Evaluation of the efficacy of radiation-modifying compounds using γH2AX as a molecular marker of DNA double-strand breaks

Radiation therapy is a widely used therapeutic approach for cancer. To improve the efficacy of radiotherapy there is an intense interest in combining this modality with two broad classes of compounds, radiosensitizers and radioprotectors. These either enhance tumour-killing efficacy or mitigate damage to surrounding non-malignant tissue, respectively. Radiation exposure often results in the formation of DNA double-strand breaks, which are marked by the induction of H2AX phosphorylation to generate γH2AX. In addition to its essential role in DDR signalling and coordination of double-strand break repair, the ability to visualize and quantitate γH2AX foci using immunofluorescence microscopy techniques enables it to be exploited as an indicator of therapeutic efficacy in a range of cell types and tissues. This review will explore the emerging applicability of γH2AX as a marker for monitoring the effectiveness of radiation-modifying compounds.

Evaluation of the spatial distribution of γH2AX following ionizing radiation

An early molecular response to DNA double-strand breaks (DSBs) is phosphorylation of the Ser-139 residue within the terminal SQEY motif of the histone H2AX1,2. This phosphorylation of H2AX is mediated by the phosphatidyl-inosito 3-kinase (PI3K) family of proteins, ataxia telangiectasia mutated (ATM), DNA-protein kinase catalytic subunit and ATM and RAD3-related (ATR)3. The phosphorylated form of H2AX, referred to as γH2AX, spreads to adjacent regions of chromatin from the site of the DSB, forming discrete foci, which are easily visualized by immunofluorecence microscopy3. Analysis and quantitation of γH2AX foci has been widely used to evaluate DSB formation and repair, particularly in response to ionizing radiation and for evaluating the efficacy of various radiation modifying compounds and cytotoxic compounds Given the exquisite specificity and sensitivity of this de novo marker of DSBs, it has provided new insights into the processes of DNA damage and repair in the context of chromatin. For example, in radiation biology the central paradigm is that the nuclear DNA is the critical target with respect to radiation sensitivity. Indeed, the general consensus in the field has largely been to view chromatin as a homogeneous template for DNA damage and repair. However, with the use of γH2AX as molecular marker of DSBs, a disparity in γ-irradiation-induced γH2AX foci formation in euchromatin and heterochromatin has been observed5-7. Recently, we used a panel of antibodies to either mono-, di- or tri- methylated histone H3 at lysine 9 (H3K9me1, H3K9me2, H3K9me3) which are epigenetic imprints of constitutive heterochromatin and transcriptional silencing and lysine 4 (H3K4me1, H3K4me2, H3K4me3), which are tightly correlated actively transcribing euchromatic regions, to investigate the spatial distribution of γH2AX following ionizing radiation8. In accordance with the prevailing ideas regarding chromatin biology, our findings indicated a close correlation between γH2AX formation and active transcription9. Here we demonstrate our immunofluorescence method for detection and quantitation of γH2AX foci in non-adherent cells, with a particular focus on co-localization with other epigenetic markers, image analysis and 3Dmodeling.

Turning event logs into process movies: animating what has really happened

Today’s information systems log vast amounts of data. These collections of data (implicitly) describe events (e.g. placing an order or taking a blood test) and, hence, provide information on the actual execution of business processes. The analysis of such data provides an excellent starting point for business process improvement. This is the realm of process mining, an area which has provided a repertoire of many analysis techniques. Despite the impressive capabilities of existing process mining algorithms, dealing with the abundance of data recorded by contemporary systems and devices remains a challenge. Of particular importance is the capability to guide the meaningful interpretation of “oceans of data” by process analysts. To this end, insights from the field of visual analytics can be leveraged. This article proposes an approach where process states are reconstructed from event logs and visualised in succession, leading to an animated history of a process. This approach is customisable in how a process state, partially defined through a collection of activity instances, is visualised: one can select a map and specify a projection of events on this map based on the properties of the events. This paper describes a comprehensive implementation of the proposal. It was realised using the open-source process mining framework ProM. Moreover, this paper also reports on an evaluation of the approach conducted with Suncorp, one of Australia’s largest insurance companies.

Implementation and evaluation of open source unified communications for SMBs

Unified Communication (UC) is the integration of two or more real time communication systems into one platform. Integrating core communication systems into one overall enterprise level system delivers more than just cost saving. These real-time interactive communication services and applications over Internet Protocol (IP) have become critical in boosting employee accessibility and efficiency, improving customer support and fostering business agility. However, some small and medium-sized businesses (SMBs) are far from implementing this solution due to the high cost of initial deployment and ongoing support. In this paper, we will discuss and demonstrate an open source UC solution, viz. “Asterisk” for use by SMBs, and report on some performance tests using SIPp. The contribution from this research is the provision of technical advice to SMBs in deploying UC, which is manageable in terms of cost, ease of deployment and support.

Navigating theory, negotiating difference and beating the system : a critical how-to of media assistance evaluation

The wave of democratisation across Europe, Africa, Asia and Latin America in the early 1990s triggered an increase in donor funding to media assistance initiatives, primarily within good governance policy frameworks. However, few media assistance projects have managed to effectively evaluate the impacts of their work. This thesis explores how the impacts of Australian media assistance on social change and governance can be most effectively evaluated and understood. The findings of this research suggest the importance of early investment in participatory planning of evaluation designs, which are then periodically revisited. These evaluation designs should be based on a theoretically sound link between models of change, evaluative questions and methods.

Youth off the Streets "Our Place, Walgett Youth and Young Families Project" Project Evaluation.

The Project: • YOTS is a major youth specific agency established in 1991. It is a non-denominational, non-discriminatory and not-for-profit organisation, providing a wide range of services and offering a full continuum of care. It seeks to build on the strengths and positive aspects of marginalised young people and communities. • The 'Our Place, Walgett Youth and Young Families Project' further develops an existing YOTS capacity to provide services to Aboriginal young people. • The project adopted an action-research and community development model in which YOTS worked in partnership with the Youth Sub-committee of the Walgett Interagency. • Specific goals/objectives of the program were to: Coordinate youth and young family activities in partnership with local services and the community to build self-esteem, pride, resilience, motivation and skills; Contribute to the prevention and reduction of homelessness, unstable and unsafe housing and disruptive mobility (Walgett/Redfern) in youth and young families; Increase and improve collaborative engagement between youth and family focused services; and, research, adapt and implement Australian and international best-practice homelessness prevention/reduction initiatives to contribute to new models of practice relevant to rural and regional areas. • The project centred around an out-reach model that focused on providing a safe space with relevant structured activities coordinated by YOTS youth and family workers. Through community and service provider consultation, it was proposed that local services could coordinate strategies and activities and run them, where possible, from the centre, providing ease of access in a safe and supportive context. • Specific activities included: Implementing regular meetings with the stakeholders and community representatives; Developing a Terms of Reference for YOTS presence in the Walgett community; Undertaking a community consultation prior to finalising program activities; Implementing a range of recreational activities (sports, music, arts and crafts) early on in the activity; Implementing young family support initiatives; implementing a volunteering program, including volunteer support to young families through intergenerational volunteering; running a series of Culture and Healing Camps in partnership with local Elders and other services; Running a series of Music Camps; Providing alternative education support and referrals in partnership with local schools; Researching, identifying and adapting other best-practice models.

Recruiting, Sampling and Data Collection with Difficult Populations: Clients of Male Sex Workers.

Although there are many potential new insights to be gained through advancing research on the clients of male sex workers, significant social, ethical and methodological challenges to accessing this population exist. This research project case explores our attempts to recruit a population that does not typically form a cohesive or coherent 'community' and often avoids self-identifying to mitigate the stigma attached to buying sex. We used an arms-length recruitment campaign that focussed on directing potential participants to our study website, which could in turn lead them to participate in an anonymous telephone interview. Barriers to reaching male sex-work clients, however, demanded the evolution of our recruitment strategy. New technologies are part of the solution to accessing a hard-to-reach population, but they only work if researchers engage responsively. We also show how we conducted an in-depth interview with a client and discuss the value of using secondary data.

Evaluation of Indigenous justice programs.: final report / Project D, Safe Aboriginal Youth Patrol Programs in New South Wales and Northbridge Policy and Juvenile Aid Group in Western Australia

The Australian Government has provided funding to evaluate the effectiveness of Indigenous law and justice programs across five subject areas to identify the best approaches to tackling crime and justice issues and better inform government funding decisions in the future. This report presents the findings of subject area "D", which examined two different approaches to delivering community and night patrol services for young people: the Safe Aboriginal Youth Patrol programs in New South Wales, and the Northbridge Policy project (the Young People in Northbridge project), in Western Australia. Night patrols can address crime either directly or indirectly, by prevention work or by addressing the social causes of crime through community development.

Indigenous Youth Justice Programs Evaluation

Diversion from the youth justice system is a critical goal for addressing the overrepresentation of Indigenous young people in the criminal justice system. In this report, four programs that were already being implemented by states and territories and identified by them under the National Indigenous Law & Justice Framework as promising practice in diversion are examined. The programs were evaluated, as part of a broader initiative, to determine whether and on what basis they represent good practice (ie are supported by evidence). State and territory governments nominated the programs for evaluation.

A case study of utilising concept knowledge in a topic specific document collection

The use of ‘topic’ concepts has shown improved search performance, given a query, by bringing together relevant documents which use different terms to describe a higher level concept. In this paper, we propose a method for discovering and utilizing concepts in indexing and search for a domain specific document collection being utilized in industry. This approach differs from others in that we only collect focused concepts to build the concept space and that instead of turning a user’s query into a concept based query, we experiment with different techniques of combining the original query with a concept query. We apply the proposed approach to a real-world document collection and the results show that in this scenario the use of concept knowledge at index and search can improve the relevancy of results.

Teaching persuasive texts : building a language of evaluation through hedging and moderated intensification

We identify two persuasive writing techniques – hedging and intensification – that pose difficulty for students in the middle years. We use examples of student writing from 3000 work samples collected as part of a larger Australian Research Council Linkage Project, URLearning (2009–2013). To realise the effective power of rhetorical persuasion, students need to be explicitly taught a range of hedging techniques to use to their advantage, and an expanded lexicon that does not rely on intensifiers. Practical teaching tips are provided for teachers.

Economic evaluation of adolescent reproductive health education interventions in Chilinh, Vietnam

This research was an economic analysis of two novel health education interventions compared to existing practice for reproductive health among young people in northern Vietnam. The research showed that implementing an educational intervention including school-based and health facility-based components was cost effective for males and females. The findings will assist decision makers in efficient allocation of scarce resources for adolescent health promotion in Vietnam and similar socio-economic contexts in Asia.

Usulan kerangka kebijakan penggunaan media sosial untuk perpustakaan perguruan tinggi

This study provides proposed core elements of social media policy that specifically designed for academic libraries.Evaluation of social media policies from five organisations and a review of the literature were used for data collection.There are 15 proposed core elements recommended: policy objectives; policy definition; scope of the policy;university’s vision and mission; policy users; disclaimer; confidentiality; copyright; privacy; workflow; publicinformation; the use of professional language; the accuracy of the information; rule for links; and university andlibrary’s voices. The results of this study provide important aspects in the development of social media policy. Theproposed core elements of the social media policy discussed in this paper is specifically designed for the academiclibraries, but can also be used for other library types. Kajian ini memuat usulan kerangka kebijakan penggunaan media sosial dari elemen-elemen inti yang disusun khusus untuk perpustakaan perguruan tinggi. Evaluasi kebijakan penggunaan media sosial dari lima organisasi dan kajian literatur digunakan untuk pengumpulan data. Ada 15 elemen inti kebijakan yang diusulkan, yaitu: tujuan kebijakan; definisi kebijakan; lingkup kebijakan; visi dan misi universitas; sasaran pengguna kebijakan; disclaimer; kerahasiaan; hak cipta; privasi; alur kerja; informasi publik; penggunaan bahasa professional; keakuratan informasi; kaidah tautan; serta suara universitas dan perpustakaan. Hasil kajian ini menyediakan aspek penting dalam pengembangan kebijakan penggunaan media sosial. Usulan elemen inti kebijakan yang diusulkan dalam kajian ini secara khusus dirancang untuk perpustakaan perguruan tinggi, tetapi dapat juga digunakan untuk perpustakaan jenis lainnya.

Design, construction and evaluation of systems to predict risk in obstetrics

We present a systematic, practical approach to developing risk prediction systems, suitable for use with large databases of medical information. An important part of this approach is a novel feature selection algorithm which uses the area under the receiver operating characteristic (ROC) curve to measure the expected discriminative power of different sets of predictor variables. We describe this algorithm and use it to select variables to predict risk of a specific adverse pregnancy outcome: failure to progress in labour. Neural network, logistic regression and hierarchical Bayesian risk prediction models are constructed, all of which achieve close to the limit of performance attainable on this prediction task. We show that better prediction performance requires more discriminative clinical information rather than improved modelling techniques. It is also shown that better diagnostic criteria in clinical records would greatly assist the development of systems to predict risk in pregnancy. We present a systematic, practical approach to developing risk prediction systems, suitable for use with large databases of medical information. An important part of this approach is a novel feature selection algorithm which uses the area under the receiver operating characteristic (ROC) curve to measure the expected discriminative power of different sets of predictor variables. We describe this algorithm and use it to select variables to predict risk of a specific adverse pregnancy outcome: failure to progress in labour. Neural network, logistic regression and hierarchical Bayesian risk prediction models are constructed, all of which achieve close to the limit of performance attainable on this prediction task. We show that better prediction performance requires more discriminative clinical information rather than improved modelling techniques. It is also shown that better diagnostic criteria in clinical records would greatly assist the development of systems to predict risk in pregnancy.

An evaluation of the neocognitron

We describe a sequence of experiments investigating the strengths and limitations of Fukushima's neocognitron as a handwritten digit classifier. Using the results of these experiments as a foundation, we propose and evaluate improvements to Fukushima's original network in an effort to obtain higher recognition performance. The neocognitron's performance is shown to be strongly dependent on the choice of selectivity parameters and we present two methods to adjust these variables. Performance of the network under the more effective of the two new selectivity adjustment techniques suggests that the network fails to exploit the features that distinguish different classes of input data. To avoid this shortcoming, the network's final layer cells were replaced by a nonlinear classifier (a multilayer perceptron) to create a hybrid architecture. Tests of Fukushima's original system and the novel systems proposed in this paper suggest that it may be difficult for the neocognitron to achieve the performance of existing digit classifiers due to its reliance upon the supervisor's choice of selectivity parameters and training data. These findings pertain to Fukushima's implementation of the system and should not be seen as diminishing the practical significance of the concept of hierarchical feature extraction embodied in the neocognitron. © 1997 IEEE.