The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer

The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a) was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic), whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p<0.05. MiR-21 and miR-146a expression was significantly increased in MyD88 negative cancers (p<0.05), indicating their participation in regulation. Significant alterations in MyD88 mRNA expression were observed between chemosensitive and chemoresistant cells and tissue. Knockdown of TLR4 in SKOV-3 ovarian cells recovered chemosensitivity. Knockdown of MyD88 alone did not. MyD88 expression was down-regulated in differentiated embryonal carcinoma (NTera2) cells, supporting the MyD88+ cancer stem cell hypothesis. Our findings demonstrate that expression of MyD88 is associated with significantly reduced patient survival and altered microRNA levels and suggest an intact/functioning TLR4/MyD88 pathway is required for acquisition of the chemoresistant phenotype. Ex vivo manipulation of ovarian cancer stem cell (CSC) differentiation can decrease MyD88 expression, providing a potentially valuable CSC model for ovarian cancer.

Profiling high-range speeding offenders : investigating criminal history, personal characteristics, traffic offences, and crash history

This paper reports profiling information for speeding offenders and is part of a larger project that assessed the deterrent effects of increased speeding penalties in Queensland, Australia, using a total of 84,456 speeding offences. The speeding offenders were classified into three groups based on the extent and severity of an index offence: once-only low-rang offenders; repeat high-range offenders; and other offenders. The three groups were then compared in terms of personal characteristics, traffic offences, crash history and criminal history. Results revealed a number of significant differences between repeat high-range offenders and those in the other two offender groups. Repeat high-range speeding offenders were more likely to be male, younger, hold a provisional and a motorcycle licence, to have committed a range of previous traffic offences, to have a significantly greater likelihood of crash involvement, and to have been involved in multiple-vehicle crashes than drivers in the other two offender types. Additionally, when a subset of offenders’ criminal histories were examined, results revealed that repeat high-range speeding offenders were also more likely to have committed a previous criminal offence compared to once only low-range and other offenders and that 55.2% of the repeat high-range offenders had a criminal history. They were also significantly more likely to have committed drug offences and offences against order than the once only low-range speeding offenders, and significantly more likely to have committed regulation offences than those in the other offenders group. Overall, the results indicate that speeding offenders are not an homogeneous group and that, therefore, more tailored and innovative sanctions should be considered and evaluated for high-range recidivist speeders because they are a high-risk road user group.

Deriving a preference-based utility measure for cancer patients from the European Organisation for the Research and Treatment of Cancer's Quality of Life Questionnaire C30 : a confirmatory versus exploratory approach

Background Multi attribute utility instruments (MAUIs) are preference-based measures that comprise a health state classification system (HSCS) and a scoring algorithm that assigns a utility value to each health state in the HSCS. When developing a MAUI from a health-related quality of life (HRQOL) questionnaire, first a HSCS must be derived. This typically involves selecting a subset of domains and items because HRQOL questionnaires typically have too many items to be amendable to the valuation task required to develop the scoring algorithm for a MAUI. Currently, exploratory factor analysis (EFA) followed by Rasch analysis is recommended for deriving a MAUI from a HRQOL measure. Aim To determine whether confirmatory factor analysis (CFA) is more appropriate and efficient than EFA to derive a HSCS from the European Organisation for the Research and Treatment of Cancer’s core HRQOL questionnaire, Quality of Life Questionnaire (QLQ-C30), given its well-established domain structure. Methods QLQ-C30 (Version 3) data were collected from 356 patients receiving palliative radiotherapy for recurrent/metastatic cancer (various primary sites). The dimensional structure of the QLQ-C30 was tested with EFA and CFA, the latter informed by the established QLQ-C30 structure and views of both patients and clinicians on which are the most relevant items. Dimensions determined by EFA or CFA were then subjected to Rasch analysis. Results CFA results generally supported the proposed QLQ-C30 structure (comparative fit index =0.99, Tucker–Lewis index =0.99, root mean square error of approximation =0.04). EFA revealed fewer factors and some items cross-loaded on multiple factors. Further assessment of dimensionality with Rasch analysis allowed better alignment of the EFA dimensions with those detected by CFA. Conclusion CFA was more appropriate and efficient than EFA in producing clinically interpretable results for the HSCS for a proposed new cancer-specific MAUI. Our findings suggest that CFA should be recommended generally when deriving a preference-based measure from a HRQOL measure that has an established domain structure.

Incidence, risk factors and estimates of a woman's risk of developing secondary lower limb lymphedema and lymphedema-specific supportive care needs in women treated for endometrial cancer

Objectives: Few studies have assessed the risk and impact of lymphedema among women treated for endometrial cancer. We aimed to quantify cumulative incidence of, and risk factors for developing lymphedema following treatment for endometrial cancer and estimate absolute risk for individuals. Further, we report unmet needs for help with lymphedema-specific issues. Methods: Women treated for endometrial cancer (n = 1243) were followed-up 3–5 years after diagnosis; a subset of 643 completed a follow-up survey that asked about lymphedema and lymphedema-related support needs. We identified a diagnosis of secondary lymphedema from medical records or self-report. Multivariable logistic regression was used to evaluate risk factors and estimates. Results: Overall, 13% of women developed lymphedema. Risk varied markedly with the number of lymph nodes removed and, to a lesser extent, receipt of adjuvant radiation or chemotherapy treatment, and use of nonsteroidal anti-inflammatory drugs (pre-diagnosis). The absolute risk of developing lymphedema was > 50% for women with 15 + nodes removed and 2–3 additional risk factors, 30–41% for those with 15 + nodes removed plus 0–1 risk factors or 6–14 nodes removed plus 3 risk factors, but ≤ 8% for women with no nodes removed or 1–5 nodes but no additional risk factors. Over half (55%) of those who developed lymphedema reported unmet need(s), particularly with lymphedema-related costs and pain. Conclusion: Lymphedema is common; experienced by one in eight women following endometrial cancer. Women who have undergone lymphadenectomy have very high risks of lymphedema and should be informed how to self-monitor for symptoms. Affected women need greater levels of support.

Learning Chinese as a heritage language in Australia and beyond : the role of capital

The benefits of learning and retaining heritage languages are well documented in the literature. Chinese heritage language learners’ commitment to their heritage language learning has gained significant research ground in social psychological and post-structural schools, with empirical evidence predominantly emerging from the North American contexts. There is scant sociological examination of similar problems conducted outside North America. The current study aims to make a contribution in this regard. The use of Bourdieu's sociological notion of capital in the Australian context complements the social psychological and post-structural work predominantly produced in the North American contexts. The initial quantitative sub-study analyses the impacts of various resources on the Chinese heritage language proficiency of 230 snowball-sampled Chinese Australian respondents to an online survey. The subsequent qualitative sub-study explores the profits of learning Chinese heritage language through interviews with a subset of the survey sample. Findings indicate that cultural, social, and symbolic capital significantly positively contributes to Chinese Australians’ Chinese heritage language proficiency, which, in return, produces profits in different forms of capital. The study suggests a reciprocal relationship between ‘capital’ and Chinese heritage language proficiency.

Functional MRI of facial emotion recognition deficits in schizophrenia and their electrophysiological correlates

Empirical evidence suggests impaired facial emotion recognition in schizophrenia. However, the nature of this deficit is the subject of ongoing research. The current study tested the hypothesis that a generalized deficit at an early stage of face-specific processing (i.e. putatively subserved by the fusiform gyrus) accounts for impaired facial emotion recognition in schizophrenia as opposed to the Negative Emotion-specific Deficit Model, which suggests impaired facial information processing at subsequent stages. Event-related potentials (ERPs) were recorded from 11 schizophrenia patients and 15 matched controls while performing a gender discrimination and a facial emotion recognition task. Significant reduction of the face-specific vertex positive potential (VPP) at a peak latency of 165 ms was confirmed in schizophrenia subjects whereas their early visual processing, as indexed by P1, was found to be intact. Attenuated VPP was found to correlate with subsequent P3 amplitude reduction and to predict accuracy when performing a facial emotion discrimination task. A subset of ten schizophrenia patients and ten matched healthy control subjects also performed similar tasks in the magnetic resonance imaging scanner. Patients showed reduced blood oxygenation level-dependent (BOLD) activation in the fusiform, inferior frontal, middle temporal and middle occipital gyrus as well as in the amygdala. Correlation analyses revealed that VPP and the subsequent P3a ERP components predict fusiform gyrus BOLD activation. These results suggest that problems in facial affect recognition in schizophrenia may represent flow-on effects of a generalized deficit in early visual processing.

Psychometric validation of the Dysexecutive Questionnaire (DEX)

This study reported on the validation of the psychometric properties, the factorability, validity, and sensitivity of the Dysexecutive Questionnaire (DEX) in 3 clinical and nonclinical samples. A mixed sample of 997 participants—community (n = 663), psychiatric (depressed [n = 92] and anxious [n = 122]), and neurologically impaired (n = 120)—completed self-report questionnaires assessing executive dysfunction, depression, anxiety, stress, general self-efficacy, and satisfaction with life. Before analyses the data were randomly split into 2 subsets (A and B). Exploratory factor analysis performed on Subset A produced a 3-factor model (Factor 1: Inhibition, Factor 2: Volition, and Factor 3: Social Regulation) in which 15 of the original 20 items provided a revised factor structure that was superior to all other structures. A series of confirmatory factor analyses performed on Subset B confirmed that this revised factor structure was valid and reliable. The revised structure, labeled the DEX-R, was found to be a reliable and valid tool for assessing behavioral symptoms of dysexecutive functioning in mixed community, psychiatric, and neurological samples.

Soluble NSF attachment protein receptor molecular mimicry by a Legionella pneumophila Dot/Icm effector

Upon infection, Legionella pneumophila uses the Dot/Icm type IV secretion system to translocate effector proteins from the Legionella-containing vacuole (LCV) into the host cell cytoplasm. The effectors target a wide array of host cellular processes that aid LCV biogenesis, including the manipulation of membrane trafficking. In this study, we used a hidden Markov model screen to identify two novel, non-eukaryotic soluble NSF attachment protein receptor (SNARE) homologs: the bacterial Legionella SNARE effector A (LseA) and viral SNARE homolog A proteins. We characterized LseA as a Dot/Icm effector of L. pneumophila, which has close homology to the Qc-SNARE subfamily. The lseA gene was present in multiple sequenced L. pneumophila strains including Corby and was well distributed among L. pneumophila clinical and environmental isolates. Employing a variety of biochemical, cell biological and microbiological techniques, we found that farnesylated LseA localized to membranes associated with the Golgi complex in mammalian cells and LseA interacted with a subset of Qa-, Qb- and R-SNAREs in host cells. Our results suggested that LseA acts as a SNARE protein and has the potential to regulate or mediate membrane fusion events in Golgi-associated pathways.

Sensorineural hearing loss after treatment for head and neck cancer : a review of the literature

Background Definitive cisplatin-based is increasingly delivered as the treatment of choice for patients with head and neck cancer. Sensorineural hearing loss is a significant long term side effect of cisplatin-based chemoradiation and is associated with potential major quality of life issues for patients. Purpose The purpose of this manuscript was to review the mechanism behind sensorineural hearing loss in patients treated with cisplatin-based chemoradiation, including incidence, the contributions of radiotherapy and cisplatin to sensorineural hearing loss and the impact of the toxicity on patient quality of life. Methods Database searches were conducted through PubMed (National Centre for Biotechnology Information) and OvidSP Medline via the Queensland University of Technology Library website. General article searches were conducted through the online search engine Google Scholar. Articles were excluded if the full-text was unavailable, they were not in English or if they were published prior to 1990. Keywords included hearing loss, ototoxicity, cancer, quality of life, cisplatin and radiotherapy. Results/Discussion The total number of journal articles accessed was 290. Due to exclusion criteria, 129 articles were deemed appropriated for review. Findings indicated that sensorineural hearing loss is a significant, long term complication for patients treated with cisplatin-based chemoradiation. Current literature recognises the ototoxic effects of cisplatin and cranial irradiation as separate entities, however the impact of combined modality therapy on sensorineural hearing loss is seldom reported. Multiple risk factors for hearing loss are described, however there are contradictory opinions on incidence and severity and the exact radiation dose threshold responsible for inducing hearing loss in patients receiving combined modality therapy. Sensorineural hearing loss creates a subset of complexities for patients with head and neck cancer and that these patients face significant quality of life impairment. Conclusion The literature review identified that sensorineural hearing loss is a major quality of life issue for patients treated with cisplatin-based chemoradiation for head and neck cancer. Further investigation evaluating the contribution of cisplatin-based chemoradiation to sensorineural hearing loss and the subsequent effect on patient quality of life is warranted.

A subexponential construction of graph coloring for multiparty computation

We show the first deterministic construction of an unconditionally secure multiparty computation (MPC) protocol in the passive adversarial model over black-box non-Abelian groups which is both optimal (secure against an adversary who possesses any tsubset is in the possession of the adversary. Unlike the deterministic constructions from Desmedt et al. (2012) our construction has subexponential complexity and is optimal at the same time, i.e., it is secure for any t

Open problem: Shifting experts on easy data

A number of online algorithms have been developed that have small additional loss (regret) compared to the best “shifting expert”. In this model, there is a set of experts and the comparator is the best partition of the trial sequence into a small number of segments, where the expert of smallest loss is chosen in each segment. The regret is typically defined for worst-case data / loss sequences. There has been a recent surge of interest in online algorithms that combine good worst-case guarantees with much improved performance on easy data. A practically relevant class of easy data is the case when the loss of each expert is iid and the best and second best experts have a gap between their mean loss. In the full information setting, the FlipFlop algorithm by De Rooij et al. (2014) combines the best of the iid optimal Follow-The-Leader (FL) and the worst-case-safe Hedge algorithms, whereas in the bandit information case SAO by Bubeck and Slivkins (2012) competes with the iid optimal UCB and the worst-case-safe EXP3. We ask the same question for the shifting expert problem. First, we ask what are the simple and efficient algorithms for the shifting experts problem when the loss sequence in each segment is iid with respect to a fixed but unknown distribution. Second, we ask how to efficiently unite the performance of such algorithms on easy data with worst-case robustness. A particular intriguing open problem is the case when the comparator shifts within a small subset of experts from a large set under the assumption that the losses in each segment are iid.

Superpixel-based appearance change prediction for long-term navigation across seasons

Changing environments pose a serious problem to current robotic systems aiming at long term operation under varying seasons or local weather conditions. This paper is built on our previous work where we propose to learn to predict the changes in an environment. Our key insight is that the occurring scene changes are in part systematic, repeatable and therefore predictable. The goal of our work is to support existing approaches to place recognition by learning how the visual appearance of an environment changes over time and by using this learned knowledge to predict its appearance under different environmental conditions. We describe the general idea of appearance change prediction (ACP) and investigate properties of our novel implementation based on vocabularies of superpixels (SP-ACP). Our previous work showed that the proposed approach significantly improves the performance of SeqSLAM and BRIEF-Gist for place recognition on a subset of the Nordland dataset under extremely different environmental conditions in summer and winter. This paper deepens the understanding of the proposed SP-ACP system and evaluates the influence of its parameters. We present the results of a large-scale experiment on the complete 10 h Nordland dataset and appearance change predictions between different combinations of seasons.

An investigation of the effect of some stable nitroxide antioxidants in prostate cancer cells

The risk of prostate cancer and disease progression may potentially be increased by oxidative stress. This project examined the stability of nitroxide antioxidants and their effects on cell growth, survival and gene regulation in prostate cancer cells. The novel nitroxide, CTMIO, synthesised here at QUT, was found to have minimal toxicity and modulated the expression of a subset of oxidative stress and antioxidant-related genes distinct from those regulated by a related derivative. This study has provided a step forward in our understanding of the mechanism of action of nitroxides within cells.

Proportionality : a valid alternative to correlation for relative data

Relative abundance data is common in the life sciences, but appreciation that it needs special analysis and interpretation is scarce. Correlation is popular as a statistical measure of pairwise association but should not be used on data that carry only relative information. Using timecourse yeast gene expression data, we show how correlation of relative abundances can lead to conclusions opposite to those drawn from absolute abundances, and that its value changes when different components are included in the analysis. Once all absolute information has been removed, only a subset of those associations will reliably endure in the remaining relative data, specifically, associations where pairs of values behave proportionally across observations. We propose a new statistic φ to describe the strength of proportionality between two variables and demonstrate how it can be straightforwardly used instead of correlation as the basis of familiar analyses and visualization methods.

A tale of two solvers: Eager and lazy approaches to bit-vectors

The standard method for deciding bit-vector constraints is via eager reduction to propositional logic. This is usually done after first applying powerful rewrite techniques. While often efficient in practice, this method does not scale on problems for which top-level rewrites cannot reduce the problem size sufficiently. A lazy solver can target such problems by doing many satisfiability checks, each of which only reasons about a small subset of the problem. In addition, the lazy approach enables a wide range of optimization techniques that are not available to the eager approach. In this paper we describe the architecture and features of our lazy solver (LBV). We provide a comparative analysis of the eager and lazy approaches, and show how they are complementary in terms of the types of problems they can efficiently solve. For this reason, we propose a portfolio approach that runs a lazy and eager solver in parallel. Our empirical evaluation shows that the lazy solver can solve problems none of the eager solvers can and that the portfolio solver outperforms other solvers both in terms of total number of problems solved and the time taken to solve them.