A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder of skeletal malformations and progressive extraskeletal ossification. We mapped FOP to chromosome 2q23-24 by linkage analysis and identified an identical heterozygous mutation (617G→A; R206H) in the glycine-serine (GS) activation domain of ACVR1, a BMP type I receptor, in all affected individuals examined. Protein modeling predicts destabilization of the GS domain, consistent with constitutive activation of ACVR1 as the underlying cause of the ectopic chondrogenesis, osteogenesis and joint fusions seen in FOP.

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1–3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region4, 5, 6, 7, 8, 9, 10, 11. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods—recursive partitioning and regression...

Concordance of disease severity among family members with ankylosing spondylitis?

Objective. The heritability of disease activity and function in ankylosing spondylitis (AS) have been estimated at 0.51 and 0.63 (i.e., 51% and 63%), respectively. We examined the concordance of disease severity among family members in terms of disease activity, function, radiological change, prevalence of iritis, and juvenile onset. Methods. Disease activity and functional impairment due to AS were studied using the Bath AS Disease Activity Index (BASDAI) and Functional Index (BASFI) self-administered questionnaires; radiographic involvement was measured using the Bath AS Radiology Index (BASRI) scale. Familial correlation of BASDAI and BASFI was assessed in 406 families with 2 or more cases, using the program PAP. Parent-child and sibling-sibling concordance for iritis and juvenile AS were also studied in these families. Heritability of radiological disease severity based on the BASRI was assessed in 29 families containing 60 affected individuals using the program SOLAR. Results. Correlations between parent-child pairs for disease activity and function were 0.07 for both. Correlations between sibling pairs for disease activity and function were 0.27 and 0.36, respectively. The children of AS parents with iritis were more likely to develop iritis [27/71 (38%)] than children of non-iritis AS parents [13/70 (19%)] (p = 0.01). Parents with JAS were more likely to have children with JAS [17/30 (57%) compared to non-JAS parents 34/111 (30%)] (p = 0.002). The heritability of radiological disease severity based on the BASRI was 0.62. Conclusion. While correlation in severity between parent and child is poor, siblings do resemble each other in terms of severity, supporting the findings of segregation studies indicating significant genetic dominance in the heritable component of disease activity. Significant parent-child concordance for iritis and juvenile disease onset suggest that there are genetic risk factors for these traits independent of those determining the risk of AS itself. The finding of significant heritability of radiological change (BASRI) provides support using an objective measure for the observed heritability of the questionnaire-assessed disease severity scores, ASDAI and BASFI.

“I have to rest all the time because you are not allowed to play”: Exploring children’s perceptions of autonomy during sleep-time in long day care services

Daytime sleep is a significant part of the daily routine for children attending early childhood education and care (ECEC) services in Australia and many other countries. The practice of sleep-time can account for a substantial portion of the day in ECEC and often involves a mandated sleep/rest period for all children, including older preschool-aged children. Yet, there is evidence that children have a reduced need for daytime sleep as they approach school entry age and that continuation of mandated sleep-time in ECEC for preschool-aged children may have a negative impact on their health, development, learning and well-being. Mandated sleep-time practices also go against current quality expectations for services to support children’s agency and autonomy in ECEC. This study documents children’s reports of their experiences of sleep-time in ECEC. Semi-structured interviews were conducted with 54 preschool-aged children (44–63 months) across four long day ECEC services that employed a range of sleep-time practices. Findings provide a snapshot of children’s views and experiences of sleep-time and perceptions of autonomy-supportive practices. These provide a unique platform to support critical reflection on sleep-time policies and practices, with a view to continuous quality improvement in ECEC. This study forms part of a programme of work from the Sleep in Early Childhood research group. Our work examines sleep practices in ECEC, the subsequent staff, parent and child experiences and impacts on family and child learning and development outcomes.

Designs for phase I clinical trials with multiple courses of subjects at different doses

The goal of this article is to provide a new design framework and its corresponding estimation for phase I trials. Existing phase I designs assign each subject to one dose level based on responses from previous subjects. Yet it is possible that subjects with neither toxicity nor efficacy responses can be treated at higher dose levels, and their subsequent responses to higher doses will provide more information. In addition, for some trials, it might be possible to obtain multiple responses (repeated measures) from a subject at different dose levels. In this article, a nonparametric estimation method is developed for such studies. We also explore how the designs of multiple doses per subject can be implemented to improve design efficiency. The gain of efficiency from "single dose per subject" to "multiple doses per subject" is evaluated for several scenarios. Our numerical study shows that using "multiple doses per subject" and the proposed estimation method together increases the efficiency substantially.

Isotonic designs for phase I trials

The purpose of a phase I trial in cancer is to determine the level (dose) of the treatment under study that has an acceptable level of adverse effects. Although substantial progress has recently been made in this area using parametric approaches, the method that is widely used is based on treating small cohorts of patients at escalating doses until the frequency of toxicities seen at a dose exceeds a predefined tolerable toxicity rate. This method is popular because of its simplicity and freedom from parametric assumptions. In this payer, we consider cases in which it is undesirable to assume a parametric dose-toxicity relationship. We propose a simple model-free approach by modifying the method that is in common use. The approach assumes toxicity is nondecreasing with dose and fits an isotonic regression to accumulated data. At any point in a trial, the dose given is that with estimated toxicity deemed closest to the maximum tolerable toxicity. Simulations indicate that this approach performs substantially better than the commonly used method and it compares favorably with other phase I designs.

Now that I have had this experience I am looking at studying…

The Community Aspirations Program in Education (CAP-ED) was started by CQUniversity’s Office of Indigenous Engagement in 2013. CAP-ED’s aim was to focus on building aspirations through small manageable learning projects, and to increase Aboriginal and Torres Strait Islander students’ participation in higher education. Initially the scope of the project was to develop and deliver an accredited certificate-level program to help Indigenous students transition into tertiary education by a) improving pathways and b) addressing their current knowledge gaps. However, the initial investigatory process and community consultation found that a more localised, targeted and intimate approach would work more effectively. In addition, a free or affordable certificate course that would meet community needs was beyond the financial scope of the project. From here, the Office of Indigenous Engagement began to explore other possibilities.

Freedom ride... I have a dream

A play in two parts on the subject of racism. Part One presents the story of the Montgomery bus boycott arising from the refusal of Rosa Parkes to give up her seat on a bus and leading to the rise of Martin Luther King, Jr. Part Two is set in contemporary Australia, in the household of a group of young people who re-create the sixties' Freedom Ride in order to heal the spirit of Auntie, an Aboriginal woman, who is the centre of their world.

‘I really needed help’: What mothers say about their post-birth care in Queensland, Australia

Background Australian mothers consistently rate postnatal care as the poorest aspect of their maternity care, and researchers and policymakers have widely acknowledged the need for improvement in how postnatal care is provided. Aim To identify and analyse mothers’ comments about postnatal care in their free text responses to an open ended question in the Having a Baby in Queensland Survey, 2010, and reflect on their implications for midwifery practice and maternity service policies. Methods The survey assessed mothers’ experiences of maternity care four months after birth. We analysed free-text data from an open-ended question inviting respondents to write ‘anything else you would like to tell us’. Of the final survey sample (N = 7193), 60% (N = 4310) provided comments, 26% (N = 1100) of which pertained to postnatal care. Analysis included the coding and enumeration of issues to identify the most common problems commented on by mothers. Comments were categorised according to whether they related to in-hospital or post-discharge care, and whether they were reported by women birthing in public or private birthing facilities. Results The analysis revealed important differences in maternal experiences according to birthing sector: mothers birthing in public facilities were more likely to raise concerns about the quality and/or duration of their in-hospital stay than those in private facilities. Conversely, mothers who gave birth in private facilities were more likely to raise concerns about inadequate post-discharge care. Regardless of birthing sector, however, a substantial proportion of all mothers spontaneously raised concerns about their experiences of inadequate and/or inconsistent breastfeeding support. Conclusion Women who birth in private facilities were more likely to spontaneously report concerns about their level of post-discharge care than women from public facilities in Queensland, and publically provided community based care is not sufficient to meet women's needs. Inadequate or inconsistent professional breastfeeding support remains a major issue for early parenting women regardless of birthing sector.

Influences on novice drivers' speed selection - a systematic review: Application and limitations of theory and methodology

Background Excessive speed is a primary contributing factor to young novice road trauma, including intentional and unintentional speeds above posted limits or too fast for conditions. The objective of this research was to conduct a systematic review of recent investigations into novice drivers’ speed selection, with particular attention to applications and limitations of theory and methodology. Method Systematic searches of peer-reviewed and grey literature were conducted during September 2014. Abstract reviews identified 71 references potentially meeting selection criteria of investigations since the year 2000 into factors that influence (directly or indirectly) actual speed (i.e., behaviour or performance) of young (age <25 years) and/or novice (recently-licensed) drivers. Results Full paper reviews resulted in 30 final references: 15 focused on intentional speeding and 15 on broader speed selection investigations. Both sets identified a range of individual (e.g., beliefs, personality) and social (e.g., peer, adult) influences, were predominantly theory-driven and applied cross-sectional designs. Intentional speed investigations largely utilised self-reports while other investigations more often included actual driving (simulated or ‘real world’). The latter also identified cognitive workload and external environment influences, as well as targeted interventions. Discussion and implications Applications of theory have shifted the novice speed-related literature beyond a simplistic focus on intentional speeding as human error. The potential to develop a ‘grand theory’ of intentional speeding emerged and to fill gaps to understand broader speed selection influences. This includes need for future investigations of vehicle-related and physical environment-related influences and methodologies that move beyond cross-sectional designs and rely less on self-reports.

'I wonder what you know...': Teachers designing requests for factual information

Optimizing the quality of early childhood education (ECE) is an international policy priority. Teacher-child interactions have been identified as the strongest indicator of quality and most potent predictor of child outcomes. This paper presents ethnomethodological and conversation analysis of an interaction between an early childhood educator with two children as they engage with each other, while performing a Web search. Analyses shows that question design can elicit qualitatively different responses with regard to sustained interactions. Understanding the design of teacher questions has pedagogic implications for the work of the teacher and for the broader quality agenda in early childhood education.

Should I stay or should I go?: Rural and remote students in first year university stem courses

Research on the achievement of rural and remote students in science and mathematics is located within a context of falling levels of participation in physical science and mathematics courses in Australian schools, and underrepresentation of rural students in higher education. International studies such as the Programme of International Student Assessment (PISA), have reported lower levels of mathematical and scientific literacy in Australian students from rural and remote schools (Thomson et al, 2011). The SiMERR national survey of science, mathematics and ICT education in rural and regional Australia (Lyons et al, 2006) identified factors affecting student achievement in rural and remote schools. Many of the issues faced by rural and remote students in their schools are likely to have implications on their university enrolments in science, technology, engineering and mathematics (STEM) courses. For example, rural and remote students are less likely to attend university in general than their city counterparts and higher university attrition rates have been reported for remote students nationally. This paper examines the responses of a sample of rural/remote Australian first year STEM students at Australian universities to two questions. These related to their intentions to complete the course; and whether -and if so, why- they had ever considered withdrawing from their course. Results indicated that rural students who were still in their course by the end of first year were no more or less likely to consider withdrawing than were their peers from more populous centres. However, almost 20% of the rural cohort had considered withdrawing at some stage in their course, and their explanations provide insights into the reasoning of those who may not persist with their courses at university. These results, in the context of the greater attrition rate of remote students from university, point to the need to identify factors that positively impact on rural and remote students’ interest and achievement in science and mathematics. It also highlights a need for future research into the particular issues remote students may face in deciding whether or not to do science at the two key transition points of senior school and university/TAFE studies, and whether or not to persist in their tertiary studies. This paper is positioned at the intersection of two problems in Australian education. The first is a context of falling levels of participation in physical science and mathematics courses in Australian universities. The second is persistent inequitable access to, and retention in, tertiary education for students from rural and remote areas. Despite considerable research attention to both of these areas over recent years these problems have thus far proved to be intractable. This paper therefore aims to briefly review the relevant Australian literature pertaining to these issues; that is, declining STEM enrolments, and the underrepresentation and retention of rural/remote students in higher education. Given the related problems in these two overlapping domains, we then explore the views of first year rural students enrolled in courses, in relation to their intentions of withdrawing (or not) and the associated reasons for their views.

Who am I? Developing pre-service teacher identity in a digital world

The notions of identity and teacher education have attracted considerable research over the years, revealing a strong correlation between teacher beliefs and practices and the resultant impact on pedagogical practices in the classroom. In an era where the use of digital technologies should be synonymous with teacher pedagogical practices and transforming education, there is a growing need for pre-service teachers to develop an identity that resonates with pedagogical practices that engage and connect with students in a positive and productive way. With many educational institutions also mandating that educators use digital technologies as a tool to support and enhance teaching, pre-service teacher education needs to ensure that students understand and develop a positive identity within this digital world. Current literature acknowledges that many educators adopt digital technologies in the classroom without sometimes fully understanding its scope or impact. It is within this context that this paper reports on a three-year study of first year pre-service education students and their understanding of identity in a digital world. More specifically, the study identifies how students currently use social and digital media in their personal and professional lives to identify themselves online in order to promote a positive image. The study also seeks to identify how these technologies and an understanding of identity can be utilised to promote a positive first year experience.