In silico analyses reveal common cellular pathways affected by loss of heterozygosity (LOH) events in the lymphomagenesis of Non-Hodgkin’s lymphoma (NHL)

Background The analysis of cellular networks and pathways involved in oncogenesis has increased our knowledge about the pathogenic mechanisms that underlie tumour biology and has unmasked new molecular targets that may lead to the design of better anti-cancer therapies. Recently, using a high resolution loss of heterozygosity (LOH) analysis, we identified a number of potential tumour suppressor genes (TSGs) within common LOH regions across cases suffering from two of the most common forms of Non-Hodgkin’s lymphoma (NHL), Follicular Lymphoma (FL) and Diffuse Large B-cell Lymphoma (DLBCL). From these studies LOH of the protein tyrosine phosphatase receptor type J (PTPRJ) gene was identified as a common event in the lymphomagenesis of these B-cell lymphomas. The present study aimed to determine the cellular pathways affected by the inactivation of these TSGs including PTPRJ in FL and DLBCL tumourigenesis. Results Pathway analytical approaches identified that candidate TSGs located within common LOH regions participate within cellular pathways, which may play a crucial role in FL and DLBCL lymphomagenesis (i.e., metabolic pathways). These analyses also identified genes within the interactome of PTPRJ (i.e. PTPN11 and B2M) that when inactivated in NHL may play an important role in tumourigenesis. We also detected genes that are differentially expressed in cases with and without LOH of PTPRJ, such as NFATC3 (nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3). Moreover, upregulation of the VEGF, MAPK and ERBB signalling pathways was also observed in NHL cases with LOH of PTPRJ, indicating that LOH-driving events causing inactivation of PTPRJ, apart from possibly inducing a constitutive activation of these pathways by reduction or abrogation of its dephosphorylation activity, may also induce upregulation of these pathways when inactivated. This finding implicates these pathways in the lymphomagenesis and progression of FL and DLBCL. Conclusions The evidence obtained in this research supports findings suggesting that FL and DLBCL share common pathogenic mechanisms. Also, it indicates that PTPRJ can play a crucial role in the pathogenesis of these B-cell tumours and suggests that activation of PTPRJ might be an interesting novel chemotherapeutic target for the treatment of these B-cell tumours.

Audit committee effectiveness : informal processes and behavioural effects

Purpose This paper seeks to investigate the conditions and processes affecting the operation and potential effectiveness of audit committees (ACs), with particular focus on the interaction between the AC, individuals from financial reporting and internal audit functions and the external auditors. Design/methodology/approach A case study approach is employed, based on direct engagement with participants in AC activities, including the AC chair, external auditors, internal auditors, and senior management. Findings The authors find that informal networks between AC participants condition the impact of the AC and that the most significant effects of the AC on governance outcomes occur outside the formal structures and processes. An AC has pervasive behavioural effects within the organization and may be used as a threat, an ally and an arbiter in bringing solutions to issues and conflicts. ACs are used in organizational politics, communication processes and power plays and also affect interpretations of events and cultural values. Research limitations/implications Further research on AC and governance processes is needed to develop better understanding of effectiveness. Longitudinal studies, focusing on the organizational and institutional context of AC operations, can examine how historical events in an organization and significant changes in the regulatory environment affect current structures and processes. Originality/value The case analysis highlights a number of significant factors which are not fully recognised either in theorizing the governance role of ACs or in the development of policy and regulations concerning ACs but which impinge on their governance contribution. They include the importance of informal processes around the AC; its influence on power relations between organizational participants; the relevance of the historical development of governance in an organization; and the possibility that the AC’s impact on governance may be greatest in non-routine situations.

Decision support for the efficient annotation of bioacoustic events

Acoustic sensors allow scientists to scale environmental monitoring over large spatiotemporal scales. The faunal vocalisations captured by these sensors can answer ecological questions, however, identifying these vocalisations within recorded audio is difficult: automatic recognition is currently intractable and manual recognition is slow and error prone. In this paper, a semi-automated approach to call recognition is presented. An automated decision support tool is tested that assists users in the manual annotation process. The respective strengths of human and computer analysis are used to complement one another. The tool recommends the species of an unknown vocalisation and thereby minimises the need for the memorization of a large corpus of vocalisations. In the case of a folksonomic tagging system, recommending species tags also minimises the proliferation of redundant tag categories. We describe two algorithms: (1) a “naïve” decision support tool (16%–64% sensitivity) with efficiency of O(n) but which becomes unscalable as more data is added and (2) a scalable alternative with 48% sensitivity and an efficiency ofO(log n). The improved algorithm was also tested in a HTML-based annotation prototype. The result of this work is a decision support tool for annotating faunal acoustic events that may be utilised by other bioacoustics projects.

Ross River virus disease activity associated with naturally occurring non-tidal flood events in Australia : A systematic review

Ross River virus (RRV) disease is the most common and widespread mosquito-borne disease in Australia, resulting in considerable health and economic cost to communities. While naturally occurring non-tidal flood events may enhance mosquito abundance, little is known about the impact of such events on RRV transmission. This paper critically reviews the existing evidence for an association between naturally occurring non-tidal flood events and RRV transmission. A systematic literature search was conducted on RRV transmission related to flooding and inundation from rain and riverine overflow. Overall, the evidence to support a positive association between flooding and RRV outbreaks is largely circumstantial, with the literature mostly reporting only coincidental occurrence between the two. However, for the Murray River, river flow and height (surrogates of flooding) were positively and significantly associated with RRV transmission. The association between non-tidal flooding and RRV transmission has not been studied comprehensively. More frequent flood events arising from climate change may result in increased outbreaks of RRV disease. Understanding the link between flood events and RRV transmission is necessary if resources for mosquito spraying and public health warnings are to be utilized more effectively and efficiently.

Detecting rare events using Kullback-Leibler divergence

One main challenge in developing a system for visual surveillance event detection is the annotation of target events in the training data. By making use of the assumption that events with security interest are often rare compared to regular behaviours, this paper presents a novel approach by using Kullback-Leibler (KL) divergence for rare event detection in a weakly supervised learning setting, where only clip-level annotation is available. It will be shown that this approach outperforms state-of-the-art methods on a popular real-world dataset, while preserving real time performance.

A multimodal physiotherapy programme plus deep water running for improving cancer-related fatigue and quality of life in breast cancer survivors

The aim of the study was to assess the feasibility and effectiveness of aquatic‐based exercise in the form of deep water running ( DWR ) as part of a multimodal physiotherapy programme ( MMPP ) for breast cancer survivors. A controlled clinical trial was conducted in 42 primary breast cancer survivors recruited from community‐based P rimary C are C entres. Patients in the experimental group received a MMPP incorporating DWR , 3 times a week, for an 8‐week period. The control group received a leaflet containing instructions to continue with normal activities. Statistically significant improvements and intergroup effect size were found for the experimental group for P iper F atigue S cale‐ R evised total score ( d = 0.7, P = 0.001), as well as behavioural/severity ( d = 0.6, P = 0.05), affective/meaning ( d = 1.0, P = 0.001) and sensory ( d = 0.3, P = 0.03) domains. Statistically significant differences between the experimental and control groups were also found for general health ( d = 0.5, P < 0.05) and quality of life ( d = 1.3, P < 0.05). All participants attended over 80% of sessions, with no major adverse events reported. The results of this study suggest MMPP incorporating DWR decreases cancer‐related fatigue and improves general health and quality of life in breast cancer survivors. Further, the high level of adherence and lack of adverse events indicate such a programme is safe and feasible.

Feature article coverage of Australian out-of-home care : portrayals and policy reform

Mandatory reporting is a key aspect of Australia’s approach to protecting children and is incorporated into all jurisdictions’ legislation, albeit in a variety of forms. In this article we examine all major newspaper’s coverage of mandatory reporting during an 18-month period in 2008-2009, when high-profile tragedies and inquiries occurred and significant policy and reform agendas were being debated. Mass media utilise a variety of lenses to inform and shape public responses and attitudes to reported events. We use frame analysis to identify the ways in which stories were composed and presented, and how language portrayed this contested area of policy. The results indicate that within an overall portrayal of system failure and the need for reform, the coverage placed major responsibility on child protection agencies for the over-reporting, under-reporting, and overburdened system identified, along with the failure of mandatory reporting to reduce risk. The implications for ongoing reform are explored along with the need for robust research to inform debate about the merits of mandatory reporting.

The whole world shook : shifts in ethnic, national and heroic identities in children's fiction about 9/11

Like many other cataclysmic events September 11, a day now popularly believed to have 'changed the world', has become a topic taken up by children's writers. This thesis, titled The Whole World Shook: Ethnic, National and Heroic Identities in Children's Fiction About 9/11, examines how cultural identities are constructed within fictional texts for young people written about the attacks on the Twin Towers. It identifies three significant identity categories encoded in 9/11 books for children: ethnic identities, national identities, and heroic identities. The thesis argues that the identities formed within the selected children's texts are in flux, privileging performances of identities that are contingent on post-9/11 politics. This study is located within the field of children's literature criticism, which supports the understanding that children's books, like all texts, play a role in the production of identities. Children's literature is highly significant both in its pedagogical intent (to instruct and induct children into cultural practices and beliefs) and in its obscurity (in making the complex simple enough for children, and from sometimes intentionally shying away from difficult things). This literary criticism informed the study that the texts, if they were to be written at all, would be complex, varied and most likely as ambiguous and contradictory as the responses to the attacks on New York themselves. The theoretical framework for this thesis draws on a range of critical theories including literary theory, cultural studies, studies of performativity and postmodernism. This critical framework informs the approach by providing ways for: (i) understanding how political and ideological work is performed in children's literature; (ii) interrogating the constructed nature of cultural identities; (iii) developing a nuanced methodology for carrying out a close textual analysis. The textual analysis examines a representative sample of children's texts about 9/11, including picture books, young adult fiction, and a selection of DC Comics. Each chapter focuses on a different though related identity category. Chapter Four examines the performance of ethnic identities and race politics within a sample of picture books and young adult fiction; Chapter Five analyses the construction of collective, national identities in another set of texts; and Chapter Six does analytic work on a third set of texts, demonstrating the strategic performance of particular kinds of heroic identities. I argue that performances of cultural identities constructed in these texts draw on familiar versions of identities as well as contribute to new ones. These textual constructions can be seen as offering some certainties in increasingly uncertain times. The study finds, in its sample of books a co-mingling of xenophobia and tolerance; a binaried competition between good and evil and global harmony and national insularity; and a lauding of both the commonplace hero and the super-human. Being a recent corpus of texts about 9/11, these texts provide information on the kinds of 'selves' that appear to be privileged in the West since 2001. The thesis concludes that the shifting identities evident in texts that are being produced for children about 9/11 offer implicit and explicit accounts of what constitute good citizenship, loyalty to nation and community, and desirable attributes in a Western post-9/11 context. This thesis makes an original contribution to the field of children's literature by providing a focussed and sustained analysis of how texts for children about 9/11 contribute to formations of identity in these complex times of cultural unease and global unrest.

Using conversation analysis for understanding children’s talk about traumatic events

This chapter provides a theoretical overview of literature that uses conversation analysis (CA) to explore children’s interactions related to trauma and associated mental health matters. The relatively new approach of using CA to understand trauma reveals the importance of talk in the process of recovery, and also how the participants co-construct talk about traumatic experiences. The chapter will explore literature using a CA approach to investigate children’s trauma talk with professionals as well as literature specifically discussing children’s talk about their traumatic experiences with people who are not qualified therapists or psychiatrists. We conclude by calling for more research using a CA approach for investigating children’s traumatic experiences due to the insight it provides into each child’s personal sense making of traumatic events with a range of people.

Charged particles and cluster ions produced during cooking activities

Previous studies showed that a significant number of the particles present in indoor air are generated by cooking activities, and measured particle concentrations and exposures have been used to estimate the related human dose. The dose evaluation can be affected by the particle charge level which is usually not considered in particle deposition models. To this purpose, in this paper we show, for the very first time, the electric charge of particles generated during cooking activities and thus extending the interest on particle charging characterization to indoor micro-environments, so far essentially focused on outdoors. Particle number, together with positive and negative cluster ion concentrations, was monitored using a condensation particle counter and two air ion counters, respectively, during different cooking events. Positively-charged particle distribution fractions during gas combustion, bacon grilling, and eggplant grilling events were measured by two Scanning Mobility Particle Sizer spectrometers, used with and without a neutralizer. Finally, a Tandem Differential Mobility Analyzer was used to measure the charge specific particle distributions of bacon and eggplant grilling experiments, selecting particles of 30, 50, 80 and 100 nm in mobility diameter. The total fraction of positively-charged particles was 4.0%, 7.9%, and 5.6% for gas combustion, bacon grilling, and eggplant grilling events, respectively, then lower than other typical outdoor combustion-generated particles.

Suppression of cluster ions during rapidly increasing particle number concentration events in the environment

We show that the cluster ion concentration (CIC) in the atmosphere is significantly suppressed during events that involve rapid increases in particle number concentration (PNC). Using a neutral cluster and air ion spectrometer, we investigated changes in CIC during three types of particle enhancement processes – new particle formation, a bushfire episode and an intense pyrotechnic display. In all three cases, the total CIC decreased with increasing PNC, with the rate of decrease being greater for negative CIC than positive. We attribute this to the greater mobility, and hence the higher attachment coefficient, of negative ions over positive ions in the air. During the pyrotechnic display, the rapid increase in PNC was sufficient to reduce the CIC of both polarities to zero. At the height of the display, the negative CIC stayed at zero for a full 10 min. Although the PNCs were not significantly different, the CIC during new particle formation did not decrease as much as during the bushfire episode and the pyrotechnic display. We suggest that the rate of increase of PNC, together with particle size, also play important roles in suppressing CIC in the atmosphere.

Urban Aboriginal and Torres Strait Islander children's exposure to stressful events : a cross sectional study

Objectives To determine the frequency and types of stressful events experienced by urban Aboriginal and Torres Strait Islander children, and to explore the relationship between these experiences and the children’s physical health and parental concerns about their behaviour and learning ability. Design, setting and participants Cross-sectional study of Aboriginal and Torres Strait Islander children aged ≤ 14 years presenting to an urban Indigenous primary health care service in Brisbane for annual child health checks between March 2007 and March 2010. Main outcome measures Parental or carer report of stressful events ever occurring in the family that may have affected the child. Results Of 344 participating children, 175 (51%) had experienced at least one stressful event. Reported events included the death of a family member or close friend (40; 23%), parental divorce or separation (28; 16%), witness to violence or abuse (20; 11%), or incarceration of a family member (7; 4%). These children were more likely to have parents or carers concerned about their behaviour (P < 0.001) and to have a history of ear (P < 0.001) or skin (P = 0.003) infections. Conclusions Children who had experienced stressful events had poorer physical health and more parental concern about behavioural issues than those who had not. Parental disclosure in the primary health care setting of stressful events that have affected the child necessitates appropriate medical, psychological or social interventions to ameliorate both the immediate and potential lifelong negative impact. However, treating the impact of stressful events is insufficient without dealing with the broader political and societal issues that result in a clustering of stressful events in the Aboriginal and Torres Strait Islander population.

Using internet search queries for infectious disease surveillance: screening diseases for suitability

Background Internet-based surveillance systems provide a novel approach to monitoring infectious diseases. Surveillance systems built on internet data are economically, logistically and epidemiologically appealing and have shown significant promise. The potential for these systems has increased with increased internet availability and shifts in health-related information seeking behaviour. This approach to monitoring infectious diseases has, however, only been applied to single or small groups of select diseases. This study aims to systematically investigate the potential for developing surveillance and early warning systems using internet search data, for a wide range of infectious diseases. Methods Official notifications for 64 infectious diseases in Australia were downloaded and correlated with frequencies for 164 internet search terms for the period 2009–13 using Spearman’s rank correlations. Time series cross correlations were performed to assess the potential for search terms to be used in construction of early warning systems. Results Notifications for 17 infectious diseases (26.6%) were found to be significantly correlated with a selected search term. The use of internet metrics as a means of surveillance has not previously been described for 12 (70.6%) of these diseases. The majority of diseases identified were vaccine-preventable, vector-borne or sexually transmissible; cross correlations, however, indicated that vector-borne and vaccine preventable diseases are best suited for development of early warning systems. Conclusions The findings of this study suggest that internet-based surveillance systems have broader applicability to monitoring infectious diseases than has previously been recognised. Furthermore, internet-based surveillance systems have a potential role in forecasting emerging infectious disease events, especially for vaccine-preventable and vector-borne diseases

Towards a consistent definition of a significant delta troponin with z-scores: A way out of chaos?

Aims: We assessed the diagnostic performance of z-scores to define a significant delta cardiac troponin (cTn) in a cohort of patients with well-defined clinical outcomes. Methods: We calculated z-scores, which are dependent on the analytical precision and biological variation, to report changes in cTn. We compared the diagnostic performances of a relative delta (%Δ), actual delta (Δ), and z-scores in 762 emergency department patients with symptoms of suspected acute coronary syndrome. cTn was measured with sensitive cTnI (Beckman Coulter), highly sensitive cTnI (Abbott), and highly sensitive cTnT (Roche) assays. Results: Receiver operating characteristic analysis showed no statistically significant differences in the areas under the curve (AUC) of z-scores and Δ with both superior compared to %Δ for all three assays (p<0.001). The AUCs of z-scores measured with the Abbott hs-cTnI (0.955) and Roche hs-cTnT (0.922) assays were comparable to Beckman Coulter cTnI (0.933) (p=0.272 and 0.640, respectively). The individualized Δ cut-off values that were required to emulate a z-score of 1.96 were: Beckman Coulter cTnI 30 ng/l, Abbott hs-cTnI 20 ng/l, and Roche hs-cTnT 7 ng/l. Conclusions: z-scores allow the use of a single cut-off value at all cTn levels, for both cTnI and cTnT and for sensitive and highly sensitive assays, with comparable diagnostic performances. This strategy of reporting significant changes as z-scores may obviate the need for the empirical development of assay-specific cut-off rules to define significant troponin changes.