Fine-mapping the HOXB region detects common variants tagging a rare coding allele : evidence for synthetic association in prostate cancer

The HOXB13 gene has been implicated in prostate cancer (PrCa) susceptibility. We performed a high resolution fine-mapping analysis to comprehensively evaluate the association between common genetic variation across the HOXB genetic locus at 17q21 and PrCa risk. This involved genotyping 700 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of 3195 SNPs in 20,440 PrCa cases and 21,469 controls in The PRACTICAL consortium. We identified a cluster of highly correlated common variants situated within or closely upstream of HOXB13 that were significantly associated with PrCa risk, described by rs117576373 (OR 1.30, P = 2.62×10(-14)). Additional genotyping, conditional regression and haplotype analyses indicated that the newly identified common variants tag a rare, partially correlated coding variant in the HOXB13 gene (G84E, rs138213197), which has been identified recently as a moderate penetrance PrCa susceptibility allele. The potential for GWAS associations detected through common SNPs to be driven by rare causal variants with higher relative risks has long been proposed; however, to our knowledge this is the first experimental evidence for this phenomenon of synthetic association contributing to cancer susceptibility.

Evaluation of legal capacity by doctors and lawyers : the need for collaborative assessment

• Balancing the interests of individual autonomy and protection is an escalating challenge confronting an ageing Australian society. • One way this is manifested is in the current ad hoc and unsatisfactory way that capacity is assessed in the context of wills, enduring powers of attorney and advance health directives. • The absence of nationally accepted assessment guidelines results in terminological and methodological miscommunication and misunderstanding between legal and medical professionals. • Expectations between legal and medical professionals can be clarified to provide satisfactory capacity assessments based upon the development of a sound assessment paradigm

The rise of englightened shareholder primacy and its impact on US corporate self-regulation

Enlightened shareholder primacy (“ESP”) is a new approach in the corporate governance (“CG”) framework. The emergence of this approach is important owing to its role in answering a vital question: is the company really a private organisation to be seen only through the economic prism of contract? Or is it public and about a wider group of interests and underwritten by communitarian concern about social responsibility? Apart from answering this question, ESP explains the changes in corporate directors’ roles and self-regulation strategies of companies.

The court and the factory the legal construction of occupational health and safety offences in Victoria

This thesis reports on an empirically based study of the manner in which Victorian Magistrates Courts constructed occupational health and safety (OHS) issues when hearing prosecutions for offences under the Industrial Safety, Health and Welfare Act 1981 (the ISHWA) and the Occupational Health and Safety Act 1985 (OHSA) from 1983 to 1991. These statutes established OHS standards for employers and other relevant parties. The State government enforced these standards through an OHS inspectorate which had a range of enforcement powers, including prosecution. After outlining the historical development of Victoria’s OHS legislation, the magistracy’s historical role in its enforcement, and the development of an enforcement culture in which inspectors viewed prosecution as a last resort, the study shows how the key provisions of the ISHWA and OHSA required occupiers of workplaces and employers to provide and maintain safe systems of work, including the guarding of dangerous machinery. Using a wide range of empirical research methods and legal materials, it shows how the enforcement policies, procedures and practices of the inspectorate heavily slanted inspectors workplace investigations and hence prosecutions towards a restricted and often superficial, analysis of incidents (or “events”) most of which involved injuries on machinery. There was evidence, however, that after the establishment of the Central Investigation Unit in 1989 cases were more thoroughly investigated and prosecuted. From 1990 the majority of prosecutions were taken under the employer’s general duty provisions, and by 1991 there was evidence that prosecutions were focusing on matters other than machinery guarding.

Health consequences of exposure to brominated flame retardants : a systematic review

Background Brominated flame retardants (BFRs), are chemicals widely used in consumer products including electronics, vehicles, plastics and textiles to reduce flammability. Experimental animal studies have confirmed that these compounds may interfere with thyroid hormone homeostasis and neurodevelopment but to date health effects in humans have not been systematically examined. Objectives To conduct a systematic review of studies on the health impacts of exposure to BFRs in humans, with a particular focus on children. Methods A systematic review was conducted using the Medline and EMBASE electronic databases up to 1 February 2012. Published cohort, cross-sectional, and case-control studies exploring the relationship between BFR exposure and various health outcomes were included. Results In total, 36 epidemiological studies meeting the pre-determined inclusion criteria were included. Plausible outcomes associated with BFR exposure include diabetes, neurobehavioral and developmental disorders, cancer, reproductive health effects and alteration in thyroid function. Evidence for a causal relationship between exposure to BFRs and health outcomes was evaluated within the Bradford Hill framework. Conclusion Although there is suggestive evidence that exposure to BFRs is harmful to health, further epidemiological investigations particularly among children, and long-term monitoring and surveillance of chemical impacts on humans are required to confirm these relationships.

Medical negligence, causation and liability for non-disclosure of risk : a post-wallace framework and critique

Through an examination of Wallace v Kam, this article considers and evaluates the law of causation in the specific context of a medical practitioner’s duty to provide information to patients concerning material risks of treatment. To supply a contextual background for the analysis which follows, Part II summarises the basic principles of causation law, while Part III provides an overview of the case and the reasoning adopted in the decisions at first instance and on appeal. With particular emphasis upon the reasoning in the courts of appeal, Part IV then examines the implications of the case in the context of other jurisprudence in this field and, in so doing, provides a framework for a structured consideration of causation issues in future non-disclosure cases under the Australian civil liability legislation. As will become clear, Wallace was fundamentally decided on the basis of policy reasoning centred upon the purpose behind the legal duty violated. Although the plurality in Rogers v Whitaker rejected the utility of expressions such as ‘the patient’s right of self-determination’ in this context, some Australian jurisprudence may be thought to frame the practitioner’s duty to warn in terms of promoting a patient’s autonomy, or right to decide whether to submit to treatment proposed. Accordingly, the impact of Wallace upon the protection of this right, and the interrelation between it and the duty to warn’s purpose, is investigated. The analysis in Part IV also evaluates the courts’ reasoning in Wallace by questioning the extent to which Wallace’s approach to liability and causal connection in non-disclosure of risk cases: depends upon the nature and classification of the risk(s) in question; and can be reconciled with the way in which patients make decisions. Finally, Part V adopts a comparative approach by considering whether the same decision might be reached if Wallace was determined according to English law.

Competition policy review : draft recommendations on competition laws

On 4 December 2013, the Prime Minister and the Minister for Small Business announced a “root and branch” review of Australia’s competition policy. The Minister for Small Business released the final Terms of Reference for the competition policy review on 27 March 2014, following consultation with the States and Territories, and announced the Review Panel headed by Professor Ian Harper. Under the terms of reference the Competition Policy Review Committee (the Harper Committee) is required to focus on three broad areas: •examining what can be done to create more competition in service areas such as health, education and intellectual property; •considering whether the structure and powers of the competition institutions (the ACCC , the NCC, the Tribunal and the AER) remain appropriate; and •examining the effectiveness of the competition provisions of the Competition and Consumer Act 2010 (Cth) (CCA) and laying down a broad framework through which the law can be streamlined and reformed over time.

Health and guardianship law : guardianship and administration application in the matter of MDC [2014] QCAT 338

The recent decision of the Queensland Civil and Administrative Tribunal (QCAT) in Guardianship and administration application in the matter of MDC [2014] QCAT 338, provides an important ruling on the limits of who can be appointed as an enduring power of attorney under the Powers of Attorney Act 1998 (Qld). In particular, the tribunal adopted a broad interpretation of the term "health provider" when considering the limits on who can be appointed as an enduring power of attorney under the legislation...

Patients Undergoing Subacute Physical Rehabilitation following an Acute Hospital Admission Demonstrated Improvement in Cognitive Functional Task Independence

Objective. This study investigated cognitive functioning among older adults with physical debility not attributable to an acute injury or neurological condition who were receiving subacute inpatient physical rehabilitation. Design. A cohort investigation with assessments at admission and discharge. Setting. Three geriatric rehabilitation hospital wards. Participants. Consecutive rehabilitation admissions () following acute hospitalization (study criteria excluded orthopaedic, neurological, or amputation admissions). Intervention. Usual rehabilitation care. Measurements. The Functional Independence Measure (FIM) Cognitive and Motor items. Results. A total of 704 (86.5%) participants (mean age = 76.5 years) completed both assessments. Significant improvement in FIM Cognitive items (-score range 3.93–8.74, all ) and FIM Cognitive total score (-score = 9.12, ) occurred, in addition to improvement in FIM Motor performance. A moderate positive correlation existed between change in Motor and Cognitive scores (Spearman’s rho = 0.41). Generalized linear modelling indicated that better cognition at admission (coefficient = 0.398, ) and younger age (coefficient = −0.280, ) were predictive of improvement in Motor performance. Younger age (coefficient = −0.049, ) was predictive of improvement in FIM Cognitive score. Conclusions. Improvement in cognitive functioning was observed in addition to motor function improvement among this population. Causal links cannot be drawn without further research.

Health consequences of exposure to e-waste : a systematic review

Background The population exposed to potentially hazardous substances through inappropriate and unsafe management practices related to disposal and recycling of end-of-life electrical and electronic equipment, collectively known as e-waste, is increasing. We aimed to summarise the evidence for the association between such exposures and adverse health outcomes. Methods We systematically searched five electronic databases (PubMed, Embase, Web of Science, PsycNET, and CINAHL) for studies assessing the association between exposure to e-waste and outcomes related to mental health and neurodevelopment, physical health, education, and violence and criminal behaviour, from Jan 1, 1965, to Dec 17, 2012, and yielded 2274 records. Of the 165 full-text articles assessed for eligibility, we excluded a further 142, resulting in the inclusion of 23 published epidemiological studies that met the predetermined criteria. All studies were from southeast China. We assessed evidence of a causal association between exposure to e-waste and health outcomes within the Bradford Hill framework. Findings We recorded plausible outcomes associated with exposure to e-waste including change in thyroid function, changes in cellular expression and function, adverse neonatal outcomes, changes in temperament and behaviour, and decreased lung function. Boys aged 8–9 years living in an e-waste recycling town had a lower forced vital capacity than did those living in a control town. Significant negative correlations between blood chromium concentrations and forced vital capacity in children aged 11 and 13 years were also reported. Findings from most studies showed increases in spontaneous abortions, stillbirths, and premature births, and reduced birthweights and birth lengths associated with exposure to e-waste. People living in e-waste recycling towns or working in e-waste recycling had evidence of greater DNA damage than did those living in control towns. Studies of the effects of exposure to e-waste on thyroid function were not consistent. One study related exposure to e-waste and waste electrical and electronic equipment to educational outcomes. Interpretation Although data suggest that exposure to e-waste is harmful to health, more well designed epidemiological investigations in vulnerable populations, especially pregnant women and children, are needed to confirm these associations. Funding Children's Health and Environment Program, Queensland Children's Medical Research Institute, The University of Queensland, Australia.

A Hybrid Queue-based Bayesian Network framework for passenger facilitation modelling

This paper presents a novel framework for the modelling of passenger facilitation in a complex environment. The research is motivated by the challenges in the airport complex system, where there are multiple stakeholders, differing operational objectives and complex interactions and interdependencies between different parts of the airport system. Traditional methods for airport terminal modelling do not explicitly address the need for understanding causal relationships in a dynamic environment. Additionally, existing Bayesian Network (BN) models, which provide a means for capturing causal relationships, only present a static snapshot of a system. A method to integrate a BN complex systems model with stochastic queuing theory is developed based on the properties of the Poisson and exponential distributions. The resultant Hybrid Queue-based Bayesian Network (HQBN) framework enables the simulation of arbitrary factors, their relationships, and their effects on passenger flow and vice versa. A case study implementation of the framework is demonstrated on the inbound passenger facilitation process at Brisbane International Airport. The predicted outputs of the model, in terms of cumulative passenger flow at intermediary and end points in the inbound process, are found to have an R2 goodness of fit of 0.9994 and 0.9982 respectively over a 10 h test period. The utility of the framework is demonstrated on a number of usage scenarios including causal analysis and ‘what-if’ analysis. This framework provides the ability to analyse and simulate a dynamic complex system, and can be applied to other socio-technical systems such as hospitals.

A framework for model integration and holistic modelling of socio-technical systems

This paper presents a layered framework for the purposes of integrating different Socio-Technical Systems (STS) models and perspectives into a whole-of-systems model. Holistic modelling plays a critical role in the engineering of STS due to the interplay between social and technical elements within these systems and resulting emergent behaviour. The framework decomposes STS models into components, where each component is either a static object, dynamic object or behavioural object. Based on existing literature, a classification of the different elements that make up STS, whether it be a social, technical or a natural environment element, is developed; each object can in turn be classified according to the STS elements it represents. Using the proposed framework, it is possible to systematically decompose models to an extent such that points of interface can be identified and the contextual factors required in transforming the component of one model to interface into another is obtained. Using an airport inbound passenger facilitation process as a case study socio-technical system, three different models are analysed: a Business Process Modelling Notation (BPMN) model, Hybrid Queue-based Bayesian Network (HQBN) model and an Agent Based Model (ABM). It is found that the framework enables the modeller to identify non-trivial interface points such as between the spatial interactions of an ABM and the causal reasoning of a HQBN, and between the process activity representation of a BPMN and simulated behavioural performance in a HQBN. Such a framework is a necessary enabler in order to integrate different modelling approaches in understanding and managing STS.

The long-term health consequences of child physical abuse, emotional abuse, and neglect : a systematic review and meta-analysis

Background Child sexual abuse is considered a modifiable risk factor for mental disorders across the life course. However the long-term consequences of other forms of child maltreatment have not yet been systematically examined. The aim of this study was to summarise the evidence relating to the possible relationship between child physical abuse, emotional abuse, and neglect, and subsequent mental and physical health outcomes. Methods and Findings A systematic review was conducted using the Medline, EMBASE, and PsycINFO electronic databases up to 26 June 2012. Published cohort, cross-sectional, and case-control studies that examined non-sexual child maltreatment as a risk factor for loss of health were included. All meta-analyses were based on quality-effects models. Out of 285 articles assessed for eligibility, 124 studies satisfied the pre-determined inclusion criteria for meta-analysis. Statistically significant associations were observed between physical abuse, emotional abuse, and neglect and depressive disorders (physical abuse [odds ratio (OR) = 1.54; 95% CI 1.16–2.04], emotional abuse [OR = 3.06; 95% CI 2.43–3.85], and neglect [OR = 2.11; 95% CI 1.61–2.77]); drug use (physical abuse [OR = 1.92; 95% CI 1.67–2.20], emotional abuse [OR = 1.41; 95% CI 1.11–1.79], and neglect [OR = 1.36; 95% CI 1.21–1.54]); suicide attempts (physical abuse [OR = 3.40; 95% CI 2.17–5.32], emotional abuse [OR = 3.37; 95% CI 2.44–4.67], and neglect [OR = 1.95; 95% CI 1.13–3.37]); and sexually transmitted infections and risky sexual behaviour (physical abuse [OR = 1.78; 95% CI 1.50–2.10], emotional abuse [OR = 1.75; 95% CI 1.49–2.04], and neglect [OR = 1.57; 95% CI 1.39–1.78]). Evidence for causality was assessed using Bradford Hill criteria. While suggestive evidence exists for a relationship between maltreatment and chronic diseases and lifestyle risk factors, more research is required to confirm these relationships. Conclusions This overview of the evidence suggests a causal relationship between non-sexual child maltreatment and a range of mental disorders, drug use, suicide attempts, sexually transmitted infections, and risky sexual behaviour. All forms of child maltreatment should be considered important risks to health with a sizeable impact on major contributors to the burden of disease in all parts of the world. The awareness of the serious long-term consequences of child maltreatment should encourage better identification of those at risk and the development of effective interventions to protect children from violence.

The role of human factors in led outdoor activity accidents: literature review and exploratory analysis

While the exact rate of incidence is unknown (due to the paucity of exposure data), it is acknowledged that safety compromising accidents and incidents occur in the led outdoor activity domain, and that they represent an important issue. Despite this, compared to other safety critical domains, very little is currently known about the key causal factors involved in such accidents and incidents. This report presents the findings derived from a review of the literature, the aim of which was to identify the Human Factors-related issues involved in accidents and incidents occurring in this area. In addition, to demonstrate the utility of systems-based, theoretically underpinned accident analysis methodologies for identifying the systemic and human contribution to accidents and incidents occurring in the led outdoor activity domain, three case-study accidents were analysed using two such approaches. In conclusion, the review identified a range of causal factors cited in the literature; however, it was noted that the majority of the research undertaken to date lacks theoretical underpinning and focuses mainly on instructor or activity leader causal factors, as opposed to the wider system failures involved. The accident analysis presented highlighted the utility of systems-based, theoretically underpinned accident analysis methodologies for analysing and learning from accidents and incidents in the led outdoor activity sector. In closing, the need for further research in the area is articulated, in particular focussing on the development of standardised and universally accepted accident and incident reporting systems and databases, the development of data driven, theoretically underpinned causal factor taxonomies, and the development and application of systems-based accident analysis methodologies.

Moving forwards with the aim of going backwards fast : high performance rowing as a learning environment

Background and Purpose: - This paper focuses on the learning culture within the high performance levels of rowing. In doing so, we explore the case of an individual’s learning as he moves across athletic, coaching and administrative functions. This exploration draws on a cultural learning framework and complementary theorisings related to reflexivity. Method - This study makes use of an intellectually, morally and collaboratively challenging approach whereby one member of the research team was also the sole participant of this study. The participant’s careers as a high performance athlete, coach and administrator, coupled with his experience in conducting empirical research presented a rare opportunity to engage in collaborative research (involving degrees of insider and outsider status for each of the research team). We acknowledge that others have looked to combine roles of coach / athlete / administrator with that of researcher however few (if any) have attempted to combine them all in one project. Moreover, coupled with the approach to reflexivity adopted in this study and the authorship contributions we consider this scholarly direction uncommon. Data were comprised of recorded research conversations, a subsequently constructed learning narrative, reflections on the narrative, a stimulated reflective piece from the participant, and a final (re)construction of the participant’s story. Accordingly, data were integrated through an iterative process of thematic analysis. Results - The cultural (i.e., the ways things get done) and structural (e.g., the rules and regulations) properties of high performance rowing were found to shape both the opportunities to be present (e.g., secure a place in the crew) and to learn (e.g., learn the skills required to perform at an Olympic level). However, the individual’s personal properties were brought to bear on re-shaping the constraints such that many limitations could be overcome. In keeping with the theory of learning cultures, the culture of rowing was found to position individuals (a coxswain in this case) differentially. In a similar manner, a range of structural features was found to be important in shaping the cultural and personal elements in performance contexts. For example, the ‘field of play’ was found to be important as a structural feature (i.e., inability of coach to communicate with athletes) in shaping the cultural and personal elements of learning in competition (e.g., positioning the coxswain as an in-boat coach and trusted crewmate). Finally, the cultural and structural elements in rowing appeared to be activated by the participant’s personal elements, most notably his orientation towards quality performance. Conclusion - The participant in this study was found to be driven by the project that he cares about most and at each turn he has bent his understanding of his sport back on itself to see if he can find opportunities to learn and subsequently explore ways to improve performance. The story here emphasises the importance of learner agency, and this is an aspect that has often been missing in recent theorising about learning. In this study, we find an agent using his ‘personal emergent powers to activate the resources in the culture and structure of his sport in an attempt to improve performance. We conclude from this account that this particular high performance rowing culture is one that provided support but nonetheless encouraged those involved, to ‘figure things out’ for themselves – be it as athletes, coaches and/or administrators.