A genetic variant of MDM4 influences regulation by multiple microRNAs in prostate cancer

The oncogene MDM4, also known as MDMX or HDMX, contributes to cancer susceptibility and progression through its capacity to negatively regulate a range of genes with tumour-suppressive functions. As part of a recent genome-wide association study it was determined that the A-allele of the rs4245739 SNP (A>C), located in the 3'-UTR of MDM4, is associated with an increased risk of prostate cancer. Computational predictions revealed that the rs4245739 SNP is located within a predicted binding site for three microRNAs (miRNAs): miR-191-5p, miR-887 and miR-3669. Herein, we show using reporter gene assays and endogenous MDM4 expression analyses that miR-191-5p and miR-887 have a specific affinity for the rs4245739 SNP C-allele in prostate cancer. These miRNAs do not affect MDM4 mRNA levels, rather they inhibit its translation in C-allele-containing PC3 cells but not in LNCaP cells homozygous for the A-allele. By analysing gene expression datasets from patient cohorts, we found that MDM4 is associated with metastasis and prostate cancer progression and that targeting this gene with miR-191-5p or miR-887 decreases in PC3 cell viability. This study is the first, to our knowledge, to demonstrate regulation of the MDM4 rs4245739 SNP C-allele by two miRNAs in prostate cancer, and thereby to identify a mechanism by which the MDM4 rs4245739 SNP A-allele may be associated with an increased risk for prostate cancer.

Effects of the sensorimotor training volume on sensorimotor function in patients following lower limb arthroplasty

Background Sensorimotor function is degraded in patients after lower limb arthroplasty. Sensorimotor training is thought to improve sensorimotor skills, however, the optimal training stimulus with regard to volume, frequency, duration, and intensity is still unknown. The aim of this study, therefore, was to firstly quantify the progression of sensorimotor function after total hip (THA) or knee (TKA) arthroplasty and, as second step, to evaluate effects of different sensorimotor training volumes. Methods 58 in-patients during their rehabilitation after THA or TKA participated in this prospective cohort study. Sensorimotor function was assessed using a test battery including measures of stabilization capacity, static balance, proprioception, and gait, along with a self-reported pain and function. All participants were randomly assigned to one of three intervention groups performing sensorimotor training two, four, or six times per week. Outcome measures were taken at three instances, at baseline (pre), after 1.5 weeks (mid) and at the conclusion of the 3 week program (post). Results All measurements showed significant improvements over time, with the exception of proprioception and static balance during quiet bipedal stance which showed no significant main effects for time or intervention. There was no significant effect of sensorimotor training volume on any of the outcome measures. Conclusion We were able to quantify improvements in measures of dynamic, but not static, sensorimotor function during the initial three weeks of rehabilitation following TKA/THA. Although sensorimotor improvements were independent of the training volume applied in the current study, long-term effects of sensorimotor training volume need to be investigated to optimize training stimulus recommendations.

"Re-thinking" the influence of regulatory capture in the development of government regulation

On 30 March 2015 the Australian Federal Government launched its "Re-Think" initiative with the objective of achieving a better tax system which delivers taxes that are lower, simpler and fairer. The discussion paper released as part of the "Re:think" initiative is designed to start a national conversation on tax reform. However, inquiries into Australia's future tax system, subsequent reforms and the introduction of new taxes are nothing new. Unfortunately, recent history also demonstrates that reform initiatives arising from reviews of the Australian tax system are often deemed a failure. The most prominent of these failures in recent times is the Minerals Resource Rent Tax (MRRT), which lasted a mere 16 months before its announced repeal. Using the established theoretic framework of regulatory capture to interpret publically observable data, the purpose of this article is to explain the failure of this arguably sound tax. It concludes that the MRRT legislation itself, through the capture by the mining companies, provided internal subsidization in the form of reduced tax and minimal or no rents. In doing so, it offers an opportunity to understand and learn from past experiences to ensure that recommendations coming out of the Re:think initiative do not suffer the same fate.

Swimming against the tide? Australian labour regulation and the fissured workplace

In The Fissured Workplace, David Weil dissects the ways in which ostensibly ‘large’ American businesses have come to shed direct employees and instead source their labour needs through a ‘complicated network of smaller business units’. As he notes, this has increased the profitability of these ‘lead’ businesses, at the expense of those who (ultimately) work for them: Wage setting and supervision shift from core businesses to a myriad of organizations, each operating under the rigorous standards of lead businesses but facing fierce competitive pressures. Although lead businesses set demanding goals and standards, and often detailed work practice requirements for subsidiary companies, the actual liability, oversight, and supervision of the workforce become the problem of one or more other organizations. And by replacing a direct employment relationship with a fissured workplace, employment itself becomes more precarious, with risk shifted onto smaller employers and individual workers, who are often cast in the role of independent businesses in their own right.

Reconciling transport models across scales: The role of volume exclusion

Diffusive transport is a universal phenomenon, throughout both biological and physical sciences, and models of diffusion are routinely used to interrogate diffusion-driven processes. However, most models neglect to take into account the role of volume exclusion, which can significantly alter diffusive transport, particularly within biological systems where the diffusing particles might occupy a significant fraction of the available space. In this work we use a random walk approach to provide a means to reconcile models that incorporate crowding effects on different spatial scales. Our work demonstrates that coarse-grained models incorporating simplified descriptions of excluded volume can be used in many circumstances, but that care must be taken in pushing the coarse-graining process too far.

Regulation beyond government: Weber, Foucault and the liberal governance of media content

This paper steps back from the question of how regulation of digital media content occurs, and whether it can be effective, to consider the rationales that inform regulation, and the ethics and practices associated with content regulation. It will be argued that Max Weber's account of bureaucratic expertise remains relevant to such discussions, particularly insofar as it intersects with Michel Foucault's concept of governmentality, and contemporary applications of the notion of 'governing at a distance'. The nature of the challenges to media regulators presented by online environments, and by digital and social media, are considered in depth, but it is argued that the significance of regulatory innovations that respond to such challenges should not be underestimated, nor should the continuing national foundations of media regulation. It will also discuss the relevance of the concept of 'soft law' to contemporary regulatory practice.

Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption

Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of approximately 2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 x 10(-8) to P = 4 x 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Down-regulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.

Social Audit Regulation Within the NGO Sector: Practices of NGOs Operating in Bangladesh and Indonesia

Social audit is one of those important mechanisms for strengthening NGOs’ accountability to poor communities (as NGOs’ key beneficiaries). However, conducting social audits within the NGO sector often rests on the individual interests and priorities of donors or NGOs themselves, effectively resulting in self-selection bias, and limiting the effectiveness and usefulness of social audits as a control and evaluation mechanism. The purpose of this chapter is to identify the prevalence, scale, and scope of social audits within the NGO sector, particularly NGOs engaging in microenterprise development programs. Accordingly, this study examined 20 NGOs operating in two countries - Bangladesh and Indonesia. Data were collected from publicly available sources and in-depth interviews with senior executives of the participating NGOs. Further, 10 interviews were conducted with a small sample of beneficiaries (individuals or groups from four of the participating NGOs) in order to gain an understanding of beneficiaries’ perceptions of the NGOs’ social audit mechanism. The findings reveal a range of approaches to social audit among NGOs, as well as the usefulness and limitations of this mechanism for strengthening NGO accountability, particularly to beneficiaries. Findings highlight that within the NGOs investigated the conduct of social audits remained voluntary and was strongly dependant on donors’ requirements. As social audit regulation within the NGO sector is minimal, the findings provide regulators with valuable guidance for better understanding the value of social audit as a mechanism to strengthen accountability of the NGO sector, particularly accountability to beneficiaries.

Sequence variants in three loci influence monocyte counts and erythrocyte volume

Blood cells participate in vital physiological processes, and their numbers are tightly regulated so that homeostasis is maintained. Disruption of key regulatory mechanisms underlies many blood-related Mendelian diseases but also contributes to more common disorders, including atherosclerosis. We searched for quantitative trait loci (QTL) for hematology traits through a whole-genome association study, because these could provide new insights into both hemopoeitic and disease mechanisms. We tested 1.8 million variants for association with 13 hematology traits measured in 6015 individuals from the Australian and Dutch populations. These traits included hemoglobin composition, platelet counts, and red blood cell and white blood cell indices. We identified three regions of strong association that, to our knowledge, have not been previously reported in the literature. The first was located in an intergenic region of chromosome 9q31 near LPAR1, explaining 1.5% of the variation in monocyte counts (best SNP rs7023923, p=8.9x10(-14)). The second locus was located on chromosome 6p21 and associated with mean cell erythrocyte volume (rs12661667, p=1.2x10(-9), 0.7% variance explained) in a region that spanned five genes, including CCND3, a member of the D-cyclin gene family that is involved in hematopoietic stem cell expansion. The third region was also associated with erythrocyte volume and was located in an intergenic region on chromosome 6q24 (rs592423, p=5.3x10(-9), 0.6% variance explained). All three loci replicated in an independent panel of 1543 individuals (p values=0.001, 9.9x10(-5), and 7x10(-5), respectively). The identification of these QTL provides new opportunities for furthering our understanding of the mechanisms regulating hemopoietic cell fate.

Common variants in TMPRSS6 are associated with iron status and erythrocyte volume

We report a genome-wide association study to iron status. We identify an association of SNPs in TPMRSS6 to serum iron (rs855791, combined P = 1.5 x 10(-20)), transferrin saturation (combined P = 2.2 x 10(-23)) and erythrocyte mean cell volume (MCV, combined P = 1.1 x 10(-10)). We also find suggestive evidence of association with blood hemoglobin levels (combined P = 5.3 x 10(-7)). These findings demonstrate the involvement of TMPRSS6 in control of iron homeostasis and in normal erythropoiesis.

A lifespan perspective on emotion regulation, stress, and well-being in the workplace

Researchers in the field of occupational stress and well-being are increasingly interested in the role of emotion regulation in the work context. Emotion regulation has also been widely investigated in the area of lifespan developmental psychology, with findings indicating that the ability to modify one's emotions represents a domain in which age-related growth is possible. In this chapter, we integrate the literatures on aging, emotion regulation, and occupational stress and well-being. To this end, we review key theories and empirical findings in each of these areas, summarize existing research on age, emotion regulation, and stress and well-being at work, and develop a conceptual model on how aging affects emotion regulation and the stress process in work settings to guide future research. According to the model, age will affect: (1) what kinds of affective work events are encountered and how often; (2) the appraisal of and initial emotional response to affective work events (emotion generation), and; (3) the management of emotions and coping with affective work events (emotion regulation). The model has implications for researchers and practitioners who want to understand and facilitate successful emotion regulation and stress reduction in the workplace among different age groups.

Differences in parent regulation beliefs and maternal postnatal depressive symptoms in early weeks

Postnatal depression is consistently associated with couple relationship qualities. Substantial infant care requirements in early weeks may highlight differences in parenting beliefs between mother and father. We calculated difference scores in parenting beliefs (disparity) in a community sample of 209 parent dyads. Contrary to previous research regarding ‘disagreement’ which could be interpreted as discord, independently measured disparity was not associated with maternal depressive symptoms. Coparenting interventions should promote respectful negotiation rather than resolution of differences.

Content regulation

This entry discusses the origins and history of media content regulation, the reasons for content regulations, and their application to different media platforms. It discusses online content regulations and the concerns that have motivated such policies with particular reference to debates about internet filtering. It is noted that, as there is growing convergence of media content, platforms, devices, and services, the debates can be expected to shift from free speech and censorship on the internet and the social protection of internet users, to wider issues of media policy reform that include cultural policy and industry development in the digital economy.

Sleep and self-regulation from birth to 7 years: A retrospective study of children with and without ADHD at 8-9 years

Objective To examine mean level differences, and longitudinal and reciprocal relations among behavioral sleep problems, emotional dysregulation, and attentional regulation across early childhood for children with and without ADHD at 8-9 years. Method This study used data from Growing Up in Australia: The Longitudinal Study of Australian Children (LSAC) – Infant Cohort (n = 4109 analyzed). Children with and without ADHD were identified at age 8-9 years via parent-report of ADHD diagnosis and the 5-item Inattention-Hyperactivity subscale from the Strengths and Difficulties Questionnaire. Maternal report of child sleep problems and self-regulation was collected at 0-1, 2-3, 4-5 and 6-7 years of age. ANOVA was used to compare mean level differences in sleep problems, emotional and attentional regulation by ADHD group. Longitudinal structural equation modeling examined the relations among sleep and self-regulation across time in children with and without ADHD. Results Children with ADHD had persistently elevated levels of sleep problems (from infancy) and emotional and attentional dysregulation compared to controls (from 2-3 years of age). Sleep problems, emotional dysregulation, and attentional regulation were stable over time for both groups. Sleep problems were associated with greater emotional dysregulation two years later from 2-3 years of age for both groups, which in turn was associated with poorer attentional regulation. There was no direct relationship between sleep problems and later attentional regulation. Conclusion Sleep problems in children with and without ADHD are associated with emotional dysregulation, which in turn contributes to poorer attentional functioning. This study highlights the importance of assessing and managing sleep problems in young children.

Early childhood profiles of sleep problems and self-regulation predict later school adjustment

Background Children’s sleep problems and self-regulation problems have been independently associated with poorer adjustment to school, but there has been limited exploration of longitudinal early childhood profiles that include both indicators. Aims This study explores the normative developmental pathway for sleep problems and self-regulation across early childhood, and investigates whether departure from the normative pathway is associated with later social-emotional adjustment to school. Sample This study involved 2880 children participating in the Growing Up in Australia: The Longitudinal Study of Australian Children (LSAC) – Infant Cohort from Wave 1 (0-1 years) to Wave 4 (6-7 years). Method Mothers reported on children’s sleep problems, emotional, and attentional self-regulation at three time points from birth to 5 years. Teachers reported on children’s social-emotional adjustment to school at 6-7 years. Latent profile analysis was used to establish person-centred longitudinal profiles. Results Three profiles were found. The normative profile (69%) had consistently average or higher emotional and attentional regulation scores and sleep problems that steadily reduced from birth to 5. The remaining 31% of children were members of two non-normative self-regulation profiles, both characterised by escalating sleep problems across early childhood and below mean self-regulation. Non-normative group membership was associated with higher teacher-reported hyperactivity and emotional problems, and poorer classroom self-regulation and prosocial skills. Conclusion Early childhood profiles of self-regulation that include sleep problems offer a way to identify children at risk of poor school adjustment. Children with escalating early childhood sleep problems should be considered an important target group for school transition interventions.