Risedronate in adults with osteogenesis imperfecta type I: Increased bone mineral density and decreased bone turnover, but high fracture rate persists

Summary Bisphosphonates can increase bone mineral density (BMD) in children with osteogenesis imperfecta (OI). In this study of adults with OI type I, risedronate increased BMD at lumbar spine (but not total hip) and decreased bone turnover. However, the fracture rate in these patients remained high. Introduction Intravenous bisphosphonates given to children with OI can increase BMD and reduce fracture incidence. Oral and/or intravenous bisphosphonates may have similar effects in adults with OI. We completed an observational study of the effect of risedronate in adults with OI type I. Methods Thirty-two adults (mean age, 39 years) with OI type I were treated with risedronate (total dose, 35 mg weekly) for 24 months. Primary outcome measures were BMD changes at lumbar spine (LS) and total hip (TH). Secondary outcome measures were fracture incidence, bone pain, and change in bone turnover markers (serum procollagen type I aminopropeptide (P1NP) and bone ALP). A meta-analysis of published studies of oral bisphosphonates in adults and children with OI was performed. Results Twenty-seven participants (ten males and seventeen females) completed the study. BMD increased at LS by 3.9% (0.815 vs. 0.846 g/cm 2, p=0.007; mean Z-score, -1.93 vs. -1.58, p=0.002), with no significant change at TH. P1NP fell by 37% (p=0.00041), with no significant change in bone ALP (p=0.15). Bone pain did not change significantly (p=0.6). Fracture incidence remained high, with 25 clinical fractures and 10 major fractures in fourteen participants (0.18 major fractures per person per year), with historical data of 0.12 fractures per person per year. The meta-analysis did not demonstrate a significant difference in fracture incidence in patients with OI treated with oral bisphosphonates. Conclusions Risedronate in adults with OI type I results in modest but significant increases in BMD at LS, and decreased bone turnover. However, this may be insufficient to make a clinically significant difference to fracture incidence.

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...

Disaster management in Nepal: Media engagement in the Post-2015 Framework for Disaster Risk Reduction

Nepal, as a consequence of its geographical location and changing climate, faces frequent threats of natural disasters. According to the World Bank’s 2005 Natural Disasters Hotspots Report, Nepal is ranked the 11th most vulnerable country to earthquake and 30th to flood risk. Geo-Hazards International (2011) has classified Kathmandu as one of the world’s most vulnerable cities to earthquakes. In the last four decades more than 32,000 people in Nepal have lost their lives and annual monetary loss is estimated at more than 15 million (US) dollars. This review identifies gaps in knowledge, and progress towards implementation of the Post Hyogo Framework of Action. Nepal has identified priority areas: community resilience, sustainable development and climate change induced disaster risk reduction. However, one gap between policy and action lies in the ability of Nepal to act effectively in accordance with an appropriate framework for media activities. Supporting media agencies include the Press Council, Federation of Nepalese Journalists, Nepal Television, Radio Nepal and Telecommunications Authority and community based organizations. The challenge lies in further strengthening traditional and new media to undertake systematic work supported by government bodies and the National Risk Reduction Consortium (NRRC). Within this context, the ideal role for media is one that is proactive where journalists pay attention to a range of appropriate angles or frames when preparing and disseminating information. It is important to develop policy for effective information collection, sharing and dissemination in collaboration with Telecommunication, Media and Journalists. The aim of this paper is to describe the developments in disaster management in Nepal and their implications for media management. This study provides lessons for government, community and the media to help improve the framing of disaster messages. Significantly, the research highlights the prominence that should be given to flood, landslides, lightning and earthquakes.

“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.

Urban growth and development of contemporary neighbourhood public space in Kathmandu Valley, Nepal

Rapid and unplanned growth of Kathmandu Valley towns over the past decades has resulted in the haphazard development of new neighbourhoods with significant consequences on their public space. This paper examines the development of public space in the valley’s new neighbourhoods in the context of the current urban growth. A case study approach of three new neighbourhoods was developed to examine the provision of public space with data collected from site observations, interviews with neighbourhood residents and other secondary sources. The cases studies consist of both planned and unplanned new neighbourhoods. Findings reveal a severe loss of public space in the unplanned new neighbourhoods. In planned new neighbourhoods, the provision of public space remains poor in terms of physical features, and thus, does not support community activities and needs. Several factors, which are an outcome of the lack of proper urban growth initiatives and control measures, such as an overall drawback in the formation of new neighbourhoods, the poor capacity of local community-based organisations and the encroachment of public land are responsible for the present development of neighbourhood public space. The problems with ongoing management of public spaces are a significant issue in both unplanned and planned new neighbourhoods.

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.

Shift in disease burden from communicable to non-communicable diseases: Aiming to achieve Universal Health Coverage in Nepal

A major barrier to accessing healthcare services is spending, and the extended time that non-communicable diseases require treatment for means that many people around the world do not have proper access to care. Saval Khanal from Sankalpa Foundation, Nepal, Lennert Veerman and Samantha Hollingworth from the University of Queensland and Lisa Nissen from Queensland University of Technology lay out the results of their study and establish a method to forecast medicine use in Nepal.

‘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.

'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.