFE who endeavour to become teacher aides. However, there is no theoretical model for mentoring teacher aides and, similar to mentoring preservice teachers, such practices vary in quality and quantity. What are mentors’ perceptions of mentoring potential teacher aides within school settings? This mixed-method research involves a survey with extended responses. The aim is to determine practices and strategies for mentoring potential teacher aides (PTAs). Results indicated that PTAs require induction about the school culture and infrastructure, which includes ethics, values, operational plans, awareness of facilities and a range of other inductions that would aid the PTA’s work practices. Findings also revealed that many of the mentoring practices employed for preservice teachers may be used for mentoring PTAs in school settings. Indeed, mentors require personal attributes to facilitate the mentoring process. They also indicated outlining the education system requirements as fundamental to workplace operations. In addition, as most PTAs work with students in the classroom, the mentor’s pedagogical knowledge can further assist PTAs to develop an understanding of effective pedagogical practices, particularly for small groups or one-on-one sessions. Finally, a mentor’s modelling of practices and providing constructive feedback about the PTA’s practices can assist the development of workplace operations. In conclusion, the survey employed in this study may assist organisations to develop protocols of practice for workplace mentors. PTAs require mentors who are versed in effective mentoring practices that can more readily guide them towards success.

Embracing diversity : empowering preservice teachers for teaching gifted and talented students

This study investigated preservice teachers’ perceptions for teaching and sustaining gifted and talented students while developing, modifying and implementing activities to cater for the diverse learner. Participants were surveyed at the end of a gifted and talented education program on their perceptions to differentiate the curriculum for meeting the needs of the student (n=22). SPSS data analysis with the five-part Likert scale indicated these preservice teachers agreed or strongly agreed they had developed skills in curriculum planning (91%) with well-designed activities (96%), and lesson preparation skills (96%). They also claimed they were enthusiastic for teaching (91%) and understanding of school practices and policies (96%). However, 46% agreed they had knowledge of syllabus documents with 50% claiming an ability to provide written feedback on student’s learning. Furthermore, nearly two-thirds suggested they had educational language from the syllabus and effective student management strategies. Preservice teachers require more direction on how to cater for diversity and begin creating sustainable societies by building knowledge from direct GAT experiences. Designing diagnostic surveys associated with university coursework can be used to determine further development for specific preservice teacher development in GAT education. Preservice teachers need to create opportunities for students to realise their potential by involving cognitive challenges through a differentiated curriculum. Differentiation requires modification of four primary areas of curriculum development (Maker, 1975) content (what we teach), process (how we teach), product (what we expect the students to do or show) and learning environment (where we teach/our class culture). Ashman and Elkins (2009) and Glasson (2008) emphasise the need for preservice teachers, teachers and other professionals to be able to identify what gifted and talented (GAT) students know and how they learn in relation to effective teaching. Glasson (2008) recommends that educators keep up to date with practices in pedagogy, support, monitoring and profiling of GAT students to create an environment conducive to achieving. Oral feedback is one method to communicate to learners about their progress but has advantages and disadvantages for some students. Oral feedback provides immediate information to the student on progress and performance (Ashman & Elkins, 2009). However, preservice teachers must have clear understandings of key concepts to assist the GAT student. Implementing teaching strategies to engage innovate and extend students is valuable to the preservice teacher in focusing on GAT student learning in the classroom (Killen, 2007). Practical teaching strategies (Harris & Hemming, 2008; Tomlinson et al., 1994) facilitate diverse ways for assisting GAT students to achieve learning outcomes. Such strategies include activities to enhance creativity, co-operative learning and problem-solving activities (Chessman, 2005; NSW Department of Education and Training, 2004; Taylor & Milton, 2006) for GAT students to develop a sense of identity, belonging and self esteem towards becoming an autonomous learner. Preservice teachers need to understand that GAT students learn in a different way and therefore should be assessed differently. Assessment can be through diverse options to demonstrate the student’s competence, demonstrate their understanding of the material in a way that highlights their natural abilities (Glasson, 2008; Mack, 2008). Preservice teachers often are unprepared to assess students understanding but this may be overcome with teacher education training promoting effective communication and collaboration in the classroom, including the provision of a variety of assessment strategies to improve teaching and learning (Callahan et al., 2003; Tomlinson et al., 1994). It is also critical that preservice teachers have enthusiasm for teaching to demonstrate inclusion, involvement and the excitement to communicate to GAT students in the learning process (Baum, 2002). Evaluating and reflecting on teaching practices must be part of a preservice teacher’s repertoire for GAT education. Evaluating teaching practices can assist to further enhance student learning (Mayer, 2008). Evaluation gauges the success or otherwise of specific activities and teaching in general (Mayer, 2008), and ensures that preservice teachers and teachers are well prepared and maintain their commitment to their students and the community. Long and Harris (1999) advocate that reflective practices assist teachers in creating improvements in educational practices. Reflective practices help preservice teachers and teachers to improve their ability to pursue improved learning outcomes and professional growth (Long & Harris, 1999). Context This study is set at a small regional campus of a large university in Queensland. As a way to address departmental policies and the need to prepare preservice teachers for engaging a diverse range of learners (see Queensland College of Teachers, Professional Standards for Teachers, 2006), preservice teachers at this campus completed four elective units within their Bachelor of Education (primary) degree. The electives include: 1. Middle years students and schools 2. Teaching strategies for engaging learners 3. Teaching students with learning difficulties, and 4. Middle-years curriculum, pedagogy and assessment. In the university-based component of this unit, preservice teachers engaged in learning about middle years students and schools, and gained knowledge of government policies pertaining to GAT students. Further explored within in this unit was the importance of: collaboration between teachers, parents/carers and school personnel in supporting middle years GAT students; incorporating challenging learning experiences that promoted higher order thinking and problem solving skills; real world learning experiences for students and; the alignment and design of curriculum, pedagogy and assessment that is relevant to the students development, interests and needs. The participants were third-year Bachelor of Education (primary) preservice teachers who were completing an elective unit as part of the middle years of schooling learning with a focus on GAT students. They were assigned one student from a local school. In the six subsequent ninety minute weekly lessons, the preservice teachers were responsible for designing learning activities that would engage and extend the GAT students. Furthermore, preservice teachers made decisions about suitable pedagogical approaches and designed the assessment task to align with the curriculum and the developmental needs of their middle years GAT student. This research aims to describe preservice teachers’ perceptions of their education for teaching gifted and talented students.

Assessing the potential impact of web services on business processes

Though web services offer unique opportunities for the design of new business processes, the assessment of the potential impact of Web services on existing business information systems is often reduced to technical aspects. This paper proposes a four-phase methodology which facilitates the evaluation of the potential use of Web services on business information systems both from a technical and from a strategic viewpoint. It is based on business process models, which are used to frame the adoption and deployment of Web services and to assess their impact on existing business processes. The application of this methodology is described using a procurement scenario.

The role of bricolage and resource constraints in high potential sustainability ventures

Sustainability decisions and their impacts may be among the greatest challenges facing the world in the 21st century (Davos 2000). Apart from adaptation on the part of established organizations these challenges are arguably going to require solutions developed by new actors However, young ventures have only recently begun generating research interest within sustainability literature (Shepherd et al. 2009). In particular, little is known about resource behaviours of these ventures and how they adapt to substantial resource constraints. One promising theory that has been identified as a way that some entrepreneurs manage constraints is bricolage: a construct defined as “making do by applying combinations of the resources at hand to new problems and opportunities” (Baker and Nelson 2005: 333). Bricolage may be critical as the means of continued venture success as these ventures are frequently developed in severe resource constraint, owing to higher levels of technical sophistication (Rothaermel and Deeds 2006). Further, they are often developed by entrepreneurs committed to personal and social goals of resourcefulness, including values that focus on conservation rather than consumption of resources (Shepherd et al. 2009). In this paper, using seven novel cases of high potential sustainability firms from CAUSEE we consider how constraints impact resource behaviours and further illustrate and extend bricolage domains previously developed by Baker and Nelson (2005) with recommendations for theory and practice provided.

Ovine bone and marrow derived progenitor cells : isolation, characterization, and osteogenic potential

Recently, research has focused on bone marrow derived multipotent mesenchymal precursor cells (MPC) for their potential clinical use in bone engineering. Prior to clinical application, MPC-based treatment concepts need to be evaluated in preclinical, immunocompetent, large animal models. Sheep in particular are considered a valid model for orthopaedic and trauma related research. However, ovine MPC and their osteogenic potential remain poorly characterized. In the present study, ex vivo expanded MPC isolated from ovine bone marrow proliferated at a higher rate than osteoblasts (OB) derived from tibial compact bone as assessed using standard 2D culture. MPC expressed the respective phenotypic profile typical for different mesenchymal cell populations (CD14-/CD31-/CD45- /CD29+/CD44+/CD166+) and showed a multilineage differentiation potential. When compared to OB, MPC had a higher mineralization potential under standard osteogenic culture conditions and expressed typical markers such as osteocalcin, osteonectin and type I collagen at the mRNA and protein level. After 4 weeks in 3D culture, MPC constructs demonstrated higher cell density and mineralization, whilst cell viability on the scaffolds was assessed >90%. Cells displayed a spindle-like morphology and formed an interconnected network. Implanted subcutaneously into NOD/SCID mice on type I collagen coated polycaprolactone-tricalciumphosphate (mPCL-TCP) scaffolds, MPC presented a higher developmental potential than osteoblasts. In summary, this study provides a detailed in vitro characterisation of ovine MPC from a bone engineering perspective and suggests that MPC provide promising means for future bone disease related treatment applications.

Best practice for prevention and treatment of cardiovascular disease through an equity lens : a review

Background: Despite declining rates of cardiovascular disease (CVD) mortality in developed countries, lower socioeconomic groups continue to experience a greater burden of the disease. There are now many evidence-based treatments and prevention strategies for the management of CVD and it is essential that their impact on the more disadvantaged group is understood if socioeconomic inequalities in CVD are to be reduced. Aims: To determine whether key interventions for CVD prevention and treatment are effective among lower socioeconomic groups, to describe barriers to their effectiveness and the potential or actual impact of these interventions on the socioeconomic gradient in CVD. Methods: Interventions were selected from four stages of the CVD continuum. These included smoking reduction strategies, absolute risk assessment, cardiac rehabilitation, secondary prevention medications, and heart failure self-management programmes. Electronic searches were conducted using terms for each intervention combined with terms for socioeconomic status (SES). Results: Only limited evidence was found for the effectiveness of the selected interventions among lower SES groups and there was little exploration of socioeconomic-related barriers to their uptake. Some broad themes and key messages were identified. In the majority of findings examined, it was clear that the underlying material, social and environmental factors associated with disadvantage are a significant barrier to the effectiveness of interventions. Conclusion: Opportunities to reduce socioeconomic inequalities occur at all stages of the CVD continuum. Despite this, current treatment and prevention strategies may be contributing to the widening socioeconomic-CVD gradient. Further research into the impact of best-practice interventions for CVD upon lower SES groups is required.