Common variants in the region around Osterix are associated with bone mineral density and growth in childhood

Peak bone mass achieved in adolescence is a determinant of bone mass in later life. In order to identify genetic variants affecting bone mineral density (BMD), we performed a genome-wide association study of BMD and related traits in 1518 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). We compared results with a scan of 134 adults with high or low hip BMD. We identified associations with BMD in an area of chromosome 12 containing the Osterix (SP7) locus, a transcription factor responsible for regulating osteoblast differentiation (ALSPAC: P = 5.8 × 10-4; Australia: P = 3.7 × 10-4). This region has previously shown evidence of association with adult hip and lumbar spine BMD in an Icelandic population, as well as nominal association in a UK population. A meta-analysis of these existing studies revealed strong association between SNPs in the Osterix region and adult lumbar spine BMD (P = 9.9 × 10-11). In light of these findings, we genotyped a further 3692 individuals from ALSPAC who had whole body BMD and confirmed the association in children as well (P = 5.4 × 10-5). Moreover, all SNPs were related to height in ALSPAC children, but not weight or body mass index, and when height was included as a covariate in the regression equation, the association with total body BMD was attenuated. We conclude that genetic variants in the region of Osterix are associated with BMD in children and adults probably through primary effects on growth.

Partial epilepsy syndrome in a Gypsy family linked to 5q31.3-q32

PURPOSE The restricted genetic diversity and homogeneous molecular basis of Mendelian disorders in isolated founder populations have rarely been explored in epilepsy research. Our long-term goal is to explore the genetic basis of epilepsies in one such population, the Gypsies. The aim of this report is the clinical and genetic characterization of a Gypsy family with a partial epilepsy syndrome. METHODS Clinical information was collected using semistructured interviews with affected subjects and informants. At least one interictal electroencephalography (EEG) recording was performed for each patient and previous data obtained from records. Neuroimaging included structural magnetic resonance imaging (MRI). Linkage and haplotype analysis was performed using the Illumina IVb Linkage Panel, supplemented with highly informative microsatellites in linked regions and Affymetrix SNP 5.0 array data. RESULTS We observed an early-onset partial epilepsy syndrome with seizure semiology strongly suggestive of temporal lobe epilepsy (TLE), with mild intellectual deficit co-occurring in a large proportion of the patients. Psychiatric morbidity was common in the extended pedigree but did not cosegregate with epilepsy. Linkage analysis definitively excluded previously reported loci, and identified a novel locus on 5q31.3-q32 with an logarithm of the odds (LOD) score of 3 corresponding to the expected maximum in this family. DISCUSSION The syndrome can be classified as familial temporal lobe epilepsy (FTLE) or possibly a new syndrome with mild intellectual deficit. The linked 5q region does not contain any ion channel-encoding genes and is thus likely to contribute new knowledge about epilepsy pathogenesis. Identification of the mutation in this family and in additional patients will define the full phenotypic spectrum.

Physical activity cost in children following an acquired brain injury : a comparative study

Background: Alterations in energy expenditure during activity post head injury has not been investigated due primarily to the difficulty of measurement. Objective: The aim of this study was to compare energy expenditure during activity and body composition of children following acquired brain injury (ABI) with data from a group of normal controls. Design: Energy expenditure was measured using the Cosmed K4b2 in a group of 15 children with ABI and a group of 67 normal children during rest and when walking and running. Mean number of steps taken per 3 min run was also recorded and body composition was measured. Results: The energy expended during walking was not significantly different between both groups. A significant difference was found between the two groups in the energy expended during running and also for the number of steps taken as children with ABI took significantly less steps than the normal controls during a 3 min run. Conclusions: Children with ABI exert more energy per activity than healthy controls when controlled for velocity or distance. However, they expend less energy to walk and run when they are free to choose their own desirable, comfortable pace than normal controls. © 2003 Elsevier Ltd. All rights reserved.

Consultation with Aboriginal and Torres Strait Islander people in early childhood education: The impact of colonial discourses

In Australian early years education, consultation and partnerships with Aboriginal and Torres Strait Islander people are central to embedding Indigenous perspectives. Building sustained and reciprocal partnerships with Aboriginal and Torres Strait Islander people supports access to local knowledges and perspectives to inform curriculum planning, as well as protocols and community processes, and contemporary responses to colonisation. Drawing on data from a doctoral study about embedding Aboriginal and Torres Strait Islander perspectives in early childhood education curricula, this paper examines interactional patterns in consultations between non-Indigenous early childhood educators and Indigenous people in real and supposed form. Data is read through whiteness studies literature and related critiques to identify how the educators positioned Indigenous people in interactional patterns and how the mobilisation of colonial discourses impacted the potential for reciprocity and sustained partnerships, despite the best of intentions. Colonial traces of positioning Indigenous people as informants, targeted resources or knowledge commissioners were shown to be most salient in interactional patterns. While these findings are contextualised within Australia, I suggest they have applicability in examining approaches to embedding Indigenous perspectives in education curricula in other colonising contexts such as Canada and New Zealand.

Adolescent sexual behavioral intentions measurement: A gender approach in the Colombian Caribbean region [Medición de la Intención en la Actividad Sexual en Adolescentes: una Aproximación de Acuerdo al Género del Caribe Colombiano]

The study of 1777 male and female adolescent students of 11-19 years in the Colombian Caribbean had two objectives: development and validation of two reproductive health intention scales and analyze gender differences. The pilot of the scale consisted of 8 items and was reduced to 6, to check the reliability and validity using factor analysis and principal components with VARIMAX rotation yielded two factors: Intention and Intention Risk Protection, explained between 69.4% and 70% respectively. In the male Protection Intent (M = 3.87 and SD = 1.29) and risk (M = 2.56 and SD = 1.18) obtained an alpha between 0.74 and 0.86, and in Protection of Intent to female (M = 3.49 and SD = 1.35) and risk (M = 1.50 and SD = 0.89) ranged between 0.78 and 086. In conclusion, the reliability and structural stability are adequate and there are gender differences in the scales.

Influence of LRP5 polymorphisms on normal variation in BMD

Genetic studies based on cohorts with rare and extreme bone phenotypes have shown that the LRP5 gene is an important genetic modulator of BMD. Using family-based and case-control approaches, this study examines the role of the LRP5 gene in determining normal population variation of BMD and describes significant association and suggestive linkage between LRP5 gene polymorphisms and BMD in >900 individuals with a broad range of BMD. Introduction: Osteoporosis is a common, highly heritable condition determined by complex interactions of genetic and environmental etiologies. Genetic factors alone can account for 50-80% of the interindividual variation in BMD. Mutations in the LRP5 gene on chromosome 11q12-13 have been associated with rare syndromes characterized by extremely low or high BMD, but little is known about the contribution of this gene to the development of osteoporosis and determination of BMD in a normal population. Materials and Methods: To examine the entire spectrum of low to high BMD, 152 osteoporotic probands, their families (597 individuals), and 160 women with elevated BMD (T score > 2.5) were recruited. BMD at the lumbar spine, femoral neck, and hip were measured in each subject using DXA. Results: PAGE sequencing of the LRP5 gene revealed 10 single nucleotide polymorphisms (SNPs), 8 of which had allele frequencies of >5%, in exons 8, 9, 10, 15, and 18 and in introns 6, 7, and 21. Within families, a strong association was observed between an SNP at nucleotide C171346A in intron 21 and total hip BMD (p < 1 × 10-5 in men only, p = 0.0019 in both men and women). This association was also observed in comparisons of osteoporotic probands and unrelated elevated BMD in women (p = 0.03), along with associations with markers in exons 8 (C135242T, p = 0.007) and 9 (C141759T, p = 0.02). Haplotypes composed of two to three of the SNPs G121513A, C135242T, G138351A, and C141759T were strongly associated with BMD when comparing osteoporotic probands and high BMD cases (p < 0.003). An SNP at nucleotide C165215T in exon 18 was linked to BMD at the lumbar spine, femoral neck, and total hip (parametric LOD scores = 2.8, 2.5, and 2.2 and nonparametric LOD scores = 0.3, 1.1, and 2.2, respectively) but was not genetically associated with BMD variation. Conclusion: These results show that common LRP5 polymorphisms contribute to the determination of BMD in the general population.

Suggestive linkage of the parathyroid receptor type 1 to osteoporosis

We have investigated the role of 23 candidate genes in the control of bone mineral density (BMD) by linkage studies in families of probands with osteoporosis (lumbar spine [LS] or femoral neck [FN] BMD T score < -2.5) and low BMD relative to an age- and gender-matched cohort (Z score < -2.0). One hundred and fifteen probands (35 male, 80 female) and 499 of their first- or second-degree relatives (223 males and 276 females) were recruited for the study. BMD was measured at the LS and FN using dual-energy X-ray absorptiometry and expressed as age- and gender-matched Z scores corrected for body mass index. The candidate genes studied were the androgen receptor, type I collagen A1 (COLIA1), COLIA2, COLIIA1, vitamin D receptor (VDR), colony-stimulating factor 1, calcium-sensing receptor, epidermal growth factor (EGF), estrogen receptor 1 (ESR1), fibrillin type 1, insulin-like growth factor 1, interleukin-1 alpha (IL-1α), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-11 (IL-11), osteopontin, parathyroid hormone (PTH), PTH-related peptide, PTH receptor type 1 (PTHR1), transforming growth factor-beta 1, and tumor necrosis factors alpha and beta. Sixty-four microsatellites lying close to or within these genes were investigated for linkage with BMD. Using the program MapMaker/Sibs there was suggestive evidence of linkage between BMD and PTHR1 (maximum LOD score obtained [MLS] 2.7-3.5). Moderate evidence of linkage was also observed with EGF (MLS 1.8), COLIA1 (MLS 1.7), COLIIA1/VDR (MLS 1.7), ESR1 (MLS 1.4), IL-1α (MLS 1.4), IL-4 (MLS 1.2), and IL-6 (MLS 1.2). Variance components analysis using the program ACT, correcting for proband-wise ascertainment, also showed evidence of linkage (p ≤0.05) at markers close to or within the candidate genes IL- 1α, PTHR1, IL-6, and COLIIA1/VDR. Further studies will be required to confirm these findings, to refine the location of gene responsible for the observed linkage, and to screen the candidate genes targeted at these loci for mutations.

Nutritional status of children with cystic fibrosis measured by total body potassium as a marker of body cell mass: Lack of sensitivity of anthropometric measures

Objective: To investigate measures aimed at defining the nutritional status of cystic fibrosis (CF) populations, this study compared standard anthropometric measurements and total body potassium (TBK) as indicators of malnutrition. Methods: Height, weight, and TBK measurements of 226 children with CF from Royal Children's Hospital, Brisbane, Australia, were analyzed. Z scores for height for age, weight for age, and weight for height were analyzed by means of the National Centre for Health Statistics reference. TBK was measured by means of whole body counting and compared with predicted TBK for age. Two criteria were evaluated with respect to malnutrition: (1) a z score < -2.0 and (2) a TBK for age <80% of predicted. Results: Males and females with CF had lower mean height-for-age and weight-for-age z scores than the National Centre for Health Statistics reference (P < .01), but mean weight-for-height z score was not significantly different. There were no significant gender differences. According to anthropometry, only 7.5% of this population were underweight and 7.6% were stunted. However, with TBK as an indicator of nutritional status, 29.9% of males and 22.0% of females were malnourished. Conclusion: There are large differences in the percentage of patients with CF identified as malnourished depending on whether anthropometry or body composition data are used as the nutritional indicator. At an individual level, weight-based indicators are not sensitive indicators of suboptimal nutritional status in CF, significantly underestimating the extent of malnutrition. Current recommendations in which anthropometry is used as the indicator of malnutrition in CF should be revised.

Malnutrition, gastroenteritis and trypsinogen concentration in hospitalised aboriginal children

Objective: To explore relationships between malnutrition and pancreatic damage in hospitalised aboriginal children. Methods: Immunoreactive trypsinogen (IRT) concentrations were measured in two populations of hospitalised aboriginal children in Australia; 472 children aged 0-3 years, in Alice Springs (Northern Territory); and 187 children aged 0-16 years in Mount Isa (Queensland). Correlation of whole blood IRT with height and weight z-scores, four-site skinfold thickness and upper arm circumference was sought. Results: In Mount Isa, the geometric mean IRT concentration rose with decreasing weight z-score. The IRT concentration was otherwise unrelated to nutritional indices. Sixty percent of the 39 Mount Isa patients with gastroenteritis and 24.5% of the 358 Alice Springs patients with gastroenteritis had an IRT concentration in the upper quartile for their population, compared with 16% for patients with other diagnoses in both populations. Conclusions: A high IRT concentration in patients with low weight z-scores is a confounding effect of gastroenteritis, and may result from subclinical pancreatic disease in gastroenteritis.

Palliative care problem severity score: Reliability and acceptability in a national study

Background The Palliative Care Problem Severity Score is a clinician-rated tool to assess problem severity in four palliative care domains (pain, other symptoms, psychological/spiritual, family/carer problems) using a 4-point categorical scale (absent, mild, moderate, severe). Aim To test the reliability and acceptability of the Palliative Care Problem Severity Score. Design: Multi-centre, cross-sectional study involving pairs of clinicians independently rating problem severity using the tool. Setting/participants Clinicians from 10 Australian palliative care services: 9 inpatient units and 1 mixed inpatient/community-based service. Results A total of 102 clinicians participated, with almost 600 paired assessments completed for each domain, involving 420 patients. A total of 91% of paired assessments were undertaken within 2 h. Strength of agreement for three of the four domains was moderate: pain (Kappa = 0.42, 95% confidence interval = 0.36 to 0.49); psychological/spiritual (Kappa = 0.48, 95% confidence interval = 0.42 to 0.54); family/carer (Kappa = 0.45, 95% confidence interval = 0.40 to 0.52). Strength of agreement for the remaining domain (other symptoms) was fair (Kappa = 0.38, 95% confidence interval = 0.32 to 0.45). Conclusion The Palliative Care Problem Severity Score is an acceptable measure, with moderate reliability across three domains. Variability in inter-rater reliability across sites and participant feedback indicate that ongoing education is required to ensure that clinicians understand the purpose of the tool and each of its domains. Raters familiar with the patient they were assessing found it easier to assign problem severity, but this did not improve inter-rater reliability.

Understanding Early Childhood Education and Care in Australia: Practices and Perspectives

A foundational text for pre-service teachers explaining the theories, policies and pedagogies that shape the provision of early childhood education and care in Australia. In order to effectively practise as an early childhood educator it is essential to understand the theories, policies and pedagogy that shape the discipline. Understanding Early Childhood Education and Care in Australia provides core foundational knowledge that is critical for best practice. Part One looks at concepts of childhood and the development of mass education before examining influential theories including developmental psychology, sociology, feminisms and critical theory. Specific approaches are also analysed including Reggio Emilia, Montessori, Multiple Intelligences and HighScope. Part Two focuses on the guiding frameworks and policies in Australia and explores in depth issues affecting Indigenous children and provisions for recognising diversity and the practice of inclusion. The final section examines teaching and leadership and considers curriculum, pedagogy and assessment, building relationships between staff and families, the care of babies and infants, the environment in which early childhood education takes place and the responsibilities and professional development of teachers. This essential reference will ensure pre-service teachers develop a sophisticated understanding of how theory underpins effective practice in early childhood education.

Childhood-as-rescue in the emergence and spread of the U.S. public school

In this volume, the editors have brought together prominent international contributors to examine the relevance of Foucauldian thought on educational theory, practice and institutional life. The result is a diverse collection that offers broad and engaging analyses of how power and knowledge are configured in the practices and norms of schooling. This text not only provides a critical examination of the significance of Foucauldian thought for education, but also discusses how Foucault's theories are arrayed in the everyday life of schools.

Submission to Queensland Law Reform Commission WP 73 Review of Child Protection Mandatory Reporting Laws for the Early Childhood Education and Care Sector

In 2015 the QLRC is conducting an inquiry into whether to extend legislative mandatory reporting duties for physical abuse and sexual abuse to early childhood education and care practitioners. The current legislation does not require these practitioners to report suspected cases of significant harm from physical or sexual absue to child welfare agencies. Based on the literature, and a multidisciplinary analysis, our overall recommendation is that we endorse the extension to selected early childhood education and care practitioners of Queensland’s current mandatory reporting duty in the Child Protection Act 1999 s 13E.

Survival, growth and quality of life in children after orthotopic liver transplantation: A 5 year experience

The aims of this study were to investigate outcome and to evaluate areas of potential ongoing concern after orthotopic liver transplantation (OLT) in children. Actuarial survival in relation to age and degree of undernutrition at the time of OLT was evaluated in 53 children (age 0.58-14.2 years) undergoing OLT for endstage liver disease. Follow-up studies of growth and quality of life were undertaken in those with a minimum follow-up period of 12 months (n = 26). The overall 3 year actuarial survival was 70%. Survival rates did not differ between age groups (actuarial 2 year survival for ages <1, 1-5 and >5 years were 70, 70 and 69% respectively) but did differ according to nutritional status at OLT (actuarial 2 year survival for children with Z scores for weight <-1 was 57%, >-1 was 95%; P = 0.004). Significant catch-up weight gain was observed by 18 months post-transplant, while height improved less rapidly. Quality of life (assessed by Vineland Adaptive Behaviour Scales incorporating socialization, daily living skills, communication and motor skills) was good (mean composite score 91 ± 19). All school-aged children except one were attending normal school. Two children had mild to moderate intellectual handicap related to post-operative intracerebral complications. Satisfactory long-term survival can be achieved after OLT in children regardless of age but the importance of pre-operative nutrition is emphasized. Survivors have an excellent chance of a good quality of life and of satisfactory catch-up weight gain and growth.

Pre-operative nutritional support in children with end-stage liver disease accepted for liver transplantation: An approach to management

Pre-operative nutritional support was studied in 28 children with end-stage liver disease awaiting orthotopic liver transplantation. Nasogastric supplemental administration of a standard semi-elemental enteral nutritional formula was compared with a similar formula enriched with branched chain amino acids, and with a group receiving oral nutrition only. The duration of treatment in all groups was similar (mean 90 days). Energy intakes in the supplemented groups were 120-150% of recommended daily intakes (RDI), whereas ad libitum intakes in the oral group ranged 58-100% RDI. A significant improvement in mean Z-score for body weight (denoting catch-up) was noted only in those children who received nasogastric supplements enriched with branched-chain amino acids. The standard enterally-fed group maintained their body weight and Z-scores did not change significantly. In contrast, body weight Z-scores in those fed orally declined significantly. Nutritional supportive therapy of malnourished children with end-stage liver disease can minimize or improve nutritional status in children awaiting liver transplantation. The use of nutritional formulae rich in branche-chain amino acids may have nutritional advantages in children with chronic liver disease which require further study and evaluation.