Within-family outliers: Segregating alleles or environmental effects? A linkage analysis of height from 5815 sibling pairs

Most information in linkage analysis for quantitative traits comes from pairs of relatives that are phenotypically most discordant or concordant. Confounding this, within-family outliers from non-genetic causes may create false positives and negatives. We investigated the influence of within-family outliers empirically, using one of the largest genome-wide linkage scans for height. The subjects were drawn from Australian twin cohorts consisting of 8447 individuals in 2861 families, providing a total of 5815 possible pairs of siblings in sibships. A variance component linkage analysis was performed, either including or excluding the within-family outliers. Using the entire dataset, the largest LOD scores were on chromosome 15q (LOD 2.3) and 11q (1.5). Excluding within-family outliers increased the LOD score for most regions, but the LOD score on chromosome 15 decreased from 2.3 to 1.2, suggesting that the outliers may create false negatives and false positives, although rare alleles of large effect may also be an explanation. Several regions suggestive of linkage to height were found after removing the outliers, including 1q23.1 (2.0), 3q22.1 (1.9) and 5q32 (2.3). We conclude that the investigation of the effect of within-family outliers, which is usually neglected, should be a standard quality control measure in linkage analysis for complex traits and may reduce the noise for the search of common variants of modest effect size as well as help identify rare variants of large effect and clinical significance. We suggest that the effect of within-family outliers deserves further investigation via theoretical and simulation studies.

Association study of the dystrobrevin-binding gene with schizophrenia in Australian and Indian samples

Numerous studies have reported association between variants in the dystrobrevin binding protein 1 (dysbindin) gene (DTNBP1) and schizophrenia. However, the pattern of results is complex and to date, no specific risk marker or haplotype has been consistently identified. The number of single nucleotide polymorphisms (SNPs) tested in these studies has ranged from 5 to 20. We attempted to replicate previous findings by testing 16 SNPs in samples of 41 Australian pedigrees, 194 Australian cases and 180 controls, and 197 Indian pedigrees. No globally significant evidence for association was observed in any sample, despite power calculations indicating sufficient power to replicate several previous findings. Possible explanations for our results include sample differences in background linkage disequilibrium and/or risk allele effect size, the presence of multiple risk alleles upon different haplotypes, or the presence of a single risk allele upon multiple haplotypes. Some previous associations may also represent false positives. Examination of Caucasian HapMap phase II genotype data spanning the DTNBP1 region indicates upwards of 40 SNPs are required to satisfactorily assess all nonredundant variation within DTNBP1 and its potential regulatory regions for association with schizophrenia. More comprehensive studies in multiple samples will be required to determine whether specific DTNBP1 variants function as risk factors for schizophrenia.

Zygosity diagnosis in the absence of genotypic data: An approach using latent class analysis

For zygosity diagnosis in the absence of genotypic data, or in the recruitment phase of a twin study where only single twins from same-sex pairs are being screened, or to provide a test for sample duplication leading to the false identification of a dizygotic pair as monozygotic, the appropriate analysis of respondents' answers to questions about zygosity is critical. Using data from a young adult Australian twin cohort (N = 2094 complete pairs and 519 singleton twins from same-sex pairs with complete responses to all zygosity items), we show that application of latent class analysis (LCA), fitting a 2-class model, yields results that show good concordance with traditional methods of zygosity diagnosis, but with certain important advantages. These include the ability, in many cases, to assign zygosity with specified probability on the basis of responses of a single informant (advantageous when one zygosity type is being oversampled); and the ability to quantify the probability of misassignment of zygosity, allowing prioritization of cases for genotyping as well as identification of cases of probable laboratory error. Out of 242 twins (from 121 like-sex pairs) where genotypic data were available for zygosity confirmation, only a single case was identified of incorrect zygosity assignment by the latent class algorithm. Zygosity assignment for that single case was identified by the LCA as uncertain (probability of being a monozygotic twin only 76%), and the co-twin's responses clearly identified the pair as dizygotic (probability of being dizygotic 100%). In the absence of genotypic data, or as a safeguard against sample duplication, application of LCA for zygosity assignment or confirmation is strongly recommended.

Evoking poetics of memory through performing site: Naik Naik, a Malaysian Australian collaboration in the world heritage setting of Melaka

Memory, time and metaphor are central triggers for artists in exploring and shaping their creative work. This paper examines the place of artists as ‘memory-keepers’, and ‘memory-makers’, in particular through engagement with the time-based art of site-specific performance. Naik Naik (Ascent) was a multi-site performance project in the historic setting of Melaka, Malaysia, and is partially recaptured through the presence and voices of its collaborating artists. Distilled from moments recalled, this paper seeks to uncover the poetics of memory to emerge from the project; one steeped in metaphor rather than narrative. It elicits some of the complex and interdependent layers of experience revealed by the artists in Naik Naik; cultural, ancestral, historical, personal, instinctual and embodied memories connected to sound, smell, touch, sensation and light, in a spatiotemporal context for which site is the catalyst. The liminal nature of memory at the heart of Naik Naik, provides a shared experience of past and present and future, performatively interwoven.

FreeS: A fast algorithm to discover frequent free subtrees using a novel canonical form

Web data can often be represented in free tree form; however, free tree mining methods seldom exist. In this paper, a computationally fast algorithm FreeS is presented to discover all frequently occurring free subtrees in a database of labelled free trees. FreeS is designed using an optimal canonical form, BOCF that can uniquely represent free trees even during the presence of isomorphism. To avoid enumeration of false positive candidates, it utilises the enumeration approach based on a tree-structure guided scheme. This paper presents lemmas that introduce conditions to conform the generation of free tree candidates during enumeration. Empirical study using both real and synthetic datasets shows that FreeS is scalable and significantly outperforms (i.e. few orders of magnitude faster than) the state-of-the-art frequent free tree mining algorithms, HybridTreeMiner and FreeTreeMiner.

Head motion and Inattention/Hyperactivity share common genetic influences: Implications for fMRI studies of ADHD

Head motion (HM) is a well known confound in analyses of functional MRI (fMRI) data. Neuroimaging researchers therefore typically treat HM as a nuisance covariate in their analyses. Even so, it is possible that HM shares a common genetic influence with the trait of interest. Here we investigate the extent to which this relationship is due to shared genetic factors, using HM extracted from resting-state fMRI and maternal and self report measures of Inattention and Hyperactivity-Impulsivity from the Strengths and Weaknesses of ADHD Symptoms and Normal Behaviour (SWAN) scales. Our sample consisted of healthy young adult twins (N = 627 (63% females) including 95 MZ and 144 DZ twin pairs, mean age 22, who had mother-reported SWAN; N = 725 (58% females) including 101 MZ and 156 DZ pairs, mean age 25, with self reported SWAN). This design enabled us to distinguish genetic from environmental factors in the association between head movement and ADHD scales. HM was moderately correlated with maternal reports of Inattention (r = 0.17, p-value = 7.4E-5) and Hyperactivity-Impulsivity (r = 0.16, p-value = 2.9E-4), and these associations were mainly due to pleiotropic genetic factors with genetic correlations [95% CIs] of rg = 0.24 [0.02, 0.43] and rg = 0.23 [0.07, 0.39]. Correlations between self-reports and HM were not significant, due largely to increased measurement error. These results indicate that treating HM as a nuisance covariate in neuroimaging studies of ADHD will likely reduce power to detect between-group effects, as the implicit assumption of independence between HM and Inattention or Hyperactivity-Impulsivity is not warranted. The implications of this finding are problematic for fMRI studies of ADHD, as failing to apply HM correction is known to increase the likelihood of false positives. We discuss two ways to circumvent this problem: censoring the motion contaminated frames of the RS-fMRI scan or explicitly modeling the relationship between HM and Inattention or Hyperactivity-Impulsivity

Policing online fraud in Australia: The emergence of a victim‐oriented approach

Online fraud is a global problem. Millions of individuals worldwide are losing money and experiencing the devastation associated with becoming a victim of online fraud. In 2014, Australians reported losses of $82 million as a result of online fraud to the Australian Competition and Consumer Commission (ACCC). Given that the ACCC is one of many agencies that receives victim complaints, and the extent of under‐reporting of online fraud, this figure is likely to represent only a fraction of the actual monetary losses incurred. The successful policing of online fraud is hampered by its transnational nature, the prevalence of false/stolen identities used by offenders, and a lack of resources available to investigate offences. In addition, police are restricted by the geographical boundaries of their own jurisdictions which conflicts with the lack of boundaries afforded to offenders by the virtual world. In response to this, Australia is witnessing the emergence of victim‐oriented policing approaches to counter online fraud victimisation. This incorporates the use of financial intelligence as a tool to proactively notify potential victims of online fraud. Using a variety of Australian examples, this paper documents the history to this new approach and considers the significance that such a shift represents to policing in a broader context. It also details the value that this approach can have to both victims and law enforcement agencies. Overall, it is argued that a victim‐oriented approach to policing online fraud can have substantial benefits to police and victims alike.

"It's not the Jedi way!": Moral ambivalence and delivering the 'good' in Star Wars

This article examines the nature of good and evil through the prism of Star Wars, arguing that the ostensible dichotomy between the ‘good’ Jedi and the ‘evil’ Sith is false, and instead both the Jedi and the Sith engage in violence, which is evil. Anakin Skywalker then arrives as the Christ-figure who becomes evil and ‘dies’ to destroy the old rigid law of the letter adhered to by the Jedi, before resurrecting and sacrificing himself to defeat the Sith transgressors. As Milbank argues, the act of selfless love by Anakin as the Christ-figure therefore produces the good, the end of violent conflict which is ontological peace, and institutes the law of love which leads to life and peace.

Pictures that ask the right questions

An article about the use of photographs as research in the writing of memoir. "I expect many people begin the writing of a memoir by looking through old photos. Pictures, after all, belong in the past, and they hold out the promise of delivering it to us again: everyone is younger, surrounded by yesterday’s world, a moment fixed in time. Even the size of the photo paper and printing tone belong back there, in a printer’s shop that doesn’t exist anymore. And yet, for the purpose of writing a memoir, the most useful pictures also reach beyond the past, and beyond their initial role in verifying your memories, or filling out the details. That is, they are more than an account. Such pictures seem to be asking questions about what happened next, in the moments and years after they were taken..."

Keeping kids sun safe: exploring parents' beliefs about their young child's sun-protective behaviours

Objectives Melanoma of the skin is the third most commonly diagnosed cancer in Australia. Given the high incidence of sunburn in children and the level of sun protection provided by parents is often infrequent and/or insufficient, this research employed qualitative methodology to examine parents' beliefs about their young child's sun safe behaviour. Methods Parents (N = 21; n = 14 mothers, n = 7 fathers) of children aged 2–5 years participated in focus groups to identify commonly held beliefs about their decision to sun protect their child. Data were analysed using thematic content analysis. Results Parents generally had knowledge of the broad sun safe recommendations; however, the specific details of the recommendations were not always known. Parents reported adopting a range of sun-protective measures for their child, which depended on the time of year. A range of advantages (e.g. reducing the risk of skin cancer, developing good habits early and parental peace of mind), disadvantages (e.g. false sense of safety and preventing vitamin D absorption), barriers (e.g. child refusal) and facilitators (e.g. routine and accessibility) to performing sun safe practices were identified. Normative pressures and expectations also affected parents' motivation to be sun safe for their child. Conclusions These identified beliefs can be used to inform interventions to improve sun safe behaviours in young children who reside in a region that has the highest skin cancer incidence in the world.

Automated feature engineering for HTTP tunnel detection

Generating discriminative input features is a key requirement for achieving highly accurate classifiers. The process of generating features from raw data is known as feature engineering and it can take significant manual effort. In this paper we propose automated feature engineering to derive a suite of additional features from a given set of basic features with the aim of both improving classifier accuracy through discriminative features, and to assist data scientists through automation. Our implementation is specific to HTTP computer network traffic. To measure the effectiveness of our proposal, we compare the performance of a supervised machine learning classifier built with automated feature engineering versus one using human-guided features. The classifier addresses a problem in computer network security, namely the detection of HTTP tunnels. We use Bro to process network traffic into base features and then apply automated feature engineering to calculate a larger set of derived features. The derived features are calculated without favour to any base feature and include entropy, length and N-grams for all string features, and counts and averages over time for all numeric features. Feature selection is then used to find the most relevant subset of these features. Testing showed that both classifiers achieved a detection rate above 99.93% at a false positive rate below 0.01%. For our datasets, we conclude that automated feature engineering can provide the advantages of increasing classifier development speed and reducing development technical difficulties through the removal of manual feature engineering. These are achieved while also maintaining classification accuracy.

A survey and analysis of the GNSS spoofing threat and countermeasures

Detection and prevention of global network satellite system (GNSS) “spoofing” attacks, or the broadcast of false global navigation satellite system services, has recently attracted much research interest. This survey aims to fill three gaps in the literature: first, to assess in detail the exact nature of threat scenarios posed by spoofing against the most commonly cited targets; second, to investigate the many practical impediments, often underplayed, to carrying out GNSS spoofing attacks in the field; and third, to survey and assess the effectiveness of a wide range of proposed defences against GNSS spoofing. Our conclusion lists promising areas of future research.

Promoting sun safety in the workplace – what works?

Objective Australia has one of the highest skin cancer incidence and mortality rates in the world. Outdoor workers are a high risk group. Australian workplaces are undergoing large scale safety related changes, yet the mandate to provide specific sun safe practices remains absent. With much of the previous research aiming to improve sun safety in the workplace being quantitative in nature, relatively little is known about why certain sun safe strategies will or will not be successful in workplaces. Methods This qualitative article explores the enablers and barriers identified during an 18-month mixed methods project conducted in Queensland, Australia which aimed to improve workplace sun safe interventions. Results A variety of key enablers and barriers to implementing sun safe interventions in the workplace were identified, including presence of an engaged workplace champion, ownership and innovation by the workers. Conclusions These findings were part of a broader integration of interlinked qualitative and quantitative methods to yield a more complete picture of the determinants of the issue, implementation process and likelihood of changes at the workplace. Implications The paper provides guidance for public and occupational health practitioners on the selection of the most promising strategies when assisting workplaces to become sun safe.

Truckies and health promotion: A “hard-to-reach” group without a “proper” workplace.

This literature review was undertaken to inform a settings based health promotion research project, conducted by a public health research team at the Queensland University of Technology (QUT). The aim of this project is to identify how transport workplaces can support their truck drivers to access healthy food options and increase physical activity. Truck drivers in Australia are at increased risk of numerous chronic diseases, in part due to the restrictions placed upon them by the environment in which they work. Barriers to good health through adequate nutrition and physical activity are the result of a complex interaction between government regulations, corporate policies, the built environment and individual factors. Few interventions target this population in a meaningful and sustainable way, though evidence exists for interventions which can be translated into truck drivers working environment.

Appendiceal sonography in children: A retrospective analysis as a platform for potential implementation of diagnostic categories

- Background Sonography is an important diagnostic tool in children with suspected appendicitis. Reported accuracy and appendiceal visualisation rates vary significantly, as does the management of equivocal ultrasound findings. The aim of this study was to audit appendiceal sonography at a tertiary children's hospital, and provide baseline data for a future prospective study. - Summary of work Records of children who underwent ultrasound studies for possible appendicitis between January 2008 and December 2010 were reviewed. Variables included patient demographics, sonographic appendix characteristics, and secondary signs. Descriptive statistics and analysis using ANOVA, Mann-Whitney U test, and ROC curves were performed. Mater Human Research Ethic Committee approval was granted. - Summary of results There were 457 eligible children. Using a dichotomous diagnostic model (including equivocal results), sensitivity was 89.6%, specificity 91.6%, and diagnostic yield of 40.7%. ROC curve analysis of a 6mm diameter cut-off was 0.88 AUC (95% CI 0.80 to 0.95). - Discussion and conclusions Sonography is an accurate test for acute appendicitis in children, with a high sensitivity and negative predictive value. A diameter of 6mm as an absolute cut-off in a binary model can lead to false findings. Results were compared with available literature. Recent publications propose categorising diameter1 and integrating secondary signs2 to improve accuracy and provide more meaningful results to clinicians. This study will be a benchmark for future studies with multiple diagnostic categorisation.