Comparison of active-set method deconvolution and matched-filtering for derivation of an ultrasound transit time spectrum

The quality of ultrasound computed tomography imaging is primarily determined by the accuracy of ultrasound transit time measurement. A major problem in analysis is the overlap of signals making it difficult to detect the correct transit time. The current standard is to apply a matched-filtering approach to the input and output signals. This study compares the matched-filtering technique with active set deconvolution to derive a transit time spectrum from a coded excitation chirp signal and the measured output signal. The ultrasound wave travels in a direct and a reflected path to the receiver, resulting in an overlap in the recorded output signal. The matched-filtering and deconvolution techniques were applied to determine the transit times associated with the two signal paths. Both techniques were able to detect the two different transit times; while matched-filtering has a better accuracy (0.13 μs vs. 0.18 μs standard deviation), deconvolution has a 3.5 times improved side-lobe to main-lobe ratio. A higher side-lobe suppression is important to further improve image fidelity. These results suggest that a future combination of both techniques would provide improved signal detection and hence improved image fidelity.

General ranked set sampling for efficient treatment comparisons

In treatment comparison experiments, the treatment responses are often correlated with some concomitant variables which can be measured before or at the beginning of the experiments. In this article, we propose schemes for the assignment of experimental units that may greatly improve the efficiency of the comparison in such situations. The proposed schemes are based on general ranked set sampling. The relative efficiency and cost-effectiveness of the proposed schemes are studied and compared. It is found that some proposed schemes are always more efficient than the traditional simple random assignment scheme when the total cost is the same. Numerical studies show promising results using the proposed schemes.

Kallikrein-related peptidases in prostate cancer: From molecular function to clinical application

Prostate cancer is a leading contributor to male cancer-related deaths worldwide. Kallikrein-related peptidases (KLKs) are serine proteases that exhibit deregulated expression in prostate cancer, with KLK3, or prostate specific antigen (PSA), being the widely-employed clinical biomarker for prostate cancer. Other KLKs, such as KLK2, show promise as prostate cancer biomarkers and, additionally, their altered expression has been utilised for the design of KLK-targeted therapies. There is also a large body of in vitro and in vivo evidence supporting their role in cancer-related processes. Here, we review the literature on studies to date investigating the potential of other KLKs, in addition to PSA, as biomarkers and in therapeutic options, as well as their current known functional roles in cancer progression. Increased knowledge of these KLK-mediated functions, including degradation of the extracellular matrix, local invasion, cancer cell proliferation, interactions with fibroblasts, angiogenesis, migration, bone metastasis and tumour growth in vivo, may help define new roles as prognostic biomarkers and novel therapeutic targets for this cancer.

Efficient regression analysis with ranked-set sampling

This article is motivated by a lung cancer study where a regression model is involved and the response variable is too expensive to measure but the predictor variable can be measured easily with relatively negligible cost. This situation occurs quite often in medical studies, quantitative genetics, and ecological and environmental studies. In this article, by using the idea of ranked-set sampling (RSS), we develop sampling strategies that can reduce cost and increase efficiency of the regression analysis for the above-mentioned situation. The developed method is applied retrospectively to a lung cancer study. In the lung cancer study, the interest is to investigate the association between smoking status and three biomarkers: polyphenol DNA adducts, micronuclei, and sister chromatic exchanges. Optimal sampling schemes with different optimality criteria such as A-, D-, and integrated mean square error (IMSE)-optimality are considered in the application. With set size 10 in RSS, the improvement of the optimal schemes over simple random sampling (SRS) is great. For instance, by using the optimal scheme with IMSE-optimality, the IMSEs of the estimated regression functions for the three biomarkers are reduced to about half of those incurred by using SRS.

Brain-specific epigenetic markers of schizophrenia

Epigenetics plays a crucial role in schizophrenia susceptibility. In a previous study, we identified over 4500 differentially methylated sites in prefrontal cortex (PFC) samples from schizophrenia patients. We believe this was the first genome-wide methylation study performed on human brain tissue using the Illumina Infinium HumanMethylation450 Bead Chip. To understand the biological significance of these results, we sought to identify a smaller number of differentially methylated regions (DMRs) of more functional relevance compared with individual differentially methylated sites. Since our schizophrenia whole genome methylation study was performed, another study analysing two separate data sets of post-mortem tissue in the PFC from schizophrenia patients has been published. We analysed all three data sets using the bumphunter function found in the Bioconductor package minfi to identify regions that are consistently differentially methylated across distinct cohorts. We identified seven regions that are consistently differentially methylated in schizophrenia, despite considerable heterogeneity in the methylation profiles of patients with schizophrenia. The regions were near CERS3, DPPA5, PRDM9, DDX43, REC8, LY6G5C and a region on chromosome 10. Of particular interest is PRDM9 which encodes a histone methyltransferase that is essential for meiotic recombination and is known to tag genes for epigenetic transcriptional activation. These seven DMRs are likely to be key epigenetic factors in the aetiology of schizophrenia and normal brain neurodevelopment.

Multidisciplinary review of teaching and assessing competency attainment by non-medical prescribers

Background Prescribing is a complex task, requiring specific knowledge and skills, and the execution of effective, context-specific clinical reasoning. Systematic reviews indicate medical prescribing errors have a median rate of 7% [IQR 2%-14%] of medication orders [1-3]. For podiatrists pursuing prescribing rights, a clear need exists to ensure practitioners develop a well-defined set of prescribing skills, which will contribute to competent, safe and appropriate practice. Aim To investigate the methods employed to teach and assess the principles of effective prescribing in the undergraduate podiatry program and compare and contrast these findings with four other non-medical professions who undertake prescribing after training at Queensland University of Technology. Method The NPS National Prescribing Competency Standards were employed as the prescribing standard. A curriculum mapping exercise was undertaken to determine whether the prescribing principles articulated in the competency standards were addressed by each profession. Results A range of methods are currently utilised to teach prescribing across disciplines. Application of prescribing competencies to the context of each profession appears to influence the teaching methods used. Most competencies were taught using a multimodal format, including interactive lectures, self-directed learning, tutorial sessions and clinical placement. In particular clinical training was identified as the most consistent form of educating safe prescribers across all five disciplines. Assessment of prescribing competency utilised multiple techniques including written and oral examinations and research tasks, case studies, objective structured clinical examination exercises and the assessment of clinical practice. Effective and reliable assessment of prescribing undertaken by students in diverse settings remains challenging e.g. that occurring in the clinical practice environment. Conclusion Recommendations were made to refine curricula and to promote efficient cross-discipline teaching by staff from the disciplines of podiatry, pharmacy, nurse practitioner, optometry and paramedic science. Students now experience a sophisticated level of multidisciplinary learning in the clinical setting which integrates the expertise and skills of experience prescribers combined with innovative information technology platforms (CCTV and live patient assessments). Further work is required to establish a practical, effective approach to the assessment of prescribing competence especially between the university and clinical settings.

The impact of inter-fraction set-up errors on the probability of pulmonary and cardiac complication in left-sided breast cancer patients

Purpose This study evaluated the impact of patient set-up errors on the probability of pulmonary and cardiac complications in the irradiation of left-sided breast cancer. Methods and Materials Using the CMS XiO Version 4.6 (CMS Inc., St Louis, MO) radiotherapy planning system's NTCP algorithm and the Lyman -Kutcher-Burman (LKB) model, we calculated the DVH indices for the ipsilateral lung and heart and the resultant normal tissue complication probabilities (NTCP) for radiation-induced pneumonitis and excess cardiac mortality in 12 left-sided breast cancer patients. Results Isocenter shifts in the posterior direction had the greatest effect on the lung V20, heart V25, mean and maximum doses to the lung and the heart. Dose volume histograms (DVH) results show that the ipsilateral lung V20 tolerance was exceeded in 58% of the patients after 1cm posterior shifts. Similarly, the heart V25 tolerance was exceeded after 1cm antero-posterior and left-right isocentric shifts in 70% of the patients. The baseline NTCPs for radiation-induced pneumonitis ranged from 0.73% - 3.4% with a mean value of 1.7%. The maximum reported NTCP for radiation-induced pneumonitis was 5.8% (mean 2.6%) after 1cm posterior isocentric shift. The NTCP for excess cardiac mortality were 0 % in 100% of the patients (n=12) before and after setup error simulations. Conclusions Set-up errors in left sided breast cancer patients have a statistically significant impact on the Lung NTCPs and DVH indices. However, with a central lung distance of 3cm or less (CLD <3cm), and a maximum heart distance of 1.5cm or less (MHD<1.5cm), the treatment plans could tolerate set-up errors of up to 1cm without any change in the NTCP to the heart.

Condition-specific associations of symptoms of depression and anxiety in adolescents and young adults with asthma and food allergy

Objective: This study examined associations of asthma and food allergy with symptoms of depression and anxiety at 14 and 21 years of age to determine whether condition-specific associations exist. Methods: Data come from 4972 adolescents in the Mater University Study of Pregnancy. Symptoms of depression and anxiety were assessed using the Youth Self-Report and Young Adult Self-Report. Results: Condition-specific associations between asthma and depression, OR=1.37 [1.12, 1.67] and between food allergy and anxiety, OR=1.26 [1.04, 1.76] were found during adolescence, but not in young adulthood. Whereas asthma was associated with resolved depression, OR=1.70 [1.13, 2.55], food allergy was associated with persistent anxiety, OR=1.26 [1.01, 1.59]. Conclusions: In adolescents, asthma is associated with an increased risk of clinically relevant symptoms of depression and food allergy with and increased risk of clinically relevant symptoms of anxiety. Future research is needed to clarify directionality and mechanisms explaining these relationships. Health professionals should be aware of the increased risk of mental health problems in adolescents with asthma or food allergy.

Evaluation of an intervention for patients with alcohol-related injuries: results of a mixed methods study

Objective: To explore the effect of education and training on the delivery of alcohol screening and brief intervention and referral to high-risk patients in a hospital setting. Main outcome measures included; delivery of training; practice change in relation to staff performing alcohol screening, brief intervention and referrals. Methods: Observational study design using mixed methods set in a tertiary referral hospital. Pre-post assessment of medical records and semi-structured interviews with key informants. Results: Routine screening for substance misuse (9% pre / 71.4% post) and wellbeing concerns (6.6% pre / 15 % post) was more frequent following the introduction of resources and staff participation in educational workshops. There was no evidence of a concomitant increase in delivery of brief intervention or referrals to services. Implementation challenges, including time constraints and staff attitudes, and enablers such as collaboration and visible pathways, were identified. Conclusion: Rates of patient screening increased, however barriers to delivery of brief intervention and referrals remained. Implementation strategies targeting specific barriers and enablers to introducing interventions are both required to improve the application of secondary prevention for patients in acute settings. Implications: Educational training, formalised liaison between services, systematised early intervention protocols, and continuous quality improvement processes will progress service delivery in this area.

Automatic ICD-10 classification of cancers from free-text death certificates

Objective Death certificates provide an invaluable source for cancer mortality statistics; however, this value can only be realised if accurate, quantitative data can be extracted from certificates – an aim hampered by both the volume and variable nature of certificates written in natural language. This paper proposes an automatic classification system for identifying cancer related causes of death from death certificates. Methods Detailed features, including terms, n-grams and SNOMED CT concepts were extracted from a collection of 447,336 death certificates. These features were used to train Support Vector Machine classifiers (one classifier for each cancer type). The classifiers were deployed in a cascaded architecture: the first level identified the presence of cancer (i.e., binary cancer/nocancer) and the second level identified the type of cancer (according to the ICD-10 classification system). A held-out test set was used to evaluate the effectiveness of the classifiers according to precision, recall and F-measure. In addition, detailed feature analysis was performed to reveal the characteristics of a successful cancer classification model. Results The system was highly effective at identifying cancer as the underlying cause of death (F-measure 0.94). The system was also effective at determining the type of cancer for common cancers (F-measure 0.7). Rare cancers, for which there was little training data, were difficult to classify accurately (F-measure 0.12). Factors influencing performance were the amount of training data and certain ambiguous cancers (e.g., those in the stomach region). The feature analysis revealed a combination of features were important for cancer type classification, with SNOMED CT concept and oncology specific morphology features proving the most valuable. Conclusion The system proposed in this study provides automatic identification and characterisation of cancers from large collections of free-text death certificates. This allows organisations such as Cancer Registries to monitor and report on cancer mortality in a timely and accurate manner. In addition, the methods and findings are generally applicable beyond cancer classification and to other sources of medical text besides death certificates.

Duty and Control in Intermediary Copyright Liability: An Australian Perspective

In the internet age, copyright owners are increasingly looking to online intermediaries to take steps to prevent copyright infringement. Sometimes these intermediaries are closely tied to the acts of infringement; sometimes – as in the case of ISPs – they are not. In 2012, the Australian High Court decided the Roadshow Films v iiNet case, in which it held that an Australian ISP was not liable under copyright’s authorization doctrine, which asks whether the intermediary has sanctioned, approved or countenanced the infringement. The Australian Copyright Act 1968 directs a court to consider, in these situations, whether the intermediary had the power to prevent the infringement and whether it took any reasonable steps to prevent or avoid the infringement. It is generally not difficult for a court to find the power to prevent infringement – power to prevent can include an unrefined technical ability to disconnect users from the copyright source, such as an ISP terminating users’ internet accounts. In the iiNet case, the High Court eschewed this broad approach in favor of focusing on a notion of control that was influenced by principles of tort law. In tort, when a plaintiff asserts that a defendant should be liable for failing to act to prevent harm caused to the plaintiff by a third party, there is a heavy burden on the plaintiff to show that the defendant had a duty to act. The duty must be clear and specific, and will often hinge on the degree of control that the defendant was able to exercise over the third party. Control in these circumstances relates directly to control over the third party’s actions in inflicting the harm. Thus, in iiNet’s case, the control would need to be directed to the third party’s infringing use of BitTorrent; control over a person’s ability to access the internet is too imprecise. Further, when considering omissions to act, tort law differentiates between the ability to control and the ability to hinder. The ability to control may establish a duty to act, and the court will then look to small measures taken to prevent the harm to determine whether these satisfy the duty. But the ability to hinder will not suffice to establish liability in the absence of control. This chapter argues that an inquiry grounded in control as defined in tort law would provide a more principled framework for assessing the liability of passive intermediaries in copyright. In particular, it would set a higher, more stable benchmark for determining the copyright liability of passive intermediaries, based on the degree of actual, direct control that the intermediary can exercise over the infringing actions of its users. This approach would provide greater clarity and consistency than has existed to date in this area of copyright law in Australia.

Shifting the Focus. Incorporating knowledge about Aboriginal engineering into main stream content

BACKGROUND OR CONTEXT The concept of 'Aboriginal engineering' has had little exposure in conventional engineering education programs, despite more than 40,000 years of active human engagement with the diverse Australian environment. The work reported in this paper began with the premise that Indigenous Student Support Through Indigenous Perspectives Embedded in Engineering Curricula (Goldfinch, et al 2013) would provide a clear and replicable means of encouraging Aboriginal teenagers to consider a career in engineering. Although that remains a key outcome of this OLT project, the direction taken by the research had led to additional insights and perspectives that have wide implications for engineering education more generally. There has only been passing reference to the achievements of Aboriginal engineering in current texts, and the very absence of such references was a prompt to explore further as our work developed. PURPOSE OR GOAL Project goals focused on curriculum-based change, including development of a model for inclusive teaching spaces, and study units employing key features of the model. As work progressed we found we needed to understand more about the principles and practices informing the development of pre-contact Aboriginal engineering strategies for sustaining life and society within the landscape of this often harsh continent. We also found ourselves being asked 'what engineering did Aboriginal cultures have?' Finding that there are no easy-to- access answers, we began researching the question, while continuing to engage with specific curriculum trials. APPROACH Stakeholders in the project had been identified as engineering educators, potential Aboriginal students and Aboriginal communities local to Universities involved in the project. We realised, early on, that at least one more group was involved - all the non-Aboriginal students in engineering classes. This realisation, coupled with recognition of the need to understand Aboriginal engineering as a set of viable, long term practices, altered the focus of our efforts. Rather than focusing primarily on finding ways to attract Aboriginal engineering students, the shift has been towards evolving ways of including knowledge about Aboriginal practices and principles in relevant engineering content. DISCUSSION This paper introduces the model resulting from the work of this project, explores its potential influence on engineering curriculum development and reports on implementation strategies. The model is a static representation of a dynamic and cyclic approach to engaging with Aboriginal engineering through contact with local communities in regard to building knowledge about the social beliefs underlying Aboriginal engineering principles and practices. Ways to engage engineering educators, students and the wider community are evolving through the continuing work of the project team and will be reported in more detail in the paper. RECOMMENDATIONS/IMPLICATIONS/CONCLUSION While engineering may be considered by some to be agnostic in regard to culture and social issues, the work of this project is drawing attention to the importance of including such issues into curriculum materials at a number of levels of complexity. The paper will introduce and explore the central concepts of the research completed to date, as well as suggesting ways in which engineering educators can extend their knowledge and understanding of Aboriginal engineering principles in the context of their own specialisations.

Genome-wide mapping of cystitis due to Streptococcus agalactiae and Escherichia coli in mice identifies a unique bladder transcriptome that signifies pathogen-specific antimicrobial defense against urinary tract infection

The most common causes of urinary tract infections (UTIs) are Gram-negative pathogens such as Escherichia coli; however, Gram-positive organisms including Streptococcus agalactiae, or group B streptococcus (GBS), also cause UTI. In GBS infection, UTI progresses to cystitis once the bacteria colonize bladder, but the host responses triggered in the bladder immediately following infection are largely unknown. Here, we used genome-wide expression profiling to map the bladder transcriptome of GBS UTI in mice infected transurethrally with uropathogenic GBS that was cultured from a 35 year-old women with cystitis. RNA from bladders was applied to Affymetrix Gene-1.0ST microarrays; qRT-PCR was used to analyze selected gene responses identified in array datasets. A surprisingly small significant gene list of 172 genes was identified at 24h; this compared to 2507 genes identified in a side-by-side comparison with uropathogenic E. coli (UPEC). No genes exhibited significantly altered expression at 2h in GBS-infected mice according to arrays despite high bladder bacterial loads at this early time point. The absence of a marked early host response to GBS juxtaposed with broad-based bladder responses activated by UPEC at 2h. Bioinformatics analyses including integrative systems-level network mapping revealed multiple activated biological pathways in the GBS cystitis transcriptome that regulate leukocyte activation, inflammation, apoptosis, and cytokine-chemokine biosynthesis. These findings define a novel, minimalistic type of bladder host response triggered by GBS UTI, which comprises collective antimicrobial pathways that differ dramatically from those activated by UPEC. Overall, this study emphasizes the unique nature of bladder immune activation mechanisms triggered by distinct uropathogens.

Stopover destination image: Using the repertory test to identify salient attributes

This paper reports a rare investigation of stopover destination image. Although the topic of destination image has been one of the most popular in the tourism literature since the 1970s, there has been a lack of research attention in relation to the context of stopover destinations for long haul international travellers. The purpose of this study was to identify attributes deemed salient to Australian consumers when considering stopover destinations for long haul travel to the United Kingdom and Europe. Underpinned by Personal Construct Theory (PCT), the study used the Repertory Test to identify 21 salient attributes, which could be used in the development of a survey instrument to measure the attractiveness of a competitive set of stopover destinations. While the list of attributes shared some commonality with general studies of destination image reported in the literature, the elicitation of a relatively large number of stopover context specific attributes highlights the potential benefit of engaging with consumers in qualitative research, such as using the Repertory Test, during the questionnaire development stage.

Development and preliminary validation of the Drinking Expectancy Sexual Vulnerabilities Questionnaire (DESV-Q): A purpose-specific instrument for rape-perception research

Background Alcohol expectancies likely play a role in people’s perceptions of alcohol-involved sexual violence. However, no appropriate measure exists to examine this link comprehensively. Objective The aim of this research was to develop an alcohol expectancy measure which captures young adults’ beliefs about alcohol’s role in sexual aggression and victimization. Method Two cross-sectional samples of young Australian adults (18–25 years) were recruited for scale development (Phase 1) and scale validation (Phase 2). In Phase 1, participants (N = 201; 38.3% males) completed an online survey with an initial pool of alcohol expectancy items stated in terms of three targets (self, men, women) to identify the scale’s factor structure and most effective items. A revised alcohol expectancy scale was then administered online to 322 young adults (39.6% males) in Phase 2. To assess the predictive, convergent, and discriminant validity of the scale, participants also completed established measures of personality, social desirability, alcohol use, general and context-specific alcohol expectancies, and impulsiveness. Results Principal axis factoring (Phase 1) and confirmatory factor analysis (Phase 2) resulted in a target-equivalent five-factor structure for the final 66-item Drinking Expectancy Sexual Vulnerabilities Questionnaire (DESV-Q). The factors were labeled: - (1) Sexual Coercion - (2) Sexual Vulnerability - (3) Confidence - (4) Self-Centeredness - (5) Negative Cognitive and Behavioral Changes The measure demonstrated effective items, high internal consistency, and satisfactory predictive, convergent, and discriminant validity. Conclusions The DESV-Q is a purpose-specific instrument that could be used in future research to elucidate people’s attributions for alcohol-involved sexual aggression and victimization.