Targeting mutant fibroblast growth factor receptors in cancer

Fibroblast growth factor receptors (FGFRs) play diverse roles in the control of cell proliferation, cell differentiation, angiogenesis and development. Activating the mutations of FGFRs in the germline has long been known to cause a variety of skeletal developmental disorders, but it is only recently that a similar spectrum of somatic FGFR mutations has been associated with human cancers. Many of these somatic mutations are gain-of-function and oncogenic and create dependencies in tumor cell lines harboring such mutations. A combination of knockdown studies and pharmaceutical inhibition in preclinical models has further substantiated genomically altered FGFR as a therapeutic target in cancer, and the oncology community is responding with clinical trials evaluating multikinase inhibitors with anti-FGFR activity and a new generation of specific pan-FGFR inhibitors.

The transition to school of children with developmental disabilities : views of parents and teachers

The transition from early intervention programs to inclusive school settings presents children with developmental disabilities with a range of social challenges. In Queensland, in the year of transition to school, many children with developmental disabilities attend an Early Childhood Development Program for 2 to 3 days each week and also begin attendance in a mainstream program with the latter increasing to full-time attendance during the year. Quantitative and qualitative data were collected by parent interviews and teacher questionnaires for 62 children participating in the Transition to School Project regarding their perceptions of the success of the transition process and the benefits and challenges of inclusion. Both parents and teachers saw a range of benefits to children from their inclusion in ‘regular’ classrooms, with parents noting the helpfulness of teachers and their support for inclusion. Challenges noted by parents included the school’s lack of preparation for their child’s particular developmental needs especially in terms of the physical environment while teachers reported challenges meeting the needs of these children within the context and resources of the classroom. Parents were more likely than teachers to view the transition as easy. Correlational analyses indicated that teachers were more likely to view the transition as easy when they felt that the child was appropriately placed in a ‘regular’ classroom. Findings from this project can inform the development of effective transition-to-school programs in the early school years for children with developmental disabilities.

Principles for use of ball projection machines in elite and developmental sport programmes

Use of ball projection machines in the acquisition of interceptive skill has recently been questioned. The use of projection machines in developmental and elite fast ball sports programmes is not a trivial issue, since they play a crucial role in reducing injury incidence in players and coaches. A compelling challenge for sports science is to provide theoretical principles to guide how and when projection machines might be used for acquisition of ball skills and preparation for competition in developmental and elite sport performance programmes. Here, we propose how principles from an ecological dynamics theoretical framework could be adopted by sports scientists, pedagogues and coaches to underpin the design of interventions, practice and training tasks, including the use of hybrid video-projection technologies. The assessment of representative learning design during practice may provide ways to optimize developmental programmes in fast ball sports and inform the principled use of ball projection machines.

Emergency health services : demand and service delivery models. Monograph 1: literature review and activity trends

Emergency Health Services (EHS), encompassing hospital-based Emergency Departments (ED) and pre-hospital ambulance services, are a significant and high profile component of Australia’s health care system and congestion of these, evidenced by physical overcrowding and prolonged waiting times, is causing considerable community and professional concern. This concern relates not only to Australia’s capacity to manage daily health emergencies but also the ability to respond to major incidents and disasters. EHS congestion is a result of the combined effects of increased demand for emergency care, increased complexity of acute health care, and blocked access to ongoing care (e.g. inpatient beds). Despite this conceptual understanding there is a lack of robust evidence to explain the factors driving increased demand, or how demand contributes to congestion, and therefore public policy responses have relied upon limited or unsound information. The Emergency Health Services Queensland (EHSQ) research program proposes to determine the factors influencing the growing demand for emergency health care and to establish options for alternative service provision that may safely meet patient’s needs. The EHSQ study is funded by the Australian Research Council (ARC) through its Linkage Program and is supported financially by the Queensland Ambulance Service (QAS). This monograph is part of a suite of publications based on the research findings that examines the existing literature, and current operational context. Literature was sourced using standard search approaches and a range of databases as well as a selection of articles cited in the reviewed literature. Public sources including the Australian Institute of Health and Welfare (AIHW), the Council of Ambulance Authorities (CAA) Annual Reports, Australian Bureau of Statistics (ABS) and Department of Health and Ageing (DoHA) were examined for trend data across Australia.

Reasonable adjustment and the assessment of students with disabilities: Australian legal issues and trends

Student assessment is particularly important, and particularly controversial, because it is the means by which student achievement is determined. Reasonable adjustment to student assessment is of equal importance as the means of ensuring the mitigation, or even elimination, of disability related barriers to the demonstration of student achievement. The significance of reasonable adjustment is obvious in the later years of secondary school, and in the tertiary sector, because failure to adjust assessment may be asserted as the reason a student did not achieve as well as anticipated or as the reason a student was excluded from a course and, as a result, from future study and employment opportunities. Even in the early years of schooling, however, assessment and its management are a critical issue for staff and students, especially in an education system like Australia’s with an ever increasing emphasis on national benchmarks testing. This paper will explain the legislation which underpins the right to reasonable adjustment in education in Australian schools. It will give examples of the kinds of adjustment which may be made to promote equality of opportunity in the area of assessment. It will also consider some of the controversies which have confronted, or which, it may be speculated, are likely to confront Australian education institutions as they work towards compliance with reasonable adjustment laws.

Event-related brain potentials dissociate the developmental time-course of automatic numerical magnitude analysis and cognitive control functions during the first three years of primary school

In this study we set out to dissociate the developmental time course of automatic symbolic number processing and cognitive control functions in grade 1-3 British primary school children. Event-related potential (ERP) and behavioral data were collected in a physical size discrimination numerical Stroop task. Task-irrelevant numerical information was processed automatically already in grade 1. Weakening interference and strengthening facilitation indicated the parallel development of general cognitive control and automatic number processing. Relationships among ERP and behavioral effects suggest that control functions play a larger role in younger children and that automaticity of number processing increases from grade 1 to 3.

Trends in policies, programs and practices in the Australasian First Year Experience literature 2000-2010. The First Year in Higher Education Research Series on Evidence-based Practice. Number 1

This publication is the first in a series of scholarly reports on research-based practice related to the First Year Experience in Higher Education. This report synthesises evidence about practice-based initiatives and pragmatic approaches in Aotearoa (New Zealand) and Australia that aim to enhance the experience of commencing students in the higher education sector. Trends in policies, programs and practices ... examines the first year experience literature from 2000-2010. It acknowledges the uniqueness of the Australasian socio-political context and its influence on the interests and output of researchers. The review surveyed almost 400 empirical reports and conceptual discussions produced over the decade that dealt with the stakeholders, institutions and the higher education sector in Australasia. The literature is examined through two theoretical constructs or “lenses”: first, a set of first year curriculum design principles and second, the generational approach to describing the maturation of initiatives. These outcomes and suggested directions for further research provide the challenges and the opportunities for FYE adherents, both scholars and practitioners, to grapple with in the next decade.

Stability and change in prosocial and antisocial behavior across the transition to school : Teacher and peer perspectives

Research Findings: The transition to school is a major developmental milestone, and behavior tendencies already evident at the point of school entry can impact upon a child's subsequent social and academic adjustment. The current study aimed to investigate stability and change in the social behavior of girls and boys across the transition from day care to 1st grade. Teacher ratings and peer nominations for prosocial and antisocial behavior were obtained for 248 children belonging to 2 cohorts: school transitioning (n = 118) and day care remaining (n = 130). Data were gathered again from all children 1 year later, following the older group's entry into school. Teacher ratings of prosocial and antisocial behavior significantly predicted teacher ratings of the same behavior at Time 2 for both cohorts. Peer reports of antisocial behavior also showed significant stability, whereas stability of peer-reported prosocial behavior varied as a function of behavior type. Practice or Policy: The results contribute to understanding of trends in early childhood social behavior that potentially influence long-term developmental trajectories. Identification of some behaviors as more stable in early childhood than others, regardless of school entry, provides useful information for both the type and timing of early interventions. © 2010 Taylor & Francis Group, LLC.

The developmental and acute phases of insulin-induced laminitis involve minimal metalloproteinase activity

Metalloproteinases have been implicated in the pathogenesis of equine laminitis and other inflammatory conditions, through their role in the degradation and remodelling of the extracellular matrix environment. Matrix metalloproteinases (MMPs) and their inhibitors are present in normal equine lamellae, with increased secretion and activation of some metalloproteinases reported in horses with laminitis associated with systemic inflammation. It is unknown whether these enzymes are involved in insulin-induced laminitis, which occurs without overt systemic inflammation. In this study, gene expression of MMP-2, MMP-9, MT1-MMP, ADAMTS-4 and TIMP-3 was determined in the lamellar tissue of normal control horses (n = 4) and horses that developed laminitis after 48 h of induced hyperinsulinaemia (n = 4), using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Protein concentrations of MMP-2 and MMP-9 were also examined using gelatin zymography in horses subject to prolonged hyperinsulinaemia for 6 h (n = 4), 12 h (n = 4), 24 h (n = 4) and 48 h (n = 4), and in normal control horses (n = 4). The only change in gene expression observed was an upregulation of MMP-9 (p < 0.05) in horses that developed insulin-induced laminitis (48 h). Zymographical analysis showed an increase (p < 0.05) in pro MMP-9 during the acute phase of laminitis (48 h), whereas pro MMP-2 was present in similar concentration in the tissue of all horses. Thus, MMP-2, MT1-MMP, TIMP-3 and ADAMTS-4 do not appear to play a significant role in the pathogenesis of insulin-induced laminitis. The increased expression of MMP-9 may be associated with the infiltration of inflammatory leukocytes, or may be a direct result of hyperinsulinaemia. The exact role of MMP-9 in basement membrane degradation in laminitis is uncertain as it appears to be present largely in the inactive form.

Food insecurity among Australian children : potential determinants, health and developmental consequences

Children in food-insecure households may be at risk of poor health, developmental or behavioural problems. This study investigated the associations between food insecurity, potential determinants and health and developmental outcomes among children. Data on household food security, socio-demographic characteristics and children’s weight, health and behaviour were collected from households with children aged 3–17 years in socioeconomically disadvantaged suburbs by mail survey using proxy-parental reports (185 households). Data were analysed using logistic regression. Approximately one-in-three households (34%) were food insecure. Low household income was associated with an increased risk of food insecurity [odds ratio (OR), 16.20; 95% confidence interval (CI), 3.52–74.47]. Children with a parent born outside of Australia were less likely to experience food insecurity (OR, 0.42; 95% CI, 0.19–0.93). Children in food-insecure households were more likely to miss days from school or activities (OR, 3.52; 95% CI, 1.46–8.54) and were more likely to have borderline or atypical emotional symptoms (OR, 2.44; 95% CI, 1.11–5.38) or behavioural difficulties (OR, 2.35; 95% CI, 1.04–5.33). Food insecurity may be prevalent among socioeconomically disadvantaged households with children. The potential developmental consequences of food insecurity during childhood may result in serious adverse health and social implications.